Université De Picardie Jules Verne

Alcohol is a major cause of hepatocellular carcinoma (HCC), accounting for 30% of cases worldwide. Sorafenib, a tyrosine kinase inhibitor (TKI), was the standard first-line treatment for advanced HCC until 2021, but sorafenib resistance is common. We explored the impact of chronic alcohol exposure (CAE) on sorafenib response and sought to identify associated resistance mechanisms. Huh-7 HCC cells were chronically exposed to alcohol for 6 months. Sorafenib resistance was assessed by measuring cell viability (IC50) and by evaluating the protein expression of signaling pathways involved in resistance using immunoblotting. RNA sequencing was performed to identify mechanisms of resistance. Sorafenib response was assessed using the RECIST 1.1 criteria in HCC patients. A retrospective study of 86 HCC patients from the CHIEF cohort (alcohol-related vs. non-alcohol-related etiologies) evaluated overall survival (OS) and progression-free survival (PFS) using the log-rank test. CAE significantly decreased cell sensitivity to sorafenib (p = 0.006), indicating increased resistance. The ERK pathway was involved. RNA sequencing of our cells identified a total of 80 differentially expressed genes associated with drug resistance and aggressiveness. Clinically, alcohol-related HCC patients were less responsive to sorafenib (35% responders vs. 65%, p = 0.014) and had significantly different OS (p = 0.0234). Median OS was 10 months (95% CI = [6.1, 15.7]) for alcohol-related HCC and 12.1 months (95% CI = [7.7, 64.9]) for other etiologies. PFS was lower in the alcohol group (5.72 months (95% CI = [4.63, 12.8]) vs. 9.66 months (95% CI = [4.40, 39.9], p = 0.0298). Sorafenib resistance due to chronic alcohol consumption is consistent in both in vitro models and clinical settings. KEY MESSAGES: Chronic alcohol exposure reduces the effectiveness of sorafenib in hepatocellular carcinoma (HCC), as demonstrated in both in vitro and clinical settings. In vitro, alcohol-exposed HCC cells showed increased sorafenib resistance, associated with activation of the ERK signaling pathway and differential expression of 80 genes linked to drug resistance and tumor aggressiveness. Clinically, patients with alcohol-related HCC had poorer responses to sorafenib and shorter overall and progression-free survival compared to patients with non-alcohol-related HCC. These findings suggest that alcohol-related HCC may require alternative or personalized therapeutic strategies beyond standard TKI treatments.

To descriptively assess the physical activity behavior of cardiac patients exposed to connected devices during rehabilitation, at 2- and 4-month post-discharge.

18 cardiac patients (52.3 ± 11.0 years) attended a therapeutic workshop on linked objects and social networks during four weeks of supervised cardiac rehabilitation. Then, they freely reported their adapted physical activity information on social networks during two periods of 8 weeks, intercepted by 2 weeks, at home.

Three patients (16.7 %) dropped out during the second 8-week period. 15 patients practiced more different physical activities during the second period compared to the first period (1.2 ± 0.4 vs. 1.8 ± 0.9, p=0.007) with no significant effect on weekly duration (90.9 ± 40.8 vs. 91.8 ± 55.9 min, p=0.290) or frequency of adapted physical activities (2.6 ± 1.8 vs. 2.6 ± 1.1, p=0.183). Walking sessions (2.3 ± 0.9 vs. 2.0 ± 1.0, p=0.033) and distance (8.7 ± 3.7 vs. 7.8 ± 3.9 km, p = 0.002) decreased between both periods, the number of bicycling sessions increased (0.0 ± 0.0 vs. 9.0 ± 3.0).

Education on connected health devices, combined with remote professional support, appears to help maintain physical activity in post-discharge cardiac patients. These preliminary findings highlight the need for further studies to assess the intervention's impact on cardiovascular rehabilitation.

Emergency departments (EDs) worldwide are facing increasing patient volumes and thus crowding, prolonged waiting times and rising healthcare costs. In France, ED visits rose from 8.5 to 16 million between 2014 and 2024. To address these challenges, several countries (including Australia, the UK and Canada) have integrated physiotherapists into EDs in advanced practice roles—primarily for musculoskeletal (MSK) conditions. In contrast, this type of integration is rare in the French healthcare system. The objective of the present study was to assess the attitudes of French emergency physicians to the incorporation of physiotherapists into ED teams.

A nationwide, cross-sectional survey of emergency physicians practising in France was conducted between 22 November 2023 and 15 February 2024. The study questionnaire assessed the physicians’ willingness to collaborate with physiotherapists, the perceived benefits of collaboration and views on task delegation. Descriptive statistics and χ² tests were used to analyse the data.

Of the 420 respondents, 333 (79.3%) expressed willingness to collaborate with physiotherapists in EDs. The most commonly cited benefits were improved quality of care n=321 (76.4%), greater patient satisfaction n=318 (75.7%), a lower physician workload n=276 (67.5%) and enhanced ED efficiency n=211 (50.2%). The conditions most frequently considered for delegation included suspected ankle sprains n=313 (74.5%), knee sprains n=277 (66.0%) and lower back pain n=271 (64.5%). Compared with junior colleagues, senior physicians with five or more years of experience were significantly more supportive of delegating cases of neck pain (n=110, 41.7%, p=0.017).

French emergency physicians are generally supportive of integrating physiotherapists into EDs, especially for the management of non-urgent MSK conditions. The physicians see physiotherapists as capable of providing on-site care and patient education, potentially improving patient flow and alleviating pressures in overcrowded EDs. These findings offer valuable insights for countries in which the integration of physiotherapy into emergency care is still emerging.