Citations

Abstract Background: Despite a large body of literature evaluating the association between recreational physical activity and epithelial ovarian cancer (EOC) risk, the extant evidence is inconclusive, and little is known about the independent association between recreational physical inactivity and EOC risk. We conducted a pooled analysis of nine studies from the Ovarian Cancer Association Consortium to investigate the association between chronic recreational physical inactivity and EOC risk. Methods: In accordance with the 2008 Physical Activity Guidelines for Americans, women reporting no regular, weekly recreational physical activity were classified as inactive. Multivariable logistic regression was utilized to estimate the ORs and 95% confidence intervals (CI) for the association between inactivity and EOC risk overall and by subgroups based upon histotype, menopausal status, race, and body mass index. Results: The current analysis included data from 8,309 EOC patients and 12,612 controls. We observed a significant positive association between inactivity and EOC risk (OR = 1.34; 95% CI, 1.14–1.57), and similar associations were observed for each histotype. Conclusions: In this large pooled analysis examining the association between recreational physical inactivity and EOC risk, we observed consistent evidence of an association between chronic inactivity and all EOC histotypes. Impact: These data add to the growing body of evidence suggesting that inactivity is an independent risk factor for cancer. If the apparent association between inactivity and EOC risk is substantiated, additional work via targeted interventions should be pursued to characterize the dose of activity required to mitigate the risk of this highly fatal disease. Cancer Epidemiol Biomarkers Prev; 25(7); 1114–24. ©2016 AACR.

ABSTRACT Introduction Most surgical treatments for male lower urinary tract symptoms and benign prostatic hyperplasia affect erectile and ejaculatory functions negatively, leading to patient dissatisfaction. Aim To determine whether water vapor thermal therapy, when conducted in a randomized controlled trial, would significantly improve lower urinary tract symptoms secondary to benign prostatic hyperplasia and urinary flow rate while preserving erectile and ejaculatory functions. Methods Men at least 50 years old with International Prostate Symptom Scores of at least 13, a peak flow rate of at least 5 to no higher than 15 mL/s, and prostate volume of 30 to 80 cm3 were randomized 2:1 between Rezūm System thermal therapy and control. Thermal water vapor (103°C) was injected into lateral and median lobes as required for treatment of benign prostatic hyperplasia. The control procedure entailed rigid cystoscopy with simulated active treatment sounds. Main Outcome Measures Blinded group (active = 136, control = 61) comparison occurred at 3 months and the active arm was followed to 12 months for International Prostate Symptom Score, peak flow rate, and sexual function using the International Index of Erectile Function and the Male Sexual Health Questionnaire for Ejaculatory Function. The minimal clinically important difference in erectile function perceived by subjects as beneficial was determined for each erectile function severity category. Subjects not sexually active were censored from sexual function analysis. Results No treatment- or device-related de novo erectile dysfunction occurred after thermal therapy. International Index of Erectile Function and Male Sexual Health Questionnaire for Ejaculatory Function scores were not different from the control group at 3 months or from baseline at 1 year. Ejaculatory bother score improved 31% over baseline (P = .0011). Also, 32% of subjects achieved minimal clinically important differences in erectile function scores at 3 months, and 27% at 1 year, including those with moderate to severe erectile dysfunction. International Prostate Symptom Score and peak flow rate were significantly superior to controls at 3 months and throughout 1 year (P < .0001). Conclusion Convective water vapor thermal therapy provides sustainable improvements for 12 months to lower urinary tract symptoms and urinary flow while preserving erectile and ejaculatory functions.

PurposeThe purpose of this study is to evaluate the impact of perioperative fluid administration on the rates of postoperative complications following head and neck reconstruction with fibular free flaps (FFF).MethodsA retrospective cohort study of subjects undergoing head and neck reconstruction with FFF was completed. The primary predictor variable was the total volume of perioperative fluids administered on the day of surgery. The primary outcome variable was the presence of medical and surgical complications occurring within 30 days of surgery. Medical and surgical complications were stratified as major or minor based on severity level. Basic demographic information, comorbidity indices, and intraoperative parameters were abstracted as covariates. Univariable and multivariable models were developed to assess for associations between total fluid volume administered on the day of surgery and postoperative medical/surgical complications occurring within 30 days of surgery.ResultsIn 154 subjects, the partial flap failure rate was 3% and there were no complete flap failures. Total fluid volume was significantly associated with the presence of postoperative medical/surgical complications (OR = 1.21; 95% CI: 1.02–1.44; p = 0.032). A cutpoint for total fluid volume predicting any severity level of postoperative complication was identified at 5,500 mL. A cutpoint for total fluid volume predicting major postoperative complications was identified at 7,000 mL.ConclusionsThe results of this study suggest that liberal fluid administration is associated with increased rates of medical/surgical complications following head and neck reconstruction with FFF. © 2016 Wiley Periodicals, Inc. Microsurgery 37:128–136, 2017.

A peptide-universal nucleotide conjugate that mimics the topoisomerase I-DNA covalent complex was synthesized and then utilized to raise monoclonal antibodies.

Abstract Rationale Granulomatous-lymphocytic interstitial lung disease (GLILD) has emerged as a major cause of morbidity in patients with common variable immunodeficiency (CVID). While GLILD is among the most serious noninfectious pulmonary complications of CVID, risk factors for this condition have not been reported. Objectives To identify clinical, physiologic, and serologic risk factors for GLILD in adults with CVID. Methods Of 345 consecutive adult patients with CVID, we identified 34 in the National Jewish Health research database who had a radiographic-pathologic diagnosis of GLILD evaluated between 2002 and 2014. Each case was age and sex matched to 52 CVID control subjects. We used logistic regression to determine independent predictors of GLILD. A mixed effects model was used to estimate the longitudinal change in percent predicted FVC. Measurements and Main Results: The mean time from CVID diagnosis to GLILD detection was 7.8 years. Compared with matched control subjects, cases were more likely to have a history of autoimmune cytopenia, hypersplenism, polyarthritis, lower marginal zone and switched memory B cells, and restrictive lung function. Multivariate analysis revealed that hypersplenism (odds ratio [OR], 24; 95% confidence interval [CI], 4.5–179.1), polyarthritis (OR, 19; 95% CI, 2.3–206.8), and percent predicted FVC (OR, 0.93; 95% CI, 0.87–0.98) were independently associated with the development of GLILD. The rate of change of percent predicted FVC (slope, P = 0.48) did not vary significantly in patients with GLILD over a mean follow-up of 7 years after diagnosis. Conclusions Hypersplenism and polyarthritis are strong risk factors for GLILD in patients with CVID. Percent predicted FVC remained stable over time in patients with GLILD.

Purpose To attempt to visualize the ligament with standard 1.5‐tesla magnetic resonance imaging (MRI) in the acute anterior cruciate ligament (ACL)–torn knee, and if it is visible, attempt to characterize it as torn or intact at its femoral, meniscal, and tibial attachment sites. Methods This was a retrospective MRI study based on arthroscopic findings of a known ACL tear in 72 patients between the years 2006 and 2010. Patients all had hamstring ACL reconstructions, no concomitant lateral collateral ligament, or posterolateral corner injury based on imaging and physical examination, and had a preoperative 1.5‐tesla MRI scan with standard sequences performed within 3 weeks of the injury. Two fellowship‐trained musculoskeletal radiologists retrospectively reviewed the preoperative MRI for visualization of the anterolateral ligament (ALL) for concomitant tears. Inter‐ and intraobserver reliability was calculated. Learning effect was analyzed to determine if radiologists' agreement improved as reads progressed. Results Both radiologists were able to visualize the ALL in 100% of the scans. Overall, ALL tears were noted in 26% by radiologist 1 and in 62% by radiologist 2. The agreement between the ligament being torn or not had a kappa of 0.54 between radiologists. The agreements in torn or not torn between radiologists in the femoral, meniscal, and tibial sites were 0.14, 0.15, and 0.31. The intraobserver reliability by radiologist 1 for femoral, meniscal, and tibial tears was 0.04, 0.57, and 0.54 respectively. For radiologist 2, they were 0.75, 0.61, and 0.55. There was no learning effect noted. Conclusions ALL tears are currently unable to be reliably identified as torn or intact on standard 1.5‐tesla MRI sequences. Proper imaging sequences are of crucial importance to reliably follow these tears to determine their clinical significance. Level of Evidence Level IV, therapeutic case series study.

Abstract To move beyond a select few genes/drugs, the successful adoption of pharmacogenomics into routine clinical care requires a curated and machine-readable database of pharmacogenomic knowledge suitable for use in an electronic health record (EHR) with clinical decision support (CDS). Recognizing that EHR vendors do not yet provide a standard set of CDS functions for pharmacogenetics, the Clinical Pharmacogenetics Implementation Consortium (CPIC) Informatics Working Group is developing and systematically incorporating a set of EHR-agnostic implementation resources into all CPIC guidelines. These resources illustrate how to integrate pharmacogenomic test results in clinical information systems with CDS to facilitate the use of patient genomic data at the point of care. Based on our collective experience creating existing CPIC resources and implementing pharmacogenomics at our practice sites, we outline principles to define the key features of future knowledge bases and discuss the importance of these knowledge resources for pharmacogenomics and ultimately precision medicine.