The acid sphingomyelinase/ceramide system in COVID-19.

Acid sphingomyelinase (ASM) cleaves sphingomyelin into the highly lipophilic ceramide, which forms large gel-like rafts/platforms in the plasma membrane. We showed that SARS-CoV-2 uses these platforms for cell entry. Lowering the amount of ceramide or ceramide blockade due to inhibitors of ASM, genetic downregulation of ASM, anti-ceramide antibodies or degradation by neutral ceramidase protected against infection with SARS-CoV-2.

Burden of liver disease progression in hospitalized patients with type 2 diabetes mellitus.

Background & Aims: There are uncertainties regarding the burden of liver disease in patients with type 2 diabetes (T2D). Thus, we aimed to quantify the burden of liver disease, identify risk factors, and estimate attributable risks in patients with T2D.

Methods: We measured adjusted hazard ratios of liver disease progression to hepatocellular carcinoma and/or decompensated cirrhosis in a 2010-2020 retrospective, bicentric, longitudinal, cohort of 52,066 hospitalized patients with T2D.

Changes in benzodiazepine use in the French general population after November 2015 terrorist attacks in Paris: an interrupted time series analysis of the national CONSTANCES cohort.

Objectives: To determine whether the terrorist attacks occurring in Paris on November 2015 have changed benzodiazepine use in the French population.

Design: Interrupted time series analysis.

Setting: National population-based cohort.

Extended Anticoagulant Treatment with Full- or Reduced-Dose Apixaban in Patients with Cancer-Associated Venous Thromboembolism: Rationale and Design of the API-CAT Study.

Cancer-associated thrombosis (CT) is associated with a high risk of recurrent venous thromboembolic (VTE) events that require extended anticoagulation in patients with active cancer, putting them at risk of bleeding. The aim of the API-CAT study (NCT03692065) is to assess whether a reduced-dose regimen of apixaban (2.5 mg twice daily [bid]) is noninferior to a full-dose regimen of apixaban (5 mg bid) for the prevention of recurrent VTE in patients with active cancer who have completed ≥6 months of anticoagulant therapy for a documented index event of proximal deep-vein thrombosis and/or pulmonary embolism.

Sociodemographic and Clinical Characteristics of Vapers Using E-Cigarettes Exclusively: The French Vapoquid Study.

Electronic cigarettes are increasingly being used as smoking cessation aids. Most studies assess the dual use of e-cigarettes and traditional cigarettes, but there remains a paucity of literature concerning individuals who use e-cigarettes exclusively. : The aim of this study is to examine the sociodemographic and clinical characteristics of exclusive e-cigarette users, and consider their willingness to quit e-cigarette use.

Mechanical loading activates the YAP/TAZ pathway and chemokine expression in the MLO-Y4 osteocyte-like cell line.

Osteocytes are mechanosensitive cells that control bone remodeling in response to mechanical loading. To date, specific signaling pathways modulated by mechanical loading in osteocytes are not well understood. Yes associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ), the main effectors of the Hippo pathway, are reported to play a role in mechanotransduction and during osteoblastogenesis.

Prenatal care providers' perceptions of the SARS-Cov-2 vaccine for themselves and for pregnant women.

Background: Prenatal care providers will play an important role in the acceptance of SARS-Cov-2 vaccination for pregnant women.

Objective: To determine the perceptions of French prenatal care providers: midwives, general practitioners (GPs) and obstetricians and gynaecologists (Ob-Gyn) regarding SARS-CoV-2 vaccination during pregnancy.

Study Design: An anonymous online survey was sent to members of French professional societies representing prenatal practitioners.

Therapeutic pipeline for individuals with cystic fibrosis with mutations nonresponsive to current cystic fibrosis transmembrane conductance regulator modulators.

Purpose Of Review: Cystic fibrosis is a severe autosomal recessive disorder caused by mutations in the cystic fibrosis transmembrane conductance regulator gene (CFTR) encoding the CFTR protein, a chloride channel expressed in many epithelial cells. New drugs called CFTR modulators aim at restoring the CFTR protein function and they will benefit most of the patients with cystic fibrosis in the near future. However, more than 10% of CFTR mutations do not produce any CFTR protein for CFTR modulators to act upon, and the purpose of this review is to provide an overview of different approaches pursued to treat patients bearing mutations nonresponsive to CFTR modulators.

Sweat Chloride Testing and Nasal Potential Difference (NPD) Are Primary Outcome Parameters in Treatment with Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Modulators.

With the advent of CFTR modulators, surrogate outcome parameters that accurately quantify the improvement in CFTR activity are needed. In vivo biomarkers that reflect CFTR ion transport and can serve as outcomes in the treatment of CFTR modulators are the sweat Cl test (SCT), the nasal potential difference (NPD) measurement or the intestinal current measurement (ICM). This review focus on the SCT and NPD.

Triple Therapy for Cystic Fibrosis -Gating and -Residual Function Genotypes.

Background: Elexacaftor-tezacaftor-ivacaftor is a small-molecule cystic fibrosis transmembrane conductance regulator (CFTR) modulator regimen shown to be efficacious in patients with at least one allele, which indicates that this combination can modulate a single allele. In patients whose other allele contains a gating or residual function mutation that is already effectively treated with previous CFTR modulators (ivacaftor or tezacaftor-ivacaftor), the potential for additional benefit from restoring Phe508del CFTR protein function is unclear.

Methods: We conducted a phase 3, double-blind, randomized, active-controlled trial involving patients 12 years of age or older with cystic fibrosis and -gating or -residual function genotypes.

LPS-Macrophages Alleviate the Outcome of Graft--Host Disease Without Aggravating Lymphoma Growth in Mice.

Despite significant therapeutic advances, graft--host disease (GvHD) remains the main life-threatening complication following allogeneic hematopoietic stem cell transplantation. The pathogenesis of GvHD is dominated by a dysregulated allogeneic immune response that drives fibrosis and autoimmunity in chronic forms. A multitude of cell therapy approaches, including infusion of myeloid cells, has been proposed to prevent GvHD through tolerance induction but yielded variable results.

MAIT cell alterations in adults with recent-onset and long-term type 1 diabetes.

Aims/hypothesis: Mucosal-associated invariant T (MAIT) cells are innate-like T lymphocytes expressing an αβ T cell antigen receptor that recognises the MHC-related 1 molecule. MAIT cells are altered in children at risk for and with type 1 diabetes, and mouse model studies have shown MAIT cell involvement in type 1 diabetes development. Since several studies support heterogeneity in type 1 diabetes physiopathology according to the age of individuals, we investigated whether MAIT cells were altered in adults with type 1 diabetes.

Intervertebral disc therapies for non-specific chronic low back pain: a systematic review and meta-analysis.

Objectives: We aim to evaluate the benefits and harms of intervertebral disc therapies (IDTs) in people with non-specific chronic low back pain (NScLBP).

Methods: We conducted a systematic review and meta-analysis of randomized trials of IDTs placebo interventions, active comparators or usual care. EMBASE, MEDLINE, CENTRAL and CINHAL databases and conference abstracts were searched from inception to June 2020.

10 years of CEMARA database in the AnDDI-Rares network: a unique resource facilitating research and epidemiology in developmental disorders in France.

Background: In France, the Ministry of Health has implemented a comprehensive program for rare diseases (RD) that includes an epidemiological program as well as the establishment of expert centers for the clinical care of patients with RD. Since 2007, most of these centers have entered the data for patients with developmental disorders into the CEMARA population-based registry, a national online data repository for all rare diseases. Through the CEMARA web portal, descriptive demographic data, clinical data, and the chronology of medical follow-up can be obtained for each center.

Impact of public health measures on the post-COVID-19 respiratory syncytial virus epidemics in France.

Since the beginning of the COVID-19 pandemic, other respiratory illnesses decreased worldwide. This study described the consequences of public health measures on respiratory syncytial virus (RSV) severe infections in France, where an interseasonal resurgence of RSV occurred recently. All patients admitted to Necker Hospital (Paris) between August 2018 and April 2021 with a diagnosis of RSV-associated acute lung respiratory infection (ALRI) were enrolled.

Accuracy of saliva and nasopharyngeal sampling for detection of SARS-CoV-2 in community screening: a multicentric cohort study.

Nasopharyngeal sampling for nucleic acid amplification testing (NAAT) is the standard diagnostic test of coronavirus disease 2019. Our objectives were to assess, in real-life conditions, the diagnostic accuracy of a nasopharyngeal point-of-care antigen (Ag) test and of saliva NAAT for detection of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in ambulatory care. This was a prospective cohort study from 19 October through 18 December 2020 in two community COVID-19 screening centers in Paris, France.

French recommendations for the management of systemic sclerosis.

Systemic sclerosis (SSc) is a generalized disease of the connective tissue, arterioles, and microvessels, characterized by the appearance of fibrosis and vascular obliteration. There are two main phenotypical forms of SSc: a diffuse cutaneous form that extends towards the proximal region of the limbs and/or torso, and a limited cutaneous form where the cutaneous sclerosis only affects the extremities of the limbs (without passing beyond the elbows and knees). There also exists in less than 10% of cases forms that never involve the skin.