BACKGROUND. In human lupus nephritis (LN), tubulointerstitial inflammation (TII) on biopsy predicts progression to endstage renal disease (ESRD). However, only about half of patients with moderate-to-severe TII develop ESRD. We hypothesized that this heterogeneity in outcome reflects different underlying inflammatory states. Therefore, we interrogated renal biopsies from LN longitudinal and cross-sectional cohorts.METHODS. Data were acquired using conventional and highly multiplexed confocal microscopy. To accurately segment cells across whole biopsies, and to understand their spatial relationships, we developed computational pipelines by training and implementing several deep-learning models and other computer vision techniques.RESULTS. High B cell densities were associated with protection from ESRD. In contrast, high densities of CD8 + , γδ, and other CD4 -CD8 -T cells were associated with both acute renal failure and progression to ESRD. B cells were often organized into large periglomerular neighborhoods with Tfh cells, while CD4 -T cells formed small neighborhoods in the tubulointerstitium, with frequency that predicted progression to ESRD.CONCLUSION. These data reveal that specific in situ inflammatory states are associated with refractory and progressive renal disease.
INTRODUCTION The use of hookah (waterpipe) is increasing rapidly among US adolescents, nearly doubling from2011-2014. Further information is needed about characteristics of those who use hookahs and how key characteristics associated with use may be changing. METHODS Data from the nationally representative 2014 National Youth Tobacco Survey (NYTS), n=22,007, were analyzed to determine adolescents' characteristics independently associated with use of hookahs, using bivariate and multivariate analyses. Additionally, NYTS 2011-2014 data were analyzed to investigate changes in prevalence of hookah use over time, by sex. RESULTS Among adolescents in 2014, female sexand past 30-day use of cigarettes or e-cigarettes were each independently associated with higher odds of past 30-day use of hookahs (AOR=1.41, 95% CI1.15-1.72; AOR=4.01, 95% CI3.19-5.05; AOR=6.85, 95% CI 5.29-8.88, respectively). Hispanic adolescents (AOR=1.91, 95% CI 1.51-2.42) and adolescents who live with someone who uses hookah (AOR=8.56, 95% CI 6.02-12.18) had greater odds of past 30-day use. From 2011 to 2014, use among males and females increased, with a percent change of 87% for males (1.60% to 2.99%) and 175% for females (1.21% to 3.33%). CONCLUSIONS These data demonstrate the magnitude of adolescent hookah use, particularly among adolescents who use electronic or traditional cigarettes. Most strikingly, rates of female adolescent use have increased much more rapidly than has male use, and adolescent females are for the first time more likely to smoke hookahs than adolescent males in the US nationwide. These findings urgently call for better understanding of the changing correlates of hookah use, including polytobacco use.
Objective. We developed a fast-track clinic (FTC) to expedite the evaluation of patients suspected of having giant cell arteritis (GCA) using vascular ultrasound. Though FTCs have demonstrated efficacy in Europe, no protocolized clinic in the United States has been developed. This study introduces a new FTC model unique to the United States, using vascular sonographers, and describes the protocols used to develop reliable findings. We evaluate clinical outcomes using vascular ultrasound and temporal artery biopsy (TAB).Methods. A retrospective review included all subjects referred to the University of Washington FTC aged 50 years old or older who received both ultrasound and TAB between November 2017 and November 2019. Ultrasound was performed by a vascular sonographer trained in GCA detection. Ultrasound results were read by a vascular surgeon and reviewed by four rheumatologists certified in musculoskeletal ultrasound who had completed a course in vascular ultrasound use in GCA and large-vessel vasculitis.Results. A total of 43 subjects underwent both vascular ultrasound and TAB. Six subjects had both positive ultrasound and TAB results. There were also seven positive ultrasound results in patients with negative TAB results, most due to detection of large-vessel GCA (LV-GCA). All 29 subjects with negative ultrasound results had negative TAB results.Conclusion. This is the first study in the United States to demonstrate a reliable FTC protocol using vascular sonographers. This protocol demonstrated good agreement between ultrasound and TAB and allowed for the detection of additional cases of LV-GCA by vascular ultrasound. Vascular ultrasound improved the rate of GCA diagnosis primarily by detecting additional cases of LV-GCA.
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