Bioprosthetic Pulmonary Valve Dysfunction in Congenital Heart Disease.

BACKGROUND: We aim to identify the incidence and timing of dysfunction and failure of stented bioprosthetic valves in the pulmonary position in congenital heart disease patients. METHODS: A total of 482 congenital heart disease patients underwent 484 stented bioprosthetic pulmonary valve implantations between 2008 and 2018. There were 164 porcine valves (Porcine) and 320 bovine pericardial valves (Pericardial) implanted. Primary endpoints were survival, valve dysfunction, and valve failure. RESULTS: Pericardial valves were implanted in older patients (22.0, interquartile range [IQR] 14-33 vs 16.0, IQR 11-23 years, P < 0.001). Five-year survival (96.7% vs 97.9%) for the Pericardial and Porcine groups, respectively, were similar, P > 0.05. Forty-six (34%) Porcine and 75 (27%) Pericardial group patients met criteria for valve dysfunction at a median echocardiographic follow-up time of 7.43 years (IQR 4.1-9.5 years) and 3.26 years (IQR 1.7-4.7 years), respectively. More Pericardial group patients suffered from at least mild late PR while late median peak gradient was higher in the Porcine group, P < .001 for both. Risk factors for valve dysfunction included decreasing patient age for the entire cohort (hazard ratio [HR] 1.02, 95% confidence interval [CI] 1.00-1.04, P = .015) and lack of anticoagulation at discharge for the Porcine group (HR 3.06, 95% CI 1.03-9.10, P = .044) but not the Pericardial group. Five-year cumulative incidence of dysfunction was 39% for the Pericardial group and 17% for the Porcine group. CONCLUSIONS: Porcine stented and bovine pericardial stented valves can be implanted in the pulmonary position in all age groups safely. However, despite similar rates of valve failure, bovine pericardial stented valves have a higher incidence of valve dysfunction at mid-term follow-up.

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.

PhenoPro: a novel toolkit for assisting in the diagnosis of Mendelian disease.

MOTIVATION: Whole-exome sequencing (WES) is now being used in clinical practice for the diagnosis of the causal genes of Mendelian diseases. In order to make the diagnosis, however, the clinical phenotypes [e.g. Human Phenotype Ontology (HPO) terms] of a patient are needed for prioritizing the variants called from the WES data of the patient. Computational tools are therefore needed to standardize and accelerate this process. RESULTS: Here, we introduce a tool named PhenoPro for prioritizing the causal gene of Mendelian disease given both the HPO terms assigned to and the variants called from the WES data of a patient. PhenoPro has been benchmarked using both simulated patients and 287 real diagnosed patients of Chinese ancestry, and shows significant improvements over five previous tools. Moreover, the addition of an internal variant data of Chinese ancestry and the variant data from the patients' parents can further improve PhenoPro's performance. To make PhenoPro a fully automated tool, we also include a natural language processing component for automated HPO term assignment from clinical reports, and demonstrate that the natural language processing is as effective as manual HPO assignment using real clinical reports. In conclusion, PhenoPro can be used as a pre-screening tool to assist in the diagnosis of Mendelian disease genes. AVAILABILITY AND IMPLEMENTATION: The web server of PhenoPro is freely available at http://app.tianlab.cn. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

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.