Les probiotiques à l'officine

De nombreuses études ont montré de multiples rôles de la flore intestinale et de la fore vaginale dans la physiologie de l hôte. C est en s appuyant sur ces études que les probiotiques sont de plus en plus testés dans la prise en charge de certaines pathologies immunitaires, infectieuses et parfois même certains cancers. Toutefois, les instances réglementaires telles que l EFSA ou l ANSES, ne reconnaissent l efficacité de ces probiotiques que peu de cas et les demandes de validation des souches se soldent souvent par un rejet. C est dans ce contexte, où finalement les probiotiques n ont pratiquement pas la validation d allégations des autorités compétentes, que le monde de l officine voit fleurir les références de compléments alimentaires ou de médicaments contenant des probiotiques. Dans une première partie, nous verrons les définitions des probiotiques, des probiotiques et des symbiotiques, puis nous aborderons le site d action des probiotiques et le rôle de la flore intestinale et vaginale dans la physiologie de l hôte. Nous étudierons ensuite dans quels domaines pathologiques les probiotiques peuvent présenter un intérêt. Dans la quatrième partie nous discuterons de leur efficacité et enfin nous verrons sous quelles formes sont retrouvés ces probiotiques à l officine, avec une présentation des médicaments sur le marché français, et une présentation des gammes de compléments alimentaires contenant des probiotiques proposées par les 7 laboratoires les plus importants du secteur.CHATENAY M.-PARIS 11-BU Pharma. (920192101) / SudocSudocFranceF

Child Labor and Psychosocial Wellbeing: Findings from Ethiopia

International audienceFor children who work, there has been little research into the intricate relationship between their home lives and their work lives and the implications that this relationship might hold for their psychosocial development and functioning. This cross-sectional study was conducted in the Amhara region, Ethiopia, between March and April 2020 on a sample of 1311 working children with the aim, in part, of exploring ways in which various dimensions of children’s psychological wellbeing are influenced by their working conditions and their family contexts. In addition to collecting data on some personal traits, family relationships, home environments, and detailed occupational characteristics, we gathered information on psychosocial wellbeing using 22 items from the Instrument for the Psychosocial Assessment of Working Children (IPAC). Exploratory factor analysis enabled us to identify five factors characterizing the dimensions of psychosocial wellbeing: work-related self-esteem, work-related stress, workplace supervision, emotional and somatic wellbeing, and self-determination. Linear regressions of these factors were then conducted on social, occupational, and environmental variables. We found that all dimensions of psychosocial wellbeing were significantly associated with the children’s working conditions. Of particular interest, work-related dimensions of wellbeing, such as stress, self-esteem, and supervision, were significantly associated with the characteristics of the home and family environment. These findings illustrate that work and working conditions must be considered jointly, along with family life and home environments, as factors in both environments affect working children’s socioemotional development and wellbeing. They also strengthen the call for a systemic approach to protecting children involved in child labor, in which families are central to all discussions

Myosteatosis as an independent risk factor for mortality after kidney allograft transplantation: a retrospective cohort study

Background Patients with end-stage renal disease may display both a loss of skeletal muscle mass and an increase in muscle fat deposits. We aimed to analyse the impact of low skeletal muscle mass index (SMI, surrogate marker of sarcopenia) and low muscle density (MD, surrogate marker of myosteatosis) on patient survival after kidney transplantation (KT). Methods In a retrospective cohort of 200 kidney transplant recipients (KTr), we measured on an unenhanced cross-sectional computed tomography scan taken at the level of the third lumbar vertebra within the previous year or at the time of KT, both SMI (muscle cross-sectional area normalized for height 2 , reported in cm 2 /m 2) and MD (mean attenuation of muscle cross-sectional area, expressed in Hounsfield units). We determined age-specific and sex-specific normality thresholds on 130 healthy subjects. The baseline factors associated with low MD were assessed by logistic regression analysis. Cox proportional hazard univariable and multivariable models were constructed to identify predictive factors of patient survival. Results Among the 200 patients of the cohort, 123 were male (62%), and mean age was 54.8 ± 13.8 years. A total of 181 KTr required renal replacement therapy before KT (91%), and 36 KTr (18%) received repeat kidney transplant after previous failed KT. Mean MD was 30.6 ± 9 HU in men and 29.7 ± 8.3 HU in women, whereas SMI was 49.7 ± 8.6 cm 2 /m 2 in men and 42.3 ± 7.3 cm 2 /m 2 in women. MD was below the 2.5th percentile for the healthy population in 49 KTr (25%), defining the myosteatosis group, while SMI was below the 2.5th percentile for the reference population in 10 KTr (5%). Independent risk factors for myosteatosis were two or more KT [adjusted odds ratio (aOR) 5.2, 95% confidence interval (95% CI): 2.22-12.4, P = 0.0001], a history of stroke (aOR 3.7, 95% CI: 1.30-10.7, P = 0.015), and body mass index > 25 kg/m 2 (aOR 2.94, 95% CI: 1.4-6.18, P = 0.004). Myosteatosis was independently associated with mortality [adjusted hazard ratio (aHR) 2.12, 95% CI: 1.06-4.24, P = 0.033], as were cardiovascular disease (HR 2.06, 95% CI: 1.02-4.15, P = 0.043) and age (aHR 1.06, 95% CI: 1.03-1.09, P = 0.0003). Low SMI was not associated with mortality. Conclusions Myosteatosis, which was more prevalent than low skeletal muscle mass, might be an important prognostic marker in patients undergoing KT

Three-Year Outcomes in Kidney Transplant Recipients Switched From Calcineurin Inhibitor-Based Regimens to Belatacept as a Rescue Therapy

International audienceBackground: The long-term benefits of conversion from calcineurin inhibitors (CNIs) to belatacept in kidney transplant recipients (KTr) are poorly documented .Methods: A single-center retrospective work to study first-time CNI to belatacept conversion as a rescue therapy [eGFR <30 ml/min/1.73 m 2 , chronic histological lesions, or CNI-induced thrombotic microangiopathy (TMA)]. Patient and kidney allograft survivals, eGFR, severe adverse events, donor-specific antibodies (DSA), and histological data were recorded over 36 months after conversion.Results: We included N = 115 KTr. The leading cause for switching was chronic histological lesions with non-optimal eGFR (56.5%). Three years after conversion, patient, and death-censored kidney allograft survivals were 88% and 92%, respectively, eGFR increased significantly from 31.5 ± 17.5 to 36.7 ± 15.7 ml/min/1.73 m 2 ( p < 0.01), the rejection rate was 10.4%, OI incidence was 5.2 (2.9–7.6) per 100 person-years. Older age was associated with death, eGFR was not associated with death nor allograft loss. No patient developed dn DSA at M36 after conversion. CNI-induced TMA disappeared in all cases without eculizumab use. Microvascular inflammation and chronic lesions remained stable.Conclusion: Post-KT conversion from CNIs to belatacept, as rescue therapy, is safe and beneficial irrespective of the switch timing and could represent a good compromise facing organ shortage. Age and eGFR at conversion should be considered in the decision whether to switch

Hyperactivation of Alk induces neonatal lethality in knock-in AlkF1178L mice.

International audienceThe ALK (Anaplastic Lymphoma Kinase) gene encodes a tyrosine kinase receptor preferentially expressed in the central and peripheral nervous systems. A syndromic presentation associating congenital neuroblastoma with severe encephalopathy and an abnormal shape of the brainstem has been described in patients harbouring de novo germline F1174V and F1245V ALK mutations. Here, we investigated the phenotype of knock-in (KI) mice bearing the AlkF1178L mutation (F1174L in human). Although heterozygous KI mice did not reproduce the severe breathing and feeding difficulties observed in human patients, behavioral tests documented a reduced activity during dark phases and an increased anxiety of mutated mice. Matings of heterozygotes yielded the expected proportions of wild-type, heterozygotes and homozygotes at birth but a high neonatal lethality was noticed for homozygotes. We documented Alk expression in several motor nuclei of the brainstem involved in the control of sucking and swallowing. Evaluation of basic physiological functions 12 hours after birth revealed slightly more apneas but a dramatic reduced milk intake for homozygotes compared to control littermates. Overall, our data demonstrate that Alk activation above a critical threshold is not compatible with survival in mice, in agreement with the extremely severe phenotype of patients carrying aggressive de novo ALK germline mutations

Machine‐learning approach for prediction of pT3a upstaging and outcomes of localized renal cell carcinoma ( UroCCR ‐15)

Objectives To assess the impact of pathological upstaging from clinically localized to locally advanced pT3a on survival in patients with renal cell carcinoma (RCC), as well as the oncological safety of various surgical approaches in this setting, and to develop a machine‐learning‐based, contemporary, clinically relevant model for individual preoperative prediction of pT3a upstaging. Materials and Methods Clinical data from patients treated with either partial nephrectomy (PN) or radical nephrectomy (RN) for cT1/cT2a RCC from 2000 to 2019, included in the French multi‐institutional kidney cancer database UroCCR, were retrospectively analysed. Seven machine‐learning algorithms were applied to the cohort after a training/testing split to develop a predictive model for upstaging to pT3a. Survival curves for disease‐free survival (DFS) and overall survival (OS) rates were compared between PN and RN after G‐computation for pT3a tumours. Results A total of 4395 patients were included, among whom 667 patients (15%, 337 PN and 330 RN) had a pT3a‐upstaged RCC. The UroCCR‐15 predictive model presented an area under the receiver‐operating characteristic curve of 0.77. Survival analysis after adjustment for confounders showed no difference in DFS or OS for PN vs RN in pT3a tumours (DFS: hazard ratio [HR] 1.08, P = 0.7; OS: HR 1.03, P > 0.9). Conclusions Our study shows that machine‐learning technology can play a useful role in the evaluation and prognosis of upstaged RCC. In the context of incidental upstaging, PN does not compromise oncological outcomes, even for large tumour sizes

Prostatic artery embolisation versus medical treatment in patients with benign prostatic hyperplasia (PARTEM): a randomised, multicentre, open-label, phase 3, superiority trialResearch in context

Summary: Background: Prostatic artery embolisation (PAE) is a minimally invasive treatment of symptomatic benign prostatic hyperplasia (BPH). Our aim was to compare patient's symptoms improvement after PAE and medical treatment. Methods: A randomised, open-label, superiority trial was set in 10 French hospitals. Patients with bothersome lower urinary tract symptoms (LUTS) defined by International Prostatic Symptom Score (IPSS) > 11 and quality of life (QoL) > 3, and BPH ≥50 ml resistant to alpha-blocker monotherapy were randomly assigned (1:1) to PAE or Combined Therapy ([CT], oral dutasteride 0.5 mg/tamsulosin hydrochloride 0.4 mg per day). Randomisation was stratified by centre, IPSS and prostate volume with a minimisation procedure. The primary outcome was the 9-month IPSS change. Primary and safety analysis were done according to the intention-to-treat (ITT) principle among patients with an evaluable primary outcome. ClinicalTrials.gov Identifier: NCT02869971. Findings: Ninety patients were randomised from September 2016 to February 2020, and 44 and 43 patients assessed for primary endpoint in PAE and CT groups, respectively. The 9-month change of IPSS was −10.0 (95% confidence interval [CI]: −11.8 to −8.3) and −5.7 (95% CI: −7.5 to −3.8) in the PAE and CT groups, respectively. This reduction was significantly greater in the PAE group than in the CT group (−4.4 [95% CI: −6.9 to −1.9], p = 0.0008). The IIEF-15 score change was 8.2 (95% CI: 2.9–13.5) and −2.8 (95% CI: −8.4 to 2.8) in the PAE and CT groups, respectively. No treatment-related AE or hospitalisation was noticed. After 9 months, 5 and 18 patients had invasive prostate re-treatment in the PAE and CT group, respectively. Interpretation: In patients with BPH ≥50 ml and bothersome LUTS resistant to alpha-blocker monotherapy, PAE provides more urinary and sexual symptoms benefit than CT up to 24 months. Funding: French Ministry of Health and a complementary grant from Merit Medical