Citations

BACKGROUND: A gender-based compensation gap among physicians is well documented. Even after adjusting for age, experience, work hours, productivity, and academic rank, the gender gap remained and widened over the course of a physician’s career. This study aimed to examine if a significant gender pay gap still existed for anesthesiologists in the United States. METHODS: In 2018, we surveyed 28,812 physician members of the American Society of Anesthesiologists to assess the association of compensation with gender and to identify possible causes of wage disparities. Gender was the primary variable examined in the model, and compensation by gender was the primary outcome. Compensation was defined as the amount reported as direct compensation on a W-2, 1099, or K-1, plus all voluntary salary reductions (eg, 401[k], health insurance). The survey directed respondents to include salary, bonuses, incentive payments, research stipends, honoraria, and distribution of profits to employees. Respondents had the option of providing a point estimate of their compensation or selecting a range in $50,000 increments. Potential confounding variables that could affect compensation were identified based on a scoping literature review and the consensus expertise of the authors. We fitted a generalized ordinal logistic regression with 7 ranges of compensation. For the sensitivity analyses, we used linear regressions of log-transformed compensation based on respondent point estimates and imputed values. RESULTS: The final analytic sample consisted of 2081 observations (response rate, 7.2%). This sample represented a higher percentage of women and younger physicians compared to the demographic makeup of anesthesiologists in the United States. The adjusted odds ratio associated with gender equal to woman was an estimated 0.44 (95% confidence interval, 0.37–0.53), indicating that for a given compensation range, women had a 56% lower odds than men of being in a higher compensation range. Sensitivity analyses found the relative percentage difference in compensation for women compared to men ranged from −8.3 to −8.9. In the sensitivity analysis based on the subset of respondents (n = 1036) who provided a point estimate of compensation, the relative percentage difference (−8.3%; 95% confidence interval, −4.7 to −11.7) reflected a $32,617 lower compensation for women than men, holding other covariates at their means. CONCLUSIONS: Compensation for anesthesiologists showed a significant pay gap that was associated with gender even after adjusting for potential confounding factors, including age, hours worked, geographic practice region, practice type, position, and job selection criteria.

Sweat out the fat with TSLP! Thymic stromal lymphopoietin (TSLP) is a cytokine that can promote immune responses that characterize allergic diseases. Choa et al . found that mice engineered to produce elevated TSLP displayed selective white adipose tissue loss that protected them from obesity, insulin resistance, and steatohepatitis (see the Perspective by Schneider). Protection was not mediated by eosinophils, regulatory T cells, or innate lymphoid cells. Rather, TLSP induced the migration of conventional T cells to sebaceous glands in the skin. Once there, these T cells promoted white adipose tissue loss by the hypersecretion of sebum, a lipid-rich substance that augments the skin’s barrier function. This mechanism, which likely evolved to enhance cutaneous antimicrobial defenses, could be possibly targeted in future treatments for obesity. —STS

The upper gastrointestinal (UGI) manifestations of inflammatory bowel diseases (IBDs) are frequently obscured by classic ileal and colonic symptoms and are reported to involve only 0.5% to 4% of adult patients. However, because of the improvement of endoscopic techniques and the growing use of esophagogastroduodenososcopy with biopsy, both asymptomatic and clinically significant esophageal, gastric, and duodenal manifestations are increasingly recognized. The UGI involvement in IBD was historically synonymous with Crohn’s disease (CD), but the doctrine of ulcerative colitis (UC) being limited to the colon has been challenged, and UC-related gastroduodenal lesions have been reported. The diagnosis of UGI IBD should ideally rely on a combination of the clinical history, endoscopic picture, and histologic features. Although endoscopic changes such as aphthoid or longitudinal ulcers and bamboo-joint-like pattern are suggestive of CD, histologic evaluation increases the sensitivity of the IBD diagnosis since histologic alterations may be present in endoscopically unremarkable mucosa. Conversely, in many cases, the histologic findings are nonspecific, and the knowledge of clinical history is vital for reaching an accurate diagnosis. The presence of epithelioid granuloma is highly suggestive of CD but is present in a minority of CD cases; thus, pathologists should be aware of how to diagnose UGI IBD in the absence of granulomata. This article reviews the most important clinical, endoscopic, and histologic features of IBD-associated esophagitis, gastritis, and duodenitis, as well as the IBD-related manifestations in the biliary tract and the postcolectomy setting.

We report an unusual case of appendicitis in a 9-year-old girl in whom the wall of the appendix contained necrotizing granulomas, as well as eggs of Enterobius vermicularis. Although luminal E vermicularis adult parasites are commonly identified in the appendix and luminal eggs are occasionally seen, intramural worms and eggs are rare. We are unaware of earlier reports of ectopic intramural eggs in the appendix. It is important to and make a correct diagnosis, as both, the patient, as well as the family should be treated for enterobiasis.

Abstract Background Eosinophils have been implicated in the pathogenesis of ulcerative colitis and have been associated with disease course and therapeutic response. However, associations between eosinophil density, histologic activity, and clinical features have not been rigorously studied. Methods A deep learning algorithm was trained to identify eosinophils in colonic biopsies and validated against pathologists’ interpretations. The algorithm was applied to sigmoid colon biopsies from a cross-sectional cohort of 88 ulcerative colitis patients with histologically active disease as measured by the Geboes score and Robarts histopathology index (RHI). Associations between eosinophil density, histologic activity, and clinical features were determined. Results The eosinophil deep learning algorithm demonstrated almost perfect agreement with manual eosinophil counts determined by 4 pathologists (interclass correlation coefficients: 0.805–0.917). Eosinophil density varied widely across patients (median 113.5 cells per mm2, interquartile range 108.9). There was no association between eosinophil density and RHI (P = 0.5). Significant differences in eosinophil density were seen between patients with Montreal E3 vs E2 disease (146.2 cells per mm2 vs 88.2 cells per mm2, P = 0.005). Patients on corticosteroids had significantly lower eosinophil density (62.9 cells per mm2 vs 124.1 cells per mm2, P = 0.006). No association between eosinophil density and biologic use was observed (P = 0.5). Conclusions We developed a deep learning algorithm to quantify eosinophils in colonic biopsies. Eosinophil density did not correlate with histologic activity but did correlate with disease extent and corticosteroid use. Future studies applying this algorithm in larger cohorts with longitudinal follow-up are needed to further elucidate the role of eosinophils in ulcerative colitis.

Abstract Background Mirikizumab (miri), a p19-directed IL-23 antibody, demonstrated efficacy and was well-tolerated in a phase 2 randomized clinical trial (NCT02891226) in patients with Crohn’s disease (CD). The histologic results at Week (W)12 induction and W52 maintenance are presented here. Methods Patients were randomized 2:1:1:2 across 4 treatment arms (PBO, 200, 600, 1000mg miri) administered intravenously (IV) every four weeks (Q4W) at Weeks 0, 4, and 8. Patients who received miri and achieved ≥1 point improvement from baseline (BL) at W12 in Simple Endoscopic Score for Crohn’s Disease (SES-CD) were re-randomized 1:1 into double-blind maintenance to continue their IV dose assignment Q4W (IV/IV) or to 300mg miri SC Q4W (IV/SC); maintenance IV arms were pooled for analysis. W12 non-improvers and all induction PBO patients received 1000mg miri Q4W from W12 through W52. Biopsies from terminal ileum and 4 colonic segments (ascending, transverse, descending, rectum) were obtained during endoscopy at W0, 12 and 52 and scored blind to treatment and response status. Ileum and colon scores were reported separately. Colon scores were derived from the sum of the 4 colonic segments, and total intestine scores from the 4 colonic segments plus ileum. Endpoints were defined post-hoc but prior to performing the analyses and only included patients with active histologic disease at BL (see Table). Histologic response was defined as: a) absence of neutrophils in lamina epithelialis, and absence of epithelial damage, erosions and ulceration or b) decrease of either RHI or GHAS ≥50% from BL. Histologic remission was defined as absence of mucosal neutrophils, epithelial damage, erosions, and ulceration. Deep histologic remission was defined as histologic remission combined with absence of chronic inflammatory cell infiltration of the lamina propria. For assessment of total intestine inflammation, the criteria for response, remission or deep remission must have been met in all 5 bowel segments. Results At W12, histologic response and remission were significantly higher in all segments of the 1000mg group versus PBO (response: ileum p<0.01, total intestine p<0.01, colon p<0.05; remission: ileum p<0.05, colon p<0.05, total intestine p<0.01). Among the W12 improvers, both histologic response and histologic remission at W52 were similar in ileum and colon in the IV/IV group, but lower in ileum than colon in the IV/SC group. All but 2 patients with remission at W52 were in deep histologic remission. Conclusion Patients treated with miri achieved and sustained histologic response and remission over 52 weeks of treatment. Among patients with W52 histologic remission, all but 2 patients achieved deep remission.

Abstract Background The histologic assessment of inflammatory bowel disease (IBD) relies on qualitative grading methods. Although widely accepted, these instruments are time consuming, require specialized training, and suffer from inter-rater disagreement. For these reasons there is a need for more consistent and less biased methods to assess IBD histology. Methods The algorithm was initially developed using hematoxylin and eosin (H&E) stained whole slide images of colon biopsies (238 ulcerative colitis [UC], 30 Crohn’s Disease [CD], and 28 endoscopically normal adjacent [ENA]). The first two stages implement convolutional neural networks (CNN) which segment 11 key anatomical features (Figure 1). The third stage extracts the features and models them for prediction. Results The first stage of the algorithm was validated on an independent test dataset by calculating the intersection-over-union (IoU) for the ground truth and prediction masks, resulting in a value of 0.97. A preliminary validation for stage 2 was performed by randomly selecting 30 unique biopsy sections from the test dataset and applying a 150um x 150um counting frame. An expert gastrointestinal pathologist confirmed correct cell identification by the algorithm for three of the primary inflammatory cell types: plasma cells, eosinophils, and neutrophils which resulted in a sensitivity/specificity of 0.76/0.99, 0.78/1.00, and 1.00/0.98 respectively. The final stage predicts RHI grades which could be directly compared to pathologist reads (Figure 2, 3, and 4). Conclusion This is the first study to demonstrate the value of machine learning to assess histologic activity in IBD. These methods lay the foundations for future work, and we believe stages 1 and 2 can be explored independently to statistically characterize the histologic changes of IBD, enabling the improvement of preexisting grading systems.

Abstract Background: A positive association between circulating C-reactive protein (CRP) and colorectal cancer survival was reported in observational studies, which are susceptible to unmeasured confounding and reverse causality. We used a Mendelian randomization approach to evaluate the association between genetically predicted CRP concentrations and colorectal cancer–specific survival. Methods: We used individual-level data for 16,918 eligible colorectal cancer cases of European ancestry from 15 studies within the International Survival Analysis of Colorectal Cancer Consortium. We calculated a genetic-risk score based on 52 CRP-associated genetic variants identified from genome-wide association studies. Because of the non-collapsibility of hazard ratios from Cox proportional hazards models, we used the additive hazards model to calculate hazard differences (HD) and 95% confidence intervals (CI) for the association between genetically predicted CRP concentrations and colorectal cancer–specific survival, overall and by stage at diagnosis and tumor location. Analyses were adjusted for age at diagnosis, sex, body mass index, genotyping platform, study, and principal components. Results: Of the 5,395 (32%) deaths accrued over up to 10 years of follow-up, 3,808 (23%) were due to colorectal cancer. Genetically predicted CRP concentration was not associated with colorectal cancer–specific survival (HD, −1.15; 95% CI, −2.76 to 0.47 per 100,000 person-years; P = 0.16). Similarly, no associations were observed in subgroup analyses by stage at diagnosis or tumor location. Conclusions: Despite adequate power to detect moderate associations, our results did not support a causal effect of circulating CRP concentrations on colorectal cancer–specific survival. Impact: Future research evaluating genetically determined levels of other circulating inflammatory biomarkers (i.e., IL6) with colorectal cancer survival outcomes is needed.

Objective Effective medical therapy and validated trial outcomes are lacking for small bowel Crohn’s disease (CD) strictures. Histopathology of surgically resected specimens is the gold standard for correlation with imaging techniques. However, no validated histopathological scoring systems are currently available for small bowel stricturing disease. We convened an expert panel to evaluate the appropriateness of histopathology scoring systems and items generated based on panel opinion. Design Modified RAND/University of California Los Angeles methodology was used to determine the appropriateness of 313 candidate items related to assessment of CD small bowel strictures. Results In this exercise, diagnosis of naïve and anastomotic strictures required increased bowel wall thickness, decreased luminal diameter or internal circumference, and fibrosis of the submucosa. Specific definitions for stricture features and technical sampling parameters were also identified. Histopathologically, a stricture was defined as increased thickness of all layers of the bowel wall, fibrosis of the submucosa and bowel wall, and muscularisation of the submucosa. Active mucosal inflammatory disease was defined as neutrophilic inflammation in the lamina propria and any crypt or intact surface epithelium, erosion, ulcer and fistula. Chronic mucosal inflammatory disease was defined as crypt architectural distortion and loss, pyloric gland metaplasia, Paneth cell hyperplasia, basal lymphoplasmacytosis, plasmacytosis and fibrosis, or prominent lymphoid aggregates at the mucosa/submucosa interface. None of the scoring systems used to assess CD strictures were considered appropriate for clinical trials. Conclusion Standardised assessment of gross pathology and histopathology of CD small bowel strictures will improve clinical trial efficiency and aid drug development.