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Glucagon-Like Peptide-1 Receptor Agonists in Hidradenitis Suppurativa
No full textInternational audienceThis cohort study investigates the potential therapeutic benefits of glucagon-like peptide-1 receptor agonists in patients with hidradenitis suppurativa
Targeting Nav1.8 with the nonopioid antagonist suzetrigine in analgesia: cause for optimism?
No full textInternational audienceThe opioid crisis has prompted an urgent search for nonopioid analgesics for both acute and chronic pain. Among these, sodium channel antagonists, particularly those targeting Nav1.7 and Nav1.8, have emerged as potential pain management solutions. Recent large trials have shown some efficacy of the new Nav1.8 allosteric inhibitor suzetrigine in acute postoperative pain, and ongoing studies are investigating its potential for painful diabetic neuropathy. If efficacy is confirmed, this type of drug might fill a significant gap in the treatment of acute and chronic pain, offering a safer alternative to opioids and marking the advent of a new class of nonopioid analgesics
Open, Laparoscopic or Robotic Approach for Intrahepatic Cholangiocarcinoma? A "Basket Study" from AFC-iCC-2009, AFC-LLR-2018, PRS-2019 and FRIES-ACHBT Cohorts
No full textInternational audienc
Complex System Exploration with Interactive Human Guidance
No full textInternational audienceThe diversity of patterns that emerge from complex systems motivates their use for scientific or artistic purposes. When exploring these systems, the challenges faced are the size of the parameter space and the strongly non-linear mapping between parameters and emerging patterns. In addition, artists and scientists who explore complex systems do so with an expectation of particular patterns. Taking these expectations into account adds a new set of challenges, which the exploration process must address. We provide design choices and their implementation to address these challenges; enabling the maximization of the diversity of patterns discovered in the user's region of interest -- which we call the constrained diversity -- in a sample-efficient manner. The region of interest is expressed in the form of explicit constraints. These constraints are formulated by the user in a system-agnostic way, and their addition enables interactive system exploration leading to constrained diversity, while maintaining global diversity
OXYTOCIN ADMINISTRATION DURING SPONTANEOUS LABOUR AND POSTPARTUM BLOOD LOSS: A FRENCH MULTICENTRE COHORT
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Sphingolipids in Extracellular Vesicles Released From the Skeletal Muscle Plasma Membrane Control Muscle Stem Cell Fate During Muscle Regeneration
No full textInternational audienceExtracellular vesicles (EVs) represent a cytokine-independent pathway though which skeletal muscle (SkM) cells influence the fate of neighbouring cells, thereby regulating SkM metabolic homeostasis and regeneration. Although SkM-EVs are increasingly being explored as a therapeutic strategy to enhance muscle regeneration or to induce the myogenic differentiation of induced pluripotent stem cells (iPSCs), the mechanisms governing their release from muscle cells remain poorly described. Moreover, because muscle regeneration involves a tightly regulated inflammatory response it also important to determine how inflammation alters SkM-EV cargo and function in order to design more effective EV-based therapies. To address this knowledge gap, we isolated and characterized the large and small EVs (lEVs, sEVs) released from SkM cells under basal conditions and in response to TNF-α, a well-established inflammatory mediator elevated in both acute muscle injury and chronic inflammatory conditions such as type 2 diabetes. We then evaluated the regenerative roles of these EV subtypes in vivo using a mouse model of cardiotoxin-induced muscle injury, with a specific focus on their bioactive sphingolipid content. Using transmission, scanning or cryo-electron microscopy, lipidomic profiling and an adenoviral construct to express labelled CD63 in myotubes, we demonstrated that SkM cells release both sEVs and lEVs primarily from the plasma membrane. Notably, sEVs were generated from specialized membrane folds enriched in the EV markers ALIX (ALG-2 interacting protein X) and TSG101, as well as lipid raft-associated lipids. During regeneration, sEVs promoted M1 macrophage polarization and migration and muscle stem cell (MuSC) differentiation, thereby accelerating muscle repair. In contrast, lEVs inhibited and promoted MuSC proliferation and impaired the transition from the pro-inflammatory to the anti-inflammatory response, an essential step for promoting MuSC differentiation. Treatment of isolated muscle fibres with SkM-EVs revealed that the distinct effects of sEVs and lEVs on MuSC behaviour and macrophage phenotype could be largely explained by differences in their lipid composition, particularly the ratio of sphingosine-1-phosphate (S1P) subspecies. However, TNF-α exposure altered these ratios in sEVs and impaired their regenerative functions on MuSC and their effect on macrophage migration and polarization. These results demonstrate for the first time the importance of the sphingolipid content of EVs released by skeletal muscle in their regenerative function within muscle tissue, largely explained by their role as carriers of different subspecies of sphingosine-1-phosphate. This suggests that modulating the sphingolipid composition of EVs could be a viable strategy to enhance the regenerative potential of muscle tissue in addition to therapeutic interventions
No evidence of an effect of the M184I/V on the doravirine/lamivudine/tenofovir switch efficacy in people living with HIV
No full textInternational audienceObjectives: The effect of the M184I/V mutation on the rate of virological failure (VF) in people living with HIV (PLWHIV) with plasma HIV RNA viral load (VL) <50 copies/mL switching to a triple-therapy regimen of doravirine+lamivudine+ tenofovir or abacavir has not been evaluated. Design: A retrospective national study of antiretroviral-experienced PLWHIV who were switched to a doravirine plus lamivudine and abacavir or tenofovir regimen in the context of maintenance (VL<50 copies/mL) was conducted. Virological failure (VF) was characterized by either two consecutive plasma viral loads (VL) ≥ 50 copies/mL or a single VL ≥ 200 copies/mL. Viral blip (VB) was defined as an isolated VL 50_200 copies/mL at any time up to month 6 after switching to the doravirine-containing regimen. Results: Among the 338 PLWHIV, doravirine was mainly associated with tenofovir+lamivudine (311/338, 92.0%). Of these, 45 had a M184I/V mutation before switching. VF at M6 was 14.0% and 17.8% in the absence and presence of M184I/V, respectively, with an adjusted odds ratio (aOR) of 2.409, 95%CI 0.574–10.113, p=0.21. The risk of VF at M6 was associated with the level of zenith plasma HIV VL, with an aOR of 1.646, 95% CI 1.163–2.328, p = 0.0049, per additional log 10 unit. The proportion of VB at M6 was 2.4% and 6.7% in PLWHIV in the absence and presence of M184I/V, respectively, with an aOR of 0.818, 95%CI 0.187–3.587, p = 0.7897. Conclusions: Among PLWHIV with antiretroviral experience, there was no evidence that switching to doravirine + lamivudine plus tenofovir affected short-term treatment response in individuals harboring HIV M184I/V mutations
Influenza vaccine effectiveness and genetic diversity: insights from end-of-season community surveillance, France, 2024-2025
No full textInternational audienceInfluenza 2024-2025 season in France was characterized by prolonged duration, unusual co-circulation of all three viruses (A(H1N1)pdm09, A(H3N2), B/Victoria) with several subclades, and substantial healthcare impact. We aimed to investigate the impact of influenza genetic diversity on vaccine effectiveness (VE).A test-negative design study was conducted to estimate VE in a large cohort from the RELAB network of community-based laboratories (n = 77,704 patients). A subset of sequenced samples (n = 2,119 patients) allowed VE estimation for several clades and subclades as well as comparison of subclade distribution by vaccination status.Vaccine coverage was 45% in patients aged 65 years and older (65+). VE based on PCR-confirmed infections was 44% (95% CI: 41-48%) and lower in 65+ individuals, at 25% (95% CI:18-31%) especially for type A virus (23%; 95% CI: 13-32%) compared to type B virus (57%; 95% CI: 35-72%).Sequencing-confirmed VE among individuals vaccinated 15 days to 3 months prior testing, was 41% (95% CI: 14-60%) for A(H1N1)pdm09 and 47% (95% CI: 21-64%) for its main subclade 5a.2a(C.1.9.3); A(H3N2) estimate was 30% (95% CI:5-48%) and 31% (95% CI:4-50%) for 2a.3a.1(J.2) sublclade. The emerging A(H1N1)pdm09 5a.2a.1 (D.3) subclade was significantly more frequent among vaccinated individuals compared to unvaccinated.The low vaccine coverage combined with the notably low effectiveness against A(H3N2) and for type A in elderly may have contributed to the high influenza activity this season. The emergence of A(H1N1)pdm09 5a.2a.1 (D.3) raises uncertainty and requires surveillance.</p
Navigated versus non‐navigated total knee arthroplasty: A large single‐implant cohort analysis of clinical outcomes and survivorship
No full textInternational audiencePurpose The aim of this study was to compare implant survival, clinical outcomes and radiographic alignment between navigated and non‐navigated total knee arthroplasty (TKA) performed with a single implant system. Methods A retrospective multicenter analysis of prospectively collected data from 6078 TKAs performed for primary osteoarthritis using a single implant system was performed. Procedures were divided into two groups: navigated ( n = 3602) and non‐navigated ( n = 2476). The primary outcome was implant survival. Secondary outcomes included re‐intervention rates, patient‐reported outcomes measures (PROMs, International Knee Society scores), and range of motion. Results Five‐year implant survival was similar between the non‐navigated (98.9%; 95% confidence interval [CI], 98.2%–99.3%) and navigated (98.3%; 95% CI, 97.6%–98.8%) groups ( p = 0.505). After adjustment for potential confounders, navigated procedures showed a slightly higher risk of surgical reintervention excluding infection (hazard ratio 1.42, 95% CI: 1.02–1.96, p = 0.036). PROM analyses were restricted to patients with both baseline and 5‐year questionnaires ( n = 470). The improvement of patient‐reported functional outcomes at 5 years was not significantly different between groups ( p = 0.893 after adjustment for potential confounders). Conclusions Navigation was equivalent to conventional instrumentation TKA with respect to implant survival. After adjusting for confounders and excluding septic revisions, navigated procedures showed a slightly higher reoperation risk. No significant advantage in functional outcomes was observed at mid‐term follow‐up. These findings do not support a clear clinical benefit for routine use of navigation in this setting. Level of Evidence Level III, retrospective comparative study