Citations

ObjectiveCurrently, there are no reliable biomarkers for predicting therapeutic response in patients with rheumatoid arthritis (RA). The synovium may unlock critical information for determining efficacy, since a reduction in the numbers of sublining synovial macrophages remains the most reproducible biomarker. Thus, a clinically actionable method for the collection of synovial tissue, which can be analyzed using high‐throughput strategies, must become a reality. This study was undertaken to assess the feasibility of utilizing synovial biopsies as a precision medicine‐based approach for patients with RA.MethodsRheumatologists at 6 US academic sites were trained in minimally invasive ultrasound‐guided synovial tissue biopsy. Biopsy specimens obtained from patients with RA and synovial tissue from patients with osteoarthritis (OA) were subjected to histologic analysis, fluorescence‐activated cell sorting, and RNA sequencing (RNA‐seq). An optimized protocol for digesting synovial tissue was developed to generate high‐quality RNA‐seq libraries from isolated macrophage populations. Associations were determined between macrophage transcriptional profiles and clinical parameters in RA patients.ResultsPatients with RA reported minimal adverse effects in response to synovial biopsy. Comparable RNA quality was observed from synovial tissue and isolated macrophages between patients with RA and patients with OA. Whole tissue samples from patients with RA demonstrated a high degree of transcriptional heterogeneity. In contrast, the transcriptional profile of isolated RA synovial macrophages highlighted different subpopulations of patients and identified 6 novel transcriptional modules that were associated with disease activity and therapy.ConclusionPerformance of synovial tissue biopsies by rheumatologists in the US is feasible and generates high‐quality samples for research. Through the use of cutting‐edge technologies to analyze synovial biopsy specimens in conjunction with corresponding clinical information, a precision medicine–based approach for patients with RA is attainable.

OBJECTIVEPatient-reported outcomes have been increasingly mandated by regulators and payers to evaluate hospital and physician performance. The purpose of this study is to delineate the differences in patient-reported experience of hospital care for cranial and spinal operations.METHODSThe authors selected all patients who underwent inpatient, elective cranial or spinal procedures and completed the Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) survey at a single, high-volume, tertiary care institution between October 2012 and September 2015. The association of the surgical procedure and diagnosis with various HCAHPS composite measures, calculated across 9 domains using standard top-box methodology, was investigated. Multivariable logistic regression models were fitted for outcomes that were significant with procedure type and diagnosis group on univariate analysis, adjusting for age, sex, case complexity, overall health rating, and education level.RESULTSA total of 1484 patients met criteria and returned an HCAHPS survey. Overall, patients undergoing a cranial procedure gave top-box (most favorable) scores more often in pain management measure (66.3% vs 59.6%, p = 0.01) compared with those undergoing spine surgery. Furthermore, despite better discharge scores (93.1% vs 87.1%, p < 0.001), spinal patients were less likely to report excellent health (7.4% vs 12.7%). Lastly, patients with a primary diagnosis of brain or spinal tumor compared with those with degenerative spinal disease and those with other neurosurgical diagnoses provided top-box scores more often regarding communication with doctors (82.7% vs 76.4% vs 75.2%, p = 0.04), pain management (71.8% vs 60.9% vs 59.1%, p = 0.002), and global rating (90.4% vs 84.0% vs 87.3%, p = 0.02). On multivariable analysis, spinal patients had significantly lower odds of reporting top-box scores in pain management (OR 0.67, 95% CI 0.52–0.85; p = 0.001), staff responsiveness (OR 0.68, 95% CI 0.53–0.87; p = 0.002), and global rating (OR 0.59, 95% CI 0.42–0.82; p = 0.002), and significantly higher odds of top-box scoring in discharge information (OR 2.15, 95% CI 1.45–3.18; p < 0.001) than cranial patients. Similarly, brain tumor cases were associated with significantly higher odds of top-box scoring in communication with doctors (OR 1.46, 95% CI 1.01–2.12; p = 0.04), pain management (OR 1.81, 95% CI 1.29–2.55; p < 0.001), staff responsiveness (OR 1.88, 95% CI 1.33–2.66; p < 0.001), and global rating (OR 2.00, 95% CI 1.26–3.17; p = 0.003) compared with degenerative spine cases.CONCLUSIONSSignificant differences in patient-reported experience with hospital care exist across different cranial and spine surgery patient populations. Overall, spinal patients, particularly those with degenerative spine disease, rated their health and their hospital experience lower relative to cranial patients. Identifying weaker areas of hospital performance in target populations can stimulate quality initiatives that aim to increase the overall hospital score.

Importance: Media reports have questioned the safety of overlapping surgical procedures, and national scrutiny has underscored the necessity of single-center evaluations of its safety; however, sample sizes are likely small. We compared the safety profiles of overlapping and nonoverlapping pediatric procedures at a single children's hospital and discussed methodological considerations of the evaluation. Data and Design: Retrospective analysis of inpatient pediatric surgical procedures (January 2013 to September 2015) at a single pediatric referral center. Overlapping and nonoverlapping procedures were matched in an unbalanced manner (m:n) by procedure. Mixed models adjusting for Vizient-predicted risk, case-mix, and surgeon compared inpatient mortality and length of stay (LOS). Results: Among 315 overlapping procedures, 256 (81.3%) were matched to 645 nonoverlapping procedures. There were 6 deaths in all. The adjusted odds ratio for mortality did not differ significantly between nonoverlapping and overlapping procedures (adjusted odds ratio = 0.94 vs overlapping; 95% CI, 0.02–48.5; P = 0.98). Wide confidence intervals were minimally improved with Bayesian methods (95% CI, 0.07–12.5). Adjusted LOS estimates were not clinically different by overlapping status (0.6% longer for nonoverlapping; 95% CI, 9.7% shorter to 12.2% longer; P = 0.91). Among the 87 overlapping procedures with the greatest overlap (≥60 min or ≥50% of operative duration), there were no deaths. Conclusions: The safety of overlapping and nonoverlapping surgical procedures did not differ at this children's center. These findings may not extrapolate to other centers. LOS or intraoperative measures may be more appropriate than mortality for safety evaluations due to low event rates for mortality.

Abstract Purpose: Current clinical parameters do not stratify indolent from aggressive prostate cancer. Aggressive prostate cancer, defined by the progression from localized disease to metastasis, is responsible for the majority of prostate cancer–associated mortality. Recent gene expression profiling has proven successful in predicting the outcome of prostate cancer patients; however, they have yet to provide targeted therapy approaches that could inhibit a patient's progression to metastatic disease. Experimental Design: We have interrogated a total of seven primary prostate cancer cohorts (n = 1,900), two metastatic castration-resistant prostate cancer datasets (n = 293), and one prospective cohort (n = 1,385) to assess the impact of TOP2A and EZH2 expression on prostate cancer cellular program and patient outcomes. We also performed IHC staining for TOP2A and EZH2 in a cohort of primary prostate cancer patients (n = 89) with known outcome. Finally, we explored the therapeutic potential of a combination therapy targeting both TOP2A and EZH2 using novel prostate cancer–derived murine cell lines. Results: We demonstrate by genome-wide analysis of independent primary and metastatic prostate cancer datasets that concurrent TOP2A and EZH2 mRNA and protein upregulation selected for a subgroup of primary and metastatic patients with more aggressive disease and notable overlap of genes involved in mitotic regulation. Importantly, TOP2A and EZH2 in prostate cancer cells act as key driving oncogenes, a fact highlighted by sensitivity to combination-targeted therapy. Conclusions: Overall, our data support further assessment of TOP2A and EZH2 as biomarkers for early identification of patients with increased metastatic potential that may benefit from adjuvant or neoadjuvant targeted therapy approaches. Clin Cancer Res; 23(22); 7072–83. ©2017 AACR.