FANCA is a component of the Fanconi anemia (FA) core complex that activates DNA interstrand crosslink repair by monoubiquitination of FANCD2. Here, we report that purified FANCA protein catalyzes bidirectional single-strand annealing (SA) and strand exchange (SE) at a level comparable to RAD52, while a disease-causing FANCA mutant, F1263Δ, is defective in both activities. FANCG, which directly interacts with FANCA, dramatically stimulates its SA and SE activities. Alternatively, FANCB, which does not directly interact with FANCA, does not stimulate this activity. Importantly, five other patient-derived FANCA mutants also exhibit deficient SA and SE, suggesting that the biochemical activities of FANCA are relevant to the etiology of FA. A cell-based DNA double-strand break (DSB) repair assay demonstrates that FANCA plays a direct role in the single-strand annealing sub-pathway (SSA) of DSB repair by catalyzing SA, and this role is independent of the canonical FA pathway and RAD52.

Surgical AF ablation during cardiac surgery improves freedom from AF. However, impact on patient-important outcomes including mortality and stroke has not shown statistical significance in current RCT evidence. Biatrial compared with left-sided lesion sets showed no difference in mortality or stroke but were associated with significantly increased freedom from AF and risk for pacemaker requirement.

Background The burden of frailty on cardiac surgical outcomes is incompletely understood. Here we perform a systematic review and meta-analysis of studies comparing frail versus pre-frail versus non-frail patients following cardiac surgery. Methods We searched MEDLINE and EMBASE databases until July 2018 for studies comparing cardiac surgery outcomes in “frail”, “pre-frail” and “non-frail” patients. Data was extracted in duplicate. Primary outcome was operative mortality. Results There were 19 observational studies with 66,448 patients. Frail patients were more likely female (risk ratio [RR]1.7; 95%CI:1.5–1.9), older (mean difference: 2.4; 95%CI:1.3–3.5 years older) with greater comorbidities and higher STS-PROM. Frailty (RR2.35; 95%CI:1.57–3.51; p < 0.0001) and pre-frailty (RR2.03; 95%CI:1.52–2.70; p < 0.00001) were associated with increased operative mortality compared with non-frail patients. Frailty was also associated with greater risk of prolonged hospital stay (RR1.83; 95%CI:1.61–2.08; p < 0.0001) and intermediate care facility discharge (RR2.71; 95%CI:1.45–5.05; p = 0.002). Frail (Hazard Ratio [HR]3.27; 95%CI:1.93–5.55; p < 0.0001) and pre-frail patients (HR2.30; 95%CI:1.29–4.09; p = 0.005) had worse mid-term mortality (median follow-up 1 years [range 0.5–4 years]). After adjustment for baseline imbalances, frailty was still associated with greater operative mortality (odds ratio [OR]1.97; 95%CI:1.51–2.57; p < 0.00001), intermediate care facility discharge (OR4.61; 95%CI:2.78–7.66; p < 0.00001) and midterm mortality (HR1.37; 95%CI:1.03–1.83; p = 0.03). Conclusion In patients undergoing cardiac surgery, frailty and pre-frailty were associated with 2-fold and 1.5-fold greater adjusted operative mortality, respectively, greater adjusted perioperative complications and frailty was associated with almost 5-fold risk of non-home discharge. Graphical abstract Burden of frailty and pre-frailty on cardiac surgical outcomes.

Objective Del Nido cardioplegia (DC) has been used extensively in pediatric cardiac surgery but the efficacy and safety in adults remains uncertain. Our objective was to perform a systematic review and meta-analysis comparing DC and blood cardioplegia (BC) in our primary endpoint of 30-day or in-hospital mortality as well as other efficacy and safety endpoints. Methods Both MEDLINE and EMBASE were searched from 1996 to 2017 for studies comparing DC and BC. Data were extracted by 2 independent investigators and aggregated in a random effects model. Results One randomized controlled trial ( n = 89), 7 adjusted ( n = 1,104), and 5 unadjusted observational studies ( n = 717) were included. There was no difference in in-hospital mortality between DC and BC (relative risk:0.67, 95% confidence interval [CI]: 0.22, 2.07; P = 0.49). DC reduced cardioplegia volume requirements (mean difference [MD]:−1.1 L, 95% CI, −1.6, −0.6; P < 0.0001), aortic cross-clamp time (MD: −8 minutes, 95% CI, −12, −3; P = 0.0004), and cardiopulmonary bypass (CPB) times (MD: −8 minutes, 95% CI, −14, −3; P = 0.03). DC reduced troponin release (standardized MD: −0.3, 95% CI, −0.5, −0.1; P = 0.001). In-hospital outcomes of stroke, atrial fibrillation, acute kidney injury/dialysis, low cardiac output state, blood transfusion, reoperation rate, postoperative left ventricular EF, intensive care unit length of stay (LOS), and in-hospital LOS were comparable between groups. Conclusions DC is a safe alternative to BC in routine adult cardiac surgery. Its use is associated with reduction in CPB and aortic cross-clamp times and may potentially offer improved myocardial protection.