Publications by authors named "Karin de Boer"

34 Publications

Letter to the editor: A reply to ESPR-D-20-13511.

Environ Sci Pollut Res Int 2021 Feb 19. Epub 2021 Feb 19.

Bèta Science Shop, Faculty of Science and Engineering and Department of Ocean Ecosystems, Energy and Sustainability Research Institute Groningen, University of Groningen, Nijenborgh 6, AG, 9747, Groningen, The Netherlands.

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http://dx.doi.org/10.1007/s11356-021-12527-3DOI Listing
February 2021

Mediterranean alien harmful algal blooms: origins and impacts.

Environ Sci Pollut Res Int 2021 Jan 17;28(4):3837-3851. Epub 2020 Aug 17.

Department of Ocean Ecosystems, Energy and Sustainability Research Institute Groningen, University of Groningen, Nijenborgh 7, AG 9747, Groningen, The Netherlands.

Harmful algal blooms (HABs) are mostly phytoplankton blooms, which have detrimental environmental and socioeconomic impacts. The Mediterranean Sea due to its enclosed nature is of special concern since it has an enormously rich native biodiversity. Though, it is also the world's most invaded marine ecosystem and is considered at very high risk of future invasions. The aim of this review study is to explore the origins, establishment, environmental, and socioeconomic impacts of HABs caused by nonnative algal species in the Mediterranean Sea. Based on this, it is also discussed whether HABs form an increasing threat in the basin, and what could possibly be done to prevent or to minimize their impacts. The increasing rate of their introduction and the harmful impacts that they have on the environment, economy, and human health makes it important to have accurate knowledge about HABs. Anthropogenic activities and climate change are considered the main contributors of alien invasions but also the main enablers of HAB events. Mediterranean HABs are adequately studied, but there are no studies purposefully concerning invasive microalgae species in the basin. In the present study, 20 species have been identified, and an attempt has been made to collect their introduction information, as well as known or suspected impacts. Future research should be focused on data mining, current legislation updates, and monitoring of Mediterranean coastlines.
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http://dx.doi.org/10.1007/s11356-020-10383-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7835144PMC
January 2021

Bisoprolol therapy does not reduce right ventricular sympathetic activity in pulmonary arterial hypertension patients.

Pulm Circ 2020 Apr-Jun;10(2):2045894019873548. Epub 2020 Apr 20.

Pulmonary Medicine, Amsterdam Cardiovascular Sciences, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands.

Right ventricular (RV) function and autonomic dysfunction are important determinants of morbidity and mortality in patients with pulmonary arterial hypertension (PAH). Although successful in animal studies, effects of beta-blocker therapy on RV function in clinical trials were disappointing. To understand this discrepancy, we studied whether beta-blocker therapy changes RV sympathetic activity. Idiopathic PAH (IPAH) patients received beta-blocker therapy (uptitrated to a maximal tolerated dose) and underwent cardiac magnetic resonance imaging, right heart catheterization, and a [C]-hydroxyephedrine positron emission tomography ([C]HED PET) scan at baseline to determine, respectively, RV ejection fraction (RVEF), RV pressures, and sympathetic activity. [C]HED, a norepinephrine analogue, allows determination of sympathetic innervation of the RV. [C]HED retention index reflects norepinephrine transporter activity. As a consequence of excessive catecholamine levels in the synaptic cleft, this transporter may be downregulated. Therefore, low [C]HED retention index indicates high sympathetic activity. 13 IPAH patients underwent [C]HED PET scans at baseline and after bisoprolol treatment. Although heart rate was reduced, systemic modulation of autonomic activity by bisoprolol did not affect local RV sympathetic nerve activity, RV function, or RV wall tension. In PAH patients, RV [C]HED retention index was lower compared to LV tracer uptake (p<0.01) and was related to systolic wall tension (R = 0.4731, p<0.01) and RV function (R = 0.44, p = 0.01). In RV failure, the tolerated dosage of bisoprolol did not result in an improvement of RV function nor in a reduction in RV sympathetic activity.
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http://dx.doi.org/10.1177/2045894019873548DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7187746PMC
April 2020

Blood pressure after PREeclampsia/HELLP by SELF monitoring (BP-PRESELF): rationale and design of a multicenter randomized controlled trial.

BMC Womens Health 2020 03 4;20(1):41. Epub 2020 Mar 4.

Department of Cardiology, Radboud university medical center, Geert-Grooteplein Zuid 10, 6525, GA, Nijmegen, The Netherlands.

Background: Hypertensive disorders of pregnancy (HDP), such as preeclampsia (PE) or the Hemolysis Elevated Liver enzymes and Low Platelets (HELLP) syndrome are associated with elevated cardiovascular disease (CVD) risks, but standardized prevention guidelines after such pregnancies are lacking. Hypertension is the first emerging risk factor after PE/HELLP pregnancies and is a major risk factor for CVD. Hypertension before the age of 55 years may lead to various manifestations of end-organ damage at relatively young age. Therefore, timely treatment of elevated blood pressure is mandatory, but many of these high-risk women have long-term undetected and untreated hypertension before adequate treatment is initiated.

Aim: The aim of our study is to assess whether home blood pressure monitoring (HBPM) in women with a previous PE/HELLP pregnancy is a valuable tool for the early detection of hypertension.

Methods: Women with a history of both early and late PE/HELLP syndrome aged 40-60 years are invited to participate. Patients with a history of CVD, known hypertension and/or use of antihypertensive medication are excluded. Women are randomized between HPBM or 'usual care'. The primary outcome is feasibility and usability of HBPM after 1 year of follow-up. Secondary outcomes will be the effectiveness of HPBM to detect hypertension, the efficacy of BP treatment, quality of life, health-related symptoms, work ability, and life-style behaviour. The results of this study will provide better strategies for timely detection and prevention of hypertension in women after PE/HELLP.

Trial Registration: ClinicalTrials.gov, NCT03228082. Registered June 15, 2017.
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http://dx.doi.org/10.1186/s12905-020-00910-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7055029PMC
March 2020

Variability of dinoflagellates and their associated toxins in relation with environmental drivers in Ambon Bay, eastern Indonesia.

Mar Pollut Bull 2020 Jan 4;150:110778. Epub 2019 Dec 4.

Department of Ocean Ecosystems, Energy and Sustainability Research Institute Groningen, Faculty of Science and Engineering, University of Groningen, Nijenborgh 7, 9747AG Groningen, the Netherlands.

The aim of the present work was to unravel which environmental drivers govern the dynamics of toxic dinoflagellate abundance as well as their associated paralytic shellfish toxins (PSTs), diarrhetic shellfish toxins (DSTs) and pectenotoxin-2 (PTX2) in Ambon Bay, Eastern Indonesia. Weather, biological and physicochemical parameters were investigated weekly over a 7-month period. Both PSTs and PTX2 were detected at low levels, yet they persisted throughout the research. Meanwhile, DSTs were absent. A strong correlation was found between total particulate PST and Gymnodinium catenatum cell abundance, implying that this species was the main producer of this toxin. PTX2 was positively correlated with Dinophysis miles cell abundance. Vertical mixing, tidal elevation and irradiance attenuation were the main environmental factors that regulated both toxins and cell abundances, while nutrients showed only weak correlations. The present study indicates that dinoflagellate toxins form a potential environmental, economic and health risk in this Eastern Indonesian bay.
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http://dx.doi.org/10.1016/j.marpolbul.2019.110778DOI Listing
January 2020

First record of the dynamics of domoic acid producing Pseudo-nitzschia spp. in Indonesian waters as a function of environmental variability.

Harmful Algae 2019 12 21;90:101708. Epub 2019 Nov 21.

Department of Ocean Ecosystems, Energy and Sustainability Research Institute Groningen, Faculty of Science and Engineering, University of Groningen, Nijenborgh 7, 9747AG Groningen, the Netherlands.

Within the past few decades, harmful algal blooms (HABs) have occurred frequently in Indonesian waters, resulting in environmental degradation, economic loss and human health problems. So far, HAB related studies mainly addressed ecological traits and species distribution, yet toxin measurements were virtually absent for Indonesian waters. The aim of the present study was to explore variability of the potentially toxic marine diatom genus Pseudo-nitzschia, as well as its neurotoxin domoic acid as a function of environmental conditions in Ambon Bay, eastern Indonesia. Weekly phytoplankton samples, oceanographic (CTD, nutrients) and meteorological (precipitation, wind) parameters were analyzed at 5 stations in the bay during the dry and wet seasons of 2018. Liquid chromatography - tandem mass spectrometry (LC-MS/MS) was used to detect particulate DA (pDA). Vegetative cells of Pseudo-nitzschia spp. and pDA were found in 98.6% and 51.4% of the samples, respectively. pDA levels were low, yet detected throughout the campaign, implying that Ambon Bay might potentially be subject to amnesic shellfish poisoning. The highest levels of both Pseudo-nitzschia spp. cell abundance and pDA were found in the wet season, showing a strong positive correlation between both parameters, compared to the dry season, (r = 0.87 and r = 0.66 (p < 0.01), respectively). Statistical analyses revealed that temperature and mixed layer depth positively correlated with Pseudo-nitzschia spp. and pDA during the dry season, while ammonium showed positive correlations in both seasons. This study represents the first successful investigation of the presence and variability of Pseudo-nitzschia spp. and its neurotoxin DA in Indonesian waters.
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http://dx.doi.org/10.1016/j.hal.2019.101708DOI Listing
December 2019

SUGAR-DIP trial: oral medication strategy versus insulin for diabetes in pregnancy, study protocol for a multicentre, open-label, non-inferiority, randomised controlled trial.

BMJ Open 2019 08 18;9(8):e029808. Epub 2019 Aug 18.

Department of Obstetrics and Gynaecology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.

Introduction: In women with gestational diabetes mellitus (GDM) requiring pharmacotherapy, insulin was the established first-line treatment. More recently, oral glucose lowering drugs (OGLDs) have gained popularity as a patient-friendly, less expensive and safe alternative. Monotherapy with metformin or glibenclamide (glyburide) is incorporated in several international guidelines. In women who do not reach sufficient glucose control with OGLD monotherapy, usually insulin is added, either with or without continuation of OGLDs. No reliable data from clinical trials, however, are available on the effectiveness of a treatment strategy using all three agents, metformin, glibenclamide and insulin, in a stepwise approach, compared with insulin-only therapy for improving pregnancy outcomes. In this trial, we aim to assess the clinical effectiveness, cost-effectiveness and patient experience of a stepwise combined OGLD treatment protocol, compared with conventional insulin-based therapy for GDM.

Methods: The SUGAR-DIP trial is an open-label, multicentre randomised controlled non-inferiority trial. Participants are women with GDM who do not reach target glycaemic control with modification of diet, between 16 and 34 weeks of gestation. Participants will be randomised to either treatment with OGLDs, starting with metformin and supplemented as needed with glibenclamide, or randomised to treatment with insulin. In women who do not reach target glycaemic control with combined metformin and glibenclamide, glibenclamide will be substituted with insulin, while continuing metformin. The primary outcome will be the incidence of large-for-gestational-age infants (birth weight >90th percentile). Secondary outcome measures are maternal diabetes-related endpoints, obstetric complications, neonatal complications and cost-effectiveness analysis. Outcomes will be analysed according to the intention-to-treat principle.

Ethics And Dissemination: The study protocol was approved by the Ethics Committee of the Utrecht University Medical Centre. Approval by the boards of management for all participating hospitals will be obtained. Trial results will be submitted for publication in peer-reviewed journals.

Trial Registration Number: NTR6134; Pre-results.
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http://dx.doi.org/10.1136/bmjopen-2019-029808DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6701578PMC
August 2019

Left atrial spindle cell sarcoma: a case report.

Eur Heart J Case Rep 2019 Mar 6;3(1):ytz005. Epub 2019 Feb 6.

Department of Cardiology, Amsterdam UMC, Vrije Universiteit Amsterdam, De Boelelaan 1117, Amsterdam, The Netherlands.

Background: Primary cardiac spindle cell sarcomas are extremely rare with only a few cases reported. They are frequently misdiagnosed on cardiac magnetic resonance (CMR) imaging as benign myxoma or thrombi and the suspicion of a malignant sarcoma arises only during surgery. This case report describes a case of cardiac spindle cell sarcoma diagnosed after surgery, where the initial diagnostic possibilities included an intramural thrombus and a cardiac myxoma.

Case Summary: A 57-year-old woman was referred to our hospital for evaluation of a possible recurrent myxoma in the left atrium on echocardiography. Cardiac magnetic resonance imaging confirmed these masses as mural thrombotic masses, with a possible remnant of myxoma. After 2 months of anticoagulation therapy, the masses did not decrease in size on CMR imaging, and surgical removal was indicated. The atrial masses were surgically resected together with a large part of the left atrium. Histological examination showed spindle cell sarcoma. Unfortunately, the resection margins were positive and it was not possible to remove more atrium. PET-CT revealed metastasis in the right femur. The patient passed away 1 year after surgery.

Discussion: The rarity of spindle cell sarcoma and its similarities to benign cardiac myxoma and thrombi on echocardiography and CMR imaging present a diagnostic challenge when evaluating patients pre-operatively. Therefore, a malignant spindle cell sarcoma may only be diagnosed during surgery, after histological examination.
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http://dx.doi.org/10.1093/ehjcr/ytz005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6439379PMC
March 2019

Pessary or Progesterone to Prevent Preterm delivery in women with short cervical length: the Quadruple P randomised controlled trial.

BMC Pregnancy Childbirth 2017 Sep 4;17(1):284. Epub 2017 Sep 4.

Department of Obstetrics and Gynaecology, Academic Medical Center (AMC), Meibergdreef 9, 1105, AZ, Amsterdam, The Netherlands.

Background: Preterm birth is in quantity and in severity the most important topic in obstetric care in the developed world. Progestogens and cervical pessaries have been studied as potential preventive treatments with conflicting results. So far, no study has compared both treatments.

Methods/design: The Quadruple P study aims to compare the efficacy of vaginal progesterone and cervical pessary in the prevention of adverse perinatal outcome associated with preterm birth in asymptomatic women with a short cervix, in singleton and multiple pregnancies separately. It is a nationwide open-label multicentre randomized clinical trial (RCT) with a superiority design and will be accompanied by an economic analysis. Pregnant women undergoing the routine anomaly scan will be offered cervical length measurement between 18 and 22 weeks in a singleton and at 16-22 weeks in a multiple pregnancy. Women with a short cervix, defined as less than, or equal to 35 mm in a singleton and less than 38 mm in a multiple pregnancy, will be invited to participate in the study. Eligible women will be randomly allocated to receive either progesterone or a cervical pessary. Following randomization, the silicone cervical pessary will be placed during vaginal examination or 200 mg progesterone capsules will be daily self-administered vaginally. Both interventions will be continued until 36 weeks gestation or until delivery, whichever comes first. Primary outcome will be composite adverse perinatal outcome of perinatal mortality and perinatal morbidity including bronchopulmonary dysplasia, intraventricular haemorrhage grade III and IV, periventricular leukomalacia higher than grade I, necrotizing enterocolitis higher than stage I, Retinopathy of prematurity (ROP) or culture proven sepsis. These outcomes will be measured up until 10 weeks after the expected due date. Secondary outcomes will be, among others, time to delivery, preterm birth rate before 28, 32, 34 and 37 weeks, admission to neonatal intensive care unit, maternal morbidity, maternal admission days for threatened preterm labour and costs.

Discussion: This trial will provide evidence on whether vaginal progesterone or a cervical pessary is more effective in decreasing adverse perinatal outcome in both singletons and multiples.

Trial Registration: Trial registration number: NTR 4414 . Date of registration January 29th 2014.
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http://dx.doi.org/10.1186/s12884-017-1454-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5584011PMC
September 2017

Adenoviral Type 35 and 26 Vectors with a Bidirectional Expression Cassette in the E1 Region Show an Improved Genetic Stability Profile and Potent Transgene-Specific Immune Response.

Hum Gene Ther 2018 03 30;29(3):337-351. Epub 2017 Nov 30.

Janssen Vaccines and Prevention, Janssen Pharmaceutical Companies of Johnson & Johnson , Leiden, the Netherlands .

Genetic vaccines based on replication-incompetent adenoviral (AdV) vectors are currently in clinical development. Monovalent AdV vectors express one antigen from an expression cassette placed in most cases in the E1 region. For many vaccines, inclusion of several antigens is necessary in order to raise protective immunity and/or target more than one pathogen or pathogen strain. On the basis of the current technology, a mix of several monovalent vectors can be employed. However, a mix of the standard monovalent AdV vectors may not be optimal with respect to manufacturing costs and the final dose per vector in humans. Alternatively, a variety of bivalent recombinant AdV vector approaches is described in the literature. It remains unclear whether all strategies are equally suitable for clinical development while preserving all the beneficial properties of the monovalent AdV (e.g., immunogenic potency). Therefore, a thorough assessment of different bivalent AdV strategies was performed in a head-to-head fashion compared with the monovalent benchmark. The vectors were tested for rescue efficiency, genetic stability, transgene expression, and potency to induce transgene-specific immune responses. We report that the vector expressing multiple antigens from a bidirectional expression cassette in E1 shows a better genetic stability profile and a potent transgene-specific immune response compared with the other tested bivalent vectors.
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http://dx.doi.org/10.1089/hum.2017.023DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5865256PMC
March 2018

Effects of exenatide on cardiac function, perfusion, and energetics in type 2 diabetic patients with cardiomyopathy: a randomized controlled trial against insulin glargine.

Cardiovasc Diabetol 2017 05 19;16(1):67. Epub 2017 May 19.

Department of Cardiology, VU University Medical Center, de Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands.

Background: Multiple bloodglucose-lowering agents have been linked to cardiovascular events. Preliminary studies showed improvement in left ventricular (LV) function during glucagon-like peptide-1 receptor agonist administration. Underlying mechanisms, however, are unclear. The purpose of this study was to investigate myocardial perfusion and oxidative metabolism in type 2 diabetic (T2DM) patients with LV systolic dysfunction as compared to healthy controls. Furthermore, effects of 26-weeks of exenatide versus insulin glargine administration on cardiac function, perfusion and oxidative metabolism in T2DM patients with LV dysfunction were explored.

Methods And Results: Twenty-six T2DM patients with LV systolic dysfunction (cardiac magnetic resonance (CMR) derived LV ejection fraction (LVEF) of 47 ± 13%) and 10 controls (LVEF of 59 ± 4%, P < 0.01 as compared to patients) were analyzed. Both myocardial perfusion during adenosine-induced hyperemia (P < 0.01), and coronary flow reserve (P < 0.01), measured by [O]HO positron emission tomography (PET), were impaired in T2DM patients as compared to healthy controls. Myocardial oxygen consumption and myocardial efficiency, measured using [C]acetate PET and CMR derived stroke volume, were not different between the groups. Eleven patients in the exenatide group and 12 patients in the insulin glargine group completed the trial. Systemic metabolic control was improved after both treatments, although, no changes in cardiac function, perfusion and metabolism were seen after exenatide or insulin glargine.

Conclusions: T2DM patients with LV systolic dysfunction did not have altered myocardial efficiency as compared to healthy controls. Exenatide or insulin glargine had no effects on cardiac function, perfusion or oxidative metabolism. Trial registration NCT00766857.
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http://dx.doi.org/10.1186/s12933-017-0549-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5438489PMC
May 2017

Cardiac function and cognition in older community-dwelling cardiac patients.

Psychogeriatrics 2017 Nov 17;17(6):356-363. Epub 2017 Apr 17.

Department of Clinical Neuropsychology, VU University, Amsterdam, the Netherlands.

Background: Cognitive deficits have been reported in older cardiac patients. An underlying mechanism for these findings may be reduced cardiac function. The relationship between cardiac function as represented by different echocardiographic measures and different cognitive function domains in older cardiac patients remains unknown.

Methods: An older (≥70 years) heterogeneous group of 117 community-dwelling cardiac patients under medical supervision by a cardiologist underwent thorough echocardiographic assessment including left ventricular ejection fraction, cardiac index, left atrial volume index, left ventricular mass index, left ventricular diastolic function, and valvular calcification. During a home visit, a neuropsychological assessment was performed within 7.1 ± 3.8 months after echocardiographic assessment; the neuropsychological assessment included three subtests of a word-learning test (encoding, recall, recognition) to examine one memory function domain and three executive function tests, including digit span backwards, Trail Making Test B minus A, and the Stroop colour-word test.

Results: Regression analyses showed no significant linear or quadratic associations between any of the echocardiographic functions and the cognitive function measures.

Conclusions: None of the echocardiographic measures as representative of cardiac function was correlated with memory or executive function in this group of community-dwelling older cardiac patients. These findings contrast with those of previous studies.
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http://dx.doi.org/10.1111/psyg.12245DOI Listing
November 2017

Practice variation of vaginal birth after cesarean and the influence of risk factors at patient level: a retrospective cohort study.

Acta Obstet Gynecol Scand 2017 Feb 3;96(2):158-165. Epub 2017 Jan 3.

Scientific Institute for Quality of Healthcare (IQ healthcare), Radboud University Nijmegen Medical Center, Nijmegen, the Netherlands.

Introduction: Large practice variation exists in mode of delivery after cesarean section, suggesting variation in implementation of contemporary guidelines. We aim to evaluate this practice variation and to what extent this can be explained by risk factors at patient level.

Material And Methods: This retrospective cohort study was performed among 17 Dutch hospitals in 2010. Women with one prior cesarean section without a contraindication for a trial of labor were included. We used multivariate logistic regression analysis to develop models for risk factor adjustments. One model was derived to adjust the elective repeat cesarean section rates; a second model to adjust vaginal birth after cesarean rates. Standardized rates of elective repeat cesarean section and vaginal birth after cesarean per hospital were compared. Pseudo-R measures were calculated to estimate the percentage of practice variation explained by the models. Secondary outcomes were differences in practice variation between hospital types and the correlation between standardized elective repeat cesarean section and vaginal birth after cesarean rates.

Results: In all, 1068 women had a history of cesarean section, of whom 71% were eligible for inclusion. A total of 515 women (67%) had a trial of labor, of whom 72% delivered vaginally. The elective repeat cesarean section rate at hospital level ranged from 6 to 54% (mean 29.8, standard deviation 11.8%). Vaginal birth after cesarean rates ranged from 50 to 90% (mean 71.8%, standard deviation 11.1%). More than 85% of this practice variation could not be explained by risk factors at patient level.

Conclusion: A large practice variation exists in elective repeat cesarean section and vaginal birth after cesarean rates that can only partially be explained by risk factors at patient level.
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http://dx.doi.org/10.1111/aogs.13059DOI Listing
February 2017

Bisoprolol in idiopathic pulmonary arterial hypertension: an explorative study.

Eur Respir J 2016 09 7;48(3):787-96. Epub 2016 Jul 7.

Dept of pulmonary medicine, Institute for cardiovascular research, VU University medical center, Amsterdam, The Netherlands Dept of physiology, Institute for cardiovascular research, VU University medical center, Amsterdam, The Netherlands

While beta-blockers are considered contraindicated in pulmonary arterial hypertension (PAH), the prognostic significance of sympathetic nervous system over-activity suggests a potential benefit of beta-blocker therapy. The aim of this randomised, placebo-controlled, crossover, single centre study was to determine the effects of bisoprolol on right ventricular ejection fraction (RVEF) in idiopathic PAH (iPAH) patients. Additional efficacy and safety parameters were explored.Patients with optimally treated, stable iPAH (New York Heart Association functional class II/III) were randomised to placebo or bisoprolol. Imaging and functional measurements were performed at baseline, crossover and end of study.18 iPAH patients were included, because inclusion faltered before enrolment of the targeted 25 patients. 17 patients completed 6 months of bisoprolol, 15 tolerated bisoprolol, one patient required intravenous diuretics. Bisoprolol was associated with a lower heart rate (17 beats per minute, p=0.0001) but RVEF remained unchanged. A drop in cardiac index (0.5 L·min(-1)·m(-2), p=0.015) was observed, along with a trend towards a decreased 6-min walking distance (6MWD).Although careful up-titration of bisoprolol was tolerated by most patients and resulted in a decreased heart rate, no benefit of bisoprolol in iPAH was demonstrated. Decreases in cardiac index and 6MWD suggest a deteriorated cardiac function. The results do not favour the use of bisoprolol in iPAH patients.
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http://dx.doi.org/10.1183/13993003.00090-2016DOI Listing
September 2016

Two cases of RIT1 associated Noonan syndrome: Further delineation of the clinical phenotype and review of the literature.

Am J Med Genet A 2016 07 25;170(7):1874-80. Epub 2016 Apr 25.

Department of Clinical Genetics, VU University Medical Center, Amsterdam, The Netherlands.

Mutations in RIT1, involved in the RAS-MAPK pathway, have recently been identified as a cause for Noonan syndrome. We present two patients with Noonan syndrome caused by a RIT1 mutation with novel phenotypic manifestations, severe bilateral lower limb lymphedema starting during puberty, and fetal hydrops resulting in intrauterine fetal death, respectively. Including our patients, a total of 52 patients have been reported with Noonan syndrome caused by a RIT1 mutation. Our report contributes to the delineation of the phenotype associated with RIT1 mutations and underlines that lymphatic involvement is part of this spectrum. In addition, we provide an overview of the currently described Noonan syndrome patients with RIT1 mutations in literature. © 2016 Wiley Periodicals, Inc.
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http://dx.doi.org/10.1002/ajmg.a.37657DOI Listing
July 2016

Development and Measurement of Guidelines-Based Quality Indicators of Caesarean Section Care in the Netherlands: A RAND-Modified Delphi Procedure and Retrospective Medical Chart Review.

PLoS One 2016 19;11(1):e0145771. Epub 2016 Jan 19.

GROW- School for Oncology and Developmental Biology, Department of Obstetrics and Gynaecology, Maastricht University Medical Center, P.O. Box 5800, 6202 AZ Maastricht, The Netherlands.

Background: There is an ongoing discussion on the rising CS rate worldwide. Suboptimal guideline adherence may be an important contributor to this rise. Before improvement of care can be established, optimal CS care in different settings has to be defined. This study aimed to develop and measure quality indicators to determine guideline adherence and identify target groups for improvement of care with direct effect on caesarean section (CS) rates.

Method: Eighteen obstetricians and midwives participated in an expert panel for systematic CS quality indicator development according to the RAND-modified Delphi method. A multi-center study was performed and medical charts of 1024 women with a CS and a stratified and weighted randomly selected group of 1036 women with a vaginal delivery were analysed. Quality indicator frequency and adherence were scored in 2060 women with a CS or vaginal delivery.

Results: The expert panel developed 16 indicators on planned CS and 11 indicators on unplanned CS. Indicator adherence was calculated, defined as the number of women in a specific obstetrical situation in which care was performed as recommended in both planned and unplanned CS settings. The most frequently occurring obstetrical situations with low indicator adherence were: 1) suspected fetal distress (frequency 17%, adherence 46%), 2) non-progressive labour (frequency 12%, CS performed too early in over 75%), 3) continuous support during labour (frequency 88%, adherence 37%) and 4) previous CS (frequency 12%), with adequate counselling in 15%.

Conclusions: We identified four concrete target groups for improvement of obstetrical care, which can be used as a starting point to reduce CS rates worldwide.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0145771PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4718610PMC
July 2016

Recurrence rate and outcome of postterm pregnancy, a national cohort study.

Eur J Obstet Gynecol Reprod Biol 2015 Oct 9;193:70-4. Epub 2015 Jun 9.

Academic Medical Center, University of Amsterdam, Department of Obstetrics and Gynaecology, Amsterdam, The Netherlands.

Objective: To assess the recurrence rate of postterm delivery (gestational age at or beyond 42+0 weeks or 294 days) and to describe maternal and perinatal outcomes after previous postterm delivery.

Study Design: From the longitudinal linked Netherlands Perinatal Registry database, we selected all singleton primiparous women who delivered between 37+0 and 42+6 weeks with a subsequent singleton pregnancy from 1999 to 2007. We excluded congenital abnormalities. We compared the recurrence rate of postterm delivery and risk of antenatal fetal death in women with and without a postterm delivery in their first pregnancy. We compared perinatal outcome (composite of perinatal mortality, Apgar score <7 and birth injury) and adverse maternal outcome (composite of maternal death, abruptio placentae, PPH>1000ml and blood transfusions) between women with a recurrent and a de novo postterm second pregnancy.

Results: Our study population consisted of 233,327 women of whom 17,874 (7.7%) delivered postterm in the first pregnancy. In the second pregnancy, 2678 (15%) women had a recurrent postterm delivery compared to 8698 (4%) women with a de novo postterm delivery (odds ratio (OR) 4.2 95% confidence interval (CI) 4.0-4.4). Subgroup analysis in recurrent and de novo postterm delivery showed no differences in composite perinatal and composite maternal outcome (OR 1.0; CI 0.7-1.5, p=0.90 and OR 1.1, CI 0.9-1.4, p=0.16), adjusted for fetal position and mode of delivery).

Conclusions: Women with a postterm delivery in the first pregnancy have a higher risk of recurrent postterm delivery. Our data suggest that there is no difference in the composite adverse perinatal outcome between recurrent and de novo postterm delivery.
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http://dx.doi.org/10.1016/j.ejogrb.2015.05.021DOI Listing
October 2015

Clinical Presentation, Long-Term Follow-Up, and Outcomes of 1001 Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy Patients and Family Members.

Circ Cardiovasc Genet 2015 Jun 27;8(3):437-46. Epub 2015 Mar 27.

Background: Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) is a progressive cardiomyopathy. We aimed to define long-term outcome in a transatlantic cohort of 1001 individuals.

Methods And Results: Clinical and genetic characteristics and follow-up data of ARVD/C index-patients (n=439, fulfilling of 2010 criteria in all) and family members (n=562) were assessed. Mutations were identified in 276 index-patients (63%). Index-patients presented predominantly with sustained ventricular arrhythmias (268; 61%). During a median follow-up of 7 years, 301 of the 416 index-patients presenting alive (72%) experienced sustained ventricular arrhythmias. Sudden cardiac death during follow-up occurred more frequently among index-patients without an implantable cardioverter-defibrillator (10/63, 16% versus 2/335, 0.6%). Overall, cardiac mortality and the need for cardiac transplantation were low (6% and 4%, respectively). Clinical characteristics and outcomes were similar in index-patients with and without mutations, as well as in those with familial and nonfamilial ARVD/C. ARVD/C was diagnosed in 207 family members (37%). Symptoms at first evaluation correlated with disease expression. Family members with mutations were more likely to meet Task Force Criteria for ARVD/C (40% versus 18%), experience sustained ventricular arrhythmias (11% versus 1%), and die from a cardiac cause (2% versus 0%) than family members without mutations.

Conclusions: Long-term outcome was favorable in diagnosed and treated ARVD/C index-patients and family members. Outcome in index-patients was modulated by implantable cardioverter-defibrillator implantation, but not by mutation status and familial background of disease. One third of family members developed ARVD/C. Outcome in family members was determined by symptoms at first evaluation and mutations.
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http://dx.doi.org/10.1161/CIRCGENETICS.114.001003DOI Listing
June 2015

In-vivo T1 cardiovascular magnetic resonance study of diffuse myocardial fibrosis in hypertrophic cardiomyopathy.

J Cardiovasc Magn Reson 2014 Apr 25;16:28. Epub 2014 Apr 25.

Department of Cardiology, ICaR-VU, VU University Medical Center, De Boelelaan 1117, Amsterdam 1081 HV, the Netherlands.

Background: In hypertrophic cardiomyopathy (HCM), autopsy studies revealed both increased focal and diffuse deposition of collagen fibers. Late gadolinium enhancement imaging (LGE) detects focal fibrosis, but is unable to depict interstitial fibrosis. We hypothesized that with T1 mapping, which is employed to determine the myocardial extracellular volume fraction (ECV), can detect diffuse interstitial fibrosis in HCM patients.

Methods: T1 mapping with a modified Look-Locker Inversion Recovery (MOLLI) pulse sequence was used to calculate ECV in manifest HCM (n = 16) patients and in healthy controls (n = 14). ECV was determined in areas where focal fibrosis was excluded with LGE.

Results: The total group of HCM patients showed no significant changes in mean ECV values with respect to controls (0.26 ± 0.03 vs 0.26 ± 0.02, p = 0.83). Besides, ECV in LGE positive HCM patients was comparable with LGE negative HCM patients (0.27 ± 0.03 vs 0.25 ± 0.03, p = 0.12).

Conclusions: This study showed that HCM patients have a similar ECV (e.g. interstitial fibrosis) in myocardium without LGE as healthy controls. Therefore, the additional clinical value of T1 mapping in HCM seems limited, but future larger studies are needed to establish the clinical and prognostic potential of this new technique within HCM.
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http://dx.doi.org/10.1186/1532-429X-16-28DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4026831PMC
April 2014

Cervical pessaries for prevention of preterm birth in women with a multiple pregnancy (ProTWIN): a multicentre, open-label randomised controlled trial.

Lancet 2013 Oct 5;382(9901):1341-9. Epub 2013 Aug 5.

Obstetrics and Gynaecology, Academic Medical Center, Amsterdam, Netherlands. Electronic address:

Background: In women with a multiple pregnancy, spontaneous preterm delivery is the leading cause of perinatal morbidity and mortality. Interventions to reduce preterm birth in these women have not been successful. We assessed whether a cervical pessary could effectively prevent poor perinatal outcomes.

Methods: We undertook a multicentre, open-label randomised controlled trial in 40 hospitals in the Netherlands. We randomly assigned women with a multiple pregnancy between 12 and 20 weeks' gestation (1:1) to pessary or control groups, using a web-based application with a computer-generated list with random block sizes of two to four, stratified by hospital. Participants and investigators were aware of group allocation. For women in the pessary group, a midwife or obstetrician inserted a cervical pessary between 16 and 20 weeks' gestation. Women in the control group did not receive the pessary, but otherwise received similar obstetrical care to those in the pessary group. The primary outcome was a composite of poor perinatal outcome: stillbirth, periventricular leucomalacia, severe respiratory distress syndrome, bronchopulmonary dysplasia, intraventricular haemorrhage, necrotising enterocolitis, proven sepsis, and neonatal death. Analyses were by modified intention to treat. This trial is registered in the Dutch trial registry, number NTR1858.

Findings: Between Sept 21, 2009, and March 9, 2012, 813 women underwent randomisation, of whom 808 were analysed (401 in the pessary group; 407 in the control group). At least one child of 53 women (13%) in the pessary group had poor perinatal outcome, compared with 55 (14%) in the control group (relative risk 0·98, 95% CI 0·69-1·39).

Interpretation: In unselected women with a multiple pregnancy, prophylactic use of a cervical pessary does not reduce poor perinatal outcome.

Funding: The Netherlands Organisation for Health Research and Development.
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http://dx.doi.org/10.1016/S0140-6736(13)61408-7DOI Listing
October 2013

Economic analysis comparing induction of labour and expectant management for intrauterine growth restriction at term (DIGITAT trial).

Eur J Obstet Gynecol Reprod Biol 2013 Oct 1;170(2):358-63. Epub 2013 Aug 1.

Academic Medical Centre, Amsterdam, The Netherlands. Electronic address:

Objective: Pregnancies complicated by intrauterine growth restriction (IUGR) are at increased risk for neonatal morbidity and mortality. The Dutch nationwide disproportionate intrauterine growth intervention trial at term (DIGITAT trial) showed that induction of labour and expectant monitoring were comparable with respect to composite adverse neonatal outcome and operative delivery. In this study we compare the costs of both strategies.

Study Design: A cost analysis was performed alongside the DIGITAT trial, which was a randomized controlled trial in which 650 women with a singleton pregnancy with suspected IUGR beyond 36 weeks of pregnancy were allocated to induction or expectant management. Resource utilization was documented by specific items in the case report forms. Unit costs for clinical resources were calculated from the financial reports of participating hospitals. For primary care costs Dutch standardized prices were used. All costs are presented in Euros converted to the year 2009.

Results: Antepartum expectant monitoring generated more costs, mainly due to longer antepartum maternal stays in hospital. During delivery and the postpartum stage, induction generated more direct medical costs, due to longer stay in the labour room and longer duration of neonatal high care/medium care admissions. From a health care perspective, both strategies generated comparable costs: on average €7106 per patient for the induction group (N=321) and €6995 for the expectant management group (N=329) with a cost difference of €111 (95%CI: €-1296 to 1641).

Conclusion: Induction of labour and expectant monitoring in IUGR at term have comparable outcomes immediately after birth in terms of obstetrical outcomes, maternal quality of life and costs. Costs are lower, however, in the expectant monitoring group before 38 weeks of gestation and costs are lower in the induction of labour group after 38 weeks of gestation. So if induction of labour is considered to pre-empt possible stillbirth in suspected IUGR, it is reasonable to delay until 38 weeks, with watchful monitoring.
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http://dx.doi.org/10.1016/j.ejogrb.2013.07.017DOI Listing
October 2013

Arrhythmogenic right ventricular dysplasia/cardiomyopathy according to revised 2010 task force criteria with inclusion of non-desmosomal phospholamban mutation carriers.

Am J Cardiol 2013 Oct 19;112(8):1197-206. Epub 2013 Jul 19.

Department of Cardiology, University Medical Center Utrecht, Utrecht, The Netherlands; Interuniversity Cardiology Institute of the Netherlands, Utrecht, The Netherlands. Electronic address:

Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) is frequently associated with desmosomal mutations. However, nondesmosomal mutations may be involved. The aim of this study was to assess the contribution of a phospholamban (PLN) gene mutation to ARVD/C diagnosis according to the revised 2010 task force criteria (TFC). In 142 Dutch patients (106 men, mean age 51 ± 13 years) with proven ARVD/C (fulfillment of 2010 TFC for diagnosis), 5 known desmosomal genes (PKP2, DSP, DSC2, DSG2, and JUP) and the nondesmosomal PLN gene were screened. After genetic analysis, phenotypic characteristics of desmosomal versus PLN mutation carriers were compared. In 59 of 142 patients with ARVD/C (42%), no desmosomal mutation was found. In 19 of 142 patients (13%), the PLN founder mutation c.40_42delAGA (p.Arg14del) was identified. PLN mutation carriers more often had low-voltage electrocardiograms (p = 0.004), inverted T waves in leads V4 to V6 (p <0.001), and additional structural (p = 0.007) or functional (p = 0.017) left ventricular impairment, whereas desmosomal mutation carriers had more solitary right ventricular abnormalities. The revised TFC included 21 of 142 patients with proven ARVD/C who did not meet the 1994 TFC, including 7 PLN mutation carriers. In conclusion, there is a substantial contribution of PLN mutation to ARVD/C diagnosis by the 2010 TFC. In 32% of patients (19 of 59) with genetically unexplained proven ARVD/C, this nondesmosomal mutation was found. PLN mutation carriers have ARVD/C characteristics, including important right ventricular involvement, and additionally more often low-voltage electrocardiograms, inverted T waves in the left precordial leads, and left ventricular involvement.
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http://dx.doi.org/10.1016/j.amjcard.2013.06.017DOI Listing
October 2013

SIMPLE: implementation of recommendations from international evidence-based guidelines on caesarean sections in the Netherlands. Protocol for a controlled before and after study.

Implement Sci 2013 Jan 3;8. Epub 2013 Jan 3.

GROW-School for Oncology and Developmental Biology, Department of Obstetrics and Gynaecology, Maastricht University Medical Centre, Maastricht, The Netherlands.

Background: Caesarean section (CS) rates are rising worldwide. In the Netherlands, the most significant rise is observed in healthy women with a singleton in vertex position between 37 and 42 weeks gestation, whereas it is doubtful whether an improved outcome for the mother or her child was obtained. It can be hypothesized that evidence-based guidelines on CS are not implemented sufficiently. Therefore, the present study has the following objectives: to develop quality indicators on the decision to perform a CS based on key recommendations from national and international guidelines; to use the quality indicators in order to gain insight into actual adherence of Dutch gynaecologists to guideline recommendations on the performance of a CS; to explore barriers and facilitators that have a direct effect on guideline application regarding CS; and to develop, execute, and evaluate a strategy in order to reduce the CS incidence for a similar neonatal outcome (based on the information gathered in the second and third objectives).

Methods: An independent expert panel of Dutch gynaecologists and midwives will develop a set of quality indicators on the decision to perform a CS. These indicators will be used to measure current care in 20 hospitals with a population of 1,000 women who delivered by CS, and a random selection of 1,000 women who delivered vaginally in the same period. Furthermore, by interviewing healthcare professionals and patients, the barriers and facilitators that may influence the decision to perform a CS will be measured. Based on the results, a tailor-made implementation strategy will be developed and tested in a controlled before-and-after study in 12 hospitals (six intervention, six control hospitals) with regard to effectiveness, experiences, and costs.

Discussion: This study will offer insight into the current CS care and into the hindering and facilitating factors influencing obstetrical policy on CS. Furthermore, it will allow definition of patient categories or situations in which a tailor-made implementation strategy will most likely be meaningful and cost effective, without negatively affecting the outcome for mother and child.

Trial Registration: http://www.clinicaltrials.gov: NCT01261676.
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http://dx.doi.org/10.1186/1748-5908-8-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3547819PMC
January 2013

Comparison of three-dimensional echocardiographic software packages for assessment of left ventricular mechanical dyssynchrony and prediction of response to cardiac resynchronization therapy.

Eur Heart J Cardiovasc Imaging 2013 Jul 30;14(7):700-10. Epub 2012 Oct 30.

Department of Cardiology 5F 003, Institute for Cardiovascular Research (ICaR-VU), VU University Medical Center, De Boelelaan 1117, Amsterdam, The Netherlands.

Aims: We directly compared TomTec and QLAB software packages for the three-dimensional echocardiographic (3DE) assessment of left ventricular (LV) dyssynchrony including their ability to predict response to cardiac resynchronization therapy (CRT) in patients with ischaemic and non-ischaemic cardiomyopathy.

Methods And Results: A total of 140 heart failure patients with the LVEF ≤35% and 60 healthy volunteers underwent 3DE. A subgroup of 60 patients underwent CRT and were evaluated before and 6-12 months after implantation. The systolic dyssynchrony index (SDI) was derived from the dispersion of time to minimum regional volume for all 16 LV segments and measured with both software packages and compared using Pearson's correlation and Bland-Altman analysis. Measurements of SDI were significantly higher using TomTec compared with QLAB in both patients (10.9 ± 3.8 vs. 9.7 ± 3.9, P < 0.001) and healthy volunteers (4.1 ± 0.8 vs. 2.4 ± 1, P < 0.001), with large biases and wide limits of agreement. A moderate correlation (r = 0.65, P < 0.001) was observed between both software packages in patients while their inter-observer and intra-observer reliability were good. Of the 60 patients undergoing CRT, reverse remodelling as a measure of response was observed in 41 patients (68%). The optimal SDI cut-off value to predict response to CRT was higher for TomTec than for QLAB (8.8 vs.7.3%, P < 0.001) and demonstrated better sensitivity and specificity (93 and 61%, respectively) compared with QLAB (88 and 33%, respectively). Response prediction in patients with non-ischaemic cardiomyopathy was excellent with a sensitivity and specificity of 95 and 100% for TomTec and 70 and 83% for QLAB using similar cut-off values of 9.1 and 9.2%, respectively.

Conclusion: Different 3DE software packages for the assessment of mechanical dyssynchrony should not be used interchangeably until better software standardization is achieved. Dyssynchrony assessment with 3DE for the prediction of response to CRT seems particularly useful in patients with non-ischaemic cardiomyopathy.
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http://dx.doi.org/10.1093/ehjci/jes218DOI Listing
July 2013

Cardiac disease and cognitive impairment: a systematic review.

Heart 2012 Sep 11;98(18):1334-40. Epub 2012 Jun 11.

Department of Clinical Neuropsychology, VU University, Amsterdam, The Netherlands.

Cognitive impairment in cardiac patients may interfere with disease management. This review describes studies examining specific cognitive impairments in cardiac patients and studies that investigate the link between echocardiographic and cognitive measures. Executive function impairments were frequently reported in different patient groups. Also, lower cardiac output and worse left ventricular diastolic function are linked to executive function deficits. In cardiac patients, special attention should be paid to these executive function impairments in view of their role in disease management and independent living. Interventions that stimulate executive function should be encouraged and integrated in cardiac treatment protocols.
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http://dx.doi.org/10.1136/heartjnl-2012-301682DOI Listing
September 2012

A recurring valvular vegetation.

Eur Heart J Cardiovasc Imaging 2012 Aug 7;13(8):E5. Epub 2012 Mar 7.

Vumc Department of Cardiology, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands.

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http://dx.doi.org/10.1093/ehjci/jes049DOI Listing
August 2012

Manifest disease, risk factors for sudden cardiac death, and cardiac events in a large nationwide cohort of predictively tested hypertrophic cardiomyopathy mutation carriers: determining the best cardiological screening strategy.

Eur Heart J 2011 May 1;32(9):1161-70. Epub 2011 Apr 1.

Department of Clinical Genetics, Academic Medical Centre, Amsterdam, the Netherlands.

Aims: We investigated the presence of a clinical diagnosis of hypertrophic cardiomyopathy (HCM), risk factors for sudden cardiac death (SCD), and cardiac events during follow-up in predictively tested-not known to have a clinical diagnosis of HCM before the DNA test-carriers of a sarcomeric gene mutation and associations with age and gender to determine the best cardiological screening strategy.

Methods And Results: One hundred and thirty-six (30%) of 446 mutation carriers were diagnosed with HCM at one or more cardiological evaluation(s). Male gender and higher age were associated with manifest disease. Incidence of newly diagnosed manifest HCM was <10% per person-year under the age of 40 years and >10% in older carriers, although numbers were small in carriers <15 years. Twenty-three percent of carriers, with and without manifest disease, had established risk factor(s) for SCD (no significant difference). During an average follow-up of 3.5 ± 1.7 years two carriers, both with manifest disease, died suddenly (0.13% per person-year). A high-risk status for SCD (≥2 risk factors and manifest HCM) was present in 17 carriers during follow-up (2.4% per person-year). Age but not gender was associated with a high-risk status for SCD.

Conclusion: Thirty percent of carriers had or developed manifest HCM after predictive DNA testing and risk factors for SCD were frequently present. Our data suggest that the SCD risk is low and risk stratification for SCD can be omitted in carriers without manifest disease and that frequency of cardiological evaluations can possibly be decreased in carriers between 15 and 40 years as long as hypertrophy is absent.
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http://dx.doi.org/10.1093/eurheartj/ehr092DOI Listing
May 2011

[Recognition of psychiatrically vulnerable pregnant women].

Ned Tijdschr Geneeskd 2010 ;154(47):A2344

AlysisZorggroep ziekenhuis Rijnstate, Afd. Psychiatrie, Arnhem, the Netherlands.

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June 2011

Pitfalls of vaccinations with WT1-, Proteinase3- and MUC1-derived peptides in combination with MontanideISA51 and CpG7909.

Cancer Immunol Immunother 2011 Feb 21;60(2):161-71. Epub 2010 Oct 21.

Department of Hematology, University Medical Center Utrecht, Lundlaan 6, Utrecht, The Netherlands.

T cells with specificity for antigens derived from Wilms Tumor gene (WT1), Proteinase3 (Pr3), and mucin1 (MUC1) have been demonstrated to lyse acute myeloid leukemia (AML) blasts and multiple-myeloma (MM) cells, and strategies to enhance or induce such tumor-specific T cells by vaccination are currently being explored in multiple clinical trials. To test safety and immunogenicity of a vaccine composed of WT1-, Pr3-, and MUC1-derived Class I-restricted peptides and the pan HLA-DR T helper cell epitope (PADRE) or MUC1-helper epitopes in combination with CpG7909 and MontanideISA51, four patients with AML and five with MM were repetitively vaccinated. No clinical responses were observed. Neither pre-existing nor naive WT1-/Pr3-/MUC1-specific CD8+ T cells expanded in vivo by vaccination. In contrast, a significant decline in vaccine-specific CD8+ T cells was observed. An increase in PADRE-specific CD4+ T helper cells was observed after vaccination but these appeared unable to produce IL2, and CD4+ T cells with a regulatory phenotype increased. Taken into considerations that multiple clinical trials with identical antigens but different adjuvants induced vaccine-specific T cell responses, our data caution that a vaccination with leukemia-associated antigens can be detrimental when combined with MontanideISA51 and CpG7909. Reflecting the time-consuming efforts of clinical trials and the fact that 1/3 of ongoing peptide vaccination trails use CpG and/or Montanide, our data need to be taken into consideration.
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http://dx.doi.org/10.1007/s00262-010-0929-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3024516PMC
February 2011