Citations

Aims Animal models have been developed that allow simulation of post-traumatic joint contracture. One such model involves contracture-forming surgery followed by surgical capsular release. This model allows testing of antifibrotic agents, such as rosiglitazone. Methods A total of 20 rabbits underwent contracture-forming surgery. Eight weeks later, the animals underwent a surgical capsular release. Ten animals received rosiglitazone (intramuscular initially, then orally). The animals were sacrificed following 16 weeks of free cage mobilisation. The joints were tested biomechanically, and the posterior capsule was assessed histologically and via genetic microarray analysis. Results There was no significant difference in post-traumatic contracture between the rosiglitazone and control groups (33° (standard deviation (sd) 11) vs 37° (sd14), respectively; p = 0.4). There was no difference in number or percentage of myofibroblasts. Importantly, there were ten genes and 17 pathways that were significantly modulated by rosiglitazone in the posterior capsule. Discussion Rosiglitazone significantly altered the genetic expression of the posterior capsular tissue in a rabbit model, with ten genes and 17 pathways demonstrating significant modulation. However, there was no significant effect on biomechanical or histological properties. Cite this article: M. P. Abdel. Effectiveness of rosiglitazone in reducing flexion contracture in a rabbit model of arthrofibrosis with surgical capsular release: A biomechanical, histological, and genetic analysis. Bone Joint Res 2016;5:11–17. doi: 10.1302/2046-3758.51.2000593

Summary: The lack of interoperability between information networks is a significant source of cost in health care. Standardized data formats decrease health care cost, improve quality of care, and facilitate biomedical research. There is no common standard digital format for storing clinical neurophysiologic data. This review proposes a new standard file format for neurophysiology data (the bulk of which is video-electroencephalographic data), entitled the Multiscale Electrophysiology Format, version 3 (MEF3), which is designed to address many of the shortcomings of existing formats. MEF3 provides functionality that addresses many of the limitations of current formats. The proposed improvements include (1) hierarchical file structure with improved organization; (2) greater extensibility for big data applications requiring a large number of channels, signal types, and parallel processing; (3) efficient and flexible lossy or lossless data compression; (4) industry standard multilayered data encryption and time obfuscation that permits sharing of human data without the need for deidentification procedures; (5) resistance to file corruption; (6) facilitation of online and offline review and analysis; and (7) provision of full open source documentation. At this time, there is no other neurophysiology format that supports all of these features. MEF3 is currently gaining industry and academic community support. The authors propose the use of the MEF3 as a standard format for neurophysiology recording and data exchange. Collaboration between industry, professional organizations, research communities, and independent standards organizations is needed to move the project forward.

Background and Purpose— Emerging evidence demonstrating the high sensitivity of early brain computed tomography (CT) brings into question the necessity of always performing lumbar puncture after a negative CT in the diagnosis of spontaneous subarachnoid hemorrhage (SAH). Our objective was to determine the sensitivity of brain CT using modern scanners (16-slice technology or greater) when performed within 6 hours of headache onset to exclude SAH in neurologically intact patients. Methods— After conducting a comprehensive literature search using Ovid MEDLINE, Ovid EMBASE, Web of Science, and Scopus, we conducted a meta-analysis. We included original research studies of adults presenting with a history concerning for spontaneous SAH and who had noncontrast brain CT scan using a modern generation multidetector CT scanner within 6 hours of symptom onset. Our study adheres to the preferred reporting items for systematic reviews and meta-analyses (PRISMA). Results— A total of 882 titles were reviewed and 5 articles met inclusion criteria, including an estimated 8907 patients. Thirteen had a missed SAH (incidence 1.46 per 1000) on brain CTs within 6 hours. Overall sensitivity of the CT was 0.987 (95% confidence intervals, 0.971–0.994) and specificity was 0.999 (95% confidence intervals, 0.993–1.0). The pooled likelihood ratio of a negative CT was 0.010 (95% confidence intervals, 0.003–0.034). Conclusions— In patients presenting with thunderclap headache and normal neurological examination, normal brain CT within 6 hours of headache is extremely sensitive in ruling out aneurysmal SAH.

Abstract Background: While numerous susceptibility loci for epithelial ovarian cancer (EOC) have been identified, few associations have been reported with overall survival. In the absence of common prognostic genetic markers, we hypothesize that rare coding variants may be associated with overall EOC survival and assessed their contribution in two exome-based genotyping projects of the Ovarian Cancer Association Consortium (OCAC). Methods: The primary patient set (Set 1) included 14 independent EOC studies (4,293 patients) and 227,892 variants, and a secondary patient set (Set 2) included six additional EOC studies (1,744 patients) and 114,620 variants. Because power to detect rare variants individually is reduced, gene-level tests were conducted. Sets were analyzed separately at individual variants and by gene, and then combined with meta-analyses (73,203 variants and 13,163 genes overlapped). Results: No individual variant reached genome-wide statistical significance. A SNP previously implicated to be associated with EOC risk and, to a lesser extent, survival, rs8170, showed the strongest evidence of association with survival and similar effect size estimates across sets (Pmeta = 1.1E−6, HRSet1 = 1.17, HRSet2 = 1.14). Rare variants in ATG2B, an autophagy gene important for apoptosis, were significantly associated with survival after multiple testing correction (Pmeta = 1.1E−6; Pcorrected = 0.01). Conclusions: Common variant rs8170 and rare variants in ATG2B may be associated with EOC overall survival, although further study is needed. Impact: This study represents the first exome-wide association study of EOC survival to include rare variant analyses, and suggests that complementary single variant and gene-level analyses in large studies are needed to identify rare variants that warrant follow-up study. Cancer Epidemiol Biomarkers Prev; 25(3); 446–54. ©2016 AACR.

SummaryTo examine the effectiveness of an initial management strategy of watchful waiting for follicular lymphoma (FL) in clinical practice, we compared outcomes for patients diagnosed 2004–2007 in the United States initially managed with watchful waiting with outcomes following initial rituximab monotherapy and chemoimmunotherapy. In total, 1754 stage II–IV patients in the National LymphoCare Study underwent watchful waiting (n = 386), rituximab monotherapy (n = 296) or rituximab plus chemotherapy (n = 1072) as initial management strategy. Female patients and those who received treatment in the Northeast or in an academic setting more commonly underwent watchful waiting versus initial chemoimmunotherapy; whereas patients with grade 3 histology, anaemia, elevated lactate dehydrogenase, extranodal involvement, B symptoms or performance status ≥1 more commonly received chemoimmunotherapy. Although time to new treatment and progression‐free survival following first‐ and second‐line therapy were improved with chemoimmunotherapy, and time to chemotherapy was improved with rituximab monotherapy, there were no differences in overall survival between watchful waiting and chemoimmunotherapy or rituximab monotherapy. With 8‐year overall survival estimates of 74%, initial management with watchful waiting in the context of sequential therapy remains a viable option for FL patients in the modern era. This trial was registered at www.clinicaltrials.gov (NCT00097565).

ABSTRACTBackgroundPatients with sinus node dysfunction (SND) have increased risk of atrial tachyarrhythmias, including atrial fibrillation (AF). To date, treatment patterns and outcomes of patients with SND and AF have not been well described.HypothesisPatients with SND and AF have higher risk of adverse cardiovascular outcomes.MethodsSinus node dysfunction was defined clinically, based on treating physician. Treatment patterns were described and logistic regression analysis performed to assess outcomes.ResultsOverall, 1710 (17.7%) out of 9631 patients had SND at enrollment. Patients with SND and AF had increased comorbid medical illnesses, more severe symptoms (European Heart Rhythm Association class IV: 17.5% vs 13.9%; P = 0.0007), and poorer quality of life (median 12‐month Atrial Fibrillation Effect on Quality of Life score: 79.6 vs 85.2; P = 0.0008). There were no differences in AF management strategy between patients with SND and those without (rate control, 69.7% vs 67.7%; rhythm control, 30.0% vs 32.0%; P = 0.11). After adjustment, patients with SND were more likely than those without SND to progress from paroxysmal AF at baseline to persistent or permanent AF at any follow‐up, or persistent AF at baseline to permanent AF at any follow‐up (odds ratio: 1.23, 95% confidence interval: 1.01‐1.49, P = 0.035). However, there was no association between SND and major risk‐adjusted outcomes.ConclusionsSinus node dysfunction is present in 1 of 6 patients with AF and is associated with increased comorbidities and higher symptom burden. However, SND is not associated with an increase in major risk‐adjusted outcomes.