Citations

Purpose: To examine the association of obesity with in-hospital mortality and complications during critical illness. Methods: We performed a retrospective analysis of a multiethnic cohort of 699 patients admitted to medical intensive care unit between January 2010 and May 2011 at Mount Sinai St. Luke’s and Mount Sinai West Hospitals, tertiary care centers in New York City. Multivariate logistic regression analysis was used to evaluate the association between obesity (body mass index [BMI] ≥ 30] and in-hospital mortality. Subgroup analysis was performed in elderly patients (age ≥65 years). Results: Compared to normal BMI, obese patients had lower in-hospital mortality (24.4% vs 17.6%, P = .04). On multivariate analysis, obesity was independently associated with lower in-hospital mortality (odds ratio [OR]: 0.49, 95% confidence interval [CI]: 0.27-0.89, P = .018). There was no significant difference in rates of mechanical ventilation, reintubation, and vasopressor requirement across BMI categories. In subgroup analysis, elderly obese patients did not display lower in-hospital mortality (adjusted OR: 0.85, 95% CI: 0.40-1.82, P = .68). Conclusion: Our study supports the hypothesis that obesity is associated with decreased mortality during critical illness. However, this finding was not observed among elderly obese patients. Further studies should explore the interaction between age, obesity, and outcomes in critical illness.

Background: Early sport specialization is not a requirement for success at the highest levels of competition and is believed to be unhealthy physically and mentally for young athletes. It also discourages unstructured free play, which has many benefits. Purpose: To review the available evidence on early sports specialization and identify areas where scientific data are lacking. Study Design: Think tank, roundtable discussion. Results: The primary outcome of this think tank was that there is no evidence that young children will benefit from early sport specialization in the majority of sports. They are subject to overuse injury and burnout from concentrated activity. Early multisport participation will not deter young athletes from long-term competitive athletic success. Conclusion: Youth advocates, parents, clinicians, and coaches need to work together with the sport governing bodies to ensure healthy environments for play and competition that do not create long-term health issues yet support athletic competition at the highest level desired.

Abstract Rationale Despite shared environmental exposures, idiopathic pulmonary fibrosis (IPF) and chronic obstructive pulmonary disease are usually studied in isolation, and the presence of shared molecular mechanisms is unknown. Objectives We applied an integrative genomic approach to identify convergent transcriptomic pathways in emphysema and IPF. Methods We defined the transcriptional repertoire of chronic obstructive pulmonary disease, IPF, or normal histology lungs using RNA-seq (n = 87). Measurements and Main Results Genes increased in both emphysema and IPF relative to control were enriched for the p53/hypoxia pathway, a finding confirmed in an independent cohort using both gene expression arrays and the nCounter Analysis System (n = 193). Immunohistochemistry confirmed overexpression of HIF1A, MDM2, and NFKBIB members of this pathway in tissues from patients with emphysema or IPF. Using reads aligned across splice junctions, we determined that alternative splicing of p53/hypoxia pathway–associated molecules NUMB and PDGFA occurred more frequently in IPF or emphysema compared with control and validated these findings by quantitative polymerase chain reaction and the nCounter Analysis System on an independent sample set (n = 193). Finally, by integrating parallel microRNA and mRNA-Seq data on the same samples, we identified MIR96 as a key novel regulatory hub in the p53/hypoxia gene-expression network and confirmed that modulation of MIR96 in vitro recapitulates the disease-associated gene-expression network. Conclusions Our results suggest convergent transcriptional regulatory hubs in diseases as varied phenotypically as chronic obstructive pulmonary disease and IPF and suggest that these hubs may represent shared key responses of the lung to environmental stresses.

Abstract Background: Autosomal-dominant polycystic kidney disease (ADPKD) is characterized by multitudes of expanding renal cysts associated with mononuclear interstitial infiltrates. Monocyte chemotactic protein-1 is produced in the kidneys and excreted in the urine (uMCP1) of these patients in increased amounts. In the TEMPO 3:4 trial, tolvaptan slowed the rate of increase in total kidney volume (TKV) and the rate of decline in estimated glomerular filtration rate (eGFR). In a sub-analysis, we determined whether tolvaptan administration for up to 3 years changed the urinary excretion of MCP-1 referenced to creatinine in 869 treated subjects compared with 438 placebo subjects. Methods: Treatment group differences of uMCP1 at 0.75, 12, 24 and 36 months were evaluated by ANCOVA with factor of treatment and covariate baseline. Results: At baseline, mean uMCP1 was 429 ± 224 pg/mg in the tolvaptan and 434 ± 233 pg/mg in the placebo groups, ∼4-fold greater than normal. Log uMCP1 associated positively with log TKV (r = 0.2645, P < 0.0001) and negatively with eGFR (r = −0.1555 P < 0.0001) and fasting urine osmolality (r = −0.1933, P < 0.0001). Tolvaptan reduced uMCP1 13.8 ± 4.4% (P < 0.0001) below placebo-treated subjects at 24 months and 14.4 ± 3.7% (P < 0.0001) at 36 months, and to the same extent in females and males. The effect of tolvaptan on uMCP1 excretion at 36 months extended across CKD Stage 1 (11.1 ± 6.4%, P = 0.0595), CKD 2 (13.9 ± 5.4%, P = 0.0050) and CKD 3 (21.4 ± 8.0%, P = 0.0020). Conclusion: Tolvaptan, administered for 3 years to patients with ADPKD, caused a sustained reduction in the urinary excretion of MCP-1 relative to placebo.

Alcohol consumption is associated with a modest increased risk of colon cancer, but its relationship with colon cancer survival has not been elucidated. Using data from a phase III randomized adjuvant trial, we assessed the association of alcohol consumption with colon cancer outcomes. Patients completed a risk factor questionnaire before randomization to FOLFOX or FOLFOX + cetuximab (N = 1984). Information was collected on lifestyle factors, including smoking, physical activity and consumption of different types of alcohol. Cox models assessed the association between alcohol consumption and outcomes of disease‐free survival (DFS), time‐to‐recurrence (TTR) and overall survival (OS), adjusting for age, sex, study arm, body mass, smoking, physical activity and performance status. No statistically significant difference in outcomes between ever and never drinkers were noted [hazard ratio (HR)DFS = 0.86, HRTTR = 0.87, HROS = 0.86, p‐values = 0.11–0.17]. However, when considering alcohol type, ever consumers of red wine (n = 628) had significantly better outcomes than never consumers (HRDFS = 0.80, HRTTR = 0.81, HROS = 0.78, p‐values = 0.01–0.02). Favorable outcomes were confirmed in patients who consumed 1‐30 glasses/month of red wine (n = 601, HR = 0.80–0.83, p‐values = 0.03–0.049); there was a suggestion of more favorable outcomes in patients who consumed >30 glasses/month of red wine (n = 27, HR = 0.33–0.38, p‐values = 0.05–0.06). Beer and liquor consumption were not associated with outcomes. Although alcohol consumption was not associated with colon cancer outcomes overall, mild to moderate red wine consumption was suggestively associated with longer OS, DFS and TTR in stage III colon cancer patients.

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.

ObjectivesTo describe medium‐ to long‐term follow‐up of patients undergoing device closure of patent foramen ovale (PFO) for stroke or transient ischemic attack (TIA).BackgroundTranscatheter device closure of PFO continues to be used for secondary prevention of cryptogenic stroke or TIA, but data are lacking regarding long‐term outcomes.MethodsWe reviewed the Mayo Clinic Rochester PFO database for patients who underwent device closure of PFO for secondary prevention of stroke/TIA from December 2001 to June 2012. Demographic, clinical, procedural, and follow‐up data were reviewed. Recurrence rate of stroke/TIA were calculated. Data were analyzed to identify risk factors of recurrent neurologic events.ResultsSeven hundred and thirty patients (mean age 53 years; 40% female) were included in our study. Most patients (72%) had cryptogenic stroke as their qualifying event for PFO closure. There were no procedure‐related deaths or strokes. The most commonly used device was the Amplatzer Septal Occluder (82%). Median follow‐up was 6 years. A 3.9% of patients had documented residual right‐to‐left shunting at last echocardiogram. Recurrent stroke and/or TIA were reported in 45 patients, (6.3% of patients with follow‐up data). Patients who experienced recurrent stroke/TIA were older and had a higher rate of diabetes and hypertension than those who did not. The presence of residual shunt did not correlate with risk of recurrent events.ConclusionsDevice closure of PFO can be performed safely with very good long‐term resolution of atrial shunting. Recurrent neurologic events after PFO closure may reflect additional comorbid risk factors unrelated to the potential for paradoxical embolism. © 2016 Wiley Periodicals, Inc.