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Objective: In lupus nephritis, tubulointerstitial inflammation (TII) is associated with in situ adaptive immune cell networks that amplify local tissue damage. Since conventional therapy appears ineffective for severe TII, and these patients often progress to renal failure, understanding in situ mechanisms might reveal new therapeutic targets. This study was undertaken to assess whether dysregulated apoptotic regulators maintain local adaptive immunity and drive inflammation in TII., Methods: This study utilized novel computational approaches that, when applied to multicolor confocal images, quantified apoptotic regulator protein expression in selected lymphocyte subsets. This approach was validated using laser-capture microdissection (LCM) coupled to quantitative polymerase chain reaction (qPCR). Furthermore, the consequences of dysregulated apoptotic mediator expression were explored in a murine model of lupus nephritis., Results: Analyses of renal biopsy tissue from patients with lupus nephritis and those with mixed cellular renal allograft rejection revealed that the B cell lymphoma 2 protein (Bcl-2) was frequently expressed in infiltrating lymphocytes, whereas expression of myeloid cell leukemia 1 was low. In contrast, the reciprocal pattern of expression was observed in tonsil germinal centers. These results were consistent with RNA expression data obtained using LCM and qPCR. Bcl-2 was also highly expressed in tubulointerstitial infiltrates in (NZB × NZW)F1 (NZB/NZW) mice. Furthermore, treatment of NZB/NZW mice with ABT-199, a selective oral inhibitor of Bcl-2, prolonged survival and prevented proteinuria and development of TII in a lupus prevention model. Interestingly, glomerular immune complexes were partially ameliorated by ABT-199 treatment, and serum anti-double-stranded DNA antibody titers were unaffected., Conclusion: These data demonstrate that Bcl-2 is an attractive therapeutic target in patients with lupus nephritis who manifest TII., Competing Interests: Financial Disclosures and Conflict of Interest: Kichul Ko gets salary support from AbbVie, Inc. Stuart Perper, Susan Westmoreland, Lisa Olson and Li Chun Wang are full-time employees of AbbVie, Inc and hold company stock., (© 2016, American College of Rheumatology.)

Background: Health care providers recommend an annual visit to a multiple sclerosis specialty care provider., Objective: To examine potential barriers to the implementation of this recommendation in the Veterans Health Administration., Design: Observational cohort study., Setting: Veterans Health Administration., Participants: Participants were drawn from the Veterans Affairs Multiple Sclerosis National Data Repository and were included if they had an outpatient visit in 2007 and were alive in 2008 (N = 14,723)., Main Outcome Measurements: Specialty care visit, receipt of medical services., Results: A total of 9643 (65.5%) participants had a specialty care visit in 2007. Veterans who were service connected, had greater medical comorbidity, and who lived in urban settings were more likely to have received a specialty care visit. Veterans who were older and had to travel greater distances to a center were less likely to have a specialty care visit., Conclusions: Access to care in rural areas and areas at a greater distance from a major medical center represent notable barriers to rehabilitation and other multiple sclerosis-related care., (Copyright © 2013 American Academy of Physical Medicine and Rehabilitation. Published by Elsevier Inc. All rights reserved.)

Consider a 3-state system with one absorbing state, such as Healthy, Sick, and Dead. Over time, the prevalence of the Healthy state will approach an 'equilibrium' value that is independent of the initial conditions. We derived this equilibrium prevalence (Prev:Equil) as a function of the local transition probabilities. We then used Prev:Equil to estimate the expected number of years spent in the healthy state over time. This estimate is similar to the one calculated by multi-state life table methods, and has the advantage of having an associated standard error. In longitudinal data for older adults, the standard error was accurate when a valid survival table was known from other sources, or when the available data set was sufficient to estimate survival accurately. Performance was better with fewer waves of data. If validated in other situations, these estimates of prevalence and years of healthy life (YHL) and their standard errors may be useful when the goal is to compare YHL for different populations., (2008 John Wiley & Sons, Ltd)