Bengtsson McCurdy (kettlebirth6)
Systematic understanding of immune aging on a whole-body scale is currently lacking. We characterized age-associated alterations in immune cells across multiple mouse organs using single-cell RNA and antigen receptor sequencing and flow cytometry-based validation. We defined organ-specific and common immune alterations and identified a subpopulation of age-associated granzyme K (GZMK)-expressing CD8+ T (Taa) cells that are distinct from T effector memory (Tem) cells. Taa cells were highly clonal, had specific epigenetic and transcriptional signatures, developed in response to an aged host environment, and expressed markers of exhaustion and tissue homing. Activated Taa cells were the primary source of GZMK, which enhanced inflammatory functions of non-immune cells. In humans, proportions of the circulating GZMK+CD8+ T cell population that shares transcriptional and epigenetic signatures with mouse Taa cells increased during healthy aging. These results identify GZMK+ Taa cells as a potential target to address age-associated dysfunctions of the immune system.Prognostic factors associated with clinical outcomes of acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) patients with central nervous system (CNS) involvement are unknown. We retrospectively studied the characteristics and outcomes of 66 (18 pediatric and 48 adult) patients with CNS leukemia with ALL (n = 41) or AML (n = 25). The median age of patients at diagnosis of CNS leukemia was 30 (range, 1-69) years. Nearly two-third patients had CNS involvement at the initial diagnosis of leukemia. Complete remission of CNS leukemia was attained in 58 (88%) patients, and probability of overall survival at 36 months after the diagnosis of CNS leukemia was 43% for the entire cohort. We identified that achieving remission of systemic leukemia and having CNS leukemia diagnosed and treated before allogeneic transplantation were the factors associated with CNS leukemia remission. Prognostic factors associated with better overall survival in patients with CNS leukemia included pediatric age, diagnosis of CNS leukemia before receiving allogenic transplantation, achieving clearance of systemic or CNS leukemia, receiving no cranial radiation in conjunction with intrathecal chemotherapy (IT), and receiving IT consolidation after achieving remission of CNS leukemia. Our findings show that patients with CNS leukemia are at considerable risk of mortality. Awareness of modifiable prognostic factors such as avoidance of cranial radiation whenever possible and use of IT consolidation can result in improved outcomes in subset of patients with CNS leukemia. Management of acute type A aortic dissection (AADA) presenting with cardiopulmonary arrest (CPA) may require aggressive cardiopulmonary resuscitation (CPR), including extracorporeal CPR (ECPR) followed by aortic repair. This study evaluated the early and long-term outcomes of the patients with preoperative CPA related to AADA. Between 9/2003 and 8/2019, 474 patients with AADA brought to our hospital, 157 (33.1%) presenting with CPA. Their mean age and prevalence of out-of-hospital CPA was 74.3±11.3 years and 90%, respectively, and causes of CPA included cardiac tamponade in 75%, hemothorax in 10%, and coronary malperfusion in 10% of cases. check details In the same time periods, 2974 patients of CPA were transported, and AADA was 4.8% of all cause of CPA. Return of spontaneous circulation (ROSC) was achieved in 26(17%), and ECPR was required in 31(20%); 131(83%) of CPA patients died before surgery, 24(15%) underwent aortic repair and 2(1%) received non-surgical care. Hospital mortality was 90% and none survived without aortic repair. Of patients achieving ROSC, 17 underwent aortic repair, 13 survived and 5 fully recovered. All patients with ECPR died; 24 before surgery and 7 postoperatively. There were significant differences in hospital mortality between patients who did and did not undergo ao