A retrospective study evaluating the impact of scattering radiation from imaging procedures on oocyte quality during ovarian stimulation for fertility preservation in young breast cancer patients.

PURPOSE: Ovarian stimulation for oocyte and embryo cryopreservation is the standard of care for fertility preservation in young breast cancer patients before gonadotoxic chemotherapy. The procedure should be started as soon as possible to avoid delay of treatment; thus, it is often performed concomitantly with tumor staging assessments. However, questions remain regarding the potential negative impact on oocyte quality that may occur due to exposure to scattered ionizing radiation from imaging techniques when staging assessment is conducted at the same time as ovarian stimulation. METHODS: We conducted a retrospective study on all breast cancer patients who performed ovarian stimulation for fertility preservation at our center between November 2012 and May 2020. RESULTS: Gynecologic and oncological characteristics were similar between patients exposed (n = 14) or not (n = 60) to ionizing radiation. Exposed patients started the ovarian stimulation sooner after diagnosis than non-exposed patients (11.5 vs 28 days, respectively, P < 0.01). Cycle parameters, including the median number of oocytes collected (10.5 vs 7, P = 0.16), maturation rates (92.5% vs 85.7%, P = 0.54), and fertilization rates (62.2% vs 65.4%, P = 0.70), were similar between groups. CONCLUSION: This study shows that scattered ionizing radiation due to staging assessment appears to be safe without compromising follicular growth and maturation. Larger studies on fertility and obstetrical outcomes are needed to confirm these preliminary data.

Endoscopic internal drainage of complex bilomas and biliary leaks by transmural or transpapillary/transfistulary access.

BACKGROUND AND AIMS: Bilomas most frequently result from postoperative bile leaks. The endoscopic conventional treatment is sphincterotomy ± stent placement. In complex cases, such as altered anatomy or failure of conventional treatment, transpapillary/transfistulary (TP/TF) drainage or EUS-guided transmural drainage (EUS-TD) may obviate additional biliary surgery. This study reports our experience with treating biloma secondary to refractory biliary leak with TP/TF drainage or EUS-TD and evaluates the safety and outcomes associated with this approach. METHODS: This observational study focused on consecutive patients managed for biliary leakage (diagnosis based on imaging and/or bile outflow from a surgical drain) at a tertiary care hospital (2007-2017). TP/TF drainage was performed by double-pigtail stent(s) placement to drain the biloma through the leak during ERCP. For EUS-TD, plastic stent(s) were placed under EUS control. Primary outcomes were a composite of clinical success (patient free of sepsis after percutaneous drain removal and, in patients with benign disease, removal of all endoscopically placed stents, without need for reintervention) and biloma regression (<3 cm) at last follow-up. RESULTS: Thirty patients (men, 57%; median age, 55 years) were included. Most biliary leaks resulted from cholecystectomy (27%) and hepatectomy (50%). Initial EUS-TD and TP/TF drainage were performed in 14 (47%) and 16 (53%) patients, respectively. At last follow-up (median, 33.2 months), clinical success and primary outcome were achieved in 70.4% of patients (EUS-TD, 75%; TP/TF, 67%). Additional surgery was necessary in 1 patient. Rate of serious adverse events was 23% (7/30), of which 13% (4/30) were procedure related. There were 4 deaths during the course of treatment, 2 of which were related to endoscopic interventions (hemorrhage and fibrillation). CONCLUSIONS: TP/TF drainage or EUS-TD is technically feasible with high clinical success and may avoid the need for additional surgery in complex cases or in patients with altered anatomy.

Measuring the invisible: perinatal health outcomes of unregistered women giving birth in Belgium, a population-based study.

BACKGROUND: The unregistered population remains under-researched because of its "invisible" status in statistics. Studies on perinatal health outcomes of unregistered women remains particularly limited. Our objectives were 1) to describe the sociodemographic profiles of women who are not legally residing in Belgium and 2) to analyze the associations of registration status with pregnancy outcomes according to socioeconomic status and nationality. METHODS: We analysed data from birth and death certificates taken from the Belgian civil registration system, linked with the National Population Registry (NPR). The data relates to all singleton babies born between 2010 and 2016 (n = 871,283), independent of their mother's NPR registration status. We used logistic regression to estimate the odds ratios for the associations between perinatal outcomes (perinatal mortality, prematurity and low birth weight) and maternal NPR registration status according to socioeconomic status and maternal nationality. RESULTS: Over the study period, 1.9% of births were to mothers without NPR-registration. Unregistered women from newer EU member states and non-European countries were particularly disadvantaged from a socioeconomic point of view. Apart from women with a South American nationality, all other groups of unregistered women had higher rates of prematurity, low birth weight, and perinatal mortality, compared to registered mothers (p < 0.0001). Unregistered women from Belgium and EU15 nationalities had particularly higher rates of prematurity, low birth weight, and perinatal mortality, compared to registered mothers, even after adjustment for socioeconomic status (p < 0.0001). The excess of perinatal mortality for non-European unregistered mothers could partly be explained by their precarious socioeconomic situation. CONCLUSIONS: This is the first study to include data on mothers who were not legally residing in Belgium. Unregistered women giving birth in Belgium are likely a heterogeneous socioeconomic group. Overall, unregistered women have increased risks of adverse perinatal outcomes, but it is likely that the causal mechanisms differ starkly between Belgian, European and non-European women. Further research is needed to understand the mechanisms behind these accrued rates. It is important to keep measuring the health outcomes of the populations which are "invisible" in national statistics, in order to identify the groups in most need of integration and access to services.

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

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.

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

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 (iK) during a single heartbeat are computed in linear and rotational dimensions. Our aim was to test the hypothesis that iK 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 (n = 28, healthy men). iK 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 (P = 0.01, P = 0.002,and P = 0.001, respectively), whereas [Formula: see text] decreased (P = 0.02). At the end of the apnea compared with normal breathing, changes in iK computed from BCG were related to changes of tMSNA and BF only in the linear dimension (r = 0.85, P < 0.0001; and r = 0.72, P = 0.002, respectively), whereas changes in linear iK of SCG were related only to changes of tMSNA (r = 0.62, P = 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 iK 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.NEW & NOTEWORTHY 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 (iK) 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, iK 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.

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

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.

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

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.

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

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.

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

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.

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

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 <104 copies (cp)/mL (n=573), (B) ≥104 Upv <107 cp/mL (n=100), and (C) Upv ≥107 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.

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

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.

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

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/1.73m2 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.

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

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.

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

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.

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

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.

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

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.

Distinct socioeconomic profile of patients hospitalised with severe COVID-19 and prepandemic respiratory infections in Brussels's deprived areas: a case-control study.

OBJECTIVE: Belgium has been hit harder by COVID-19 than other countries in Europe. While clinical risk factors are well studied, socioeconomic risk factors remained underexplored. This study's objective was to analyse the social and clinical profile of patients hospitalised for COVID-19 during the two waves of 2020, compared with a control population in 2019 in two hospitals located in Brussels' most deprived area. DESIGN AND METHODS: We did a case-control study by using the minimal clinical data set in two Brussels hospitals. All patients hospitalised for COVID-19 in 2020, divided into two waves (n=3220), were compared with all patients hospitalised for viral pneumonia and respiratory diseases in 2019 (control population n=2950). Multinomial regression models were used to estimate the relative risk ratios of the association between the COVID-19 hospitalised populations (waves 1 and 2) and risk factors (social and clinical) stratified by age. RESULTS: Patients under 65 years of age and hospitalised for COVID-19 presented significantly higher rates (relative rate ratio (95% CI)), especially for the first wave, of obesity 1.6 (1.2-2.2), African nationalities 1.4 (1.0-1.8), lack of health insurance 1.6 (1.3-2.1), living in high-density population areas 1.6 (1.3-2.1) and low incomes 1.7 (1.4-2.1), compared with the control population For patients over 65 years of age, we did not observe significant excess of COVID-19 hospitalisations for any risk factors, except diabetes during for the second wave but we have a significant excess mortality rate than the control population for both waves (p<0.002). CONCLUSIONS: The social and clinical profile of patients hospitalised for COVID-19 compared with a population hospitalised for viral respiratory diseases differed between age groups and waves. For younger patients, risk factors were linked to patients' precarious situations. This study underlines the role of selected social health determinants and the importance of routinely collecting social data, along with clinical data, particularly among vulnerable populations.

Social and clinical risk factors associated with hospitalized COVID-19 patients in Brussels's deprived and multiethnic areas.

BACKGROUND: In Belgium, the Brussels-Capital region was severely affected by the COVID-19 epidemic. Various hypotheses were mentioned in order to explain Brussels' excess disease spreading and mortality rate, but socioeconomic risk factors are increasingly recognized. This study's objective was to analyze clinical and social profiles of patients hospitalized for COVID-19, by nationality groups, in two hospitals located in Brussels's deprived and multiethnic areas. METHODS: Data covered hospitalized COVID-19 patients from two Brussels hospitals (n = 787) between the 1st of March 2020 and the 31st of June 2020. Social data was collected using hospital records, and clinical data was extracted from hospitals' COVID-19 databases. Multivariable logistic regression models were used to estimate the odds ratios (OR) of the association between two outcomes (Intensive Care Unit admission and mortality) and risk factors (social and clinical). RESULTS: Patients from Sub-Saharan Africa were younger, had a higher prevalence of obesity, lacked health insurance, and had the highest proportion of Intensive Care Unit (ICU) admission (27.7%) but the lowest mortality rates than other nationality groups. Patients from North Africa had a higher prevalence of diabetes compared to other nationality groups and a high proportion of European patients came from nursing homes. Patients deprived of health insurance had a higher risk of ICU admission compared to those who had insurance (OR IC95%; 1,9 1.1-3.6, p = 0.03). Other risk factors as sex and obesity were significantly associated to ICU admission and, age and hypertension were significantly associated to mortality. CONCLUSION: Social and clinical profile of the patients differs between the nationality groups, and some risk factors for Intensive Care Unit admission and mortality were linked to more patients' precarious situation as the availability of health insurance. This study underlines the role of selected social health determinants and the importance of routinely collecting social along with clinical data.

Social inequalities and long-term health impact of COVID-19 in Belgium: protocol of the HELICON population data linkage.

INTRODUCTION: Data linkage systems have proven to be a powerful tool in support of combating and managing the COVID-19 pandemic. However, the interoperability and the reuse of different data sources may pose a number of technical, administrative and data security challenges. METHODS AND ANALYSIS: This protocol aims to provide a case study for linking highly sensitive individual-level information. We describe the data linkages between health surveillance records and administrative data sources necessary to investigate social health inequalities and the long-term health impact of COVID-19 in Belgium. Data at the national institute for public health, Statistics Belgium and InterMutualistic Agency are used to develop a representative case-cohort study of 1.2 million randomly selected Belgians and 4.5 million Belgians with a confirmed COVID-19 diagnosis (PCR or antigen test), of which 108 211 are COVID-19 hospitalised patients (PCR or antigen test). Yearly updates are scheduled over a period of 4 years. The data set covers inpandemic and postpandemic health information between July 2020 and January 2026, as well as sociodemographic characteristics, socioeconomic indicators, healthcare use and related costs. Two main research questions will be addressed. First, can we identify socioeconomic and sociodemographic risk factors in COVID-19 testing, infection, hospitalisations and mortality? Second, what is the medium-term and long-term health impact of COVID-19 infections and hospitalisations? More specific objectives are (2a) To compare healthcare expenditure during and after a COVID-19 infection or hospitalisation; (2b) To investigate long-term health complications or premature mortality after a COVID-19 infection or hospitalisation; and (2c) To validate the administrative COVID-19 reimbursement nomenclature. The analysis plan includes the calculation of absolute and relative risks using survival analysis methods. ETHICS AND DISSEMINATION: This study involves human participants and was approved by Ghent University hospital ethics committee: reference B.U.N. 1432020000371 and the Belgian Information Security Committee: reference Beraadslaging nr. 22/014 van 11 January 2022, available via https://www.ehealth.fgov.be/ehealthplatform/file/view/AX54CWc4Fbc33iE1rY5a?filename=22-014-n034-HELICON-project.pdf. Dissemination activities include peer-reviewed publications, a webinar series and a project website.The pseudonymised data are derived from administrative and health sources. Acquiring informed consent would require extra information on the subjects. The research team is prohibited from gaining additional knowledge on the study subjects by the Belgian Information Security Committee's interpretation of the Belgian privacy framework.

Combined introduction of anti-IL2 receptor antibodies, mycophenolic acid and tacrolimus: effect on malignancies after renal transplantation in a single-centre retrospective cohort study.

BACKGROUND: Several studies suggest that the introduction of tacrolimus (TRL), mycophenolic acid (MPA) and interleukin 2 receptor antibodies (IL2Ra) as single drugs more than a decade ago has not increased the risk of malignancy after renal transplantation. However, only limited data are available on their carcinogenic effects when used in combination as a potent immunosuppressive regimen. METHODS: A retrospective single-centre cohort study on 929 adult renal transplant recipients. Investigation of the effect of two consecutive immunosuppressive regimens [1993-98, N = 405, anti-lymphocyte antibodies, cyclosporine and azathioprine (AZA); 1999-2007, N = 524, predominantly IL2Ra, TRL and MPA] on the incidence rate of skin cancer, solid tumours and post-transplant lymphoproliferative disease (PTLD). RESULTS: In total, 365 malignancies developed among 113 patients. As compared to the previous cyclosporine and AZA-based immunosuppression, the introduction of the new immunosuppressive regimen did not increase the incidence rate of skin cancer [rate ratio 0.84; 95% confidence interval (CI) 0.48-1.46], solid tumours (0.89; 95% CI 0.46-1.67) and PTLD (0.82; 95% CI 0.28-2.21). Patients treated with the more recent regimens less frequently developed multiple skin cancers and invasive squamous cell cancer. Skin cancer after transplantation was strongly associated with the development of solid tumours (odds ratio 5.2; P < 0.0001). The introduction of the new immunosuppressive drugs reduced the incidence of first year acute rejection from 34.8 to 13.2% (P < 0.0001). CONCLUSION: Although significantly more efficient in the prevention of acute rejection, the introduction of TRL, MPA and IL2Ra-based immunosuppression after kidney transplantation was not associated with an increased incidence of skin cancer, solid tumours or PTLD.