Sex Differences in Failure-to-Rescue After Coronary Artery Bypass Grafting.

BACKGROUND: Female patients experience worse outcomes after coronary artery bypass grafting (CABG). We investigated whether rates of failure-to-rescue (FTR), a systems-based quality indicator, were greater in women who underwent CABG. METHODS: A retrospective review was conducted on 20 045 patients who underwent isolated, nonemergent CABG between January 2002 and August 2019 at a single academic center. FTR was defined as postoperative death within 30 days after stroke, renal failure, reoperation, and prolonged ventilation. Propensity score matching was performed utilizing preoperative variables, excluding sex. RESULTS: A total of 4980 propensity score-matched pairs were identified. In the matched analysis, women experienced higher rates of postoperative stroke (1.9% vs 1.2%; P = .008), prolonged ventilation (13.3% vs 10.0%, P < .001), and 30-day mortality (2.6% vs 1.8%; P = .01). Rates of FTR after stroke (P = .36), renal failure (P = .11), reoperation (P = .86), and prolonged ventilation (P = .48) were not statistically significant between female and male patients. CONCLUSIONS: Women who underwent isolated, nonemergent CABG had statistically similar frequencies of FTR compared with their male counterparts despite experiencing greater rates of morbidity and mortality. Further efforts to narrow the sex outcome gap after CABG should focus on preoperative and intraoperative phases of care instead of postoperative management.

Chromosomal instability in in vitro cultured mouse hematopoietic cells associated with oxidative stress.

Hematopoietic stem cells (HSCs) that give rise to all blood cell types are important vehicles for cell-based and gene therapies. After isolation from the bone marrow, HSCs are often cultured in laboratory settings for purposes of ex vivo expansion, gene transduction, and bone marrow transplantation for the treatment of various disorders of the blood and immune systems. Here we demonstrate that during in vitro culturing outside of hypoxic bone marrow niches, HSCs may genetically alter even after short durations of time. Lineage(-) Scal-1(+) c-Kit(+) (LSK) cells that are enriched with HSCs revealed significant levels of genomic instability following culture, as evidenced by the emergence of aneuploid cells. To further determine the effects of in vitro culturing conditions, whole bone marrow cells were cultured in a hypoxic environment of 3% oxygen, mimicking conditions within the body's bone marrow, following which, cells proved to undergo less genetic alterations. Proper dosages of the antioxidant N-Acetyl-Cysteine (NAC) similarly decreased occurrences of chromosomal change. Furthermore, analysis of aged hematopoietic cells revealed enhanced in vitro normoxic culture-induced chromosomal instability compared to that of young hematopoietic cells due to noted increased oxidative stress in aged cells. These results reveal that in vitro cell culturing does indeed cause genomic instability in hematopoietic cells. Reduced oxygen to physiological levels and additions of antioxidants can be employed as possible strategies to lower oxidative stress and decrease chances of chromosomal transformation. Because hematopoietic cells are commonly processed in laboratory settings before transplantation for patient treatment, our findings also raise a concern on the therapeutic use of cultured hematopoietic cells.