We sought to evaluate the association between obesity and response to anti-tumor necrosis factor-α (TNF) agents, through a systematic review and meta-analysis. Through a systematic search through January 24, 2017, we identified randomized controlled trials (RCTs) or observational studies in adults with select immune-mediated inflammatory diseases–inflammatory bowel diseases (IBD), rheumatoid arthritis (RA), spondyloarthropathies (SpA), psoriasis and psoriatic arthritis (PsA)–treated with anti-TNF agents, and reporting outcomes, stratified by body mass index (BMI) categories or weight. Primary outcome was failure to achieve clinical remission or response or treatment modification. We performed random effects meta-analysis and estimated odds ratios (OR) and 95% confidence interval (CI). Based on 54 cohorts including 19,372 patients (23% obese), patients with obesity had 60% higher odds of failing therapy (OR,1.60; 95% CI,1.39–1.83;I² = 71%). Dose-response relationship was observed (obese vs. normal BMI: OR,1.87 [1.39–2.52]; overweight vs. normal BMI: OR,1.38 [1.11–1.74],p = 0.11); a 1kg/m² increase in BMI was associated with 6.5% higher odds of failure (OR,1.065 [1.043–1.087]). These effects were observed across patients with rheumatic diseases, but not observed in patients with IBD. Effect was consistent based on dosing regimen/route, study design, exposure definition, and outcome measures. Less than 10% eligible RCTs reported outcomes stratified by BMI. Obesity is an under-reported predictor of inferior response to anti-TNF agents in patients with select immune-mediated inflammatory diseases. A thorough evaluation of obesity as an effect modifier in clinical trials is warranted, and intentional weight loss may serve as adjunctive treatment in patients with obesity failing anti-TNF therapy.

OBJECTIVE. We describe the findings of unenhanced chest CT in 10 patients with acute schistosomiasis.CONCLUSION. Despite the absence of pulmonary symptoms in four individuals, all patients had parenchymal abnormalities. Small pulmonary nodules were the most common finding, identified in nine patients. These nodules ranged in size from 2 to 5 mm in five patients, with larger nodules ranging up to 15 mm seen in four patients. In one patient, the only parenchymal abnormality was a single 5-mm focus of ground-glass attenuation. No relationship was seen between either the presence of pulmonary symptoms or the presence of peripheral eosinophilia and the severity of parenchymal disease. No additional significant findings were identified.

Objective: Obstructive sleep apnea (OSA) is common among bariatric surgery patients and is associated with perioperative risk. Preoperative screening is recommended, but some screening tools lack validation, and their relative performance is unclear in this population. The study objective was to compare the ability of four existing tools (STOP‐BANG, NO‐OSAS, No‐Apnea, and the Epworth Sleepiness Scale [ESS]) to screen for moderate to severe OSA in a diverse bariatric cohort.Methods: Data from patients presenting for first‐time bariatric surgery who underwent a sleep study within 1 year of the initial encounter were retrospectively reviewed. Performance of the four tools for detecting moderate to severe OSA was compared based on the area under the receiver operating characteristic curves (AUC).Results: Of the included 214 patients (83.2% female, median age 39 years), 45.3% had moderate to severe OSA. Based on AUC, STOP‐BANG (0.75 [95% CI: 0.68‐0.81], N = 185), NO‐OSAS (0.76 [95% CI: 0.69‐0.82], N = 185), and No‐Apnea (0.69 [95% CI: 0.62‐0.76], N = 190) had similar performance (P > 0.16). Compared with STOP‐BANG and NO‐OSAS, ESS (0.61 [95% CI: 0.54‐0.68], N = 198) had a significantly lower AUC (P < 0.01). Hispanic/Latino self‐identification, sex, or obesity class did not significantly modify test performance.Conclusions: STOP‐BANG and NO‐OSAS may be preferable to No‐Apnea and ESS when screening bariatric surgery patients for moderate to severe OSA. Efforts to screen bariatric patients for OSA are recommended. image

We previously demonstrated that a protein of M(r) 75,000 (p75) is localized to cortical granules (CGs) in mouse oocytes and eggs and is released upon activation or fertilization of eggs (K.E. Pierce, M. C. Siebert, G. S. Kopf, R. M. Schultz, and P. G. Calarco, 1990, Dev. Biol. 141, 381-392). To examine the temporal pattern of synthesis of p75 during the early stages of CG formation, growing oocytes, which were isolated from juvenile mice, were incubated for 4 hr in medium containing [35S]methionine, and radiolabeled proteins were immunoprecipitated using an antiserum that detects p75. Synthesis of p75 is detected at low levels in the smallest oocytes examined (less than 20 microns). Synthesis of p75 relative to total protein synthesis increases about 12-fold during oocyte growth from the 20-40 microns size and then remains constant throughout the remaining period of oocyte growth (40-70 microns). In the fully grown, germinal vesicle (GV)-intact oocyte (70-80 microns), immunoprecipitated p75 comprises approximately 1.5% of the total amount of radiolabeled protein. Three hours after the transfer of these oocytes to a medium that supports resumption of meiosis and GV breakdown in vitro, oocytes subjected to a 1-hr labeling pulse display a 35% decrease in the relative level of p75 synthesis. By 15 hr of maturation, p75 synthesis was reduced to 14% of that in the fully grown, GV-intact oocyte and this is similar to the level of p75 synthesis in ovulated eggs. The level of p75 synthesis following in vitro translation of total egg RNA is only 38% lower than that obtained from total oocyte RNA. In addition, synthesis of p75 is observed following in vitro translation of oocyte, but not egg, poly(A)+ RNA. These results are consistent with p75 synthesis during oocyte maturation being under translational control.

Background and Aims: Prior work has shown that MRI-derived proton density fat fraction (PDFF) can diagnose metabolic dysfunction-associated steatotic liver disease (MASLD) noninvasively, but there is a paucity of data on the performance of PDFF to classify more advanced forms of the MASLD spectrum. The purpose of this study was to assess the diagnostic performance of PDFF for the diagnoses of MASLD, metabolic dysfunction-associated steatohepatitis (MASH), and fibrotic MASH in adults with obesity undergoing bariatric surgery, using contemporaneous intraoperative liver biopsy as a reference. Approach and Results: PDFF was evaluated alone and with other potential classifiers (imaging, serum and anthropometric), using Bayesian Information Criterion-based stepwise logistic regression models. Areas under the receiver operating characteristic (ROC) curves (AUC) were computed for all models and single classifiers. Cross-validated sensitivity and specificity were calculated at Youden-based PDFF classification thresholds. Data analysis from 140 patients demonstrated that PDFF was the most accurate single classifier, with high AUC for MASLD (0.95), MASH (0.85), and fibrotic MASH (0.82) (all p <0.001). Multivariable models, including PDFF, outperformed those without PDFF. The Youden-based threshold for PDFF was 4.4% for MASLD (sensitivity: 87%, specificity: 86%), 6.9% for MASH (sensitivity: 77%, specificity: 66%), and 13.5% for fibrotic MASH (sensitivity: 67%, specificity: 85%). Conclusions: PDFF was the most accurate single classifier for diagnosing MASLD, MASH, and fibrotic MASH. The most accurate multivariable classification models for MASLD, MASH, and fibrotic MASH included PDFF, demonstrating the central importance of PDFF for noninvasive assessment of the MASLD spectrum.

Obesity has reached epidemic proportions, accounting for increased morbidity, disability, health care expenditures, and mortality. Certain metabolic and comorbid conditions disproportionately affect women. Unfortunately, nonsurgical options for treatment are limited. Knowledge accrued over the past 2 decades regarding physiological and hormonal determinants of weight regulation has contributed to growing evidence regarding efficacious behavioral, dietary, and pharmacologic treatments. In this review, the biology of excess adiposity is summarized in the context of a shifting paradigm, approaching obesity as a chronic metabolic disease. Relevant updates are discussed regarding long-term lifestyle approaches and novel drug therapies, with attention to some issues specific to women.