Molybdenum Occupational Study in a French Cohort of Workers

International audienceAbstract Objectives Occupational exposure to molybdenum has been poorly documented to date. Here, we present a retrospective study evaluating urinary molybdenum concentration before and after shift over a period of 2 years in exposed workers. Methods This retrospective study was conducted across eight industrial sites in France and included all workers undergoing medical follow-up for occupational molybdenum exposure. A mean of six sequential samples (before and after shift) was performed for each worker. The urinary molybdenum concentration was determined using a validated method of inductively coupled plasma-mass spectrometry. A mixed linear model was built and linear regression was used to verify the extent to which the urinary molybdenum concentration depends on the age of the workers and the sampling period. Additionally, an analysis based on individual trajectory was also performed. Results Seventy-seven workers were included in the present study. Post-shift urinary molybdenum concentrations were significantly higher than pre-shift values [median (95th percentile) 37.9 (91.1), versus 60.6 (190.0) µg g−1 creatinine, respectively, P < 0.009]. No accumulation of molybdenum over time was observed. The urinary molybdenum concentrations were not influenced by age. Four workers presented high post-shift values as a result of not adhering to protection measures (maxima of 529.8, 359.7, 386.3, and 1459.7 µg g−1 creatinine, respectively). Conclusions To our knowledge, this is the first study of occupational molybdenum exposure in France to include an individual trajectory analysis. No accumulation of molybdenum was seen but high post-shift molybdenum urinary concentrations were observed for some workers. The study emphasizes the importance of molybdenum monitoring in exposed workers

Difficulties interpreting concentrations in fatal cases: example of 2,5-dimethoxy-4-chloroamphetamine

International audienceCases of intestinal microsporidiosis infection are underestimated and affect both immunocompromized and immunocompetent patients. Real-time PCR is superseding microscopic examination for its diagnosis in medical analysis laboratories. However, few manufacturers include microsporidia in their PCR panel for the diagnosis of infectious gastroenteritis. Here, we evaluated the performances of the real-time PCR assays microsporidia generic and microsporidia typing (Bio-Evolution, France) on the Rotor-Gene Q real-time PCR cycler (Qiagen, France). We included 45 negative and 44 positive stool samples for Enterocytozoon bieneusi ( n = 34, with various genotypes), Encephalitozoon intestinalis ( n = 4), Encephalitozoon hellem ( n = 4), and Encephalitozoon cuniculi ( n = 2). We also studied a four-year survey of an inter-laboratory quality control program including 9 centers that used this commercial assay. Sensitivity and specificity of the microsporidia generic assay were 86.4% and 93.3%, respectively. Encephalitozoon hellem and Encephalitozoon cuniculi were detected by the microsporidia generic PCR assay but not by the microsporidia typing PCR assay. These results were consistent with the results of the inter-laboratory quality control program. In conclusion, Bio-Evolution Real-time PCR assays are useful tools for intestinal microsporidiosis, but negative results for microsporidia typing assays require supplementary analyses to confirm E. hellem or E. cuniculi infections.Les microsporidioses intestinales sont des infections sous-estimées affectant à la fois les patients immunodéprimés et immunocompétents. Le diagnostic microscopique en laboratoire médical est aujourd’hui supplanté par la PCR en temps réel. Cependant, peu de fabricants incluent les microsporidies dans leurs panels PCR pour le diagnostic des gastro-entérites infectieuses. Ici, nous avons évalué les performances des tests PCR en temps réel microsporidia generic et microsporidia typing (Bio-Evolution, France) sur le thermocycleur PCR en temps réel Rotor-Gene Q (Qiagen, France). Nous avons inclus 45 échantillons de selles négatifs et 44 échantillons positifs pour Enterocytozoon bieneusi ( n = 34, avec divers génotypes), Encephalitozoon intestinalis ( n = 4), Encephalitozoon hellem ( n = 4) et Encephalitozoon cuniculi ( n = 2). Nous avons également analysé les résultats sur 4 ans d’un programme de contrôle qualité inter-laboratoires dont 9 centres ont utilisé ces kits commerciaux. La sensibilité et la spécificité du kit microsporidia generic étaient respectivement de 86,4 % et 93,3 %. Encephalitozoon hellem et E. cuniculi ont été détectés par le kit microsporidia generic mais pas par le kit microsporidia typing. Ces résultats étaient cohérents avec ceux du programme de contrôle de qualité inter-laboratoires. En conclusion, les tests de PCR en temps réel Bio-Evolution sont des outils intéressants pour la microsporidiose intestinale, mais un résultat négatif pour le test de typage microsporidia nécessite une analyse supplémentaire pour confirmer les infections à E. hellem ou E. cuniculi

Grossesses après chirurgie bariatrique: recommandations pour la pratique clinique (groupe BARIA-MAT)

International audienceThe outcome of pregnancies after bariatric surgery seems favorable with a reduction in the incidence of gestational diabetes, hypertensive disorders and macrosomia. However, an increase in newborns of low weight for gestational age and prematurity are observed. Nutritional deficiencies of varying severity for the mother and the newborn are reported, as well as surgical complications with a prognosis conditioned by the diagnostic difficulties during pregnancy. Our multidisciplinary working group proposes clinical practical guidelines developed according to the methodology of the HAS and covering the timing between surgery and pregnancy, contraception, preferred type of surgery for women of childbearing age, systematic nutritional support and management of nutritional deficiencies, screening and management of gestational diabetes, weight gain during pregnancy, gastric banding management, surgical emergencies, obstetrical management, and specific care in the postpartum period and for newborns.L’issue des grossesses après chirurgie bariatrique semble favorable associant réduction de l’incidence du diabète gestationnel, des troubles hypertensifs et de la macrosomie. Néanmoins une augmentation de l’incidence des nouveaux nés de petit poids pour l’âge gestationnel et de la prématurité est constatée dans plusieurs études. Des carences nutritionnelles de sévérité variable pour la mère et le nouveau-né set des complications chirurgicales avec un pronostic conditionné par les difficultés diagnostiques sont également observées. Notre groupe de travail multidisciplinaire propose une série de recommandations élaborées selon la méthodologie de la HAS et concernent les questions suivantes: quel délai entre la chirurgie et la grossesse ? Quelle contraception ? Quel type de chirurgie pour les femmes en âge de procréer ? Quel support nutritionnel et quelle gestion des carences nutritionnelles ? Quel dépistage et quelle gestion du diabète gestationnel ? Quelle prise de poids optimale ? Comment gérer l’anneau gastrique au cours de la grossesse ? Comment prendre en charge les urgences chirurgicales, la prise en charge obstétricale et les soins spécifiques pendant la période post-partum et pour les nouveau-nés

Management of surgical complications of previous bariatric surgery in pregnant women. A systematic review from the BARIA-MAT Study Group

International audienceConsidering the large and increasing population of women of childbearing age with history of bariatric surgery, surgical complications of bariatric surgery during pregnancy may become more frequent in the future. The aim of this study was to analyze the clinical presentation, diagnostic procedures, and treatment of surgical complications of bariatric surgery during pregnancies. A systematic literature search was performed in accordance with the PRISMA (preferred reporting items for systematic review and meta-analysis) guidelines to identify all studies published up to and including December 2018 that included women with previous bariatric surgery undergoing emergency surgery during pregnancy. Sixty-eight studies were selected, including 120 women with previous bariatric surgery undergoing emergency surgery during pregnancy. Fifty cases were reported as case reports and 70 in case series. Included patients had previous history of Roux-en-Y gastric bypass (n = 99), laparoscopic adjustable gastric banding (n = 17), Scopinaro procedure (n = 2), vertical banded gastroplasty (n = 1), or one-anastomosis gastric bypass (n = 1). Final diagnosis in 50 case reports was internal hernia in 26 cases, bowel intussusception in 10, intestinal obstruction in 2, laparoscopic adjustable gastric banding slippage in 3, bowel volvulus in 3, gastric or jejunal perforation in 2, and other complications in 4 cases. Maternal and fetal death occurred in 3 (2.5%) and 9 cases (7.5%), respectively. In the case series, the majority of women were operated for internal hernia and laparoscopic adjustable gastric banding slippage. Surgical complications of previous bariatric surgery during pregnancy have potentially severe outcomes. Availability of multidisciplinary expertise, including bariatric/digestive surgeons, and education of healthcare providers and women on clinical signs that require urgent surgical examination are recommended in this setting. Prompt diagnosis is fundamental and based on clinical and laboratory findings and on radiologic examinations if needed, including computed tomography scan or magnetic resonance if available. Rapid surgical exploration is mandatory in case of high clinical and/or radiologic suspicion. (C) 2019 American Society for Bariatric Surgery. Published by Elsevier Inc. All rights reserved

Effect of Tocilizumab vs Usual Care in Adults Hospitalized With COVID-19 and Moderate or Severe Pneumonia

International audienceImportance Severe pneumonia with hyperinflammation and elevated interleukin-6 is a common presentation of coronavirus disease 2019 (COVID-19).Objective To determine whether tocilizumab (TCZ) improves outcomes of patients hospitalized with moderate-to-severe COVID-19 pneumonia.Design, Setting, and Particpants This cohort-embedded, investigator-initiated, multicenter, open-label, bayesian randomized clinical trial investigating patients with COVID-19 and moderate or severe pneumonia requiring at least 3 L/min of oxygen but without ventilation or admission to the intensive care unit was conducted between March 31, 2020, to April 18, 2020, with follow-up through 28 days. Patients were recruited from 9 university hospitals in France. Analyses were performed on an intention-to-treat basis with no correction for multiplicity for secondary outcomes.Interventions Patients were randomly assigned to receive TCZ, 8 mg/kg, intravenously plus usual care on day 1 and on day 3 if clinically indicated (TCZ group) or to receive usual care alone (UC group). Usual care included antibiotic agents, antiviral agents, corticosteroids, vasopressor support, and anticoagulants.Main Outcomes and Measures Primary outcomes were scores higher than 5 on the World Health Organization 10-point Clinical Progression Scale (WHO-CPS) on day 4 and survival without need of ventilation (including noninvasive ventilation) at day 14. Secondary outcomes were clinical status assessed with the WHO-CPS scores at day 7 and day 14, overall survival, time to discharge, time to oxygen supply independency, biological factors such as C-reactive protein level, and adverse events.Results Of 131 patients, 64 patients were randomly assigned to the TCZ group and 67 to UC group; 1 patient in the TCZ group withdrew consent and was not included in the analysis. Of the 130 patients, 42 were women (32%), and median (interquartile range) age was 64 (57.1-74.3) years. In the TCZ group, 12 patients had a WHO-CPS score greater than 5 at day 4 vs 19 in the UC group (median posterior absolute risk difference [ARD] −9.0%; 90% credible interval [CrI], −21.0 to 3.1), with a posterior probability of negative ARD of 89.0% not achieving the 95% predefined efficacy threshold. At day 14, 12% (95% CI −28% to 4%) fewer patients needed noninvasive ventilation (NIV) or mechanical ventilation (MV) or died in the TCZ group than in the UC group (24% vs 36%, median posterior hazard ratio [HR] 0.58; 90% CrI, 0.33-1.00), with a posterior probability of HR less than 1 of 95.0%, achieving the predefined efficacy threshold. The HR for MV or death was 0.58 (90% CrI, 0.30 to 1.09). At day 28, 7 patients had died in the TCZ group and 8 in the UC group (adjusted HR, 0.92; 95% CI 0.33-2.53). Serious adverse events occurred in 20 (32%) patients in the TCZ group and 29 (43%) in the UC group (P = .21).Conclusions and Relevance In this randomized clinical trial of patients with COVID-19 and pneumonia requiring oxygen support but not admitted to the intensive care unit, TCZ did not reduce WHO-CPS scores lower than 5 at day 4 but might have reduced the risk of NIV, MV, or death by day 14. No difference on day 28 mortality was found. Further studies are necessary for confirming these preliminary results.Trial Registration ClinicalTrials.gov Identifier: NCT0433180

Effect of anakinra versus usual care in adults in hospital with COVID-19 and mild-to-moderate pneumonia (CORIMUNO-ANA-1): a randomised controlled trial

International audienc

Sarilumab in adults hospitalised with moderate-to-severe COVID-19 pneumonia (CORIMUNO-SARI-1): An open-label randomised controlled trial

International audienc

A highly virulent variant of HIV-1 circulating in the Netherlands

We discovered a highly virulent variant of subtype-B HIV-1 in the Netherlands. One hundred nine individuals with this variant had a 0.54 to 0.74 log10 increase (i.e., a ~3.5-fold to 5.5-fold increase) in viral load compared with, and exhibited CD4 cell decline twice as fast as, 6604 individuals with other subtype-B strains. Without treatment, advanced HIV-CD4 cell counts below 350 cells per cubic millimeter, with long-term clinical consequences-is expected to be reached, on average, 9 months after diagnosis for individuals in their thirties with this variant. Age, sex, suspected mode of transmission, and place of birth for the aforementioned 109 individuals were typical for HIV-positive people in the Netherlands, which suggests that the increased virulence is attributable to the viral strain. Genetic sequence analysis suggests that this variant arose in the 1990s from de novo mutation, not recombination, with increased transmissibility and an unfamiliar molecular mechanism of virulence