Nieuwegein, Netherlands
Nieuwegein, Netherlands

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Blok J.L.,University of Groningen | Boersma M.,University of Groningen | Terra J.B.,University of Groningen | Spoo J.R.,University of Groningen | And 5 more authors.
Journal of the European Academy of Dermatology and Venereology | Year: 2015

Background Treatment of hidradenitis suppurativa (HS) is a difficult undertaking, especially as there is no consensus on what surgical technique is preferred. At our centre severe HS (Hurley II/III) is operated under general anaesthesia, mostly with the STEEP procedure. Objectives To investigate characteristics, surgical outcomes and patient satisfaction of HS patients who underwent deroofing or STEEP under general anaesthesia. Methods A clinical records-based retrospective analysis was conducted of all patients who had surgery under general anaesthesia between 1999 and 2013. Patient satisfaction was retrospectively investigated with questionnaires. Results A total of 482 operations (363 primary operations and 119 re-operations) were performed during the study period. The proportion of women in the included population was 68%. The median diagnostic delay (patient's and doctor's delay) was 6.5 years. Relapses occurred after 29.2% of primary operations. Women had higher relapse rates than men [odds ratio 2.85 (1.07;7.61)]. Hypergranulation of the wound was the most common complication and occurred in 7% of all operations. The median score patients attributed to the medical effect of surgery was eight of 10 (zero corresponding to very dissatisfied and 10 to very satisfied). Conclusion The diagnostic delay in HS is long due to a lack of knowledge in both patients and health care professionals, indicating that there is a need for education. Deroofing and the STEEP are effective surgical procedures in severe cases of HS and lead to a relatively high patient satisfaction. The postoperative relapse risk is higher in women. Prospective studies are required for the development of clear guidelines on the appropriate choice of surgery. © 2015 European Academy of Dermatology and Venereology.

Lokhorst H.M.,University Utrecht | Van Der Holt B.,Hovon Data Center | Cornelissen J.J.,Erasmus Medical Center | Raymakers R.,University Utrecht | And 10 more authors.
Blood | Year: 2012

To prospectively evaluate allogeneic stem cell transplantation (allo-SCT) for myeloma as part of first-line therapy, a donor versus no-donor analysis was performed of patients treated in the HOVON-50 study, a study that was originally designed to examine thalidomide combined with intensive therapy. Two hundred sixty patients having received an autologous-SCT fulfilled the criteria to be included, 138 patients without an HLA-identical sibling donor and 122 patients with a donor. After a median follow-up of 77 months, complete remission, progression-free survival (PFS), and overall survival were not significantly different between the 2 groups. PFS at 6 years was 28% for patients with a donor versus 22% for patients without a donor (P = .19) and overall survival at 6 years from high-dose melphalan was 55%, irrespective of having a donor (P = .68). Cumulative incidence of nonrelapse mortality at 6 years after autologous-SCT was 16% in the donor group versus 3% in the no-donor group (P < .001). However, PFS was significantly prolonged in the 99 patients who actually proceeded to allo-SCT compared with the 115 patients who continued maintenance or received a second high-dose melphalan, but the difference did not translate into a prolonged survival benefit. These results do not support a general application of allo-SCT in all myeloma patients as part of first-line therapy. © 2012 by The American Society of Hematology.

Blok J.L.,University of Groningen | Spoo J.R.,University of Groningen | Leeman F.W.J.,Antonius Hospital | Jonkman M.F.,University of Groningen | Horvath B.,University of Groningen
Journal of the European Academy of Dermatology and Venereology | Year: 2015

Background: Surgery is the only curative treatment for removal of the persistent sinus tracts in the skin that are characteristic of severe hidradenitis suppurativa (HS). Complete resection of the affected tissue by wide excision is currently regarded as the preferred surgical technique in these cases. However, relatively large amounts of healthy tissue are removed with this method and suitable skin-tissue-saving techniques aiming at creating less-extensive surgical defects are therefore needed in severe HS. Method: We describe a skin-tissue-saving surgical technique for HS Hurley stage II-III disease: the Skin-Tissue-sparing Excision with Electrosurgical Peeling (STEEP) procedure. Discussion: In contrast to wide excisions that generally reach into the deep subcutaneous fat, the fat is maximally spared with the STEEP procedure by performing successive tangential excisions of lesional tissue until the epithelialized bottom of the sinus tracts has been reached. From here, secondary intention healing can occur. In addition, fibrotic tissue is completely removed in the same manner as this also serves as a source of recurrence. This tissue-sparing technique results in low recurrence rates, high patient satisfaction with relatively short healing times and favourable cosmetic outcomes without contractures. © 2014 European Academy of Dermatology and Venereology.

Barc J.,ICIN Netherlands Heart Institute | Van Haelst P.L.,Antonius Hospital | Caliskan K.,Erasmus University Rotterdam | Hoedemaekers Y.M.,University of Groningen | And 7 more authors.
Journal of the American College of Cardiology | Year: 2014

BACKGROUND: Familial forms of primary sinus bradycardia have sometimes been attributed to mutations in HCN4, SCN5A, and ANK2. In these studies, no structural cardiac alterations were reported in mutation carriers. However, a cluster of reports in the literature describe patients presenting with sinus bradycardia in association with left ventricular noncompaction cardiomyopathy (LVNC), pointing to a shared genetic cause. OBJECTIVES: This study sought to identify the genetic defect underlying the combined clinical presentation of bradycardia and LVNC, hypothesizing that these 2 clinical abnormalities have a common genetic cause. METHODS: Exome sequencing was carried out in 2 cousins from the index family that were affected by the combined bradycardia-LVNC phenotype; shared variants thus identified were subsequently overlaid with the chromosomal regions shared among 5 affected family members that were identified using single nucleotide polymorphism array analysis. RESULTS: The combined linkage analysis and exome sequencing in the index family identified 11 novel variants shared among the 2 affected cousins. One of these, p.Gly482Arg in HCN4, segregated with the combined bradycardia and LVNC phenotype in the entire family. Subsequent screening of HCN4 in 3 additional families with the same clinical combination of bradycardia and LVNC identified HCN4 mutations in each. In electrophysiological studies, all found HCN4 mutations showed a more negative voltage dependence of activation, consistent with the observed bradycardia. CONCLUSIONS: Although mutations in HCN4 have been previously linked to bradycardia, our study provides the first evidence to our knowledge that mutations in this ion channel gene also may be associated with structural abnormalities of the myocardium. © 2014 by the American College of Cardiology Foundation.

Van Der Valk M.E.,University Utrecht | Mangen M.-J.J.,University Utrecht | Leenders M.,University Utrecht | Dijkstra G.,University of Groningen | And 17 more authors.
Gut | Year: 2014

Objective The introduction of anti tumour necrosis factor-α (anti-TNFα) therapy might impact healthcare expenditures, but there are limited data regarding the costs of inflammatory bowel diseases (IBD) following the introduction of these drugs. We aimed to assess the healthcare costs and productivity losses in a large cohort of IBD patients. Design Crohn's disease (CD) and ulcerative colitis (UC) patients from seven university hospitals and seven general hospitals were invited to fill-out a web-based questionnaire. Cost items were derived from a 3 month follow-up questionnaire and categorised in outpatient clinic, diagnostics, medication, surgery and hospitalisation. Productivity losses included sick leave of paid and unpaid work. Costs were expressed as mean 3-month costs per patients with a 95% CI obtained using non-parametric bootstrapping. Results A total of 1315 CD patients and 937 UC patients were included. Healthcare costs were almost three times higher in CD as compared with UC, €1625(95% CI €1476 to €1775) versus €595 (95% CI €505 to €685), respectively (p<0.01). Anti-TNFα use was the main costs driver, accounting for 64% and 31% of the total cost in CD and UC. Hospitalisation and surgery together accounted for 19% and <1% of the healthcare costs in CD and 23% and 1% in UC, respectively. Productivity losses accounted for 16% and 39% of the total costs in CD and UC. Conclusions We showed that healthcare costs are mainly driven by medication costs, most importantly by anti-TNFα therapy. Hospitalisation and surgery accounted only for a minor part of the healthcare costs.

News Article | November 8, 2016

uBiome, the leading microbial genomics company, has appointed Dr. Elisabeth Bik – who joins the uBiome team in a full-time role from Stanford University School of Medicine – as its new Science Editor. Dr. Bik is regarded by her research peers as one of the world’s authorities on the science of the microbiome. At uBiome, Dr. Bik’s primary focus will be on leading the ongoing publication of scientific findings by the company. Since 2002, Dr. Bik has been a Research Associate at Stanford University School of Medicine, where she has specialized in the composition of the intestinal microbiota of healthy subjects and those with liver diseases, the microbiota of marine mammals, and isolating and detecting microbial DNA from clinical samples. Additionally, since 2014, she has been the editor of the highly respected online Microbiome Digest, a daily summary of scientific papers about microbiome and microbiology research, with a considerable readership in the scientific community. Dr. Bik will continue to edit Microbiome Digest as part of her new position with uBiome. Dr. Bik has authored and co-authored over 30 papers, including the influential Diversity of the Human Intestinal Microbial Flora, which has been cited well over 4,000 times. This ground-breaking research, carried out in collaboration with Stanford’s infectious disease specialist, Dr. Paul B. Eckburg, was published in 2005 – three years before the Human Microbiome Project commenced its work. Described by the journal Nature as a “sharp-eyed microbiologist,” in April 2016, Dr. Bik worked closely with two editors-in-chief at microbiology journals to conduct an analysis of over 20,000 published microbiology, immunology, cancer research, and general science papers, specifically looking for images that were inappropriately duplicated or altered. Such images were found in 3.8% of the papers analyzed. The reputable website Retraction Watch subsequently described her as a “behind-the-scenes force in scientific integrity.” After receiving her PhD at Utrecht University in the Netherlands, Dr. Bik worked at the Dutch National Institute for Health, and the St. Antonius Hospital in Nieuwegein, Utrecht in the Netherlands. In 2002, she joined the Department of Microbiology and Immunology at Stanford University School of Medicine, where, in May 2016, she was awarded Stanford’s prestigious “Microbiome Pioneer” award for her ongoing contributions to science in editing and publishing Microbiome Digest. Dr. Bik brings her considerable experience and expertise to uBiome, a pioneer of applying next generation high-throughput DNA sequencing technology to deliver highly detailed analyses of the human microbiome, the ecosystem of trillions of bacteria that populate the human body. Bacteria in the gut play critical roles in good health, such as supporting digestion and the synthesis of vitamins. However, pathogenic bacteria are associated with a range of conditions – some of them serious – such as celiac disease and inflammatory bowel diseases (including both Crohn’s disease and ulcerative colitis), irritable bowel syndrome, esophageal reflux and esophageal cancer, Clostridium difficile infection, colorectal cancer, and many others. Dr. Elisabeth Bik, new uBiome Science Editor, says: “As someone who has worked in and around the area for over twenty years, it’s rewarding that there has been such a huge increase in interest in the microbiome recently, but, of course, this has been driven by remarkable research driven by my peers and by uBiome. Publishing is, of course, a cornerstone of science, which is why I’m happy that uBiome is placing such great emphasis on ensuring that its work goes through the rigorous time-tested peer-review process, and I’m delighted that I’ll be enabling them to do so as the new Science Editor.” Dr. Jessica Richman, co-founder and CEO of uBiome, says: “We’ve long been inspired by Dr. Bik’s work to disseminate information about our field through the Microbiome Digest. We’re delighted to welcome her to our team and thrilled to work with such a respected expert.” uBiome was founded in 2012 by researchers educated at Stanford, Oxford, and UCSF. The company is funded by Andreessen Horowitz, Y Combinator, and other leading investors. uBiome’s mission is to explore important research questions about the microbiome and to develop accurate and reliable clinical tests based on the microbiome.

News Article | November 7, 2016

WASHINGTON - Nov. 2, 2016 - Results from a randomized, multicenter trial failed to show non-inferiority of hybrid, ultra-thin strut sirolimus-eluting stents (Osiro SES) with a biodegradable polymer compared to thin-strut everolimus-eluting stents (Xience EES) with a durable polymer in terms of in-segment late lumen loss in successfully treated chronic total occlusions. In addition, although the rate of binary restenosis was low overall in this complex lesion subset, it was higher with the Osirio SES compared with the Xience EES. Findings from the PRISON IV trial were reported today at the 28th annual Transcatheter Cardiovascular Therapeutics (TCT) scientific symposium. Sponsored by the Cardiovascular Research Foundation (CRF), TCT is the world's premier educational meeting specializing in interventional cardiovascular medicine. The study was also published in the Journal of the American College of Cardiology (JACC): Cardiovascular Interventions. "Treating chronic total occlusions can be challenging due to their long lengths and the presence of greater degrees of calcium. They often require long stents with high radial strength to maintain acute gain and to minimize late vessel recoil after percutaneous coronary intervention," said lead investigator, Koen Teeuwen, MD from St. Antonius Hospital in Nieuwegein, The Netherlands. Between February 2012 and June 2015, a total of 330 consecutive patients with successfully recanalized native total or chronic total coronary occlusions were randomized to the hybrid sirolimus-eluting stent or the everolimus-eluting stent in two Belgian and six Dutch high-volume PCI centers. Follow-up angiography was performed at nine months after the procedure. In addition, clinical follow-up was obtained during the hospital stay and at one, six, nine and 12 months. The primary non-inferiority end point was in-segment late lumen loss assessed at nine months by angiography. Secondary angiographic end points included: in-stent late lumen loss, minimal lumen diameter, in-stent and in-segment percentage of diameter stenosis, binary restenosis and reocclusions at nine months. Secondary individual and composite clinical end points were clinically indicated target lesion revascularization/target vessel revascularization, myocardial infarction, death (cardiac and non-cardiac), stent thrombosis, target vessel failure, and major adverse cardiac events. At nine months, angiography was available in 281 of 330 (85%) patients. The primary non-inferiority end point of in-segment late lumen loss was not met for SES compared with EES (0.13±0.63 mm vs. 0.02±0.47 mm; P=0.08, 2-sided; difference=0.11 mm; 95% confidence interval, -0.01 to 0.25; Pnon-inferiority=0.11, 1-sided). In-stent late lumen loss was comparable between SES and EES (0.12±0.59 versus 0.07±0.46 mm; P=0.52). The incidence of in-stent/in-segment binary restenosis was higher with SES compared to EES (8.0% vs. 2.1%; P=0.028) with comparable rates of reocclusions (2.2% vs. 1.4%; P=0.68). Clinically indicated target lesion and vessel revascularization (9.2% vs. 4.0%; P=0.08 and 9.2% vs. 6.0%; P=0.33), target vessel failure (9.9% vs. 6.6%; P=0.35) and definite or probable stent thrombosis (0.7% vs. 0.7%; P=1.0) were comparable in the SES and EES group. Clinical follow-up at 12 months was available in 99% of all subjects. Clinically indicated target lesion and vessel revascularization, target vessel failure and MACE were comparable between both groups. Two subjects in the SES group received non-clinical TLR with balloon angioplasty after observing severe stent strut malapposition with optical coherence tomography at nine months. There was only one probable or definite stent thrombosis in each stent group (0.7% vs. 0.7%; P=1.0). "The findings of the study show that the non-inferiority of in-segment late lumen loss was not met for SES against EES in successfully recanalized chronic total occlussions," said Dr. Teeuwen. "In addition, the rate of binary restenosis was significantly higher with SES. Future developments in stent technology should focus on the challenging characteristics of CTOs to improve device efficacy and clinical outcomes." The PRISON IV trial was funded by unrestricted research grants from Biotronik and Abbott Vascular. Dr. Teeuwen reported no relevant disclosures. The Cardiovascular Research Foundation (CRF) is a nonprofit research and educational organization dedicated to helping doctors improve survival and quality of life for people suffering from heart and vascular disease. For over 25 years, CRF has helped pioneer innovations in interventional cardiology and has educated doctors on the latest treatments for heart disease. Transcatheter Cardiovascular Therapeutics (TCT) is the annual scientific symposium of CRF and the world's premier educational meeting specializing in interventional cardiovascular medicine. Now in its 28th year, TCT features major medical research breakthroughs and gathers leading researchers and clinicians from around the world to present and discuss the latest evidence-based research in the field. For more information, visit http://www. and http://www. .

van Well G.T.J.,VU University Amsterdam | van Well G.T.J.,Maastricht University | Sanders M.S.,VU University Amsterdam | Sanders M.S.,Antonius Hospital | And 4 more authors.
PLoS ONE | Year: 2012

Genetic variation in innate immune response genes contributes to inter-individual differences in disease manifestation and degree of complications upon infection. We recently described an association of single nucleotide polymorphisms (SNPs) in TLR9 with susceptibility to meningococcal meningitis (MM). In this study, we investigate the association of SNPs in multiple pathogen recognition and immune response genes with clinical features that determine severity and outcome (especially hearing loss) of childhood MM and pneumococcal meningitis (PM). Eleven SNPs in seven genes (TLR2, TLR4, TLR9, NOD1, NOD2, CASP1, and TRAIL) were genotyped in 393 survivors of childhood bacterial meningitis (BM) (327 MM patients and 66 PM patients). Genotype distributions of single SNPs and combination of SNPs were compared between thirteen clinical characteristics associated with severity of BM. After correction for multiple testing, TLR4+896 mutant alleles were highly associated with post-meningitis hearing loss, especially MM (p = 0.001, OR 4.0 for BM, p = 0.0004, OR 6.2 for MM). In a multigene analysis, combined carriership of the TLR2+2477 wild type (WT) with TLR4+896 mutant alleles increases the risk of hearing loss (p<0.0001, OR 5.7 in BM and p = 0.0001, OR 7.6 in MM). Carriage of one or both mutant alleles in TLR4+896 and TLR9 -1237 increases the risk for hearing loss (p = 0.0006, OR 4.1 in BM). SNPs in immune response genes contribute to differences in clinical severity and outcome of BM. The TLR system seems to play an important role in the immune response to BM and subsequent neuronal damage as well as in cochlear inflammation. Genetic markers may be used for identification of high-risk patients by creating prediction rules for post-meningitis hearing loss and other sequelae, and provide more insight in the complex immune response in the CNS possibly resulting in new therapeutic interventions. © 2012 van Well et al.

Ter Schure J.M.A.,University Utrecht | De Vries M.,Antonius Hospital | Weel J.F.L.,Medical Center Leeuwarden | Van Roon E.N.,Medical Center Leeuwarden | Faber T.E.,Medical Center Leeuwarden
Pediatric Infectious Disease Journal | Year: 2013

Introduction: Dientamoeba fragilis infection in children is common, and its incidence has increased since the introduction of more sensitive molecular techniques. There is no consensus on the optimal treatment. Current medical practice in the Netherlands is to treat symptomatic children with clioquinol or metronidazole. This study attempts to obtain more information about the clinical picture of D. fragilis infection in children and to evaluate responses to both antiparasitic drugs. Methods: Children <18 years of age with a positive stool polymerase chain reaction test for D. fragilis infection were retrospectively evaluated. Clinical data and effectiveness of treatment were analyzed by examining patient's hospital records from the Medical Centre Leeuwarden by repeated analysis of stool samples by the Centre for Infectious Diseases in Friesland. Results: We analyzed 238 patients with an average age of 8.5 years (±4.2 years). Most patients were symptomatic (95.8%) and presented with abdominal pain (72.7%), loose stools (32.8%) and hard stools (24.8%). Coinfection with other gastrointestinal pathogens was present in 29 patients (12.2%). A higher incidence of infection was found in the winter. Clioquinol had a higher clinical success rate than metronidazole (74.7% versus 55.2%, P= 0.047). Conclusion: These results suggest that clioquinol could be more effective than metronidazole in alleviating symptoms of D. fragilis infection in children, but double-blind prospective placebo-controlled studies should be performed before final conclusions can be made. Copyright © 2013 by Lippincott Williams & Wilkins.

Vasak B.,University Utrecht | Graatsma E.M.,University Utrecht | Hekman-Drost E.,Gelre Hospital | Eijkemans M.J.,University Utrecht | And 3 more authors.
American Journal of Obstetrics and Gynecology | Year: 2013

Objective We sought to study whether uterine electromyography (EMG) can identify inefficient contractions leading to first-stage labor arrest followed by cesarean delivery in term nulliparous women with spontaneous onset of labor. Study Design EMG was recorded during spontaneous labor in 119 nulliparous women with singleton term pregnancies in cephalic position. Electrical activity of the myometrium during contractions was characterized by its power density spectrum (PDS). Results Mean PDS peak frequency in women undergoing cesarean delivery for first-stage labor arrest was significantly higher (0.55 Hz), than in women delivering vaginally without (0.49 Hz) or with (0.51 Hz) augmentation of labor (P =.001 and P =.01, respectively). Augmentation of labor increased the mean PDS frequency when comparing contractions before and after start of augmentation. This increase was only significant in women eventually delivering vaginally. Conclusion Contraction characteristics measured by uterine EMG correlate with progression of labor and are influenced by labor augmentation. © 2013 Mosby, Inc. All rights reserved.

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