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Bridging the Gap: How Distance to Hospitals Limits HCV Treatment Initiation in France
No full textInternational audienceLETTER TO THE EDITORIn their recent study, Ouzan et al. [1] showed the feasibility and effectiveness of simplified, non-specialist-led models for hepatitis C care in France and advocated for targeted training of non-specialists to facilitate treatment prescription, minimise unnecessary specialist referrals, and reach marginalised and high-risk populations. They recalled..
Overall Survival After Allogeneic Transplantation in Advanced Cutaneous T-Cell Lymphomas (CUTALLO): A Propensity Score–Matched Controlled Prospective Study
No full textInternational audienceCutaneous T-cell lymphomas (CTCLs) are rare, usually refractory, and sometimes fatal diseases. Patients presenting with advanced-stage CTCL usually exhibit poor long-term survival outcomes. Only very few treatments have improved progression-free survival (PFS) in advanced CTCL, and no treatment has increased overall survival (OS). In 2023, the results of the CUTALLO trial supported the hypothesis that hematopoietic stem-cell transplantation (HSCT) was associated with significantly longer PFS as compared with standard-of-care treatment among advanced-stage patients although HSCT did not significantly affect OS. We provide herein the final OS data pertaining to the same patient population after a longer median follow-up of 38.9 months. Of the 99 patients included in the analysis, 55 (56%) were assigned to the HSCT group, whereas 44 (44%) were allocated to the non-HSCT group. The updated survival analysis reported that 16 of 55 patients (29%) in the HSCT group and 22 of 44 patients (50%) in the non-HSCT group died. The median OS was not reached in the HSCT group and 51.5 months (95% CI, 26.9 to 51.5) in the non-HSCT group (hazard ratio, 0.40 [95% CI, 0.20 to 0.80]). Compared with the standard of care for advanced CTCL, after extended follow-up, allogeneic HSCT was associated with significantly longer OS. ClinicalTrials.gov NCT02520908
Exploring Occlusal Caries Management over 2 Decades in France among General Dental Practitioners
No full textInternational audienceObjectives: Despite being a central concept in dentistry, minimum intervention dentistry (MID) still faces a gap between evidence and practice. The aim of this study was to investigate the management decisions of French general dental practitioners (FrGDPs) for occlusal carious lesions (OCL) in 2023 and to compare the results to those obtained in 2002 and 2012 using the same questionnaire. Methods: An online, cross-sectional survey was conducted using a precoded questionnaire among the French dental practice–based research network (ReCOL). The structured questionnaire assessed the restorative threshold and management strategies for OCL. Three simulated clinical scenarios are presented: 1 illustrating a discrete progression of an OCL (assessing the intervention threshold) and 2 clinical cases (focusing on diagnosis and caries management). Descriptive and statistical analyses were performed to study the evolution over 2 decades. Results: The response rate was 45.4%. The 2023 sample included 56% female dentists and was younger and less experienced than the 2002 and 2012 population studies. In 2023, 68.5% of the respondents stated a restorative threshold when the OCL reached the outer third of dentine. Over the last 2 decades, this threshold has been significantly delayed to later stages of carious progression and so is shifting the cavity preparation to a more conservative approach. Over the 2 decades, for clinical cases 1 and 2, diagnosis, management strategies, and material selection have significantly evolved toward earlier grades of carious extension, a more micro- and non-invasive approach, and composite (P < 0.0001). Substantial variability persists among respondents. Conclusions: The results reveal a significant shift over the last 2 decades among FrGDPs toward MID. Initial and continuing education are key factors in the improved implementation of MID into practice. Resistance and variability act as barriers, and uncertainty proves to be a challenge, all of which require further investigation. Knowledge Transfer Statement: This 2-decade study on the diagnosis and management of dental caries provides valuable insights for dental practitioners, academic institutions, policy-makers, and health system stakeholders. The findings underscore the importance of education, consideration of barriers, and tolerance for uncertainty. These findings are important for raising awareness of, and helping to reduce, the gap between evidence and clinical practice
Cardiogenic shock: Who benefits from heart replacement therapy?
No full textInternational audienceBackgroundThe characteristics of patients requiring heart replacement therapy (HRT) in cardiogenic shock (CS) are poorly described. This study aims to characterize the clinical profile of CS patients undergoing HRT.MethodsFRENSHOCK is a prospective registry including 772 CS patients from 49 centres. HRT included heart transplantation (HTx) and ventricular assist devices (VADs). The primary endpoint was the rate of in-hospital HRT. The secondary endpoint was the rate of HRT performed between discharge and 1-year follow-up.ResultsAmong 772 patients, 49 (6.3 %) underwent in-hospital HRT (11 LVADs, 4 BiVADs, 34 HTx), including 10 (20.4 %) who died before discharge. Multivariate analysis identified several independent factors for in-hospital HRT: Prior ICD (aOR 1.18 [1.09–1.27], p < 0.01), signs/symptoms of right heart failure (aOR 1.06 [1.01–1.12] p = 0.02), bilirubin level ≥ 18.9 mg/L (aOR 1.06 [1.01–1.12], p = 0.02), use of dobutamine (aOR 1.11 [1.01–1.23], p = 0.049) or levosimendan (aOR 1.10 [1.01–1.21], p = 0.04), and acute mechanical circulatory support (aMCS) (aOR 1.16 [1.08–1.25], p < 0.01). Subsequently, 29 patients (3.8 % of the cohort, 5.6 % of in-hospital survivors) underwent HRT between discharge and 1-year follow-up. Ventricular arrhythmia (aOR 1.08 [1.01–1.17], p = 0.04) and aMCS (aOR 1.23 [1.12–1.35], p < 0.01) were associated with HRT between discharge and the 1-year follow-up.ConclusionIn this large cohort of unselected CS patients, HRT was performed in more than 10 % of cases (6.3 % in-hospital and 3.8 % between discharge and 1-year follow-up), with a comparable in-hospital mortality rate to non-HRT patients. Further studies are needed to optimize the selection criteria for HRT in CS patients
Shaping the physical world to our ends through the left PF technical-cognition area
No full textInternational audienceOur propensity to materiality, which consists in using, making, creating, and passing on technologies, has enabled us to shape the physical world according to our ends. To explain this proclivity, scientists have calibrated their lens to either low-level skills such as motor cognition or high-level skills such as language or social cognition. Yet, little has been said about the intermediate-level cognitive processes that are directly involved in mastering this materiality, that is, technical cognition. We aim to focus on this intermediate level for providing new insights into the neurocognitive bases of human materiality. Here, we show that a technical-reasoning process might be specifically at work in physical problem-solving situations. We found via two distinct neuroimaging studies that the area PF (parietal F) within the left parietal lobe is central for this reasoning process in both tool-use and non-tool-use physical problem-solving and can work along with social-cognitive skills to resolve day-to-day interactions that combine social and physical constraints. Our results demonstrate the existence of a specific cognitive module in the human brain dedicated to materiality, which might be the supporting pillar allowing the accumulation of technical knowledge over generations. Intensifying research on technical cognition could nurture a comprehensive framework that has been missing in fields interested in how early and modern humans have been interacting with the physical world through technology, and how this interaction has shaped our history and culture
Japanese Are Less Human-Centred than French: A New View on Spontaneous Perspective-Taking in Easterners
No full textInternational audiencePerspective-taking is fundamental to social interaction. In line with psychosocial ideas that Eastern societies value the individual’s interdependence, recent experimental work suggests that they are more inclined to endorse another person’s perspective than people from Western countries. There are, however, more cultural differences between those societies than interdependence. Because Eastern societies also sustain a more holistic nature of cognition, people from Eastern countries may simply tend to interpret the surrounding world from a less ego-centred perspective. Direct support for this idea was found when comparing the responses of Japanese and French participants in level-2 visuo-spatial perspective-taking tasks. As predicted, we observed a less egocentric bias in Japanese than in French participants. Crucially, this bias was not caused directly by a greater proportion endorsing the point of view of another person but rather indirectly by a higher disposition to spontaneously adopt non-human-centred perspectives
Mitochondrial respiration in white adipose tissue is dependent on body mass index and tissue location in patients undergoing oncological or parietal digestive surgery
No full textInternational audienceAdipose tissue (AT), is a major endocrine organ that plays a key role in health and disease. However, adipose dysfunctions, especially altered energy metabolism, have been under‐investigated as white adipocytes have relatively low mitochondrial density. Nevertheless, recent studies suggest that mitochondria could play a major role in AT disorders and that AT mitochondrial activity could depend on adiposity level and location. This clinical study aimed to evaluate mitochondrial respiration and metabolism in human visceral (vAT) and subcutaneous (scAT) AT and their relationship with body mass index (BMI). This clinical study enrolled 67 patients (30 females/37 males) scheduled for digestive surgery without chemotherapy and parietal infection. BMI ranged from 15.4 to 51.9 kg·m −2 and body composition was estimated by computed tomographic images. Mitochondrial respiration was measured in situ in digitonin‐permeabilized AT using high‐resolution respirometry and a substrate/inhibitor titration approach. Protein levels of mitochondrial and lipid metabolism key elements were evaluated by Western blot. Maximal mitochondrial respiration correlated negatively with BMI ( p < .01) and AT area ( p < .001) regardless of the anatomical location. However, oxidative phosphorylation respiration was significantly higher in vAT (2.22 ± 0.15 pmol·sec −1 ·mg −1 ) than scAT (1.79 ± 0.17 pmol·sec −1 ·mg −1 ) ( p < 0.001). In line with oxygraphy results, there were higher levels of mitochondrial respiratory chain complexes in low‐BMI patients and vAT. Mitochondrial respiration decreased with increasing BMI in both scAT and vAT, without sex‐associated difference. Mitochondrial respiration appeared to be higher in vAT than scAT. These differences were both qualitative and quantitative. Clinical Trials Registration ID NCT05417581
Simultaneous Activation of Beta‐Oxidation and De Novo Lipogenesis in MASLD ‐ HCC : A New Paradigm
No full textInternational audienceMetabolic dysfunction‐associated steatotic liver disease (MASLD) is the most common cause of hepatocellular carcinoma (HCC). In this study, we combine metabolomic and gene expression analysis to compare HCC tissues with non‐tumoural tissues (NTT). Methods A non‐targeted metabolomic strategy LC–MS was applied to 52 pairs of human MASLD‐HCC and NTT separated into 2 groups according to fibrosis severity F0F1‐F2 versus F3F4. The expression of genes related to de Novo lipogenesis (DNL) and fatty acid oxidation (FAO) has been analysed by quantitative RT‐PCR and/or interrogation of RNA‐seq datasets in 259 pairs of tissues (MASLD‐HCC vs. VIRUS‐HCC). Results Metabolomic analysis revealed that acylcarnitines were the main discriminating metabolites according to fibrosis severity when we compared MASLD‐HCC‐F0F1‐F2 versus NTT and MASLD‐HCC‐F3F4 versus NTT. Based on these metabolomic data, the analysis of a panel of 15 selected genes related to DNL and FAO indicated that there is no difference between the 2 groups of MASLD‐HCC. In contrast the same comparative gene analysis according to the aetiology of HCC: MASLD‐HCC versus VIRUS‐HCC showed that both aetiologies shared the same upregulation of genes involved in DNL. However, five genes involved in FAO (HADHA, CRAT, CPT1, CPT2 and PPARA) are upregulated exclusively in MASLD‐HCC. This result indicates that FAO and DNL pathways are simultaneously activated in MASLD‐HCC in contrast to VIRUS‐HCC. Conclusions These results suggest that, the involvement of adaptive metabolic pathways is different depending on the aetiology of HCC. Moreover, the dogma that simultaneous activation of FAO and DNL is incompatible in cancer would not apply to MASLD‐HCC
Is MUC5B rs35705950 promoter polymorphism associated with chronic lung allograft dysfunction?
No full textInternational audienceBackground : Chronic lung allograft dysfunction (CLAD) is the main cause of death following lung transplantation (LT). Its pathophysiology and risk factors remain poorly understood. Donor or recipient genetic characteristics could be involved. MUC5B promoter rs35705950 polymorphism is one of the major genetic factors associated with pulmonary fibrosis. We aimed to correlate the MUC5B genotype of recipients and donors with LT outcomes. Methods : Recipient and donor blood samples from the Cohort in Lung Transplantation biobank were used. MUC5B status was determined by quantitative PCR using probes for rs35705950 polymorphism. CLAD occurrence and phenotype were blindly adjudicated. Results : 210 recipient–donor pairs were analysed. At 5 years, 68 patients (32.4%) had CLAD. The MUC5B rs35705950 polymorphism, whether in the donor or the recipient, was not associated with CLAD at 5 years (OR 1.07 (95% CI 0.53–2.11), p=0.8, and OR 0.79 (95% CI 0.37–1.60), p=0.5, respectively), CLAD-free survival or CLAD phenotype. The prevalence of the recipients’ T allele differed among underlying respiratory diseases (20.0% in interstitial lung disease, 8.4% in emphysema, 13.4% in cystic fibrosis and 5.6% for others, p=0.03). Risk of antibody-mediated rejection (AMR) was independent of the donor MUC5B polymorphism genotype, whereas the presence of the T allele in the recipient was associated with a reduced occurrence of AMR (OR 0.26 (95% CI 0.08–0.69), p=0.015). Conclusion : MUC5B rs35705950 polymorphism in the donor or the recipient does not affect LT outcomes. The significant association between the recipients’ polymorphism and reduced AMR occurrence has yet to be confirmed
Optimized use of the FilmArray Meningitis/Encephalitis panel for early discontinuation of antibiotic therapy
No full textInternational audienceIntroduction : La prise en charge des suspicions de méningite ou d’encéphalite repose sur une antibiothérapie empirique immédiate, souvent initiée avant la confirmation microbiologique. Dans ce contexte, le panel syndromique FilmArray® Méningite/Encéphalite (FAME) offre une réponse diagnostique rapide, mais son coût élevé soulève la question de son utilisation rationnelle. L’étude multicentrique FAMOuS (FilmArray® Meningitis/Encephalitis Optimization Study) visait à évaluer l’impact réel de FAME sur les décisions thérapeutiques précoces et à proposer un algorithme d’aide à la décision pour optimiser son emploi en routine hospitalière.Méthodes : Nous avons analysé rétrospectivement les données biologiques, les traitements instaurés avant et après obtention des résultats FAME, ainsi que les évolutions cliniques de 783 patients pris en charge dans six hôpitaux français sur une période de trois ans. Les indications, les résultats FAME, les modifications thérapeutiques et les examens complémentaires ont été comparés afin d’identifier les leviers d’optimisation.Résultats : Parmi les 783 panels réalisés, 80 % étaient négatifs, 7 % positifs pour une étiologie bactérienne et 13 % pour une origine virale. Aucun faux négatif bactérien n’a été observé. Les résultats positifs ont entraîné une modification thérapeutique dans 74 % des cas, contre 50 % pour les résultats négatifs. Les détections dans des prélèvements contenant <10 leucocytes ont concerné exclusivement des patients immunodéprimés ou des enfants de moins de 2 ans.Conclusion : L’étude FAMOuS a permis de concevoir un algorithme décisionnel basé sur les résultats du panel FAME et les profils cliniques des patients. Ce flowchart, appliqué en routine, pourrait éviter jusqu’à 33 % d’examens complémentaires non nécessaires et favoriser l’arrêt précoce de certaines antibiothérapies, sans compromettre la sécurité des patients