Belgian Cohort Research Articles

Rabies post-exposure prophylaxis: a retrospective analysis of timing of initiation and antibody responses in a Belgian cohort.

BackgroundWe aimed to determine the timeliness of rabies post-exposure prophylaxis (PEP) and the proportion of individuals with an adequate antibody response post-PEP among those attending the Belgian national reference center. MethodsRetrospective analysis of patient records who attended our center from 2018-2023. Delay was defined as rabies immunoglobulin (RIG) and vaccine initiation beyond 2 calendar days after exposure. Antibodies were measured by rapid fluorescent focus inhibition test (RFFIT) after PEP in high-risk exposures. A titer ≥0.5 IU/ml was considered adequate. ResultsWe reviewed 317 patient records. Among individuals with inland exposure (n=103), 85% timely received PEP. Among travelers exposed abroad (n=214), administration of RIG and vaccine initiation were timely in 30% and 50% of cases, respectively. An adequate antibody response was detected in 99.5% (195/196) individuals. ConclusionSubstantial PEP delays among travelers were observed. The robust antibody responses suggest that routine serological follow-up is not necessary for all patients.

Interpersonal Stressors Predicting Inflammation in Adolescents: Moderation by Emotion Regulation and Heart Rate Variability?

This study assessed interpersonal stressors (peer adversity and parental rejection) as predictors of adolescents’ circulating inflammatory markers, while examining emotion regulation and parasympathetic nervous system activity (at rest, reactivity, and recovery) as potential protective moderators. Data were collected in a Belgian cohort of adolescents in 2017 (n=185, 51.4% boys, 10-18y) and 2018 (n=98), and included serum inflammatory markers (CRP, TNFα, IFNγ, IL-6, IL-8 and IL-10), peer adversity, parental rejection, emotion regulation and heart rate variability (RMSSD-HRV, at rest and in 2018 also in response to a Trier Social Stress Test). Contrary to the hypothesis, interpersonal stressors were negatively related to TNFα (in 2017 and 2018), IFNγ (in 2017 and longitudinally) and IL-6 (in 2018). In 23% of the tested associations, HRV at rest was a significant moderator: the negative stressor-inflammation associations were present only among adolescents with low HRV resting values. No significant moderation by HRV reactivity or recovery was detected. After correction for multiple testing, all above-mentioned significant findings disappeared. These unexpected findings may suggest that the positive association between stress exposure and circulating markers of inflammation is not yet detectable in adolescence and perhaps becomes evident only later in life.

6.M. Scientific session: Risk And Resilience Factors Of Mental Health During COVID: European Multi-country Data Findings

Abstract The COVID-19 pandemic significantly affected mental health. It worsened the mental health and well-being of those already vulnerable or exposed to excess pandemic-related stress. In addition, lockdowns and other measures created additional obstacles to mental health support access. In response, the European Commission funded the RESPOND project in 2020, aimed at enhancing the preparedness of mental health systems for pandemics and global crises. As part of the RESPOND project, (meta-)analyses were conducted on prospective cohort datasets, national health register data, and multi-country individual participant data (IPD). The aim was to examine whether there was a change in prevalence rates of mental health conditions (e.g., anxiety and depression) in the general adult population of the EU during, compared to before and in between, the COVID-19 pandemic waves. Analyses on risk factors (e.g. sociodemographic- and economic factors, severity of COVID-19 infection, (lack of) social activity and support, and loneliness) associated with psychological distress and mental disorders as well as resilience and well-being (coping strategies and core value orientations) in the general population or specific vulnerable groups were conducted as well. This workshop will feature five talks covering various aspects of the RESPOND epidemiological analyses. First, an introduction and rationale of the RESPOND study on short- and long-term impacts of the COVID-19 pandemic and outbreak response, will be provided. Subsequently, findings from the multi-country longitudinal COvid MEntal healTh Survey (COMET) on forecasting psychological distress throughout the pandemic will be presented. Second, findings from the French TEMPO (Trajectoires EpideMiologiques en POpulation) cohort and merged datasets will be presented indicating associations and interactions between socioeconomic factors, mental health, and public health behaviours during the pandemic. Third, using data of a large Belgian prospective cohort, fluctuations in risk of psychological distress across study waves and the factors associated with individual trajectories of psychological distress during the COVID-19 pandemic will be presented. Fourth, the risk of SARS-CoV-2 infection, severe COVID-19 outcomes, and death among individuals with various mental disorders, based on Spanish health records, will be presented with specific attention to sex differences. Finally, based on the IPD meta-analyses of 9 European cohorts, findings on stressor reactivity, resilience trajectories, and factors associated with resilient outcomes and vulnerability are presented. By presenting a selection of findings from large datasets together, we aim to facilitate discussions on critical topics such as vulnerability and resilience to mitigate mental health impacts in future public health crises. Key messages • Targeting specific individual vulnerabilities appears to be more effective in reducing the pandemics’ mental health impact than solely responding to pandemic-related fluctuations. • Research and harmonised data on vulnerability and resilience factors are essential for guiding the development of targeted interventions and support systems for vulnerable populations during crises.

105P Frequency and clinical characterization of SORD-related neuropathy in a Belgian cohort

105P Frequency and clinical characterization of SORD-related neuropathy in a Belgian cohort

Staging of immuno-virological dynamics during acute HIV infection in a Belgian prospective cohort study

BackgroundThe events during acute HIV infection (AHI) set the stage for the subsequent course of the disease. Early initiation of antiretroviral therapy (ART) has been associated with favorable immunovirological outcomes, yet the precise impact of ART timing during AHI remains unclear, particularly on lymphoid tissues. Materials and methodsThe ACS cohort is a prospective cohort study in Belgium, collecting longitudinal clinical data and human bodily material (HBM) from people diagnosed and treated during AHI. The aim of the cohort is to study the impact of ART initiation during AHI on HIV reservoir and immune dysfunction in peripheral blood and anatomical sanctuary sites, as well as its effect on the gut microbiome. The cohort consists of two HBM sampling trajectories: one limited (blood, stool and leukapheresis) and a more extensive one (blood, stool, leukapheresis, colonoscopy, inguinal lymph node excision and lumbar puncture). Here we describe the baseline characteristics, immunovirological outcomes, safety and tolerability of HBM sampling. ResultsBetween March 2016 and April 2024, 47 participants were enrolled, predominantly men who have sex with men (MSM), with a median age of 36 years [IQR 30–43.5]. Almost 90 % of participants initiated ART within 72 h after study inclusion, irrespective of HBM sampling trajectory. The timing of ART initiation according to the Fiebig stage did not significantly impact immune recovery (CD4/CD8 ratio ≥1) or the time to viral suppression. Approximately 40 % of participants opted for the extensive HBM sampling trajectory during AHI. However, the participation rate for the extensive trajectory decreased by nearly half at the longitudinal follow-up timepoint. In general, study-related procedures were safe and well-tolerated, with limited procedure-related adverse events (AEs). Inguinal lymph node excision was associated with the highest AE rate, in line with previous reports. ConclusionsOur findings reaffirm the beneficial effect of ART initiation during AHI on long term immunovirological outcomes, regardless of Fiebig stage at treatment initiation. Additionally, we demonstrate that the collection of HBM during and longitudinally after AHI is safe and feasible, without compromising time to ART initiation. Cohorts that integrate comprehensive clinical data with high-quality HBM samples are essential to longitudinally study the impact of early ART on reservoir dynamics and immune responses across various anatomical sites after AHI.

Imatinib Adherence and Persistence in Patients with Chronic Myeloid Leukemia in Belgium: Evidence from Real-World Data.

Imatinib adherence and persistence are key components of the successful treatment of Chronic Myeloid Leukemia (CML). In Belgium, there is no study assessing these behaviors at a national level. Our study aimed to provide the first nationwide measure and to identify associated pharmacy-based predictors (age, gender, comorbidities). We also assessed mortality and transplantation incidence according to adherence status. Based on medico-administrative database linkage, we identified a retrospective Belgian cohort of 1194 patients diagnosed with CML between 2004 and 2016 and treated with imatinib. Adherence was measured over 24 months, considering the proportion of days covered (PDC). Persistence was measured as the time until discontinuation (gap of ≥90 days). Multivariable Poisson regression models with robust standard error were conducted to identify predictors associated with adherence (≥90% PDC). To identify factors associated with persistence, a multivariable Cox regression was performed. At six months, 60.3% of patients were adherent, declining to 41.5% at 12 months, and to 30.1% at two-year follow-up (n=998). Adherence was greater at a younger age (eg 31-40 years vs ≥75 years, adjusted prevalence ratio (aPR) 1.73; 95% confidence interval (CI): 1.09-2.77) and among patients with no comorbidity (0 vs ≥2 comorbidities (aPR 1.56; 95% CI: 1.11-2.19). The median persistence was 334.5 days (Q1:200-Q3:505.5); persistence at 24 months was 83.6% (n=998). Only age was associated with higher risk of discontinuation, with adjusted hazard ratio (aHR) of 6.05 for patients ≥75 years (95% CI: 5.52-6.58). Transplants and deaths mainly occurred in patients defined as non-adherent at 24 months. This Belgian nationwide representative study revealed a critical low level of imatinib adherence, which decreased over time even though persistence was high at six months. We pinpointed pharmacy-based predictors that were easily identifiable by health care stakeholders in order to undertake interventions to improve adherence.

Hypoglossal Nerve Stimulation Therapy in a Belgian Cohort of Obstructive Sleep Apnea Patients.

Hypoglossal nerve stimulation (HGNS) has emerged as a widespread and innovative treatment option for selected moderate-to-severe obstructive sleep apnea (OSA) patients who cannot be treated effectively with traditional treatment modalities. In this observational cohort study, the objective and subjective outcomes of Belgian OSA patients treated with HGNS therapy were analyzed at 6 and 12 months post-implantation. Thirty-nine patients implanted with a respiration-synchronized HGNS device at the Antwerp University Hospital w ere included in this study. Patients underwent baseline in-laboratory polysomnography and a follow-up sleep study 6 and 12 months post-implantation. Questionnaires on patient experience and daytime sleepiness were filled out and data on objective therapy usage were collected. All 39 patients completed the 6-month follow-up and 21 patients (54%) completed the 12-month follow-up. Median AHI decreased from 33.8 [26.1;45.0] to 10.2 [4.8;16.4] at the 6-month follow-up, and to 9.6 [4.1;16.4] at the 12-month follow-up (p < 0.001). The surgical success rate, according to the Sher20 criteria, was 80% and 76% at the 6- and 12-month follow-ups, respectively. Median ESS improved from 12.0 [7.0;18.0] at baseline to 6.0 [2.5;11.0] at 6 months (p < 0.001) and to 6.5 [2.8;11.5] at 12 months (p = 0.012). Objective therapy usage was 7.4 [6.6;8.0] and 7.0 [5.9:8.2] h/night at the 6- and 12-month follow-ups, respectively. A high overall clinical effectiveness of HGNS therapy, as shown by a mean disease alleviation of 58%, was demonstrated at 12 months post-implantation. Overall, HGNS therapy using respiration-synchronized neurostimulation of the XII cranial nerve resulted in a significant improvement in both objective and subjective OSA outcomes, with a high level of patient satisfaction and high treatment adherence.

Anxiety and depression in people with post-COVID condition: a Belgian population-based cohort study three months after SARS-CoV-2 infection.

Since the onset of the COVID-19 pandemic, most research has focused on the management of the acute symptoms of the disease. Yet some people tend to experience symptoms beyond the acute phase, defined as Post-COVID-19 Condition (PCC). This study aims to assess the impact of COVID-19 and PCC on anxiety and depression. This is a prospective longitudinal cohort study among the Belgian adult population with recent SARS-CoV-2 infection for which contact tracing was initiated. A total of 3127 people were followed-up just after their infection and three months later (from April 2021 to January 2022). Anxiety and depression were assessed at the two stages using the GAD-7 (Generalized Anxiety Disorder) and the PHQ-9 (Patient Health Questionnaire). Three months after infection, participants with PCC (50%) had an increased probability of having both anxiety and depressive symptoms (p < 0.001). The proportion with anxiety and depressive symptoms at three months were significantly higher in people with PCC (11% and 19%) compared to people without persistent COVID symptoms (3.8% and 4.2%) and to a matched sub-sample not infected with SARS-CoV-2 (6.5% and 4.3%). Having at least one acute COVID-19 symptom (p < 0.001), experiencing financial loss following the infection (p < 0.001), and different PCC symptoms were associated with anxiety and depressive symptoms worsening over time. This study showed that three months after a SARS-CoV-2 infection, one in two people suffer from PCC with significant consequences for their mental health. Follow-up on mental health must therefore have an important place in people suffering from PCC.

Challenges in Chlamydial Serology: Insights from a Belgian and a Dutch Population Cohort.

Serology routinely serves as a diagnostic tool to confirm Chlamydia infections in humans. Particularly in delayed settings, such as post-outbreak scenarios where the acute phase of infection has subsided, serology is invaluable. Multiple studies, nonetheless, indicate deficiencies in specificity and sensitivity of current chlamydial antibody detection assays. Incorporation of multiple antigens per target is known to improve the accuracy of chlamydial serological assays. We, therefore, used the recomLine test (Mikrogen diagnostics) on serological samples of two cohorts, as it is the only commercially available test allowing detection of antibodies against three human pathogenic Chlamydia species (C. trachomatis, C. pneumoniae and C. psittaci) using multiple antigens per target. The first cohort (n = 156; samples collected between 2008 and 2022 during a C. trachomatis screening initiative) comprised women from the Netherlands (NL) with past exposure to C. trachomatis, while the second cohort (n = 44; samples collected in 2018 in a health examination survey) consisted of Belgian citizens (BE) with occupational or recreational exposure to chickens, representing a risk population for C. psittaci. The test indicated a statistically equivalent C. pneumoniae seroprevalence in both cohorts (39.10% in NL and 34.09% in BE; p = 0.337). As expected C. trachomatis seroprevalence was significantly higher (p < 0.001) in the Dutch cohort (48.72%), as compared to the Belgian cohort (4.55%). Lastly, C. psittaci seroprevalence did not significantly differ between the two groups (2.27% in BE and 1.92% in NL; p = 0.633), even though a higher prevalence was expected for the Belgian cohort. This prompts us to question whether the Belgian cohort truly constituted a C. psittaci risk population or whether the recomLine test is susceptible to cross-reaction of species-specific antibodies, thereby increasing C. psittaci prevalence in the Dutch cohort. We advocate for the development of affordable, highly sensitive antibody detection assays that can effectively distinguish between chlamydial species, addressing the increasing demand for enhanced serological testing methodologies.

Near Adult Height and Body Mass Index Changes in Growth Hormone Treated Short Children with Noonan Syndrome: The Belgian Experience

Introduction: A variable near adult height (NAH) outcome after growth hormone (GH) therapy in Noonan syndrome (NS) patients with short stature has been reported. The main objective of this study was to evaluate NAH and body mass index (BMI) evolution in a large Belgian cohort of NS patients treated for short stature. The secondary objectives were to investigate whether sex, genotype, the presence of a thoracic deformity, and/or a heart anomaly might affect NAH and to validate the recently developed NAH prediction model by Ranke et al. Methods: Clinical and auxological data of GH treated short NS patients born before 2001 were extracted from the national Belgrow registry. NAH was available in 54 (35 male) genotyped NS using a gene panel of 9 genes, showing pathogenic variants in PTPN11 in 32 and in SOS1 in 5 patients, while in 17 patients gene panel analysis was inconclusive (no-mutation group). Results: After a median (P10; P90) duration of 5.4 (2.2; 10.3) years of GH therapy with a median dose of 0.05 mg/kg/day NS patients reached a median NAH of −1.7 (−3.1; −0.8) SDS. Median total height gain was 1.1 (0.1; 2.3) SDS. Sex, genotype, and the presence of a thoracic or cardiac malformation did not correlate with NAH or total height gain. Linear regression modelling revealed that height SDS at start (β = 0.90, p β = 0.27; p = 0.005), birth weight SDS (β = 0.15; p = 0.051), age at start (β = 0.07; p = 0.032) were independently associated with NAH SDS. Median BMI SDS increased significantly (p Conclusion: Long-term GH therapy at a dose of 0.05 mg/kg/day in short NS patients is effective in improving adult height and BMI, irrespective of the genotype and presence or absence of cardiac and or thoracic anomalies.

Use of the "Sepsis Risk Calculator" in Belgian Newborns: A Retrospective Cohort Study.

Prevention of early-onset neonatal sepsis (EONS) is a frequent reason why many newborns receive unnecessary antibiotics. The Sepsis Risk Calculator (SRC) was developed by the Kaiser Permanente Institute as a multivariate risk assessment of EONS, aiming to reduce laboratory testing and empiric neonatal antibiotic therapy. Our objective was to assess the potential of the SRC in reducing antibiotic use in our setting. Late preterm and term newborns who received antibiotics from 2019 to 2020 in a tertiary Belgian hospital were included. Newborn-specific data were collected and entered into the online SRC, retrospectively calculating a sepsis risk score and providing recommendations for antibiotic administration. False-positive indications for treatment by the SRC were estimated based on previously published data. Antibiotic therapy rates according to the SRC recommendations were compared to the actual rate of antibiotic therapy. Of 5891 births, 414 newborns received antibiotics and were eligible for this study, representing a rate of 7.6% of newborns receiving antibiotics following our current guidelines. The SRC would have recommended antibiotic administration for 2.7%, reducing antibiotic therapy by 64.5%. Of 5 possible cases of EONS, 3 would have received antibiotics in the first 24 hours according to the SRC. In this Belgian cohort, use of the SRC has the potential to significantly decrease by 64.5% the newborns that receive antibiotics. This reduction would primarily concern asymptomatic newborns. If use of the SRC was to be implemented in Belgian maternities, strict clinical surveillance practices should be ensured.

Prevalence of metabolic dysfunction-associated fatty liver disease after pancreatic surgery in a historical Belgian cohort and review of the literature.

Metabolic dysfunction-associated fatty liver disease (MAFLD) has been reported as a complication after pancreatic surgery. The aim of this study is to assess this phenomenon in a Belgian population, specifically in a period in time when less perioperative chemotherapy was given. We performed a retrospective monocentric cohort study with 124 selected patients who underwent pancreatic surgery - pancreaticoduodenectomy (PD), distal pancreatectomy (DP) or total pancreatectomy - between 2005 and 2014. Steatosis was assessed radiologically, using Hounsfield units on liver and spleen. Data on imaging, liver function, weight and other relevant parameters were gathered preoperatively as well as 2 and 6 months, 1 and 2 years after surgery. Thirty-eight (31%) out of 124 patients developed liver steatosis at least at one point in time in the two years following surgery, with a prevalence of 21.0% at 2 months, 28.6% at 6 months, 16.4% at 1 year and 20.8 % at 2 years. A statistically significant association with preoperative AST and ALT values, administration of pancreatic enzyme supplementation as a surrogate for pancreatic exocrine insufficiency (PEI) and weight loss at 2 years was detected. MAFLD is seen in 31% of patients with PD or DP pancreatic resection in this retrospective analysis of a monocentric Belgian cohort. Both early and late onset of MAFLD was observed, implying that long-term follow-up is necessary. Clinical impact as well as a direct correlation with patients' weight and oral enzyme supplements needs to be further investigated.

P581 Age-related patterns in biological therapy use and surgery among patients with IBD: Insights from the Belgian PANTHER cohort

Abstract Background Inflammatory bowel diseases (IBD) are predominantly diagnosed during the second to third life decade. However, the disease may manifest itself at any age and current understanding of differences in clinical presentation and therapy use among age groups is still limited. We aimed to analyse age-related patterns in biological and surgical treatment among patients with IBD. Methods This study utilized data from the PANTHER cohort, a prospective Belgian inception cohort including 473 adult patients with IBD from 3 Belgian referral centres. Patient inclusion took place from 2015 to 2023. Patients were categorized into groups based on the age at diagnosis: 'young adult-onset' (18-39 years), 'adult-onset' (40-59 years), and ‘elderly-onset’ (³60 years). Baseline characteristics and treatments were analysed using Chi square, Mann-Whitney U tests, log-rank tests and/or Cox regression in SPSS. Results Baseline characteristics are shown in Table 1. No significant differences were found between age groups in terms of IBD diagnosis, gender, median follow-up duration, and smoking status. Use of biologics differed significantly across age groups with highest uptake in young-adult onset patients (65.8%, P&amp;lt;0.001). Significant differences were found in selection of first biologic with vedolizumab as most frequently selected option in the elderly compared to anti-TNF in the youngest age group (P=0.002). Time to initiation of a biological was earlier in the youngest cohort (P=0.002, Figure 1). Cox regression analysis revealed that older age at diagnosis (HR 0.987, 95%CI [0.98;0.996], P=0.006), UC (HR 0.495, 95%CI [0.50;0.39], P&amp;lt;0.001) and centre of follow-up (Brussels vs Leuven: HR 0.663, 95%CI [0.4;1], P=0.048) were associated with a lower risk of biological initiation. When analysing CD separately, independent risk factors associated with biological use were perianal disease (HR 2.26, 95%CI [1.6;3.2], P&amp;lt;0.001), L3 (HR 1.85, 95%CI [1.3;2.6], P&amp;lt;0.001,) and L4 (HR 12.7, 95%CI [1.6;98.7], P=0.015,) location (compared to L1 location). In UC patients, E2 (HR 7.9, 95%CI [2.8;22.4], P&amp;lt;0.001) and E3 (HR 6.9, 95%CI [2.4;19.3], P&amp;lt;0.001) were related to earlier use of biologics. During follow-up, 19% of CD and 5.1% of UC patients required IBD-related surgery. Univariate analysis showed a higher need for surgery in younger patients (P=0.042), however, this difference was no longer significant when analysing CD (P=0.272) and UC (P=0.09) patients as separate groups. Conclusion Analysis of the PANTHER Biobank reveals significant age-related variation in the administration of biological therapies among IBD patients.

Real-world Effectiveness and Safety of Risankizumab in Patients with Moderate to Severe Multirefractory Crohn's Disease: A Belgian Multicentric Cohort Study.

As real-world data on risankizumab in patients with moderate to severe Crohn's disease (CD) are scarce, we evaluated its effectiveness and safety in multirefractory Belgian patients. Data from consecutive adult CD patients who started risankizumab before April 2023 were retrospectively collected at 6 Belgian centers. Clinical remission and response were defined using the 2-component patient-reported outcome. Endoscopic response was defined as a decrease in baseline Simple Endoscopic Score with ≥50%. Both effectiveness end points were evaluated at week 24 and/or 52, while surgery-free survival and safety were assessed throughout follow-up. A total of 69 patients (56.5% female, median age 37.2 years, 85.5% exposed to ≥4 different advanced therapies and 98.6% to ustekinumab, 14 with an ostomy) were included. At week 24, 61.8% (34 of 55) and 18.2% (10 of 55) of patients without an ostomy achieved steroid-free clinical response and remission, respectively. At week 52, these numbers were 58.2% (32 of 55) and 27.3% (15 of 55), respectively. Endoscopic data were available in 32 patients, of whom 50.0% (16 of 32) reached endoscopic response within the first 52 weeks. Results in patients with an ostomy were similar (steroid-free clinical response and remission, 42.9% and 14.3%, respectively). During a median follow-up of 68.3 weeks, 18.8% (13 of 69) of patients discontinued risankizumab, and 20.3% (14 of 69) of patients underwent CD-related intestinal resections. The estimated surgery-free survival at week 52 was 75.2%. No new safety issues were observed. In this real-world cohort of multirefractory CD patients, risankizumab was effective in inducing both clinical remission and endoscopic response. Risankizumab was well tolerated with no safety issues.

Longitudinal patterns of inflammatory mediators after acute HIV infection correlate to intact and total reservoir.

Despite the beneficial effects of antiretroviral therapy (ART) initiation during acute HIV infection (AHI), residual immune activation remains a hallmark of treated HIV infection. Plasma concentrations of 40 mediators were measured longitudinally in 39 early treated participants of a Belgian AHI cohort (HIV+) and in 21 HIV-negative controls (HIV-). We investigated the association of the inflammatory profile with clinical presentation, plasma viral load, immunological parameters, and in-depth characterization of the HIV reservoir. While levels of most soluble mediators normalized with suppressive ART, we demonstrated the persistence of a pro-inflammatory signature in early treated HIV+ participants in comparison to HIV- controls. Examination of these mediators demonstrated a correlation with their levels during AHI, which seemed to be viremia-driven, and suggested involvement of an activated myeloid compartment, IFN-γ-signaling, and inflammasome-related pathways. Interestingly, some of these pro-inflammatory mediators correlated with a larger reservoir size and slower reservoir decay. In contrast, we also identified soluble mediators which were associated with favorable effects on immunovirological outcomes and reservoir, both during and after AHI. These data highlight how the persistent pro-inflammatory profile observed in early ART treated individuals is shaped during AHI and is intertwined with viral dynamics.

Maternal and fetal outcomes after planned cesarean or vaginal delivery in twin pregnancy: a comparison between 2 third level birth centers

Background Twin pregnancy is associated with higher risks of adverse perinatal outcomes for both the mother and the babies. Among the many challenges in the follow-up of twin pregnancies, the mode of delivery is the last but not the least decision to be made, with the main influencing factors being amnionicity and fetal presentation. The aim of the study was to compare perinatal outcomes in two European centers using different protocols for twin birth in case of non-cephalic second twin; the Italian patients being delivered mainly by cesarean section with those in Belgium being routinely offered the choice of vaginal delivery (VD). Methods This was a dual center international retrospective observational study. The population included 843 women with a twin pregnancy ≥ 32 weeks (dichorionic or monochorionic diamniotic pregnancies) and a known pregnancy outcome. The population was stratified according to chorionicity. Demographic and pregnancy data were reported per pregnancy, whereas neonatal outcomes were reported per fetus. We used multiple logistic regression models to adjust for possible confounding variables and to compute the adjusted odds ratio (adjOR) for each maternal or neonatal outcome. Results The observed rate of cesarean delivery was significantly higher in the Italian cohort: 85% for dichorionic pregnancies and 94.4% for the monochorionic vs 45.2% and 54.4% respectively in the Belgian center (p-value < 0.001). We found that Belgian cohort showed significantly higher rates of NICU admission, respiratory distress at birth and Apgar score of < 7 after 5 min. Despite these differences, the composite severe adverse outcome was similar between the two groups. Conclusion In this study, neither the presentation of the second twin nor the chorionicity affected maternal and severe neonatal outcomes, regardless of the mode of delivery in two tertiary care centers, but VD was associated to a poorer short-term neonatal outcome.

Phylogenetic Analysis of Hepatitis C Virus Infections in a Large Belgian Cohort Using Next-Generation Sequencing of Full-Length Genomes.

The hepatitis C virus (HCV) epidemic in Western countries is primarily perpetuated by the sub-populations of men who have sex with men (MSM) and people who inject drugs (PWID). Understanding the dynamics of transmission in these communities is crucial for removing the remaining hurdles towards HCV elimination. We sequenced 269 annotated HCV plasma samples using probe enrichment and next-generation sequencing, obtaining 224 open reading frames of HCV (OR497849-OR498072). Maximum likelihood phylogenies were generated on the four most prevalent subtypes in this study (HCV1a, 1b, 3a, 4d) with a subsequent transmission cluster analysis. The highest rate of clustering was observed for HCV4d samples (13/17 (76.47%)). The second highest rate of clustering was observed in HCV1a samples (42/78 (53.85%)) with significant association with HIV-positive MSM. HCV1b and HCV3a had very low rates of clustering (2/83 (2.41%) and (0/29)). The spread of the prevalent subtype HCV1b appears to have been largely curtailed, and we demonstrate the onwards transmission of HCV1a and HCV4d in the HIV-positive MSM population across municipal borders. More systematic data collection and sequencing is needed to allow a better understanding of the HCV transmission among the community of PWID and overcome the remaining barriers for HCV elimination in Belgium.

Comprehensive antibody and cytokine profiling in hospitalized COVID-19 patients in relation to clinical outcomes in a large Belgian cohort

The immune response in patients with Coronavirus Disease 2019 (COVID-19) is highly variable and is linked to disease severity and mortality. However, antibody and cytokine responses in the early disease stage and their association with disease course and outcome are still not completely understood. In this large, multi-centre cohort study, blood samples of 434 Belgian COVID-19 hospitalized patients with different disease severities (ranging from asymptomatic/mild to critically ill) from the first wave of the COVID-19 pandemic were obtained. Baseline antibody and cytokine responses were characterized and associations with several clinical outcome parameters were determined. Anti-spike immunoglobulin (Ig)G and IgM levels were elevated in patients with a more severe disease course. This increased baseline antibody response however was associated with decreased odds for hospital mortality. Levels of the pro-inflammatory cytokines IL-6, IP-10 and IL-8, the anti-inflammatory cytokine IL-10 and the antiviral cytokines IFN-α, IFN-β and IFN-λ1 were increased with disease severity. Remarkably, we found significantly lower levels of IFN-λ2,3 in critically ill patients compared to patients of the moderate and severe disease category. Finally, levels of IL-8, IL-6, IP-10, IL-10, IFN-α, IFN-β, IFN-γ and IFN-λ1 at baseline were positively associated with mortality, whereas higher IFN-λ2,3 levels were negatively associated with mortality.

Belgian medication exposure during pregnancy (BeMeP), a new nationwide linked database: Linkage methods and prevalence of medication use.

This study aimed to describe the implementation of a new retrospective Belgian national cohort of pregnant women, the Belgian Medication Exposure during Pregnancy (BeMeP). We linked the national dispensing data to birth and death certificates and hospital stay data for a 7-year period between 2010 and 2016 for the first time in Belgium. We presented the characteristics of pregnancy events associated with the mothers enrolled in the linkage study. Next, we constructed a cohort of pregnancies and compared some characteristics computed using the BeMeP database with the national statistics. Finally, we described the use of medications during pregnancy based on the first level of the Anatomical Therapeutic Chemical (ATC) classification. We included 630 457 pregnant women with 900 024 pregnancy-related events (843 780 livebirths, 1937 stillbirths, 6402 ectopic events, and 47 905 abortions) linked to medication exposure information. Overall, 96.3% of live births and 83.5% of stillbirths (national statistics as reference) were captured from the BeMeP. During pregnancy, excluding the week of birth, 78.9% of live birth pregnancies and 79.6% of stillbirth pregnancies were exposed to at least one medication. The most frequently dispensed medications were anti-infectives (ATC code J = 50.2%) for live births and for stillbirths (44.0%). We linked information on pregnancies, all reimbursed medications dispensed by community pharmacists, all medications dispensed during hospitalization, sociodemographic status, and infant health to create the BeMeP database. The database represents a valuable potential resource for studying exposure-outcome associations for medication use during pregnancy.

Genetic Screening of ZNF687 and PFN1 in a Paget's Disease of Bone Cohort Indicates an Important Role for the Nuclear Localization Signal of ZNF687.

Paget's disease of bone (PDB) is a common, late-onset bone disorder, characterized by focal increases of bone turnover that can result in bone lesions. Heterozygous pathogenic variants in the Sequestosome 1 (SQSTM1) gene are found to be the main genetic cause of PDB. More recently, PFN1 and ZNF687 have been identified as causal genes in patients with a severe, early-onset, polyostotic form of PDB, and an increased likelihood to develop giant cell tumors. In our study, we screened the coding regions of PFN1 and ZNF687 in a Belgian PDB cohort (n = 188). In the PFN1 gene, no variants could be identified, supporting the observation that variants in this gene are extremely rare in PDB. However, we identified 3 non-synonymous coding variants in ZNF687. Interestingly, two of these rare variants (p.Pro937His and p.Arg939Cys) were clustering in the nuclear localization signal of the encoded ZNF687 protein, also harboring the p.Pro937Arg variant, a previously reported disease-causing variant. In conclusion, our findings support the involvement of genetic variation in ZNF687 in the pathogenesis of classical PDB, thereby expanding its mutational spectrum.