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Precut disc of lyophilized amniotic membrane for recurrent full thickness macular hole management
No full textInternational audienc
EEG–Metabolic Coupling and Time Limit at VO2max During Constant-Load Exercise
No full textInternational audienceBackground: Exercise duration at maximum oxygen uptake (V˙O2max) appears to be influenced not only by metabolic factors but also by the interplay between brain dynamics and ventilatory regulation. This study examined how cortical activity, assessed via electroencephalography (EEG), relates to performance and acute fatigue regulation during a constant-load cycling test. We hypothesized that oscillatory activity in the theta, alpha, and beta bands would be associated with ventilatory coordination and endurance capacity. Methods: Thirty trained participants performed a cycling test to exhaustion at 90% maximal aerobic power. EEG and gas exchange were continuously recorded; ratings of perceived exertion were assessed immediately after exhaustion. Results: Beta power was negatively correlated with time spent at V˙O2max (r = −0.542, p = 0.002). Theta and Alpha power alone showed no direct associations with endurance, but EEG–metabolic ratios revealed significant correlations. Specifically, the time to reach V˙O2max correlated with Alpha/V˙O2 (p < 0.001), Alpha/V˙CO2 (p < 0.001), and Beta/V˙CO2 (p = 0.002). The time spent at V˙O2max correlated with Theta/V˙O2 (p = 0.002) and Theta/V˙CO2 (p < 0.001). The time-to-exhaustion was correlated with Theta/V˙CO2 (p < 0.001) and Alpha/V˙CO2 (p < 0.001). Conclusions: These findings indicate that cortical oscillations were associated with different aspects of acute fatigue regulation. Beta activity was associated with fatigue-related neural strain, whereas Theta and Alpha bands, when normalized to metabolic load, were consistent with a role in ventilatory coordination and motor control. EEG–metabolic ratios may provide exploratory indicators of brain–metabolism interplay during high-intensity exercise and could help guide future brain-body interactions in endurance performance
Determinants of successful completion and short-term benefits associated with temporary alcohol abstinence during Dry January in France: A prospective cohort study
No full textInternational audienceObjective: Temporary alcohol abstinence campaigns (TAAC), such as Dry January, aim to encourage behavioural change in the general population. Despite its popularity, a comprehensive evaluation of the French version has not yet been conducted. This prospective study aimed to identify characteristics associated with successful completion of the challenge (i.e., remaining alcohol-free throughout January), and to assess improvements in drinking refusal self-efficacy, sleep quality, and mental and physical health.Methods: A sample of 2123 French adults participating in Dry January 2024 completed both a baseline and a one-month follow-up questionnaire online. A broad range of variables were assessed, including demographic and contextual factors, alcohol use patterns and motives, drinking refusal self-efficacy, and health-related outcomes.Results: Key factors positively associated with successful completion included previous participation, registration, and higher baseline self-efficacy in resisting alcohol in social situations. Among registrants, greater engagement with support emails significantly increased the likelihood of abstinence. In contrast, smoking and identifying one's drinking as excessive were linked to lower odds of completion. The campaign was associated with improvements in drinking refusal self-efficacy, mental well-being, sleep quality, and physical health - particularly among participants who completed the full month without alcohol.Conclusions: This study offers the first evaluation of the French version of Dry January, highlighting the factors influencing challenge completion and short-term benefits of participation. The findings add support to the value of TAAC as scalable and impactful public health tools and underscore the importance of tailored support strategies to maximize participant success and behavioural change
Safety and efficacy of a dexamethasone-sparing regimen with daratumumab and lenalidomide in patients with frailty and newly diagnosed multiple myeloma (IFM2017-03): a phase 3, open-label, multicentre, randomised, controlled trial
No full textInternational audienceBACKGROUND: Patients with frailty and newly diagnosed multiple myeloma have worse outcomes due to higher rates of adverse events (AEs) and treatment discontinuation. This study evaluated a dexamethasone-sparing regimen of daratumumab plus lenalidomide versus lenalidomide plus dexamethasone in frail patients with newly diagnosed multiple myeloma.METHODS: In this prospective, randomised, open-label trial, conducted at 61 active Intergroup Francophone of Myeloma centres, patients aged 65 years or older with newly diagnosed multiple myeloma and an Eastern Cooperative Oncology Group proxy frailty score of 2 or more were randomly assigned 2:1 to receive daratumumab (1800 mg subcutaneously) plus oral lenalidomide (25 mg daily for 21 days of a 28 day cycle) and dexamethasone (20mg weekly) for two cycles (dexamethasone-sparing group) or lenalidomide (25 mg daily) and oral dexamethasone (20 mg weekly; control group), with stratification by International Staging System, age, and centre. The primary endpoint was progression-free survival. Efficacy was assessed in the intention-to-treat population and safety was assessed in all patients exposed to at least one dose of randomised intervention. This trial is registered with ClinicalTrials.gov, NCT03993912, and is complete.FINDINGS: From Oct 18, 2019 to July 20, 2021, 335 patients were screened, of whom 295 patients were randomly assigned (200 to lenalidomide plus daratumumab, 95 to lenalidomide plus dexamethasone). The median age was 81 years (IQR 77-84), with 180 (61%) aged older than 80 years, and 151 (51%) patients were female and 144 (49%) were male. Median follow-up was 46·3 months (IQR 46·0-52·7). Median progression-free survival was 53·4 months (95% CI 35·3-not reached) in the dexamethasone-sparing group versus 22·5 months (16·5-39·0) in the control group (hazard ratio [HR] 0·51, 95% CI 0·37-0·70, p<0·0001). The most common grade 3-5 AEs were neutropenia (110 [55%] of 200 patients in the dexamethasone-sparing group vs 23 [24%] of 95 patients in the control group), and infection (38 [19%] vs 20 [21%]). Serious adverse events occurred in 126 patients (63%) in the dexamethasone-sparing group and 66 patients (69%) in the control group. AEs leading to death occurred in 23 patients (12%) in the dexamethasone-sparing group and 12 patients (13%) in the control group, with 4 (2%) and 2 (2%) grade 5 treatment-emergent adverse events, respectively.INTERPRETATION: In the IFM2017-03 trial, use of lenalidomide plus daratumumab, with dexamethasone limited to the first 2 treatment cycles, reduced the risk of progression or death compared with lenalidomide plus dexamethasone, with no additional safety concerns. Lenalidomide plus daratumumab could therefore be considered as a treatment option for older patients with frailty and newly diagnosed multiple myeloma. FUNDING: The study was funded by Johnson and Johnson
Insulin receptor variants: Extending the traditional Mendelian spectrum
No full textInternational audiencePurpose: INSR encodes the insulin receptor, the essential entrainer of growth and metabolism to nutritional cues. INSR variants cause a spectrum of monogenic insulin resistance (IR) syndromes, namely, type A insulin resistance, Rabson-Mendenhall, and Donohue syndromes. However, to our knowledge, no large cohort studies focused on variant classification and its diagnostic value have been described.Methods: This multicentric cohort study included 73 patients carrying INSR variants, referred for IR by 52 centers from 6 countries. Variants were classified using new bioinformatic tools relying on different prediction mechanisms and the American College of Medical Genetics and Genomics guidelines.Results: Besides expanding the INSR mutational spectrum, this study suggested a semidominant inheritance in several Donohue/Rabson-Mendenhall syndrome families. Questioning strictly Mendelian inheritance, heterozygous loss-of-function (LoF) variants were mostly found in overweight patients, with a higher LoF frequency in IR patients than in the general population (odds ratio 5.77). Diagnostic challenges arose when trying to refine classification criteria for variants of uncertain significance. Among the variant effect predictors assessed, MISTIC and AlphaMissense outperformed REVEL.Conclusion: The spectrum of INSR-related disorders extends beyond traditional entities. Heterozygous INSR LoF variants may increase IR susceptibility. International collaboration and functional assays are needed to drive precision medicine forward
Monocyte HLA-DR expression in septic shock patients: insights from a 20-year real-world cohort of 1023 cases
No full textInternational audiencePurpose: Septic patients simultaneously experience hyperinflammation and immunosuppression, the latter driving ICU-acquired infections, prolonged stays in ICU, and increased mortality. As immunostimulant therapies enter clinical trials, effective stratification is critical to identify patients with the most profound immune dysfunction. Monocyte HLA-DR expression (mHLA-DR) has emerged as the most reliable and actionable biomarker of sepsis-induced immunosuppression.Methods: We conducted a real-world, 20-year cohort study of 1023 septic shock patients, measuring mHLA-DR by standardized flow cytometry during the first week of ICU admission. Primary outcomes included day-28 and day-90 mortality, and ICU-acquired infections.Results: Low mHLA-DR (< 8000 AB/C, a threshold already used in phase II trials) was significantly associated with increased mortality and ICU-acquired infections. This association held across static and dynamic measures, multivariate analyses, Kaplan-Meier survival curves, and trajectory clustering (K-means).Conclusions: This large real-world study confirms that mHLA-DR is a robust enrichment biomarker for identifying the most immunosuppressed septic shock patients at higher risk of adverse outcomes. Importantly, time-course analysis suggests that early immune downregulation may represent a physiological adaptation, while delayed and persistent immunosuppression is associated with worse outcomes. Early single time-point measurements may fail to identify patients who are unlikely to develop delayed immunosuppression. Tracking mHLA-DR trajectories after the initial ICU days is essential for detecting persistent immune dysfunction and selecting patients in case of immunostimulant approaches
Investigation of whether renal tumours with caval thrombi induce particular risks: a multicentre study (UroCCR‐174 CAVORISK)
No full textInternational audienceObjective: To compare outcomes of nephrectomy for left-sided (n = 70) vs right-sided (n = 118) renal tumours with caval thrombi.Methods: In this retrospective analysis (June 2008-February 2023), we evaluated peri-operative variables, 30-day complications, estimated glomerular filtration rate (eGFR), and survival rates.Results: Patients in the left-sided renal tumour group experienced significantly longer operating times (240 vs 193 min; P < 0.001), greater blood loss (1700 vs 1000 mL, P = 0.042), and more complications (53% vs 35%, P = 0.015). Postoperative renal function was worse in the left-sided vs the right-sided renal tumour group, with lower immediate postoperative eGFR (P = 0.035) and a higher dialysis rate (17% vs 6.8%, P = 0.026). However, overall survival and recurrence-free survival were similar (P = 0.8 and P = 0.43, respectively).Conclusions: Left-sided renal tumours with caval thrombi present a higher risk of complications and acute kidney injury requiring dialysis, potentially due to left renal vein ischaemia during surgery and anatomical proximity to the superior mesenteric artery. Thorough preoperative planning and limited clamping time are essential
An optimized model for HEV infection in the HepaRG cell line
No full textHepatitis E virus (HEV) causes acute hepatitis that can progress to fulminant or chronic hepatitis. For decades, the lack of a pertinent and robust cell culture system for HEV has delayed our understanding on this hepatotropic virus. HepaRG cells are one of the few hepatocyte-derived cell lines able to replicate HEV. These cells can differentiate (dHepaRG) into hepatocytes and cholangiocytes upon treatment with dimethyl sulfoxyde (DMSO) and are very relevant to study interactions between pathogens and hepatocyte innate immunity. However, the suitability of the HepaRG model to study HEV need to be further investigated. In this study, we found that HEV can infect proliferating HepaRG cells and that DMSO-induced differentiation is not necessary for HEV infection. Moreover, even if treatment with DMSO is needed to maintain optimal differentiation and polarization of dHepaRG, its presence is detrimental for HEV infection. Overall, this study shows that dHepaRG cells cultured without DMSO is a suitable model to study HEV and its interaction with the hepatocyte innate system
The technical-reasoning network is recruited when people observe others make or teach how to make tools: An fMRI study
No full textInternational audienceCumulative technological culture is defined as the increase in efficiency and complexity of tools over generations. The role of social cognitive skills in cultural transmission has been long acknowledged. However, recent accounts emphasized the importance of non-social cognitive skills during the social transmission of technical content with a focus on technical reasoning. Here, we contribute to this double process approach by reporting an fMRI study about the neurocognitive origins of social learning. Participants watched videos depicting tool-making episodes in three social-learning conditions: reverse engineering, observation, and teaching. Our results showed that the technical-reasoning network, centered around the area PF of the left inferior parietal cortex, was preferentially activated when watching tool-making episodes. Additionally, teaching elicited the right middle temporal gyrus. This study suggests that technical reasoning underpins technological culture, while social cognition enhances learners' technical reasoning by guiding attention to key aspects of the technology
