Hôpital Saint-Vincent-de-Paul

HIV-1 transmission depends on the structure and immune cell composition of mucosal epithelia. Transmission mechanisms involve direct infection of CD4+ T-cells or macrophages, and indirect viral transfer to CD4+ T-cells from Langerhans cells (LCs) or dendritic cells (DCs). LCs-mediated HIV-1 transfer is inhibited by the neuropeptide calcitonin gene-related peptide (CGRP), due to upstream activation in LCs of the transient receptor potential vanilloid 1 (TRPV1) ion channel. Herein, we investigated the potential anti-HIV-1 roles of cannabidiol (CBD), the non-psychoactive compound in Cannabis sativa, which has well-described immunosuppressive functions and principally activates TRPV1 over its cognate CB1 and CB2 receptors. We found that via TRPV1 activation, CBD inhibits in-vitro infection of mucosal HIV-1 cellular targets. Specifically, CBD inhibits macrophages HIV-1 direct infection, and CD4+ T-cells HIV-1 direct infection or upon viral transfer from LCs and DCs. Moreover, inhibition of macrophages infection and LCs-mediated HIV-1 transfer involves secreted CGRP. Importantly, CBD also blocks early events of HIV-1 transmission ex-vivo in human inner foreskin tissues, namely formation of epidermal LC-T-cell conjugates and resulting CD4+ T-cells infection. Altogether, CBD inhibits infection of all HIV-1 cellular targets, and commercial CBD products might be repositioned as novel HIV-1 pre-exposure prophylaxis, namely CBD PrEP.

Stomal hyperflow, a frequent complication of ileostomy, is associated with high morbidity and mortality, particularly when linked to intestinal failure. This situation, especially when conventional treatments fail, often results in a poor prognosis for the patient.In this case report, we present the history of a patient suffering from stomal hyperflow with intestinal failure, in the context of short small bowel syndrome following multifocal venous mesenteric ischaemia. In a critical condition at the time of admission to our hospital, he was able to benefit from The Insides® System, a chyme reinstillation device, with the aim of improving his general condition and ultimately enabling surgical restoration of digestive continuity.This system led to clinical and biological improvement, allowing surgery to restore continuity. However, certain difficulties related to the use of the device were also encountered during management.

In women with multiple sclerosis (MS), disease-modifying therapy (DMT) management during pregnancy might impact relapse risk. To estimate the effect of DMT management during pregnancy on MS relapse rate and compare different therapeutic strategies. This was a multicenter retrospective cohort study using data from January 1990 to December 2023. Data were extracted in December 2023 from the French MS registry. Among 52 955 women in the registry, we included pregnancies identified through childbirths in patients with relapsing-onset MS who were monitored for at least 18 months before delivery and 9 months after. Pregnancies occurring less than 18 months apart or with missing month of birth were excluded. Mediation analysis was used to estimate the total, direct, and indirect (mediated by DMT management) effects of pregnancy. Different therapeutic strategies were compared: DMT interruption, switching to or maintaining interferon β or glatiramer acetate, switching to or maintaining natalizumab until the third trimester, and switching to or maintaining intravenous anti-CD20 and interrupting it 3 months before conception. The primary outcome was the annualized relapse rate (ARR) during the preconception, gestation, and postpartum periods. Within a causal inference framework, counterfactual ARRs were estimated using longitudinal g-computation, combining a random forest algorithm for predicting DMTs, and a mixed-effects Poisson model for relapses. We included 6341 pregnancies occurring in 4998 women (mean [SD] age at conception, 31.5 [4.5] years). DMT management during pregnancy significantly increased ARR during gestation (causal rate ratio [cRR], 1.13; 95% CI, 1.06-1.22) and postpartum (cRR, 1.08; 95% CI, 1.01-1.16) periods. This led to a deleterious total effect of pregnancy on ARR, particularly in women receiving natalizumab before pregnancy with prolonged interruption (ie, interruption before the second trimester or resumption more than 3 months after delivery; cRR, 2.18; 95% CI, 1.76-2.69), and in women receiving fingolimod (cRR, 2.15; 95% CI, 1.60-2.93). Compared to DMT interruption, anti-CD20 strategy was the most effective (cRR, 0.38; 95% CI, 0.25-0.52), followed by the natalizumab strategy with short interruption (cRR, 0.80; 95% CI, 0.71-0.90), whereas interferon β (cRR, 0.93; 95% CI, 0.86-0.99) and glatiramer acetate strategies (cRR, 0.91; 95% CI, 0.84-0.99) were less effective. In this study, DMT management during pregnancy significantly increased relapse risk, particularly in patients receiving natalizumab with prolonged interruption or fingolimod. The strategy based on the use of anti-CD20 before pregnancy was the most effective to mitigate this risk.

H. Ghesquières and C. Thieblemont equally contributing author. Introduction: Marginal zone lymphomas (MZL) are traditionally categorized into three subtypes: extranodal (EMZL), splenic (SMZL), and nodal (NMZL). Current histological classifications (ICC and WHO) identify monoclonal B-cell lymphocytosis of MZL type (MBL-MZ) as a precursor state, and separate cutaneous MZL as a distinct entity—but fail to provide a clinically relevant classification integrating all disease sites. The FIL NF10 study proposed a fourth subtype—disseminated MZL—encompassing biologically diverse conditions. To refine MZL classification, we developed RECLASS, an algorithm-based system harmonizing histological and clinical criteria. Methods: The RECLASS system acknowledges MBL-MZ (i.e., lymphocytosis ± bone marrow involvement, in the absence of lymphadenopathy or any organ involvement) and primary cutaneous MZL (i.e., with no evidence of extracutaneous disease) as distinct entities and disregards blood and bone marrow involvement in subtyping. Classification follows these hierarchical rules: (1) If any mucosal site is involved: EMZL; (2) If no mucosal site is involved and spleen is involved (enlargement or focal lesion): SMZL; (3) If neither condition is met: NMZL. Leveraging data from the REALYSA French prospective cohort (all MZL cases between 12/2018 and 12/2022), we analyzed subtype distribution and disease dissemination according to (a) treating physicians from the REALYSA database (i.e., as per WHO2016 classification), (b) the FIL and (c) the RECLASS classifying and staging system. Results: Among 302 patients, the number of EMZL cases varied across classifications (140 physicians/WHO2016 versus 109 FIL vs. 175 RECLASS). FIL's unique “disseminated” category (115 patients) was reclassified within EMZL, SMZL, or NMZL under RECLASS. Therefore, SMZL cases increased under RECLASS (40 FIL vs. 67 RECLASS), as did NMZL cases (46 FIL vs. 56 RECLASS). RECLASS identified only one case of primary cutaneous MZL and 11 of MBL-MZ—these subtypes not being managed by hematologists unless systemic therapy is needed. Dissemination was reported in 219 (73%) cases by local physicians, but only in 113 (FIL, 37%) and 94 (RECLASS, 31%) patients based on structured classification. All 14 patients with ENT involvement were classified as EMZL in RECLASS, and were localized disease. Conclusion: RECLASS introduces a refined classification system for MZL, aligning with histological criteria while improving clinical relevance. Validation in independent international cohorts is ongoing. Research funding declaration: LYSARC—data collection, data quality check and data management Keywords: pathology and classification of lymphomas; extranodal non-Hodgkin lymphoma; indolent non-Hodgkin lymphoma No potential sources of conflict of interest.

Nitrous oxide (N2O) was originally used for medical and industrial purposes, but its recreational use has dramatically increased, raising a major global public health concern. Chronic inhalation is associated with neurological, metabolic, and psychiatric complications, as well as addiction. To address these challenges, the PROTOSIDE network was developed to provide a multidisciplinary approach to management and prevention. This initiative relies on competence centers integrating specialists in emergency medicine, neurology, clinical biochemistry, and addiction medicine. PROTOSIDE aims to standardize diagnostic protocols, optimize patient care pathways, and strengthen addictovigilance. A strong emphasis is placed on prevention, including awareness campaigns and collaboration with healthcare professionals and educators. By facilitating access to advanced biochemical analyses (homocysteine, methylmalonic acid) and promoting international guidelines, PROTOSIDE represents an innovative model for a global response to N2O misuse. This integrated approach enhances clinical management, reduces complications, and harmonizes public health strategies.