Preoperative Factors Predict Postoperative Trajectories of Pain and Disability Following Surgery for Degenerative Lumbar Spinal Stenosis.

STUDY DESIGN: Longitudinal analysis of prospectively collected data. OBJECTIVE: Investigate potential predictors of poor outcome following surgery for degenerative lumbar spinal stenosis (LSS). SUMMARY OF BACKGROUND DATA: LSS is the most common reason for an older person to undergo spinal surgery, yet little information is available to inform patient selection. METHODS: We recruited LSS surgical candidates from 13 orthopedic and neurological surgery centers. Potential outcome predictors included demographic, health, clinical, and surgery-related variables. Outcome measures were leg and back numeric pain rating scales and Oswestry disability index scores obtained before surgery and after 3, 12, and 24 postoperative months. We classified surgical outcomes based on trajectories of leg pain and a composite measure of overall outcome (leg pain, back pain, and disability). RESULTS: Data from 529 patients (mean [SD] age = 66.5 [9.1] yrs; 46% female) were included. In total, 36.1% and 27.6% of patients were classified as experiencing a poor leg pain outcome and overall outcome, respectively. For both outcomes, patients receiving compensation or with depression/depression risk were more likely, and patients participating in regular exercise were less likely to have poor outcomes. Lower health-related quality of life, previous spine surgery, and preoperative anticonvulsant medication use were associated with poor leg pain outcome. Patients with ASA scores more than two, greater preoperative disability, and longer pain duration or surgical waits were more likely to have a poor overall outcome. Patients who received preoperative chiropractic or physiotherapy treatment were less likely to report a poor overall outcome. Multivariable models demonstrated poor-to acceptable (leg pain) and excellent (overall outcome) discrimination. CONCLUSION: Approximately one in three patients with LSS experience a poor clinical outcome consistent with surgical non-response. Demographic, health, and clinical factors were more predictive of clinical outcome than surgery-related factors. These predictors may assist surgeons with patient selection and inform shared decision-making for patients with symptomatic LSS. LEVEL OF EVIDENCE: 2.

Mutational Landscapes of Smoking-Related Cancers in Caucasians and African Americans: Precision Oncology Perspectives at Wake Forest Baptist Comprehensive Cancer Center.

Background: Cancers related to tobacco use and African-American ancestry are under-characterized by genomics. This gap in precision oncology research represents a major challenge in the health disparities in the United States. Methods: The Precision Oncology trial at the Wake Forest Baptist Comprehensive Cancer Center enrolled 431 cancer patients from March 2015 to May 2016. The composition of these patients consists of a high representation of tobacco-related cancers (e.g., lung, colorectal, and bladder) and African-American ancestry (13.5%). Tumors were sequenced to identify mutations to gain insight into genetic alterations associated with smoking and/or African-American ancestry. Results: Tobacco-related cancers exhibit a high mutational load. These tumors are characterized by high-frequency mutations in TP53, DNA damage repair genes (BRCA2 and ATM), and chromatin remodeling genes (the lysine methyltransferases KMT2D or MLL2, and KMT2C or MLL3). These tobacco-related cancers also exhibit augmented tumor heterogeneities. Smoking related genetic mutations were validated by The Cancer Genome Atlas dataset that includes 2,821 cases with known smoking status. The Wake Forest and The Cancer Genome Atlas cohorts (431 and 7,991 cases, respectively) revealed a significantly increased mutation rate in the TP53 gene in the African-American subgroup studied. Both cohorts also revealed 5 genes (e.g. CDK8) significantly amplified in the African-American population. Conclusions: These results provide strong evidence that tobacco is a major cause of genomic instability and heterogeneity in cancer. TP53 mutations and key oncogene amplifications emerge as key factors contributing to cancer outcome disparities among different racial/ethnic groups.

Effects of oral ATP supplementation on anaerobic power and muscular strength.

PURPOSE: We examined 14 d of oral adenosine 5'-triphosphate (ATP) supplementation on indices of anaerobic capacity and muscular strength. METHODS: Twenty-seven healthy males successfully completed the trial, after randomly receiving in a double-blind manner an oral dose of low dose (150 mg) or high dose (225 mg) ATP, or matched placebo. To improve absorption characteristics, the ATP was enterically coated. Total blood ATP (whole blood and plasma ATP) concentrations, two Wingate anaerobic power tests (30 s), and muscular strength (1RM and three sets of repetitions to fatigue at 70% of 1RM) were measured under three conditions: (i) baseline; (ii) acutely (7d later, no prior supplementation and 75 min after ATP ingestion); and (iii) after 14 d of daily ingestion (post). RESULTS: Statistical analyses showed no significant between or within group treatment effects for whole blood ATP or plasma ATP concentrations for any treatment condition. We also did not observe any treatment effects for any Wingate testing parameter including peak PO, total work, average PO for 30 s, or post-Wingate lactate accumulation. Overall, we observed no significant between group treatment effects for any muscular strength parameter. We did observe several within group differences for the group ingesting the high ATP dosage including 1RM (6.6%; P < 0.04) and repetitions to fatigue during set 1 of posttesting (18.5%; P < 0.007) and total lifting volume at post (22%; P < 0.003). CONCLUSIONS: We conclude that enterically coated oral ATP supplementation may provide small ergogenic effects on muscular strength under some treatment conditions.