High-dose Chemotherapy Impairs Cardiac Autonomic Control of Hospitalized Cancer Patients Undergoing Autologous Hematopoietic Stem Cell Transplantation

BackgroundAutologous hematopoietic stem cell transplantation (HSCT) patients have intermediary and late cardiac autonomic dysfunction, which is an independent mortality predictor. However, it is unknown when this HSCT-related autonomic dysfunction begins during hospitalization for HSCT and whether cardiac autonomic control (CAC) is related to cardiotoxicity in these patients.Patients and MethodsCAC was assessed in 36 autologous-HSCT inpatients (HSCT group) and 23 cancer-free outpatients (CON group) using heart rate variability analysis. The HSCT group was assessed at five time-points from admission to hospital discharge during hospitalization period. The CON group was assessed once. The severity of cardiotoxicity (CTCAE 5.0) and cardiac troponin I were recorded.ResultsThe CAC was significantly reduced after high-dose chemotherapy (HDC) (reduction of MNN, SDNN, RMSSD, LFms² and HFnu, and increase of LFnu and LF/HF; P<0.05). At the onset of neutropenia, pNN50 and HFms² were also reduced (P<0.05) compared to the admission ones. Although both groups were similar regarding CAC at hospital admission, the HSCT patients showed impaired CAC at hospital discharge (P<0.05). The LF/HF was positively associated with cardiac troponin I and RMSSD was inversely associated with the severity of cardiotoxicity (P≤0.05).ConclusionCAC worsened during hospitalization for autologous-HSCT, mainly after HDC. In addition, it seems associated to early signs of cardiotoxicity in these patients.     

Understanding the impact of radical changes in diet and the gut microbiota on brain function and structure: rationale and design of the EMBRACE study

BackgroundBariatric surgery leads to profound changes in gut microbiota and dietary patterns, both of which may interact to impact gut-brain communication. Though cognitive function improves postsurgery, there is a large variability in outcomes. How bariatric surgery-induced modifications in the gut microbiota and dietary patterns influence the variability in cognitive function is still unclear.ObjectivesTo elucidate the associations between bariatric surgery-induced changes in dietary and gut microbiota patterns with cognition and brain structure.SettingUniversity hospital.MethodsA total of 120 adult patients (≥30 years) scheduled to undergo a primary bariatric surgery along with 60 age-, sex-, and body mass index-matched patients on the surgery waitlist will undergo assessments 3-months presurgery and 6- and 12-month postsurgery (or an equivalent time for the waitlist group). Additionally, 60 age-and sex-matched nonbariatric surgery eligible individuals will complete the presurgical assessments only. Evaluations will include sociodemographic and health behavior questionnaires, physiological assessments (anthropometrics, blood-, urine-, and fecal-based measures), neuropsychological cognitive tests, and structural magnetic resonance imaging. Cluster analyses of the dietary and gut microbiota changes will define the various dietary patterns and microbiota profiles, then using repeated measures mixed models, their associations with global cognitive and structural brain alterations will be explored.ResultsThe coordinating study site (Centre intégré universitaire de santé et de services sociaux du Nord-de-l’Île-de-Montréal, QC, Canada), provided the primary ethical approval (Research Ethics Board#: MP-32-2022-2412).ConclusionsThe insights generated from this study can be used to develop individually-targeted neurodegenerative disease prevention strategies, as well as providing critical mechanistic information.     

Etomidate as an induction agent for endotracheal intubation in critically ill patients: A meta-analysis of randomized trials

PurposeWe performed a meta-analysis of randomized controlled trials to evaluate if etomidate impacted mortality in critically ill adults when compared with other induction agents.Materials and methodsWe searched PubMed, Embase, and the Cochrane Central Register of Controlled Trials for randomized controlled trials which compared etomidate with any other induction agent in critically ill adult patients undergoing endotracheal intubation. The primary outcome was mortality at the main timepoint defined by the study. We conducted a fixed-effects meta-analysis for the risk ratio. Using that risk ratio and 95% confidence interval, we then estimated the probability of any harm (RR > 1) and the number needed to harm ≤100 (RR ≥ 1.05).ResultsWe included 11 randomized trials comprising 2704 patients. We found that etomidate increased mortality (319/1359 [23%] vs. 267/1345 [20%]; risk ratio (RR) = 1.16; 95% confidence interval (CI), 1.01–1.33; P = 0.03; I² = 0%; number needed to harm = 31). The probabilities of any increase and a 1% increase (NNH ≤100) in mortality were 98.1% and 92.1%, respectively.ConclusionsThis meta-analysis found a high probability that etomidate increases mortality when used as an induction agent in critically ill patients with a number needed to harm of 31.     

SOHO State of the Art Updates and Next Questions | Optimal Timing of Blinatumomab for the Treatment of B-Acute Lymphoblastic Leukemia

Blinatumomab is a CD19 targeting bi-specific T-cell engager antibody construct developed for the treatment of CD19 expressing B-cell malignancies. Numerous adult and pediatric B-ALL clinical trials have demonstrated blinatumomab's efficacy in the relapse setting as well as in patients with residual disease after upfront chemotherapy. The safety profile of blinatumomab is also favorable, making it a feasible option for most patients. Several key questions remain, including the role of blinatumomab as a replacement for toxic elements of standard chemotherapy regimens in the upfront setting, its role as a bridge to hematopoietic stem cell transplantation, or whether previous blinatumomab impacts the efficacy of subsequent CAR-T cell therapy.