Mutation position is an important determinant for predicting cancer neoantigens.

Tumor-specific mutations can generate neoantigens that drive CD8 T cell responses against cancer. Next-generation sequencing and computational methods have been successfully applied to identify mutations and predict neoantigens. However, only a small fraction of predicted neoantigens are immunogenic.

Preoperative Treatment of Obstructive Sleep Apnea With Positive Airway Pressure is Associated With Decreased Incidence of Atrial Fibrillation After Cardiac Surgery.

Objective: Based on clinical studies in the nonsurgical population that positive airway pressure (PAP) therapy for patients with obstructive sleep apnea (OSA) provides benefits for those with atrial fibrillation, the authors tested the hypothesis that PAP in patients with OSA reduces the incidence of postoperative atrial fibrillation (POAF) after cardiac surgery.

Design: Retrospective analysis.

Setting: Single-center university hospital.

Obstructive Sleep Apnea Is an Independent Predictor of Postoperative Atrial Fibrillation in Cardiac Surgery.

Objective: To test the hypothesis that obstructive sleep apnea (OSA) is a risk factor for development of postoperative atrial fibrillation (POAF) after cardiac surgery.

Design: Retrospective analysis.

Setting: Single-center university hospital.

P-wave characteristics on routine preoperative electrocardiogram improve prediction of new-onset postoperative atrial fibrillation in cardiac surgery.

Objective: To test the hypothesis that including preoperative electrocardiogram (ECG) characteristics with clinical variables significantly improves the new-onset postoperative atrial fibrillation prediction model.

Design: Retrospective analysis.

Setting: Single-center university hospital.

Decentralization of care for adults with congenital heart disease in the United States: a geographic analysis of outpatient surgery.

Background: Guidelines recommend that adults with congenital heart disease (CHD) undergo noncardiac surgery in regionalized centers of expertise, but no studies have assessed whether this occurs in the United States. We hypothesized that adults with CHD are less likely than children to receive care at specialized CHD centers.

Methods: Using a comprehensive state ambulatory surgical registry (California Ambulatory Surgery Database, 2005-2011), we calculated the proportion of adult and pediatric patients with CHD who had surgery at a CHD center, distance to the nearest CHD center, and distance to the facility where surgery was performed.

Perioperative morbidity and mortality after noncardiac surgery in young adults with congenital or early acquired heart disease: a retrospective cohort analysis of the National Surgical Quality Improvement Program database.

An increasing number of patients with congenital heart disease survive to adulthood. Expert opinion suggests that noncardiac surgery is a high-risk event, but few data describe perioperative outcomes in this population. Using the National Surgical Quality Improvement Program database, we identified a cohort of patients aged 18 to 39 years with prior heart surgery who underwent noncardiac surgery between 2005 and 2010.

Factors contributing to adverse perioperative events in adults with congenital heart disease: a structured analysis of cases from the closed claims project.

Objective: Prior investigations have suggested that the rapidly growing population of adults with congenital heart disease is at increased risk of perioperative morbidity and mortality, but information is limited on the nature of those perioperative factors that may relate to adverse outcomes. We sought to use a national claims database to describe the contribution of perioperative factors to adverse outcomes and compare contributing factors in cardiac vs. noncardiac operations.

Temporal changes in survival after cardiac surgery are associated with the thirty-day mortality benchmark.

Objective: To assess the hypothesis that postoperative survival exhibits heterogeneity associated with the timing of quality metrics.

Data Sources: Retrospective observational study using the Nationwide Inpatient Sample from 2005 through 2009.

Study Design: Survival analysis was performed on all admission records with a procedure code for major cardiac surgery (n = 595,089).

Perioperative morbidity and mortality of cardiothoracic surgery in patients with a do-not-resuscitate order.

Background. Do-not-resuscitate (DNR) orders are often active in patients with multiple comorbidities and a short natural life expectancy, but limited information exists as to how often these patients undergo high-risk operations and of the perioperative outcomes in this population. Methods.

Resource use trends in extracorporeal membrane oxygenation in adults: an analysis of the Nationwide Inpatient Sample 1998-2009.

Objective: The study objective was to determine whether significant trends over time have occurred in resource use associated with the use of extracorporeal membrane oxygenation in critically ill adults.

Methods: All adult admissions involving extracorporeal membrane oxygenation were examined by using the Nationwide Inpatient Sample database (years 1998-2009). Trends in volume, outcome, and resource use (including hospital charges, length of stay, and charges per day) were analyzed.

Heart transplantation with or without prior mechanical circulatory support in adults with congenital heart disease.

Objectives: Recent analyses establish that heart transplantation is increasing among adults with congenital heart disease (ACHD), but the effects of pretransplant mechanical circulatory support (MCS) on perioperative and post-transplant outcomes have not been examined in the ACHD population.

Methods: Scientific Registry of Transplant Recipients data on all adult heart transplants from September 1987 to September 2012 (n = 47 160) were classified based on primary diagnosis codes as CHD or non-CHD and MCS or non-MCS. Demographic, procedural, outcome and survival variables were compared between MCS and non-MCS ACHD patient groups.

Perioperative outcomes of major noncardiac surgery in adults with congenital heart disease.

Background: An increasing number of patients with congenital heart disease are surviving to adulthood. Consensus guidelines and expert opinion suggest that noncardiac surgery is a high-risk event, but few data describe perioperative outcomes in this population.

Methods: By using the Nationwide Inpatient Sample database (years 2002 through 2009), the authors compared patients with adult congenital heart disease (ACHD) who underwent noncardiac surgery with a non-ACHD comparison cohort matched on age, sex, race, year, elective or urgent or emergency procedure, van Walraven comborbidity score, and primary procedure code.

Case report: a thrombus in the venous reservoir while using bivalirudin in a patient with heparin-induced thrombocytopenia undergoing heart transplantation.

Direct thrombin inhibitors are heparin alternatives for anticoagulation during cardiopulmonary bypass in patients with heparin-induced thrombocytopenia. We report a case of a large thrombus forming in the venous reservoir while using bivalirudin. We suggest that blood stasis associated with the full venous reservoir maintained in this case led to formation of a large thrombus at the top of the venous canister.

Gene expression profiling: classification of mice with left ventricle systolic dysfunction using microarray analysis.

Objective: We tested the hypothesis that a set of differentially expressed genes could be used to classify mice according to cardiovascular phenotype after prolonged catecholamine stress.

Design: Prospective, randomized study.

Setting: University-based research laboratory.

DDA3 recruits microtubule depolymerase Kif2a to spindle poles and controls spindle dynamics and mitotic chromosome movement.

Dynamic turnover of the spindle is a driving force for chromosome congression and segregation in mitosis. Through a functional genomic analysis, we identify DDA3 as a previously unknown regulator of spindle dynamics that is essential for mitotic progression. DDA3 depletion results in a high frequency of unaligned chromosomes, a substantial reduction in tension across sister kinetochores at metaphase, and a decrease in the velocity of chromosome segregation at anaphase.

Aurora A regulates the activity of HURP by controlling the accessibility of its microtubule-binding domain.

HURP is a spindle-associated protein that mediates Ran-GTP-dependent assembly of the bipolar spindle and promotes chromosome congression and interkinetochore tension during mitosis. We report here a biochemical mechanism of HURP regulation by Aurora A, a key mitotic kinase that controls the assembly and function of the spindle. We found that HURP binds to microtubules through its N-terminal domain that hyperstabilizes spindle microtubules.

HURP controls spindle dynamics to promote proper interkinetochore tension and efficient kinetochore capture.

Through a functional genomic screen for mitotic regulators, we identified hepatoma up-regulated protein (HURP) as a protein that is required for chromosome congression and alignment. In HURP-depleted cells, the persistence of unaligned chromosomes and the reduction of tension across sister kinetochores on aligned chromosomes resulted in the activation of the spindle checkpoint. Although these defects transiently delayed mitotic progression, HeLa cells initiated anaphase without resolution of these deficiencies.

A Xenopus cell-free system for analysis of the Chfr ubiquitin ligase involved in control of mitotic entry.

The checkpoint protein Chfr delays entry into mitosis in the presence of mitotic stress. We have analyzed the Chfr checkpoint pathway in the Xenopus cell-free system. We showed that Chfr is a ubiquitin ligase that targets polo-like kinase (Plk1) for degradation, leading to delayed activation of the Cdc25C phosphatase and prolonged inhibitory phosphorylation of Cdc2 at the G2/M transition.

The checkpoint protein Chfr is a ligase that ubiquitinates Plk1 and inhibits Cdc2 at the G2 to M transition.

The checkpoint protein Chfr delays entry into mitosis, in the presence of mitotic stress (Scolnick, D.M., and T.