Citations

Objective Synovitis is a prevalent feature in patients with knee osteoarthritis ( OA ) and meniscal tear and is associated with pain and cartilage damage. Patient‐reported swelling is also prevalent in this population. The aim of this study was to investigate the cross‐sectional association between patient‐reported swelling and effusion‐synovitis detected by magnetic resonance imaging ( MRI ) in patients with OA and meniscal tear. Methods We used baseline data from a multicenter, randomized controlled trial, Meniscal Tear in Osteoarthritis Research ( METEOR ). MRI ‐identified effusion‐synovitis, a proxy for effusion and synovitis on noncontrast MRI s, was graded as none/small versus medium/large. Using MRI ‐identified effusion‐synovitis as the gold standard, we assessed the sensitivity, specificity, and positive predictive value of patient self‐reported swelling in the previous week (none, intermittent, constant) to detect effusion and synovitis. Results We analyzed data from 276 patients. Twenty‐five percent of patients reported no swelling, 40% had intermittent swelling, and 36% had constant swelling. Fifty‐two percent had MRI ‐identified medium/large–grade effusion‐synovitis. As compared with MRI ‐identified effusion‐synovitis, any patient‐reported swelling (versus none) had a sensitivity of 84% (95% confidence interval [95% CI ] 77–89), a specificity of 34% (95% CI 26–43), and a positive predictive value of 57% (95% CI 54–61). A history of constant swelling (versus none or intermittent) showed a sensitivity of 46% (95% CI 37–54), a specificity of 75% (95% CI 67–82), and a positive predictive value of 66% (95% CI 58–74). Conclusion We found that the sensitivity and specificity of patient‐reported swelling were modest when compared with effusion‐synovitis detected by MRI . These data urge caution against using patient‐reported swelling as a proxy of inflammation manifesting as effusion‐synovitis.

Intensive systolic blood pressure (SBP) control improved outcomes in SPRINT (Systolic Blood Pressure Intervention Trial). Our objective was to expand on reported findings by analysis of baseline characteristics, primary outcomes, adverse events, follow-up blood pressure, and medication use differences by baseline SBP (tertile 1 [T1], <132; tertile 2 [T2], 132–145; and tertile 3 [T3], >145 mm Hg). Participants with higher baseline SBP tertile were more often women and older, had higher cardiovascular risk, and lower utilization of antihypertensive medications, statins, and aspirin. Achieved SBP in both treatment arms was slightly higher in T2 and T3 compared with T1 and fewer in the T3 groups achieved SBP targets compared with T1 and T2 groups. The primary composite outcome with intensive versus standard SBP treatment was reduced by 30% in T1, 23% in T2, and 17% in T3 with no evidence of an interaction ( P =0.77). Event rates were lower in the intensive arm, and there was no evidence that this benefit differed by SBP tertile. There was no difference in the hazard for serious adverse events in any of the 3 tertiles. Medication utilization differed across the SBP tertiles at baseline with a lesser percentage of diuretics and angiotensin-converting enzyme inhibitors/angiotensin receptor blocker drugs in the higher tertiles—a finding that reversed during the trial. The beneficial effects of intensive SBP lowering were not modified by the level of baseline SBP. Within the parameters of this population, these findings add support for clinicians to treat blood pressure to goal irrespective of baseline SBP.

AbstractEosinophil-associated diseases (EADs) are rare, heterogeneous disorders characterized by the presence of eosinophils in tissues and/or peripheral blood resulting in immunopathology. The heterogeneity of tissue involvement, lack of sufficient animal models, technical challenges in working with eosinophils, and lack of standardized histopathologic approaches have hampered progress in basic research. Additionally, clinical trials and drug development for rare EADs are limited by the lack of primary and surrogate endpoints, biomarkers, and validated patient-reported outcomes. Researchers with expertise in eosinophil biology and eosinophil-related diseases reviewed the state of current eosinophil research, resources, progress, and unmet needs in the field since the 2012 meeting of the NIH Taskforce on the Research of Eosinophil-Associated Diseases (TREAD). RE-TREAD focused on gaps in basic science, translational, and clinical research on eosinophils and eosinophil-related pathogenesis. Improved recapitulation of human eosinophil biology and pathogenesis in murine models was felt to be of importance. Characterization of eosinophil phenotypes, the role of eosinophil subsets in tissues, identification of biomarkers of eosinophil activation and tissue load, and a better understanding of the role of eosinophils in human disease were prioritized. Finally, an unmet need for tools for use in clinical trials was emphasized. Histopathologic scoring, patient- and clinician-reported outcomes, and appropriate coding were deemed of paramount importance for research collaborations, drug development, and approval by regulatory agencies. Further exploration of the eosinophil genome, epigenome, and proteome was also encouraged. Although progress has been made since 2012, unmet needs in eosinophil research remain a priority.Review on eosinophil biology and eosinophil-related disorders (2012–2017) with a focus on continued unmet needs in eosinophil-associated diseases.

AbstractThe Alzheimer's Association's Research Roundtable met in November 2017 to explore the new National Institute on Aging and the Alzheimer's Association Research Framework for Alzheimer's disease. The meeting allowed experts in the field from academia, industry, and government to provide perspectives on the new National Institute on Aging and the Alzheimer's Association Research Framework. This review will summarize the “A, T, N System” (Amyloid, Tau, and Neurodegeneration) using biomarkers and how this may be applied to clinical research and drug development. In addition, challenges and barriers to the potential adoption of this new framework will be discussed. Finally, future directions for research will be proposed.

AbstractBackgroundMutations in the parkin gene (PRKN) are the most commonly identified genetic factors in early onset Parkinson disease (EOPD), with biallelic mutations, resulting in a clinical phenotype. However, normal variation is also common in PRKN, particularly in the form of copy number variation (CNV), challenging interpretation of genetic testing results. Here we report a case of a 29‐year‐old male with EOPD and two deletions in PRKN detected by chromosomal microarray (CMA).MethodsThe proband was clinically examined by a neurologist for postural instability with frequent falls, bradykinesia, gait freezing with festination, and hypophonia. Chromosomal microarray analysis (CMA) was performed on the proband and his parents using the Affymetrix CytoScan HD microarray. Subsequent fluorescence in situ hybridization (FISH) was performed on the proband and both parents.ResultsChromosomal microarray detected the presence of two deletions of PRKN in the proband. Parental CMA analysis was performed to determine the clinical significance of this finding, as well as to demonstrate phase of these deletions. Parental CMA revealed that one deletion was paternally inherited and one deletion was de novo. A custom FISH approach was then successfully used to phase the deletions.ConclusionChromosomal microarray and fluorescence in situ hybridization analysis of this trio identified two deletions in PRKN occurring in trans, providing a genetic etiology for the clinical diagnosis of EOPD. The determination of inheritance and phase of the deletions was critical to the proper interpretation of these results. These findings highlight the utility of CMA in the detection of clinically relevant CNVs in cases of EOPD, and also serve to emphasize the importance of follow‐up FISH and parental testing.