Place du médecin généraliste dans le diagnostic des troubles de la reméthylation d’apparition tardive

La prévalence de l’hyperhomocystéinémie est estimée à 5 % dans la population générale. Si l’étiologie principale est la carence en vitamines en particulier B6, B9 et B12, les hyperhomocystéinémies peuvent dans de rares cas avoir une origine génétique et résulter des troubles de la reméthylation de l’homocystéine. L’objectif de ce travail est de présenter à travers un article deux cas cliniques hétérogènes (une forme précoce et une forme tardive) sur un trouble de la reméthylation (déficit sévère en MTHFR) et de rapporter pour la première fois en français les dernières recommandations émises dans le cadre du projet E-HOD pour le diagnostic et le traitement de ces pathologies. Afin de sensibiliser les médecins généralistes à ces pathologies, une recherche bibliographique sur les troubles de la reméthylation d’apparition tardive a été réalisée dont la synthèse conduit à suspecter ce diagnostic chez un patient en errance diagnostique, ayant eu des avis spécialisés multiples, avec une histoire familiale de maladie « inconnue », et qui présente un phénotype compatible. Ainsi, ce diagnostic doit être évoqué en deuxième intention pour une épilepsie, un trouble de la marche, une atteinte pyramidale, un syndrome cérébelleux, une neuropathie périphérique, un syndrome psychiatrique atypique surtout lorsqu’ils sont associés à des troubles cognitifs précoces ou une déficience intellectuelle, un syndrome hémolytique et urémique, une insuffisance rénale progressive, une thrombose atypique ou récurrente, une anémie macrocytaire ou encore un déficit visuel sévère, une maculopathie, une atrophie du nerf optique. Lorsqu’un trouble de la reméthylation est suspecté, le dosage de l’homocystéine sanguine doit être réalisé en première intention et une vigilance doit être accordée au respect des recommandations préanalytiques. Enfin, la mise en œuvre de concertations pluridisciplinaires entre les médecins généralistes, les biochimistes et les métaboliciens du centre hospitalier universitaire référent est conseillée

Abstinence is associated with better outcomes in patients with alcohol-related hepatocellular carcinoma: Results of an observational study

Background: Patients with alcohol-related cirrhosis and hepatocellular carcinoma (HCC) may have reduced survival compared to those with HCC related to other causes. The impact of abstinence in alcohol-related HCC is unknown. We compared access to curative treatment and the prognosis of patients with HCC according to the cause of cirrhosis and evaluated the impact of abstinence on the prognosis of patients with alcohol-related HCC. Patients and methods: Data for patients with cirrhosis and HCC were prospectively collected in a single center. A logistic regression model was used to identify factors associated with access to curative treatment. Multivariate Fine and Gray proportional hazards models were used to identify factors associated with 5-year survival after adjustment for lead-time bias. Results: Two hundred patients were included, 114 (57 %) with non-alcohol-related HCC and 86 (43 %) with alcohol-related HCC (35 abstainers, 51 consumers). During follow-up, 21 patients were transplanted and 156 died. The proportion of patients who had access to curative treatment was 65 % in abstainers, 44 % in consumers, and 57 % in patients with non-alcohol-related cirrhosis (p = 0.06). In multivariate analyses, abstinence was not associated with better access to curative treatment. After adjustment for lead-time bias, the 5-year cumulative incidence of overall death was significantly lower in abstainers than in consumers and in patients with non-alcohol-related cirrhosis (52 % vs. 78 % vs. 81 %, respectively, p = 0.04). In multivariate analyses, abstainers had lower risk of death than consumers (SHR: 0.47, 95 % CI: 0.28–0.80, p = 0.005). Conclusion: Abstinence improves the outcome of patients with alcohol-related cirrhosis once HCC has occurred.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Abstinence is associated with better outcomes in patients with alcohol-related hepatocellular carcinoma: Results of an observational study.

Patients with alcohol-related cirrhosis and hepatocellular carcinoma (HCC) may have reduced survival compared to those with HCC related to other causes. The impact of abstinence in alcohol-related HCC is unknown. We compared access to curative treatment and the prognosis of patients with HCC according to the cause of cirrhosis and evaluated the impact of abstinence on the prognosis of patients with alcohol-related HCC. Data for patients with cirrhosis and HCC were prospectively collected in a single center. A logistic regression model was used to identify factors associated with access to curative treatment. Multivariate Fine and Gray proportional hazards models were used to identify factors associated with 5-year survival after adjustment for lead-time bias. Two hundred patients were included, 114 (57 %) with non-alcohol-related HCC and 86 (43 %) with alcohol-related HCC (35 abstainers, 51 consumers). During follow-up, 21 patients were transplanted and 156 died. The proportion of patients who had access to curative treatment was 65 % in abstainers, 44 % in consumers, and 57 % in patients with non-alcohol-related cirrhosis (p = 0.06). In multivariate analyses, abstinence was not associated with better access to curative treatment. After adjustment for lead-time bias, the 5-year cumulative incidence of overall death was significantly lower in abstainers than in consumers and in patients with non-alcohol-related cirrhosis (52 % vs. 78 % vs. 81 %, respectively, p = 0.04). In multivariate analyses, abstainers had lower risk of death than consumers (SHR: 0.47, 95 % CI: 0.28-0.80, p = 0.005). Abstinence improves the outcome of patients with alcohol-related cirrhosis once HCC has occurred

Toxicity of carbon dioxide: a review

International audienceThe toxicity of carbon dioxide has been established for close to a century. A number of animal experiments have explored both acute and long-term toxicity with respect to the lungs, the cardiovascular system, and the bladder, showing inflammatory and possible carcinogenic effects. Carbon dioxide also induces multiple fetal malformations and probably reduces fertility in animals. The aim of the review is to recapitulate the physiological and metabolic mechanisms resulting from CO(2) inhalation. As smokers are exposed to a high level of carbon dioxide (13%) that is about 350 times the level in normal air, we propose the hypothesis that carbon dioxide plays a major role in the long term toxicity of tobacco smoke

Clinical and molecular characterization of adult patients with late‐onset MTHFR deficiency

5,10‐Methylenetetrahydrofolate reductase (MTHFR) deficiency usually presents as a severe neonatal disease. This study aimed to characterize natural history, biological and molecular data, and response to treatment of patients with late‐onset MTHFR deficiency. The patients were identified through the European Network and Registry for Homocystinuria and Methylation Defects and the Adult group of the French Society for Inherited Metabolic Diseases; data were retrospectively colleted. To identify juvenile to adult‐onset forms of the disease, we included patients with a diagnosis established after the age of 10 years. We included 14 patients (median age at diagnosis: 32 years; range: 11‐54). At onset (median age: 20 years; range 9‐38), they presented with walking difficulties (n = 8), cognitive decline (n = 3) and/or seizures (n = 3), sometimes associated with mild mental retardation (n = 6). During the disease course, symptoms were almost exclusively neurological with cognitive dysfunction (93%), gait disorders (86%), epilepsy (71%), psychiatric symptoms (57%), polyneuropathy (43%), and visual deficit (43%). Mean diagnostic delay was 14 years. Vascular events were observed in 28% and obesity in 36% of the patients. One patient remained asymptomatic at the age of 55 years. Upon treatment, median total homocysteine decreased (from 183 μmol/L, range 69‐266, to 90 μmol/L, range 20‐142) and symptoms improved (n = 9) or stabilized (n = 4). Missense pathogenic variants in the C‐terminal regulatory domain of the protein were over‐represented compared to early‐onset cases. Residual MTHFR enzymatic activity in skin fibroblasts (n = 4) was rather high (17%‐58%). This series of patients with late‐onset MTHFR deficiency underlines the still unmet need of a prompt diagnosis of this treatable disease