Hürthle cell carcinoma of the thyroid (HCC) is a form of thyroid cancer recalcitrant to radioiodine therapy that exhibits an accumulation of mitochondria. We performed whole-exome sequencing on a cohort of primary, recurrent, and metastatic tumors, and identified recurrent mutations in DAXX, TP53, NRAS, NF1, CDKN1A, ARHGAP35, and the TERT promoter. Parallel analysis of mtDNA revealed recurrent homoplasmic mutations in subunits of complex I of the electron transport chain. Analysis of DNA copy-number alterations uncovered widespread loss of chromosomes culminating in near-haploid chromosomal content in a large fraction of HCC, which was maintained during metastatic spread. This work uncovers a distinct molecular origin of HCC compared with other thyroid malignancies.

Background: The Food and Drug Administration has approved several pharmacotherapies for the treatment of obesity. This study assesses the cost-effectiveness of six pharmacotherapies and lifestyle intervention for people with mild obesity (body mass indices [BMIs] 30 to 35). Methods: A microsimulation model was constructed to compare seven weight loss strategies plus no treatment: intensive lifestyle intervention, orlistat, phentermine, phentermine/topiramate, lorcaserin, liraglutide, and semaglutide. Weight loss, quality-of-life scores, and costs were estimated using clinical trials and other published literature. Endpoints included costs, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios (ICERs) with a willingness-to-pay (WTP) threshold of $100 000/QALY. Results were analysed at 1-, 3-, and 5-year time horizons.Results: At each of the three follow-up periods, phentermine was the costeffective strategy, with ICERs of $46 258/QALY, $20 157/QALY, and $17 880/QALY after 1, 3, and 5 years, respectively. Semaglutide was the most effective strategy in the 3-and 5-year time horizons, with total QALYs of 2.224 and 3.711, respectively. However, the ICERs were prohibitively high at $1 437 340/QALY after 3 years and $576 931/QALY after 5 years. Deterministic and probabilistic sensitivity analyses indicated these results were robust. Conclusions:Phentermine is the cost-effective pharmacologic weight-loss strategy.Although semaglutide is the most effective, it is not cost-effective because of its high price.This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

IMPORTANCEThe prevalence of workplace mistreatment and its association with the well-being of emergency medicine (EM) residents is unclear. More information about the sources of mistreatment might encourage residency leadership to develop and implement more effective strategies to improve professional well-being not only during residency but also throughout the physician's career. OBJECTIVETo examine the prevalence, types, and sources of perceived workplace mistreatment during training among EM residents in the US and the association between mistreatment and suicidal ideation. DESIGN, SETTING, AND PARTICIPANTS In this survey study conducted from February 25 to 29, 2020, all residents enrolled in EM residencies accredited by the Accreditation Council for Graduate Medical Education (ACGME) who participated in the 2020 American Board of Emergency Medicine computer-based In-training Examination were invited to participate. A multiple-choice, 35-item survey was administered after the examination asking residents to self-report the frequency, sources, and types of mistreatment experienced during residency training and whether they had suicidal thoughts. MAIN OUTCOMES AND MEASURESThe types and frequency of workplace mistreatment and the sources of the mistreatment were identified, and rates of self-reported suicidality were obtained.Multivariable logistic regression models were used to examine resident and program characteristics associated with suicidal thoughts. RESULTSOf 8162 eligible EM residents, 7680 (94.1%) responded to at least 1 question on the survey; 6503 (79.7%) completed the survey in its entirety. A total of 243 ACGME-accredited residency programs participated, and 1 did not. The study cohort included 4768 male residents (62.1%), 2698 female residents (35.1%), 4919 non-Hispanic White residents (64.0%), 2620 residents from other racial/ethnic groups (Alaska Native, American Indian, Asian or Pacific Islander, African American, Mexican American, Native Hawaiian, Puerto Rican, other Hispanic, or mixed or other race) (34.1%), 483 residents who identified as lesbian, gay, bisexual, transgender, queer, or other (LGBTQ+) (6.3%), and 5951 residents who were married or in a relationship (77.5%). Of the total participants, 3463 (45.1%) reported exposure to some type of workplace mistreatment (eg, discrimination, abuse, or harassment) during the most recent academic year. A frequent source of mistreatment was identified as patients and/or patients' families; 1234 respondents (58.7%) reported gender discrimination, 867 (67.5%) racial discrimination, 282 (85.2%) physical abuse, and 723 (69.1%) sexual harassment from patients and/or family members. Suicidal thoughts occurring during the past year were reported by 178 residents (2.5%), with similar prevalence by gender (108 men [2.4%]; 59 women [2.4%]) and race/ethnicity (113 non-Hispanic White residents [2.4%]; 65 residents from other racial/ethnic groups [2.7%]).

Objective: To assess relative clinical and economic performance of the revised American Thyroid Association (ATA) thyroid cancer guidelines compared to current standard of care. Background: Diagnosis of thyroid cancer in the United States has tripled whereas mortality has only marginally increased. Most patients present with small papillary carcinomas and have historically received at least a total thyroidectomy as a treatment. In 2015, the ATA released the revised guidelines recommending an option for active surveillance (AS) of small papillary thyroid carcinoma and thyroid lobectomy for larger unifocal tumors. Methods: We created a Markov microsimulation model to evaluate the performance of the ATA's 2015 guidelines compared to the ATA's 2009 guidelines. We modeled a cohort of simulated patients with demographic and thyroid nodule characteristics representative of those presenting clinically in the United States. Outcome measures include life expectancy, quality-adjusted life years, costs, and frequency of surgical adverse events. Results: In our base case analysis, the ATA 2015 strategy dominates the ATA 2009 strategy. The ATA 2015 strategy delivers greater discounted average quality-adjusted life years (13.09 vs 12.43) at a lower discounted average cost ($14,752 vs $20,126). Deaths due to thyroid cancer under the 2015 strategy are higher than the 2009 strategy but this is offset by a reduction in surgical deaths, leading to greater average life expectancy under the ATA 2015 strategy. The optimal strategy is sensitive to patients who experience a greater decrement in quality of life while undergoing AS. Conclusions: The ATA 2015 Guidelines represent a cost-effective strategy regarding AS and extent of surgery.