Publications by authors named "Judith Racape"

40 Publications

Gonadal Function Recovery in Patients With Advanced Hodgkin Lymphoma Treated With a PET-Adapted Regimen: Prospective Analysis of a Randomized Phase III Trial (AHL2011).

J Clin Oncol 2021 Jun 22:JCO2100068. Epub 2021 Jun 22.

Department of Haematology, University Hospital F Mitterrand and Inserm UMR1231, Dijon, France.

Purpose: The prospective, randomized AHL2011 trial demonstrated that the use of the doxorubicin, bleomycin, vinblastine, and dacarbazine regimen (ABVD) after two cycles of bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP) in early responders on the basis of a positron emission tomography (PET)-driven strategy was safe and minimized toxicity compared with standard 6 BEACOPP cycles. This substudy investigated the benefit of this strategy in gonadal function and fertility in patients under 45 years old.

Methods: Ovarian function was assessed by serum measurement of follicle-stimulating hormone (FSH), estradiol, and anti-müllerian hormone in women, and semen analysis, FSH, and testosterone levels were used to evaluate testicular function in men at baseline, end of treatment, and during 5 years of follow-up.

Results: A total of 145 women and 424 men, enrolled between May 19, 2011, and April 29, 2014, were included. The risk of premature ovarian insufficiency (FSH > 24 IU/L) and of having a low ovarian reserve (anti-müllerian hormone < 0.5 ng/mL) was reduced after treatment in the PET-driven group (odds ratio [OR], 0.20; 95% CI, 0.08 to 0.50; = .001 and OR, 0.15; 95% CI, 0.04 to 0.56, = .005, respectively). Both parameters were correlated with age and dose of alkylating agents. However, no significant differences were observed in terms of pregnancy rates. Men in the PET-driven group had a higher recovery rate of sperm parameters after treatment compared with the standard BEACOPP group, as well as a lower risk of severe testicular damage (OR, 0.26; 95% CI, 0.13 to 0.5; < .0001) and a higher likelihood of achieving pregnancy (OR, 3.7; 95% CI, 1.4 to 9.3; = .004).

Conclusion: Although both treatments affected ovarian reserve and spermatogenesis, the PET-driven strategy decreased the risk of gonadal dysfunction and infertility in advanced Hodgkin lymphoma.
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http://dx.doi.org/10.1200/JCO.21.00068DOI Listing
June 2021

SARS-CoV-2 screening among people living in homeless shelters in Brussels, Belgium.

PLoS One 2021 15;16(6):e0252886. Epub 2021 Jun 15.

Research Center in Epidemiology, Biostatistics and Clinical Research, School of Public Health, Université Libre de Bruxelles (ULB), Brussels, Belgium.

Background: Subgroups of precarious populations such as homeless people are more exposed to infection and at higher risk of developing severe forms of COVID-19 compared to the general population. Many of the recommended prevention measures, such as social distancing and self-isolation, are not feasible for a population living in shelters characterised by physical proximity and a high population density. The objective of the study was to describe SARS-CoV-2 infection prevalence in homeless shelters in Brussels (Belgium), and to identify risk factors and infection control practices associated with SARS-CoV-2 positivity rates.

Methods: A total of 1994 adults were tested by quantitative PCR tests in 52 shelters in Brussels (Belgium) between April and June, 2020, in collaboration with Doctors of the World. SARS-CoV-2 prevalence is here described site by site, and we identify risk factors associated with SARS-CoV-2 positivity rates. We also investigate associations between seropositivity and reported symptoms.

Results: We found an overall prevalence of 4.6% for the period, and a cluster of high rates of SARS-CoV-2 positivity (20-30% in two shelters). Among homeless people, being under 40 years of age (OR (CI95%) 2.3 (1.2-4.4), p = 0.02), having access to urgent medical care (AMU) (OR(CI95%): 2.4 (1.4-4.4)], p = 0.02), and sharing a room with someone who tested positive (OR(CI95%): 5.3 (2.9-9.9), p<0.0001) were factors associated with SARS-CoV-2 positivity rates. 93% of those who tested positive were asymptomatic.

Conclusion: This study shows high rates of SARS-COV-2 infection positive tests in some shelters, with a high proportion of asymptomatic cases. The survey reveals how important testing and isolation measures are, together with actions taken by medical and social workers during the outbreak.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0252886PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8205130PMC
June 2021

Specific Host Signatures for the Detection of Tuberculosis Infection in Children in a Low TB Incidence Country.

Front Immunol 2021 15;12:575519. Epub 2021 Mar 15.

Laboratory of Vaccinology and Mucosal Immunity, Université Libre de Bruxelles, Brussels, Belgium.

Diagnosis of tuberculosis (TB) in children remains challenging due to unspecific clinical presentation and low bacillary load. In low TB incidence countries, most cases are diagnosed by a contact screening strategy after exposure to an index TB case. Due to the severity of TB in young children, the priority is to determine whether a child is infected or not, whereas differential diagnosis between active TB (aTB) and latent TB constitutes a second step. In Belgium, a low TB incidence country, we prospectively included 47 children with a defined infection status (12 children with aTB, 18 with latent TB, and 17 uninfected) (exploratory cohort), and determined the optimal combinations of cytokines secreted by their peripheral blood mononuclear cells in response to a 5-days stimulation with four different mycobacterial antigens, in an attempt to classify the children according to their infectious status. Correct identification of all infected children was obtained by several combinations of two purified protein derivative (PPD)-induced cytokines (IFN-γ and either GM-CSF, MIP-1α, sCD40L or TNF-α), or by combining PPD-induced IFN-γ with culture-filtrate protein-10 (CFP-10)-induced TNF-α. Alternatively, combining CFP-10-induced TNF-α and IP-10 with heparin-binding haemagglutinin (HBHA)-induced-IFN-γ was more effective in testing recently BCG-vaccinated children or those suspected to be infected with non-tuberculous mycobacteria, providing a correct classification of 97% of the infected children. This combination also correctly classified 98% of the children from a validation cohort comprising 40 infected children and 20 non-infected children. Further differentiation between aTB and children with latent TB was more difficult. Combining ESAT-6-induced MIP1-α and IP-10, CFP-10-induced MIG, and HBHA-induced MIG provided a correct classification of 77% of the children from the exploratory cohort but only of 57.5% of those from the validation cohort. We conclude that combining the measurement of 2-4 cytokines induced by three different mycobacterial antigens allows an excellent identification of infected children, whereas differentiating children with aTB from those with latent TB remains far from perfect.
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http://dx.doi.org/10.3389/fimmu.2021.575519DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8005539PMC
June 2021

Quantification of Cardiac Kinetic Energy and Its Changes During Transmural Myocardial Infarction Assessed by Multi-Dimensional Seismocardiography.

Front Cardiovasc Med 2021 8;8:603319. Epub 2021 Mar 8.

Department of Cardiology, Erasme Hospital, Université Libre de Bruxelles, Brussels, Belgium.

Seismocardiography (SCG) records cardiac and blood-induced motions transmitted to the chest surface as vibratory phenomena. Evidences demonstrate that acute myocardial ischemia (AMI) profoundly affects the SCG signals. Multidimensional SCG records cardiac vibrations in linear and rotational dimensions, and scalar parameters of kinetic energy can be computed. We speculate that AMI and revascularization profoundly modify cardiac kinetic energy as recorded by SCG. Under general anesthesia, 21 swine underwent 90 min of myocardial ischemia induced by percutaneous sub-occlusion of the proximal left anterior descending (LAD) coronary artery and subsequent revascularization. Invasive hemodynamic parameters were continuously recorded. SCG was recorded during baseline, immediately and 80 min after LAD sub-occlusion, and immediately and 60 min after LAD reperfusion. K was automatically computed for each cardiac cycle ( ) in linear ( ) and rotational ( ) dimensions. K was calculated as well during systole and diastole ( and , respectively). Echocardiography was performed at baseline and after revascularization, and the left ventricle ejection fraction (LVEF) along with regional left ventricle (LV) wall abnormalities were evaluated. Upon LAD sub-occlusion, 77% of STEMI and 24% of NSTEMI were observed. Compared to baseline, troponins increased from 13.0 (6.5; 21.3) ng/dl to 170.5 (102.5; 475.0) ng/dl, and LVEF dropped from 65.0 ± 0.0 to 30.6 ± 5.7% at the end of revascularization (both < 0.0001). Regional LV wall abnormalities were observed as follows: anterior MI, 17.6% (three out of 17); septal MI, 5.8% (one out of 17); antero-septal MI, 47.1% (eight out of 17); and infero-septal MI, 29.4% (five out of 17). In the linear dimension, , , and dropped by 43, 52, and 53%, respectively ( < 0.0001, < 0.0001, and = 0.03, respectively) from baseline to the end of reperfusion. In the rotational dimension, and dropped by 30 and 36%, respectively ( = 0.0006 and < 0.0001, respectively), but did not change ( = 0.41). All the hemodynamic parameters, except the pulmonary artery pulse pressure, were significantly correlated with the parameters of , except for the diastolic component. In this very context of experimental AMI with acute LV regional dysfunction and no concomitant AMI-related heart valve disease, linear and rotational K parameters, in particular, systolic ones, provide reliable information on LV contractile dysfunction and its effects on the downstream circulation. Multidimensional SCG may provide information on the cardiac contractile status expressed in terms of K during AMI and reperfusion. This automatic system may empower health care providers and patients to remotely monitor cardiovascular status in the near future.
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http://dx.doi.org/10.3389/fcvm.2021.603319DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7982421PMC
March 2021

Donor-Derived Myeloid Heme Oxygenase-1 Controls the Development of Graft-Versus-Host Disease.

Front Immunol 2020 18;11:579151. Epub 2021 Jan 18.

Institute for Medical Immunology, Université Libre de Bruxelles, Gosselies, Belgium.

Graft-versus-host disease (GVHD) remains a major clinical drawback of allogeneic hematopoietic stem cell transplantation (HSCT). Here, we investigated how the stress responsive heme catabolizing enzyme heme oxygenase-1 (HO-1, encoded by ) regulates GVHD in response to allogeneic hematopoietic stem cell transplantation in mice and humans. We found that deletion of the allele, specifically in the myeloid compartment of mouse donor bone marrow, promotes the development of aggressive GVHD after allogeneic transplantation. The mechanism driving GVHD in mice transplanted with allogeneic bone marrow lacking HO-1 expression in the myeloid compartment involves enhanced T cell alloreactivity. The clinical relevance of these observations was validated in two independent cohorts of HSCT patients. Individuals transplanted with hematopoietic stem cells from donors carrying a long homozygous (GT) repeat polymorphism (L/L) in the promoter, which is associated with lower HO-1 expression, were at higher risk of developing severe acute GVHD as compared to donors carrying a short (GT) repeat (S/L or S/S) polymorphism associated with higher HO-1 expression. In this study, we showed the unique importance of donor-derived myeloid HO-1 in the prevention of lethal experimental GVHD and we corroborated this observation by demonstrating the association between human (GT) microsatellite polymorphisms and the incidence of severe acute GVHD in two independent HSCT patient cohorts. Donor-derived myeloid HO-1 constitutes a potential therapeutic target for HSCT patients and large-scale prospective studies in HSCT patients are necessary to validate the HO-1 L/L genotype as an independent risk factor for developing severe acute GVHD.
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http://dx.doi.org/10.3389/fimmu.2020.579151DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7849683PMC
June 2021

Assessment of left ventricular twist by 3D ballistocardiography and seismocardiography compared with 2D STI echocardiography in a context of enhanced inotropism in healthy subjects.

Sci Rep 2021 01 12;11(1):683. Epub 2021 Jan 12.

Department of Cardiovascular Diseases, Erasme Hospital, Université Libre de Bruxelles (ULB), Brussels, Belgium.

Ballistocardiography (BCG) and Seismocardiography (SCG) assess the vibrations produced by cardiac contraction and blood flow, respectively, by means of micro-accelerometers and micro-gyroscopes. From the BCG and SCG signals, maximal velocities (V), integral of kinetic energy (iK), and maximal power (P) can be computed as scalar parameters, both in linear and rotational dimensions. Standard echocardiography and 2-dimensional speckle tracking imaging echocardiography were performed on 34 healthy volunteers who were infused with increasing doses of dobutamine (5-10-20 μg/kg/min). Linear V of BCG predicts the rates of left ventricular (LV) twisting and untwisting (both p < 0.0001). The linear P of both SCG and BCG and the linear iK of BCG are the best predictors of the LV ejection fraction (LVEF) (p < 0.0001). This result is further confirmed by mathematical models combining the metrics from SCG and BCG signals with heart rate, in which both linear P and iK strongly correlate with LVEF (R = 0.7, p < 0.0001). In this setting of enhanced inotropism, the linear V of BCG, rather than the V of SCG, is the metric which best explains the LV twist mechanics, in particular the rates of twisting and untwisting. P and iK metrics are strongly associated with the LVEF and account for 50% of the variance of the LVEF.
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http://dx.doi.org/10.1038/s41598-020-79933-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7804966PMC
January 2021

Mothers' experiences of perinatal care in Belgian public hospitals: exploring the social inequalities. Protocol for a cross-sectional survey.

BMJ Open 2020 11 30;10(11):e038400. Epub 2020 Nov 30.

Research Centre in Social Approaches to Health, School of Public Health, Université libre de Bruxelles, Brussels, Belgium.

Introduction: In Europe, the social inequalities in perinatal health are usually found to be to the disadvantage of non-European immigrants and women with lower levels of education and income. Among the possible underlying mechanisms are inadequate access to healthcare services and suboptimal care. To explore this hypothesis in the Belgian context, our research will describe detailed maternal socioeconomic and migration characteristics, explore how these factors relate to each other, and how they relate to women's perinatal care trajectories and experiences of care.

Methods: Using a modified version of the Migrant-Friendly Maternity Care Questionnaire, we will survey 900 mothers of Belgian nationality or a nationality from a North or Sub-Saharan African country, and having given birth in four maternity wards in Brussels. The questionnaire has been adapted to the study objectives and the Belgian context. Interviewers will administer the 116-item questionnaire to all women agreeing to participate and meeting inclusion criteria, within 14 days of having given birth. Clinical information will be extracted from hospital records.

Analysis: We will estimate the associations of women's socioeconomic and migration characteristics with:Women's antenatal care trajectories (timing of first antenatal consultation, minimum recommended number of consultations, and problems accessing care).Obstetric practices such as episiotomies, emergency caesarean sections, and inductions.Patient experience such as feelings of discrimination, respect, and understanding of information.We will use descriptive statistics, multiple correspondence analysis, and simple and multiple logistic regressions.

Ethics And Dissemination: Ethical approval has been obtained from the hospital Ethics Committees and from the Université libre de Bruxelles (No: P2017/055/B406201730877). Written informed consent will be sought from all participants.In addition to disseminating findings and recommendations to the scientific community through open-source journal articles and conferences, we will also address local organisations and healthcare professionals via a written report and seminars.
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http://dx.doi.org/10.1136/bmjopen-2020-038400DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7705495PMC
November 2020

Antibiotics versus no therapy in kidney transplant recipients with asymptomatic bacteriuria (BiRT): a pragmatic, multicentre, randomized, controlled trial.

Clin Microbiol Infect 2021 Mar 10;27(3):398-405. Epub 2020 Sep 10.

Department of Nephrology, Universitair Ziekenhuis Antwerpen, Universiteit Antwerpen, Antwerp, Belgium.

Objectives: Many transplant physicians screen for and treat asymptomatic bacteriuria (ASB) during post-kidney-transplant surveillance. We investigated whether antibiotics are effective in reducing the occurrence of symptomatic urinary tract infection (UTI) in kidney transplant recipients with ASB.

Methods: We performed this multicentre, randomized, open-label trial in kidney transplant recipients who had ASB and were ≥2 months post-transplantation. We randomly assigned participants to receive antibiotics or no therapy. The primary outcome was the incidence of symptomatic UTI over the subsequent 12 months.

Results: One hundred and ninety-nine kidney transplant recipients with ASB were randomly assigned to antibiotics (100 participants) or no therapy (99 participants). There was no significant difference in the occurrence of symptomatic UTI between the antibiotic and no-therapy groups (27%, 27/100 versus 31%, 31/99; univariate Cox model: hazard ratio 0.83, 95%CI: 0.50-1.40; log-rank test: p 0.49). Over the 1-year study period, antibiotic use was five times higher in the antibiotic group than in the no-therapy group (30 antibiotic days/participant, interquartile range 20-41, versus 6, interquartile range 0-15, p < 0.001). Overall, 155/199 participants (78%) had at least one further episode of bacteriuria during the follow-up. Compared with the participant's baseline episode of ASB, the second episode of bacteriuria was more frequently caused by bacteria resistant to clinically relevant antibiotics (ciprofloxacin, cotrimoxazole, third-generation cephalosporin) in the antibiotic group than in the no-therapy group (18%, 13/72 versus 4%, 3/83, p 0.003).

Conclusions: Applying a screen-and-treat strategy for ASB does not reduce the occurrence of symptomatic UTI in kidney transplant recipients who are more than 2 months post-transplantation. Furthermore, this strategy increases antibiotic use and promotes the emergence of resistant organisms.
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http://dx.doi.org/10.1016/j.cmi.2020.09.005DOI Listing
March 2021

Influence of sympathetic activation on myocardial contractility measured with ballistocardiography and seismocardiography during sustained end-expiratory apnea.

Am J Physiol Regul Integr Comp Physiol 2020 10 2;319(4):R497-R506. Epub 2020 Sep 2.

Department of Cardiology, Erasme Hospital, Université Libre de Bruxelles, Brussels, Belgium.

Ballistocardiography (BCG) and seismocardiography (SCG) assess vibrations produced by cardiac contraction and blood flow, respectively, through micro-accelerometers and micro-gyroscopes. BCG and SCG kinetic energies (KE) and their temporal integrals (K) during a single heartbeat are computed in linear and rotational dimensions. Our aim was to test the hypothesis that K from BCG and SCG are related to sympathetic activation during maximal voluntary end-expiratory apnea. Multiunit muscle sympathetic nerve traffic [burst frequency (BF), total muscular sympathetic nerve activity (tMSNA)] was measured by microneurography during normal breathing and apnea ( = 28, healthy men). K of BCG and SCG were simultaneously recorded in the linear and rotational dimension, along with oxygen saturation ([Formula: see text]) and systolic blood pressure (SBP). The mean duration of apneas was 25.4 ± 9.4 s. SBP, BF, and tMSNA increased during the apnea compared with baseline ( = 0.01, = 0.002,and = 0.001, respectively), whereas [Formula: see text] decreased ( = 0.02). At the end of the apnea compared with normal breathing, changes in K computed from BCG were related to changes of tMSNA and BF only in the linear dimension ( = 0.85, < 0.0001; and = 0.72, = 0.002, respectively), whereas changes in linear K of SCG were related only to changes of tMSNA ( = 0.62, = 0.01). We conclude that maximal end expiratory apnea increases cardiac kinetic energy computed from BCG and SCG, along with sympathetic activity. The novelty of the present investigation is that linear K of BCG is directly and more strongly related to the rise in sympathetic activity than the SCG, mainly at the end of a sustained apnea, likely because the BCG is more affected by the sympathetic and hemodynamic effects of breathing cessation. BCG and SCG may prove useful to assess sympathetic nerve changes in patients with sleep disturbances. Ballistocardiography (BCG) and seismocardiography (SCG) assess vibrations produced by cardiac contraction and blood flow, respectively, through micro-accelerometers and micro-gyroscopes. Kinetic energies (KE) and their temporal integrals (K) during a single heartbeat are computed from the BCG and SCG waveforms in a linear and a rotational dimension. When compared with normal breathing, during an end-expiratory voluntary apnea, K increased and was positively related to sympathetic nerve traffic rise assessed by microneurography. Further studies are needed to determine whether BCG and SCG can probe sympathetic nerve changes in patients with sleep disturbances.
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http://dx.doi.org/10.1152/ajpregu.00142.2020DOI Listing
October 2020

Birthweight of babies born to migrant mothers - What role do integration policies play?

SSM Popul Health 2019 Dec 21;9:100503. Epub 2019 Oct 21.

Manitoba Centre for Health Policy, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Canada.

Birthweights of babies born to migrant women are generally lower than those of babies born to native-born women. Favourable integration policies may improve migrants' living conditions and contribute to higher birthweights. We aimed to explore associations between integration policies, captured by the Migrant Integration Policy Index (MIPEX), with offspring birthweight among migrants from various world regions. In this cross-country study we pooled 31 million term birth records between 1998 and 2014 from ten high-income countries: Australia, Belgium, Canada, Denmark, Finland, Japan, Norway, Spain, Sweden and United Kingdom (Scotland). Birthweight differences in grams (g) were analysed with regression analysis for aggregate data and random effects models. Proportion of births to migrant women varied from 2% in Japan to 28% in Australia. The MIPEX score was not associated with birthweight in most migrant groups, but was positively associated among native-born (mean birthweight difference associated with a 10-unit increase in MIPEX: 105 g; 95% CI: 24, 186). Birthweight among migrants was highest in the Nordic countries and lowest in Japan and Belgium. Migrants from a given origin had heavier newborns in countries where the mean birthweight of native-born was higher and vice versa. Mean birthweight differences between migrants from the same origin and the native-born varied substantially across destinations (70 g-285 g). Birthweight among migrants does not correlate with MIPEX scores. However, birthweight of migrant groups aligned better with that of the native-born in destination counties. Further studies may clarify which broader social policies support migrant women and have impacts on perinatal outcomes.
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http://dx.doi.org/10.1016/j.ssmph.2019.100503DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6978482PMC
December 2019

Stillbirth Among Arab Women in Canada, 1981-2015.

Public Health Rep 2020 Mar/Apr;135(2):245-252. Epub 2020 Jan 22.

Departments of Obstetrics, Gynecology, and Reproductive Science, and Population Health Science and Policy, Icahn School of Medicine at Mount Sinai, Blavatnik Family Women's Health Research Institute, New York, NY, USA.

Objectives: The Arabic-speaking population is increasing in Europe and North America. Evidence suggests that Arab migrants have a greater risk of adverse birth outcomes than nonmigrants, but the risk of stillbirth is largely understudied. We examined inequality in stillbirth rates between Arab women and the French and English majority of women in Quebec, Canada.

Methods: We conducted a retrospective study of all births in Quebec from 1981 through 2015. We computed stillbirth rates by period and cause of death, and we used log binomial regression to estimate the association between Arabic mother tongue and stillbirth, adjusted for maternal characteristics.

Results: Stillbirth rates per 1000 births overall were lower among women with Arabic mother tongue (3.89) than among women with French or English mother tongue (4.52), and rates changed little over time. However, Arabic-speaking women from Arab countries had a higher adjusted risk of stillbirth than French- or English-speaking women (risk ratio = 1.23; 95% confidence interval, 1.07-1.42). Congenital anomalies, termination of pregnancy, and undetermined causes contributed to a disproportionate number of stillbirths among women with Arabic mother tongue compared with the French- and English-speaking majority.

Conclusions: Arabic-speaking women from Arab countries have higher risks of stillbirth compared with the French and English majority in Quebec. Strategies to reduce stillbirth risk among Arabic speakers should focus on improving identification of causes of death.
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http://dx.doi.org/10.1177/0033354919900894DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7036609PMC
May 2020

Digenic inheritance of human primary microcephaly delineates centrosomal and non-centrosomal pathways.

Hum Mutat 2020 02 27;41(2):512-524. Epub 2019 Nov 27.

Institut de Recherche Interdisciplinaire en Biologie Humaine et Moléculaire, Université Libre de Bruxelles, Brussels, Belgium.

Primary microcephaly (PM) is characterized by a small head since birth and is vastly heterogeneous both genetically and phenotypically. While most cases are monogenic, genetic interactions between Aspm and Wdr62 have recently been described in a mouse model of PM. Here, we used two complementary, holistic in vivo approaches: high throughput DNA sequencing of multiple PM genes in human patients with PM, and genome-edited zebrafish modeling for the digenic inheritance of PM. Exomes of patients with PM showed a significant burden of variants in 75 PM genes, that persisted after removing monogenic causes of PM (e.g., biallelic pathogenic variants in CEP152). This observation was replicated in an independent cohort of patients with PM, where a PM gene panel showed in addition that the burden was carried by six centrosomal genes. Allelic frequencies were consistent with digenic inheritance. In zebrafish, non-centrosomal gene casc5 -/- produced a severe PM phenotype, that was not modified by centrosomal genes aspm or wdr62 invalidation. A digenic, quadriallelic PM phenotype was produced by aspm and wdr62. Our observations provide strong evidence for digenic inheritance of human PM, involving centrosomal genes. Absence of genetic interaction between casc5 and aspm or wdr62 further delineates centrosomal and non-centrosomal pathways in PM.
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http://dx.doi.org/10.1002/humu.23948DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7496698PMC
February 2020

Secular trends in stillbirth by maternal socioeconomic status in Spain 2007-15: a population-based study of 4 million births.

Eur J Public Health 2019 12;29(6):1043-1048

Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.

Introduction: Stillbirth, one of the urgent concerns of preventable perinatal deaths, has wide-reaching consequences for society. We studied secular stillbirth trends by maternal socioeconomic status (SES) in Spain.

Methods: We developed a population-based observational study, including 4 083 919 births during 2007-15. We estimate stillbirth rates and secular trends by maternal SES. We also evaluated the joint effect of maternal educational attainment and the Human Development Index (HDI) of women's country of origin on the risk of stillbirth. The data and statistical analysis can be accessed for reproducibility in a GitHub repository: https://github.com/migariane/Stillbirth.

Results: We found a consistent pattern of socioeconomic inequalities in the risk of delivering a stillborn, mainly characterized by a persistently higher risk, over time, among women with lower SES. Overall, women from countries with low HDIs and low educational attainments had approximately a four times higher risk of stillbirth (RR: 4.44; 95%CI: 3.71-5.32). Furthermore, we found a paradoxical reduction of the stillbirth gap over time between the highest and the lowest SESs, which is mostly due to the significant and increasing trend of stillbirth risk among highly educated women of advanced maternal age.

Conclusion: Our findings highlight no improvement in stillbirth rates among women of lower SES and an increasing trend among highly educated women of advanced maternal age over recent years. Public health policies developing preventive programmes to reduce stillbirth rates among women with lower SES are needed as well as the necessity of further study to understand the growing trend of age-related stillbirths among highly educated women in Spain.
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http://dx.doi.org/10.1093/eurpub/ckz086DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6896972PMC
December 2019

Is the socioeconomic status of immigrant mothers in Brussels relevant to predict their risk of adverse pregnancy outcomes?

BMC Pregnancy Childbirth 2018 Oct 26;18(1):422. Epub 2018 Oct 26.

Research centre in Health Policies and Health Systems, Ecole de Santé Publique, Université Libre de Bruxelles (ULB), Route de Lennik 808, 1070, Bruxelles, Belgium.

Background: Understanding and tackling perinatal health inequities in industrialized countries requires analysing the socioeconomic determinants of adverse pregnancy outcomes among immigrant populations. Studies show that among certain migrant groups, education is not associated with adverse pregnancy outcomes. We aim to extend this analysis to further dimensions of socioeconomic status (SES) and to other settings. The objective of this study is to identify sociodemographic characteristics associated with adverse pregnancy outcomes, according to the origin of mothers residing in Brussels.

Methods: We analysed all singleton live births in Brussels between 2005 and 2010 (n = 97,844). The data arise from the linkage between three administrative databases. Four groups of women were included according to their place of birth: Belgium, EU, North Africa, and Sub-Saharan Africa. For each group, logistic regression was carried out to estimate the odds ratios of low birthweight (LBW) and small for gestational age (SGA) according to SES indicators (household income, maternal employment status, maternal education) and single parenthood.

Results: Three key findings emerge from this study: 1) 25% of children were born into a household under the poverty threshold. This proportion was much higher for mothers born outside of the EU. 2) For North African immigrants, SES indicators didn't influence the pregnancy outcomes, whereas their risk of LBW increased with single parenthood. 3) For Sub-Saharan Africans the risk of LBW increased with low household income.

Conclusion: In a region where immigrant mothers are at high poverty risk, we observe a classic social gradient in perinatal outcomes only for mothers born in Belgium or the EU. In the other groups, SES influences perinatal outcomes less systematically. To develop interventions to reduce inequities from birth, it's important to identify the determinants of perinatal health among immigrants and to understand the underlying mechanisms in different contexts.
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http://dx.doi.org/10.1186/s12884-018-2043-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6204002PMC
October 2018

Host and microbial factors in kidney transplant recipients with Escherichia coli acute pyelonephritis or asymptomatic bacteriuria: a prospective study using whole-genome sequencing.

Nephrol Dial Transplant 2019 05;34(5):878-885

Department of Microbiology, CUB-Hôpital Erasme, Université Libre de Bruxelles, Brussels, Belgium.

Background: Urinary tract infection is the most common infection among kidney transplant recipients (KTRs). Many transplant physicians fear that host compromise will allow low-virulence strains to cause pyelonephritis in KTRs, so they often treat asymptomatic bacteriuria with antibiotics. Identification of the host/microbe factors that determine the clinical presentation (i.e. pyelonephritis versus asymptomatic bacteriuria) once an Escherichia coli strain enters a KTRs bladder could inform management decisions.

Methods: We prospectively collected all E. coli isolates causing either pyelonephritis or asymptomatic bacteriuria in KTRs at our institution (December 2012-June 2015). Whole-genome sequencing was used to assess bacterial characteristics (carriage of 48 virulence genes and phylogenetic and clonal background). Host parameters were also collected.

Results: We analysed 72 bacteriuria episodes in 54 KTRs (53 pyelonephritis, 19 asymptomatic bacteriuria). The pyelonephritis and asymptomatic bacteriuria isolates exhibited a similar total virulence gene count per isolate [median 18 (range 5-33) and 18 (5-30), respectively; P = 0.57] and for individual virulence genes differed significantly only for the prevalence of the pap operon (pyelonephritis 39%,versus asymptomatic bacteriuria 0%; P = 0.002). No other significant between-group differences were apparent for 86 other bacterial and host variables.

Conclusions: Our findings suggest that bacterial adherence plays a role in the pathogenesis of pyelonephritis in KTRs despite significantly altered host urinary tract anatomy and weakened immunity. Whether KTRs might benefit from targeted therapies (e.g. vaccination or inhibitors of fimbrial adhesion) has yet to be studied.
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http://dx.doi.org/10.1093/ndt/gfy292DOI Listing
May 2019

Evaluation of total body weight and body mass index cut-offs for increased cefazolin dose for surgical prophylaxis.

Int J Antimicrob Agents 2016 Dec 5;48(6):633-640. Epub 2016 Oct 5.

Department of Infectious Diseases, CUB-Erasme Hospital, Université Libre de Bruxelles, Route de Lennik 808, 1070 Brussels, Belgium.

French and American guidelines recommend increased dosage regimens of cefazolin (CFZ) for surgical prophylaxis in patients with a body mass index (BMI) ≥ 35 kg/m or with a total body weight (TBW) ≥ 120 kg. The objective of this study was to evaluate the accuracy of these cut-offs in identifying patients who require CFZ dose adjustment. A pharmacokinetic study was conducted in patients of varying TBW and BMI who received 2 g of CFZ intravenously for prophylaxis prior to digestive surgery. Adequacy of therapy, defined as a serum concentration of unbound CFZ (fCFZ) ≥ 4 mg/L, was evaluated 180 min (T) and 240 min (T) after the start of CFZ infusion. Possible factors associated with insufficient fCFZ levels were also assessed. A P-value of <0.05 was considered statistically significant. A total of 63 patients were included in the study, categorised according to BMI (<35 kg/m, 20 patients; and ≥35 kg/m, 43 patients) and TBW (<120 kg, 41 patients; and ≥120 kg, 22 patients). All patients had adequate drug levels at T but only 40/63 patients (63%) had adequate levels at T. At T, therapy was adequate in 15/20 patients (75%) and 25/43 patients (58%) with BMI <35 kg/m and ≥35 kg/m, respectively (P = 0.20), and in 28/41 patients (68%) and 12/22 patients (55%) with TBW <120 kg and ≥120 kg, respectively (P = 0.28). No factor associated with insufficient fCFZ was identified. In conclusion, current BMI and TBW cut-offs are poor indicators of which patients could benefit from increased CFZ dosage regimens.
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http://dx.doi.org/10.1016/j.ijantimicag.2016.08.019DOI Listing
December 2016

Human leucocyte antigen (HLA) class I and II typing in Belgian multiple sclerosis patients.

Acta Neurol Belg 2017 Mar 28;117(1):61-65. Epub 2016 Oct 28.

HLA Laboratory, Hôpital Erasme, Université Libre de Bruxelles, Brussels, Belgium.

This is one of the first studies to compare the frequencies of different human leucocyte antigen (HLA) class I and II alleles and haplotype HLA-DRB1*15-DQB1*06 in a cohort of 119 patients with multiple sclerosis (MS) and a cohort of 124 healthy controls in Belgium. An association with MS was found for the HLA-DRB1*15 (odds ratio [OR] 2.60 [95% confidence interval (CI) 1.51-4.50]) and HLA-DQB1*06 (OR 1.97 [95% CI 1.18-3.29]) alleles, and for haplotype DRB1*15-DQB1*06 (OR 2.63 [95% CI 1.52-4.56]). The HLA-B*07 allele also tended to be more frequent in MS patients (OR 1.46 [95% CI 0.80-2.65]) and more frequent among MS patients with than in those without the HLA-DRB1*15 allele (26/54 [48.1%] versus 6/65 [9.2%]; p value <0.0001). Other alleles were underrepresented in MS patients, such as the HLA-DRB1*07 (OR 0.39 [95% CI 0.21-0.73]) and HLA-A*02 (OR 0.56 [95% CI 0.34-0.94]), showing a protective role against the disease. The HLA-B*44 (OR 0.58 [95% CI 0.31-1.09]) and HLA-DRB1*04 (OR 0.75 [95% CI 0.42-1.34]) alleles tended to be less frequent in MS patients. Altogether, the significant results observed in this population are in line with those from other countries and confirm that propensity to MS can be due to a complex presence of various HLA class I and class II alleles.
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http://dx.doi.org/10.1007/s13760-016-0716-0DOI Listing
March 2017

Preemptive reduction of immunosuppression upon high urinary polyomavirus loads improves patient survival without affecting kidney graft function.

Transpl Infect Dis 2016 Dec 20;18(6):872-880. Epub 2016 Oct 20.

Department of Nephrology, Dialysis and Transplantation, Cliniques Universitaires de Bruxelles, Hôpital Erasme, Brussels, Belgium.

Background: Polyomavirus (PV) is a major cause of kidney graft disease. Monitoring by polymerase chain reaction (PCR) on blood is currently recommended. In order to avoid irreversible lesions, we investigated the clinical impact of preemptive reduction of immunosuppression (IS) in kidney transplant recipients (KTR) upon detection of high urinary PV (Upv) load, including BK virus and JC virus.

Material And Methods: From 2000 to 2011, in our single center, 789 consecutive KTR were distributed into 4 groups, according to the maximal Upv levels (by PCR) during the first year and the therapeutic option: (A) Upv <10 copies (cp)/mL (n=573), (B) ≥10 Upv <10 cp/mL (n=100), and (C) Upv ≥10 cp/mL (n=116); in group C, the IS drug doses were reduced in subgroup Ca (n=102) only, as 14 patients (subgroup Cb) were at risk for graft rejection.

Results: The preemptive reduction of IS (group Ca) increased patient survival as compared with all other groups (P<.05), did not modify graft function, and increased graft survival vs group A (risk ratio: 5.7, confidence interval: 1.8-18.1, P=.003). Differences for risk factors are as follows (groups Ca vs A): incidence of human leukocyte antigen (HLA) immunization (>5% panel reactive antibodies): 3% vs 8% (P=.05), number of HLA mismatches: 2.7 vs 2.5 (P=.049), and incidence of acute rejection: 9.8% vs 24.2% (P=.005). PV-associated nephropathy occurred only in group Ca (2% of total grafts) without effect on patient or graft outcome.

Conclusion: The reduction of IS in patients with high Upv loads is beneficial for patient survival and does not affect graft survival or graft function.
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http://dx.doi.org/10.1111/tid.12603DOI Listing
December 2016

Chronic kidney disease as major determinant of the renal risk related to on-pump cardiac surgery: a single-center cohort study.

Acta Chir Belg 2016 Aug 2;116(4):217-224. Epub 2016 Jun 2.

c Department of Intensive Care , Hôpital Erasme, Université Libre De Bruxelles , Brussels , Belgium.

Background: Cardiac surgery-associated acute kidney injury (CSA-AKI) is a common complication and is associated with the poorest outcomes. Therefore, early prediction of CSA-AKI remains a major issue. Severity scores such as the STS score could estimate the risk of AKI preoperatively. The main objective of this study was to evaluate the risk factors of on-pump CSA-AKI and to assess the performance of the STS score in order to predict CSA-AKI.

Patients: We identified 252 patients with on-pump cardiac surgery, and the STS score was defined retrospectively.

Results: AKI occurred in 14.6% (n = 37/252) of patients and renal replacement therapy was required in 21.6% of AKI (n = 8/37). CSA-AKI was associated with 35.1% in-hospital mortality (vs. 1.4%) and nearly doubled length of stay (14.5 vs. 8.0 d). The risk of CSA-AKI was mainly determined by preoperative morbidities such as chronic kidney disease, peripheral vascular disease, and severe congestive heart failure. Long cardio-pulmonary bypass time was also a determinant. CSA-AKI + patients exhibited higher STS renal risk (5.6% vs. 2.0%; p < 0.0001), resulting in a good discrimination between AKI + and AKI - patients (area under curve [AUC] 0.80). Interestingly, a basal renal function ≤55 ml/min/1.73m was as good as the STS score to predict CSA-AKI (AUC 0.75; P 0.26).

Conclusions: On-pump CSA-AKI was observed in nearly 15% of cases and was associated with poorer outcomes. Interestingly, the risk of CSA-AKI could be estimated preoperatively, thanks to the basal renal function, which exhibited an equal performance to the STS score.
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http://dx.doi.org/10.1080/00015458.2016.1156929DOI Listing
August 2016

Acute Kidney Injury in Elderly Patients With Chronic Kidney Disease: Do Angiotensin-Converting Enzyme Inhibitors Carry a Risk?

J Clin Hypertens (Greenwich) 2016 06 14;18(6):514-21. Epub 2016 Apr 14.

Department of Nephrology, Dialysis and Renal Transplantation, Hôpital Erasme, Université Libre de Bruxelles, Brussels, Belgium.

In contrast to angiotensin receptor blockers (ARBs), mainly excreted by the liver, the dosage of angiotensin-converting enzyme (ACE) inhibitors, cleared by the kidney, must be adapted to account for renal clearance in patients with chronic kidney disease (CKD) to avoid acute kidney injury (AKI). Community-acquired AKI and the use of ACE inhibitors or ARBs in the emergency department were retrospectively assessed in 324 patients with baseline stage 3 or higher CKD. After stepwise regression analysis, the use of ACE inhibitors (odds ratio [OR], 1.9; 95% confidence interval [CI], 1.1-3.1; P=.02) and the presence of dehydration (OR, 30.8; 95% CI, 3.9-239.1) were associated with AKI. A total of 45% of patients using ACE inhibitors experienced overdosing, which causes most of the excess risk of AKI. These results suggest that dosage adjustment of ACE inhibitors to renal function or substitution of ACE inhibitors with ARBs could reduce the incidence of AKI. Moreover, ACE inhibitors and ARBs should be stopped in cases of dehydration.
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http://dx.doi.org/10.1111/jch.12795DOI Listing
June 2016

Are all immigrant mothers really at risk of low birth weight and perinatal mortality? The crucial role of socio-economic status.

BMC Pregnancy Childbirth 2016 Apr 8;16:75. Epub 2016 Apr 8.

Research centre in Health Policies and Health Systems, Ecole de Santé Publique, Université Libre de Bruxelles (ULB), Bruxelles, 1070, Belgium.

Background: Increasing studies show that immigrants have different perinatal health outcomes compared to native women. Nevertheless, we lack a systematic examination of the combined effects of immigrant status and socioeconomic factors on perinatal outcomes. Our objectives were to analyse national Belgian data to determine 1) whether socioeconomic status (SES) modifies the association between maternal nationality and perinatal outcomes (low birth weight and perinatal mortality); 2) the effect of adopting the Belgian nationality on the association between maternal foreign nationality and perinatal outcomes.

Methods: This study is a population-based study using the data from linked birth and death certificates from the Belgian civil registration system. Data are related to all singleton births to mothers living in Belgium between 1998 and 2010. Perinatal mortality and low birth weight (LBW) were estimated by SES (maternal education and parental employment status) and by maternal nationality (at her own birth and at her child's birth). We used logistic regression to estimate the odds ratios for the associations between nationality and perinatal outcomes after adjusting for and stratifying by SES.

Results: The present study includes, for the first time, all births in Belgium; that is 1,363,621 singleton births between 1998 and 2010. Compared to Belgians, we observed an increased risk of perinatal mortality in all migrant groups (p < 0.0001), despite lower rates of LBW in some nationalities. Immigrant mothers with the Belgian nationality had similar rates of perinatal mortality to women of Belgian origin and maintained their protection against LBW (p < 0.0001). After adjustment, the excess risk of perinatal mortality among immigrant groups was mostly explained by maternal education; whereas for sub-Saharan African mothers, mortality was mainly affected by parental employment status. After stratification by SES, we have uncovered a significant protective effect of immigration against LBW and perinatal mortality for women with low SES but not for high SES.

Conclusions: Our results show a protective effect of migration in relation to perinatal mortality and LBW among women of low SES. Hence, the study underlines the importance of taking into account socioeconomic status in order to understand more fully the relationship between migration and perinatal outcomes. Further studies are needed to analyse more finely the impact of socio-economic characteristics on perinatal outcomes.
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http://dx.doi.org/10.1186/s12884-016-0860-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4826554PMC
April 2016

The linear relationship between systolic pulmonary artery pressure and mean pulmonary artery pressure is maintained regardless of autonomic or rhythm disturbances.

Respir Res 2016 Mar 31;17:33. Epub 2016 Mar 31.

Department of Cardiac Surgery, Université Libre de Bruxelles, Hôpital Académique Erasme, 808 Route de Lennick, B-1070, Brussels, Belgium.

Background: In the pulmonary circulation, there is a linear relationship between systolic pulmonary arterial pressure (SPAP) and mean pulmonary arterial pressure (MPAP). The aim of this study was to determine the passive or active nature of this mechanism by exploring the relationship in patients with and without autonomic rhythm control of the heart and pulmonary circulation.

Methods: Pulmonary arterial pressure recordings from non-transplanted patients and patients with heart transplants or double lung transplants were retrospectively reviewed. The relationships between systolic, diastolic, and mean pulmonary arterial pressures were explored.

Results: A linear relationship was observed between the SPAP and MPAP, whether patients were paced (MPAP = 0.56 SPAP + 3.86 mmHg, r (2)  = 0.889), treated with inotropes (MPAP = 0.55 SPAP + 5.52 mmHg, r (2)  = 0.947) or pulmonary vasodilators (MPAP = 0.58 SPAP + 2.41 mmHg, r (2)  = 0.927), were exercising (MPAP = 0.61 SPAP + 1.18 mmHg, r (2)  = 0.967), had a heart transplant (MPAP = 0.66 SPAP +0.87 mmHg, r (2)  = 0.849), a double lung transplant (MPAP = 0.7 SPAP +0.48 mmHg, r (2)  = 0.915), or no intervention (MPAP = 0.59 SPAP +1.75 mmHg, r (2)  = 0.937).

Conclusion: We demonstrate that the linear relationship between SPAP and MPAP remains in several situations. Therefore, we conclude that the underlying mechanism is a passive consequence of the elastic properties of the cardiopulmonary unit.
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http://dx.doi.org/10.1186/s12931-016-0350-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4815171PMC
March 2016

The DESCARTES-Nantes survey of kidney transplant recipients displaying clinical operational tolerance identifies 35 new tolerant patients and 34 almost tolerant patients.

Nephrol Dial Transplant 2016 06 12;31(6):1002-13. Epub 2016 Jan 12.

Department of Translational Medicine, Amedeo Avogadro University, AOU Maggiore della Carità di Novara, Novara, Italy.

Background: Kidney recipients maintaining a prolonged allograft survival in the absence of immunosuppressive drugs and without evidence of rejection are supposed to be exceptional. The ERA-EDTA-DESCARTES working group together with Nantes University launched a European-wide survey to identify new patients, describe them and estimate their frequency for the first time.

Methods: Seventeen coordinators distributed a questionnaire in 256 transplant centres and 28 countries in order to report as many 'operationally tolerant' patients (TOL; defined as having a serum creatinine <1.7 mg/dL and proteinuria <1 g/day or g/g creatinine despite at least 1 year without any immunosuppressive drug) and 'almost tolerant' patients (minimally immunosuppressed patients (MIS) receiving low-dose steroids) as possible. We reported their number and the total number of kidney transplants performed at each centre to calculate their frequency.

Results: One hundred and forty-seven questionnaires were returned and we identified 66 TOL (61 with complete data) and 34 MIS patients. Of the 61 TOL patients, 26 were previously described by the Nantes group and 35 new patients are presented here. Most of them were noncompliant patients. At data collection, 31/35 patients were alive and 22/31 still operationally tolerant. For the remaining 9/31, 2 were restarted on immunosuppressive drugs and 7 had rising creatinine of whom 3 resumed dialysis. Considering all patients, 10-year death-censored graft survival post-immunosuppression weaning reached 85% in TOL patients and 100% in MIS patients. With 218 913 kidney recipients surveyed, cumulative incidences of operational tolerance and almost tolerance were estimated at 3 and 1.5 per 10 000 kidney recipients, respectively.

Conclusions: In kidney transplantation, operational tolerance and almost tolerance are infrequent findings associated with excellent long-term death-censored graft survival.
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http://dx.doi.org/10.1093/ndt/gfv437DOI Listing
June 2016

Delayed Graft Function in Kidney Transplants: Time Evolution, Role of Acute Rejection, Risk Factors, and Impact on Patient and Graft Outcome.

J Transplant 2015 10;2015:163757. Epub 2015 Sep 10.

Department of Nephrology, Dialysis and Transplantation and Department of Abdominal Surgery, CUB, Erasmus Hospital, Route de Lennik 808, 1070 Brussels, Belgium.

Background. Although numerous risk factors for delayed graft function (DGF) have been identified, the role of ischemia-reperfusion injury and acute rejection episodes (ARE) occurring during the DGF period is ill-defined and DGF impact on patient and graft outcome remains controversial. Methods. From 1983 to 2014, 1784 kidney-only transplantations from deceased donors were studied. Classical risk factors for DGF along with two novel ones, recipient's perioperative saline loading and residual diuresis, were analyzed by logistic regression and receiver operating characteristic (ROC) curves. Results. Along with other risk factors, absence of perioperative saline loading increases acute rejection incidence (OR = 1.9 [1.2-2.9]). Moreover, we observed two novel risk factors for DGF: patient's residual diuresis ≤500 mL/d (OR = 2.3 [1.6-3.5]) and absence of perioperative saline loading (OR = 3.3 [2.0-5.4]). Area under the curve of the ROC curve (0.77 [0.74-0.81]) shows an excellent discriminant power of our model, irrespective of rejection. DGF does not influence patient survival (P = 0.54). However, graft survival is decreased only when rejection was associated with DGF (P < 0.001).  Conclusions. Perioperative saline loading efficiently prevents ischemia-reperfusion injury, which is the predominant factor inducing DGF. DGF per se has no influence on patient and graft outcome. Its incidence is currently close to 5% in our centre.
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http://dx.doi.org/10.1155/2015/163757DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4581567PMC
October 2015

UMOD polymorphism rs12917707 is not associated with severe or stable IgA nephropathy in a large Caucasian cohort.

BMC Nephrol 2014 Aug 28;15:138. Epub 2014 Aug 28.

Nephrology-Renal Transplantation Department, CHU de Saint Etienne & EA3064, GIMAP, Université Jean Monnet, Saint Etienne 42055 Cedex 02, France.

Background: Genetic factors are suspected in the pathogenesis of IgA nephropathy, as well as in the course of IgA nephropathy progression towards end stage renal failure. UMOD polymorphism rs12917707 is known to associate with end stage renal failure of mixed aetiologies.

Methods: We tested a large cohort of Caucasian patients for association of rs12917707 with IgA nephropathy showing a benign, stable course and with IgA nephropathy that progressed toward end stage renal failure.

Results: No association was observed between either groups, and a non-significant trend was observed for more severe IgA nephropathy with the allele reported to protect against end stage renal failure of mixed aetiologies.

Conclusion: We conclude that UMOD is unlikely to play a role in IgA nephropathy pathogenesis nor progression to end stage renal failure, and suggest that UMOD effects are restricted to some causes of renal disease, e.g. diabetes or hypertension.
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http://dx.doi.org/10.1186/1471-2369-15-138DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4236674PMC
August 2014

Biochemical parameters after cholecalciferol repletion in hemodialysis: results From the VitaDial randomized trial.

Am J Kidney Dis 2014 Nov 22;64(5):696-705. Epub 2014 May 22.

Nephrology Department, Erasme Hospital, Université Libre de Bruxelles, Brussels, Belgium.

Background: The 2009 KDIGO (Kidney Disease: Improving Global Outcomes) chronic kidney disease-mineral and bone disorder clinical practice guideline suggests correcting 25-hydroxyvitamin D3 (25[OH]D) levels<30ng/mL in patients treated with maintenance hemodialysis, but does not provide a specific treatment protocol.

Study Design: 2-center, double-blind, randomized, 13-week, controlled trial followed by a 26-week open-label study.

Setting & Participants: 55 adult maintenance hemodialysis patients with 25(OH)D levels<30ng/mL were recruited from June 2008 through October 2009.

Intervention: Cholecalciferol, 25,000IU, per week orally versus placebo for 13 weeks, then 26 weeks of individualized cholecalciferol prescription based on NKF-KDOQI (National Kidney Foundation-Kidney Disease Outcomes Quality Initiative) guidelines.

Outcomes: Primary end point was the percentage of patients with 25(OH)D levels≥30ng/mL at 13 weeks. Secondary outcomes included the percentage of patients with normal calcium, phosphorus, and intact parathyroid hormone (iPTH) blood levels. Safety measures included incidence of hypercalcemia and hypervitaminosis D.

Measurements: Blood calcium and phosphate were measured weekly; iPTH, 25(OH)D, 1,25-dihydroxyvitamin D3 (1,25[OH]2D), and bone turnover markers, trimonthly; fetuin A and fibroblast growth factor 23 (FGF-23) serum levels and aortic calcification scores were determined at weeks 0 and 39.

Results: The primary end point significantly increased in the treatment group compared with the placebo group (61.5% vs 7.4%; P<0.001), as well as 1,25(OH)2D levels (22.5 [IQR, 15-26] vs 11 [IQR, 10-15]pg/mL; P<0.001) and the proportion of patients achieving the target calcium level (76.9% vs 48.2%; P=0.03). Incidence of hypercalcemia and phosphate and iPTH levels were similar between groups. The second 26-week study phase did not significantly modify the prevalence of 25(OH)D level≥30ng/mL in patients issued from the placebo group.

Limitations: Small size of the study population.

Conclusions: Oral weekly administration of 25,000IU of cholecalciferol for 13 weeks is an effective, safe, inexpensive, and manageable way to increase 25(OH)D and 1,25(OH)2D levels in hemodialysis patients. Further evaluation of clinical end points is suggested.
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http://dx.doi.org/10.1053/j.ajkd.2014.04.020DOI Listing
November 2014

Ticlopidine and clopidogrel, sometimes combined with aspirin, only minimally increase the surgical risk in renal transplantation: a case-control study.

Nephrol Dial Transplant 2014 Feb 24;29(2):463-6. Epub 2013 Nov 24.

Department of Nephrology and Dialysis, CHU Charleroi, Charleroi, Belgium.

Background: Patients undergoing kidney transplantation are sometimes being treated with antiplatelet agents such as ticlopidine or clopidogrel. Some teams refuse to wait-list these patients for fear of bleeding during transplant surgery.

Methods: We retrospectively reviewed the records of 702 adult patients with a kidney transplant alone between 2000 and 2010. Nineteen (2.7%) patients were taking clopidogrel or ticlopidine when called in for transplantation. Furthermore, 10 of these 19 patients were also taking low-dose aspirin (ASA). We compared the risk of bleeding peri- and postoperatively, and the occurrence of cardiovascular complications within 30 days after renal transplantation between 19 cases and 39 controls randomly selected within the cohort.

Results: Platelets were administered to 7 cases (37%) versus 0 controls (P<0.001). A single case (5.3%) presented with significant bleeding during surgery following an implantation biopsy, and required 4 red bood cell (RBC) units. During the first day, 3 of the 19 cases (16%) and 1 of the 39 controls required RBC (P=0.1). No reoperation was performed for bleeding. After the transplant, clopidogrel or ticlopidine was resumed in only two patients. The platelet count and haemoglobin were similar between cases and controls at Day 30. No cardiovascular event occurred in cases or controls during the first month post-transplantation. At 5 years, graft and patient survival was similar in cases and controls.

Conclusions: Clopidogrel and ticlopidine, sometimes in combination with ASA, are associated with a low risk of bleeding during renal transplantation and does not seem to be a contraindication for renal transplant surgery.
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http://dx.doi.org/10.1093/ndt/gft385DOI Listing
February 2014

Effect of adopting host-country nationality on perinatal mortality rates and causes among immigrants in Brussels.

Eur J Obstet Gynecol Reprod Biol 2013 Jun 26;168(2):145-50. Epub 2013 Jan 26.

CR Epidemiology, Biostatistic and Clinical Research, School of Public Health, Free University of Brussels, Brussels, Belgium.

Objectives: Perinatal mortality rates vary between ethnic groups but the relation with immigrant status is unclear. Previous research suggested that birth outcomes may either improve or deteriorate with duration of residence, depending on the migrant group. The objectives of this study are to describe and measure inequalities in pregnancy outcomes, perinatal mortality and causes of perinatal deaths according to current citizenship versus national origin of the mother, in Brussels.

Study Design: This is a population-based cohort study using data from linked birth and death certificates from the Belgian civil registration system. The data relate to all babies born between 1998 and 2008, whose mothers were living in Brussels, irrespective of the place of delivery. We used a logistic regression to estimate the odds ratios (ORs) for the association between mortality, causes of deaths and nationality.

Results: Women from Morocco, sub-Saharan Africa and Turkey experience an 80% excess in perinatal mortality (p<0.0001) compared to Belgians, but this excess of perinatal mortality is not observed for mothers with Belgian citizenship at delivery. For sub-Saharan African women, this excess is caused mainly by immaturity-related conditions and reflects a high rate of preterm deliveries, low birth weight and a low socio-economic level. Moroccan and Turkish mothers have favourable pregnancy outcomes that persist after adopting Belgian nationality, but they experience a strong excess of perinatal mortality, mainly due to congenital anomalies and asphyxia or unexplained deaths prior to the onset of labour.

Conclusion: In Brussels, perinatal mortality varies according to nationality but those differences do not persist after adopting Belgian nationality. The explanation of this positive effect is probably due to a mix of determinants such as acculturation, use of health services or cultural contexts. Further analysis should help to better understand the results observed.
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http://dx.doi.org/10.1016/j.ejogrb.2012.12.039DOI Listing
June 2013

Prevention of tunneled cuffed hemodialysis catheter-related dysfunction and bacteremia by a neutral-valve closed-system connector: a single-center randomized controlled trial.

Am J Kidney Dis 2013 Mar 8;61(3):459-65. Epub 2012 Dec 8.

Department of Nephrology, Erasme Hospital, Université Libre de Bruxelles, Brussels, Belgium.

Background: Hemodialysis (HD) tunneled cuffed catheters may be fitted with neutral-valve closed-system connectors. Such connectors, which are flushed with saline solution and used for 3 consecutive HD sessions, provide a mechanically closed positive-pressure barrier and potentially may be useful to prevent catheter-related bacteremia and dysfunction.

Study Design: Single-center randomized controlled trial.

Setting & Participants: 66 adult HD patients with a tunneled cuffed catheter.

Intervention: Neutral-valve closed-system connector (Tego Needlefree Hemodialysis Connector) versus trisodium citrate, 46.7%, locking solution (Citra-Lock; control group).

Outcomes: Primary composite outcome was the incidence rate of catheter-related dysfunction or bacteremia. Secondary outcomes were the separate incidence rates of catheter-related dysfunction and bacteremia and the cost of both procedures.

Measurements: Catheter dysfunction was defined as the requirement of urokinase and/or a mean blood flow ≤250 mL/min during 2 consecutive HD sessions. Catheter-related bacteremia was defined as ≥2 positive blood cultures. Time of catheter use was calculated and the incidence rate of complications was expressed per 100 person-years.

Results: 66 patients were followed up for a median of 86 (IQR, 29-200) days. The composite primary outcome was not significantly reduced in the closed-system-connector intervention group versus the citrate-locking-solution control group (63.56 vs 71.51 per 100 person-years; P = 0.3). Catheter dysfunction in the intervention group was not decreased versus controls (59.59 vs 51.64 per 100-person-years; P = 0.9). Only 6 catheter-related bacteremia events were identified, one in the intervention group (3.97 vs 19.86 per 100 person-years; P = 0.06).

Limitations: Small size of the patient population and single-center study.

Conclusions: Superiority of the closed-system connector in terms of prevention of the primary efficacy end point compared to the standard locking solution was not observed. Further evaluation in a larger study is suggested.
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http://dx.doi.org/10.1053/j.ajkd.2012.10.014DOI Listing
March 2013

Shipping donor kidneys within Eurotransplant: outcomes after renal transplantation in a single-centre cohort study.

Nephrol Dial Transplant 2012 Sep 7;27(9):3638-44. Epub 2012 May 7.

Renal Transplantation Clinic, Department of Nephrology, ULB Hopital Erasme, Brussels, Belgium.

Background: Shipment of organs during the allocation process aims to improve human leucocyte antigen (HLA) matching but can also have a detrimental effect by prolonging cold ischaemia. The overall effect of organ exchange on post-transplant outcomes in the Eurotransplant (ET) region has not been investigated.

Methods: This is a retrospective single-centre cohort study to investigate the effect of shipment of renal allografts on cold ischaemia times and the incidence of acute rejection (AR) and graft survival in 661 transplantations of deceased donor kidneys.

Results: Forty-six per cent (N = 301) of the patients received a locally procured and 54% (N = 360) a shipped donor kidney. Locally procured donors tended to be older, more often hypertensive and had less frequently died from trauma. Recipients of shipped kidneys were at higher immunological risk, being younger, more frequently retransplanted and immunized against HLA antigens. Shipped kidneys had a 2.2-h prolongation of cold ischaemia time (18.0 versus 20.2 h; P < 0.0001) but significantly less HLA A, B and DR mismatches (2.20 versus 2.84; P < 0.0001). Recipients of shipped kidneys had an increased incidence of first-year AR [19 versus 13%; odds ratio 1.62 (1.06-2.49); P = 0.026] and death-censored graft loss [hazard ratio 1.6 (1.1-2.4); P = 0.01] that was no longer statistically significant after adjustments for risk factors by multivariable modelling.

Conclusions: Shipment of kidneys in the ET region is associated with a modest increase in cold ischaemia time and significantly better HLA matching. This allows for successful transplantation of higher risk patients with no significant penalty with regard to AR rates or death-censored graft survival.
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http://dx.doi.org/10.1093/ndt/gfs142DOI Listing
September 2012