Oosterhout

Derde wetenschapsboek van het Amphia Ziekenhuis Breda/Oosterhout

Derde wetenschapsboek van het

Amphia Ziekenhuis Breda/Oosterhout

Najaar 2011

© 2011 Amphia Ziekenhuis Breda Oosterhout Alle rechten voorbehouden. Niets uit deze uitgave mag worden verveelvoudigd, opgeslagen in een geautomatiseerd 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 jo 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 bloemlezingen, readers en andere compilatie- of andere werken (artikel 16 Auteurswet 1912), in welke vorm dan ook, dient men zich tot de samenstellers/uitgever 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 uitgever aansprakelijkheid aanvaarden voor eventuele schade die zou kunnen voortvloeien uit enige fout die in deze uitgave zou kunnen voorkomen.

Woord vooraf Een van de nieuwste beleidsvisies van de STZ, de samenwerkende Topklinische Ziekenhuizen van Nederland, benadrukt de mogelijkheden én noodzaak van wetenschappelijk onderzoek in de Topklinische Ziekenhuizen. De mogelijkheden zijn enorm. Door de omvang van de ziekenhuizen, de goede samenwerking met Universitaire Centra en de breedte van de vakgebieden zijn juist Topklinische ziekenhuizen uitstekende werkplaatsen voor onderzoek. Daarnaast kan geconstateerd worden dat voor veel wetenschappelijk onderzoek grote patiëntenpopulaties nodig zijn. Ook daarin kunnen dit soort ziekenhuizen voorzien, daar waar Academische ziekenhuizen, door hun topreferentiële functie, deze grote populaties vaak ontberen. Het Amphia zet zich daarom al jaren in voor hoogwaardig klinisch onderzoek in de geneeskunde. De infrastructuur voor dit onderzoek neemt jaar na jaar in omvang en kracht toe. Het verrichten van onderzoek is een van de speerpunten van het opleidings- en wetenschapsbeleid van het Amphia. Ook in 2010 heeft er weer een breed scala aan onderzoek plaatsgevonden. Vrijwel alle vakgebieden hebben onderzoek verricht en velen hebben daarover gepubliceerd. Dit derde wetenschapsboek geeft enerzijds een overzicht van dat onderzoek, en anderzijds een blik op de mensen áchter dat onderzoek. Namens het Directiecomité van het Amphia Ziekenhuis dank ik iedereen die direct of indirect bijgedragen heeft aan al het wetenschappelijk onderzoek. Ik wens u veel leesplezier! Dr. J.J. Meij, Directeur Innovatie Lid Directiecomité

Dr. J.J. Meij, directeur

Woord vooraf

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Inhoud Anesthesiologie . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .9 Apotheek . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17 Cardiologie . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19 Cardiothoracale chirurgie. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 39 Chirurgie . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 45 Dermatologie . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 65 Gynaecologie . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 75 Interne geneeskunde en Maag- darm- levergeneeskunde . . . . . . . 85 Kaakchirurgie . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 93 Kindergeneeskunde. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 95 Laboratorium voor Microbiologie en Infectiepreventie . . . . . . . . . 99 Longgeneeskunde . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 115 Neurologie . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 129 Oogheelkunde . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 139 Orthopedie . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 147 Psychiatrie . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 155 Radiologie . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 157 Reumatologie . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 161 Revalidatie . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 163 Seksuologie . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 165 Urologie . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 167 Publicaties Medisch Specialisten 2010 . . . . . . . . . . . . . . . . . . . 173 Publicaties Arts-assistenten 2010 . . . . . . . . . . . . . . . . . . . . . . 195

Inhoud

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Anesthesiologie Kerngegevens zorgkern Anesthesiologie • 26 anesthesiologen: J. Bach Kolling, mw. A. Besselink, S.F. de Boer, H.P. van Driel, M.J.P.G. van Eerd, F.E.A. Geisler, G. van Gelder, dr. B.M. Gerritse, dr. V.L.H. Hoffmann, L.H. Jacobs, A. van Keeken, J. Konings, E.B. Lachitjaran, F. de Loos, P.P.M. Maas, dr. B.J.M. van der Meer, R.J. Meulemans, F.X. O’Connor, T.A. Rijpstra, P.M.J. Rosseel, dr. R. van Seventer, C.M.P. Theunissen, dr. W.A. Visser, M.A.J. Voets, E. Winters, mw. S.I.M. van Zijll Langhout-Kokke • 8 assistenten niet in opleiding • subspecialismen: cardio-anesthesiologie, pijnbestrijding, algemene anesthesiologie

Samenvattingen gepubliceerde artikelen Visser WA, Kolling JB, Groen GJ, Tetteroo E, van Dijl R, Rosseel PM, van der Meer NJ. Persistent cortical blindness after a thoracic epidural test dose of bupivacaine. Anesthesiology. 2010 Feb;112(2):493-5. Thoracic epidural anesthesia is considered as an essential component of the perioperative care for patients undergoing lung resection. Although neurologic adverse events have been associated with this technique, permanent injury is rare. These events primarily involve the peripheral nervous system; for example, nerve root injury. We present a case of persistent cortical blindness after a test dose of bupivacaine was administered into an uneventfully placed thoracic epidural catheter. PMID: 20068456 [PubMed - indexed for MEDLINE]

Gerritse BM, Schalkwijk A, Pelzer BJ, Scheffer GJ, Draaisma JM. Advanced medical life support procedures in vitally compromised children by a helicopter emergency medical service. BMC Emerg Med. 2010 Mar 8;10:6.

Anesthesiologie

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BACKGROUND: To determine the advanced life support procedures provided by an Emergency Medical Service (EMS) and a Helicopter Emergency Medical Service (HEMS) for vitally compromised children. Incidence and success rate of several procedures were studied, with a distinction made between procedures restricted to the HEMS-physician and procedures for which the HEMS is more experienced than the EMS. METHODS: Prospective study of a consecutive group of children examined and treated by the HEMS of the eastern region of the Netherlands. Data regarding type of emergency, physiological parameters, NACA scores, treatment, and 24hour survival were collected and subsequently analysed. RESULTS: Of the 558 children examined and treated by the HEMS on scene, 79% had a NACA score of IV-VII. 65% of the children had one or more advanced life support procedures restricted to the HEMS and 78% of the children had one or more procedures for which the HEMS is more experienced than the EMS. The HEMS intubated 38% of all children, and 23% of the children intubated and ventilated by the EMS needed emergency correction because of potentially lethal complications. The HEMS provided the greater part of intraosseous access, as the EMS paramedics almost exclusively reserved this procedure for children in cardiopulmonary resuscitation. The EMS provided pain management only to children older than four years of age, but a larger group was in need of analgesia upon

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arrival of the HEMS, and was subsequently treated by the HEMS. CONCLUSIONS: The Helicopter Emergency Medical Service of the eastern region of the Netherlands brings essential medical expertise in the field not provided by the emergency medical service. The Emergency Medical Service does not provide a significant quantity of procedures obviously needed by the paediatric patient. PMID: 20211021 [PubMed - indexed for MEDLINE] PMCID: PMC2843599

Van Zaane B, Nierich AP, Brandon Bravo Bruinsma GJ, Rosseel PM, Ramjankhan FZ, de Waal EE, Buhre WF, Moons KG. Diagnostic accuracy of modified transoesophageal echocardiography for pre-incision assessment of aortic atherosclerosis in cardiac surgery patients. Br J Anaesth. 2010 Aug;105(2):131-8. Epub 2010 Jun 10. BACKGROUND: Epiaortic ultrasound scanning (EUS) is regarded as the reference standard for detecting atherosclerosis in the ascending aorta (AA). Combined with appropriate surgical modifications, EUS use can significantly reduce the incidence of postoperative stroke when detecting severe AA atherosclerosis. A recently introduced modification of conventional transoesophageal echocardiography (TOE), known as the A-View method, has proven capable of inspecting the distal AA. The objective of this study was to quantify the diagnostic accuracy of modified TOE in assessing atherosclerosis of the distal AA. METHODS: After approval by the institutional medical ethical committee and after obtaining written informed consent, 465 consecutive patients above 65 yr old, undergoing elective cardiac surgery with a median sternotomy, were included. The study followed a cross-sectional diagnostic design.


All consecutive patients underwent modified TOE followed by EUS (reference standard) to assess the severity of distal AA atherosclerosis. We constructed contingency tables to compare the presence (and severity) of atherosclerosis, detected by the two techniques. RESULTS: The positive predictive value of modified TOE for the detection of clinically significant atherosclerosis was 67%, and the negative predictive value was 97%. The sensitivity was 95% and the specificity was 79%. One patient suffered a pulmonary haemorrhage, although he recovered without further sequelae. We did not observe any clinical significant haemodynamic or ventilatory effects. CONCLUSIONS: The high negative predictive value and sensitivity show that modified TOE yields adequate diagnostic accuracy for excluding clinically relevant aorta atherosclerosis without significant cardiopulmonary side-effects, provided that the A-View catheter is introduced carefully. PMID: 20538739 [PubMed - indexed for MEDLINE]

Chu K, Rosseel P, Trelles M, Gielis P. Surgeons without borders: a brief history of surgery at Médecins Sans Frontières. World J Surg. 2010 Mar;34(3):411-4. Médecins Sans Frontières (MSF) is a humanitarian organization that performs emergency and elective surgical services in both conflict and non-conflict settings in over 70 countries. In 2006 MSF surgeons departed on approximately 125 missions, and over 64,000 surgical interventions were carried out in some 20 countries worldwide. Historically, the majority of MSF surgical projects began in response to conflicts or natural disasters. During an emergency response, MSF has resources to set up major operating facilities within 48 h in remote areas. One of MSF strengths is its supply chain. Large pre-packaged surgical kits, veritable ‘operating theatres to go,’ can be readied in enormous crates and quickly loaded onto planes. In more stable contexts, MSF has also strengthened the delivery of surgical services within a country’s public health system. The MSF surgeon is the generalist in the broadest sense and performs vascular, obstetrical, orthopaedic, and other specialized surgical procedures. The organization aims to provide surgical services only temporarily. When there is a decrease in acute needs a program will be closed, or more importantly, turned over to the Ministry of Health or another non-governmental organization. The long-term solution to alleviating the global burden of surgical disease lies in building up a domestic surgical workforce capable of responding to the major causes of surgery-related morbidity and mortality. However, given that even countries with the resources of the United States suffer from an insufficiency of surgeons, the need for international emergency organizations to provide surgical assistance during acute emergencies will remain for the foreseeable future. PMID: 19672649 [PubMed - indexed for MEDLINE]

Rosseel P, Trelles M, Guilavogui S, Ford N, Chu K. Ten years of experience training nonphysician anesthesia providers in Haiti. World J Surg. 2010 Mar;34(3):453-8.

Anesthesiologie

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Surgery is increasingly recognized as an effective means of treating a proportion of the global burden of disease, especially in resource-limited countries. Often non-physicians, such as nurses, provide the majority of anesthesia; however, their training and formal supervision is often of low priority or even non-existent. To increase the number of safe anesthesia providers in Haiti, Médecins Sans Frontières has trained nurse anesthetists (NAs) for over 10 years. This article describes the challenges, outcomes, and future directions of this training program. From 1998 to 2008, 24 students graduated. Nineteen (79%) continue to work as NAs in Haiti and 5 (21%) have emigrated. In 2008, NAs were critical in providing anesthesia during a post-hurricane emergency where they performed 330 procedures. Mortality was 0.3% and not associated with lack of anesthesiologist supervision. The completion rate of this training program was high and the majority of graduates continue to work as nurse anesthetists in Haiti. Successful training requires a setting with a sufficient volume and diversity of operations, appropriate anesthesia equipment, a structured and comprehensive training program, and recognition of the training program by the national ministry of health and relevant professional bodies. Preliminary outcomes support findings elsewhere that NAs can be a safe and effective alternative where anesthesiologists are scarce. Training non-physician anesthetists is a feasible and important way

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to scale up surgical services resource limited settings. PMID: 19655194 [PubMed - indexed for MEDLINE]

Heijnen EB, Bentala M, van der Meer NJ. Purpura in a patient receiving vancomycin: a leukoclastic vasculitis? J Cardiothorac Vasc Anesth. 2011 Apr;25(2):390-1. Epub 2010 Apr 27. PMID: 20427206 [PubMed - in process]

Jongerden IP, de Smet AM, Kluytmans JA, te Velde LF, Dennesen PJ, Wesselink RM, Bouw MP, Spanjersberg R, Bogaers-Hofman D, van der Meer NJ, de Vries JW, Kaasjager K, van Iterson M, Kluge GH, van der Werf TS, Harinck HI, Bindels AJ, Pickkers P, Bonten MJ. Physicians’ and nurses’ opinions on selective decontamination of the digestive tract and selective oropharyngeal decontamination: a survey. Crit Care. 2010;14(4):R132. Epub 2010 Jul 13. INTRODUCTION: Use of selective decontamination of the digestive tract (SDD) and selective oropharyngeal decontamination (SOD) in intensive care patients has been controversial for years. Through regular questionnaires we determined expectations concerning SDD (effectiveness) and experience with SDD and SOD (workload and patient friendliness), as perceived by nurses and physicians. METHODS: A survey was embedded in a group-randomized, controlled, cross-over multicenter study in the Netherlands in which, during three 6-month periods, SDD, SOD or standard care was used in random order. At the end of each study period, all nurses and physicians from participating intensive care units received study questionnaires.


RESULTS: In all, 1024 (71%) of 1450 questionnaires were returned by nurses and 253 (82%) of 307 by physicians. Expectations that SDD improved patient outcome increased from 71% and 77% of respondents after the first two study periods to 82% at the end of the study (P = 0.004), with comparable trends among nurses and physicians. Nurses considered SDD to impose a higher workload (median 5.0, on a scale from 1 (low) to 10 (high)) than SOD (median 4.0) and standard care (median 2.0). Both SDD and SOD were considered less patient friendly than standard care (medians 4.0, 4.0 and 6.0, respectively). According to physicians, SDD had a higher workload (median 5.5) than SOD (median 5.0), which in turn was higher than standard care (median 2.5). Furthermore, physicians graded patient friendliness of standard care (median 8.0) higher than that of SDD and SOD (both median 6.0). CONCLUSIONS: Although perceived effectiveness of SDD increased as the trial proceeded, both among physicians and nurses, SOD and SDD were, as compared to standard care, considered to increase workload and to reduce patient friendliness. Therefore, education about the importance of oral care and on the effects of SDD and SOD on patient outcomes will be important when implementing these strategies. TRIAL REGISTRATION: ISRCTN35176830. PMID: 20626848 [PubMed - indexed for MEDLINE] PMCID: PMC2945100

13 Zaludik J, Schuitemaker F, DeWaal R, Veldhuijzen B, van der Meer N. Severe lactate acidosis and cardiogenic shock: a rare manifestation of a phaeochromocytoma. Anaesth Intensive Care. 2010 May;38(3):593-4. PMID: 20518121 [PubMed - indexed for MEDLINE]

Tolsma M, Kröner A, van den Hombergh CL, Rosseel PM, Rijpstra TA, Dijkstra HA, Bentala M, Schultz MJ, van der Meer NJ. The clinical value of routine chest radiographs in the first 24 hours after cardiac surgery. Anesth Analg. 2011 Jan;112(1):139-42. Epub 2010 Nov 3. BACKGROUND: Chest radiographs (CXRs) are obtained frequently in the intensive care unit (ICU). Whether these CXRs should be performed routinely or on clinical indication only is often debated. The aim of our study was to investigate the incidence and clinical significance of abnormalities found on routine postoperative CXRs in cardiac surgery patients and whether a restricted use of CXRs would influence the number of significant findings. METHODS: We prospectively included all consecutive patients who underwent cardiac surgery during a 2-month period. Two or three CXRs were performed in the first 24 hours of ICU stay. After ICU admission and after drain removal, a clinical assessment was performed before a CXR was obtained. All CXR abnormalities were noted and it was also noted whether they led to an intervention. For the admission CXR and the drain removal CXR, a comparison was made between CXRs clinically indicated by the physician and those not clinically indicated. RESULTS: Two hundred fourteen patients were included. The majority of patients underwent coronary arterial bypass grafting

Anesthesiologie

(60%), heart valve surgery (21%), or a combination of these (14%). In total, 534 CXRs were performed (2.5 per patient). Abnormalities were found on 179 CXRs (33.5%) and 13 CXR results led to an intervention (2.4%). The association between clinically indicated CXRs and the presence of CXR abnormalities was poor. For 32 (10%) of the 321 admission and drain removal CXRs, clinical indications were stated by the physician beforehand. If these CXRs would not have been performed routinely, 68 abnormalities would have been missed, of which 5 led to an intervention. CONCLUSIONS: Partial elimination of routine CXRs in the first 24 hours after cardiac surgery seems possible for the majority of patients, but it is limited by the insensitivity of clinical assessment in predicting clinically important abnormalities detectable by CXRs. PMID: 21048091 [PubMed - indexed for MEDLINE]

Complete publicatielijst

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Gerritse BM, Schalkwijk A, Pelzer BJ, Scheffer GJ, Draaisma JM. Advanced medical life support procedures in vitally compromised children by a helicopter emergency medical service. BMC Emerg Med. 2010 Mar 8;10:6. De Vries J, Rijpstra TA, van der Meer NJM. Cardiac tamponade as a result of pericardial effusion in pneumococcal infections. Neth J Crit Care 2010:14(2):109-10. Van Zaane B, Nierich AP, Brandon Bravo Bruinsma GJ, Rosseel PM, Ramjankhan FZ, de Waal EE, Buhre WF, Moons KG. Diagnostic accuracy of modified transoesophageal echocardiography for pre-incision assessment of aortic atherosclerosis in cardiac surgery patients. Br J Anaesth. 2010 Aug;105(2):131-8. Epub 2010 Jun 10. Visser WA, Kolling JB, Groen GJ, Tetteroo E, van Dijl R, Rosseel PM, van der Meer NJ. Persistent cortical blindness after a thoracic epidural test dose of bupivacaine. Anesthesiology. 2010 Feb;112(2):493-5. Jongerden IP, de Smet AM, Kluytmans JA, te Velde LF, Dennesen PJ, Wesselink RM, Bouw MP, Spanjersberg R, Bogaers-Hofman D, van der Meer NJ, de Vries JW, Kaasjager K, van Iterson M, Kluge GH, van der Werf TS, Harinck HI, Bindels AJ, Pickkers P, Bonten MJ. Physicians’ and nurses’ opinions on selective decontamination of the digestive tract and selective oropharyngeal decontamination: a survey. Crit Care. 2010;14(4):R132. Epub 2010 Jul 13. Gerritse BM, Dirven PJ, Draaisma JMT, Scheffer GJ. Prehospitale echografie in Nederland door het Mobiel Medisch Team. Nederlands Tijdschrift voor Anesthesiologie. Ned Tijdschr voor Anesthesiologie. 2010;22(2):17-21. Heijnen EB, Bentala M, van der Meer NJ. Purpura in a patient receiving vancomycin: a leukoclastic vasculitis? J Cardiothorac Vasc Anesth. 2011 Apr;25(2):390-1. Epub 2010 Apr 27. Zaludik J, Schuitemaker F, DeWaal R, Veldhuijzen B, van der Meer N. Severe lactate acidosis and cardiogenic shock: a rare manifestation of a phaeochromocytoma. Anaesth Intensive Care. 2010 May;38(3):593-4.


Chu K, Rosseel P, Trelles M, Gielis P. Surgeons without borders: a brief history of surgery at Médecins Sans Frontières. World J Surg. 2010 Mar;34(3):411-4. Rosseel P, Trelles M, Guilavogui S, Ford N, Chu K. Ten years of experience training nonphysician anesthesia providers in Haiti. World J Surg. 2010 Mar;34(3):453-8. Tolsma M, Kröner A, van den Hombergh CL, Rosseel PM, Rijpstra TA, Dijkstra HA, Bentala M, Schultz MJ, van der Meer NJ. The clinical value of routine chest radiographs in the first 24 hours after cardiac surgery. Anesth Analg. 2011 Jan;112(1):139-42. Epub 2010 Nov 3. Gerritse BM, Pelzer B, Draaisma JMT, Scheffer GJ. The deployment of a Helicopter Emergency Medical Service for vitally compromised children in the Netherlands. Internet Journal of Aeromedical Transportation. 2010;2:1.

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Anesthesiologie

Apotheek Kerngegevens Apotheek • 6 ziekenhuisapothekers: P.R.M. van Hattum, mw. V.S. Koster, P.A.O. Smithuis, N.E. van ’t Veer, mw. R.R.E.C.M. Verzijl-Zeegers, mw. M.H.G. Winters • 2 assistenten in opleiding

Samenvattingen gepubliceerde artikelen Ter Laak MA, Temmink AH, Koeken A, van ‘t Veer NE, van Hattum PR, Cobbaert CM. Recognition of impaired atomoxetine metabolism because of low CYP2D6 activity. Pediatr Neurol. 2010Sep;43(3):159-62. Ten out of 100 children treated for attention deficit hyperactivity disorder with standard doses of atomoxetine were selected by a neurologist for cytochrome P450 2D6 and cytochrome P450 2C19 genotyping, based on late response (>9 weeks) and adverse effects (gastrointestinal problems, sleeping disorders, malaise, inactivity, and mood instabilities). After genotyping, eight children were confirmed to have compromised cytochrome P450 2D6 activity because of at least one nonfunctional or less functional allele. Cytochrome P450 C19 is a minor pathway in atomoxetine metabolism and therefore of less importance. Tailored therapeutic advice was given to the neurologist. Four children with compromised cytochrome P450 2D6 activity responded better after decreasing their atomoxetine dose. The other four ceased treatment because of initial adverse effects. These cases indicate that compromised atomoxetine metabolism can be recognized, based on adverse effects and late response to atomoxetine. Physicians should be aware of the typical pattern of adverse effects and late response in atomoxetine treatment, possibly indicating compromised cytochrome P450 2D6 activity. Cytochrome P450 2D6 genotyping before atomoxetine treatment may be beneficial in preventing overdosing or early cessation. Further research is needed to establish the cost versus benefit ratio of prospective

Apotheek

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cytochrome P450 2D6 genotyping in atomoxetine treatment. Copyright 2010 Elsevier Inc. All rights reserved. PMID: 20691935 [PubMed - indexed for MEDLINE]

Willemsen I, Cooper B, van Buitenen C, Winters M, Andriesse G, Kluytmans J. Improving quinolone use in hospitals by using a bundle of interventions in an interrupted time series analysis. Antimicrob Agents Chemother. 2010 Sep;54(9):3763-9. Epub 2010 Jun 28. The objectives of the present study were to determine the effects of multiple targeted interventions on the level of use of quinolones and the observed rates of resistance to quinolones in Escherichia coli isolates from hospitalized patients. A bundle consisting of four interventions to improve the use of quinolones was implemented. The outcome was measured from the monthly levels of use of intravenous (i.v.) and oral quinolones and the susceptibility patterns for E. coli isolates from hospitalized patients. Statistical analyses were performed using segmented regression analysis and segmented Poisson regression models. Before the bundle was implemented, the annual use of quinolones was 2.7 defined daily doses (DDDs)/100 patient

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days. After the interventions, in 2007, this was reduced to 1.7 DDDs/100 patient days. The first intervention, a switch from i.v. to oral medication, was associated with a stepwise reduction in i.v. quinolone use of 71 prescribed daily doses (PDDs) per month (95% confidence interval [CI] = 47 to 95 PDDs/month, P < 0.001). Intervention 2, introduction of a new antibiotic guideline and education program, was associated with a stepwise reduction in the overall use of quinolones (reduction, 107 PDDs/month [95% CI = 58 to 156 PDDs/month). Before the interventions the quinolone resistance rate was increasing, on average, by 4.6% (95% CI = 2.6 to 6.1%) per year. This increase leveled off, which was associated with intervention 2 and intervention 4, active monitoring of prescriptions and feedback. Trends in resistance to other antimicrobial agents did not change. This study showed that the hospital-wide use of quinolones can be significantly reduced by an active policy consisting of multiple interventions. There was also a stepwise reduction in the rate of quinolone resistance associated with the bundle of interventions. PMID: 20585135 [PubMed - indexed for MEDLINE] PMCID: PMC2934965

Complete publicatielijst Willemsen I, Cooper B, van Buitenen C, Winters M, Andriesse G, Kluytmans J. Improving quinolone use in hospitals by using a bundle of interventions in an interrupted time series analysis. Antimicrob Agents Chemother. 2010 Sep;54(9):3763-9. Epub 2010 Jun 28. Ter Laak MA, Temmink AH, Koeken A, van ‘t Veer NE, van Hattum PR, Cobbaert CM. Recognition of impaired atomoxetine metabolism because of low CYP2D6 activity. Pediatr Neurol. 2010 Sep;43(3):159-62.


Cardiologie Grenzen verleggen, technieken verbeteren om patiëntvriendelijker te werken

De cardiologiemaatschap in het Amphia Ziekenhuis is een van de grootste van Nederland. Vooral de verrichtingen op het gebied van percutane hartkleppen zijn bijzonder, omdat deze in eerste instantie in slechts enkele Nederlandse ziekenhuizen werden uitgevoerd en het Amphia het eerste niet-academische ziekenhuis was dat de ingreep verrichtte.

Dr. M. Meuwissen

Het vakgebied cardiologie is in vijf hoofdtakken te verdelen: algemene cardiologie (hart- en vaatziekten in brede zin), beeldvorming (echocardiografie, cardiale CT en MRI), interventiecardiologie (stenten dotterbehandelingen, vervanging hartklep),

Cardiologie

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congenitale cardiologie (aangeboren hartgebreken) en elektrofysiologie (behandeling van hartritmestoornissen). In het Amphia Ziekenhuis vinden – behalve harttransplantaties – alle behandelingen plaats.

Hartritmestoornissen ‘We doen veel, qua volume en qua mogelijkheden’, constateert cardioloog dr. Martijn Meuwissen, ‘en vooral ook veel bijzondere verrichtingen.’ Hij verwijst hiermee onder andere naar de elektrofysiologische behandelingen bij hartritmestoornissen, zoals katheterablatie, pacemakers en ICD’s (implanteerbare cardioverter-defibrillators). Bij een katheterablatie brengt een cardioloog via een katheter die via de lies(slag)ader naar het hart wordt opgevoerd kleine littekens aan in het hartspierweefsel. Die littekens blokkeren prikkels die zijn ontstaan op een verkeerde plaats of schakelen deze prikkels uit. Hiermee doven de soms levensbedreigende hartritmestoornissen uit.

Subcutane ICD 20

Als deze levensbedreigende hartritmestoornissen oncontroleerbaar zijn wordt er meestal een ICD geïmplanteerd. Een ICD is een inwendige defibrillator. Dit apparaatje zorgt voor een constante controle van het hartritme. Zo nodig vindt een schokje plaats om het ritme weer te normaliseren. Meuwissen: ‘Nieuw bij deze techniek is de ICD die net onder de huid geplaatst wordt (subcutane ICD), wat veel voordelen kan bieden bij bijvoorbeeld jonge mensen, die dit device noodzakelijkerwijs tientallen jaren dragen. De toekomst zal ons waarschijnlijk ICD’s en pacemakers brengen die draadloos hun werk verrichten. Nu vindt het uitlezen van de ICD al wel op afstand plaats; de zogenaamde home monitoring. Wij cardiologen doen een extra fellowship elektrofysiologie om dit soort ingrepen te mogen en kunnen verrichten.’

Minimaal invasieve ingrepen Er is ook innovatie op het gebied van de interventiecardiologie. Naast de percutane aortaklepimplantatie kunnen ook andere kleppen percutaan (minimaal invasief) worden gerepareerd. Een ernstig lekkende (mitralis)klep komt in de praktijk het meest voor. ‘Niet alle patiënten kunnen zware ingrepen doorstaan. Daarom is het fijn als je met een incisie in de lies een tube in de ader kunt inbrengen die een clipje bevat. Je schuift dat clipje op de goede plaats onder de lekkende mitraalklep en via het echoapparaat kun je zien dat de lekkage stopt. Enkele uren later is de patiënt alweer mobiel.’ Meuwissen toont een filmpje van de leverancier, waarbij het plaatsen van een MitraClip nauwkeurig is te volgen. Op een vergelijkbare manier, via de lies, zijn onderzoeken gedaan naar het plaatsen van betere stents in de kransslagader. Dit zijn kleine ‘zeefjes’ die in uitgezette vorm een verstopte kransslagader openhouden om met een goede bloedstroom de hartspier van de benodigde zuurstof te voorzien. Deze zogenoemde dottertechniek bestaat sinds 1966 en is in 1976


voor het eerst in de kransslagader van het hart toegepast. ‘Tegenwoordig wordt er bijna altijd een type stent geplaatst dat ongeveer in 1990 werd geïntroduceerd. Sinds 2000 gebruiken we stents waar medicatie op is aangebracht. Die zorgt ervoor dat de stents langer ‘goed’ en open blijven. Er zijn veel nieuwe ontwikkelingen. De nieuwste stents gaan op den duur ‘oplossen’: bioabsorbable stents. Ook zijn deze dunner en beweeglijker en daardoor kunnen we ook technisch ingewikkelder procedures uitvoeren.’

Meer onderzoeken Een onderzoek met de naam ‘Renale sympatische denervatie’ richt zich op een nieuwe methode om een hoge bloeddruk te behandelen. ‘Eigenlijk komt dat neer op het wegbranden van de nierslagaderzenuwen’, zegt Meuwissen. ‘Elk orgaan heeft vaten en zenuwen. Zo ook de nier. De nier is tevens het belangrijkste orgaan voor de bloeddrukregulatie. De nier ontvangt prikkels vanuit de hersenen via zenuwen die in de wand van de nierslagader lopen. Als je die hersenimpulsen blokkeert, dan zien we dat de bloeddruk minder hoog wordt. Deze jonge techniek is zeer veelbelovend en waarschijnlijk een goed alternatief voor mensen die niet goed reageren op de reguliere medicatie of die hiervan veel bijwerkingen hebben. Deze nieuwe behandeling zal in nauwe samenwerking plaatsvinden met o.a. de interne geneeskunde met wie we een vasculair overleg in het Amphia hebben opgezet.’ Weer een ander onderzoek houdt zich bezig met ondersteuning bij een shock. Hierbij wordt een tijdelijke LVAD (left ventricular assist device) aangebracht. Dat werkt als een soort steunhart. Er zijn verschillende soorten devices met hetzelfde doel: het hart ondersteunen om bij patiënten in shock voldoende bloed en dus zuurstof rond te pompen om de organen hiervan te voorzien. Het Amphia heeft de beschikking over de Impella, een soort centrifugaalpompje gebaseerd op een eeuwenoude techniek: de schroef van Archimedes. Deze schroef in een miniatuurvorm (4 mm in doorsnede) kan met 50.000 toeren 2,5 tot 5 liter per minuut rondpompen. ‘Nieuw daarbij is dat we buiten het Amphia Ziekenhuis met dit soort ondersteuningen soms mensen kunnen helpen die al lang op de wachtlijst voor een harttransplantatie staan. Daarbij blijkt uit de gegevens dat ze soms jarenlang gered zijn met zo’n kunsthart. Een speciale werkgroep houdt zich nu daarmee bezig.’

Samenwerken Meuwissen legt uit dat de zorgkern Cardiologie veel samenwerkt met de zorgkern Hartchirurgie. ‘We vinden het belangrijk om elkaar te versterken, om samen te werken in het vinden van nieuwe en minimaal invasieve methoden waar de patiënt bij is gebaat. Zo gaan we in de toekomst ook meer samen ‘opereren’ en onze expertise bundelen, wat de kwaliteit van de behandeling ten goede moet komen.’ Het grootste verschil tussen de twee zorgkernen is dat hartchirurgen voornamelijk ingrepen verrichten onder complete narcose

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en cardiologen vooral met plaatselijke verdoving. ‘De ontwikkelingen in ons vakgebied komen erop neer dat we de grenzen verleggen, de technieken verbeteren en daarbij de complicaties van behandelingen kunnen verminderen om zo de kwaliteit van de zorg voor de patiënt te verbeteren’, concludeert Meuwissen.

Overzicht lopende onderzoeken

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• • • • • • • • • • • •

Optimale medicamenteuze behandeling van hartritmestoornissen Optimale medicamenteuze behandeling van hartfalen Optimale medicamenteuze behandeling van atherosclerose Optimale behandeling van acute coronaire syndromen Nieuwe medicijngecoate stents bij diverse patiëntengroepen Nieuwe medicijngecoate ballon bij restenose Nieuwe bifurcatiestents bij complexe vernauwingen Nieuwe stentmethode bij meervatslijden bij een acuut hartinfarct Bloedstroommetingen ter bepaling van functionele ernst van dubieuze vernauwingen Percutane hartklepimplantaties Op afstand uitlezen ICD Naast bovenstaande studies zijn er samenwerkingsverbanden met afdelingen cardiologie van verschillende andere academische en niet-academische ziekenhuizen waaronder UMCU, AMC, AZG, St. Antonius Ziekenhuis te Nieuwegein en het Maasstadziekenhuis.

Kerngegevens zorgkern Cardiologie • 15 cardiologen: dr. A.M.W. Alings, A.A. van den Bos, W.A.J. Bruggeling, H.M.A. Corbeij, dr. P.H.J.M. Dunselman, H.P.J. de Haan, dr. P. den Heijer, N. Masalha, dr. M. Meuwissen, dr. S.G. Molhoek, J.A.M. te Riele, dr. T.A. Simmers, dr. S. Strikwerda, dr. J. Vos, dr. R.P. Wielenga • 1 chef de clinique • 2 assistenten in opleiding • 6-8 assistenten niet in opleiding • 4 nurse practitioners • Subspecialismen: algemene cardiologie (hart- en vaatziekten in brede zin), beeldvorming (echocardiografie, cardiale CT en MRI), interventiecardiologie (stenten dotterbehandelingen, vervanging hartklep), congenitale cardiologie (aangeboren hartgebreken) en elektrofysiologie (behandeling van hartritmestoornissen)

Samenvattingen gepubliceerde artikelen Van Gelder IC, Smit MD, Alings M, Crijns HJ. Upstream therapy in patients with early atrial fibrillation. The relevance of routine versus aggressive upstream rhythm control


for prevention of atrial fibrillation in heart failure (RACE 3) study. Neth Heart J. 2010 Nov;18(11):522-3. PMID: 21113375 [PubMed - in process] PMCID: PMC2989488

Wallentin L, Yusuf S, Ezekowitz MD, Alings M, Flather M, Franzosi MG, Pais P, Dans A, Eikelboom J, Oldgren J, Pogue J, Reilly PA, Yang S, Connolly SJ; RE-LY investigators. Efficacy and safety of dabigatran compared with warfarin at different levels of international normalised ratio control for stroke prevention in atrial fibrillation: an analysis of the RE-LY trial. Lancet. 2010 Sep 18;376(9745):975-83. BACKGROUND: Effectiveness and safety of warfarin is associated with the time in therapeutic range (TTR) with an international normalised ratio (INR) of 2·0-3·0. In the Randomised Evaluation of Long-term Anticoagulation Therapy (RE-LY) trial, dabigatran versus warfarin reduced both stroke and haemorrhage. We aimed to investigate the primary and secondary outcomes of the RE-LY trial in relation to each centre’s mean TTR (cTTR) in the warfarin population. METHODS: In the RE-LY trial, 18?113 patients at 951 sites were randomly assigned to 110 mg or 150 mg dabigatran twice daily versus warfarin dose adjusted to INR 2·0-3·0. Median follow-up was 2·0 years. For 18?024 patients at 906 sites, the cTTR was estimated by averaging TTR for individual warfarin-treated patients calculated by the Rosendaal method. We compared the outcomes of RE-LY across the three treatment groups within four groups defined by the quartiles of cTTR. RE-LY is registered with ClinicalTrials.gov, number NCT00262600. FINDINGS: The quartiles of cTTR for patients in the warfarin group were: less than 57·1%, 57·1-65·5%, 65·5-72·6%, and greater than 72·6%. There were no significant interactions between cTTR and prevention of stroke and systemic embolism with either 110 mg dabigatran (interaction p=0·89) or 150 mg dabigatran (interaction p=0·20) versus warfarin. Neither were any significant interactions recorded with cTTR with regards to intracranial bleeding with 110 mg dabigatran (interaction p=0·71) or 150 mg dabigatran (interaction p=0·89) versus warfarin. There was a significant interaction between cTTR and major bleeding when comparing 150 mg dabigatran with warfarin (interaction p=0·03), with less bleeding events at lower cTTR but similar events at higher cTTR, whereas rates of major bleeding were lower with 110 mg dabigatran than with warfarin irrespective of cTTR. There were significant interactions between cTTR and effects of both 110 mg and 150 mg dabigatran versus warfarin on the composite of all cardiovascular events (interaction p=0·036 and p=0·0006, respectively) and total mortality (interaction p=0·066 and p=0·052, respectively) with reduced event rates at low cTTR, and similar rates at high cTTR. INTERPRETATION: The benefits of 150 mg dabigatran at reducing stroke, 110 mg dabigatran at reducing bleeding, and both doses at reducing intracranial bleeding versus warfarin were consistent irrespective of centres’ quality of INR control. For all vascular events, non-haemorrhagic events, and mortality, advantages of dabigatran were greater

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at sites with poor INR control than at those with good INR control. Overall, these results show that local standards of care affect the benefits of use of new treatment alternatives. FUNDING: Boehringer Ingelheim. Copyright © 2010 Elsevier Ltd. All rights reserved. Comment in: Lancet. 2010 Sep 18;376(9745):935-7; Nat Rev Cardiol. 2010 Nov;7(11):598; Ann Intern Med. 2011 Jan 18;154(2):JC1-6; Lancet. 2011 Feb 5;377(9764):464-5; author reply 465. PMID: 20801496 [PubMed - indexed for MEDLINE]

Van Gelder IC, Groenveld HF, Crijns HJ, Tuininga YS, Tijssen JG, Alings AM, Hillege HL, Bergsma-Kadijk JA, Cornel JH, Kamp O, Tukkie R, Bosker HA, Van Veldhuisen DJ, Van den Berg MP; RACE II Investigators. Lenient versus strict rate control in patients with atrial fibrillation. N Engl J Med. 2010 Apr 15;362(15):1363-73. Epub 2010 Mar 15. BACKGROUND: Rate control is often the therapy of choice for atrial fibrillation. Guidelines recommend strict rate control, but this is not based on clinical evidence. We hypothesized that lenient rate control is not inferior to strict rate control for preventing cardiovascular morbidity and mortality in patients with permanent atrial fibrillation. METHODS: We randomly assigned

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614 patients with permanent atrial fibrillation to undergo a lenient rate-control strategy (resting heart rate <110 beats per minute) or a strict rate-control strategy (resting heart rate <80 beats per minute and heart rate during moderate exercise <110 beats per minute). The primary outcome was a composite of death from cardiovascular causes, hospitalization for heart failure, and stroke, systemic embolism, bleeding, and life-threatening arrhythmic events. The duration of follow-up was at least 2 years, with a maximum of 3 years. RESULTS: The estimated cumulative incidence of the primary outcome at 3 years was 12.9% in the lenient-control group and 14.9% in the strict-control group, with an absolute difference with respect to the lenientcontrol group of -2.0 percentage points (90% confidence interval, -7.6 to 3.5; P<0.001 for the prespecified noninferiority margin). The frequencies of the components of the primary outcome were similar in the two groups. More patients in the lenient-control group met the heart-rate target or targets (304 [97.7%], vs. 203 [67.0%] in the strict-control group; P<0.001) with fewer total visits (75 [median, 0], vs. 684 [median, 2]; P<0.001). The frequencies of symptoms and adverse events were similar in the two groups. CONCLUSIONS: In patients with permanent atrial fibrillation, lenient rate control is as effective as strict rate control and is easier to achieve. (ClinicalTrials.gov number, NCT00392613.) 2010 Massachusetts Medical SocietComment in: N Engl J Med. 2010 Apr 15;362(15):1439-41; Ann Intern Med. 2010 Aug 17;153(4):JC2-4; N Engl J Med. 2010 Jul 22;363(4):392; author reply 393-4; Kardiol Pol. 2010 Jun;68(6):725-6; N Engl J Med. 2010 Jul 22;363(4):392-3; author reply 393-4; Evid Based Med. 2010 Oct;15(5):147-8; N Engl J Med. 2010 Jul 22;363(4):393; author reply 393-4. PMID: 20231232 [PubMed - indexed for MEDLINE]


Piazza N, Grube E, Gerckens U, Schuler G, Linke A, den Heijer P, Kovacs J, Spyt T, Laborde JC, Morel MA, Nuis RJ, Garcia-Garcia HM, de Jaegere P, Serruys PW. A clinical protocol for analysis of the structural integrity of the Medtronic CoreValve System frame and its application in patients with 1-year minimum follow-up. EuroIntervention. 2010 Jan;5(6):680-6. AIMS: The optimal clinical protocol to detect fractures of transcatheter aortic valves is unknown. To the best of our knowledge, there are no published reports describing stent or frame fractures following transcatheter aortic valve implantation. The purpose of this study is two-fold: (1) to determine the optimal fluoroscopic protocol to identify potential fractures of the Medtronic CoreValve frame; and (2) to implement this protocol in the analysis of the fluoroscopic films of patients implanted with the CoreValve device with 1-year minimum followup. METHODS AND RESULTS: Considering the resolution of fluoroscopy (approximately 0.2 mm), we used a 0.2 mm diamond-cutter to create a single fracture in a single strut of two CoreValve frames. An intact CoreValve prosthesis was used as control. These prostheses were subsequently implanted in post-mortem heart specimens. A protocol involving still frames and rotational (left-right and cranial-caudal) fluoroscopic imaging was then applied to the heart specimens. The experimentally induced fractures were detectable on the rotational cine runs (left-right and cranial-caudal); in some of the fixed acquisition sequences, however, the fractures were undetectable. The fluoroscopic protocol was retrospectively applied to the films of 58 patients who underwent implantation with the CoreValve System between October 2005 and August 2008 and had at least 1-year follow-up. The mean and median follow-up times were 22 months and 24 months, respectively (range 12 to 36 months). Rotational cine films (only left-right lateral) were available in 39 patients (60%). No frame fractures of the CoreValve frame were identified. CONCLUSIONS: Rotational cine runs in the left-right and cranial-caudal directions should be mandatory in the clinical assessment of the structural integrity of the CoreValve frame. No frame fractures were identified in 58 patients implanted with the Medtronic CoreValve device with 2-year mean follow-up. PMID: 20142218 [PubMed - indexed for MEDLINE]

McMurray JJ, Dunselman P, Wedel H, Cleland JG, Lindberg M, Hjalmarson A, Kjekshus J, Waagstein F, Apetrei E, Barrios V, Böhm M, Kamenský G, Komajda M, Mareev V, Wikstrand J; CORONA Study Group. Coenzyme Q10, rosuvastatin, and clinical outcomes in heart failure: a pre-specified substudy of CORONA (controlled rosuvastatin multinational study in heart failure). J Am Coll Cardiol. 2010 Oct 5;56(15):1196-204. OBJECTIVES: The purpose of this study was to determine whether coenzyme Q10 is an independent predictor of prognosis in heart failure. BACKGROUND: Blood and tissue concentrations of the essential cofactor coenzyme Q10 are decreased by statins, and this could

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be harmful in patients with heart failure. METHODS: We measured serum coenzyme Q10 in 1,191 patients with ischemic systolic heart failure enrolled in CORONA (Controlled Rosuvastatin Multinational Study in Heart Failure) and related this to clinical outcomes. RESULTS: Patients with lower coenzyme Q10 concentrations were older and had more advanced heart failure. Mortality was significantly higher among patients in the lowest compared to the highest coenzyme Q10 tertile in a univariate analysis (hazard ratio: 1.50, 95% confidence interval: 1.04 to 2.6, p = 0.03) but not in a multivariable analysis. Coenzyme Q10 was not an independent predictor of any other clinical outcome. Rosuvastatin reduced coenzyme Q10 but there was no interaction between coenzyme Q10 and the effect of rosuvastatin. CONCLUSIONS: Coenzyme Q10 is not an independent prognostic variable in heart failure. Rosuvastatin reduced coenzyme Q10, but even in patients with a low baseline coenzyme Q10, rosuvastatin treatment was not associated with a significantly worse outcome. (Controlled Rosuvastatin Multinational Study in Heart Failure [CORONA]; NCT00206310). Copyright © 2010 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved. Comment in: J Am Coll Cardiol. 2011 Apr 5;57(14):1569; author reply 1569; J Am Coll Cardiol. 2010 Oct 5;56(15):1205-6.

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PMID: 20883926 [PubMed - indexed for MEDLINE]

CURRENT-OASIS 7 Investigators, Mehta SR, Bassand JP, Chrolavicius S, Diaz R, Eikelboom JW, Fox KA, Granger CB, Jolly S, Joyner CD, Rupprecht HJ, Widimsky P, Afzal R, Pogue J, Yusuf S, Collaborators (572) [Dunselman P et al...) Dose comparisons of clopidogrel and aspirin in acute coronary syndromes. N Engl J Med. 2010 Sep 2;363(10):930-42. BACKGROUND: Clopidogrel and aspirin are widely used for patients with acute coronary syndromes and those undergoing percutaneous coronary intervention (PCI). However, evidencebased guidelines for dosing have not been established for either agent. METHODS: We randomly assigned, in a 2-by-2 factorial design, 25,086 patients with an acute coronary syndrome who were referred for an invasive strategy to either double-dose clopidogrel (a 600-mg loading dose on day 1, followed by 150 mg daily for 6 days and 75 mg daily thereafter) or standarddose clopidogrel (a 300-mg loading dose and 75 mg daily thereafter) and either higher-dose aspirin (300 to 325 mg daily) or lower-dose aspirin (75 to 100 mg daily). The primary outcome was cardiovascular death, myocardial infarction, or stroke at 30 days. RESULTS: The primary outcome occurred in 4.2% of patients assigned to double-dose clopidogrel as compared with 4.4% assigned to standard-dose clopidogrel (hazard ratio, 0.94; 95% confidence interval [CI], 0.83 to 1.06; P=0.30). Major bleeding occurred in 2.5% of patients in the double-dose group and in 2.0% in the standard-dose group (hazard ratio, 1.24; 95% CI, 1.05 to 1.46; P=0.01). Double-dose clopidogrel was associated with a significant reduction in the secondary outcome of stent thrombosis among the 17,263 patients who underwent PCI (1.6% vs. 2.3%; hazard ratio, 0.68; 95% CI, 0.55 to 0.85; P=0.001). There was no significant difference between higher-dose


and lower-dose aspirin with respect to the primary outcome (4.2% vs. 4.4%; hazard ratio, 0.97; 95% CI, 0.86 to 1.09; P=0.61) or major bleeding (2.3% vs. 2.3%; hazard ratio, 0.99; 95% CI, 0.84 to 1.17; P=0.90). CONCLUSIONS: In patients with an acute coronary syndrome who were referred for an invasive strategy, there was no significant difference between a 7-day, doubledose clopidogrel regimen and the standard-dose regimen, or between higher-dose aspirin and lower-dose aspirin, with respect to the primary outcome of cardiovascular death, myocardial infarction, or stroke. (Funded by Sanofi-Aventis and Bristol-Myers Squibb; ClinicalTrials.gov number, NCT00335452.) Collaborators (572) Erratum in N Engl J Med. 2010 Oct 14;363(16):1585. Comment in: Expert Opin Pharmacother. 2011 Jan;12(1):149-51; Ann Intern Med. 2011 Jan 18;154(2):JC1-7; N Engl J Med. 2010 Dec 16;363(25):2466; author reply 2467-8; N Engl J Med. 2010 Dec 16;363(25):2465-6; author reply 2467-8; N Engl J Med. 2010 Sep 2;363(10):976-7; N Engl J Med. 2010 Dec 16;363(25):2466-7; author reply 2467-8. PMID: 20818903 [PubMed - indexed for MEDLINE]

Inglis SC, McMurray JJ, Böhm M, Schaufelberger M, van Veldhuisen DJ, Lindberg M, Dunselman P, Hjalmarson A, Kjekshus J, Waagstein F, Wedel H, Wikstrand J; CORONA Study Group. Intermittent claudication as a predictor of outcome in patients with ischaemic systolic heart failure: analysis of the Controlled Rosuvastatin Multinational Trial in Heart Failure trial (CORONA). Eur J Heart Fail. 2010 Jul;12(7):698-705. Epub 2010 May 25. AIMS: To examine the relationship between baseline intermittent claudication and outcomes in patients enrolled in the Controlled Rosuvastatin Multinational Trial in Heart Failure trial (CORONA). Intermittent claudication is an independent predictor of worse outcome in coronary heart disease, but its prognostic importance in heart failure (HF) is unknown. Patients aged >or=60 years with NYHA class II-IV, low ejection fraction HF of ischaemic aetiology were enrolled in CORONA. Rosuvastatin did not reduce the primary outcome or all-cause mortality. METHODS AND RESULTS: To determine whether intermittent claudication was an independent predictor of clinical outcomes, a three-step multivariable model was built: (i) demographic/clinical variables, (ii) biochemical measures added, (iii) high-sensitivity C-reactive protein and N-terminal pro B-type natriuretic-peptide added. Of the 5011 patients, 637 (12.7%) had intermittent claudication at baseline. Patients with intermittent claudication were more likely to be male (83 vs. 75%), be a current smoker (19 vs. 9%), and have diabetes mellitus (36 vs. 29%) relative to those without intermittent claudication. Over a median 33-month follow-up, 2168 patients died or were hospitalized for HF. Patients with intermittent claudication had an increased risk of death (any cause) (adjusted hazard ratio 1.36, 95% CI 1.19-1.56, P < 0.0001), death from worsening HF (1.35, 1.03-1.77, P = 0.028), sudden death (1.24, 1.00-1.54, P = 0.05), and risk of non-fatal or fatal myocardial infarction (time to first event 1.67, 1.24-2.27, P < 0.001). In the full multivariable model, intermittent claudication remained an independent predictor of most

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outcomes evaluated. CONCLUSION: Intermittent claudication is a relatively common symptom in ischaemic HF and an independent predictor of worse outcome. Clinical Trial Registration Information: NCT00206310-http://clinicaltrials.gov/ct2/show/NCT00206310?term= corona&rank=2. PMID: 20501489 [PubMed - indexed for MEDLINE]

van der Harst P, Slart RH, Tio RA, Dunselman PH, Willemsen AT, van den Heuvel AF, Voors AA, van Veldhuisen DJ; CORONA Study Group. [Dunselman P. et al...] Effects of rosuvastatin on coronary flow reserve and metabolic mismatch in patients with heart failure (from the CORONA Study). Am J Cardiol. 2010 Feb 15;105(4):517-21. Epub 2010 Jan 5. In patients with heart failure (HF), statin treatment might improve myocardial perfusion, but could also have detrimental effects on myocardial metabolism. A predefined substudy of the Controlled Rosuvastatin Multinational Trial in Heart Failure (CORONA) trial sought to determine the effects of statin treatment on myocardial blood flow reserve and cardiac metabolism. Sixteen

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patients with HF (New York Heart Association class II or III) were randomized to rosuvastatin 10 mg/day (n = 8) or placebo treatment (n = 8). At baseline and after 6 months of treatment, nitrogen-13 ammonia at rest and after dipyridamole stress and 18-fluorodeoxyglucose positron emission tomography were performed. Rosuvastatin treatment significantly lowered total (-36%, p <0.01) and low-density lipoprotein (-47%, p <0.001) cholesterol and C-reactive protein levels (-36%, p <0.05). Myocardial perfusion reserve (ratio) changed from 1.64 +/- 0.90 to 1.30 +/0.37 in placebo-treated and from 1.51 +/- 0.18 to 1.55 +/- 0.34 in rosuvastatin-treated patients (p = NS). Metabolic mismatch changed from 4.25 +/- 2.37% to 4.38 +/- 3.81% in placebotreated and from 5.13 +/- 2.75% to 3.50 +/- 2.73% in rosuvastatin-treated patients (p = NS). In conclusion, changes regarding myocardial perfusion and metabolic mismatch after 6 months of rosuvastatin treatment in patients with HF did not suggest any beneficial or adverse effects in this pilot study, although due to the small numbers of patients small effects might have been missed. *Collaborators (28): Kjekshus J, Apetrei E, Barrios V, Bohm M, Cleland JG, Cornel JH, Dunselman P, Fonseca C, Goudev A, Grande P, Gullestad L, Hjalmarson A, Hradec J, Janosi A, Kamensky G, Komajda M, Korewicki J, Kuusi T, Mach F, Mareev V, McMurray JJ, Ranjith N, Schaufelberger M, Vanhaecke J, van Veldhuisen DJ, Waagstein F, Wedel H, Wikstrand J. Copyright 2010 Elsevier Inc. All rights reserved. PMID: 20152247 [PubMed - indexed for MEDLINE]

Lorgelly PK, Briggs AH, Wedel H, Dunselman P, Hjalmarson A, Kjekshus J, Waagstein F, Wikstrand J, Jánosi A, van Veldhuisen DJ, Barrios V, Fonseca C, McMurray JJ; CORONA Study Group. An economic evaluation of rosuvastatin treatment in systolic heart failure: evidence from the CORONA trial. Eur J Heart Fail. 2010 Jan;12(1):66-74.


AIMS: To estimate the cost-effectiveness of 10 mg rosuvastatin daily for older patients with systolic heart failure in the Controlled Rosuvastatin Multinational Study in Heart Failure (CORONA) trial. METHODS AND RESULTS: This within trial analysis of CORONA used major cardiovascular (CV) events as the outcome measure. Resource use was valued and the costs of hospitalizations, procedures, and statin use compared. Cost-effectiveness was estimated as cost per major CV event avoided. There were significantly fewer major CV events in the rosuvastatin group compared with the placebo group (1.04 vs. 1.20 per patient; difference 0.164; 95% CI: 0.075-0.254, P < 0.001). The average cost of CV hospitalizations and procedures was significantly lower for those receiving rosuvastatin (pound1531 vs. pound1769; difference pound238; 95% CI: pound73-403, P = 0.005); the additional cost of the statin resulted in significantly higher total costs for the rosuvastatin group ( pound1769 vs. pound2072; difference pound303; 95% CI: pound138-468, P < 0.001). Overall, rosuvastatin was found to cost pound1840 (95% CI: pound562-6028) per major CV event avoided. CONCLUSION: This economic analysis showed that a significant reduction in major CV events with rosuvastatin led to significantly reduced costs of CV hospitalizations and procedures. The reduction in associated costs for major CV events was found to offset partially (by 44%) the cost of rosuvastatin treatment in patients with systolic heart failure. Collaborators (68): Dunselman P, Hjalmarson A, Janssonz L, Kjekshus J, Lindberg M, McMurray JJ, Waagstein F, Wedel H, Wikstrand J, Dunselman P, Hjalmarson A, Kjekshus J, McMurray JJ, Waagstein F, Wedel H, Wikstrand J, Kjekshus J, Dunselman P, Hjalmarson A, Apetrei E, Böhm M, Cleland JG, Corne JH, Goudev A, Grande P, Gullestad L, Hradec J, Jánosi A, Kamensky G, Komajda M, Korewicki J, Kuusi T, Mach F, Mareev V, Ranjith N, Schaufelberger M, Vanhaecke J, Apetrei E, Barrios V, Böhm M, Cleland JG, Corne JH, Fonseca C, Goudev A, Grande P, Gullestad L, Wikstrand J, Jánosi A, Kamensky G, Komajda M, Korewicki J, Kuusi T, Mach F, Mareev V, Ranjith N, Schaufelberger M, Vanhaecke J, van Veldhuisen DJ, Dargie H, DeMets D, Collins R, Feyz J, Massie B, Fredlund BO, Holmberg M, Saldeen K, Samuelsson O, Swedberg K. PMID: 20023047 [PubMed - indexed for MEDLINE] PMCID: PMC2796144

Jongbloed MR, Kelder TP, DEN Uijl DW, Bartelings MM, Molhoek SG, Tukkie R, Schalij MJ. Anatomical perspective on radiofrequency ablation of AV nodal reentry tachycardia after Mustard correction for transposition of the great arteries. Pacing Clin Electrophysiol. 2010 Oct 4. [Epub ahead of print]. 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

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the intraatrial baffle. This position was chosen to deliver radiofrequency current. (PACE 2010; 1-4). ©2010, The Authors. Journal compilation ©2010 Wiley Periodicals, Inc. PMID: 21029125 [PubMed - as supplied by publisher]

Claessen BE, Bax M, Delewi R, Meuwissen M, Henriques JP, Piek JJ. The Doppler flow wire in acute myocardial infarction. Heart. 2010 Apr;96(8):631-5. Contemporary mechanical reperfusion therapy for acute myocardial infarction is aimed at early and complete restoration of myocardial perfusion. However, successful restoration of epicardial blood flow does not guarantee restoration of flow at the myocardial tissue level. The incidence of inadequate myocardial reperfusion after primary percutaneous coronary intervention (PCI) varies from 15-70%, based upon the diagnostic modality used. The Doppler flow guidewire can be used immediately after primary PCI to identify patients with apparently restored epicardial flow but impaired reperfusion at the myocardial microcirculatory and tissue level. Characteristic findings by intracoronary Doppler flow velocity measurements such as a reduced coronary flow velocity reserve, and, in particular, systolic flow velocity reversal and a short diastolic

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deceleration time are associated with the presence of microvascular obstruction. Detection of microvascular obstruction by the Doppler flow wire directly after primary PCI can identify patients who may benefit from adjunctive therapy after primary PCI. PMID: 20357393 [PubMed - indexed for MEDLINE]

Van der Schaaf RJ, Claessen BE, Vis MM, Hoebers LP, Koch KT, Baan J Jr, Meuwissen M, Engstrom AE, Kikkert WJ, Tijssen JG, de Winter RJ, Piek JJ, Henriques JP. Effect of multivessel coronary disease with or without concurrent chronic total occlusion on oneyear mortality in patients treated with primary percutaneous coronary intervention for cardiogenic shock. Am J Cardiol. 2010 Apr 1;105(7):955-9. Epub 2010 Feb 13. Despite early revascularization, mortality remains high in patients with ST-segment elevation myocardial infarction (STEMI) complicated by cardiogenic shock. It has been shown that the effect of multivessel disease (MVD) on mortality in patients with STEMI treated with primary percutaneous coronary intervention is mainly caused by the presence of chronic total occlusion (CTO) in a noninfarct-related coronary artery. Whether this association also exists in patients with STEMI with cardiogenic shock is unknown. In our institution, 292 consecutive patients with STEMI complicated by cardiogenic shock were admitted from 1997 to 2005 and treated with primary percutaneous coronary intervention. Patients were classified as having single vessel disease, MVD without CTO, and CTO. Cox regression analysis was used for multivariate analysis. The 1-year mortality rate of patients with single-vessel disease, MVD, and CTO was 31%, 47%, and 63%, respectively. After adjustment for possible confounders, MVD alone was not an independent predictor of 1-year mortality (hazard ratio 1.5, 95% confidence interval 0.98 to 2.3,


p = 0.07). In contrast, CTO in a noninfarct-related artery was an independent predictor of 1-year mortality (hazard ratio 2.1, 95% confidence interval 1.5 to 3.1, p <0.01). In conclusion, the presence of CTO in a non-infarct-related artery was an independent predictor of 1-year mortality. In contrast, MVD alone lost its predictivesignificance after multivariate analysis. Copyright 2010 Elsevier Inc. All rights reserved. PMID: 20346312 [PubMed - indexed for MEDLINE]

Engström AE, Vis MM, Bouma BJ, van den Brink RB, Baan J Jr, Claessen BE, Kikkert WJ, Sjauw KD, Meuwissen M, Koch KT, de Winter RJ, Tijssen JG, Piek JJ, Henriques JP. Right ventricular dysfunction is an independent predictor for mortality in ST-elevation myocardial infarction patients presenting with cardiogenic shock on admission. Eur J Heart Fail. 2010 Mar;12(3):276-82. Epub 2010 Jan 19. AIMS: Despite improvement in prognosis for ST-elevation myocardial infarction (STEMI) patients, mortality remains high in STEMI patients presenting with cardiogenic shock (CS). Right ventricular (RV) dysfunction is an established independent predictor for adverse prognosis in STEMI patients without CS. The purpose of our study was to determine the prognostic value of RV dysfunction on admission in STEMI patients presenting in CS. METHODS AND RESULTS: Two hundred and ninety-two consecutive STEMI patients with CS on admission were treated by primary percutaneous coronary intervention (PCI) from January 1997 through March 2005. RV function was assessed by measurement of tricuspid annular plane systolic excursion (TAPSE) on early echocardiography in 184 of 292 patients. Right ventricular dysfunction was defined as a TAPSE of
Verouden NJ, Haeck JD, Kuijt WJ, Meuwissen M, Koch KT, Henriques JP, Baan J, Vis MM, Piek JJ, Tijssen JG, de Winter RJ. Clinical and angiographic predictors of ST-segment recovery after primary percutaneous coronary intervention. Am J Cardiol. 2010 Jun 15;105(12):1692-7. Epub 2010 Apr 27.

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Important determinants of incomplete ST-segment recovery in patients undergoing primary percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI) have been incompletely characterized. Early risk stratification could identify patients with STEMI and incomplete ST-segment recovery who may benefit from adjunctive therapy. For the present study, we analyzed 12-lead electrocardiograms from 2,124 patients with STEMI who underwent primary PCI at our institution from 2000 to 2007. ST-segment recovery was defined as percent change in cumulative ST-segment deviation between preprocedural and immediately postprocedural electrocardiograms and categorized as incomplete when <50%. A total of 1,032 patients (49%) had incomplete ST-segment recovery. After multivariable adjustment, age >60 years (adjusted odds ratio [OR] 1.28, 95% confidence interval [CI] 1.06 to 1.54, p = 0.011), diabetes mellitus (OR 1.36, 95% CI 1.02 to 1.82, p = 0.034), left anterior descending coronary artery-related STEMI (OR 1.92, 95% CI 1.61 to 2.30, p<0.001), and multivessel disease (OR 1.34, 95% CI 1.10 to 1.63, p = 0.004) were independent predictors of incomplete ST-segment recovery. Current smoking (OR 0.79, 95% CI 0.65 to 0.95, p = 0.013) and a preprocedural Thrombolysis In Myocardial Infarction grade <3 flow (OR 0.70, 95% CI 0.53 to 0.93, p = 0.014) were inversely related to ST-segment recovery. Incomplete ST-segment recovery was a strong predictor of

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long-term mortality (hazard ratio 2.07, 95% CI 1.59 to 2.69, p <0.001) in addition to identified characteristics that independently predicted incomplete ST-segment recovery. In conclusion, incomplete ST-segment recovery at the end of PCI occurred significantly more often in the presence of an age >60 years, nonsmoking, diabetes mellitus, left anterior descending coronary artery-related STEMI, multivessel disease, and preprocedural Thrombolysis In Myocardial Infarction grade 3 flow. Patients with STEMI and these clinical features are at increased risk of impaired myocardial salvage and are appropriate candidates for adjunctive therapy. PMID: 20538116 [PubMed - indexed for MEDLINE]

Engström AE, Vis MM, Bouma BJ, Claessen BE, Sjauw KD, Baan J Jr, Meuwissen M, Koch KT, de Winter RJ, Tijssen JG, Piek JJ, Henriques JP. Mitral regurgitation is an independent predictor of 1-year mortality in ST-elevation myocardial infarction patients presenting in cardiogenic shock on admission. Acute Card Care. 2010 Jun;12(2):51-7. BACKGROUND: Cardiogenic shock (CS) remains the most serious complication of acute STelevation myocardial infarction (STEMI). Mitral regurgitation (MR) is a frequent complication of STEMI and a well-known predictor of mortality in STEMI without CS. The purpose of this study was to determine the prognostic significance of MR in STEMI patients with CS on admission. METHODS: Mitral regurgitation was assessed in 147 consecutive STEMI patients with CS on admission and treated by primary percutaneous coronary intervention (PCI). Color Doppler of MR was graded with a 0 to 3 scale (none, n = 26; 1 = mild, n = 62; 2 = moderate, n = 40; 3 = severe, n = 19). RESULTS: Overall one-year mortality in the study cohort was 27%. One-year mortality was 8%, 23%, 30% and 58% for patients with no, mild, moderate and severe MR respectively


(P <0.001). For each grade of MR increase, the odds for mortality increased with 71% (OR: 1.71; 95% CI: 1.02-2.87; P = 0.043) when adjusted for age, gender, previous myocardial infarction, left ventricular ejection fraction (LVEF) <40%, multivessel disease and no-reflow. CONCLUSIONS: The presence of MR on early echocardiography is an important independent predictor of one-year mortality in STEMI patients with CS on admission treated by primary PCI. PMID: 20482326 [PubMed - indexed for MEDLINE]

Claessen BE, Kikkert WJ, Engstrom AE, Hoebers LP, Damman P, Vis MM, Koch KT, Baan J Jr, Meuwissen M, van der Schaaf RJ, de Winter RJ, Tijssen JG, Piek JJ, Henriques JP. Primary percutaneous coronary intervention for ST elevation myocardial infarction in octogenarians: trends and outcomes. Heart. 2010 Jun;96(11):843-7. Epub 2009 Dec 4. OBJECTIVE: The general population is gradually ageing in the western world. Therefore, the number of octogenarians undergoing primary percutaneous coronary intervention (PCI) for STelevation myocardial infarction (STEMI) is increasing. We aim to provide insight into temporal trends in the annual proportions of octogenarians among STEMI patients undergoing primary PCI and their clinical characteristics and outcomes over an 11-year observational period. DESIGN: Single-centre observational study. PATIENTS: Between 1997 and 2007, 4506 STEMI patients were treated with primary PCI at the authors’ institution. Patients aged over 80 years were identified. MAIN OUTCOME MEASURES: Temporal trends in the annual proportion of octogenarian STEMI patients and their baseline characteristics, 30-day and 1-year mortality were analysed. RESULTS: A total of 379 octogenarians (8.4% of the total population) was treated with primary PCI between 1997 and 2007. Over time, the annual proportion of octogenarians gradually increased from four of 113 (3.5%) in 1997 to 51 of 579 (8.8%) in 2007 (p for trend <0.01). In the total cohort of 379 patients, 30-day mortality was 21% (81 patients) and 1-year mortality was 28% (107 patients). There was no improvement in survival among octogenarian STEMI patients over the 11-year study period. CONCLUSION: The annual proportion of octogenarian STEMI patients increased significantly over the 11-year study period. Mortality among these high-risk patients was high and did not improve during the study period. Unfortunately, little is known about the optimal treatment of the elderly as they are underrepresented in many randomised clinical trials. Further studies into the optimal STEMI management strategy for the elderly are warranted. Comment in: Heart. 2010 Jun;96(11):813-4. PMID: 19966111 [PubMed - indexed for MEDLINE]

Claessen BE, Hoebers LP, van der Schaaf RJ, Kikkert WJ, Engstrom AE, Vis MM, Baan J Jr, Koch KT, Meuwissen M, van Royen N, de Winter RJ, Tijssen JG, Piek JJ, Henriques JP. Prevalence and impact of a chronic total occlusion in a non-infarct-related artery on

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long-term mortality in diabetic patients with ST elevation myocardial infarction. Heart. 2010 Dec;96(24):1968-72. Epub 2010 Oct 7. BACKGROUND: Recently, a chronic total occlusion (CTO) in a non-infarct-related artery (nonIRA) and not multivessel disease (MVD) alone was identified as an independent predictor of mortality after ST elevation myocardial infarction (STEMI). Patients with diabetes mellitus (DM) constitute a patient group with a high prevalence of MVD and high mortality after STEMI. The prevalence of CTO in a non-IRA was studied and its impact on long-term mortality in STEMI patients with DM was investigated. METHODS: Between 1997 and 2007 4506 patients with STEMI were admitted and treated with primary percutaneous coronary intervention (PCI). Patients with DM were identified. The patients were categorised as having single vessel disease (SVD), MVD without CTO and CTO based on the angiogram before PCI. RESULTS: A total of 539 patients (12%) had DM. MVD with or without a CTO was present in 33% of non-diabetic patients and in 51% of diabetic patients. The prevalence of a CTO in a non-IRA was 21% in STEMI patients with DM and 12% in STEMI patients without DM (p<0.01). Kaplan-Meier estimates for 5-year mortality in STEMI patients with DM were 25%, 21% and 47% in patients with SVD, MVD without a CTO and

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MVD with a CTO in a non-IRA, respectively. A CTO in a non-IRA was an independent predictor of 5-year mortality (HR 2.2, 95% CI 1.3 to 3.5, p<0.01). CONCLUSION: The prevalence of a CTO in a non-IRA was increased in STEMI patients with DM. The presence of a CTO in a non-IRA was a strong and independent predictor of 5-year mortality. These results suggest that, particularly in the high-risk subgroup of STEMI patients with DM, MVD has prognostic implications only if a concurrent CTO is present. Comment in: Heart. 2010 Dec;96(24):1955-6. PMID: 20930044 [PubMed - indexed for MEDLINE]

Complete publicatielijst Piazza N, Grube E, Gerckens U, Schuler G, Linke A, den Heijer P, Kovacs J, Spyt T, Laborde JC, Morel MA, Nuis RJ, Garcia-Garcia HM, de Jaegere P, Serruys PW. A clinical protocol for analysis of the structural integrity of the Medtronic CoreValve System frame and its application in patients with 1-year minimum follow-up. EuroIntervention. 2010 Jan;5(6):680-6. Van de Hoef TP, Chamuleau SAJ, Koch KT, Baan J, Vis MM, Tijssen JGP, R.J. de Winter RJ, Henriques JPS, Piek JJ, Meuwissen M. A normal reference coronary flow reserve is associated with a lower mortality in patients with stable coronary artery disease*. Eur Heart J 2010 sep;31(Suppl.1):313:P1915. Meuwissen M, Chamuleau SAJ, Koch KT, de Winter RJ, Vis MM, Baan Jr J, Tijssen JGP, Henriques JJP, Piek JJ. A normal relative coronary flow reserve is associated with a lower mortality in patients with stable coronary artery disease. J Am Coll Cardiol 2010;55(Suppl.1):A204.E1927.


Claessen B, Kikkert WJ, Koch KT, Vis MM, Baan Jr J, Meuwissen M, de Winter RJ, Tijssen JGP, Piek JJ, Henriques JPS. Age and one-year mortality after ST elevation myocardial infarction treated with primary percutaneous intervention. J Am Coll Cardiol 2010;55(Suppl.1):A187.E1745. Lorgelly PK, Briggs AH, Wedel H, Dunselman P, Hjalmarson A, Kjekshus J, Waagstein F, Wikstrand J, Jánosi A, van Veldhuisen DJ, Barrios V, Fonseca C, McMurray JJ; CORONA Study Group. An economic evaluation of rosuvastatin treatment in systolic heart failure: evidence from the CORONA trial. Eur J Heart Fail. 2010 Jan;12(1): 66-74. De Jong JSSG, van der Bilt IAC, Meuwissen M, van den Brink RBA, de Voogt WA, Wellens H. Wilde AAW. An online platform for ECG education and teaching files: ECGpedia.org. Eur Heart J 2010 sep;31(Suppl.1):313:P1683. Jongbloed MR, Kelder TP, DEN Uijl DW, Bartelings MM, Molhoek SG, Tukkie R, Schalij MJ. Anatomical perspective on radiofrequency ablation of AV nodal reentry tachycardia after Mustard correction for transposition of the great arteries. Pacing Clin Electrophysiol. 2010 Oct 4. [Epub ahead of print]. Alings M, Göhl K, Wardeh A, Nimeth C, Tukkie R, Trinks S, Kainz W, Vireca E, Delaney C, Kaltofen G. Automaticity Registry: 1 year follow-up results of automatic algorithms in Boston Scientific pacemakers. Europace. 2010;12(suppl 1):56P/58. [CardioStim, 2010]. Verouden NJ, Haeck JD, Kuijt WJ, Meuwissen M, Koch KT, Henriques JP, Baan J, Vis MM, Piek JJ, Tijssen JG, de Winter RJ. Clinical and angiographic predictors of ST-segment recovery after primary percutaneous coronary intervention. Am J Cardiol. 2010 Jun 15;105(12):1692-7. Epub 2010 Apr 27. Alings M, Goehl K, Wardeh AJ, Nimeth C, Tukkie R, Trinks S, Kainz W, Vireca E, Delaney C, Kaltofen G. Clinical use of automatic features in implantable pacemakers: results of the AUTOMATICITY registry. Eur Heart J 2010;31(suppl 1):845. [ESC, 2010]. McMurray JJ, Dunselman P, Wedel H, Cleland JG, Lindberg M, Hjalmarson A, Kjekshus J, Waagstein F, Apetrei E, Barrios V, Böhm M, Kamenský G, Komajda M, Mareev V, Wikstrand J; CORONA Study Group. Coenzyme Q10, rosuvastatin, and clinical outcomes in heart failure: a pre-specified substudy of CORONA (controlled rosuvastatin multinational study in heart failure). J Am Coll Cardiol. 2010 Oct 5;56(15):1196-204. Oldgren J, Alings M, Darius H, Eikelboom J, Ezekowitz M, Parekh A, Pogue J, Reilly P, Yusuf S, Wallentin L, Connolly S. Dabigatran versus warfarin in atrial fibrillation patients with low, moderate and high CHADS2 score: a RE-LY subgroup analysis. J. Am. Coll. Cardiol. 2010;55;A1.E2. [ACC 2010]. Van den Broek KC, Pedersen SS, van der Voort PH, Alings M, Denollet J. Depressive symptoms are associated with mortality in ICD patients. Europace. 2010;12(suppl 1): 136P/59. [CardioStim, 2010].

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CURRENT-OASIS 7 Investigators, Mehta SR, Bassand JP, Chrolavicius S, Diaz R, Eikelboom JW, Fox KA, Granger CB, Jolly S, Joyner CD, Rupprecht HJ, Widimsky P, Afzal R, Pogue J, Yusuf S, Collaborators (572) [Dunselman P et al...) Dose comparisons of clopidogrel and aspirin in acute coronary syndromes. N Engl J Med. 2010 Sep 2;363(10):930-42. Van Etten J, van Osch P, van Keulen PHJ, Bruggeling WAJ. Eerste beschrijving van endocarditis door Cardiobacterium hominis in Nederland: een case report. Hartbulletin. feb 2010;41(1):8-11. Van der Schaaf RJ, Claessen BE, Vis MM, Hoebers LP, Koch KT, Baan J Jr, Meuwissen M, Engstrom AE, Kikkert WJ, Tijssen JG, de Winter RJ, Piek JJ, Henriques JP. Effect of multivessel coronary disease with or without concurrent chronic total occlusion on one-year mortality in patients treated with primary percutaneous coronary intervention for cardiogenic shock. Am J Cardiol. 2010 Apr 1;105(7):955-9. Epub 2010 Feb 13. Van der Harst P, Slart RH, Tio RA, Dunselman PH, Willemsen AT, van den Heuvel AF, Voors AA, van Veldhuisen DJ; CORONA Study Group. [Dunselman P. et al...] Effects of rosuvastatin on coronary flow reserve and metabolic mismatch in patients with heart failure (from the CORONA Study). Am J Cardiol. 2010 Feb 15;105(4):517-21. Epub 2010 Jan 5. Wallentin L, Yusuf S, Ezekowitz MD, Alings M, Flather M, Franzosi MG, Pais P, Dans A, Eikelboom J, Oldgren J, Pogue J, Reilly PA, Yang S, Connolly SJ; RE-LY investigators. Efficacy and safety of dabigatran compared with warfarin at different levels of international normalised ratio control for stroke prevention in atrial fibrillation: an analysis of the RE-LY trial. Lancet. 2010 Sep 18;376(9745):975-83. Van den Broek KC, Alings M, van der Voort PH, Denollet J. Emotional distress in ICD patients: the role of etiology and indication. Europace. 2010;12(suppl 1): 136P/5. [CardioStim, 2010]. Versteeg H, van den Broek KC, Theuns DAMJ, Mommersteeg PMC, Alings M, van der Voort PH, Jordaens L, Pedersen SS. Impact of CRT on health status in ICD patients: a multicenter study. Europace. 2010;12(suppl 1):216P/3. [CardioStim, 2010]. Inglis SC, McMurray JJ, Böhm M, Schaufelberger M, van Veldhuisen DJ, Lindberg M, Dunselman P, Hjalmarson A, Kjekshus J, Waagstein F, Wedel H, Wikstrand J; CORONA Study Group. Intermittent claudication as a predictor of outcome in patients with ischaemic systolic heart failure: analysis of the Controlled Rosuvastatin Multinational Trial in Heart Failure trial (CORONA). Eur J Heart Fail. 2010 Jul;12(7):698-705. Epub 2010 May 25. Van Gelder IC, Groenveld HF, Crijns HJ, Tuininga YS, Tijssen JG, Alings AM, Hillege HL, Bergsma-Kadijk JA, Cornel JH, Kamp O, Tukkie R, Bosker HA, Van Veldhuisen DJ, Van


den Berg MP; RACE II Investigators. Lenient versus strict rate control in patients with atrial fibrillation. N Engl J Med. 2010 Apr 15;362(15):1363-73. Epub 2010 Mar 15. Engström AE, Vis MM, Bouma BJ, Claessen BE, Sjauw KD, Baan J Jr, Meuwissen M, Koch KT, de Winter RJ, Tijssen JG, Piek JJ, Henriques JP. Mitral regurgitation is an independent predictor of 1-year mortality in ST-elevation myocardial infarction patients presenting in cardiogenic shock on admission. Acute Card Care. 2010 Jun;12(2):51-7. Claessen B, Vis MM, Koch KT, Baan Jr J, Jr, Meuwissen M, de Winter RJ, Tijssen JG, Piek JJ, Henriques JP. Multivessel versus culprit-only primary percutaneous coronary intervention in patients with multivessel disease and ST-elevation myocardial infarction complicated with cardiogenic shock. J Am Coll Cardiol 2010;55(Suppl.1):A185.E1734. Habibovic M, van den Broek KC, Alings M, van der Voort PH, Theuns DAMJ, Denollet J. Predictors of post-traumatic stress 18 months post ICD implantation. Europace. 2010;12(suppl 1):24/5. [CardioStim, 2010]. Claessen BE, Hoebers LP, van der Schaaf RJ, Kikkert WJ, Engstrom AE, Vis MM, Baan J Jr, Koch KT, Meuwissen M, van Royen N, de Winter RJ, Tijssen JG, Piek JJ, Henriques JP. Prevalence and impact of a chronic total occlusion in a non-infarct-related artery on long-term mortality in diabetic patients with ST elevation myocardial infarction. Heart. 2010 Dec;96(24):1968-72. Epub 2010 Oct 7. Claessen BE, Kikkert WJ, Engstrom AE, Hoebers LP, Damman P, Vis MM, Koch KT, Baan J Jr, Meuwissen M, van der Schaaf RJ, de Winter RJ, Tijssen JG, Piek JJ, Henriques JP. Primary percutaneous coronary intervention for ST elevation myocardial infarction in octogenarians: trends and outcomes. Heart. 2010 Jun;96(11):843-7. Epub 2009 Dec 4. Engström AE, Vis MM, Bouma BJ, van den Brink RB, Baan J Jr, Claessen BE, Kikkert WJ, Sjauw KD, Meuwissen M, Koch KT, de Winter RJ, Tijssen JG, Piek JJ, Henriques JP. Right ventricular dysfunction is an independent predictor for mortality in ST-elevation myocardial infarction patients presenting with cardiogenic shock on admission. Eur J Heart Fail. 2010 Mar;12(3):276-82. Epub 2010 Jan 19. Claessen BE, Bax M, Delewi R, Meuwissen M, Henriques JP, Piek JJ. The Doppler flow wire in acute myocardial infarction. Heart. 2010 Apr;96(8):631-5. Van Gelder IC, Smit MD, Alings M, Crijns HJ. Upstream therapy in patients with early atrial fibrillation. The relevance of routine versus aggressive upstream rhythm control for prevention of atrial fibrillation in heart failure (RACE 3) study. Neth Heart J. 2010 Nov;18(11):522-3.

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Cardiothoracale chirurgie Kerngegevens zorgkern Cardiothoracale chirurgie • 6 cardiothoracaal chirurgen: M. Bentala, mw. C.A. Boot, P.A.E. Hiddema, B.P. van Putte, M.M. Vrakking, J. Witkop • chef de clinique: mw. M. Gaionoli • 3 assistenten niet in opleiding

Samenvattingen gepubliceerde artikelen Malvindi PG, van Putte BP, Heijmen RH, Schepens MA, Morshuis WJ. Reoperations for aortic false aneurysms after cardiac surgery. Ann Thorac Surg. 2010 Nov;90(5):1437-43. BACKGROUND: Aortic false aneurysm is a rare complication after cardiac surgery. Aortic dissection, infection, arterial wall degeneration, and poor surgical technique are recognized as risk factors for the occurrence of postsurgical false aneurysm. Despite some recent reports about percutaneous false aneurysm exclusion, a complex surgical reoperation is needed in most of the cases. METHODS: We retrospectively reviewed our experience in 43 patients who received a reoperation for postsurgical aortic false aneurysm in the last 14 years. Thirty-three patients were male. The mean age was 60 ± 12 years. Most of the patients received prior aortic surgery on the aortic root, the ascending aorta, the aortic arch, and the descending thoracic aorta (38 patients). False aneurysm was diagnosed during follow-up evaluation in the absence of any symptoms in 23 cases. Univariate and multivariate analyses on 18 perioperative variables were performed. RESULTS: In-hospital mortality was 6.9% (3 patients). The postoperative course was complicated in 17 cases (39%). At multivariate analysis, a preoperative history of coronary artery disease and postoperative sepsis were independent risk factors for hospital mortality. Survival rates at 1, 5, and 10 years were 94%, 79%, and 68%, respectively. Freedom from reoperation was 86% at 1 year and 72% at 5 and 10 years. CONCLUSIONS: Despite a high postoperative complication rate, a reoperation for postsurgical aortic false aneurysm can be

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performed with acceptable mortality and good mid-term and long-term outcomes. Copyright © 2010 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved. Comment in: Ann Thorac Surg. 2010 Nov;90(5):1443. PMID: 20971235 [PubMed - indexed for MEDLINE]

Den Hengst WA, Van Putte BP, Hendriks JM, Stockman B, van Boven WJ, Weyler J, Schramel FM, Van Schil PE. Long-term survival of a phase I clinical trial of isolated lung perfusion with melphalan for resectable lung metastases. Eur J Cardiothorac Surg. 2010 Nov;38(5):621-7. Epub 2010 May 15. OBJECTIVE: Surgical resection of lung metastases is a widely accepted procedure but 5-year survival rates remain low and vary between 20% and 50%. Isolated lung perfusion (ILuP) is an experimental technique to deliver a high dose of chemotherapy to the lung, without systemic toxicity. Long-term survival of ILuP has not been reported yet and was determined in a phase I clinical trial. METHODS: From May 2001 to December 2004, a phase I clinical trial was conducted to define the maximum tolerated dose (MTD) of ILuP with melphalan. Twenty-nine procedures

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were performed in 23 patients. The primary tumour was colorectal inv 10 patients, renal in eight, sarcoma in four and salivary gland in one. Toxicity results were previously reported and the MTD of melphalan was determined at 45 mg when given at 37°C. Follow-up was updated and long-term survival is reported. RESULTS: Follow-up was complete, except for one patient who was lost to follow-up after 8 months. After a median follow-up of 62 months, 6 out of 23 patients were alive and free of recurrent disease. One patient died after a subsequent operation. Sixteen patients developed recurrent disease, of whom 11 died. Nine patients had intrathoracic recurrent disease only, one intra- and extrathoracic recurrences each and five extrathoracic only. In one patient, the location of recurrence was not known. Overall- and disease-free 5-year survival rates were 54.8 ± 10.6% and 27.5 ± 9.5%, respectively with an overall median survival time (MST) of 84 months (95% confidence interval (CI): 41-128) and disease-free MST of 19 months (95%b CI: 4-34). Lung function and diffusion capacity initially dropped 1 month after perfusion, slightly improving afterwards. Radiographic follow-up with chest computed tomography showed no long-term toxicity from ILuP. CONCLUSION: ILuP can be applied without major long-term pulmonary toxicity. Five-year survival rate, overall and disease-free MST in this phase I clinical trial are promising. This is another incentive to perform further studies with ILuP. Copyright © 2010 European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved. PMID: 20478715 [PubMed - in process]

Yilmaz A, Geuzebroek GS, Van Putte BP, Boersma LV, Sonker U, De Bakker JM, Van Boven WJ. Completely thoracoscopic pulmonary vein isolation with ganglionic plexus ablation


and left atrial appendage amputation for treatment of atrial fibrillation. Eur J Cardiothorac Surg. 2010 Sep;38(3):356-60. Epub 2010 Mar 12. OBJECTIVE: Percutaneous catheter pulmonary vein isolation (PVI) has been the preferred choice for invasive treatment of symptomatic, drug-refractory lone atrial fibrillation (AF). Incomplete ablation lines, procedure-related morbidity and long-term success remain, however, a problem. A minimally invasive surgical approach can provide an attractive and secure balternative. Surgery offers an epicardial, bipolar approach under direct vision, but the invasiveness of surgery remains a problem. Therefore, we developed a completely thoracoscopic procedure. The objective of this study was to assess the feasibility, safety and effectiveness of a completely thoracoscopic surgical procedure to cure lone AF. METHODS: Bilateral ‘video-assisted thoracoscopy’ was performed to isolate the bilateral pairs of pulmonary veins using bipolar RF-energy, to ablate the ganglionic plexus (GP) and to amputate the left atrial appendage. Preoperative, in-hospital and follow-up data were collected for our first 30 patients. RESULTS: AF was paroxysmal in 63%, persistent in 27% and permanent in 10% of cases. The mean (+ or - SD) left atrial diameter was 42.1 + or - 7.4mm and the mean duration of AF was 79.0 + or - 63.9 months. Freedom from AF was obtained in 77% of the patients during a mean follow-up of 11.6 months. Forty-three percent of the patients had previously undergone a percutaneous PVI and were all free from AF during follow-up. Mean operation time was 137.4 + or - 24.7 min. All patients were extubated in the operating room and left the recovery room within 12 h. The mean hospital stay was 5.1 + or - 1.8 days. Two patients ultimately underwent a median sternotomy. No CVAs or pacemaker implantation were identified and none of the patients died. CONCLUSION: We report our initial experience of a completely thoracoscopic PVI with GPablation and amputation of the left atrial appendage and demonstrate that the procedure is feasible, safe and effective for the treatment of lone AF. Copyright 2010 European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved. PMID: 20227287 [PubMed - in process]

Malvindi PG, van Putte BP, Heijmen RH, Schepens MA, Morshuis WJ. Reoperations on the aortic root: experience in 46 patients. Ann Thorac Surg. 2010 Jan;89(1):81-6. BACKGROUND: The increasing use of biologic conduits and the advances in reparative aortic root procedures has increased the number of patients who may require reoperation on the aortic root. Although the primary operation yields excellent results with a low risk for morbidity and mortality, reoperation on the aortic root is still challenging. METHODS: We reviewed retrospectively our experience in 46 patients (38 men; mean age, 57 +/- 11 years) who underwent aortic root reoperations in the last 7 years. Of these, 42 had received prior aortic root replacement. The indications for reoperation included prosthesis infection in 16, false aneurysm in 16, and degenerative or postdissection aneurysm and valve prosthesis failure.


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Aortic root re-replacement was performed in 39 patients (85%) and closure of false aneurysm in 7. Univariate and multivariate analysis on 22 perioperative variables were performed. RESULTS: In-hospital mortality was 6.5% (3 patients). The postoperative course was complicated in 19 (41%). At multivariate analysis, perioperative myocardial infarction was a risk factor for hospital mortality (2 patients). Survival was 88% at 1 year and 74% at 5 years. No differences were found in survival according to redo indication. Freedom from reoperation on the aortic root was 100% at 1 year and 90% at 5 years. CONCLUSIONS: Reoperation on the aortic root can be performed with acceptable mortality and good midterm and long-term outcome; however, the postoperative complication rate is still high. 2010 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved. PMID: 20103210 [PubMed - indexed for MEDLINE]

Tolsma M, Kröner A, van den Hombergh CL, Rosseel PM, Rijpstra TA, Dijkstra HA, Bentala M, Schultz MJ, van der Meer NJ. The clinical value of routine chest radiographs in the first 24 hours after cardiac surgery. Anesth Analg. 2011 Jan;112(1):139-42. Epub 2010 Nov 3. 42

BACKGROUND: Chest radiographs (CXRs) are obtained frequently in the intensive care unit (ICU). Whether these CXRs should be performed routinely or on clinical indication only is often debated. The aim of our study was to investigate the incidence and clinical significance of abnormalities found on routine postoperative CXRs in cardiac surgery patients and whether a restricted use of CXRs would influence the number of significant findings. METHODS: We prospectively included all consecutive patients who underwent cardiac surgery during a 2-month period. Two or three CXRs were performed in the first 24 hours of ICU stay. After ICU admission and after drain removal, a clinical assessment was performed before a CXR was obtained. All CXR abnormalities were noted and it was also noted whether they led to an intervention. For the admission CXR and the drain removal CXR, a comparison was made between CXRs clinically indicated by the physician and those not clinically indicated. RESULTS: Two hundred fourteen patients were included. The majority of patients underwent coronary arterial bypass grafting (60%), heart valve surgery (21%), or a combination of these (14%). In total, 534 CXRs were performed (2.5 per patient). Abnormalities were found on 179 CXRs (33.5%) and 13 CXR results led to an intervention (2.4%). The association between clinically indicated CXRs and the presence of CXR abnormalities was poor. For 32 (10%) of the 321 admission and drain removal CXRs, clinical indications were stated by the physician beforehand. If these CXRs would not have been performed routinely, 68 abnormalities would have been missed, of which 5 led to an intervention. CONCLUSIONS: Partial elimination of routine CXRs in the first 24 hours after cardiac surgery seems possible for the majority of patients, but it is limited by the insensitivity of clinical assessment in predicting clinically important abnormalities detectable by CXRs. PMID: 21048091 [PubMed - indexed for MEDLINE]


Complete publicatielijst Yilmaz A, Geuzebroek GS, Van Putte BP, Boersma LV, Sonker U, De Bakker JM, Van Boven WJ. Completely thoracoscopic pulmonary vein isolation with ganglionic plexus ablation and left atrial appendage amputation for treatment of atrial fibrillation. Eur J Cardiothorac Surg. 2010 Sep;38(3):356-60. Epub 2010 Mar 12. Den Hengst WA, Van Putte BP, Hendriks JM, Stockman B, van Boven WJ, Weyler J, Schramel FM, Van Schil PE. Long-term survival of a phase I clinical trial of isolated lung perfusion with melphalan for resectable lung metastases. Eur J Cardiothorac Surg. 2010 Nov;38(5):621-7. Epub 2010 May 15. Malvindi PG, van Putte BP, Heijmen RH, Schepens MA, Morshuis WJ. Reoperations for aortic false aneurysms after cardiac surgery. Ann Thorac Surg. 2010 Nov;90(5):1437-43. Malvindi PG, van Putte BP, Heijmen RH, Schepens MA, Morshuis WJ. Reoperations on the aortic root: experience in 46 patients. Ann Thorac Surg. 2010 Jan;89(1):81-6. Tolsma M, Kröner A, van den Hombergh CL, Rosseel PM, Rijpstra TA, Dijkstra HA, Bentala M, Schultz MJ, van der Meer NJ. The clinical value of routine chest radiographs in the first 24 hours after cardiac surgery. Anesth Analg. 2011 Jan;112(1):139-42. Epub 2010 Nov 3.


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Chirurgie Kwaliteit en veiligheid in de zorg

De chirurgen van het Amphia Ziekenhuis richten zich op vijf subspecialismen: maag-lever-darmchirurgie, oncologische chirurgie, traumachirurgie, vaatchirurgie en longchirurgie. ‘Daarnaast beslaat ons vak nog enkele kleinere deelgebieden, zoals hoofd-halschirurgie en kinderchirurgie’, vult dhr. R.M.P.H. Crolla aan.

R.M.P.H. Crolla

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Zelf is Crolla vooral bezig op het vakgebied van hoofd-halschirurgie, maag- en darmchirurgie en minimaal invasieve chirurgie. Daarnaast richt hij zich op het verbeteren van de kwaliteit en de veiligheid van de zorg. Sinds 2001 is het Amphia Ziekenhuis een opleidingsziekenhuis voor chirurgen. ‘Eerst werkten we hierin samen met het UMC Utrecht en later is dat veranderd in het Erasmus Ziekenhuis. Daar hebben we opnieuw een netwerk mee opgebouwd.’

Onderzoeksactiviteiten

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Belangrijke promotieonderzoeken werden recent gedaan door aio de heer A. te Slaa, chirurg de heer E. Veen en aio mevrouw J. Schreinemakers. Te Slaa onderzocht de toepasbaarheid van intermitterende pneumatische compressie na een perifere bypassoperatie tegen optredend oedeem. De werking hiervan werd vergeleken met het dragen van compressiekousen. Deze conventionele methode bleek vooralsnog de aangewezen behandelmethode voor dit oedeem. In het proefschrift dat hij – volledig in het Amphia Ziekenhuis – schreef getiteld Current Peripheral Bypass Surgery beschreef hij aspecten van de kwaliteit van leven na perifere bypasschirurgie, een meetmethode om dit oedeem te kwantificeren en beeldvormend onderzoek naar het ontstaan van dit oedeem. Veen hield zich bezig met Quality Assessment in Surgery (the role of complication registration). Hij onderzocht in zijn opleidingsziekenhuizen het gebruik van een elektronisch registratiesysteem voor complicaties. Registreren bleek moeilijk door variabele interpretatie van de classificatie van complicaties en soms door het ontbreken van heldere definities. Meer dan de helft van de ongewenste gebeurtenissen die in het chirurgische proces optreden, bleken te gebeuren buiten de operatie zelf. Veen adviseert daarom het gebruik van veiligheidschecklijsten, systematische evaluatie van het zorgproces en het behandelteam en introductie van verbeterprogramma’s.

Verdere promotieonderzoeken Mw. Schreinemakers ten slotte deed onderzoek naar Surgical Strategies in Endocrine Tumors. Ze onderzocht de chirurgische behandeling van endocriene tumoren. Ze toonde de aanwezigheid aan van biomarkers in papillair schildkliercarcinoom. Ook constateerde ze dat PET-positieve uitzaaiingen van een papillair schildkliercarcinoom een slechtere prognose hebben dan PET-negatieve klieren. Ze formuleerde een beleid voor het aantal te verwijderen bijschildklieren bij MEN1- en MEN2-syndroom. Verder onderzocht ze de chirurgische behandeling van bijniertumoren waarbij ze onder meer een direct verband aantoonde tussen de omvang van een feochromocytoom en de hoogte van de hormoonproductie. Andere leden van het chirurgisch team, zoals P. Gobardhan, G. Marres en D. Vos, zijn vergevorderd met promotieonderzoeken. Crolla hecht groot belang aan onderzoeksactiviteiten door arts-assistenten, een activiteit die begeleid wordt door opleider


dr. Van der Laan. ‘Over het algemeen gaat het om niet-gesubsidieerde onderzoeken die gebaseerd zijn op een klinische vraagstelling, in het kader van de beste zorg voor de patiënt. Bijvoorbeeld vergelijkende onderzoeken naar verschillende behandelmethoden. De laatste vijftien jaar deden we veel mee aan richtinggevende multicenteronderzoeken.’

Surpass-checklist Crolla hecht veel belang aan de kwaliteit en veiligheid van de zorg. Hij was mede-auteur van artikelen in het New England Journal of Medicine over de Surpass Checklist. ‘Ik las de aankondiging van het onderzoek door mw. Boermeester van het AMC en was direct enthousiast. De Surpass is een checklist van 110 items in elf lijsten, om te kijken of een patiënt gereed is voor een operatie. Daarbij is veel aandacht voor alle transfermomenten en er zijn diverse stopmomenten ingebouwd. Zevenduizend patiënten werden geïncludeerd.’ Crolla beschrijft hoe er in eerste instantie bij het implementeren van de lijst wat tegenzin bestond in de maatschap. ‘Zo’n lijst geeft minder plek om te improviseren. Maar al gauw bleek dat bij de vijf ziekenhuizen die participeerden (Amphia, AMC, OLVG, Jeroen Boschziekenhuis, Leiderdorp en Maastricht), de mortaliteit halveerde van 1,5 naar 0,7 procent. Ook namen de complicaties af met 60 procent. Dat zijn natuurlijk resultaten!’ Crolla werd dezelfde dag nog geïnterviewd voor een radioprogramma. Net als veel collega’s begon de chirurg zijn loopbaan in eerste instantie met traumatologie. ‘Tot ik in aanraking kwam met andere vakgebieden. De vaatchirurgie bleek voor mij niet zo interessant, het maag-darmgebied juist wel. Bijna de helft van de chirurgische patiënten heeft maag-darmklachten. De diagnose vergt een scherpe blik. Het is alsof je een puzzel oplost. Vervolgens ga je een beleid inzetten. Ook vind ik de lange arts-patiëntrelaties erg prettig.’

Toekomstplannen De ambities voor de toekomst liggen vooral in de groei naar een groter aantal assistenten. ‘We merken dat we vanwege onze omvang en inhoud van zorg een interessant ziekenhuis zijn voor assistenten en chirurgen.’ Ook hebben de maatschapleden plannen om in toenemende mate mee te doen aan multicenteronderzoeken om zichzelf en het ziekenhuis nog beter op de kaart te zetten. ‘Sinds de fusie hebben we een periode van overleven achter de rug. Nu is het tijd om te gaan uitbouwen. Met een grotere groep kunnen we beter subspecialiseren. Al zal in de periferie altijd de patiëntenzorg primair zijn.’

Kerngegevens zorgkern Chirurgie • 15 chirurgen: R.M.P.H. Crolla, H.G.W. de Groot, dr. G.H. Ho, dr. L. van der Laan, dr. E.J.T. Luiten, dr. J.K.S. Nuytinck, dr. E.J.H. van Rhede van der Kloot, dr. A.M. Rijken, P.J.H.J. Romme, G.P. van der Schelling, dr. E.J. Veen, mw. D.I. Vos, dr. J.P.A.M. Vroemen, J.C.H. van der Waal, dr. J.H. Wijsman

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• 7-10 assistenten in opleiding • 17 assistenten niet in opleiding • Subspecialismen: maag-, darm-, oncologische chirurgie, traumatologie, vaatchirurgie, longchirurgie, algemene chirurgie

Samenvattingen gepubliceerde artikelen Flu HC, Lardenoye JH, Veen EJ, Van Berge Henegouwen DP, Hamming JF. Functional status as a prognostic factor for primary revascularization for critical limb ischemia. J Vasc Surg. 2010 Feb;51(2):360-71.e1. BACKGROUND: Lower extremity arterial revascularization (LEAR) is the gold-standard for critical lower limb ischemia (CLI). The goal of this study was twofold. First, we evaluated the long-term functional status of patients undergoing primary LEAR for CLI. Second, prognostic factors of long-term functional status and survival after primary LEAR for CLI were assessed. METHODS: All primary LEAR procedures were analyzed. Patients were stratified by preoperative functional status: ambulatory (group I) vs nonambulatory (group II). Patients were followed-up

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after 3 and 6 years. Adverse events (AEs) were categorized according to predefined standards: minor, surgical, failed revascularization, and systemic. Associated patient demographic/clinical data were analyzed using univariate and multivariate methods. RESULTS: There were 106 LEAR patients (group I: n = 42, 40% vs group II: n = 64, 60%). Group II patients were significantly older (75 vs 62 years; P = .00), were classified ASA 3-4 more frequently (78% vs 52%; P < .02), had more cardiac disease (n = 42, 66% vs n = 10, 24%; P = .00), renal disease (n = 26, 41% vs n = 7, 17%; P = .00), diabetes (n = 36, 56% vs n = 8, 19%; P = .00), hypertension (n = 47, 73% vs n = 13, 31%; P = .00) and severe CLI (n = 42, 66% vs n = 18, 38%; P < .01). Group II patients had a higher incidence of death (65.6% vs 14.3%; P = .00), minor AEs (n = 38, 26% vs n = 10, 22%; P = .00), surgical AEs (n = 48, 33% vs n = 12, 26%; P < .02) and systemic AEs (n = 24, 86% vs n = 4, 9%; P < .02). Also more unplanned reinterventions occurred in group II (n = 148, 76% vs n = 47, 24%; P = .00). Nonambulatory status was a multivariate independent predictor of nonambulatory status after LEAR during 6 years follow-up (odds ration [OR[: 21.47; 95% confidence interval [CI]: 2.76-166.77; P = .00). Pulmonary disease (OR: 7.49; 95% CI: 2.17-25.80; P = .00), not prescribing beta-blockers (OR: 4.67; 95% CI: 1.28-17.03; P < .02), nonambulatory status (OR: 22.99; 95% CI: 6.27-84.24; P = .00), and systemic AEs (OR: 9.66; 95% CI: 1.84-50.57; P < .01) were independent predictors of death. Functional status was not improved in group II after long-term follow-up. CONCLUSION: Nonambulatory patients suffer from extensive comorbid conditions. They are accompanied with an increased occurrence of AEs, unplanned reinterventions, and poor long-term survival rates. Successful LEAR did not improve their functional status after 6 years. This emphasizes that attempts for limb salvage must be carefully considered in these patients. Copyright 2010. Published by Mosby, Inc. PMID: 20141960 [PubMed - in process]


Kaas L, Riet RP, Vroemen JP, Eygendaal D. The epidemiology of radial head fractures: A possible link to osteoporosis? J Shoulder Elbow Surg. 2010 Feb 9. [Epub ahead of print]. INTRODUCTION: Recent literature shows an increased mean age of female patients with radial head fractures compared with male patients with radial head fractures. However, data on epidemiology of radial head fractures and specifically in relation to age distribution and malefemale ratios of radial head fracture are scarce. MATERIALS AND METHODS: A retrospective database search was performed to identify all patients with a radial head fracture over a 3-year period. RESULTS: A total of 328 radial head fractures were diagnosed in 322 patients. The incidence was 2.8 per 10,000 inhabitants per year. The male-female ratio was 2:3. The mean age was 48.0 years (range, 14-88 years; SD, 14.8). The mean age of female patients (52.8 years) was significantly higher than that of male patients (40.5 years) (P = .001). As the age increases above 50 years, the number of female patients becomes significantly higher than the number of male patients (P = .001). An associated osseous injury was present in 40 patients (12.4%). CONCLUSIONS: Radial head fractures are common, and associated injuries are frequent. Copyright © 2010 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Mosby,

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Inc. All rights reserved. PMID: 20149972 [PubMed - as supplied by publisher]

Flu HC, Ploeg AJ, Marang-van de Mheen PJ, Veen EJ, Lange CP, Breslau PJ, Roukema JA, Hamming JF, Lardenoye JW. Patient and procedure-related risk factors for adverse events after infrainguinal bypass. J Vasc Surg. 2010 Mar;51(3):622-7. BACKGROUND: Current medical practice urges individual health care facilities and medical professionals to obtain and provide detailed insight in quality of care with the possibility of comparing data between institutions. Adverse event (AE) analysis serves as a mainstay in quality assessment in vascular surgery, but the comparison of AE data between facilities can be complex. The aim of the present study was to assess independent risk factors for AE occurrence: patient, disease and operation characteristics besides general differences between health care facilities. METHODS: All AEs after infrainguinal bypass graft procedures (BGPs) in three health care facilities in the Netherlands were evaluated. AEs were defined identically in the facilities. RESULTS: Of 601 BGPs performed, 662 AEs were registered. Independent predictors of AEs were female gender (odds ratio [OR], 2.13; 95% confidence interval [CI], 1.39-3.26; P < .01), age >or=60 years (OR, 0.57; 95% CI, 0.34-0.95; P = .03), American Society of Anesthesiologists classification 3-4 (OR, 1.79; 95% CI, 1.01-3.17; P = .05), comorbidities of pulmonary disease (OR, 2.99; 95% CI, 1.67-5.34; P < .01) and diabetes mellitus (OR, 2.49; 95% CI, 1.58-3.94; P < .01), distal anastomosis level at below knee femoropopliteal BGP (OR, 2.01; 95% CI, 1.263.22; P < .01), femorotibial BGP (OR, 2.40; 95% CI, 1.37-4.19; P < .01), and popliteopedal BGP (OR, 92.39; 95% CI, 11.13-766.98; P < .01). One health care facility had significantly fewer

Chirurgie

AEs than the other two (OR, 0.21; 95% CI, 0.13-0.35; P < .01). CONCLUSION: Age, gender, comorbidity, and type of surgery are all independent predictors of AE occurrence in vascular surgery. After adjustment for differences in these factors, one health care facility still had lower AE occurrence, which needs to be examined further. PMID: 20206807 [PubMed - indexed for MEDLINE]

Vogelaar FJ, Mesker WE, Rijken AM, van Pelt GW, van Leeuwen AM, Tanke HJ, Tollenaar RA, Liefers GJ. Clinical impact of different detection methods for disseminated tumor cells in bone marrow of patients undergoing surgical resection of colorectal liver metastases: a prospective follow-up study. BMC Cancer. 2010 Apr 20;10:153. BACKGROUND: Large number of patients with colorectal liver metastasis show recurrent disease after curative surgical resection. Identification of these high-risk patients may guide therapeutic strategies. The aim of this study was to evaluate whether the presence of disseminated tumor cells in bone marrow from patients undergoing surgical resection of colorectal liver metastases can predict clinical outcome. METHODS: Sixty patients with colorectal

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liver metastases were planned for a curative resection between 2001 and 2007. All patients underwent bone marrow aspiration before surgery. Detection of tumor cells was performed using immunocytochemical staining for cytokeratin (CK-ICC) combined with automated microscopy or indirectly using reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: Disseminated tumor cells were found in 15 of the 46 patients (33%) using CK-ICC and in 9 of 44 of the patients (20%) using RT-PCR. Patients with negative results for RT-PCR had a significant better disease-free survival after resection of their liver metastases (p = 0.02). This group also showed significant better overall survival (p = 0.002). CK-ICC did not predict a worse clinical outcome. CONCLUSIONS: The presence of disseminated tumor cells in bone marrow detected using RT-PCR did predict a worse clinical outcome. The presence of cells detected with CK-ICC did not correlate with poor prognosis. PMID: 20406480 [PubMed - indexed for MEDLINE] PMCID: PMC2876078

Gisbertz SS, Tutein Nolthenius RP, de Borst GJ, van der Laan L, Overtoom TT, Moll FL, de Vries JP. Remote endarterectomy versus supragenicular bypass surgery for long occlusions of the superficial femoral artery: medium-term results of a randomized controlled trial (the REVAS trial). Ann Vasc Surg. 2010 Nov;24(8):1015-23. BACKGROUND: To investigate the optimal surgical treatment, remote superficial femoral artery endarterectomy (RSFAE) or supragenicular bypass, for Transatlantic Inter-Society Consensus (TASC) C and D lesions of the superficial femoral artery. Medium-term results will be presented. METHODS: The study randomized 116 patients, 61 to RSFAE and 55 to supragenicular bypass


surgery. Indications for surgery were claudication in 77, rest pain in 21, or tissue loss in 18. RESULTS: Primary patency after 3 years of follow-up was 47% for RSFAE and 60% for bypass (p = 0.107), assisted primary patency was 63 and 69% (p = 0.406), and secondary patency was 69 and 73% (p = 0.541), respectively. For venous (n = 25) and prosthetic grafts (n = 30) at 3-year follow-up, primary patency was 65% and 56 versus 47% for RSFAE (p = 0.143), assisted primary patency was 84% and 56 versus 63% for RSFAE (p = 0.052), and secondary patency was 89% and 59 versus 69% for RSFAE (p = 0.046), respectively. Limb salvage was 97% after RSFAE and 95% after bypass surgery (p = 0.564). CONCLUSION: RSFAE is a minimally invasive option for surgical repair of TASC C and D superficial femoral artery obstructions, with assisted primary and secondary patency rates comparable with bypass surgery. Venous bypass grafting is superior to both RSFAE and polytetrafluoroethylene grafting, but only 45% of patients had a sufficient saphenous vein available. If the saphenous vein is not applicable, RSFAE should be considered because it is less invasive and prosthetic graft material can be avoided. Copyright © 2010 Annals of Vascular Surgery Inc. Published by Elsevier Inc. All rights reserved. PMID: 21035693 [PubMed - in process]

Te Slaa A, Mulder P, Dolmans D, Castenmiller P, Ho G, van der Laan L. Reliability and reproducibility of a clinical application of a simple technique for repeated circumferential leg measurements. Phlebology. 2011;26:14-9. Epub 2010 Sep 29. OBJECTIVE: The aim of this study is to determine the reliability and reproducibility of repeated tape measurements to assess the leg circumference during a long period. METHODS: A tape measure is a simple instrument that is applicable in the presence of oedema. Measurements were performed by four observers on 11 volunteers. Four measurements were done in the first week (short term), a fifth measurement at two weeks (medium term) and a sixth measurement was done at 12 weeks (long term). RESULTS: The short-, medium- and long-term intra-class correlation coefficients for repeated measurements were 0.90, 0.89 and 0.78, respectively. The short-term and long-term reproducibility indices equalled 4.4% and 6.5%. If only a single observer would be involved, the short-term intra-class correlation coefficients would improve to 0.94 (reproducibility index 3.3%). CONCLUSION: Tape measurements have been proved to be a reliable and reproducible method to asses the lower limb circumference. PMID: 20881309 [PubMed - as supplied by publisher]

Perez RS, Zollinger PE, Dijkstra PU, Thomassen-Hilgersom IL, Zuurmond WW, Rosenbrand KC, Geertzen JH; CRPS I task force. [van der Laan L et al...] Evidence based guidelines for complex regional pain syndrome type 1. BMC Neurol. 2010 Mar 31;10:20. BACKGROUND: Treatment of complex regional pain syndrome type I (CRPS-I) is subject to discussion. The purpose of this study was to develop multidisciplinary guidelines for

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treatment of CRPS-I. METHOD: A multidisciplinary task force graded literature evaluating treatment effects for CRPS-I according to their strength of evidence, published between 1980 to June 2005. Treatment recommendations based on the literature findings were formulated and formally approved by all Dutch professional associations involved in CRPS-I treatment. RESULTS: For pain treatment, the WHO analgesic ladder is advised with the exception of strong opioids. For neuropathic pain, anticonvulsants and tricyclic antidepressants may be considered. For inflammatory symptoms, free-radical scavengers (dimethylsulphoxide or acetylcysteine) are advised. To promote peripheral blood flow, vasodilatory medication may be considered. Percutaneous sympathetic blockades may be used to increase blood flow in case vasodilatory medication has insufficient effect. To decrease functional limitations, standardised physiotherapy and occupational therapy are advised. To prevent the occurrence of CRPS-I after wrist fractures, vitamin C is recommended. Adequate perioperative analgesia, limitation of operating time, limited use of tourniquet, and use of regional anaesthetic techniques are recommended for secondary prevention of CRPS-I. CONCLUSIONS: Based on the literature identified and the extent of evidence found for therapeutic interventions for CRPS-I, we conclude that further research is needed into each of the therapeutic modalities discussed in

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the guidelines. *Collaborators: Beems T, van den Brink HR, van Eijs F, Goris RJ, Haagh WA, van Hilten JJ, Huygen FJ, Kemler MA, van Kleef M, van der Laan L, Oerlemans HM, Patijn J, Ruijgrok JM, Slebus FG, Strackee SD, Tibboel D, Theuvenet P, Veldman PJ, van de Ven-Stevens LA, Verhoeven AC, Versteegen GJ, Wemekamp H, Kuis W. PMID: 20356382 [PubMed - indexed for MEDLINE] PMCID: PMC2861029

Te Slaa A, Dolmans DE, Ho GH, Mulder PG, van der Waal JC, de Groot HG, van der Laan L. Evaluation of A-V Impulse technology as a treatment for oedema following polytetrafluoroethylene femoropopliteal surgery in a randomised controlled trial. Eur J Vasc Endovasc Surg. 2010 Jul 26. [Epub ahead of print] OBJECTIVE: To investigate the efficacy of A-V impulse technology (A-V) for oedema prevention and treatment following PTFE femoropopliteal surgery. DESIGN: Prospective randomized clinical trial. MATERIALS: 36 patients undergoing PTFE femoropopliteal bypass reconstructions, either being treated postoperatively with a compression stocking (CS) (Group-1, n = 19) or with A-V (Group-2, n = 17). METHODS: Patients in treatment group-1 used a CS postoperatively during 1 week day and night, patients in group-2 were treated with A-V postoperatively at night during one week. The lower leg circumference was measured preoperatively and at five postoperative time points. RESULTS: Limb circumference has increased postoperatively on day 1 (CS 1.5%/A-V 1.4%), on day 4 (5.7%/6.3%), on day 7 (6.6%/6.1%), on day 14 (7.9%/7.7%) and on day 90 (5.8%/5.2%). Differences between treatment groups were not significant. A re-operation gives a significant 3.9% increase in circumference as compared to a first


operation (95% CI: 1.5-6.4%; p = 0.002). CONCLUSION: No significant differences were found in the extent of developed edema between the groups following PTFE femoropopliteal bypass surgery. A redo peripheral bypass operation results in significantly more postoperative oedema than a first-time performed bypass operation. PMID: 20667751 [PubMed - as supplied by publisher]

Menke V, Castenmiller PH, Versteijlen RJ, Van der Laan L. Stent grafting a ruptured para-anastomotic iliac aneurysm. Vasc Endovascular Surg. 2010 Aug;44(6):479-82. Epub 2010 Jun 10. In this case report, we present an 83-year-old man with a ruptured para-anastomotic aneurysm who underwent a stent graft in spite of his condition of acute shock. Our patient presented at the emergency room (ER) with acute abdominal pain. Shortly after arrival, he collapsed because of a ruptured para-anastomotic aneurysm after the previous aorto-bi-iliac aneurysm repair in 1984. He was charged with a cardiac history that made him unsuitable for surgery. We chose for resuscitation followed by inflation of an aortic balloon that made the patient hemodynamically stable. He then underwent iliac stent grafting and was discharged from the hospital at 22 days after the procedure. The mortality rate of patients with a ruptured para-anastomotic aortic aneurysm arriving at hospital ranges from 32% to 70%. Endovascular stent placement for ruptured iliac aneurysmal arteries can be a safe treatment in selected patients. PMID: 20538732 [PubMed - in process]

Nienhuijs SW, Rutten HJ, Luiten EJ, van Driel OJ, Reemst PH, Lemmens VE, de Hingh IH. Reduction of in-hospital mortality following regionalisation of pancreatic surgery in the south-east of The Netherlands. Eur J Surg Oncol. 2010 Jul;36(7):652-6. Epub 2010 May 26. BACKGROUND: In the late nineties of the former century, surgery for pancreatic and periampullary cancer in the southern part of The Netherlands was performed mainly in lowvolume hospitals (<5 resections/year). Results reported by the Comprehensive Cancer Center South (CCCS) in 2005 revealed the clearly disappointing results of this practice. The former stimulated the regionalisation of pancreatic surgery by 3 collaborating surgical units into one non-academic teaching hospital in the eastern part of the CCCS-region starting from July 2005. METHODS: All of the 76 patients in this regional cohort group in whom a resection of a (peri-) pancreatic tumour was performed with curative intent have been followed up prospectively. The results of surgical morbidity and in-hospital mortality were compared with the results of the CCCS cohort group which were reported previously. RESULTS: Ever since the regionalisation the annual number of patients undergoing resection of a pancreatic tumour increased from 10 to 33, resulting in a total number of 76 patients. Post-operative complications, reoperation rate and in-hospital mortality decreased significantly to 34.2%, 18.4% and 2.6% respectively,

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as compared to 71.9%, 37.8 and 24.4% in the time period before regionalisation (p < 0.01). CONCLUSION: These unique comparative prospective data derived from daily practice in a collaborative surgical region in The Netherlands (CCCS) support the need for centralisation of pancreatic surgery in order to improve standard of care in pancreatic surgery. This can be achieved by collaboration in a large regional hospital. PMID: 20537840 [PubMed - indexed for MEDLINE]

Van Santvoort HC, Besselink MG, Bakker OJ, Hofker HS, Boermeester MA, Dejong CH, van Goor H, Schaapherder AF, van Eijck CH, Bollen TL, van Ramshorst B, Nieuwenhuijs VB, Timmer R, Laméris JS, Kruyt PM, Manusama ER, van der Harst E, van der Schelling GP, Karsten T, Hesselink EJ, van Laarhoven CJ, Rosman C, Bosscha K, de Wit RJ, Houdijk AP, van Leeuwen MS, Buskens E, Gooszen HG; Dutch Pancreatitis Study Group*. A step-up approach or open necrosectomy for necrotizing pancreatitis. N Engl J Med. 2010 Apr 22;362(16):1491-502. BACKGROUND: Necrotizing pancreatitis with infected necrotic tissue is associated with a high

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rate of complications and death. Standard treatment is open necrosectomy. The outcome may be improved by a minimally invasive step-up approach. METHODS: In this multicenter study, we randomly assigned 88 patients with necrotizing pancreatitis and suspected or confirmed infected necrotic tissue to undergo primary open necrosectomy or a step-up approach to treatment. The step-up approach consisted of percutaneous drainage followed, if necessary, by minimally invasive retroperitoneal necrosectomy. The primary end point was a composite of major complications (new-onset multiple-organ failure or multiple systemic complications, perforation of a visceral organ or enterocutaneous fistula, or bleeding) or death. RESULTS: The primary end point occurred in 31 of 45 patients (69%) assigned to open necrosectomy and in 17 of 43 patients (40%) assigned to the step-up approach (risk ratio with the step-up approach, 0.57; 95% confidence interval, 0.38 to 0.87; P=0.006). Of the patients assigned to the stepup approach, 35% were treated with percutaneous drainage only. New-onset multiple-organ failure occurred less often in patients assigned to the step-up approach than in those assigned to open necrosectomy (12% vs. 40%, P=0.002). The rate of death did not differ significantly between groups (19% vs. 16%, P=0.70). Patients assigned to the step-up approach had a lower rate of incisional hernias (7% vs. 24%, P=0.03) and new-onset diabetes (16% vs. 38%, P=0.02). CONCLUSIONS: A minimally invasive step-up approach, as compared with open necrosectomy, reduced the rate of the composite end point of major complications or death among patients with necrotizing pancreatitis and infected necrotic tissue. (Current Controlled Trials number, ISRCTN13975868.) *Collaborators (110).


Comment in: N Engl J Med. 2010 Sep 23;363(13):1286; author reply 1287; N Engl J Med. 2010 Sep 23;363(13):1286-7; author reply 1287; N Engl J Med. 2010 Apr 22;362(16):1535-7; Expert Rev Gastroenterol Hepatol. 2010 Dec;4(6):701-8; Endoscopy. 2011 Jan;43(1):47-53. PMID: 20410514 [PubMed - indexed for MEDLINE]

Franken JM, Veen EJ. Hepatic portal venous gas. J Gastrointestin Liver Dis. 2010 Dec; 19(4):360. PMID: 21188324 [PubMed - indexed for MEDLINE]

Veen EJ, Janssen-Heijnen ML, Bosma E, de Jongh MA, Roukema JA. The accuracy of complications documented in a prospective complication registry. J Surg Res. 2010 Sep 24. [Epub ahead of print] BACKGROUND: The objectives of this study were to evaluate the accuracy of a prospective complication registry for documenting complications and identify possible factors for nonregistering. METHODS: Five hundred randomly selected patients admitted at the Department of Surgery of St. Elisabeth Hospital Tilburg, The Netherlands, in the year 2005, were evaluated for incidence and type of complications by an examination of their medical records and compared with a prospective complication registry. The system was independently reviewed by two persons for missing complications. Patient files with missing complications in the registry were screened for factors possibly responsible for non-registering. RESULTS: Two hundred thirteen complications were detected, 58 (27%) missing in the registry. There were 50 different types of complications documented. The number of events missing per category were: drug-related (50%, n = 4), organ dysfunction (44%, n = 14), infection-related (25%, n = 19), surgery/interventionrelated (23%, n = 14), and hospital-provider errors (19%, n = 7). Not all clinically important complications were adequately documented (e.g., anastomotic leakage). The kappa score was 0.695, making the interrater reliability substantial. CONCLUSION: The accuracy of registering complications is fairly acceptable compared to the ranges mentioned in literature. It is disappointing that clinically important events are missing in the registry. The inaccuracy could be explained by a great diversity of documented events, due to a broad definition, suggesting ignorance of the responsible team of which events to register. Crown Copyright © 2010. Published by Elsevier Inc. All rights reserved. PMID: 20934713 [PubMed - as supplied by publisher]

Veen EJ, Janssen-Heijnen ML, de Jongh MA, Roukema JA. Incidence and type of complications in non-operated patients at a surgical ward. Patient Saf Surg. 2010 Jul 20; 4(1):11.

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BACKGROUND: This study was designed to analyze a group of non-operated patients admitted to our surgical ward for incidence and type of documented complication. We classified and categorised these complications according to the definition of the Association of Surgeons of the Netherlands (ASN). Our main interest was to identify adverse events for non-operated patients that are caused by medical management and thus preventable. METHODS: Complications were prospectively collected in our registry, which is part of an electronic medical patient file, and in retrospective analysed. All non-operated patients admitted to our surgical ward between January 2003 and January 2006 have been analysed for type and incidence of complications. RESULTS: We recorded 437 complications in 364 (8%) of 4602 non-operated patients and we categorised 196 (45%) of these events in the Hospital - Provider group. In this last category 161 (82%) events were related to medical management and appeared to be preventable. Numerous different types of complications were recorded (n = 69) among the 437 events. Of all the complications, 75 (17%) were found to be a negative effect/failure of therapy. CONCLUSION: The incidence of complications in non-operated patients at our surgical ward was 8%, with a great variety in types of events documented. Almost half of all complications (45%) were recorded in the Hospital-Provider category and appeared to be preventable, which needs further

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investigation. PMID: 20646291 [PubMed - in process] PMCID: PMC2918551

Kaas L, Turkenburg JL, van Riet RP, Vroemen JPAM, Eygendaal D. Magnetic resonance imaging findings in 46 elbows with a radial head fracture. Acta Orthopaedica. (2010);18,373-376. BACKGROUND AND PURPOSE: Radial head fractures are common, and may be associated with other injuries of clinical importance. We present the results of a standard additional MRI scan for patients with a radial head fracture. PATIENTS AND METhods: 44 patients (mean age 47 years) with 46 radial head fractures underwent MRI. 17 elbows had a Mason type-I fracture, 23 a Mason type-II fracture, and 6 elbows had a Mason type-III fracture. RESULTS: Associated injuries were found in 35 elbows: 28 elbows had a lateral collateral ligament lesion, 18 had capitellar injury, 1 had a coronoid fracture, and 1 elbow had medial collateral ligament injury. INTERPRETATION: The incidence of associated injuries with radial head fractures found with MRI was high. The clinical relevance should be investigated. PMID: 20450424 [PubMed - indexed for MEDLINE] PMCID: PMC2876842

De Vries EN, Prins HA, Crolla RM, den Outer AJ, van Andel G, van Helden SH, Schlack WS, van Putten MA, Gouma DJ, Dijkgraaf MG, Smorenburg SM, Boermeester MA; SURPASS


Collaborative Group. Effect of a comprehensive surgical safety system on patient outcomes. N Engl J Med. 2010 Nov 11;363(20):1928-37. BACKGROUND: Adverse events in patients who have undergone surgery constitute a large proportion of iatrogenic illnesses. Most surgical safety interventions have focused on the operating room. Since more than half of all surgical errors occur outside the operating room, it is likely that a more substantial improvement in outcomes can be achieved by targeting the entire surgical pathway. METHODS: We examined the effects on patient outcomes of a comprehensive, multidisciplinary surgical safety checklist, including items such as medication, marking of the operative side, and use of postoperative instructions. The checklist was implemented in six hospitals with high standards of care. All complications occurring during admission were documented prospectively. We compared the rate of complications during a baseline period of 3 months with the rate during a 3-month period after implementation of the checklist, while accounting for potential confounders. Similar data were collected from a control group of five hospitals. RESULTS: In a comparison of 3760 patients observed before implementation of the checklist with 3820 patients observed after implementation, the total number of complications per 100 patients decreased from 27.3 (95% confidence interval [CI], 25.9 to 28.7) to 16.7 (95% CI, 15.6 to 17.9), for an absolute risk reduction of 10.6 (95% CI, 8.7 to 12.4). The proportion of patients with one or more complications decreased from 15.4% to 10.6% (P<0.001). In-hospital mortality decreased from 1.5% (95% CI, 1.2 to 2.0) to 0.8% (95% CI, 0.6 to 1.1), for an absolute risk reduction of 0.7 percentage points (95% CI, 0.2 to 1.2). Outcomes did not change in the control hospitals. CONCLUSIONS: Implementation of this comprehensive checklist was associated with a reduction in surgical complications and mortality in hospitals with a high standard of care. (Netherlands Trial Register number, NTR1943.). Comment in: N Engl J Med. 2010 Nov 11;363(20):1963-5. PMID: 21067384 [PubMed - indexed for MEDLINE]

Swank HA, Vermeulen J, Lange JF, Mulder IM, van der Hoeven JA, Stassen LP, Crolla RM, Sosef MN, Nienhuijs SW, Bosker RJ, Boom MJ, Kruyt PM, Swank DJ, Steup WH, de Graaf EJ, Weidema WF, Pierik RE, Prins HA, Stockmann HB, Tollenaar RA, van Wagensveld BA, Coene PP, Slooter GD, Consten EC, van Duijn EB, Gerhards MF, Hoofwijk AG, Karsten TM, Neijenhuis PA, Blanken-Peeters CF, Cense HA, Mannaerts GH, Bruin SC, Eijsbouts QA, Wiezer MJ, Hazebroek EJ, van Geloven AA, Maring JK, D’Hoore AJ, Kartheuser A, Remue C, van Grevenstein HM, Konsten JL, van der Peet DL, Govaert MJ, Engel AF, Reitsma JB, Bemelman WA; Dutch Diverticular Disease (3D) Collaborative Study Group. The ladies trial: laparoscopic peritoneal lavage or resection for purulent peritonitis and Hartmann’s procedure or resection with primary anastomosis for purulent or faecal peritonitis in perforated diverticulitis (NTR2037). BMC Surg. 2010 Oct 18;10:29.

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BACKGROUND: Recently, excellent results are reported on laparoscopic lavage in patients with purulent perforated diverticulitis as an alternative for sigmoidectomy and ostomy.The objective of this study is to determine whether LaparOscopic LAvage and drainage is a safe and effective treatment for patients with purulent peritonitis (LOLA-arm) and to determine the optimal resectional strategy in patients with a purulent or faecal peritonitis (DIVA-arm: perforated DIVerticulitis: sigmoidresection with or without Anastomosis). METHODS/DESIGN: In this multicentre randomised trial all patients with perforated diverticulitis are included. Upon laparoscopy, patients with purulent peritonitis are treated with laparoscopic lavage and drainage, Hartmann’s procedure or sigmoidectomy with primary anastomosis in a ratio of 2:1:1 (LOLA-arm). Patients with faecal peritonitis will be randomised 1:1 between Hartmann’s procedure and resection with primary anastomosis (DIVA-arm). The primary combined endpoint of the LOLA-arm is major morbidity and mortality. A sample size of 132:66:66 patients will be able to detect a difference in the primary endpoint from 25% in resectional groups compared to 10% in the laparoscopic lavage group (two sided alpha = 5%, power = 90%). Endpoint of the DIVA-arm is stoma free survival one year after initial surgery. In this arm 212 patients are needed to significantly demonstrate a difference of 30% (log rank test two sided alpha = 5%

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and power = 90%) in favour of the patients with resection with primary anastomosis. Secondary endpoints for both arms are the number of days alive and outside the hospital, health related quality of life, health care utilisation and associated costs. DISCUSSION: The Ladies trial is a nationwide multicentre randomised trial on perforated diverticulitis that will provide evidence on the merits of laparoscopic lavage and drainage for purulent generalised peritonitis and on the optimal resectional strategy for both purulent and faecal generalised peritonitis. TRIAL REGISTRATION: Nederlands Trial Register NTR2037. PMID: 20955571 [PubMed - indexed for MEDLINE] PMCID: PMC2974662

Van de Wall BJ, Draaisma WA, Consten EC, van der Graaf Y, Otten MH, de Wit GA, van Stel HF, Gerhards MF, Wiezer MJ, Cense HA, Stockmann HB, Leijtens JW, Zimmerman DD, Belgers E, van Wagensveld BA, Sonneveld ED, Prins HA, Coene PP, Karsten TM, Klaase JM, Statius Muller MG, Crolla RM, Broeders IA; Dutch Diverticular Disease (3D) Collaborative Study Group. DIRECT trial. Diverticulitis recurrences or continuing symptoms: Operative versus conservative treatment. A multicenter randomised clinical trial. BMC Surg. 2010 Aug 6;10:25. BACKGROUND: Persisting abdominal complaints are common after an episode of diverticulitis treated conservatively. Furthermore, some patients develop frequent recurrences. These two groups of patients suffer greatly from their disease, as shown by impaired health related quality of life and increased costs due to multiple specialist consultations, pain medication and productivity losses.Both conservative and operative management of patients with persisting


abdominal complaints after an episode of diverticulitis and/or frequently recurring diverticulitis are applied. However, direct comparison by a randomised controlled trial is necessary to determine which is superior in relieving symptoms, optimising health related quality of life, minimising costs and preventing diverticulitis recurrences against acceptable morbidity and mortality associated with surgery or the occurrence of a complicated recurrence after conservative management.We, therefore, constructed a randomised clinical trial comparing these two treatment strategies. METHODS/DESIGN: The DIRECT trial is a multicenter randomised clinical trial. Patients (18-75 years) presenting themselves with persisting abdominal complaints after an episode of diverticulitis and/or three or more recurrences within 2 years will be included and randomised. Patients randomised for conservative treatment are treated according to the current daily practice (antibiotics, analgetics and/or expectant management). Patients randomised for elective resection will undergo an elective resection of the affected colon segment. Preferably, a laparoscopic approach is used.The primary outcome is health related quality of life measured by the Gastro-intestinal Quality of Life Index, Short-Form 36, EQ5D and a visual analogue scale for pain quantification. Secondary endpoints are morbidity, mortality and total costs. The total follow-up will be three years. DISCUSSION: Considering the high incidence and the multicenter design of this study, it may be assumed that the number of patients needed for this study (n = 214), may be gathered within one and a half year.Depending on the expertise and available equipment, we prefer to perform a laparoscopic resection on patients randomised for elective surgery. Should this be impossible, an open technique may be used as this also reflects the current situation. TRIAL REGISTRATION: (Trial register number: NTR1478). PMID: 20691040 [PubMed - indexed for MEDLINE] PMCID: PMC2928179

De Haan J, den Hartog D, Tuinebreijer WE, Iordens GI, Breederveld RS, Bronkhorst MW, Bruijninckx MM, De Vries MR, Dwars BJ, Eygendaal D, Haverlag R, Meylaerts SA, Mulder JW, Ponsen KJ, Roerdink WH, Roukema GR, Schipper IB, Schouten MA, Sintenie JB, Sivro S, Van den Brand JG, Van der Meulen HG, Van Thiel TP, Van Vugt AB, Verleisdonk EJ, Vroemen JP, Waleboer M, Willems WJ, Polinder S, Patka P, van Lieshout EM, Schep NW. Functional treatment versus plaster for simple elbow dislocations (FuncSiE): a randomized trial. BMC Musculoskelet Disord. 2010 Nov 12;11:263. BACKGROUND: Elbow dislocations can be classified as simple or complex. Simple dislocations are characterized by the absence of fractures, while complex dislocations are associated with fractures. After reduction of a simple dislocation, treatment options include immobilization in a static plaster for different periods of time or so-called functional treatment. Functional treatment is characterized by early active motion within the limits of pain with or without the use of a sling or hinged brace. Theoretically, functional treatment should prevent stiffness

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without introducing increased joint instability. The primary aim of this randomized controlled trial is to compare early functional treatment versus plaster immobilization following simple dislocations of the elbow. METHODS/DESIGN: The design of the study will be a multicenter randomized controlled trial of 100 patients who have sustained a simple elbow dislocation. After reduction of the dislocation, patients are randomized between a pressure bandage for 5-7 days and early functional treatment or a plaster in 90 degrees flexion, neutral position for pro-supination for a period of three weeks. In the functional group, treatment is started with early active motion within the limits of pain. Function, pain, and radiographic recovery will be evaluated at regular intervals over the subsequent 12 months. The primary outcome measure is the Quick Disabilities of the Arm, Shoulder, and Hand score. The secondary outcome measures are the Mayo Elbow Performance Index, Oxford elbow score, pain level at both sides, range of motion of the elbow joint at both sides, rate of secondary interventions and complication rates in both groups (secondary dislocation, instability, relaxation), health-related quality of life (Short-Form 36 and EuroQol-5D), radiographic appearance of the elbow joint (degenerative changes and heterotopic ossifications), costs, and cost-effectiveness. DISCUSSION: The successful completion of this trial will provide evidence on the effectiveness of a functional treatment for

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the management of simple elbow dislocations. TRIAL REGISTRATION: The trial is registered at the Netherlands Trial Register (NTR2025). PMID: 21073734 [PubMed - indexed for MEDLINE] PMCID: PMC2994812

Gobardhan PD, Elias SG, Madsen EV, van Wely B, van den Wildenberg F, Theunissen EB, Ernst MF, Kokke MC, van der Pol C, Borel Rinkes IH, Wijsman JH, Bongers V, van Gorp J, van Dalen T. Prognostic value of lymph node micrometastases in breast cancer: a multicenter cohort study. Ann Surg Oncol. 2011 Jun;18(6):1657-64. Epub 2010 Dec 14. BACKGROUND: To evaluate the prognostic meaning of lymph node micrometastases in breast cancer patients. METHODS: Between January 2000 and January 2003, 1411 patients with a cT(1-2)N(0) invasive breast carcinoma underwent surgery in 7 hospitals in the Netherlands. Sentinel lymph node biopsy was done in all patients. Based on lymph node status, patients were divided into 4 groups: (p)N(0) (n = 922), (p)N(1micro) (n = 103), (p)N(1a) (n = 285), and (p)N(=1b) (n = 101). Median follow-up was 6.4 years. RESULTS: At the end of follow-up, 1121 women were still alive (79.4%), 184 had died (13.0%), and 106 were lost to follow-up (7.5%). Breast cancer recurred in 244 patients: distant metastasis (n = 165), locoregional relapse (n = 83), and contralateral breast cancer (n = 44). Following adjustment for possible confounding characteristics and for adjuvant systemic treatment, overall survival (OS) remained comparable for (p)N(0) and (p)N(1micro) and was significantly worse for (p)N(1a) and (p)N(=1b) (hazard ratio [HR] 1.18; 95% confidence interval [95% CI] 0.58-2.39, HR 2.47; 95% CI 1.69-3.63, HR 4.36; 95% CI 2.70-7.04, respectively). Disease-free survival (DFS) was similar too in the (p)


N(0) and (p)N(1micro) group, and worse for (p)N(1a) and (p)N(=1b) (HR 0.96; 95% CI 0.561.67 vs HR 1.64; 95% CI 1.19-2.27, HR 2.95; CI 1.98-4.42). The distant metastases rate also did not differ significantly between the (p)N(0) and (p)N(1micro) group and was worse for (p)N(1a) and (p)N(=1b) (HR 1.22; 95% CI 0.60-2.49, HR 2.26; 95% CI 1.49-3.40, HR 3.49; CI 2.12-5.77). CONCLUSIONS: In breast cancer patients survival is not affected by the presence of micrometastatic lymph node involvement. PMID: 21153885 [PubMed - in process] PMCID: PMC3087878

Geertsema D, Gobardhan PD, Madsen EV, Albregts M, van Gorp J, de Hooge P, van Dalen T. Discordance of intraoperative frozen section analysis with definitive histology of sentinel lymph nodes in breast cancer surgery: complementary axillary lymph node dissection is irrelevant for subsequent systemic therapy. Ann Surg Oncol. 2010: 17(10); 2690-5. BACKGROUND: In breast cancer surgery, intraoperative frozen section (FS) analysis of sentinel lymph nodes (SLNs) enables axillary lymph node dissection (ALND) during the same operative procedure. In case of discordance between a “negative” FS analysis and definitive histology, an ALND as a second operation is advocated since additional lymph node metastases may be present. The clinical implications of the subsequent ALND in these patients were evaluated. MATERIALS AND METHODS: Between November 2000 and May 2008, 879 consecutive breast cancer patients underwent surgery including sentinel lymph node biopsy (SLNB) with intraoperative FS analysis of 2 central cuts from axillary SLNs. Following fixation and serial sectioning, SLNs were further examined postoperatively with hematoxylin and eosin (H&E) and immunohistochemical techniques. For patients with a discordant FS examination, the effect of the pathology findings of the subsequent ALND specimen on subsequent nonsurgical therapy were evaluated. RESULTS: FS analysis detected axillary metastases in the SLN(s) in 200 patients (23%), while the definitive pathology examination detected metastases in SLNs in another 151 patients (17%). A complementary ALND was performed in 108 of the 151 patients with discordant FS. Additional tumor positive axillary lymph nodes were found in 17 patients (16%), leading to “upstaging” in 7 (6%). Subsequent nonsurgical treatment was adjusted in 4 patients (4%): all 4 had more extensive locoregional radiotherapy; no patient received additional hormonal and/or chemotherapy. CONCLUSION: Discordance between intraoperative FS analysis and definitive histology of SLNs is common. In this selection of patients, a substantial proportion had additional lymph node metastases, but postsurgical treatment was rarely adjusted based on the findings of the complementary ALND. PMID: 20422461 [PubMed - indexed for MEDLINE] PMCID: PMC2941713

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Van Santvoort HC, Besselink MG, Bakker OJ, Hofker HS, Boermeester MA, Dejong CH, van Goor H, Schaapherder AF, van Eijck CH, Bollen TL, van Ramshorst B, Nieuwenhuijs VB, Timmer R, Laméris JS, Kruyt PM, Manusama ER, van der Harst E, van der Schelling GP, Karsten T, Hesselink EJ, van Laarhoven CJ, Rosman C, Bosscha K, de Wit RJ, Houdijk AP, van Leeuwen MS, Buskens E, Gooszen HG; Dutch Pancreatitis Study Group*. A step-up approach or open necrosectomy for necrotizing pancreatitis. N Engl J Med. 2010 Apr 22;362(16):1491-502. Talsma K, Veen HF, de Groot HGW, Veen EJ. Chirurgische techniek. Cervicale mediastinoscopie. Ned Tijdschr Heelkd. 2010 november;19(8):298-302. Vogelaar FJ, Mesker WE, Rijken AM, van Pelt GW, van Leeuwen AM, Tanke HJ, Tollenaar RA, Liefers GJ. Clinical impact of different detection methods for disseminated tumor cells in bone marrow of patients undergoing surgical resection of colorectal liver metastases: a prospective follow-up study. BMC Cancer. 2010 Apr 20;10:153. Van de Wall BJ, Draaisma WA, Consten EC, van der Graaf Y, Otten MH, de Wit GA, van Stel HF, Gerhards MF, Wiezer MJ, Cense HA, Stockmann HB, Leijtens JW, Zimmerman DD, Belgers E, van Wagensveld BA, Sonneveld ED, Prins HA, Coene PP, Karsten TM, Klaase JM, Statius Muller MG, Crolla RM, Broeders IA; Dutch Diverticular Disease (3D) Collaborative Study Group. DIRECT trial. Diverticulitis recurrences or continuing symptoms: Operative versus conservative treatment. A multicenter randomised clinical trial. BMC Surg. 2010 Aug 6;10:25. Stolwijk AWM, van Wensen A, van Hooft MAA, Franken JM, Somford MP, van der Laan L, Vos DI. Een vorstperiode van drie weken: analyse van de gevolgen voor een perifeer ziekenhuis en de bruikbaarheid van een triagesysteem. Ned Tijdschr Traumatologie. 2010;18(3):66-73. De Vries EN, Prins HA, Crolla RM, den Outer AJ, van Andel G, van Helden SH, Schlack WS, van Putten MA, Gouma DJ, Dijkgraaf MG, Smorenburg SM, Boermeester MA; SURPASS Collaborative Group. Effect of a comprehensive surgical safety system on patient outcomes. N Engl J Med. 2010 Nov 11;363(20):1928-37. Te Slaa A, Dolmans DE, Ho GH, Mulder PG, van der Waal JC, de Groot HG, van der Laan L. Evaluation of A-V impulse technology as a treatment for oedema following polytetrafluoroethylene femoropopliteal surgery in a randomised controlled trial. Eur J Vasc Endovasc Surg. 2010 Jul 26. [Epub ahead of print] Perez RS, Zollinger PE, Dijkstra PU, Thomassen-Hilgersom IL, Zuurmond WW, Rosenbrand KC, Geertzen JH; CRPS I task force. [van der Laan L et al...] Evidence based guidelines for complex regional pain syndrome type 1. BMC Neurol. 2010 Mar 31;10:20. Flu HC, Lardenoye JH, Veen EJ, Van Berge Henegouwen DP, Hamming JF. Functional status as a prognostic factor for primary revascularization for critical limb ischemia. J Vasc Surg. 2010 Feb;51(2):360-71.e1.


De Haan J, den Hartog D, Tuinebreijer WE, Iordens GI, Breederveld RS, Bronkhorst MW, Bruijninckx MM, De Vries MR, Dwars BJ, Eygendaal D, Haverlag R, Meylaerts SA, Mulder JW, Ponsen KJ, Roerdink WH, Roukema GR, Schipper IB, Schouten MA, Sintenie JB, Sivro S, Van den Brand JG, Van der Meulen HG, Van Thiel TP, Van Vugt AB, Verleisdonk EJ, Vroemen JP, Waleboer M, Willems WJ, Polinder S, Patka P, van Lieshout EM, Schep NW.Functional treatment versus plaster for simple elbow dislocations (FuncSiE): a randomized trial. BMC Musculoskelet Disord. 2010 Nov 12;11:263. Sauren RJ, Haans D, van der Laan L. Hemorrhage after percutaneous transluminal angioplasty localized in the lateral abdominal wall: A rare location. Vasc. Dis. Management. 2010 dec;7(12):E240-4. Franken JM, Veen EJ. Hepatic portal venous gas. J Gastrointestin Liver Dis. 2010 Dec;19(4):360. Heijnen S, Vroemen J, Eygendaal D, Vos D. Hoekstabiele plaatostheosynthese van de proximale humerus fractuur. Ned Tijdschr Traumatol. 2010;6:162-6. De Leur K, Castenmiller PH, van der Laan L. Idiopathic mid-aortic syndrome in a young adult: a case report. Vasc. Dis. Management. 2010 dec;7(12):E245-7. Veen EJ, Janssen-Heijnen ML, de Jongh MA, Roukema JA. Incidence and type of complications in non-operated patients at a surgical ward. Patient Saf Surg. 2010 Jul 20;4(1):11. Somford MP, Reynders D, Rijken AM. Internal herniation in an unusual peritoneal aperture. J Abdom Surg. 2010 Spring:5-6. Kaas L, Turkenburg JL, van Riet RP, Vroemen JPAM, Eygendaal D. Magnetic resonance imaging findings in 46 elbows with a radial head fracture. Acta Orthopaedica, (2010);18,373-376. Flu HC, Ploeg AJ, Marang-van de Mheen PJ, Veen EJ, Lange CP, Breslau PJ, Roukema JA, Hamming JF, Lardenoye JW. Patient and procedure-related risk factors for adverse events after infrainguinal bypass. J Vasc Surg. 2010 Mar;51(3):622-7. Gobardhan PD, Elias SG, Madsen EV, van Wely B, van den Wildenberg F, Theunissen EB, Ernst MF, Kokke MC, van der Pol C, Borel Rinkes IH, Wijsman JH, Bongers V, van Gorp J, van Dalen T. Prognostic value of lymph node micrometastases in breast cancer: a multicenter cohort study. Ann Surg Oncol. 2011 Jun;18(6):1657-64. Epub 2010 Dec 14. Somford MP, Sturm MF, Vroemen JP. Reconstruction of isolated scaphoid dislocation with carpal dissociation, associated with a carpal anomaly. Strategies Trauma Limb Reconstr. 2010;5(2):105-110. Somford MP, Sturm MF, Vroemen JP. Reconstruction of isolated scaphoid dislocation with carpal dissociation, associated with a carpal anomaly. Strategies Trauma Limb Reconstr. 2010;5(2):105-110. Nienhuijs SW, Rutten HJ, Luiten EJ, van Driel OJ, Reemst PH, Lemmens VE, de Hingh IH. Reduction of in-hospital mortality following regionalisation of pancreatic surgery in

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the south-east of The Netherlands. Eur J Surg Oncol. 2010 Jul;36(7):652-6. Epub 2010 May 26. Te Slaa A, Mulder P, Dolmans D, Castenmiller P, Ho G, van der Laan L. Reliability and reproducibility of a clinical application of a simple technique for repeated circumferential leg measurements. Phlebology. 2011;26:14-9. Epub 2010 Sep 29. Gisbertz SS, Tutein Nolthenius RP, de Borst GJ, van der Laan L, Overtoom TT, Moll FL, de Vries JP. Remote endarterectomy versus supragenicular bypass surgery for long occlusions of the superficial femoral artery: medium-term results of a randomized controlled trial (the REVAS trial). Ann Vasc Surg. 2010 Nov;24(8):1015-23. Snel BJ, Somford MP, Veen EJ. Repositie van pertrochantere fractuur bij patiënte met bovenbeenamputatie. Ned Tijdschr Traumatol. 2010;6:19-20. Menke V, Castenmiller PH, Versteijlen RJ, Van der Laan L. Stent grafting a ruptured paraanastomotic iliac aneurysm. Vasc Endovascular Surg. 2010 Aug;44(6):479-82. Epub 2010 Jun 10. Veen EJ, Janssen-Heijnen ML, Bosma E, de Jongh MA, Roukema JA. The accuracy of complications documented in a prospective complication registry. J Surg Res. 2010 Sep 24. [Epub ahead of print] Kaas L, Riet RP, Vroemen JP, Eygendaal D. The epidemiology of radial head fractures: A possible link to osteoporosis? J Shoulder Elbow Surg. 2010 Feb 9. [Epub ahead of print]. Swank HA, Vermeulen J, Lange JF, Mulder IM, van der Hoeven JA, Stassen LP, Crolla RM, Sosef MN, Nienhuijs SW, Bosker RJ, Boom MJ, Kruyt PM, Swank DJ, Steup WH, de Graaf EJ, Weidema WF, Pierik RE, Prins HA, Stockmann HB, Tollenaar RA, van Wagensveld BA, Coene PP, Slooter GD, Consten EC, van Duijn EB, Gerhards MF, Hoofw]ijk AG, Karsten TM, Neijenhuis PA, Blanken-Peeters CF, Cense HA, Mannaerts GH, Bruin SC, Eijsbouts QA, Wiezer MJ, Hazebroek EJ, van Geloven AA, Maring JK, D’Hoore AJ, Kartheuser A, Remue C, van Grevenstein HM, Konsten JL, van der Peet DL, Govaert MJ, Engel AF, Reitsma JB, Bemelman WA; Dutch Diverticular Disease (3D) Collaborative Study Group. The ladies trial: laparoscopic peritoneal lavage or resection for purulent peritonitis and Hartmann’s procedure or resection with primary anastomosis for purulent or faecal peritonitis in perforated diverticulitis (NTR2037). BMC Surg. 2010 Oct 18;10:29. Klompenhouwer EG, Rijken AM, van der Schelling GP. Trocarhernia’s: een zeldzame maar potentieel gevaarlijke complicatie van laparoscopisch chirurgie. Ned Tijdschr Heelkd. 2010 okt;19(7):263-5.


Dermatologie Kerngegevens zorgkern Dermatologie • 8 dermatologen: mw. A. Barentsen-Erceg, mw. dr. A.Y.R.L.J. Bracke, mw. S.J. Caers, W.J.A. de Kort, dr. J.E.M. Körver, mw. dr. D.I.M. Kuijpers, mw. F.J.M.A. van Neer, dr. T.E.C. Nijsten • 2 assistenten niet in opleiding • 1 assistent in opleiding • subspecialismen: flebologie, dermato-oncologie

Samenvattingen gepubliceerde artikelen Erceg A, Greebe RJ, Bovenschen HJ, Seyger MM. A comparative study of pulsed 532-nm potassium titanyl phosphate laser and electrocoagulation in the treatment of spider nevi. Dermatol Surg. 2010 May;36(5):630-5. Epub 2010 Apr 2. OBJECTIVE: To assess the clinical efficacy and safety of potassium titanyl phosphate (KTP) laser treatment and electrocoagulation (EC) for the treatment of spider nevi (SN). METHOD: A randomized single-blind intrapatient comparison study was performed. A blinded observer and patients reported the clinical treatment outcome and pain on a visual analogue scale (0-10). Side effects were noted if present. RESULTS: Mean physician-rated clinical efficacy scores+/standard error of the mean were 7.7+/-0.7 for KTP laser and 6.2+/-0.9 for EC treatment (p=.05). Patient-rated mean clinical efficacy of KTP laser was 8.3+/-0.6 and of EC was 7.3+/-0.7 (p=.09). Stratification for potential confounding bias, such as location of SN, central bulging vein, and diameter (p=.25) of the treated SN did not reveal any statistically significant differences between the treatments. Treatment with KTP or EC did not result in scarring or pigmentary changes. Pain was reported for KTP treatment (3.1+/-0.4) and EC (6.4+/-0.7) (p<.05). CONCLUSION: Clinical efficacy of KTP laser and EC for SN is comparable, although there is a

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tendency toward an advantage in favor of the KTP laser. KTP laser treatment was less painful. Comment in: Dermatol Surg. 2010 May;36(5):636-7. PMID: 20384753 [PubMed - indexed for MEDLINE]

Husson O, Holterhues C, Nijsten T, Van de Poll-Franse LV. Melanoma survivors are dissatisfied with perceived information about their diagnosis, treatment and follow-up care. [letter]. Br J Dermatol. 2010; 163:879-81. PMID: 20854404 [PubMed - indexed for MEDLINE]

Wakkee M, Herings RM, Nijsten T. Psoriasis may not be an independent risk factor for acute ischemic heart disease hospitalizations: Results of a large population-based Dutch cohort. J Invest Dermatol. 2010; 130:962-7. Although psoriasis has been associated with components of the metabolic syndrome, its association with myocardial infarction is less clear. A cohort study was conducted using hospital and pharmacy records of 2.5 million Dutch residents between 1997 and 2008. The risk of

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ischemic heart disease (IHD) hospitalizations was compared between psoriasis patients and a matched reference cohort. Additional adjustments were made for healthcare consumption and use of cardiovascular drugs. A total of 15,820 psoriasis patients and 27,577 reference subjects were included, showing an incidence rate of 611 and 559 IHD per 100,000 person-years, respectively (P=0.066). The age- and gender-adjusted risk of IHD was comparable between both cohorts (hazard ratio (HR)=1.10, 95% confidence interval 0.99-1.23). Before cohort entry, psoriasis patients used more antihypertensive, antidiabetic, and lipid-lowering drugs and were more often hospitalized. Adjusting for these confounders decreased the HR for IHD, but it remained comparable between both populations. There was no different risk of IHD between the subgroup of patients who only used topicals versus those who received systemic therapies or inpatient care for their psoriasis. This study, therefore, suggests that psoriasis is not a clinically relevant risk factor for IHD hospitalizations on the population level. Comment in: J Invest Dermatol. 2010 Apr;130(4):919-22. PMID: 19812600 [PubMed - indexed for MEDLINE]

Mols F, Holterhues C, Nijsten T, van de Poll-Franse LV. Personality is associated with health status and impact of cancer among melanoma survivors. Eur J Cancer. 2010 Feb;46(3):573-80. Epub 2009 Oct 8. OBJECTIVE: We aimed to investigate the prevalence of Type D personality (the conjoint effects of negative affectivity and social inhibition) among melanoma survivors and to obtain insight into its effects on health status, impact of cancer and health care utilisation. METHODS: We selected all patients diagnosed with melanoma between 1998 and 2007 from three large


regional hospitals in the Netherlands. In total, 699 survivors, alive in January 2008, received a questionnaire including Type D personality scale (DS14), impact of cancer questionnaire (IOC) and SF-36 and 80% responded (n=562). RESULTS: Twenty-two percent of survivors (n=125) were classified as Type D. They reported a clinically and statistically significant worse general health (57.8 versus 75.6), social functioning (73.1 versus 88.7), mental health (61.7 versus 80.6), more emotional role limitations (67.8 versus 89.4) and less vitality (54.5 versus 72.8) than non-Type D patients. Additionally, they reported a statistically and clinically relevant higher impact of cancer on body changes, negative self-evaluation, negative outlook on life, life interferences and health worry. Furthermore, they were more worried about the influence of the sun on their skin and acted accordingly. No differences were found in health care utilisation. CONCLUSIONS: Type D personality has a distinct negative impact on health status in melanoma survivors and is an important factor to screen for in clinical practice. Giving special attention to these patients is important while they are more likely to experience a strong impact of cancer which cannot be explained by socio-demographical or clinical characteristics. Copyright (c) 2009 Elsevier Ltd. All rights reserved. PMID: 19819126 [PubMed - indexed for MEDLINE]

67 Spuls PI, Lecluse LL, Poulsen ML, Bos JD, Stern RS, Nijsten T. How good are clinical severity and outcome measures for psoriasis?: quantitative evaluation in a systematic review. J Invest Dermatol. 2010 Apr;130(4):933-43. Epub 2009 Dec 31. A large number of clinical measures of psoriasis are used in clinical trials and daily practice. These measures lack uniformity and validation. However, valid outcome and severity measures for psoriasis are a prerequisite for fully informative clinical research and evidence-based medicine. The purpose of this study was to identify all clinical measures of psoriasis severity and outcome in use and to evaluate the quality of these measures using clinimetric criteria; we identified 53 separate clinical measures, which were regrouped into 11 measures for quality analysis. No measure could be scored on all items used in the clinimetric analysis. The Lattice System Physician’s Global Assessment and Physician’s Global Assessment were most highly noted. We conclude that none of the psoriasis measures is adequately validated. The Psoriasis Area and Severity Index is the most commonly used clinical measure in research, but it has substantial limitations such as low response distribution, no consensus on interpretability, and low responsiveness in mild disease. Nevertheless, because of its widespread use the Psoriasis Area and Severity Index permits some degree of comparison of results among clinical trials. Overall, no best instrument was identified, and different situations may call for different measures. Comment in: Arch Dermatol. 2011 Jan;147(1):95-8. PMID: 20043014 [PubMed - indexed for MEDLINE]

Dermatologie

De Haas ER, Nijsten T, de Vries E. Population education in preventing skin cancer: from childhood to adulthood. J Drugs Dermatol. 2010 Feb;9(2):112-6. Skin cancer is the most commonly diagnosed cancer in populations of predominantly Caucasian origins. As the main cause of skin cancer is excessive sun exposure among a sun-sensitive population, most skin cancers are theoretically avoidable, and prevention is an important topic for public health purposes. The development of skin cancer may be limited by effective primary prevention campaigns, causing people to protect themselves from the sun. In order to be effective, the right people need to become aware of the risks and benefits; they also need to be convinced that they can take effective protective measures. Secondary skin cancer prevention aims to avoid skin cancer morbidity and mortality and is, therefore, mainly aimed at early detection of cutaneous melanomas. Around the world, elderly men are the worst off in terms of melanoma mortality statistics and would be an important target group for secondary prevention. Several prevention initiatives have been developed, including awareness campaigns and voluntary skin cancer screening days. So far, few of these initiatives have proven to be successful in changing population behavior and/or skin cancer related mortality. Most of these

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initiatives appealed more to (young) women rather than the elderly males who would benefit most. In this review, various aspects of primary and secondary skin cancer prevention are discussed, including the results of some of the primary and secondary prevention initiatives. PMID: 20214171 [PubMed - indexed for MEDLINE]

Joosse A, De Vries E, van Eijck CH, Eggermont AM, Nijsten T, Coebergh JW. Reactive oxygen species and melanoma: an explanation for gender differences in survival? Pigment Cell Melanoma Res. 2010 Jun;23(3):352-64. Epub 2010 Mar 10. Epidemiological research consistently shows a female advantage in melanoma survival. So far, no definite candidate for the explanation of this phenomenon has emerged. We propose that gender differences in oxidative stress caused by radical oxygen species (ROS) underlie these survival differences. It is known that males express lower amounts of anti-oxidant enzymes, resulting in more oxidative stress than females. The primary melanoma environment is characterized by high ROS levels, from exogenous sources as well as ROS production within melanoma cells themselves. ROS are known to be able to promote metastasis through a wide variety of mechanisms. We hypothesize that the higher levels of ROS in men enhance selection of ROS-resistance in melanoma cells. Subsequently, ROS can stimulate the metastatic potential of melanoma cells. In addition, due to the lower anti-oxidant defenses in men, ROS produced by melanoma cells cause more damage to healthy tissues surrounding the tumor, further stimulating metastasis. Therefore, ROS may explain the observed differences between males and females in melanoma survival. PMID: 20218981 [PubMed - indexed for MEDLINE]


Koomen ER, de Vries E, van Kempen LC, van Akkooi AC, Guchelaar HJ, Louwman MW, Nijsten T, Coebergh JW. Epidemiology of extracutaneous melanoma in the Netherlands. Cancer Epidemiol Biomarkers Prev. 2010 Jun;19(6):1453-9. Epub 2010 May 25. BACKGROUND: Reliable population-based incidence and survival data on extracutaneous melanoma (ECM) are sparse. METHODS: Incidence data (1989-2006) from the Netherlands Cancer Registry were combined with vital status on January 1, 2008. Age-adjusted annual incidence rates were calculated by direct standardization, and the estimated annual percentage change was estimated to detect changing trends in incidence. Additionally, we carried out cohort-based relative survival analysis. RESULTS: Ocular melanomas were the most common ECM subsite with European standardized incidence rates (ESR) of 10.7 and 8.2 per 1,000,000 person-years for males and females, respectively. In comparison, for cutaneous melanoma (CM), the ESRs for men and women were 122 and 155 per million person-years, respectively. No statistically significant trends in the incidence of ECM were detected, whereas an annual increase of 4.4% for men and 3.6% for women was detected in the incidence of CM. Relative survival for ECM was poor, but differed largely between anatomic subtypes ranging from a 5-year relative survival of 74% for ocular melanomas to 15% for certain subsites of mucosal melanomas. CONCLUSIONS: Of all ECM subsites, ocular melanomas had the highest incidence and the best survival. Mucosal melanomas were the second most frequent subsite of ECM. Five-year relative survival for all ECM subtypes was worse if compared with CM. No statistically significant trends in the incidence of (subsites of) ECM were determined. IMPACT: This study gives insight into the relative sizes of the different subgroups of ECM as well as an estimate of 5-year survival, which varies substantially by subsite. Copyright 2010 AACR. PMID: 20501769 [PubMed - indexed for MEDLINE]

Holterhues C, Vries E, Louwman MW, Koljenovic S, Nijsten T. Incidence and trends of cutaneous malignancies in the Netherlands, 1989-2005. J Invest Dermatol. 2010 Jul;130(7):1807-12. Epub 2010 Mar 25. Epidemiology of rare cutaneous malignancies in the general population is poorly documented. This descriptive study aimed to estimate the incidence and trends of all skin malignancies between 1989 and 2005. Data on skin tumors were extracted from the Netherlands Cancer registry (except for basal cell carcinoma (BCC) data-only available from Comprehensive Cancer Centre South) and categorized according to the International Classification of Diseases for Oncology, third edition, codes. Age-standardized incidence rates (European standardized population rate, ESR) per 100,000 person-years were calculated per year and for the period between 2001 and 2005. Estimated annual percentage changes (EAPCs) were estimated by Poisson regression models. A total of 356,620 skin tumors were diagnosed between 1989 and 2005. Excluding BCC, squamous cell carcinoma (SCC), and melanoma, the remaining skin tumors

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constituted about 2% of all skin malignancies. The incidence of melanoma showed the steepest increase (EAPC, 4.0%), and ESR was close to that observed for SCC (EAPC, 2.3%) between 2001 and 2005 (17.1 versus 19.6). Hematolymphoid tumors (ESR=0.74) were mainly cutaneous T-cell lymphomas (60.8%). No significant increases in incidence were observed for lymphomas, and appendageal, fibromatous, and myomatous carcinomas during 1989-2005. In addition to keratinocytic cancers and melanoma, there is a wide variety of skin tumors that constitute <2% of all skin malignancies. The incidence of UV-related skin tumors increased significantly and more steeply than did those of other skin malignancies. PMID: 20336085 [PubMed - indexed for MEDLINE]

Van der Geld CW, van den Bos RR, van Ruijven PW, Nijsten T, Neumann HA, van Gemert MJ. The heat-pipe resembling action of boiling bubbles in endovenous laser ablation. Lasers Med Sci. 2010 Nov;25(6):907-9. Epub 2010 Jul 20. Endovenous laser ablation (EVLA) produces boiling bubbles emerging from pores within the hot fiber tip and traveling over a distal length of about 20 mm before condensing. This

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evaporation-condensation mechanism makes the vein act like a heat pipe, where very efficient heat transport maintains a constant temperature, the saturation temperature of 100 degrees C, over the volume where these non-condensing bubbles exist. During EVLA the above-mentioned observations indicate that a venous cylindrical volume with a length of about 20 mm is kept at 100 degrees C. Pullback velocities of a few mm/s then cause at least the upper part of the treated vein wall to remain close to 100 degrees C for a time sufficient to cause irreversible injury. In conclusion, we propose that the mechanism of action of boiling bubbles during EVLA is an efficient heat-pipe resembling way of heating of the vein wall. PMID: 20644976 [PubMed indexed for MEDLINE] PMCID: PMC2935543

Biemans AA, Van Den Bos RR, Nijsten T. Endovenous therapies of varicose veins: indications, procedures, efficacy and safety. G Ital Dermatol Venereol. 2010 Apr;145(2): 161-73. Venous insufficiency of the lower-extremity is common and the prevalence increases with age. Chronic venous insufficiency has a high impact on patients’ health related quality of life (HRQOL) and is associated with considerable health care costs. In addition to classical symptoms, it may result in skin changes and venous ulcers. Since more than hundred years, surgical ligation of the junction with or without stripping has been the standard of care in the treatment of insufficient great and small saphenous veins. However, the recurrence rates are relatively high and surgery may be associated with serious adverse events, considerable down time and is cosmetically suboptimal. In the last decade several minimally invasive techniques


have been introduced, to improve efficacy, patients’ HRQOL and treatment satisfaction, and to reduce serious side effects, costs and postoperative pain. Dermatologists have played an important role in the development of minimal invasive therapies Ultrasound guided foam sclerotherapy, endovenous laser therapy and radiofrequency ablation are the most commonly used therapies, and challenge surgery as the gold standard of care in patients with varicose veins. The objective of this review is to inform clinicians about these three therapeutic options for saphenous varicose veins and to describe and compare the indications, procedures, efficacy and safety profile. PMID: 20467390 [PubMed - indexed for MEDLINE]

Nijsten T, Bergstresser PR. Patient advocacy groups: let’s stick together. J Invest Dermatol. 2010 Jul;130(7):1757-9. PMID: 20548309 [PubMed - indexed for MEDLINE]

Ruiter R, Visser LE, Eijgelsheim M, Rodenburg EM, Hofman A, Coebergh JW, Nijsten T, Stricker BH. High-ceiling diuretics are associated with an increased risk of basal cell carcinoma in a population-based follow-up study. Eur J Cancer. 2010;46:2467-72. Copyright 2010. Published by Elsevier Ltd. PMID: 20605443 [PubMed - indexed for MEDLINE]

Flohil SC, de Vries E, van Meurs JB, Fang Y, Stricker BH, Uitterlinden AG, Nijsten T. Vitamin D-binding protein polymorphisms are not associated with development of (multiple) basal cell carcinomas. Exp Dermatol. 2010 Dec;19(12):1103-5. Epub 2010 Aug 31. Vitamin D-binding protein (VDBP) single nucleotide polymorphisms (SNP) may affect skin carcinogenesis. The objective was to test the association between two functional VDBP SNPs and the susceptibility to (multiple) basal cell carcinomas (BCCs). Of the 7983 participants, 5790 (72.5%) and 5823 (72.9%) participants were genotyped for rs7041 and rs4588, respectively, and three haplotypes (Gc1s, Gc2 and Gc1f) were analysed. Two hundred and thirty-three persons developed a BCC of whom 122 (52.4%) developed multiple BCCs during a mean follow-up of 11.6 years. The VDBP genotype was not associated with (multiple) BCC development using Cox proportional hazards and Andersen-Gill analyses, respectively. Stratifying age groups demonstrated that in the youngest age-group, the A/T variant of rs7041 was associated with BCC development [adjusted hazard ratio (HR) = 1.88 (95%CI 1.10-3.20)], while homozygote Gc1s carriers had a significantly lower BCC risk [adjusted HR = 0.53 (95%CI 0.31-0.91)]. In conclusion, the VDBP polymorphisms were not associated with susceptibility to (multiple) BCCs, but age-gene interactions were observed. © 2010 John Wiley & Sons A/S. PMID: 20812960 [PubMed - indexed for MEDLINE]

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Kiiski V, de Vries E, Flohil SC, Bijl MJ, Hofman A, Stricker BH, Nijsten T. Risk factors for single and multiple basal cell carcinomas. Arch Dermatol. 2010 Aug;146(8):848-55. OBJECTIVE: To investigate the incidence of single and multiple basal cell carcinoma (BCC) lesions and associated risk factors. DESIGN: A prospective, population-based cohort study (from January 1, 1990, through December 31, 2007). SETTING: Two cohorts of 10 994 Dutch people, 55 years or older, were studied in 1990 (first cohort) and 1999 (second cohort). PATIENTS: Patients with BCC lesions were identified from the Dutch national pathology laboratories network, hospitals, and general practices. MAIN OUTCOME MEASURES: The associations between determinants and single and multiple BCC lesions were studied by estimating odds ratios (ORs) and hazards ratios, using multivariate logistic regression and Andersen-Gill models, respectively. RESULTS: Of the eligible 10 820 cohort members, 524 (4.8%) had BCC, of whom 361 had single and 163 (31.1%) had multiple lesions. Age and red hair were significant risk factors for a first BCC lesion in a multivariate model. In the Andersen-Gill model, people who developed a first BCC lesion after 75.0 years of age were significantly less likely to develop multiple lesions (> or =75.0 years adjusted OR, 0.58; 95% confidence interval [CI], 0.47-0.71). Red hair (adjusted OR, 1.43; 95% CI,

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1.05-1.94), high educational level (1.42; 1.12-1.81), and a first BCC lesion located on the upper extremities (1.49; 1.02-2.15) were associated with a significantly increased risk of developing multiple lesions. CONCLUSION: Patients who are relatively young at their first BCC diagnosis, those with red hair, those with higher socioeconomic status, and/or those with a BCC lesion on their upper extremities have a higher risk of developing multiple lesions and require closer follow-up over time. PMID: 20713815 [PubMed - indexed for MEDLINE]

Complete publicatielijst Erceg A, Greebe RJ, Bovenschen HJ, Seyger MM. A comparative study of pulsed 532-nm potassium titanyl phosphate laser and electrocoagulation in the treatment of spider nevi. Dermatol Surg. 2010 May;36(5):630-5. Epub 2010 Apr 2. Biemans AA, Van Den Bos RR, Nijsten T. Endovenous therapies of varicose veins: indications, procedures, efficacy and safety. G Ital Dermatol Venereol. 2010 Apr;145(2):161-73. Koomen ER, de Vries E, van Kempen LC, van Akkooi AC, Guchelaar HJ, Louwman MW, Nijsten T, Coebergh JW. Epidemiology of extracutaneous melanoma in the Netherlands. Cancer Epidemiol Biomarkers Prev. 2010 Jun;19(6):1453-9. Epub 2010 May 25. Ruiter R, Visser LE, Eijgelsheim M, Rodenburg EM, Hofman A, Coebergh JW, Nijsten T, Stricker BH. High-ceiling diuretics are associated with an increased risk of basal cell carcinoma in a population-based follow-up study. Eur J Cancer. 2010;46:2467-72.


Spuls PI, Lecluse LL, Poulsen ML, Bos JD, Stern RS, Nijsten T. How good are clinical severity and outcome measures for psoriasis?: quantitative evaluation in a systematic review. J Invest Dermatol. 2010 Apr;130(4):933-43. Epub 2009 Dec 31. Holterhues C, Vries E, Louwman MW, Koljenovic S, Nijsten T. Incidence and trends of cutaneous malignancies in the Netherlands, 1989-2005. J Invest Dermatol. 2010 Jul;130(7):1807-12. Epub 2010 Mar 25. Husson O, Holterhues C, Nijsten T, Van de Poll-Franse LV. Melanoma survivors are dissatisfied with perceived information about their diagnosis, treatment and follow-up care. [letter]. Br J Dermatol. 2010; 163:879-81. Nijsten T, Bergstresser PR. Patient advocacy groups: let’s stick together. J Invest Dermatol. 2010 Jul;130(7):1757-9. Mols F, Holterhues C, Nijsten T, van de Poll-Franse LV. Personality is associated with health status and impact of cancer among melanoma survivors. Eur J Cancer. 2010 Feb;46(3):573-80. Epub 2009 Oct 8. De Haas ER, Nijsten T, de Vries E. Population education in preventing skin cancer: from childhood to adulthood. J Drugs Dermatol. 2010 Feb;9(2):112-6. Wakkee M, Herings RM, Nijsten T. Psoriasis may not be an independent risk factor for acute ischemic heart disease hospitalizations: results of a large population-based Dutch cohort. J Invest Dermatol. 2010; 130:962-7. Joosse A, De Vries E, van Eijck CH, Eggermont AM, Nijsten T, Coebergh JW. Reactive oxygen species and melanoma: an explanation for gender differences in survival? Pigment Cell Melanoma Res. 2010 Jun;23(3):352-64. Epub 2010 Mar 10. Kiiski V, de Vries E, Flohil SC, Bijl MJ, Hofman A, Stricker BH, Nijsten T. Risk factors for single and multiple basal cell carcinomas. Arch Dermatol. 2010 Aug;146(8):848-55. Van der Geld CW, van den Bos RR, van Ruijven PW, Nijsten T, Neumann HA, van Gemert MJ. The heat-pipe resembling action of boiling bubbles in endovenous laser ablation. Lasers Med Sci. 2010 Nov;25(6):907-9. Epub 2010 Jul 20. Flohil SC, de Vries E, van Meurs JB, Fang Y, Stricker BH, Uitterlinden AG, Nijsten T. Vitamin D-binding protein polymorphisms are not associated with development of (multiple) basal cell carcinomas. Exp Dermatol. 2010 Dec;19(12):1103-5. Epub 2010 Aug 31.

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Gynaecologie Kerngegevens zorgkern Gynaecologie • 17 gynaecologen: J. van Bavel, L.W.A.R. Berger, dr. P.F.J. van Bommel, mw. M.G.K. Dijksterhuis, dr. H.W.H. Feijen, dr. D.A. Gietelink, dr. D.J. Hendriks, dr. R. Heydanus, mw. J.C.M. Jeurgens-Borst, G.J.A. Knol, mw. A.L.M. Kok, mw. dr. M.S. Lunshof, dr. D.N.M. Papatsonis, mw. M.F.M. Shekary-Moonen, mw. D.J.C. Smalbraak, mw. M.C.S. Vermeer, dr. H.J. Vonsée • 6 assistenten niet in opleiding • 3 assistenten in opleiding • 1 baios • 2 fertiliteitsartsen • subspecialismen: algemene gynaecologie, prenatale diagnostiek, fertiliteit, bekkenbodem, oncologie, psychosomatiek, zwangerschap en verloskunde

Samenvattingen gepubliceerde artikelen Wessels MW, Kuchinka B, Heydanus R, Smit BJ, Dooijes D, de Krijger RR, Lequin MH, de Jong EM, Husen M, Willems PJ, Casey B. Polyalanine expansion in the ZIC3 gene leading to X-linked heterotaxy with VACTERL association, a new polyalanine disorder? J Med Genet. 2010 May;47(5):351-5. BACKGROUND: The VACTERL association is a non-random association of congenital defects with an unknown aetiology in the majority of patients. METHODS: A male newborn is reported with features of the VACTERL association, including anal atresia, laryngeal and oesophageal atresia with tracheo-oesophageal fistula, dextroposition of the heart with persistent left superior vena cava, and unilateral multicystic kidney. As the clinical picture of this patient overlaps with that of X-linked heterotaxy caused by ZIC3 mutations, the ZIC3 coding region was sequenced. RESULTS: In a patient with the VACTERL association a 6-nucleotide insertion

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was found in the GCC repeat of the ZIC3 gene, which is predicted to expand the amino-terminal polyalanine repeat from 10 to 12 polyalanines. The polyalanine expansion is a novel ZIC3 mutation which was not found in 336 chromosomes from 192 ethnically matched controls. The mutation was also not present in the mother, suggesting it occurred de novo in the patient and is therefore a pathogenetic mutation. CONCLUSION: It is hypothesized that this novel and de novo polyalanine expansion in ZIC3 contributes to the VACTERL association in this patient. A newborn male is described with features of the VACTERL association, including anal atresia, laryngeal and oesophageal atresia with tracheo-oesophageal fistula, dextroposition of the heart with persistent left superior vena cava, and unilateral multicystic kidney. As the clinical picture of the VACTERL association overlaps with X-linked heterotaxy caused by ZIC3 mutations, the ZIC3 coding region was sequenced, and a 6-nucleotide insertion was found that is predicted to expand the amino-terminal polyalanine repeat from 10 to 12 polyalanines. This novel mutation was not present in the mother, nor in 336 chromosomes from 192 ethnically matched controls. It is hypothesised that this novel and de novo polyalanine expansion in the ZIC3 gene contributes to the VACTERL association in this patient. PMID: 20452998 [PubMed - indexed for MEDLINE]

76 De Boer TA, Gietelink DA, Hendriks JC, Vierhout ME. Factors influencing success of pelvic organ prolapse repair using porcine dermal implant Pelvicol®. Eur J Obstet Gynecol Reprod Biol. 2010 Mar;149(1):112-6. Epub 2009 Dec 31. OBJECTIVE: To evaluate factors influencing pelvic organ prolapse (POP) recurrence after repair surgery with a porcine dermal collagen implant (Pelvicol®) STUDY DESIGN: From December 2003 to August 2005, 78 patients with mainly stage 3 pelvic organ prolapse by the Pelvic Organ Prolapse Quantification (POP-Q) system underwent vaginal repair using porcine dermal implant. Assessments were made preoperatively and at 6 weeks and one year follow-up. These included physical examination with POP-Q, Incontinence Impact Questionnaire, Urogenital Distress Inventory and the Defaecatory Distress Inventory and questions from the Patient Global Impression of Improvement. Data were recorded on changes in functional status, mesh erosion and adverse events. Procedural success was defined as POP-Q stage 0/1. RESULTS: 71 patients returned for one year follow-up. The overall cure rate was 74.6%. The chance of a successful operation in the younger group was significantly higher than in the older group (OR: 7.5; 95% CI 1.38, 40.69), but this effect is lower and no longer significant after adjusting for compartment (post, anterior, post+anterior) (adjusted OR: 5.5; 95% CI 0.92, 32.6). CONCLUSIONS: A low complication rate and satisfactory overall results were observed in a group of women after POP repair surgery with Pelvicol®. Whether these results are better or worse than with conventional surgery or non-resorbable mesh implantation is unclear and can only be determined in a randomized controlled trial. There was a strong tendency


towards better results in the younger women than in the older women, but the reason for this phenomenon is unclear. Copyright © 2009 Elsevier Ireland Ltd. All rights reserved. PMID: 20045242 [PubMed - as supplied by publisher]

Bakker JJ, Verhoeven CJ, Janssen PF, van Lith JM, van Oudgaarden ED, Bloemenkamp KW, Papatsonis DN, Mol BW, van der Post JA. Outcomes after internal versus external tocodynamometry for monitoring labor. N Engl J Med. 2010 Jan 28;362(4):306-13. BACKGROUND: It has been hypothesized that internal tocodynamometry, as compared with external monitoring, may provide a more accurate assessment of contractions and thus improve the ability to adjust the dose of oxytocin effectively, resulting in fewer operative deliveries and less fetal distress. However, few data are available to test this hypothesis. METHODS: We performed a randomized, controlled trial in six hospitals in The Netherlands to compare internal tocodynamometry with external monitoring of uterine activity in women for whom induced or augmented labor was required. The primary outcome was the rate of operative deliveries, including both cesarean sections and instrumented vaginal deliveries. Secondary outcomes included the use of antibiotics during labor, time from randomization to delivery, and adverse neonatal outcomes (defined as any of the following: an Apgar score at 5 minutes of less than 7, umbilical-artery pH of less than 7.05, and neonatal hospital stay of longer than 48 hours). RESULTS: We randomly assigned 1456 women to either internal tocodynamometry (734) or external monitoring (722). The operative-delivery rate was 31.3% in the internaltocodynamometry group and 29.6% in the external-monitoring group (relative risk with internal monitoring, 1.1; 95% confidence interval [CI], 0.91 to 1.2). Secondary outcomes did not differ significantly between the two groups. The rate of adverse neonatal outcomes was 14.3% with internal monitoring and 15.0% with external monitoring (relative risk, 0.95; 95% CI, 0.74 to 1.2). No serious adverse events associated with use of the intrauterine pressure catheter were reported. CONCLUSIONS: Internal tocodynamometry during induced or augmented labor, as compared with external monitoring, did not significantly reduce the rate of operative deliveries or of adverse neonatal outcomes. (Current Controlled Trials number, ISRCTN13667534; Netherlands Trial number, NTR285.) 2010 Massachusetts Medical Society. PMID: 20107216 [PubMed - indexed for MEDLINE]

Wessels MW, Kuchinka B, Heydanus R, Smit BJ, Dooijes D, de Krijger RR, Lequin MH, de Jong EM, Husen M, Willems PJ, Casey B. Polyalanine expansion in the ZIC3 gene leading to X-linked heterotaxy with VACTERL association: a new polyalanine disorder? J Med Genet. 2010 May;47(5):351-5.

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BACKGROUND: The VACTERL association is a non-random association of congenital defects with an unknown aetiology in the majority of patients. METHODS: A male newborn is reported with features of the VACTERL association, including anal atresia, laryngeal and oesophageal atresia with tracheo-oesophageal fistula, dextroposition of the heart with persistent left superior vena cava, and unilateral multicystic kidney. As the clinical picture of this patient overlaps with that of X-linked heterotaxy caused by ZIC3 mutations, the ZIC3 coding region was sequenced. RESULTS: In a patient with the VACTERL association a 6-nucleotide insertion was found in the GCC repeat of the ZIC3 gene, which is predicted to expand the amino-terminal polyalanine repeat from 10 to 12 polyalanines. The polyalanine expansion is a novel ZIC3 mutation which was not found in 336 chromosomes from 192 ethnically matched controls. The mutation was also not present in the mother, suggesting it occurred de novo in the patient and is therefore a pathogenetic mutation. CONCLUSION: It is hypothesized that this novel and de novo polyalanine expansion in ZIC3 contributes to the VACTERL association in this patient. A newborn male is described with features of the VACTERL association, including anal atresia, laryngeal and oesophageal atresia with tracheo-oesophageal fistula, dextroposition of the heart with persistent left superior vena cava, and unilateral multicystic kidney. As the clinical picture

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of the VACTERL association overlaps with X-linked heterotaxy caused by ZIC3 mutations, the ZIC3 coding region was sequenced, and a 6-nucleotide insertion was found that is predicted to expand the amino-terminal polyalanine repeat from 10 to 12 polyalanines. This novel mutation was not present in the mother, nor in 336 chromosomes from 192 ethnically matched controls. It is hypothesised that this novel and de novo polyalanine expansion in the ZIC3 gene contributes to the VACTERL association in this patient. PMID: 20452998 [PubMed - indexed for MEDLINE]

Kaandorp SP, Goddijn M, van der Post JA, Hutten BA, Verhoeve HR, Hamulyák K, Mol BW, Folkeringa N, Nahuis M, Papatsonis DN, Büller HR, van der Veen F, Middeldorp S. Aspirin plus heparin or aspirin alone in women with recurrent miscarriage. N Engl J Med. 2010 Apr 29;362(17):1586-96. Epub 2010 Mar 24. BACKGROUND: Aspirin and low-molecular-weight heparin are prescribed for women with unexplained recurrent miscarriage, with the goal of improving the rate of live births, but limited data from randomized, controlled trials are available to support the use of these drugs. METHODS: In this randomized trial, we enrolled 364 women between the ages of 18 and 42 years who had a history of unexplained recurrent miscarriage and were attempting to conceive or were less than 6 weeks pregnant. We then randomly assigned them to receive daily 80 mg of aspirin plus open-label subcutaneous nadroparin (at a dose of 2850 IU, starting as soon as a viable pregnancy was demonstrated), 80 mg of aspirin alone, or placebo. The primary outcome measure was the live-birth rate. Secondary outcomes included rates of miscarriage, obstetrical complications, and maternal and fetal adverse events. RESULTS: Live-birth rates did not differ


significantly among the three study groups. The proportions of women who gave birth to a live infant were 54.5% in the group receiving aspirin plus nadroparin (combination-therapy group), 50.8% in the aspirin-only group, and 57.0% in the placebo group (absolute difference in livebirth rate: combination therapy vs. placebo, -2.6 percentage points; 95% confidence interval [CI], -15.0 to 9.9; aspirin only vs. placebo, -6.2 percentage points; 95% CI, -18.8 to 6.4). Among 299 women who became pregnant, the live-birth rates were 69.1% in the combination-therapy group, 61.6% in the aspirin-only group, and 67.0% in the placebo group (absolute difference in live-birth rate: combination therapy vs. placebo, 2.1 percentage points; 95% CI, -10.8 to 15.0; aspirin alone vs. placebo -5.4 percentage points; 95% CI, -18.6 to 7.8). An increased tendency to bruise and swelling or itching at the injection site occurred significantly more frequently in the combination-therapy group than in the other two study groups. CONCLUSIONS: Neither aspirin combined with nadroparin nor aspirin alone improved the live-birth rate, as compared with placebo, among women with unexplained recurrent miscarriage. (Current Controlled Trials number, ISRCTN58496168.) 2010 Massachusetts Medical Society Comment in: Ann Intern Med. 2010 Oct 19;153(8):JC4-7; N Engl J Med. 2010 Apr 29;362(17):1630-1; N Engl J Med. 2010 Aug 26;363(9):887-8; author reply 888; N Engl J Med. 2010 Aug 26;363(9):887; author reply 888. PMID: 20335572 [PubMed - indexed for MEDLINE]

Vlemmix F, Rosman AN, Fleuren MA, Rijnders ME, Beuckens A, Haak MC, Akerboom BM, Bais JM, Kuppens SM, Papatsonis DN, Opmeer BC, van der Post JA, Mol BW, Kok M. Implementation of the external cephalic version in breech delivery. Dutch national implementation study of external cephalic version. BMC Pregnancy Childbirth. 2010 May 10;10:20. BACKGROUND: Breech presentation occurs in 3 to 4% of all term pregnancies. External cephalic version (ECV) is proven effective to prevent vaginal breech deliveries and therefore it is recommended by clinical guidelines of the Royal Dutch Organisation for Midwives (KNOV) and the Dutch Society for Obstetrics and Gynaecology (NVOG). Implementation of ECV does not exceed 50 to 60% and probably less.We aim to improve the implementation of ECV to decrease maternal and neonatal morbidity and mortality due to breech presentations. This will be done by defining barriers and facilitators of implementation of ECV in the Netherlands. An innovative implementation strategy will be developed based on improved patient counselling and thorough instructions of health care providers for counselling. METHOD/DESIGN: The ultimate purpose of this implementation study is to improve counselling of pregnant women and information of clinicians to realize a better implementation of ECV.The first phase of the project is to detect the barriers and facilitators of ECV. The next step is to develop an implementation strategy to inform and counsel pregnant women with a breech presentation, and to inform and educate care providers. In the third phase, the effectiveness of the developed implementation strategy

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will be evaluated in a randomised trial. The study population is a random selection of midwives and gynaecologists from 60 to 100 hospitals and practices. Primary endpoints are number of counselled women. Secondary endpoints are process indicators, the amount of fetes in cephalic presentation at birth, complications due to ECV, the number of caesarean sections and perinatal condition of mother and child. Cost effectiveness of the implementation strategy will be measured. DISCUSSION: This study will provide evidence for the cost effectiveness of a structural implementation of external cephalic versions to reduce the number of breech presentations at term. TRIAL REGISTRATION: Dutch Trial Register (NTR): 1878. PMID: 20459717 [PubMed - indexed for MEDLINE] PMCID: PMC2874762

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Vijgen SM, Koopmans CM, Opmeer BC, Groen H, Bijlenga D, Aarnoudse JG, Bekedam DJ, van den Berg PP, de Boer K, Burggraaff JM, Bloemenkamp KW, Drogtrop AP, Franx A, de Groot CJ, Huisjes AJ, Kwee A, van Loon AJ, Lub A, Papatsonis DN, van der Post JA, Roumen FJ, Scheepers HC, Stigter RH, Willekes C, Mol BW, Van Pampus MG; HYPITAT study group. An economic analysis of induction of labour and expectant monitoring in women with gestational hypertension or pre-eclampsia at term (HYPITAT trial). BJOG. 2010 Dec; 117(13):1577-85. Epub 2010 Sep 14. OBJECTIVE: To assess the economic consequences of labour induction compared with expectant monitoring in women with gestational hypertension or pre-eclampsia at term. DESIGN: An economic analysis alongside 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: Women diagnosed with gestational hypertension or pre-eclampsia between 36(+0) and 41(+0) weeks of gestation, randomly allocated to either induction of labour or expectant monitoring. METHODS: A trial-based cost-effectiveness analysis was performed from a societal perspective during a 1-year time horizon. MAIN OUTCOME MEASURES: One-year costs were estimated and health outcomes were expressed as the prevalence of poor maternal outcome defined as either maternal complications or progression to severe disease. RESULTS: The average costs of induction of labour (n = 377) were €7077 versus €7908 for expectant monitoring (n = 379), with an average difference of -€831 (95% CI -€1561 to -€144). This 11% difference predominantly originated from the antepartum period: per woman costs were €1259 for induction versus €2700 for expectant monitoring. During delivery, more costs were generated following induction (€2190) compared with expectant monitoring (€1210). No substantial differences were found in the postpartum, follow-up and for non-medical costs. CONCLUSION: In women with gestational hypertension or mild pre-eclampsia at term, induction of labour is less costly than expectant monitoring because of differences in resource use in the antepartum period. As the trial already demonstrated that induction of labour results in less progression to severe disease without resulting in a higher caesarean


section rate, both clinical and economic consequences are in favour of induction of labour in these women. TRIAL REGISTRATION: The trial has been registered in the clinical trial register as ISRCTN08132825.© 2010 The Authors Journal compilation © RCOG 2010 BJOG An International Journal of Obstetrics and Gynaecology. Comment in: BJOG. 2010 Dec;117(13):1575-6; BJOG. 2011 May;118(6):763; author reply 764. PMID: 20840526 [PubMed - indexed for MEDLINE]

Prick BW, Steegers EA, Jansen AJ, Hop WC, Essink-Bot ML, Peters NC, Uyl-de Groot CA, Papatsonis DN, Akerboom BM, Metz GC, Bremer HA, van Loon AJ, Stigter RH, van der Post JA, van Alphen M, Porath M, Rijnders RJ, Spaanderman ME, Schippers DH, Bloemenkamp KW, Boers KE, Scheepers HC, Roumen FJ, Kwee A, Schuitemaker NW, Mol BW, van Rhenen DJ, Duvekot JJ. Well being of obstetric patients on minimal blood transfusions (WOMB trial). BMC Pregnancy Childbirth. 2010 Dec 16;10:83. BACKGROUND: Primary postpartum haemorrhage is an obstetrical emergency often causing acute anaemia that may require immediate red blood cell (RBC) transfusion. This anaemia results in symptoms such as fatigue, which may have major impact on the health-related quality of life. RBC transfusion is generally thought to alleviate these undesirable effects although it may cause transfusion reactions. Moreover, the postpartum haemoglobin level seems to influence fatigue only for a short period of time. At present, there are no strict transfusion criteria for this specific indication, resulting in a wide variation in postpartum policy of RBC transfusion in the Netherlands. METHODS/DESIGN: The WOMB trial is a multicentre randomised non-inferiority trial. Women with acute anaemia due to postpartum haemorrhage, 12-24 hours after delivery and not initially treated with RBC transfusion, are eligible for randomisation. Patients with severe physical complaints are excluded. Patients are randomised for either RBC transfusion or expectant management. Health related quality of life (HRQoL) will be assessed at inclusion, at three days and one, three and six weeks postpartum with three validated measures (Multi-dimensional Fatigue Inventory, ShortForm-36, EuroQol-5D). Primary outcome of the study is physical fatigue three days postpartum. Secondary outcome measures are general and mental fatigue scores and generic health related quality of life scores, the number of RBC transfusions, length of hospital stay, complications and health-care costs. The primary analysis will be by intention-to-treat. The various longitudinal scores will be evaluated using Repeated Measurements ANOVA. A costs benefit analysis will also be performed. The power calculation is based on the exclusion of a difference in means of 1.3 points or greater in favour of RBC transfusion arm regarding physical fatigue subscale. With missing data not exceeding 20%, 250 patients per arm have to be randomised (one-sided alpha = 0.025, power = 80%). DISCUSSION: This study will provide evidence for a guideline regarding RBC transfusion in the postpartum patient suffering from acute anaemia. Equivalence in fatigue score, remaining HRQoL scores

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and physical complications between both groups is assumed, in which case an expectant management would be preferred to minimise transfusion reactions and costs. PMID: 21162725 [PubMed - indexed for MEDLINE] PMCID: PMC3022737

Speksnijder L, Rutten JH, van den Meiracker AH, de Bruin RJ, Lindemans J, Hop WC, Visser W. Amino-terminal pro-brain natriuretic peptide (NT-proBNP) is a biomarker of cardiac filling pressures in pre-eclampsia. Eur J Obstet Gynecol Reprod Biol. 2010 Nov;153(1):12-5. Epub 2010 Jul 31. OBJECTIVE: To evaluate if amino-terminal pro-brain natriuretic peptide (NT-proBNP) plasma levels reflect intracardiac filling pressures in pre-eclamptic patients. STUDY DESIGN: In a cross-sectional study we investigated 22 untreated critically ill pre-eclamptic women between 22 and 34 weeks gestation. All patients underwent intra-arterial blood pressure and central hemodynamic measurements and NT-proBNP was determined in stored plasma. Baseline characteristics, plasma NT-proBNP concentrations and relevant laboratory variables were

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investigated for correlations with hemodynamic values using Spearman’s rank correlation test. RESULTS: No significant correlations were demonstrated between NT-proBNP concentrations and variables associated with the severity of the pre-eclampsia. We found significant positive correlations between NT-proBNP and diastolic pulmonary pressure (r = 0.59; p = 0.005) and pulmonary capillary wedge pressure (PCWP) (r = 0.51; p = 0.015). Multiple linear regression analysis showed that the association between NT-proBNP and PCWP was not affected by creatinine level. CONCLUSION: NT-proBNP is a biomarker of left ventricular cardiac filling pressures in untreated pre-eclamptic patients. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved. PMID: 20674138 [PubMed - indexed for MEDLINE]

Complete publicatielijst Vijgen SM, Koopmans CM, Opmeer BC, Groen H, Bijlenga D, Aarnoudse JG, Bekedam DJ, van den Berg PP, de Boer K, Burggraaff JM, Bloemenkamp KW, Drogtrop AP, Franx A, de Groot CJ, Huisjes AJ, Kwee A, van Loon AJ, Lub A, Papatsonis DN, van der Post JA, Roumen FJ, Scheepers HC, Stigter RH, Willekes C, Mol BW, Van Pampus MG; HYPITAT study group. An economic analysis of induction of labour and expectant monitoring in women with gestational hypertension or pre-eclampsia at term (HYPITAT trial). BJOG. 2010 Dec;117(13):1577-85. Epub 2010 Sep 14. Kaandorp SP, Goddijn M, van der Post JA, Hutten BA, Verhoeve HR, Hamulyák K, Mol BW, Folkeringa N, Nahuis M, Papatsonis DN, Büller HR, van der Veen F, Middeldorp S. Aspirin plus heparin or aspirin alone in women with recurrent miscarriage. N Engl J Med. 2010 Apr 29;362(17):1586-96. Epub 2010 Mar 24.


De Boer TA, Gietelink DA, Hendriks JC, Vierhout ME. Factors influencing success of pelvic organ prolapse repair using porcine dermal implant Pelvicol((R)). Eur J Obstet Gynecol Reprod Biol. 2010 Mar;149(1):112-6. Epub 2009 Dec 31. Vlemmix F, Rosman AN, Fleuren MA, Rijnders ME, Beuckens A, Haak MC, Akerboom BM, Bais JM, Kuppens SM, Papatsonis DN, Opmeer BC, van der Post JA, Mol BW, Kok M. Implementation of the external cephalic version in breech delivery. Dutch national implementation study of external cephalic version. BMC Pregnancy Childbirth. 2010 May 10;10:20. Koopmans CM, Bijlenga D, Groen H, Vijgen SMC, Aarnoudse JG, Bekedam DJ, van den Berg PP, de Boer K, Burggraaff JM, Bloemenkamp KWM, Drogtrop AP, Franx A, de Groot CJM, Huisjes AJM, Kwee A, van Loon AJ, Lub A, Papatsonis DNM, van der Post JAM, Roumen FJME, Scheepers HCJ, Willekes C, Mol BWJ, van Pampus MG. Liever inleiden dan afwachten bij aterme zwangerschapshypertensie en milde preëclampsie: HYPITATstudie Ned Tijdschr Geneeskd. 2010;154:A1660. Bakker JJ, Verhoeven CJ, Janssen PF, van Lith JM, van Oudgaarden ED, Bloemenkamp KW, Papatsonis DN, Mol BW, van der Post JA. Outcomes after internal versus external tocodynamometry for monitoring labor. N Engl J Med. 2010 Jan 28;362(4):306-13. Wessels MW, Kuchinka B, Heydanus R, Smit BJ, Dooijes D, de Krijger RR, Lequin MH, de Jong EM, Husen M, Willems PJ, Casey B. Polyalanine expansion in the ZIC3 gene leading to X-linked heterotaxy with VACTERL association, a new polyalanine disorder? J Med Genet. 2010 May;47(5):351-5. Wessels MW, Kuchinka B, Heydanus R, Smit BJ, Dooijes D, de Krijger RR, Lequin MH, de Jong EM, Husen M, Willems PJ, Casey B. Polyalanine expansion in the ZIC3 gene leading to X-linked heterotaxy with VACTERL association: a new polyalanine disorder? J Med Genet. 2010 May;47(5):351-5. Prick BW, Steegers EA, Jansen AJ, Hop WC, Essink-Bot ML, Peters NC, Uyl-de Groot CA, Papatsonis DN, Akerboom BM, Metz GC, Bremer HA, van Loon AJ, Stigter RH, van der Post JA, van Alphen M, Porath M, Rijnders RJ, Spaanderman ME, Schippers DH, Bloemenkamp KW, Boers KE, Scheepers HC, Roumen FJ, Kwee A, Schuitemaker NW, Mol BW, van Rhenen DJ, Duvekot JJ Well being of obstetric patients on minimal blood transfusions (WOMB trial). BMC Pregnancy Childbirth. 2010 Dec 16;10:83. Wilmink FA, Hukkelhoven CWPM, Lunshof S, Mol BW, van der Post J, Papatsonis DNM. Neonatal outcome following primary elective caesarean section beyond 37 weeks of gestation; a 7-year retrospective analysis of a national registry. [Abstract] SMFM 30th Annual Meeting – The Pregnancy Meeting. Chicago, February 1-6, 2010. Van Oostwaard M, Langenveld J, Bijloo R, Ganzevoort W, Papatsonis DNM, Mol BW. Outcomes of subsequent pregnancies of women with severe hypertensive disorders between 34 and 37 weeks of gestation in the first (index) pregnancy. [Abstract] SMFM 30th Annual Meeting - The Pregnancy Meeting. Chicago, February 1-6, 2010.

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Interne geneeskunde en Maag- darm- levergeneeskunde Kerngegevens zorgkern Interne geneeskunde en Maag- darm- levergeneeskunde • 18 internisten: (internist-nefroloog) dr. R.C. Bakker, (internist-oncoloog/hematoloog) mw. R.S. Boersma, mw. dr. P.W.G. de Buf-Vereijken, mw. T.T. Cnossen, (algemeen internist) mw. S.A.M. Ennercker-Jans, dr. J.W.J. Esser, dr. R.W. van Etten, mw. A.M. van Gent, G.J. Goverde, (internist-vasculair geneeskundige) dr. C. van Guldener, (internist-oncoloog) mw. J.B. Heijns, mw. dr. M.A. van Leeuwen-Artz, O.J.L. Loosveld, (internist-endocrinoloog) dr. S.W. van Thiel, dr. A.J. ten Tije, B.F.E. Veldhuijzen, (internist-infectioloog) G.P. Verburg, P. van Wijngaarden • 6 MDL-artsen: A.G.L. Bodelier, I.M. Harkema, mw. M.J. van Heerde, dr. A.W.M. Milligen de Wit, dr. M.C.M. Rijk, dr. T.C.J. Seerden • 11 assistenten niet in opleiding • 12 assistenten in opleiding • subspecialismen: diabetes, endocrinologie, hematologie, infectieziekten, nefrologie, oncologie, maag- darm- leverziekten

Samenvattingen gepubliceerde artikelen Mamede S, van Gog T, van den Berge K, Rikers RM, van Saase JL, van Guldener C, Schmidt HG. Effect of availability bias and reflective reasoning on diagnostic accuracy among internal medicine residents. JAMA. 2010 Sep 15;304(11):1198-203. CONTEXT: Diagnostic errors have been associated with bias in clinical reasoning. Empirical evidence on the cognitive mechanisms underlying biases and effectiveness of educational strategies to counteract them is lacking. OBJECTIVES: To investigate whether recent experience

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with clinical problems provokes availability bias (overestimation of the likelihood of a diagnosis based on the ease with which it comes to mind) resulting in diagnostic errors and whether reflection (structured reanalysis of the case findings) counteracts this bias. DESIGN, SETTING, AND PARTICIPANTS: Experimental study conducted in 2009 at the Erasmus Medical Centre, Rotterdam, with 18 first-year and 18 second-year internal medicine residents. Participants first evaluated diagnoses of 6 clinical cases (phase 1). Subsequently, they diagnosed 8 different cases through nonanalytical reasoning, 4 of which had findings similar to previously evaluated cases but different diagnoses (phase 2). These 4 cases were subsequently diagnosed again through reflective reasoning (phase 3). MAIN OUTCOME MEASURES: Mean diagnostic accuracy scores (perfect score, 4.0) on cases solved with or without previous exposure to similar problems through nonanalytical (phase 2) or reflective (phase 3) reasoning and frequency that a potentially biased (ie, phase 1) diagnosis was given. RESULTS: There were no main effects, but there was a significant interaction effect between ‘years of training’ and ‘recent experiences with similar problems.’ Results consistent with an availability bias occurred for the second-year residents, who scored lower on the cases similar to those previously encountered (1.55; 95% confidence interval [CI], 1.15-1.96) than on the other cases (2.19; 95% CI, 1.73-2.66; P =.03).

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This pattern was not seen among the first-year residents (2.03; 95% CI, 1.55-2.51 vs 1.42; 95% CI, 0.92-1.92; P =.046). Second-year residents provided the phase 1 diagnosis more frequently for phase 2 cases they had previously encountered than for those they had not (mean frequency per resident, 1.44; 95% CI, 0.93-1.96 vs 0.72; 95% CI, 0.28-1.17; P =.04). A significant main effect of reasoning mode was found: reflection improved the diagnoses of the similar cases compared with nonanalytical reasoning for the second-year residents (2.03; 95% CI, 1.49-2.57) and the first-year residents (2.31; 95% CI, 1.89-2.73; P =.006). CONCLUSION: When faced with cases similar to previous ones and using nonanalytic reasoning, second-year residents made errors consistent with the availability bias. Subsequent application of diagnostic reflection tended to counter this bias; it improved diagnostic accuracy in both first- and second-year residents. Comment in: JAMA. 2010 Sep 15;304(11):1233-5. PMID: 20841533 [PubMed - indexed for MEDLINE]

Andriesse GI, Donmez M, Vissers J, van Wijngaarden P. Acute hepatitis, maar niet A, B, of C: overweeg E. Ned Tijdschr Geneeskd. 2010 Aug 21;154(33):1536-1539. OBJECTIVE: To determine the percentage of hepatitis E virus (HEV) infections in serum samples from patients with negative serology for hepatitis A, B and C and to find out what may be the harmful consequences of a missed diagnosis of acute HEV infection. DESIGN: Retrospective study. METHOD: Serum samples were selected from patients with infectious hepatitis who tested negative for hepatitis A, B and C virus. Serum samples that had elevated alanine aminotransferase (ALT; > 34 U/l) were included in this study. All samples were then tested for


HEV using an enzyme-linked immunosorbent assay (ELISA) and immunoblot assay. Of patients with serological evidence of acute HEV, files were checked for the originally documented diagnosis at hospital discharge. RESULTS: In the period October 2007-September 2008, 139 serum samples met the inclusion criteria. In 23 serum samples the ELISA was positive (IgM positive and/or Ig total positive); in 16/23 serum samples immunoblot assay was also positive. The percentage of confirmed HEV infections was 11.5% (16/139). In only one patient was the originally documented diagnosis correct. Several patients underwent invasive diagnostic procedures and treatment as a result of an incorrect diagnosis. CONCLUSION: Hepatitis E serology should be a standard tool in the diagnostic workup of infectious hepatitis patients in the Netherlands. PMID: 20735873 [PubMed - indexed for MEDLINE]

Cnossen TT, Usvyat L, Kotanko P, van der Sande FM, Kooman JP, Carter M, Leunissen KM, Levin NW. Comparison of outcomes on continuous ambulantory peritoneal dialysis versus automated peritoneal dialysis: results from a USA database. Perit Dial Int. 2010 Sep 9. [Epub ahead of print]. 87 OBJECTIVE: Automated peritoneal dialysis (APD) is being increasingly used as an alternative to continuous ambulatory peritoneal dialysis (CAPD). However, there has been concern regarding reduced sodium removal leading to hypertension and resulting in a faster decline in residual renal function (RRF). The objective of the present study was to compare patient and technique survival and other relevant parameters between patients treated with APD and patients treated with CAPD. METHODS: Data for incident patients were retrieved from the database of the Renal Research Institute, New York. Treatment modality was defined 90 days after the start of dialysis treatment. In addition to technique and patient survival, RRF, blood pressure, and laboratory parameters were also compared. RESULTS: 179 CAPD and 441 APD patients were studied. Mean as-treated survival was 1407 days [95% confidence interval (CI) 1211 - 1601] in CAPD patients and 1616 days (95% CI 1478 - 1764) in APD patients. Adjusted hazard ratio (HR) for mortality was 1.31 in CAPD compared to APD (95% CI 0.76 - 2.25, p = NS). Unadjusted as-treated technique survival was lower in CAPD compared to APD, with HR 2.84 (95% CI 1.65 - 4.88, p = 0.002); adjusted HR was 1.81 (95% CI 0.94 - 3.57, p = 0.08). Peritonitis rate was 0.3 episodes/patient-year for CAPD and APD; exit-site/tunnel infection rate was 0.1 and 0.3 episodes/patient-year for CAPD and APD respectively (p = NS). CONCLUSIONS: Patient survival was not significantly different between APD and CAPD patients, whereas technique survival appeared to be higher in APD patients and could not be explained by differences in infectious complications. No difference in blood pressure control or decline in RRF was observed between the 2 modalities. Based on these results, APD appears to be an acceptable alternative to CAPD, although technique prescription should always follow individual judgment. PMID: 20829519 [PubMed - as supplied by publisher]


Cnossen TT, Kooman JP, Konings CJ, Uszko-Lencer NH, Leunissen KM, van der Sande FM. Peritoneal dialysis in patients with primary cardiac failure complicated by renal failure. Blood Purif. 2010;30(2):146-52. Epub 2010 Sep 15. BACKGROUND/AIMS: Clinical outcome in cardiorenal syndrome type II and treated with peritoneal dialysis (PD). METHODS: Retrospective analysis over a period of 10 years. RESULTS: Twenty-four patients with mean age at start of dialysis of 67 ± 10 years had mean survival on dialysis of 1.03 ± 0.84 years (median survival 1.0 year). The number of hospitalizations for cardiovascular causes were reduced (13.7 ± 26.5 predialysis vs. 3.5 ± 8.8 days/patient/month postdialysis, p = 0.001). Patients who survived longer than the median survival time (n = 12) also had a reduced number of hospitalizations for all causes (3.7 ± 3.8 predialysis vs. 1.4 ± 2.1 days/patient/month postdialysis, p = 0.041), a lower age (62 ± 10 vs. 71 ± 8 years, p = 0.013) and fewer had diabetes (2 vs. 7 patients, p = 0.039), but left ventricular ejection fraction was not different. CONCLUSION: After starting PD for cardiorenal syndrome, hospitalizations for cardiovascular causes were reduced for all patients. Survival after starting PD is highly variable. Age and diabetes seem to be significant prognostic factors, but not left ventricular ejection

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fraction.Copyright © 2010 S. Karger AG, Basel. PMID: 20847552 [PubMed - indexed for MEDLINE]

Cnossen TT, Gladziwa U, van de Kerkhof JJ, Schalkwijk CG, Scheijen J, van Amersfoort J, Moret K, Beerenhout CH, Kooman JP The influence of bicarbonate/lactate-buffered PDfluids on N{varepsilon}-(Carboxyethyl)Lysine and N{varepsilon}-(Carboxymethyl)Lysine in peritoneal effluent. Perit Dial Int. 2011 Mar;31(2):189-193. Epub 2010 Jul 29. OBJECTIVE: Accumulation of advanced glycation end products (AGEs) may be involved in the pathogenesis of peritoneal membrane dysfunction. As glycoxidation may play an important role in AGE formation, peritoneal dialysis fluids with low levels of glucose degradation products (GDPs) might result in a reduction in AGE concentration in the peritoneal effluent. The aim of this study was to compare the effects of conventional glucose-containing dialysis solutions and low GDP level fluids on the concentration of the AGEs N(e)-(carboxymethyl)lysine (CML) and N(e)-(carboxyethyl)lysine (CEL) in peritoneal effluent. DESIGN: Prospective randomized control study. METHODS: 23 patients were treated with either conventional glucose-containing fluid (n = 11, group A) or low level GDP fluid (n = 12, group B) during a period of 12 weeks. Before and after this period, CML and CEL were measured in peritoneal effluent. RESULTS: In groups A and B there were changes in CML concentrations [respectively 13.7 ± 17.0 and -16.0 ± 46.0 nmol/L (NS)] and CEL concentrations (respectively 20.3 ± 26.6 and -8.8 ± 18.9 nmol/L, p = 0.015). Residual renal function (RRF) in groups A and B was, respectively, 6.8 and 6.1 mL/ min (NS). CML, but not CEL, in the peritoneal effluent was inversely related to RRF (r = -0.67, p < 0.05). CONCLUSION: CEL, but not CML, in the peritoneal effluent appears to be influenced


by the prescription of low GDP level fluid, probably due to the highly reduced concentration of methylglyoxal, which is needed for formation of CEL. CML is primarily influenced by RRF. PMID: 20671103 [PubMed - as supplied by publisher]

Zaludik J, Schuitemaker F, DeWaal R, Veldhuijzen B, van der Meer N. Severe lactate acidosis and cardiogenic shock: a rare manifestation of a phaeochromocytoma. Anaesth Intensive Care. 2010 May;38(3):593-4. PMID: 20518121 [PubMed - indexed for MEDLINE]

Uchida N, Galasso D, Seerden TC, Carnuccio A, Zachariah K, Costamagna G, Larghi A. EUS-FNA of extracolonic lesions by using the forward-viewing linear echoendoscope. Gastrointest Endosc. 2010 Dec;72(6):1321-3. Epub 2010 Jul 1. PMID: 20579992 [PubMed - indexed for MEDLINE]

Larghi A, Seerden TC, Galasso D, Carnuccio A, Familiari P, Mutignani M, Zachariah K, Costamagna G. EUS-guided therapeutic interventions for uncommon benign pancreaticobiliary disorders by using a newly developed forward-viewing echoendoscope (with videos). Gastrointest Endosc. 2010 Jul;72(1):213-5. Epub 2010 Mar 6. PMID: 20207354 [PubMed - indexed for MEDLINE]

Mutignani M, Seerden T, Tringali A, Feisal D, Perri V, Familiari P, Costamagna G. Endoscopic hemostasis with fibrin glue for refractory postsphincterotomy and postpapillectomy bleeding. Gastrointest Endosc. 2010 Apr;71(4):856-60. BACKGROUND: Bleeding is a feared complication of endoscopic sphincterotomy and papillectomy. Fibrin glue has been proposed as an effective adjunct in securing hemostasis. However, its use has been limited by the risk of early occlusion of the injecting needle, and its role has not been defined in the setting of refractory post-ERCP bleeding. We present a modified technique of endoscopic hemostasis with diluted fibrin glue in the setting of postsphincterotomy and postpapillectomy bleeds. OBJECTIVE: We aimed to verify that diluted fibrin glue can be easily and successfully injected and is effective in the endoscopic treatment of refractory post-ERCP bleeding. DESIGN: Case series. SETTING: A tertiary-care academic medical center. PATIENTS: Six patients with refractory post-ERCP bleeding were treated (3 after sphincterotomy and 3 after papillectomy) with fibrin glue injection. INTERVENTION: Endoscopic hemostasis with diluted fibrin glue injection. MAIN OUTCOME MEASUREMENTS: Successful endoscopic hemostasis with diluted fibrin glue injection. RESULTS: One session of fibrin glue injection stopped the refractory post-ERCP bleeding in all 6 patients. LIMITATION: Small number of patients. CONCLUSION: This case series provides evidence that our modified injection technique of diluted fibrin glue


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allowed an easy submucosal injection and may be considered to be an effective endoscopic modality to treat refractory post-ERCP bleeding. Copyright 2010. Published by Mosby, Inc. PMID: 20363432 [PubMed - indexed for MEDLINE]

Van der Meulen-de Jong AE, Morreau H, Becx MC, Crobach LF, van Haastert M, ten Hove WR, Kleibeuker JH, Meijssen MA, Nagengast FM, Rijk MC, Salemans JM, Stronkhorst A, Tuynman HA, Vecht J, Verhulst ML, de Vos tot Nederveen Cappel WH, Walinga H, Weinhardt OK, Westerveld BD, Witte AM, Wolters HJ, Vasen HF. High detection rate of adenomas in familial colorectal cancer. Gut. 2011 Jan;60(1):73-6. Epub 2010 Sep 9. BACKGROUND AND AIMS: Subjects with one first-degree relative (FDR) with colorectal cancer (CRC) <50 years old or two FDRs with CRC have an increased risk for CRC (RR 4-6). Current guidelines recommend colonoscopic surveillance of such families. However, information about the yield of surveillance is limited. The aim of the present study was to evaluate the outcome of surveillance and to identify risk factors for the development of adenomas. PATIENTS AND METHODS: Subjects were included if they fulfilled the following criteria: asymptomatic subjects

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aged between 45 and 65 years, with one FDR with CRC <50 years old (group A) or two FDRs with CRC diagnosed at any age (group B). Subjects with a personal history of inflammatory bowel disease or colorectal surgery were excluded. RESULTS: A total of 551 subjects (242 male) met the selection criteria. Ninety-five subjects with a previous colonoscopy were excluded. Two of 456 remaining subjects (0.4%) were found to have a colorectal tumour (one CRC and one carcinoid). Adenomas were detected in 85 (18.6%) and adenomas with advanced pathology in 37 subjects (8.1%). 30 subjects (6.6%) had multiple (>1) adenomas. Men were more often found to have an adenoma than women (24% vs 14.3%; p=0.01). Adenomas were more frequent in group B compared with group A (22.0% vs 15.6%; p=0.09). CONCLUSION: The yield of colonoscopic surveillance in familial CRC is substantially higher than the yield of screening reported for the general population. PMID: 20833659 [PubMed - indexed for MEDLINE]

Complete publicatielijst Andriesse GI, Donmez M, Vissers J, van Wijngaarden P. Acute hepatitis, maar niet A, B, of C: overweeg E. Ned Tijdschr Geneeskd. 2010 Aug 21;154(33):1536-1539. Cnossen TT, Usvyat L, Kotanko P, van der Sande FM, Kooman JP, Carter M, Leunissen KM, Levin NW. Comparison of outcomes on continuous ambulantory peritoneal dialysis versus automated peritoneal dialysis: results from a USA database. Perit Dial Int. 2010 Sep 9. [Epub ahead of print]. Mamede S, van Gog T, van den Berge K, Rikers RM, van Saase JL, van Guldener C, Schmidt HG. Effect of availability bias and reflective reasoning on diagnostic accuracy among internal medicine residents. JAMA. 2010 Sep 15;304(11):1198-203.


Mutignani M, Seerden T, Tringali A, Feisal D, Perri V, Familiari P, Costamagna G. Endoscopic hemostasis with fibrin glue for refractory postsphincterotomy and postpapillectomy bleeding. Gastrointest Endosc. 2010 Apr;71(4):856-60. Uchida N, Galasso D, Seerden TC, Carnuccio A, Zachariah K, Costamagna G, Larghi A. EUS-FNA of extracolonic lesions by using the forward-viewing linear echoendoscope. Gastrointest Endosc. 2010 Dec;72(6):1321-3. Epub 2010 Jul 1. Larghi A, Seerden TC, Galasso D, Carnuccio A, Familiari P, Mutignani M, Zachariah K, Costamagna G. EUS-guided therapeutic interventions for uncommon benign pancreaticobiliary disorders by using a newly developed forward-viewing echoendoscope (with videos). Gastrointest Endosc. 2010 Jul;72(1):213-5. Epub 2010 Mar 6. Van der Mark SC, Segers D, Baker RC, van Wijngaarden P. Het DRESS – syndroom bij gebruik van sulfasalazine: Geneesmiddelexantheem met eosinofilie en systemische symptomen. Ned Tijdschr Geneeskd. 2010 Dec 11;154(49):2287-2290. Cnossen TT, Kooman JP, Konings CJ, Uszko-Lencer NH, Leunissen KM, van der Sande FM. Peritoneal dialysis in patients with primary cardiac failure complicated by renal failure. Blood Purif. 2010;30(2):146-52. Epub 2010 Sep 15. Van den Berge CKA, van Guldener C, Verburg GP. Recidiverende pericarditis en eosinofilie bij een jonge vrouw. Tijdschrift voor Infectieziekten. 2010;5:180-3. Zaludik J, Schuitemaker F, DeWaal R, Veldhuijzen B, van der Meer N. Severe lactate acidosis and cardiogenic shock: a rare manifestation of a phaeochromocytoma. Anaesth Intensive Care. 2010 May;38(3):593-4. Cnossen TT, Gladziwa U, van de Kerkhof JJ, Schalkwijk CG, Scheijen J, van Amersfoort J, Moret K, Beerenhout CH, Kooman JP The influence of bicarbonate/lactate-buffered PDfluids on N{varepsilon}-(Carboxyethyl)Lysine and N{varepsilon}-(Carboxymethyl)Lysine in peritoneal effluent. Perit Dial Int. 2011 Mar;31(2):189-193. Epub 2010 Jul 29. Van der Meulen-de Jong AE, Morreau H, Becx MC, Crobach LF, van Haastert M, ten Hove WR, Kleibeuker JH, Meijssen MA, Nagengast FM, Rijk MC, Salemans JM, Stronkhorst A, Tuynman HA, Vecht J, Verhulst ML, de Vos tot Nederveen Cappel WH, Walinga H, Weinhardt OK, Westerveld BD, Witte AM, Wolters HJ, Vasen HF. High detection rate of adenomas in familial colorectal cancer. Gut. 2011 Jan;60(1):73-6. Epub 2010 Sep 9.


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Kaakchirurgie Kerngegevens zorgkern Kaakchirurgie • 6 kaakchirurgen: dr. J.E. Bergsma, J.T.M. van Gemert, dr. P.J.J. Gooris, E. van Hooft, G. Mensink, dr. A.B.E. Voute • 2 assistenten in opleiding • 4 assistenten niet in opleiding • subspecialisme: implantologie

Samenvattingen gepubliceerde artikelen Dik EA, van Es RJ, Bergsma JE. A toxic reaction of the oral mucosa to alendronate (Fosamax). Ned Tijdschr Tandheelkd. 2010 Jul-Aug;117(7-8):387-90. A 90-year old woman attended a department of Oral and Maxillofacial Surgery with a tongue that had been painful for at least 3 months. Clinical examination revealed extensive bullous and ulcerative lesions located on the tongue, the oral vestibule and the buccal mucosa on both sides. A variety of diseases may be causative of ulcerative stomatitis: autoimmune diseases (like Pemphigus vulgaris, Erosive Lichen Planus, SLE or M. Crohn), or a viral, bacterial or mycotical infection, vitamin deficiency, a toxic reaction to medication or an immune deficiency. After an extensive, clinical examination, a definitive diagnosis still had not been achieved. The patient suffered from osteoporosis, for which she used alendronate (Fosamax). A study of the literature described a possible relationship between the occurrence of oral ulcers and the use of oral biphosphonates. Since a toxic reaction to alendronate was suspected, the use of Fosamax tablets was suspended. Three months later a complete recovery of the oral mucosa was observed. PMID: 20726498 [PubMed - indexed for MEDLINE]

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Complete publicatielijst Dik EA, van Es RJ, Bergsma JE. [A toxic reaction of the oral mucosa to alendronate (Fosamax)]. Ned Tijdschr Tandheelkd. 2010 Jul-Aug;117(7-8):387-90. Van Hooft E, Becking AG, van Spronsen PH, Tuinzing DB. Het streven naar faciale harmonie. Ned Tijdschr Tandheelkd. 2010 aug; 117:391-395

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Kindergeneeskunde Kerngegevens zorgkern Kindergeneeskunde • 12 kinderartsen: mw. C.D. Aarts-Tesselaar, dr. R.H.T. van Beek, dr. A.R. Hulsmann, M.H. Jonkers, J. Kooijman, M.C. Küthe, mw. dr. S.A. de Man, P.W.J. van Mossevelde, mw. S.M.H.B. de Pont, L. Torn, mw. dr. A.A.P.H. Vaessen-Verberne, mw. E.J.M. Veldkamp • H. van Wering, Fellow • 3 assistenten niet in opleiding • 3 assistenten in opleiding • 1 baios • 1 daios • 1 tagio

Samenvattingen gepubliceerde artikelen Koopman M, Brackel HJ, Vaessen-Verberne AA, Hop WC, van der Ent CK; on behalf of the COMBO-Rint Research GroupCOMBO-Rint Research Group members are listed in the Acknowledgment Section. Evaluation of interrupter resistance in methacholine challenge testing in children. Pediatr Pulmonol. 2010 Nov 17. [Epub ahead of print] Bronchial hyperresponsiveness (BHR) is a key feature of asthma and is assessed using bronchial provocation tests. The primary outcome in such tests (a 20% decrease in forced expiratory volume in 1?sec (FEV(1))) is difficult to measure in young patients. This study evaluated the sensitivity and specificity of the interrupter resistance (R(int)) technique, which does not require active patient participation, by comparing it to the primary outcome measure. Methacholine challenge tests were performed in children with a history of moderate asthma and BHR. Mean and individual changes in R(int) and FEV(1) were studied. A receiver operating characteristic (ROC) curve was used to describe sensitivity and specificity of R(int).Seventythree children (median age: 9.2 years; range: 6.3-13.4 years) participated. There was a

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significant (P?
Vaessen-Verberne AA, van den Berg NJ, van Nierop JC, Brackel HJ, Gerrits GP, Hop WC, Duiverman EJ; COMBO Study Group*. Combination therapy salmeterol/fluticasone versus doubling dose of fluticasone in children with asthma. Am J Respir Crit Care Med. 2010 Nov 15;182(10):1221-7. Epub 2010 Jul 9. RATIONALE: For children with symptomatic asthma despite low to moderate doses of inhaled corticosteroids, evidence is still lacking whether to add a long-acting bronchodilator or to increase the dose of inhaled corticosteroids. OBJECTIVE: To evaluate whether salmeterol/ fluticasone propionate (SFP), 50/100 µg twice a day, is noninferior regarding symptom

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control compared with fluticasone propionate (FP), 200 µg twice a day Diskus in children with symptomatic asthma. METHODS: A multicenter, randomized, parallel-group, double-blind study was performed comparing SFP and FP treatment during 26 weeks on asthma control and lung function. MEASUREMENTS AND MAIN RESULTS: A total of 158 children, 6-16 years old, still symptomatic on FP, 100 µg twice a day, during a 4-week run-in period, were included. Percentage of symptom-free days during the last 10 weeks of the treatment period did not differ between treatment groups (per protocol analysis: adjusted mean difference [FP minus SFP] 2.6%; 95% confidence interval, -8.1 to 13.4). Both groups showed substantial improvements of about 25 percent points in symptom-free days (both P < 0.001 from baseline). Lung function measurements (FEV(1), FVC, PEF rate, and maximal expiratory flow) did not differ between groups except for a slight advantage in maximal expiratory flow in the SFP group at 1 week. No differences were found between FP and SFP regarding exacerbation rates, adverse events, or growth. CONCLUSIONS: In our study the efficacy on symptom control and lung function of the combination of a long-acting bronchodilator with inhaled corticosteroid is equal to doubling the dose of the inhaled corticosteroid in children still symptomatic on a moderate dose of inhaled corticosteroid. *Collaborators (23): Brinkhorst G, van den Berg NJ, van Nierop JC, Landstra AM, Vaessen-Verberne AA, Kuethe MC, Brackel HJ, Thio BJ, Versteegh FG, Duiverman EJ, Nuijsink M, Kouwenberg JM, Droog RP, Overberg PC, de Vries TW, Hendriks JJ, Jöbsis Q, Gerrits GP, Hop WC, Heijnens JW, van der Ent CK, van Gent R, Brand PL. Department of Pediatrics, Amphia Hospital, Breda, the Netherlands. [email protected] Comment in: Am J Respir Crit Care Med. 2010 Nov 15;182(10):1219-20. PMID: 20622031 [PubMed - indexed for MEDLINE]


Küthe MC, Vaessen-Verberne AA, Bindels PJ, van Aalderen WM. Children with asthma on inhaled corticosteroids managed in general practice or by hospital paediatricians: is there a difference? Prim Care Respir J. 2010 Mar;19(1):62-7, 8p following 67. AIM: To investigate whether there are differences in asthma characteristics between two populations of children with moderate asthma requiring inhaled corticosteroids (ICS) who are treated in general practice or in hospital practice. PATIENTS AND METHODS: 45 children from general practice and 62 from hospital practice, diagnosed with asthma and treated with ICS, were analysed in terms of lung function parameters, asthma control (ACQ), and use of medication. RESULTS: Children in general practice did not differ significantly from those in paediatric practice with respect to mean age, lung function tests, and corrected daily dose of ICS. The median ACQ score was higher (representing poorer control) in the general practice group than in the paediatric practice group (0.67 and 0.33 respectively, p < 0.05). Fewer children (22.7%) from the general practice group than from the paediatric group (98.4%) had planned review visits (p< 0.01). Prescriptions for a combination ICS/long-acting beta2-agonist (LABA) inhaler were 28.9% in the general practice group and 6.5% in the paediatric group (p<0.05). CONCLUSION: The hospital-based group was better controlled with less frequent use of combination therapy. Our observations stress the necessity for regular review visits for children with moderately severe asthma especially in general practice. Comment in: Prim Care Respir J. 2010 Sep;19(3):285; Prim Care Respir J. 2010 Mar;19(1):1-2. PMID: 19997688 [PubMed - indexed for MEDLINE]

Koolen BB, Pijnenburg MW, Brackel HJ, Landstra AM, van den Berg NJ, Merkus PJ, Hop WC, Vaessen-Verberne AA. Validation of a web-based version of the asthma control test and childhood asthma control test. Pediatr Pulmonol. 2011 Apr 1. [Epub ahead of print]. RATIONALE: Recent guidelines focus on adjusting asthma treatment to the level of asthma control. The availability of a web-based asthma control questionnaire offers the possibility to assess asthma control without the need of outpatient clinic visits. The aim of this study was to evaluate the agreement between web-based and paper-based versions of the Asthma Control Test (ACT) and Childhood Asthma Control Test (C-ACT), short-term reproducibility and satisfaction with both versions. METHODS: One hundred seventy-three children with stable asthma and a normal lung function were randomized to fill in a web-based or paper-based version of the C-ACT (4-11 years) or ACT (12-18 years). According to a cross-over design, they completed the opposite version after 1 week. Reproducibility was evaluated by repeating the 2nd version (web- or paper-based) 7 days later. RESULTS: Eighty-eight children filled in the C-ACT, 68 children filled in the ACT. Intraclass Correlation Coefficient (ICC) forweb-based versus paper-based C-ACT was 0.81 (95% confidence interval [95% CI] 0.72-0.87). For ACT this was 0.84 (95% CI 0.76-0.90). For web-based and paper-based C-ACT the reproducibility ICC was 0.82 (95% CI 0.67-0.90) and

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0.75 (95% CI 0.59-0.85), respectively. The reproducibility ICC of the ACT for web- and paperbased versions was 0.93 (95% CI 0.87-0.97) and 0.77 (95% CI 0.59-0.88), respectively. Eighty-six percent of patients preferred the web-based version. CONCLUSION: The web-based version of the C-ACT and ACT is reproducible and comparable with the paper-based version in assessing asthma control. Most children and their parents prefer the web-based version. Pediatr. Pulmonol. © 2011 Wiley-Liss, Inc. Copyright © 2011 Wiley-Liss, Inc. PMID: 21462363 [PubMed - as supplied by publisher]


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Küthe MC, Vaessen-Verberne AA, Bindels PJ, van Aalderen WM. Children with asthma on inhaled corticosteroids managed in general practice or by hospital paediatricians: is there a difference? Prim Care Respir J. 2010 Mar;19(1):62-7, 8p following 67. Vaessen-Verberne AA, van den Berg NJ, van Nierop JC, Brackel HJ, Gerrits GP, Hop WC, Duiverman EJ; COMBO Study Group*. Combination therapy salmeterol/fluticasone versus doubling dose of fluticasone in children with asthma. Am J Respir Crit Care Med. 2010 Nov 15;182(10):1221-7. Epub 2010 Jul 9. Koolen BB, Pijnenburg MWH, Brackel HJL, Landstra AM, van den Berg NJ, Merkus PJFM, Hop WCJ, Vaessen-Verberne AAPH. Detecting uncontrolled asthma in children: (Childhood) Asthma Control Test versus GINA-guidelines and Asthma Control Questionnaire. Eur Resp J. 2010;36:879s (ERS Barcelona). Koopman M, Brackel HJ, Vaessen-Verberne AA, Hop WC, van der Ent CK; on behalf of the COMBO-Rint Research GroupCOMBO-Rint Research Group members are listed in the Acknowledgment Section. Evaluation of interrupter resistance in methacholine challenge testing in children. Pediatr Pulmonol. 2010 Nov 17. [Epub ahead of print] Hulsmann AR, Oranje AP. Neonatale dermatologie. Praktische Pediatrie. 2010;4:232-6. Koolen BB, Pijnenburg MW, Brackel HJ, Landstra AM, van den Berg NJ, Merkus PJ, Hop WC, Vaessen-Verberne AA. Validation of a web-based version of the asthma control test and childhood asthma control test. Pediatr Pulmonol. 2011 Apr 1. [Epub ahead of print].


Laboratorium voor Microbiologie en Infectiepreventie De preventie van besmettingen in ziekenhuizen

Het Laboratorium voor Microbiologie en Infectiepreventie in het Amphia Ziekenhuis bestaat uit twee componenten. Medische microbiologie richt zich op de diagnostiek en behandeling van infectieziekten. Infectiepreventie richt zich met name op het voorkómen van infecties en van de verspreiding van infecties van patiënt tot patiënt. De artsen-microbiologen van het Laboratorium voor Microbiologie en Infectiepreventie van het Amphia Ziekenhuis werken in een maatschap samen met de artsen-microbiologen uit Tilburg (St. Elisabeth Ziekenhuis en Tweesteden Ziekenhuis), Roosendaal (Franciscus Ziekenhuis) en Bergen op Zoom (Lievensberg Ziekenhuis).

mw. dr. L.E. Willemsen

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Gepromoveerd In 2010 promoveerde dr. Ina (L.E.) Willemsen op haar proefschrift Improving Antimicrobial Use & Control of Resistant Micro-organisms in the Hospital. Dat is bijzonder, want ze heeft geen universitaire maar een hbo-opleiding microbiologie. ‘Ik kwam in 1999 in het Amphia Ziekenhuis werken als microbiologisch analist en later als kwaliteitsfunctionaris. Ik heb in dit ziekenhuis heel veel ontwikkelingskansen gekregen. In overleg met prof. dr. Kluytmans begon ik aan mijn promotieonderzoek en ondertussen heb ik ook de opleiding tot adviseur infectiepreventie gevolgd. Ook voor de toekomst zijn er perspectieven. Het vak infectiepreventie groeit en daarnaast worden vanuit de zorgkern Infectiepreventie steeds meer studies geïnitieerd.’

Onderzoek naar resistentiebeleid

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In haar onderzoek keek ze naar de aanwezigheid en verspreiding van resistente microorganismen en de relatie met antibioticagebruik. ‘We hebben de juistheid van antibioticagebruik gemeten op het niveau van de individuele patiënt. Hierdoor konden risicofactoren worden aangewezen die geassocieerd bleken te zijn met een onjuist gebruik. Vooral het antibioticum ciprofloxacine bleek frequent onjuist en onterecht te worden gebruikt. De resistentie tegen dit antibioticum steeg de laatste jaren ook sterk.’ Willemsen legt uit dat het mooie van haar onderzoek is dat het een verbeterproject is. Interventies gericht op het verbeteren van het ciprofloxacinegebruik waren effectief en hadden ook effect op de stijgende trend in de resistentie. ‘Minder gebruik leidt voor de patiënt tot een verminderde kans op complicaties en kortere opnameduur, terwijl het ziekenhuis kosten bespaart als er minder antibiotica worden gebruikt. Op de dag van mijn promotie heb ik hierover ’s morgens al een interview gehad dat op de radio werd uitgezonden en het NOS-journaal haalde. Het is een actueel onderwerp. Binnen Europa doen we het goed qua antibioticabeleid, maar het kan altijd nog beter. Een aanzienlijk deel van de voorgeschreven antibiotica wordt namelijk onterecht toegediend of er is een beter alternatief.’

Resistente bacteriën Willemsen geeft aan dat het Amphia Ziekenhuis bekendstaat om het restrictieve antibioticagebruik. ‘Daar zijn we aan te herkennen als je de getallen op een rijtje zet. Mijn advies voor collegae in Nederland is dan ook om eens goed naar het antibioticabeleid te kijken. Er valt vast nog wel wat te verbeteren. Daarnaast hoop ik dat het antibioticagebruik buiten het ziekenhuis, in de eerste lijn maar ook in de veterinaire sector, onder controle komt. Ik eet zelf geen vlees, maar dat deed ik ook al niet voor bekend werd dat bijna alle kip besmet is met resistente bacteriën.’ Een van de onderzoeken uit het promotieonderzoek van Willemsen is de TRIANGLestudie. Dit is een onderzoek naar de spreiding van bijzonder resistente gramnegatieve bacteriën in achttien ziekenhuizen. ‘De naam TRIANGLe symboliseert de driehoek tussen


antibiotica, verspreiding en resistentie’, legt Willemsen uit. ‘Uit dit onderzoek bleek dat de verspreiding van de aanwezige bijzonder resistente bacteriën onder controle was, mede door het strenge infectiepreventiebeleid. We zitten dus op de goede weg.’

Een ander aandachtsgebied: onderzoek naar MRSA ‘Veel van onze onderzoeken leiden tot praktische resultaten. Bijvoorbeeld het onderzoek naar verspreiding van MRSA op de polikliniek. Aanleiding hiervoor was de vee-gerelateerde MRSA. Van oudsher komen in dit ziekenhuis veel varkenshouders. En al deze patiënten moesten onder strikte isolatiemaatregelen gezien worden op de polikliniek. Spreekkamers moesten nadien gereinigd en gedesinfecteerd worden. Als er toch een patiënt zonder isolatiemaatregelen gezien werd op de poli en die bleek achteraf MRSA-positief te zijn, moesten alle contacten getest worden om een mogelijke verspreiding op te sporen. Uit een retrospectieve analyse van alle contactonderzoeken bleek dat er in 7 jaar nooit een besmetting was gevonden. Naar aanleiding hiervan is besloten dat mensen behorende tot de MRSA-risicogroep op de polikliniek niet meer in strikte isolatie hoeven, voor hen ook wel zo prettig. Het personeel wordt twee keer per jaar onderzocht en daarbij zijn geen aanwijzingen voor besmetting op de polikliniek gevonden. Het ziet ernaar uit dat ons onderzoek gaat leiden tot een landelijke richtlijn.’ Ze voegt toe dat er meerdere projecten lopen binnen de zorgkern Infectiepreventie die door ZonMW en andere overheidsinstanties worden gesubsidieerd.

Protocollen en infectieregistratie Een ander belangrijk onderdeel van het werk van hygiënisten is het schrijven van protocollen voor ziekenhuisafdelingen. ‘Wij bemoeien ons echt overal mee. Voorbeelden zijn reiniging en desinfectie van apparatuur, oppervlakten of lichaamsdelen, bouwwerkzaamheden, isolatiemaatregelen, hygiënisch handelen op de operatiekamer, ingebruikname nieuwe apparatuur. Voor de Da Vinci-robot van zorgkern Urologie hebben wij een infectieregistratie opgestart, waarbij we iedere behandelde patiënt onderzoeken op postoperatieve infecties. Zo houd je een vinger aan de pols bij nieuwe ontwikkelingen.’

Kerngegevens Laboratorium Microbiologie en Infectiepreventie • 4 artsen-microbiologen: P.H.J. van Keulen, prof. dr. J.A.J.W. Kluytmans, dr. J. H. Marcelis, mw. dr. G.J. van Hooydonk (chef de clinique) • buitengewoon staflid: dr. M.F. Peeters • 2 consultants infectiepreventie: mw. drs. M.M.L. van Rijen, mw. dr. L.E. Willemsen • 4 adviseurs infectiepreventie: H.P.M. Coertjens, mw. A.B. Moen, mw. Y.J.A.M. Hendriks, mw. V.A.T.C. Weterings • 1 adviseur infectiepreventie in opleiding: mw. C.M. van Leest • 3 assistenten in opleiding


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• CAM-studie: Onderzoek naar onbekende risico’s voor MRSA-infecties. We zien steeds vaker patiënten met MRSA in het ziekenhuis die niet tot een van de bekende risicogroepen behoren. Als nieuwe onbekende risico’s gevonden worden is het mogelijk hier gericht op te screenen bij binnenkomst in het ziekenhuis. • VET-studie: Onderzoek naar het voorkomen van MRSA-kolonisatie bij dierenartsen en de mate van verspreiding naar gezinsleden. • POM-studie: Onderzoek naar het voorkomen van MRSA-kolonisatie bij varkenshouders en de mate van verspreiding naar gezinsleden. Tevens wordt virulentie van veegerelateerde MRSA vergeleken met de virulentie van de niet-veegerelateerde MRSA. • SoM-studie: In deze studie wordt onderzocht of ESBL-gekoloniseerde patiënten in contactisolatie op een eenpersoonskamer of op een meerpersoonskamer verpleegd moeten worden, met als uitkomstmaat de mate van verspreiding op een zorgkern. • CAPITA-studie: Dit is een externe studie gecoördineerd vanuit het Julius Centrum waarin de effectiviteit van een pneumokokkenvaccinatie wordt onderzocht. • Accomplish-studie: Dit is een externe interventiestudie gecoördineerd vanuit het Erasmus Medisch Centrum waarin de relatie tussen handhygiëne en de prevalentie van ziekenhuisinfecties wordt onderzocht. • I MIND studie: Dit is een interventie studie waarin gestreefd wordt naar het verbeteren van de handhygiëne compliance onder ziekenhuismedewerkers. Meegenomen is het effect van de verhoogde handhygiëne compliance op het voorkomen van kruistransmissie tussen patiënten.

Samenvattingen gepubliceerde artikelen Oostdijk EA, de Smet AM, Blok HE, Thieme Groen ES, van Asselt GJ, Benus RF, Bernards SA, Frenay IH, Jansz AR, de Jongh BM, Kaan JA, Leverstein-van Hall MA, Mascini EM, Pauw W, Sturm PD, Thijsen SF, Kluytmans JA, Bonten MJ. Ecological effects of selective decontamination on resistant gram-negative bacterial colonization. Am J Respir Crit Care Med. 2009 Dec 3. [Epub ahead of print]. RATIONALE: Selective Digestive tract Decontamination (SDD) and Selective Oropharyngeal Decontamination (SOD) eradicate Gram-negative bacteria (GNB) from the intestinal en respiratory tract in intensive-care-unit (ICU) patients, but its effect on antibiotic resistance remains controversial. OBJECTIVES: We quantified the effects of SDD and SOD on bacterial ecology in 13 ICUs that participated in a study, in which SDD, SOD or standard care was used during consecutive periods of 6 months (NEJM 2009;360:20). METHODS: Point prevalence surveys of rectal and respiratory samples were performed once monthly in all patients in ICU (receiving or not receiving SOD/SDD). Effects of SDD on rectal and of SDD/SOD on respiratory tract carriage with GNB were determined by comparing results from consecutive point prevalence surveys


during intervention (6 months for SDD and 12 months for SDD/SOD) to consecutive point prevalence data in the pre- and post-intervention periods. MEASUREMENTS AND MAIN RESULTS: During SDD average proportions of patients with intestinal colonization with GNB resistant to either ceftazidime, tobramycin or ciprofloxacin were 5%, 7% and 7%, and increased to 15%, 13% and 13% post-intervention (p<0.05). During SDD/SOD resistance levels in the respiratory tract were /=10% for all three antibiotics post-intervention (p<0.05). CONCLUSION: SOD and SDD have marked effects on the bacterial ecology in an ICU with rising ceftazidime resistance prevalence rates in the respiratory tract during intervention and a considerable rebound effect of ceftazidime resistance in the intestinal tract after discontinuation of SDD. PMID: 19965807 [PubMed – indexed for MEDLINE]

Kluytmans JA. Methicillin-resistant Staphylococcus aureus in food products: cause for concern or case for complacency? Clin Microbiol Infect. 2010 Jan;16(1):11-5. The widespread use of antimicrobial agents, in combination with insufficient infection control measures, is the main driver of the current pandemic of antimicrobial resistance in human pathogens. The use of antimicrobials in food animal production also contributes, because resistant organisms and resistance genes can spread from animals to humans by direct contact or through the food chain. An important, traditionally human, pathogen, methicillin-resistant Staphylococcus aureus (MRSA), is currently endemic in many hospitals around the world and has also emerged in the community. Recently, a new reservoir of MRSA has been identified in food production animals and people in contact with these animals. This involves a specific clone, multilocus sequence type 398 (ST398), which has spread extensively among animals. ST398 has also been found in up to 11.9% of retail meat samples in several surveys from different parts of the world, posing a potential threat to human health. PMID: 20002686 [PubMed - indexed for MEDLINE]

Bode LG, Kluytmans JA, Wertheim HF, Bogaers D, Vandenbroucke-Grauls CM, Roosendaal R, Troelstra A, Box AT, Voss A, van der Tweel I, van Belkum A, Verbrugh HA, Vos MC. Preventing surgical-site infections in nasal carriers of Staphylococcus aureus. N Engl J Med. 2010 Jan 7;362(1):9-17. BACKGROUND: Nasal carriers of Staphylococcus aureus are at increased risk for health careassociated infections with this organism. Decolonization of nasal and extranasal sites on hospital admission may reduce this risk. METHODS: In a randomized, double-blind, placebocontrolled, multicenter trial, we assessed whether rapid identification of S. aureus nasal carriers by means of a real-time polymerase-chain-reaction (PCR) assay, followed by treatment with


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mupirocin nasal ointment and chlorhexidine soap, reduces the risk of hospital-associated S. aureus infection. RESULTS: From October 2005 through June 2007, a total of 6771 patients were screened on admission. A total of 1270 nasal swabs from 1251 patients were positive for S. aureus. We enrolled 917 of these patients in the intention-to-treat analysis, of whom 808 (88.1%) underwent a surgical procedure. All the S. aureus strains identified on PCR assay were susceptible to methicillin and mupirocin. The rate of S. aureus infection was 3.4% (17 of 504 patients) in the mupirocin-chlorhexidine group, as compared with 7.7% (32 of 413 patients) in the placebo group (relative risk of infection, 0.42; 95% confidence interval [CI], 0.23 to 0.75). The effect of mupirocin-chlorhexidine treatment was most pronounced for deep surgical-site infections (relative risk, 0.21; 95% CI, 0.07 to 0.62). There was no significant difference in all-cause in-hospital mortality between the two groups. The time to the onset of nosocomial infection was shorter in the placebo group than in the mupirocin-chlorhexidine group (P=0.005). CONCLUSIONS: The number of surgical-site S. aureus infections acquired in the hospital can be reduced by rapid screening and decolonizing of nasal carriers of S. aureus on admission. (Current Controlled Trials number, ISRCTN56186788.) 2010 Massachusetts Medical Society

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Comment in: Future Microbiol. 2010 May;5(5):701-3; N Engl J Med. 2010 Jan 7;362(1):75-7; N Engl J Med. 2010 Apr 22;362(16):1541; author reply 1542-4; N Engl J Med. 2010 Apr 22; 362(16):1540; author reply 1542-3; N Engl J Med. 2010 Apr 22;362(16):1540-1; author reply 1542-3; Ann Intern Med. 2010 May 18;152(10):JC5-9. PMID: 20054045 [PubMed - indexed for MEDLINE]

Van Cleef BA, Broens EM, Voss A, Huijsdens XW, Züchner L, Van Benthem BH, Kluytmans JA, Mulders MN, Van De Giessen AW. High prevalence of nasal MRSA carriage in slaughterhouse workers in contact with live pigs in The Netherlands. Epidemiol Infect. 2010 May;138(5):756-63. Epub 2010 Feb 9. Livestock-associated MRSA has been found in various animals, livestock farmers and retail meat. This study aimed to determine the prevalence and determinants of nasal MRSA carriage in pig slaughterhouse workers. Three large pig slaughterhouses in The Netherlands were studied in 2008 using human and environmental samples. The overall prevalence of nasal MRSA carriage in employees of pig slaughterhouses was 5.6% (14/249) (95% CI 3.4-9.2) and working with live pigs was the single most important factor for being MRSA positive (OR 38.2, P<0.0001). At the start of the day MRSA was only found in environmental samples from the lairages (10/12), whereas at the end of the day MRSA was found in the lairages (11/12), the dirty (5/12) and clean (3/12) areas and green offal (1/3). The MRSA status of the environmental samples correlated well with the MRSA status of humans working in these sections (r=0.75). In conclusion, a high prevalence of nasal MRSA carriage was found in pig-slaughterhouse workers, and working with live pigs is the most important risk factor. Exact transmission routes from


animals to humans remain to be elucidated in order to enable application of targeted preventive measures. PMID: 20141647 [PubMed - indexed for MEDLINE]

Bosch T, de Neeling AJ, Schouls LM, van der Zwaluw KW, Kluytmans JA, Grundmann H, Huijsdens XW. PFGE diversity within the methicillin-resistant Staphylococcus aureus clonal lineage ST398. BMC Microbiol. 2010 Feb 9;10:40. BACKGROUND: Livestock has recently been identified as a new reservoir of methicillin-resistant Staphylococcus aureus (MRSA). Most isolates belong to ST398 and are non-typeable with PFGE using SmaI, making it difficult to study transmission and outbreaks. Therefore, a new PFGE using Cfr9I, a neoschizomer of SmaI was optimized and evaluated to investigate ST398 isolates. RESULTS: After optimizing and evaluating the Cfr9I PFGE, clear and reproducible banding patterns were obtained from all previously non-typeable MRSA (NT(SmaI) -MRSA) isolates. The PFGE patterns of ST398 isolates showed more diversity than with spa-typing and/or MLST. The PFGE results showed diversity within and between the two most prevalent spa-types of NT(SmaI) -MRSA (t011 and t108). No match was found, when comparing banding patterns of the NT(SmaI) -MRSA with 700 different PFGE types, obtained with SmaI digestion, in our database of more than 4000 strains. Furthermore, possible transmission among veterinarians and their family members was investigated and an outbreak of ST398 MRSA in a residential care facility was confirmed with the Cfr9I PFGE. CONCLUSIONS: The adjusted PFGE can be used as a method for selecting important and distinct ST398 isolates for further research. The adjustments in the PFGE protocol using Cfr9I are easy to implement to study the ST398 clonal lineage in laboratories which already have a PFGE facility. PMID: 20144202 [PubMed - indexed for MEDLINE] PMCID: PMC2850908

Jager MM, Murk JL, Pique R, Wulf MW, Leenders AC, Buiting AG, Bogaards JA, Kluytmans JA, Vandenbroucke-Grauls CM. Prevalence of carriage of meticillin-susceptible and meticillin-resistant Staphylococcus aureus in employees of five microbiology laboratories in The Netherlands. J Hosp Infect. 2010 Mar;74(3):292-4. Epub 2010 Feb 10. PMID: 20149482 [PubMed - indexed for MEDLINE]

Verkade EJ, Verhulst CJ, Huijsdens XW, Kluytmans JA. In vitro activity of tigecycline against methicillin-resistant Staphylococcus aureus, including livestock-associated strains. Eur J Clin Microbiol Infect Dis. 2010 May;29(5):503-7. Epub 2010 Feb 26.


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The in vitro activity of tigecycline was determined using a well-defined collection of methicillinresistant Staphylococcus aureus (MRSA) isolates (n = 202), including 33 livestock-associated strains. Susceptibility testing was performed using the Etest system. Among the 202 MRSA strains, three (1.5%) had a minimum inhibitory concentration (MIC) value for tigecycline greater than 0.5 mg/l, which are considered to be resistant. When these strains were tested using Iso-Sensitest medium, the MICs were substantially lower and no resistance was found. This discrepancy warrants further investigations into the preferred test conditions for tigecycline. In conclusion, tigecycline showed good activity against MRSA strains in vitro. PMID: 20186450 [PubMed - indexed for MEDLINE] PMCID: PMC2854363

Van Cleef BA, Verkade EJ, Wulf MW, Buiting AG, Voss A, Huijsdens XW, van Pelt W, Mulders MN, Kluytmans JA. Prevalence of livestock-associated MRSA in communities with high pig-densities in The Netherlands. PLoS One. 2010 Feb 25;5(2):e9385. BACKGROUND: Recently, livestock-associated methicillin-resistant Staphylococcus aureus CC398

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has been discovered in animals, livestock farmers and retail meat. This cross-sectional study aimed to determine the spread to persons not in direct contact with livestock in areas with a high density of pig farms. METHODOLOGY/PRINCIPAL FINDINGS: With a random mailing in 3 selected municipalities in The Netherlands, adult persons were asked to fill in a questionnaire and to take a nose swab. In total, complete information was obtained on 583 persons. Of the 534 persons without livestock-contact, one was positive for MRSA (0.2%; 95% confidence interval, <0.01-1.2). Of the 49 persons who did indicate to be working at or living on a livestock farm, 13 were positive for MRSA (26.5%; 95% confidence interval, 16.1-40.4). All spa-types belonged to CC398. CONCLUSIONS/SIGNIFICANCE: Livestock-associated MRSA has a high prevalence in people with direct contact with animals. At this moment it has not spread from the farms into the community. PMID: 20195538 [PubMed - indexed for MEDLINE] PMCID: PMC2828479

Wassenberg MW, Kluytmans JA, Box AT, Bosboom RW, Buiting AG, van Elzakker EP, Melchers WJ, van Rijen MM, Thijsen SF, Troelstra A, Vandenbroucke-Grauls CM, Visser CE, Voss A, Wolffs PF, Wulf MW, van Zwet AA, de Wit GA, Bonten MJ. Rapid screening of methicillin-resistant Staphylococcus aureus using PCR and chromogenic agar: a prospective study to evaluate costs and effects. Clin Microbiol Infect. 2010 Dec;16(12):1754-61. Pre-emptive isolation of suspected methicillin-resistant Staphylococcus aureus (MRSA) carriers is considered essential for controlling the spread of MRSA, but noncolonized patients will be isolated unnecessarily as a result of a delay in diagnosis of 3-5 days with conventional cultures.


We determined costs per isolation day avoided, and incremental costs of rapid MRSA screening tests when added to conventional screening, but with decisions on isolation measures based on PCR results. A prospective multicentre study evaluating BD GeneOhm MRSA PCR (`IDI’) (BD Diagnostics, San Diego, CA, USA), Xpert MRSA (`GeneXpert’) (Cepheid, Sunnyvale, CA, USA) and chromogenic agar (MRSA-ID) (bioMérieux, Marcy-l’Etoile, France) was performed in 14 Dutch hospitals. Among 1764 patients at risk, MRSA prevalence was 3.3% (n=59). Duration of isolation was 19.7 and 16.1 h with IDI and GeneXpert, respectively, and would have been 30.0 and 76.2 h when based on chromogenic agar and conventional cultures, respectively. Negative predictive values (at a patient level) were 99.5%, 99.1% and 99.5% for IDI, GeneXpert and chromogenic agar, respectively. Numbers of isolation days were reduced by 60% and 47% with PCR-based and chromogenic agar-based screening, respectively. The cost per test was €56.22 for IDI, €69.62 for GeneXpert and €2.08 for chromogenic agar, and additional costs per extra isolation day were €26.34. Costs per isolation day avoided were €95.77 (IDI) and €125.43 (GeneXpert). PCR-based decision-making added €153.64 (IDI) and €193.84 (GeneXpert) per patient to overall costs and chromogenic testing would have saved €30.79 per patient. Rapid diagnostic testing safely reduces the number of unnecessary isolation days, but only chromogenic screening, and not PCR-based screening, can be considered as cost saving. © 2010 The Authors. Journal Compilation © 2010 European Society of Clinical Microbiology and Infectious Diseases. PMID: 20219077 [PubMed - in process]

Köck R, Becker K, Cookson B, van Gemert-Pijnen JE, Harbarth S, Kluytmans J, Mielke M, Peters G, Skov RL, Struelens MJ, Tacconelli E, Navarro Torné A, Witte W, Friedrich AW. Methicillin-resistant Staphylococcus aureus (MRSA): burden of disease and control challenges in Europe. Euro Surveill. 2010 Oct 14;15(41):19688. Methicillin-resistant Staphylococcus aureus (MRSA) isa major cause of healthcare- and community-associated infections worldwide. Within the healthcare setting alone, MRSA infections are estimated to affect more than 150,000 patients annually in the European Union (EU), resulting in attributable extra in-hospital costs of EUR 380 million for EU healthcare systems. Pan-European surveillance data on bloodstream infections show marked variability among EU Member States in the proportion of S. aureus that are methicillin-resistant, ranging from less than 1% to more than 50%. In the past five years, the MRSA bacteraemia rates have decreased significantly in 10 EU countries with higher endemic rates of MRSA infections. In addition to healthcare-associated infections, new MRSA strains have recently emerged as community and livestock-associated human pathogens in most EU Member States. The prevention and control of MRSA have therefore been identified as public health priorities in the EU. In this review, we describe the current burden of MRSA infections in healthcare and community settings across Europe and outline the main threats caused by recent changes in the


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epidemiology of MRSA. Thereby, we aim at identifying unmet needs of surveillance, prevention and control of MRSA in Europe. Erratum in: Euro Surveill. 2010;15(42). pii: 19694. PMID: 20961515 [PubMed - indexed for MEDLINE]

Willemsen I, van der Kooij T, van Benthem B, Wille J, Kluytmans J. Appropriateness of antimicrobial therapy: a multicentre prevalence survey in the Netherlands, 2008-2009. Euro Surveill. 2010 Nov 18;15(46). pii: 19715. A survey was carried out to determine the prevalence and appropriateness of antimicrobial therapy (AMT) in the Netherlands and to identify determinants for inappropriate AMT. Prevalence surveys of patients hospitalised in the Netherlands were performed three times in 2008 and 2009. Patients’ demographic, infection-related and AMT-related data were collected from hospital wards. A total of 19 hospitals participated, consisting of a mix of university, teaching and general hospitals, which were distributed evenly across the country. The appropriateness of AMT was assessed using a standardised algorithm based on local AMT prescription guidelines. A total of 7,853 patients were included, of which 2,327 (29.6%) patients

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were on AMT (range: 20.8–39.5%). In 372 patients (16% of patients on AMT), treatment was considered inappropriate. In 265 (11.4%) patients on AMT, appropriateness of treatment was not judged because of insufficient information. The percentage of patients without a judgment varied considerably between the participating hospitals (range: 1.3–36.2%). Appropriate AMT use was significantly associated with a patient being in an intensive care unit, having a central venous catheter and being given beta-lactamase-sensitive penicillins. The use of fluoroquinolones was significantly associated with more frequent inappropriate use. There was considerable and significant variation between the participating hospitals in the amount of antimicrobials prescribed and the appropriateness of their use. To improve the completeness and reliability of such surveys, there is a need for intensive training of observers and medical staff in recording information. PMID: 21144427 [PubMed - indexed for MEDLINE]

Budding AE, Vandenbroucke-Grauls CM, Melles DC, van Duijkeren E, Kluytmans JA, Savelkoul PH. Binary IS typing for Staphylococcus aureus. PLoS One. 2010 Oct 27;5(10): e13671. BACKGROUND: We present an easily applicable test for rapid binary typing of Staphylococcus aureus: binary interspace (IS) typing. This test is a further development of a previously described molecular typing technique that is based on length polymorphisms of the 16S-23S rDNA interspace region of S. aureus. METHODOLOGY/PRINCIPAL FINDINGS: A novel approach of IS-typing was performed in which binary profiles are created. 424 human and animal derived MRSA and MSSA isolates were tested and a subset of these isolates was compared with multi


locus sequence typing (MLST) and Amplified Fragment Length Polymorphism (AFLP). Binary IS typing had a high discriminatory potential and a good correlation with MLST and AFLP. CONCLUSIONS/SIGNIFICANCE: Binary IS typing is easy to perform and binary profiles can be generated in a standardized fashion. These two features, combined with the high correlation with MLST clonal complexes, make the technique applicable for large-scale inter-laboratory molecular epidemiological comparisons. PMID: 21060683 [PubMed - indexed for MEDLINE] PMCID: PMC2965118

Bonten MJ, Kluytmans J, Kulberg BJ. Carbapenemase-resistentie van gramnegatieve bacteriën. [Carbapenem resistance in gram-negative bacteria]. Ned Tijdschr Geneeskd. 2010;154:A1947. Antibiotic resistance poses a serious threat to the successful treatment of hospitalized patients. Micro-organisms that produce carbapenamases, such as Klebsiella pneumoniae carbapenamases (KPCs) represent the next step in the continuously emerging problem of antibiotic resistance. Restrictions on antibiotic use plus optimal adherence to infection control measures will be crucial to limit the spread of KPC in hospitals in the Netherlands in the coming years. PMID: 21029499 [PubMed - indexed for MEDLINE]

Kluytmans J, Vandenbroucke-Grauls C, van der Meer JW. Antibiotica-resistentie: maatregelen hoognodig. [Antibiotic resistance: measures urgently needed]. Ned Tijdschr Geneeskd. 2010;154:A2261. Antimicrobial resistance is increasing rapidly and there are hardly any new antimicrobial agents to be expected in the coming years. The number of patients affected by extended spectrum beta-lactamase producing organisms (ESBLs) is rising and there are strong indications that this is caused in part by the use of antimicrobial agents in animal husbandry. There are many arguments against the widespread use of antimicrobial agents in food-production animals, but this has not resulted in decreased usage so far. The current situation is critical and requires immediate action. In human healthcare the prescription of ‘rescue’ antibiotics, e.g. carbapenems, has to be restricted and controlled. In animal husbandry the use of antibiotics has to be reduced dramatically and a more sustainable approach to food production has to be supported by government and consumers. PMID: 20858324 [PubMed - indexed for MEDLINE]

Jongerden IP, de Smet AM, Kluytmans JA, te Velde LF, Dennesen PJ, Wesselink RM, Bouw MP, Spanjersberg R, Bogaers-Hofman D, van der Meer NJ, de Vries JW, Kaasjager K, van Iterson M, Kluge GH, van der Werf TS, Harinck HI, Bindels AJ, Pickkers P, Bonten MJ.


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Physicians’ and nurses’ opinions on selective decontamination of the digestive tract and selective oropharyngeal decontamination: a survey. Crit Care. 2010;14(4):R132. Epub 2010 Jul 13. INTRODUCTION: Use of selective decontamination of the digestive tract (SDD) and selective oropharyngeal decontamination (SOD) in intensive care patients has been controversial for years. Through regular questionnaires we determined expectations concerning SDD (effectiveness) and experience with SDD and SOD (workload and patient friendliness), as perceived by nurses and physicians. METHODS: A survey was embedded in a group-randomized, controlled, cross-over multicenter study in the Netherlands in which, during three 6-month periods, SDD, SOD or standard care was used in random order. At the end of each study period, all nurses and physicians from participating intensive care units received study questionnaires. RESULTS: In all, 1024 (71%) of 1450 questionnaires were returned by nurses and 253 (82%) of 307 by physicians. Expectations that SDD improved patient outcome increased from 71% and 77% of respondents after the first two study periods to 82% at the end of the study (P = 0.004), with comparable trends among nurses and physicians. Nurses considered SDD to impose a higher

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workload (median 5.0, on a scale from 1 (low) to 10 (high)) than SOD (median 4.0) and standard care (median 2.0). Both SDD and SOD were considered less patient friendly than standard care (medians 4.0, 4.0 and 6.0, respectively). According to physicians, SDD had a higher workload (median 5.5) than SOD (median 5.0), which in turn was higher than standard care (median 2.5). Furthermore, physicians graded patient friendliness of standard care (median 8.0) higher than that of SDD and SOD (both median 6.0). CONCLUSIONS: Although perceived effectiveness of SDD increased as the trial proceeded, both among physicians and nurses, SOD and SDD were, as compared to standard care, considered to increase workload and to reduce patient friendliness. Therefore, education about the importance of oral care and on the effects of SDD and SOD on patient outcomes will be important when implementing these strategies. TRIAL REGISTRATION: ISRCTN35176830. PMID: 20626848 [PubMed - indexed for MEDLINE] PMCID: PMC2945100

Cohen Stuart J, Leverstein-Van Hall MA; Dutch Working Party on the Detection of Highly Resistant Microorganisms.* [Kluytmans JA et al... ]. Guideline for phenotypic screening and confirmation of carbapenemases in Enterobacteriaceae. Int J Antimicrob Agents. 2010 Sep;36(3):205-10. Epub 2010 Jul 3. Adequate detection of carbapenemase-producing Enterobacteriaceae is crucial for infection control measures and appropriate choice of antimicrobial therapy. This guideline aims to improve the detection of carbapenemase-producing Enterobacteriaceae in the routine setting of clinical microbiology laboratories. Detection of carbapenemases in Enterobacteriaceae includes


a screening step followed by a genotypic and optional phenotypic confirmatory step. For all Enterobacteriaceae, the meropenem screening breakpoint to detect carbapenemases is set at >or=0.5mg/L or a zone diameter of or=2mg/L or a zone diameter
Andriesse GI, Donmez M, Vissers J, van Wijngaarden P. Acute hepatitis, maar niet A, B, of C: overweeg E. Ned Tijdschr Geneeskd. 2010 Aug 21;154(33):1536-1539. OBJECTIVE: To determine the percentage of hepatitis E virus (HEV) infections in serum samples from patients with negative serology for hepatitis A, B and C and to find out what may be the harmful consequences of a missed diagnosis of acute HEV infection. DESIGN: Retrospective study. METHOD: Serum samples were selected from patients with infectious hepatitis who tested negative for hepatitis A, B and C virus. Serum samples that had elevated alanine aminotransferase (ALT; > 34 U/l) were included in this study. All samples were then tested for HEV using an enzyme-linked immunosorbent assay (ELISA) and immunoblot assay. Of patients with serological evidence of acute HEV, files were checked for the originally documented diagnosis at hospital discharge. RESULTS: In the period October 2007-September 2008, 139 serum samples met the inclusion criteria. In 23 serum samples the ELISA was positive (IgM positive and/or Ig total positive); in 16/23 serum samples immunoblot assay was also positive. The percentage of confirmed HEV infections was 11.5% (16/139). In only one patient was the originally documented diagnosis correct. Several patients underwent invasive diagnostic procedures and treatment as a result of an incorrect diagnosis. CONCLUSION: Hepatitis E serology should be a standard tool in the diagnostic workup of infectious hepatitis patients in the Netherlands. PMID: 20735873 [PubMed - indexed for MEDLINE]


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Willemsen I, Cooper B, van Buitenen C, Winters M, Andriesse G, Kluytmans J. Improving quinolone use in hospitals by using a bundle of interventions in an interrupted time series analysis. Antimicrob Agents Chemother. 2010 Sep;54(9):3763-9. Epub 2010 Jun 28. The objectives of the present study were to determine the effects of multiple targeted interventions on the level of use of quinolones and the observed rates of resistance to quinolones in Escherichia coli isolates from hospitalized patients. A bundle consisting of four interventions to improve the use of quinolones was implemented. The outcome was measured from the monthly levels of use of intravenous (i.v.) and oral quinolones and the susceptibility patterns for E. coli isolates from hospitalized patients. Statistical analyses were performed using segmented regression analysis and segmented Poisson regression models. Before the bundle was implemented, the annual use of quinolones was 2.7 defined daily doses (DDDs)/100 patient days. After the interventions, in 2007, this was reduced to 1.7 DDDs/100 patient days. The first intervention, a switch from i.v. to oral medication, was associated with a stepwise reduction in i.v. quinolone use of 71 prescribed daily doses (PDDs) per month (95% confidence interval [CI] = 47 to 95 PDDs/month, P < 0.001). Intervention 2, introduction of a new antibiotic guideline and

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education program, was associated with a stepwise reduction in the overall use of quinolones (reduction, 107 PDDs/month [95% CI = 58 to 156 PDDs/month). Before the interventions the quinolone resistance rate was increasing, on average, by 4.6% (95% CI = 2.6 to 6.1%) per year. This increase leveled off, which was associated with intervention 2 and intervention 4, active monitoring of prescriptions and feedback. Trends in resistance to other antimicrobial agents did not change. This study showed that the hospital-wide use of quinolones can be significantly reduced by an active policy consisting of multiple interventions. There was also a stepwise reduction in the rate of quinolone resistance associated with the bundle of interventions. PMID: 20585135 [PubMed - indexed for MEDLINE] PMCID: PMC2934965

Complete publicatielijst Andriesse GI, Donmez M, Vissers J, van Wijngaarden P. Acute hepatitis, maar niet A, B, of C: overweeg E. Ned Tijdschr Geneeskd. 2010 Aug 21;154(33):1536-1539. Kluytmans J, Vandenbroucke-Grauls C, van der Meer JW. Antibiotica-resistentie: maatregelen hoognodig. [Antibiotic resistance: measures urgently needed]. Ned Tijdschr Geneeskd. 2010;154:A2261. Willemsen I, van der Kooij T, van Benthem B, Wille J, Kluytmans J. Appropriateness of antimicrobial therapy: a multicentre prevalence survey in the Netherlands, 2008-2009. Euro Surveill. 2010 Nov 18;15(46). pii: 19715. Kluytmans J, Murk J. Bacitracin and Gramicidin. In: Kucers’ The Use of Antibiotics, 6th ed. ISBN: 9780340927670. Chapter 77:975-979.


Kluytmans J. Beschouwing pandemie van Nieuwe Influenza-A-virus (H1N1). Ned. Tijdschrif Med Microbiol. 2010;18:8-9. Budding AE, Vandenbroucke-Grauls CM, Melles DC, van Duijkeren E, Kluytmans JA, Savelkoul PH. Binary IS typing for Staphylococcus aureus. PLoS One. 2010 Oct 27;5(10):e13671. Bonten MJ, Kluytmans J, Kulberg BJ. Carbapenemase-resistentie van gramnegatieve bacteriën. [Carbapenem resistance in gram-negative bacteria]. Ned Tijdschr Geneeskd. 2010;154:A1947. Oostdijk EA, de Smet AM, Blok HE, Thieme Groen ES, van Asselt GJ, Benus RF, Bernards SA, Frenay IH, Jansz AR, de Jongh BM, Kaan JA, Leverstein-van Hall MA, Mascini EM, Pauw W, Sturm PD, Thijsen SF, Kluytmans JA, Bonten MJ. Ecological effects of selective decontamination on resistant gram-negative bacterial colonization. Am J Respir Crit Care Med. 2009 Dec 3. [Epub ahead of print]. Van Etten J, van Osch P, van Keulen PHJ, Bruggeling WAJ. Eerste beschrijving van endocarditis door Cardiobacterium hominis in Nederland: een case report. Hartbulletin. feb 2010;41(1):8-11.Cohen Stuart J, Leverstein-Van Hall MA; Dutch Working Party on the Detection of Highly Resistant Microorganisms.* [Kluytmans JA et al... ]. Guideline for phenotypic screening and confirmation of carbapenemases in Enterobacteriaceae. Int J Antimicrob Agents. 2010 Sep;36(3):205-10. Epub 2010 Jul 3. Van Cleef BA, Broens EM, Voss A, Huijsdens XW, Züchner L, Van Benthem BH, Kluytmans JA, Mulders MN, Van de Giessen AW. High prevalence of nasal MRSA carriage in slaughterhouse workers in contact with live pigs in The Netherlands. Epidemiol Infect. 2010 May;138(5):756-63. Epub 2010 Feb 9. Willemsen I, Cooper B, van Buitenen C, Winters M, Andriesse G, Kluytmans J. Improving quinolone use in hospitals by using a bundle of interventions in an interrupted time series analysis. Antimicrob Agents Chemother. 2010 Sep;54(9):3763-9. Epub 2010 Jun 28. Verkade EJ, Verhulst CJ, Huijsdens XW, Kluytmans JA. In vitro activity of tigecycline against methicillin-resistant Staphylococcus aureus, including livestock-associated strains. Eur J Clin Microbiol Infect Dis. 2010 May;29(5):503-7. Epub 2010 Feb 26. Kluytmans J, Murk J. Lincomycin and Clindamycin. In: Kucers’ The Use of Antibiotics, 6th ed. ISBN: 9780340927670. Chapter 79:987-1007. Kluytmans JA. Methicillin-resistant Staphylococcus aureus in food products: cause for concern or case for complacency? Clin Microbiol Infect. 2010 Jan;16(1):11-5. Köck R, Becker K, Cookson B, van Gemert-Pijnen JE, Harbarth S, Kluytmans J, Mielke M, Peters G, Skov RL, Struelens MJ, Tacconelli E, Navarro Torné A, Witte W, Friedrich AW. Methicillin-resistant Staphylococcus aureus (MRSA): burden of disease and control challenges in Europe. Euro Surveill. 2010 Oct 14;15(41):19688.


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Ammerlaan H, Kluytmans J. Methicillin-resistant Staphylococcus aureus (MRSA) colonization. In: Infection Diseases, 3rd ed. ISBN: 978-0-323-04579-7. vol. 1, Chapter 36:769-771 . Kluytmans J, Murk J. Mupirocin. In: Kucers’ The Use of Antibiotics sixth edition. ISBN: 9780340927670. Chapter 78:980-986. Bosch T, de Neeling AJ, Schouls LM, van der Zwaluw KW, Kluytmans JA, Grundmann H, Huijsdens XW. PFGE diversity within the methicillin-resistant Staphylococcus aureus clonal lineage ST398. BMC Microbiol. 2010 Feb 9;10:40. Jongerden IP, de Smet AM, Kluytmans JA, te Velde LF, Dennesen PJ, Wesselink RM, Bouw MP, Spanjersberg R, Bogaers-Hofman D, van der Meer NJ, de Vries JW, Kaasjager K, van Iterson M, Kluge GH, van der Werf TS, Harinck HI, Bindels AJ, Pickkers P, Bonten MJ. Physicians’ and nurses’ opinions on selective decontamination of the digestive tract and selective oropharyngeal decontamination: a survey. Crit Care. 2010;14(4):R132. Epub 2010 Jul 13. Jager MM, Murk JL, Pique R, Wulf MW, Leenders AC, Buiting AG, Bogaards JA, Kluytmans JA, Vandenbroucke-Grauls CM. Prevalence of carriage of meticillin-susceptible and meticillin-resistant Staphylococcus aureus in employees of five microbiology laboratories in The Netherlands. J Hosp Infect. 2010 Mar;74(3):292-4. Epub 2010 Feb 10. Van Cleef BA, Verkade EJ, Wulf MW, Buiting AG, Voss A, Huijsdens XW, van Pelt W, Mulders MN, Kluytmans JA. Prevalence of livestock-associated MRSA in communities with high pig-densities in The Netherlands. PLoS One. 2010 Feb 25;5(2):e9385. Bode LG, Kluytmans JA, Wertheim HF, Bogaers D, Vandenbroucke-Grauls CM, Roosendaal R, Troelstra A, Box AT, Voss A, van der Tweel I, van Belkum A, Verbrugh HA, Vos MC. Preventing surgical-site infections in nasal carriers of Staphylococcus aureus. N Engl J Med. 2010 Jan 7;362(1):9-17. Wassenberg MW, Kluytmans JA, Box AT, Bosboom RW, Buiting AG, van Elzakker EP, Melchers WJ, van Rijen MM, Thijsen SF, Troelstra A, Vandenbroucke-Grauls CM, Visser CE, Voss A, Wolffs PF, Wulf MW, van Zwet AA, de Wit GA, Bonten MJ. Rapid screening of methicillin-resistant Staphylococcus aureus using PCR and chromogenic agar: a prospective study to evaluate costs and effects. Clin Microbiol Infect. 2010 Dec;16(12):1754-61.


Longgeneeskunde Veelbelovend onderzoek naar onder meer asbestkanker

Bijzonder bij de zorgkern Longgeneeskunde is het aantal aandachtsgebieden. Superspecialistische spreekuren zijn in ontwikkeling. Ook levert de zorgkern een grote bijdrage aan onderzoek naar de diverse vormen van longkanker. Dr. Joachim G.J.V. Aerts geeft aan dat het onderzoek zich steeds meer richt op het immuunsysteem. In het Amphia Ziekenhuis is voor COPD-patiënten een superspecialistisch spreekuur in voorbereiding. Voor mensen met slaapapneu is in Oosterhout een speciale slaapkliniek en ook in de behandeltechnieken bij mensen met longkanker heeft het ziekenhuis een regiofunctie. Alle behandelingen kunnen worden uitgevoerd en zeker op het gebied van longkanker is veel expertise aanwezig.

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Immuunsysteem ‘De trend in de aanpak van kanker in het algemeen en ook van longkanker is aan het veranderen’, opent Aerts. ‘Er gaat steeds meer aandacht naar het immuunsysteem. We zijn ons gaan afvragen: waarom krijgt iemand niet overal kanker, maar in één specifiek gebied? Wat is er anders aan die cellen waardoor het daar fout gaat? Blijkbaar wordt op die plek de afweer voor de gek gehouden, waardoor het misgaat. Op meerdere manieren. De ene cel maakt allerlei stofjes aan waardoor er geen antireactie op gang komt bij de afweercellen. De andere cel schermt zichzelf af waardoor hij zich niet bekendmaakt aan het immuunsysteem. Daardoor kan de tumor groeien. Dat brengt je tot de gedachte dat er iets moet zijn wat je kunt doen om dat afweersysteem te versterken, slimmer te maken. Die belangstelling voor het immuunsysteem is heel recent. We weten nog niet genoeg en zijn volop onderzoek aan het doen. Bijvoorbeeld: welke typen cellen spelen een rol bij welke soort kanker en kun je door beïnvloeding van die cel zorgen dat een bepaalde behandeling beter werkt?’

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Aerts stuurt een landelijk onderzoek aan waarin het Amphia Ziekenhuis participeert. ‘Daarbij verzamelen we van heel veel longkankerpatiënten bloed en bestuderen dat op afweerremmende cellen. We onderzoeken of we die kunnen beïnvloeden met een bepaald soort chemotherapie. We zijn nu nog in het verzamel-en-volgstadium, pas later kunnen we gaan sturen met de chemo. Maar een en ander ziet er nu al veelbelovend uit.’ Aerts vult aan dat de bepalingen plaatsvinden in het Erasmus Ziekenhuis, waar hij ook in deeltijd aangesteld is als associate professor. ‘Daar is een groot laboratorium waar we samen met een bioloog allerlei onderzoek verrichten. Vanuit het Amphia Ziekenhuis worden heel veel patiënten geïncludeerd. Overigens werken we als ziekenhuizen onderling steeds meer samen, ook met de Universiteit van Tilburg hebben we afspraken gemaakt over samenwerking.’

Asbestkanker Over het onderzoek van longarts en wetenschapscoördinator Aerts naar asbestkanker (mesothelioom) is breed gepubliceerd, onder andere in De Telegraaf. ‘Juist van asbestkankercellen is bekend dat ze het immuunsysteem heel erg voor de gek houden. De tumor schermt zichzelf af waardoor hij niet herkend wordt. Het lichaam weet niet dat de tumor er is en ontwikkelt geen afweerreactie. We hebben bij mensen tumorcellen weggehaald en kapotgemaakt en bij mensen voorloper-afweercellen uit het bloed gehaald en die in contact gebracht met die kapotgemaakte tumorcellen, zodat ze buiten het lichaam geleerd werd om tegen die tumor een reactie te maken. Bij inspuiting van die cellen is inderdaad een reactie ontstaan. Eigenlijk ontwikkel je zo een vaccin tegen asbestkanker. Dit is een heel nieuwe techniek, die we voor het eerst in de wereld hebben


gedaan. Er is nog verder onderzoek nodig om te kijken hoe gunstig het voor mensen werkt. Het vervolgtraject is te kijken of we kunnen voorkomen dat tumorcellen stofjes afgeven aan het bloed en dan vervolgens gaan we die reacties uitlokken.’ Ook dit is een multicenteronderzoek.

Het belang van onderzoek ‘Over het algemeen is de prognose bij longkanker niet goed’, stelt Aerts. ‘Toch vind ik het een prachtig vakgebied, want de dingen die je bij patiënten bereikt, zijn zeer waardevol. We zijn voor 75 procent met palliatieve behandelingen bezig en voor 25 procent curatief. Daarbij zie je de nieuwe methoden en nieuwe medicatiemogelijkheden toenemen, waardoor mensen steeds langer blijven leven. Daarom is onderzoek zo belangrijk én het samenwerken daarbij tussen perifere en academische ziekenhuizen. Dit jaar zijn er zes promovendi begeleid en onze maatschap creëert bewust ruimte voor onderzoek.’

Promotieonderzoek naar verschillen in normaal en kwaadaardig weefsel In 2010 promoveerde assistent in opleiding Cor (K.H.) van der Leest op een beeldvormingsonderzoek naar diagnostiek met reflectiespectroscopie en PET-scans bij patiënten met longkanker. Het onderzoek vond plaats in het Erasmus en in het Amphia Ziekenhuis. Dr. van der Leest legt uit hoe reflectiespectroscopie werkt. ‘Als je licht schijnt op longweefsel, dan wordt een deel gereflecteerd en een deel geabsorbeerd. Het gereflecteerde licht wordt door de spectrometer gehaald en als je de mate van de reflectie uitzet in de golflengte dan krijg je een patroon waaruit je informatie kunt halen. Zoals het zuurstofgehalte (de saturatie), de vaatdiameter en de bloedvolumefractie.’ Van der Leest vertelt dat de techniek is ontdekt in het Erasmus bij de zorgkern Radiotherapie, Center for Optical Diagnostics and Therapy. ‘Mijn voorganger was met het onderzoek begonnen en is erop gepromoveerd onder begeleiding van dr. J.G. Aerts in het Franciscus Gasthuis Rotterdam. Daaruit bleek dat het zuurstofgehalte in kwaadaardig weefsel lager was. Ik ben daarop doorgegaan en heb gekeken naar verschillende typen tumoren binnen het longcarcinoom. Er bleken inderdaad verschillen te zijn. Toen dr. Aerts naar het Amphia Ziekenhuis ging, ben ik meegegaan om samen het onderzoek voort te zetten.’

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Lymfeklieren ‘Daarnaast hebben we iets nieuws gedaan, namelijk in lymfeklieren gekeken. Bij een vergelijking tussen normale en kwaadaardige lymfeklieren bleek ook verschil in bloedvolumefractie en zuurstofsaturatie. Mensen met longkanker hebben vaak vergrote klieren, maar op grond van een CT-scan kun je niet zeggen of een vergrote klier ook een kwaadaardige klier is, want er kan ook een ontsteking zitten. Het is erg belangrijk om wel te weten of het kwaadaardig is, vanwege de behandeling. Gewoonlijk moet je de klier aanprikken om te kijken of er kwaadaardige cellen zijn. Met onze techniek is het mogelijk meer informatie te verkrijgen over de klier en zou je beter de waarschijnlijkheid van maligniteit kunnen inschatten.’ Van der Leest plaatst een kanttekening bij het onderzoek. ‘We hebben normale kleine klieren afgezet tegen vergrote kwaadaardige klieren. De volgende stap zou moeten zijn dat je vergrote normale klieren tegen vergrote kwaadaardige klieren afzet. Dus eigenlijk staat het onderzoek nog in de kinderschoenen.’ Feit is wel dat het onderzoek duidelijke resultaten opleverde, al heeft het nog geen consequenties voor de huidige behandelingstechnieken. ‘Het is een begin en we hebben erover gepubliceerd in The Journal of Thoracic Oncology.’ Van der Leest is bij het Amphia Ziekenhuis in opleiding voor longziektespecialist. Inmiddels solliciteerde hij bij het Erasmus Ziekenhuis om ook daar een deel van de opleiding te doen. Hij koos voor longziekten omdat hij de longen een bijzonder orgaan vindt, waarbij veel verschillende behandelingen worden toegepast. ‘COPD- en oncologiebehandelingen, maar ook infectiologie en de behandeling van auto-immuunziekten.’


Innovatie en opleiding Van der Leest beschrijft dat het Amphia Ziekenhuis een grote zorgkern Longgeneeskunde heeft, met drie onderdelen die alle standaardzorg leveren. ‘Opvallend, omdat je het niet in alle ziekenhuizen ziet, is de niet-invasieve beademing op de zorgkern. Ten tweede is hier een speciale zorgkern met alleen oncologiepatiënten voor chemokuren en voor de behandeling van complicaties. Bovendien is er ook een zorgkern voor patiënten na longchirurgie.’ Innovatief vindt hij de EUS- en EBUS-technieken om longweefsel te vergaren. Via deze technieken kan kanker in de lymfeklieren worden opgespoord en dat is van belang voor het opsporen van longkanker. De afkorting staat voor endoscopic ultrasound/endobronchial ultrasound. Bij het onderzoek wordt endoscopie of bronchoscopie gecombineerd met een echo-onderzoek. Als opleidingsziekenhuis beschrijft hij het Amphia als ‘groot’. ‘Dat heeft voor- en nadelen. Voordeel is dat er veel dingen gebeuren. Er is veel productie, veel patiënten, dus je ziet veel. Om een beeld te geven: als opleidingseis moet je honderd bronchoscopieën in je hele opleiding hebben gedaan. Die heb ik in het eerste jaar al gedaan… Van thoracoscopieën moet je er vijf doen tijdens de opleiding. Ik deed er zes in het eerste jaar, terwijl ze daar in academische ziekenhuizen bij wijze van spreken voor moeten vechten om dat rond te krijgen. Een nadeel is dat je vooral de standaardpathologie ziet en voor de echte ‘witte raven’ moet je toch naar een academisch ziekenhuis. Het is niet voor niets dat de opleiding altijd in beide ziekenhuistypen plaatsvindt.’ Verder beschrijft Van der Leest zijn opleidingsplaats als: ‘Een heel leuke maatschap, met veel ruimte voor verantwoordelijkheden, een laagdrempelig overleg en een prettige sfeer.’

Kerngegevens zorgkern Longgeneeskunde • 9 longartsen: dr. J.G.J.V. Aerts, J. Asin, T.A. Bantje, H.N.A. Belderbos, R.S. Djamin, dr. M.J.J.H. Grootenboers, A.M. Janssens, V.M.J. Linsen, N.C. van Walree • 1 chef de clinique • 5 assistenten in opleiding • 4 assistenten niet in opleiding • subspecialismen: astma en allergologie, COPD, interstitiële longziekten, longkanker, slaapapneu en niet-invasieve (masker)thuisbeademing

Samenvattingen gepubliceerde artikelen Hegmans JP, Veltman JD, Lambers ME, de Vries IJ, Figdor CG, Hendriks RW, Hoogsteden HC, Lambrecht BN, Aerts JG. Consolidative dendritic cell-based immunotherapy elicits cytotoxicity against malignant mesothelioma. Am J Respir Crit Care Med. 2010 Feb 18. [Epub ahead of print]

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RATIONALE: We previously demonstrated that dendritic cell-based immunotherapy induced protective antitumor immunity with a prolonged survival rate in mice. However, the clinical relevance is still in question. To examine this, we designed a clinical trial using chemotherapy followed by antigen-pulsed dendritic cell vaccination in mesothelioma patients. OBJECTIVES: The aim of this study was to assess the safety and immunological response induced by the administration of tumor lysate-pulsed dendritic cells in patients with mesothelioma. METHODS: Ten patients with malignant pleural mesothelioma received three vaccinations of clinicalgrade autologous dendritic cells intradermally and intravenously at 2-week intervals after chemotherapy. Each vaccine was composed of 50 x 10(6) mature dendritic cells pulsed with autologous tumor lysate and keyhole limpet hemocyanin (KLH) as surrogate marker. Delayedtype hypersensitivity activity to tumor antigens and KLH was assessed, both in vivo and in vitro. Peripheral blood mononuclear cells during the treatment were analyzed for immunological responses. MEASUREMENTS AND MAIN RESULTS: Administration of dendritic cells pulsed with autologous tumor lysate in patients with mesothelioma was safe with moderate fever as the only side effect. There were no grade 3 or 4 toxicities associated with the vaccines or any evidence of autoimmunity. Local accumulations of infiltrating T cells were found at the site

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of vaccination. The vaccinations induced distinct immunological responses to KLH, both in vitro and in vivo. Importantly, after three vaccinations, cytotoxic activity against autologous tumor cells was detected in a subgroup of patients. CONCLUSIONS: This study demonstrated that autologous tumor lysate-pulsed dendritic cell-based therapy is feasible, well-tolerated, and capable of inducing immunological response to tumor cells in mesothelioma patients. Clinical trial registered with www.clinicaltrials.gov (NCT00280982). PMID: 20167848 [PubMed - indexed for MEDLINE]

Surmont V, Smit EF, de Jonge M, Aerts JG, Nackaerts K, Vernhout R, Gras J, Van Wijk A, Phernambucq EC, van Meerbeeck JP, Senan S, Kraaij CJ, Chouaki N, Praag J, van Klaveren RJ. Pemetrexed and cisplatin with concurrent radiotherapy for locally advanced non-small cell and limited disease small cell lung cancer: Results from 2 phase I studies. Lung Cancer. 2010 Sep;69(3):302-6. Epub 2010 Jan 22. BACKGROUND: The objectives were to determine the maximum tolerated dose (MTD) of pemetrexed and cisplatin with concurrent radiotherapy. Secondary objectives include incidence and nature of acute and late toxicities, tumor response and overall survival. PATIENTS AND METHODS: Treatment naïve patients received 1 cycle of cisplatin 80mg/m(2) in study I (stage III NSCLC), 75mg/m(2) in study II (LD-SCLC) and pemetrexed 500mg/m(2) before the phase I part. In study I, patients were treated in cohorts with escalating cisplatin doses (60-80mg/m(2)), pemetrexed doses (400-500mg/m(2)) and concurrent escalating radiotherapy doses (66Gy in 33-27 fractions). In study II, patients were treated with cisplatin 75mg/m(2) and escalating pemetrexed doses (400-500mg/m(2)) with concurrent escalating radiotherapy doses (50-62Gy).


RESULTS: The trials closed prematurely: study I because of poor accrual, study II because of sponsor decision. Thirteen patients were treated: 4 with NSCLC, 9 with LD-SCLC. No doselimiting toxicity was observed. There was no grade 4 toxicity, grade 3 hematological toxicity was mild. One patient developed grade 3 acute esophagitis, but was able to complete radiotherapy without delay. Two patients experienced grade 2 late pulmonary toxicity, 1 complete response, 6 partial responses and 1 progressive disease were observed. CONCLUSIONS: Although the studies stopped too early to assess MTD, we have demonstrated that the combination of cisplatin and pemetrexed with concurrent radiotherapy up to 66Gy (33x2Gy) is well tolerated and this new combination shows activity in NSCLC. Pemetrexed is the first 3rd generation cytotoxic found to be tolerable at full dose with concurrent radiotherapy. Copyright © 2009 Elsevier Ireland Ltd. All rights reserved. PMID: 20096951 [PubMed - as supplied by publisher]

Kanick SC, van der Leest C, Aerts JG, Hoogsteden HC, Kascáková S, Sterenborg HJ, Amelink A. Integration of single-fiber reflectance spectroscopy into ultrasound-guided endoscopic lung cancer staging of mediastinal lymph nodes. J Biomed Opt. 2010 Jan-Feb;15(1):017004. We describe the incorporation of a single-fiber reflectance spectroscopy probe into the endoscopic ultrasound fine-needle aspiration (EUS-FNA) procedure utilized for lung cancer staging. A mathematical model is developed to extract information about the physiological and morphological properties of lymph tissue from single-fiber reflectance spectra, e.g., microvascular saturation, blood volume fraction, bilirubin concentration, average vessel diameter, and Mie slope. Model analysis of data from a clinical pilot study shows that the singlefiber reflectance measurement is capable of detecting differences in the physiology between normal and metastatic lymph nodes. Moreover, the clinical data show that probe manipulation within the lymph node can perturb the in vivo environment, a concern that must be carefully considered when developing a sampling strategy. The data show the feasibility of this novel technique; however, the potential clinical utility has yet to be determined. PMID: 20210478 [PubMed - indexed for MEDLINE]

Tournoy KG, Bolly A, Aerts JG, Pierard P, De Pauw R, Leduc D, Leloup A, Pieters T, Slabbynck H, Janssens A, Carron K, Schrevens L, Pat K, De Keukeleire T, Dooms C. The value of endoscopic ultrasound after bronchoscopy to diagnose thoracic sarcoidosis. Eur Respir J. 2010 Jun;35(6):1329-35. Epub 2009 Nov 6. A clinicoradiological presentation of thoracic sarcoidosis requires histopathology in order to establish the diagnosis. Flexible bronchoscopy has a reasonable diagnostic yield and is the procedure of first choice for diagnosis. Endoscopic ultrasound (endoscopic ultrasound-guided

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fine needle aspiration/endobronchial ultrasound-guided transbronchial needle aspiration) can help in the diagnosis of sarcoidosis. An implementation strategy of endoscopic ultrasound for the diagnosis of sarcoidosis following negative flexible bronchoscopy results was examined prospectively in 15 clinics. A total of 137 patients (92 males; median age 43 yrs) were included, and sarcoidosis was found in 115 (84%). Alternative diagnoses were tuberculosis, lymphangitis carcinomatosa, pneumoconiosis and alveolitis. All patients were sent for flexible bronchoscopy, which was performed in 121 (88%), resulting in a definite diagnosis in 57 (42%). A total of 80 patients were sent for endoscopic ultrasound, which could be performed in 72 (90%), yielding a definite diagnosis in 47 (59%). Endoscopic ultrasound following negative flexible bronchoscopy avoided a surgical procedure in 47 out of 80 patients. The sensitivity of flexible bronchoscopy for sarcoidosis was 45% (95% confidence interval 35-54%), but 62% (50-72%) if biopsy specimens were taken. The sensitivity of endoscopic ultrasound following negative flexible bronchoscopy results was 71% (58-82%). With this strategy, 97 out of 115 (84% (76-90%)) of proven sarcoidosis was diagnosed using endoscopy. This large prospective implementation study (trial number NCT00888212; ClinicalTrials.gov) shows that endoscopic ultrasound is valuable for diagnosing sarcoidosis after negative flexible bronchoscopy results.

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PMID: 19897553 [PubMed - indexed for MEDLINE]

Surmont V, Aerts JG, van Klaveren RJ, Tournoy K, Tan KY, Vernhout RM, Schmitz PI, Legrand C, Hoogsteden HC, van Meerbeeck JP. A randomized phase II study comparing two schedules of the 21-day regimen of gemcitabine and carboplatin in advanced non-small cell lung cancer. Oncology. 2010;78(3-4):267-70. Epub 2010 Jun 7. PURPOSE: Carboplatin area under the curve (AUC) 5 ml/min on day 1 with gemcitabine 1,250 mg/m(2) on day 1 and day 8 is a widely used regimen in advanced non-small cell lung cancer. Grade 3-4 thrombocytopenia and neutropenia are frequent. The aim of this study is to investigate whether toxicity of gemcitabine/carboplatin could be reduced by administering carboplatin on day 8 instead of day 1 without a decrease in response rate (RR). METHODS: Patients received gemcitabine 1,250 mg/m(2) on days 1 and 8, carboplatin AUC 5 on day 1 (arm A) or day 8 (arm B). Drugs were administered over a 21-day cycle. Toxicity and RR were evaluated weekly and every second cycle, respectively. RESULTS: 71 patients were enrolled into the study. We found 79% (95% CI 61-91%) grade 3-4 toxicity (neutropenia and thrombocytopenia) in arm A and 50% (95% CI 32-68%) in arm B; 66% grade 3-4 thrombocytopenia in arm A and 26% in arm B. We observed 30% grade 4 hematological toxicity in arm A and 3% in arm B. In arm A an overall RR of 20% (95% CI 7.7-38.6%) was seen, and 18.2% (95% CI 7-35.5%) in arm B. CONCLUSIONS: Although the study was prematurely closed, the current data are of interest. The schedule with carboplatin on day 8 is associated with substantially lower grade 3-4 neutropenia and thrombocytopenia with comparable dose intensity and RR. Copyright 2010 S. Karger AG, Basel. PMID: 20523087 [PubMed - indexed for MEDLINE]


Veltman JD, Lambers ME, van Nimwegen M, de Jong S, Hendriks RW, Hoogsteden HC, Aerts JG, Hegmans JP. Low-dose cyclophosphamide synergizes with dendritic cell-based immunotherapy in antitumor activity. J Biomed Biotechnol. 2010;2010:798467. Epub 2010 May 23. Clinical immunotherapy trials like dendritic cell-based vaccinations are hampered by the tumor’s offensive repertoire that suppresses the incoming effector cells. Regulatory T cells are instrumental in suppressing the function of cytotoxic T cells. We studied the effect of lowdose cyclophosphamide on the suppressive function of regulatory T cells and investigated if the success rate of dendritic cell immunotherapy could be improved. For this, mesothelioma tumor-bearing mice were treated with dendritic cell-based immunotherapy alone or in combination with low-dose of cyclophosphamide. Proportions of regulatory T cells and the cytotoxic T cell functions at different stages of disease were analyzed. We found that low-dose cyclophosphamide induced beneficial immunomodulatory effects by preventing the induction of Tregs, and as a consequence, cytotoxic T cell function was no longer affected. Addition of cyclophosphamide improved immunotherapy leading to an increased median and overall survival. Future studies are needed to address the usefulness of this combination treatment for mesothelioma patients. PMID: 20508851 [PubMed - in process] PMCID: PMC2874992

Kant KM, Noordhoek Hegt V, Aerts JG. A patient with four-year survival after nonsmall cell lung carcinoma with a solitary metachronous small bowel metastasis. J Oncol. 2010;2010:616130. Epub 2010 Mar 7. Solitary small bowel metastasis secondary to lung cancer is very uncommon. In this report, we present a patient with NSCLC and a metachronous solitary metastasis of the jejunum. She is alive without evidence of disease and doing well four years after palliative surgery, radiotherapy, and chemotherapy. To the best of our knowledge, this is the first case report describing a prolonged survival in a patient with a symptomatic solitary small bowel metastasis treated with palliative surgery, chemo- and radiotherapy instead of complete surgical resection. PMID: 20224647 [PubMed - in process] PMCID: PMC2833307

Veltman JD, Lambers ME, van Nimwegen M, Hendriks RW, Hoogsteden HC, Hegmans JP, Aerts JG. Zoledronic acid impairs myeloid differentiation to tumour-associated macrophages in mesothelioma. Br J Cancer. 2010 Aug 24;103(5):629-41. Epub 2010 Jul 27.

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BACKGROUND: Suppressive immune cells present in tumour microenvironments are known to augment tumour growth and hamper efficacy of antitumour therapies. The aminobisphosphonate Zoledronic acid (ZA) is considered as an antitumour agent, as recent studies showed that ZA prolongs disease-free survival in cancer patients. The exact mechanism is a topic of debate; it has been suggested that ZA targets tumour-associated macrophages (TAMs). METHODS: We investigate the role of ZA on the myeloid differentiation to TAMs in murine mesothelioma in vivo and in vitro. Mice were intraperitoneally inoculated with a lethal dose of mesothelioma tumour cells and treated with ZA to determine the effects on myeloid differentiation and survival. RESULTS: We show that ZA impaired myeloid differentiation. Inhibition of myeloid differentiation led to a reduction in TAMs, but the number of immature myeloid cells with myeloid-derived suppressor cell (MDSC) characteristics was increased. In addition, ZA affects the phenotype of macrophages leading to reduced level of TAM-associated cytokines in the tumour microenvironment. No improvement of survival was observed. CONCLUSION: We conclude that ZA leads to a reduction in macrophages and impairs polarisation towards an M2 phenotype, but this was associated with an increase in the number of immature myeloid cells, which might diminish the effects of ZA on survival.

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PMID: 20664588 [PubMed - indexed for MEDLINE] PMCID: PMC2938257

Kanick SC, van der Leest C, Djamin RS, Janssens AM, Hoogsteden HC, Sterenborg HJ, Amelink A, Aerts JG. Characterization of mediastinal lymph node physiology in vivo by optical spectroscopy during endoscopic ultrasound-guided fine needle aspiration. J Thorac Oncol. 2010 Jul;5(7):981-7. INTRODUCTION: Esophageal endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) is a minimally invasive staging procedure for mediastinal lymph nodes in patients diagnosed with lung cancer. But, a substantial false negative rate necessitates that patients returning a negative EUS-FNA result must undergo a subsequent surgical staging procedure. This study incorporates a fiberoptic reflectance spectroscopy device into the EUS-FNA procedure to asses the vascular physiology within the sampled lymph node. The aims of this pilot study were to determine the feasibility of incorporating a reflectance spectroscopy device into the EUSFNA clinical procedure and to gather preliminary information about the vascular physiology within the center of normal and metastatic lymph nodes. METHODS: This study included 10 patients with proven or suspected lung cancer and an indication for EUS-FNA. The procedure was performed on seven normal (unenlarged, positron emission tomography negative) nodes and seven suspicious (enlarged, positron emission tomography positive), with the malignant status of all nodes cytologically confirmed. Reflectance spectra were acquired using a single optical fiber that fits through the end of the EUS-FNA biopsy needle, with an outer fiber diameter of 0.38 mm. RESULTS: The procedure was successfully performed and did not introduce


complications. Model-based analysis of single fiber reflectance spectra provided quantitative information about the vascular physiology within the sampled lymph node. We observed that metastatic lymph nodes were characterized by lower microvascular oxygen saturation (50% versus 84%, p < 0.01) and lower blood volume fraction (5.6% versus 13.5%, p < 0.01) than normal nodes. CONCLUSIONS: Single fiber reflectance spectroscopy has the potential to detect abnormal lymph node physiology. PMID: 20593548 [PubMed - indexed for MEDLINE]

Veltman JD, Lambers ME, van Nimwegen M, Hendriks RW, Hoogsteden HC, Aerts JG, Hegmans JP. COX-2 inhibition improves immunotherapy and is associated with decreased numbers of myeloid-derived suppressor cells in mesothelioma. Celecoxib influences MDSC function. BMC Cancer. 2010 Aug 30;10:464. BACKGROUND: Myeloid-derived suppressor cells (MDSC) are a heterogeneous population of immature cells that accumulates in tumour-bearing hosts. These cells are induced by tumourderived factors (e.g. prostaglandins) and have a critical role in immune suppression. MDSC suppress T and NK cell function via increased expression of arginase I and production of reactive oxygen species (ROS) and nitric oxide (NO). Immune suppression by MDSC was found to be one of the main factors for immunotherapy insufficiency. Here we investigate if the in vivo immunoregulatory function of MDSC can be reversed by inhibiting prostaglandin synthesis by specific COX-2 inhibition focussing on ROS production by MDSC subtypes. In addition, we determined if dietary celecoxib treatment leads to refinement of immunotherapeutic strategies. METHODS: MDSC numbers and function were analysed during tumour progression in a murine model for mesothelioma. Mice were inoculated with mesothelioma tumour cells and treated with cyclooxygenase-2 (COX-2) inhibitor celecoxib, either as single agent or in combination with dendritic cell-based immunotherapy. RESULTS: We found that large numbers of infiltrating MDSC co-localise with COX-2 expression in those areas where tumour growth takes place. Celecoxib reduced prostaglandin E2 levels in vitro and in vivo. Treatment of tumour-bearing mice with dietary celecoxib prevented the local and systemic expansion of all MDSC subtypes. The function of MDSC was impaired as was noticed by reduced levels of ROS and NO and reversal of T cell tolerance; resulting in refinement of immunotherapy. CONCLUSIONS: We conclude that celecoxib is a powerful tool to improve dendritic cell-based immunotherapy and is associated with a reduction in the numbers and suppressive function of MDSC. These data suggest that immunotherapy approaches benefit from simultaneously blocking cyclooxygenase-2 activity. PMID: 20804550 [PubMed - indexed for MEDLINE] PMCID: PMC2939552

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Kant KM, Noordhoek Hegt V, Aerts JG. A patient with four-year survival after nonsmall cell lung carcinoma with a solitary metachronous small bowel metastasis. J Oncol. 2010;2010:616130. Epub 2010 Mar 7. Surmont V, Aerts JG, van Klaveren RJ, Tournoy K, Tan KY, Vernhout RM, Schmitz PI, Legrand C, Hoogsteden HC, van Meerbeeck JP. A randomized phase II study comparing two schedules of the 21-day regimen of gemcitabine and carboplatin in advanced nonsmall cell lung cancer. Oncology. 2010;78(3-4):267-70. Epub 2010 Jun 7. Kant KM, Djamin RS, Belderbos HNA. Acute respiratoire insufficientie op basis van COPD: To be ventilated or not to be ventilated. A en I: nascholingstijdschrift voor perioperatieve geneeskunde. 2010 maart;2(1). Kanick SC, van der Leest C, Djamin RS, Janssens AM, Hoogsteden HC, Sterenborg HJ, Amelink A, Aerts JG. Characterization of mediastinal lymph node physiology in vivo by optical spectroscopy during endoscopic ultrasound-guided fine needle aspiration. J Thorac Oncol. 2010 Jul;5(7):981-7. Hegmans JP, Veltman JD, Lambers ME, de Vries IJ, Figdor CG, Hendriks RW, Hoogsteden HC, Lambrecht BN, Aerts JG. Consolidative dendritic cell-based immunotherapy elicits cytotoxicity against malignant mesothelioma. Am J Respir Crit Care Med. 2010 Feb 18. [Epub ahead of print] Veltman JD, Lambers ME, van Nimwegen M, Hendriks RW, Hoogsteden HC, Aerts JG, Hegmans JP. COX-2 inhibition improves immunotherapy and is associated with decreased numbers of myeloid-derived suppressor cells in mesothelioma. Celecoxib influences MDSC function. BMC Cancer. 2010 Aug 30;10:464. Hou J, Aerts JG, den Hamer B, van IJcken W, den Bakker M, Riegman P, van der Leest C, van der Spek P, Foekens JA, Hoogsteden HC, Grosveld F, Philipsen S. Gene expressionbased classification of non-small cell lung carcinomas and survival prediction. PLoS One. 2010 Apr 22;5(4):e10312. Kanick SC, van der Leest C, Aerts JG, Hoogsteden HC, Kascáková S, Sterenborg HJ, Amelink A. Integration of single-fiber reflectance spectroscopy into ultrasound-guided endoscopic lung cancer staging of mediastinal lymph nodes. J Biomed Opt. 2010 JanFeb;15(1):017004. Veltman JD, Lambers ME, van Nimwegen M, de Jong S, Hendriks RW, Hoogsteden HC, Aerts JG, Hegmans JP. Low-dose cyclophosphamide synergizes with dendritic cellbased immunotherapy in antitumor activity. J Biomed Biotechnol. 2010;2010:798467. Epub 2010 May 23. Aerts JGJV, van Walree NC. Moleculaire diagnostiek en longkanker. Bulletin. 2010 nov;34:15-17. Surmont V, Smit EF, de Jonge M, Aerts JG, Nackaerts K, Vernhout R, Gras J, Van Wijk A, Phernambucq EC, van Meerbeeck JP, Senan S, Kraaij CJ, Chouaki N, Praag J, van


Klaveren RJ. Pemetrexed and cisplatin with concurrent radiotherapy for locally advanced non-small cell and limited disease small cell lung cancer: Results from 2 phase I studies. Lung Cancer. 2010 Sep;69(3):302-6. Epub 2010 Jan 22. Tournoy KG, Bolly A, Aerts JG, Pierard P, De Pauw R, Leduc D, Leloup A, Pieters T, Slabbynck H, Janssens A, Carron K, Schrevens L, Pat K, De Keukeleire T, Dooms C. The value of endoscopic ultrasound after bronchoscopy to diagnose thoracic sarcoidosis. Eur Respir J. 2010 Jun;35(6):1329-35. Epub 2009 Nov 6. Veltman JD, Lambers ME, van Nimwegen M, Hendriks RW, Hoogsteden HC, Hegmans JP, Aerts JG. Zoledronic acid impairs myeloid differentiation to tumour-associated macrophages in mesothelioma. Br J Cancer. 2010 Aug 24;103(5):629-41. Epub 2010 Jul 27.

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Neurologie Kerngegevens zorgkern Neurologie • 10 neurologen: R. van Dijl, dr. P.M.M. van Erven, R.J. de Graaf, H.B.M. van Lieshout, M.J.M. Remmers, dr. E.A.C.M. Sanders, J-P.M. Stroy, H.B.C. Verbiest, dr. J.E. Visser, dr. J.C.M. Zijlmans • 2 neuroloog/kinderneurologen: mw. dr. I.A.W. Kotsopoulos, mw. dr. J.F. de Rijk-van Andel • 7 assistenten niet in opleiding • subspecialisme: kinderneurologie

Samenvattingen gepubliceerde artikelen Jinnah HA, Ceballos-Picot I, Torres RJ, Visser JE, Schretlen DJ, Verdu A, Laróvere LE, Chen CJ, Cossu A, Wu CH, Sampat R, Chang SJ, de Kremer RD, Nyhan W, Harris JC, Reich SG, Puig JG; for the Lesch-Nyhan Disease International Study Group. Attenuated variants of Lesch-Nyhan disease. Brain 2010;133:671-689. Epub Feb 22. Lesch-Nyhan disease is a neurogenetic disorder caused by deficiency of the enzyme hypoxanthine-guanine phosphoribosyltransferase. The classic form of the disease is described by a characteristic syndrome that includes overproduction of uric acid, severe generalized dystonia, cognitive disability and self-injurious behaviour. In addition to the classic disease, variant forms of the disease occur wherein some clinical features are absent or unusually mild. The current studies provide the results of a prospective and multi-centre international study focusing on neurological manifestations of the largest cohort of Lesch-Nyhan disease variants evaluated to date, with 46 patients from 3 to 65 years of age coming from 34 families. All had evidence for overproduction of uric acid. Motor abnormalities were evident in 42 (91%), ranging from subtle clumsiness to severely disabling generalized dystonia. Cognitive function was affected in 31 (67%) but it was never severe. Though none exhibited self-injurious behaviours,

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many exhibited behaviours that were maladaptive. Only three patients had no evidence of neurological dysfunction. Our results were compared with a comprehensive review of 78 prior reports describing a total of 127 Lesch-Nyhan disease variants. Together these results define the spectrum of clinical features associated with hypoxanthine-guanine phosphoribosyltransferase deficiency. At one end of the spectrum are patients with classic Lesch-Nyhan disease and the full clinical phenotype. At the other end of the spectrum are patients with overproduction of uric acid but no apparent neurological or behavioural deficits. Inbetween are patients with varying degrees of motor, cognitive, or behavioural abnormalities. Recognition of this spectrum is valuable for understanding the pathogenesis and diagnosis of all forms of hypoxanthineguanine phosphoribosyltransferase deficiency. PMID: 20176575 [PubMed - as supplied by publisher]

Zijlmans JC. The role of imaging in the diagnosis of vascular parkinsonism. Neuroimaging Clin N Am. 2010 Feb;20(1):69-76. Parkinsonism is a syndrome that features bradykinesia (slowness of the initiation of voluntary

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movement) and at least 1 of the following conditions: rest tremor, muscular rigidity, or postural instability. Criteria for the clinical diagnosis of vascular parkinsonism (VP) have been proposed, which are derived from a postmortem examination study. Computed tomography and magnetic resonance imaging can support this clinical diagnosis with positive imaging findings. Dopamine transporter single-photon emission computed tomography may also be of help to distinguish VP from Parkinson disease and other parkinsonisms. PMID: 19959019 [PubMed - indexed for MEDLINE]

Jahanshahi M, Jones CR, Zijlmans J, Katzenschlager R, Lee L, Quinn N, Frith CD, Lees AJ. Dopaminergic modulation of striato-frontal connectivity during motor timing in Parkinson’s disease. Brain. 2010 Mar;133(Pt 3):727-45. Patients with Parkinson’s disease experience motor and perceptual timing difficulties, which are ameliorated by dopaminergic medication. We investigated the neural correlates of motor timing in Parkinson’s disease, including the effects of dopaminergic medication on patterns of brain activation. Eight patients with Parkinson’s disease and eight healthy controls were scanned with H(15)(2)O positron emission tomography while engaged in three tasks: synchronization (right index finger tapping in synchrony with a tone presented at 1 Hz), continuation (tapping at 1 Hz in the absence of a tone), and a control simple reaction time task. During the first 6 scans, the patients were assessed after overnight withdrawal of medication. Scans 7-12 were completed with the patients in the ‘ON’ state, after injections of apomorphine, a dopamine receptor agonist. For the healthy controls, relative to the control reaction time task, motor timing (synchronization + continuation) was associated with significantly greater activation in


left medial prefrontal cortex (Brodmann area 10, 32), right hippocampus, bilateral angular gyrus (Brodmann area 39), left posterior cingulate (Brodmann area 31) and left nucleus accumbens/ caudate. This pattern of brain activation during motor timing was not observed for patients, who showed significantly greater activation in bilateral cerebellum, right thalamus and left midbrain/substantia nigra compared to the control participants. Relative to the externally-paced synchronization task, the internally controlled continuation task was associated with greater activation in the dorsolateral prefrontal cortex (Brodmann area 46/9) in both the control and Parkinson’s disease groups. Analysis of medication-related effects indicated that cortical activation was significantly more predominant during motor timing when the patients were ‘ON’ medication, whereas pallidal and cerebellar activations were evident ‘OFF’ medication. Effective connectivity analysis established that activity in the left caudate nucleus was associated with increased activity in the right lentiform nucleus and cerebellum ‘OFF’ medication, and with increased activity in the prefrontal cortex ‘ON’ medication. These results suggest that in Parkinson’s disease, in the ‘OFF’ medication state, excessive inhibitory pallidal outflow is associated with a lack of adequate frontal activation and reliance on the cerebellum for motor timing. In contrast, our results establish for the first time that administration of dopaminergic medication increases striatal-frontal connectivity between the caudate nucleus and prefrontal cortex during motor timing. PMID: 20305278 [PubMed - indexed for MEDLINE]

Visser WA, Kolling JB, Groen GJ, Tetteroo E, van Dijl R, Rosseel PM, van der Meer NJ. Persistent cortical blindness after a thoracic epidural test dose of bupivacaine. Anesthesiology. 2010 Feb;112(2):493-5. Thoracic epidural anesthesia is considered as an essential component of the perioperative care for patients undergoing lung resection. Although neurologic adverse events have been associated with this technique, permanent injury is rare. These events primarily involve the peripheral nervous system; for example, nerve root injury. We present a case of persistent cortical blindness after a test dose of bupivacaine was administered into an uneventfully placed thoracic epidural catheter. PMID: 20068456 [PubMed - indexed for MEDLINE]

De Stefano N, Filippi M, Confavreux C, Vermersch P, Simu M, Sindic C, Hupperts R, Bajenaru O, Edan G, Grimaldi L, Marginean I, Medaer R, Orefice G, Pascu I, Pelletier J, Sanders E, Scarpini E, Mancardi GL. The results of two multicenter, open-label studies assessing efficacy, tolerability and safety of protiramer, a high molecular weight synthetic copolymeric mixture, in patients with relapsing-remitting multiple sclerosis. Mult Scler. 2009 Feb;15(2):238-43. Epub 2008 Nov 5.

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OBJECTIVE: Two pilot studies were conducted to evaluate safety, tolerability, and efficacy of two doses of Protiramer (TV-5010) in patients with relapsing-remitting multiple sclerosis. BACKGROUND: Both glatiramer acetate and TV-5010 are synthetic copolymers comprised the same four amino acids in a defined molar ratio. TV-5010 has higher average molecular weight than Glatiramer acetate and might be hypothesized that glatiramoids with higher molecular weight might be more immunoreactive than lower molecular weight peptides, thus increasing therapeutic potential and allowing for less frequent dosing. METHODS: In the two separate studies, after a 10 week pretreatment period, TV-5010 was given subcutaneously once weekly at 15 mg and 30 mg for 36 weeks. The primary end point was a reduction in the number of magnetic resonance imaging active lesions (i.e., T1-weigthed gadolinium-enhancing and new T2-weighted lesions) between the pretreatment period and the end of study. RESULTS: Both TV-5010 doses were generally well tolerated. The treatment with TV-5010 at a dose of 15 mg/wk did not show any significant effect. In contrast, in patients treated with at a dose of 30 mg/wk, a significant reduction in the mean number of gadolinium-enhancing (-58.8%; P = 0.0013) and new T2-W (-50%; P = 0.0002) lesions was observed. However, a large decrease in the mean number of both gadolinium-enhancing (-55%) and new T2-W (-40%) lesions during the

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pretreatment period made difficult the interpretation of the efficacy assessments. CONCLUSIONS: Further studies are needed to confirm these preliminary data on safety and efficacy of TV-5010 at a weekly dose of 30 mg. PMID: 18987103 [PubMed - indexed for MEDLINE]

Jongen PJ, Lehnick D, Sanders E, Seeldrayers P, Fredrikson S, Andersson M, Speck J; FOCUS study group*. Health-related quality of life in relapsing remitting multiple sclerosis patients during treatment with glatiramer acetate: a prospective, observational, international, multi-centre study. Health Qual Life Outcomes. 2010 Nov 15;8:133. BACKGROUND: Glatiramer acetate (GA) and interferon-beta (INFb) are first-line disease modifying drugs for relapsing remitting multiple sclerosis (RRMS). Treatment with INFb is associated with a significant increase in health-related quality of life (HR-QoL) in the first 12 months. It is not known whether HR-QoL increases during treatment with GA. METHODS: 197 RRMS patients, 106 without and 91 with prior immunomodulation/immunosuppression, were studied for HR-QoL (Leeds Multiple Sclerosis-QoL [LMS-QoL] scale, score range 0 - 32), fatigue (Fatigue Impact Scale [FIS]) and depressed mood (Beck Depression Inventory-Short Form [BDI-SF]) at baseline and 6 and 12 months after start of GA treatment. RESULTS: At 6 and 12 months mean LMS-QoL scores were significantly increased in the treatment-naive patient group (p < 0.001), not in the pre-treated group. At month 12 43% of treatment-naïve patients had improved HR-QoL (increase LMS-QoL score 3 or more points) (p < 0.001). Likewise, mean FIS scores were decreased at months 6 and 12 in the treatment-naïve group (p < 0.01), not in the pre-treated group. In both groups mean BDI-SF scores did not change. No demographic or


clinical baseline factor was predictive of HR-QoL increase. HR-QoL changes were zero to negative for patients who had discontinued GA before month 12 (28.4% of patients). CONCLUSIONS: In RRMS patients without prior immunomodulation/immunosuppression treatment with GA was associated with an increase in HR-QoL in the first 6 months, that was sustained at 12 months. In 4 out of 10 patients HR-QoL improved. Increase in HR-QoL was associated with decrease in fatigue. *Collaborators (40): Sanders, de Graaf, Temmink, van Dijl, Verbiest, Anten, Koeman, Strikwerda, Frequin, Baal, Heerema, Keyser, Heersema, Heerings, de Graaf, Dellemijn, Valkenburg, Hiel, Kornips, Breuer, Witjes, Driessen, Gijsbers, Baard, Berendes, Groeneveld, den Hartog, Schiphof, Schyns-Soeterboek, Keyser, Visser, Jongen, Andersson, Fredrikson, Martin, Svenningsson, Nilsson, Lycke, Dubois, Seeldrayers. PMID: 21078142 [PubMed - in process] PMCID: PMC2999586

Poewe W, Antonini A, Zijlmans JC, Burkhard PR, Vingerhoets F. Levodopa in the treatment of Parkinson’s disease: an old drug still going strong. Clin Interv Aging. 2010 Sep 7;5:229-38. 133 After more than 40 years of clinical use, levodopa (LD) remains the gold standard of symptomatic efficacy in the drug treatment of Parkinson’s disease (PD). Compared with other available dopaminergic therapies, dopamine replacement with LD is associated with the greatest improvement in motor function. Long-term treatment with LD is, however, often complicated by the development of various types of motor response oscillations over the day, as well as drug-induced dyskinesias. Motor fluctuations can be improved by the addition of drugs such as entacapone or monoamine oxidase inhibitors, which extend the half-life of levodopa or dopamine, respectively. However, dyskinesia control still represents a major challenge. As a result, many neurologists have become cautious when prescribing therapy with LD. This review summarizes the available evidence regarding the use of LD to treat PD and will also address the issue of LD delivery as a critical factor for the drug’s propensity to induce motor complications. PMID: 20852670 [PubMed - indexed for MEDLINE]

Visser JE, Oude Nijhuis LB, Janssen L, Bastiaanse CM, Borm GF, Duysens J, Bloem BR. Dynamic posturography in Parkinson’s disease: diagnostic utility of the “first trial effect”. Neuroscience. 2010 Jun 30;168(2):387-94. Epub 2010 Apr 7. Previous dynamic posturography studies demonstrated clear abnormalities in balance responses in Parkinson’s disease (PD) patients compared to controls at the group level, but its clinical value in the diagnostic process and fall risk estimation in individual patients leaves for improvement. Therefore, we investigated whether a new approach, focusing on the balance responses to the very first and fully unpractised trial rather than a pooled mean

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response to a series of balance perturbations, could further improve the diagnostic utility of dynamic posturography. Following the first trial, subjects were exposed to repeated balance perturbations, which also permitted us to investigate the training responses. Fourteen patients with PD and 18 age-matched controls were enrolled, who received a series of multidirectional postural perturbations, induced by support surface rotations. We measured trunk and upper arm kinematics and electromyographic responses, and evaluated group differences at three levels: the postural response to the very first backward perturbation; pooled first and habituated postural responses; and habituation rates. Analysis of the first trial responses yielded similar results as evaluation of the mean response over trials: forward flexion of the trunk induced by backward perturbations was decreased in patients, accompanied by increased muscle responses present. Moreover, trunk movement and muscle activity were equally present in both groupssuggesting a preserved training response in PD patients. Early masseter activity in both groups might be indicative of a startle-like component to the balance response. In terms of diagnostic utility, focusing on the first trial response or habituation rate is no better than analysis of pooled responses to a series of perturbations. The apparently preserved training response in PD patients suggests that balance reactions in PD can be improved by repeated exposure, and

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this may have implications for future exercise studies. Early masseter activity warrants further studies to evaluate a potential startle component in the pathophysiology of balance disorders. 2010. Published by Elsevier Ltd. PMID: 20381589 [PubMed - indexed for MEDLINE]

D Lau LM, Siepman DA, Remmers MJ, Terwindt GM, Hintzen RQ. Acute disseminating encephalomyelitis following legionnaires disease. Arch Neurol. 2010 May;67(5):623-6. OBJECTIVE: To describe 2 patients presenting with severe neurological deficits and extensive lesions on brain magnetic resonance imaging after having experienced Legionella pneumonia. DESIGN: Case reports. SETTING: University hospital. PATIENTS: Two patients who developed severe neurological symptoms, including encephalopathic signs, following Legionella infection, with widespread lesions on magnetic resonance imaging compatible with demyelination. RESULTS: After extensive ancillary investigations, a diagnosis of acute disseminating encephalomyelitis was considered most likely. Steroid therapy was initiated in 1 of the patients, followed by plasmapheresis. In both patients, clinical and radiological signs gradually recovered, with only slight residual deficits. CONCLUSION: In patients presenting with neurological symptoms after an episode of pneumonia, Legionella infection and a subsequent immunemediated process such as acute disseminating encephalomyelitis should be considered. PMID: 20457963 [PubMed - indexed for MEDLINE]

Willemsen MA, Verbeek MM, Kamsteeg EJ, de Rijk-van Andel JF, Aeby A, Blau N, Burlina A, Donati MA, Geurtz B, Grattan-Smith PJ, Haeussler M, Hoffmann GF, Jung H,


de Klerk JB, van der Knaap MS, Kok F, Leuzzi V, de Lonlay P, Megarbane A, Monaghan H, Renier WO, Rondot P, Ryan MM, Seeger J, Smeitink JA, Steenbergen-Spanjers GC, Wassmer E, Weschke B, Wijburg FA, Wilcken B, Zafeiriou DI, Wevers RA. Tyrosine hydroxylase deficiency: a treatable disorder of brain catecholamine biosynthesis. Brain. 2010 Jun;133(Pt 6):1810-22. Epub 2010 Apr 29. Tyrosine hydroxylase deficiency is an autosomal recessive disorder resulting from cerebral catecholamine deficiency. Tyrosine hydroxylase deficiency has been reported in fewer than 40 patients worldwide. To recapitulate all available evidence on clinical phenotypes and rational diagnostic and therapeutic approaches for this devastating, but treatable, neurometabolic disorder, we studied 36 patients with tyrosine hydroxylase deficiency and reviewed the literature. Based on the presenting neurological features, tyrosine hydroxylase deficiency can be divided in two phenotypes: an infantile onset, progressive, hypokinetic-rigid syndrome with dystonia (type A), and a complex encephalopathy with neonatal onset (type B). Decreased cerebrospinal fluid concentrations of homovanillic acid and 3-methoxy-4-hydroxyphenylethylene glycol, with normal 5-hydroxyindoleacetic acid cerebrospinal fluid concentrations, are the biochemical hallmark of tyrosine hydroxylase deficiency. The homovanillic acid concentrations and homovanillic acid/5-hydroxyindoleacetic acid ratio in cerebrospinal fluid correlate with the severity of the phenotype. Tyrosine hydroxylase deficiency is almost exclusively caused by missense mutations in the TH gene and its promoter region, suggesting that mutations with more deleterious effects on the protein are incompatible with life. Genotype-phenotype correlations do not exist for the common c.698G>A and c.707T>C mutations. Carriership of at least one promotor mutation, however, apparently predicts type A tyrosine hydroxylase deficiency. Most patients with tyrosine hydroxylase deficiency can be successfully treated with l-dopa. PMID: 20430833 [PubMed - indexed for MEDLINE]

Ketelslegers IA, Neuteboom RF, Boon M, Catsman-Berrevoets CE, Hintzen RQ; Dutch Pediatric MS Study Group* [Rijk-van Andel JF. et al...]. A comparison of MRI criteria for diagnosing pediatric ADEM and MS. Neurology. 2010 May 4;74(18):1412-5. Epub 2010 Mar 24. BACKGROUND: Brain MRI is a useful tool for diagnosing inflammatory demyelinating disorders in children. However, it remains unclear which are the most reliable criteria for distinguishing multiple sclerosis (MS) from monophasic disorders such as acute disseminated encephalomyelitis (ADEM). We therefore compared the 4 current sets of MRI criteria in our Dutch pediatric cohort and determined which are the most useful in clinical practice for distinguishing ADEM from MS. METHODS: We included 49 children who had had a demyelinating event and an MRI scan within 2 months of their first clinical attack. Twenty-one patients had ADEM and remained

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relapse-free after at least 2 years of follow-up. Twenty-eight patients had a definitive diagnosis of MS. We assessed the sensitivity and specificity of the following MRI criteria: Barkhof criteria, KIDMUS criteria, Callen MS-ADEM criteria, and Callen diagnostic MS criteria. RESULTS: The Callen MS-ADEM criteria had the best combination of sensitivity (75%) and specificity (95%). The KIDMUS criteria had higher specificity (100%), but much lower sensitivity (11%). The Barkhof criteria had a sensitivity of 61% and a specificity of 91%. The Callen diagnostic MS criteria were the most sensitive (82%), but were only 52% specific for distinguishing a first attack of MS from ADEM. CONCLUSIONS: The results in our cohort demonstrate that the new Callen criteria for multiple sclerosis-acute disseminated encephalomyelitis (MS-ADEM) are the most useful for differentiating a first attack of MS from monophasic ADEM. Although the Callen diagnostic MS criteria are more sensitive, they lack the specificity necessary to differentiate MS from ADEM. *Collaborators (14): Van Dijk KG, Eikelenboom MJ, Gooskens RH, Peeters EA, Poll-The BT, de Rijk-van Andel JF, Rotteveel JJ, Samijn JP, Snoeck IN, Stroink H, Vermeulen RJ, Verrips A, Vles JS, Willemsen MA. Comment in: Neurology. 2010 May 4;74(18):1404-5. PMID: 20335562 [PubMed - indexed for MEDLINE]

136 Neuteboom RF, Ketelslegers IA, Boon M, Catsman-Berrevoets CE, Hintzen RQ; Dutch Study Group on Childhood Multiple Sclerosis and Acute Disseminated Encephalomyelitis* [De Rijk-van Andel JF et al...]. Barkhof magnetic resonance imaging criteria predict early relapse in pediatric multiple sclerosis. Pediatr Neurol. 2010 Jan;42(1):53-5. We sought to identify clinical and radiologic features predicting early relapse after a diagnosis of multiple sclerosis in children. In this nationwide retrospective multicenter study in The Netherlands, we included 28 children with multiple sclerosis with onset before age 16 years. Magnetic resonance images and clinical features at the onset of disease were evaluated. The mean follow-up time was 55 months. Twenty children (71%) had a relapse during follow-up. We found that the presence of at least three of four Barkhof magnetic resonance imaging criteria at the onset of multiple sclerosis signs is predictive of early relapse after a diagnosis of multiple sclerosis in children (P<0.05). *Collaborators (15): Vles JS, Gooskens RH, Stroink H, Vermeulen RJ, Eikelenboom J, Rotteveel JJ, Peeters EA, Snoeck IN, Poll-The BT, De Rijk-Van Andel JF, Heersema DJ, Verrips A, Samijn JP, Van Dijk K, Willemsen MA. PMID: 20004863 [PubMed - indexed for MEDLINE]

Complete publicatielijst Ketelslegers IA, Neuteboom RF, Boon M, Catsman-Berrevoets CE, Hintzen RQ; Dutch Pediatric MS Study Group* [Rijk-van Andel JF. et al...]. A comparison of MRI criteria for diagnosing pediatric ADEM and MS. Neurology. 2010 May 4;74(18):1412-5. Epub 2010 Mar 24.


De Lau LM, Siepman DA, Remmers MJ, Terwindt GM, Hintzen RQ. Acute disseminating encephalomyelitis following legionnaires disease. Arch Neurol. 2010 May;67(5): 623-6. Jinnah HA, Ceballos-Picot I, Torres RJ, Visser JE, Schretlen DJ, Verdu A, Laróvere LE, Chen CJ, Cossu A, Wu CH, Sampat R, Chang SJ, de Kremer RD, Nyhan W, Harris JC, Reich SG, Puig JG; for the Lesch-Nyhan Disease International Study Group. Attenuated variants of Lesch-Nyhan disease. Brain 2010;133:671-689. Epub Feb 22. Neuteboom RF, Ketelslegers IA, Boon M, Catsman-Berrevoets CE, Hintzen RQ; Dutch Study Group on Childhood Multiple Sclerosis and Acute Disseminated Encephalomyelitis* [De Rijk-van Andel JF et al...]. Barkhof magnetic resonance imaging criteria predict early relapse in pediatric multiple sclerosis. Pediatr Neurol. 2010 Jan;42(1):53-5. Jahanshahi M, Jones CR, Zijlmans J, Katzenschlager R, Lee L, Quinn N, Frith CD, Lees AJ. Dopaminergic modulation of striato-frontal connectivity during motor timing in Parkinson’s disease. Brain. 2010 Mar;133(Pt 3):727-45. Visser JE, Oude Nijhuis LB, Janssen L, Bastiaanse CM, Borm GF, Duysens J, Bloem BR. Dynamic posturography in Parkinson’s disease: diagnostic utility of the “first trial effect”. Neuroscience. 2010 Jun 30;168(2):387-94. Epub 2010 Apr 7. Jongen PJ, Lehnick D, Sanders E, Seeldrayers P, Fredrikson S, Andersson M, Speck J; FOCUS study group*. Health-related quality of life in relapsing remitting multiple sclerosis patients during treatment with glatiramer acetate: a prospective, observational, international, multi-centre study. Health Qual Life Outcomes. 2010 Nov 15;8:133. Sanders EACM. Het belang, het herkennen en behandelen van de ziekte van Alzheimer. Neurologie Actueel. 2010 september;13:6. Poewe W, Antonini A, Zijlmans JC, Burkhard PR, Vingerhoets F. Levodopa in the treatment of Parkinson’s disease: an old drug still going strong. Clin Interv Aging. 2010 Sep 7;5: 229-38. Sanders EACM. Multipele Sclerose en cognitie. Utrecht: Academical Pharmaceutical Productions, 2010. ISBN 978-90-5761-094-3. Sanders EACM, Zwanikken CP, Beenakker EAC. Multipele sclerose Handboek: een leidraad voor de praktijk Utrecht: Academical Pharmaceutical Productions, 2010. ISBN 978-90-5761-099-8. Sanders EACM. Multipele sclerose in combinatie met andere immuun ziekten. Multipele sclerose jaargang 4, deel 2, 2010. Sanders EACM, Zwanikken CP, de Vries-Knoppert WAEJ. Multiple sclerose lexicon, dl. 4: Multipele sclerose en oogheelkunde Utrecht: Academical Pharmaceutic Productions, 2010. ISBN 978-90-5761-100-1.

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Hintzen R, Berrevoets-Catsman CE. - redactie: Sanders EACM, Zwanikken CP. Multiple sclerose lexicon, dl. 5: Multipele sclerose en kinderneurologie Utrecht: Academical Pharmaceutic Productions, 2010. ISBN 978-90-5761-102-5. Geurts JJG, Visser LH, Vrancken PH. - redactie: Sanders EACM, Zwanikken CP. Multiple sclerose lexicon, dl. 6: Multipele sclerose en psychologie. Utrecht: Academical Pharmaceutic Productions, 2010. ISBN 978-90-5761-106-3. Sanders EACM. Orale therapie voor multipele sclerose: de resultaten van de CLARITYstudie. Neurologie Actueel 5, 7, juli 2010 Visser WA, Kolling JB, Groen GJ, Tetteroo E, van Dijl R, Rosseel PM, van der Meer NJ. Persistent cortical blindness after a thoracic epidural test dose of bupivacaine. Anesthesiology. 2010 Feb;112(2):493-5. Zijlmans JCM, Hovestadt A, Berendse HW, Visser JE, Bloem BR, Boon AJW, van Hilten JJ, de Koning-Tijssen MAJ, Nijssen PCG, van Laar T. Rasagiline (Azilect) effectief als symptoombestrijding? Papaver. 2010;33(4):6-7. Sanders EACM. Retina dikte en cerebraal atrofie bij multiple sclerose. Neurologie Actueel 2010 oktober;13:7 De Stefano N, Filippi M, Confavreux C, Vermersch P, Simu M, Sindic C, Hupperts R, Bajenaru O, Edan G, Grimaldi L, Marginean I, Medaer R, Orefice G, Pascu I, Pelletier J, Sanders E, Scarpini E, Mancardi GL. The results of two multicenter, open-label studies assessing efficacy, tolerability and safety of protiramer, a high molecular weight synthetic copolymeric mixture, in patients with relapsing-remitting multiple sclerosis. Mult Scler. 2009 Feb;15(2):238-43. Epub 2008 Nov 5. Zijlmans JC. The role of imaging in the diagnosis of vascular parkinsonism. Neuroimaging Clin N Am. 2010 Feb;20(1):69-76. Wens SCA, Sanders EACM. Twee patiënten met pijn, koorts en een progressieve tetraparese. Tijdschrift voor Neurologie en Neurochirurgie. 2010; 11(6):245-252. Willemsen MA, Verbeek MM, Kamsteeg EJ, de Rijk-van Andel JF, Aeby A, Blau N, Burlina A, Donati MA, Geurtz B, Grattan-Smith PJ, Haeussler M, Hoffmann GF, Jung H, de Klerk JB, van der Knaap MS, Kok F, Leuzzi V, de Lonlay P, Megarbane A, Monaghan H, Renier WO, Rondot P, Ryan MM, Seeger J, Smeitink JA, Steenbergen-Spanjers GC, Wassmer E, Weschke B, Wijburg FA, Wilcken B, Zafeiriou DI, Wevers RA. Tyrosine hydroxylase deficiency: a treatable disorder of brain catecholamine biosynthesis. Brain. 2010 Jun;133(Pt 6):1810-22. Epub 2010 Apr 29.


Oogheelkunde “Onze specialisten zijn opgeleid in Rotterdam, Amsterdam, Utrecht, Nijmegen, Leiden en Turijn”

Het team van Oogheelkunde bestaat uit een gevarieerde groep specialisten. Oogarts en opleider dr. Giorgio Porro vindt het belangrijk dat er veel aandacht is voor onderzoek.

Dr. G.L. Porro

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Dr. Porro is in Turijn opgeleid als oogarts en in 1995 kwam hij naar Nederland voor zijn promotie. “Ik richtte me in mijn studie op oogaandoeningen bij kinderen met hersenbeschadiging en Nederland was in die tijd het beste onderzoeksland op dit gebied.” Hij kwam naar het UMC Utrecht en zijn proefschrift Vision and Visual Behaviour in Responsive and Unresponsive Neurologically Impaired Children (1998) maakte zo’n indruk dat het beloond werd met de Dondersprijs voor het beste oogheelkundige proefschrift van het jaar 1997/1998. Vernieuwend was o.a. de introductie van de BEFIE-test (BEhavioural visual FIEld test in a clinical setting), een gedragsmatige methode om het perifere gezichtsveld bij kinderen te bepalen. De combinatie van neurologische afwijkingen bij kinderen (kinder-neurophthalmologie) behoort ook tot zijn wetenschappelijke aandachtsgebieden.

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Porro combineert zijn werk in het topklinische Amphia Ziekenhuis nog steeds met twee dagen per maand in het UMC Utrecht. Op deze dagen leidt hij een bijzonder oogheelkundig spreekuur voor kinderen met aangeboren of verworven hersenletsel. “Soms verwijs ik patiënten van het Amphia door naar Utrecht voor mijn specialistische onderzoek. Met de BEFIE-test kunnen we – spelenderwijs – meten wat eerst onmogelijk leek. Bij kinderen met een hersenbeschadiging ontplooit het visuele systeem zich vertraagd of onvoldoende, waardoor het kind de informatie die via het oog binnenkomt moeizamer (onvoldoende) kan interpreteren. Dit heet een CVI, of een cerebrale visuele stoornis. Vanaf de zesde maand kunnen we bij deze kinderen al visuele oogreflexen testen, die pas later meer bewust optreden. De interpretatie van dit gedrag geeft een indruk van het gezichtsveld van deze kinderen. In het verleden kwam het voor dat ze met een (onverklaarbaar) gezichtsvelddefect gezien werden als autistisch, of verdacht werden van een angststoornis, terwijl het echte probleem lag in de hersenschade die een gezichtsveldafwijking veroorzaakte.” Al in Turijn begon hij met publicaties op dit gebied. “Waarom ik juist belangstelling kreeg voor dit gebied?” Porro denkt even na. “Ik denk vooral omdat het een nieuw en onontgonnen gebied was, waar nog niet veel over gepubliceerd was. Dat daagde me net zo uit als de vragen van de ouders die sommige gedragingen van hun kind niet konden verklaren. Daarnaast is een kind met een hersenaandoening een zwaar lot voor ouders en is het fijn om daarin iets te kunnen betekenen. Hopelijk is het in de toekomst, door middel van visuele stimulatie of training, mogelijk om de visuele vermogens van het kind te verbeteren.”

Subspecialisaties van collega’s Naast het wetenschappelijk onderzoek in het UMC Utrecht, waar hij ook promovendi begeleidt, heeft Porro een bijzondere interesse voor het opleiden van assistenten in


opleiding. Door zijn inspanningen om zich chirurgisch te kunnen bekwamen (in Italië werd hij niet als oogchirurg opgeleid), hecht hij veel belang aan het verbeteren van de chirurgische vaardigheden van de aio’s en aan het stimuleren van hun wetenschappelijke belangstelling. “Het feit dat we in het Amphia mogen opleiden zie ik als een keurmerk voor het ziekenhuis. De opleidingsvisitaties houden ons scherp en de eisen voor opleiders lijken elk jaar strenger te worden.” Ook vindt hij het belangrijk dat collega’s veel onderzoeksactiviteiten ontplooien. “Ik wil hier niet alleen mijn verhaal vertellen, maar ook de onderzoeksinspanningen van mijn collega-oogartsen en hun subspecialisaties benadrukken. We zijn een zeer opleidingsgeoriënteerde groep en de meesten van ons publiceren jaarlijks als auteur of coauteur, via wetenschappelijke artikelen, voordrachten of posters.”

Het team van oogheelkunde • Dr. Colen: een autoriteit op glaucoomgebied, veelgevraagd op congressen. Hij heeft onder andere het GDX-apparaat wereldwijd gevalideerd. Dit is een apparaat dat een scan maakt van de binnenkant van de ogen en diverse afwijkingen van de oogzenuw van het ‘normale’ markeert. Hij publiceert nog steeds over zijn aandachtsgebied glaucoom met collega’s van het Oogziekenhuis Rotterdam. • Mw. dr. Willemse: gepromoveerd op erfelijke (oog)aandoeningen, doet onderzoek samen met collega’s van de Erasmus Universiteit Rotterdam en publiceert o.a. in Nature Genetics. Een andere belangstelling van haar is de kinderoogheelkunde, waarvoor zij een belangrijk onderzoek naar kindermishandeling (onder andere het shakenbabysyndroom [staat zo in VD]) uitvoert. • Dr. Van Dooren: gepromoveerd op cornea-aandoening, doet onderzoek samen met collega’s van de Erasmus Universiteit Rotterdam, waar hij ook parttime werkzaam is. Hij is een topexpert op het gebied van corneatransplantaties. • Mw. Van Liempt: gespecialiseerd in kinderoogheelkunde en traanwegafwijkingen, zij is nauw betrokken bij de landelijke werkgroep kinderoogheelkunde en is momenteel bezig om de richtlijnen voor de R.O.P. (retinopathie van de prematuriteit) op te zetten. • Mw. Tigchelaar: een veelgevraagd specialist op het gebied van medische retina, waarover zij regelmatig een voordracht houdt. Dit jaar werd zij tijdens de bijeenkomst van het Nederlands Oogheelkundig Genootschap (NOG) beloond met de tweede posterprijs. • Mw. Hartman: doet onderzoek en klinische behandelingen van de ziekte van Graves in samenwerking met het AMC in Amsterdam en hoogleraar prof. Maurits. • Mw. dr. De Grip: is zeer actief in het vakgebied ooglidchirurgie en laserbehandeling voor refractieafwijkingen. Ook doet zij veldonderzoek bij gehandicapte kinderen en ze is een frequent gevraagde spreker over de oogheelkundige afwijkingen bij het downsyndroom. Ze is verbonden aan de landelijke stichting Visio.

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• De heren Van Dobben de Bruijn en Bakker: gespecialiseerd in voorsegment- en cataractchirurgie, ze zijn autoriteiten op het gebied van kunstlenzen en de toepassing daarvan.

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De enige subspecialisatie die het Amphia Ziekenhuis niet aanbiedt, is chirurgische retina. “Dit is een dagelijkse routine voor het Erasmus MC of het Oogziekenhuis Rotterdam. Omdat Rotterdam niet ver weg is, is het veel logischer om daarheen te verwijzen.” Innovatief in het Amphia Ziekenhuis zijn de superspecialistische spreekuren (traanwegafwijkingen, refractiechirurgie, glaucoom, hoornvliesafwijkingen, laserbehandelingen voor refractieafwijkingen, ooglidchirurgie, behandeling maculadegeneratie, kinderoogheelkunde, medische retina, neurophthalmologie, kinderoogheelkunde). Bij superspecialistische spreekuren zijn expertteams betrokken die worden samengesteld rondom een aandoening, zodat deze patiënten niet allerlei afdelingen hoeven af te lopen. In het kader van de beste zorg voor de patiënt zijn er kwaliteitsindicatoren en klinische besprekingen. Porro: “We hebben hier specialisten die divers opgeleid zijn in Rotterdam, Amsterdam, Utrecht, Nijmegen, Leiden en Turijn. Iedereen heeft een verschillend geformeerde achtergrond en samen ontwikkelen we werkwijzen die we steeds verder verfijnen.” Een ambitie voor de toekomst is een betere stroomlijning, om de wachtlijsten in te korten. “Ook willen we op den duur een eigen RVE binnen het Amphia. Toekomstmuziek die hopelijk snel realiteit wordt.”

Actueel Bijzonder bij de zorgkern Oogheelkunde in het Amphia Ziekenhuis is ook dat er onder meer drie klinisch geschoolde optometristen werkzaam zijn. “Deze hbo-geschoolde functie bevindt zich tussen opticien en oogarts in en vormt een waardevolle toevoeging voor het vakgebied. Deze professionals worden door de vergrijzing steeds belangrijker. Ook andere ziekenhuizen in de omgeving, zoals in Tilburg, nemen steeds meer optometristen aan. Het zou mooi zijn om de opleiding optometrie in het Amphia te verwerven, dat zou een bijzondere wetenschappelijke input voor onze afdeling opleveren.”

Kerngegevens zorgkern Oogheelkunde • 10 oogartsen: G.A. Bakker, dr. T.P. Colen, F.J. Dobben de Bruijn, dr. B.T.H. van Dooren, mw. G. de Grip, mw. L. Hartman, mw. I.L.A. van Liempt, dr. G.L. Porro, mw. O.A.M. Tigchelaar-Besling en mw. dr. J.J.M. Willemse-Assink • 2 assistenten in opleiding uit het Erasmus MC te Rotterdam • Subspecialismen: traanwegafwijkingen, refractiechirurgie, glaucoom, hoornvliesafwijkingen, laserbehandelingen voor refractieafwijkingen, ooglidchirurgie,


behandeling maculadegeneratie, kinderoogheelkunde, medische retina, neurophthalmologie (met name bij kinderen), scheelzien en erfelijke aandoeningen

Overzicht lopende onderzoeken • Impairment of peripheral vision and its measurement (oogheelkunde) • Visuele functies bij kinderen met cerebrale parese als gevolg van een infarct in de arteria cerebri media • Visuele functies bij kinderen met cerebrale parese als gevolg van een infarct in de arteria cerebri posterior • Visuele functies bij kinderen met periventriculaire leukomalacie • Visuele functies bij kinderen na hemisferectomie • Visuele functies bij kinderen na epilepsiechirurgie • Visuele functies na kindermishandeling • Traumatic Opticopathy (TON): to treat or not to treat • Visual fields defects (VFD) by Sturge Weber Syndrome (SWS) • Landelijke richtlijnen R.O.P : NED ROP • OCT en MS • Ocular surface disease and dry eyes • Endotheeldichtheid na DSAEK en Top-hat • Femtosecond incisions • Pentacon Study na corneatransplantatie in keratoconus • Travalert Study en glaucoom • The ability of short-wavelength automated perimetry to predict conversion to glaucoma • A genome-wide association study: refractive errors and myopia

Samenvattingen gepubliceerde artikelen Van der Schoot J, Reus NJ, Colen TP, Lemij HG. The ability of short-wavelength automated perimetry to predict conversion to glaucoma. Ophthalmology. 2010 Jan;117(1):30-4. Epub 2009 Nov 6. PURPOSE: Short-wavelength automated perimetry (SWAP) has been claimed to predict conversion to glaucoma 3 to 4 years before standard automated perimetry (SAP) defects occur. This study compared the moment of glaucomatous conversion between SWAP and SAP. DESIGN: Prospective, longitudinal follow-up study. PARTICIPANTS: Four hundred sixteen subjects with ocular hypertension (intraocular pressure >/=22 and
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The moment of onset of a reproducible defect in SAP was compared with that in SWAP. RESULTS: Of the 416 initial participants, 24 eyes of 21 subjects showed conversion in SAP. Of these eyes, 22 did not show earlier conversion in SWAP than in SAP. Standard automated perimetry even showed earlier conversion than SWAP in 15 cases. In only 2 eyes did SWAP show earlier conversion by up to 18 months. CONCLUSIONS: These results do not support the notion that SWAP generally predicts conversion to glaucoma in SAP. Instead, SAP appears to be at least as sensitive to conversion as SWAP in a large majority of eyes. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article. Copyright 2010 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved. PMID: 19896194 [PubMed - indexed for MEDLINE]

Van Rij G, Bartels MC, Bleyen I, van Dooren BT, Saelens IE. Femtosecond incisions. Ophthalmology. 2010 Jul;117(7):1458-9; author reply 1459. Comment in: Ophthalmology. 2009 Sep;116(9):1638-43. PMID: 20609994 [PubMed - indexed for MEDLINE]

144 Solouki AM, Verhoeven VJ, van Duijn CM, Verkerk AJ, Ikram MK, Hysi PG, Despriet DD, van Koolwijk LM, Ho L, Ramdas WD, Czudowska M, Kuijpers RW, Amin N, Struchalin M, Aulchenko YS, van Rij G, Riemslag FC, Young TL, Mackey DA, Spector TD, Gorgels TG, Willemse-Assink JJ, Isaacs A, Kramer R, Swagemakers SM, Bergen AA, van Oosterhout AA, Oostra BA, Rivadeneira F, Uitterlinden AG, Hofman A, de Jong PT, Hammond CJ, Vingerling JR, Klaver CC. A genome-wide association study identifies a susceptibility locus for refractive errors and myopia at 15q14. Nat Genet. 2010 Oct;42(10):897-901. Epub 2010 Sep 12. Refractive errors are the most common ocular disorders worldwide and may lead to blindness. Although this trait is highly heritable, identification of susceptibility genes has been challenging. We conducted a genome-wide association study for refractive error in 5,328 individuals from a Dutch population-based study with replication in four independent cohorts (combined 10,280 individuals in the replication stage). We identified a significant association at chromosome 15q14 (rs634990, P = 2.21 × 10?¹4). The odds ratio of myopia compared to hyperopia for the minor allele (minor allele frequency = 0.47) was 1.41 (95% CI 1.16-1.70) for individuals heterozygous for the allele and 1.83 (95% CI 1.42-2.36) for individuals homozygous for the allele. The associated locus is near two genes that are expressed in the retina, GJD2 and ACTC1, and appears to harbor regulatory elements which may influence transcription of these genes. Our data suggest that common variants at 15q14 influence susceptibility for refractive errors in the general population. PMID: 20835239 [PubMed - indexed for MEDLINE]


Complete publicatielijst Solouki AM, Verhoeven VJ, van Duijn CM, Verkerk AJ, Ikram MK, Hysi PG, Despriet DD, van Koolwijk LM, Ho L, Ramdas WD, Czudowska M, Kuijpers RW, Amin N, Struchalin M, Aulchenko YS, van Rij G, Riemslag FC, Young TL, Mackey DA, Spector TD, Gorgels TG, Willemse-Assink JJ, Isaacs A, Kramer R, Swagemakers SM, Bergen AA, van Oosterhout AA, Oostra BA, Rivadeneira F, Uitterlinden AG, Hofman A, de Jong PT, Hammond CJ, Vingerling JR, Klaver CC. A genome-wide association study identifies a susceptibility locus for refractive errors and myopia at 15q14. Nat Genet. 2010 Oct;42(10):897-901. Epub 2010 Sep 12. Beckers HJM, Webers CAB, Busch MJWM, Brink HMA, Colen TP, Schouten JSAG. Bevorderen van therapietrouw bij patiënten met glaucoom. [abstract] . 204e NOG vergadering. Maastricht, 25 maart 2010. Willemse J, Tigchelaar O, Porro G. Even een prikje? Onderbelichte risico’s van retrobulbaire verdoving. [Abstract], 204e NOG vergadering. Maastricht, 25 maart 2010. Van Rij G, Bartels MC, Bleyen I, van Dooren BT, Saelens IE. Femtosecond incisions. Ophthalmology. 2010 Jul;117(7):1458-9; author reply 1459. Porro G, Wittebol Post D. Impairment of peripheral vision and its measurement. In: Visual impairment of children due to damage to the brain. Dutton G, Bax M. [Editors]. Clinics in developmental medicine No. 186, London: Mac Keith Press, 2010. Chapter 5, pag. 85-97. ISBN 978-1-898683-86-5. Van Rij G, Bartels MC, Bleyen I, van Dooren BTH, Saelens IEY. Mushroom keratoplastiek na eerdere conventionele perforerende hoornvliestransplantaties. [abstract]. 204e NOG vergadering. Maastricht, 25 maart 2010. Van der Schoot J, Reus NJ, Colen TP, Lemij HG. The ability of short-wavelength automated perimetry to predict conversion to glaucoma. Ophthalmology. 2010 Jan;117(1):30-4. Epub 2009 Nov 6. Simonse E, Willemse JJM, van Beek RHT, Porro G. TO(N) TREAT OR NOT TO(N) TREAT? [Abstract], 204e NOG vergadering. Maastricht, 25 maart 2010. Van Dooren BTH, Bleyen I, Bartels MC, Saelens IEY, Van Rij G. “Top Hat” penetrerende en endotheliale keratoplastiek: evaluatie van endotheelcelverval. [abstract]. 204e NOG vergadering. Maastricht, 25 maart 2010.

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Orthopedie Kerngegevens zorgkern Orthopedie • 13 orthopedisch chirurgen: mw. dr. A. Beumer, A.F.A. van Beurden, dr. S.B.T. Bolder, mw. M.P.J. van den Borne, L.H.G.J. Elmans, mw. dr. D. Eygendaal, dr. R.C.I. van Geenen, W.H.J.C. van Heeswijk, E.A. Hoebink, J.A.A.M. van den Hout, A.J.P. Joosten, dr. A.F.C.M. Moonen, dr. R.C.I. Wagenmakers • 2 assistenten niet in opleiding • subspecialismen: wervelkolom, kinderorthopedie, bovenste extremiteit, onderste extremiteit, traumatologie, sportorthopedie

Samenvattingen gepubliceerde artikelen Kaas L, Riet RP, Vroemen JP, Eygendaal D. The epidemiology of radial head fractures. J Shoulder Elbow Surg. 2010 Feb 9. [Epub ahead of print] INTRODUCTION: Recent literature shows an increased mean age of female patients with radial head fractures compared with male patients with radial head fractures. However, data on epidemiology of radial head fractures and specifically in relation to age distribution and malefemale ratios of radial head fracture are scarce. MATERIALS AND METHODS: A retrospective database search was performed to identify all patients with a radial head fracture over a 3-year period. RESULTS: A total of 328 radial head fractures were diagnosed in 322 patients. The incidence was 2.8 per 10,000 inhabitants per year. The male-female ratio was 2:3. The mean age was 48.0 years (range, 14-88 years; SD, 14.8). The mean age of female patients (52.8 years) was significantly higher than that of male patients (40.5 years) (P = .001). As the age increases above 50 years, the number of female patients becomes significantly higher than the number of male patients (P = .001). An associated osseous injury was present in 40 patients (12.4%). CONCLUSIONS: Radial head fractures are common, and associated injuries are frequent. Copyright

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© 2010 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Mosby, Inc. All rights reserved. PMID: 20149972 [PubMed - as supplied by publisher]

Hermans JJ, Beumer A, de Jong TA, Kleinrensink GJ. Anatomy of the distal tibiofibular syndesmosis in adults: a pictorial essay with a multimodality approach. J Anat. 2010 Dec;217(6):633-45. A syndesmosis is defined as a fibrous joint in which two adjacent bones are linked by a strong membrane or ligaments.This definition also applies for the distal tibiofibular syndesmosis, which is a syndesmotic joint formed by two bones and four ligaments. The distal tibia and fibula form the osseous part of the syndesmosis and are linked by the distal anterior tibiofibular ligament, the distal posterior tibiofibular ligament, the transverse ligament and the interosseous ligament. Although the syndesmosis is a joint, in the literature the term syndesmotic injury is used to describe injury of the syndesmotic ligaments. In an estimated 1–11% of all ankle sprains, injury of the distal tibiofibular syndesmosis occurs. Forty percent of patients still have complaints of

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ankle instability 6 months after an ankle sprain. This could be due to widening of the ankle mortise as a result of increased length of the syndesmotic ligaments after acute ankle sprain. As widening of the ankle mortise by 1 mm decreases the contact area of the tibiotalar joint by 42%, this could lead to instability and hence early osteoarthritis of the tibiotalar joint. In fractures of the ankle, syndesmotic injury occurs in about 50% of type Weber B and in all of type Weber C fractures. However,in discussing syndesmotic injury, it seems the exact proximal and distal boundaries of the distal tibiofibular syndesmosis are not well defined. There is no clear statement in the Ashhurst and Bromer etiological, the Lauge-Hansen genetic or the Danis-Weber topographical fracture classification about the exact extent of the syndesmosis. This joint is also not clearly defined in anatomical textbooks, such as Lanz and Wachsmuth. Kelikian and Kelikian postulate that the distal tibiofibular joint begins at the level of origin of the tibiofibular ligaments from the tibia and ends where these ligaments insert into the fibular malleolus. As the syndesmosis of the ankle plays an important role in the stability of the talocrural joint, understanding of the exact anatomy of both the osseous and ligamentous structures is essential in interpreting plain radiographs, CT and MR images, in ankle arthroscopy and in therapeutic management. With this pictorial essay we try to fill the hiatus in anatomic knowledge and provide a detailed anatomic description of the syndesmotic bones with the incisura fibularis, the syndesmotic recess, synovial fold and tibiofibular contact zone and the four syndesmotic ligaments. Each section describes a separate syndesmotic structure, followed by its clinical relevance and discussion of remaining questions. © 2010 The Authors. Journal of Anatomy © 2010 Anatomical Society of Great Britain and Ireland. PMID: 21108526 [PubMed - indexed for MEDLINE]


Reuver JM, Dayerizadeh N, Burger B, Elmans L, Hoelen M, Tulp N. Total ankle replacement outcome in low volume centers: short-term followup. Foot Ankle Int. 2010 Dec;31(12):1064-8. BACKGROUND: The indication for total ankle replacement (TAR) as an alternative to ankle fusion continues to be a much-debated topic. The reported survival of TAR at midterm followup is approximately 90%. The aim of this study was to compare functional outcome and survival of TAR in low volume centers versus high volume centers. MATERIALS AND METHODS: A retrospective cohort study was carried out in four low volume centers. Sixty-four Salto TARs were performed between 2003 and 2007 in 60 patients. Fifty-five (59 TAR) patients were eligible for followup with 28 men. Standardized American Orthopaedic Foot and Ankle Society (AOFAS) scores, patient satisfaction, and range of motion (ROM) were measured. Standardized and dynamic radiographs were used for evaluation of radiolucencies, ROM and component alignment. RESULTS: Seven of the 59 ankle prostheses had to be revised: five for loosening and two for deep infection. Three of the five revised for loosening went on to fusion, and in two a revision of one of the components was performed. Both infected ankles were fused. Five patients declined to participate this study, among these two were TAR failures. Survival with revision as the endpoint was 86% at final followup. The average AOFAS score was 75 (SD ± 15). On dynamic radiographs the ROM was 22 degrees (SD ± 8) in the tibiotalar joint. CONCLUSION: This study demonstrated that functional results of total ankle replacement in low volume centers were comparable to most high volume centers but survival was lower especially when we consider our shorter followup than most comparable series. PMID: 21189206 [PubMed - indexed for MEDLINE]

Baumfeld JA, van Riet RP, Zobitz ME, Eygendaal D, An KN, Steinmann SP. Triceps tendon properties and its potential as an autograft. J Shoulder Elbow Surg. 2010 Jul;19(5):697-9. Epub 2010 Apr 22. BACKGROUND: Although the triceps tendon has been used as a graft for ligament reconstruction about the elbow, and has been postulated to be useful as a graft in the treatment of massive rotator cuff tears, no data exists on the tensile properties of the triceps tendon. The purpose of this study was to define the tensile properties of the medial, lateral, and central thirds of the triceps tendon, in order to examine its potential as an autograft for upper extremity pathology. MATERIALS AND METHODS: Ten fresh frozen upper extremity specimens were used. The triceps tendon was dissected from its musculotendinous junction and left attached to its insertion at the olecranon. The tendon was split into thirds and its tensile properties were recorded using a materials testing machine. RESULTS: The lateral portion was significantly thinner and less stiff than the medial and central portions (P < .05). It failed at significantly lower ultimate load than the central portion (P < .05). There were no significant differences between the medial,

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central, and lateral portions of the triceps tendons with regards to ultimate stress (P = .20) or modulus of elasticity (P = .64). CONCLUSION: Data from the current study were compared to available literature regarding tensile properties of the rotator cuff and elbow ligaments. Both the medial and central portions of the triceps tendon offer sufficient strength to be used in the reconstruction of the rotator cuff or ligament reconstruction in the elbow. 2010. Published by Mosby, Inc. PMID: 20413332 [PubMed - indexed for MEDLINE]

Kaas L, Turkenburg JL, van Riet RP, Vroemen JPAM, Eygendaal D. Magnetic resonance imaging findings in 46 elbows with a radial head fracture. Acta Orthopaedica, (2010);18,373-376. BACKGROUND AND PURPOSE: Radial head fractures are common, and may be associated with other injuries of clinical importance. We present the results of a standard additional MRI scan for patients with a radial head fracture. PATIENTS AND METHODS: 44 patients (mean age 47 years) with 46 radial head fractures underwent MRI. 17 elbows had a Mason type-I fracture,

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23 a Mason type-II fracture, and 6 elbows had a Mason type-III fracture. RESULTS: Associated injuries were found in 35 elbows: 28 elbows had a lateral collateral ligament lesion, 18 had capitellar injury, 1 had a coronoid fracture, and 1 elbow had medial collateral ligament injury. INTERPRETATION: The incidence of associated injuries with radial head fractures found with MRI was high. The clinical relevance should be investigated. PMID: 20450424 [PubMed - indexed for MEDLINE] PMCID: PMC2876842

De Haan J, den Hartog D, Tuinebreijer WE, Iordens GI, Breederveld RS, Bronkhorst MW, Bruijninckx MM, De Vries MR, Dwars BJ, Eygendaal D, Haverlag R, Meylaerts SA, Mulder JW, Ponsen KJ, Roerdink WH, Roukema GR, Schipper IB, Schouten MA, Sintenie JB, Sivro S, Van den Brand JG, Van der Meulen HG, Van Thiel TP, Van Vugt AB, Verleisdonk EJ, Vroemen JP, Waleboer M, Willems WJ, Polinder S, Patka P, van Lieshout EM, Schep NW.Functional treatment versus plaster for simple elbow dislocations (FuncSiE): a randomized trial. BMC Musculoskelet Disord. 2010 Nov 12;11:263. BACKGROUND: Elbow dislocations can be classified as simple or complex. Simple dislocations are characterized by the absence of fractures, while complex dislocations are associated with fractures. After reduction of a simple dislocation, treatment options include immobilization in a static plaster for different periods of time or so-called functional treatment. Functional treatment is characterized by early active motion within the limits of pain with or without the use of a sling or hinged brace. Theoretically, functional treatment should prevent stiffness without introducing increased joint instability. The primary aim of this randomized controlled


trial is to compare early functional treatment versus plaster immobilization following simple dislocations of the elbow. METHODS/DESIGN: The design of the study will be a multicenter randomized controlled trial of 100 patients who have sustained a simple elbow dislocation. After reduction of the dislocation, patients are randomized between a pressure bandage for 5-7 days and early functional treatment or a plaster in 90 degrees flexion, neutral position for pro-supination for a period of three weeks. In the functional group, treatment is started with early active motion within the limits of pain. Function, pain, and radiographic recovery will be evaluated at regular intervals over the subsequent 12 months. The primary outcome measure is the Quick Disabilities of the Arm, Shoulder, and Hand score. The secondary outcome measures are the Mayo Elbow Performance Index, Oxford elbow score, pain level at both sides, range of motion of the elbow joint at both sides, rate of secondary interventions and complication rates in both groups (secondary dislocation, instability, relaxation), health-related quality of life (Short-Form 36 and EuroQol-5D), radiographic appearance of the elbow joint (degenerative changes and heterotopic ossifications), costs, and cost-effectiveness. DISCUSSION: The successful completion of this trial will provide evidence on the effectiveness of a functional treatment for the management of simple elbow dislocations. TRIAL REGISTRATION: The trial is registered at

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the Netherlands Trial Register (NTR2025). PMID: 21073734 [PubMed - indexed for MEDLINE] PMCID: PMC2994812

Cefo I, Eygendaal D. Arthroscopic arthrolysis for posttraumatic elbow stiffness. J Shoulder Elbow Surg. 2011 Mar;20(3):434-9. BACKGROUND: Loss of motion of the elbow joint is a common finding after elbow trauma. Restoration of motion of the posttraumatic stiff elbow can be a difficult, time-consuming, and costly challenge. Arthroscopic capsular release of stiff elbows has recently been introduced as a safe but technically demanding technique. The outcome in 27 patients treated by arthroscopic capsular release was assessed. MATERIALS AND METHODS: We evaluated 27 patients (17 women) who were an average age of 42 years (range, 14-65) at 3, 12, and 24 months after arthroscopic capsular release of a posttraumatic stiff elbow. Range of motion (ROM) and Elbow Function Assessment (EFA) were measured. RESULTS: Before the arthroscopic procedure, the mean flexion was 123° (SD 8°), extension was 24° (SD 9°), and total ROM was 99° (SD 11°), and after surgery, flexion improved significantly to 133° (SD 5°), extension to 7° (SD 6°), and total ROM to 125° (SD 10°). The mean (SD) EFA showed improvement from 69 (SD 4) preoperatively to 91 (SD 4) postoperatively. The postoperative outcomes at 3, 12 and 24 months were similar. One postoperative superficial infection of the lateral portal occurred and was successfully treated with oral antibiotics. No vascular or neurologic complications were noted. DISCUSSION: Historical data underscore the fact that arthroscopic release of posttraumatic elbow contracture is technically demanding but can effective improve the elbow arc of motion. CONCLUSION:

Orthopedie

Arthroscopic capsular release of the elbow is a safe and reliable treatment for patients with a posttraumatic elbow contracture. Copyright © 2011 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Mosby, Inc. All rights reserved. PMID: 21397792 [PubMed - in process]

Reininga IH, Zijlstra W, Wagenmakers R, Boerboom AL, Huijbers BP, Groothoff JW, Bulstra SK, Stevens M. Minimally invasive and computer-navigated total hip arthroplasty: a qualitative and systematic review of the literature. BMC Musculoskelet Disord. 2010 May 17;11:92. BACKGROUND: Both minimally invasive surgery (MIS) and computer-assisted surgery (CAS) for total hip arthroplasty (THA) have gained popularity in recent years. We conducted a qualitative and systematic review to assess the effectiveness of MIS, CAS and computer-assisted MIS for THA. METHODS: An extensive computerised literature search of PubMed, Medline, Embase and OVIDSP was conducted. Both randomised clinical trials and controlled clinical trials on the effectiveness of MIS, CAS and computer-assisted MIS for THA were included. Methodological

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quality was independently assessed by two reviewers. Effect estimates were calculated and a best-evidence synthesis was performed. RESULTS: Four high-quality and 14 medium-quality studies with MIS THA as study contrast, and three high-quality and four medium-quality studies with CAS THA as study contrast were included. No studies with computer-assisted MIS for THA as study contrast were identified. Strong evidence was found for a decrease in operative time and intraoperative blood loss for MIS THA, with no difference in complication rates and risk for acetabular outliers. Strong evidence exists that there is no difference in physical functioning, measured either by questionnaires or by gait analysis. Moderate evidence was found for a shorter length of hospital stay after MIS THA. Conflicting evidence was found for a positive effect of MIS THA on pain in the early postoperative period, but that effect diminished after three months postoperatively. Strong evidence was found for an increase in operative time for CAS THA, and limited evidence was found for a decrease in intraoperative blood loss. Furthermore, strong evidence was found for no difference in complication rates, as well as for a significantly lower risk for acetabular outliers. CONCLUSIONS: The results indicate that MIS THA is a safe surgical procedure, without increases in operative time, blood loss, operative complication rates and component malposition rates. However, the beneficial effect of MIS THA on functional recovery has to be proven. The results also indicate that CAS THA, though resulting in an increase in operative time, may have a positive effect on operative blood loss and operative complication rates. More importantly, the use of CAS results in better positioning of acetabular component of the prosthesis. PMID: 20470443 [PubMed - indexed for MEDLINE] PMCID: PMC2879237


Complete publicatielijst Hermans JJ, Beumer A, de Jong TA, Kleinrensink GJ. Anatomy of the distal tibiofibular syndesmosis in adults: a pictorial essay with a multimodality approach. J Anat. 2010 Dec;217(6):633-45. Cefo I, Eygendaal D. Arthroscopic arthrolysis for posttraumatic elbow stiffness. J Shoulder Elbow Surg. 2011 Mar;20(3):434-9. De Haan J, den Hartog D, Tuinebreijer WE, Iordens GI, Breederveld RS, Bronkhorst MW, Bruijninckx MM, De Vries MR, Dwars BJ, Eygendaal D, Haverlag R, Meylaerts SA, Mulder JW, Ponsen KJ, Roerdink WH, Roukema GR, Schipper IB, Schouten MA, Sintenie JB, Sivro S, Van den Brand JG, Van der Meulen HG, Van Thiel TP, Van Vugt AB, Verleisdonk EJ, Vroemen JP, Waleboer M, Willems WJ, Polinder S, Patka P, van Lieshout EM, Schep NW.Functional treatment versus plaster for simple elbow dislocations (FuncSiE): a randomized trial. BMC Musculoskelet Disord. 2010 Nov 12;11:263. Heijnen S, Vroemen J, Eygendaal D, Vos D. Hoekstabiele plaatostheosynthese van de proximale humerus fractuur. Ned Tijdschr Traumatol. 2010;6:162-6. Ploegmakers JJW, Wagenmakers R. Kenmerkende fracturen voor kindermishandeling. Ned Tijdschr Orthopedie. 2010 december;4. Kaas L, Turkenburg JL, van Riet RP, Vroemen JPAM, Eygendaal D. Magnetic resonance imaging findings in 46 elbows with a radial head fracture. Acta Orthopaedica, (2010);18,373-376. Reininga IH, Zijlstra W, Wagenmakers R, Boerboom AL, Huijbers BP, Groothoff JW, Bulstra SK, Stevens M. Minimally invasive and computer-navigated total hip arthroplasty: a qualitative and systematic review of the literature. BMC Musculoskelet Disord. 2010 May 17;11:92. Hooft M, Kint PAM, Eygendaal D. Osteoid Osteoma bootst een hemofilie arthropathie van de elleboog na. Ned Tijdschr Orthopedie. 2010;17(3):125-7 Kaas L, van Dijk CN, Eygendaal D. Radiuskopfracturen en begeleidend letsel; de stand van zaken. Ned Tijdschr Traumatol. 2010;4:94-99. Kaas L, Riet RP, Vroemen JP, Eygendaal D. The epidemiology of radial head fractures. J Shoulder Elbow Surg. 2010 Feb 9. [Epub ahead of print] Reuver JM, Dayerizadeh N, Burger B, Elmans L, Hoelen M, Tulp N. Total ankle replacement outcome in low volume centers: short-term followup. Foot Ankle Int. 2010 Dec;31(12):1064-8. Baumfeld JA, van Riet RP, Zobitz ME, Eygendaal D, An KN, Steinmann SP. Triceps tendon properties and its potential as an autograft. J Shoulder Elbow Surg. 2010 Jul;19(5): 697-9. Epub 2010 Apr 22.

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Psychiatrie Kerngegevens zorgkern Psychiatrie • 6 psychiaters: mw. I. Bakker, G.G. Hulsebos, M.R. Ju, E. van Os, B.S. Resida en W. Stuve • 2 haios 155

Samenvatting gepubliceerd artikel Birkenhäger TK, Pluijms EM, Ju MR, Mulder PG, den Broek WW. Influence of age on the efficacy of electroconvulsive therapy in major depression: a retrospective study. J Affect Disord. 2010 Oct;126(1-2):257-61. Epub 2010 Mar 19. BACKGROUND: Several variables have been studied as possible predictors for the efficacy of ECT, results from the few studies assessing the influence of age on the efficacy of ECT were inconsistent. In older patients suffering from severe depression, ECT is often the treatment of choice, therefore, investigating the influence of age on ECT response is considered relevant. METHOD: At two depression units, 141 patients meeting DSM-IV criteria for major depression and scores of at least 18 on the 17-item Hamilton Rating Scale for Depression (HAM-D) were treated with bilateral ECT, twice weekly. Clinical evaluation of depressive symptoms was performed each week; scores on the HAM-D were obtained 1-3 days prior to ECT and 1-3 days after termination of the ECT course. The primary outcome criterion was defined a priori as the mean change on the HAM-D score. The influence of age on mean change on the HAM-D score was analyzed with multiple linear regression analysis, adjusted for three covariables: center, duration of the index episode and presence of psychotic features. RESULTS: Age as a continuous variable had no significant effect on the efficacy of ECT as measured by mean change on the HAM-D score (SE 0.057, p=0.84). LIMITATIONS: The disproportionate distribution of patients among the three age groups appears to be the major limitation

Psychiatrie

of the present study. CONCLUSION: This study suggests that the efficacy of ECT in elderly depressed patients is at least equal to that in younger depressed patients. Copyright 2010 Elsevier B.V. All rights reserved. PMID: 20303601 [PubMed - indexed for MEDLINE]

Publicatielijst Birkenhäger TK, Pluijms EM, Ju MR, Mulder PG, den Broek WW. Influence of age on the efficacy of electroconvulsive therapy in major depression: a retrospective study. J Affect Disord. 2010 Oct;126(1-2):257-61. Epub 2010 Mar 19.

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Radiologie Kerngegevens zorgkern Radiologie • 16 radiologen: K. Borsje, H.F.C.M. Brands, H.A.J. Dijkstra, G.P.J. Geenen, H.A.W. Haans, Th.E.A.M. de Jong, P.A.M. Kint, M.M. Krouwels, P.A.M. Raaijmakers, M.G. Romijn, E. Sanders, M.F.A.M. Sturm, dr. E. Tetteroo, J.L. Turkenburg, R.J. Versteijlen, L.D. Vos • subspecialismen: interventieradiologie, mammaradiologie

Samenvattingen gepubliceerde artikelen Visser WA, Kolling JB, Groen GJ, Tetteroo E, van Dijl R, Rosseel PM, van der Meer NJ. Persistent cortical blindness after a thoracic epidural test dose of bupivacaine. Anesthesiology. 2010 Feb;112(2):493-5. Thoracic epidural anesthesia is considered as an essential component of the perioperative care for patients undergoing lung resection. Although neurologic adverse events have been associated with this technique, permanent injury is rare. These events primarily involve the peripheral nervous system; for example, nerve root injury. We present a case of persistent cortical blindness after a test dose of bupivacaine was administered into an uneventfully placed thoracic epidural catheter. PMID: 20068456 [PubMed - indexed for MEDLINE]

Tolsma M, Kröner A, van den Hombergh CL, Rosseel PM, Rijpstra TA, Dijkstra HA, Bentala M, Schultz MJ, van der Meer NJ. The clinical value of routine chest radiographs in the first 24 hours after cardiac surgery. Anesth Analg. 2011 Jan;112(1):139-42. Epub 2010 Nov 3. BACKGROUND: Chest radiographs (CXRs) are obtained frequently in the intensive care unit (ICU). Whether these CXRs should be performed routinely or on clinical indication only is often debated. The aim of our study was to investigate the incidence and clinical significance

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of abnormalities found on routine postoperative CXRs in cardiac surgery patients and whether a restricted use of CXRs would influence the number of significant findings. METHODS: We prospectively included all consecutive patients who underwent cardiac surgery during a 2-month period. Two or three CXRs were performed in the first 24 hours of ICU stay. After ICU admission and after drain removal, a clinical assessment was performed before a CXR was obtained. All CXR abnormalities were noted and it was also noted whether they led to an intervention. For the admission CXR and the drain removal CXR, a comparison was made between CXRs clinically indicated by the physician and those not clinically indicated. RESULTS: Two hundred fourteen patients were included. The majority of patients underwent coronary arterial bypass grafting (60%), heart valve surgery (21%), or a combination of these (14%). In total, 534 CXRs were performed (2.5 per patient). Abnormalities were found on 179 CXRs (33.5%) and 13 CXR results led to an intervention (2.4%). The association between clinically indicated CXRs and the presence of CXR abnormalities was poor. For 32 (10%) of the 321 admission and drain removal CXRs, clinical indications were stated by the physician beforehand. If these CXRs would not have been performed routinely, 68 abnormalities would have been missed, of which 5 led to an intervention. CONCLUSIONS: Partial elimination of routine CXRs in the first 24 hours after

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cardiac surgery seems possible for the majority of patients, but it is limited by the insensitivity of clinical assessment in predicting clinically important abnormalities detectable by CXRs. PMID: 21048091 [PubMed - indexed for MEDLINE]

Kaas L, Turkenburg JL, van Riet RP, Vroemen JPAM, Eygendaal D. Magnetic resonance imaging findings in 46 elbows with a radial head fracture. Acta Orthopaedica. (2010);18,373-376. BACKGROUND AND PURPOSE: Radial head fractures are common, and may be associated with other injuries of clinical importance. We present the results of a standard additional MRI scan for patients with a radial head fracture. PATIENTS AND METHODS: 44 patients (mean age 47 years) with 46 radial head fractures underwent MRI. 17 elbows had a Mason type-I fracture, 23 a Mason type-II fracture, and 6 elbows had a Mason type-III fracture. RESULTS: Associated injuries were found in 35 elbows: 28 elbows had a lateral collateral ligament lesion, 18 had capitellar injury, 1 had a coronoid fracture, and 1 elbow had medial collateral ligament injury. INTERPRETATION: The incidence of associated injuries with radial head fractures found with MRI was high. The clinical relevance should be investigated. PMID: 20450424 [PubMed - indexed for MEDLINE] PMCID: PMC2876842


Complete publicatielijst Kaas L, Turkenburg JL, van Riet RP, Vroemen JPAM, Eygendaal D. Magnetic resonance imaging findings in 46 elbows with a radial head fracture. Acta Orthopaedica, (2010);18,373-376. Hooft M, Kint PAM, Eygendaal D. Osteoid Osteoma bootst een hemofilie arthropathie van de elleboog na. Ned Tijdschr Orthopedie. 2010;17(3):125-7 Visser WA, Kolling JB, Groen GJ, Tetteroo E, van Dijl R, Rosseel PM, van der Meer NJ. Persistent cortical blindness after a thoracic epidural test dose of bupivacaine. Anesthesiology. 2010 Feb;112(2):493-5. Tolsma M, Kröner A, van den Hombergh CL, Rosseel PM, Rijpstra TA, Dijkstra HA, Bentala M, Schultz MJ, van der Meer NJ. The clinical value of routine chest radiographs in the first 24 hours after cardiac surgery. Anesth Analg. 2011 Jan;112(1):139-42. Epub 2010 Nov 3.

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Reumatologie Kerngegevens zorgkern Reumatologie • 5 reumatologen: mw. C.W.Y. Appels, mw. N.H.A.M. Denissen, mw. dr. B. Lechkar, F.M.A. Slaats, mw. P.A.J.M. Vos 161

Samenvattingen gepubliceerde artikelen Vos PA, DeGroot J, Huisman AM, Oostveen JC, Marijnissen AC, Bijlsma JW, van El B, Zuurmond AM, Lafeber FP. Skin and urine pentosidine weakly correlate with joint damage in a cohort of patients with early signs of osteoarthritis (CHECK). Osteoarthritis Cartilage. 2010 Oct;18(10):1329-36. Epub 2010 Jul 29. OBJECTIVES: Age-related changes in articular cartilage are likely to play a role in the aetiology of osteoarthritis (OA). One of the major age-related changes in cartilage is the accumulation of advanced-glycation-endproducts (AGEs). Since, cartilage tissue is not readily available from patients for studying AGE levels, alternative approaches such as analyzing skin and urine are needed to study the role of cartilage AGE levels in OA. METHODS: Paired human skin and cartilage samples were obtained post mortem. Paired skin and urine samples were obtained from the CHECK cohort (early OA patients). Pentosidine levels were measured by high-performance liquid chromatography (HPLC). As marker of cumulative cartilage damage X-rays of both knees and hips were scored. Urinary CTXII (uCTXII) levels were measured, to assess current cartilage breakdown. RESULTS: Cartilage and skin pentosidine correlate well (R=0.473, P=0.05). Skin pentosidine was higher in mild (summed (Kellgren & Lawrence K&L) over four large joints =4) compared to no (summed K&L=3) radiographic OA (P=0.007). Urinary pentosidine was not different between these two groups. Skin pentosidine levels were not related to cartilage breakdown (highest vs lowest tertile of uCTXII). Urinary pentosidine, however, was higher in the highest compared to the lowest uCTXII tertile (P=0.009). Multiple regression analysis showed age to be the only predictor of the summed K&L score and age, creatinine clearance and urinary

Reumatologie

pentosidine as predictors of uCTXII. CONCLUSION: The higher skin and urinary pentosidine levels in those with mild compared to no radiographic joint damage and low vs high cartilage breakdown respectively suggest that AGEs may contribute to disease susceptibility and/or progression. However, relations are weak and cannot be used as surrogate markers of severity of OA. PMID: 20673850 [PubMed - in process]

Complete publicatielijst Van Onna M, Derksen RHW, Vos PAJM, Ton E. Longfibrose voorafgaand aan miscroscopische polyangitits: meer dan alleen co-incidentie? Ned Tijdschr Reumatol. 2010;13(1):77. Vos PA, DeGroot J, Huisman AM, Oostveen JC, Marijnissen AC, Bijlsma JW, van El B, Zuurmond AM, Lafeber FP. Skin and urine pentosidine weakly correlate with joint damage in a cohort of patients with early signs of osteoarthritis (CHECK). Osteoarthritis Cartilage. 2010 Oct;18(10):1329-36. Epub 2010 Jul 29.

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Revalidatie Kerngegevens zorgkern Revalidatie • 11 revalidatie artsen: mw. S. de Groot-Borsje (CVA, spasticiteit, MS, Parkinson), mw. S.A.M. Lambregts (kinderrevalidatie), mw. M.A. Luijkx (klinische revalidatie), dr. J.W.G. Meijer (neurorevalidatie, neuromusculaire aandoeningen, spasticiteit), mw. A. Pruijssen (neuro en orthopedische revalidatie), mw L.J.M. Rijnders (neurorevalidatie, gedragsmatige revalidatie), mw. N.D.M. Ringeling-van Leusen (hand-, gedragsmatige -, orthopedische revalidatie), W.L.M. Smulders (orthopedische en chirurgische revalidatie, prothesiologie), dr. D. Steenbeek (kinderrevalidatie), mw. A.D. van Velzen (kinderrevalidatie), mw. A. Xanthouli (klinische revalidatie) • 2 longartsen: mw. Van Ambadiang (klinische revalidatie), mw. E. Hoefman (neurorevalidatie, oncologische revalidatie), mw. P.J.H.A. van Hoof (orthopedische revalidatie, gedragsmatige revalidatie), H.J.A.M. Otten (longrevalidatie), D. van Ranst (longrevalidatie) • 3 algemene artsen: mw. V. Ambadiang (klinische revalidatie), mw. E. Hoefman (neurorevalidatie, oncologische revalidatie), mw. P.J.H.A. van Hoof (orthopedische revalidatie, gedragsmatige revalidatie)

Samenvattingen gepubliceerde artikelen Steenbeek D, Ketelaar M, Lindeman E, Galama K, Gorter JW. Interrater reliability of goal attainment scaling in rehabilitation of children with cerebral palsy. Arch Phys Med Rehabil. 2010 Mar;91(3):429-35. OBJECTIVES: To determine the interrater reliability of Goal Attainment Scaling (GAS) in the routine practice of interdisciplinary rehabilitation of children with cerebral palsy, and to examine the difference in the interrater reliability of the scores between GAS scales constructed by the children’s own therapists and the scales constructed by independent therapists. DESIGN:

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Individually tailored GAS scales, based on predetermined criteria, were constructed at the start of a 6-month rehabilitation period. The outcome was rated independently by 2 therapists at the end of the treatment period. Two different data sets were acquired, one consisting of scores on GAS scales constructed by the children’s own therapists, the other of scores on GAS scales constructed by matched independent raters of the same profession. SETTING: A children’s unit of a medium-sized rehabilitation center in The Netherlands. PARTICIPANTS: Physical therapists (n=8), occupational therapists (n=8), and speech therapists (n=4) participated in pairs. They constructed 2 sets of 64 GAS scales each, for 23 children with cerebral palsy. INTERVENTIONS: A 6-month interdisciplinary pediatric rehabilitation program. MAIN OUTCOME MEASURE: Interrater reliability was assessed using linear-weighted Cohen’s kappa. RESULTS: The scales constructed by the children’s therapists had an interrater reliability of .82 (95% confidence interval [CI], .73-.91). The interrater reliability for scales constructed by the independent raters was .64 (95% CI, .49-.79). The main reason for disagreement between raters was discrepancies in the professionals’ interpretation of the children’s capacities versus their actual performance during assessment. CONCLUSIONS: The interrater reliability of GAS used under optimal conditions was good, particularly for scales constructed by the children’s own therapists.

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Copyright 2010 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved. PMID: 20298835 [PubMed - indexed for MEDLINE]

Complete publicatielijst Rameckers E, Steenbeek D, Dekkers K, Galama K, Ketelaar M. From needs to steps for task-specific therapy for children with physical disabilities. Dev Med Child Neurol. 2010;52(suppl 4):23 Abstract. Steenbeek D, Ketelaar M, Gorter JW, Galama K, Lindeman E. Goal Attainment Scaling in de kinderrevalidatie: een waardevol instrument voor uitkomstmeting. Revalidata. 2010 augustus;156:28-29. Steenbeek D, Ketelaar M, Lindeman E, Galama K, Gorter JW. Interrater reliability of goal attainment scaling in rehabilitation of children with cerebral palsy. Arch Phys Med Rehabil. 2010 Mar;91(3):429-35.


Seksuologie Kerngegevens zorgkern Seksuologie • mw. J. van Essen, mw. H. Pastoor

Samenvatting gepubliceerd artikel De Niet JE, de Koning CM, Pastoor H, Duivenvoorden HJ, Valkenburg O, Ramakers MJ, Passchier J, de Klerk C, Laven JS. Psychological well-being and sexarche in women with polycystic ovary syndrome. Hum Reprod. 2010 Jun;25(6):1497-503. Epub 2010 Mar 31. BACKGROUND: The characteristics of polycystic ovary syndrome (PCOS) such as hyperandrogenism and anovulation can be highly stressful and might negatively affect psychological well-being and sexuality. The objective of this study was to evaluate the association between PCOS characteristics and psychological well-being as well as sexarche. METHODS: Patients (n = 1148) underwent standardized clinical evaluation. Psychological wellbeing was investigated in 480 patients with the Rosenberg self-esteem scale (RSES), the body cathexis scale (BCS) and the fear of negative appearance evaluation scale (FNAES). Sexarche was also assessed. RESULTS: Amenorrhoea was associated with lower self-esteem (P = 0.03), greater fear of negative appearance evaluation (P = 0.01) and earlier sexarche (P= 0.004). Hyperandrogenism and acne were associated with poorer body satisfaction (P = 0.03, 0.02, respectively). Hirsutism and BMI were negatively associated with all psychological variables (RSES, P = 0.01; BCS, P = 0.05; FNAES, P = 0.02 and RSES, P = 0.03; BCS, P = 0.001; FNAES, P = 0.03, respectively). CONCLUSIONS: Our results suggest that menstrual irregularities might be related to sexarche. Moreover, this study stresses that the treatment of women with PCOS should notably focus on physical but also on psychological and sexual characteristics. PMID: 20356900 [PubMed - indexed for MEDLINE]

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Publicatielijst De Niet JE, de Koning CM, Pastoor H, Duivenvoorden HJ, Valkenburg O, Ramakers MJ, Passchier J, de Klerk C, Laven JS. Psychological well-being and sexarche in women with polycystic ovary syndrome. Hum Reprod. 2010 Jun;25(6):1497-503. Epub 2010 Mar 31.

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Urologie Ook eigen onderzoek bij zorgkern Urologie

De urologen in het Amphia Ziekenhuis participeren in meerdere internationale multicenteronderzoeken. Daarnaast doen ze ook eigen onderzoek, bijvoorbeeld naar de instellingen van echoapparatuur en naar de best functionerende JJ-katheters. De zorgkern Urologie houdt zich bezig met aandoeningen van de nieren en blaas (bij mannen en vrouwen), de geslachtsorganen en de prostaat (bij mannen). Vooral prostaataandoeningen komen frequent voor. Met een onderzoek naar de aanwezigheid van de stof PSA in het bloed is aantoonbaar of mannen een verhoogd risico hebben op een prostaatcarcinoom. Daarbij spelen ook erfelijkheidsfactoren mee. E.H.G.M. Oomens

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Eric Oomens: “Momenteel doen wij in het Amphia Ziekenhuis met een flink aantal patiënten mee aan de internationale PRIAS-studie, die ook loopt in onder meer Scandinavië, Japan en Canada. Het is namelijk zo dat we niet alle prostaatcarcinomen behandelen. Een ingreep betekent kans op bijwerkingen als impotentie en incontinentie. PRIAS levert een prima programma om niet-agressieve vormen nauwkeurig te volgen en pas op een later tijdstip in te grijpen als het echt noodzakelijk wordt.” Het onderzoek levert een heleboel gegevens op, waarmee later gekeken kan worden of er prognostische factoren zijn waardoor carcinomen bij bepaalde patiënten sneller risicovol worden. “Daarmee kunnen we onze criteria om wel of niet in te grijpen scherper maken.”

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Een ander onderzoek waar de urologen van het Amphia Ziekenhuis bij betrokken zijn, is de IMPACT-studie. Oomens toont een website waar de uroloog een aantal factoren in kan voeren, zoals gegevens van de echo, het inwendig onderzoek, de grootte van de prostaat en het PSA-gehalte. Vervolgens verschijnt de prostaatwijzer, waarop in percentages het risico op prostaatkanker wordt gevisualiseerd. “Het is een hulpmiddel dat ons helpt om een beslissing te nemen over wel of niet biopteren. Bij een percentage groter dan twintig procent is het advies om in te grijpen.” Oomens is als coauteur betrokken bij een aantal artikelen dat hierover verschijnt. Aan het multicenteronderzoek doen ook mee: het Erasmus MC in Rotterdam, het UMCG in Groningen, het Antoni van Leeuwenhoek Ziekenhuis in Amsterdam en het St. Elisabeth Ziekenhuis in Tilburg.

Eigen onderzoek Naast het includeren van patiënten voor internationale onderzoeken initieert de zorgkern Urologie ook eigen onderzoek. Een goed voorbeeld daarvan is het High Intensity Focused Ultrasound (HIFU)-onderzoek dat dr. Jansen onlangs presenteerde op de voorjaarsvergadering van de Nederlandse Vereniging voor Urologie (NVU). Hierbij werden de resultaten gepresenteerd van een behandeling met ultrageluid bij patiënten met een beginstadium van prostaatkanker of met een recidief na bestraling, zowel in het Amphia als in de andere twee centra waar deze therapie wordt toegepast. Een ander onderzoek dat in het Amphia Ziekenhuis werd ontwikkeld is de BIOPRES-studie. “Een echoapparaat voor prostaatonderzoek via de endeldarm heeft twee standen: end-firing en side-firing. Tot voor kort was nog nooit onderzocht of een van de instellingen meer effectief is bij de detectie van prostaatkanker. Dit onderzoek loopt nu twee jaar en er deden tot nu toe ruim 400 patiënten mee. Dat betekent dat we op tweederde van de studie zijn. Dit soort studies draagt bij aan de beste zorg voor de patiënt. Ook vinden we dat al onze artsassistenten tijdens hun periode hier bij een of meer onderzoeken betrokken moeten zijn.” Als lid van de visitatiecommissie van de NVU was Oomens onlangs in het St. Antonius Ziekenhuis in Nieuwegein. “Dan zie je hoe gefocust ze daar zijn op onderzoek. Bij elke


nieuwigheid kijken ze direct: hoe ga ik dat onderzoeken en wat kan ik erover publiceren. Dat is een mindset die ik hier in het Amphia Ziekenhuis nog een beetje mis. Er zou meer wetenschappelijke spin-off moeten zijn, meer reclame. We zijn nog te bescheiden hier.”

Bekkenbodemcentrum Als laatste noemt Oomens het JJ-onderzoek dat in juni start. Een JJ-katheter is een inwendig drainageslangetje dat in de urineleider tussen nier en blaas wordt achtergelaten na een operatie. Bij drie merken wordt gekeken welk de minste hinder voor patiënten oplevert en tegelijkertijd het meeste inbrenggemak oplevert. De Amphia Academie is ingeschakeld om in juni – als er een nieuwe arts-assistent start – het onderzoek op gang te brengen. Oomens is een enthousiast verteller, die eigenlijk bij toeval met het vakgebied in aanraking kwam. “Tijdens mijn opleiding kwam ik op de afdeling Urologie van het Dijkzigt terecht. Daar ervaarde ik hoeveel pathologie er rondom zo’n klein orgaanstelsel mogelijk was en hoe divers de ingrepen waren. Laparoscopisch, endoscopisch, grote open operaties, echt een uitdaging qua chirurgische vaardigheden.” Prettig aan zijn vak vindt hij ook dat hij de intake, de behandeling én de follow-up zelf verzorgt. “Je volgt de patiënt gedurende het hele traject. Ook de patiëntengroep is heel divers. Zelf behandel ik naast volwassen mannen en vrouwen ook veel kinderen. Samen met gynaecologie houden we een superspecialistisch spreekuur: het Bekkenbodemcentrum. Daar vinden allerlei behandelingen plaats rondom incontinentie- en verzakkingsklachten.”

Da Vinci-robot Sinds april 2011 gebruiken urologen van het Amphia Ziekenhuis de innovatieve Da Vinci-robot om de prostaat te verwijderen bij patiënten met prostaatkanker. Er stonden al berichten over in dagblad BN De Stem en op de Amphia-website is een filmpje te vinden van de robot. De ingrepen zijn minimaal invasief en veilig. Daarnaast hopen de urologen op betere resultaten van de operatie, dus meer genezen patiënten en minder negatieve bijeffecten als impotentie en incontinentie. Oomens: “Binnenkort gaan we hem ook inzetten voor operaties aan de nieren en de blaas. Het is de bedoeling dat ook andere specialismen gebruik gaan maken van de robot. Een investering van bijna twee miljoen euro dien je optimaal te benutten.” Robotoperaties vinden onder volledige narcose plaats. Van elke ingreep wordt ook een digitale opname gemaakt, wat handig is voor latere evaluatie van de ingreep. Overigens gebeurde deze vastlegging ook al bij de andere (laparoscopische) ingrepen in de urologie.

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Kerngegevens zorgkern Urologie • 6 urologen: dhr. P.J. van den Broeke, dhr. H. Jansen, mw. I.E.W. van Onna, dhr. E.H.G.M. Oomens, dhr. P.J. Posthumus en dhr. D.K.E. van der Schoot • 2 assistenten in opleiding • Subspecialismen: oncologie (kwaadaardige aandoeningen), stenen (in nieren, urineleiders of blaas), functionele urologie (incontinentie, plasklachten en neurologische blaasproblemen), andrologie (erectiestoornissen, fertiliteit en ouder wordende man), kinderen (aangeboren afwijkingen), algemeen (vergrote prostaat en plasbuisafwijkingen) • Ingrepen: ongeveer 2.500 per jaar


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Multicenter: • IMPACT-studie • PRIAS-studie • FAST-NL-studie • PORTRET-studie ( gynaecologen + urologen) Singlecenter-Amphia: • BIOPRES-onderzoek • observationeel onderzoek naar effect van Lynoral op PSA bij patiënten met CRPC • HIFU-onderzoek • retrospectief onderzoek naar kwaliteit van TURblaas • JJ-studie • studie naar kwaliteit van PNL-operaties in Amphia

Samenvattingen gepubliceerde artikelen Van den Bergh R, Vasarainen H, van der Poel HG, Vis-Maters JJ, Rietbergen JB, Pickles T, Cornel EB, Valdagni R, Jaspars JJ, van der Hoeven J, Staerman F, Oomens EH, Rannikko A, Roemeling S, Steyerberg EW, Roobol MJ, Schröder FH, Bangma CH. Short-term outcomes of the prospective multicentre ‘Prostate Cancer Research International: Active Surveillance’ study. BJU Int. 2010 Apr;105(7):956-62. Epub 2009 Oct 8. OBJECTIVE: To evaluate the short-term outcomes of the prospective international Prostate Cancer Research International: Active Surveillance (‘PRIAS’) study (Dutch Trial Register NTR1718), as active surveillance (AS) for early prostate cancer might provide a partial solution to the current overtreatment dilemma in this disease. PATIENTS AND METHODS: The first 500 (of >950) participants with asymptomatic T1c/T2 prostate cancer, with a prostate-specific antigen (PSA) level of

frequent PSA measurements, digital rectal examinations, and standard repeat biopsies (the first after 1 year). The primary outcome is survival free of active therapy; the secondary endpoints are reasons for stopping AS, findings in 1-year repeat biopsies, and outcomes after radical prostatectomy (RP). RESULTS: Patients were included between December 2006 and July 2008. The median (25-75th percentile) follow-up after diagnosis was 1.02 (0.6-1.5) years. The 2-year survival rate free from active therapy was 73%. Of the 82 men who changed to active therapy during the follow-up, 68 (83%) did so based on the protocol. Of the 261 repeat biopsies available for analysis, 90 (34%) showed no cancer, while 57 (22%) showed a Gleason score of >6 or more than two positive biopsy cores. There was a relatively unfavourable PSA doubling time of 0-10 years in 53% (102/194) and 62% (33/53) of men with favourable and unfavourable re-biopsy results, respectively. After RP, four of 24 (17%) men had T3 disease and 12 (50%) had a Gleason score of >6. CONCLUSION: AS seems feasible, but mortality outcomes are unknown. A strict follow-up protocol including standard 1-year repeat biopsies resulted in a quarter of men stopping AS after 2 years. PMID: 19817747 [PubMed - as supplied by publisher]

Meijer RP, van Onna IE, Kok ET, Bosch R. The risk profiles of three clinical types of carcinoma in situ of the bladder. BJU Int. 2010 Dec 16. [Epub ahead of print]. OBJECTIVE: To further clarify the risk profiles of three clinical types of carcinoma in situ (CIS) of the bladder. MATERIALS AND METHODS: Population-based data from the Comprehensive Cancer Centre Middle Netherlands, as part of the nationwide Netherlands Cancer Registry, were used for patients presenting with CIS in the period from 1987 to 2009. Patients with muscle-invasive bladder cancer on primary diagnosis were excluded. The patients were divided into three groups according to their ‘clinical type’, being primary, concomitant or secondary CIS. RESULTS: Overall, 90 patients with CIS were identified with a mean age of 63.4 years, predominantly men (91.1%). Primary CIS (P-CIS) was found in 43 patients (47.8%), concomitant CIS (C-CIS) in 21 patients (23.3%) and secondary CIS (S-CIS) in 26 patients (28.9%). Mean follow up was 81.3 months (range 8-222 months). Recurrence of disease was observed in 68.9% of patients, with significantly more recurrences in the S-CIS group (88.5%). Progression to muscle-invasive disease was seen in 17 patients (18.9%): eight patients (18.7%) with P-CIS, four (19.0%) with C-CIS and five (19.2%) with S-CIS. Overall, 29 patients underwent a cystectomy, equally distributed over the three groups. The duration of bladder preservation was worse in the C-CIS group but did not differ significantly between the groups. Overall survival at 5 years was 79.6% for the total group, with poorer results for the C-CIS group, although the difference was not significant. CONCLUSIONS: Carcinoma in situ is clearly an entity that requires meticulous treatment and thorough follow up because of its high recurrence rate (68.9%) and high rate of progression to muscle-invasive bladder cancer (18.9%). The C-CIS group appears to have a poorer

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prognosis with a shorter duration of bladder preservation and a worse overall survival. © 2010 the authors; BJU International © 2010 BJU International. PMID: 21166747 [PubMed - as supplied by publisher]


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Boormans JL, van der Schoot DKE, Oomens EGHM. Een secundaire tumor in de prostaat: metastase van een adenocarcinoom van de long. Ned Tijdschr Urol. 2010 jun;18(4): 107-9. Jansen H. HIFU: High Intensity Focused Ultrasound, de Bredase ervaring. Ned Tijdschr Urol. 2010 feb;18(1):26-9. Van den Bergh R, Vasarainen H, van der Poel HG, Vis-Maters JJ, Rietbergen JB, Pickles T, Cornel EB, Valdagni R, Jaspars JJ, van der Hoeven J, Staerman F, Oomens EH, Rannikko A, Roemeling S, Steyerberg EW, Roobol MJ, Schröder FH, Bangma CH. Shortterm outcomes of the prospective multicentre ‘Prostate Cancer Research International: Active Surveillance’ study. BJU Int. 2010 Apr;105(7):956-62. Epub 2009 Oct 8. Meijer RP, van Onna IE, Kok ET, Bosch R. The risk profiles of three clinical types of carcinoma in situ of the bladder. BJU Int. 2010 Dec 16. [Epub ahead of print].


Publicaties Medisch Specialisten 2010 Artikelen, abstracts en boekbijdragen

Hegmans JP, Veltman JD, Lambers ME, de Vries IJ, Figdor CG, Hendriks RW, Hoogsteden HC, Lambrecht BN, Aerts JG. Consolidative Dendritic Cell-Based Immunotherapy Elicits Cytotoxicity Against Malignant Mesothelioma. Am J Respir Crit Care Med. 2010 Feb 18. [Epub ahead of print] Surmont V, Smit EF, de Jonge M, Aerts JG, Nackaerts K, Vernhout R, Gras J, Van Wijk A, Phernambucq EC, van Meerbeeck JP, Senan S, Kraaij CJ, Chouaki N, Praag J, van Klaveren RJ. Pemetrexed and cisplatin with concurrent radiotherapy for locally advanced non-small cell and limited disease small cell lung cancer: Results from 2 phase I studies. Lung Cancer. 2010 Sep;69(3):302-6. Epub 2010 Jan 22. Kanick SC, van der Leest C, Aerts JG, Hoogsteden HC, Kascáková S, Sterenborg HJ, Amelink A. Integration of single-fiber reflectance spectroscopy into ultrasound-guided endoscopic lung cancer staging of mediastinal lymph nodes. J Biomed Opt. 2010 JanFeb;15(1):017004. Tournoy KG, Bolly A, Aerts JG, Pierard P, De Pauw R, Leduc D, Leloup A, Pieters T, Slabbynck H, Janssens A, Carron K, Schrevens L, Pat K, De Keukeleire T, Dooms C. The value of endoscopic ultrasound after bronchoscopy to diagnose thoracic sarcoidosis. Eur Respir J. 2010 Jun;35(6):1329-35. Epub 2009 Nov 6. Surmont V, Aerts JG, van Klaveren RJ, Tournoy K, Tan KY, Vernhout RM, Schmitz PI, Legrand C, Hoogsteden HC, van Meerbeeck JP. A randomized phase II study comparing two schedules of the 21-day regimen of gemcitabine and carboplatin in advanced nonsmall cell lung cancer. Oncology. 2010;78(3-4):267-70. Epub 2010 Jun 7. Veltman JD, Lambers ME, van Nimwegen M, de Jong S, Hendriks RW, Hoogsteden HC, Aerts JG, Hegmans JP. Low-dose cyclophosphamide synergizes with dendritic

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Geurts JJG, Visser LH, Vrancken PH. - redactie: Sanders EACM, Zwanikken CP. Multiple Sclerose Lexicon, dl. 6: Multipele Sclerose en Psychologie. Utrecht: Academical Pharmaceutic Productions, 2010. ISBN 978-90-5761-106-3. Hintzen R, Berrevoets-Catsman CE. - redactie: Sanders EACM, Zwanikken CP. Multiple Sclerose Lexicon, dl. 5: Multipele Sclerose en Kinderneurologie Utrecht: Academical Pharmaceutic Productions, 2010. ISBN 978-90-5761-102-5. Sanders EACM, Zwanikken CP, de Vries-Knoppert WAEJ. Multiple Sclerose Lexicon, dl. 4: Multipele Sclerose en Oogheelkunde Utrecht: Academical Pharmaceutic Productions, 2010. ISBN 978-90-5761-100-1. Sanders EACM, Zwanikken CP, Beenakker EAC. Multipele Sclerose Handboek: een leidraad voor de praktijk Utrecht: Academical Pharmaceutical Productions, 2010. ISBN 978-905761-099-8. Sanders EACM. Retina dikte en cerebraal atrofie bij multiple sclerose. Neurologie Actueel 2010 oktober;13:7. Sanders EACM. Het belang, het herkennen en behandelen van de ziekte van Alzheimer. Neurologie Actueel. 2010 september;13:6. Sanders EACM. Orale therapie voor multipele sclerose: de resultaten van de CLARITYstudie. Neurologie Actueel 2010 juli;5, 7. Sanders EACM. Multipele sclerose in combinatie met andere immuun ziekten. Multipele Sclerose jaargang 4, deel 2, 2010. Wens SCA, Sanders EACM. Twee patiënten met pijn, koorts en een progressieve tetraparese. Tijdschr Neurol Neurochirurgie. 2010; 11(6):245-252. Sanders EACM. Multipele Sclerose en Cognitie. Utrecht: Academical Pharmaceutical Productions, 2010. ISBN 978-90-5761-094-3. Van Santvoort HC, Besselink MG, Bakker OJ, Hofker HS, Boermeester MA, Dejong CH, van Goor H, Schaapherder AF, van Eijck CH, Bollen TL, van Ramshorst B, Nieuwenhuijs VB, Timmer R, Laméris JS, Kruyt PM, Manusama ER, van der Harst E, van der Schelling GP, Karsten T, Hesselink EJ, van Laarhoven CJ, Rosman C, Bosscha K, de Wit RJ, Houdijk AP, van Leeuwen MS, Buskens E, Gooszen HG; Dutch Pancreatitis Study Group*. A stepup approach or open necrosectomy for necrotizing pancreatitis. N Engl J Med. 2010 Apr 22;362(16):1491-502. Boormans JL, van der Schoot DKE, Oomens EGHM. Een secundaire tumor in de prostaat: metastase van een adenocarcinoom van de long. Ned Tijdschr Urol. 2010 jun;18(4): 107-9. Zaludik J, Schuitemaker F, DeWaal R, Veldhuijzen B, van der Meer N. Severe lactate acidosis and cardiogenic shock: a rare manifestation of a phaeochromocytoma. Anaesth Intensive Care. 2010 May;38(3):593-4.


Uchida N, Galasso D, Seerden TC, Carnuccio A, Zachariah K, Costamagna G, Larghi A. EUS-FNA of extracolonic lesions by using the forward-viewing linear echoendoscope. Gastrointest Endosc. 2010 Dec;72(6):1321-3. Epub 2010 Jul 1. Larghi A, Seerden TC, Galasso D, Carnuccio A, Familiari P, Mutignani M, Zachariah K, Costamagna G. EUS-guided therapeutic interventions for uncommon benign pancreaticobiliary disorders by using a newly developed forward-viewing echoendoscope (with videos). Gastrointest Endosc. 2010 Jul;72(1):213-5. Epub 2010 Mar 6. Mutignani M, Seerden T, Tringali A, Feisal D, Perri V, Familiari P, Costamagna G. Endoscopic hemostasis with fibrin glue for refractory postsphincterotomy and postpapillectomy bleeding. Gastrointest Endosc. 2010 Apr;71(4):856-60. Steenbeek D, Ketelaar M, Gorter JW, Galama K, Lindeman E. Goal Attainment Scaling in de kinderrevalidatie: een waardevol instrument voor uitkomstmeting. Revalidata. 2010 augustus;156:28-29. Rameckers E, Steenbeek D, Dekkers K, Galama K, Ketelaar M. From needs to steps for task-specific therapy for children with physical disabilities. Dev Med Child Neurol. 2010;52(suppl 4):23 [Abstract]. Visser WA, Kolling JB, Groen GJ, Tetteroo E, van Dijl R, Rosseel PM, van der Meer NJ. Persistent cortical blindness after a thoracic epidural test dose of bupivacaine. Anesthesiology. 2010 Feb;112(2):493-5. Willemse J, Tigchelaar O, Porro G. Even een prikje? Onderbelichte risico’s van retrobulbaire verdoving. [Abstract]. 204e NOG vergadering. Maastricht, 25 maart 2010. Kaas L, Turkenburg JL, van Riet RP, Vroemen JPAM, Eygendaal D. Magnetic resonance imaging findings in 46 elbows with a radial head fracture. Acta Orthopaedica, (2010);18,373-376. Koopman M, Brackel HJ, Vaessen-Verberne AA, Hop WC, van der Ent CK; on behalf of the COMBO-Rint Research GroupCOMBO-Rint Research Group members are listed in the Acknowledgment Section.. Evaluation of interrupter resistance in methacholine challenge testing in children. Pediatr Pulmonol. 2010 Nov 17. [Epub ahead of print] Vaessen-Verberne AA, van den Berg NJ, van Nierop JC, Brackel HJ, Gerrits GP, Hop WC, Duiverman EJ; COMBO Study Group*. Combination therapy salmeterol/fluticasone versus doubling dose of fluticasone in children with asthma. Am J Respir Crit Care Med. 2010 Nov 15;182(10):1221-7. Epub 2010 Jul 9. Küthe MC, Vaessen-Verberne AA, Bindels PJ, van Aalderen WM. Children with asthma on inhaled corticosteroids managed in general practice or by hospital paediatricians: is there a difference? Prim Care Respir J. 2010 Mar;19(1):62-7, 8p following 67. Koolen BB, Pijnenburg MW, Brackel HJ, Landstra AM, van den Berg NJ, Merkus PJ, Hop WC, Vaessen-Verberne AA. Validation of a web-based version of the asthma control test and childhood asthma control test. Pediatr Pulmonol. 2011 Apr 1. [Epub ahead of print].


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Koolen BB, Pijnenburg MWH, Brackel HJL, Landstra AM, van den Berg NJ, Merkus PJFM, Hop WCJ, Vaessen-Verberne AAPH. Detecting uncontrolled asthma in children: (Childhood) Asthma Control Test versus GINA-guidelines and Asthma Control Questionnaire. Eur Resp J. 2010;36:879s (ERS Barcelona). Flu HC, Lardenoye JH, Veen EJ, Van Berge Henegouwen DP, Hamming JF. Functional status as a prognostic factor for primary revascularization for critical limb ischemia. J Vasc Surg. 2010 Feb;51(2):360-71.e1. Flu HC, Ploeg AJ, Marang-van de Mheen PJ, Veen EJ, Lange CP, Breslau PJ, Roukema JA, Hamming JF, Lardenoye JW. Patient and procedure-related risk factors for adverse events after infrainguinal bypass. J Vasc Surg. 2010 Mar;51(3):622-7. Franken JM, Veen EJ. Hepatic portal venous gas. J Gastrointestin Liver Dis. 2010 Dec;19(4):360. Veen EJ, Janssen-Heijnen ML, Bosma E, de Jongh MA, Roukema JA. The accuracy of complications documented in a prospective complication registry. J Surg Res. 2010 Sep 24. [Epub ahead of print] Veen EJ, Janssen-Heijnen ML, de Jongh MA, Roukema JA. Incidence and type of complications in non-operated patients at a surgical ward. Patient Saf Surg. 2010 Jul 20;4(1):11. Talsma K, Veen HF, de Groot HGW, Veen EJ. Chirurgische techniek. Cervicale mediastinoscopie. Ned Tijdschr Heelkd. 2010 november;19(8):298-302. Ter Laak MA, Temmink AH, Koeken A, van ‘t Veer NE, van Hattum PR, Cobbaert CM. Recognition of impaired atomoxetine metabolism because of low CYP2D6 activity. Pediatr Neurol. 2010 Sep;43(3):159-62. Zaludik J, Schuitemaker F, DeWaal R, Veldhuijzen B, van der Meer N. Severe lactate acidosis and cardiogenic shock: a rare manifestation of a phaeochromocytoma. Anaesth Intensive Care. 2010 May;38(3):593-4. Van den Berge CKA, van Guldener C, Verburg GP. Recidiverende pericarditis en eosinofilie bij een jonge vrouw. Tijdschr Infectieziekten. 2010;5:180-3. Jinnah HA, Ceballos-Picot I, Torres RJ, Visser JE, Schretlen DJ, Verdu A, Laróvere LE, Chen CJ, Cossu A, Wu CH, Sampat R, Chang SJ, de Kremer RD, Nyhan W, Harris JC, Reich SG, Puig JG; for the Lesch-Nyhan Disease International Study Group. Attenuated variants of Lesch-Nyhan disease. Brain 2010;133:671-689. Epub Feb 22. Visser JE, Oude Nijhuis LB, Janssen L, Bastiaanse CM, Borm GF, Duysens J, Bloem BR. Dynamic posturography in Parkinson’s disease: diagnostic utility of the “first trial effect”. Neuroscience. 2010 Jun 30;168(2):387-94. Epub 2010 Apr 7. Visser WA, Kolling JB, Groen GJ, Tetteroo E, van Dijl R, Rosseel PM, van der Meer NJ. Persistent cortical blindness after a thoracic epidural test dose of bupivacaine. Anesthesiology. 2010 Feb;112(2):493-5.


Stolwijk AWM, van Wensen A, van Hooft MAA, Franken JM, Somford MP, van der Laan L, Vos DI. Een vorstperiode van drie weken: analyse van de gevolgen voor een perifeer ziekenhuis en de bruikbaarheid van een triagesysteem. Ned Tijdschr Traumatologie. 2010;18(3):66-73. Heijnen S, Vroemen J, Eygendaal D, Vos D. Hoekstabiele plaatostheosynthese van de proximale humerus fractuur. Ned Tijdschr Traumatol. 2010;6:162-6. Van Onna M, Derksen RHW, Vos PAJM, Ton E. Longfibrose voorafgaand aan miscroscopische polyangitits: meer dan alleen co-incidentie? Ned Tijdschr Reumatol. 2010;13(1):77. Vos PA, DeGroot J, Huisman AM, Oostveen JC, Marijnissen AC, Bijlsma JW, van El B, Zuurmond AM, Lafeber FP. Skin and urine pentosidine weakly correlate with joint damage in a cohort of patients with early signs of osteoarthritis (CHECK). Osteoarthritis Cartilage. 2010 Oct;18(10):1329-36. Epub 2010 Jul 29. Kaas L, Riet RP, Vroemen JP, Eygendaal D. The epidemiology of radial head fractures: A possible link to osteoporosis? J Shoulder Elbow Surg. 2010 Feb 9. [Epub ahead of print]. Somford MP, Sturm MF, Vroemen JP. Reconstruction of isolated scaphoid dislocation with carpal dissociation, associated with a carpal anomaly. Strategies Trauma Limb Reconstr. 2010;5(2):105-110. Heijnen S, Vroemen J, Eygendaal D, Vos D. Hoekstabiele plaatostheosynthese van de proximale humerus fractuur. Ned Tijdschr Traumatol. 2010;6:162-6. Kaas L, Turkenburg JL, van Riet RP, Vroemen JPAM, Eygendaal D. Magnetic resonance imaging findings in 46 elbows with a radial head fracture. Acta Orthopaedica, (2010);18,373-376. De Haan J, den Hartog D, Tuinebreijer WE, Iordens GI, Breederveld RS, Bronkhorst MW, Bruijninckx MM, De Vries MR, Dwars BJ, Eygendaal D, Haverlag R, Meylaerts SA, Mulder JW, Ponsen KJ, Roerdink WH, Roukema GR, Schipper IB, Schouten MA, Sintenie JB, Sivro S, Van den Brand JG, Van der Meulen HG, Van Thiel TP, Van Vugt AB, Verleisdonk EJ, Vroemen JP, Waleboer M, Willems WJ, Polinder S, Patka P, van Lieshout EM, Schep NW.Functional treatment versus plaster for simple elbow dislocations (FuncSiE): a randomized trial. BMC Musculoskelet Disord. 2010 Nov 12;11:263. Te Slaa A, Dolmans DE, Ho GH, Mulder PG, van der Waal JC, de Groot HG, van der Laan L. Evaluation of A-V impulse technology as a treatment for oedema following polytetrafluoroethylene femoropopliteal surgery in a randomised controlled trial. Eur J Vasc Endovasc Surg. 2010 Jul 26. [Epub ahead of print] Reininga IH, Zijlstra W, Wagenmakers R, Boerboom AL, Huijbers BP, Groothoff JW, Bulstra SK, Stevens M. Minimally invasive and computer-navigated total hip arthroplasty: a qualitative and systematic review of the literature. BMC Musculoskelet Disord. 2010 May 17;11:92. Aerts JGJV, van Walree NC. Moleculaire diagnostiek en longkanker. IKR Bulletin. 2010 nov;34:15-17.


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Andriesse GI, Donmez M, Vissers J, van Wijngaarden P. Acute hepatitis, maar niet A, B, of C: overweeg E. Ned Tijdschr Geneeskd. 2010 Aug 21;154(33):1536-1539. Van der Mark SC, Segers D, Baker RC, van Wijngaarden P. Het DRESS – syndroom bij gebruik van sulfasalazine: Geneesmiddelexantheem met eosinofilie en systemische symptomen. Ned Tijdschr Geneeskd. 2010 Dec 11;154(49):2287-2290. Gobardhan PD, Elias SG, Madsen EV, van Wely B, van den Wildenberg F, Theunissen EB, Ernst MF, Kokke MC, van der Pol C, Borel Rinkes IH, Wijsman JH, Bongers V, van Gorp J, van Dalen T. Prognostic value of lymph node micrometastases in breast cancer: a multicenter cohort study. Ann Surg Oncol. 2011 Jun;18(6):1657-64. Epub 2010 Dec 14. Solouki AM, Verhoeven VJ, van Duijn CM, Verkerk AJ, Ikram MK, Hysi PG, Despriet DD, van Koolwijk LM, Ho L, Ramdas WD, Czudowska M, Kuijpers RW, Amin N, Struchalin M, Aulchenko YS, van Rij G, Riemslag FC, Young TL, Mackey DA, Spector TD, Gorgels TG, Willemse-Assink JJ, Isaacs A, Kramer R, Swagemakers SM, Bergen AA, van Oosterhout AA, Oostra BA, Rivadeneira F, Uitterlinden AG, Hofman A, de Jong PT, Hammond CJ, Vingerling JR, Klaver CC. A genome-wide association study identifies a susceptibility locus for refractive errors and myopia at 15q14. Nat Genet. 2010 Oct;42(10):897-901. Epub 2010 Sep 12. Willemse J, Tigchelaar O, Porro G. Even een prikje? Onderbelichte risico’s van retrobulbaire verdoving. [Abstract]. 204e NOG vergadering. Maastricht, 25 maart 2010. Van Beek J, Willemse J, Porro G. Relapsing polychondritis en oogafwijkingen. [Abstract]. 204e NOG vergadering. Maastricht, 25 maart 2010. Willemsen I, Cooper B, van Buitenen C, Winters M, Andriesse G, Kluytmans J. Improving quinolone use in hospitals by using a bundle of interventions in an interrupted time series analysis. Antimicrob Agents Chemother. 2010 Sep;54(9):3763-9. Epub 2010 Jun 28. Zijlmans JC. The role of imaging in the diagnosis of vascular parkinsonism. Neuroimaging Clin N Am. 2010 Feb;20(1):69-76. Jahanshahi M, Jones CR, Zijlmans J, Katzenschlager R, Lee L, Quinn N, Frith CD, Lees AJ. Dopaminergic modulation of striato-frontal connectivity during motor timing in Parkinson’s disease. Brain. 2010 Mar;133(Pt 3):727-45. Zijlmans JCM, Hovestadt A, Berendse HW, Visser JE, Bloem BR, Boon AJW, van Hilten JJ, de Koning-Tijssen MAJ, Nijssen PCG, van Laar T. Rasagiline (Azilect) effectief als symptoombestrijding? Papaver. 2010;33(4):6-7. Poewe W, Antonini A, Zijlmans JC, Burkhard PR, Vingerhoets F. Levodopa in the treatment of Parkinson’s disease: an old drug still going strong. Clin Interv Aging. 2010 Sep 7;5:229-38.


Publicaties Arts-assistenten 2010 Artikelen, abstracts en boekbijdragen

Cefo I, Eygendaal D. Arthroscopic arthrolysis for posttraumatic elbow stiffness. J Shoulder Elbow Surg. 2011 Mar;20(3):434-9. Van Cleef BA, Verkade EJ, Wulf MW, Buiting AG, Voss A, Huijsdens XW, van Pelt W, Mulders MN, Kluytmans JA. Prevalence of livestock-associated MRSA in communities with high pig-densities in The Netherlands. PLoS One. 2010 Feb 25;5(2):e9385. Van Cleef BA, Broens EM, Voss A, Huijsdens XW, Züchner L, Van Benthem BH, Kluytmans JA, Mulders MN, Van De Giessen AW. High prevalence of nasal MRSA carriage in slaughterhouse workers in contact with live pigs in The Netherlands. Epidemiol Infect. 2010 May;138(5):756-63. Epub 2010 Feb 9. Gobardhan PD, Elias SG, Madsen EV, van Wely B, van den Wildenberg F, Theunissen EB, Ernst MF, Kokke MC, van der Pol C, Borel Rinkes IH, Wijsman JH, Bongers V, van Gorp J, van Dalen T. Prognostic value of lymph node micrometastases in breast cancer: a multicenter cohort study. Ann Surg Oncol. 2011 Jun;18(6):1657-64. Epub 2010 Dec 14. Geertsema D, Gobardhan PD, Madsen EV, Albregts M, van Gorp J, de Hooge P, van Dalen T. Discordance of intraoperative frozen section analysis with definitive histology of sentinel lymph nodes in breast cancer surgery: complementary axillary lymph node dissection is irrelevant for subsequent systemic therapy. Ann Surg Oncol, 2010: 17(10); 2690-5. Kaas L, Riet RP, Vroemen JP, Eygendaal D. The epidemiology of radial head fractures. J Shoulder Elbow Surg. 2010 Feb 9. [Epub ahead of print] Kaas L, van Dijk CN, Eygendaal D. Radiuskopfracturen en begeleidend letsel; de stand van zaken. Ned Tijdschr Traumatol. 2010;4:94-99. Kant KM, Djamin RS, Belderbos HNA. Acute respiratoire insufficientie op basis van COPD: To be ventilated or not to be ventilated. A en I: Nascholingstijdschrift voor perioperatieve geneeskunde. 2010 maart;2(1).

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De Leur K, Castenmiller PH, van der Laan L. Idiopathic Mid-Aortic Syndrome in a Young Adult: A Case Report. Vasc. Dis. Management. 2010 dec;7(12):E245-7. Marres GMH, Leenen LPH, van der Slikke JW, Vermetten E. Evaluation of a web portal for e-support after a disaster: opportunities and lessons learned. Eur J Trauma Emerg Surg 2010;36:1-238. Marres GMH, van der Eijk J, Bemelman M, Leenen LPH. Evaluation of admissions to the Major Incident Hospital based on a standardized protocol. Eur J Trauma Emerg Surg 2011;37(1):19-29. Marres GMH, Leenen LPH, van der Slikke JW, Vermetten E. Use of a web portal for support and research after a disaster - opportunities and lessons learned. Interactive J Med Res – August 2010. http://knol.google.com/k/use-of-a-web-portal-for-support-andresearch-after-a-disaster-opportunities-and# Nowe V, Geboers I, Spinhoven MJ, Carp L, Van den Brande J, Peeters M, Vermorken JB. Sorafenib in metastatic angiosarcoma of the uterus: response and quality of life. Belg J Med Oncol. 2010;4:209-11. Somford MP, Reynders D, Rijken AM. Internal herniation in an unusual peritoneal aperture. J Abdom Surg. 2010 Spring:5-6. Baumfeld JA, van Riet RP, Zobitz ME, Eygendaal D, An KN, Steinmann SP. Triceps tendon properties and its potential as an autograft. J Shoulder Elbow Surg. 2010 Jul;19(5): 697-9. Epub 2010 Apr 22. Somford MP, Reynders D, Rijken AM. Internal herniation in an unusual peritoneal aperture. J Abdom Surg. 2010 Spring:5-6. Speksnijder L, Rutten JH, van den Meiracker AH, de Bruin RJ, Lindemans J, Hop WC, Visser W. Amino-terminal pro-brain natriuretic peptide (NT-proBNP) is a biomarker of cardiac filling pressures in pre-eclampsia. Eur J Obstet Gynecol Reprod Biol. 2010 Nov;153(1):12-5. Epub 2010 Jul 31. Speksnijder L, Rousian M, Steegers EA, Koning AH, Steensma A. Reliability of threedimensional ultrasound measurements of the levator ani hiatus using virtual reality. Ultrasound Obstet Gynecol. 2010;36(Suppl. 1):128. Speksnijder L, Duvekot JJ, Duschek EJ, Jebbink MC, Bremer HA. Spontaneous pneumomediastinum: a rare presentation of diabetic ketoacidosis in a pregnant woman. Obstetric Medicine. 2010;3:158–160.


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Uitgave: Prelum Uitgevers, Houten Ontwerp omslag en binnenwerk: CO2 Premedia bv, Amersfoort Vormgeving: CO2 Premedia bv, Amersfoort Druk- en bindwerk: Drukkerij Wilco b.v., Amersfoort Oplage: 1000 exemplaren Interviews: Leonore Pulleman Tekstpartners, Breda Overzicht publicaties: Jan van Trier Eindredactie: Joachim Aerts, Leonore Pulleman, Eric Verheijden Verspreiding: Kenniskern Amphia Academie De Kenniskern Amphia Academie maakt deel uit van het Amphia Ziekenhuis Breda/ Oosterhout


Oosterhout

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