Citations

Significance HIV-1 requires integration for efficient gene expression, and the local chromatin environment significantly influences the level of HIV-1 transcription. Silent, integrated proviruses constitute the latent HIV reservoir. As HIV-1 commandeers cellular factors to dictate its preferred integration sites, these interactions consequentially influence latency. We examined the impact of polyadenylation specificity factor CPSF6, which binds HIV-1 capsid, and the integrase-binding chromatin reader LEDGF/p75 on viral infection and integration site distribution. Integration sites were determined in cells knocked down or knocked out for one or both host factors. Our data indicate that CPSF6 directs HIV-1 to transcriptionally active chromatin, where LEDGF/p75 predominantly directs the positions of integration within genes. These findings clarify the roles of cellular forces that dictate HIV-1 integration preferences and hence virus pathogenesis.

Purpose Factors associated with early mortality after surgery and treatment with adjuvant chemotherapy in colon cancer are poorly understood. We aimed to characterize the determinants of early mortality in a large cohort of colon cancer trial participants. Methods A pooled analysis of 37,568 patients in 25 randomized trials of adjuvant systemic therapy was conducted. Multivariable logistic regression models with several definitions of early mortality (30, 60, and 90 days, and 6 months) were constructed, adjusting for clinically and statistically significant variables. A nomogram for 6-month mortality was developed and validated. Results Median age among patients was 61 years, patient demographics included 54% men and 90% White, 29% and 71% had stage II and III disease, respectively, and 79%, 20%, and 1% had an Eastern Cooperative Oncology Group performance status (PS) of 0, 1, and ≥ 2, respectively. Early mortality was low: 0.3% at 30 days, 0.6% at 60 days, 0.8% at 90 days, and 1.4% at 6 months. Of those patients who died by 6 months post–random assignment, 40% had documented disease recurrence prior to death. Early disease recurrence was associated with a markedly increased risk of death during the first 6 months post-treatment (hazard ratio, 82.6; 95%CI, 66.9 to 102.1). In prognostic analyses, advanced age, male sex, poorer PS, increasing ratio of positive to examined lymph nodes, earlier decade of enrollment, and higher tumor stage and grade predicted a greater likelihood of early mortality, whereas treatment received was not strongly predictive. A multivariable model for 6-month mortality showed strong optimism-adjusted discrimination (concordance index, 0.73) and calibration. Conclusion Early mortality was infrequent but more prevalent in patients with advanced age and a PS of ≥ 2, underscoring the need to carefully consider the risk-to-benefit ratio when making treatment decisions in these subgroups.

Abstract Peterson, BJ, Fitzgerald, JS, Dietz, CC, Ziegler, KS, Baker, SE, and Snyder, EM. Off-ice anaerobic power does not predict on-ice repeated shift performance in hockey. J Strength Cond Res 30(9): 2375–2381, 2016—Anaerobic power is a significant predictor of acceleration and top speed in team sport athletes. Historically, these findings have been applied to ice hockey although recent research has brought their validity for this sport into question. As ice hockey emphasizes the ability to repeatedly produce power, single bout anaerobic power tests should be examined to determine their ability to predict on-ice performance. We tested whether conventional off-ice anaerobic power tests could predict on-ice acceleration, top speed, and repeated shift performance. Forty-five hockey players, aged 18–24 years, completed anthropometric, off-ice, and on-ice tests. Anthropometric and off-ice testing included height, weight, body composition, vertical jump, and Wingate tests. On-ice testing consisted of acceleration, top speed, and repeated shift fatigue tests. Vertical jump (VJ) ( r = −0.42; r = −0.58), Wingate relative peak power (WRPP) ( r = −0.32; r = −0.43), and relative mean power (WRMP) ( r = −0.34; r = −0.48) were significantly correlated ( p ≤ 0.05) to on-ice acceleration and top speed, respectively. Conversely, none of the off-ice tests correlated with on-ice repeated shift performance, as measured by first gate, second gate, or total course fatigue; VJ ( r = 0.06; r = 0.13; r = 0.09), WRPP ( r = 0.06; r = 0.14; r = 0.10), or WRMP ( r = −0.10; r = −0.01; r = −0.01). Although conventional off-ice anaerobic power tests predict single bout on-ice acceleration and top speed, they neither predict the repeated shift ability of the player, nor are good markers for performance in ice hockey.

Background— Clinical trials of implantable cardioverter defibrillators (ICDs) for primary prevention enrolled a limited number of women. We sought to examine clinical practice data to compare survival rates among women with heart failure with or without a primary prevention ICD. Methods and Results— We linked data from 264 US hospitals included in the Get With The Guidelines for Heart Failure registry with data from the Centers for Medicare and Medicaid Services. From these sources, we propensity score matched 430 women with heart failure who received a primary prevention ICD to 430 women who did not; we further adjusted using a Cox proportional hazards model. Median follow-up was 3.4 and 3.0 years. For comparison, we matched 859 men receiving an ICD with 859 who did not; median follow-up was 3.9 versus 2.9 years. In the matched cohorts, an ICD was associated with similarly better survival in women (hazard ratio, 0.78; 95% confidence interval, 0.66–0.92; P =0.003) and men (hazard ratio, 0.76; 95% confidence interval, 0.67–0.87 P <0.001). There was no interaction between sex and presence of an ICD with respect to survival ( P =0.79). Conclusions— Among patients with heart failure with reduced left ventricular ejection fraction, a primary prevention ICD was associated with a significant survival advantage among women and among men. These findings support guideline-directed use of primary prevention ICDs in eligible patients.

In the United States alone, there are currently approximately 14.5 million cancer survivors, and this number is expected to increase to 20 million by 2020. Cancer therapies can cause significant injury to the vasculature, resulting in angina, acute coronary syndromes (ACS), stroke, critical limb ischemia, arrhythmias, and heart failure, independently from the direct myocardial or pericardial damage from the malignancy itself. Consequently, the need for invasive evaluation and management in the cardiac catheterization laboratory (CCL) for such patients has been increasing. In recognition of the need for a document on special considerations for cancer patients in the CCL, the Society for Cardiovascular Angiography and Interventions (SCAI) commissioned a consensus group to provide recommendations based on the published medical literature and on the expertise of operators with accumulated experience in the cardiac catheterization of cancer patients. © 2016 Wiley Periodicals, Inc.

Studies have demonstrated associations between cardiovascular factors and Alzheimer disease (AD) with minimal focus on other neurodegenerative diseases. Utilizing cross-sectional data from 17,532 individuals in the National Alzheimer’s Coordinating Center, Uniform Data Set, we compared the presence of cardiovascular factors [body mass index (BMI), atrial fibrillation, hypertension, hyperlipidemia, and diabetes] in individuals carrying a diagnosis of Probable AD (ProbAD), Possible AD, vascular dementia, dementia with Lewy bodies (DLB), frontotemporal dementia, Parkinson disease, progressive supranuclear palsy, or corticobasal degeneration, with that of normals. Generalized linear mixed models were fitted with age at visit, gender, and cardiovascular factors as fixed effects and Alzheimer’s Disease Centers as random effects. In late life, only BMI of ProbAD and DLB patients was statistically significantly lower than that in normals (P–values <0.001). When accounting for colinearity within cardiovascular factors, a low BMI was a comorbidity of certain dementia etiologies as compared with normals. These data support a concept of disease-specific associations with certain cardiovascular factors.

AbstractBackgroundPedicle screws are a preferred method for spinal fixation because of their three‐column support and rigid posterior stabilization. The purpose of this study was to evaluate the outcome of patients requiring pedicle screw redirection, and to describe a technique using cone‐beam computed tomography (cbCT).MethodsA retrospective review of 30 patients undergoing revision spinal fusion with redirection of pedicle screws was performed. Fifty pedicle screws were redirected in these patients using cbCT‐based 3D image guidance. They were graded pre‐ and post‐operatively using an established grading system.ResultsNo complications occurred in this study as a result of redirection. No pedicle breach was noted in all of the redirected pedicle screws.ConclusionRedirection of misplaced pedicle screws using cbCT‐based 3D image guidance seems to be safe and accurate in our experience. Further studies are needed to establish its safety, accuracy, fusion rate, and clinical outcome compared with other methods. Copyright © 2016 John Wiley & Sons, Ltd.