Thrombin-mediated activation of PAR1 enhances doxorubicin-induced cardiac injury in mice
This study by Grover et al used preclinical models to determine the contribution of cardiac myocytes and fibroblasts for doxorubicin-induced cardiac toxicity and the mechanism of PAR1 activation in this process.
Third-dose SARS-CoV-2 mRNA vaccine increases Omicron variant neutralization in patients with chronic myeloid disorders
Omicron variants have led to ongoing significant health care challenges of COVID-19, especially in patients with underlying comorbidities. In this study, Harrington and colleagues report on the immunogenicity of a third dose of SARS-CoV-2 mRNA vaccine in patients with chronic myeloid disorders. The authors found an increased T-cell response and viral neutralization after a third dose of the COVID vaccine in these patients. Impaired cellular responses and breakthrough infections, however, were observed in vaccinated patients taking the JAK1/2 inhibitor ruxolitinib.
Obstetric and perioperative management of patients with factor XI deficiency: a retrospective observational study
Factor XI (FXI) deficiency is an inherited bleeding disorder that is a risk for life-threatening bleeding during childbirth or surgery. Data regarding obstetric and perioperative management of this condition, however, are scarce. Here, Handa and coauthors describe the real-world experience of managing FXI deficiency in a large population of obstetric patients.
Outcomes of subsequent neoplasms after umbilical cord blood transplantation in Europe
Kaposi sarcoma-associated herpesvirus (KSHV) is a polyclonal B-cell lymphoproliferative disorder that occurs in immunocompromised hosts. Although the etiology of the disease has been elucidated, questions remain about the cell types harboring KSHV, and diagnostic tests would be helpful for clinical care. In this report, de Frémont and colleagues show that peripheral blood phenotyping is a promising tool for diagnosing active multicentric Castleman disease, especially in acutely ill patients with coagulation disorders precluding and delaying lymph node sampling.
Sustained hematologic remission after discontinuation of sutimlimab treatment in patients with cold agglutinin disease
Gelbenegger and colleagues provide the first report of a sustained hematologic remission after the discontinuation of sutimlimab that (1) provides provocative early data suggesting that some patients can safely come off therapy and (2) suggests possible effects of sutimlimab on the antibody response in cold agglutinin disease. Future studies will be needed to confirm these findings and identify patients most likely to successfully come off treatment.
AKT supports the metabolic fitness of multiple myeloma cells by restricting FOXO activity
In this article, Bloedjes and colleagues demonstrate that negative regulation of the forkhead box O (FOXO) transcription factors (TF) by AKT is crucial to prevent metabolic shutdown in myeloma cells, thus contributing to their metabolic adaptability. The expression of several key metabolic genes involved in glycolysis, the tricarboxylic acid (TCA) cycle and OXPHOS, are repressed by FOXO TFs. Moreover, the FOXO-dependent repression of glycolysis- and TCA-associated genes correlates with a favorable prognosis in a large multiple myeloma (MM) patient cohort by a gene expression profile analysis. The authors conclude that repression of FOXO by AKT is essential to sustain glycolysis and the TCA cycle activity in MM cells, and as such predicts patient survival.
