Fatal late-onset CAR T-cell-mediated encephalitis after axicabtagene-ciloleucel in a patient with large B-cell lymphoma.

Treatment with CD19-directed (CAR) T cells has evolved as a standard of care for multiply relapsed or refractory large B-cell lymphoma (r/r LBCL). A common side effect of this treatment is the immune effector cell-associated neurotoxicity syndrome (ICANS). Severe ICANS can occur in up to 30% to 40% of patients treated with axicabtagene-ciloleucel (axi-cel), usually within the first 4 weeks after administration of the dose and usually responding well to steroids. We describe a case of progressive central neurotoxicity occurring 9 months after axi-cel infusion in a patient with r/r LBCL who had undergone a prior allogeneic hematopoietic cell transplant. Despite extensive systemic and intrathecal immunosuppression, neurological deterioration was inexorable and eventually fatal within 5 months. High CAR T-cell DNA copy numbers and elevated levels of interleukin-1 (IL-1) and IL-6 were found in the cerebral spinal fluid as clinical symptoms emerged, and CAR T-cell brain infiltration was observed on autopsy, suggesting that CAR T cells played a major pathogenetic role. This case of unexpected, devastating, late neurotoxicity warrants intensified investigation of neurological off-target effects of CD19-directed CAR T cells and highlights the need for continuous monitoring for late toxicities in this vulnerable patient population.

Erythropoietin in the Evaluation of Treatment Outcomes in Patients with Polytrauma.

Polytrauma is a term describing patients with injuries involving multiple body regions that compromises function of the body and/or organ involved. The aim of the study was to evaluate the potential role of erythropoietin in predicting poorer outcome in trauma patients. This prospective study included 86 patients admitted to the Emergency Center of Serbia due to polytrauma assigned according to Injury Severity Score (ISS). The patients were further evaluated using the Acute Physiology and Chronic Health Evaluation II and Sequential Organ Failure Assessment scores and erythropoietin levels. There was a significant difference among erythropoietin levels at admission, after 48 and 72 hours, and on day 7 of hospital stay, with significantly higher levels in patients with ISS values 49-75. Based on the results, ROC curves were used to identify cut-off levels to predict ISS score with critical clinical course. It was concluded that erythropoietin could be a good marker of injury severity. Further research has to be performed to determine the cut-off values of erythropoietin that are significant for injury severity.

Incidence of diabetes mellitus among children of Italian migrants substantiates the role of genetic factors in the pathogenesis of type 1 diabetes.

UNLABELLED: To investigate the role of genetic and environmental factors in the pathogenesis of type 1 diabetes mellitus (T1D), we carried out a study in Germany aimed at comparing the prevalence and incidence of T1D among children of migrant Italians from high-risk (Sardinia) and low-risk (continental Italy) regions versus German children. Children from Italy were identified by the "Baden-Wuerttemberg (BW) Diabetes Incidence Registry", which registered 4017 newly diagnosed T1D patients, aged 0-14 years, between 1987 and 2003. Data relating to T1D children from Sardinia were elicited from more than 2000 questionnaires. Our findings were: (1) T1D is more frequent among German children than among children of Italian migrants [incidence rate (IR) 14.8/100,000/year, 95% confidence interval (CI) 14.4-15.4 vs. IR 10.8/100,000/year, 95% CI 8.2-13.6); (2) the incidence of T1D among Italian children residing in Germany is similar to that of Italian children in the home country (IR 10.8/100,000/year, 95% CI 8.2-13.6 vs. 8.4/100,000/year, 95% CI 7.9-8.9); (3) the prevalence of T1D among Sardinian children is higher than that among German children (0.11%, 95% CI 0.11-0.12) independent of the place where the Sardinian children are living (Sardinian children in Germany 2.3%, 95% CI 0.5-6.5 vs. Sardinian children in Sardinia 0.30%, 95% CI 0.27-0.32). CONCLUSION: Children from high- and low-risk areas of Italy have incidence rates of T1D that are closer to those of their native regions than to those of German children, indicating that genetic factors play a predominant role in the pathogenesis of T1D.