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Abstract Background and study aims Despite the clinical efficacy of peroral endoscopic myotomy (POEM), postoperative symptomatic gastroesophageal reflux disease (GERD) remains a major concern. While it is known that length of the gastric myotomy affects postoperative GERD, the clinical relevance of variation in esophageal myotomy length is not well known. We performed a systematic review and meta-analysis of studies comparing outcomes of short versus standard myotomy length in patients with achalasia. Patients and methods We searched multiple databases from inception through November 2020 to identify studies that reported on outcomes of achalasia patients who underwent short compared with standard esophageal myotomy. Meta-analysis was performed to determine pooled odds ratio (OR) of clinical success, GERD outcomes, and adverse events with the two techniques. Results 5 studies with 474 patients were included in the final analysis (short myotomy group 214, standard myotomy group 260). There was no difference in clinical success (OR 1.17, 95 % confidence interval [CI] 0.54–2.52; I2 0 %; P = 0.69), postoperative symptomatic GERD (OR 0.87, 95 %CI 0.44–1.74; I2 29 %; P = 0.70), and overall adverse events (OR 0.52, 95 %CI 0.19–1.38; I2 40 %; P = 0.19), between the two groups. Incidence of postoperative erosive esophagitis as determined by endoscopy was lower in the short myotomy group (OR 0.50, 95 %CI 0.24–1.03; I2 0 %; P = 0.06). Conclusion Our analysis showed that performing POEM with short esophageal myotomy in achalasia was as safe and effective as standard myotomy, with lower incidence of postoperative erosive esophagitis.

AbstractNiemann‐Pick disease type C (NPC) is a rare, genetic, progressive neurodegenerative disorder with high unmet medical need. We investigated the safety and efficacy of arimoclomol, which amplifies the heat shock response to target NPC protein misfolding and improve lysosomal function, in patients with NPC. In a 12‐month, prospective, randomised, double‐blind, placebo‐controlled, phase 2/3 trial (ClinicalTrials.gov identifier: NCT02612129), patients (2‐18 years) were randomised 2:1 to arimoclomol:placebo, stratified by miglustat use. Routine clinical care was maintained. Arimoclomol was administered orally three times daily. The primary endpoint was change in 5‐domain NPC Clinical Severity Scale (NPCCSS) score from baseline to 12 months. Fifty patients enrolled; 42 completed. At month 12, the mean progression from baseline in the 5‐domain NPCCSS was 0.76 with arimoclomol vs 2.15 with placebo. A statistically significant treatment difference in favour of arimoclomol of −1.40 (95% confidence interval: −2.76, −0.03; P = .046) was observed, corresponding to a 65% reduction in annual disease progression. In the prespecified subgroup of patients receiving miglustat as routine care, arimoclomol resulted in stabilisation of disease severity over 12 months with a treatment difference of −2.06 in favour of arimoclomol (P = .006). Adverse events occurred in 30/34 patients (88.2%) receiving arimoclomol and 12/16 (75.0%) receiving placebo. Fewer patients had serious adverse events with arimoclomol (5/34, 14.7%) vs placebo (5/16, 31.3%). Treatment‐related serious adverse events (n = 2) included urticaria and angioedema. Arimoclomol provided a significant and clinically meaningful treatment effect in NPC and was well tolerated.

The NCCN Guidelines for Uterine Neoplasms provide recommendations for diagnostic workup, clinical staging, and treatment options for patients with endometrial cancer or uterine sarcoma. These NCCN Guidelines Insights focus on the recent addition of molecular profiling information to aid in accurate diagnosis, classification, and treatment of uterine sarcomas.

Background: The management of patients with locally advanced or metastatic differentiated thyroid cancer (DTC) that is refractory to radioiodine (RAI) remains a therapeutic challenge. The multi-tyrosine kinase inhibitors (TKIs) sorafenib and lenvatinib have been approved based on phase 3 clinical trials. Patients and Methods: We aimed at describing the efficacy and safety of TKI treatment of RAI-refractory DTC in a real-world setting at six German referral centers. One hundred and one patients with locally advanced or metastatic RAI-refractory DTC treated with sorafenib, lenvatinib, and/or pazopanib were included. Progression-free survival (PFS) and overall survival (OS) probabilities were estimated by using the Kaplan-Meier method. Results: Ninety-seven of 101 patients had progressive disease before TKI initiation. The median PFS for first-line treatment with sorafenib ( n = 33), lenvatinib ( n = 53), and pazopanib ( n = 15) was 9 (95% confidence interval 5.2–12.8), 12 (4.4–19.6), and 12 months (4.4–19.6), respectively. The median OS for first-line treatment was 37 (10–64) for sorafenib, 47 (15.5–78.5) for lenvatinib, and 34 months (20.2–47.8) for pazopanib. Serious complications (e.g., hemorrhage, acute coronary syndrome, and thrombosis/venous thromboembolism) occurred in 16 out of 75 (21%) patients taking lenvatinib, in 3 out of 42 (7%) patients taking sorafenib, and in 3 out of 24 (13%) patients taking pazopanib. Conclusions: Sorafenib, lenvatinib, and pazopanib are effective treatment options in the majority of patients with RAI-refractory DTC. The PFS and six-month survival rate in patients treated with lenvatinib und pazopanib appear to compare favorably with sorafenib in the first-line treatment setting. However, a more advanced disease stage at treatment initiation in sorafenib- and pazopanib-treated patients in the era before TKI-approval and the retrospective nature of this study precludes a direct comparison of TKIs.

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.

Abstract Context Identification of modifiable risk factors, including genetic and acquired disorders of lipid and lipoprotein metabolism, is increasingly recognized as an opportunity to prevent premature cardiovascular disease (CVD) in at-risk youth. Pediatric endocrinologists are at the forefront of this emerging public health concern and can be instrumental in beginning early interventions to prevent premature CVD-related events during adulthood. Aim In this article, we use informative case presentations to provide practical approaches to the management of pediatric dyslipidemia. Cases We present 3 scenarios that are commonly encountered in clinical practice: isolated elevation of low-density lipoprotein cholesterol (LDL-C), combined dyslipidemia, and severe hypertriglyceridemia. Treatment with statin is indicated when the LDL-C is ≥190 mg/dL (4.9 mmol/L) in children ≥10 years of age. For LDL-C levels between 130 and 189 mg/dL (3.4-4.89 mmol/L) despite dietary and lifestyle changes, the presence of additional risk factors and comorbid conditions would favor statin therapy. In the case of combined dyslipidemia, the primary treatment target is LDL-C ≤130 mg/dL (3.4 mmol/L) and the secondary target non-high-density lipoprotein cholesterol <145 mg/dL (3.7 mmol/L). If the triglyceride is ≥400 mg/dL (4.5 mmol/L), prescription omega-3 fatty acids and fibrates are considered. In the case of triglyceride >1000 mg/dL (11.3 mmol/L), dietary fat restriction remains the cornerstone of therapy, even though the landscape of medications is changing. Conclusion Gene variants, acquired conditions, or both are responsible for dyslipidemia during childhood. Extreme elevations of triglycerides can lead to pancreatitis. Early identification and management of dyslipidemia and cardiovascular risk factors is extremely important.

OBJECTIVE Sustained postoperative opioid use after elective surgery is a matter of growing concern. Herein, the authors investigated incidence and predictors of long-term opioid use among patients undergoing elective lumbar spine surgery, especially as a function of opioid prescribing practices at postoperative discharge (dose in morphine milligram equivalents [MMEs] and type of opioid). METHODS The OptumLabs Data Warehouse (OLDW) was queried for postdischarge opioid prescriptions for patients undergoing elective lumbar decompression and discectomy (LDD) or posterior lumbar fusion (PLF) for degenerative spine disease. Only patients who received an opioid prescription at postoperative discharge and those who had a minimum of 180 days of insurance coverage prior to surgery and 180 days after surgery were included. Opioid-naive patients were defined as those who had no opioid fills in 180 days prior to surgery. The following patterns of long-term postoperative use were investigated: additional fills (at least one opioid fill 90–180 days after surgery), persistent fills (any span of opioid use starting in the 180 days after surgery and lasting at least 90 days), and Consortium to Study Opioid Risks and Trends (CONSORT) criteria for persistent use (episodes of opioid prescribing lasting longer than 90 days and 120 or more total days’ supply or 10 or more prescriptions in 180 days after the index fill). Multivariable logistic regression was performed to identify predictors of long-term use. RESULTS A total of 25,587 patients were included, of whom 52.7% underwent PLF (n = 13,486) and 32.5% (n = 8312) were opioid-naive prior to surgery. The rates of additional fills, persistent fills, and CONSORT use were 47%, 30%, and 23%, respectively, after PLF and 35.4%, 19%, and 14.2%, respectively, after LDD. The rates among opioid-naive patients were 18.9%, 5.6%, and 2.5% respectively, after PLF and 13.3%, 2.0%, and 0.8%, respectively, after LDD. Using multivariable logistic regression, the following were identified to be significantly associated with higher risk of long-term opioid use following PLF: discharge opioid prescription ≥ 500 MMEs, prescription of a long-acting opioid, female sex, multilevel surgery, and comorbidities such as depression and drug abuse (all p < 0.05). Elderly (age ≥ 65 years) and opioid-naive patients were found to be at lower risk (all p < 0.05). Similar results were obtained on analysis for LDD with the following significant additional risk factors identified: discharge opioid prescription ≥ 400 MMEs, prescription of tramadol alone at discharge, and inpatient surgery (all p < 0.05). CONCLUSIONS In an analysis of pharmacy claims from a national insurance database, the authors identified incidence and predictors of long-term opioid use after elective lumbar spine surgery.

Objective: We aimed to investigate prospective associations between milk bioactives related to metabolic health (glucose, insulin, leptin, C reactive protein [CRP], and interleukin 6 [IL-6]) and incident formula initiation at 3 and 6 months postpartum. Design: This study included 363 mother–infant dyads who were fully breastfed at 1 month and participated in the prospective Mothers and Infants Linked for Healthy Growth study from pregnancy to 6 months postpartum. Associations between milk glucose, leptin, insulin, CRP, and IL-6 at 1 and 3 months and incident formula feeding (FF) at 3 and 6 months, respectively, were tested using multiple logistic regression, adjusting for numerous potential confounders such as maternal age and prepregnancy body mass index. Results: At 3 months postpartum, 1-month glucose (odds ratio [OR] 0.45 [95% confidence interval (CI): 0.27–0.75], p ≤ 0.01) and smaller decreases in glucose from 1 to 3 months (OR 0.51 [95% CI: 0.28–0.92], p = 0.03) were associated with lower odds of FF, whereas 1-month leptin (OR 2.30 [95% CI: 1.30–4.07], p < 0.01) and larger increase in insulin (OR 1.86 [95% CI: 1.23–2.81], p < 0.01) and leptin (OR 2.17 [95% CI: 1.29–3.68], p < 0.01) from 1 to 3 months were associated with increased odds of FF. At 6 months, insulin increases (OR 2.08 [95% CI: 1.03–4.17], p = 0.04) were associated with higher odds of FF. Conclusions: In a cohort of women with established lactation, 1-month milk glucose, insulin, and leptin predicted initiation of FF at 3 months. Early milk composition may provide a window into mammary gland function, allowing identification of women at risk of not meeting their breastfeeding goals.