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Purpose: Biomarkers for juvenile idiopathic arthritis-associated uveitis (JIA-U) are needed. We aimed to measure inflammatory biomarkers in tears as a non-invasive method to identify biomarkers of uveitis activity.Methods: Tears were collected from children with JIA-U (n=20) and pediatric controls (n=20) using Schirmer strips. S100A8, A9, A12, IL-18, IL-8, IP-10, MCP-1, RANTES, and sICAM-1 were measured by ELISA and Luminex assays. Levels of biomarkers were compared between children with JIA-U and controls, and active and inactive JIA-U.Results: IL-8, sICAM-1, and S100A12 levels were similar between JIA-U and controls, but differed by activity. Active JIA-U had significantly increased S100A12 compared to inactive JIA-U (mean 27,722.5 pg/ML (SE 1.3) vs. 5,937.2 (1.3), p=0.002), IL-8 (73.5 [1.2] vs. 36.2 [1.2], p=0.009), and sICAM-1 (15,822.7 [1.2) vs. 8,778.0 [1.6], p=0.024).Conclusion: We detected inflammatory biomarkers non-invasively in tears of children with JIA-U. IL-8, sICAM-1, and S100A12 are potential biomarkers for uveitis activity. [ABSTRACT FROM AUTHOR]

Objectives/hypothesis: Dysphagia is a treatment-related complication of head and neck cancer (HNCA). We demonstrate the predictive value of a modified head and neck swallow scale (m-HNSW) adapted from the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Head and Neck 35 (EORTC-QLQ-H&N35).Study Design: Retrospective Cohort Study.Methods: Retrospective, single-center cohort study utilizing a prospectively collected database of HNCA patients in a high-volume tertiary referral center. 736 HNCA patients more than 2 years from completion of treatment were identified. EORTC-QLQ-H&N35 data collected from at least one of three defined episodes of care were used. The m-HNSW uses three questions to form a 9-point dysphagia scale. A Cox proportional hazards model was used to determine the effect of the m-HNSW while controlling for demographics, tumor staging, site, and treatment.Results: Using data from 3, 6, 12 months from treatment, we analyzed a subset that included 328 patients. Three months after the completion of therapy, the m-HNSW score had a significant association with 1 (HR = 1.24, P = .0005) and 5 year survival (HR = 1.19, P = .0002) after accounting for body mass index. Six (HR = 1.14, P = .014) and 12 month (hazard ratio (HR) = 1.33, P < .0001) scores post completion of therapy predict 5-year survival. An increase of the m-HNSW score by 1 point was associated with an increase in death by 24%, and 19% at 1 and 5 years following therapy.Conclusions: The m-HNSW is a simple assessment of dysphagia using previously validated EORTC-QLC-H&N35 data that when taken at 3, 6, and 12 months after completion of therapy is predictive of overall survival.Level Of Evidence: 4 Laryngoscope, 131:2478-2482, 2021. [ABSTRACT FROM AUTHOR]

Adolescents with epilepsy are at risk for deficits in working memory, which could lead to learning difficulties and poor academic outcomes. We used task-based functional magnetic resonance imaging (fMRI) to examine potential disruption in working memory function in adolescents with epilepsy as compared to healthy controls. We recruited 29 adolescents (13–17 years) with non-lesional epilepsy and 20 healthy controls. All participants performed an N-back fMRI task and neuropsychological testing. A general linear model approach was used to create group activation maps of N-back fMRI for epilepsy and control groups and both groups combined (p < 0.05 corrected for multiple comparisons). Functionally defined regions of interest (ROIs) were identified based on clusters of combined group activation (z > 5). Subsets of these functional ROIs corresponding to cingulo-opercular and fronto-parietal networks were selected and differences in functional connectivity between the epilepsy and control groups were assessed. Adolescents with epilepsy had significantly poorer working memory scores compared to controls. For the N-back fMRI task, there were no significant differences in group activation. Functional connectivity was significantly reduced between the left frontal operculum and anterior cingulate gyrus (cingulo-opercular network) in adolescents with epilepsy compared to controls. This study demonstrates working memory deficits and an altered pattern of connectivity in brain networks supporting working memory in adolescents with epilepsy. Working memory performance was worse in adolescents with epilepsy; though scores were not directly correlated with reduced connectivity. These results suggest the neural substrates of working memory in adolescents with epilepsy may differ from those in typically-developing adolescents, and require further investigation to understand the reasons for poorer working memory performance. [ABSTRACT FROM AUTHOR]

Introduction: To identify phenotypes of type 1 diabetes based on glucose curves from continuous glucose-monitoring (CGM) using functional data (FD) analysis to account for longitudinal glucose patterns. We present a reliable prediction model that can accurately predict glycemic levels based on past data collected from the CGM sensor and real-time risk of hypo-/hyperglycemic for individuals with type 1 diabetes. Methods: A longitudinal cohort study of 443 type 1 diabetes patients with CGM data from a completed trial. The FD analysis approach, sparse functional principal components (FPCs) analysis was used to identify phenotypes of type 1 diabetes glycemic variation. We employed a nonstationary stochastic linear mixed-effects model (LME) that accommodates between-patient and within-patient heterogeneity to predict glycemic levels and real-time risk of hypo-/hyperglycemic by creating specific target functions for these excursions. Results: The majority of the variation (73%) in glucose trajectories was explained by the first two FPCs. Higher order variation in the CGM profiles occurred during weeknights, although variation was higher on weekends. The model has low prediction errors and yields accurate predictions for both glucose levels and real-time risk of glycemic excursions. Conclusions: By identifying these distinct longitudinal patterns as phenotypes, interventions can be targeted to optimize type 1 diabetes management for subgroups at the highest risk for compromised long-term outcomes such as cardiac disease or stroke. Further, the estimated change/variability in an individual's glucose trajectory can be used to establish clinically meaningful and patient-specific thresholds that, when coupled with probabilistic predictive inference, provide a useful medical-monitoring tool. [ABSTRACT FROM AUTHOR]

Abstract Background Diffusion tensor imaging (DTI) is a non-invasive MRI technique that has been used to quantify CNS abnormalities in various pathologic conditions. This study was designed to quantify the anisotropic diffusion properties in the brain of neonatal rats with hydrocephalus (HCP) and to investigate association between DTI measurements and cytopathology. Methods DTI data were acquired between postnatal day 7 (P7) and P12 in 12 rats with HCP induced at P2 and in 15 age-matched controls. Animals were euthanized at P11 or P22/P23 and brains were processed with immunohistochemistry for glial fibrillary acidic protein (GFAP), ionized calcium-binding adaptor molecule (Iba-1), and luxol fast blue (LFB) to assess astrocytosis, microglial reactivity and degree of myelination, respectively. Results Hydrocephalic rats were consistently found to have an abnormally low (at corrected p-level of Conclusions This study demonstrates the feasibility of employing DTI on the brain in experimental hydrocephalus in neonatal rats and reveals impairments in multiple regions of interest in both grey and white matter. A strong correlation was found between the immunohistochemical results and the changes in anisotropic diffusion properties.

Objectives/Hypothesis: Veterans have an increasing prevalence of obstructive sleep apnea (OSA) and high levels of intolerance to positive airway pressure (PAP). The hypoglossal nerve stimulator (HNS) is a promising alternative surgical treatment for OSA in these patients, many of whom suffer from mental health conditions such as post‐traumatic stress disorder (PTSD) that may negatively affect their ability to use PAP. Our aims were: 1) to assess postoperative changes in OSA severity and sleepiness in a veteran only population after HNS; 2) to compare postoperative changes in OSA severity, sleepiness and HNS adherence between veterans with and without PTSD; and 3) to compare HNS adherence in our population to HNS adherence in the current literature as well as published PAP adherence data. Study Design: Retrospective and prospective case series. Methods: Clinical data on consecutive patients undergoing HNS in a Veterans Affairs hospital were examined for demographic data as well as medical, sleep, and mental health comorbidities. The overall cohort as well as subsets of patients with and without PTSD were examined for postoperative changes in OSA severity (apnea hypopnea index [AHI], lowest oxygen saturation (LSAT]), and sleepiness (Epworth sleepiness scale [ESS]), as well as for device adherence. PTSD and depression symptomatology were measured using the PTSD Checklist 5 (PCL‐5) and Patient Health Questionnaire 9 (PHQ‐9). Results: Forty‐six veterans were included. Forty‐four patients were male (95.6%), 45 were white (97.8%), and the mean age was 61.3 years. Twenty‐six patients met PCL‐5 criteria for PTSD and 17 did not. OSA severity and sleepiness improved significantly in the overall cohort after HNS; median (IQR) AHI decreased from 39.2 (24.0, 63.0) to 7.4 (1.2, 20.8) events/hour (P <.0001), mean LSAT increased from 81% to 88% (P <.0001) and mean ESS decreased from 10.9 to 6.7 (P <.0001). These improvements were similar between patients with and without PTSD (P =.434–.918). Overall device adherence was 6.1 hours/night for the overall cohort and was not significantly different between patients with and without PTSD (P =.992). Conclusions: HNS is an efficacious therapy in a veteran population, providing patients with significant improvements in OSA severity and sleepiness. Veterans with and without PTSD benefited similarly from HNS when comparing improvements in sleep apnea severity and sleepiness as well as device usage. Adherence was similar to previously published HNS adherence data and better than PAP adherence reported in the literature. Level of Evidence: 4 Laryngoscope, 131:S1–S11, 2021 [ABSTRACT FROM AUTHOR]

Objective: This retrospective cohort study examined whether bariatric surgery is associated with reduced risk of breast cancer among pre- and postmenopausal women. Background: Obesity is associated with increased risk of breast cancer, but the impact of weight loss on breast cancer risk has been difficult to quantify. Methods: The cohort included obese (body mass index -¥35 kg/m²) patients enrolled in an integrated health care delivery system between 2005 and 2012 (with follow-up through 2014). Female bariatric surgery patients (N = 17,998) were matched on body mass index, age, study site, and comorbidity index to 53,889 women with no bariatric surgery. Kaplan-Meier curves and Cox proportional hazards models were used to examine incident breast cancer up to 10 years after bariatric surgery. Pre- and postmenopausal women were examined separately, and further classified by estrogen receptor (ER) status. Results: The analysis included 301 premenopausal and 399 postmenopausal breast cancer cases. In multivariable adjusted models, bariatric surgery was associated with a reduced risk of both premenopausal (HR = 0.72, 95% CI, 0.54-0.94) and postmenopausal (HR = 0.55, 95% CI, 0.42-0.72) breast cancer. Among premenopausal women, the effect of bariatric surgery was more pronounced among ER-negative cases (HR=0.36, 95% CI, 0.16-0.79). Among postmenopausal women, the effect was more pronounced in ERpositive cases (HR = 0.52, 95% CI, 0.39-0.70). Conclusions: Bariatric surgery was associated with a reduced risk of breast cancer among severely obese women. These findings have significant public health relevance because the prevalence of obesity continues to rise, and few modifiable breast cancer risk factors have been identified, especially for premenopausal women. [ABSTRACT FROM AUTHOR]