Enriched housing differentially alters allostatic load and cardiopulmonary responses to wildfire-related smoke in male and female mice.

Living conditions are an important modifier of individual health outcomes and may lead to higher allostatic load (AL). However, housing-induced cardiovascular and immune effects contributing to altered environmental responsiveness remain understudied. This investigation was conducted to examine the influence of enriched (EH) versus depleted housing (DH) conditions on cardiopulmonary functions, systemic immune responses, and allostatic load in response to a single wildfire smoke (WS) exposure in mice. Male and female C57BL/6J mice were divided into EH or DH for 22 weeks, and cardiopulmonary assessments measured before and after exposures to either one-hr filtered air (FA) or flaming eucalyptus WS exposure. Male and female DH mice exhibited increased heart rate (HR) and left ventricular mass (LVM), as well as reduced stroke volume and end diastolic volume (EDV) one week following exposure to WS. Female DH mice displayed significantly elevated levels of IL-2, IL-17, corticosterone and hemoglobin A1c (HbA1c) following WS, while female in EH mice higher epinephrine levels were detected. Female mice exhibited higher AL than males with DH, which was potentiated post-WS exposure. Thus, DH increased susceptibility to extreme air pollution in a gender-dependent manner suggesting that living conditions need to be evaluated as a modifier of toxicological responses.

Management of hyperleukocytosis and impact of leukapheresis among patients with acute myeloid leukemia (AML) on short- and long-term clinical outcomes: a large, retrospective, multicenter, international study.

Hyperleukocytosis in acute myeloid leukemia (AML) is associated with inferior outcomes. There is limited high quality evidence to support the benefits of leukapheresis. We retrospectively collected data from patients with newly-diagnosed AML who presented with a white cell count (WBC) >50 × 109/L to 12 centers in the United States and Europe from 2006 to 2017 and received intensive chemotherapy. Logistic regression models estimated odds ratios for 30-day mortality and achievement of composite complete remission (CRc). Cox proportional hazard models estimated hazard ratios for overall survival (OS). Among 779 patients, clinical leukostasis was reported in 27%, and leukapheresis was used in 113 patients (15%). Thirty-day mortality was 16.7% (95% CI: 13.9-19.3%). Median OS was 12.6 months (95% CI: 11.5-14.9) among all patients, and 4.5 months (95% CI: 2.7-7.1) among those ≥65 years. Use of leukapheresis did not significantly impact 30-day mortality, achievement of CRc, or OS in multivariate analysis based on available data or in analysis based on multiple imputation. Among patients with investigator-adjudicated clinical leukostasis, there were statistically significant improvements in 30-day mortality and OS with leukapheresis in unadjusted analysis, but not in multivariate analysis. Given the significant resource use, cost, and potential complications of leukapheresis, randomized studies are needed to evaluate its value.