An update on thalassemia intermedia

Thalassemia intermedia is a genetically diverse group of diseases that is the result of an imbalance in the production of the alpha and beta chains with ensuing chronic hemolysis, ineffective erythropoiesis, and iron overload. Resulting complications include bone changes, hypercoagulability, and end-organ damage due to iron overload. This decade has witnessed major breakthroughs in the management of thalassemia. In this article, we examine these novelties in therapy including iron chelation therapy, stem cell transplant, and gene therapy. Iron chelation therapy has been revolutionized with the advent of deferasirox, a once-daily oral iron chelator, that has been shown to be safe and efficacious. Gene therapy was also at the core of this revolution with the discovery of novel gene elements and viral vectors allowing for better control and improved outcomes.La thalass\ue9mie interm\ue9diaire englobe un groupe de maladies diverses r\ue9sultant d\u2019un d\ue9s\ue9quilibre entre la production des cha\ueenes alfa et b\ueata qui aboutit \ue0 une h\ue9molyse chronique, une \ue9rythropo\uef\ue8se inefficace et une surcharge en fer. Les complications engendr\ue9es par cette maladie sont un changement dans la constitution des os, un \ue9tat d\u2019hypercoagulabilit\ue9, et des organes majeurs endommag\ue9s suite au surplus de fer. La derni\ue8re d\ue9cennie a vu d\u2019importantes avanc\ue9es dans le traitment de la thalass\ue9mie. Sont examin\ue9es ici les toutes derni\ue8res th\ue9rapeutiques : la ch\ue9lation du fer, la greffe de cellules souches et la th\ue9rapie g\ue9n\ue9tique. L\u2019introduction de deferasirox, un ch\ue9lateur du fer administr\ue9 une fois par jour par voie orale, a r\ue9volutionn\ue9 la ch\ue9lation du fer et s\u2019est impos\ue9 comme \ue9tant un m\ue9dicament s\ufbr et efficace. La th\ue9rapie g\ue9n\ue9tique a aussi \ue9t\ue9 une innovation charni\ue8re dans les nouveaux traitements, surtout avec la d\ue9couverte r\ue9cente d\u2019\ue9l\ue9-ments g\ue9n\ue9tiques et vecteurs viraux qui permettent un meilleur contr\uf4le et am\ue9liorent les r\ue9sultats

Hepatocellular carcinoma in hepatitis-negative patients with thalassemia intermedia: a closer look at the role of siderosis

Abstract Patients with thalassemia are often exposed to several risk factors for developing hepatocellular carcinoma (HCC) due to their repeated transfusions. However, even transfusion-independent patients with thalassemia intermedia (TI) can develop HCC, which is mainly attributed to a state of iron overload. We report here two cases and review the literature for the association between TI and HCC. Along with our cases, a total of 36 cases of HCC in thalassemic patients were reported in the literature. Of these, 22 (61%) were TI patients with 6 (27%) of them being hepatitis B and C negative. There was no consistency in their characteristics; therefore, we recommended screening thresholds for HCC in TI patients based on their total liver iron concentration (LIC)

Mortalité par sepsis et choc septique dans les maladies psychiatriques sévères : une revue systématique et méta-analyse

Contexte : des données contradictoires ont été rapportées concernant les résultats de mortalité associés à la septicémie et au choc septique chez les patients atteints de maladie mentale sévère (severe mental illness = SMI) par rapport à ceux sans maladie mentale (non-SMI). Les patients SMI présentent dans la plupart des pathologies somatiques des taux de mortalité plus élevés que leurs homologues non SMI. Cependant, plusieurs études récentes ont montré un taux de mortalité par sepsis ou choc septique significativement plus faible chez les patients SMI par rapport aux patients non-SMI.Objectif : l’objectif principal était de déterminer dans une méta-analyse si les patients SMI et non-SMI ont des taux de mortalité par sepsis ou choc septique à la sortie de l’hôpital ou à court terme (£ 30 jours) significativement différents. Les objectifs secondaires étaient de comparer les mortalité les taux de mortalité ajustés jusqu'à la sortie de l'hôpital ou, s'ils ne sont pas disponibles, à 30 jours ; ainsi que les taux de mortalité à long terme non ajustés et ajustés s'ils sont déclarés ; la durée du séjour en soins intensifs et à l'hôpital et le taux de ré hospitalisation.Méthodologie : les bases de données PubMed et Web of Science ont été explorées à la date du 4 juillet 2023 . Critères d’inclusion : l’ensemble des articles rapportant des résultats de mortalité par sepsis ou choc septique à la sortie de l'hôpital ou à court terme (£ 30 jours) chez les patients SMI et non-SMI âgés de 16 ans ou plus ont été inclus. Analyses statistiques. Pour le critère de jugement principal, les risques de biais (RoB) des études incluses ont été évalués à l'aide de l'échelle de Newcastle et d'Ottawa [4]. L'hétérogénéité statistique (c'est-à-dire la variation aléatoire entre les études) a été recherchée par inspection visuelle des forest plot et avec le test non paramétrique Q de Cochran et la statistique I2.Résultats : au total, 5 815 études ont été examinées, dont 6 incluses dans la revue systématique. Parmi ces 6 études, 4 ont fourni des données brutes adaptées à une méta-analyse sur notre critère de jugement principal. Les résultats ont montré un taux de mortalité plus faible chez les patients atteints de SMI par rapport aux patients non-SMI, avec un OR de 0,61, IC à 95 % [0,58-0,65], IP 95 %. IC [0,49-0,77]. La proportion de variabilité totale due à l'hétérogénéité entre les études était élevée dans notre analyse du critère de jugement principal avec un I2 = 91 %.Interprétation : nos résultats suggèrent que les patients SMI ont un meilleur pronostic vital après un sepsis ou un choc septique en comparaison aux patients non SMI. Nous relevons toutefois une forte hétérogénéité, probablement explicable par des facteurs qui n’ont pas été rapportés dans les études, comme les paramètres immunologiques et la prescription de médicaments psychotropes, pouvant influencer potentiellement le pronostique. Des études supplémentaires sont nécessaires pour confirmer ces résultats qui ouvrent une piste thérapeutique potentielle dans le traitement du sepsis et du choc septique

Approaches to management of beta-thalassemia intermedia

Thalassemia intermedia is a genetically diverse group of diseases that is the result of an imbalance in the production of the alpha and beta chains with ensuing chronic hemolysis, ineffective erythropoiesis, and iron overload.Resulting complications include bone changes, hypercoagulability, and end-organ damage due to iron overload. This decade has witnessed major breakthroughs in the management of thalassemia. In this article, we examine these novelties in therapy including iron chelation therapy, stem cell transplant, and gene therapy.Iron chelation therapy has been revolutionized with the advent of deferasirox, a once-daily oral iron chelator, that has been shown to be safe and efficacious.Gene therapy was also at the core of this revolution with the discovery of novel gene elements and viral vectors allowing for better control and improved outcomes

Hepatocellular carcinoma in hepatitis-negative patients with thalassemia intermedia : a closer look at the role of siderosis

Patients with thalassemia are often exposed to several risk factors for developing hepatocellular carcinoma (HCC) due to their repeated transfusions. However, even transfusion-independent patients with thalassemia intermedia (TI) can develop HCC, which is mainly attributed to a state of iron overload. We report here two cases and review the literature for the association between TI and HCC. Along with our cases, a total of 36 cases of HCC in thalassemic patients were reported in the literature. Of these, 22 (61%) were TI patients with 6 (27%) of them being hepatitis B and C negative. There was no consistency in their characteristics; therefore, we recommended screening thresholds for HCC in TI patients based on their total liver iron concentration (LIC

Temporal variation in oral microbiome composition of patients undergoing autologous hematopoietic cell transplantation with keratinocyte growth factor

Abstract Introduction Autologous hematopoietic cell transplantation (AHCT) is a well-established treatment for lymphoma. Unintended effects of this therapy include oral mucositis (OM) and gastrointestinal toxicities, resulting in poor clinical outcomes. The gut microbiome has been previously linked to transplant toxicities among allogeneic recipients, but little is known about the effects of AHCT on the oral microbiome. Methods Seven patients with non-Hodgkin or Hodgkin lymphoma undergoing AHCT with palifermin (keratinocyte growth factor) were included. Buccal swab samples were collected at baseline and 14- and 28-days post-treatment. Oral microbial communities were characterized with 16 S rRNA amplicon sequencing. Temporal trends in community composition, alpha diversity, and beta diversity were investigated. Results A significant reduction in the relative abundance of the genera Gemella and Actinomyces were observed from baseline. No significant temporal differences in alpha diversity were observed. Significant changes in beta diversity were recorded. Conclusion Results of this pilot study suggest treatment with AHCT and palifermin affects the oral microbiome, resulting in temporal shifts in oral microbial community composition. Future studies are warranted to confirm these trends and further investigate the effects of AHCT on the oral microbiome and how these shifts may affect health outcomes

Severe mental illness and mortality in sepsis and septic shock: a systematic review and meta-analysis

International audienceBackground: There have been conflicting reports regarding the case-fatality outcomes associated with sepsis and septic shock in patients with severe mental illness (SMI).Methods: We searched Medline®, Web of Science® and the Cochrane Library® databases (from inception to 4-July-2023) for papers reporting outcomes associated with sepsis and septic shock in adult with (cases) vs. without SMI (controls). The main study outcome was the unadjusted case-fatality rate at hospital discharge, or 30 days if unavailable. Secondary outcomes included the rates of adjusted case-fatality at hospital discharge.Results: A total of six studies were included in the systematic review, of which four provided data for meta-analysis involving 2,124,072 patients. Compared to controls, patients with SMI were younger and more frequently women. Unadjusted analyses showed that SMI patients had a lower case-fatality rate associated with sepsis and septic shock than their non-SMI counterparts (OR 0.61, 95% CI [0.58–0.65], PI 95% CI [0.49–0.77], I2 = 91%). Meta-regression and subgroup analyses showed that the denominator of the study population (i.e. septic shock or sepsis) was associated with the outcome with an R2 of 59.7%.Conclusion: In conclusion, our study reveals a survival advantage of SMI patients over their non-SMI counterparts. Further research is needed to fully elucidate the mechanisms involved and to develop targeted interventions that can improve the prognosis of both SMI and non-SMI patients facing sepsis