A novel prostate cancer subtyping classifier based on luminal and basal phenotypes.

BACKGROUND: Prostate cancer (PCa) is a clinically heterogeneous disease. The creation of an expression-based subtyping model based on prostate-specific biological processes was sought. METHODS: Unsupervised machine learning of gene expression profiles from prospectively collected primary prostate tumors (training, n = 32,000; evaluation, n = 68,547) was used to create a prostate subtyping classifier (PSC) based on basal versus luminal cell expression patterns and other gene signatures relevant to PCa biology. Subtype molecular pathways and clinical characteristics were explored in five other clinical cohorts. RESULTS: Clustering derived four subtypes: luminal differentiated (LD), luminal proliferating (LP), basal immune (BI), and basal neuroendocrine (BN). LP and LD tumors both had higher androgen receptor activity. LP tumors also had a higher expression of cell proliferation genes, MYC activity, and characteristics of homologous recombination deficiency. BI tumors possessed significant interferon γactivity and immune infiltration on immunohistochemistry. BN tumors were characterized by lower androgen receptor activity expression, lower immune infiltration, and enrichment with neuroendocrine expression patterns. Patients with LD tumors had less aggressive tumor characteristics and the longest time to metastasis after surgery. Only patients with BI tumors derived benefit from radiotherapy after surgery in terms of time to metastasis (hazard ratio [HR], 0.09; 95% CI, 0.01-0.71; n = 855). In a phase 3 trial that randomized patients with metastatic PCa to androgen deprivation with or without docetaxel (n = 108), only patients with LP tumors derived survival benefit from docetaxel (HR, 0.21; 95% CI, 0.09-0.51). CONCLUSIONS: With the use of expression profiles from over 100,000 tumors, a PSC was developed that identified four subtypes with distinct biological and clinical features. PLAIN LANGUAGE SUMMARY: Prostate cancer can behave in an indolent or aggressive manner and vary in how it responds to certain treatments. To differentiate prostate cancer on the basis of biological features, we developed a novel RNA signature by using data from over 100,000 prostate tumors-the largest data set of its kind. This signature can inform patients and physicians on tumor aggressiveness and susceptibilities to treatments to help personalize cancer management.

Plasminogen Activator Inhibitor-1 as a Marker of Esophageal Functional Changes in Pediatric Eosinophilic Esophagitis.

BACKGROUND & AIMS: Esophageal remodeling in eosinophilic esophagitis (EoE) can lead to esophageal rigidity with eventual luminal compromise and stenoses. Gauging esophageal functional alterations in EoE is challenging. An epithelial marker of functional remodeling would impact EoE management. METHODS: Esophageal biopsy specimens from children with and without EoE and primary human esophageal epithelial cells were used for PAI-1 immunohistochemistry, and cell proliferation experiments. PAI-1 immunostaining and basal cell hyperplasia were assessed in the context of concurrently obtained esophageal compliance measures on endoscopic functional lumen imaging probe (EndoFLIP). RESULTS: EndoFLIPs were performed in 45 children (32 with and 13 without EoE). Epithelial PAI-1 was increased in patients with active EoE versus inactive or control patients (P < .01). Esophageal compliance was lower in EoE patients versus controls, particularly in the proximal esophagus (P < .001). Proximal compliance was the strongest predictor of EoE (AUROC 0.88, 95% CI 0.77, 0.98) with esophageal compliance of less than 2.6%mL/mmHg demonstrating 82% sensitivity and 84% specificity for EoE. PAI-1 inhibition significantly diminished esophageal epithelial cell proliferation, suggesting PAI-1 could trigger basal cell hyperplasia. A composite mid-esophageal BZH + PAI-1 score was the strongest predictor of altered compliance (P = .02, AUROC 0.89 (95% CI 0.80, 0.99). CONCLUSIONS: PAI-1 is significantly elevated in pediatric EoE and distinguishes altered compliance in children. PAI-1 may be a novel disease marker and therapeutic target.

Severe acne and its variants: Exploring its natural history and heritability.

BACKGROUND: Acne vulgaris varies in clinical severity, from minimal comedonal disease to severe hemorrhagic and ulcerative lesions with scarring. While a family history confers a higher risk for developing acne, the correlation between heritability and clinical severity remains unclear. OBJECTIVE: To examine the natural history and heritability of severe acne with scarring in patients undergoing isotretinoin therapy. METHODS: A total of 101 subjects with severe acne with scarring and its variants, including acne conglobata and acne fulminans, were enrolled. All subjects and adult family members underwent an interview regarding their acne, and a corresponding "historical" Investigator's Global Assessment (hIGA) score (0 = clear, 1 = almost clear, 2 = mild, 3 = moderate, 4 = severe, 5 = very severe) was assigned. Study assessors performed an "examination" Investigator's Global Assessment (eIGA) based on the clinical examination of each subject (0 = clear, 1 = almost clear, 2 = mild, 3 = moderate, 4 = severe, 5 = very severe). A detailed family history and pedigree were documented. RESULTS: Most subjects were Caucasian (44.5%) and male (79.2%) who had previously used doxycycline and/or minocycline (86.1%). The mean eIGA and hIGA scores were 2.7 and 4.4, respectively. 37.2% of subjects had one first-degree relative with a history of moderate or severe acne with scarring; of note, of the patients with hemorrhagic disease, 30% had at least one parent with moderate or severe acne. CONCLUSIONS: Severe forms of acne often "cluster" in families, underscoring the heritable nature of acne and the prognostic value of a family history of moderate or severe disease.

Deep Learning Estimation of 10-2 and 24-2 Visual Field Metrics Based on Thickness Maps from Macula OCT.

PURPOSE: To develop deep learning (DL) systems estimating visual function from macula-centered spectral-domain (SD) OCT images. DESIGN: Evaluation of a diagnostic technology. PARTICIPANTS: A total of 2408 10-2 visual field (VF) SD OCT pairs and 2999 24-2 VF SD OCT pairs collected from 645 healthy and glaucoma subjects (1222 eyes). METHODS: Deep learning models were trained on thickness maps from Spectralis macula SD OCT to estimate 10-2 and 24-2 VF mean deviation (MD) and pattern standard deviation (PSD). Individual and combined DL models were trained using thickness data from 6 layers (retinal nerve fiber layer [RNFL], ganglion cell layer [GCL], inner plexiform layer [IPL], ganglion cell-IPL [GCIPL], ganglion cell complex [GCC] and retina). Linear regression of mean layer thicknesses were used for comparison. MAIN OUTCOME MEASURES: Deep learning models were evaluated using R2 and mean absolute error (MAE) compared with 10-2 and 24-2 VF measurements. RESULTS: Combined DL models estimating 10-2 achieved R2 of 0.82 (95% confidence interval [CI], 0.68-0.89) for MD and 0.69 (95% CI, 0.55-0.81) for PSD and MAEs of 1.9 dB (95% CI, 1.6-2.4 dB) for MD and 1.5 dB (95% CI, 1.2-1.9 dB) for PSD. This was significantly better than mean thickness estimates for 10-2 MD (0.61 [95% CI, 0.47-0.71] and 3.0 dB [95% CI, 2.5-3.5 dB]) and 10-2 PSD (0.46 [95% CI, 0.31-0.60] and 2.3 dB [95% CI, 1.8-2.7 dB]). Combined DL models estimating 24-2 achieved R2 of 0.79 (95% CI, 0.72-0.84) for MD and 0.68 (95% CI, 0.53-0.79) for PSD and MAEs of 2.1 dB (95% CI, 1.8-2.5 dB) for MD and 1.5 dB (95% CI, 1.3-1.9 dB) for PSD. This was significantly better than mean thickness estimates for 24-2 MD (0.41 [95% CI, 0.26-0.57] and 3.4 dB [95% CI, 2.7-4.5 dB]) and 24-2 PSD (0.38 [95% CI, 0.20-0.57] and 2.4 dB [95% CI, 2.0-2.8 dB]). The GCIPL (R2 = 0.79) and GCC (R2 = 0.75) had the highest performance estimating 10-2 and 24-2 MD, respectively. CONCLUSIONS: Deep learning models improved estimates of functional loss from SD OCT imaging. Accurate estimates can help clinicians to individualize VF testing to patients.

OCT Angiography Artifacts in Glaucoma.

PURPOSE: To determine the prevalence of different types of artifacts seen in OCT angiography (OCTA) images of healthy and glaucoma eyes and evaluate the characteristics associated with poor-quality images. DESIGN: Retrospective study. PARTICIPANTS: A total of 649 eyes of 368 healthy, glaucoma suspect, and glaucoma patients. METHODS: Angiovue (Optovue Inc) high-density (HD) and non-HD optic nerve head and macula OCTA images of participants were evaluated by 4 expert reviewers for the presence of different artifacts, including eye movement, defocus, shadow, decentration, segmentation error, blink, and Z offset in the superficial vascular layer. Each OCTA scan was designated to have good or poor quality based on the presence of artifacts. The association of demographic and ocular characteristics with the likelihood of obtaining poor-quality OCTA images was evaluated. MAIN OUTCOME MEASURES: The prevalence of OCTA artifacts and the factors associated with increased likelihood of capturing poor-quality OCTA images. RESULTS: A total of 5263 OCTA images were evaluated. Overall, 33.9% of the OCTA images had poor quality. The majority of images with acceptable quality scores (QS ≥ 4) had no artifacts (76.6%). Other images had 1 (13.6%) or 2 or more artifacts (9.8%). Older age (P < 0.001), male gender (P = 0.045), worse visual field mean deviation (P < 0.001), absence of eye tracking (P < 0.001), and macular scan area (P < 0.001) were associated with a higher likelihood of obtaining poor-quality images. In images with acceptable QS, the commercially available quality measures including QS and signal strength index had the area under the receiver operating characteristic curves of 0.65 (95% confidence interval [CI], 0.62-0.69) and 0.70 (95% CI, 0.68-0.73) to detect good-quality images, respectively. CONCLUSIONS: OCTA artifacts associated with poor-quality images are frequent, and their prevalence is affected by ocular and patient characteristics. One should not rely solely on the quantitative assessments that are provided automatically by OCTA instruments. A systematic scan review should be conducted to ensure appropriate interpretation of OCTA images. Given the high prevalence of poor-quality OCTA images, the images should be reacquired whenever an apparent and correctable artifact is present on a captured image.

Comparative Efficacy and Speed of Onset of Action of Infliximab vs Golimumab in Ulcerative Colitis.

BACKGROUND & AIMS: With several options available for patients with moderate-severe ulcerative colitis (UC), rapidity of symptom resolution could be an important differentiator. We compared the efficacy and speed of onset of action of infliximab vs golimumab induction therapy using patient-level data from phase 3 trials (ACT-1, ACT-2, and PURSUIT-SC). METHODS: We compared differences in proportions of patients who achieved the composite outcome of a rectal bleeding score=0 and stool frequency score ≤1 (patient-reported outcome 2 remission) at weeks 2 and 6 of treatment with standard-dose infliximab vs golimumab using logistic generalized estimating equation. Overall efficacy for inducing clinical remission (Mayo clinic score <3) was compared using logistic regression. Analyses were adjusted for sex, disease extent, baseline clinical and endoscopic severity, C-reactive protein, albumin, body weight and concomitant medications (immunomosuppressives, corticosteroids, and 5-aminsalicylates). RESULTS: Trial populations were similar and no differences were observed among the placebo groups in the studies. A significantly higher proportion patients treated with infliximab than golimumab achieved patient-reported outcome 2 remission at week 2 (35% vs 30%; adjusted odds ratio [OR], 1.71; 95% CI, 1.15-2.55) and at week 6 (50.0% vs 38.9%; adjusted OR, 2.0; 95% CI, 1.40-2.94). Infliximab-treated patients were also significantly more likely to achieve clinical remission than golimumab-treated patients (adjusted OR, 3.01; 95% CI, 1.95-4.70), with consistent findings in patients with moderate or severe UC. CONCLUSIONS: Based on a patient-level analysis of data from phase 3 trials, infliximab resolves symptoms more rapidly and has greater efficacy for inducing remission than golimumab in patients with moderate-to-severe UC.

Ganglion Cell Complex Thickness and Macular Vessel Density Loss in Primary Open-Angle Glaucoma.

PURPOSE: To characterize the change rate of ganglion cell complex (GCC) thickness and macular vessel density in healthy, preperimetric glaucoma and primary open-angle glaucoma (POAG) eyes. DESIGN: Prospective, longitudinal study. PARTICIPANTS: One hundred thirty-nine eyes (23 healthy eyes, 36 preperimetric glaucoma eyes, and 80 POAG eyes) of 94 patients who had at least 3 visits were included from the Diagnostic Innovations in Glaucoma Study. The mean follow-up was 2.0 years for healthy eyes, 2.6 years for preperimetric glaucoma eyes, and 2.6 years for POAG eyes. METHODS: OCT angiography (OCTA)-based vessel density and OCT-based structural thickness of the same 3×3-mm2 GCC scan slab were evaluated. The dynamic range-based normalized rates of vessel density and thickness change were calculated and compared within each diagnostic group. The association between the rates of thickness and vessel density change and potential factors were evaluated. MAIN OUTCOME MEASURES: The rates of GCC thinning and macular vessel density loss. RESULTS: Significant rates of GCC thinning and macular vessel density decrease were detectable in all diagnostic groups (all P < 0.05). In healthy eyes and preperimetric glaucoma eyes, the normalized rates of GCC thinning and macular vessel density decrease were comparable (all P > 0.1). In contrast, the normalized rate (mean, 95% confidence interval) of macular vessel density decrease in the POAG eyes (-7.12 [-8.36, -5.88]%/year) was significantly faster than GCC thinning (-2.13 [-3.35, -0.90]%/year; P < 0.001). In the POAG group, more than two thirds of the eyes showed faster macular vessel density decrease than GCC thinning; faster macular vessel density decrease rate was associated significantly with worse glaucoma severity (P = 0.037). The association between GCC thinning rate and glaucoma severity was not significant (P = 0.586). Intraocular pressure during follow-up significantly affected the rate of GCC thinning in all groups (all P < 0.05) but showed no association with the rate of macular vessel density decrease. CONCLUSIONS: Both GCC thinning and macular vessel density decrease were detectable over time in all diagnostic groups. In POAG eyes, macular vessel density decrease was faster than GCC thinning and was associated with severity of disease. Macular vessel density is useful for evaluating glaucoma progression, particularly in more advanced disease.

Evaluation of Quantitative Imaging Biomarkers for Early-phase Clinical Trials of Steatohepatitis in Adolescents.

OBJECTIVES: Early-phase pediatric nonalcoholic fatty liver disease (NAFLD) clinical trials are designed with noninvasive parameters to assess potential efficacy. Increasingly, these parameters include magnetic resonance imaging (MRI)-derived proton density fat fraction (PDFF) and MR elastography (MRE)-derived shear stiffness as biomarkers of hepatic steatosis and fibrosis, respectively. Understanding fluctuations in these measures is essential for calculating trial sample sizes, interpreting results, and planning clinical drug trials in children with NAFLD. Lack of such data in children constitutes a critical knowledge gap. Therefore, the primary aim of this study was to assess whole-liver MRI-PDFF change in adolescents with nonalcoholic steatohepatitis (NASH) over 12 weeks. METHODS: Adolescents 12 to 19 years with biopsy-proven NASH undergoing standard-of-care treatment were enrolled. Baseline and week-12 assessments of anthropometrics, transaminases, MRI-PDFF, and MRE stiffness were obtained. RESULTS: Fifteen adolescents were included (mean age 15.7 [SD 2.9] years). Hepatic MRI-PDFF was stable over 12 weeks (mean absolute change -0.8%, P = 0.24). Correlation between baseline and week-12 values of MRI-PDFF was high (ICC = 0.97, 95% CI 0.90-0.99). MRE stiffness was stable (mean percentage change 2.7%, P = 0.44); correlation between baseline and week-12 values was moderate (ICC = 0.47; 95% CI 0-0.79). Changes in weight, BMI, and aminotransferases were not statistically significant. CONCLUSION: In adolescents with NASH, fluctuations in hepatic MRI-PDFF and MRE stiffness over 12 weeks of standard-of-care were small. These data on the natural fluctuations in quantitative imaging biomarkers can serve as a reference for interventional trials in pediatric NASH and inform the interpretation and planning of clinical trials.

Sociodemographic and clinical characteristics associated with vitamin D status in newly diagnosed pediatric cancer patients.

Vitamin D deficiency and insufficiency are associated with serious sequelae in childhood cancer survivors. However, data on vitamin D deficiency in children with newly diagnosed cancer are scarce and the role of sociodemographic factors and vitamin D supplementation is largely unknown. We assessed vitamin D status and its socio-demographic and clinical correlates in 163 children with newly diagnosed cancer, using 25-hydroxy vitamin D (25(OH)D) concentrations and assessed longitudinal changes following vitamin D supplementation. Sixty-five percent of the patients with newly diagnosed cancer had low 25(OH)D concentrations. Fifty-two patients (32%) were vitamin D deficient (≤20 ng/mL 25(OH)D concentration), and 53(33%) were insufficient (21-29 ng/mL 25(OH)D concentration). Age over 10 (P = 0.019), Hispanic ethnicity (P = 0.002), and female sex (P = 0.008) were significantly associated with lower 25(OH)D concentration at diagnosis. Vitamin D supplementation resulted in significant increase in 25(OH)D concentrations (P < 0.001). However, following supplementation in the longitudinal analysis, this increase was less pronounced in Hispanic patients vs. non-Hispanic (P = 0.007), and in children with solid tumors vs. hematological malignancies (P = 0.003). Vitamin D deficiency and insufficiency are common in children with newly diagnosed cancer. Hispanic patients, females and older children were at higher risk for vitamin D deficiency and insufficiency. Although supplementation appeared to increase 25(OH)D concentrations over time, this increase was not as pronounced in certain subsets of patients. Prospective trials of the effects of vitamin D supplementation on bone health in children with newly diagnosed cancer are warranted, particularly in Hispanics and patients with solid tumors.

Evaluation of long-term course in children with eosinophilic esophagitis reveals distinct histologic patterns and clinical characteristics.

BACKGROUND: Eosinophilic esophagitis (EoE) is a chronic and increasingly prevalent antigen-driven disease. There is a paucity of information on long-term course in children. OBJECTIVE: We sought to understand the longitudinal trajectory of pediatric EoE during routine clinical care. METHODS: We prospectively enrolled children into an EoE database and reviewed their medical and pathologic records over 13 years. RESULTS: From 2011 to 2015, 146 children with EoE seen for their first visit at our center had 2 or more years of follow-up and 3 or more endoscopies over an average follow-up period of 5.13 years (range, 2-13 years). Longitudinal eosinophilic inflammation during treatment demonstrated 3 patterns over time. Children with less than 15 eosinophils/high-power field (hpf) for greater than 75% of their follow-up period were termed continuous responders (CRs). Children with waxing and waning inflammation of less than 15 eosinophils/hpf for less than 75% but 25% or more of the follow-up period were termed intermittent responders (IRs). Nonresponders (NRs) were defined as having less than 15 eosinophils/hpf for less than 25% of their follow-up. Fifty-nine (40%) of 146 patients were CRs, 65 (45%) of 146 were IRs, and 22 (15%) of 146 were NRs. CRs differed from IRs and NRs on the parameter of male/female ratio (1:1 in CRs, 4:1 in IRs, and 6:1 in NRs; P < .001) and in their initial response to any therapy, including proton pump inhibitors (P < .001). Endoscopic severity correlated with esophageal eosinophilia (r = 0.73, P < .001). On multivariate analysis, female sex and initial therapeutic response to medications or elimination diet were associated with long-term control of esophageal eosinophilia. CONCLUSIONS: Long-term pediatric EoE followed 3 different longitudinal trajectories of inflammation. The long-term histologic groups differed significantly in biological sex and initial therapeutic response.

A Longitudinal Analysis of Nurse Suicide in the United States (2005-2016) With Recommendations for Action.

BACKGROUND: Previous studies have demonstrated nurses are at risk of suicide. This is the first national longitudinal study of U.S. nurse suicide. AIMS: To identify the longitudinal incidence, method, and risks of nurse suicide in the United States. METHODS: 2005 to 2016 Centers for Disease Control and Prevention National Violent Death Reporting System retrospective analysis of suicide incident rate ratios (IRR). RESULTS: A total of 1,824 nurse and 152,495 non-nurse suicides were evaluated. Nurses were at greater risk of suicide than the general population (female IRR 1.395, 95% confidence intervals [CI] 1.323, 1.470, p < .001; male IRR 1.205, 95% CI 1.083, 1.338, p < .001). Female nurses who completed suicide did so most frequently by pharmacologic poisoning (n = 399, 27.2% vs. n = 8,843, 26.9%), whereby male nurses and the general public used firearms (n = 148, 41.7% vs. n = 57,887, 48.4%). Job problems were more likely in nurses (female odds ratio [OR] 1.989, 95% CI 1.695, 2.325, p < .001; male OR 1.814, 95% CI 1.380, 2.359, p < .001), as well as mental health history (female OR 1.126, 95% CI 1.013, 1.253, p < .027; male OR 1.302, 95% CI 1.048, 1.614, p = .016) and leaving a suicide note (female OR 1.221, 95% CI 1.096, 1.360, p < .001; male OR 1.756 [1.412, 2.181], p < .001). LINKING EVIDENCE TO ACTION: The increased risk of suicide in nurses is congruent with previous reports. The consistency in results increases confidence that findings are generalizable and warrant action. The use of pharmacologic poisoning as a method of suicide, most often by opioids and benzodiazepines, indicates a need for improved identification and treatment of nurses with substance use. Workplace wellness programs need to focus on reducing workplace stressors. Further research is indicated to determine best prevention methods. Policy indications include the need to accurately track gender in nursing, enhance substance use disorder programs, and mandate suicide prevention activities.

Impact of Obesity on Disease Activity and Patient-Reported Outcomes Measurement Information System (PROMIS) in Inflammatory Bowel Diseases.

INTRODUCTION: We conducted a cohort study on the impact of obesity on disease activity and Patient-Reported Outcomes Measurement Information System (PROMIS) measures in the inflammatory bowel disease (IBD) Partners cohort. METHODS: We performed a cross-sectional and longitudinal study within IBD Partners, an internet-based cohort of >15,000 patients living with Crohn's disease (CD) and ulcerative colitis (UC). We included adult patients with IBD, with recorded body mass index (BMI), with at least 6 months of follow-up, excluding patients with BMI < 18.5 kg/m. We evaluated the independent effect of World Health Organization classes of obesity on risk of clinical relapse or persistent disease activity (using validated disease activity indexes) and PROMIS measures, using multivariate logistic regression and linear regression, respectively. RESULTS: We included 7,296 patients with IBD (4,748 patients with CD, 19.5% obese; 2,548 patients with UC with intact colon, 20.3% obese). Obesity was independently, and in a dose-dependent fashion, associated with an increased risk of persistent disease activity or relapse in both patients with CD (class II or III obesity vs normal BMI: adjusted odds ratio, 1.86; 95% confidence interval, 1.30-2.68) and UC (adjusted odds ratio, 2.97; 95% confidence interval, 1.75-5.17). Obesity was also independently associated with higher anxiety, depression, fatigue, pain, and inferior social function scores in patients with CD and UC at baseline and with worsening depression, fatigue, pain, and social function in patients with CD on longitudinal assessment. DISCUSSION: Obesity at baseline is independently associated with worsening disease activity and PROMIS measures in patients with IBD.

The effects of provider-prescribed obesogenic drugs on post-laparoscopic sleeve gastrectomy outcomes: a retrospective cohort study.

BACKGROUND: Laparoscopic sleeve gastrectomy (LSG) is one of the most commonly performed bariatric procedures and has proven effective in providing weight loss. However, considerable variance has been noted in the degree of weight loss. Physician prescription practices may be negatively affecting weight loss post-LSG and, thus, contributing to the broad range of weight loss outcomes. The aim of our study was to determine whether commonly prescribed obesogenic medications negatively affect weight loss outcomes post-LSG. SUBJECTS/METHODS: This single center retrospective cohort study performed at a University hospital included 323 patients (≥18 years) within the University California, San Diego Healthcare System who underwent LSG between 2007 and 2016. We identified a list of 32 commonly prescribed medications that have weight gain as a side effect. We compared the percent excess weight loss (%EWL) of patients divided into two groups based on post-LSG exposure to obesogenic medications. A linear regression model was used to analyze %EWL at 12 months post-LSG while controlling for age, initial body mass index (BMI), and use of leptogenic medications. RESULTS: A total of 150 patients (Meds group) were prescribed obesogenic medications within the one-year post-LSG follow up period, whereas 173 patients (Control group) were not prescribed obesogenic medications. The Meds group lost significantly less weight compared to the Control group (%EWL ± SEM at 12 months 53.8 ± 2.4 n = 78, 65.0 ± 2.6, n = 84 respectively, P = 0.002). This difference could not be attributed to differences in age, gender, initial BMI, co-morbidities, or prescription of leptogenic medications between the two groups. CONCLUSIONS: The use of provider-prescribed obesogenic medications was associated with worse weight loss outcomes post-LSG. Closer scrutiny of patient medications may be necessary to help improve outcomes of weight loss treatments.

Measurement Floors and Dynamic Ranges of OCT and OCT Angiography in Glaucoma.

PURPOSE: To determine if OCT angiography (OCTA)-derived vessel density measurements can extend the available dynamic range for detecting glaucoma compared with spectral-domain (SD) OCT-derived thickness measurements. DESIGN: Observational, cross-sectional study. PARTICIPANTS: A total of 509 eyes from 38 healthy participants, 63 glaucoma suspects, and 193 glaucoma patients enrolled in the Diagnostic Innovations in Glaucoma Study. METHODS: Relative vessel density and tissue thickness measurement floors of perifoveal vessel density (pfVD), circumpapillary capillary density (cpCD), circumpapillary retinal nerve fiber (cpRNFL) thickness, ganglion cell complex (GCC) thickness, and visual field (VF) mean deviation (MD) were investigated and compared with a previously reported linear change point model (CPM) and locally weighted scatterplot smoothing curves. MAIN OUTCOME MEASURES: Estimated vessel density and tissue thickness measurement floors and corresponding dynamic ranges. RESULTS: Visual field MD ranged from -30.1 to 2.8 decibels (dB). No measurement floor was found for pfVD, which continued to decrease constantly until very advanced disease. A true floor (i.e., slope of approximately 0 after observed CPM change point) was detected for cpRNFL thickness only. The post-CPM estimated floors were 49.5±2.6 µm for cpRNFL thickness, 70.7±1.0 µm for GCC thickness, and 31.2±1.1% for cpCD. Perifoveal vessel density reached the post-CPM estimated floor later in the disease (VF MD, -25.8±3.8 dB) than cpCD (VF MD, -19.3±2.4 dB), cpRNFL thickness (VF MD, -17.5±3.3 dB), and GCC thickness (VF MD, -13.9±1.8 dB; P < 0.001). The number of available measurement steps from normal values to the CPM estimated floor was greatest for cpRNFL thickness (8.9), followed by GCC thickness (7.4), cpCD (4.5), and pfVD (3.8). CONCLUSIONS: In late-stage glaucoma, particularly when VF MD is worse than -14 dB, OCTA-measured pfVD is a promising tool for monitoring progression because it does not have a detectable measurement floor. However, the number of steps within the dynamic range of a parameter also needs to be considered. Although thickness parameters reached the floor earlier than OCTA-measured pfVD, there are more such steps with thickness than OCTA parameters.

Should partial nephrectomy be considered "elective" in patients with stage 2 chronic kidney disease? A comparative analysis of functional and survival outcomes after radical and partial nephrectomy.

PURPOSE: To compare renal function and survival outcomes in patients with baseline chronic kidney disease (CKD) stage 2 undergoing partial (PN) or radical nephrectomy (RN), as nephron-sparing surgery is considered to be elective in this group. METHODS: Retrospective analysis of patients with CKD stage 2 and T1/T2 renal mass undergoing PN or RN from 2001 to 2015. Patients were stratified into substage CKD 2a or CKD 2b and analyzed between types of surgery. Primary outcome was overall survival (OS), eGFR < 45 at last follow-up was the secondary outcome. Multivariable analysis (MVA) was conducted for predictors of eGFR < 45 and OS. Kaplan-Meier analyses were conducted for freedom from eGFR < 45 and OS. RESULTS: 1213 patients analyzed (CKD 2a 609/CKD 2b 604) on MVA, RN (OR 3.68, p = 0.001) and CKD 2b (OR 3.3, p = 0.002) were independently associated with development of eGFR < 45 at last follow-up and RN (OR 3.76, p = 0.005) and eGFR < 45 (OR 2.51, p = 0.029) were associated with decreased OS. Kaplan-Meier analyses revealed that patients with CKD 2a/PN had the highest 5-year freedom from eGFR < 45 (94.3%) compared to CKD 2a/RN patients (91.5%), CKD2b/PN patients (87.6%) and CKD 2b/RN patients 82.0% (p < 0.001). Kaplan-Meier analyses for OS demonstrated that patients with CKD 2a/PN had significantly greater 5-year OS (97.6%) compared to CKD 2a/RN patients (95.2%), CKD 2b/PN patients (93.2%), and CKD 2b/RN patients (92.4%, p = 0.043). CONCLUSIONS: Patients with baseline CKD stage 2, particularly CKD 2b and undergoing RN, are at increased risk of GFR < 45, which was associated with decreased OS. In patients with CKD 2b, a nephron-sparing strategy is indicated and should be prioritized when feasible.

Non-alcoholic fatty liver disease in pediatric type 2 diabetes: Metabolic and histologic characteristics in 38 subjects.

BACKGROUND: Obesity and type 2 diabetes (T2D) is risk factors for non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH). In children with T2D and liver biopsies, we investigated correlations between NAFLD/NASH and transaminase activity, A1c, lipids, and histologic changes in repeat biopsies. METHODS: Liver histology of children with T2D was evaluated using the NASH CRN scoring system and NAFLD Activity Score (NAS). We included results ≤6 months from biopsy and A1c nearest biopsy. RESULTS: Thirty-eight subjects (21 females, 17 males, 63.2% Hispanic, 15.8% Caucasian) had T2D diagnosed at 13.4 ± 2.7 years, 78.9% using metformin and 50% on insulin. Histological diagnosis of NAFLD occurred at mean age 14.3 ± 2.3 years, notable for NASH in 61%. Steatosis grade was higher in children with NASH than those without (mean 2.6 ± 0.7 vs 2.1 ± 0.5 (P < 0.001). Stage 3 fibrosis was noted only in subjects with NASH (26%). ALT was higher in NASH vs those without (112 ± 56 vs 85 ± 112, P = 0.016). NAS correlated with A1c (r = 0.51, P < 0.01) and triglycerides (r = 0.5, P < 0.01), and inversely with high-density lipoprotein (HDL) (r = -0.42, P = 0.04). Males had lower HDL and higher triglycerides (P < 0.04). In eight subjects with repeat biopsies, NAS was equal (37.5%) or improved (62.5%), and steatosis decreased (68.1% to 32.8%, P = 0.027). CONCLUSIONS: In children with T2D and NAFLD, NASH is common. Having advanced fibrosis in 26% of NASH cases at this age is concerning. Better control of lipids, weight, and diabetes may help avoid worsening in NAS.

Esophageal Compliance Quantifies Epithelial Remodeling in Pediatric Patients With Eosinophilic Esophagitis.

BACKGROUND: The management of eosinophilic esophagitis (EoE) relies on the severity of esophageal eosinophilia, yet there is poor evidence of its prediction of esophageal fibrotic remodeling and subsequent complications such as dysphagia, food impactions, or strictures. Functional luminal imaging planimetry (FLIP) has had limited use in pediatric patients to evaluate esophageal tissue mechanics. We aimed to standardize the FLIP technique and to measure esophageal compliance in children with EoE in comparison to controls. METHODS: Subjects were enrolled into a prospective observational study and had FLIP performed at the time of endoscopy. We calculated esophageal distensibility and compliance for the total and segmental esophagus independently (ie, proximal, middle, and distal esophageal segments). We evaluated esophageal biopsies for eosinophilia and epithelial remodeling, calculated endoscopy scores, and documented patient symptoms. RESULTS: We enrolled 11 EoE and 12 controls subjects, aged 5 to 18 years old. While EoE subjects had lower esophageal compliance (P = 0.004) than controls, the difference in distensibility did not reach significance (P = 0.151). Epithelial remodeling severity was more strongly correlated with compliance than with distensibility. Epithelial remodeling scores ≥2 had a significant association with lower compliance both segmentally and in the entire esophagus (P = 0.029), but not with distensibility. Compliance measures were more sensitive in detecting subjects with remodeling score ≥2 than distensibility (79% vs 64%). CONCLUSIONS: Compliance is a more sensitive measure of esophageal epithelial remodeling in children compared to distensibility, and a more appropriate measure of esophageal tissue mechanics. Standardized placement of the FLIP catheter is important to accurately assess esophageal compliance.

Clinical Practice Approach to Nonalcoholic Fatty Liver Disease by Pediatric Gastroenterologists in the United States.

OBJECTIVES: Nonalcoholic fatty liver disease (NAFLD) is common; however, no information is available on how pediatric gastroenterologists in the United States manage NAFLD. Therefore, study objectives were to understand how pediatric gastroenterologists in the US approach the management of NAFLD, and to identify barriers to care for children with NAFLD. METHODS: We performed structured one-on-one interviews to ascertain each individual pediatric gastroenterologist's approach to the management of NAFLD in children. Responses were recorded from open-ended questions regarding screening for comorbidities, recommendations regarding nutrition, physical activity, medications, and perceived barriers to care. RESULTS: Response rate was 72.0% (486/675). Mean number of patients examined per week was 3 (standard deviation [SD] 3.5). Dietary intervention was recommended by 98.4% of pediatric gastroenterologists. Notably, 18 different dietary recommendations were reported. A majority of physicians provided targets for exercise frequency (72.6%, mean 5.6 days/wk, SD 1.6) and duration (69.9%, mean 40.2 minutes/session, SD 16.4). Medications were prescribed by 50.6%. Almost one-half of physicians (47.5%) screened for type 2 diabetes, dyslipidemia, and hypertension. Providers who spent more than 25 minutes at the initial visit were more likely to screen for comorbidities (P = 0.003). Barriers to care were reported by 92.8% with 29.0% reporting ≥3 barriers. CONCLUSIONS: The majority of US pediatric gastroenterologists regularly encounter children with NAFLD. Varied recommendations regarding diet and exercise highlight the need for prospective clinical trials. NAFLD requires a multidimensional approach with adequate resources in the home, community, and clinical setting.

Effect of inhaled corticosteroid use on weight (BMI) in pediatric patients with moderate-severe asthma.

OBJECTIVES: Assess the relationship between inhaled corticosteroid use (ICS) and weight (BMI) in pediatric patients with moderate-severe asthma. Assess if the number of emergency department (ED) visits correlates with overall BMI trajectory. Assess the trend of prescribing biologic therapy in pediatric patients with moderate-severe asthma and determine its relationship with weight (BMI). METHODS: A retrospective chart review was performed on 93 pediatric patients with moderate-severe asthma to determine the relationship between ICS use and weight (BMI), biologic therapy and BMI, and number of ED visits and BMI trajectory. A mixed effects model was employed with the correlation between repeated measures accounted for through the random effects. RESULTS: There is a statistically significant increase of 0.369 kg/m2 in BMI trajectory per year in subjects on high-dose steroids compared to an increase of 0.195 kg/m2 in the low dose group (p < 0.05). The BMI of subjects initiated on biologic therapy (omalizumab or mepolizumab) had a statistically significant decrease in BMI trajectory of 0.818 kg/m2 per year (p < 0.05). Subjects with ≥5 ED visits due to asthma exacerbations had a significantly higher BMI trajectory (p < 0.05). CONCLUSIONS: The potency of ICS use in pediatric patients with moderate-severe asthma affects BMI trajectory; the higher the dose, the greater the projected BMI increase per year. Initiation of biologic therapy decreased BMI trajectory over time. Lastly, those with frequent ED visits had a higher BMI trend. Future prospective studies are warranted that further evaluate the potential metabolic impacts of ICS and assess the effects of biologic therapy on BMI.

Nurse suicide in the United States: Analysis of the Center for Disease Control 2014 National Violent Death Reporting System dataset.

OBJECTIVE: This study explored nurse suicide in the United States. METHODS: Characteristics were compared between occupations using 2014 National Violent Death Reporting System data. RESULTS: Female nurse suicides were significantly higher (11.97/100,000) than in the female population (7.58/100,000) (p < 0.001); similarly male nurses (39.8/100,000) compared to the male population (28.2/100,000) (p < 0.001). Benzodiazepines and opioids were the most commonly used substances used in clinician suicide. CONCLUSION: These results suggest a public health imperative for future research and development of effective preventative strategies for nurses; a largely understudied population.