Wetenschappelijke publicaties

Overzicht wetenschappelijke publicaties 2012

Wetenschappelijke publicaties

©2013 Amphia Ziekenhuis Alle rechten voorbehouden. Niets uit deze uitgave mag worden verveelvoudigd, opgeslagen in een geauto matiseerd gegevensbestand, of openbaar gemaakt, in enige vorm of op enige wijze, hetzij elektronisch, mechanisch, door fotokopieën, opnamen, of enige andere manier, zonder voorafgaande toestemming van de uitgever. Voor zover het maken van kopieën uit deze uitgave is toegestaan op grond van artikel 16B Auteurswet 1912 j° het Besluit van 20 juni 1974, St.b. 351, zoals gewijzigd bij Besluit van 23 augustus 1985, St.b. 471 en artikel 17 Auteurswet 1912, dient men de daarvoor wettelijk verschuldigde vergoedingen te voldoen aan de Stichting Reprorecht. Voor het overnemen van gedeelte(n) uit deze uitgave in bloem lezingen, readers en andere compilatie- of andere werken (artikel 16 Auteurswet 1912), in welke vorm dan ook, dient men zich tot de samenstellers/vormgever te wenden. De inzichten in de geneeskunde en wetenschap zijn voortdurend aan verandering onderhevig als gevolg van onderzoek en ervaring. De auteurs en uitgever zijn uiterst zorgvuldig te werk gegaan, om ervoor te zorgen dat de in dit boek verstrekte informatie, in overeenstemming is met de huidige kennis van zaken. Dit ontslaat de gebruiker van het boek echter niet van de verplichting om aan de hand van bestaande richtlijnen, protocollen en wetenschappelijke informatie te controleren of de daar verstrekte informatie afwijkt van de gegevens in dit boek en daarmee vast te stellen of de inhoud nog in overeenstemming is met de huidige stand van zaken ten aanzien van kennis en handelen. Ondanks alle aan de samenstelling van deze uitgave bestede zorg, zullen noch de samenstellers, noch de vormgever aansprakelijkheid aanvaarden voor eventuele schade die zou kunnen voortvloeien uit enige fout die in deze uitgave zou kunnen voorkomen.

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Voorwoord

Dit is het vijfde wetenschapsboek van het Amphia Ziekenhuis. Net als voorgaande jaren geeft het een goed overzicht van de diverse wetenschappelijke activiteiten van het afgelopen jaar. Veel specialisten hebben ook nu weer naast hun reguliere werk zaamheden bijgedragen aan wetenschappelijk onderzoek. Dit is noodzakelijk om de geneeskunde verder te brengen en genezing dichterbij. Hierin spelen STZ ziekenhuizen inmiddels een centrale rol. Door hun goede infrastructuur voor wetenschap en op leiding, en hun grote patiëntenpopulatie zijn zij de leveranciers van omvangrijke patiëntencohorten die noodzakelijk zijn voor de noodzakelijke bewijskracht (power) achter wetenschappelijke studies en experimenten. Gelukkig zijn steeds meer patiën ten bereid om ook daaraan mee te werken. Op deze plaats is ook een woord van dank op zijn plaats aan al die patiënten die belangeloos meewerken aan nieuwe studies. Op het gebied van de primaire STZ-taken, te weten wetenschap, onderwijs en oplei ding heeft het Amphia Ziekenhuis zich wederom bewezen. Door middel van de hier gepresenteerde onderzoeksresultaten, maar ook door een zeer geslaagde hernieuwing van haar lidmaatschap en het doorstaan van bijbehorende visitaties. Ik wens u veel genoegen met het doorlezen en spreek namens het Directiecomité mijn dank uit aan auteurs van de artikelen en de samenstellers van dit boek.

Dr. J.J. (Hans) Meij, directeur Innovatie

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Wetenschapsbureau “In de zorg betaalt men voor de Mercedes evenveel als voor de Fiat Panda” Decaan prof. dr. Jo Caris en wetenschapscoördinator dr. Attie Tuinenburg van het Wetenschapsbureau van de Amphia Academie zetten zich in voor meer wetenschappelijk onderzoek van hoog niveau. Dat gebeurt onder meer door het ondersteunen en stimuleren van onderzoekers. Een belangrijk uitgangspunt is integratie van zorg, opleiding en onderzoek, zowel voor de praktijk als in het beleid. “Hiermee streven we naar een optimaal onderzoeksklimaat.” Het Amphia Ziekenhuis is een Samenwerkend Topklinisch opleidingsZiekenhuis (STZ). Anders dan bij academische ziekenhuizen valt het niet altijd mee om tijd vrij te maken voor onderzoek. Medici en paramedici besteden het grootste deel van hun tijd en aandacht aan de zorg voor patiënten, en terecht.

Wetenschapscoördinator dr. Attie Tuinenburg (links) en decaan prof.dr. Jo Caris.

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Attie Tuinenburg: “Wat wij als wetenschapsbureau kunnen doen, is het voor de onder zoekers zo gemakkelijk mogelijk maken om onderzoek te doen. We kunnen ondersteu nen met bijvoorbeeld methodologische en statistische hulp. Daarnaast verbeteren we de procedures rondom onderzoek binnen het ziekenhuis.” Een belangrijk uitgangspunt voor het onderzoek in het Amphia Ziekenhuis is integratie van zorg, opleiding en on derzoek, zowel voor de praktijk als in het beleid. “De nadruk ligt op de samenhang tussen de kwaliteit van zorg, de organisatie van zorg, en de kosten. We stimuleren onderzoek dat de eigen discipline overstijgt, dus waarbij zorgkernen samenwerken.” Maatschappelijke relevantie Naast een duidelijk omschreven klinische relevantie benadrukken Caris en Tuinenburg ook het toenemende belang van de maatschappelijke relevantie van wetenschappelijk onderzoek. Zo kan een andere behandeling naast reductie van bijvoorbeeld morbiditeit ook leiden tot een snellere terugkeer van de patiënt op de arbeidsmarkt, of kan een minder invasieve behandeling leiden tot een hogere kwaliteit van leven en lagere kos ten. De maatschappij (publiek, patiëntenorganisaties, politiek, verzekeraars) verwacht hiervoor tegenwoordig steeds meer aandacht. Bijna al het wetenschappelijk onderzoek dat in het Amphia Ziekenhuis wordt uitgevoerd bevat deze elementen zonder dat ze nadrukkelijk benoemd worden. Het accentueren van de klinische en maatschappelijke relevantie kan als voordeel hebben dat er eerder tweede en derde geldstromen be schikbaar worden gesteld ter financiering van het betreffende onderzoek. Organisatorisch onderzoek Het woord ‘organisatie’ valt regelmatig tijdens het gesprek. Jo Caris is opgeleid als organisatiepsycholoog en zat dertig jaar lang in besturen van zorginstellingen. Hij promoveerde op het onderwerp ‘Kwaliteit van consulten’. Caris als hoogleraar Organisatieontwikkeling in de Zorg verbonden aan de TiasNimbas Business School (Universiteit Tilburg). Onderzoek via de ‘Theory of Constraints’ (waarbij naar optima lisering van processen wordt gekeken) en de discussie over tussenafdelingen, zoals een PACU (post anesthesia care unit) zijn voorbeelden van organisatorische thema’s met zorginhoudelijke en kwaliteitsconsequenties. Caris stelt dat de toenemende complexiteit van de zorg aanzet tot nadenken over beheersbaarheid en bestuurbaar heid. “De zorg is de enige sector waar kwaliteit nog losgekoppeld is van kosten. Maar je koopt toch ook geen auto zonder dat daar een prijskaartje aan hangt? In de zorg betaalt men voor de Mercedes evenveel als voor de Fiat Panda. Maar als je een boodschappenwagen zoekt dan koop je toch geen Jaguar, als je de kosten zelf moet betalen? Voegt het waarde toe om personen van 93 jaar te opereren? Misschien wel, maar het is belangrijk om op voorhand wél die vraag te stellen en de consequenties goed te onderkennen.”

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Industrie-geïnitieerd en eigen onderzoek Waarom is het belangrijk dat er onderzoek in het Amphia Ziekenhuis plaatsvindt? “Het is voor de kwaliteit van zorg van belang dat de zorgverleners op de hoogte zijn van de meest recente ontwikkelingen en onderzoeksresultaten. Door deel te nemen aan bijvoorbeeld industrie-geïnitieerd onderzoek staan de zorgverlener en de patiënt op de voorste rij wat betreft behandeling”, antwoordt Tuinenburg. “Maar ook studies geïnitieerd door onderzoekers uit het Amphia Ziekenhuis leiden tot verbetering van zorg of zorgprocessen waar de patiënt voordeel bij heeft.” Tuinenburg benadrukt dat samenwerking met academische ziekenhuizen gestimuleerd wordt. “Veel onderzoek wordt daar opgestart. Kennis, ervaring en data uit STZ-ziekenhuizen zijn daarbij onmisbaar.” Attie Tuinenburg is opgeleid als arts en epidemioloog en deed haar promotieonderzoek (zowel lab- als klinisch onderzoek) naar hart- en vaatziekten en slagaderverkalking bij patiënten met stollingsstoornissen. In maart 2013 promoveerde ze. “Deze functie past prima bij mij. Ik ben bezig met wetenschapsinhoud, methodologie en statistiek. Daar bij is een artsenopleiding een groot voordeel, ik kan snel schakelen en aansluiten bij de beroepspraktijk.” Caris en Tuinenburg vullen elkaar naar eigen zeggen aan door de combinatie van methodisch en organisatorisch denken en dat zorgt voor een stevige bundeling van krachten. Ambitie en groei De wetenschap ontwikkelt zich in Amphia! Jo Caris en Attie Tuinenburg zijn recent gestart in het Amphia Ziekenhuis. Met Jan van Trier (bibliothecaris), Elmar Beekman (Kernproject Subsidies, Sponsoring en Fondsenwerving) en Birgitte SchaerlaeckensJordan (ambtelijk secretaris AMOA (Adviescommisssie Mensgebonden Onderzoek Amphia) vormen zij op dit moment het Wetenschapsbureau. Caris: “De afgelopen weken hebben we veel onderzoekers gesproken. En de komende tijd richten we ons op wetenschappelijke inhoudelijke ondersteuning, beleidsontwikkeling, procesverbe tering (AMOA/METC) en wetenschapspromotie. De komende jaren streven we naar een optimaal wetenschapsklimaat in het Amphia Ziekenhuis, waarbij het Weten schapsbureau goed toegankelijk is en onderzoekers op alle benodigde gebieden kan ondersteunen.”

Wetenschapsbureau

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Inhoud Anesthesiologie

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Cardiologie

14

Cardiothoracale Chirurgie

35

Chirurgie

37

Dermatologie

64

Gynaecologie

65

Interne Geneeskunde en Maag- Darm- Levergeneeskunde

77

Keel-, Neus- en Oorheelkunde

86

Kindergeneeskunde

89

Klinisch Chemisch Hematologisch Laboratorium

95

Klinische Farmacie

99

Klinische Geriatrie

102

Laboratorium voor Microbiologie en Infectiepreventie

103

Longgeneeskunde

122

Mondziekten, Kaak- en Aangezichtschirurgie

136

Neurologie

139

Nucleaire Geneeskunde

142

Oogheelkunde

144

Orthopedie

147

Pathologie

158

Radiologie

159

Reumatologie

165

Seksuologie

170

Sportgeneeskunde

171

Urologie

172

Kwaliteit & Veiligheid

177

Zorginnovatie

182

Publicaties medisch specialisten 2012

184

Publicaties arts-assistenten 2012

213

Publicaties overige werknemers 2012

217

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Anesthesiologie Kerngegevens Zorgkern Anesthesiologie • 28 anesthesiologen: A. (Anna) Besselink-Lobanova, S.F. (Sjoerd) de Boer, H.P. (Henk) van Driel, M.J.P.G. (Maarten) van Eerd, F.E.A. (Ferd) Geisler, G. (Gerhard) van Gelder, dr. B.M. (Bas) Gerritse, C. (Carla) van Gompel, dr. V.L.H. (Vincent) Hoffmann, L.H. (Lode) Jacobs, G.M.J. (Greg) Jansen, A. (Aad) van Keeken, J.D.L. (Johan) Konings, E.B. (Edmund) Lachitjaran, F. (Frank) de Loos, P.P.M. (Paul) Maas, dr. B.J.M. (Nardo) van der Meer, R.J. (Robert) Meulemans, F.X. (Frank) O’Connor, P.M.J. (Peter) Rosseel, T.A. (Tom) Rijpstra, D.B. (David) Schockman, T.V. (Thierry) Scohy, G.C.H. (Gilbert) Tjiang, W.A. (Anton) Visser, M.A.J. (Michael) Voets, E. (Erik) Winters, S.I.M. (Simone) van Zijll Langhout-Kokke. • 5 assistenten niet in opleiding • 3 assistenten in opleiding • Chef de clinique: P.A.V. (Peter) Frietman, P. (Pim) van der Heiden, I. (Iris) Witsch • Internist-intensivist: R.A.L. (Ruud) de Waal, F.J. (Frits) Schuitemaker • Longarts-intensivist: H.N.A. (Huub) Belderbos

Samenvattingen gepubliceerde artikelen Van der Kleij SC, Koolen BB, Newhall DA, Gerritse BM, Rosseel PM, Rijpstra TA, Geisler FE, van der Meer NJ.Clinical evaluation of a new tracheal impedance cardiography method. Anaesthesia. 2012 Jul;67(7):729-33. Epub 2012 Mar 15. Non-invasive cardiac output measurement by means of impedance cardiography has been evaluated before, and agreement with other methods has been variable. We decided to study a newly developed tracheal impedance device, that is claimed to be more accurate and reliable. This incorporates new software and mathematical formulae, that are designed to reduce signal noise from diathermy, leading to impro ved accuracy. In 25 cardiothoracic surgery patients, simultaneous measurements were performed using both pulmonary artery thermodilution and the tracheal impedance device, at five peri-operative time points: before skin incision; after weaning from cardiopulmonary bypass; after sternal closure; and 30 min and 2 h after arrival in the intensive care unit. Mean cardiac output, bias and 95% limits of agreement were 5.3, 0.03 and -2.8 to 2.8 l.min(-1) , respectively. Tracheal impedance showed good correla tion with measurement trends using thermodilution in 88% of measurements, with a mean (95% limit of agreement) angular bias of -9.0° (-83.3 to 65.3°). However, the wide limits of agreement and high percentage error of 53% that were apparent in this study mean that, in its present guise, tracheal impedance is not an acceptable alternative to thermodilution in cardiac surgical patients. Anaesthesia © 2012 The Association of Anaesthetists of Great Britain and Ireland. PMID: 22420758

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Dieleman JM, Nierich AP, Rosseel PM, van der Maaten JM, Hofland J, Diephuis JC, Schepp RM, Boer C, Moons KG, van Herwerden LA, Tijssen JG, Numan SC, Kalkman CJ, van Dijk D; Dexamethasone for Cardiac Surgery (DECS) Study Group*. [van der Meer NJ et al...]. Intraoperative high-dose dexamethasone for cardiac surgery: a randomized controlled trial. JAMA. 2012 Nov 7;308(17):1761-7. CONTEXT: Prophylactic corticosteroids are often administered during cardiac surgery to attenuate the inflammatory response to cardiopulmonary bypass and surgical trauma; however, evidence that routine corticosteroid use can prevent major adverse events is lacking. OBJECTIVE: To quantify the effect of intraoperative high-dose dexamethasone on the incidence of major adverse events in patients undergoing cardiac surgery. DESIGN, SETTING, AND PARTICIPANTS: A multicenter, randomized, double-blind, placebo-controlled trial of 4494 patients aged 18 years or older undergoing cardiac surgery with cardiopulmonary bypass at 8 cardiac surgical centers in The Netherlands enrolled between April 13, 2006, and November 23, 2011. INTERVENTION: Patients were randomly assigned to receive a single intraoperative dose of 1 mg/kg dexamethasone (n = 2239) or placebo (n = 2255). MAIN OUTCOME MEASURES: A composite of death, myocardial infarction, stroke, renal failure, or respiratory failure, within 30 days of randomization. RESULTS: Of the 4494 patients who underwent randomization, 4482 (99.7%) could be evaluated for the primary outcome. A total of 157 patients (7.0%) in the dexa methasone group and 191 patients (8.5%) in the placebo group reached the primary study end point (relative risk, 0.83; 95% CI, 0.67-1.01; absolute risk reduction, -1.5%; 95% CI, -3.0% to 0.1%; P = .07). Dexamethasone was associated with reductions in post operative infection, duration of postoperative mechanical ventilation, and lengths of intensive care unit and hospital stays. In contrast, dexamethasone was associated with higher postoperative glucose levels. CONCLUSION: In our trial of adults undergoing cardiac surgery, the use of intra operative dexamethasone did not reduce the 30-day incidence of major adverse events compared with placebo. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00293592.

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Collaborators (42) : Bredée JJ, Buhre WF, Dieleman JM, van Dijk D, van Herwerden LA, Kalkman CJ, van Klarenbosch J, Moons KG, Nathoe HM, Numan SC, Ottens TH, Roes KC, Sauer AM, Slooter AJ, Nierich AP, Ennema JJ, Rosseel PM, van der Meer NJ, van der Maaten JM, Cernak V, Hofland J, van Thiel RJ, Diephuis JC, Schepp RM, Haenen J, de Lange F, Boer C, de Jong JR, Tijssen JG, Hofland J, de Jong JR. PMID: 23117776

Van Seventer R, Vos C, Giezeman M, Meerding WJ, Arnould B, Regnault A, van Eerd M, Martin C, Huygen F. Validation of the Dutch Version of the DN4 Diagnostic Question naire for Neuropathic Pain. Pain Pract. 2013 Jun;13(5):390-8. Epub 2012 Oct 31. Difficulties in diagnosing neuropathic pain in routine clinical practice support the need for validated and easy-to-use diagnostic tools. The DN4 neuropathic pain diagnostic questionnaire aims to discriminate neuropathic pain from nociceptive pain, but needs clinical validation. A total of 269 patients with chronic pain in three pain clinics were included in the study of which 248 had analyzable data. The mean duration of pain was 4.9 years. The most frequent etiologies were posttraumatic (36%), (pseudo) radi cular (14%), and mechanical back pain (12%). The mean intensity of pain at visit was 5.6 on a 0-10 scale. Hundred and ninety-six of 248 patients had an identical pain diagnosis from both physicians: 85 had neuropathic pain, 57 had nociceptive pain, and 54 had mixed pain. Among patients with identical diagnoses of neuropathic or nociceptive pain, using a receiver operating characteristic curve analysis, the area under the curve (AUC) was 0.81 for the DN4 7-item and 0.82 for the 10-item version. A cutoff point of 5/10 for the full questionnaire resulted in a sensitivity of 75% and a specificity of 79%, while a cutoff point of 4/7 for the partial questionnaire resulted in a sensitivity of 74% and a specificity of 79%. The items “”brushing,”” “”painful cold,”” and “”numbness”” were most discriminating. The DN4 is an easy-to-use screening tool that is reliable for discriminating between neuropathic and nociceptive pain conditions in daily practice. Item-specific scores provide important information in addition to the total score. © 2012 The Authors Pain Practice © 2012 World Institute of Pain. PMID: 23113981

Hulsman N, Gerritse BM. Het cardiale trauma. A&I : nascholingstijdschrift over perioperatieve geneeskunde. 2012;4(4):33-37. Cardiaal letsel kan worden onderverdeeld in stomp en penetrerend letsel. Stompe cardiale traumata kunnen, afhankelijk van de omvang van het trauma, worden onderverdeeld in een contusio en een commotio cordis. Ook kan bij een hoogener-

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getisch trauma letsel ontstaan aan de anatomische structuren van het hart (hartkleppen, coronairarteriën en septum). De belangrijkste complicatie van stomp en penetrerend cardiaal letsel is een tamponnade. Bij de opvang van een multitrauma is het herkennen van cardiaal letsel en eventuele complicaties cruciaal. Niemeijer ND, van Daele PL, Caliskan K, Oei FB, Loosveld OJ, van der Meer NJ. Löffler endocarditis: a rare cause of acute cardiac failure. J Cardiothorac Surg. 2012 Oct 10;7(1):109. [Epub ahead of print] We describe a patient with acute cardiogenic shock due to cardiac involvement in idiopathic hypereosinophilic syndrome (Loffler endocarditis). At the echocardiography, there was a huge mass in the left ventricular cavity, resulting in inflow- and outflow tract obstruction. The posterior leaflet of the mitral valve apparatus was completely embedded in a big (organized) thrombus mass. The patient was treated with high dose corticosteroids, however without effect. Partial remission was achieved after treatment with hydroxycarbamide. He was also treated with anticoagulants and high dose beta-blockers. The patient’s condition improved remarkably after correction of the mitral valve insufficiency by a mitral valve bioprothesis. PMID: 23046536

Jansen NE, van Leiden HA, Haase-Kromwijk BJ, van der Meer NJ, Vorstius Kruijff EV, van der Lely N, van Zon H, Meinders AJ, Mosselman MJ, Hoitsma AJ. Inzet van getrainde donatiedeskundigen: vaker toestemming van nabestaanden voor orgaanen weefseldonatie* [Appointing ‘trained donation practitioners’ results in a higher family consent rate in the Netherlands: a multicenter study]. Ned Tijdschr Geneeskd. 2012;156(6):A4300. [234-241]. OBJECTIVE: The process of obtaining consent for organ and tissue donation is complex for both families and professionals. The objective of this study was to assess whether the long-term guidance of the relatives of ICU patients, in combination with the trai ning of staff on communicating on organ donation, is of overriding importance in in creasing the donation consent rate. A multicentre study was conducted at 3 hospitals for this purpose. DESIGN: Multicentre study. METHOD: We compared the family consent rate for donation at 1 intervention hospital with those from 2 control hospitals between December 2007 and November 2009. At the intervention hospital, trained donation practitioners guided 66 families throug hout the ICU hospitalisation until they had reached decisions regarding donation. At the first control hospital, where no family guidance or training took place, 107 families were approached. At the second control hospital, ‘hostesses’ not trained in discussing

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donation-related questions supported 99 families during the period of hospitalisation. A total of 272 families of potential donors were approached and asked to consent for donation. We compared consent rates, and evaluated the families’ experiences by means of a questionnaire sent approximately 4 months after death. RESULTS: Family consent rates were significantly higher at the intervention hospital (57.6%) than at the control hospitals (34.6% and 39.4%, respectively). The response rate to the questionnaire was 69%. The answers revealed no confounding variables that could have influenced the consent rate. CONCLUSION: The appointment of trained donation practitioners at the intervention hospital, who guided families during the period of ICU hospitalisation and the dona tion decision-making process, resulted in a significantly higher consent rate. Comment in [More donation: through the community, the government or the market?]. [Ned Tijdschr Geneeskd. 2012] [More donation: through the community, the government or the market?]. Bos GM. Ned Tijdschr Geneeskd. 2012; 156(6):A4556. PMID: 22316682

Scohy Th V. Perioperatieve driedimensionale transoesofagiale echocardiografie : Inleiding in de praktische toepassing. A&I. 2012 dec;4(4). 3D TEE is een logisch vervolg op de 2D-echocardiografie en stelt ons in staat om perioperatief betrouwbare en gedetailleerde uitspraken te doen, m.n. aangaande klepafwijkingen. De 3D echografische technologie moet gezien worden als een aanvulling op de al bestaande 2D en dopplerechografie. 3D-echocardiografie heeft een duidelijk voordeel wat betreft LVEF-meting en morfologische en functionele analyse van hartafwijkingen. Toekomstig onderzoek zal deze nieuwe technologie in het juiste perspectief plaatsen. Visser WA, Ermens AA, De Boer HD, Van Os E. Rocuronium reversed by sugammadex for electroconvulsive therapy in a patient with prolonged duration of action of succi nylcholine. Anaesth Intensive Care. 2011 Nov;39(6):1153-4. No abstract available. Comment on: Anaesth Intensive Care. 2011 Jul;39(4):764-5. PMID: 22165379

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Visser WA. Spinal anesthesia failure after local anesthetic injection into cerebrospinal fluid. Reg Anesth Pain Med. 2011 Nov-Dec;36(6):631. Comment on: Reg Anesth Pain Med. 2011 Jul-Aug;36(4):322-6. Fuzier R [et al...]: Spinal anesthesia failure after local anesthetic injection into cerebrospinal fluid: a multicenter prospective analysis of its incidence and related risk factors in 1214 patients. PMID: 22024704

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Cardiologie Kerngegevens Zorgkern Cardiologie • 15 cardiologen: dr. A.M.W. (Marco) Alings, dr. B.J.L. (Ben) van den Branden, W.A.J. (Wim) Bruggeling, dr. P.H.J.M. (Peter) Dunselman, H.P.J. (Henry) de Haan, dr. P. (Peter) den Heijer, dr. B. (Bart) Hooft van Huysduynen, dr. M. (Martijn) Meuwissen, S.G (Sander) Molhoek, dr. J. (Jeroen) Schaap, dr. B. (Bas) Schölzel, dr. S. (Sipke) Strikwerda, dr. J. (Jeroen) Vos, dr. R.P. (Rob) Wielenga, dr. W.J.M. Dewilde • Chef de clinique: dr. D.P.W. (Driek) Beelen, cardioloog • 3 assistenten in opleiding • 10 assistenten niet in opleiding • 4 verpleegkundig specialisten • Subspecialismen: algemene cardiologie (hart- en vaatziekten in brede zin), beeldvorming (echocardiografie, cardiale CT en MRI), interventiecardiologie (stenten dotterbehandelingen, vervanging hartklep), elektrofysiologie (behandeling van hartritmestoornissen)

Samenvattingen gepubliceerde artikelen Van der Werf C, Nederend I, Hofman N, van Geloven N, Ebink C, Frohn-Mulder IM, Alings AM, Bosker HA, Bracke FA, van den Heuvel F, Waalewijn RA, Bikker H, van Tintelen JP, Bhuiyan ZA, van den Berg MP, Wilde AA. Familial evaluation in catecholami nergic polymorphic ventricular tachycardia: disease penetrance and expression in cardiac ryanodine receptor mutation-carrying relatives. Circ Arrhythm Electrophysiol. 2012 Aug 1;5(4):748-56. Epub 2012 Jul 10. BACKGROUND: Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited arrhythmia syndrome associated with mutations in the cardiac ryanodine receptor gene (Ryr2) in the majority of patients. Previous studies of CPVT patients mainly involved probands, so current insight into disease penetrance, expression, genotype-phenotype correlations, and arrhythmic event rates in relatives carrying the Ryr2 mutation is limited. METHODS AND RESULTS: One-hundred sixteen relatives carrying the Ryr2 mutation from 15 families who were identified by cascade screening of the Ryr2 mutation causing CPVT in the proband were clinically characterized, including 61 relatives from 1 family. Fifty-four of 108 antiarrhythmic drug-free relatives (50%) had a CPVT pheno type at the first cardiological examination, including 27 (25%) with nonsustained ventricular tachycardia. Relatives carrying a Ryr2 mutation in the C-terminal channelforming domain showed an increased odds of nonsustained ventricular tachycardia (odds ratio, 4.1; 95% CI, 1.5-11.5; P=0.007, compared with N-terminal domain) compared with N-terminal domain. Sinus bradycardia was observed in 19% of relatives, whereas other supraventricular dysrhythmias were present in 16%. Ninety-eight (most actively treated) relatives (84%) were followed up for a median of 4.7 years (range, 0.3-19.0 years). During follow-up, 2 asymptomatic relatives experienced exercise-induced syncope. One relative was not being treated, whereas the other was noncompliant.

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None of the 116 relatives died of CPVT during a 6.7-year follow-up (range, 1.4-20.9 years). CONCLUSIONS: Relatives carrying an Ryr2 mutation show a marked phenotypic diversity. The vast majority do not have signs of supraventricular disease manifestations. Mutation location may be associated with severity of the phenotype. The arrhythmic event rate during follow-up was low. PMID: 22787013

Van den Broek KC, Kupper N, van der Voort PH, Alings M, Denollet J, Nyklícek I. Trajecto ries of Perceived Emotional and Physical Distress in Patients with an Implantable Car dioverter Defibrillator. Int J Behav Med. 2012 Nov 17. [Epub ahead of print]. BACKGROUND: Little is known about the course of emotional and physical distress in patients with an implantable cardioverter defibrillator (ICD). PURPOSE: We examined (1) trajectories of emotional and physical distress in the first 18 months postimplantation and (2) predictors of these trajectories, including demograp hical, clinical, and personality factors. METHODS: Dutch patients with an ICD (N?=?645) completed measures on anxiety, de pression, somatic symptoms, and perceived disability at the time of implantation, and 2, 12, and 18 months postimplantation. Measures on Type D personality (tendency to in hibit the expression of negative emotions) and anxiety sensitivity (tendency to fear anxiety-related sensations) were also completed at baseline. RESULTS: Latent class analysis (LatentGOLD) identified six to seven distinct trajectories, varying largely in overall levels of distress, and remaining relatively stable after a small initial decline. Multinomial regression showed that Type D personality and anxiety sen sitivity were the most prominent predictors, particularly of trajectories that reflected higher distress levels. Cardiac resynchronization therapy and coronary artery disease also increased the risk for distress, whereas ICD indication and shocks did not. CONCLUSIONS: The course of emotional and physical distress may be relatively stable after ICD implantation. In clinical practice, identification of patients with high risk of higher levels of emotional and physical distress may be warranted; as such, patients with high levels of anxiety sensitivity or a Type D personality should be identified and offered behavioral support. PMID: 23160996

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Borer JS, Böhm M, Ford I, Komajda M, Tavazzi L, Sendon JL, Alings M, Lopez-de-Sa E, Swedberg K; SHIFT Investigators*. Effect of ivabradine on recurrent hospitalization for worsening heart failure in patients with chronic systolic heart failure: the SHIFT Study. Eur Heart J. 2012 Nov;33(22):2813-20. Epub 2012 Aug 27. AIMS: We explored the effect of treatment with ivabradine, a pure heart rate-slowing agent, on recurrent hospitalizations for worsening heart failure (HF) in the SHIFT trial. METHODS AND RESULTS: SHIFT was a double-blind clinical trial in which 6505 patients with moderate-to-severe HF and left ventricular systolic dysfunction, all of whom had been hospitalized for HF during the preceding year, were randomized to ivabradine or to placebo on a background of guideline-recommended HF therapy (including maximi zed ß-blockade). In total, 1186 patients experienced at least one additional HF hospitali zation during the study, 472 suffered at least two, and 218 suffered at least 3. Patients with additional HF hospitalizations had more severe disease than those without. Iva bradine was associated with fewer total HF hospitalizations [902 vs. 1211 events with placebo; incidence rate ratio, 0.75, 95% confidence interval (CI), 0.65-0.87, P = 0.0002] during the 22.9-month median follow-up. Ivabradine-treated patients evidenced lower risk for a second or third additional HF hospitalization [hazard ratio (HR): 0.66, 95% CI, 0.55-0.79, P < 0.001 and HR: 0.71, 95% CI, 0.54-0.93, P = 0.012, respectively]. Similar ob servations were made for all-cause and cardiovascular hospitalizations. CONCLUSION: Treatment with ivabradine, on a background of guidelines-based HF therapy, is associated with a substantial reduction in the likelihood of recurrent hospi talizations for worsening HF. This benefit can be expected to improve the quality of life and to substantially reduce health-care costs. Comment in: Time to move on from ‘time-to-first’: should all events be included in the analysis of clinical trials? [Eur Heart J. 2012] Time to move on from ‘time-to-first’: should all events be included in the analysis of clinical trials?Anker SD, McMurray JJ. Eur Heart J. 2012 Nov; 33(22):2764-5. Epub 2012 Aug 27. PMID: 22927555

Easton JD, Lopes RD, Bahit MC, Wojdyla DM, Granger CB, Wallentin L, Alings M, Goto S, Lewis BS, Rosenqvist M, Hanna M, Mohan P, Alexander JH, Diener HC; ARISTOTLE Com mittees and Investigators Apixaban compared with warfarin in patients with atrial fi brillation and previous stroke or transient ischaemic attack: a subgroup analysis of the ARISTOTLE trial. Lancet Neurol. 2012 Jun;11(6):503-11. Epub 2012 May 8. BACKGROUND: In the ARISTOTLE trial, the rate of stroke or systemic embolism was re duced by apixaban compared with warfarin in patients with atrial fibrillation (AF). Pa Cardiologie

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tients with AF and previous stroke or transient ischaemic attack (TIA) have a high risk of stroke. We therefore aimed to assess the efficacy and safety of apixaban compared with warfarin in prespecified subgroups of patients with and without previous stroke or TIA. METHODS: Between Dec 19, 2006, and April 2, 2010, patients were enrolled in the ARISTOTLE trial at 1034 clinical sites in 39 countries. 18,201 patients with AF or atrial flutter were randomly assigned to receive apixaban 5 mg twice daily or warfarin (tar get international normalised ratio 2·0-3·0). The median duration of follow-up was 1·8 years (IQR 1·4-2·3). The primary efficacy outcome was stroke or systemic embolism, analysed by intention to treat. The primary safety outcome was major bleeding in the on-treatment population. All participants, investigators, and sponsors were masked to treatment assignments. In this subgroup analysis, we estimated event rates and used Cox models to compare outcomes in patients with and without previous stroke or TIA. The ARISTOTLE trial is registered with ClinicalTrials.gov, number NTC00412984. FINDINGS: Of the trial population, 3436 (19%) had a previous stroke or TIA. In the sub group of patients with previous stroke or TIA, the rate of stroke or systemic embolism was 2·46 per 100 patient-years of follow-up in the apixaban group and 3·24 in the war farin group (hazard ratio [HR] 0·76, 95% CI 0·56 to 1·03); in the subgroup of patients without previous stroke or TIA, the rate of stroke or systemic embolism was 1·01 per 100 patient-years of follow-up with apixaban and 1·23 with warfarin (HR 0·82, 95% CI 0·65 to 1·03; p for interaction=0·71). The absolute reduction in the rate of stroke and systemic embolism with apixaban versus warfarin was 0·77 per 100 patient-years of follow-up (95% CI -0·08 to 1·63) in patients with and 0·22 (-0·03 to 0·47) in those wit hout previous stroke or TIA. The difference in major bleeding with apixaban compared with warfarin was 1·07 per 100 patient-years (95% CI 0·09-2·04) in patients with and 0·93 (0·54-1·32) in those without previous stroke or TIA. INTERPRETATION: The effects of apixaban versus warfarin were consistent in patients with AF with and without previous stroke or TIA. Owing to the higher risk of these out comes in patients with previous stroke or TIA, the absolute benefits of apixaban might be greater in this population. FUNDING: Bristol-Myers Squibb and Pfizer. Copyright © 2012 Elsevier Ltd. All rights reserved. *Collaborators (1129) Erratum in: Lancet Neurol. 2012 Dec;11(12):1021. Comment in: Reducing the risk of recurrent stroke in patients with AF.Hart RG, Eikel boom JW. Lancet Neurol. 2012 Jun; 11(6):479-81. Epub 2012 May 8. PMID: 22572202 Cardiologie

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Bogale N, Priori S, Cleland JG, Brugada J, Linde C, Auricchio A, van Veldhuisen DJ, Lim bourg T, Gitt A, Gras D, Stellbrink C, Gasparini M, Metra M, Derumeaux G, Gadler F, Buga L, Dickstein K; Scientific Committee, National Coordinators, and Investigators* [Alings M et al...]. The European CRT Survey: 1 year (9-15 months) follow-up results. Eur J Heart Fail. 2012 Jan;14(1):61-73. METHODS AND RESULTS: Patients who had a successful CRT implantation were enrol led from 141 centres in 13 countries between November 2008 and June 2009. Baseline demographics, clinical and implantation data were collected, with a follow-up of ~1 year (9-15 months). The current report describes clinical outcomes including symptom severity, cardiovascular (CV) hospitalization, and survival. A total of 2438 patients were enrolled, and follow-up data were acquired from 2111 patients (87%). The population in cluded important groups of patients poorly represented in randomized controlled tri als, including very elderly patients and those with prior device implantation, atrial fibrillation, and/or QRS duration <120 ms. Investigators reported substantial improve ment in New York Heart Association (NYHA) functional class at follow-up. Patient selfassessment indicated that 81% of the patients felt improved, 16% reported no change, and 4% reported deterioration. During follow-up, 207 (10%) patients died, 346 (16%) had a CV hospitalization, and 501 (24%) died or had CV hospitalization. Worse NYHA functional class, atrial fibrillation, ischaemic aetiology, and device type (CRT-P, i.e. CRT alone) were associated with poorer survival. Women had a better outcome, as did pa tients who had a CRT-D (with an implantable cardioverter defibrillator function) de vice. CONCLUSIONS: Outcomes including death and hospitalization in this European CRT survey were consistent with results from clinical trials of CRT. At 1 year follow-up, most patients who received a CRT device considered their symptoms improved compared with their pre-implant assessment. Although prospective, this is an observational stu dy of successful CRT implantations, and outcomes in subgroup analyses must be inter preted with appropriate conservatism. *Collaborators (40): Dickstein K, Priori S, Auricchio A, Bogale N, Brugada J, Cleland JG, Derumeaux G, Gitt A, Gras D, Komajda M, Linde C, Morgan J, van Veldhuisen DJ, Fruhwald F, Strohmer B, Goethals M, Vijgen J, Trochu JN, Gras D, Kindermann M, Stell brink C, McDonnald K, Keane D, Ben Gal T, Glikson M, Metra M, Gasparini M, Maass A, Jordaens L, Alings M, Larsen AI, Færestrand S, Delgado J, Mont L, Persson H, Gadler F, Brunner-La Rocca HP, Osswald S, Squire I, Morgan J. PMID: 22179034

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Schwartz GG, Olsson AG, Abt M, Ballantyne CM, Barter PJ, Brumm J, Chaitman BR, Hol me IM, Kallend D, Leiter LA, Leitersdorf E, McMurray JJ, Mundl H, Nicholls SJ, Shah PK, Tardif JC, Wright RS; dal-OUTCOMES Investigators* [Alings MA et al...]. Effects of dalce trapib in patients with a recent acute coronary syndrome. N Engl J Med. 2012 Nov 29;367(22):2089-99. Epub 2012 Nov 5. BACKGROUND: In observational analyses, higher levels of high-density lipoprotein (HDL) cholesterol have been associated with a lower risk of coronary heart disease events. However, whether raising HDL cholesterol levels therapeutically reduces cardiovascular risk remains uncertain. Inhibition of cholesteryl ester transfer protein (CETP) raises HDL cholesterol levels and might therefore improve cardiovascular outcomes. METHODS: We randomly assigned 15,871 patients who had had a recent acute corona ry syndrome to receive the CETP inhibitor dalcetrapib, at a dose of 600 mg daily, or placebo, in addition to the best available evidence-based care. The primary efficacy end point was a composite of death from coronary heart disease, nonfatal myocardial infarction, ischemic stroke, unstable angina, or cardiac arrest with resuscitation. RESULTS: At the time of randomization, the mean HDL cholesterol level was 42 mg per deciliter (1.1 mmol per liter), and the mean low-density lipoprotein (LDL) cholesterol level was 76 mg per deciliter (2.0 mmol per liter). Over the course of the trial, HDL cholesterol levels increased from baseline by 4 to 11% in the placebo group and by 31 to 40% in the dalcetrapib group. Dalcetrapib had a minimal effect on LDL cholesterol levels. Patients were followed for a median of 31 months. At a prespecified interim ana lysis that included 1135 primary end-point events (71% of the projected total number), the independent data and safety monitoring board recommended termination of the trial for futility. As compared with placebo, dalcetrapib did not alter the risk of the pri mary end point (cumulative event rate, 8.0% and 8.3%, respectively; hazard ratio with dalcetrapib, 1.04; 95% confidence interval, 0.93 to 1.16; P=0.52) and did not have a significant effect on any component of the primary end point or total mortality. The median C-reactive protein level was 0.2 mg per liter higher and the mean systolic blood pressure was 0.6 mm Hg higher with dalcetrapib as compared with placebo (P<0.001 for both comparisons). CONCLUSIONS: In patients who had had a recent acute coronary syndrome, dalcetrapib increased HDL cholesterol levels but did not reduce the risk of recurrent cardiovascular events. (Funded by F. Hoffmann-La Roche; dal-OUTCOMES ClinicalTrials. gov number, NCT00658515.). Comment in Dalcetrapib in patients with an acute coronary syndrome. [N Engl J Med. 2013] Dalcetrapib in patients with an acute coronary syndrome.Schwartz GG, Olsson AG, Barter PJ. N Engl J Med. 2013 Feb 28; 368(9):869-70.

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Dalcetrapib in patients with an acute coronary syndrome. [N Engl J Med. 2013] Dalcetrapib in patients with an acute coronary syndrome.Tomoda H. N Engl J Med. 2013 Feb 28; 368(9):869. Lipids. Dalcetrapib raises HDL-cholesterol level, but does not reduce cardiac risk. [Nat Rev Cardiol. 2013] Lipids. Dalcetrapib raises HDL-cholesterol level, but does not reduce cardiac risk.Lim GB. Nat Rev Cardiol. 2013 Jan; 10(1):5. Epub 2012 Nov 20. *Collaborators (1041) PMID: 23126252

Teeuwen K, Adriaenssens T, Van den Branden BJ, Henriques JP, Van der Schaaf RJ, Koolen JJ, Vermeersch PH, Bosschaert MA, Tijssen JG, Suttorp MJ. A randomized multicenter comparison of hybrid sirolimus-eluting stents with bioresorbable polymer versus everolimus-eluting stents with durable polymer in total coronary occlusion: rationale and design of the Primary Stenting of Occluded Native Coronary Arteries IV study. Trials. 2012 Dec 15;13:240. BACKGROUND: Percutaneous recanalization of total coronary occlusion (TCO) was historically hampered by high rates of restenosis and reocclusions. The PRISON II trial demonstrated a significant restenosis reduction in patients treated with sirolimuseluting stents compared with bare metal stents for TCO. Similar reductions in restenosis were observed with the second-generation zotarolimus-eluting stent and everolimuseluting stent. Despite favorable anti-restenotic efficacy, safety concerns evolved after identifying an increased rate of very late stent thrombosis (VLST) with drug-eluting stents (DES) for the treatment of TCO. Late malapposition caused by hypersensitivity reactions and chronic inflammation was suggested as a probable cause of these VLST. New DES with bioresorbable polymer coatings were developed to address these safety concerns. No randomized trials have evaluated the efficacy and safety of the newgeneration DES with bioresorbable polymers in patients treated for TCO. METHODS/DESIGN: The prospective, randomized, single-blinded, multicenter, noninferiority PRISON IV trial was designed to evaluate the safety, efficacy, and angiograp hic outcome of hybrid sirolimus-eluting stents with bioresorbable polymers (Orsiro; Biotronik, Berlin, Germany) compared with everolimus-eluting stents with durable polymers (Xience Prime/Xpedition; Abbott Vascular, Santa Clara, CA, USA) in patients with successfully recanalized TCOs. In total, 330 patients have been randomly allocated to each treatment arm. Patients are eligible with estimated duration of TCO =4 weeks with evidence of ischemia in the supply area of the TCO. The primary endpoint is insegment late luminal loss at 9-month follow-up angiography. Secondary angiographic endpoints include in-stent late luminal loss, minimal luminal diameter, percentage of diameter stenosis, in-stent and in-segment binary restenosis and reocclusions at 9-month follow-up. Additionally, optical coherence tomography is performed in the Cardiologie

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first 60 randomized patients at 9 months to assess neointima thickness, percentage of neointima coverage, and stent strut malapposition and coverage. Personnel blinded to the allocated treatment will review all angiographic and optical coherence assessments. Secondary clinical endpoints include major adverse cardiac events, clini cally driven target vessel revascularization, target vessel failure and stent thrombosis to 5-year clinical follow-up. An independent clinical event committee blinded to the allocated treatment will review all clinical events. TRIAL REGISTRATION: Clinical Trials.gov: NCT01516723. Patient recruitment started in February 2012. PMID: 23241457 - PMCID: PMC3543352

Post S, Post MC, van den Branden BJ, Eefting FD, Goumans MJ, Stella PR, van Es HW, Wildbergh TX, Rensing BJ, Doevendans PA. Early statin treatment prior to primary PCI for acute myocardial infarction: REPERATOR, a randomized placebo-controlled pilot trial. Catheter Cardiovasc Interv. 2012 Nov 1;80(5):756-65. Epub 2012 Mar 14. OBJECTIVE: The aim of this pilot study was to determine whether early atorvastatin treatment will reduce left ventricle (LV) remodeling, infarct size, and improve micro vascular perfusion. BACKGROUND: In animal studies, early statin therapy reduces reperfusion injury after a percutaneous coronary intervention (PCI) for acute myocardial infarction (AMI). METHODS: Forty-two consecutive patients (82% male, mean age 61.2 ± 9.8) who underwent a primary PCI for a first ST-elevated AMI were randomized for pretreat ment with atorvastatin 80 mg (n = 20) or placebo (n = 22) and continued with the same dosage daily for 1 week. All patients received atorvastatin 80 mg once daily 7 days after primary PCI. The LV function and infarct size were measured by magnetic resonance imaging within 1 day, at 1 week, and 3 months follow up. The primary endpoint was the end-systolic volume index (ESVI) at 3 months. Secondary endpoints were global LV function measurements, myocardial infarct size, biochemical cardiac markers, TIMI flow, and ST-T elevation resolution. RESULTS: ESVI 3 months after AMI was 25.1 mL/m(2) in the atorvastatin arm and 25.0 mL/m(2) in the placebo arm (P = 0.74). The differences in change from baseline to 3 months follow up in global LV function and myocardial infarct size did not differ between both treatment arms. Furthermore, biochemical markers, TIMI flow, and ST-T elevation resolution did not differ between atorvastatin and placebo arm.

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CONCLUSIONS: In this pilot study, pretreatment with atorvastatin in an acute myocardial infarction does not result in an improved cardiac function, microvascular perfusion, or decreased myocardial infarct size. Copyright © 2012 Wiley Periodicals, Inc.

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Comment in: Statin pleiotropy in acute myocardial infarction--is it about timing? [Catheter Cardiovasc Interv. 2012] Statin pleiotropy in acute myocardial infarction--is it about timing?Puri R, Tuzcu EM. Catheter Cardiovasc Interv. 2012 Nov 1; 80(5):766-7. PMID: 22419603

Van den Branden BJ, Swaans MJ, Post MC, Rensing BJ, Eefting FD, Jaarsma W, Van der Heyden JA. Percutaneous edge-to-edge mitral valve repair in high-surgical-risk patients: do we hit the target? JACC Cardiovasc Interv. 2012 Jan;5(1):105-11. OBJECTIVES: This study sought to assess the feasibility and safety of percutaneous edgeto-edge mitral valve (MV) repair in patients with an unacceptably high operative risk. BACKGROUND: MV repair for mitral regurgitation (MR) can be accomplished by use of a clip that approximates the free edges of the mitral leaflets. METHODS: All patients were declined for surgery because of a high logistic EuroSCORE (>20%) or the presence of other specific surgical risk factors. Transthoracic echocardio graphy was performed before and 6 months after the procedure. Differences in New York Heart Association (NYHA) functional class, quality of life (QoL) using the Minnesota questionnaire, and 6-min walk test (6-MWT) distances were reported. RESULTS: Fifty-five procedures were performed in 52 patients (69.2% male, age 73.2 ± 10.1 years, logistic EuroSCORE 27.1 ± 17.0%). In 3 patients, partial clip detachment occur red; a second clip was placed successfully. One patient experienced cardiac tampo nade. Two patients developed inguinal bleeding, of whom 1 needed surgery. Six patients (11.5%) died during 6-month follow-up (5 patients as a result of progressive heart failure and 1 noncardiac death). The MR grade before repair was =3 in 100%; after 6 months, a reduction in MR grade to =2 was present in 79% of the patients. Left ventricular (LV) end-diastolic diameter, LV ejection fraction, and systolic pulmonary artery pressure improved significantly. Accompanied improvements in NYHA functio nal class, QoL index, 6-MWT distances, and log N-terminal pro-B-type natriuretic pepti de were observed. CONCLUSIONS: In a high-risk population, MR reduction can be achieved by percutaneous edge-to-edge valve repair, resulting in LV remodeling with improvement of functional capacity after 6 months. Copyright © 2012 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved. PMID: 22230156

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Van den Branden BJ, Rahel BM, Laarman GJ, Slagboom T, Kelder JC, Ten Berg JM, Suttorp MJ. Five-year clinical outcome after primary stenting of totally occluded native coronary arteries: a randomised comparison of bare metal stent implantation with sirolimus-eluting stent implantation for the treatment of total coronary occlusions (PRISON II study). EuroIntervention. 2012 Feb;7(10):1189-96. AIMS: The aim of this study was to examine the five-year clinical outcome in patients enrolled in the Primary Stenting of Totally Occluded Native Coronary Arteries II (PRI SON II) study. METHODS AND RESULTS: Patients with totally occluded coronary arteries were rando mised to either sirolimus-eluting stent (SES, n=100) or bare metal stent (BMS, n=100) implantation. At five years, patients in the SES group had significantly lower rates of target lesion revascularisation (12% vs. 30%, p=0.001), target vessel revascularisation (17% vs. 34%, p=0.009) and major adverse cardiac events (12% vs. 36%, p<0.001). There were no significant differences in death and myocardial infarction. Eight (8%) cases of stent thrombosis (seven definite and one probable; one early, one late, and six very late) were noticed in the SES group versus three cases (3%, one definite and two possi ble; all very late) in the BMS group (p=0.21). CONCLUSIONS: The results of the present study show that the documented superior short-term angiographic and clinical results of SES in patients with total coronary occlusions are maintained during long-term 5-year follow-up as compared with BMS. On the other hand, there is a trend to a higher stent thrombosis rate in the SES group. PMID: 22030323

Parving HH, Brenner BM, McMurray JJ, de Zeeuw D, Haffner SM, Solomon SD, Chaturvedi N, Persson F, Desai AS, Nicolaides M, Richard A, Xiang Z, Brunel P, Pfeffer MA; ALTITUDE Investigators. [Dunselman PH et al...] Cardiorenal end points in a trial of aliskiren for type 2 diabetes. N Engl J Med. 2012 Dec 6;367(23): 2204-13. Epub 2012 Nov 3. BACKGROUND: This study was undertaken to determine whether use of the direct renin inhibitor aliskiren would reduce cardiovascular and renal events in patients with type 2 diabetes and chronic kidney disease, cardiovascular disease, or both. METHODS: In a double-blind fashion, we randomly assigned 8561 patients to aliskiren (300 mg daily) or placebo as an adjunct to an angiotensin-converting-enzyme inhibitor or an angiotensin-receptor blocker. The primary end point was a composite of the time to cardiovascular death or a first occurrence of cardiac arrest with resuscitation; non fatal myocardial infarction; nonfatal stroke; unplanned hospitalization for heart failu re; end-stage renal disease, death attributable to kidney failure, or the need for

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renal-replacement therapy with no dialysis or transplantation available or initiated; or doubling of the baseline serum creatinine level. RESULTS: The trial was stopped prematurely after the second interim efficacy analysis. After a median follow-up of 32.9 months, the primary end point had occurred in 783 patients (18.3%) assigned to aliskiren as compared with 732 (17.1%) assigned to placebo (hazard ratio, 1.08; 95% confidence interval [CI], 0.98 to 1.20; P=0.12). Effects on secon dary renal end points were similar. Systolic and diastolic blood pressures were lower with aliskiren (between-group differences, 1.3 and 0.6 mm Hg, respectively) and the mean reduction in the urinary albumin-to-creatinine ratio was greater (betweengroup difference, 14 percentage points; 95% CI, 11 to 17). The proportion of patients with hyperkalemia (serum potassium level, =6 mmol per liter) was significantly higher in the aliskiren group than in the placebo group (11.2% vs. 7.2%), as was the proportion with reported hypotension (12.1% vs. 8.3%) (P<0.001 for both comparisons). CONCLUSIONS: The addition of aliskiren to standard therapy with renin-angiotensin system blockade in patients with type 2 diabetes who are at high risk for cardiovascu lar and renal events is not supported by these data and may even be harmful. (Funded by Novartis; ALTITUDE ClinicalTrials.gov number, NCT00549757.). Collaborators (817) Comment in Diabetes: Add-on aliskiren has limited benefit. [Nat Rev Endocrinol. 2013] Diabetes: Add-on aliskiren has limited benefit.Mitchell F. Nat Rev Endocrinol. 2013 Jan; 9(1):2. Epub 2012 Nov 20. Diabetes. Dual RAAS blocker trial stopped prematurely. [Nat Rev Cardiol. 2013] Diabetes. Dual RAAS blocker trial stopped prematurely.Cully M. Nat Rev Cardiol. 2013 Jan; 10(1):5. Epub 2012 Nov 20. Diabetes: Dual RAAS blocker trial stopped prematurely. [Nat Rev Nephrol. 2013] Diabetes: Dual RAAS blocker trial stopped prematurely.Cully M. Nat Rev Nephrol. 2013 Jan; 9(1):3. Epub 2012 Nov 20. PMID: 23121378

Valente MA, Damman K, Dunselman PH, Hillege HL, Voors AA. Urinary proteins in heart failure. Prog Cardiovasc Dis. 2012 Jul-Aug;55(1):44-55. Renal insufficiency is common in patients with heart failure (HF), with both acute kidney injury and worsening renal function being associated with poor prognosis. The interplay between cardiac and renal failure has been termed the cardiorenal syndrome and is currently the subject of intense investigation. Urinary biochemistry has several

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advantages over blood or serum analyses, including lower costs, better patient com fort, and higher sensitivity to renal injury. However, urinalysis is currently not part of routine daily practice in cardiology. Recent advances in proteomics have allowed identification of numerous novel urinary biomarkers, many of which show promise in HF populations. In this review, we aim to provide an overview of both traditional and novel urinary biomarkers, examining evidence for diagnostic and prognostic value in HF as well as potential clinical utility. Copyright © 2012 Elsevier Inc. All rights reserved. PMID: 22824109

Gullestad L, Ueland T, Kjekshus J, Nymo SH, Hulthe J, Muntendam P, Adourian A, Böhm M, van Veldhuisen DJ, Komajda M, Cleland JG, Wikstrand J, McMurray JJ, Aukrust P; CORONA Study Group [Dunselman PH et al...]. Galectin-3 predicts response to statin therapy in the Controlled Rosuvastatin Multinational Trial in Heart Failure (CORONA). Eur Heart J. 2012 Sep;33(18):2290-6. Epub 2012 Apr 17. AIMS: To investigate whether plasma galectin-3, a mediator of fibrogenesis, can identify patients with chronic heart failure (HF) for whom statins are effective. METHODS AND RESULTS: Patients with ischaemic systolic HF enrolled in the Control led Rosuvastatin Multinational Trial in Heart Failure (CORONA) were randomly assig ned to 10 mg/day of rosuvastatin or placebo. Galectin-3 was measured in plasma. The primary outcome was cardiovascular death, myocardial infarction, or stroke. Of 1492 patients, 411 had a primary event during a median follow-up of 32.8 months. There was an interaction between baseline galectin-3 and rosuvastatin on the primary endpoint (P-value for interaction = 0.036). Among patients with below the median plasma concentrations of galectin-3 (= 19.0 ng/mL), those assigned to rosuvastatin had a lower primary event rate [hazard ratio (HR) 0.65; 95% confidence interval (CI), 0.460.92; P= 0.014], lower total mortality (HR 0.70; 95% CI, 0.50-0.98; P= 0.038), and lower event rate of all-cause mortality and HF hospitalizations (HR 0.72; 95% CI, 0.54-0.98; P= 0.017) compared with placebo, but no benefit was observed in patients with higher levels of galectin-3. The combination of concurrently low concentrations of galectin-3 and N-terminal pro-B-type natriuretic peptide (<102.7 pmol/L) identified patients with a large benefit with rosuvastatin (HR 0.33; 95% CI, 0.16-0.67; P= 0.002). CONCLUSION: Patients with systolic HF of ischaemic aetiology who have galectin-3 values <19.0 ng/mL may benefit from rosuvastatin treatment. However, the data from this post hoc analysis should be interpreted with caution since the overall results of the CORONA study did not show a significant effect on the primary endpoint.

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Comment in Tailored therapy for heart failure: the role of biomarkers. [Eur Heart J. 2012] Tailored therapy for heart failure: the role of biomarkers.Wollert KC. Eur Heart J. 2012 Sep; 33(18):2246-8. Epub 2012 May 18. Collaborators (29)*: Aires N, Janson L, Dunselman P, Hjalmarson A, Waagstein F, Kjekshus J, McMurray J, Wedel H, Wikstrand J, Dunselman P, Hjalmarson A, Kjekshus J, McMurray J, Waagstein F, Wedel H, Wikstrand J, Kjekshus J, Dunselman P, Hjalmarson A, Dargie H, DeMets D, Collins R, Feyzi J, Massie B, Fredlund BO, Holmberg M, Saldeen K, Samuelsson O, Swedberg K. PMID: 22513778

Morrow DA, Braunwald E, Bonaca MP, Ameriso SF, Dalby AJ, Fish MP, Fox KA, Lipka LJ, Liu X, Nicolau JC, Ophuis AJ, Paolasso E, Scirica BM, Spinar J, Theroux P, Wiviott SD, Strony J, Murphy SA; TRA 2P–TIMI 50 Steering Committee and Investigators* [Dunselman PH et al...]. Vorapaxar in the secondary prevention of atherothrombotic events. N Engl J Med. 2012 Apr 12;366(15):1404-13. Epub 2012 Mar 24. N Engl J Med. 2012 Apr 12;366(15):1404-13. doi: 10.1056/NEJMoa1200933. Epub 2012 Mar 24. Vorapaxar in the secondary prevention of atherothrombotic events. Morrow DA, Braunwald E, Bonaca MP, Ameriso SF, Dalby AJ, Fish MP, Fox KA, Lipka LJ, Liu X, Nicolau JC, Ophuis AJ, Paolasso E, Scirica BM, Spinar J, Theroux P, Wiviott SD, Strony J, Murphy SA; TRA 2PTIMI 50 Steering Committee and Investigators. BACKGROUND: Thrombin potently activates platelets through the protease-activated receptor PAR-1. Vorapaxar is a novel antiplatelet agent that selectively inhibits the cellular actions of thrombin through antagonism of PAR-1. METHODS: We randomly assigned 26,449 patients who had a history of myocardial infarction, ischemic stroke, or peripheral arterial disease to receive vorapaxar (2.5 mg daily) or matching placebo and followed them for a median of 30 months. The primary efficacy end point was the composite of death from cardiovascular causes, myocardial infarction, or stroke. After 2 years, the data and safety monitoring board recommen ded discontinuation of the study treatment in patients with a history of stroke owing to the risk of intracranial hemorrhage. RESULTS: At 3 years, the primary end point had occurred in 1028 patients (9.3%) in the vorapaxar group and in 1176 patients (10.5%) in the placebo group (hazard ratio for the vorapaxar group, 0.87; 95% confidence interval [CI], 0.80 to 0.94; P<0.001). Cardiovas cular death, myocardial infarction, stroke, or recurrent ischemia leading to revasculari zation occurred in 1259 patients (11.2%) in the vorapaxar group and 1417 patients (12.4%) in the placebo group (hazard ratio, 0.88; 95% CI, 0.82 to 0.95; P=0.001). Moderate or severe bleeding occurred in 4.2% of patients who received vorapaxar and 2.5% of those who received placebo (hazard ratio, 1.66; 95% CI, 1.43 to 1.93; P<0.001). There was an

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increase in the rate of intracranial hemorrhage in the vorapaxar group (1.0%, vs. 0.5% in the placebo group; P<0.001). CONCLUSIONS: Inhibition of PAR-1 with vorapaxar reduced the risk of cardiovascular death or ischemic events in patients with stable atherosclerosis who were receiving standard therapy. However, it increased the risk of moderate or severe bleeding, including intracranial hemorrhage. (Funded by Merck; TRA 2P-TIMI 50 ClinicalTrials.gov number, NCT00526474.). *Collaborators (2178). Comment in: Destroy user interface controlAntiplatelet therapy: Vorapaxar beneficial in setting of prior MI, but not in patients who have experienced a stroke. [Nat Rev Cardiol. 2012] Antiplatelet therapy: Vorapaxar beneficial in setting of prior MI, but not in patients who have experienced a stroke.Mearns BM. Nat Rev Cardiol. 2012 Apr 10; 9(6):311. Epub 2012 Apr 10. Destroy user interface control[In Process Citation]. [Kardiol Pol. 2012] [In Process Citation].Januszkiewicz L. Kardiol Pol. 2012; 70(10):1076. PMID: 22443427

Houthuizen P, Van Garsse LA, Poels TT, de Jaegere P, van der Boon RM, Swinkels BM, Ten Berg JM, van der Kley F, Schalij MJ, Baan J Jr, Cocchieri R, Brueren GR, van Straten AH, den Heijer P, Bentala M, van Ommen V, Kluin J, Stella PR, Prins MH, Maessen JG, Prinzen FW. Left bundle-branch block induced by transcatheter aortic valve implanta tion increases risk of death. Circulation. 2012 Aug 7;126(6):720-8. Epub 2012 Jul 12. BACKGROUND: Transcatheter aortic valve implantation (TAVI) is a novel therapy for treatment of severe aortic stenosis. Although 30% to 50% of patients develop new left bundle-branch block (LBBB), its effect on clinical outcome is unclear. METHODS AND RESULTS: Data were collected in a multicenter registry encompassing TAVI patients from 2005 until 2010. The all-cause mortality rate at follow-up was compared between patients who did and did not develop new LBBB. Of 679 patients analyzed, 387 (57.0%) underwent TAVI with the Medtronic CoreValve System and 292 (43.0%) with the Edwards SAPIEN valve. A total of 233 patients (34.3%) developed new LBBB. Median follow-up was 449.5 (interquartile range, 174-834) days in patients with and 450 (interquartile range, 253-725) days in patients without LBBB (P=0.90). All-cause mortality was 37.8% (n=88) in patients with LBBB and 24.0% (n=107) in patients without LBBB (P=0.002). By multivariate regression analysis, independent predictors of

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all-cause mortality were TAVI-induced LBBB (hazard ratio [HR], 1.54; confidence interval [CI], 1.12-2.10), chronic obstructive lung disease (HR, 1.56; CI, 1.15-2.10), female sex (HR, 1.39; CI, 1.04-1.85), left ventricular ejection fraction =50% (HR, 1.38; CI, 1.02-1.86), and baseline creatinine (HR, 1.32; CI, 1.19-1.43). LBBB was more frequent after implantation of the Medtronic CoreValve System than after Edwards SAPIEN implantation (51.1% and 12.0%, respectively; P<0.001), but device type did not influence the mortality risk of TAVI-induced LBBB. CONCLUSIONS: All-cause mortality after TAVI is higher in patients who develop LBBB than in patients who do not. TAVI-induced LBBB is an independent predictor of mortality. Comments: The transcatheter valve revolution: time for a compensatory pause. [Circulation. 2012] The transcatheter valve revolution: time for a compensatory pause.Welt FG, Davidson MJ, Eisenhauer AC. Circulation. 2012 Aug 7; 126(6):674-6. Epub 2012 Jul 12. PMID: 22791865

Van de Hoef TP, Nolte F, Damman P, Delewi R, Bax M, Chamuleau SA, Voskuil M, Siebes M, Tijssen JG, Spaan JA, Piek JJ, Meuwissen M. Diagnostic accuracy of combined intracoronary pressure and flow velocity information during baseline conditions: adenosine-free assessment of functional coronary lesion severity. Circ Cardiovasc Interv. 2012 Aug 1;5(4):508-14. Epub 2012 Jul 10. BACKGROUND: The assessment of functional coronary lesion severity using intracoro nary physiological parameters such as coronary flow velocity reserve and the more widely used fractional flow reserve relies critically on the establishment of maximal hyperemia. We evaluated the diagnostic accuracy of the stenosis resistance index during nonhyperemic conditions, baseline stenosis resistance index, compared with established hyperemic intracoronary hemodynamic parameters, because achievement of hyperemia can be cumbersome in daily clinical practice. METHODS AND RESULTS: A total of 232 patients, including 299 lesions (mean stenosis diameter 55%±11%), underwent myocardial perfusion scintigraphy for documentation of reversible perfusion defects. Distal coronary pressure and flow velocity were assessed with sensor-equipped guidewires during baseline and maximal hyperemia, induced by an intracoronary bolus of adenosine (20-40 µg). We determined stenosis resistance (SR) during baseline and hyperemic conditions as well as fractional flow reserve and coronary flow velocity reserve. The discriminative value for myocardial ischemia on myocardial perfusion scintigraphy of all parameters was compared using receiver-operating-characteristic curves. Baseline SR showed good agreement with myocardial perfusion scintigraphy. The diagnostic performance of baseline SR (area

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under the curve, 0.77; 95% CI, 0.71-0.83) was as accurate as fractional flow reserve and coronary flow velocity reserve (area under the curve, 0.77; 95% CI, 0.71-0.83 and area under the curve, 0.75; 95% CI, 0.68-0.81 respectively; P>0.05 compared with baseline SR for both). However, hyperemic SR, combining both pressure and flow velocity infor mation during hyperemia, was superior to all other parameters (area under the curve, 0.81; 95% CI, 0.76-0.87; P<0.05 compared with all other parameters). CONCLUSIONS: Combined pressure and flow velocity measurements during baseline conditions may provide a useful tool for functional lesion severity assessment without the need for potent vasodilators. Comment in: Letter by Michiels et al regarding article, “”Diagnostic accuracy of combined intracoro nary pressure and flow velocity information during baseline conditions: adenosine-free assessment of functional coronary lesion severity””. [Circ Cardiovasc Interv. 2012] Letter by Michiels et al regarding article, “”Diagnostic accuracy of combined intracoro nary pressure and flow velocity information during baseline conditions: adenosine-free assessment of functional coronary lesion severity””.Michiels V, Eeckhout E, Muller O. Circ Cardiovasc Interv. 2012 Dec; 5(6):e84; author reply e86-7. Basal stenosis resistance: another adenosine-free contender for the lesion assessment crown? [Circ Cardiovasc Interv. 2012] Basal stenosis resistance: another adenosine-free contender for the lesion assessment crown Kern MJ. Circ Cardiovasc Interv. 2012 Aug 1; 5(4):456-8. Letter by Sen et al regarding article, “”Diagnostic accuracy of combined intracoronary pressure and flow velocity information during baseline conditions: adenosine-free assessment of functional coronary lesion severity””. [Circ Cardiovasc Interv. 2012] Letter by Sen et al regarding article, “”Diagnostic accuracy of combined intracoronary pressure and flow velocity information during baseline conditions: adenosine-free assessment of functional coronary lesion severity””.Sen S, Davies JE, Escaned J. Circ Cardiovasc Interv. 2012 Dec; 5(6):e85; author reply e86-7. PMID: 22787017

Olde Nordkamp LR, Knops RE, Bardy GH, Blaauw Y, Boersma LV, Bos JS, Delnoy PP, van Dessel PF, Driessen AH, de Groot JR, Herrman JP, Jordaens LJ, Kooiman KM, Maass AH, Meine M, Mizusawa Y, Molhoek SG, van Opstal J, Tijssen JG, Wilde AA. Rationale and design of the PRAETORIAN trial: a Prospective, RAndomizEd comparison of subcuTaneOus and tRansvenous ImplANtable cardioverter-defibrillator therapy. Am Heart J. 2012 May;163(5):753-760.e2.

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BACKGROUND: Implantable cardioverter-defibrillators (ICDs) are widely used to prevent fatal outcomes associated with life-threatening arrhythmic episodes in a variety of cardiac diseases. These ICDs rely on transvenous leads for cardiac sensing and defibrillation. A new entirely subcutaneous ICD overcomes problems associated with transvenous leads. However, the role of the subcutaneous ICD as an adjunctive or primary therapy in patients at risk for sudden cardiac death is unclear. STUDY DESIGN: The PRAETORIAN trial is an investigator-initiated, randomized, controlled, multicenter, prospective 2-arm trial that outlines the advantages and disadvantages of the subcutaneous ICD. Patients with a class I or IIa indication for ICD therapy without an indication for bradypacing or tachypacing are included. A total of 700 patients are randomized to either the subcutaneous or transvenous ICD (1:1). The study is powered to claim noninferiority of the subcutaneous ICD with respect to the composite primary endpoint of inappropriate shocks and ICD-related complications. After noninferiority is established, statistical analysis is done for potential superiority. Secondary endpoint comparisons of shock efficacy and patient mortality are also made. CONCLUSION: The PRAETORIAN trial is a randomized trial that aims to gain scientific evidence for the use of the subcutaneous ICD compared with the transvenous ICD in a population of patients with conventional ICD with respect to major ICD-related adverse events. This trial is registered at ClinicalTrials.gov with trial ID NCT01296022. Copyright © 2012 Mosby, Inc. All rights reserved. PMID: 22607851 Olde Nordkamp LR, Knops RE, Bardy GH, Blaauw Y, Boersma LV, Bos JS, Delnoy PP, van Dessel PF, Driessen AH, de Groot JR, Herrman JP, Jordaens LJ, Kooiman KM, Maass AH, Meine M, Mizusawa Y, Molhoek SG, van Opstal J, Tijssen JG, Wilde AA. Rationale and design of the PRAETORIAN trial: a Prospective, RAndomizEd comparison of subcu TaneOus and tRansvenous ImplANtable cardioverter-defibrillator therapy. Am Heart J. 2012 May;163(5):753-760.e2. A case of radiofrequency catheter ablation of atrioventricular (AV) nodal reentry tachycardia, in a patient with transposition of the great arteries after venous rerouting according to Mustard, is described. An electroanatomical map of the His and AV nodal region was created from inside the systemic venous atrium. Retrograde mapping of the pulmonary venous atrium was performed and the arterial catheter retracted to a position in close proximity to the venous catheter inside the intraatrial baffle. This position was chosen to deliver radiofrequency current. ©2010, The Authors. Journal compilation ©2012 Wiley Periodicals, Inc. PMID: 21029125 Xxx

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Schaap J, de Groot JA, Nieman K, Meijboom WB, Boekholdt SM, Post MC, Van der Heyden JA, de Kroon TL, Rensing BJ, Moons KG, Verzijlbergen JF. Hybrid myocardial perfusion SPECT/CT coronary angiography and invasive coronary angiography in patients with stable angina pectoris lead to similar treatment decisions. Heart. 2013 Feb;99(3):188-94. Epub 2012 Oct 19. OBJECTIVES: To evaluate to what extent treatment decisions for patients with stable angina pectoris can be made based on hybrid myocardial perfusion single-photon emission CT (SPECT) and CT coronary angiography (CCTA). It has been shown that hybrid SPECT/CCTA has good performance in the diagnosis of significant coronary artery disease (CAD). The question remains whether these imaging results lead to similar treatment decisions as compared to standalone SPECT and invasive coronary angiography (CA). METHODS: We prospectively included 107 patients (mean age 62.8±10.0 years, 69% male) with stable anginal complaints and an intermediate to high pre-test likelihood for CAD. Hybrid SPECT/CCTA was performed prior to CA in all patients. The study outcome was the treatment decision categorised as: no revascularisation, percutane ous coronary intervention (PCI) or coronary artery bypass grafting (CABG). Treatment decisions were made by two interventional cardiologists and one cardiothoracic sur geon in two steps: first, based on the results of hybrid SPECT/CCTA; second, based on SPECT and CA. RESULTS: Revascularisation (PCI or CABG) was indicated in 54 (50%) patients based on SPECT and CA. Percentage agreement of treatment decisions in all patients based on hybrid SPECT/CCTA versus SPECT and CA on the necessity of revascularisation was 92%. Percentage agreement of treatment decisions in patients with matched, unmat ched and normal hybrid SPECT/CCTA findings was 95%, 84% and 100%, respectively. CONCLUSIONS: Panel evaluation shows that patients could be accurately indicated for and deferred from revascularisation based on hybrid SPECT/CCTA. PMID: 23086965

Schaap J, Kauling RM, Boekholdt SM, Post MC, Van der Heyden JA, de Kroon TL, van Es HW, Rensing BJ, Verzijlbergen JF. Usefulness of coronary calcium scoring to myocardial perfusion SPECT in the diagnosis of coronary artery disease in a predominantly high risk population. Int J Cardiovasc Imaging. 2013 Mar;29(3):677-84. Epub 2012 Aug 18. Coronary calcium scoring (CCS) adds to the diagnostic performance of myocardial perfusion single-photon emission computed tomography (SPECT) to assess the presence of significant coronary artery disease (CAD). Patients with a high pre-test

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likelihood are expected to have a high CCS which potentially could enhance the diagnostic performance of myocardial perfusion SPECT in this specific patient group. We evaluated the added value of CCS to SPECT in the diagnosis of significant CAD in patients with an intermediate to high pre-test likelihood. In total, 129 patients (mean age 62.7 ± 9.7 years, 65 % male) with stable anginal complaints and intermediate to high pre-test likelihood of CAD (median 87 %, range 22-95) were prospectively included in this study. All patients received SPECT and CCS imaging preceding invasive coronary angiography (CA). Fractional flow reserve (FFR) measurements were acquired from pa tients with angiographically estimated 50-95 % obstructive CAD. For SPECT a SSS > 3 was defined significant CAD. For CCS the optimal cut-off value for significant CAD was determined by ROC curve analysis. The reference standard for significant CAD was a FFR of <0.80 acquired by CA. Significant CAD was demonstrated in 64 patients (49.6 %). Optimal CCS cut-off value for significant CAD was >182.5. ROC curve analysis for prediction of the presence of significant CAD for SPECT, CCS and the combination of CCS and SPECT resulted in an area under the curve (AUC) of 0.88 (95 % CI 81-94), 0.75 (95 % CI 66-83 %) and 0.92 (95 % CI 87-97 %) respectively. The difference of the AUC between SPECT and the combination of CCS and SPECT was 0.05 (P = 0.12). The additi on of CCS did not significantly improve the diagnostic performance of SPECT in the evaluation of patients with a predominantly high pre-test likelihood of CAD. PMID: 22903741

Schaap J, Kauling RM, Boekholdt SM, Post MC, Van der Heyden JA, de Kroon TL, Rensing BJ, Verzijlbergen JF. Zero coronary calcium in the presence of severe isolated left main stenosis detected by CT coronary angiography in a patient with typical angina and equivocal myocardial perfusion SPECT. J Nucl Cardiol. 2012 Feb;19(1):165-8. [No abstract available] PMID: 21901576

Snijder RJ, Schaap J, Verzijlbergen JF, Post MC. Imaging of an unusual case of a completely unroofed coronary sinus without persistent left superior vena cava. Eur Heart J Cardiovasc Imaging. 2013 Mar;14(3):297. Epub 2012 Sep 21. [No abstract available] PMID: 23002197

Scholzel BE, Post MC, Thijs Plokker HW, Snijder RJ. Clinical worsening during long-term follow-up in inoperable chronic thromboembolic pulmonary hypertension. Lung. 2012 Apr;190(2):161-7. Epub 2011 Dec 8.

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BACKGROUND: Pulmonary endarterectomy is the treatment of choice in chronic thromboembolic pulmonary hypertension (CTEPH). Modern pulmonary vasoactive medication (like endothelin receptor antagonists, phosphodiesterase type 5 inhibitors, and prostacyclins) is used in patients with an inoperable disease and improved prognosis. We evaluate mortality and time to clinical worsening (TtCW) in inoperable CTEPH patients during long-term follow-up. METHODS: All 32 patients with inoperable CTEPH were enrolled between June 2002 and January 2009. TtCW was defined as the combination of death, need for intra venous pulmonary arterial hypertension medication, or 15% decrease in 6-minute walk distance (6-MWD) without improvement in functional class. The Cox propor tional hazard regression was used to identify predictors. RESULTS: During a mean follow-up of 3.4 years (range = 0.2-10.2 years), 11 patients died (34%). The 1- and 3-year survival rates were 87 and 77%, respectively. Baseline functional class, 6-MWD, mean pulmonary artery pressure, and pulmonary vascular resistance were predictors for survival. Clinical worsening occurred in 16 patients (50%). The 1- and 3-year rates of freedom from clinical worsening were 74 and 60%, respectively. The only predictor for clinical worsening was the baseline 6-MWD. CONCLUSION: Despite the improvement in medical treatment of inoperable CTEPH, the mortality rate is still high, and clinical worsening occurred in a substantial number of patients during a follow-up of more than 3 years. PMID: 22160210

Simmers TA. Remote care: bidding our ICD patients a fond farewell? Neth Heart J. 2012 Feb;20(2):71-6. Remote follow-up has proven its safety and efficacy in the literature, and indeed in daily use. It saves the patient time and travel, allows earlier detection of events, and reduces inappropriate shocks. At the same time, it is not infallible and definitely not a universal substitute for in-office visits, as the 5 cases below demonstrate. It saves time, but also takes some time, with problems and challenges we were hitherto not familiar with. Hopes for the future include uniform definitions regarding policy and responsibi lities, reimbursement, even better connectivity, better alert management and remote programmability. To end on a more utopic note, it would be a huge step forward if devices and leads were so reliable that we did not need remote care to detect malfunctions. PMID: 22231154. PMCID: PMC3265701

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Cardiothoracale Chirurgie Kerngegevens Zorgkern Cardiothoracale Chirurgie • 5 cardiothoracaal chirurgen: M. (Mohamed) Bentala, mw. C.A. (Connie) Boot, P.A.E. (Peter) Hiddema, J. (Jan) Witkop, M.M. (Ries) Vrakking • Chef de clinique: S. (Sander) Bramer, cardiothoracaal chirurg • 1 assistenten niet in opleiding • 3 verpleegkundig specialisten

Samenvattingen gepubliceerde artikelen Houthuizen P, Van Garsse LA, Poels TT, de Jaegere P, van der Boon RM, Swinkels BM, Ten Berg JM, van der Kley F, Schalij MJ, Baan J Jr, Cocchieri R, Brueren GR, van Straten AH, den Heijer P, Bentala M, van Ommen V, Kluin J, Stella PR, Prins MH, Maessen JG, Prinzen FW. Left bundle-branch block induced by transcatheter aortic valve implan tation increases risk of death. Circulation. 2012 Aug 7;126(6):720-8. Epub 2012 Jul 12. BACKGROUND: Transcatheter aortic valve implantation (TAVI) is a novel therapy for treatment of severe aortic stenosis. Although 30% to 50% of patients develop new left bundle-branch block (LBBB), its effect on clinical outcome is unclear. METHODS AND RESULTS: Data were collected in a multicenter registry encompassing TAVI patients from 2005 until 2010. The all-cause mortality rate at follow-up was compared between patients who did and did not develop new LBBB. Of 679 patients analyzed, 387 (57.0%) underwent TAVI with the Medtronic CoreValve System and 292 (43.0%) with the Edwards SAPIEN valve. A total of 233 patients (34.3%) developed new LBBB. Median follow-up was 449.5 (interquartile range, 174-834) days in patients with and 450 (interquartile range, 253-725) days in patients without LBBB (P=0.90). All-cause mortality was 37.8% (n=88) in patients with LBBB and 24.0% (n=107) in patients without LBBB (P=0.002). By multivariate regression analysis, independent predictors of all-cause mortality were TAVI-induced LBBB (hazard ratio [HR], 1.54; confidence interval [CI], 1.12-2.10), chronic obstructive lung disease (HR, 1.56; CI, 1.15-2.10), female sex (HR, 1.39; CI, 1.04-1.85), left ventricular ejection fraction =50% (HR, 1.38; CI, 1.02-1.86), and baseline creatinine (HR, 1.32; CI, 1.19-1.43). LBBB was more frequent after implantation of the Medtronic CoreValve System than after Edwards SAPIEN implantation (51.1% and 12.0%, respectively; P<0.001), but device type did not influence the mortality risk of TAVI-induced LBBB.


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CONCLUSIONS: All-cause mortality after TAVI is higher in patients who develop LBBB than in patients who do not. TAVI-induced LBBB is an independent predictor of mortality. Comments: The transcatheter valve revolution: time for a compensatory pause. [Circulation. 2012] The transcatheter valve revolution: time for a compensatory pause.Welt FG, Davidson MJ, Eisenhauer AC. Circulation. 2012 Aug 7; 126(6):674-6. Epub 2012 Jul 12. PMID: 22791865 Staartjes WR, van Putte BP, Schramel FM. Contralateral pneumothorax draining via postpneumonectomy space. Ann Thorac Surg. 2012 Aug;94(2):e35-6. Epub 2012 May 10. Contralateral pneumothorax is a rare complication after pneumonectomy. We present a patient with bullous emphysema and a defect in the medial wall of a ventrally located bulla that drained via the postpneumonectomy space, producing subcutaneous emphysema without a pneumothorax in the remaining lung. The patient fully recovered after conservative treatment. Copyright © 2012 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved. PMID: 22579904


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Chirurgie Innovatief onderzoek bij de Zorgkern Chirurgie: de ARM-studie en een studie naar I-125-zaadjes in longen Bij de zorgkern Chirurgie van Amphia Ziekenhuis lopen meerdere onderzoeken, waaronder ‘ARM’ en ‘I-125’. “Vooral de relevante klinische studies doen we graag”, zegt dr. Paul Gobardhan. Op het gebied van borstkanker staat het Amphia Ziekenhuis qua grootte in de top drie van perifere topklinische ziekenhuizen. Het aantal patiënten is groot en de bereidheid tot onderzoeken van de chirurgen is navenant. Oncologie is een van de speerpunten van het Amphia Ziekenhuis. Het onderzoek Axillary Reverse Mapping (ARM) brengt de kwaliteit van leven voor oncologiepatiënten op een hoger plan. “Met deze studie heeft het ziekenhuis een voortrekkersrol in Nederland. Het is de eerste prospectieve gerandomiseerde studie met deze techniek.

Dr. Paul Gobardhan (links) en coördinerend co-assistent Maarten Beek.

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Bovendien is het één van de weinige multicenter trials die geïnitieerd wordt vanuit het Amphia Ziekenhuis”, meldt dr. Ernest Luiten, initiatiefnemer van dit onderzoek. Voor de studie ontving Amphia een beurs van Pink Ribbon. Tijdens een borstkanker operatie wordt de schildwachtklier verwijderd. Als deze een uitzaaiing bevat, vindt op dit moment in veel gevallen een aanvullende ingreep plaats waarbij de chirurg alle andere lymfeklieren in de oksel ook verwijdert (aanvullende okselklierdissectie). Veel vrouwen hebben na zo’n okselklierdissectie last van oedeem in de arm en gevoelsklachten. Blauw kan blijven zitten Nu is gebleken dat de chirurg bij deze okselklierdissectie ook klieren verwijdert die het lymfevocht uit de arm afvoeren, de armklieren. “In feite hoef je deze specifieke klieren niet te verwijderen”, zegt Luiten. Het ARM-onderzoek biedt een alternatief. Gobardhan: “Het is eigenlijk heel eenvoudig. In plaats van klieren die we zouden moeten verwijde ren blauw te maken, zoals bij de schildwachtklierprocedure, maken we nu de klieren die we kunnen laten zitten blauw. Eigenlijk het omgekeerde als bij de schildwachtklierprocedure.” Er wordt een blauwe vloeistof in de bovenarm gespoten die de armklieren markeert. De chirurg laat deze bij de helft van de patiënten zitten en neemt daar alleen de lymfeklieren weg die in relatie staan tot de borst. Bij de andere groep haalt hij zowel borst- als armklieren weg, wat in feite overeenkomt met de standaardprocedure we reldwijd. Daarna wordt bij beide groepen het oedeem gemeten gedurende twee jaar. Voordelen Uit eerder kleinschalig onderzoek is gebleken dat ‘laten zitten’ van armklieren wellicht geen nadelige invloed heeft voor de patiënte, maar juist een voordeel oplevert: name lijk minder vochtophoping (oedeem), minder gevoelsstoornissen en een betere functie van de schouder. Dat zorgt voor een betere kwaliteit van leven. Het onderzoek is dubbelblind gerandomiseerd, deelnemers weten dus van tevoren niet bij welke groep ze horen. Om het ontstaan van oedeem te meten, maken de onderzoekers gebruik van de bravometer. Eigenlijk een langwerpige bak water waar een arm in past, waarna onderzoekers de hoeveelheid overlopend water meten. Subsidie Pink Ribbon Naast de chirurgen dr. Paul Gobardhan en dr. Ernest Luiten zijn ook epidemioloog Adri Voogd en radioloog i.o. Lisa Klompenhouwer bij de studie betrokken. Het is een multicenter studie, tot nu toe met ziekenhuizen uit Breda, Ede, Den Haag, Eindhoven en Dordrecht. Coördinerend coassistent Maarten Beek hoopt op het ARM-onderzoek te promoveren. Over de aanleiding tot het onderzoek zegt Luiten: “Ik las er een artikel over en kreeg onmiddellijk het idee om dit verder te onderzoeken.” Gobardhan pakte het op en mede door een flinke subsidie van Pink Ribbon kwam het onderzoek op gang. Maarten Beek nam de coördinatie op zich. “Ik werd gebeld tijdens mijn coschap pen. Ik heb er heel even over nagedacht en toen snel ‘ja’ gezegd. De begeleiding van Paul en zijn collega’s is prima.” Luiten: “In principe is dit voor Maarten een promotietraject met een proefschrift als afronding.” Beek: “Het onderzoek heeft me nu al in

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allerlei ziekenhuizen en bij meerdere congressen gebracht. Dat is leerzaam en zeker ook gezellig.” Geen problemen bij uitzaaiing “De bereidheid van patiënten om mee te doen aan het onderzoek is groot”, weet Beek. “We zijn pas net van start gegaan en hebben hier nu de eerste drie patiënten geïncludeerd. Wat betreft het ‘dubbelblinde’ van het onderzoek: ik heb gemerkt dat het belangrijk is om goed uit te leggen waarom deelnemers niet weten bij welke van de twee groepen ze horen. Namelijk als ze dat weten, dan kunnen ze onbewust de onderzoeksresultaten beïnvloeden. Na de twee jaar dat we ze meten, krijgen ze het uiteraard wel te horen.” Hij vult aan dat mensen ook bereid zijn om mee te doen vanwege het voordeel dat het voor toekomstige patiënten kan bieden. En Gobardhan benadrukt nogmaals dat de risico’s van ‘laten zitten’ te verwaarlozen zijn. “Ook klieren die heel soms toch uitzaaiingen hebben, kunnen blijven zitten. Door de chemotherapie en hormonale therapie en eventueel bestraling die volgt, leidt dit niet tot problemen.” Gulden middenweg Luiten geeft aan dat de percentages van mogelijk aangetaste klieren zelfs lager zijn dan getallen uit een geruchtmakende Amerikaanse studie. Daarbij werd zelfs een aan vullende okselklierdissectie in geselecteerde patiëntengroepen achterwege gelaten. Zonder nadelige gevolgen voor de patiënten. Dit laatste is echter geen gemeengoed in de medische wereld en een aanvullende okselklierdissectie staat daarmee ter discussie. “De ARM-studie is dus een gulden middenweg, een selectieve okselklierdissectie”, zegt Luiten. Gobardhan geeft aan dat het sparen van lymfebanen wel wat meer handigheid van de chirurg vraagt. Beek vertelt dat bij een eerdere pilotstudie bij 43 patiënten klie ren zijn weggehaald (ook klieren die nu blauw worden gemaakt en blijven zitten) en dat daar geen metastasen in zijn aangetroffen. “We verwachten dus geen uitzaaiingen en mocht dit toch het geval zijn, dan zal dit naar verwachting op de lange termijn geen problemen opleveren.” Hoewel natuurlijk in dit stadium nog niets over de resultaten gezegd kan worden (daar zijn zo’n 300 patiënten voor nodig), is de werkhypothese dat er een reductie ontstaat van de postoperatieve complicaties. Naast de gerandomiseerde studie loopt nog een tweede registratiestudie, die de resultaten registreert van patiënten waarbij de borstkanker vanaf de start kon worden aangetoond in de okselklieren aan de hand van een positieve cytologische punctie. Bij deze groep verwijdert de chirurg de armklieren in alle gevallen en onderzoekt deze apart. Deze registratiestudie levert straks unieke gegevens op met mogelijk nieuwe behandelinzichten. Jodiumzaadjes in longen Sinds 2009 gebruikt de chirurgie van het Amphia Ziekenhuis radioactieve zaadjes om bij borstkankerpatiënten de tumor te lokaliseren. Deze voor Nederland en ook interna tionaal bijzondere lokalisatietechniek werd door Luiten geïntroduceerd in het Amphia Ziekenhuis. Hij nam deze mee vanuit zijn vorige werkkring in Eindhoven/Geldrop. Het gaat om I-125-(jodium)zaadjes ter grootte van een hagelslagje, die op foto’s goed te zien zijn en met een probe gemakkelijk te lokaliseren. Bij patiënten met heel kleine Chirurgie

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afwijkingen in de longen gebruikten artsen meestal een ijzerdraadje voor het lokalise ren, maar dit draadje kan verschuiven. “Zo ontstond het idee om ook hier de radio actieve zaadjes te gebruiken, om heel precies te kunnen opereren”, zegt Gobardhan. “Dit zaadje kan de longarts of radioloog met een prik onder de CT-scan in de long bren gen en het kan enkele maanden stabiel blijven zitten. Bij operaties kan de longchirurg heel precies het zaadje met wat omliggend weefsel verwijderen via een kijkoperatie. Zo ontstaan geen grote wonden met latere littekens, dus de operatie is veel minder belastend voor de patiënt. De procedure bleek goed te bevallen en dit is tot op heden nog nooit vastgelegd in een publicatie. Het is mooi om een bestaande techniek op een ander gebied toe te passen en dat hebben wij gedaan in het Amphia Ziekenhuis. Samen met de afdelingen Longgeneeskunde, Radiologie, Nucleaire geneeskunde en Pathologie. Het artikel verschijnt binnenkort in European Journal of Surgical Oncology en dit is de eerste publicatie wereldwijd over dit onderwerp. Dus daar zijn we best trots op.” Gobardhan besluit met de opmerking dat het prettig is dat het ziekenhuis Weten schapsdagen heeft en het Wetenschapsboek uitgeeft. “Via deze inspanningen kunnen we van elkaar leren, ook disciplineoverstijgend.”

“Wat is er mooier dan iemand opleiden die beter wordt dan jijzelf?” Als het gaat om onderzoeken, wil vaatchirurg dr. Lijckle van der Laan het niet hebben over ‘ik’, maar over ‘wij’. “Je doet het altijd als team. Met collega’s vanuit je eigen discipline, maar vaak ook uit andere disciplines. Dat is het mooie van onderzoeken, dat je tegelijkertijd van elkaar leert.” Van elkaar leren blijkt een rode draad te zijn tijdens het gesprek met de enthousiaste opleider heelkunde. Een ander terugkerend onderwerp van gesprek is ‘onderzoekslijn’. Van der Laan is van mening dat onderzoeken alleen zinvol zijn als er een promotietraject aan vastzit. Als voorbeeld noemt hij het onderzoek waar dr. Dagmar Vos op promoveert als traumachi rurg, dat gaat over het verwijderen van osteosynthesemateriaal. Een onderzoek waar het Amphia Ziekenhuis bij betrokken is, evenals ziekenhuizen in Utrecht en Tilburg. Drive Van der Laan belicht in dit artikel vier onderzoekstrajecten. Waarom vindt hij het doen van onderzoek zo belangrijk? “Mijn persoonlijke drive is dat ik een draai wil maken in de gedachtegang, naar het belang en de mening van de patiënt zelf. Ik geloof in genees kunst. Daarom ervaar ik het als een nederlaag als ik iemand geopereerd heb die vervol gens binnen een week overlijdt. Ik geloof in custom-made. En daarbij is niet-ingrijpen

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ook een beleid. Niet voor elke patiënt is opereren de juiste oplossing. Zeker bij oudere patiënten is het zaak om goed na te denken bij welk beleid zíj het beste gebaat zijn.” Chirurgische behandeling oudere patiënt De eerste onderzoekslijn is ‘Uitkomst van de chirurgische behandeling van de oudere patiënt’. Van der Laan: “Als je in de literatuur kijkt, ben je boven de 65 al een oudere patiënt. Maar dat is helemaal niet oud. De oudere patiënt is bij mij boven de 80 jaar. En daar is nog heel weinig over bekend qua behandeling. Wat moet je doen en wat niet meer? Daar is de overheid ook erg mee bezig, wat wordt vergoed en wat niet meer. Maar ik denk dat wij dat als dokter voor de individuele patiënt horen te bepalen.” Rondom de oudere patiënt draaien twee promotietrajecten. Ten eerste gaat anios Kevin de Leur promoveren op de uitkomst van de chirurgische technieken rondom perifeer vaatlijden. Van der Laan is zijn begeleider. “Onder welke omstandigheden leg je bij ouderen wel of niet een shunt aan? Internisten zijn vaak voorstander, maar wij niet altijd. Daarom is dit onderzoek heel interessant. De Leur heeft gekeken naar aneurysma’s. Het blijkt dat iemand boven de tachtig jaar die een stent krijgt een hogere mortaliteit heeft dan een jonger iemand.” Ook is gekeken naar heupfracturen bij mensen van boven de negentig jaar. In zo’n groot ziekenhuis als Amphia komt dat circa twintig keer per jaar voor. Zo ontstond in enkele jaren de grootste onderzoeks

Dr. Lijckle van der Laan

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populatie van de wereld op dit gebied . Ook hiernaar doet promovendus De Leur onderzoek en dit gebeurt retrospectief. Van der Laan: “Na het verzamelen van alle gegevens moet je die vervolgens prospectief bekijken.” Daarom loopt er een grote studie naar mensen met ernstig vaatlijden die vaak ’s nachts wakker liggen van de pijn en wondjes hebben die niet genezen. Amputeren is niet de eerste keus. De reguliere aanpak is dotteren, een bypass aanleggen en als dat niet voldoende oplevert volgt (alsnog) een amputatie. “Bij alle patiënten vanaf zeventig kijken we naar de kwaliteit van leven: als we iets doen en daarna. Met scores leggen we vast hoe ziek ze zijn. Dan vergelijken we patiënten tussen de zeventig en tachtig met een groep van tachtig jaar en ouder, om te zien of de laatste groep een grotere kans op overlijden heeft. Nu lijkt het erop dat direct amputeren bij de oudste groep een betere overleving geeft, alleen... de patiënt is wel zijn been kwijt. Als dokter denk je dan: oei. Maar misschien is het voor die patiënt minder erg en kiest hij graag voor langer leven en voor amputatie in plaats van een bypass. Daar willen we nu achter komen. We hebben hiervoor een subsidie gekregen van verzekeraar Nuts-Ohra.” De tweede promovendus, Jelle Raats, doet onderzoek naar de diverse behandelopties van kritieke ischemie bij de oudere patiënt. Beide promotietrajecten verlopen in samenwerking met andere disciplines. Biochemische markers bij de intensive-carepatiënt Het promotietraject van assistent Zaïnna Meijer is de tweede onderzoekslijn: ‘De rol van diverse biochemische markers bij de chirurgische intensive-carepatiënt’. Dit onderzoek loopt met de afdelingen biochemie en intensive care. De promotie wordt verwacht in 2014 en er is al gepubliceerd in PLoS ONE en Journal of Surgical Research. Meijer heeft gekeken naar de voorspelling van problemen en complicaties bij de chirurgische intensive-carepatiënt. Er is met een model gekeken naar CRP, lactaat en procalcitonine. Dit onderzoek krijgt een vervolg met het onderzoeken van andere lactaten. Onderzoek naar opleiding Deze derde onderzoekslijn is opgezet in samenwerking met de regio Rotterdam door assistent Niels Hopmans. Hij analyseert of de opleiding in de regio Rotterdam, waar het Amphia Ziekenhuis onderdeel van is, goed is opgezet. Hij bekijkt onder meer de manier waarop beoordelingsgesprekken plaatsvinden en het begrip van de professionele kenmerken. Ook kijkt hij of de Arbeidstijdenwet invloed heeft op het aantal en de kwaliteit van chirurgische ingrepen. Bijzonder is dat het Amphia Ziekenhuis aan het onderzoek heeft meebetaald, vanwege het belang van het onderwerp. Perifeer vaatlijden De vierde onderzoekslijn omvat meerdere promotietrajecten. Twee jaar terug is Alexander te Slaa gepromoveerd op oedeemvorming na perifere bypasschirurgie en de rol van kwaliteit van leven. “Hij onderzocht of een nieuwe techniek toepasbaar was, maar dat was helaas niet zo”, zegt Van der Laan.

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Te Slaa werd opgevolgd door Jeroen Donker, die in april 2013 zijn bul haalde. In eerste instantie ging Donker door op de uitkomsten van bypasschirurgie en keek hij boven dien naar het voorkomen van infecties bij deze chirurgievorm. Hierbij is samengewerkt met de afdeling van prof. dr. Jan Kluytmans, het laboratorium voor microbiologie en in fectiepreventie (LMI). Onder meer om de rol van Staphylococcus aureus nader te onderzoeken. Perifeer vaatlijden is ook op een andere manier benaderd, namelijk door te kijken naar kwaliteit van leven en de rol van de verpleegkundig specialist. Van der Laan: “Dat zijn twee speerpunten van mij: kwaliteit van leven én de oudere patiënt. Dat zie je in de diverse onderzoeken terug.” Over deze vierde onderzoekslijn zegt de chirurg: “Kort gezegd blijkt uit de resultaten dat de kwaliteit van leven van de patiënt zeer complex bepaald wordt, in het bijzonder bij perifeer vaatlijden. Als ik opereer aan een bypass, gaat het met de patiënt het eerste halfjaar heel goed, maar na twee of drie jaar is zijn conditie er vaak weer net zo aan toe als voor de operatie. Dat komt omdat er bij een oudere patiënt veel meer problemen omheen zitten. Dan help ik ze met de bypass en dan blijkt bijvoorbeeld de slijtage van de heup de levenskwaliteit negatief te beïnvloeden.” Deze onderzoekslijn wordt nu voortgezet door Jasper de Slegt. Hij is anios en bezig om te promoveren op het voorkomen van infecties in de vaatchirurgie. “Dit onderzoek doen we ook samen met het LMI”, zegt Van der Laan. “De Slegt kijkt wat dieper. Bij welke operaties spelen infecties een rol, enzovoorts.” De komende drie maanden doet De Slegt alleen maar onderzoek. Hij is vrijgesteld van andere taken dankzij een subsidie uit het Wetenschapsfonds van het Amphia Ziekenhuis en een financiële bijdrage van de maatschap Heelkunde. Opleider heelkunde “Ook opleiden doe je met zijn allen”, zegt Van der Laan. “Als opleidingsgroep hebben we een lokaal opleidingsplan gemaakt. Daarnaast krijgt iedere assistent die hier komt een persoonlijk plan. Tijdens elke stage is een assistent gekoppeld aan een chirurg op de polikliniek en vindt een constante beoordeling en evaluatie plaats. Er is ruimte voor gesprekken en coördinatie en dat is niet in alle ziekenhuizen zo.” De chirurg stelt zich eerst bescheiden op, maar vertelt na enig aandringen dat assistenten heel graag naar het Amphia Ziekenhuis komen om opgeleid te worden en dat ze naderhand ook laai end enthousiast zijn over het doorgemaakte traject. “Onze opleidingsassistenten draaien bijvoorbeeld geen diensten ’s nachts door de week. En de assistenten niet in opleiding krijgen net zo goed intensieve begeleiding. Na drie maanden gaan we met ze in gesprek over hun verdere mogelijkheden.” Tussen de regels door is te horen dat het de nodige inzet vraagt om artsen in opleiding te begeleiden. Van der Laan zet zich ook regelmatig in op zijn compensatiedag. Elke vrijdag houden zijn collega’s hem ‘operatievrij’ zodat hij tijd aan de opleidingen kan besteden. Wat is zijn drive om dit te doen? Hij antwoordt met een wedervraag: “Wat is er nu mooier dan iemand opleiden die beter wordt dan jijzelf?” Na elk opleidingstraject volgen persoonlijke gesprekken in een ontspannen sfeer om te praten over de toekomst. “Wat is de volgende stap, waar kunnen ze gaan solliciteren? Bovendien is er ieder jaar een diner met alle chirurgen,

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plus iedereen die hier vier jaar in opleiding is geweest. Na zo’n intensief traject blijft de betrokkenheid. We doen aan teambuilding. Toevallig is er vanavond een barbecue bij mij thuis met zestig man inclusief alle assistenten in opleiding.” Van der Laan is trots op de onderzoeksbereidheid van zijn afdeling. “Het is een team sport”, zegt hij. “Uit onze onderzoeken blijkt de kracht van onze maatschap. Ik ben er trots op. We publiceren op jaarbasis meer dan vijftien artikelen over eigen onderzoek in wetenschappelijke vakbladen van niveau. Dat is veel voor een perifeer ziekenhuis. Waarom we dat doen? We willen niet alleen snijdende chirurgen zijn, zoals wel eens over ons vakgebied wordt gedacht. Integendeel, we ambiëren een hoog niveau.”

Kerngegevens Zorgkern Chirurgie • 15 chirurgen: R.M.P.H. (Rogier) Crolla, H.G.W. (Hans) de Groot , dr. G.H. (Gwan) Ho, dr. L. (Lijckle) van der Laan, dr. E.J.T. (Ernest) Luiten, dr. J.K.S. (Hans) Nuytinck, dr. E.J.H. (Eric) van Rhede van der Kloot, dr. A.M. (Arjen) Rijken, P.J.H.J. (Piet) Romme, G.P. (George) van der Schelling, dr. E.J. (Eelco) Veen, mw. D.I. (Dagmar) Vos, dr. J.P.A.M. (Jos) Vroemen, J.C.H. (Jan) van der Waal, dr. J.H. (Jan) Wijsman • E.L.L. (Eric) Twiss: traumatoloog • Dr. H.C. (Hans) Flu: fellow vaatchirurgie • Dr. P.D. (Paul) Gobardhan: fellow GE • 10 assistenten in opleiding • 16 assistenten niet in opleiding • Subspecialismen: GE-oncologische chirurgie, traumatologie, vaatchirurgie, longchirurgie, mammachirurgie, algemene chirurgie

Overzicht lopende onderzoeken • Axillary Reverse Mapping (ARM). • I-125 als longlokalisatiemiddel. • I-125 in bijschildklieren (te starten). • Galblaasstudie (kwaliteit van leven na een galblaasoperatie en veiligheid van opereren). • Uitkomst van de chirurgische behandeling van de oudere patiënt. • Rol van diverse biochemische markers bij de chirurgische intensive care patiënt. • Onderzoek naar diverse aspecten van de chirurgische opleiding. • Perifeer vaatlijden. • Implant removal after fracture healing. • Deelname aan diverse landelijke chirurgische/oncologische studies.

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Samenvattingen gepubliceerde artikelen Postma EL, Verkooijen HM, van Esser S, Hobbelink MG, van der Schelling GP, Koelemij R, Witkamp AJ, Contant C, van Diest PJ, Willems SM, Borel Rinkes IH, van den Bosch MA, Mali WP, van Hillegersberg R; ROLL study group [Van der Schelling G, Rijken A, Nuytinck J, Luiten E, Tetteroo E, Dijkstra H, Raaymakers P, Van Noorden P, Baas J, Vos D, Wijsman J, et al...]. Efficacy of ‘radioguided occult lesion localisation’ (ROLL) versus ‘wire-guided localisation’ (WGL) in breast conserving surgery for non-palpable breast cancer: a randomised controlled multicentre trial. Breast Cancer Res Treat. 2012 Nov;136(2):469-78. Epub 2012 Sep 30. For the management of non-palpable breast cancer, accurate pre-operative localisation is essential to achieve complete resection with optimal cosmetic results. Radioguided occult lesions localisation (ROLL) uses the radiotracer, injected intratumourally for sentinel lymph node identification to guide surgical excision of the primary tumour. In a multicentre randomised controlled trial, we determined if ROLL is superior to the standard of care (i.e. wire-guided localisation, WGL) for preoperative tumour localisation. Women (>18 years.) with histologically proven non-palpable breast cancer and eligible for breast conserving treatment with sentinel node procedure were randomised to ROLL or WGL. Patients allocated to ROLL received an intra-tumoural dose of 120 Mbq technetium-99 m nanocolloid. The tumour was surgically removed, guided by gamma probe detection. In the WGL group, ultrasound- or mammographyguided insertion of a hooked wire provided surgical guidance for excision of the prima ry tumour. Primary outcome measures were the proportion of complete tumour excisions (i.e. with negative margins), the proportion of patients requiring re-excision and the volume of tissue removed. Data were analysed according to intention-to-treat principle. This study is registered at ClinincalTrials.gov, number NCT00539474. In total, 314 patients with 316 invasive breast cancers were enrolled. Complete tumour removal with negative margins was achieved in 140/162 (86 %) patients in the ROLL group ver sus 134/152 (88 %) patients in the WGL group (P = 0.644). Re-excision was required in 19/162 (12 %) patients in the ROLL group versus 15/152 (10 %) (P = 0.587) in the WGL group. Specimen volumes in the ROLL arm were significantly larger than those in the WGL arm (71 vs. 64 cm(3), P = 0.017). No significant differences were seen in the durati on and difficulty of the radiological and surgical procedures, the success rate of the sentinel node procedure, and cosmetic outcomes. In this first multicentre randomised controlled comparison of ROLL versus WGL in patients with histologically proven breast cancer, ROLL is comparable to WGL in terms of complete tumour excision and re-excision rates. ROLL, however, leads to excision of larger tissue volumes. Therefore, ROLL cannot replace WGL as the standard of care. *Collaborators (32): Van der Schelling G, Rijken A, Nuytinck J, Luiten E, Tetteroo E, Dijkstra H, Raaymakers P, Van Noorden P, Baas J, Vos D, Wijsman J, Koelemij R, Theunissen E, van Esser S, van Wieringen A, Lavalaye J, Bollen T, Appelman M, Postma EL, Glaap L, Witkamp AJ, Rinkes IH, van Hillegersberg R, Hobbelink M,

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Fernandez A, Stapper G, van den Bosch M, Mali W, Verkooijen H, Willems SM, van Diest PJ, Contant C. PMID: 23053639

Gobardhan PD, Wijsman JH, van Dalen T, Klompenhouwer EG, van der Schelling GP, Los J, Voogd AC, Luiten EJ. ARM: axillary reverse mapping - the need for selection of patients. Eur J Surg Oncol. 2012 Aug;38(8):657-61. Epub 2012 May 17. BACKGROUND: Axillary reverse mapping (ARM) is a technique that discerns axillary lymphatic drainage of the arm from the breast. This study was performed to evaluate both the feasibility of this technique and the proportion of metastatic involvement of ARM-nodes. PATIENTS AND METHODS: Patients with invasive breast cancer and an indication for axillary lymph node dissection (ALND) were enrolled in the study: patients with a tumor-positive sentinel lymph node (SLN(+)-group) and patients who had axillary metastases proven by preoperative cytology (CP-N(+)-group) were distinguished. ARM was performed in all patients by injecting blue dye. During surgery ARM-nodes were identified and removed first, followed by ALND. RESULTS: Between October 2009 and June 2011 93 patients underwent ARM. There were 43 patients in the SLN(+)-group and 50 patients in the CP-N(+)-group. No significant differences in visualization rate of ARM-nodes between the groups (86 vs 94% respectively, P = 0.196) were identified. In the SLN(+)-group none of the ARM-nodes contained metastases versus 11 patients (22%) in the CP-N(+)-group (P = 0.001). Patients receiving neoadjuvant systemic therapy had a significantly lower risk of additional axillary lymph node metastases (24.6 vs 44.4%, P = 0.046). DISCUSSION: The ARM procedure is technically feasible with a high visualization rate. The proportion of patients with metastases in the ARM-nodes was significantly higher in patients with proven axillary metastases than in patients with a positive SLN. Patients with SLN metastases appear to be good candidates for the ARM technique and possibly also patients with proven axillary metastases receiving neoadjuvant chemotherapy. Copyright © 2012 Elsevier Ltd. All rights reserved. PMID: 22607749

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Smits RW, Gobardhan PD, Poortmans PhM, Tetteroo E, van der Schelling GP. Primair Plaveiselselcarcinoom van de mamma; een zwarte zwaan onder de borstmaligniteiten. Ned Tijdschr Heelkd. 2012;21(3):123-9. Gobardhan PD, Rijken AM. Gezien [rubriek] : Verassing tijdens laparotomie. Medisch Contact. 2012;25:1528. Gobardhan PD, de Wall LL, van der Laan L, Ten Tije AJ, van der Meer DC, Tetteroo E, Poortmans PM, Luiten EJ. The role of radioactive iodine-125 seed localization in breast-conserving therapy following neoadjuvant chemotherapy. Ann Oncol. 2013 Mar;24(3):668-73. Epub 2012 Nov 8. BACKGROUND: Neoadjuvant chemotherapy (NAC) is increasingly used in the frame work of breast-conserving therapy (BCT). Localization of the initial tumor is essential to guide surgical resection after NAC. This study describes the results obtained with I-125 seed localization in BCT including NAC. PATIENTS AND METHODS: Between January 2009 and December 2010, 85 patients treated with NAC and BCT after I-125 seed localization were included. Radiological and pathological response and resection margins were retrospectively evaluated. RESULTS: BCT was carried out in 85 patients without secondary local excisions. Nineteen patients with unifocal tumors and seven patients with multifocal tumors showed a complete pathological response (P = 0.18). Tumor-free resection margins were obtained in 78 patients (50 patients with unifocal and 28 patients with multifocal tumors, P = 0.27). Focally involved margins were found in four patients (two patients with a unifocal and two patients with a multifocal tumor, P = 0.27). A subsequent mastectomy was carried out in three patients (two patients with multifocal tumors, P = 0.29). CONCLUSIONS: BCT after NAC can be carried out successfully after initial localization with I-125 seeds in both unifocal and multifocal breast tumors with complete resection rates of >90%. PMID: 23139261

Crolla RM, van der Laan L, Veen EJ, Hendriks Y, van Schendel C, Kluytmans J. Reduction of surgical site infections after implementation of a bundle of care. PLoS One. 2012;7(9):e44599. Epub 2012 Sep 4. BACKGROUND: Surgical Site Infections (SSI) are relatively frequent complications after colorectal surgery and are associated with substantial morbidity and mortality.

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OBJECTIVE: Implementing a bundle of care and measuring the effects on the SSI rate. DESIGN: Prospective quasi experimental cohort study. METHODS: A prospective surveillance for SSI after colorectal surgery was performed in the Amphia Hospital, Breda, from January 1, 2008 until January 1, 2012. As part of a National patient safety initiative, a bundle of care consisting of 4 elements covering the surgical process was introduced in 2009. The elements of the bundle were peri operative antibiotic prophylaxis, hair removal before surgery, perioperative normother mia and discipline in the operating room. Bundle compliance was measured every 3 months in a random sample of surgical procedures. RESULTS: Bundle compliance improved significantly from an average of 10% in 2009 to 60% in 2011. 1537 colorectal procedures were performed during the study period and 300 SSI (19.5%) occurred. SSI were associated with a prolonged length of stay (mean additional length of stay 18 days) and a significantly higher 6 months mortality (Adjusted OR: 2.71, 95% confidence interval 1.76-4.18). Logistic regression showed a significant decrease of the SSI rate that paralleled the introduction of the bundle. The adjusted Odds ratio of the SSI rate was 36% lower in 2011 compared to 2008. CONCLUSION: The implementation of the bundle was associated with improved compliance over time and a 36% reduction of the SSI rate after adjustment for confounders. This makes the bundle an important tool to improve patient safety. PMID: 22962619 - PMCID: PMC3433450

Boersema GS, Gobardhan PD, Luiten EJ, Rijken AM. Een vrouw met cutane metastasering na behandeling van een mammacarcinoom. [A woman with cutaneous metastases after treatment for breast carcinoma]. Ned Tijdschr Oncol. 2012;9(3):111-4. Cutaneous metastases are a rare phenomenon after treatment for a primary carci noma with an incidence between 0.7-9.0%. Cutaneous metastases are most seen in female patients with breast cancer or male patients with a lung carcinoma and are mostly situated near the primary tumor site. We present a case of a woman, treated for primary lobular breast carcinoma, with solitary cutaneous metastases. De Leur K, van Zeeland ML, Ho GH, de Groot HG, Veen EJ, van der Laan L. Treatment for critical lower limb ischemia in elderly patients. World J Surg. 2012 Dec;36(12):2937-43. BACKGROUND: Critical limb ischemia (CLI) has a poor outcome when left untreated. The benefits of revascularization in the very elderly might be limited because of co-morbidities and short life expectancy. Therefore, optimal management of CLI in Chirurgie

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the elderly is not straightforward. We analyzed treatment results for elderly patients with CLI (Rutherford 4 or 5/6) in our clinic. METHODS: Hospital charts of all patients>70 years of age diagnosed with Rutherford stage 4-6 peripheral arterial disease between January 2006 and December 2009 were reviewed. We divided patients into two age groups (70-79 and =80 years) to compare treatment results. Primary interventions were defined as conservative, endovascular, reconstructive surgery, and amputation. Outcome measures were mortality, reinter vention, and major amputation rates. RESULTS: There were 191 patients [99 (52%) were women], median age 78.4 years, range 70-98 years. Altogether, 119 (62%) patients were aged 70-79 years, and 72 (38%) were =80 years. The primary intervention was equally divided over the two age groups (p=0.21). Trans-Atlantic Inter-Society Consensus Document on Management of Peripheral Arterial Disease (TASC II) classifications of aortoiliac lesions were not significantly different regarding intervention (p=0.62) or age (p=0.39). TASC II classification of femoropopliteal lesions was significantly different relative to intervention (p<0.01) but not different between age groups (p=0.68). Mortality rate after reconstructive surgery was significant higher in the oldest age group (p<0.01). After conservative treatment, endovascular treatment, or amputation, the mortality rates were not significantly different between the two age groups (respectively, p=0.06, p=0.33, p=0.76). Reintervention rate was 51% in the 70- to 79-year group com pared to 32% in the =80-year group. After initial treatment, major amputations were performed in 10% in the 70- to 79-year group compared to 13% in the =80-year group. CONCLUSIONS: In patients aged=80 years, surgical revascularization resulted in a significant higher mortality rate in our clinic, whereas primary conservative, endo vascular treatment and amputation resulted in similar mortality in both age groups. When considering surgical revascularization in the very elderly, surgeons should focus on careful patient selection. PMID: 22965534

Van Wely BJ, van den Wildenberg JH, Gobardhan PD, van Dalen Th, Borel Rinkes IH, Theunissen EB, Wijsman JH, Ernst M, van der Pol CC, Madsen EV, Wauters CA, de Wilt JH, Strobbe LJ. Axillary recurrences after SLNB: a multicentre analysis and follow-up of SLN negative breast cancer patients. Eur J Surg Oncol. 2012 Oct;38(10):925-31. Epub 2012 May 26. INTRODUCTION: The objective of this study was to conduct a multicentre data analysis to identify prognostic factors for developing an axillary recurrence (AR) after negative sentinel lymph node biopsy (SLNB) in a large cohort of breast cancer patients with long follow-up.

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PATIENTS AND METHODS: The prospective databases from different hospitals of clinically node negative breast cancer patients operated on between, 2000 and 2002 were analyzed. SLNB was performed and pathological analysis done by local patholo gists according to national guidelines. Adjuvant treatment was given according to contemporary guidelines. Multivariate analysis was performed using all available variables, a p-value of <0,05 was considered to be significant. RESULTS: A total of 929 patients who did not undergo axillary lymph node dissection were identified. After a median follow up of 77 (range 1-106) months, fifteen patients developed an isolated AR (AR rate 1,6%). Multivariate analysis showed that young age (p = 0.007) and the absence of radiotherapy (p = 0.010) significantly increased the risk of developing an AR. Distant metastasis free survival (DMFS) was significantly worse for patients with an AR compared to all other breast cancer patients (p < 0,0001). CONCLUSION: Even after long-term follow up, the risk of developing an AR after a negative SLN in breast cancer is low. Young age and absence of radiation therapy are highly significant factors for developing an axillary recurrence. DMFS is worse for AR patients compared to patients initially diagnosed with N0 or N1 disease. Copyright © 2012 Elsevier Ltd. All rights reserved. PMID: 22633152

Donker JM, Tijnagel MJ, van Zeeland ML, Veen EJ, van der Laan L. Anastomoses in the common femoral artery, vascular clips or sutures? A feasibility study. Ann Vasc Surg. 2013 Feb;27(2):194-8. Epub 2012 Jul 25. BACKGROUND: The Vessel Closure System (VCS) is commercially available since 1997. This clip system has proven to be successful for vascular anastomoses in access surge ry. There is little experience with the VCS in peripheral vascular surgery. METHODS: A trial was conducted for patients with peripheral arterial disease, who required either a femoral artery endarterectomy or a peripheral bypass procedure. Patients were randomized into two groups: a VCS group, in which the proximal anastomoses were made using VCS clips; and a control group, in which both proximal and distal anastomoses were performed using Prolene sutures. Outcomes assessed were the speed of anastomosis and patency. Adverse events were monitored. RESULTS: In the VCS group, 12 patients underwent anastomoses using VCS clips. In the control group, 12 patients underwent vascular reconstruction using sutures. In the VCS group, the mean speed of anastomosis was 1.9 mm/min, whereas the mean speed in the control group was 2.5 mm/min; this was not significantly different (P = 0.096). After a follow-up of 12 months, there was no difference in patency. In the VSC group, two serious adverse events occurred, which required emergency surgery. Chirurgie

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CONCLUSION: Anastomosis in the femoral artery using VCS clips is not faster than that using running Prolene sutures, and in our small sample, two serious adverse events in the VCS group were observed. These results do not support the further use of vascular clips in peripheral vascular surgery. Copyright © 2013 Elsevier Inc. All rights reserved. PMID: 22840340

Te Slaa A, Dolmans DE, Ho GH, Moll FL, van der Laan L. Pathophysiology and treatment of edema following femoropopliteal bypass surgery. Vascular. 2012 Dec;20(6):350-9. Epub 2012 Sep 14. Substantial lower-limb edema affects the majority of patients who undergo peripheral bypass surgery. Edema has impairing effects on the microvascular and the macrovas cular circulation, causes discomfort and might delay the rehabilitation process of the patient. However, the pathophysiology of this edema is not well understood. The Cochrane Library and Medline were used to retrieve literature on edema following peripheral bypass surgery. Factors other than local wound healing alone are suggested in the literature to play a role, given the severity and duration of this edema. Hypere mia, microvascular permeability, reperfusion-associated inflammation and lymphatic disruptions are likely to facilitate the development of edema. Preventive methods could be lymphatic-sparing surgery, intraoperative antioxidative therapy and posto perative elevation. Successful treatment strategies to reduce postoperative edema are based on lymph massage and external compression. In conclusion, the pathophysio logy of edema following peripheral surgery is not fully understood, although reper fusion-associated inflammation and lymphatic disruptions are likely to play a crucial role. When future less-invasive techniques prove to be successful, postoperative edema might be minimized. Until then, a careful lymphatic-sparing dissection should be executed when performing a peripheral bypass reconstruction. Postoperatively, the use of compression stockings and leg elevation are currently the golden standards. PMID: 22983547

Kodde IF, van Zeeland, MLP, de Groot HGW, van der Laan L. Successful conservative management of aortic graft infections with intra-abdominal abscesses by percuta neous drainage and specific antibiotic therapy. Vasc Dis Man. 2012;9(11):E189-192. ABSTRACT: Aortic graft infection is a rare but lethal complication of aortic surgery. Standard treatment consists of sepsis control by graft excision, antibiotics, and securing flow to distal circulation. We describe 2 patients with a proven infection of a central vascular prosthesis who were unable to tolerate surgical intervention. Conservative therapy comprised drainage of abscesses and specific intravenous Chirurgie

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antibiotics directed at the cultured microorganisms. Both patients were discharged home with oral antibiotics after 6 weeks of hospitalization. As long as oral antibiotics were continued, no infectious complications occurred. Conservative treatment with antibiotics and drainage of intra-abdominal abscesses after ruptured abdominal aneurysm repair may lead to midterm survival in selected cases Boersema GS, Veen EJ, van der Laan L. Cholecystitis acuta en salmonella sepsis. Ned Tijdschr Heelkd. 2012;21(5):247-8. Klompenhouwer EG, Helleman JN, Geenen GP, Ho GH, Vos LD, Van der Laan L. Reinter ventions following endovascular abdominal aortic aneurysm repair, the learning curve of time. J Cardiovasc Surg (Torino). 2012 Nov 8. [Epub ahead of print]. AIM: The DREAM and EVAR-1 trial show a higher reintervention rate after endovascular aneurysm repair (EVAR) compared to open repair. Since the initiation of these trials, endovascular-graft design and the experiences with EVAR have evolved substantially. The aim of this study was to compare the need for reinterventions in our recent EVAR procedures with our early procedures. METHODS: A retrospective review of our prospectively maintained database of all patients undergoing an elective EVAR for infrarenal abdominal aortic aneurysm (AAA) was performed. The 68 patients treated between 2000 and 2006 were defined as the “”Early EVAR”” group; the 41 patients treated between 2006 and 2008 were defined as the “”Recent EVAR”” group. The median follow-up was 63.3 (range 2-111) and 43.7 (range 1-61) months in the Early and Recent EVAR group respectively. RESULTS: Treatment related mortality occurred in three (4.4%) patients in the Early EVAR group. No treatment related mortality occurred in the Recent EVAR group. In the Early EVAR group 16 reinterventions occurred in 13 patients (19.1%) and in the Recent EVAR group three reinterventions occurred in three patients (7.5%). This difference was statistically significant (P=0.039). CONCLUSION: In our center, continued experiences with EVAR, improvement of graft design and a different management of complications have led to a significant decrease in reinterventions after EVAR. These findings and a review of the literature suggests that current need for reintervention after EVAR is substantially less than reported in the early trials. PMID: 23138601

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Luiten EJ, Rijken AM. TNM Classificatie en prognose (5 jaarsoverleving) bij dikke darm kanker met/zonder chemotherapie. Hèt HNPCC-Lynch Journaal. 2012 sep;1(2):36-37. Sentinel lymph node biopsy in breast cancer : procedural issues and prognostic impact of detecting micrometastases / Gobardhan PD. - [S.l. : s.n.], 2012 [Amsterdam : Buijten & Schipperheijn]. Proefschrift Universiteit Utrecht. ISBN 978-946-108-297-8. Barentsz MW, van Dalen T, Gobardhan PD, Bongers V, Perre CI, Pijnappel RM, van den Bosch MA, Verkooijen HM. Intraoperative ultrasound guidance for excision of non-palpable invasive breast cancer: a hospital-based series and an overview of the literature. Breast Cancer Res Treat. 2012 Aug;135(1):209-19. Epub 2012 Jul 25. Intraoperative ultrasound (IOUS) can be used in the operation theatre for localization of non-palpable breast cancers. In this prospective cohort study, we compared the yield of IOUS to guidewire localization (GWL). A total of 258 consecutive patients with non-palpable invasive breast cancer underwent breast conserving surgery between 1999 and 2010. GWL was performed in 138 (54 %) and IOUS in 120 (46 %) patients. Tumor dimensions, resection volume, margin status and re-excision rates were compa red by means of multivariate regression analysis. The groups were similar in terms of age, histological subtype and presence of DCIS. Lesions in the IOUS group were larger (1.24 vs. 0.98 cm, P < 0.001), while microcalcifications were more common in the GWL group (19 vs. 3 %, P < 0.001). Even after stratification for tumor diameter, presence of DCIS and findings on mammography, resection volumes were similar in both groups. Tumor-free resection margins were obtained in >93 % of patients (93.5 % with GWL vs. 93.3 % with IOUS, P = 0.958) and re-excision was performed in 11 % of patients under going GWL and 12.5 % of patients undergoing IOUS (P = 0.684). For localization of non-palpable breast cancer, IOUS is a reliable alternative to GWL, as it achieves similar results in terms of complete tumor removal, re-excision rate and excised volume. PMID: 22872521

Gobardhan PD, Madsen EV, van Dalen T, Perre CI, Bongers V. Ultrasound-guided sentinel node procedure for nonpalpable breast carcinoma. Nucl Med Commun. 2012 Jan;33(1):80-3. PURPOSE: Peritumoral and periareolar tracer injection techniques lead to different lymphatic drainage in sentinel lymph node biopsy procedures. In a prospective study, the visualization and identification rates of the ultrasound (US)-guided tracer injection technique for palpable and nonpalpable breast tumors were evaluated. METHODS: In 1262 consecutive patients with cT1?2N0 breast cancer, sentinel lymph node biopsy was performed following peritumoral tracer injection. In the case of nonpalpable breast lesions, Tc-99m nanocolloid injections were given using a 7.5

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MHz US probe. In the case of ultrasonographically nonvisible microcalcifications, the US-guided injection technique was wire guided. RESULTS: In 331 patients with nonpalpable breast lesions (26.2%), the lymphoscinti graphic visualization and surgical retrieval rates of axillary sentinel lymph nodes (SLNs) were 98.5 and 99.4%, respectively. For internal mammary (IM) SLNs, these rates were 21.1 and 17.8%, respectively. These rates were similar in patients with palpable and nonpalpable tumors. Axillary metastases were detected in 38.7% of the patients with palpable tumors versus 16.5% of those with nonpalpable tumors (P<0.001), whereas IM metastases were found in 4.8 and 3.0% of patients, respectively (P=0.165). CONCLUSION: In nonpalpable breast lesions, the US-guided injection technique is an accurate technique for SLN identification and retrieval. The substantial rates of IM metastases in both palpable and nonpalpable lesions favor a peritumoral tracer injection technique. PMID: 22044865

Donker JM, van der Laan L, Hendriks YJ, Kluytmans JA. Evaluation of staphylococcus aureus nasal carriage screening before vascular surgery. PLoS One. 2012;7(6):e38127. Epub 2012 Jun 7. INTRODUCTION: Staphylococcus aureus is the most important pathogen in the deve lopment of surgical site infections (SSI). Patients who carry S. aureus in the nose are at increased risk for the development of SSI in cardiothoracic and orthopedic surgery. In these populations it has been shown that the risk for SSI can be substantially redu ced by eradicating S. aureus carriage. For vascular surgery the relation between nasal carriage and surgical site infections has not been clearly investigated. For this reason we performed this study to analyze the relation between S. aureus nasal carriage and SSI in our vascular surgery population. METHODS: A prospective cohort study was undertaken, including all patients undergoing vascular surgery between January first 2010 and December 31th 2010. Before surgery patients were screened for S. aureus nasal carriage using a PCR technique. The presence of SSI was recorded based on criteria of the CDC. RESULTS: Screening was performed in 224. Of those, 55 (24.5%) were positive, 159 (71.0%) were negative and 10 (4.5%) were inconclusive. In the screened vascular population 4 S. aureus SSI occurred in the 55 carriers compared with 6 in 159 noncarriers (p = 0.24). A stratified analysis revealed a 10-fold increased risk in nasal carriers undergoing central reconstruction surgery (3 S. aureus SSI in 20 procedures versus 1 in 65 procedures in non-carriers, p = 0.039).

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DISCUSSION: In patients undergoing central reconstruction surgery nasals carriers are at increased risk for the development of S. aureus SSI. These patients will probably benefit from perioperative treatment to eradicate nasal carriage. PMID: 22685553

Castenmiller PH, de Leur K, de Jong TE, van der Laan L. Clinical results after coil embolization of the ovarian vein in patients with primary and recurrent lower-limb varices with respect to vulval varices. Phlebology. 2012 Mar 22. [Epub ahead of print]. OBJECTIVE: To study the effect of coil embolization of the insufficient ovarian vein (IOV) on varices of the lower limb (VLL). METHOD: From December 2005 until May 2008, we selected all patients with phlebo grams that were performed in our hospital to confirm the diagnosis of insufficiency of the ovarian vein. The CEAP (clinical, aetiological, anatomical and pathological elements) classification was used to classify the lower-limb venous disease in each patient. All patients with suspected IOV in combination with VLL underwent a phlebo graphy. If IOV was found, coil embolization of the ovarian vein(s) was performed. RESULTS: IOV was found in 43 of 44 patients (98%). After coil embolization of the ovarian vein(s), VLL disappeared in five patients (12%) without any further treatment. Improvement in CEAP classification was measured in 13 patients (31%). In 21 (88%) of 24 patients with vulval varices, coil embolization of the ovarian vein(s) resulted in disappearance of vulval varices. CONCLUSIONS: In only 31% of the patients with IOV in combination with VLL, phlebo graphy and coil embolization of the ovarian vein(s) did improve CEAP classification. However, coil embolization of the ovarian vein resulted in disappearance of the vulval varices in 88% of the patients. PMID: 22442360

Boersema GS, van der Laan L. ‘Spontaan’ vrij lucht in de buikholte. Ned Tijdschr Heelkd. 2012;21(4):185-186.

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Meyer ZC, Schreinemakers JM, van der Laan L. The value of C-reactive protein and lactate in the acute abdomen in the emergency department. World J Emerg Surg. 2012 Jul 16;7(1):22. CASE PRESENTATION: This report describes the presentation of three critically ill pa tients with non-traumatic acute abdominal pain and increased concentrations of the biomarkers C-reactive protein (CRP) and lactate. In these three patients an exploratory laparotomy was carried out. Remarkably, the laparotomy showed no intra-abdominal abnormalities. We discuss the usefulness of these biomarkers in practice and their in fluence on establishing a diagnose and making a decision to perform an intervention. CONCLUSION: We conclude that biomarkers lactate and CRP in patients with acute abdominal pain should only be used in adjunct to the history and clinical findings, as they are not specific and can be misleading in establishing a diagnosis. In addition, relying on these biomarkers may contribute to more diagnostic examinations and/or unnecessary invasive interventions (for example laparotomy). PMID: 22800189 - PMCID: PMC3438050

Winkes MB, Luiten EJ, van Zoest WJ, Sala HA, Hoogeveen AR, Scheltinga MR. Long-term results ofn surgical decompression of chronic exertional compartment syndrome of the forearm in motocross racers. Am J Sports Med. 2012 Feb;40(2):452-8. Epub 2011 Oct 26. BACKGROUND: Chronic exertional compartment syndrome (CECS) is occasionally observed in the forearm flexor muscles of motocross racers. Long-term results of fasciectomy and fasciotomy for this syndrome are scarce. PURPOSE: To study the long-term effects of 2 surgical techniques for forearm flexor CECS. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: A database of patients with forearm CECS who underwent surgery was analyzed. Long-term pain reduction (visual analog scale [VAS], 0-100) and efficacy were evaluated using a questionnaire. RESULTS: Data of 24 motocross racers were available for analysis. Intracompartmental pressures during rest, during provocation, and after 1 and 5 minutes of provocation were 15 ± 4, 78 ± 24, 29 ± 10, and 25 ± 7 mm Hg, respectively. Painful sensations in the forearm were reduced from 53 to 7 (median VAS; P < .001). Both fasciectomy (n = 14)

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and fasciotomy (n = 10) were equally effective. More than 95% (23/24) of the patients were satisfied with the postoperative result after 5 ± 2 years’ follow-up. CONCLUSION: Surgical fasciotomy and fasciectomy of the forearm flexor compart ment are equally successful in motocross racers suffering from forearm CECS. PMID: 22031858

Dr. Ernest Luiten (links) en Maarten Beek.

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Luiten EJ, Oldenburg H. Windgassen E. Operatie van borst en oksel. B : Het blad over borstkanker. 2012;2(2):10-15. Van der Sangen MJ, Scheepers SW, Poortmans PM, Luiten EJ, Nieuwenhuijzen GA, Voogd AC. Detection of local recurrence following breast-conserving treatment in young women with early breast cancer: Optimization of long-term follow-up strate gies. Breast. 2012 Sep 15. pii: S0960-9776(12)00186-5. [Epub ahead of print]. The detection of a local recurrence (LR) in young women with breast cancer after breast-conserving treatment (BCT) was investigated to compare the impact of diffe rent long-term follow-up strategies. Between 1988 and 2005, 937 women aged =40 years were treated with BCT for early-stage breast cancer in the southern part of the Netherlands. Up to October 2009, 152 had developed an isolated LR. Information on follow-up visits was available for 124 of them. Fifty-four LRs (44%) were diagnosed within 5 years and 70 (56%) more than 5 years after BCT. Fifty-six LRs (45%) were detected during routine follow-up visits and 68 (55%) presented between two visits. Sixty-six LRs (53%) were diagnosed in patients reporting symptoms. In 31 patients (25%) the LR was found by mammography alone. About a quarter of the LRs was larger than 2 cm in diameter. These results imply that current follow-up strategies for young women with BCT do not guarantee a timely detection of LR. Copyright © 2012 Elsevier Ltd. All rights reserved. PMID: 22989668

Maaskant-Braat AJ, Roumen RM, Voogd AC, Pijpers R, Luiten EJ, Rutgers EJ, Nieuwenhuijzen GA. Sentinel Node and Recurrent Breast Cancer (SNARB): results of a nationwide registration study. Ann Surg Oncol. 2013 Feb;20(2):620-6. Epub 2012 Sep 1. BACKGROUND: Knowledge of regional lymph node involvement is important in patients with recurrent breast cancer for obtaining better locoregional control and predicting prognosis. To determine technical feasibility, validity, aberrant drainage rates, and clinical consequences of performing repeat sentinel node biopsy (SNB) in patients with locally recurrent breast cancer we conducted the “”Sentinel Node and Recurrent Breast Cancer (SNARB)”” study. METHODS: A total of 150 patients with locally recurrent breast cancer underwent lymphatic mapping and SNB. In case of an intact axillary lymph node basin, ipsilateral axillary lymph node dissection (ALND) was performed subsequently.

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RESULTS: A total of 41 patients previously underwent breast conserving therapy (BCT) with SNB, 82 patients BCT with ALND, and 21 patients a mastectomy, of which 9 with SNB and 12 with ALND. In 95 patients (63.3 %) a sentinel node was identified and in 78 patients (52 %) the sentinel node was successfully removed. In 18 patients (22.8 %) a (micro)metastasis was found on pathologic examination. Confirmation ALND in 18 patients showed no axillary lymph node metastases. Aberrant drainage pathways were visualized in 58.9 % of the patients, significantly more frequently after a previous ALND (79.3 %) than after a previous SNB (25.0 %) (P < .0001). Overall, the result of this repeat SNB led to a change in the adjuvant treatment plan in 16.5 % of the patients with a successful repeat SNB. CONCLUSIONS: Repeat SNB is technically feasible and provides reliable results in patients with locally recurrent breast cancer, leading to change in management in 1 of 6 patients. PMID: 22941173

Stoot JH, Wong-Lun-Hing EM, Limantoro I, Visschers R, Busch OR, Van Hillegersberg R, De Jong KM, Rijken AM, Kazemier G, Olde Damink SW, Lodewick TM, Bemelmans MH, van Dam RM, Dejong CH; Dutch Liver Collaborative Group. Laparoscopic liver resection in the Netherlands: how far are we? Dig Surg. 2012;29(1):70-8. Epub 2012 Mar 15. BACKGROUND: The objective of this study was to provide a systematic review on the introduction of laparoscopic liver surgery in the Netherlands, to investigate the initial experience with laparoscopic liver resections and to report on the current status of laparoscopic liver surgery in the Netherlands. METHODS: A systematic literature search of laparoscopic liver resections in the Netherlands was conducted using PubMed/MEDLINE. Analysis of initial experience with laparoscopic liver surgery was performed by case-control comparison of patients undergoing laparoscopic left lateral sectionectomy matched with patients undergoing the open procedure in the Netherlands between the years 2000 and 2008. Further more, a nationwide survey was conducted in 2011 on the current status of laparoscopic liver surgery. RESULTS: The systematic review revealed only 6 Dutch reports on actual laparoscopic liver surgery. Matched case-control comparison showed significant differences in the length of hospital stay, blood loss and operation time. Complications did not differ sig nificantly between the two groups (26 vs. 21%). The 2011 survey showed that 21 centers in the Netherlands performed formal liver resections and that 49 (5% of total) laparo scopic liver resections were performed in 2010. CONCLUSION: The systematic review revealed that very few laparoscopic liver resecti ons were performed in the Netherlands in the previous millennium. The matched Chirurgie

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case-control comparison of laparoscopic and open left lateral resection showed a reduction in hospital length of stay with comparable morbidity. The laparoscopic technique has been slowly adopted in the Netherlands, but its popularity seems to increase in recent years. Copyright © 2012 S. Karger AG, Basel. PMID: 22441623

Van Walsum GA, de Ridder JA, Verhoef C, Bosscha K, van Gulik TM, Hesselink EJ, Ruers TJ, van den Tol MP, Nagtegaal ID, Brouwers M, van Hillegersberg R, Porte RJ, Rijken AM, Strobbe LJ, de Wilt JH; Dutch Liver Surgeons Group Resection of liver metastases in patients with breast cancer: survival and prognostic factors. Eur J Surg Oncol. 2012 Oct;38(10):910-7. Epub 2012 Jun 7. AIMS: Patients with breast cancer metastasized to the liver have a median survival of 4-33 months and treatment options are usually restricted to palliative systemic thera py. The aim of this observational study was to evaluate the effectiveness and safety of resection of liver metastases from breast cancer and to identify prognostic factors for overall survival. METHODS: Patients were identified using the national registry of histo- and cytopa thology in the Netherlands (PALGA). Included were all patients who underwent resection of liver metastases from breast cancer in 11 hospitals in The Netherlands of the last 20 years. Study data were retrospectively collected from patient files. RESULTS: A total of 32 female patients were identified. Intraoperative and postopera tive complications occurred in 3 and 11 patients, respectively. There was no postopera tive mortality. After a median follow up period of 26 months (range, 0-188), 5-year and median overall survival after partial liver resection was 37% and 55 months, respectively. The 5-year disease-free survival was 19% with a median time to recurren ce of 11 months. Solitary metastases were the only independent significant prognostic factor at multivariate analysis. CONCLUSION: Resection of liver metastases from breast cancer is safe and might provide a survival benefit in a selected group of patients. Especially in patients with solitary liver metastasis, the option of surgery in the multimodality management of patients with disseminated breast cancer should be considered. Copyright © 2012 Elsevier Ltd. All rights reserved. PMID: 22682709

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Bosma E, Veen EJ, de Jongh MA, Roukema JA. Variable impact of complications in general surgery: a prospective cohort study. Can J Surg. 2012 Jun;55(3):163-70. BACKGROUND: Registering complications is important in surgery, since complications serve as outcome measures and indicators of quality of care. Few studies have ad dressed the variation in severity and consequences of complications. We hypothesized that complications show much variation in consequences and severity. METHODS: We conducted a prospective observational cohort study to evaluate con sequences and severity of complications in surgical practice. All recorded complicati ons of patients admitted to our hospital between June 1, 2005, and Dec. 31, 2007, were prospectively recorded in an electronic database. Complications were classified according to the system of the Trauma Registry of the American College of Surgeons. We graded the severity of complications according to the system proposed by Clavien and colleagues, and the consequences of each complication were registered. RESULTS: During the study period, 3418 complications were recorded; consequences and severity were recorded in 89% of them. Of 3026 complications, 987 (33%) were grade I, 781 (26%) were grade IIa, 1020 (34%) were grade IIb, 150 (5%) were grade III and 88 (3%) were grade IV. The consequences and severity of identically registered compli cations showed a large degree of variation, best illustrated by wound infections, which were grade I in 50%, grade IIa in 22%, grade IIb in 28% and grade III and IV in 0.3% of patients. CONCLUSION: Severity should be routinely presented when reporting complications in clinical practice and surgical research papers to adequately compare quality of care and results of clinical trials. PMID: 22449724 - PMCID: PMC3364303

De Leur K, Hoebink E, Veen E. Hevige pijn aan de rug. Medisch Contact. 2012 okt;67(43):2391. Vos D, Hanson B, Verhofstad M. Implant removal of osteosynthesis: the Dutch practice. Results of a survey. J Trauma Manag Outcomes. 2012 Aug 3;6(1):6. BACKGROUND: The aim of this survey study was to evaluate the current opinion and practice of trauma and orthopaedic surgeons in the Netherlands in the removal of implants after fracture healing. METHODS: A web-based questionnaire consisting of 44 items was sent to all active members of the Dutch Trauma Society and Dutch Orthopaedic Trauma Society to determine their habits and opinions about implant removal.

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RESULTS: Though implant removal is not routinely done in the Netherlands, 89% of the Dutch surgeons agreed that implant removal is a good option in case of pain or functional deficits. Also infection of the implant or bone is one of the main reasons for removing the implant (> 90%), while making money was a motivation for only 1% of the respondents. In case of younger patients (< 40 years of age) only 34% of the surge ons agreed that metal implants should always be removed in this category. Orthopae dic surgeons are more conservative and differ in their opinion about this subject compared to general trauma surgeons (p = 0.002). Though the far majority removes elastic nails in children (95%).Most of the participants (56%) did not agree that leaving implants in is associated with an increased risk of fractures, infections, allergy or malig nancy. Yet in case of the risk of fractures, residents all agreed to this statement (100%) whereas staff specialists disagreed for 71% (p < 0.001). According to 62% of the surge ons titanium plates are more difficult to remove than stainless steel, but 47% did not consider them safer to leave in situ compared to stainless steel. The most mentioned postoperative complications were wound infection (37%), unpleasant scarring (24%) and postoperative hemorraghe (19%). CONCLUSION: This survey indicates that there is no general opinion about implant removal after fracture healing with a lack of policy guidelines in the Netherlands. In case of symptomatic patients a majority of the surgeons removes the implant, but this is not standard practice for every surgeon. PMID: 22863279 - PMCID: PMC3485133

Vos DI, Verhofstad MH, Hanson B, van der Graaf Y, van der Werken C. Clinical outcome of implant removal after fracture healing. Design of a prospective multicentre clinical cohort study. BMC Musculoskelet Disord. 2012 Aug 15;13:147. BACKGROUND: The clinical results of removal of metal implants after fracture healing are unknown and the question whether to remove or to leave them in is part of discus sion worldwide. We present the design of a prospective clinical multicentre cohort study to determine the main indications for and expectations of implant removal, the influence on complaints, the incidence of surgery related complications and the socio-economic consequences of implant removal. METHODS/DESIGN: In a prospective multicentre clinical cohort study at least 200 patients with a healed fracture after osteosynthesis with a metal implant are included for analyzing the outcome after removal. Six hospitals in the Netherlands are participa ting. Special questionnaires are designed. The follow up after surgery will be at least six months. The primary endpoint is the incidence of surgery related complications. Secondary endpoints are the influence of removal on preoperative symptoms and complaints and the socio-economic consequences.

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DISCUSSION: By performing this study we hope to find profound arguments to remove or not to remove metal implants after fracture healing that can help to develop clear guidelines for daily practice. TRIAL REGISTRATION: NTR1297, http://www.trialregister.nl/trialreg/admin/rctview. asp?TC=1297. URL: http://www.biomedcentral.com/1471-2474/13/147 PMID: 22894749 - PMCID: PMC3493388

Kaas L, Sierevelt IN, Vroemen JP, van Dijk CN, Eygendaal D. Osteoporosis and radial head fractures in female patients: a case-control study. J Shoulder Elbow Surg. 2012 Nov;21(11):1555-8. Epub 2012 Jun 11. BACKGROUND: Identifying radial head fractures as fragility fractures may improve case-findings for osteoporosis and thus be an indicator other fragility fractures. MATERIALS AND METHODS: Thirty-five women aged = 50 years with a radial head fracture and 57 controls were retrospectively selected and matched for age in strata of 5 years. Peripheral bone mineral density (BMD) measurement was performed at the calcaneus. A T score of less than -2.7 was considered osteoporosis. If the T value was between -1.4 and -2.7, an additional dual energy X-ray (DXA) scan was performed. RESULTS: The patients were a median age of 60 years compared with 58 years for the control patients (P = .33). The mean T score of the patients was -1.8 (standard deviation [SD], 1.0; range, -2.2 to -0.3) compared with -1.2 (SD, 1.2; range, -4.0 to 1.3) for the control patients (P = .04). Osteoporosis was diagnosed in 11 patients and in 5 control patients. The patients had an increased risk of osteoporosis compared with the control patients (odds ratio, 3.4; P = .027). CONCLUSIONS: This study confirms that radial head fractures in women aged = 50 years are potentially osteoporotic fractures. Offering these patients a BMD measure ment may prevent future osteoporotic fractures, such as hip and spine fractures. Copyright © 2012 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Mosby, Inc. All rights reserved. PMID: 22694879

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Dermatologie Kerngegevens Zorgkern Dermatologie • 7 dermatologen: mw. A. (Angelina) Barentsen-Erceg, dr. A.R.L.J. (Annick) Bracke, mw. S.J. (Sarah) Caers, W.J.A. (Wim) de Kort, dr. J.E.M. (John) Körver, mw. dr. D.I.M. (Danielle) Kuijpers, mw. F.J.A.M. (Francoise) van Neer • 2 assistenten niet in opleiding • 2 assistenten in opleiding • Subspecialismen: flebologie, dermato-oncologie

Samenvattingen gepubliceerde artikelen Erceg A. Innovation of vascular laser for clinical practice; from vascular to inflammatory targets. [S.l. : s.n.], 2012 (Nijmegen : Ipskamp Drukkers). Proefschrift Radboud Universiteit Nijmegen. ISBN 978-909-027-115-6.

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Gynaecologie Kerngegevens Zorgkern Gynaecologie • 16 gynaecologen: J. (Jeroen) van Bavel, dr. P.F.J. (Peter) van Bommel, mw. M.G.K. (Marja) Dijksterhuis, dr. H.W.H. (Harry) Feijen, dr. D.A. (Dirk) Gietelink, dr. D.J. (Dave) Hendriks, dr. R. (Roger) Heydanus, mw. J.C.M (Anneke) Jeurgens-Borst, G.J.A. (Gerhard) Knol, mw. A.L.M. (Angela) Kok, mw. dr. M.S. (Simone) Lunshof , dr. D.N.M. (Dimitri) Papatsonis, mw. M.F.M. (Mariska) Shekary-Moonen, mw. D.J.C. (Ineke) Smalbraak, mw. M.C.S. (Ellen) Vermeer, dr. H.J. (Henk) Vonsée • 8 assistenten niet in opleiding • 1 assistent in opleiding • 1 baios • 3 fertiliteitsartsen • Subspecialismen: benigne gynaecologie, prenetale diagnostiek, fertiliteit, bekkenbodem, oncologie, psychosomatiek, verloskunde: pre-partum, intra-partum en post-partum

Samenvattingen gepubliceerde artikelen De Vogel J, van der Leeuw-van Beek A, Gietelink D, Vujkovic M, de Leeuw JW, van Bavel J, Papatsonis D. The effect of a mediolateral episiotomy during operative vaginal delivery on the risk of developing obstetrical anal sphincter injuries. Am J Obstet Gynecol. 2012 May;206(5):404.e1-5. Epub 2012 Mar 15. OBJECTIVE: The objective of the study was to evaluate the frequency of obstetrical anal sphincter injuries (OASIS) in women undergoing operative vaginal deliveries (OVD) and to assess whether a mediolateral episiotomy is protective for developing OASIS in these deliveries. STUDY DESIGN: We performed a retrospective cohort study. Maternal and obstetrical characteristics of the 2861 women who delivered liveborn infants by an OVD at term in the years 2001-2009 were extracted from a clinical obstetrics database and were analyzed in a logistic regression model. RESULTS: The frequency of OASIS was 5.7%. Women with a mediolateral episiotomy were at significantly lower risk for OASIS compared with the women without a medio lateral episiotomy in case of an OVD (adjusted odds ratio, 0.17; 95% confidence interval, 0.12-0.24). CONCLUSION: We found a 6-fold decreased odds for developing OASIS when a mediolateral episiotomy was performed in OVD. Therefore, we advocate the use of a mediolateral episiotomy in all operative vaginal deliveries to reduce the incidence of OASIS. Copyright © 2012 Mosby, Inc. All rights reserved. PMID: 22425401

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Huppelschoten AG, van Duijnhoven NT, van Bommel PF, Kremer JA, Nelen WL. Do infertile women and their partners have equal experiences with fertility care? Fertil Steril. 2012 Nov 29. [Epub ahead of print]. OBJECTIVE: To study the possible differences between women and their partners’ experiences with patient-centered fertility care. DESIGN: A cross-sectional study. SETTING: Thirty-two Dutch fertility clinics. PATIENT(S): A total of 1,620 infertile women and their partners, under treatment in one of the participating clinics, were randomly selected to participate in this study. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Level of patient-centeredness, measured with the vali dated Patient-Centeredness Questionnaire-Infertility questionnaire (PCQ-Infertility). RESULT(S): Questionnaires from 696 women and 520 partners were analyzed. No significant difference in PCQ-Infertility total score was found between women and their partners. The partners scored significantly higher on the subscales “respect for patients values” and “staff’s competence” compared with the women. CONCLUSION(S): Patients’ experiences with fertility care are only slightly different between women and their partners. This can be valuable in the process of improve ment of patient-centered fertility care, one of the core dimensions of quality of care. Copyright © 2013 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved. PMID: 23200687 [PubMed - as supplied by publisher]

Vollebregt A, Fischer K, Gietelink D, van der Vaart CH. Effects of Vaginal Prolapse Sur gery on Sexuality in Women and Men; results from a RCT on repair with and without mesh. J Sex Med. 2012 Apr;9(4):1200-11. Epub 2012 Feb 9. INTRODUCTION: In pelvic organ prolapse (POP) repair, the use of synthetic mesh is not only increasing but also a subject of discussion. The focus shifts from anatomical toward functional outcome, with sexual function being an important parameter. One of the concerns with mesh usage in POP surgery is the possible negative effect on sexual function.

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AIM: To compare and assess sexual function in women and men after primary cystocele repair with or without trocar-guided transobturator mesh. Methods. One hundred twenty-five women with a symptomatic cystocele stage = II were included in this multicenter randomized controlled trial and assessed at baseline and 6-month follow-up. MAIN OUTCOME MEASURES: Female sexual function was measured by the Female Sexual Function Index (FSFI) and male sexual function by the Male Sexual Health Questionnaire. A subgroup analysis of women with a participating partner was perfor med. RESULTS: In the mesh group, 54/59 women vs. 53/62 in the anterior colporrhaphy group participated. In men, 29 vs. 30 participated. After surgery, FSFI scores were com parable for both treatment groups. However, within group analysis showed significant improvement on the domains pain (effect size = 0.5), lubrication (effect size = 0.4), and overall satisfaction (effect size = 0.5) in the colporrhaphy group. This improvement was not observed in the mesh group. A subgroup of women with a participating partner reported significantly higher baseline domain scores as compared with other women and did not report a significant improvement of sexual functioning irrespective of treatment allocation. Worsening of baseline sexual function was reported by 43% of women in the mesh group compared with 18% in anterior colporrhaphy group (P = 0.05). Male sexual functioning did not change in either group. CONCLUSIONS: Women after an anterior colporrhaphy report a significant and clini cally relevant improvement of their sexual functioning, whereas women after a mesh procedure did not. Vollebregt A, Fischer K, Gietelink D, and van der Vaart CH. Effects of vaginal prolapse surgery on sexuality in women and men; results from a RCT on repair with and without mesh. J Sex Med **;**:**-**. © 2012 International Society for Sexual Medicine. PMID: 22321388

Schuit E, Hukkelhoven CW, Manktelow BN, Papatsonis DN, de Kleine MJ, Draper ES, Steyerberg EW, Vergouwe Y. Prognostic models for stillbirth and neonatal death in very preterm birth: a validation study. Pediatrics. 2012 Jan;129(1):e120-7. Epub 2011 Dec 12. OBJECTIVES: To validate externally 2 prognostic models for stillbirth and neonatal death in very preterm infants who are either known to be alive at the onset of labor or admitted for neonatal intensive care. PATIENTS AND METHODS: All infants, with gestational age 22 to 32 weeks, of European ethnicity, known to be alive at the onset of labor (n = 17?582) and admitted for neo

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natal intensive care (n = 11?578), who were born in the Netherlands between January 1, 2000, and December 31, 2007. The main outcome measures were stillbirth or death within 28 days for infants known to be alive at the onset of labor and death before discharge from the NICU for infants admitted for intensive care. Model performance was studied with calibration plots and c statistic. RESULTS: Of the infants known to be alive at the onset of labor, 16.7% (n = 2939) died during labor or within 28 days of birth, and 7.8% (n = 908) of the infants admitted for neonatal intensive care died before discharge from intensive care. The prognostic model for infants known to be alive at the onset of labor showed good calibration and excellent discrimination (c statistic 0.92). The prognostic model for infants admitted for neonatal intensive care showed good calibration and good discrimination (c statis tic 0.82). CONCLUSIONS: The 2 prognostic models for stillbirth and neonatal death in very pre term Dutch infants showed good performance, suggesting their use in clinical practice in the Netherlands and possibly other Western countries. PMID: 22157141

Wilmink FA, Hukkelhoven CW, Mol BW, van der Post JA, Steegers EA, Papatsonis DN. Neonatal outcome following elective cesarean section of twin pregnancies beyond 35 weeks of gestation. Am J Obstet Gynecol. 2012 Dec;207(6):480.e1-7. Epub 2012 Sep 14. OBJECTIVE: We sought to assess neonatal morbidity and mortality of elective cesarean section (CS) of uncomplicated twin pregnancies per week of gestation >35(+0). STUDY DESIGN: We performed a retrospective cohort study in our nationwide data base including all elective CS of twin pregnancies. Two main composite outcome mea sures were defined, ie, severe adverse neonatal outcome and mild neonatal morbidity. RESULTS: We report on 2228 neonates. More than 17% were born <37(+0) weeks of gestation. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for severe adverse neonatal outcome at 35(+0-6), 36(+0-6), and 37(+0-6) weeks were, OR, 9.4; 95% CI, 3.2-27.6; OR, 1.7; 95% CI, 0.5-5.3; and OR, 0.7; 95% CI, 0.2-2.0, respectively; and for mild neonatal morbidity, OR, 4.7; 95% CI, 2.6-8.7; OR, 4.9; 95% CI, 3.1-7.9; and 1.4; 95% CI, 0.9-2.1, respectively, compared to neonates born =38(+0) weeks of gestation. CONCLUSION: In uncomplicated twin pregnancies elective CS can best be performed between 37(+0) and 39(+6) weeks of gestation. Copyright © 2012 Mosby, Inc. All rights reserved. PMID: 23017224 Xxx

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Bakker JJ, Janssen PF, van Halem K, van der Goes BY, Papatsonis DN, van der Post JA, Mol BW. Internal versus external tocodynamometry during induced or augmented labour. Cochrane Database Syst Rev. 2012 Dec 12;12:CD006947. BACKGROUND: Uterine contractions can be registered by external tocodynamometry (ET) or, after rupture of the membranes, by internal tocodynamometry (IT). Monitoring of the frequency of contractions is important especially when intravenous oxytocin is used as excessive uterine activity (hyperstimulation or tachysystole) can cause fetal distress. During induction of labour as well as during augmentation with intravenous oxytocin, some clinicians choose to monitor frequency and strength of contractions with IT rather than with ET as an intrauterine pressure catheter measures intrauterine activity more accurately than an extra-abdominal tocodynamometry device. Howe ver, insertion of an intrauterine catheter has higher costs and also potential risks for mother and child. OBJECTIVES: To assess the effectiveness of IT compared with using ET when intra venous oxytocin is used for induction or augmentation of labour. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group’s Trials Register (11 April 2012) and PubMed (1966 to 7 March 2012). SELECTION CRITERIA: We included all published randomised controlled trials with data from women in whom IT was compared with ET in induced or augmented labour with oxytocin. We excluded trials that employed quasi-randomised methods of treatment allocation. We found no unpublished or ongoing studies on this subject. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial eligibility and risk of bias, and independently extracted data. Data were checked for ac curacy. Where necessary, we contacted study authors for additional information. MAIN RESULTS: Three studies involving a total of 1945 women were included. Overall, risk of bias across the three trials was mixed. No serious complications were reported in the trials and no neonatal or maternal deaths occurred. The neonatal outcome was not statistically different between groups: Apgar score less than seven at five minutes (RR 1.78, 95% CI 0.83 to 3.83; three studies, n = 1945); umbilical artery pH less than 7.15 (RR 1.31, 95% CI 0.95 to 1.79; one study, n = 1456); umbilical artery pH less than 7.16 (RR 1.23, 95% CI 0.39 to 3.92; one study, n = 239); admission to the neonatal intensive care unit (RR 0.34, 95% CI 0.07 to 1.67; two studies, n = 489); and more than 48 hours hospitalisation (RR 0.92, 95% CI 0.71 to 1.20; one study, n = 1456). The pooled risk for instrumental delivery (including caesarean section, ventouse and forceps extraction) was not statistically significantly different (RR 1.05, 95% CI 0.91 to 1.21; three studies, n = 1945). Hyperstimulation was reported in two studies (n = 489), but there was no statistically significant difference between groups (RR 1.21, 95% CI 0.78 to 1.88).

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AUTHORS’ CONCLUSIONS: This review found no differences between the two types of monitoring (internal or external tocodynamometry) for any of the maternal or neo natal outcomes. Given that this review is based on three studies (N = 1945 women) of moderate quality, there is insufficient evidence to recommend the use of one form of tocodynamometry over another for women where intravenous oxytocin was adminis tered for induction or augmentation of labour. PMID: 23235636

Lambeek AF, De Hundt M, Vlemmix F, Akerboom BM, Bais JM, Papatsonis DN, Mol BW, Kok M. Risk of developmental dysplasia of the hip in breech presentation: the effect of successful external cephalic version. BJOG. 2013 Apr;120(5):607-12. Epub 2012 Nov 12. OBJECTIVE: To evaluate the effect of successful external cephalic version on the inci dence of developmental dysplasia of the hip (DDH) requiring treatment in singleton breech presentation at term. DESIGN: Observational cohort study. SETTING: Three large teaching hospitals in the Netherlands. POPULATION: Women with a singleton breech presentation of 34 weeks of gestation or more, who underwent an external cephalic version attempt. METHODS: We made a comparison of the incidence of DDH between children born in breech presentation and children born in cephalic presentation after a successful external cephalic version. MAIN OUTCOME MEASURE: The incidence of DDH requiring either conservative treat ment, with a harness, or surgical treatment. RESULTS: A total of 498 newborns were included in the study, of which 40 (8%) were diagnosed with DDH and 35 required treatment. Multivariate analysis showed that female gender (OR 2.79, 95% CI 1.23-6.35) and successful external cephalic version (OR 0.29, 95% CI 0.09-0.95) were independently associated with DDH. CONCLUSIONS: A successful external cephalic version is associated with a lower inci dence of DDH, although a high percentage of children born after a successful external cephalic version still appear to have DDH. A larger cohort study is needed to establish the definite nature of this relationship. Until then, we recommend the same screening policy for infants born in cephalic position after a successful external cephalic version as for infants born in breech position.

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© 2012 The Authors BJOG An International Journal of Obstetrics and Gynaecology © 2012 RCOG. PMID: 23145903

Freeman LM, Bloemenkamp KW, Franssen MT, Papatsonis DN, Hajenius PJ, van Huizen ME, Bremer HA, van den Akker ES, Woiski MD, Porath MM, van Beek E, Schuitemaker N, van der Salm PC, Fong BF, Radder C, Bax CJ, Sikkema M, van den Akker-van Marle ME, van Lith JM, Lopriore E, Uildriks RJ, Struys MM, Mol BW, Dahan A, Middeldorp JM. Remi fentanil patient controlled analgesia versus epidural analgesia in labour. A multicentre randomized controlled trial. BMC Pregnancy Childbirth. 2012 Jul 2;12:63. BACKGROUND: Pain relief during labour is a topic of major interest in the Netherlands. Epidural analgesia is considered to be the most effective method of pain relief and recommended as first choice. However its uptake by pregnant women is limited com pared to other western countries, partly as a result of non-availability due to logistic problems. Remifentanil, a synthetic opioid, is very suitable for patient controlled anal gesia. Recent studies show that epidural analgesia is superior to remifentanil patient controlled analgesia in terms of pain intensity score; however there was no difference in satisfaction with pain relief between both treatments. METHODS/DESIGN: The proposed study is a multicentre randomized controlled study that assesses the cost-effectiveness of remifentanil patient controlled analgesia com pared to epidural analgesia. We hypothesize that remifentanil patient controlled anal gesia is as effective in improving pain appreciation scores as epidural analgesia, with lower costs and easier achievement of 24 hours availability of pain relief for women in labour and efficient pain relief for those with a contraindication for epidural analgesia. Eligible women will be informed about the study and randomized before active labour has started. Women will be randomly allocated to a strategy based on epidural analge sia or on remifentanil patient controlled analgesia when they request pain relief during labour. Primary outcome is the pain appreciation score, i.e. satisfaction with pain relief. Secondary outcome parameters are costs, patient satisfaction, pain scores (pain-inten sity), mode of delivery and maternal and neonatal side effects.The economic analysis will be performed from a short-term healthcare perspective. For both strategies the cost of perinatal care for mother and child, starting at the onset of labour and ending ten days after delivery, will be registered and compared. DISCUSSION: This study, considering cost effectiveness of remifentanil as first choice analgesia versus epidural analgesia, could strongly improve the care for 180.000 wo men, giving birth in the Netherlands yearly by giving them access to pain relief during labour, 24 hours a day. TRIAL REGISTRATION NUMBER: Dutch Trial Register NTR2551, http://www.trialregister.nl. PMID: 22748068 - PMCID: PMC3464937 Xxx

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Tajik P, van der Tuuk K, Koopmans CM, Groen H, van Pampus MG, van der Berg PP, van der Post JA, van Loon AJ, de Groot CJ, Kwee A, Huisjes AJ, van Beek E, Papatsonis DN, Bloemenkamp KW, van Unnik GA, Porath M, Rijnders RJ, Stigter RH, de Boer K, Schee pers HC, Zwinderman AH, Bossuyt PM, Mol BW. Should cervical favourability play a role in the decision for labour induction in gestational hypertension or mild pre-eclampsia at term? An exploratory analysis of the HYPITAT trial. BJOG. 2012 Aug;119(9):1123-30. Epub 2012 Jun 18. OBJECTIVE: To examine whether cervical favourability (measured by cervical length and the Bishop score) should inform obstetricians’ decision regarding labour induction for women with gestational hypertension or mild pre-eclampsia at term. DESIGN: A post hoc analysis of the Hypertension and Pre-eclampsia Intervention Trial At Term (HYPITAT). SETTING: Obstetric departments of six university and 32 teaching and district hospitals in the Netherlands. POPULATION: A total of 756 women diagnosed with gestational hypertension or pre-eclampsia between 36 + 0 and 41 + 0 weeks of gestation randomly allocated to induction of labour or expectant management. METHODS: Data were analysed using logistic regression modelling. MAIN OUTCOME MEASURES: The occurrence of a high-risk maternal situation defined as either maternal complications or progression to severe disease. Secondary outco mes were caesarean delivery and adverse neonatal outcomes. RESULTS: The superiority of labour induction in preventing high-risk situations in women with gestational hypertension or mild pre-eclampsia at term varied signifi cantly according to cervical favourability. In women who were managed expectantly, the longer the cervix the higher the risk of developing maternal high-risk situations, whereas in women in whom labour was induced, cervical length was not associated with a higher probability of maternal high-risk situations (test of interaction P = 0.03). Similarly, the beneficial effect of labour induction on reducing the caesarean section rate was stronger in women with an unfavourable cervix. CONCLUSION: Against widely held opinion, our exploratory analysis showed that women with gestational hypertension or mild pre-eclampsia at term who have an unfavourable cervix benefited more from labour induction than other women. TRIAL REGISTRATION: The trial has been registered in the clinical trial register as IS RCTN08132825.

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© 2012 The Authors BJOG An International Journal of Obstetrics and Gynaecology © 2012 RCOG. PMID: 22703475 - PMCID:PMC3440582

Van Oostwaard MF, Langenveld J, Bijloo R, Wong KM, Scholten I, Loix S, Hukkelhoven CW, Vergouwe Y, Papatsonis DN, Mol BW, Ganzevoort W. Prediction of recurrence of hypertensive disorders of pregnancy between 34 and 37 weeks of gestation: a retro spective cohort study. BJOG. 2012 Jun;119(7):840-7. Epub 2012 Apr 2. OBJECTIVE: To assess the recurrence risk of late-preterm hypertensive disease of preg nancy, and to determine whether potential risk factors are predictive. DESIGN: Retrospective cohort study. SETTING: Three secondary and three tertiary care hospitals in the Netherlands. POPULATION: We identified women with a hypertensive disorder in the index preg nancy and delivery at 34-37 weeks of gestation, between January 2000 and December 2002. METHODS: Data were extracted from medical files and women were approached for additional information on subsequent pregnancies. An adverse outcome was defined as the recurrence of a hypertensive disorder in the next subsequent pregnancy. MAIN OUTCOME MEASURES: Absolute risk of recurrence and a prediction model con taining demographic and clinical factors predictive for adverse outcome. RESULTS: We identified 425 women who matched the criteria, of whom 351 could be contacted. Of these women, 189 (54%) had had a subsequent pregnancy. Hypertensive disorders recurred in 96 (51%, 95% CI 43-58%) women, of whom 17 (9%, 95% CI 5-14%) delivered again before 37 weeks of gestation. Chronic hypertension and maternal age were the strongest predictors for recurrence. Women undergoing recurrence had a nine-fold chance of developing chronic hypertension (37% versus 6%, OR 8.7, 95% CI 3.3-23). CONCLUSIONS: Women with hypertensive disorders and late-preterm delivery have a 50% chance of recurrence, but only a 9% chance of recurrence resulting in delivery before 37 weeks of gestation. Women with chronic hypertension are prone to develop recurrence, and women with a recurrence more often developed chronic hypertension. © 2012 The Authors BJOG An International Journal of Obstetrics and Gynaecology © 2012 RCOG.

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PMID: 22469065

Halem KV, Bakker JJ, Verhoeven CJ, Papatsonis DN, Oudgaarden ED, Janssen P, Bloe menkamp KW, Mol BW, Van Der Post JA. Does use of an intrauterine catheter during labor increase risk of infection? J Matern Fetal Neonatal Med. 2012 Apr;25(4):415-8. Epub 2011 Jun 7. OBJECTIVE: To determine whether the use of an intrauterine catheter during labor is related to the occurrence of infection in mother or newborn during labor and up to 3 weeks postpartum. METHODS: We performed a follow-up study of 1435 women who participated in a previously published multicentre randomized controlled trial in the Netherlands that assigned women in whom labor was induced or augmented with intravenous oxytocin to internal or external tocodynamometry. In the present post hoc analysis, we assessed the risk for infection, defined as a composite measure of any clinical sign of infection, treatment with antibiotics or sepsis during labor or in the postpartum period up to 3 weeks in mother or newborn. RESULTS: There were 64 cases with indication of infection in the intrauterine catheter group (8.8%) versus 74 cases in the external monitoring group (10.4%). Relative risk: 0.91, 95% confidence interval: 0.77-1.1, and p: 0.33. CONCLUSION: Use of an intrauterine catheter during labor does not increase the risk of infection. PMID: 21649507

Lim AC, Schuit E, Papatsonis D, van Eyck J, Porath MM, van Oirschot CM, Hummel P, Hasaart TH, Kleiverda G, de Graaf IM, van Ginkel AA, Mol BW, Bruinse HW. Effect of 17-alpha hydroxyprogesterone caproate on cervical length in twin pregnancies. Ultrasound Obstet Gynecol. 2012 Oct;40(4):426-30. OBJECTIVES: Previous studies on singleton pregnancies have indicated that proges togens may reduce the rate of cervical shortening during pregnancy. The aim of this study was to investigate whether treatment with 17-alpha hydroxyprogesterone capro ate (17-OHPC) has an effect on cervical shortening in twin pregnancies. METHODS: This was a secondary analysis of patients who had participated in a multi center randomized clinical trial on the effectiveness of 17-OHPC in preventing preterm birth in multiple pregnancies (the AMPHIA-trial). We included all trial participants with

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a twin gestation who had undergone repeat cervical length measurements during pregnancy. We performed a separate analysis of women with repeat measurements in centers where this was standard protocol for multiple pregnancies. The rate of cervical shortening for both the 17-OHPC group and the placebo group was analyzed using a linear mixed model. RESULTS: Of the 671 patients who participated in the trial, 282 (42%) had a twin preg nancy and underwent two or more cervical length measurements. Of these women, 140 were monitored in centers where repeat measurements were standard protocol. We observed an overall reduction of cervical length from 44.3 mm at 14-18 weeks to 30.0 mm at 30-34 weeks’ gestation. In the 17-OHPC group, cervical length decreased by 1.04 mm each gestational week, while this was 1.11 mm per week for the placebo group (P = 0.6). For the overall group, each 10% decrease in cervical length led to an increase in the risk of preterm birth (hazard ratio, 1.14; 95% CI, 1.08-1.21). CONCLUSION: In women with a twin pregnancy, there is progressive shortening of the cervix during pregnancy, regardless of 17-OHPC use. Copyright © 2012 ISUOG. Published by John Wiley & Sons, Ltd. PMID: 23008102

Schuit E, Hukkelhoven CW, Manktelow BN, Papatsonis DN, de Kleine MJ, Draper ES, Steyerberg EW, Vergouwe Y. Voorspellen van sterfte bij zeer premature kinderen. [Pre dicting death in very preterm infants]. Ned Tijdschr Geneeskd. 2012 Sep 22;156 38:A4846 [1574-80]. DOEL: Validatie in de Nederlandse situatie van 2 Britse prognostische modellen die het risico op ster f te voorspellen bij kinderen die zeer prematuur worden geboren. De kinderen zijn in leven bij het begin van de baring (model 1) of zijn opgenomen op de neonatale intensivecare-unit (NICU; model 2). OPZET: Cohortstudie. METHODE: Alle kinderen met een Europese etniciteit die waren geboren na een zwan gerschapsduur van 22-32 weken in Nederland in de periode 1 januari 2000-31 december 2007 werden geïncludeerd. In totaal waren er 17.582 kinderen in leven bij het begin van de baring, van wie 11.578 werden opgenomen op de NICU. Sterfte was gedefinieerd als foetale sterfte of sterfte binnen 28 dagen na de geboor te (model 1) of neonatale sterfte vóór ontslag van de NICU (model 2). De prestaties van beide modellen werden bepaald op basis van kalibratie en discriminerend vermogen. RESULTATEN: Van de kinderen die in leven waren bij het begin van de baring, overleden 2939 (16,7%) tijdens de baring of binnen 28 dagen. Van de op de NICU opgenomen kin Xxx

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deren overleden 908 (7,8%) vóór ontslag. Beide modellen hadden een goede kalibratie en een goed tot zeer goed discriminerend vermogen: de ‘area under the receiver opera ting charac-teristic curve’ (AUC) was 0,92 voor model 1 en 0,82 voor model 2. CONCLUSIE: De 2 Britse modellen voorspelden het risico op sterfte goed voor Neder landse zeer prematuur geboren kinderen. De modellen zijn gebaseerd op kenmerken die eenvoudig te bepalen zijn, zoals geslacht, zwangerschapsduur, geschat te geboor tegewicht en pluraliteit van de zwangerschap, en kunnen behulpzaam zijn in de Neder landse gynaecologische en neonatologische praktijk.

Liem SM, Bekedam DJ, Bloemenkamp KW, Kwee A, Papatsonis D, van der Post JA, Lim AC, Scheepers HC, Willekes C, Duvekot JJ, Spaanderman M, Porath M, van Eyck J, Haak MC, Marielle G van Pampus MG, Bruinse HW, Mol BW, Hegeman MA. Correction: Pes saries in multiple pregnancy as a prevention of preterm birth: the ProTwin Trial. BMC Pregnancy and Childbirth. 2012 may 23;12:37. Correction: Hegeman MA, Bekedam DJ, Bloemenkamp KWM, Dimitri AK Papatsonis, van der Post NM, Joris AM, et al: Pessaries in multiple pregnancy as a prevention of preterm birth: the ProTwin Trial. BMC Pregnancy Childbirth 2009, 9:44.

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Interne Geneeskunde en Maag-, Darm-, Levergeneeskunde Kerngegevens Zorgkern Interne Geneeskunde en Maag-, Darm-, Levergeneeskunde • 19 Internisten: dr. R.C. (René) Bakker , mw. R.S. (Rinske) Boersma, mw. dr. P.W.G. (Peggy) du Buf – Vereijken, mw. T.T. (Nynke) Cnossen, mw. S.A.M. (Simone) Ennecker-Jans, dr. J.W.J. (Joost) van Esser, dr. R.W. (Ronald) van Etten (medisch manager), mw. A.M. (Astrid) van Gent, G.J. (Gerard) Goverde, dr. C. (Coen) van Guldener, mw. J.B. (Joan) Heijns, mw. dr. M.H.W. (Mariëtte) Kappers, mw. dr. M.A. (Marieke) van Leeuwen – Artz, O.J.L. (Olaf) Loosveld, dr. S.W. (Sjoerd) van Thiel, dr. A.J. (Bert-Jan) ten Tije, B.F.E. (Bernard) Veldhuijzen, G.P. (Gerrit) Verburg, P. (Peter) van Wijngaarden • 6 MDL-artsen: A.G.L. (Alexander) Bodelier, I.M. (Ivar) Harkema, mw. M.J. (Marianne) van Heerde, dr. A.W.M (Marc) van Milligen de Wit, dr. M.C.M. (Marno) Rijk, dr. T.C.J (Tom) Seerden • Gemiddeld 10 assistenten niet in opleiding • Gemiddeld 10 assistenten in opleiding • Subspecialismen: diabetes, endocrinologie, hematologie, infectieziekten, nefrologie, oncologie, maag- darm- leverziekten, vasculaire geneeskunde

Samenvattingen gepubliceerde artikelen Meulenbeld HJ, van Werkhoven ED, Coenen JL, Creemers GJ, Loosveld OJ, de Jong PC, Ten Tije AJ, Fosså SD, Polee M, Gerritsen W, Dalesio O, de Wit R. Randomised phase II/III study of docetaxel with or without risedronate in patients with metastatic Castration Resistant Prostate Cancer (CRPC), the Netherlands Prostate Study (NePro). Eur J Cancer. 2012 Nov;48(16):2993-3000. Epub 2012 Jun 6. BACKGROUND: This multicentre, randomised, open label, phase II/III study aimed to investigate the potential benefit of adding risedronate (R) to docetaxel (D) in patients with metastatic Castration Resistant Prostate Cancer (CRPC). PATIENTS AND METHODS: CRPC patients with bone metastasis were randomly assigned to receive D 75 mg/m(2) every 3 weeks and prednisone as first line chemo therapy, with or without R 30 mg oral once daily. The primary end-point was time to progression (TTP). A composite end-point of objective progression by RECIST criteria, PSA progression, or pain progression, whichever occurred first, was applied. The study had 80% power to detect an improvement of 30% in median TTP in the DR group (two-sided a=0.05). RESULTS: Five hundred and ninety-two men (301 D versus 291 DR) were randomised. TTP was 7.4 [D] versus 6.5 [DR] months (p=0.75). PSA and pain response rates were similar, 66.3% [D] versus 65.9% [DR] and 27.9% [D] versus 31.2% [DR], respectively. Median overall survival (OS) was 18.4 [D] versus 19.2 [DR] months (p=0.33). There were no differences in toxicity.

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CONCLUSION: The addition of the third generation bisphosphonate, risedronate, in the setting of effective first line docetaxel based chemotherapy did not increase efficacy, as indicated by the lack of improvement in TTP, OS, PSA- and pain response. Copyright © 2012 Elsevier Ltd. All rights reserved. PMID: 22677260

Robbrecht DG, Alidjan F, Eikemans B, Haans DA, van Guldener C, van Wijngaarden P. Panniculitis mesenterica: uiteenlopende presentaties. [Mesenteric panniculitis: variable presentations]. Ned Tijdschr Geneeskd. 2012;155(25):A4555 [1047-52]. Mesenteric panniculitis is a non-specific inflammation of the mesenteric adipose tissue, with varying degrees of fibrosis and fat necrosis. It can be associated with varying diseases and conditions, such as autoimmune disease and cancer. Many doctors are not familiar with this disease or do not know how to interpret the signs and symptoms. Here, we describe three patients illustrating the variety of clinical course, diagnostics, prognosis and treatment. A 44-year-old woman suffering from episodic abdominal pain was diagnosed with uncomplicated mesenteric panniculitis. The disease was stable while maintaining a conservative approach. In a 43-year-old woman, mesenteric panniculitis was complicated by autoimmune haemolytic anaemia. After treatment with corticosteroids, she made a full recovery from both disorders. Finally, a 73-year-old man was diagnosed with mesenteric panniculitis and auto-immune haemolytic anaemia, which both appeared to be consequences of an angioimmunoblastic T-cell lymphoma. PMID: 22748362

Joosen AM, Boersma RS, Ermens AA. De kunst van het kijken : Uw diagnose? Ned Tijdschr Hematologie. 2012; 9: 130-131. Cnossen TT, Konings CJ, Fagel WJ, van der Sande FM, van Geel K, Leunissen KM, Kooman JP. Fluid State and Blood Pressure Control: No Differences Between APD and CAPD. ASAIO J. 2012 Mar;58(2):132-6. The aim of this study was to compare fluid state, ambulatory blood pressure, and sodiumremoval in automated peritoneal dialysis (APD) and continuous ambulatory peritonealdialysis (CAPD). This observational, cross-sectional study comprised 20 APD and 24 CAPD patients with a mean duration on peritoneal dialysis of 30±26 and 21 ±23 months, respectively. Sixty-four percent of the patients were treated with icodextrin. The methods used were 24 hr dialysate and urine collections, standardized 3.86%


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glucose peritoneal equilibration test (PET), bioimpedance analysis, and 24 hr ambula tory blood pressure monitoring. Extracellular water (ECW) corrected for body weight was 0.23 6 0.03 L/kg both in APD and CAPD patients. The slope normovolemia value according to Chamney was 0.0 6 0.2 L/kg in APD patients and 0.0 6 0.05 L/kg in CAPD patients (not significant [NS]). Mean systolic blood pressure (SBP) and diastolic blood pressure (DBP) were respectively, 132 ± 25 and 79 ± 8 mm Hg in APD and 129 ± 16 and 76 ± 11 mm Hg in CAPD patients (NS). Sodium concentration in dialysate was respectively, 129.5 ± 3.5 mmol/L in APD and 132.4 ± 4.1 mmol/L in CAPD (p= 0.017). Dialysate sodium removal was 80.6 ± 78.4 mmol/24 hr in APD and 108.7 ± 96.8 mmol/24 hr in CAPD patients (NS). Natriuresis was respectively, in APD 76.6 ± 65.5 mmol/24 hr and in CAPD 93.5 ± 61.7 mmol/24 hr (NS). Total sodium removal was 149.5 ± 76.6 mmol/24 hr in APD and 198.4 ± 75.0 mmol/24 hr in CAPD (p= .039). Despite a higher daily sodium removal in CAPD patients, fluid state and blood pressure were not different between APD and CAPD. In general, volume status and blood pressure appeared to be reasonably control led in this unselected population. PMID: 22370683

Cnossen TT, Kooman JP, Krepel HP, Konings CJ, Uszko-Lencer NH, Leunissen KM, van der Sande FM. Prospective study on clinical effects of renal replacement therapy in treatment-resistant congestive heart failure. Nephrol Dial Transplant. 2012 Jul;27(7):2794-9. Epub 2012 Apr 6. BACKGROUND/AIMS: Clinical outcome in cardiorenal syndrome (CRS) Type 2 and treatment with dialysis. METHODS: Prospective observational non-randomized study. RESULTS: Twenty-three patients were included, mean age 66±21 years. Twelve (52%) patients were treated with peritoneal dialysis (PD) and 11 (48%) with intermit tent haemodialysis (IHD). Median survival time after start of dialysis was 16 months. Hospitalizations for cardiovascular causes were reduced (1.4±0.6 pre-dialysis versus 0.4±0.6 days/patient/month post-dialysis, P=0.000), without significant changes in hospitalization for all causes (1.8±1.6 versus 2.1±2.9 days/patient/month). New York Heart Association (NYHA) class (3.8±0.4 at start versus 2.4±0.7 after 4 months, P=0.000, versus 2.7±0.9 after 8 months, P=0.001) and quality of life tended to improve (63±21 at start, versus 41±20 after 4 months, versus 51±25 after 8 months; P=0.056). Left ventricular ejection fraction did not change. The number of technical complications associated with dialysis therapy was relatively high in this population.


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CONCLUSIONS: After starting dialysis for CRS, hospitalizations for cardiovascular causes were reduced, but not hospitalizations for all causes. Functional NYHA class improved and quality of life tended to improve, without evidence for a change in cardiac function. In this small study, no differences between IHD and PD were observed. PMID: 22492829

Cnossen TT. New developments in Peritoneal Dialysis. Maastricht : Universitaire Pers, 2012. ISBN: 9789461591272. De Jong EM, van Etten RW. Een vrouw met een pijnlijke heup. [A woman with a painful hip]. Ned Tijdschr Geneeskd. 2012;156(5):A2984. [156(12):530]. A 85-year-old woman suffered persisting pain in her left hip after a fall. On X-ray no fracture was seen. Her infection parameters were high and she developed a delirium and a painful swelling on her left hip. Examination with ultrasound showed free gas in the soft tissue of the left hip. A CT-scan of the abdomen and left upper leg showed a ruptured abscess in the left kidney with free gas, spreading through the M. iliopsoas into the upper left leg. On request of the patient and her family no treatment was given. PMID: 22296890

De Wee EM, Klaij K, Eikenboom HC, Van Der Bom JG, Fijnvandraat K, Laros-Van Gorkom BA, Mauser-Bunschoten EP, Meijer K, Goverde G, Van Der Linden PW, Rijken DC, Leebeek FW; WiN Study Group*. Effect of fibrinolysis on bleeding phenotype in mode rate and severe von Willebrand disease. Haemophilia. 2012 May;18(3):444-51. Epub 2011 Sep 12. Patients with von Willebrand disease (VWD), the most common inherited bleeding disorder, display large variation in bleeding tendency, which is not completely related to VWF levels. The cause of variability in clinical expression is largely unknown. The effect of plasma fibrinolytic capacity on bleeding tendency in VWD patients has not been investigated. We hypothesized that enhanced fibrinolysis may result in a more severe bleeding phenotype. Therefore, we measured the fibrinolytic potential in patients with moderate or severe VWD to investigate the contribution of fibrinolysis to the bleeding tendency. Fibrinolytic potential was measured as plasma clot lysis time (CLT) with and without addition of potato carboxypeptidase inhibitor (PCI) in 638 patients with moderate or severe VWD who participated in a nationwide multicentre cross-sectional study. Bleeding severity was measured using the Bleeding Score (BS).


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The CLTs were significantly longer, indicative of hypofibrinolysis, in men compared to women with VWD [106.2 (IQR 95.7-118.1) vs. 101.9 (IQR 92.8-114.0) min]. The CLTs prolonged with increasing age. No association was found between VWF or FVIII levels and CLT, or between VWF or FVIII levels and CLT(+PCI) . No association was observed for BS in a model with 10log-transformed CLT, adjusted for age, gender, VWF:Act and FVIII [b = 6.5 (95%CI -0.3 to 13.4)]. Our study showed that the plasma fibrinolytic poten tial does not influence bleeding tendency in VWD patients and therefore does not explain the variability in bleeding phenotype in VWD. *Collaborators (26): Fijnvandraat K, Kamphuisen PW, Kors A, Zweegman S, Degenaar-Dujardin ME, Goverde GJ, Jonkers MH, Dors N, Hofhuis WJ, Nijziel MR, Meijer K, Tamminga RY, van der Linden PW, Ypma PF, van der Bom JG, Eikenboom HC, Smiers FJ, Granzen B, Hamulyák K, Brons P, Laros-van Gorkom BA, Nováková I, de Goede-Bolder A, Leebeek FW, de Wee EM, Mauser-Bunschoten EP. © 2011 Blackwell Publishing Ltd. PMID: 21910790

Van den Berge K, Mamede S, van Gog T, Romijn JA, van Guldener C, van Saase JL, Rikers RM. Accepting diagnostic suggestions by residents: a potential cause of diagnostic error in medicine. Teach Learn Med. 2012;24(2):149-54. BACKGROUND: Psychological research has shown that people tend toward accepting rather than refuting hypotheses. Diagnostic suggestions may evoke such confirmatory tendencies in physicians, which may lead to diagnostic errors. PURPOSE: This study investigated the influence of a suggested diagnosis on physicians’ diagnostic decisions on written clinical cases. It was hypothesized that physicians would tend to go along with the suggestions and therefore would have more difficulty rejecting incorrect suggestions than accepting correct suggestions. METHODS: Residents (N = 24) had to accept or reject suggested diagnoses on 6 cases. Three of those suggested diagnoses were correct, and 3 were incorrect. RESULTS: Results showed the mean correct evaluation score on cases with a correct suggested diagnosis (M = 2.21, SD = 0.88) was significantly higher than the score on


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cases with an incorrect suggested diagnosis (M = 1.42, SD = 0.97), meaning physicians indeed found it easier to accept correct diagnoses than to reject incorrect diagnoses, t(23) = 2.74, p < .05, d = .85, despite equal experience with the diagnoses. CONCLUSION: These findings indicate that suggested diagnoses may evoke confirmatory tendencies and consequently may lead to diagnostic errors. PMID: 22490096

Veringa SJ, Nanayakkara PW, van Ittersum FJ, Vegting IL, van Guldener C, Smulders YM, ter Wee PM, Stehouwer CD. Effect of a treatment strategy consisting of pravastatin, vitamin E, and homocysteine lowering on arterial compliance and distensibility in patients with mild-to-moderate chronic kidney disease. Clin Nephrol. 2012 Oct;78(4):263-72. BACKGROUND: Arterial stiffness is increased in chronic kidney disease (CKD). Intervention studies aimed at reduction of arterial stiffness in dialysis patients have been disappointing. We therefore investigated the effect of pravastatin, vitamin E, and homocysteine lowering on arterial compliance and distensibility coefficients in mild-to-moderate CKD. METHODS: This is a sub-study of the ATIC study, a randomized, double-blind trial in 93 CKD patients. The treatment group received pravastatin to which vitamin E supplementation was added after 6 months and homocysteine lowering therapy after another 6 months. Measurement of the distensibility coefficient (DC) and the compliance coefficient (CC) of the common carotid (CCA), femoral (FA) and brachial artery (BA) was performed at 0, 6, 12, 18 months. Young’s elastic modulus (YEM) was measured in the common carotid artery. RESULTS: After 18 months, CCA-DC increased from mean (SD) 15.15 (6.67) to 16.52 (6.37) 10-3kPa-1 in the treatment and decreased from 18.44 (8.19) to 16.26 (7.35) in the placebo group (p = 0.057). CCA-CC increased from 0.64 (0.24) to 0.71 (0.26) mm2kPa-1 in the treatment and decreased from 0.77 (0.28) to 0.69 (0.25) in the placebo group (p < 0.0001). FA-DC had increased from 6.64 (3.45) to 11.46 (6.83) in the treatment group, and from 6.46 (2.85) to 7.08 (2.73) in the placebo group (p = 0.0001). FA-CC had increased from 0.46 (0.24) to 0.74 (0.44) in the treatment group, and from 0.48 (0.27) to 0.53 (0.21) in the placebo group (p = 0.008). BA-DC and CC, and CCA YEM were not significantly different between the groups.


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CONCLUSION: In patients with mild-to-moderate CKD, 18 months of treatment consisting of pravastatin, vitamin E and homocysteine lowering resulted in significant improvement of compliance and distensibility in CCA and FA. Since pravastatin was used throughout the observation period, it remains unclear whether the beneficial effects are attributable solely to the ongoing effect of pravastatin treatment, or if the additional interventions further slowed the progression of vascular stiffness. Therefore, larger studies with a longer period of follow-up observing the separate effects are needed. PMID: 22981031

Lankhorst S, Kappers MH, van Esch JH, Danser AH, van den Meiracker AH. Mechanism of hypertension and proteinuria during angiogenesis inhibition: evolving role of endo thelin-1. J Hypertens. 2013 Mar;31(3):444-54. Angiogenesis inhibition by blocking vascular endothelial growth factor (VEGF)-media ted signalling with monoclonal antibodies or tyrosine kinase inhibitors has become an established treatment of various forms of cancer. This treatment is frequently associated with the development of hypertension and proteinuria. As VEGF increases the expression and the activity of nitric oxide synthase in endothelial cells, a decrease in the bioavailability of nitric oxide has been proposed as a key mechanism leading to hypertension during angiogenesis inhibition. However, results of clinical and experimental studies exploring this possibility are conflicting. Rarefaction, that is a structural decrease of microcirculatory vessels, has been reported during antiangio genic treatment, but evidence that it plays a role in development of hypertension is lacking. Elevated circulating and urinary levels of endothelin-1 have been observed in clinical and experimental studies with angiogenesis inhibitors. Furthermore, the observation that endothelin receptor blockers can prevent or revert the rise in blood pressure during angiogenesis inhibition and attenuate proteinuria provides strong evidence that an activated endothelin-signalling pathway is a final common mediator of angiogenesis inhibition-induced rise in blood pressure and renal toxicity. PMID: 23221987

Van den Meiracker AH, Lankhorst S, van Esch JH, Danser AH, Kappers MH. Hyperten sion induced by antiangiogenic therapy: clinical and pathophysiological aspects. Eur J Hosp Pharm. 2012;19:3 327-329. Angiogenesis inhibition with humanised monoclonal antibodies to vascular endothelial growth factor (VEGF) or with VEGF receptor tyrosine kinase inhibitors targeting VEGF receptors has become an established treatment for various forms


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of cancer. Unfortunately, inhibition of the VEGF pathway is associated with serious side effects including hypertension. The development of this hypertension is likely to be multifactorial with a major role of the endothelin system. Although initially considered as a toxic effect, the development of hypertension may predict a favourable antitumour response. As a consequence, hypertension should not be a reason for dose reduction or discontinuation of antiangiogenic therapy but should be treated with antihypertensive therapy according to existing guidelines. Niemeijer ND, van Daele PL, Caliskan K, Oei FB, Loosveld OJ, van der Meer NJ. Loffler endocarditis: a rare cause of acute cardiac failure. J Cardiothorac Surg. 2012 Oct 10;7(1):109. [Epub ahead of print] ABSTRACT: We describe a patient with acute cardiogenic shock due to cardiac involve ment in idiopathic hypereosinophilic syndrome (Loffler endocarditis). At the echocar diography, there was a huge mass in the left ventricular cavity, resulting in inflow- and outflow tract obstruction. The posterior leaflet of the mitral valve apparatus was completely embedded in a big (organized) thrombus mass. The patient was treated with high dose corticosteroids, however without effect. Partial remission was achieved after treatment with hydroxycarbamide. He was also treated with anticoagulants and high dose beta-blockers. The patient’s condition improved remarkably after correction of the mitral valve insufficiency by a mitral valve bioprothesis. PMID: 23046536

Slort W, Vilrokx C, Belderbos H, Loosveld O,Thijssen F, Frankenhuis R, Bennink C. Specialisten en huisartsen spreken met ongeneeslijk zieke oncologische patiënten over de laatste levensfase. Een regionale pilot met ‘Advance Care Planning’. Ned-Vlaams Tijdschr voor Palliatieve Zorg. 2012;12(2):28-39. Background: Discussing various end-of-life issues with palliative care patients in time is considered to be an essential requirement for the delivery of high-quality pallia tive care. Besides, the several doctors treating a palliative care patient in hospital and at home frequently communicate insufficiently with each other about this proactive palliative care. Aim: Implementation of a newly developed method of ‘Advance Care Planning’ will en courage oncology specialists and general practitioners to discuss various end-of-life is sues with palliative care patients and with each other. Method: We registered the number of palliative care patients included by oncology specialists, how often these specialists communicated with general practitioners about a patient, and how often general practitioners informed specialists of patients’ ‘Advance Care Planning’ preferences. Besides, patients, surviving next-of-kin, specialists


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and general practitioners were interviewed about their experiences with the ‘Advance Care Planning’ method. Results: The specialists included 97 patients. Of the 84 times the specialist telep honed the general practitioner, this was 59 times successful. General practitioners in formed the specialist of preferences of 33 patients; with 32 of them the resuscitation status was discussed. The 17 patients and 10 surviving next-of-kin who were intervie wed felt that they were well-informed about their condition and consequently could ti mely arrange their affairs. The ‘Advance Care Planning’ method was appreciated as useful by the participating specialists and general practitioners. Conclusion: Our results suggest that the new ‘Advance Care Planning’ method was usable and encouraged oncology specialists and general practitioners to discuss endof-life issues with their palliative care patients.

Van Esch S, Van Milligen de Wit M, Van Laarhoven K, Rensma PL. Episodic electrolyte disorders and renal failure due to a rare disease: the McKittrick-Wheelock syndrome. Clin Kidney J. 2012;5(2):166-167. We describe a patient with intermittent bouts of malaise and muscle weakness due to profound electrolyte disturbances. Colonoscopy showed a giant villous adenoma of the sigmoid. The patient was diagnosed with a McKittrickWheelock syndrome with pre-renal disease and electrolyte disorders due to periodic rectal fluid loss. The diagnosis was delayed by the patient’s misinterpretation of the doctor’s questions. In cases where the patient’s history is contrary to what the data reveal, the expected culprit organ should be investigated early in the course of the disease. Extracting rele vant and guiding information out of the patient’s history remains an important skill.

Ahmed Ali U, Bruno MJ, Issa Y, Gooszen HG, Fockens P, Boermeester MA; Pancreatitis Werkgroep Nederland* [van Milligen de Wit AW et al...]. Betere pijncontrole bij chronische pancreatitis door vroege chirurgie? [Better pain management in chronic pancreatitis through early surgery?]. Ned Tijdschr Geneeskd. 2012;156(5):196. A4469. The most important symptom in patients with chronic pancreatitis is pain. This is often difficult to treat. The current treatment consists of, successively, optimal medical treatment, endoscopic intervention and finally surgical intervention. Previous research has indicated that early surgical intervention leads to better pain management and preservation of pancreatic function. Recently, the randomised multicentre ‘Early sur gery versus optimal current step up practice for chronic-pancreatitis’ (ESCAPE) trial was started in order to evaluate whether early surgery provides better reduction of pain in comparison with present treatment. In addition, serious complications, mortality, cost-effectiveness, quality of life, pancreas insufficiency, alternative pain scores, hospital admissions and the number of interventions will be assessed. Interne Geneeskunde en Maag-, Darm-, Levergeneeskunde

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*Collaborators (77): Boermeester MA, Gouma DJ, Busch OR, van Gulik TM, Issa Y, Ahmed Ali U, Roeterdink A, van Brunschot S, Fockens P, van Hooft JE, Laméris JS, Dijkgraaf MG, Dejong CH, van Dam R, Stassen LP, de Ridder RJ, Masclee A, Keulemans Y, Cappendijk V, Rosman C, Tan AC, van Eijck CH, Bruno MJ, Poley JW, Weigel J, van Duijvendijk P, Hesselink EJ, Erkelens W, Bosscha K, Lips DJ, Römkens T, van Munster I, Scheffer B, van der Harst E, Hadithi H, Kubben F, Consten EC, Brink MA, Schwartz MP, Karsten TM, Gerhards JM, Festen S, Jansen JM, Spillenaar-Bilgen EJ, Spanier BW, Wahab PJ, van Ramshorst B, Boerma D, Hazebroek E, Timmer R, Weusten BL, Bollen TL, Bie mond H, Heisterkamp J, Grubben MJ, van Milligen de Wit AW, Hofker HS, van Dulle men HM, Buskens E, van Goor H, Drenth J, Gooszen HG, Zeguers V, van Wezel H, van der Eng H, Hermans JJ, Molenaar IQ, van Grevenstein WM, Besselink MG, van Santvoort HC, Bakker OJ, Vleggaar FP, Siersema PD, van Erpecum KJ, van Leeuwen MS, Kruyt PM, Witteman BJ. PMID: 22296905

Verheijden NA, ten Tije AJ, Haanen JB. Gemetastaseerd melanoom. Gloort er licht aan de horizon? [Metastatic melanoma: is there glimmer at the horizon?]. Ned Tijdschrift Oncol. 2012;9(4):171-175. Prognosis of metastatic melanoma is poor. However, there are some promising developments, such as vemurafenib; an inhibitor of mutated BRAF. BRAF is a seronin threonin kinase enzyme. In the BRIM-3 trial, patients with stage IIIc and IV metastatic melanoma were treated with vemurafenib. Vemurafenib showed positive effects on survival and progression free survival in comparison with dacarbazine, the standard therapy. We illustrate a 45-year old man with metastatic melanoma, who was treated with vemurafenib. There was an obvious response on this treatment with little side effects. Besides, we illustrate another 55-year old patient with metastatic melanoma with evident regression of disease. This patient suffered from extreme photosensitivity, an important side effect of vemurafenib. Vemurafenib seems to be a promising addition to the therapeutic regime of metastatic melanoma with V600E BRAF mutation. Coming trials need to investigate whether the duration of this response can be prolonged, for example by combination of therapies. Ten Tije AJ, Cnossen N. Nierfunctie en oncologische middelen op oudere leeftijd. In: Compendium behandeling van kanker bij ouderen / Nortier JW, Schouten HC [et al...]. Den Haag: Academic Pharmaceutical Productions, 2012. ISBN 9789057611179. Gobardhan PD, de Wall LL, van der Laan L, Ten Tije AJ, van der Meer DC, Tetteroo E, Poortmans PM, Luiten EJ. The role of radioactive iodine-125 seed localization in breastconserving therapy following neoadjuvant chemotherapy. Ann Oncol. 2013 Mar;24(3):668-73. Epub 2012 Nov 8. Interne Geneeskunde en Maag-, Darm-, Levergeneeskunde

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BACKGROUND: Neoadjuvant chemotherapy (NAC) is increasingly used in the frame work of breast-conserving therapy (BCT). Localization of the initial tumor is essential to guide surgical resection after NAC. This study describes the results obtained with I-125 seed localization in BCT including NAC. PATIENTS AND METHODS: Between January 2009 and December 2010, 85 patients treated with NAC and BCT after I-125 seed localization were included. Radiological and pathological response and resection margins were retrospectively evaluated. RESULTS: BCT was carried out in 85 patients without secondary local excisions. Nineteen patients with unifocal tumors and seven patients with multifocal tumors showed a complete pathological response (P = 0.18). Tumor-free resection margins were obtained in 78 patients (50 patients with unifocal and 28 patients with multifocal tumors, P = 0.27). Focally involved margins were found in four patients (two patients with a unifocal and two patients with a multifocal tumor, P = 0.27). A subsequent mastectomy was carried out in three patients (two patients with multifocal tumors, P = 0.29). CONCLUSIONS: BCT after NAC can be carried out successfully after initial localization with I-125 seeds in both unifocal and multifocal breast tumors with complete resection rates of >90%. PMID: 23139261

Van Der Sande FM, Cnossen TT, Cornelis T, Konings CJ, Kooman JP, Leunissen KM. Peri toneal dialysis in patients with heart failure. Minerva Urol Nefrol. 2012 Sep;64(3):163-72. Both in dialysis patients and non-uremic patients heart failure is associated with an adverse prognosis. In a state of abrupt worsening of cardiac function, acute cardioge nic shock or decompensated congestive heart failure, acute kidney injury may occur, whereas in a more chronic worsening of cardiac function chronic kidney injury may oc cur. Recently, the term cardiorenal syndrome was adopted and defined as “a pathophy siological disorder of the heart and kidneys whereby acute or chronic dysfunction in one organ may induce acute or chronic dysfunction in the other organ”. Despite better treatment techniques and the continuous development of new medications volume overload in patients with cardiorenal syndrome is difficult to treat. Especially treat ment of cardiorenal syndrome type I and II is notoriously difficult. Peritoneal dialysis might be, because of the gradual fluid removal, a therapeutic option in these patients. However, data on the effect of peritoneal dialysis in patients with heart failure with fluid overload and/or renal impairment are scarce. In this review, the role of peritoneal dialysis in the treatment cardiorenal syndrome type I, II and IV will be discussed. PMID: 22971681 Xxx

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Keel-, Neus- en Oorheelkunde Kerngegevens Zorgkern Keel-, Neus- en Oorheelkunde • 7 KNO-artsen: P.E. (Paul) Briët, J. (Jasper) Companjen, M.L.C.H. (Milou) Heiligers, E.A. (Eric) Janssen, G.L.E. (Geert) Küppers, A.J.M (Antoon) van der Rijt, dr. G.K.A. (Gijs) van Wermeskerken • 1 chef de clinique: dr. F.C.A. (Ferdinand) Timmer • 1 co-assistent (per 3 weken, het gehele jaar door)

Samenvattingen gepubliceerde artikelen De Ru JA, Martens EP, Tabor MP, van Wermeskerken GKA. Adenotonsillectomie bij kinderen: een kritische kanttekening bij de ZATT-richtlijn. Ned Tijdschr KNO Heelkd. 2012;18:27-29.

Schutte HW, Timmer FC, van den Hoogen FJ. Een meisje met chronische unilaterale ri norroe. [Chronic unilateral rhinorrhea in Childhood]. Ned Tijdschr Geneeskd. 2012;156(18):A3220. A 13-year-old patient was referred to the ENT department because of a ring-shaped radiopaque foreign body in her right nasal cavity demonstrated on an orthopantomo gram. Her medical history revealed long-standing right-sided rhinorrhea thought to be caused by an inhalation allergy. In case of unilateral rhinorrhea in a child a nasal foreign body has to be excluded. PMID: 22551747

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Kindergeneeskunde Kerngegevens Zorgkern Kindergeneeskunde • 13 kinderartsen: mw. C.D. (Coranne) Aarts-Tesselaar, dr. R.H.T. (Ron) van Beek, dr. A.R. (Anthon) Hulsmann, M.H. (Marc) Jonkers, J. (Jaap) Kooijman, M.C. (Maarten) Küthe, mw. dr. S.A. (Stella) de Man, P.W.J. (Paul) van Mossevelde, mw. S.M.H.B. (Saskia) de Pont, L. (Leo) Torn, Mw. dr. A.A.P.H. (Anja) Vaessen-Verberne, mw. E.J.M. (Esther) Veldkamp, dr. H.M. (Herbert) Wering • 3 assistenten in opleiding • 6 ssistenten niet in opleiding • 2 baios • 1 bagio • 1 tagio

Samenvattingen gepubliceerde artikelen Kuethe MC, Sixma HJ, Vaessen-Verberne AA, Booij JC, van Aalderen WM. Assessing quality of care in pediatric asthma: applicability of a revised version of the QUOTECNSLD questionnaire. J Asthma. 2012 Nov;49(9):966-76. Epub 2012 Oct 1. AIM: To establish the validity and applicability of a revised version of the QUality Of care Through the patient’s Eyes-Chronic Non Specific Lung Disease (QUOTE-CNSLD) instrument in a population of children with controlled and partly controlled asthma. METHODS: Randomized controlled trial evaluating quality of care in three follow-up settings: follow-up by the general practitioner, the pediatrician, and the specialized asthma nurse, for a period of 2 years. RESULTS: One hundred and seven children were recruited, 45 from general practice and 62 from hospital practice. The revised QUOTE-CNSLD instrument completed by parents at baseline (T0), after 1 year (T1) and after 2 years (T2) showed that a process-, a structure-, and an asthma-specific domain could be deduced (Cronbach’s a of 0.81, 0.82, and 0.62). A separate five-item “”child-specific”” questionnaire about their caregiver, completed by children, has a Cronbach’s a of 0.88. The revised instrument could discriminate between quality of care in different follow-up settings for children with stable asthma, and the asthma-specific domain showed particularly discrimina tive properties. Quality aspects with potential for improvement could be derived from the scores in all three study groups. CONCLUSION: The revised QUOTE-CNSLD instrument is applicable in a pediatric population with stable asthma and it has discriminative value between different follow-up settings. PMID: 23025477

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Simonse E, de Kort SW, Valk-Swinkels CG, van ‘t Veer NE, Veldkamp EJ, van Beek RH. Puzzelen met Pubers. Tijdschrift Kindergeneeskunde 2012; 80(4):99-101. Auto-intoxications in adolescents are common, but the type of intoxication is not always obvious at presentation. Patient 1 was admitted with a coma and other signs of neurological dysfunction. This presentation was due to an auto-intoxication with Fero-Gradumet‡ . Iron has a toxic effect on the gastrointestinal mucosa, causes capillary leak by damage of the endothelial layer and leads to systemic toxicity when iron is distributed into the organs. Patient 2 was admitted with a coma, bradycardia, low oxygen saturation and seizures. These symptoms were caused by an auto-intoxication with nail polish remover pads. These pads contain gammabutyrolactone, a precursor of gammahydroxybutyrate (GHB). Ingestion of these pads can cause the same symptoms as a GHB intoxication. In every critically ill patient, stabilisation of airway, breathing and circulation (A, B and C) is the most important. These two cases show that the cause of the symptoms can be due to unusual auto-intoxications. Meijler DP, van Mossevelde PW, van Beek RH. Dehydratie door -mond kapot[Dehydration due to “mouth broken”]. Ned Tijdschr Tandheelkd. 2012 Sep;119(9):417-8. Two children were admitted to a medical centre due to dehydration after an oral injury and the extraction of a tooth. One child complained of “”mouth broken””. Dehydration is the most common water-electrolyte imbalance in children. Babies and young child ren are prone to dehydration due to their relatively large body surface area, the high percentage extracellular fluid, and the limited ability of the kidneys to conserve water. After the removal ofa tooth, after an oral trauma or in case of oral discomfort, a child is at greater risk of dehydration by reduced fluid and food intake due to oral pain and/ or discomfort and anxiety to drink. In those cases, extra attention needs to be devoted to the intake of fluids. PMID: 23050378

Simonse E, Mulder PG, van Beek RH. Analgesic effect of breast milk versus sucrose for analgesia during heel lance in late preterm infants. Pediatrics. 2012 Apr;129(4):657-63. Epub 2012 Mar 5. OBJECTIVE: The purpose of this trial was to investigate whether breast milk (either breastfed or bottle-fed) has a better analgesic effect than sucrose in newborns born at a postmenstrual age between 32 and 37 weeks. METHODS: We conducted a randomized controlled trial at a secondary care neonatal unit in the Netherlands on 71 preterm neonates (postmenstrual age at birth 32-37

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weeks), undergoing heel lance with an automated piercing device. Newborns were randomly assigned to breast milk (either breastfed or bottle-fed) administered during heel lance or oral sucrose administered before heel lance. We assessed the Premature Infant Pain Profile (PIPP) score (range, 0-21) to investigate whether there was a diffe rence in pain score between neonates receiving breast milk and those receiving sucro se solution. RESULTS: There was no significant difference in mean PIPP score between neonates receiving breast milk (6.1) and those receiving sucrose (5.5), with a mean difference of 0.6 (95% confidence interval -1.6 to 2.8; P = .58). CONCLUSIONS: From this study, it cannot be concluded that breast milk has a better analgesic effect than sucrose in late preterm infants. From the results, it follows with 95% confidence that the analgesic effect of breast milk is not >1.6 points better and not > 2.8 points worse on the PIPP scale (SD 3.7) than the analgesic effect of sucrose in late preterm infants. PMID: 22392168

Van Beek RH, van Elburg RM, Moonen RJ, van Goudoever JB. Aminozuren. In: Werkboek enterale en parenterale voeding bij pasgeborenen / red. H.N. Lafeber ... [et al.]. Amster dam : VU University Press, 2012. ; p. 39-42. ISBN 978-908-659-619-5. Van Elburg RM, van Beek RH, van Goudoever JB. Prebiotica en Probiotica. In: Werkboek enterale en parenterale voeding bij pasgeborenen / red. H.N. Lafeber ... [et al.]. ; p. 108-111. Amsterdam : VU University Press, 2012. ISBN 978-908-659-619-5 Van Goudoever JB, Rövekamp-Abels WW, Glas BS, van Beek RH. Bijvoeding. In: Werkboek enterale en parenterale voeding bij pasgeborenen / red. H.N. Lafeber ... [et al.]. Amsterdam : VU University Press, 2012. ; p. 141-144. ISBN 978-908-659-619-5 Hulsmann AR, Joosten KF. Apneu. In: Werkboek kinderlongziekten / red. Rene van Gent ... [et al.]. - 2e dr. ; p. 37-46. Amsterdam : VU University Press, 2012. ISBN 978-908-659628-7. Vrijlandt EJ, Hulsmann AR. Bronchopulmonale dysplasie. In: Werkboek kinderlongziekten / red. Rene van Gent ... [et al.]. - 2e dr. ; p. 242-250. Amsterdam : VU University Press, 2012. ISBN 978-908-659-628-7. Van Houdt JK, Nowakowska BA, Sousa SB, van Schaik BD, Seuntjens E, Avonce N, Sifrim A, Abdul-Rahman OA, van den Boogaard MJ, Bottani A, Castori M, Cormier-Daire V, Deardorff MA, Filges I, Fryer A, Fryns JP, Gana S, Garavelli L, Gillessen-Kaesbach G, Hall BD, Horn D, Huylebroeck D, Klapecki J, Krajewska-Walasek M, Kuechler A, Lines MA,

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Maas S, Macdermot KD, McKee S, Magee A, de Man SA, Moreau Y, Morice-Picard F, Obersztyn E, Pilch J, Rosser E, Shannon N, Stolte-Dijkstra I, Van Dijck P, Vilain C, Vogels A, Wakeling E, Wieczorek D, Wilson L, Zuffardi O, van Kampen AH, Devriendt K, Hennekam R, Vermeesch JR. Heterozygous missense mutations in SMARCA2 cause. Nicolaides-Baraitser syndrome. Nat Genet. 2012 Feb 26;44(4):445-9. S1. Nicolaides-Baraitser syndrome (NBS) is characterized by sparse hair, distinctive facial morphology, distal-limb anomalies and intellectual disability. We sequenced the exo mes of ten individuals with NBS and identified heterozygous variants in SMARCA2 in eight of them. Extended molecular screening identified nonsynonymous SMARCA2 mutations in 36 of 44 individuals with NBS; these mutations were confirmed to be de novo when parental samples were available. SMARCA2 encodes the core catalytic unit of the SWI/SNF ATP-dependent chromatin remodeling complex that is involved in the regulation of gene transcription. The mutations cluster within sequences that encode ultra-conserved motifs in the catalytic ATPase region of the protein. These alterations likely do not impair SWI/SNF complex assembly but may be associated with disrupted ATPase activity. The identification of SMARCA2 mutations in humans provides insight into the function of the Snf2 helicase family. PMID: 22366787

Verhagen JM, Diderich KE, Oudesluijs G, Mancini GM, Eggink AJ, Verkleij-Hagoort AC, Groenenberg IA, Willems PJ, du Plessis FA, de Man SA, Srebniak MI, van Opstal D, Huls man LO, van Zutven LJ, Wessels MW. Phenotypic variability of atypical 22q11.2 deletions not including TBX1. Am J Med Genet A. 2012 Aug 14. [Epub ahead of print] Interstitial deletions of the chromosome 22q11.2 region are the most common micro deletions in humans. The TBX1 gene is considered to be the major candidate gene for the main features in 22q11.2 deletion syndrome, including congenital heart malforma tions, (para)thyroid hypoplasia, and craniofacial abnormalities. We report on eight patients with atypical deletions of chromosome 22q11.2. These deletions comprise the distal part of the common 22q11.2 deleted region but do not encompass the TBX1 gene. Ten similar patients with overlapping distal 22q11.2 deletions have been reported pre viously. The clinical features of these patients are described and compared to those found in the classic 22q11.2 deletion syndrome. We discuss the possible roles of a positi on effect or haploinsufficiency of distally located genes (e.g., CRKL) in the molecular pathogenesis of the 22q11.2 deletion syndrome. © 2012 Wiley Periodicals, Inc. PMID: 22893440

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Van den Bosch GE, Merkus PJ, Buysse CM, Boehmer AL, Vaessen-Verberne AA, van Veen LN, Hop WC, de Hoog M. Risk factors for pediatric intensive care admission in children with acute asthma. Respir Care. 2012 Sep;57(9):1391-7. Epub 2012 Feb 17. INTRODUCTION: Severe acute asthma in children is associated with substantial morbidity and may require pediatric ICU (PICU) admission. The aim of the study was to determine risk factors for PICU admission. METHODS: The study used a retrospective multicenter case-control design. The cases included children admitted to the PICU because of severe acute asthma and a history of out-patient treatment by pediatricians or pediatric pulmonologists. Controls were children with asthma without a PICU admission for severe acute asthma. The children were matched for sex, age, hospital, and time elapsed since the diagnosis of asthma. Fourteen possible risk factors were analyzed. RESULTS: Sixty-six cases were matched to 164 controls. In univariate analysis, all but one of the analyzed variables were significantly associated with PICU-hospitalization. After multivariate conditional logistic regression analysis, 4 risk factors remained significant. These included active or passive smoking, allergies, earlier hospitalization for asthma, and non-sanitized home. CONCLUSIONS: Physicians and parents should be aware of these risk factors, and efforts should be made to counteract them. Copyright 2012 Daedalus Enterprises Comment: Severe acute asthma: an attempt to identify the quiet before the storm. Myers TR. Respir Care. 2012 Sep; 57(9):1526-7. PMID: 22348677

Brand PLP, Boehmer ALM, Vaessen-Verberne AAPH. Recidiverend piepen en benauwd heid bij kinderen jonger dan 4 jaar. Praktische Pediatrie 2012;6(2):75-80. De Vries E, Vaessen-Verberne AAPH. Recidiverende luchtweginfecties bij peuters en kleuters. Wanneer is verder onderzoek nodig? Praktische Pediatrie. 2012;6(2):94-97. Vaessen A. Een kind met chronisch hoesten. in: Probleemgeoriënteerd denken in de kindergeneeskunde / Bot PN, Draaisma JM, Swart JF [red.]. Utrecht : De Tijdstroom, 2012. ISBN 978-905-898-202-5. Duiverman EJ, Vaessen-Verberne A, van Ewijk E. Diagnostiek: anamnese. In: Werkboek kinderlongziekten / red. Rene van Gent ... [et al.]. - 2e dr. Amsterdam : VU University Press, 2012. ISBN 978-908-659-628-7. Kindergeneeskunde

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Van de Griend EJ, Vaessen-Verberne A, de Jongste J. Astma. In: Werkboek kinderlongziekten / red. Rene van Gent ... [et al.]. Amsterdam : VU University Press, 2012. ISBN: 978-908-659-628-7. Simonse E, Valk-Swinkels CG, van ‘t Veer NE, Ermens AA, Veldkamp EJ. Iron autointoxi cation in a 16-year-old girl: a protective role for hepcidin? Ann Clin Biochem. 2013 Jan;50(Pt 1):76-9. Epub 2012 Oct 29. Intentional iron overdose appears to be an increasingly common form of attempted suicide. We present a case of iron overdose in a 16-year-old girl who was found uncon scious in her bed and brought to our emergency department. The most remarkable diagnostic findings were the patient’s comatose condition, divergent eye position and positive Babinski foot pad reflexes. Laboratory tests showed hyperglycaemia and mild metabolic acidosis. A computed tomography scan of the cerebrum showed no signs of intracerebral haemorrhage or elevated intracerebral pressure. Toxicology screening showed no use of acetaminophen, ethanol or drugs of abuse. The patient was stabili zed and monitored on the intensive care ward. When she woke up, she confessed to having taken Fero-Gradumet(‡). Retrospectively analysed, the serum iron concentra tion in the first blood sample (seven hours after ingestion) was 62 µmol/L which cor responds with moderate iron intoxication. The patient received whole bowel irrigation with 2 L polyethyleneglycol solution and de-ironing treatment with intravenous defe roxamine 20 mg/kg in eight hours. She was discharged from the hospital after three days in a good clinical condition. Retrospectively, serum hepcidin concentrations were determined and evaluated in conjunction with serum iron concentrations and the installed treatment. Before medical de-ironing interventions were started, we saw that the serum iron concentration in our patient was already declining. At the same time, we observed a sharp increase in the serum hepcidin concentration. After normalization of serum iron concentrations, hepcidin normalized as well. PMID: 23108765

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Klinisch Chemisch Hematologisch Laboratorium Kerngegevens Zorgkern Klinisch Chemisch Hematologisch Laboratorium • 5 Laboratoriumspecialisten Klinisch Chemie: dr. Ir. A.A.M. (Ton) Ermens, dr. A.J. (Adriaan) van Gammeren, mw. dr. Ir. M.J.M. (Monique) de Groot, dr. M.H.M. (Marc) Thelen, dr. R.N. (René) Idema • 2 assistenten in opleiding

Samenvattingen gepubliceerde artikelen Uzun S, Djamin RS, Kluytmans J, Van’t Veer NE, Ermens AA, Pelle AJ, Mulder P, van der Eerden MM, Aerts J. Influence of macrolide maintenance therapy and bacterial colo nisation on exacerbation frequency and progression of COPD (COLUMBUS): study protocol for a randomised controlled trial. Trials. 2012 Jun 9;13:82. BACKGROUND: Chronic obstructive pulmonary disease (COPD) is characterised by progressive development of airflow limitation that is poorly reversible. Because of a poor understanding of COPD pathogenesis, treatment is mostly symptomatic and new therapeutic strategies are limited. There is a direct relationship between the severity of the disease and the intensity of the inflammatory response. Besides smoking, one of the hypotheses for the persistent airway inflammation is the presence of recurrent infections. Macrolide antibiotics have bacteriostatic as well as anti-inflammatory properties in patients with cystic fibrosis and other inflammatory pulmonary diseases. There is consistent evidence that macrolide therapy reduces infectious exacerbations, decreases the requirement for additional antibiotics and improves nutritional measu res. Because of these positive effects we hypothesised that maintenance macrolide therapy may also have beneficial effects in patients with COPD who have recurrent exacerbations. The effects on development of bacterial resistance to macrolides due to this long-term treatment are unknown. Until now, studies investigating macrolide therapy in COPD are limited. The objective of this study is to assess whether main tenance treatment with macrolide antibiotics in COPD patients with three or more exacerbations in the previous year decreases the exacerbation rate in the year of treatment and to establish microbial resistance due to the long-term treatment. METHODS/DESIGN: The study is set up as a prospective randomised double-blind placebo-controlled single-centre trial. A total of 92 patients with COPD who have had at least three exacerbations of COPD in the previous year will be included. Subjects will be randomised to receive either azithromycin 500 mg three times a week or placebo. Our primary endpoint is the reduction in the number of exacerbations of COPD in the year of treatment.


95


DISCUSSION: We investigate whether long-term therapy with macrolide antibiotics can prevent exacerbations in patients with COPD. Additionally, our study aims to assess the effect of long-term use of macrolide on the development of antimicrobial resistance and on inflammatory parameters related to COPD. We believe this study will provide more data on the effects of macrolide treatment in patients in COPD and will add more knowledge on its working mechanisms. TRIAL REGISTRATION: http://www.clinicaltrials.gov NCT00985244. PMID: 22682323 - PMCID: PMC3478173

Joosen AM, Boersma RS, Ermens AA. De kunst van het kijken : Uw diagnose? Ned Tijdschr Hematologie. 2012; 9: 130-131. Ermens AA, Otten R. Pappenheimer bodies in a splenectomized patient with alcohol abuse. Blood. 2012 Apr 26;119(17):3878. [No abstract available]. PMID: 22675729

Simonse E, Valk-Swinkels CG, van ‘t Veer NE, Ermens AA, Veldkamp EJ. Iron autointoxi cation in a 16-year-old girl: a protective role for hepcidin? Ann Clin Biochem. 2013 Jan;50(Pt 1):76-9. Epub 2012 Oct 29. Intentional iron overdose appears to be an increasingly common form of attempted suicide. We present a case of iron overdose in a 16-year-old girl who was found un conscious in her bed and brought to our emergency department. The most remarkable diagnostic findings were the patient’s comatose condition, divergent eye position and positive Babinski foot pad reflexes. Laboratory tests showed hyperglycaemia and mild metabolic acidosis. A computed tomography scan of the cerebrum showed no signs of intracerebral haemorrhage or elevated intracerebral pressure. Toxicology screening showed no use of acetaminophen, ethanol or drugs of abuse. The patient was stabili zed and monitored on the intensive care ward. When she woke up, she confessed to having taken Fero-Gradumet(‡). Retrospectively analysed, the serum iron concentra tion in the first blood sample (seven hours after ingestion) was 62 µmol/L which corresponds with moderate iron intoxication. The patient received whole bowel irriga tion with 2 L polyethyleneglycol solution and de-ironing treatment with intravenous


96


deferoxamine 20 mg/kg in eight hours. She was discharged from the hospital after three days in a good clinical condition. Retrospectively, serum hepcidin concentrations were determined and evaluated in conjunction with serum iron concentrations and the installed treatment. Before medical de-ironing interventions were started, we saw that the serum iron concentration in our patient was already declining. At the same time, we observed a sharp increase in the serum hepcidin concentration. After normalization of serum iron concentrations, hepcidin normalized as well. PMID: 23108765

Kaufmann JO, Smit JW, Huisman W, Idema RN, Bakker E, Giordano PC. Basic haemoglo binopathy diagnostics in Dutch laboratories; providing an informative test result. Int J Lab Hematol. 2012 Dec 14. [Epub ahead of print]. INTRODUCTION: After a first survey in 2001, the Dutch Association of Hematological Laboratory Research (VHL) advised its members to adopt a basic protocol for haemo globinopathy carrier detection and to provide genetic information with all positive results to allow health-care professionals to inform carriers about potential genetic risks. This article reports on the compliance with these recommendations and their consequences. METHODS: Clinical chemists of all 106 Dutch laboratories were invited to answer a survey on patient population, diagnostic techniques used, (self-reported) knowledge, use and effect of the additional information. RESULTS: The average increase in diagnostic output was over 60% and the recommen ded basic protocol was applied by 65% of the laboratories. Over 84% of the laborato ries reported to be aware of the additional recommendations and 77% to be using them. Most laboratories with limited diagnostic requests were still sending their cases to other laboratories and included the genetic information received from these laboratories in their diagnostic reports. The effect of information on subsequent ‘family analysis’ was estimated to be between 26 and 50%. CONCLUSIONS: The present study shows an increase in diagnostic potential for haemoglobinopathy over the last decade, especially in the larger cities. Low ‘family testing’ rates were mostly found in areas with lower carrier prevalence or associated with local reluctance to pass the information to carriers. In spite of a dramatic im provement, too many carriers are still not informed because of lack of awareness among health-care providers and more education is needed. © 2012 Blackwell Publishing Ltd. PMID: 23241064


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Visser WA, Ermens AA, De Boer HD, Van Os E. Rocuronium reversed by sugammadex for electroconvulsive therapy in a patient with prolonged duration of action of succi nylcholine. Anaesth Intensive Care. 2011 Nov;39(6):1153-4. No abstract available. Comment on: Anaesth Intensive Care. 2011 Jul;39(4):764-5. PMID: 22165379

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Klinische Farmacie Kerngegevens Zorgkern Klinische Farmacie • 7 ziekenhuisapothekers: P.R.M. (Paul) van Hattum, mw. V.S (Victorine) Koster, C.H.P. (Chris) Pellicaan, P.A.O. (Peter) Smithuis, N.E. (Nils) van ’t Veer, mw. R.R.E.C.M. (Relin) Verzijl-Zeegers, mw. M.F.G. (Marjolein)Winters • 2 assistenten in opleiding • 1 apotheker EMD • 1 project apotheker

Samenvattingen gepubliceerde artikelen Simonse E, de Kort SW, Valk-Swinkels CG, van ‘t Veer NE, Veldkamp EJ, van Beek RH. Puzzelen met Pubers. Tijdschrift Kindergeneeskunde 2012; 80(4):99-101. Auto-intoxications in adolescents are common, but the type of intoxication is not always obvious at presentation. Patient 1 was admitted with a coma and other signs of neurological dysfunction. This presentation was due to an auto-intoxication with Fero-Gradumet‡ . Iron has a toxic effect on the gastrointestinal mucosa, causes capillary leak by damage of the endothelial layer and leads to systemic toxicity when iron is distributed into the organs. Patient 2 was admitted with a coma, bradycardia, low oxygen saturation and seizures. These symptoms were caused by an auto-intoxication with nail polish remover pads. These pads contain gammabutyrolactone, a precursor of gamma hydroxybutyrate (GHB). Ingestion of these pads can cause the same symptoms as a GHB intoxication. In every critically ill patient, stabilisation of airway, breathing and circulation (A, B and C) is the most important. These two cases show that the cause of the symptoms can be due to unusual auto-intoxications. Uzun S, Djamin RS, Kluytmans J, Van’t Veer NE, Ermens AA, Pelle AJ, Mulder P, van der Eerden MM, Aerts J. Influence of macrolide maintenance therapy and bacterial coloni sation on exacerbation frequency and progression of COPD (COLUMBUS): study proto col for a randomised controlled trial. Trials. 2012 Jun 9;13:82. BACKGROUND: Chronic obstructive pulmonary disease (COPD) is characterised by progressive development of airflow limitation that is poorly reversible. Because of a poor understanding of COPD pathogenesis, treatment is mostly symptomatic and new therapeutic strategies are limited. There is a direct relationship between the severity of the disease and the intensity of the inflammatory response. Besides smoking, one of the hypotheses for the persistent airway inflammation is the presence of recurrent infections. Macrolide antibiotics have bacteriostatic as well as anti-inflammatory properties in patients with cystic fibrosis and other inflammatory pulmonary diseases. There is consistent evidence that macrolide therapy reduces infectious exacerbations, decreases the requirement for additional antibiotics and improves nutritional measu res. Because of these positive effects we hypothesised that maintenance macrolide therapy may also have beneficial effects in patients with COPD who have recurrent

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exacerbations. The effects on development of bacterial resistance to macrolides due to this long-term treatment are unknown. Until now, studies investigating macrolide therapy in COPD are limited. The objective of this study is to assess whether mainte nance treatment with macrolide antibiotics in COPD patients with three or more exacerbations in the previous year decreases the exacerbation rate in the year of treatment and to establish microbial resistance due to the long-term treatment. METHODS/DESIGN: The study is set up as a prospective randomised double-blind placebo-controlled single-centre trial. A total of 92 patients with COPD who have had at least three exacerbations of COPD in the previous year will be included. Subjects will be randomised to receive either azithromycin 500 mg three times a week or placebo. Our primary endpoint is the reduction in the number of exacerbations of COPD in the year of treatment. DISCUSSION: We investigate whether long-term therapy with macrolide antibiotics can prevent exacerbations in patients with COPD. Additionally, our study aims to assess the effect of long-term use of macrolide on the development of antimicrobial resistance and on inflammatory parameters related to COPD. We believe this study will provide more data on the effects of macrolide treatment in patients in COPD and will add more knowledge on its working mechanisms. TRIAL REGISTRATION: http://www.clinicaltrials.gov NCT00985244. PMID: 22682323 - PMCID: PMC3478173

Simonse E, Valk-Swinkels CG, van ‘t Veer NE, Ermens AA, Veldkamp EJ. Iron autointoxi cation in a 16-year-old girl: a protective role for hepcidin? Ann Clin Biochem. 2013 Jan;50(Pt 1):76-9. Epub 2012 Oct 29. Intentional iron overdose appears to be an increasingly common form of attempted suicide. We present a case of iron overdose in a 16-year-old girl who was found un conscious in her bed and brought to our emergency department. The most remarkable diagnostic findings were the patient’s comatose condition, divergent eye position and positive Babinski foot pad reflexes. Laboratory tests showed hyperglycaemia and mild metabolic acidosis. A computed tomography scan of the cerebrum showed no signs of intracerebral haemorrhage or elevated intracerebral pressure. Toxicology screening showed no use of acetaminophen, ethanol or drugs of abuse. The patient was stabili zed and monitored on the intensive care ward. When she woke up, she confessed to having taken Fero-Gradumet(‡). Retrospectively analysed, the serum iron concentra tion in the first blood sample (seven hours after ingestion) was 62 µmol/L which cor responds with moderate iron intoxication. The patient received whole bowel irrigation with 2 L polyethyleneglycol solution and de-ironing treatment with intravenous defe roxamine 20 mg/kg in eight hours. She was discharged from the hospital after three

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days in a good clinical condition. Retrospectively, serum hepcidin concentrations were determined and evaluated in conjunction with serum iron concentrations and the installed treatment. Before medical de-ironing interventions were started, we saw that the serum iron concentration in our patient was already declining. At the same time, we observed a sharp increase in the serum hepcidin concentration. After normalization of serum iron concentrations, hepcidin normalized as well. PMID: 23108765

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Klinische Geriatrie Kerngegevens Zorgkern Klinische Geriatrie • 5 geriaters: H.M. ( Hanneke) Beerens, J.I. (Jonneke) Eikelboom, M.Th. (Theo)Feitsma, R.A.M. (Richard) de Jonckheere, D.C. (Dominique) de Lange • 2 assistenten in opleiding • 2 assistenten niet in opleiding (waaronder vaak 1 verpleeghuisarts in opleiding) • 2 verpleegkundig specialisten • Subspecialismen: algemene geriatrie, valpoli, geheugenpoli, polyfarmacie, medisch ethische kwesties en einde leven beslissingen.

Samenvatting gepubliceerde artikelen Eikelboom JI, ten Cate OT, Jaarsma D, Raat JA, Schuwirth L, van Delden JJ. A framework for the ethics review of education research. Med Educ. 2012 Aug;46(8):731-3. [No abstract available]

PMID: 22803748

Van Thiel GJ, Dankerlui-Eikelboom JL. Technologie in de fysiotherapie: instrumenten van zorg. Ned Tijdschr voor Fysiother. 2012;122(2):42-5.

Technology in physiotherapy: instruments of care Healthcare technology is of enor mous value in the diagnosis and treatment of disorders. Its use has grown exponential ly, also among physiotherapists. Physiotherapy practices have been transformed from offices with a few small treatment rooms to entire floors filled with equipment. How and why did this happen? And – more importantly – how should we value this deve lopment? These questions are related to the use of technology, but are not technical questions. In order to answer these questions, we need to think about ethical issues. Here, we aim to shed some light on the ethics of healthcare technology. Reiser’s historical analysis enables us to understand how the introduction of technology has proven so success ful. This article provides insight into the mechanisms involved in the introduction of new technologies, without paying much attention to the changes their introduction bring to healthcare practice. The introduction of technologies raises two types of question: questions about ‘due care’ regarding a new technology and questions about the desi rability of the new technology. Both are relevant to the optimization of technological aspects of care, but each requires a different approach. In everyday practice, questions of due care are easier to tackle. In the last part of the article we discuss different ethical aspects of healthcare techno logy, to highlight their importance. Physiotherapists should be encouraged to reflect on these issues. Hopefully, this will contribute to the considered introduction of medi cal technology into professional practice and to the preservation of valued compo nents of care that can be influenced by the use of technology. Xxx

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Laboratorium voor Microbiologie en Infectiepreventie Kerngegevens Zorgkern Laboratorium voor Microbiologie en Infectiepreventie • 4 medisch microbiologen: prof.dr. J.A.J.W. (Jan) Kluytmans, J.H. (Jan) Marcelis, P.H.J. (Peter) van Keulen, dr. G.J. (Jolanda) van Hooydonk-Elving, dr. C.M. (Kees) Verduin • dr. E. (Eveline) Snelders, moleculair microbioloog • 1 meewerkend teamleidinggevende infectiepreventie / research mw. drs. M.M.L. (Miranda) van Rijen, • 1 projectmedewerker infectiepreventie: mw. dr. L.E. (Ina) Willemsen • 4 adviseurs infectiepreventie: H.P.M. (Henk) Coertjens, mw. A.B. (Gonny) Moen, Mw. Y.J.A.M. (Yvonne) Hendriks, mw. V.A.T.C. (Veronica) Weterings • 2 adviseurs infectiepreventie in opleiding: mw. C.M. (Marie-Louise) van Leest, E. (Esther) Weterings • 1 meewerkend teamleidinggevende laboratorium medische microbiologie; mw C.I.M. (Angela) Vrolijk • 2 assistenten in opleiding: E.J.M.(Erwin Verkade), B.A.G.L. (Brigitte) van Cleef • 1 bedrijfsmanager a.i. R. (Rob) de Vooght

Samenvattingen gepubliceerde artikelen Ammerlaan HS, Harbarth S, Buiting AG, Crook DW, Fitzpatrick F, Hanberger H, Herwaldt LA, van Keulen PH, Kluytmans JA, Kola A, Kuchenbecker RS, Lingaas E, Meessen N, Morris-Downes MM, Pottinger JM, Rohner P, dos Santos RP, Seifert H, Wisplinghoff H, Ziesing S, Walker AS, Bonten MJ. Secular trends in nosocomial bloodstream infections: antibiotic-resistant bacteria increase the total burden of infection. Clin Infect Dis. 2013 Mar;56(6):798-805. Epub 2012 Dec 7. BACKGROUND: It is unknown whether rising incidence rates of nosocomial bloodstream infections (BSIs) caused by antibiotic-resistant bacteria (ARB) replace antibiotic-susceptible bacteria (ASB), leaving the total BSI rate unaffected. METHODS: We investigated temporal trends in annual incidence densities (events per 100 000 patient-days) of nosocomial BSIs caused by methicillin-resistant Staphylococcus aureus (MRSA), ARB other than MRSA, and ASB in 7 ARB-endemic and 7 ARB-nonendemic hospitals between 1998 and 2007. RESULTS: 33 130 nosocomial BSIs (14% caused by ARB) yielded 36 679 microorganisms. From 1998 to 2007, the MRSA incidence density increased from 0.2 to 0.7 (annual in crease, 22%) in ARB-nonendemic hospitals, and from 3.1 to 11.7 (annual increase, 10%) in ARB-endemic hospitals (P = .2), increasing the incidence density difference between ARB-endemic and ARB-nonendemic hospitals from 2.9 to 11.0. The non-MRSA ARB incidence density increased from 2.8 to 4.1 (annual increase, 5%) in ARB-nonendemic hospitals, and from 1.5 to 17.4 (annual increase, 22%) in ARB-endemic hospitals (P < .001), changing the incidence density difference from -1.3 to 13.3. Trends in ASB inci dence densities were similar in both groups (P = .7). With annual increases of 3.8% and 5.4% of all nosocomial BSIs in ARB-nonendemic and ARB-endemic hospitals, respectively (P < .001), the overall incidence density difference of 3.8 increased to 24.4. Laboratorium voor Microbiologie en Infectiepreventie

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CONCLUSIONS: Increased nosocomial BSI rates due to ARB occur in addition to infections caused by ASB, increasing the total burden of disease. Hospitals with high ARB infection rates in 2005 had an excess burden of BSI of 20.6 per 100 000 patient-days in a 10-year period, mainly caused by infections with ARB. PMID: 23223600 Veenemans J, Mouton JW, Kluytmans JA, Donnely R, Verhulst C, van Keulen PH. Effect of manganese in test media on in vitro susceptibility of Enterobacteriaceae and Acinetobacter baumannii to tigecycline. J Clin Microbiol. 2012 Sep;50(9):3077-9. We assessed the effect of increasing manganese concentrations in test media (0.001 to 1,024 mg/liter) on MICs of tigecycline. For both broth microdilution (BMD) and Etests, this effect was negligible for physiological concentrations, but MICs increased when concentrations exceeded 8 mg/liter. Susceptibility testing should be performed on media with standardized low manganese content. PMID: 22718943 - PMCID: PMC3421825

Donker JM, van der Laan L, Hendriks YJ, Kluytmans JA. Evaluation of staphylococcus aureus nasal carriage screening before vascular surgery. PLoS One. 2012;7(6):e38127. Epub 2012 Jun 7. INTRODUCTION: Staphylococcus aureus is the most important pathogen in the deve lopment of surgical site infections (SSI). Patients who carry S. aureus in the nose are at increased risk for the development of SSI in cardiothoracic and orthopedic surgery. In these populations it has been shown that the risk for SSI can be substantially redu ced by eradicating S. aureus carriage. For vascular surgery the relation between nasal carriage and surgical site infections has not been clearly investigated. For this reason we performed this study to analyze the relation between S. aureus nasal carriage and SSI in our vascular surgery population. METHODS: A prospective cohort study was undertaken, including all patients under going vascular surgery between January first 2010 and December 31th 2010. Before surgery patients were screened for S. aureus nasal carriage using a PCR technique. The presence of SSI was recorded based on criteria of the CDC. RESULTS: Screening was performed in 224. Of those, 55 (24.5%) were positive, 159 (71.0%) were negative and 10 (4.5%) were inconclusive. In the screened vascular population 4 S. aureus SSI occurred in the 55 carriers compared with 6 in 159 noncarriers (p = 0.24). A stratified analysis revealed a 10-fold increased risk in nasal carriers undergoing central reconstruction surgery (3 S. aureus SSI in 20 procedures versus 1 in 65 procedures in non-carriers, p = 0.039).


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DISCUSSION: In patients undergoing central reconstruction surgery nasals carriers are at increased risk for the development of S. aureus SSI. These patients will probably benefit from perioperative treatment to eradicate nasal carriage. PMID: 22685553 Crolla RM, van der Laan L, Veen EJ, Hendriks Y, van Schendel C, Kluytmans J. Reduction of surgical site infections after implementation of a bundle of care. PLoS One. 2012;7(9):e44599. Epub 2012 Sep 4. BACKGROUND: Surgical Site Infections (SSI) are relatively frequent complications after colorectal surgery and are associated with substantial morbidity and mortality. OBJECTIVE: Implementing a bundle of care and measuring the effects on the SSI rate. DESIGN: Prospective quasi experimental cohort study. METHODS: A prospective surveillance for SSI after colorectal surgery was performed in the Amphia Hospital, Breda, from January 1, 2008 until January 1, 2012. As part of a National patient safety initiative, a bundle of care consisting of 4 elements covering the surgical process was introduced in 2009. The elements of the bundle were peri operative antibiotic prophylaxis, hair removal before surgery, perioperative normother mia and discipline in the operating room. Bundle compliance was measured every 3 months in a random sample of surgical procedures. RESULTS: Bundle compliance improved significantly from an average of 10% in 2009 to 60% in 2011. 1537 colorectal procedures were performed during the study period and 300 SSI (19.5%) occurred. SSI were associated with a prolonged length of stay (mean additional length of stay 18 days) and a significantly higher 6 months mortality (Adjusted OR: 2.71, 95% confidence interval 1.76-4.18). Logistic regression showed a significant decrease of the SSI rate that paralleled the introduction of the bundle. The adjusted Odds ratio of the SSI rate was 36% lower in 2011 compared to 2008. CONCLUSION: The implementation of the bundle was associated with improved compliance over time and a 36% reduction of the SSI rate after adjustment for confounders. This makes the bundle an important tool to improve patient safety. PMID: 22962619 - PMCID: PMC3433450


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Kluytmans-van den Bergh MF, Kluytmans JA. Editorial Commentary: Control of Multi drug-Resistant Microorganisms: Beyond the Hospital. Clin Infect Dis. 2012 Dec;55(11):1512-4. Epub 2012 Sep 5. Comment on: Rate of transmission of extended-spectrum beta-lactamase-producing entero bacteriaceae without contact isolation. [Clin Infect Dis. 2012] Rate of transmission of extended-spectrum beta-lactamase-producing enterobacteriaceae without contact isolation.Tschudin-Sutter S, Frei R, Dangel M, Stranden A, Widmer AF. PMID: 22955440

Kluytmans JA, Overdevest IT, Willemsen I, Kluytmans-van den Bergh MF, van der Zwaluw K, Heck M, Rijnsburger M, Vandenbroucke-Grauls CM, Savelkoul PH, Johnston BD, Gordon D, Johnson JR. Extended-spectrum beta-lactamase-producing Escherichia coli from retail chicken meat and humans: comparison of strains, plasmids, resistance genes, and virulence factors. Clin Infect Dis. 2013 Feb;56(4):478-87. Epub 2012 Dec 14. BACKGROUND: The worldwide prevalence of extended-spectrum ß-lactamase (ESBL)producing Enterobacteriaceae is increasing rapidly both in hospitals and in the com munity. A connection between ESBL-producing bacteria in food animals, retail meat, and humans has been suggested. We previously reported on the genetic composition of a collection of ESBL-producing Escherichia coli (ESBL-EC) from chicken meat and humans from a restricted geographic area. Now, we have extended the analysis with plasmid replicons, virulence factors, and highly discriminatory genomic profiling methods. METHODS: One hundred forty-five ESBL-EC isolates from retail chicken meat, human rectal carriers, and blood cultures were analyzed using multilocus sequence typing, phylotyping, ESBL genes, plasmid replicons, virulence genes, amplified fragment length polymorphism (AFLP), and pulsed-field gel electrophoresis (PFGE). RESULTS: Three source groups overlapped substantially when their genetic composition was compared. A combined analysis using all variables yielded the highest resolution (Wilks lambda [ ]: 0.08). Still, a prediction model based on the combined data classified 40% of the human isolates as chicken meat isolates. AFLP and PFGE showed that the isolates from humans and chicken meat could not be segregated and identified 1 perfect match between humans and chicken meat.


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CONCLUSIONS: We found significant genetic similarities among ESBL-EC isolates from chicken meat and humans according to mobile resistance elements, virulence genes, and genomic backbone. Therefore, chicken meat is a likely contributor to the recent emergence of ESBL-EC in human infections in the study region. This raises serious food safety questions regarding the abundant presence of ESBL-EC in chicken meat. PMID: 23243181

Bernards AT, Bonten MJM, Cohen-Stuart J, Diederen B, Goessens WHF, Grundmann H, Kluytmans JAJW, Kluytmans - van den Bergh MFQ, Leverstein - van Hall MA, Mouton JW, al Naiemi N. Troelstra A, Vandenbroucke - Grauls CMJE, Vos MC, Voss A. Recommendations of the NVMM guideline Laboratory detection of highly resistant microorganisms. Ned Tijdschr Med Microbiol. 2012;20:13-5. Koningstein M, Groen L, Geraats-Peters K, Lutgens S, Rietveld A, Jira P, Kluytmans J, de Greeff SC, Hermans M, Schneeberger PM. The use of typing methods and infection prevention measures to control a bullous impetigo outbreak on a neonatal ward. Antimicrob Resist Infect Control. 2012 Nov 20;1(1):37. BACKGROUND: We describe an outbreak of Bullous Impetigo (BI), caused by a (methicillin susceptible, fusidic acid resistant) Staphylococcus aureus (SA) strain, spa-type t408, at the neonatal and gynaecology ward of the Jeroen Bosch hospital in the Netherlands, from March-November 2011. METHODS: We performed an outbreak investigation with revision of the hygienic protocols, MSSA colonization surveillance and environmental sampling for MSSA including detailed typing of SA isolates. Spa typing was performed to discriminate be tween the SA isolates. In addition, Raman-typing was performed on all t408 isolates. RESULTS: Nineteen cases of BI were confirmed by SA positive cultures. A cluster of nine neonates and three health care workers (HCW) with SA t408 was detected. These strains were MecA-, PVL-, Exfoliative Toxin (ET)A-, ETB+, ETAD-, fusidic acidresistant and methicillin susceptible. Eight out of nine neonates and two out of three HCW t408 strains yielded a similar Raman type. Positive t408 HCW were treated and infection control procedures were reinforced. These measures stopped the outbreak. CONCLUSIONS: We conclude that treatment of patients and HCW carrying a predo minant SA t408, and re-implementing and emphasising hygienic measures were effective to control the outbreak of SA t408 among neonates. PMID: 23168170 - PMCID: PMC3546034


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Van Cleef BA, van Rijen M, Ferket M, Kluytmans JA. Self-sampling is appropriate for detection of Staphylococcus aureus: a validation study. Antimicrob Resist Infect Control. 2012 Nov 8;1(1):34. BACKGROUND: Studies frequently use nasal swabs to determine Staphylococcus aureus carriage. Self-sampling would be extremely useful in an outhospital research situation, but has not been studied in a healthy population. We studied the similarity of self-samples and investigator-samples in nares and pharynxes of healthy study subjects (hospital staff) in the Netherlands. METHODS: One hundred and five nursing personnel members were sampled 4 times in random order after viewing an instruction paper: 1) nasal self-sample, 2) pharyngeal self-sample, 3) nasal investigator-sample, and 4) pharyngeal investigator-sample. RESULTS: For nasal samples, agreement is 93% with a kappa coefficient of 0.85 (95% CI 0.74-0.96), indicating excellent agreement, for pharyngeal samples agreement is 83% and the kappa coefficient is 0.60 (95% CI 0.43-0.76), indicating good agreement. In both sampling sites self-samples even detected more S. aureus than investigatorsamples. CONCLUSIONS: This means that self-samples are appropriate for detection of Staphylococcus aureus and methicillin-resistant Staphylococcus aureus. PMID: 23137281 - PMCID: PMC3546066

Verkade E, Bergmans AM, Budding AE, van Belkum A, Savelkoul P, Buiting AG, Kluytmans J. Recent emergence of Staphylococcus aureus clonal complex 398 in human blood cultures. PLoS One. 2012;7(10):e41855. Epub 2012 Oct 18. BACKGROUND: Recently, a clone of MRSA with clonal complex 398 (CC398) has emerged that is related to an extensive reservoir in animals, especially pigs and veal calves. It has been reported previously that methicillin-susceptible variants of CC398 circulate among humans at low frequency, and these have been isolated in a few cases of bloodstream infections (BSI). The purpose of this study was to determine the prevalence of S. aureus CC398 in blood cultures taken from patients in a geographic area with a high density of pigs. METHODOLOGY/PRINCIPAL FINDINGS: In total, 612 consecutive episodes of S. aureus BSI diagnosed before and during the emergence of CC398 were included. Three strains (2 MSSA and 1 MRSA) that were isolated from bacteremic patients between 2010-2011 were positive in a CC398 specific PCR. There was a marked increase in prevalence of S. aureus CC398 BSI isolated between 2010-2011 compared to the combined collections that were isolated between 1996-1998 and 2002-2005 (3/157, 1.9% vs. 0/455, 0.0%; p = 0.017). Laboratorium voor Microbiologie en Infectiepreventie

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CONCLUSIONS/SIGNIFICANCE: In conclusion, in an area with a relative high density of pigs, S. aureus CC398 was found as a cause of BSI in humans only recently. This indicates that S. aureus CC398 is able to cause invasive infections in humans and that the prevalence is rising. Careful monitoring of the evolution and epidemiology of S. aureus CC398 in animals and humans is therefore important. PMID: 23094014 - PMCID: PMC3475701

Feingold BJ, Silbergeld EK, Curriero FC, van Cleef BA, Heck ME, Kluytmans JA. Livestock density as risk factor for livestock-associated methicillin-resistant Staphylococcus aureus, the Netherlands. Emerg Infect Dis. 2012 Nov;18(11):1841-9. To determine whether persons living in areas of high animal density are at increased risk for carrying livestock-associated methicillin-resistant Staphylococcus aureus (LA-MRSA), we used an existing dataset of persons in the Netherlands with LA-MRSA carriage and controls who carried other types of MRSA. Results of running univariate and multivariate logistic regression models indicated that living in livestock-dense areas increases the odds of nasal carriage of LA-MRSA. We found that doubling pig, cattle, and veal calf densities per municipality increased the odds of LA-MRSA carriage over carriage of other types of MRSA by 24.7% (95% CI 0.9%-54.2%), 76.9% (95% CI 11.3%-81.3%), and 24.1% (95% CI 5.5%-45.9%), respectively, after adjusting for direct animal contact, living in a rural area, and the probable source of MRSA carriage. Controlling the spread of LA-MRSA thus requires giving attention to community members in animal-dense regions who are unaffiliated with livestock farming. PMID: 23092646 - PMCID: PMC3559158

Feingold BJ, Silbergeld EK, Curriero FC, van Cleef BA, Heck ME, Kluytmans JA. Livestock density as risk factor for livestock-associated methicillin-resistant Staphylococcus aureus, the Netherlands. Emerg Infect Dis. 2012 Nov;18(11):1841-9. Multilocus sequence typing (MLST) is one of the most reliable methods for typing of Escherichia coli, including extended-spectrum-ß-lactamase-producing E. coli (ESBL-EC). We investigated the performance of a new typing method, SpectraCell RA (River Diag nostics, Madison, WI), in comparison on MLST on a well-defined collection of ESBL-EC isolates obtained from chicken meat and humans. Ninety-two ESBL-EC isolates obtained from meat and 59 ESBL-EC isolates obtained from human rectal swabs and clinical blood cultures were typed using MLST and SpectraCell RA. The sensitivity and specificity of SpectraCell RA were calculated, using MLST as a reference method. Subsequently, the results of SpectraCell RA were used to determine the relatedness of ESBL-EC isolates from chicken and humans. Using MLST as the gold standard, the


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performance of SpectraCell RA was evaluated for 3 different cutoff values: 0.99975, 0.99955, and 0.99935. Depending on the cutoff value, the sensitivity was mediocre to unacceptably low, with values of 9.4%, 43.9%, and 66.7%, respectively. When sensitivity increased, the specificity decreased rapidly, from 95.6% to 69.8% and 34.4%, respectively. Also, the number of clusters containing both human and meat samples varied from 0 (0.0%) to 14 (38.9%). Our study shows that SpectraCell RA is not a suitable typing method for ESBL-EC when evaluating relationships of ESBL-EC at the population level. PMID: 23035198 - PMCID: PMC3502991

Wintermans BB, Reuland EA, Wintermans RG, Bergmans AM, Kluytmans JA. The costeffectiveness of ESBL detection: towards molecular detection methods? Clin Microbiol Infect. 2013 Jul;19(7):662-5. Epub 2012 Sep 12. Correct detection of extended-spectrum beta-lactamases (ESBLs) is crucial for infecti on control and antibiotic choice. We performed a study to determine the cost-effecti veness of phenotypical testing, which can be inaccurate, and genotypical tests, which are considered to be more reliable but also more expensive. All patients that had been in isolation in the Amphia hospital because of the detection of ESBL according to the ESBL Etest were included in the survey. All strains were retested using the double disk confirmation test (DDCT) and a genotypical method. This was a commercially available microarray (Check-Points). Discordant results were confirmed by PCR and sequencing. In total 174 patients were included. In 24 of 174 (14%) patients, ESBL carriage could not be confirmed with the microarray. This was verified with PCR and sequencing. The mean duration of isolation was 15 days, adding up to a total number of isolation days of 2571. False-positive results according to the microarray resulted in a total of 279 days of unnecessary isolation for the Etest and 151 days for the DDCT. Using Etest to detect the presence of ESBL results in a false-positive outcome in 14% of the cases. This results in unnecessary isolation of patients, which can be omitted by using a genotypic method. © 2012 The Authors. Clinical Microbiology and Infection © 2012 European Society of Clinical Microbiology and Infectious Diseases. PMID: 22971154

Voss A, Kluytmans J, Pittet D. A new journal and new global perspective on infection control and public health. Antimicrob Resist Infect Control. 2012 Jan 26;1(1):4. [No abstract available] PMID: 22958813 - PMCID: PMC3415120


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Van Rijen MM, Bode LG, Baak DA, Kluytmans JA, Vos MC. Reduced costs for Staphy lococcus aureus carriers treated prophylactically with mupirocin and chlorhexidine in cardiothoracic and orthopaedic surgery. PLoS One. 2012;7(8):e43065. Epub 2012 Aug 14. BACKGROUND: A multi centre double-blind randomised-controlled trial (M-RCT), carried out in the Netherlands in 2005-2007, showed that hospitalised patients with S. aureus nasal carriage who were treated prophylactically with mupirocin nasal oint ment and chlorhexidine gluconate medicated soap (MUP-CHX), had a significantly lower risk of health-care associated S. aureus infections than patients receiving place bo (3.4% vs. 7.7%, RR 0.42, 95% CI 0.23-0.75). The objective of the present study was to determine whether treatment of patients undergoing elective cardiothoracic or ortho paedic surgery with MUP-CHX (screen-and-treat strategy) affected the costs of patient care. METHODS: We compared hospital costs of patients undergoing cardiothoracic or orthopaedic surgery (n=415) in one of the participating centres of the M-RCT. Data from the ‘Planning and Control’ department were used to calculate total hospital costs of the patients. Total costs were calculated including nursing days, costs of surgery, costs for laboratory and radiological tests, functional assessments and other costs. Costs for personnel, materials and overhead were also included. Mean costs in the two treatment arms were compared using the t-test for equality of means (two-tailed). Subgroup analysis was performed for cardiothoracic and orthopaedic patients. RESULTS: An investigator-blinded analysis revealed that costs of care in the treatment arm (MUP-CHX, n=210) were on average € 1911 lower per patient than costs of care in the placebo arm (n=205) (€ 8602 vs. € 10513, p=0.01). Subgroup analysis showed that MUP-CHX treated cardiothoracic patients cost € 2841 less (n=280, € 9628 vs € 12469, p=0.006) and orthopaedic patients € 955 less than non-treated patients (n=135, € 6097 vs € 7052, p=0.05). CONCLUSIONS: In conclusion, in patients undergoing cardiothoracic or orthopaedic surgery, screening for S. aureus nasal carriage and treating carriers with MUP-CHX results in a substantial reduction of hospital costs. PMID: 22916209 - PMCID: PMC3419251


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Huijskens EG, van Erkel AJ, Palmen FM, Buiting AG, Kluytmans JA, Rossen JW. Viral and bacterial aetiology of community-acquired pneumonia in adults. Influenza Other Respi Viruses. 2012 Aug 22. [Epub ahead of print]. Please cite this paper as: Huijskens et al. (2012) Viral and bacterial aetiology of com munity-acquired pneumonia in adults. Influenza and Other Respiratory Viruses DOI: 10.1111/j.1750-2659.2012.00425.x. Background Modern molecular techniques reveal new information on the role of respiratory viruses in community-acquired pneumonia. In this study, we tried to determine the prevalence of respiratory viruses and bacteria in patients with community-acquired pneumonia who were admitted to the hospital. Methods Between April 2008 and April 2009, 408 adult patients (aged between 20 and 94 years) with community-acquired pneumonia were tested for the presence of respiratory pathogens using bacterial cultures, real-time PCR for viruses and bacteria, urinary antigen testing for Legionella and Pneumococci and serology for the presence of viral and bacterial pathogens. Results Pathogens were identified in 263 (64·5%) of the 408 patients. The most common single organisms in these 263 patients were Streptococcus pneumoniae (22·8%), Coxiella burnetii (6·8%) and influenza A virus (3·8%). Of the 263 patients detected with pathogens, 117 (44·5%) patients were posi tive for one or more viral pathogens. Of these 117 patients, 52 (44·4%) had no bacterial pathogen. Multiple virus infections (=2) were found in 16 patients. Conclusion In conclusion, respiratory viruses are frequently found in patients with CAP and may therefore play an important role in the aetiology of this disease. © 2012 Blackwell Publishing Ltd. PMID: 22908940

Van Cleef BA, Kluytmans JA, van Benthem BH, Haenen A, Monen J, Daniels-Haardt I, Jurke A, Friedrich AW. Cross border comparison of MRSA bacteraemia between The Netherlands and North Rhine-Westphalia (Germany): a cross-sectional study. PLoS One. 2012;7(8):e42787. Epub 2012 Aug 3. BACKGROUND: We describe the impact of methicillin-resistant Staphylococcus aureus (MRSA) in two neighbouring regions in Europe with a comparable population size, North Rhine-Westphalia (NRW) in Germany and the Netherlands. METHODOLOGY/PRINCIPAL FINDINGS: We compared the occurrence of MRSA in blood cultures from surveillance systems. In the Netherlands in 2009, 14 of 1,510 (0.9%) Stap hylococcus aureus bacteraemia episodes under surveillance were MRSA. Extrapolation using the number of clinical admissions results in a total of 29 MRSA bacteraemia episodes in the Netherlands or 1.8 episodes per 1,000,000 inhabitants. In 2010 in NRW, 1,029 MRSA bacteraemias were reported, resulting in 57.6 episodes of MRSA bacterae mia per 1,000,000 inhabitants: a 32-fold higher incidence than in the Netherlands.


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CONCLUSION/SIGNIFICANCE: Based on an estimated attributable mortality of 15%, the Dutch approach would save approximately 150 lives per year by the prevention of bacteraemia only. PMID: 22880109 - PMCID: PMC3411841

Reuland EA, Overdevest IT, Al Naiemi N, Kalpoe JS, Rijnsburger MC, Raadsen SA, Ligtenberg-Burgman I, van der Zwaluw KW, Heck M, Savelkoul PH, Kluytmans JA, Vandenbroucke-Grauls CM. High prevalence of ESBL-producing Enterobacteriaceae carriage in Dutch community patients with gastrointestinal complaints. Clin Microbiol Infect. 2013 Jun;19(6):542-9. Epub 2012 Jul 3. The aim of this study was to determine the rate of carriage of ESBL-producing Entero bacteriaceae (ESBL-E) in the community in the Netherlands and to gain understanding of the epidemiology of these resistant strains. Faecal samples from 720 consecutive patients presenting to their general practitioner, obtained in May 2010, and between December 2010 and January 2011, were analysed for presence of ESBL-E. Species identi fication and antibiotic susceptibility testing were performed according to the Dutch national guidelines. PCR, sequencing and microarray were used to characterize the genes encoding for ESBL. Strain typing was performed with amplified fragment length polymorphism (AFLP) and multilocus sequence typing (MLST). Seventy-three of 720 (10.1%) samples yielded ESBL-producing organisms, predominantly E. coli. No carbapen emases were detected. The most frequent ESBL was CTX-M-15 (34/73, 47%). Co-resis tance to gentamicin, ciprofloxacin and cotrimoxazole was found in (9/73) 12% of the ESBL-E strains. AFLP did not show any clusters, and MLST revealed that CTX-M-15producing E. coli belonged to various clonal complexes. Clonal complex ST10 was pre dominant. This study showed a high prevalence of ESBL-producing Enterobacteriaceae in Dutch primary care patients with presumed gastrointestinal discomfort. Hence, also in the Netherlands, a country with a low rate of consumption of antibiotics in humans, resistance due to the expansion of CTX-M ESBLs, in particular CTX-M-15, is emerging. The majority of ESBL-producing strains do not appear to be related to the international clonal complex ST131. © 2012 The Authors. Clinical Microbiology and Infection © 2012 European Society of Clinical Microbiology and Infectious Diseases. PMID: 22757622


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Oostdijk EA, de Smet AM, Kesecioglu J, Bonten MJ; Dutch SOD-SDD Trialists Group* [Kluytmans JA et al...]. Decontamination of cephalosporin-resistant Enterobacteriaceae during selective digestive tract decontamination in intensive care units. J Antimicrob Chemother. 2012 Sep;67(9):2250-3. Epub 2012 May 29. OBJECTIVES: Prevalences of cephalosporin-resistant Enterobacteriaceae are increasing globally, especially in intensive care units (ICUs). The effect of selective digestive tract decontamination (SDD) on the eradication of cephalosporin-resistant Enterobacteria ceae from the intestinal tract is unknown. We quantified eradication rates of cepha losporin-resistant and cephalosporin-susceptible Enterobacteriaceae during SDD in patients participating in a 13 centre cluster-randomized study and from a single-centre cohort. METHODS: All SDD patients colonized with Enterobacteriaceae in the intestinal tract at ICU admission were included. Cephalosporin resistance was defined as resistance to ceftazidime, cefotaxime or ceftriaxone and aminoglycoside resistance as resistance to tobramycin or gentamicin. Duration of rectal colonization was determined by screening twice weekly during ICU stay. Swabs were inoculated on selective medium supplemented with tobramycin or cefotaxime. RESULTS: Five hundred and seven (17%) of 2959 SDD patients with at least one rectal sample were colonized with Enterobacteriaceae at ICU admission: 77 (15%) with cep halosporin-resistant Enterobacteriaceae and 50 (10%) with aminoglycoside-resistant Enterobacteriaceae. Fifty-six (73%) patients colonized with cephalosporin-resistant Enterobacteriaceae were successfully decontaminated before ICU discharge, as were 343 (80%) patients colonized with cephalosporin-susceptible Enterobacteriaceae (P = 0.17). For aminoglycoside resistance, 31 (62%) patients were decontaminated, as were 368 patients (81%) colonized with aminoglycoside-susceptible Enterobacteria ceae (P? 0.05 for all comparisons). CONCLUSIONS: SDD can successfully eradicate cephalosporin-resistant Enterobacteria ceae from the intestinal tract.


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*Collaborators (32): Kalkman CJ, Joore HJ, Leverstein-van Hall MA, Blok HE, Kluytmans JA, van der Meer NJ, Mascini EM, Kaasjager K, Bosch FH, Benus RF, van der Werf TS, van der Hoeven JG, Pickkers P, Sturm PD, Voss A, Bernards AT, Kuijper EJ, Harinck HI, Bindels AJ, Jansz AR, Wesselink RM, de Jongh BM, Dennesen PJ, van Asselt GJ, Velde LF, Frenay IH, Schweitzer A, van Iterson M, Thijsen SF, Kluge GH, de Vries JW, Kaan JA. PMID: 22643189

Verkade E, Bosch T, Hendriks Y, Kluytmans J. Outbreak of methicillin-resistant Staphylococcus aureus ST398 in a Dutch nursing home. Infect Control Hosp Epidemiol. 2012 Jun;33(6):624-6. Epub 2012 Apr 24. We describe an outbreak of methicillin-resistant Staphylococcus aureus (MRSA) ST398 in a nursing home in the Netherlands. Seven residents and 4 healthcare workers were identified with MRSA ST398, but 2 of the healthcare workers carried other strains. This study demonstrates that MRSA ST398 can spread in nursing homes. PMID: 22561720

Wassenberg M, Kluytmans J, Erdkamp S, Bosboom R, Buiting A, van Elzakker E, Melchers W, Thijsen S, Troelstra A, Vandenbroucke-Grauls C, Visser C, Voss A, Wolffs P, Wulf M, van Zwet T, de Wit A, Bonten M. Costs and benefits of rapid screening of me thicillin-resistant Staphylococcus aureus carriage in intensive care units: a prospective multicenter study. Crit Care. 2012 Feb 7;16(1):R22. INTRODUCTION: Pre-emptive isolation of suspected methicillin-resistant Staphylo coccus aureus (MRSA) carriers is a cornerstone of successful MRSA control policies. Implementation of such strategies is hampered when using conventional cultures with diagnostic delays of three to five days, as many non-carriers remain unnecessarily isolated. Rapid diagnostic testing (RDT) reduces the amount of unnecessary isolation days, but costs and benefits have not been accurately determined in intensive care units (ICUs). METHODS: Embedded in a multi-center hospital-wide study in 12 Dutch hospitals we quantified cost per isolation day avoided using RDT for MRSA, added to conventional cultures, in ICUs. BD GeneOhm¸ MRSA PCR (IDI) and Xpert MRSA (GeneXpert) were subsequently used during 17 and 14 months, and their test characteristics were cal culated with conventional culture results as reference. We calculated the number of pre-emptive isolation days avoided and incremental costs of adding RDT. RESULTS: A total of 163 patients at risk for MRSA carriage were screened and MRSA prevalence was 3.1% (n=5). Duration of isolation was 27.6 and 21.4 hours with IDI


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and GeneXpert, respectively, and would have been 96.0 hours when based on conven tional cultures. The negative predictive value was 100% for both tests. Numbers of isolation days were reduced by 44.3% with PCR-based screening at the additional costs of € 327.84 (IDI) and € 252.14 (GeneXpert) per patient screened. Costs per isolation day avoided were € 136.04 (IDI) and € 121.76 (GeneXpert). CONCLUSIONS: In a low endemic setting for MRSA, RDT safely reduced the number of unnecessary isolation days on ICUs by 44%, at the costs of € 121.76 to € 136.04 per isolation day avoided. Comment in: Methicillin-resistant Staphylococcus aureus carriage at ICU admission: to screen (rapidly) or not to screen? [Crit Care. 2012] Methicillin-resistant Staphylococcus aureus carriage at ICU admission: to screen (rapidly) or not to screen?Lucet JC. Crit Care. 2012 Dec 12; 16(2):120. Epub 2012 Dec 12. PMID: 22314204 - PMCID: PMC3396263

De Smet AM, Bonten MJ, Kluytmans JA. For whom should we use selective decontamination of the digestive tract? Curr Opin Infect Dis. 2012 Apr;25(2):211-7. PURPOSE OF REVIEW: This review discusses the relevant studies on selective decontamination of the digestive tract (SDD) published between 2009 and mid-2011. RECENT FINDINGS: In a multicenter cluster-randomized cross-over study in the Netherlands, SDD and selective oropharyngeal decontamination (SOD) were associated with higher survival at day 28, with a lower incidence of ICU-acquired bacteremia and with less acquisition of respiratory tract colonization with antibiotic resistant pathogens, compared to standard care. A post-hoc analysis of this study suggests that SDD might be more effective in surgical patients and SOD in nonsurgical patients. In a randomized study perioperative use of SDD in patients undergoing gas trointestinal surgery was associated with lower incidences of anastomotic leakages. A Cochrane meta-analysis, not including any of the before mentioned studies, repor ted a reduction of respiratory tract infections in studies by using topical antibiotics only and higher survival rates when topical antibiotics were combined with parenteral antibiotics. SUMMARY: Recent studies show that in ICUs with low levels of antibiotic resistance, SDD and SOD improved patient outcome and reduced infections and carriage with antibiotic-resistant pathogens. The effect in settings with higher levels of antibiotic resistance remains to be determined as well as the efficacy of SDD and SOD in specific patient groups. PMID: 22274728 Laboratorium voor Microbiologie en Infectiepreventie

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Melsen WG, de Smet AM, Kluytmans JA, Bonten MJ; Dutch SOD-SDD Trialists’ Group*. Selective decontamination of the oral and digestive tract in surgical versus non-surgi cal patients in intensive care in a cluster-randomized trial. Br J Surg. 2012 Feb;99(2):2327. Epub 2011 Oct 24. BACKGROUND: Selective digestive decontamination (SDD) and selective oropharyn geal decontamination (SOD) are effective in improving survival in patients under intensive care. In this study possible differential effects in surgical and non-surgical patients were investigated. METHODS: This was a post hoc subgroup analysis of data from a cluster-randomized multicentre trial comparing three groups (SDD, SOD or standard care) to quantify effects among surgical and non-surgical patients. The primary study outcome was 28day mortality rate. Duration of mechanical ventilation, duration of intensive care unit (ICU) and hospital length of stay, and bacteraemia rates were secondary outcomes. RESULTS: The subgroup analyses included a total of 2762 surgical and 3165 non-surgical patients. Compared with standard care, adjusted odds ratios (ORs) for mortality were comparable in SDD-treated surgical and non-surgical patients: 0.86 (95 per cent confi dence interval 0.69 to 1.09; P = 0.220) and 0.85 (0.70 to 1.03; P = 0.095) respectively. However, duration of mechanical ventilation, ICU stay and hospital stay were signifi cantly reduced in surgical patients who had SDD. SOD did not reduce mortality com pared with standard treatment in surgical patients (adjusted OR 0.97, 0.77 to 1.22; P = 0.801); in non-surgical patients it reduced mortality (adjusted OR 0.77, 0.63 to 0.94; P = 0.009) by 16.6 per cent, representing an absolute mortality reduction of 5.5 per cent with number needed to treat of 18. CONCLUSION: Subgroup analysis found similar effects of SDD in reducing mortality in surgical and non-surgical ICU patients, whereas SOD reduced mortality only in nonsurgical patients. The hypothesis-generating findings mandate investigation into me chanisms between different ICU populations. Copyright © 2011 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd. Comment in: Selective decontamination of the oral and digestive tract in surgical versus nonsurgical patients in intensive care in a cluster-randomized trial (Br J Surg 2012; 99: 232-237). Selective decontamination of the oral and digestive tract in surgical versus nonsurgical patients in intensive care in a cluster-randomized trial (Br J Surg 2012; 99: 232-237).Ytrebø LM. Br J Surg. 2012 Feb; 99(2):238.


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*Collaborators (14): Dennesen PJ, Kluge GH, te Velde LF, van Iterson M, van der Werf TS, van der Meer NJ, Bindels AJ, Bosch FH, de Vries JW, Harinck HI, Joore JC, Kalkman CJ, Wesselink RM, Pickkers P. PMID: 22021072

Voets GM, Platteel TN, Fluit AC, Scharringa J, Schapendonk CM, Stuart JC, Bonten MJ, Hall MA; National ESBL Surveillance Working Group* [Kluytmans JA et al...]. Popu lation distribution of Beta-lactamase conferring resistance to third-generation cephalosporins in human clinical Enterobacteriaceae in the Netherlands. PLoS One. 2012;7(12):e52102. Epub 2012 Dec 20. There is a global increase in infections caused by Enterobacteriaceae with plas mid-borne ß-lactamases that confer resistance to third-generation cephalosporins. The epidemiology of these bacteria is not well understood, and was, therefore, investigated in a selection of 636 clinical Enterobacteriaceae with a minimal inhibitory concentration >1 mg/L for ceftazidime/ceftriaxone from a national survey (75% E. coli, 11% E. cloacae, 11% K. pneumoniae, 2% K. oxytoca, 2% P. mirabilis). Isolates were investi gated for extended-spectrum ß-lactamases (ESBLs) and ampC genes using microarray, PCR, gene sequencing and molecular straintyping (Diversilab and multi-locus sequence typing (MLST)). ESBL genes were demonstrated in 512 isolates (81%); of which 446 (87%) belonged to the CTX-M family. Among 314 randomly selected and sequenced isolates, bla(CTX-M-15) was most prevalent (n = 124, 39%), followed by bla(CTX-M-1) (n = 47, 15%), bla(CTX-M-14) (n = 15, 5%), bla(SHV-12) (n = 24, 8%) and bla(TEM-52) (n = 13, 4%). Among 181 isolates with MIC =16 mg/L for cefoxitin plasmid encoded AmpCs were detected in 32 and 27 were of the CMY-2 group. Among 102 E. coli isolates with MIC =16 mg/L for cefoxitin ampC promoter mutations were identified in 29 (28%). Based on Diversilab genotyping of 608 isolates (similarity cut-off >98%) discrim inatory indices of bacteria with ESBL and/or ampC genes were 0.994, 0.985 and 0.994 for E. coli, K. pneumoniae and E. cloacae, respectively. Based on similarity cut-off >95% two large clusters of E. coli were apparent (of 43 and 30 isolates) and 21 of 21 that were typed by belonged to ST131 of which 13 contained bla(CTX-M-15). Our findings demon strate that bla(CTX-M-15) is the most prevalent ESBL and we report a larger than previ ously reported prevalence of ampC genes among Enterobacteriaceae responsible for resistance to third-generation cephalosporins. *Collaborators (32): Bonten MJ, van Dam AP, Gasthuis OL, Andriesse G, Kluytmans JA, Vreede RW, Sebens FW, Sabbe LJ, Schellekens JF, Vogels WH, Arends JP, Dorigo-Zetsma JW, Waar K, Vlaminckx BJ, Horrevorts AM, Sturm P, Stals FS, Wintermans RG, Moffie B, Hendrickx BG, Buiting AG, Verhoef L, Tjhie HT, Wolfhagen MJ, Diederen BM, Thijssen SF, Mascini EM, van Griethuysen A, Wever PC, Fleer A, Wagenvoort JH, Bernards AT. PMID: 23284886 - PMCID: PMC3527366


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Van der Bij AK, van Dijk K, Muilwijk J, Thijsen SF, Notermans DW, de Greeff S, van de Sande-Bruinsma N; ISIS-AR study group* [Kluytmans JA et al...]. Clinical breakpoint changes and their impact on surveillance of antimicrobial resistance in Escherichia coli causing bacteraemia. Clin Microbiol Infect. 2012 Nov;18(11):E466-72. Epub 2012 Aug 27. Dutch laboratories are currently changing their breakpoint criteria from mostly Clinical Laboratory and Standards Institute (CLSI) breakpoints to European Committee on Antimicrobial Susceptibility Testing (EUCAST) breakpoints. To evaluate the impact of these changes, we studied antimicrobial resistance trends of Escherichia coli in blood specimens from January 2008 to January 2012 using CLSI and EUCAST break points and compared them with the antimicrobial susceptibility test (AST) interpreta tions reported by Dutch laboratories participating in the Infectious Disease Surveillance Information System for Antibiotic Resistance (ISIS-AR). ISIS-AR collects AST interpretations, including underlying minimal inhibitory concentrations (MICs) of routi nely cultured bacterial species on a monthly basis from Dutch laboratories. MICs of Etests or automated systems were reinterpreted according to the CLSI 2009 and EUCAST 2010 guidelines. Trends in non-susceptibility (i.e. intermediate resistant and resistant) over time were analysed by the Cochran-Armitage test for trend. The effects of the change from CLSI to EUCAST breakpoints on non-susceptibility were small. The re were no differences in non-susceptibility to amoxicillin, amoxicillin/clavulanic acid, cefuroxim, gentamicin and co-trimoxazol and only small differences (1-1.5%) for ci profloxacin between AST interpretations by CLSI or EUCAST. However, for ceftazidime, and cefotaxime/ceftriaxone the proportion of non-susceptibility was substantially higher when EUCAST breakpoints were used (2-3%). The effects on time trends of the change in guidelines were limited, with only substantial differences for the oxyminocephalosporins. Our study shows that the implementation of EUCAST breakpoints has a limited effect on the proportion of non-susceptible isolates and time trends in E. coli for most, but not all, antimicrobial agents. *Collaborators (47): Sabbe LJ, Frénay HM, Maraha B, van Keulen PH, Kluytmans JA, de Jongh BM, Vlaminckx BJ, de Brauwer EI, Stals FS, Bakker LJ, Dorigo-Zetsma JW, Sebens FW, Mattsson EE, Kaan JA, Thijsen SF, Buiting AG, Wintermans RG, van Hees BC, Brimi combe RW, Ruijs GJ, Wolfhagen MJ, van Zeijl JH, Renders NH, Bernards AT, Wintermans RG, Heilmann FG, Halaby T, Overbeek BP, Schellekens JF, Jansen CL, Vlaspolder F, Alblas J, van der Bij AK, De Kraker M, Leenstra T, Leverstein-van Hall M, Monen J, Muilwijk J, van de Sande-Bruinsma N, Tjhie HT, Sturm PD, Diederen BM, van Zwet AA, Deege MP, Boel CH, Weersink AJ, Hendrickx BG © 2012 The Authors. Clinical Microbiology and Infection © 2012 European Society of Clinical Microbiology and Infectious Diseases. PMID: 22925456


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Uzun S, Djamin RS, Kluytmans J, Van’t Veer NE, Ermens AA, Pelle AJ, Mulder P, van der Eerden MM, Aerts J. Influence of macrolide maintenance therapy and bacterial colonisation on exacerbation frequency and progression of COPD (COLUMBUS): study protocol for a randomised controlled trial. Trials. 2012 Jun 9;13:82. BACKGROUND: Chronic obstructive pulmonary disease (COPD) is characterised by progressive development of airflow limitation that is poorly reversible. Because of a poor understanding of COPD pathogenesis, treatment is mostly symptomatic and new therapeutic strategies are limited. There is a direct relationship between the severity of the disease and the intensity of the inflammatory response. Besides smoking, one of the hypotheses for the persistent airway inflammation is the presence of recurrent infections. Macrolide antibiotics have bacteriostatic as well as anti-inflammatory properties in patients with cystic fibrosis and other inflammatory pulmonary diseases. There is consistent evidence that macrolide therapy reduces infectious exacerbations, decreases the requirement for additional antibiotics and improves nutritional measu res. Because of these positive effects we hypothesised that maintenance macrolide therapy may also have beneficial effects in patients with COPD who have recurrent exacerbations. The effects on development of bacterial resistance to macrolides due to this long-term treatment are unknown. Until now, studies investigating macrolide therapy in COPD are limited. The objective of this study is to assess whether main tenance treatment with macrolide antibiotics in COPD patients with three or more exacerbations in the previous year decreases the exacerbation rate in the year of treatment and to establish microbial resistance due to the long-term treatment. METHODS/DESIGN: The study is set up as a prospective randomised double-blind placebo-controlled single-centre trial. A total of 92 patients with COPD who have had at least three exacerbations of COPD in the previous year will be included. Subjects will be randomised to receive either azithromycin 500 mg three times a week or placebo. Our primary endpoint is the reduction in the number of exacerbations of COPD in the year of treatment. DISCUSSION: We investigate whether long-term therapy with macrolide antibiotics can prevent exacerbations in patients with COPD. Additionally, our study aims to assess the effect of long-term use of macrolide on the development of antimicrobial resistance and on inflammatory parameters related to COPD. We believe this study will provide more data on the effects of macrolide treatment in patients in COPD and will add more knowledge on its working mechanisms. TRIAL REGISTRATION: http://www.clinicaltrials.gov NCT00985244. PMID: 22682323 - PMCID: PMC3478173


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Morroy G, Wielders CC, Kruisbergen MJ, van der Hoek W, Marcelis JH, Wegdam-Blans MC, Wijkmans CJ, Schneeberger PM. Large regional differences in serological follow-up of Q fever patients in the Netherlands. PLoS One. 2013;8(4):e60707. Epub 2013 Apr 5. BACKGROUND: During the Dutch Q fever epidemic more than 4,000 Q fever cases were notified. This provided logistical challenges for the organisation of serological follow-up, which is considered mandatory for early detection of chronic infection. The aim of this study was to investigate the proportion of acute Q fever patients that received serological follow-up, and to identify regional differences in follow-up rates and contributing factors, such as knowledge of medical practitioners. METHODS: Serological datasets of Q fever patients diagnosed between 2007 and 2009 (N = 3,198) were obtained from three Laboratories of Medical Microbiology (LMM) in the province of Noord-Brabant. One LMM offered an active follow-up service by approaching patients; the other two only tested on physician’s request. The medical microbiologist in charge of each LMM was interviewed. In December 2011, 240 general practices and 112 medical specialists received questionnaires on their knowledge and practices regarding the serological follow-up of Q fever patients. RESULTS: Ninety-five percent (2,226/2,346) of the Q fever patients diagnosed at the LMM with a follow-up service received at least one serological follow-up within 15 months of diagnosis. For those diagnosed at a LMM without this service, this was 25% (218/852) (OR 54, 95% CI 43-67). Although 80% (162/203) of all medical practitioners with Q fever patients reported informing patients of the importance of serological follow-up, 33% (67/203) never requested it. CONCLUSIONS: Regional differences in follow-up are substantial and range from 25% to 95%. In areas with a low follow-up rate the proportion of missed chronic Q fever is potentially higher than in areas with a high follow-up rate. Medical practitioners lack knowledge regarding the need, timing and implementation of serological follow-up, which contributes to patients receiving incorrect or no follow-up. Therefore, this infor mation should be incorporated in national guidelines and patient information forms. PMID: 23577152 - PMCID: PMC3618034


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Longgeneeskunde Driedelig biomarkeronderzoek bij longcarcinoom schetst onderzoeksklimaat Longgeneeskunde Het Amphia Ziekenhuis werkt samen met het Erasmus Ziekenhuis in het Biopemonderzoek. Met de uitkomsten willen de onderzoekers kunnen voorspellen hoe patiënten reageren op het medicijn Alimta. Doel is om de therapie met Alimta beter te individualiseren. “We zullen hier in het Amphia Ziekenhuis de meeste patiënten includeren.” Biopem staat voor ‘Biomarkers for improving the (cost-)effectiveness and safety of pemetrexed’. In april 2012 begon arts-assistent Sabine Visser met haar promotieonder zoek bij dr. Joachim Aerts op het gebied longgeneeskunde. Het onderzoek bestaat uit drie onderdelen. Bijwerkingen “Je moet dat zo zien”, zegt Visser. “Mensen met een vergevorderd stadium adenocar cinoom (een vorm van het niet-kleincellig longcarcinoom) zijn zelden meer te genezen. Hun levensduur is wel te verlengen en hun kwaliteit van leven is te verbeteren met Alimta (pemetrexed). Een – overigens dure – vorm van chemotherapie die per infuus wordt ingebracht. Alleen geldt dat niet voor alle patiënten die we hiermee behandelen.

Xxx Arts-assistent Sabine Visser

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Bij de een reageert de tumor beter dan bij de ander en de hoeveelheid bijwerkingen kan erg variëren. Er kan sprake zijn van gastro-intestinale problemen zoals misselijkheid en obstipatie, vermoeidheid en neuropathie. En het kan de bloedcelproductie vanuit het beenmerg aantasten, omdat chemotherapie nu eenmaal op alle cellen inwerkt. Wat wij nu onderzoeken, is of we vooraf signalen kunnen vinden die voorspellen welke mensen er wel of juist niet goed op de medicatie reageren. Zodat we de mensen waar bij we bijwerkingen of een slechte tumorrespons verwachten bijvoorbeeld beter een ander middel kunnen geven en dus veel gerichter kunnen behandelen.” Visser voegt toe dat mensen soms weinig van het carcinoom merken. Met de resultaten van dit onderzoek kunnen de artsen voorkomen dat ze medicatie krijgen die wél belastend is. “En dat verbetert de kwaliteit van leven, iets wat in deze fase van de ziekte erg belangrijk is.” Tweehonderd patiënten Het onderzoek vindt plaats in het Amphia Ziekenhuis en het Erasmus Ziekenhuis, onder leiding van dr. Aerts, die in beide werkzaam is. “Daarnaast zijn er nog twee andere centra betrokken”, zegt Visser. “In totaal hebben we 200 patiënten nodig en er zijn niet zoveel patiënten die deze vorm van kanker hebben. Tachtig procent van de mensen met longkanker heeft een niet-kleincellig longcarcinoom en daar weer tachtig procent van heeft een adenocarcinoom. Daarom nemen we in het onderzoek ook mensen met longvlieskanker (mesothelioom) mee, dat een vergelijkbare behandeling heeft.” In oktober en november 2012 heeft Visser de eerste patiënten geïncludeerd en het duurt nog tot 2014 voor er genoeg patiënten zijn gevonden. Daarna worden ze gevolgd en wordt geregistreerd hoe ze op de medicatie reageren, of er progressie is, hoe de levensduur is en hoe de kwaliteit van leven is. Voor het project is een subsidie verstrekt en de projectduur is drie jaar. Iedereen dezelfde medicatie Hoe zit het nu met die drie onderdelen van het onderzoek? Visser legt het bondig uit: “We werken niet met placebo, er zijn geen interventies, iedereen krijgt dezelfde medicijnen. Voor de eerste biomarker nemen we bij iedere geïncludeerde patiënt naast de normale bloedafname ook een extra buisje bloed af. Daarmee kijken we wat er gebeurt qua omzetting van het medicijn in de cel door de bloedspiegels te bekijken.” Bij de tweede biomarker kijken de onderzoekers naar weefsel. Bij dit onderdeel krijgt eerder afgenomen tumorweefsel een kleuring. “We denken dat er enkele voorspellen de genexpressies zijn. Als de blokjes weefsel gekleurd zijn, dan kijken we of er een relatie is tussen kleurscore en levensduur of progressie.” Dan is er nog een derde vorm en daarbij vindt ook afname van een extra buisje bloed plaats, maar nu kijken de onderzoekers naar DNA-verschillen. Visser: “De Alimta-medicatie komt via de bloedbaan in de tumorcel terecht, wordt daar omgezet en verlaat de cel weer. Daarbij spelen diverse eiwitten een rol. Als bijvoorbeeld stukjes in de receptorcel afwijken, kan dat zorgen voor een andere werking van het middel. Naar die verschillen kijken we dus.”

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Prima sfeer en begeleiding Het onderzoek vindt plaats met een studiegroep over meerdere centra. “Maar het Amphia Ziekenhuis vormt wel een zwaartepunt, omdat we hier de meeste patiënten includeren”, zegt Visser. Ze is erg tevreden over de begeleiding die ze krijgt van de begeleider dr. Aerts. “Ik ben behoorlijk vrij in mijn handelen, maar begeleiding en sturing worden wel aangeboden. Dat evenwicht is heel belangrijk. Bovendien is de sfeer hier op Longgeneeskunde heel prettig. Op deze afdeling is een mooi onderzoeksklimaat aan het ontstaan. Ik wil hier graag de opleiding volgen tot longarts.”

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Kerngegevens Zorgkern Longgeneeskunde • 9 Longartsen: dr. J.G.J.V. (Joachim) Aerts, J. (Jerryll) Asin, T.A. (Theo) Bantje, H.N.A. (Huub) Belderbos, R.S. (Remco) Djamin, dr. M.J.J.H. (Marco) Grootenboers, A.M. (André) Janssens, V.M.J. (Vic) Linsen, N.C. (Nico) van Walree • 1 chef de clinique: dr. V. (Vicky) Nowé, longarts • 5 assistenten in opleiding • 6 assistenten niet in opleiding • Subspecialismen: astma en allergologie, COPD, interstitiële longziekten, longziekten, longkanker, slaapapneu en niet invasieve (masker)thuisbeademing

Samenvattingen gepubliceerde artikelen Uzun S, Djamin RS, Kluytmans J, Van’t Veer NE, Ermens AA, Pelle AJ, Mulder P, van der Eerden MM, Aerts J. Influence of macrolide maintenance therapy and bacterial colonisation on exacerbation frequency and progression of COPD (COLUM BUS): study protocol for a randomised controlled trial. Trials. 2012 Jun 9;13:82. BACKGROUND: Chronic obstructive pulmonary disease (COPD) is characterised by progressive development of airflow limitation that is poorly reversible. Because of a poor understanding of COPD pathogenesis, treatment is mostly symptomatic and new therapeutic strategies are limited. There is a direct relationship between the se verity of the disease and the intensity of the inflammatory response. Besides smoking, one of the hypotheses for the persistent airway inflammation is the presence of recur rent infections. Macrolide antibiotics have bacteriostatic as well as anti-inflammatory properties in patients with cystic fibrosis and other inflammatory pulmonary diseases. There is consistent evidence that macrolide therapy reduces infectious exacerbations, decreases the requirement for additional antibiotics and improves nutritional mea sures. Because of these positive effects we hypothesised that maintenance macrolide therapy may also have beneficial effects in patients with COPD who have recurrent exacerbations. The effects on development of bacterial resistance to macrolides due to this long-term treatment are unknown. Until now, studies investigating macrolide therapy in COPD are limited. The objective of this study is to assess whether mainte nance treatment with macrolide antibiotics in COPD patients with three or more exac erbations in the previous year decreases the exacerbation rate in the year of treatment and to establish microbial resistance due to the long-term treatment. METHODS/DESIGN: The study is set up as a prospective randomised double-blind placebo-controlled single-centre trial. A total of 92 patients with COPD who have had at least three exacerbations of COPD in the previous year will be included. Subjects will be randomised to receive either azithromycin 500 mg three times a week or placebo. Our primary endpoint is the reduction in the number of exacerbations of COPD in the year of treatment. DISCUSSION: We investigate whether long-term therapy with macrolide antibiotics can prevent exacerbations in patients with COPD. Additionally, our study aims to

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assess the effect of long-term use of macrolide on the development of antimicrobial resistance and on inflammatory parameters related to COPD. We believe this study will provide more data on the effects of macrolide treatment in patients in COPD and will add more knowledge on its working mechanisms. TRIAL REGISTRATION: http://www.clinicaltrials.gov NCT00985244. PMID: 22682323 - PMCID: PMC3478173

Hou J, Lambers M, den Hamer B, den Bakker MA, Hoogsteden HC, Grosveld F, Hegmans J, Aerts J, Philipsen S. Expression profiling-based subtyping identifies novel non-small cell lung cancer subgroups and implicates putative resistance to pemetrexed therapy. J Thorac Oncol. 2012 Jan;7(1):105-14. INTRODUCTION: A challenge of cancer therapy is to optimize therapeutical options to individual patients. Cancers with similar histology may show dramatically different responses to therapy, indicating that a refined approach needs to be developed to classify tumors by intrinsic characteristics that may predict response to chemotherapy. Global expression profile-based classification has the potential to identify such tu mor-intrinsic subclasses. Pemetrexed effectiveness has been related to the expression of its target thymidylate synthase. The relatively frequent resistance of squamous cell carcinoma to Pemetrexed is correlated with high levels of thymidylate synthase expression. METHODS: A global expression profile-based molecular classification of non-small cell lung cancer (NSCLC) was performed. Gene expression was used to predict Pemetrexed responsiveness. The distinct molecular attributes of NSCLCs predicted likely to be resistant to Pemetrexed were bioinformatically characterized. We tested if routine immunohistochemical markers can be used to distinguish putative Peme trexed responders, predicted by gene signatures, from nonresponders. RESULTS: Ninety NSCLCs were divided into six subclasses by gene expression signa tures. The relevance of this novel phenotyping was linked to other tumor characteris tics. Two of the subclasses correlated to putative Pemetrexed resistance. In addition, the identified signature genes characterizing putative Pemetrexed responsiveness predicted therapeutic benefit in a subset of squamous cell carcinoma. CONCLUSIONS: Gene expression signatures can be used to identify NSCLC subgroups and have potential to predict resistance to Pemetrexed therapy. We suggest that a combination of classical pathological markers can be used to identify molecular tumor subclasses associated with predicted Pemetrexed response. PMID: 22134068

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Cornelissen R, Aerts JG, Hegmans JP. Immuno-Oncology and Immunotherapy. In: Mesotheliomas - Synonyms and Definition, Epidemiology, Etiology, Pathogenesis, Cyto-Histopathological Features, Clinic, Diagnosis, Treatment, Prognosis / Alexander Zubritsky [ed.] - [s.l.] : Intech, 2012. Chapt. 8 ; p. 97-120. ISBN: 978-953-307-845-8. Heuvers ME, Hegmans JP, Stricker BH, Aerts JG. Improving lung cancer survival; time to move on. BMC Pulm Med. 2012 Dec 13;12:77. BACKGROUND: During the past decades, numerous efforts have been made to decrease the death rate among lung cancer patients. Nonetheless, the improvement in long-term survival has been limited and lung cancer is still a devastating disease. DISCUSSION: With this article we would like to point out that survival of lung cancer could be strongly improved by controlling two pivotal prognostic factors: stage and treatment. This is corresponding with recent reports that show a decrease in lung cancer mortality by screening programs. In addition, modulation of the patient’s immune system by immunotherapy either as monotherapy or combined with conventional cancer treatments offers the prospect of tailoring treatments much more precisely and has also been shown to lead to a better response to treatment and overall survival of non-small cell lung cancer patients. SUMMARY: Since only small improvements in survival can be expected in advanced disease with the use of conventional therapies, more research should be focused on lung cancer screening programs and patient tailored immunotherapy with or without conventional therapies. If these approaches are clinically combined in a standard multidisciplinary policy we might be able to advance the survival of patients with lung cancer. PMID: 23234250 - PMCID: PMC3528634

Heuvers ME, Aerts JG, Cornelissen R, Groen H, Hoogsteden HC, Hegmans JP. Patient-tailored modulation of the immune system may revolutionize future lung cancer treatment. BMC Cancer. 2012 Dec 5;12:580. Cancer research has devoted most of its energy over the past decades on unraveling the control mechanisms within tumor cells that govern its behavior. From this we know that the onset of cancer is the result of cumulative genetic mutations and epigenetic alterations in tumor cells leading to an unregulated cell cycle, unlimited replicative potential and the possibility for tissue invasion and metastasis. Until recent ly it was often thought that tumors are more or less undetected or tolerated by the patient’s immune system causing the neoplastic cells to divide and spread without resistance. However, it is without any doubt that the tumor environment contains a wide variety of recruited host immune cells. These tumor infiltrating immune cells influence anti-tumor responses in opposing ways and emerges as a critical regulator Longgeneeskunde

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of tumor growth. Here we provide a summary of the relevant immunological cell types and their complex and dynamic roles within an established tumor microenvironment. For this, we focus on both the systemic compartment as well as the local presence within the tumor microenvironment of late-stage non-small cell lung cancer (NSCLC), admitting that this multifaceted cellular composition will be different from earlier stages of the disease, between NSCLC patients. Understanding the paradoxical role that the immune system plays in cancer and increasing options for their modulation may alter the odds in favor of a more effective anti-tumor immune response. We predict that the future standard of care of lung cancer will involve patient-tailor-made combination therapies that associate (traditional) chemotherapeutic drugs and biolog icals with immune modulating agents and in this way complement the therapeutic armamentarium for this disease. PMID: 23217146 - PMCID: PMC3533940

Cornelissen R, Lievense LA, Heuvers ME, Maat AP, Hendriks RW, Hoogsteden HC, Hegmans JP, Aerts JG. Dendritic cell-based immunotherapy in mesothelioma. Immunotherapy. 2012 Oct;4(10):1011-22. Mesothelioma is a rare thoracic malignancy with a dismal prognosis. Current treat ment options are scarce and clinical outcomes are rather disappointing. Due to the immunogenic nature of mesothelioma, several studies have investigated immunother apeutic strategies to improve the prognosis of patients with mesothelioma. In the last decade, progress in knowledge of the modulation of the immune system to attack the tumor has been remarkable, but the optimal strategy for immunotherapy has yet to be unraveled. Because of their potent antigen-presenting capacity, dendritic cells are acknowledged as a promising agent in immunotherapeutic approaches in a number of malignancies. This review gives an update and provides a future perspective in which immunotherapy may improve the outcome of mesothelioma therapy. PMID: 23148753

Heuvers ME, Wisnivesky J, Stricker BH, Aerts JG. Generalizability of results from the National Lung Screening Trial. Eur J Epidemiol. 2012 Sep;27(9):669-72. Epub 2012 Aug 8. Lung cancer is the major cause of cancer-related death worldwide, with a 5-year surviv al of only 16%. Most lung cancer cases are diagnosed at an advanced incurable stage. As earlier stages have a better prognosis, the key to reducing mortality could be early diagnosis of the disease. At present, low-dose computed tomographic (CT) screening has shown promising data. Lung cancer death rates were reduced by 20% when CT screening is compared to chest radiography in a high-risk group. There are many advantages of CT screening in lung cancer, however there are also some important issues that should be taken into account. Therefore, the applicability of the results to Longgeneeskunde

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clinical practice is not clear yet. In this Commentary we discuss different aspects that play important roles in the balance between harms and benefits of screening, inclu ding overdiagnosis, availability of treatment options worldwide, ethical considerations, costs, and prolonged life expectancy. We conclude that clinicians should be cautious in generalizing findings to the total population of smokers and take into account that the use of lung cancer screening in clinical practice may have limitations. PMID: 22872503

Cornelissen R, Heuvers ME, Maat AP, Hendriks RW, Hoogsteden HC, Aerts JG, Hegmans JP. New roads open up for implementing immunotherapy in mesothelioma. Clin Dev Immunol. 2012;2012:927240. Epub 2012 Jun 24. Treatment options for malignant mesothelioma are limited, and the results with con ventional therapies have been rather disappointing to this date. Chemotherapy is the only evidence-based treatment for mesothelioma patients in good clinical condition, with an increase in median survival of only 2 months. Therefore, there is urgent need for a different approach to battle this malignancy. As chronic inflammation precedes mesothelioma, the immune system plays a key role in the initiation of this type of tumour. Also, many immunological cell types can be found within the tumour at diffe rent stages of the disease. However, mesothelioma cells can evade the surveillance capacity of the immune system. They build a protective tumour microenvironment to harness themselves against the immune system’s attacks, in which they even abuse immune cells to act against the antitumour immune response. In our opinion, modu lating the immune system simultaneously with the targeting of mesothelioma tumour cells might prove to be a superior treatment. However, this strategy is chal lenging since the tumour microenvironment possesses numerous forms of defence strategies. In this paper, we will discuss the interplay between immunological cells that can either inhibit or stimulate tumour growth and the challenges associated with immunotherapy. We will provide possible strategies and discuss opportunities to overcome these problems. PMID: 22778767 - PMCID: PMC3388483

Van Belle S, Swieboda-Sadlej A, Karanikiotis C, Labourey JL, Galid A, Wheeler T, Pujol B, Aerts JG. A final analysis from the CHOICE study examining darbepoetin alfa use for chemotherapy-induced anaemia in current European clinical practice. Curr Med Res Opin. 2012 Jul;28(7):1079-87. Epub 2012 Jun 21. OBJECTIVES: The CHOICE study was a prospective, multicentre, observational study designed to assess the level of adherence in current clinical practice to the European product label and the EORTC guidelines for the treatment of chemotherapy-induced anaemia with darbepoetin alfa (DA). Longgeneeskunde

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METHODS: Hb levels and red blood cell (RBC) transfusion requirements were evaluat ed among 1900 patients with solid tumours in 11 European countries. The primary outcome measure was the proportion of patients with a target Hb level of ≥10-≥12 g/dL after 9 weeks’ DA treatment. RESULTS: The full analysis set included 1887 patients (mean ± SD 62.4 ± 11.4 years); 1585 (84%) had a current disease stage of ≥3. Common chemotherapy regimens were non-platinum + non-taxane based (n = 696 [37%]) or platinum + non-taxane based (n = 660 [35%]). Breast cancer (n = 575): The mean ± SD Hb level at baseline was 9.9 ± 0.8 g/dL (n = 568). Target Hb level was reached by 187 (55%) patients. Colorectal cancer (n = 310): At baseline the mean ± SD Hb level was 9.8 ± 0.8 g/dL (n = 306). Target Hb level was reached by 107 patients (56%). Ovarian cancer (n = 301): The mean ± SD Hb level at baseline was 9.7 ± 0.8 g/dL (n = 294). Target Hb level was reached by 81 pa tients (44%). Lung cancer (n = 701): At baseline the mean ± SD Hb level was 9.8 ± 0.9 g/dL (n = 692). Target Hb level was reached by 142 patients (39%). Safety: Five severe or life-threatening adverse drug reactions were seen (three patients with breast cancer, one patient with colorectal cancer and one patient with ovarian cancer). Lim itations: Potential bias could not be excluded due to the study’s observational nature. CONCLUSIONS: DA initiation and target Hb ranges adhered to current guidelines in the majority of patients. Furthermore, this study demonstrates faster achievement of the target range and reduced transfusion requirements are associated with initiation of DA at Hb levels of 9-<10 g/dL and 10-<11 g/dL rather than <9 g/dL. PMID: 22642867

Aerts JG, Swieboda-Sadlej A, Karanikiotis C, Labourey JL, Galid A, Wheeler T, Pujol B, Van Belle S. Use of darbepoetin alfa in European clinical practice for the management of chemotherapy-induced anaemia in four tumour types: final data from the CHOICE study. Curr Med Res Opin. 2012 Jul;28(7):1089-99. Epub 2012 Jun 21. OBJECTIVES: The CHOICE study was a prospective, multicentre, observational study designed to assess levels of adherence in current clinical practice to the European product label and EORTC guidelines for the treatment of chemotherapy-induced anaemia (CIA) with darbepoetin alfa (DA). Here we present data split by tumour types: breast, colorectal, ovarian and lung. METHODS: Haemoglobin (Hb) levels and red blood cell transfusion requirements were evaluated among patients with solid tumours in 11 European countries. The primary outcome measure was the proportion of patients with a target Hb level of ≥10- 12 g/dL. RESULTS: The full analysis set included 1887 patients (mean ± SD 62.4 ± 11.4 years); 1585 (84%) had a current disease stage of ≥3. Common chemotherapy regimens were Longgeneeskunde

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non-platinum + non-taxane based (n = 696 [37%]) or platinum + non-taxane based (n = 660 [35%]). Breast cancer (n = 575): The mean ± SD Hb level at baseline was 9.9 ± 0.8 g/dL (n = 568). Target Hb level was reached by 187 (55%) patients. Colorectal cancer (n = 310): At baseline the mean ± SD Hb level was 9.8 ± 0.8 g/dL (n = 306). Target Hb level was reached by 107 patients (56%). Ovarian cancer (n = 301): The mean ± SD Hb level at baseline was 9.7 ± 0.8 g/dL (n = 294). Target Hb level was reached by 81 patients (44%). Lung cancer (n = 701): At baseline the mean ± SD Hb level was 9.8 ± 0.9 g/dL (n = 692). Target Hb level was reached by 142 patients (39%). Safety: Five severe or life-threaten ing adverse drug reactions were seen (three patients with breast cancer, one patient with colorectal cancer and one patient with ovarian cancer). Limitations: Potential bias could not be excluded due to the study’s observational nature. CONCLUSIONS: This study demonstrates that the recommendations are adhered to in clinical practice, with the mean starting Hb level <10 g/dL irrespective of tumour type. Furthermore, DA is likely to be effective and well tolerated for the treatment of CIA in patients with breast, colorectal, ovarian or lung cancer. PMID: 22642866

Van der Leest C, Amelink A, van Klaveren RJ, Hoogsteden HC, Sterenborg HJ, Aerts JG. Optical detection of preneoplastic lesions of the central airways. Immunotherapy. 2012 Oct;4(10):1011-22. Current routine diagnosis of premalignant lesions of the central airways is hampered due to a limited sensitivity (white light bronchoscopy) and resolution (computer to mography (CT), positron emission tomography (PET)) of currently used techniques. To improve the detection of these subtle mucosal abnormalities, novel optical imaging bronchoscopic techniques have been developed over the past decade. In this review we highlight the technological developments in the field of endoscopic imaging, and describe their advantages and disadvantages in clinical use. PMID: 22550600 - PMCID: PMC3324886

Heuvers ME, Stricker BH, Aerts JG. Generalizing lung-cancer screening results. N Engl J Med. 2012 Jan 12;366(2):192-3. [No abstract available] Erratum in: N Engl J Med. 2012 Feb 16;366(7):672. Aerts, Joachin G [corrected to Aerts, Joachim G]. PMID: 22236243[

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Heuvers ME, Aerts JG, Hegmans JP, Veltman JD, Uitterlinden AG, Ruiter R, Rodenburg EM, Hofman A, Bakker M, Hoogsteden HC, Stricker BH, van Klaveren RJ. History of tuberculosis as an independent prognostic factor for lung cancer survival. Lung Cancer. 2012 Jun;76(3):452-6. Epub 2012 Jan 9. INTRODUCTION: It is well known that pulmonary tuberculosis is associated with an increased risk of lung cancer. We investigated whether a history of pulmonary tu berculosis is an independent risk factor for lung cancer survival in Caucasian patients. METHODS: The data of the prospective population-based cohort of The Rotterdam Study were used. During a mean follow-up time of 18 years, there were 214 incident cases of pathology-proven lung cancer in a source population of 7983 study partici pants. History of tuberculosis was assessed at baseline by interviewers using standar dized questionnaires. Associations of lung cancer survival with the occurrence of pulmonary tuberculosis were assessed using Cox’s proportional hazard regression analysis adjusted for age, gender, pack-years, educational level and tumor stage. RESULTS: A history of tuberculosis was reported in 13 of the 214 subjects with lung cancer. The survival of patients with lung cancer was significantly shorter in subjects with a history of pulmonary tuberculosis (HR=2.36, CI95%: 1.1-4.9), than in subjects without a history of pulmonary tuberculosis with a mean difference of 311 days. CONCLUSION: The presence of a history of pulmonary tuberculosis may be an important prognostic factor in the survival of lung cancer. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved. PMID: 22226628 [PubMed - indexed for MEDLINE]

Carvalho RH, Haberle V, Hou J, van Gent T, Thongjuea S, van Ijcken W, Kockx C, Brouwer R, Rijkers E, Sieuwerts A, Foekens J, van Vroonhoven M, Aerts J, Grosveld F, Lenhard B, Philipsen S. Genome-wide DNA methylation profiling of non-small cell lung carcinomas. Epigenetics Chromatin. 2012 Jun 22;5(1):9. BACKGROUND: Non-small cell lung carcinoma (NSCLC) is a complex malignancy that owing to its heterogeneity and poor prognosis poses many challenges to diagnosis, prognosis and patient treatment. DNA methylation is an important mecha nism of epigenetic regulation involved in normal development and cancer. It is a very stable and specific modification and therefore in principle a very suitable marker for epigenetic phenotyping of tumors. Here we present a genome-wide DNA methylation

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analysis of NSCLC samples and paired lung tissues, where we combine MethylCap and next generation sequencing (MethylCap-seq) to provide comprehensive DNA methylation maps of the tumor and paired lung samples. The MethylCap-seq data were validated by bisulfite sequencing and methyl-specific polymerase chain reaction of selected regions. RESULTS: Analysis of the MethylCap-seq data revealed a strong positive correlation between replicate experiments and between paired tumor/lung samples. We identi fied 57 differentially methylated regions (DMRs) present in all NSCLC tumors analyzed by MethylCap-seq. While hypomethylated DMRs did not correlate to any particular functional category of genes, the hypermethylated DMRs were strongly associated with genes encoding transcriptional regulators. Furthermore, subtelomeric regions and satellite repeats were hypomethylated in the NSCLC samples. We also identified DMRs that were specific to two of the major subtypes of NSCLC, adenocarcinomas and squamous cell carcinomas. CONCLUSIONS: Collectively, we provide a resource containing genome-wide DNA methylation maps of NSCLC and their paired lung tissues, and comprehensive lists of known and novel DMRs and associated genes in NSCLC. PMID: 22726460 - PMCID: PMC3407794

Slort W, Vilrokx C, Belderbos H, Loosveld O,Thijssen F, Frankenhuis R, Bennink C. Specialisten en huisartsen spreken met ongeneeslijk zieke oncologische patiënten over de laatste levensfase. Een regionale pilot met ‘Advance Care Planning’. Ned-Vlaams Tijdschr voor Palliatieve Zorg. 2012;12(2):28-39. Background: Discussing various end-of-life issues with palliative care patients in time is considered to be an essential requirement for the delivery of high-quality pallia tive care. Besides, the several doctors treating a palliative care patient in hospital and at home frequently communicate insufficiently with each other about this proactive palliative care. Aim: Implementation of a newly developed method of ‘Advance Care Planning’ will en courage oncology specialists and general practitioners to discuss various end-of-life is sues with palliative care patients and with each other. Method: We registered the number of palliative care patients included by oncology specialists, how often these specialists communicated with general practitioners about a patient, and how often general practitioners informed specialists of patients’ ‘Advance Care Planning’ preferences. Besides, patients, surviving next-of-kin, specialists and general practitioners were interviewed about their experiences with the ‘Advance Care Planning’ method.

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Results: The specialists included 97 patients. Of the 84 times the specialist tele phoned the general practitioner, this was 59 times successful. General practitioners in formed the specialist of preferences of 33 patients; with 32 of them the resuscitation status was discussed. The 17 patients and 10 surviving next-of-kin who were inter viewed felt that they were well-informed about their condition and consequently could timely arrange their affairs. The ‘Advance Care Planning’ method was appreciat ed as useful by the participating specialists and general practitioners. Conclusion: Our results suggest that the new ‘Advance Care Planning’ method was usable and encouraged oncology specialists and general practitioners to discuss endof-life issues with their palliative care patients.

Büller HR, Gallus AS, Pillion G, Prins MH, Raskob GE; Cassiopea Investigators* [Grootenboers MJ et al...]. Enoxaparin followed by once-weekly idrabiotaparinux versus eno xaparin plus warfarin for patients with acute symptomatic pulmonary embolism: a randomised, double-blind, double-dummy, non-inferiority trial. Lancet. 2012 Jan 14;379(9811):123-9. Epub 2011 Nov 28. BACKGROUND: Treatment of pulmonary embolism with low-molecular-weight heparin and vitamin K antagonists, such as warfarin, is not ideal. We aimed to assess non-inferiority of idrabiotaparinux, a reversible longlasting indirect inhibitor of activat ed factor X, to warfarin in patients with acute symptomatic pulmonary embolism. METHODS: In our randomised, double-blind, double-dummy, non-inferiority trial, we enrolled adults with objectively documented acute symptomatic pulmonary embolism attending 291 centres in 37 countries. We excluded patients who were pregnant, had active bleeding, kidney failure, or malignant hypertension, or were at high risk of death, bleeding, or adverse reactions to study drugs. We randomly allocated patients to receive 5-10 days’ enoxaparin 1·0 mg/kg twice daily followed by subcutaneous idrabiotaparinux (starting dose 3·0 mg) or adjusted-dose warfarin (target international normalised ratio 2·0-3·0); regimens lasted 3 months or 6 months dependent on clinical presentation. Block randomisation was done with a central interactive computerised system, stratified by study centre and intended treatment duration. The primary efficacy outcome was recurrent venous thromboembolism at 99 days after randomisation. We estimated the odds ratio and 95% CI with a Mantel-Haenzsel x(2) analysis (non-inferiority margin 2·0) in the intention-to-treat population. The main safety outcome was clinically relevant bleeding (major or non-major) in all patients at day 99. This study is registered with ClinicalTrials.gov, number NCT00345618.

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FINDINGS: Between Aug 1, 2006, and Jan 31, 2010, we enrolled 3202 patients aged 18-96 years. 34 (2%) of 1599 patients randomly allocated to receive enoxaparin-idra biotaparinux and 43 (3%) of 1603 patients randomly allocated to receive noxaparinwarfarin had recurrent venous thromboembolism (odds ratio 0·79, 95% CI 0·50-1·25; p(non-inferiority)=0·0001). 72 (5%) of 1599 patients in the enoxaparin-idrabio taparinux group and 106 (7%) of 1603 patients in the enoxaparin-warfarin group had clinically relevant bleeding (0·67, 0·49-0·91; p(superiority)=0·0098). We noted similar differences in outcomes in those patients treated to 6 months. INTERPRETATION: Idrabiotaparinux could provide an attractive alternative to warfarin for the long-term treatment of pulmonary embolism, and seems to be associated with reduced bleeding. FUNDING: Sanofi-Aventis (Paris, France). Collaborators (314): Grootenboers M. [et al... ] Copyright © 2012 Elsevier Ltd. All rights reserved. Comment in: Idrabiotaparinux treatment for venous thromboembolism. [Lancet. 2012] Idrabiotaparinux treatment for venous thromboembolism.Eikelboom JW, Weitz JI. Lancet. 2012 Jan 14; 379(9811):96-8. Epub 2011 Nov 27. Anticoagulation therapy: Idrabiotaparinux noninferior to warfarin for long-term treatment of pulmonary embolism. [Nat Rev Cardiol. 2011] Anticoagulation therapy: Idrabiotaparinux noninferior to warfarin for long-term treatment of pulmonary embolism.Lim GB. Nat Rev Cardiol. 2011 Dec 13; 9(2):68. Epub 2011 Dec 13. PMID: 22130488

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Mondziekten, Kaak- en Aangezichtschirurgie Kerngegevens Zorgkern Mondziekten, Kaak- en Aangezichtschirurgie • 6 kaakchirurgen: dr. J.E. (Eelco) Bergsma, J.M.T. (Jan) van Gemert, dr. P.J.J (Peter) Gooris, E. (Eric) van Hooft, dr. G. (Gertjan) Mensink, dr. A.B.E. (Bert) Voûte • 2 assistenten in opleiding • 3 assistenten niet in opleiding • Subspecialismen: implantologie, orthognatische chirurgie; oncologie; traumatologie; orale pathologie; orbitopathie; aangezichtschirurgie; kaakgewrichtspathologie

Samenvattingen gepubliceerde artikelen Buijs GJ, van Bakelen NB, Jansma J, de Visscher JG, Hoppenreijs TJ, Bergsma JE, Stegenga B, Bos RR. A randomized clinical trial of biodegradable and titanium fixation systems in maxillofacial surgery. J Dent Res. 2012 Mar;91(3):299-304. Epub 2012 Jan 23. Biodegradable fixation systems could reduce or delete the problems associated with metallic systems, since removal is not necessary. The aim of this study was to establish the effectiveness and safety of biodegradable plates and screws as potential alter natives to metallic ones. This multi-center randomized controlled trial was conducted from December 2006 to July 2009. Included were patients who underwent mandi bular and/or Le Fort I osteotomies and those with fractures of the mandible, maxilla, and zygoma. The patients were assigned to a titanium control group (KLS Martin) or to a biodegradable test group (Inion CPS). The primary outcome measure was ‘bone hea ling 8 weeks post-operatively’. The Intention-To-Treat (ITT) analysis of 113 patients in the titanium group and 117 patients in the biodegradable group yielded a significant difference (p < 0.001), primarily because in 25 patients (21%) who were randomized to the biodegradable group, the surgeon made the decision to switch to titanium intraoperatively. Despite this ‘inferior’ primary outcome result, biodegradable plates and screws could be safely used when it was possible to apply them. The benefits of using biodegradable systems (fewer plate removal operations) should be confirmed during a follow-up of minimally 5 years (Controlled-trials.com ISRCTN number 44212338). PMID: 22269272

Mensink G, Richard van Merkesteyn JP. No chisels in BSSO? J Craniomaxillofac Surg. 2012 Dec 26. [Epub ahead of print]. No abstract available PMID: 23273649


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Den Besten CA, Mensink G, van Merkesteyn JP. Skeletal stability after mandibular advancement in bilateral sagittal split osteotomies during adolescence. J Craniomaxillofac Surg. 2012 Dec 17. [Epub ahead of print]. Bilateral sagittal split osteotomy (BSSO) is the most frequently performed surgery for correcting mandibular retrognathia. Few studies have reported the use of BSSO in young patients, as growth may cause relapse. The aim of the present study was to determine the amount of relapse after performing BSSO in patients aged less than 18 years. Patients who had a mandibular advancement by BSSO surgery between January 2003 and June 2008 were evaluated. Eighteen patients were treated before the age of 18 years and compared with patients treated at 20-24 years of age. Cephalometric ra diographs were used to determine the amount of relapse. For patients aged less than 18 years, the mean horizontal relapse after 1 year was 0.5 mm, (10.9% of perioperative advancement). For patients aged 20-24 years, the mean relapse was 0.9 mm, (16.4% of perioperative advancement). There were no significant differences between the age groups (p > 0.05). In conclusion, the BSSO procedure is a relatively stable procedure, even during adolescence. Copyright © 2012 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved. PMID: 23253633

Mensink G, Zweers A, Wolterbeek R, Dicker GG, Groot RH, van Merkesteyn RJ. Neuro sensory disturbances one year after bilateral sagittal split osteotomy of the mandibula performed with separators: a multi-centre prospective study. J Craniomaxillofac Surg. 2012 Dec;40(8):763-7. Epub 2012 Mar 20. Bilateral sagittal split osteotomy (BSSO) is an effective and commonly used treatment to correct mandibular hypo- and hyperplasia. Hypoesthesia of the inferior alveolar nerve (IAN) is a common complication of this surgical procedure. This prospective multi-centre study aimed to determine the incidence of neurosensory disturbances of the IAN after BSSO procedures performed without the use of chisels. Our study group comprised 158 patients, with a follow-up period of 1 year, who underwent BSSO (with or without Le Fort I) that incorporated the use of sagittal split separators and splitters but no chisels. The percentage of BSSO split procedures that resulted in IAN damage was 5.1%. The percentage of patients (without genioplasty) who experienced IAN damage was 8.9%. The concomitant genioplasty in combination with BSSO was significantly associated with hypoesthesia. Peri-operative removal of the wisdom


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tooth or a Le Fort I procedure did not influence post-operative hypoesthesia. We believe that the use of splitting forceps and elevators without chisels leads to a lower incidence of persistent post-operative hypoesthesia 1 year after BSSO of the mandible, without increasing the risk of a bad split. Copyright © 2012 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved. Comment in: Role of chisels in BSSO? [J Craniomaxillofac Surg. 2013] Role of chisels in BSSO?Hanzelka T, Foltán R. J Craniomaxillofac Surg. 2013 Mar; 41(2):87. Epub 2012 Aug 11. PMID: 22440316


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Neurologie Kerngegevens Zorgkern Neurologie • 12 neurologen: R. (Ron) van Dijl, dr. P.M.M. (Paul) van Erven, R.J. (Robert-Jan) de Graaf, mw. dr. I.A.W. (Irene) Kotsopoulos, H.B.M. (Hans) van Lieshout, M.J.M. (Michel) Remmers, mw. dr. J.F. (Johanneke) de Rijk - van Andel, dr. E.A.C.M. (Evert) Sanders, J.P.M. (Jan-Pieter) Stroy, H.B.C. (Henk) Verbiest, J.E. (Jasper) Visser, dr. J.C.M. (Jan) Zijlmans • 2 neurologen/kinderneurologen: mw. dr. I.A.W. (Irene) Kotsopoulos, mw. dr. J.F. (Johanneke) de Rijk - van Andel • 7 assistenten niet in opleiding • 3 research verpleegkundigen • Subspecialisme: kinderneurologie

Samenvattingen gepubliceerde artikelen Van Vliet R, Breedveld G, de Rijk-van Andel J, Brilstra E, Verbeek N, Verschuuren-Bemel mans C, Boon M, Samijn J, Diderich K, van de Laar I, Oostra B, Bonifati V, Maat-Kievit A. PRRT2 phenotypes and penetrance of paroxysmal kinesigenic dyskinesia and infantile convulsions. Neurology. 2012 Aug 21;79(8):777-84. Epub 2012 Aug 8. OBJECTIVE: To describe the phenotypes and penetrance of paroxysmal kinesigenic dyskinesia (PKD), a movement disorder characterized by attacks of involuntary move ments occurring after sudden movements, infantile convulsion and choreoathetosis (ICCA) syndrome, and benign familial infantile convulsions (BFIC), caused by PRRT2 mutations. METHODS: We performed clinical and genetic studies in 3 large families with ICCA, 2 smaller families with PKD, and 4 individuals with sporadic PKD. Migraine was also present in several individuals. RESULTS: We detected 3 different PRRT2 heterozygous mutations: the recurrent p.Arg217Profs*8 mutation, previously reported, was identified in 2 families with ICCA, 2 families with PKD, and one individual with sporadic PKD; one novel missense mutation (p.Ser275Phe) was detected in the remaining family with ICCA; and one novel truncat ing mutation (p.Arg217*) was found in one individual with sporadic PKD. In the 2 remaining individuals with sporadic PKD, PRRT2 mutations were not detected. Impor tantly, PRRT2 mutations did not cosegregate with febrile convulsions or with migraine. The estimated penetrance of PRRT2 mutations was 61%, if only the PKD phenotype was considered; however, if infantile convulsions were also taken into account, the penetrance was nearly complete. Considering our findings and those reported in literature, 23 PRRT2 mutations explain ~56% of the families analyzed.

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CONCLUSIONS: PRRT2 mutations are the major cause of PKD or ICCA, but they do not seem to be involved in the etiology of febrile convulsions and migraine. The identification of PRRT2 as a major gene for the PKD-ICCA-BFIC spectrum allows better disease classification, molecular confirmation of the clinical diagnosis, and genetic testing and counseling. PMID: 22875091

Ketelslegers IA, Catsman-Berrevoets CE, Neuteboom RF, Boon M, van Dijk KG, Eikelenboom MJ, Gooskens RH, Niks EH, Overweg-Plandsoen WC, Peeters EA, Peeters-Scholte CM, Poll-The BT, de Rijk-van Andel JF, Samijn JP, Snoeck IN, Stroink H, Vermeulen RJ, Verrips A, Vles JS, Willemsen MA, Rodrigues Pereira R, Hintzen RQ. Incidence of acquired demyelinating syndromes of the CNS in Dutch children: a nationwide study. J Neurol. 2012 Sep;259(9):1929-35. Epub 2012 Feb 17. Acquired demyelinating syndromes (ADS) can be a first presentation of multiple sclerosis (MS) in children. The incidence of these disorders in Europe is currently unknown. Children (<18 years old) living in the Netherlands who presented with ADS were included from January 1, 2007 to December 31, 2010 by the Dutch pediatric MS study group and the Dutch surveillance of rare pediatric disorders. Demographic and clinical data were collected. Eighty-six patients were identified over 4 years, resulting in an incidence of 0.66/1,00,000 per year. Most patients presented with polyfocal ADS without encephalopathy (30%), followed by polyfocal ADS with encephalopathy (24%), optic neuritis (ON, 22%), monofocal ADS (16%), transverse myelitis (3%), and neuromy elitis optica (3%). Patients with polyfocal ADS with encephalopathy were younger (me dian 3.9 years) than patients with ON (median 14.6 years, p < 0.001) or monofocal ADS (median 16.0 years, p < 0.001). Patients with polyfocal ADS without encephalopathy (median 9.2 years) were also younger than monofocal ADS patients (median 16.0 years, p < 0.001). There was a slight female preponderance in all groups except the ON group, and a relatively large number of ADS patients (29%) reported a non-European ancestry. Familial autoimmune diseases were reported in 23%, more often in patients with relapsing disease than monophasic disease (46 vs. 15%, p = 0.002) and occurring most often in the maternal family (84%, p < 0.001). During the study period, 23% of patients were subsequently diagnosed with MS. The annual incidence of ADS in the Netherlands is 0.66/1,00,000 children/year. A polyfocal disease onset of ADS was most common. PMID: 22349866

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Glass PG, Lees AJ, Bacellar A, Zijlmans J, Katzenschlager R, Silveira-Moriyama L. The clinical features of pathologically confirmed vascular parkinsonism. J Neurol Neurosurg Psychiatry. 2012 Oct;83(10):1027-9. OBJECTIVE: To evaluate in detail the clinical features in a large series of pathologically confirmed cases of vascular Parkinsonism (VP). BACKGROUND: In the absence of widely accepted diagnostic criteria for VP patho logical confirmation of diagnosis is necessary to ensure diagnostic reliability, and has only been reported in a few small series. DESIGN/METHODS: The archival records of the Queen Square Brain Bank (QSBB) have been used to identify cases of Parkinsonism where cerebrovascular disease was the only pathological finding. Clinical notes were scrutinised and milestones of disease progression were compared with other atypical Parkinsonian syndromes from previous QSBB studies. RESULTS: Twenty-eight cases were included. Mean age of onset and disease duration were 70.6 (SD± 6.42) and 10.5 (SD± 66.1) years respectively. Bradykinesia was present in all cases, rigidity in 96%, falls in 76%, pyramidal signs in 54%, urinary incontinence in 50% and dementia in 39%.Visual hallucinations in 0%. Two-thirds had an insidious onset and a relentless rather than stepwise progression of disability. When compared with other Parkinsonian syndromes, VP had an older age of onset. CONCLUSIONS: In comparison with other Parkinsonian syndromes the patients were older and had an extremely low frequency of visual hallucinations compared with Parkinson’s disease. PMID: 22960987

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Nucleaire Geneeskunde Kerngegevens Zorgkern Nucleaire Geneeskunde • 2 nucleair geneeskundigen: J. (Jim) Baas, P.J. (Peter) van Noorden

Samenvattingen gepubliceerde artikelen Postma EL, Verkooijen HM, van Esser S, Hobbelink MG, van der Schelling GP, Koelemij R, Witkamp AJ, Contant C, van Diest PJ, Willems SM, Borel Rinkes IH, van den Bosch MA, Mali WP, van Hillegersberg R; ROLL study group [Van Noorden P, Baas J. et al...]. Efficacy of ‘radioguided occult lesion localisation’ (ROLL) versus ‘wire-guided localisa tion’ (WGL) in breast conserving surgery for non-palpable breast cancer: a randomised controlled multicentre trial. Breast Cancer Res Treat. 2012 Nov;136(2):469-78. Epub 2012 Sep 30. For the management of non-palpable breast cancer, accurate pre-operative localisation is essential to achieve complete resection with optimal cosmetic results. Radioguided occult lesions localisation (ROLL) uses the radiotracer, injected intra-tumourally for sentinel lymph node identification to guide surgical excision of the primary tumour. In a multicentre randomised controlled trial, we determined if ROLL is superior to the standard of care (i.e. wire-guided localisation, WGL) for preoperative tumour localisa tion. Women (>18 years.) with histologically proven non-palpable breast cancer and eli gible for breast conserving treatment with sentinel node procedure were randomised to ROLL or WGL. Patients allocated to ROLL received an intra-tumoural dose of 120 Mbq technetium-99 m nanocolloid. The tumour was surgically removed, guided by gamma probe detection. In the WGL group, ultrasound- or mammography-guided insertion of a hooked wire provided surgical guidance for excision of the primary tumour. Primary outcome measures were the proportion of complete tumour excisions (i.e. with nega tive margins), the proportion of patients requiring re-excision and the volume of tissue removed. Data were analysed according to intention-to-treat principle. This study is registered at ClinincalTrials.gov, number NCT00539474. In total, 314 patients with 316 invasive breast cancers were enrolled. Complete tumour removal with negative mar gins was achieved in 140/162 (86 %) patients in the ROLL group versus 134/152 (88 %) patients in the WGL group (P = 0.644). Re-excision was required in 19/162 (12 %) pa tients in the ROLL group versus 15/152 (10 %) (P = 0.587) in the WGL group. Specimen volumes in the ROLL arm were significantly larger than those in the WGL arm (71 vs. 64 cm(3), P = 0.017). No significant differences were seen in the duration and difficulty of the radiological and surgical procedures, the success rate of the sentinel node procedure, and cosmetic outcomes. In this first multicentre randomised controlled comparison of ROLL versus WGL in patients with histologically proven breast cancer, ROLL is comparable to WGL in terms of complete tumour excision and re-excision rates. ROLL, however, leads to excision of larger tissue volumes. Therefore, ROLL cannot replace WGL as the standard of care.


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*Collaborators (32): Van der Schelling G, Rijken A, Nuytinck J, Luiten E, Tetteroo E, Dijkstra H, Raaymakers P, Van Noorden P, Baas J, Vos D, Wijsman J, Koelemij R, Theunis sen E, van Esser S, van Wieringen A, Lavalaye J, Bollen T, Appelman M, Postma EL, Glaap L, Witkamp AJ, Rinkes IH, van Hillegersberg R, Hobbelink M, Fernandez A, Stapper G, van den Bosch M, Mali W, Verkooijen H, Willems SM, van Diest PJ, Contant C. PMID: 23053639


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Oogheelkunde Kerngegevens Zorgkern Oogheelkunde • 12 oogartsen: G.A. (Bert) Bakker, dr. T.P. (Thomas) Colen, F.J. (Fijs) van Dobben de Bruijn, dr. B.T.H. (Bart) van Dooren, mw. G. (Trudy) de Grip, mw. L.J.C. (Lidy) Hartman, mw. O. (Olivera) Jovanovic, mw. I.L.A. (Irene) van Liempt, dr. G.L. (Giorgio) Porro, mw. O.A.M. (Odette) Tigchelaar-Besling, mw. dr. J.J.M. (Jacqueline) Willemse-Assink, mw. C. (Christien) Weenen • 3 assistenten in opleiding • Subspecialismen: cornea, refractiechirurgie en laserbehandeling, traanwegchirurgie, ooglidchirurgie, Graves, glaucoom, medische retina, kinderoogheelkunde, neuropht halmologie, strabismus en ophthalmogenetica

Samenvattingen gepubliceerde artikelen Beckers HJ, Webers CA, Busch MJ, Brink HM, Colen TP, Schouten JS; The Dutch Adherence Study Group. Adherence improvement in Dutch glaucoma patients: a randomized controlled trial. Acta Ophthalmol. 2012 Oct 1. [Epub ahead of print]. Purpose: To study the effect of patient education and the TravAlert(‡) -Eyot(‡) drop guider on intraocular pressure (IOP) and adherence in patients with primary open angle glaucoma (POAG) or ocular hypertension (OHT) monitored with the TravAlert(‡) dosing aid. Methods: Multicentre, randomized, controlled clinical trial among 18 Dutch hospitals. Patients were randomized to one of the four study arms: (1) use of the dosing aid, (2) use of the dosing aid with the drop guider, (3) use of the dosing aid together with patient education or (4) use of the dosing aid and drop guider together with patient education. IOP was recorded at baseline and after 3 and 6 months. Data on adherence generated by the dosing aid were collected and studied at the end of the study. Results: Mean IOP dropped from 20.3 ± 5.7 mmHg at baseline to 16.3 ± 4.0 mmHg (right eye) after 6 months and from 20.2 ± 5.9 mmHg to 16.4 ± 4.1 mmHg (left eye). The mean adherence rate was 0.91 ± 0.1. IOP and adherence rate were not statistically different between the study arms. Patients with ‘drug holidays’ had a significantly higher mean IOP after 6 months. Patients who used the drop guider were less adhe rent. A lower adherence level was also associated with new patients with glaucoma and patients with a lower level of knowledge on glaucoma. Conclusion: Patient education is especially useful for new patients with glaucoma. The use of a drop guider does not improve adherence. Especially patients with ‘drug holidays’ are at risk for developing uncontrolled IOP levels. Copyright © 2012 Acta Ophthalmologica Scandinavica Foundation. PMID: 23025424

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Bleyen I, Saelens IE, van Dooren BT, van Rij G. Spontaneous corneal clearing after Descemet’s stripping. Ophthalmology. 2013 Jan;120(1):215. Comment on: Spontaneous corneal clearing after Descemet’s stripping without endothelial replacement. [Ophthalmology. 2012] Spontaneous corneal clearing after Descemet’s stripping without endothelial replacement. Shah RD, Randleman JB, Grossniklaus HE. Ophthalmology. 2012 Feb; 119(2):256-60. Epub 2011 Oct 7. Comment in: Spontaneous corneal clearing after Descemet’s stripping. Author reply. [Ophthalmology. 2013] Spontaneous corneal clearing after Descemet’s stripping. Author reply. Shah RD, Randleman JB. Ophthalmology. 2013 Jan; 120(1):215-6. PMID: 23283191

Van Koolwijk LM, Ramdas WD, Ikram MK, Jansonius NM, Pasutto F, Hysi PG, Macgregor S, Janssen SF, Hewitt AW, Viswanathan AC, ten Brink JB, Hosseini SM, Amin N, Despriet DD, Willemse-Assink JJ, Kramer R, Rivadeneira F, Struchalin M, Aulchenko YS, Weisschuh N, Zenkel M, Mardin CY, Gramer E, Welge-Lüssen U, Montgomery GW, Carbonaro F, Young TL; DCCT/EDIC Research Group, Bellenguez C, McGuffin P, Foster PJ, Topouzis F, Mitchell P, Wang JJ, Wong TY, Czudowska MA, Hofman A, Uitterlinden AG, Wolfs RC, de Jong PT, Oostra BA, Paterson AD; Wellcome Trust Case Control Consortium 2, Mackey DA, Bergen AA, Reis A, Hammond CJ, Vingerling JR, Lemij HG, Klaver CC, van Duijn CM. Common genetic determinants of intraocular pressure and primary open-angle glaucoma. PLoS Genet. 2012;8(5):e1002611. Epub 2012 May 3. Intraocular pressure (IOP) is a highly heritable risk factor for primary open-angle glaucoma and is the only target for current glaucoma therapy. The genetic factors which determine IOP are largely unknown. We performed a genome-wide association study for IOP in 11,972 participants from 4 independent population-based studies in The Netherlands. We replicated our findings in 7,482 participants from 4 additional cohorts from the UK, Australia, Canada, and the Wellcome Trust Case-Control Consor tium 2/Blue Mountains Eye Study. IOP was significantly associated with rs11656696, located in GAS7 at 17p13.1 (p=1.4x10(-8)), and with rs7555523, located in TMCO1 at 1q24.1 (p=1.6x10(-8)). In a meta-analysis of 4 case-control studies (total N = 1,432 glaucoma cases), both variants also showed evidence for association with glaucoma (p=2.4x10(-2) for rs11656696 and p=9.1x10(-4) for rs7555523). GAS7 and TMCO1 are highly expressed in the ciliary body and trabecular meshwork as well as in the lamina

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cribrosa, optic nerve, and retina. Both genes functionally interact with known glau coma disease genes. These data suggest that we have identified two clinically relevant genes involved in IOP regulation. Collaborators (59): Donnelly P, Barroso I, Blackwell JM, Bramon E, Brown MA, Casas JP, Corvin A, Deloukas P, Duncanson A, Jankowski J, Markus HS, Mathew CG, Palmer CN, Plomin R, Rautanen A, Sawcer SJ, Trembath RC, Viswanathan AC, Wood NW, Spencer CC, Band G, Bellenguez C, Freeman C, Hellenthal G, Giannoulatou E, Pirinen M, Pearson R, Strange A, Su Z, Vukcevic D, Donnelly P, Langford C, Hunt SE, Edkins S, Gwilliam R, Blackburn H, Bumpstead SJ, Dronov S, Gillman M, Gray E, Hammond N, Jayakumar A, McCann OT, Liddle J, Potter SC, Ravindrarajah R, Ricketts M, Waller M, Weston P, Widaa S, Whittaker P, Barroso I, Deloukas P, Mathew CG, Blackwell JM, Brown MA, Corvin A, McCarthy MI, Spencer CC. PMID: 22570627 - PMCID: PMC3342933

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Orthopedie Kerngegevens Zorgkern Orthopedie • 14 orthopedisch chirurgen: mw. Dr. A. Beumer (Annechien), A.F.A. (Ad) van Beurden, R. (Ronald) Boer, dr. S.B.T. (Stefan) Bolder, mw. M.P.J. (Maaike) van den Borne, L.H.G.J. (Leon) Elmans, mw. dr. D. (Denise) Eygendaal, dr. R.C.I. (Rutger) van Geenen , W.H.J.C. (Wim) van Heeswijk, E.A. (Eric) Hoebink, J.A.A.M. (Joost) van den Hout, A.J.P. (Peter) Joosten, dr. A.F.C.M. (Sjors) Moonen, dr. R. (Robert) Wagenmakers • 2 assistenten niet in opleiding • 2 assistent in opleiding • 1 fellow orthopedie • Subspecialismen: wervelkolom, kinderorthopedie, bovenste extremiteit, onderste extremiteit, traumatologie, sportorthopedie

Samenvattingen gepubliceerde artikelen Hebert-Davies J, Laflamme GY, Rouleau D; HEALTH and FAITH investigators. [Van den Hout JA, Joosten AJ, Bolder SB, Eygendaal D, Moonen AF, van Geenen RC, Hoebink EA, Wagenmakers R et al...]. Bias towards dementia: are hip fracture trials excluding too many patients? A systematic review. Injury. 2012 Dec;43(12):1978-84. Epub 2012 Sep 19. Patients with hip fractures are older and often present many co-morbidities, including dementia. These patients cannot answer quality of life questionnaires and are generally excluded from trials. We hypothesized that a significant number of patients are being excluded from these studies and this may impact outcomes. This was a two part study; the first analyzing databases of two ongoing large-scale multi-centred hip fracture trials and the second being a systematic review. The FAITH and HEALTH studies were analyzed for exclusion incidence directly related to demen tia. The second part consisted of a systematic search of all relevant studies within the last 20 years. In the FAITH study, a total of 1690 subjects were excluded, 375 (22.2%) of which were due to dementia or cognitive impairment. In the HEALTH study, 575 were excluded with dementia/cognitive impairment representing 207 patients (36%). Following the systematic review, 251 articles were identified 17 of which were retained. The overall prevalence of dementia was 27.9% (range 2-51%). Only two studies com pared demented and non-demented groups. In these studies significant increases in both mortality and complications were found. In summary, when investigating hip fractures, choosing appropriate objective endpoints is essential to ensure results are also applicable to patients with dementia. Copyright © 2012 Elsevier Ltd. All rights reserved. Collaborators (604): [Van den Hout JA, Joosten AJ, Bolder SB, Eygendaal D, Moonen AF, van Geenen RC, Hoebink EA, Wagenmakers R et al...] PMID: 22999009

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Beumer A. [et al...]. Richtlijn aspecifieke klachten arm, nek en/of schouders. Utrecht: CBO, 2012. De geautoriseerde multidisciplinaire richtlijn ‘Aspecifieke arm, nek en/of schouder klachten’ is een document met aanbevelingen ter ondersteuning van de dagelijkse praktijkvoering van allen die betrokken zijn bij de diagnostiek, behandeling en functioneren van patiënten met aspecifieke arm, nek en/of schouderklachten. De richtlijn is opgesteld door een breed samengestelde werkgroep bestaande uit vertegenwoordigers van verschillende beroepsgroepen, waaronder fysiotherapeuten, psychologen, orthopedisch chirurgen, anesthesiologen, bedrijfsartsen, ergotherapeu ten, plastisch chirurgen, reumatologen, revalidatieartsen, oefentherapeuten, etc. De tekst berust op de resultaten van wetenschappelijk onderzoek en aansluitende meningsvorming gericht op het expliciteren van goed medisch handelen. De richtlijn is in november 2012 door alle betrokken partijen geaccordeerd. Van den Borne MP, Elbers LA. Anatomie, pathologie en fysiologie van de schouder. Quintesse. 2012 (1):6-15. De schouder is een complex onderdeel van het bewegingsapparaat. Het faciliteert alle bewegingen van de arm en daarmee het directe contact met onze leefwereld. De functionele anatomie en fysiologie van de schouder worden bepaald door verschil lende structuren, die de schakels vormen in de bewegingsketen. De bewegingsketen is echter zo sterk als haar zwakste schakel. Dat geldt zeker voor de schouder, die kwets baar kan zijn. Pathologische veranderingen in de structuren van de schouder door trauma, sport of werk kunnen de functionele mogelijkheden ondermijnen. Dit leidt tot verlies van beweeglijkheid, kracht of gevoel. In dit artikel worden enkele veelvoorkomende aandoeningen gepresenteerd die dit illustreren. Kennis van anatomie, fysiologie en pathologie worden in een kader geplaatst dat de basis vormt voor het stellen van een juiste diagnose. Het moet helpen de professionele blik te verbreden in het belang van de zorg voor de patiënt. Van den Bekerom MP, van den Borne MP. Conservatieve en operatieve behandeling van veelvoorkomende niet-traumatologische schouderaandoeningen. Quintesse. 2012 (1): 22-28. In dit artikel wordt een overzicht gegeven van de conservatieve en operatieve behandelingsmogelijkheden van het subacromiaal pijnsyndroom, letsel aan rotator cuff, frozen shoulder, schouderinstabiliteit en schouderartrose. Het vormt een leidraad voor de diverse behandelingsmodaliteiten die per aandoening beschikbaar zijn. De

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niet-operatieve behandeling heeft in het algemeen de voorkeur. De nadruk ligt op het overzicht; een algoritme of richtlijn voor behandeling van de individuele patiënt wordt niet beoogd. Lindenhovius A, Karanicolas PJ, Bhandari M, Ring D; COAST Collaborative* [Elmans LH et al...]. Radiographic arthrosis after elbow trauma: interobserver reliability. J Hand Surg Am. 2012 Apr;37(4):755-9. Epub 2012 Mar 6. PURPOSE: This study measured observer variation in radiographic rating of elbow arthrosis. METHODS: Thirty-seven independent orthopedic surgeons graded the extent of elbow arthrosis in 20 consecutive sets of plain radiographs, according to the Broberg and Morrey rating system (grade 0, normal joint; grade 1, slight joint-space narrowing with minimum osteophyte formation; grade 2, moderate joint-space narrowing with moderate osteophyte formation; and grade 3, severe degenerative change with gross destruction of the joint). The kappa multirater measure (?) was used to estimate relia bility between observers, with 0 indicating no agreement above chance, and 1 indi cating perfect agreement. RESULTS: There was fair agreement in arthrosis ratings between surgeons. Surgeons with more than 10 years of experience had greater agreement than did surgeons with less experience, and surgeons who treated more than 10 elbow fractures per year had better agreement than did those treating fewer fractures. In post hoc analyses, 2 sim plified binary rating systems (eg, “”none or mild”” vs “”moderate or severe”” arthrosis) resulted in moderate agreement among observers. CONCLUSIONS: The 4 grades of the Broberg and Morrey classification system have only fair interobserver reliability that is influenced by subspecialty and experience. Binary rating systems might be more reliable. TYPE OF STUDY/LEVEL OF EVIDENCE: Diagnostic III. Copyright © 2012 American Society for Surgery of the Hand. All rights reserved. *Collaborators (36): Allan C, Axelrod T, Baratz M, Beingessner D, Cassidy C, Coles C, Conflitti J, Rocca GD, van Dijk C, Elmans LH, Feibe R, Frihagen F, Gosens T, Greenberg J, Grosso E, Harness N, van der Heide H, Jeray K, Kalainov D, van Kampen A, Kawamura S, Kloen P, McCormac B, McKee M, Page R, Pesantez R, Peters A, Petrisor B, Poolman R, Richardson M, Seiler J, Swiontkowski M, Trumble T, Wright T, Zalavras C, Zura R. PMID: 22397846

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Van Wagenberg JM, Turkenburg JL, Rahusen FT, Eygendaal D. The posterior transtriceps approach for intra-articular elbow diagnostics, definitely not forgotten. Skeletal Radiol. 2013 Jan;42(1):55-9. Epub 2012 May 11. BACKGROUND/AIMS: The elbow is among the most common joints that are aspirated and/or injected. An intra-articular approach should be a convenient and a safe proce dure with minimal risk of complications. Several approaches to access the elbow joint have been outlined in the literature, but a comparative study is lacking. This study eva luates the technical feasibility of the lesser-performed posterior transtriceps approach with MR arthrography and compares it to the classic lateral radiocapitellar approach. PATIENTS AND METHODS: Using fluoroscopy guidance, MR arthrographies of the elbow were performed in 51 consecutive patients from 2006 to 2011. A classical lateral radiocapitellar approach was performed in 29 and a posterior transtriceps approach in 22 elbows. Studies were retrospectively reviewed with special attention to the extent of extra-articular contrast extravasation. This was a level IV diagnostic study. RESULTS: Contrast leakage occurred in 12 radiocapitellar approaches, which caused a diagnostic dilemma in one subject. There was only a minimal amount of contrast leakage in five subjects using the transtriceps approach and no diagnostic dilemmas occurred. Results show no significant differences between the approaches. No com plications occurred in the posterior transtriceps group and all MR arthrographies were diagnostic. CONCLUSIONS: The posterior transtriceps approach is a technical feasible procedure, is easy to perform, and avoids a diagnostic dilemma in presumed injuries to the lateral collateral ligament complex. Our results show a tendency of even lesser amount of contrast leakage, further promoting a more widespread usage of the posterior transtriceps approach. PMID: 22576971

Kaas L, Sierevelt IN, Vroemen JP, van Dijk CN, Eygendaal D. Osteoporosis and radial head fractures in female patients: a case-control study. J Shoulder Elbow Surg. 2012 Nov;21(11):1555-8. Epub 2012 Jun 11. BACKGROUND: Identifying radial head fractures as fragility fractures may improve case-findings for osteoporosis and thus be an indicator other fragility fractures. MATERIALS AND METHODS: Thirty-five women aged = 50 years with a radial head fracture and 57 controls were retrospectively selected and matched for age in strata of 5 years. Peripheral bone mineral density (BMD) measurement was performed at the calcaneus. A T score of less than -2.7 was considered osteoporosis. If the T value was between -1.4 and -2.7, an additional dual energy X-ray (DXA) scan was performed. Orthopedie

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RESULTS: The patients were a median age of 60 years compared with 58 years for the control patients (P = .33). The mean T score of the patients was -1.8 (standard deviation [SD], 1.0; range, -2.2 to -0.3) compared with -1.2 (SD, 1.2; range, -4.0 to 1.3) for the control patients (P = .04). Osteoporosis was diagnosed in 11 patients and in 5 control patients. The patients had an increased risk of osteoporosis compared with the control patients (odds ratio, 3.4; P = .027). CONCLUSIONS: This study confirms that radial head fractures in women aged = 50 years are potentially osteoporotic fractures. Offering these patients a BMD measure ment may prevent future osteoporotic fractures, such as hip and spine fractures. Copyright © 2012 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Mosby, Inc. All rights reserved. PMID: 22694879

Kaas L, Struijs PA, Ring D, van Dijk CN, Eygendaal D. Treatment of Mason type II radial head fractures without associated fractures or elbow dislocation: a systematic review. J Hand Surg Am. 2012 Jul;37(7):1416-21. Epub 2012 May 22. PURPOSE: There is no consensus as to the best treatment of Mason type II fractures without concomitant elbow fractures or dislocation. The aim of this systematic review was to compare the results of operative and nonoperative treatment of these injuries. METHODS: We systematically screened the databases of PubMed, EMBASE, and Cochrane Library until September 2011 for studies on nonoperative or operative treatment of Mason type II fractures. We defined successful treatment as an excellent or good result according to the Broberg and Morrey score, Mayo Elbow Performance Score, or Radin score. Exclusion criteria were duration of follow-up of less than 6 months, an improperly described therapy or combination of therapies, skeletal immaturity, and articles written in languages other than English. RESULTS: Among 717 studies, 9 retrospective case series (level IV) describing 224 patients satisfied our inclusion criteria. Nonoperative treatment was successful in 114 of 142 patients (80%) pooled from the studies (42% to 96% success in individual studies). Open reduction and internal fixation was successful in 76 of 82 patients (93%) (81% to 100% success in individual studies). CONCLUSIONS: Only a few studies with a low level of evidence address the treatment of isolated, displaced, partial articular fractures. There is a need for sufficiently powe red randomized, controlled trials.

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CLINICAL RELEVANCE: There is insufficient evidence to draw firm conclusions on the optimal treatment of isolated, displaced, partial articular Mason type II fractures. Copyright © 2012 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved. PMID: 22622090 Kodde IF, Rahusen FT, Eygendaal D. Long-term results after ulnar collateral ligament reconstruction of the elbow in European athletes with interference screw technique and triceps fascia autograft. J Shoulder Elbow Surg. 2012 Dec;21(12):1656-63. Epub 2012 Sep 13. BACKGROUND: In the last decade, there has been increasing interest in medial ulnar collateral ligament (MUCL) reconstruction techniques for MUCL insufficiency of the elbow. All case series are based on American and Asian Athletes and use primarily a palmaris longus tendon or gracilis tendon as an autograft in reconstructions. A new technique is the interference screw fixation. Evidence that supports the use of this technique is mainly from controlled laboratory studies. The purpose was to evaluate the interference screw technique for MUCL reconstructions in a European, clinical setting, with a triceps tendon fascia autograft. METHODS: Twenty consecutive athletes with diagnosed MUCL insufficiency who underwent a MUCL reconstruction using the interference screw technique were reviewed retrospectively. Indications for reconstruction were medial elbow pain and/or instability caused by insufficiency of the MUCL that prevented the athlete from sport activity after a minimum of 3 months of conservative treatment. RESULTS: At a mean follow-up of 55 months (range, 36-94), the mean Mayo Elbow Performance Index (MEPI) score improved from 82 to 91 points (range, 80-100); P < .001. In the end, 6 patients (30%) quit the sport activities they were preoperatively participating in, all because of reasons unrelated to the MUCL reconstruction. There were excellent results on the Conway scale in 18 patients. CONCLUSION: Good results are reported based on the postoperative MEPI and Conway scores with clinically stable MUCL reconstructions without signs of break-out or fractures on radiographic follow-up. However, the dropout, even after successful reconstruction in European athletes, is high. Copyright © 2012 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Mosby, Inc. All rights reserved. PMID: 22981358

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Eygendaal D. The assessment and management of posterolateral instability. In: Operative Elbow Surgery / Stanley D, Trail I [eds.]. Edinburgh [etc.] : Churchill Livingstone Elsevier, 2012. Chapter 26. ISBN 978-070-203-099-4. Eygendaal D, Kaas L. Ulnar Collateral Ligament Injury. In: Evidence-Based Orthopedics / Bhandari M. [et al...]. Oxford : Wiley-Blackwell, 2012. Chapter 91. ISBN 978-140-518-476-2. De Leur K, Eric Hoebink E, Veen E. Hevige pijn aan de rug. Medisch Contact. 2012 okt;67(43):2391. Stevens M, Paans N, Wagenmakers R, van Beveren J, van Raay JJ, van der Meer K, Stewart R, Bulstra SK, Reininga IH, van den Akker-Scheek I. The influence of over weight/obesity on patient-perceived physical functioning and health-related quality of life after primary total hip arthroplasty. Obes Surg. 2012 Apr;22(4):523-9. BACKGROUND: Overweight/obesity in patients after total hip arthroplasty (THA) is a growing problem and is associated with postoperative complications and a negative effect on functional outcome. The objective of this study is to determine to what extent overweight/obesity is associated with physical functioning and health-related quality of life 1 year after primary THA. METHODS: A retrospective analysis of prospectively collected data from 653 patients who had undergone a primary THA was conducted. Physical functioning, health-related quality of life, body mass index (BMI), comorbidity, and postoperative complications were assessed by means of a questionnaire and from medical records. To determine to what extent overweight/obesity is associated with physical functio ning and health-related quality of life after THA, a structural equation model (SEM) analysis was conducted. RESULTS: The association of BMI corrected for age, gender, complications, and comor bidity with physical functioning is -0.63. This means that an increase in 1 kg/m2 BMI leads to a reduction of 0.63 points in the physical functioning score as measured with the Western Ontario and McMaster Universities Osteoarthritis Index (100-point scale). The prevalence of complications or comorbidity leads to a reduction of, respectively, 5.63 and 7.25 (one or two comorbidities) and 14.50 points in the case of more than two comorbidities on the physical functioning score. The same pattern is observed for health-related quality of life. CONCLUSIONS: The influence of overweight/obesity on physical functioning and health-related quality of life is low. The impact of complications and comorbidity is considerable. Refusing a patient a THA solely on the basis of overweight or obesity does not seem justified. PMID: 21800224

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Paans N, Stevens M, Wagenmakers R, van Beveren J, van der Meer K, Bulstra SK, van den Akker-Scheek I. Changes in body weight after total hip arthroplasty: short-term and long-term effects. Phys Ther. 2012 May;92(5):680-7. Epub 2012 Jan 6. BACKGROUND: Elevated body weight is associated with hip osteoarthritis (OA) and subsequently with total hip arthroplasty (THA). Patients with hip OA who are overweight often mention their restricted mobility as a factor that thwarts their attempts to be physically active and lose weight. There is some evidence that THA increases physical activity, but none for losing body weight after THA. OBJECTIVE: The purpose of this study was to analyze the short-term (1-year) and long-term (4.5-year) effects of a THA on body weight. DESIGN: This was an observational, multicenter cohort study. METHODS: For the short-term effect, all patients (N=618) were analyzed; for the long-term effect, a random subgroup (n=100) was analyzed. Preoperative and postoperative body weight and height were self-reported. Patients were categorized according to their preoperative body mass index (BMI <25 kg/m(2)=normal weight, 25-30 kg/m(2)=overweight, >30 kg/m(2)=obese). Clinical relevancy was set at a minimum of 5% weight loss compared with baseline. RESULTS: The mean age of the study group was 70 years (SD=8), 74% were women, and mean preoperative body mass was 79 kg (SD=14). One year after THA, a signifi cant decrease in body weight of 1% and 3.4% occurred for the overweight and obese BMI categories, respectively. After 4.5 years, a significant decrease in body weight of 6.4% occurred for the obese BMI category. LIMITATIONS: Height and weight-and thus BMI-were self-reported. CONCLUSION: Patients in the overweight and obese groups showed a decrease, albeit not clinically relevant, in body weight after 1 year. After 4.5 years, a decrease that was relevant clinically was observed in the patients who were obese. It can be concluded that no clinically relevant reduction of weight occurred after THA, except in the long term for patients who were obese. PMID: 22228604

Reininga IH, Stevens M, Wagenmakers R, Bulstra SK, Groothoff JW, Zijlstra W. Subjects with hip osteoarthritis show distinctive patterns of trunk movements during gait-a body-fixed-sensor based analysis. J Neuroeng Rehabil. 2012 Jan 20;9:3.

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BACKGROUND: Compensatory trunk movements during gait, such as a Duchenne limp, are observed frequently in subjects with osteoarthritis of the hip, yet angular trunk movements are seldom included in clinical gait assessments. Hence, the objec tive of this study was to quantify compensatory trunk movements during gait in subjects with hip osteoarthritis, outside a gait laboratory, using a body-fixed-sensor based gait analysis. Frontal plane angular movements of the pelvis and thorax and spatiotemporal parameters of persons who showed a Duchenne limp during gait were compared to healthy subjects and persons without a Duchenne limp. METHODS: A Body-fixed-sensor based gait analysis approach was used. Two bodyfixed sensors were positioned at the dorsal side of the pelvis and on the upper thorax. Peak-to-peak frontal plane range of motion (ROM) and spatiotemporal parameters (walking speed, step length and cadence) of persons with a Duchenne limp during gait were compared to healthy subjects and persons without a Duchenne limp. Participants were instructed to walk at a self-selected low, preferred and high speed along a hospital corridor. Generalized estimating equations (GEE) analyses were used to assess group differences between persons with a Duchenne limp, without a Duchenne limp and healthy subjects. RESULTS: Persons with a Duchenne limp showed a significantly larger thoracic ROM during walking compared to healthy subjects and to persons without a Duchenne limp. In both groups of persons with hip osteoarthritis, pelvic ROM was lower than in healthy subjects. This difference however only reached significance in persons without a Duchenne limp. The ratio of thoracic ROM relative to pelvic ROM revealed distinct differences in trunk movement patterns. Persons with hip osteoarthritis walked at a significantly lower speed compared to healthy subjects. No differences in step length and cadence were found between patients and healthy subjects, after correction for differences in walking speed. CONCLUSIONS: Distinctive patterns of frontal plane angular trunk movements during gait could be objectively quantified in healthy subjects and in persons with hip osteoarthritis using a body-fixed-sensor based gait analysis approach. Therefore, frontal plane angular trunk movements should be included in clinical gait assessments of persons with hip osteoarthritis. PMID: 22264234

Reininga IH, Stevens M, Wagenmakers R, Bulstra SK, van den Akker-Scheek I. Minimally invasive total hip and knee arthroplasty-implications for the elderly patient. Clin Geriatr Med. 2012 Aug;28(3):447-58. Epub 2012 Jun 22. Overall, it can be concluded that because of the aging society, an increasing number of elderly people will be undergoing total joint arthroplasty. These elderly patients

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have an increased risk for serious complications after primary THA or TKA. However, the overall complication rates remain low. The use of MIS total joint arthroplasty is also increasing, although its risks and benefits are still an ongoing issue of debate in the orthopedic community. MIS total joint arthroplasty aims at decreasing the surgical incision and minimizing damage to the underlying soft tissue to accelerate postopera tive recovery and an earlier return to normal function. A critical look at the literature on MIS shows that the term minimally invasive is often used for a conventional total joint arthroplasty performed through a smaller skin incision. Research has shown promising results of using MIS in elderly patients; it seems that compared with younger patients, elderly patients benefit more from a minimally invasive approach. PMID: 22840307

Stevens M, Reininga IH, Bulstra SK, Wagenmakers R, van den Akker-Scheek I. Physical activity participation among patients after total hip and knee arthroplasty. Clin Geriatr Med. 2012 Aug;28(3):509-20. Epub 2012 May 24. No abstract available. PMID: 22840311

Reininga IH, Stevens M, Wagenmakers R, Boerboom AL, Groothoff JW, Bulstra SK, Zijlstra W. Comparison of gait in patients following a computer-navigated minimally invasive anterior approach and a conventional posterolateral approach for total hip arthroplasty: A randomized controlled trial. J Orthop Res. 2012 Aug 8. [Epub ahead of print]. Minimally invasive total hip arthroplasty (MIS THA) aims at minimizing damage to muscles and tendons to accelerate postoperative recovery. Computer navigation allows a precise prosthesis alignment without complete visualization of the bony landmarks during MIS THA. A randomized controlled trial (RCT) was conducted to determine the effectiveness of a computer-navigated MIS anterior approach for THA compared to a conventional posterolateral THA technique on the restoration of physical functioning during recovery following surgery. Thirty-five patients underwent computer-navigated MIS THA via the anterior approach, and 40 patients underwent conventional THA using the conventional posterolateral approach. Gait analysis was performed preoperatively, 6 weeks, and 3 and 6 months postoperatively using a body-fixed-sensor based gait analysis system. Walking speed, step length, cadence, and frontal plane angular movements of the pelvis and thorax were assessed. The same data were obtained from 30 healthy subjects. No differences were found in the recovery of spatiotemporal parameters or in angular movements of the pelvis and

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thorax following the computer-navigated MIS anterior approach or the conventional posterolateral approach. Although gait improved after surgery, small differences in several spatiotemporal parameters and angular movements of the trunk remained at 6 months postoperatively between both patient groups and healthy subjects. Copyright © 2012 Orthopaedic Research Society. PMID: 22886805

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Pathologie Kerngegevens Zorgkern Pathologie • 5 pathologen: mw. L.S.M. (Luthy) Alcalá, mw. dr. D.E. (Dorothee) Arnold, K.E.S. (Kristoff) Duthoi, J. (Jan) Los, dr. P.E.J. (Peter) de Wit

Samenvattingen gepubliceerde artikelen Gobardhan PD, Wijsman JH, van Dalen T, Klompenhouwer EG, van der Schelling GP, Los J, Voogd AC, Luiten EJ. ARM: axillary reverse mapping - the need for selection of patients. Eur J Surg Oncol. 2012 Aug;38(8):657-61. Epub 2012 May 17. BACKGROUND: Axillary reverse mapping (ARM) is a technique that discerns axillary lymphatic drainage of the arm from the breast. This study was performed to evaluate both the feasibility of this technique and the proportion of metastatic involvement of ARM-nodes. PATIENTS AND METHODS: Patients with invasive breast cancer and an indication for axillary lymph node dissection (ALND) were enrolled in the study: patients with a tumor-positive sentinel lymph node (SLN(+)-group) and patients who had axillary metastases proven by preoperative cytology (CP-N(+)-group) were distinguished. ARM was performed in all patients by injecting blue dye. During surgery ARM-nodes were identified and removed first, followed by ALND. RESULTS: Between October 2009 and June 2011 93 patients underwent ARM. There were 43 patients in the SLN(+)-group and 50 patients in the CP-N(+)-group. No sig nificant differences in visualization rate of ARM-nodes between the groups (86 vs 94% respectively, P = 0.196) were identified. In the SLN(+)-group none of the ARM-nodes contained metastases versus 11 patients (22%) in the CP-N(+)-group (P = 0.001). Patients receiving neoadjuvant systemic therapy had a significantly lower risk of additional axillary lymph node metastases (24.6 vs 44.4%, P = 0.046). DISCUSSION: The ARM procedure is technically feasible with a high visualization rate. The proportion of patients with metastases in the ARM-nodes was significantly higher in patients with proven axillary metastases than in patients with a positive SLN. Patients with SLN metastases appear to be good candidates for the ARM technique and possibly also patients with proven axillary metastases receiving neoadjuvant chemotherapy. Copyright © 2012 Elsevier Ltd. All rights reserved. PMID: 22607749

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Radiologie Kerngegevens Zorgkern Radiologie • 19 radiologen: R.A.H.M. (Ruud) Aarts, K. (Koen) Borsje, H.F.C.M. (Hein) Brands, H.A.J. (Homme) Dijkstra, G.P.J. (Gé) Geenen, H.A.W. (Dirk) Haans, Th.E.A.M. (Thijs) de Jong, P.A.M. (Peter) Kint, M.M. (Mark) Krouwels, mw. I. (Ilse) Niers-Stobbe, P.A.M. (Peter) Raaijmakers, M.G. (Mark) Romijn, E. (Evert) Sanders, M.F.A.M. (Maarten) Sturm, dr. E. (Eric) Tetteroo, J.L. (Jeroen) Turkenburg, R.J. (Rob) Versteylen, L.D. (Douwe) Vos, T.T. (Thomas) de Weert • Subspecialismen: interventieradiologie, mammaradiologie

Samenvattingen gepubliceerde artikelen Postma EL, Verkooijen HM, van Esser S, Hobbelink MG, van der Schelling GP, Koelemij R, Witkamp AJ, Contant C, van Diest PJ, Willems SM, Borel Rinkes IH, van den Bosch MA, Mali WP, van Hillegersberg R; ROLL study group [Tetteroo E, Dijkstra H, Raaymakers P et al...]. Efficacy of ‘radioguided occult lesion localisation’ (ROLL) versus ‘wire-guided localisation’ (WGL) in breast conserving surgery for non-palpable breast cancer: a ran domised controlled multicentre trial. Breast Cancer Res Treat. 2012 Nov;136(2):469-78. Epub 2012 Sep 30. For the management of non-palpable breast cancer, accurate pre-operative localisa tion is essential to achieve complete resection with optimal cosmetic results. Radio guided occult lesions localisation (ROLL) uses the radiotracer, injected intra-tumourally for sentinel lymph node identification to guide surgical excision of the primary tumour. In a multicentre randomised controlled trial, we determined if ROLL is superior to the standard of care (i.e. wire-guided localisation, WGL) for preoperative tumour localisa tion. Women (>18 years.) with histologically proven non-palpable breast cancer and eli gible for breast conserving treatment with sentinel node procedure were randomised to ROLL or WGL. Patients allocated to ROLL received an intra-tumoural dose of 120 Mbq technetium-99 m nanocolloid. The tumour was surgically removed, guided by gamma probe detection. In the WGL group, ultrasound- or mammography-guided insertion of a hooked wire provided surgical guidance for excision of the primary tumour. Primary outcome measures were the proportion of complete tumour excisions (i.e. with nega tive margins), the proportion of patients requiring re-excision and the volume of tissue removed. Data were analysed according to intention-to-treat principle. This study is registered at ClinincalTrials.gov, number NCT00539474. In total, 314 patients with 316 invasive breast cancers were enrolled. Complete tumour removal with negative margins was achieved in 140/162 (86 %) patients in the ROLL group versus 134/152 (88 %) patients in the WGL group (P = 0.644). Re-excision was required in 19/162 (12 %) patients in the ROLL group versus 15/152 (10 %) (P = 0.587) in the WGL group. Specimen volumes in the ROLL arm were significantly larger than those in the WGL arm (71 vs. 64 cm(3), P = 0.017). No significant differences were seen in the duration and difficulty

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of the radiological and surgical procedures, the success rate of the sentinel node proce dure, and cosmetic outcomes. In this first multicentre randomised controlled compari son of ROLL versus WGL in patients with histologically proven breast cancer, ROLL is comparable to WGL in terms of complete tumour excision and re-excision rates. ROLL, however, leads to excision of larger tissue volumes. Therefore, ROLL cannot replace WGL as the standard of care. *Collaborators (32): Van der Schelling G, Rijken A, Nuytinck J, Luiten E, Tetteroo E, Dijkstra H, Raaymakers P, Van Noorden P, Baas J, Vos D, Wijsman J, Koelemij R, Theunissen E, van Esser S, van Wieringen A, Lavalaye J, Bollen T, Appelman M, Postma EL, Glaap L, Witkamp AJ, Rinkes IH, van Hillegersberg R, Hobbelink M, Fernandez A, Stapper G, van den Bosch M, Mali W, Verkooijen H, Willems SM, van Diest PJ, Contant C. PMID: 23053639

Klompenhouwer EG, Helleman JN, Geenen GP, Ho GH, Vos LD, Van der Laan L. Reinterventions following endovascular abdominal aortic aneurysm repair, the learning curve of time. J Cardiovasc Surg (Torino). 2012 Nov 8. [Epub ahead of print]. AIM: The DREAM and EVAR-1 trial show a higher reintervention rate after endovascular aneurysm repair (EVAR) compared to open repair. Since the initiation of these trials, endovascular-graft design and the experiences with EVAR have evolved substantially. The aim of this study was to compare the need for reinterventions in our recent EVAR procedures with our early procedures. METHODS: A retrospective review of our prospectively maintained database of all patients undergoing an elective EVAR for infrarenal abdominal aortic aneurysm (AAA) was performed. The 68 patients treated between 2000 and 2006 were defined as the “”Early EVAR”” group; the 41 patients treated between 2006 and 2008 were defined as the “”Recent EVAR”” group. The median follow-up was 63.3 (range 2-111) and 43.7 (range 1-61) months in the Early and Recent EVAR group respectively. RESULTS: Treatment related mortality occurred in three (4.4%) patients in the Early EVAR group. No treatment related mortality occurred in the Recent EVAR group. In the Early EVAR group 16 reinterventions occurred in 13 patients (19.1%) and in the Recent EVAR group three reinterventions occurred in three patients (7.5%). This difference was statistically significant (P=0.039).

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CONCLUSION: In our center, continued experiences with EVAR, improvement of graft design and a different management of complications have led to a significant decrease in reinterventions after EVAR. These findings and a review of the literature suggests that current need for reintervention after EVAR is substantially less than reported in the early trials. PMID: 23138601

Bekken JA, Vos JA, Aarts RA, de Vries JP, Fioole B. DISCOVER: Dutch Iliac Stent trial: COVERed balloon-expandable versus uncovered balloon-expandable stents in the common iliac artery: study protocol for a randomized controlled trial. Trials. 2012 Nov 19;13:215. BACKGROUND: Iliac artery atherosclerotic disease may cause intermittent claudication and critical limb ischemia. It can lead to serious complications such as infection, ampu tation and even death. Revascularization relieves symptoms and prevents these com plications. Historically, open surgical repair, in the form of endarterectomy or bypass, was used. Over the last decade, endovascular repair has become the first choice of treatment for iliac arterial occlusive disease. No definitive consensus has emerged about the best endovascular strategy and which type of stent, if any, to use. However, in more advanced disease, that is, long or multiple stenoses or occlusions, literature is most supportive of primary stenting with a balloon-expandable stent in the common iliac artery (Jongkind V et al., J Vasc Surg 52:1376-1383,2010). Recently, a PTFE-covered balloon-expandable stent (Advanta V12, Atrium Medical Inc., Hudson, NH, USA) has been introduced for the iliac artery. Covering stents with PTFE has been shown to lead to less neo-intimal hyperplasia and this might lower restenosis rates (Dolmatch B et al. J Vasc Interv Radiol 18:527-534,2007, Marin ML et al. J Vasc Interv Radiol 7:651-656,1996, Virmani R et al. J Vasc Interv Radiol 10:445-456,1999). However, only one RCT, of medio cre quality has been published on this stent in the common iliac artery (Mwipatayi BP et al. J Vasc Surg 54:1561-1570,2011, Bekken JA et al. J Vasc Surg 55:1545-1546,2012). Our hypothesis is that covered balloon-expandable stents lead to better results when compared to uncovered balloon-expandable stents. METHODS/DESIGN: This is a prospective, randomized, controlled, double-blind, multi-center trial. The study population consists of human volunteers aged over 18 years, with symptomatic advanced atherosclerotic disease of the common iliac artery, defined as stenoses longer than 3 cm and occlusions. A total of 174 patients will be included. The control group will undergo endovascular dilatation or revascularization of the common iliac artery, followed by placement of one or more uncovered balloon-

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expandable stents. The study group will undergo the same treatment, however one or more PTFE-covered balloon-expandable stents will be placed. When necessary, the aorta, external iliac artery, common femoral artery, superficial femoral artery and deep femoral artery will be treated, using the standard treatment. The primary endpoint is absence of binary restenosis rate. Secondary endpoints are reocclusion rate, targetlesion revascularization rate, clinical success, procedural success, hemodynamic success, major amputation rate, complication rate and mortality rate. Main study parameters are age, gender, relevant co-morbidity, and several patient, disease and procedure-related parameters. TRIAL REGISTRATION: Dutch Trial Register, NTR3381. PMID: 23164097

Robbrecht DG, Alidjan F, Eikemans B, Haans DA, van Guldener C, van Wijngaarden P. Panniculitis mesenterica: uiteenlopende presentaties. [Mesenteric panniculitis: variable presentations]. Ned Tijdschr Geneeskd. 2012;155(25):A4555 [1047-52]. Mesenteric panniculitis is a non-specific inflammation of the mesenteric adipose tissue, with varying degrees of fibrosis and fat necrosis. It can be associated with vary ing diseases and conditions, such as autoimmune disease and cancer. Many doctors are not familiar with this disease or do not know how to interpret the signs and symptoms. Here, we describe three patients illustrating the variety of clinical course, diagnostics, prognosis and treatment. A 44-year-old woman suffering from episodic abdominal pain was diagnosed with uncomplicated mesenteric panniculitis. The disease was stable while maintaining a conservative approach. In a 43-year-old woman, mesenteric panniculitis was complicated by autoimmune haemolytic anaemia. After treatment with corticosteroids, she made a full recovery from both disorders. Finally, a 73-yearold man was diagnosed with mesenteric panniculitis and auto-immune haemolytic anaemia, which both appeared to be consequences of an angioimmunoblastic T-cell lymphoma. PMID: 22748362

Castenmiller PH, de Leur K, de Jong TE, van der Laan L. Clinical results after coil embolization of the ovarian vein in patients with primary and recurrent lower-limb varices with respect to vulval varices. Phlebology. 2012 Mar 22. [Epub ahead of print]. OBJECTIVE: To study the effect of coil embolization of the insufficient ovarian vein (IOV) on varices of the lower limb (VLL).

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METHOD: From December 2005 until May 2008, we selected all patients with phlebo grams that were performed in our hospital to confirm the diagnosis of insufficiency of the ovarian vein. The CEAP (clinical, aetiological, anatomical and pathological elements) classification was used to classify the lower-limb venous disease in each patient. All patients with suspected IOV in combination with VLL underwent a phlebography. If IOV was found, coil embolization of the ovarian vein(s) was performed. RESULTS: IOV was found in 43 of 44 patients (98%). After coil embolization of the ovarian vein(s), VLL disappeared in five patients (12%) without any further treatment. Improvement in CEAP classification was measured in 13 patients (31%). In 21 (88%) of 24 patients with vulval varices, coil embolization of the ovarian vein(s) resulted in disappearance of vulval varices. CONCLUSIONS: In only 31% of the patients with IOV in combination with VLL, phlebog raphy and coil embolization of the ovarian vein(s) did improve CEAP classification. However, coil embolization of the ovarian vein resulted in disappearance of the vulval varices in 88% of the patients. PMID: 22442360

Gobardhan PD, de Wall LL, van der Laan L, Ten Tije AJ, van der Meer DC, Tetteroo E, Poortmans PM, Luiten EJ. The role of radioactive iodine-125 seed localization in breast-conserving therapy following neoadjuvant chemotherapy. Ann Oncol. 2013 Mar;24(3):668-73. Epub 2012 Nov 8. BACKGROUND: Neoadjuvant chemotherapy (NAC) is increasingly used in the frame work of breast-conserving therapy (BCT). Localization of the initial tumor is essential to guide surgical resection after NAC. This study describes the results obtained with I-125 seed localization in BCT including NAC. PATIENTS AND METHODS: Between January 2009 and December 2010, 85 patients treated with NAC and BCT after I-125 seed localization were included. Radiological and pathological response and resection margins were retrospectively evaluated. RESULTS: BCT was carried out in 85 patients without secondary local excisions. Nine teen patients with unifocal tumors and seven patients with multifocal tumors showed a complete pathological response (P = 0.18). Tumor-free resection margins were obtained in 78 patients (50 patients with unifocal and 28 patients with multifocal tumors, P = 0.27). Focally involved margins were found in four patients (two patients with a unifocal and two patients with a multifocal tumor, P = 0.27). A subsequent mastectomy was carried out in three patients (two patients with multifocal tumors, P = 0.29).

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CONCLUSIONS: BCT after NAC can be carried out successfully after initial localization with I-125 seeds in both unifocal and multifocal breast tumors with complete resection rates of >90%. PMID: 23139261

Smits RW, Gobardhan PD, Poortmans PhM, Tetteroo E, van der Schelling GP. Primair Plaveiselselcarcinoom van de mamma; een zwarte zwaan onder de borstmaligniteiten. Ned Tijdschr Heelkd. 2012;21(3):123-9. Van Wagenberg JM, Turkenburg JL, Rahusen FT, Eygendaal D. The posterior transtri ceps approach for intra-articular elbow diagnostics, definitely not forgotten. Skeletal Radiol. 2013 Jan;42(1):55-9. Epub 2012 May 11. BACKGROUND/AIMS: The elbow is among the most common joints that are aspirated and/or injected. An intra-articular approach should be a convenient and a safe proce dure with minimal risk of complications. Several approaches to access the elbow joint have been outlined in the literature, but a comparative study is lacking. This study eva luates the technical feasibility of the lesser-performed posterior transtriceps approach with MR arthrography and compares it to the classic lateral radiocapitellar approach. PATIENTS AND METHODS: Using fluoroscopy guidance, MR arthrographies of the elbow were performed in 51 consecutive patients from 2006 to 2011. A classical lateral radiocapitellar approach was performed in 29 and a posterior transtriceps approach in 22 elbows. Studies were retrospectively reviewed with special attention to the extent of extra-articular contrast extravasation. This was a level IV diagnostic study. RESULTS: Contrast leakage occurred in 12 radiocapitellar approaches, which caused a diagnostic dilemma in one subject. There was only a minimal amount of contrast leakage in five subjects using the transtriceps approach and no diagnostic dilemmas occurred. Results show no significant differences between the approaches. No com plications occurred in the posterior transtriceps group and all MR arthrographies were diagnostic. CONCLUSIONS: The posterior transtriceps approach is a technical feasible procedure, is easy to perform, and avoids a diagnostic dilemma in presumed injuries to the lateral collateral ligament complex. Our results show a tendency of even lesser amount of contrast leakage, further promoting a more widespread usage of the posterior transtriceps approach. PMID: 22576971

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Reumatologie Mensen die vroeger in een rolstoel belandden, krijgen we nu weer aan het werk! In 2012 promoveerde dr. Petra Vos op een interessant reumatologisch onderzoek over het proces van artrose. Een onderzoek dat is geïnitieerd door het Reumafonds. Ze legt uit dat de slijtage van gewrichten (artrose) een groot aandachtsgebied is binnen de reumatologie. “Vroeger dachten we dat kraakbeencellen hetzelfde bleven.” “We weten inmiddels dat bepaalde eiwit-suikerverbindingen die ontstaan tijdens het leven een rol spelen bij slijtage. En dat heeft een negatieve invloed op het kraakbeen.” Voor het onderzoek volgde Petra Vos gedurende tien jaar een groot aantal patiënten tussen de 45 en 65 jaar met de eerste verschijnselen van artrose. Daarbij is gekeken: wat gebeurt er nu allemaal in die gewrichten? Hoe verloopt het allereerste begin en wat kun je daarvan leren? Welke mensen krijgen uiteindelijk zoveel klachten dat er een nieuwe heup of knie nodig is? Over de resultaten zegt Vos: “Versuikering van eiwitten is bij de start van het onderzoek meer aanwezig bij mensen met enige vorm van artrose vergeleken met mensen zonder artrose. Hoe de toename na vijf jaar is, blijkt lastig te voorspellen.” Overigens heeft vorig jaar pas de eerste patiënt de volle tien jaar doorlopen. De studie loopt dus nog steeds.

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CHECK De naam van het artroseonderzoek is CHECK (Cohort Heup En Cohort Knie), naar de onderzoeksgebieden. Het onderzoek vond plaats in Utrecht, er waren geen patiën ten uit haar latere werkkring – het Amphia Ziekenhuis – bij betrokken. Vos bleef het onderzoek ‘er even naast doen’ en reisde hiervoor vaak heen en weer tussen Breda en Utrecht. Ze publiceerde diverse artikelen over CHECK in wetenschappelijke tijd schriften als Osteoarthritis and Cartilage en Journal of Orthopaedic Research. Optimum tussen bewegen en belasten Overigens deed Vos al eerder mee aan onderzoek naar eiwit-suikerverbindingen en het begin van artrose, maar dan bij dieren. “Na goedkeuring van een DEC*, hebben we bij honden een kleine beschadiging in het kraakbeen aangebracht. Dit kan een trigger zijn om artrose te laten ontstaan. Toen is gekeken naar verschillende condities en wat er dan gebeurt. Is er verschil bij wel en niet belasten? Kun je extra eiwit-suiker verbindingen laten aanmaken door suiker in het gewricht te spuiten? Helaas waren de meeste resultaten zeer teleurstellend. Het aanbrengen van suiker had niet veel effect.” Toch vond het onderzoek niet voor niets plaats. “Meer belasten lijkt te leiden tot meer kans op artrose. Wat ook steeds duidelijker blijkt, is dat kraakbeen niet zo passief is. Vroeger dachten we altijd dat kraakbeencellen levenslang hetzelfde bleven. Nu blijkt dat ze in staat zijn tot een stukje herstel. Met deze kennis is het nu belangrijk om bij patiënten te kijken hoe het juiste optimum is te bereiken tussen bewegen en belasten.” De arts geeft aan dat het niet ethisch zou zijn om dit dierenonderzoek met mensen uit te voeren. “Bovendien is het beste onderzoeksmoment bij het ontstaan van een beschadiging en dat weet je bij mensen met artrose nooit precies.” Onderzoeken naar nieuwe medicatie Het Amphia Ziekenhuis is geen opleidingsziekenhuis voor reumatologie. Vos: “Die ambitie is er wel, maar de reumatologen die afstuderen vinden bijna onmiddellijk een werkplek.” Bovendien besteden de reumatologen tussen de zeventig en tachtig procent van hun tijd aan poliklinische behandeling, dus heel veel tijd voor opleiding en onderzoek is momenteel niet beschikbaar. Toch is er een samenwerkingsverband met het Erasmus in oprichting om de knowhow van Rotterdam te koppelen aan de grote patiënten aantallen in Breda en Oosterhout. “Daar doen we graag aan mee, alleen al om te leren van de academische inzichten. Ook geven we regelmatig ondersteuning bij onderzoeken naar het verplaatsen van therapieën uit het ene stadium van reuma naar een ander stadium. Die onderzoeken zijn elders gestart en wij includeren hier patiënten. Dat geldt ook voor deelname aan onderzoeken die zich richten op een andere manier van ingrijpen in het systeem. En onderzoeken naar therapietrouw en niet te vergeten naar dure geneesmiddelen, of deze op den duur afgebouwd of vervangen kunnen worden. Het voordeel van medicijnonderzoeken is dat we ook snel kennis verzamelen over wat nieuwe medicijnen precies doen.” *DEC = dierexperimentencommissie. Dit is een commissie bestaande uit deskundigen die adviseert over uit te voeren dierexperimenten t.b.v. wetenschappelijk onderzoek en onderwijs, ook brengen zij alternatieven in beeld. De commissie voorkomt onnodige dierproeven, bevordert het welzijn van proefdieren en sugge reert alternatieven waar mogelijk.

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Ook jonge patiënten “Reumatologie is een relatief jong onderzoeksgebied”, zegt Vos. “Vroeger was het een onderdeel van interne geneeskunde.” De arts geeft aan dat ook niet iedereen weet wat reumatologen precies doen. “Vaak denken mensen dat hier alleen maar oude mensen komen. Dat is beslist niet waar! Ook jonge mensen kunnen reuma krijgen. Sommigen komen hier al met achttien jaar.” Zelf vindt de reumatoloog dat een van de mooie dingen van het vak: de lange behandeltrajecten. Ze begeleidt mensen jarenlang. Onderzoekt patiënten, schrijft steeds de best passende medicatie voor, rekening houdend met levensloopfactoren als kinderwens, et cetera. Dynamische puzzel “Bovendien is het een dynamisch vak, waarbij je vaak een heleboel factoren bij elkaar puzzelt om uit te vinden wat er aan de hand is. We hebben in het Amphia Ziekenhuis ook een dagbehandeling naast de poli, die we beheren samen met Interne Genees kunde en Maag-, Darm- en Levergeneeskunde.” Wensen zijn er zeker nog. “Omdat Bewegen een belangrijk speerpunt van het ziekenhuis is, zouden wij graag met alle betrokken specialismen op één locatie zitten. Dat is nu nog niet het geval.” Zelfstandige discipline Tijdens de artsenopleiding wist Vos al snel dat ze geen snijder was, maar een beschou wend vak wilde. Ze begon in de interne geneeskunde maar vond dat te divers. “Niet voor niets zie je geen algemene internisten meer, iedereen is zich gaan specialiseren.” Reumatologie sprak al snel aan. “Het is een zelfstandige discipline, we hebben veel in eigen hand. Diagnoses zijn snel te maken en de link met de tegenhanger immunologie is interessant. Door de snelle ontwikkeling van nieuwe medicatie kunnen we ook veel voor mensen betekenen. Waar ze vroeger in een rolstoel belandden, kunnen we ze nu weer aan het werk helpen.” Vergeleken met de academische omgeving in Utrecht is ze blij met haar keuze voor het perifere Amphia Ziekenhuis. “Patiëntenzorg is voor mij het belangrijkste en met zulke grote patiëntenaantallen is er veel diversiteit aan ‘klachten’. Dat maakt het erg boeiend.” • 5 reumatologen: mw. C.W.Y. (Cathelijne) Appels, mw. N.H.A.M. (Natasja) Denissen, mw. B. (Bouchra) Lechkar, F.M.A. (Frank) Slaats, mw. dr. P.A.J.M. (Petra) Vos • 2 verpleegkundig specialisten • 4 reumaconsulenten • 1 research verpleegkundige

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Kerngegevens Zorgkern Reumatologie Overzicht lopende onderzoeken • U Act Early: bij mensen met nieuwe reumatoïde artritis starten met medicijnen die tot nu toe op dat moment niet ingezet mochten worden. • TARA en POEET: afbouwen van anti-TNF na langdurige remissie. • PREDICT: meten van therapietrouw.

Samenvattingen gepubliceerde artikelen Vos PA, Mastbergen SC, Huisman AM, de Boer TN, DeGroot J, Polak AA, Lafeber FP. In end stage osteoarthritis, cartilage tissue pentosidine levels are inversely related to parameters of cartilage damage. Osteoarthritis Cartilage. 2012 Mar;20(3):233-40. Epub 2011 Dec 21. OBJECTIVES: Age is the most prominent predisposition for development of osteo arthritis (OA). Age-related changes of articular cartilage are likely to play a role. Advan ced glycation endproducts (AGEs) accumulate in cartilage matrix with increasing age and adversely affect the biomechanical properties of the cartilage matrix and influen ce chondrocyte activity. In clinical studies AGEing of cartilage and its relation to actual cartilage damage can only be measured by surrogate markers (e.g., serum, skin or urine AGE levels and imaging or biochemical markers of cartilage damage). In this study actual cartilage AGE levels were directly related to actual cartilage damage by use of cartilage obtained at joint replacement surgery. METHODS: Cartilage and urine samples were obtained from 69 patients undergoing total knee replacement. Samples were analyzed for pentosidine as marker of AGE. Cartilage damage was evaluated macroscopically, histologically, and biochemically. RESULTS: Cartilage and urine pentosidine both increased with increasing age. The higher the macroscopic, histological, and biochemical cartilage damage the lower the cartilage pentosidine levels were. In multiple regression analysis age is not found to be a confounder. CONCLUSION: There is an inverse relation between cartilage AGEs and actual cartilage damage in end-stage OA. This is likely due to ongoing (ineffective) increased turnover of cartilage matrix proteins even in end stage disease. Copyright 2011, Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved. PMID: 22227209

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Vos PA, DeGroot J, Barten-van Rijbroek AD, Zuurmond AM, Bijlsma JW, Mastbergen SC, Lafeber FP. Elevation of cartilage AGEs does not accelerate initiation of canine experi mental osteoarthritis upon mild surgical damage. J Orthop Res. 2012 sep;30(9):1398404. Epub 2012 Mar 2. Osteoarthritis is a highly prevalent disease, age being the main risk factor. The agerelated accumulation of advanced-glycation-endproducts (AGEs) adversely affects the mechanical and biochemical properties of cartilage. The hypothesis that accumulation of cartilage AGEs in combination with surgically induced damage predisposes to the development of osteoarthritis was tested in vivo in a canine model. To artificially increase cartilage AGEs, right knee joints of eight dogs were repeatedly injected with ribose/threose (AGEd-joints). Left joints with vehicle alone served as control. Subsequently, minimal surgically applied cartilage damage was induced and loading restrained as much as possible. Thirty weeks after surgery, joint tissues of all dogs were analyzed for biochemical and histological features of OA. Cartilage pentosidine levels were ~5-fold enhanced (p = 0.001 vs. control-joints). On average, no statistically significant differences in joint degeneration were found between AGEd and controljoints. Enhanced cartilage pentosidine levels did correlate with less cartilage proteogly can release (R = -0.762 and R = -0.810 for total and newly-formed proteoglycans, respectively; p = 0.028 and 0.015 for both). The current data support the diminished cartilage turnover, but only a tendency towards enhanced cartilage damage in AGEd articular cartilage was observed. As such, elevated AGEs do not unambiguously accelerate the development of early canine OA upon minimal surgical damage. Copyright © 2012 Orthopaedic Research Society. PMID: 22388985

Vos P. Age and osteoarthritis: are AGEs the link. [Utrecht : Universiteit Utrecht] ; Rotterdam : Optima, 2012. ISBN 9789461692054.

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Seksuologie Kerngegevens Zorgkern Seksuologie • mw. J. (Coby) van Essen, mw. H. (Hester) Pastoor

Samenvattingen gepubliceerde artikelen Pastoor H, Jedeloo S. Seksualiteit. [Zorgbasics]. Den Haag: Boom Lemma Uitgevers, 2012. ISBN: 978-90-5931-857-1. De Niet JE, Pastoor H, Timman R, Laven, JS. Psycho-social and sexual well-Being in women with polycystic ovary syndrome. In: Polycystic Ovary Syndrome / Srabani Mukherjee [ed.]. [s.l.] : Intech, 2012. ISBN 978-953-51-0094-2.

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Sportgeneeskunde Kerngegevens Zorgkern Sportgeneeskunde • 2 sportartsen: A.M.W.W. (Ton) Langenhorst, mw. A.A.M. (Anne) van Vegchel – Hindriks • Subspecialismen: overbelastingsblessures

Samenvattingen gepubliceerde artikelen Van de Pol D, Kuijer PP, Langenhorst T, Maas M. High Prevalence of Self-Reported Symptoms of Digital Ischemia in Elite Male Volleyball Players in the Netherlands: A Cross-Sectional National Survey. Am J Sports Med. 2012 Aug 27. [Epub ahead of print]. BACKGROUND: In the past 3 years, 6 volleyball players with ischemic digits and small microemboli in the digital arteries of the dominant hand presented themselves in our hospital. These complaints were caused by an aneurysmatic dilation of the posterior circumflex humeral artery (PCHA) with distal occlusion and digital emboli in the iso lateral limb. All were elite male volleyball players active in the national top league. Little is known about the exact symptoms associated with PCHA pathological lesions with digital emboli (PCHAP with DE) and its prevalence in elite volleyball players. If vascular injury can be identified at an early stage, thromboembolic complications and irrever sible damage to the digits might be prevented. PURPOSE: To assess the prevalence of symptoms that are consistent with digital ischemia and may be caused by PCHAP with DE in elite male volleyball players in the Netherlands. STUDY DESIGN: Cross-sectional study; Level of evidence, 3. METHODS: A questionnaire survey was performed among elite volleyball players in the Dutch national top league and the Dutch beach volleyball team. The questionnaire was constructed using literature-based data on symptoms associated with PCHAP with DE, together with data retrieved from medical files. RESULTS: A total of 99 of the 107 athletes participated, with a response rate of 93%. The most frequently reported symptoms associated with PCHAP with DE were cold, blue, or pale digits in the dominant hand during or immediately after practice or com petition. The prevalence of these symptoms ranged from 11% to 27%. The prevalence of cold digits during practice and competition was 27%. The prevalence of cold, blue, and pale digits during or immediately after practice and competition was 12%. CONCLUSION: An unexpectedly high percentage of elite volleyball players reported symptoms that are associated with PCHAP with DE in the dominant hand. Because these athletes are considered potentially at risk for developing critical digital ischemia, further analysis of the presence of digital ischemia and PCHA injury is warranted. PMID: 22926747

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Urologie Kerngegevens Zorgkern Urologie • 6 urologen: P.J. (Pieter) van den Broeke, H. (Harald) Jansen, mw. I E.W. (Ilze) van Onna, E.H.G.M. (Eric) Oomens, P.J. (Péjé) Posthumus, D.K.E. (Deric) van der Schoot • 2 assistenten in opleiding • 1 assistent niet in opleiding • Subspecialismen: oncologie (kwaadaardige aandoeningen), stenen (in nieren, urineleiders of blaas), functionele urologie (incontinentie, plasklachten en neuro logische blaasproblemen), andrologie (erectiestoornissen, fertiliteit en ouder wordende man), kinderen (aangeboren afwijkingen), algemeen (vergrote prostaat en plasbuisafwijkingen)

Samenvattingen gepubliceerde artikelen Koning CC, Blank LE, Koedooder C, van Os RM, van de Kar M, Jansen E, Battermann JJ, Beijert M, Gernaat C, van Herpen KA, Hoekstra C, Horenblas S, Jobsen JJ, Krol AD, Lybeert ML, van Onna IE, Pelger RC, Poortmans P, Pos FJ, van der Steen-Banasik E, Slot A, Visser A, Pieters BR. Brachytherapy after external beam radiotherapy and limited sur gery preserves bladders for patients with solitary pT1-pT3 bladder tumors. Ann Oncol. 2012 Nov;23(11):2948-53. Epub 2012 Jun 19. BACKGROUND: Several French, Belgian and Dutch radiation oncologists have reported good results with the combination of limited surgery after external beam radiotherapy (EBRT) followed by brachytherapy in early-stage muscle-invasive bladder cancer. PATIENTS AND METHODS: Data from 12 of 13 departments which are using this approach have been collected retrospectively, in a multicenter database, resulting in 1040 patients: 811 males and 229 females with a median age of 66 years, range 28-92 years. Results were analyzed according to tumor stage and diameter, histology grade, age and brachytherapy technique, continuous low-dose rate (CLDR) and pulsed dose rate (PDR). RESULTS: At 1, 3 and 5 years, the local recurrence-free probability was 91%, 80% and 75%, metastasis-free probability was 91%, 80% and 74%, disease-free probability was 85%, 68% and 61% and overall survival probability was 91%, 74% and 62%, respectively. The differences in the outcome between the contributing departments were small. After multivariate analysis, the only factor influencing the local control rate was the brachytherapy technique. Toxicity consisted mainly of 24 fistula, 144 ulcers/necroses and 93 other types. CONCLUSIONS: EBRT followed by brachytherapy, combined with limited surgery, offers excellent results in terms of bladder sparing for selected groups of patients suffering from bladder cancer. PMID: 22718135

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Van Vugt HA, Kranse R, Steyerberg EW, van der Poel HG, Busstra M, Kil P, Oomens EH, de Jong IJ, Bangma CH, Roobol MJ. Prospective validation of a risk calculator which calculates the probability of a positive prostate biopsy in a contemporary clinical cohort. Eur J Cancer. 2012 Aug;48(12):1809-15. Epub 2012 Mar 7. BACKGROUND: Prediction models need validation to assess their value outside the development setting. OBJECTIVE: To assess the external validity of the European Randomised study of Screening for Prostate Cancer (ERSPC) Risk Calculator (RC) in a contemporary clinical cohort. METHODS: The RC calculates the probability of a positive sextant prostate biopsy (P(posb)) using serum prostate-specific antigen (PSA), results of digital rectal examina tion, transrectal ultrasound (TRUS) and ultrasound assessed prostate volume. We prospectively validated the RC in 320 biopsied men (55-75years), with no previous prostate biopsy, included in five Dutch hospitals in 2008-2011. If the P(posb) was ≥20% a biopsy was recommended. The performance of the RC was tested by comparing the observed outcomes to predicted probabilities, using the area under the curve (AUC) and decision curves analyses. RESULTS: Compared to the screening cohort, men in the clinical cohort differed. They had higher PSA levels (median 6.8 versus 4.3ng/ml, p<0.01), less TRUS-lesions (27% versus 34%, p=0.01) and more prostate cancer (PCa) at biopsy (43% versus 25%, p<0.01). Mainly eight biopsy cores were taken. Despite the differences between these cohorts, the mean observed probability agreed with the mean predicted probability (43% versus 40%). The RC predicted P(posb) better than a model with PSA and digital rectal examination, AUC 0.77 (95% confidence interval (CI) 0.72-0.83) and 0.71 (95%CI 0.65-0.76, p<0.01), respectively. This was confirmed by the decision curves analysis. Under the 20% threshold, 17% (11/63) of the biopsied men were diagnosed with PCa. Two of 11 men had an important cancer (Gleason 3+4). CONCLUSIONS: The ERSPC RC performs well in a Dutch clinical cohort in men with previous PSA tests and contemporary biopsy schemes, and outperforms a PSA and DRE-based approach in the decision to perform a biopsy. Copyright © 2012 Elsevier Ltd. All rights reserved. PMID: 22406050

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Van Vugt HA, Roobol MJ, Busstra M, Kil P, Oomens EH, de Jong IJ, Bangma CH, Steyerberg EW, Korfage I. Compliance with biopsy recommendations of a prostate cancer risk calculator. BJU Int. 2012 May;109(10):1480-8. Epub 2011 Sep 20. Study Type - Diagnostic (cohort) Level of Evidence 2b What’s known on the subject? and What does the study add? So far, few publications have shown that a prediction model influences the behaviour of both physicians and patients. To our knowledge, it was unknown whether urologists and patients are compliant with the recommenda tions of a prostate cancer risk calculator and their reasons for non-compliance. Recom mendations of the European Randomized study of Screening for Prostate Cancer risk calculator (ERSPC RC) about the need of a prostate biopsy were followed in most patients. In most cases of non-compliance with ‘no biopsy’ recommendations, a PSA level = 3 ng/mL was decisive to opt for biopsy. Before implementation of the ERSPC RC in urological practices at a large scale, it is important to obtain insight into the use of guidelines that might counteract the adoption of the use of the RC as a result of opposing recommendations. OBJECTIVES: To assess both urologist and patient compliance with a ‘no biopsy’ or ‘biopsy’ recommendation of the European Randomized study of Screening for Prostate Cancer (ERSPC) Risk Calculator (RC), as well as their reasons for non-compliance. To assess determinants of patient compliance. PATIENTS AND METHODS: The ERSPC RC calculates the probability on a positive sextant prostate biopsy (P(posb) ) using serum prostate-specific antigen (PSA) level, outcomes of digital rectal examination and transrectal ultrasonography, and ultraso nographically assessed prostate volume. A biopsy was recommended if P(posb) =20%. Between 2008 and 2011, eight urologists from five Dutch hospitals included 443 pa tients (aged 55-75 years) after a PSA test with no previous biopsy. Urologists calculated the P(posb) using the RC in the presence of patients and completed a questionnaire about compliance. Patients completed a questionnaire about prostate cancer know ledge, attitude towards prostate biopsy, self-rated health (12-Item Short Form Health Survey), anxiety (State Trait Anxiety Inventory-6, Memorial Anxiety Scale for Prostate Cancer) and decision-making measures (Decisional Conflict Scale). RESULTS: Both urologists and patients complied with the RC recommendation in 368 of 443 (83%) cases. If a biopsy was recommended, almost all patients (96%; 257/269) complied, although 63 of the 174 (36%) patients were biopsied against the recommen dation of the RC. Compliers with a ‘no biopsy’ recommendation had a lower mean P(posb) than non-compliers (9% vs 14%; P < 0.001). Urologists opted for biopsies against the recommendations of the RC because of an elevated PSA level (= 3 ng/mL) (78%; 49/63) and patients because they wanted certainty (60%; 38/63).

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CONCLUSIONS: Recommendations of the ERSPC RC on prostate biopsy were followed in most patients. The RC hence may be a promising tool for supporting clinical decisi on-making. © 2011 THE AUTHORS. BJU INTERNATIONAL PMID: 21933335

Van Vugt HA, Roobol MJ, van der Poel HG, van Muilekom EH, Busstra M, Kil P, Oomens EH, Leliveld A, Bangma CH, Korfage I, Steyerberg EW. Selecting men diagnosed with prostate cancer for active surveillance using a risk calculator: a prospective impact study. BJU Int. 2012 Jul;110(2):180-7. Epub 2011 Nov 23. OBJECTIVES: † To assess urologists’ and patients’ compliance with treatment recommendations based on a prostate cancer risk calculator (RC) and the reasons for non-compliance. † To assess the difference between patients who were compliant and non-compliant with recommendations based on this RC. PATIENTS AND METHODS: † Eight urologists from five Dutch hospitals included 240 patients with prostate cancer (PCa), aged 55-75 years, from December 2008 to February 2011. † The urologists used the European Randomized Study of Screening for Prostate Cancer RC which predicts the probability of potentially indolent PCa (P[indolent]), using serum prostate-specific antigen (PSA), prostate volume and patho logical findings on biopsy. † Inclusion criteria were PSA <20 ng/mL, clinical stage T1 or T2a-c disease, <50% positive sextant biopsy cores, = 20 mm cancer tissue, = 40 mm benign tissue and Gleason = 3 + 3. If the P(indolent) was >70%, active surveillance (AS) was recommended, and active treatment (AT) otherwise. † After the treatment decision, patients completed a questionnaire about their treatment choice, related (dis)advantages, and validated measurements of other factors, e.g. anxiety.

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RESULTS: † Most patients (45/55, 82%) were compliant with an AS recommendation. Another 54 chose AS despite an AT recommendation (54/185, 29%). † The most common reason for non-compliance with AT recommendations by urologists was the patient’s preference for AS (n= 30). These patients most often reported the delay of physical side effects of AT as the main advantage (n= 19). † Those who complied with AT recommendations had higher mean PSA levels (8 vs 7 ng/mL, P= 0.02), higher mean amount of cancer tissue (7 vs 3 mm, P < 0.001), lower mean P(indolent) (36% vs 55%, P < 0.001), and higher mean generic anxiety scores (42 vs 38, P= 0.03) than those who did not comply. CONCLUSIONS: † AS recommendations were followed by most patients, while 29% with AT recommendations chose AS instead. † Although further research is needed to validate the RC threshold, the current version is already useful in treatment decision-making in men with localized PCa. © 2011 BJU INTERNATIONAL. PMID: 22112199

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Kwaliteit & Veiligheid Kenniskern Kwaliteit & Veiligheid draagt bij aan alle Amphia-speerpunten Kwaliteit en patiëntveiligheid raken het gehele ziekenhuis. Waar is de Kenniskern Kwaliteit en Veiligheid eigenlijk níét bij betrokken? De activiteiten en onderzoeken die door de kenniskern worden uitgevoerd, zijn daarom belangrijk voor zowel patiënten als medewerkers. In de kenniskern komen talloze ziekenhuisactiviteiten samen. Waar houdt Kwaliteit en Veiligheid zich dan allemaal mee bezig? Onder meer met prestatie-indicatoren, onderzoek van calamiteiten, accreditatie van het ziekenhuis, informatiebeveiliging, veiligheidsrondes en interne audits. De kenniskern is ook betrokken bij de Raad van Qualiteit, de commissie Evaluatie van de ziekenhuissterfte (CEZ), de commissie Or gaan- en weefseldonatie, de Meldingen Incidenten Patiëntenzorg (MIP)-commissie en de klachtencommissie. Prof. dr. Rob Slappendel, manager Kwaliteit en Veiligheid en anesthesioloog, legt uit dat de kenniskern in juli 2009 is ontstaan vanuit de eerdere stafdienst SKI (Strategie, Kwaliteit en Innovatie). Met Slappendel als manager staat er een medisch specialist aan het hoofd van de afdeling, wat de toegang tot medisch specialisten vergemakkelijkt en het draagvlak vergroot bij de thema’s die in het zieken huis spelen. “Destijds heb ik daar even over nagedacht”, zegt Slappendel. “En toen heb ik gezegd dat ik het een jaar ging doen om te kijken hoe het zou uitpakken. Dat ik hier nu nog steeds ben, betekent dat ik hier met plezier werk en af en toe successen boek.” De onderzoeken van deze kenniskern springen misschien minder in het oog, maar ze zijn net zo belangrijk als de onderzoeken vanuit de medische specialismen. Een belangrijk onderzoek was in 2012 een onderzoek van Slappendel over de reductie van het aantal bloedtransfusies. Een ander onderzoek in 2012, van de onderzoekers Vorstius Kruijff, Slappendel, Van der Meer en De Vos, betrof de afnemende ziekenhuissterfte en (het verbeteren van) de gevolgen daarvan op orgaandonatie. Bloedtransfusie Slappendel deed onderzoek met als doel een daling van het aantal bloedtransfusies. “We hebben gekeken of we de compliance, dus het naleven van de regelgeving, tot honderd procent konden realiseren bij de uitgifte van transfusies. Uiteindelijk introdu ceerden we een door ons gemaakte checklist waarmee het resultaat inderdaad bereikt werd. We wonnen daarmee de tweede plaats van de IGZ ZorgVeiligPrijs.” Dit resultaat hangt – veelzeggend – ingelijst naast het bureau van Slappendel. “Bij dit onderzoek is veel samengewerkt met andere afdelingen en dat is een richting die we steeds meer willen ingaan.” Door de focus op kwaliteit en patiëntveiligheid draagt de kenniskern direct bij aan alle speerpunten van het ziekenhuis (oncologie, hart-long-vaten, bewe gen, moeder-kind en gezond ouder worden).


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Dr. Maartje de Vos,Edwin Vorstius Kruyff (zittend) en prof.dr. Rob Slappendel.


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Ziekenhuissterfte en orgaandonatie Vorstius Kruijff zet zich met de commissie Orgaan- en weefseldonatie in voor beleid rondom het optimaal benutten van het orgaanen weefselpotentieel binnen het ziekenhuis. Ook is hij betrokken bij de CEZ-commissie. In deze commissie wordt via dossierscreening gezocht naar vermijdbare ziekenhuissterfte, met als doel dit sterfte cijfer te reduceren. “Door het dalen van de ziekenhuissterfte– wat natuurlijk op zich heel positief is – neemt wel het aantal potentiële orgaanen weefseldonaties af. Dit wordt ook beïnvloedt door een daling van het aantal verkeersongelukken.” Vorstius Kruijff heeft onderzocht hoe het donorpotentieel meer benut kan worden. Bijvoor beeld door het bevorderen van inschrijving in het donorregister via het ziekenhuis, uitbreiding van de mogelijkheden voor orgaandonatie op de Spoedeisende Hulp, donorwerving buiten het ziekenhuis en training van professionals in de communicatie rond donatie. “Op dit moment zijn er twaalf mensen binnen de Intensive Care van het Amphia Ziekenhuis speciaal opgeleid om de communicatie rond donatie bij familie te verbeteren.” De training vindt plaats via ‘blended learning’: een combinatie van e-learning en vaardigheidstraining. Accreditatie voor deze opleiding is aangevraagd. Te starten onderzoek Op dit moment zijn er veel initiatieven in Nederland om de kwaliteit van de ziekenhuis zorg naar een nog hoger niveau te tillen. Compliance officer Moniek Huisman: “De belangen zijn soms tegenstrijdig. Je hebt te maken met patiënten, zorgverzekeraars, ziekenhuisbesturen, professionals in loondienst of in maatschappen, overheid, inspectie en werknemers. Om toch grip te krijgen op de kwaliteit zijn diverse regels verplichtin gen, instrumenten en richtlijnen ontwikkeld.” Binnen Kwaliteit en Veiligheid zal Huisman een nieuw onderzoek starten waarbij gekeken wordt in hoeverre het nauwkeurig navolgen van de richtlijnen (compliance) daadwerkelijk leidt tot verbetering van de zorgkwaliteit. Ook wil ze onderzoeken of honderd procent compliance eenvoudig te bereiken is, onder welke voorwaarden dat mogelijk is en of het verbetering oplevert voor de patiëntveiligheid. Het onderzoek bevindt zich nog in de verkennende fase. Wetenschapsbeleid Bij de medewerkers van de Kenniskern Kwaliteit en Veiligheid bestaat een duidelijke wens om meer samen te werken met de Amphia Academie en het Bedrijfsinformatie centrum (BIC). Met name bij scholing, maar ook bij het verkrijgen van relevante gegevens vanuit de database van het BIC . Slappendel ervaart op dit moment nog te weinig samenhang in het wetenschapsbeleid binnen het ziekenhuis. “De gewenste onderzoekslijn mag ziekenhuisbreed nog duidelijker uitgezet worden. Daar zijn ze binnen de Academie ook mee aan het werk.” Op vrijdag 6 september 2013 vonden de oraties plaats van bijzonder hoogleraren prof. dr. Slappendel en prof. dr. Caris (zie het artikel over de Amphia Academie), die horen bij hun respectievelijke leerstoelen Veiligheid en kwaliteit in de zorg en Organisatie-ontwikkeling in de zorg.


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Kerngegevens Kenniskern Kwaliteit & Veiligheid • 1 Manager Kwaliteit & Veiligheid: prof.dr. R. Slappendel • 4 Beleidsmedewerkers: M. Goossens, B. Tecklenburg, E. Vorstius Kruijff, dr. M. de Vos, T. Schipperen • 1 Compliance Officer: M. Huisman • 1 Security Officer: T. Schipperen • 3 Ambtelijk secretarissen: G. Forman, S. Scholte-van Gurp, M.Rijppaert-Vrij (klachtencommissie, MIP commissie, Raad van Qualiteit, Commissie evaluatie Ziekenhuissterfte (CEZ)) • 2 Klachtenfunctionarissen: T. de Bruijn- Goumans, A. van Run • 2 Donatiefunctionarissen: B. Tecklenburg, E. Vorstius Kruijff

Overzicht lopende onderzoeken • Reductie in het aantal bloedtransfusies via een checklist • Leidt compliance tot kwaliteitsverbetering? • Optimaliseren donorpotentieel (organen en weefsels) • Verminderen vermijdbare ziekenhuissterfte; optimaliseren patiëntbeleving

Samenvattingen gepubliceerde artikelen Vorstius Kruijff EP, Slappendel R, de Vos ML, van der Meer NJ. Mogelijk minder donoren door daling ziekenhuissterfte [Possibly fewer donors due to decreasing hospital mortality rates]. Ned Tijdschr Geneeskd. 2012;156(42):A4418 [1775-9]. Over the past ten years, the mortality rate at the Amphia Hospital in the Netherlands has decreased and the average age at death has increased significantly. This down ward trend in hospital mortality rates is a national trend in the Netherlands. In additi on, in recent years road traffic fatalities have steadily decreased. Both trends have had a significant impact on the availability of potential organ and tissue donors. Currently the main barriers to donation are the limited number of registrations in the donor registry and obtaining permission from relatives. To achieve the maximum number of donors, several initiatives must be undertaken. These include hospitals encouraging registration in the donor registry, training of professionals in communication skills concerning donation, increasing opportunities for organ donations in the emergency department and recruiting donors extramurally. If no measures are taken, a decreasing number of patients with end-stage organ failure will be able to profit from organ transplantation. PMID: 23031233


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Van der Voort PH, van der Veer SN, de Vos ML. The use of indicators to improve the quality of intensive care: theoretical aspects and experiences from the Dutch intensive care registry. Acta Anaesthesiol Scand. 2012 Oct;56(9):1084-91. Epub 2012 Apr 10. In the concept of total quality management that was originally developed in industry, the use of quality indicators is essential. The implementation of quality indicators in the intensive care unit to improve the quality of care is a complex process. This process can be described in seven subsequent steps of an indicator-based quality improve ment (IBQI) cycle. With this IBQI cycle, a continuous quality improvement can be achieved with the use of indicator data in a benchmark setting. After the development of evidence-based indicators, a sense of urgency has to be created, registration should start, raw data must be analysed, feedback must be given, and interpretation and con clusions must be made, followed by a quality improvement plan. The last step is the implementation of changes that needs a sense of urgency, and this completes the IBQI cycle. Barriers and facilitators are found in each step. They should be identified and ad dressed in a multifaceted quality improvement strategy. © 2012 The Authors. Acta Anaesthesiologica Scandinavica © 2012 The Acta Anaesthe siologica Scandinavica Foundation. PMID: 22490006

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Zorginnovatie Kerngegevens Kenniskern Zorginnovatie • 1 Manager Innovatie, mw drs M.C. Bennink • 1 Projectmedewerker, mw drs C.V Vilrokx

Samenvattingen gepubliceerde artikelen Slort W, Vilrokx C, Belderbos H, Loosveld O,Thijssen F, Frankenhuis R, Bennink C. Specia listen en huisartsen spreken met ongeneeslijk zieke oncologische patiënten over de laatste levensfase. Een regionale pilot met ‘Advance Care Planning’. Ned-Vlaams Tijdschr voor Palliatieve Zorg. 2012;12(2):28-39. Background: Discussing various end-of-life issues with palliative care patients in time is considered to be an essential requirement for the delivery of high-quality pallia tive care. Besides, the several doctors treating a palliative care patient in hospital and at home frequently communicate insufficiently with each other about this proactive palliative care. Aim: Implementation of a newly developed method of ‘Advance Care Planning’ will en courage oncology specialists and general practitioners to discuss various end-of-life is sues with palliative care patients and with each other. Method: We registered the number of palliative care patients included by oncology specialists, how often these specialists communicated with general practitioners about a patient, and how often general practitioners informed specialists of patients’ ‘Advance Care Planning’ preferences. Besides, patients, surviving next-of-kin, specialists and general practitioners were interviewed about their experiences with the ‘Advance Care Planning’ method. Results: The specialists included 97 patients. Of the 84 times the specialist telep honed the general practitioner, this was 59 times successful. General practitioners in formed the specialist of preferences of 33 patients; with 32 of them the resuscitation status was discussed. The 17 patients and 10 surviving next-of-kin who were intervie wed felt that they were well-informed about their condition and consequently could ti mely arrange their affairs. The ‘Advance Care Planning’ method was appreciated as useful by the participating specialists and general practitioners. Conclusion: Our results suggest that the new ‘Advance Care Planning’ method was usable and encouraged oncology specialists and general practitioners to discuss endof-life issues with their palliative care patients.

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De Vries EN, Prins HA, Bennink MC, Neijenhuis P, van Stijn I, van Helden SH, van Putten MA, Smorenburg SM, Gouma DJ, Boermeester MA. Nature and timing of incidents in tercepted by the SURPASS checklist in surgical patients. BMJ Qual Saf. 2012 Jun;21(6):503-8. Epub 2012 Mar 23. INTRODUCTION: More than half of in-hospital adverse events can be attributed to a surgical discipline. Checklists can effectively decrease errors and adverse events. Howe ver, the mechanisms by which checklists lead to increased safety are unclear. This stu dy aimed to assess the number, nature and timing of incidents intercepted by use of the Surgical Patient Safety System (SURPASS) checklist, a patient-specific multidiscipli nary checklist that covers the entire surgical patient pathway. METHODS: The checklist was implemented in two academic hospitals and four tea ching hospitals in the Netherlands. Users of the checklist had three options for each item that was checked: ‘not applicable’, ‘yes’ and ‘intercepted by checklist’. In each hos pital, the first 1000 completed checklists were entered into an online central database. RESULTS: In six participating hospitals, 6313 checklists were collected. One or more inci dents were intercepted in 2562 checklists (40.6%). In total, 6312 incidents were inter cepted. After correction for the number of items and the extent of adherence in each part of the checklist, the number of intercepted incidents was highest in the preopera tive and postoperative stages. CONCLUSIONS: The checklist intercepts many potentially harmful incidents across all stages of the surgical patient pathway. The majority of incidents were intercepted in the preoperative and postoperative stages of the pathway. The degree to which these incidents would have been intercepted by a single checklist in the operating room only, compared with a checklist for the entire surgical pathway, remains a subject for future study. PMID: 22447822

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Van den Branden BJ, Swaans MJ, Post MC, Rensing BJ, Eefting FD, Jaarsma W, Van der Heyden JA. Percutaneous edge-to-edge mitral valve repair in high-surgical-risk patients: do we hit the target? JACC Cardiovasc Interv. 2012 Jan;5(1):105-11. Van den Branden BJ, Rahel BM, Laarman GJ, Slagboom T, Kelder JC, Ten Berg JM, Suttorp MJ. Five-year clinical outcome after primary stenting of totally occluded native coronary arteries: a randomised comparison of bare metal stent implantation with sirolimus-eluting stent implantation for the treatment of total coronary occlusions (PRISON II study). EuroIntervention. 2012 Feb;7(10):1189-96. Cnossen TT, Konings CJ, Fagel WJ, van der Sande FM, van Geel K, Leunissen KM, Kooman JP. Fluid State and Blood Pressure Control: No Differences Between APD and CAPD. ASAIO J. 2012 Mar;58(2):132-6. Cnossen TT, Kooman JP, Krepel HP, Konings CJ, Uszko-Lencer NH, Leunissen KM, van der Sande FM. Prospective study on clinical effects of renal replacement therapy in treatment-resistant congestive heart failure. Nephrol Dial Transplant. 2012 Jul;27(7):2794-9. Epub 2012 Apr 6. Cnossen TT. New developments in Peritoneal Dialysis. Maastricht : Universitaire Pers, 2012. ISBN: 9789461591272. Van Der Sande FM, Cnossen TT, Cornelis T, Konings CJ, Kooman JP, Leunissen KM. Peri toneal dialysis in patients with heart failure. Minerva Urol Nefrol. 2012 Sep;64(3):163-72. Ten Tije AJ, Cnossen N. Nierfunctie en oncologische middelen op oudere leeftijd. In: Compendium behandeling van kanker bij ouderen / Nortier JW, Schouten HC [et al...]. Den Haag: Academic Pharmaceutical Productions, 2012. ISBN 9789057611179. Beckers HJ, Webers CA, Busch MJ, Brink HM, Colen TP, Schouten JS; The Dutch Adherence Study Group. Adherence improvement in Dutch glaucoma patients: a randomized controlled trial. Acta Ophthalmol. 2012 Oct 1. [Epub ahead of print]. Crolla RM, van der Laan L, Veen EJ, Hendriks Y, van Schendel C, Kluytmans J. Reduction of surgical site infections after implementation of a bundle of care. PLoS One. 2012;7(9):e44599. Epub 2012 Sep 4. Postma EL, Verkooijen HM, van Esser S, Hobbelink MG, van der Schelling GP, Koelemij R, Witkamp AJ, Contant C, van Diest PJ, Willems SM, Borel Rinkes IH, van den Bosch MA, Mali WP, van Hillegersberg R; ROLL study group [Dijkstra H et al...]. Efficacy of ‘radiog uided occult lesion localisation’ (ROLL) versus ‘wire-guided localisation’ (WGL) in breast conserving surgery for non-palpable breast cancer: a randomised controlled multicen tre trial. Breast Cancer Res Treat. 2012 Nov;136(2):469-78. Epub 2012 Sep 30.


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Uzun S, Djamin RS, Kluytmans J, Van’t Veer NE, Ermens AA, Pelle AJ, Mulder P, van der Eerden MM, Aerts J. Influence of macrolide maintenance therapy and bacterial colonisation on exacerbation frequency and progression of COPD (COLUMBUS): study protocol for a randomised controlled trial. Trials. 2012 Jun 9;13:82. Bleyen I, Saelens IE, van Dooren BT, van Rij G. Spontaneous corneal clearing after Descemet’s stripping. Ophthalmology. 2013 Jan;120(1):215. Parving HH, Brenner BM, McMurray JJ, de Zeeuw D, Haffner SM, Solomon SD, Chaturvedi N, Persson F, Desai AS, Nicolaides M, Richard A, Xiang Z, Brunel P, Pfeffer MA; ALTITUDE Investigators. [Dunselman PH et al...] Cardiorenal end points in a trial of aliskiren for type 2 diabetes. N Engl J Med. 2012 Dec ;367(23):2204-13. Epub 2012 Nov 3. Valente MA, Damman K, Dunselman PH, Hillege HL, Voors AA. Urinary proteins in heart failure. Prog Cardiovasc Dis. 2012 Jul-Aug;55(1):44-55. Gullestad L, Ueland T, Kjekshus J, Nymo SH, Hulthe J, Muntendam P, Adourian A, Böhm M, van Veldhuisen DJ, Komajda M, Cleland JG, Wikstrand J, McMurray JJ, Aukrust P; CORONA Study Group [Dunselman PH et al...]. Galectin-3 predicts response to statin therapy in the Controlled Rosuvastatin Multinational Trial in Heart Failure (CORONA). Eur Heart J. 2012 Sep;33(18):2290-6. Epub 2012 Apr 17. Morrow DA, Braunwald E, Bonaca MP, Ameriso SF, Dalby AJ, Fish MP, Fox KA, Lipka LJ, Liu X, Nicolau JC, Ophuis AJ, Paolasso E, Scirica BM, Spinar J, Theroux P, Wiviott SD, Strony J, Murphy SA; TRA 2P–TIMI 50 Steering Committee and Investigators* [Dunselman PH et al...]. Vorapaxar in the secondary prevention of atherothrombotic events. N Engl J Med. 2012 Apr 12;366(15):1404-13. Epub 2012 Mar 24. Van Seventer R, Vos C, Giezeman M, Meerding WJ, Arnould B, Regnault A, van Eerd M, Martin C, Huygen F. Validation of the Dutch Version of the DN4 Diagnostic Question naire for Neuropathic Pain. Pain Pract. 2013 Jun;13(5):390-8. Epub 2012 Oct 31. Eikelboom JI, ten Cate OT, Jaarsma D, Raat JA, Schuwirth L, van Delden JJ. A framework for the ethics review of education research. Med Educ. 2012 Aug;46(8):731-3. Van Thiel GJ, Dankerlui-Eikelboom JL. Technologie in de fysiotherapie: instrumenten van zorg. Ned Tijdschr voor Fysiother. 2012;122(2):42-5. Lindenhovius A, Karanicolas PJ, Bhandari M, Ring D; COAST Collaborative* [Elmans LH et al...]. Radiographic arthrosis after elbow trauma: interobserver reliability. J Hand Surg Am. 2012 Apr;37(4):755-9. Epub 2012 Mar 6. Erceg A. Innovation of vascular laser for clinical practice; from vascular to inflammatory targets. [S.l. : s.n.], 2012 (Nijmegen : Ipskamp Drukkers). - Proefschrift Radboud Universiteit Nijmegen. ISBN 978-909-027-115-6. Publicaties medisch specialisten 2012

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Ammerlaan HS, Harbarth S, Buiting AG, Crook DW, Fitzpatrick F, Hanberger H, Herwaldt LA, van Keulen PH, Kluytmans JA, Kola A, Kuchenbecker RS, Lingaas E, Meessen N, Morris-Downes MM, Pottinger JM, Rohner P, dos Santos RP, Seifert H, Wisplinghoff H, Ziesing S, Walker AS, Bonten MJ. Secular trends in nosocomial bloodstream infections: antibiotic-resistant bacteria increase the total burden of infection. Clin Infect Dis. 2013 Mar;56(6):798-805. Epub 2012 Dec 7. Veenemans J, Mouton JW, Kluytmans JA, Donnely R, Verhulst C, van Keulen PH. Effect of manganese in test media on in vitro susceptibility of Enterobacteriaceae and Acinetobacter baumannii to tigecycline. J Clin Microbiol. 2012 Sep;50(9):3077-9. Donker JM, van der Laan L, Hendriks YJ, Kluytmans JA. Evaluation of staphylococcus aureus nasal carriage screening before vascular surgery. PLoS One. 2012;7(6):e38127. Epub 2012 Jun 7. Crolla RM, van der Laan L, Veen EJ, Hendriks Y, van Schendel C, Kluytmans J. Reduction of surgical site infections after implementation of a bundle of care. PLoS One. 2012;7(9):e44599. Epub 2012 Sep 4. Kluytmans-van den Bergh MF, Kluytmans JA. Editorial Commentary: Control of Multi drug-Resistant Microorganisms: Beyond the Hospital. Clin Infect Dis. 2012 Dec;55(11):1512-4. Epub 2012 Sep 5. Kluytmans JA, Overdevest IT, Willemsen I, Kluytmans-van den Bergh MF, van der Zwaluw K, Heck M, Rijnsburger M, Vandenbroucke-Grauls CM, Savelkoul PH, Johnston BD, Gordon D, Johnson JR. Extended-spectrum beta-lactamase-producing Escherichia coli from retail chicken meat and humans: comparison of strains, plasmids, resistance genes, and virulence factors. Clin Infect Dis. 2013 Feb;56(4):478-87. Epub 2012 Dec 14. Bernards AT, Bonten MJM, Cohen-Stuart J, Diederen B, Goessens WHF, Grundmann H, Kluytmans JAJW, Kluytmans - van den Bergh MFQ, Leverstein - van Hall MA, Mouton JW, al Naiemi N. Troelstra A, Vandenbroucke - Grauls CMJE, Vos MC, Voss A. Recom mendations of the NVMM guideline Laboratory detection of highly resistant micro organisms. Ned Tijdschr Med Microbiol. 2012;20:13-5. Ammerlaan HS, Harbarth S, Buiting AG, Crook DW, Fitzpatrick F, Hanberger H, Herwaldt LA, van Keulen PH, Kluytmans JA, Kola A, Kuchenbecker RS, Lingaas E, Meessen N, Morris-Downes MM, Pottinger JM, Rohner P, dos Santos RP, Seifert H, Wisplinghoff H, Ziesing S, Walker AS, Bonten MJ. Secular trends in nosocomial bloodstream infections: antibiotic-resistant bacteria increase the total burden of infection. Clin Infect Dis. 2013 Mar;56(6):798-805. Epub 2012 Dec 7.


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Veenemans J, Mouton JW, Kluytmans JA, Donnely R, Verhulst C, van Keulen PH. Effect of manganese in test media on in vitro susceptibility of Enterobacteriaceae and Acinetobacter baumannii to tigecycline. J Clin Microbiol. 2012 Sep;50(9):3077-9. Koningstein M, Groen L, Geraats-Peters K, Lutgens S, Rietveld A, Jira P, Kluytmans J, de Greeff SC, Hermans M, Schneeberger PM. The use of typing methods and infection prevention measures to control a bullous impetigo outbreak on a neonatal ward. Antimicrob Resist Infect Control. 2012 Nov 20;1(1):37. Van Cleef BA, van Rijen M, Ferket M, Kluytmans JA. Self-sampling is appropriate for detection of Staphylococcus aureus: a validation study. Antimicrob Resist Infect Control. 2012 Nov 8;1(1):34. Verkade E, Bergmans AM, Budding AE, van Belkum A, Savelkoul P, Buiting AG, Kluytmans J. Recent emergence of Staphylococcus aureus clonal complex 398 in human blood cultures. PLoS One. 2012;7(10):e41855. Epub 2012 Oct 18. Feingold BJ, Silbergeld EK, Curriero FC, van Cleef BA, Heck ME, Kluytmans JA. Livestock density as risk factor for livestock-associated methicillin-resistant Staphylococcus aureus, the Netherlands. Emerg Infect Dis. 2012 Nov;18(11):1841-9. Overdevest IT, Heck M, van der Zwaluw K, Willemsen I, van de Ven J, Verhulst C, Kluytmans JA. Comparison of SpectraCell RA typing and multilocus sequence typing for extended-spectrum-ß-lactamase-producing Escherichia coli. J Clin Microbiol. 2012 Dec;50(12):3999-4001. Epub 2012 Oct 3. Wintermans BB, Reuland EA, Wintermans RG, Bergmans AM, Kluytmans JA. The cost-effectiveness of ESBL detection: towards molecular detection methods? Clin Microbiol Infect. 2013 Jul;19(7):662-5. Epub 2012 Sep 12. Voss A, Kluytmans J, Pittet D. A new journal and new global perspective on infection control and public health. Antimicrob Resist Infect Control. 2012 Jan 26;1(1):4. Van Rijen MM, Bode LG, Baak DA, Kluytmans JA, Vos MC. Reduced costs for Staphylo coccus aureus carriers treated prophylactically with mupirocin and chlorhexidine in cardiothoracic and orthopaedic surgery. PLoS One. 2012;7(8):e43065. Epub 2012 Aug 14. Huijskens EG, van Erkel AJ, Palmen FM, Buiting AG, Kluytmans JA, Rossen JW. Viral and bacterial aetiology of community-acquired pneumonia in adults. Influenza Other Respi Viruses. 2012 Aug 22. [Epub ahead of print]. Van Cleef BA, Kluytmans JA, van Benthem BH, Haenen A, Monen J, Daniels-Haardt I, Jurke A, Friedrich AW. Cross border comparison of MRSA bacteraemia between The Netherlands and North Rhine-Westphalia (Germany): a cross-sectional study. PLoS One. 2012;7(8):e42787. Epub 2012 Aug 3. Publicaties medisch specialisten 2012

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Reuland EA, Overdevest IT, Al Naiemi N, Kalpoe JS, Rijnsburger MC, Raadsen SA, Ligtenberg-Burgman I, van der Zwaluw KW, Heck M, Savelkoul PH, Kluytmans JA, Vandenbroucke-Grauls CM. High prevalence of ESBL-producing Enterobacteriaceae carriage in Dutch community patients with gastrointestinal complaints. Clin Microbiol Infect. 2013 Jun;19(6):542-9. Epub 2012 Jul 3. Oostdijk EA, de Smet AM, Kesecioglu J, Bonten MJ; Dutch SOD-SDD Trialists Group* [Kluytmans JA et al...]. Decontamination of cephalosporin-resistant Enterobacteria ceae during selective digestive tract decontamination in intensive care units. J Antimicrob Chemother. 2012 Sep;67(9):2250-3. Epub 2012 May 29. Verkade E, Bosch T, Hendriks Y, Kluytmans J. Outbreak of methicillin-resistant Staphylococcus aureus ST398 in a Dutch nursing home. Infect Control Hosp Epidemiol. 2012 Jun;33(6):624-6. Epub 2012 Apr 24. Wassenberg M, Kluytmans J, Erdkamp S, Bosboom R, Buiting A, van Elzakker E, Melchers W, Thijsen S, Troelstra A, Vandenbroucke-Grauls C, Visser C, Voss A, Wolffs P, Wulf M, van Zwet T, de Wit A, Bonten M. Costs and benefits of rapid screening of methicillin-resistant Staphylococcus aureus carriage in intensive care units: a prospective multicenter study. Crit Care. 2012 Feb 7;16(1):R22. De Smet AM, Bonten MJ, Kluytmans JA. For whom should we use selective decontamination of the digestive tract? Curr Opin Infect Dis. 2012 Apr;25(2):211-7. Melsen WG, de Smet AM, Kluytmans JA, Bonten MJ; Dutch SOD-SDD Trialists’ Group*. Selective decontamination of the oral and digestive tract in surgical versus non-surgi cal patients in intensive care in a cluster-randomized trial. Br J Surg. 2012 Feb;99(2):2327. Epub 2011 Oct 24. Voets GM, Platteel TN, Fluit AC, Scharringa J, Schapendonk CM, Stuart JC, Bonten MJ, Hall MA; National ESBL Surveillance Working Group* [Kluytmans JA et al...]. Population distribution of Beta-lactamase conferring resistance to third-generation cephalosporins in human clinical Enterobacteriaceae in the Netherlands. PLoS One. 2012;7(12):e52102. Epub 2012 Dec 20. Van der Bij AK, van Dijk K, Muilwijk J, Thijsen SF, Notermans DW, de Greeff S, van de Sande-Bruinsma N; ISIS-AR study group* [Kluytmans JA et al...]. Clinical breakpoint changes and their impact on surveillance of antimicrobial resistance in Escherichia coli causing bacteraemia. Clin Microbiol Infect. 2012 Nov;18(11):E466-72. Epub 2012 Aug 27. Uzun S, Djamin RS, Kluytmans J, Van’t Veer NE, Ermens AA, Pelle AJ, Mulder P, van der Eerden MM, Aerts J. Influence of macrolide maintenance therapy and bacterial colonisation on exacerbation frequency and progression of COPD (COLUMBUS): study protocol for a randomised controlled trial. Trials. 2012 Jun 9;13:82. Publicaties medisch specialisten 2012

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Kuethe MC, Sixma HJ, Vaessen-Verberne AA, Booij JC, van Aalderen WM. Assessing quality of care in pediatric asthma: applicability of a revised version of the QUOTECNSLD questionnaire. J Asthma. 2012 Nov;49(9):966-76. Epub 2012 Oct 1. Donker JM, van der Laan L, Hendriks YJ, Kluytmans JA. Evaluation of staphylococcus aureus nasal carriage screening before vascular surgery. PLoS One. 2012;7(6):e38127. Epub 2012 Jun 7. Gobardhan PD, de Wall LL, van der Laan L, Ten Tije AJ, van der Meer DC, Tetteroo E, Poortmans PM, Luiten EJ. The role of radioactive iodine-125 seed localization in breast-conserving therapy following neoadjuvant chemotherapy. Ann Oncol. 2013 Mar;24(3):668-73. Epub 2012 Nov 8. Crolla RM, van der Laan L, Veen EJ, Hendriks Y, van Schendel C, Kluytmans J. Reduction of surgical site infections after implementation of a bundle of care. PLoS One. 2012;7(9):e44599. Epub 2012 Sep 4. De Leur K, van Zeeland ML, Ho GH, de Groot HG, Veen EJ, van der Laan L. Treatment for critical lower limb ischemia in elderly patients. World J Surg. 2012 Dec;36(12):2937-43. Donker JM, Tijnagel MJ, van Zeeland ML, Veen EJ, van der Laan L. Anastomoses in the common femoral artery, vascular clips or sutures? A feasibility study. Ann Vasc Surg. 2013 Feb;27(2):194-8. Epub 2012 Jul 25. Klompenhouwer EG, Helleman JN, Geenen GP, Ho GH, Vos LD, Van der Laan L. Reinterventions following endovascular abdominal aortic aneurysm repair, the learning curve of time. J Cardiovasc Surg (Torino). 2012 Nov 8. [Epub ahead of print]. Castenmiller PH, de Leur K, de Jong TE, van der Laan L. Clinical results after coil embolization of the ovarian vein in patients with primary and recurrent lower-limb varices with respect to vulval varices. Phlebology. 2012 Mar 22. [Epub ahead of print]. Kodde IF, van Zeeland, MLP, de Groot HGW, van der Laan L. Successful conservative management of aortic graft infections with intra-abdominal abscesses by percutane ous drainage and specific antibiotic therapy. Vasc Dis Man. 2012;9(11):E189-192. Te Slaa A, Dolmans DE, Ho GH, Moll FL, van der Laan L. Pathophysiology and treatment of edema following femoropopliteal bypass surgery. Vascular. 2012 Dec;20(6):350-9. Epub 2012 Sep 14. Boersema GS, van der Laan L. ‘Spontaan’ vrij lucht in de buikholte. Ned Tijdschr Heelkd. 2012;21(4):185-186. Boersema GS, Veen EJ, van der Laan L. Cholecystitis acuta en salmonella sepsis. Ned Tijdschr Heelkd. 2012;21(5):247-8. Publicaties medisch specialisten 2012

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Meyer ZC, Schreinemakers JM, van der Laan L. The value of C-reactive protein and lactate in the acute abdomen in the emergency department. World J Emerg Surg. 2012 Jul 16;7(1):22. Van de Pol D, Kuijer PP, Langenhorst T, Maas M. High Prevalence of Self-Reported Symptoms of Digital Ischemia in Elite Male Volleyball Players in the Netherlands: A Cross-Sectional National Survey. Am J Sports Med. 2012 Aug 27. [Epub ahead of print]. Niemeijer ND, van Daele PL, Caliskan K, Oei FB, Loosveld OJ, van der Meer NJ. Loffler endocarditis: a rare cause of acute cardiac failure. J Cardiothorac Surg. 2012 Oct 10;7(1):109. [Epub ahead of print]. Meulenbeld HJ, van Werkhoven ED, Coenen JL, Creemers GJ, Loosveld OJ, de Jong PC, Ten Tije AJ, Fosså SD, Polee M, Gerritsen W, Dalesio O, de Wit R. Randomised phase II/III study of docetaxel with or without risedronate in patients with metastatic Castration Resistant Prostate Cancer (CRPC), the Netherlands Prostate Study (NePro). Eur J Cancer. 2012 Nov;48(16):2993-3000. Epub 2012 Jun 6. Slort W, Vilrokx C, Belderbos H, Loosveld O,Thijssen F, Frankenhuis R, Bennink C. Specialisten en huisartsen spreken met ongeneeslijk zieke oncologische patiënten over de laatste levensfase. Een regionale pilot met ‘Advance Care Planning’. Ned-Vlaams Tijdschr voor Palliatieve Zorg. 2012;12(2):28-39. Gobardhan PD, Wijsman JH, van Dalen T, Klompenhouwer EG, van der Schelling GP, Los J, Voogd AC, Luiten EJ. ARM: axillary reverse mapping - the need for selection of patients. Eur J Surg Oncol. 2012 Aug;38(8):657-61. Epub 2012 May 17. Gobardhan PD, de Wall LL, van der Laan L, Ten Tije AJ, van der Meer DC, Tetteroo E, Poortmans PM, Luiten EJ. The role of radioactive iodine-125 seed localization in breast-conserving therapy following neoadjuvant chemotherapy. Ann Oncol. 2013 Mar;24(3):668-73. Epub 2012 Nov 8. Gobardhan PD, Wijsman JH, van Dalen T, Klompenhouwer EG, van der Schelling GP, Los J, Voogd AC, Luiten EJ. ARM: axillary reverse mapping - the need for selection of patients. Eur J Surg Oncol. 2012 Aug;38(8):657-61. Epub 2012 May 17. Postma EL, Verkooijen HM, van Esser S, Hobbelink MG, van der Schelling GP, Koelemij R, Witkamp J, Contant C, van Diest PJ, Willems SM, Borel Rinkes IH, van den Bosch MA, Mali WP, van Hillegersberg R; ROLL study group [Luiten E, et al...]. Efficacy of ‘radio guided occult lesion localisation’ (ROLL) versus ‘wire-guided localisation’ (WGL) in breast conserving surgery for non-palpable breast cancer: a randomised controlled multicentre trial. Breast Cancer Res Treat. 2012 Nov;136(2):469-78. Epub 2012 Sep 30.


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Colofon Vormgeving Commond - Content for Brands, Breda Interviews Leonore Pulleman van Tekstpartners, Breda Fotografie Esther Hereijgers, Breda Overzicht publicaties Jan van Trier Eindredactie Attie Tuinenburg, Judith Jansen, Leonore Pulleman Verspreiding Kenniskern Amphia Academie

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