Nicolas Molinari

Background: Critically ill patients frequently experienced acquired muscle dysfunction, which adversely affects outcomes. The relationship between calorie intake, muscle dysfunction and outcomes remains unclear. This study aims to determine if early calorie intake affects patients' outcomes through changes in skeletal muscle mass or quality, and to explore changes in muscle structure and underlying molecular pathways using limb muscle biopsies in a piglet model. Methods: This translational study combines data from a prospective observational study including critically ill patients and a 72‐h ventilated piglet model with early high calorie full enteral nutrition, both recording serial ultrasound measurements of limb muscle thickness and stiffness. Patients were classified into two trajectory groups based on thickness, stiffness and calorie intake. Adjusted mediation analysis quantified the effect of calorie intake on outcomes explained by muscle trajectories. The primary endpoint was ventilator‐free days at Day 28 (VFD28). In vivo limb muscle biopsies from piglets were analysed. Results: Among 102 patients, 21% and 28% exhibited decreased thickness and stiffness by Day 7, respectively; 36% received high‐calorie intake at Day 7. Patients categorized into the ‘decreased trajectory group’ for both thickness and stiffness showed lower VFD28 ( p < 0.01) and longer ICU stay ( p < 0.01) compared to the ‘stable trajectory group’. High‐calorie intake was associated with significantly lower VFD28 (−8.7 days [−14.7 to −1.7]; p = 0.01), longer ICU stay ( p < 0.01) and higher ICU mortality ( p < 0.01). Decreased muscle trajectories mediated, respectively, 42% and 28% of the association between high‐calorie intake and VFD 28. The porcine model showed a limb muscle stiffness reduction associated with muscle fibre atrophy and increased intramuscular lipid content linked to decreased protein synthesis (IGF‐1 and myostatin downregulation), increased autophagy (ATG5, ATG7 and P62 increased activity) and impaired fatty acid metabolism (carnitine palmitoyltransferase 1B reduced expression). Conclusions: This study demonstrates that early calorie intake in critically ill patients adversely affects muscle mass and quality, mediating negative outcomes. The porcine model helps elucidate underlying mechanisms, with early high‐calorie intake resulting in a metabolic oversupply state associated with metabolic disorders leading to muscle fibre atrophy and lipid accumulation. These results highlight the importance of targeted nutritional strategies to preserve muscle health in critically ill patients.

Chronic obstructive pulmonary disease (COPD) and asthma exacerbations in France cause substantial morbidity, mortality, and healthcare costs. Although their occurrence is influenced by environmental and socioeconomic factors, nationwide analyses quantifying the impact of air pollution, climate extremes, and social deprivation are limited. Understanding these determinants is crucial to guide interventions and reduce the economic burden of these diseases. We conducted a retrospective, population-based study using the French National Hospital Discharge PMSI database (period 2018-2022). Hospitalization records were linked with publicly available datasets capturing air pollutants (PM₂.₅, PM₁₀, NO₂, O₃), greenhouse gas emissions, meteorological variables, population density, land use, and socioeconomic deprivation indices. Exposures were assigned to patients based on their municipality of residence or, for time-varying factors, using the nearest monitoring station. 473,990 COPD and 187,332 asthma patients were matched for sex, birth year, and date of first hospitalization. Associations between environmental and socioeconomic exposures and exacerbation risk were evaluated using univariate conditional logistic regression. Population attributable fractions (PAFs) were subsequently calculated to quantify excess hospitalizations and estimate associated healthcare costs. Poverty emerged as the primary factor driving higher healthcare costs, with annual incremental costs of €21.5 million for COPD (PAF 4.92%) and €9.5 million for asthma (PAF 18.83%). Air pollution effects differed by disease. PM₂.₅ and O₃ were mainly associated with COPD, with annual costs of €17 million (PAF 3.85%) and €18 million (PAF 4.06%), respectively. Greenhouse gases and NO₂ contributed to exacerbations in both conditions: greenhouse gases accounted for €9 million in COPD (PAF 2.11%) and €5.5 million in asthma (PAF 10.33%), while NO₂ costs were €13.5 million for COPD (PAF 3.04%) and €3.5 million for asthma (PAF 6.87%). Extreme temperatures generated €4 million in annual costs for COPD patients (PAF 0.88%). Annual expenditures for exacerbations attributable to high population density were €11 million for COPD (PAF 2.48%) and €7 million for asthma (PAF 13.70%). This study underscores the critical contribution of the exposome to the economic burden of COPD and asthma exacerbations in France. Our findings provide an evidence-based framework for implementing targeted interventions addressing material deprivation, air pollution, and high population density, which can improve clinical outcomes while enhancing cost-efficiency in the healthcare system.

Background & Aims: Transjugular intrahepatic portosystemic shunt (TIPS) improves survival in refractory ascites. A careful patient's selection is mandatory as TIPS can lead to complications. Liver volumetry is predictive of outcomes before hepatic surgery, but data on its role before TIPS placement are scarce. We aimed to evaluate whether liver and spleen volume measurements are associated with prognosis after TIPS placement in patients with ascites. Methods: We analysed data from three French centers, treated with TIPS between 2017 and February 2022. Inclusion criteria encompassed a TIPS placement for refractory or recurrent ascites and availability of cross‐sectional imaging. Exclusion criteria included non‐cirrhotic portal hypertension, other indications for TIPS, hepatocellular carcinoma beyond Milan criteria, and extrahepatic malignancy. Liver and spleen volumes were measured using pre‐TIPS CT or MRI scans. The primary endpoint was 1‐year transplant‐free survival (TFS). Secondary endpoints were overt hepatic encephalopathy (HE), recurrence of ascites, acute variceal bleeding, and jaundice. Results: The 160 patients were included (median age 60 years, male gender 83.8%, alcohol‐related cirrhosis 58.8%, with active alcohol consumption in 25.6%, Child‐Pugh B cirrhosis in 81.2%, median MELD score was 12). The 1‐year TFS was 60.1%. Multivariate analysis identified serum creatinine (HR = 1.01 95% CI [1.00–1.01], p = 0.04), total bilirubin (HR = 1.02 95% CI [1.02–1.04], p = 0.004), and portal pressure gradient (HR = 1.09 95% CI [1.01–1.18], p = 0.03) as independent factors associated with TFS. Neither liver‐to‐spleen volume ratios (LSVR) ( p = 0.36) nor liver volume index ( p = 0.92) were significantly associated with death or LT. Overall, 38.1% of patients developed overt HE after TIPS, with lower platelet count (HR = 1.01 95% CI [1.00–1.01], p = 0.04) emerging as an independent predictor. No radiological characteristics were associated with the recurrence of ascites. Conclusions: In this multicenter study, liver and spleen volumes were not associated with transplant‐free survival or liver‐related outcomes in patients undergoing TIPS for ascites. These findings suggest that liver volumetry should not be a determining factor in patient selection for TIPS placement.

Introduction: Understanding the influence of environmental and socioeconomic factors, collectively known as the exposome, on severe exacerbation risks in chronic obstructive pulmonary disease (COPD) and asthma is crucial for enhancing patient care. Methods: We assessed the impact of the exposome on COPD and asthma severe exacerbations in France between 2018 and 2022, combining data from the French National Hospital Discharge Programme de Médicalisation des Systèmes d'Information database and open data for multiple environmental exposition. Using a retrospective matched case–control design, 473 990 patients with COPD and 187 332 patients with asthma were matched for sex, birth year and date of first hospitalisation. Conditional logistic regressions were performed to quantify ORs of exacerbations within the studied population. Results: In a multivariate model, exposure to extreme cold temperatures and exceeding WHO standards for nitrogen dioxide (NO ₂ ), fine particulate matter and ozone increased the odds of COPD exacerbation. Only exceeding NO ₂ was related to an increased risk of asthma exacerbation. Patients with COPD or asthma living in urban or artificial areas or near livestock farms were much more likely to have a severe exacerbation, whereas those living near water, wetlands or green spaces were protected from this risk. Higher poverty rates and long-term tobacco smoking were linked to a greater likelihood of COPD exacerbations. Conclusions: The study highlights how exposome factors influence bronchial diseases and underscores the benefit of open-access data for advancing research. COPD and asthma exacerbations account for numerous deaths and cost billions and will increase with global warming, identifying modifiable environmental risk factors, improving patient care and helping shape valuable public health policies.

Background: Continuous positive airway pressure (CPAP) effectiveness can be compromised by adverse effects. Despite its potential impact on adherence and sleepiness, aerophagia remains under-recognized and poorly characterized. This ancillary analysis of the InterfaceVent study aimed to identify risk factors for aerophagia in a large real-life cohort of CPAP-treated patients and to assess its association with both CPAP adherence and sleepiness. Methods: InterfaceVent was a prospective, real-life, cross-sectional study. Adults treated for at least 3 months with CPAP were included. Patients self-reported mask-related side effects using visual analogue scales. Aerophagia was defined as a dichotomous outcome based on patient-reported symptoms and CPAP non-adherence as mean nightly usage p < 0.001). CPAP usage was significantly lower in the aerophagia group (median 6.37 vs. 6.75 h/day; p = 0.001), whereas non-adherence, did not significantly differ between groups (10.7% vs. 7.5%; p = 0.20). Conclusions: This ancillary analysis of the InterfaceVent study highlights the burden of aerophagia in CPAP-treated patients and identifies modifiable and non-modifiable risk factors. Better recognition and management of this under-reported side effect may improve CPAP adherence and patient comfort. Trial registration: InterfaceVent is registered with ClinicalTrials.gov (NCT03013283). The first registration date is 23 December 2016.