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.

Evolution in caesarean section practices in North Kivu: Impact of caregiver training.

INTRODUCTION: A caesarean section is a major obstetric procedure that can save the life of mother and child. Its purpose is to protect the mother's health from the complications of childbirth and to protect the baby's health. In sub-Saharan Africa (SSA), there are major inequalities in access to caesarean sections and significant variations in practices to determine the indications for the procedure. Periodic analyses of maternal deaths have shown that more than half of maternal and new born deaths are due to suboptimal care and are therefore potentially preventable. The objective of our study is to assess the impact of health staff training under the PADISS project (to support the health system's integrated development) on the quality of CS procedures in North Kivu, by comparing two periods. MATERIAL AND METHODS: The populations compared were recruited from the referral hospitals in North Kivu, DRC (Democratic Republic of Congo). The first (group 1) was made up of patient files studied retrospectively for the period from 01/11/2013 to 01/01/2016. The second group (group 2), studied prospectively, comprised patient files from June 2019 to January 2020. Obstetric, maternal and foetal data were compared. Statistical analyses were performed using STATA/IC 15.0 for Windows. Univariate and multiple logistic regression was performed to determine which characteristics are associated with maternal and perinatal morbidity and mortality. A p value < 0.05 was considered statistically significant. RESULTS: CS frequency was approximately 17% in both study periods. We observed a CS frequency of about 34% at North Kivu provincial hospital for the two populations studied. The main indications for CS were dystocia, foetal distress and scarred uterus for both populations. In the population studied prospectively, after the implementation of health staff training, there were fewer incidence rate of dystocia, foetal distress and neonatal death, a more complete patient record, shorter hospital stay, and fewer blood transfusions but more incidence rate of scarred uterus, post-operative complications and low birth weight. Intervention had no statistically significant impact on low birth weight (OR = 1.9, p = 0.13), on neonatal mortality (OR = 0.69, p = 0.21). CONCLUSION: Our study shows a decrease in neonatal deaths, dystocia and foetal distress, but an increase in post-operative complications, maternal deaths and cases of scarred uterus and low birth weight. However, multiple logistic regression did no support the conclusion.

Immuno-Diagnosis of Active Tuberculosis by a Combination of Cytokines/Chemokines Induced by Two Stage-Specific Mycobacterial Antigens: A Pilot Study in a Low TB Incidence Country.

Active tuberculosis (aTB) remains a major killer from infectious disease, partially due to delayed diagnosis and hence treatment. Classical microbiological methods are slow and lack sensitivity, molecular techniques are costly and often unavailable. Moreover, available immuno-diagnostic tests lack sensitivity and do not differentiate between aTB and latent TB infection (LTBI). Here, we evaluated the performance of the combined measurement of different chemokines/cytokines induced by two different stage-specific mycobacterial antigens, Early-secreted-antigenic target-6 (ESAT-6) and Heparin-binding-haemagglutinin (HBHA), after a short in vitro incubation of either peripheral blood mononuclear cells (PBMC) or whole blood (WB). Blood samples were collected from a training cohort comprising 22 aTB patients, 22 LTBI subjects and 17 non-infected controls. The concentrations of 13 cytokines were measured in the supernatants. Random forest analysis identified the best markers to differentiate M. tuberculosis-infected from non-infected subjects, and the most appropriate markers to differentiate aTB from LTBI. Logistic regression defined predictive abilities of selected combinations of cytokines, first on the training and then on a validation cohort (17 aTB, 27 LTBI, 25 controls). Combining HBHA- and ESAT-6-induced IFN-γ concentrations produced by PBMC was optimal to differentiate infected from non-infected individuals in the training cohort (100% correct classification), but 2/16 (13%) patients with aTB were misclassified in the validation cohort. ESAT-6-induced-IP-10 combined with HBHA-induced-IFN-γ concentrations was selected to differentiate aTB from LTBI, and correctly classified 82%/77% of infected subjects as aTB or LTBI in the training/validation cohorts, respectively. Results obtained on WB also selected ESAT-6- and HBHA-induced IFN-γ concentrations to provided discrimination between infected and non-infected subjects (89%/90% correct classification in the training/validation cohorts). Further identification of aTB patients among infected subjects was best achieved by combining ESAT-6-induced IP-10 with HBHA-induced IL-2 and GM-CSF. Among infected subjects, 90%/93% of the aTB patients were correctly identified in the training/validation cohorts. We therefore propose a two steps strategy performed on 1 mL WB for a rapid identification of patients with aTB. After elimination of most non-infected subjects by combining ESAT-6 and HBHA-induced IFN-γ, the combination of IP-10, IL-2 and GM-CSF released by either ESAT-6 or HBHA correctly identifies most patients with aTB.

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.

Preliminary report of patients with meningiomas exposed to Cyproterone Acetate, Nomegestrol Acetate and Chlormadinone Acetate - Monocentric ongoing study on progestin related meningiomas.

INTRODUCTION: The relationship between meningioma and progestins has not been elucidated. Meningioma regression after acetate cyproterone (CA) withdrawal has been reported. Our purpose was to evaluate the meningioma evolution after withdrawal of progestins in patients who underwent long-term exposure to CA, nomegestrol acetate (NA), chlormadinone acetate (ChlA). METHODS: Our study retrospectively included 69 patients with intracranial meningioma and exposed to one of these 3 progestins between December 2006 and March 2019. In each patient, clinico-radiological (MRI) follow-up was performed every 6 months after diagnosis and treatment withdrawal recommendation. Statistical analyses were applied to compare tumor location and respect of prescription rules between the 3 groups. RESULTS: The mean hormonal exposure was 16 years in CA group (n = 46), 16 years in NA group (n = 12) and 9.7 years in ChlA group (n = 11). A higher rate of "out of label" use was observed in the CA group (p = 0.003). Multiple meningiomas were demonstrated in more than 60% of cases in each group. Anterior skull base location was noted in 60.5% of cases in CA group, 25% of cases in NA group and 36.7% of cases in ChlA group (p = 0.05). Incomplete tumor regression was recorded in 11 cases of CA group and in 2 cases of ChlA group. CONCLUSION: In CA group, our results suggest a strong relationship between this treatment and development of intracranial meningioma. In presence of voluminous asymptomatic meningioma, treatment can be delayed due to the potential regression after withdrawal. On the contrary in NA and ChlA groups, further studies are needed.

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

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 (BEACOPPescalated) in early responders on the basis of a positron emission tomography (PET)-driven strategy was safe and minimized toxicity compared with standard 6 BEACOPPescalated 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; P = .001 and OR, 0.15; 95% CI, 0.04 to 0.56, P = .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 BEACOPPescalated group, as well as a lower risk of severe testicular damage (OR, 0.26; 95% CI, 0.13 to 0.5; P < .0001) and a higher likelihood of achieving pregnancy (OR, 3.7; 95% CI, 1.4 to 9.3; P = .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.

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

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

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 M. tuberculosis 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 in vitro 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 M. tuberculosis-infected children. This combination also correctly classified 98% of the children from a validation cohort comprising 40 M. tuberculosis 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 M. tuberculosis-infected children, whereas differentiating children with aTB from those with latent TB remains far from perfect.

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

Introduction: 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. Methods: 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. iK was automatically computed for each cardiac cycle (iK CC ) in linear (iK Lin ) and rotational (iK Rot ) dimensions. iK was calculated as well during systole and diastole (iK Sys and iK Dia , 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. Results: 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 p < 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, i K L i n C C , i K L i n S y s , and i K L i n D i a dropped by 43, 52, and 53%, respectively (p < 0.0001, p < 0.0001, and p = 0.03, respectively) from baseline to the end of reperfusion. In the rotational dimension, i K R o t C C and i K R o t S y s dropped by 30 and 36%, respectively (p = 0.0006 and p < 0.0001, respectively), but i K R o t D i a did not change (p = 0.41). All the hemodynamic parameters, except the pulmonary artery pulse pressure, were significantly correlated with the parameters of iK, except for the diastolic component. Conclusions: In this very context of experimental AMI with acute LV regional dysfunction and no concomitant AMI-related heart valve disease, linear and rotational iK 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 iK during AMI and reperfusion. This automatic system may empower health care providers and patients to remotely monitor cardiovascular status in the near future.

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

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 (VMax), integral of kinetic energy (iK), and maximal power (PMax) 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 VMax of BCG predicts the rates of left ventricular (LV) twisting and untwisting (both p < 0.0001). The linear PMax 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 PMax and iK strongly correlate with LVEF (R = 0.7, p < 0.0001). In this setting of enhanced inotropism, the linear VMax of BCG, rather than the VMax of SCG, is the metric which best explains the LV twist mechanics, in particular the rates of twisting and untwisting. PMax and iK metrics are strongly associated with the LVEF and account for 50% of the variance of the LVEF.

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

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.

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

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.

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.

Stillbirth Among Arab Women in Canada, 1981-2015.

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.

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

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 HMOX1) regulates GVHD in response to allogeneic hematopoietic stem cell transplantation in mice and humans. We found that deletion of the Hmox1 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)n repeat polymorphism (L/L) in the HMOX1 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)n 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 HMOX1 (GT)n 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.

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.