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OBJECTIVE: Regionalization of surgery for non–small cell lung cancer (NSCLC) to high-volume centers (HVCs) improves perioperative outcomes but frequently increases patient travel distance. Travel might decrease rates of adjuvant chemotherapy (AC) use, however, the relationship of distance, volume, and receipt of AC with outcomes is unknown. Our objective was to evaluate the association of distance, volume, and receipt of AC with overall survival among patients with NSCLC. METHODS: Patients with stage I to IIIA (N0-N1) NSCLC were identified between 2004 and 2018 using the National Cancer Database. Distance to surgical facility was categorized into quartiles (

Background Post-discharge venous thromboembolism (VTE) chemoprophylaxis decreases VTEs following cancer surgery, however identifying high-risk patients remains difficult. Our objectives were to (1) identify factors available at hospital discharge associated with post-discharge VTE following hepatectomy for malignancy and (2) develop and validate a post-discharge VTE risk calculator to evaluate patient-specific risk. Methods Patients who underwent hepatectomy for malignancy from 2014 to 2017 were identified from the ACS NSQIP hepatectomy procedure targeted module. Multivariable logistic regression identified factors associated with post-discharge VTE. A post-discharge VTE risk calculator was constructed, and predicted probabilities of post-discharge VTE were calculated. Results Among 11 172 patients, 95 (0.9%) developed post-discharge VTE. Post-discharge VTE was associated with obese BMI (OR 2.29 vs. normal BMI [95%CI 1.31–3.99]), right hepatectomy/trisegmentectomy (OR 1.63 vs. partial/wedge [95%CI 1.04–2.57]), and several inpatient postoperative complications: renal insufficiency (OR 5.29 [95%CI 1.99–14.07]), transfusion (OR 1.77 [95%CI 1.12–2.80]), non-operative procedural intervention (OR 2.97 [95%CI 1.81–4.86]), and post-hepatectomy liver failure (OR 2.22 [95%CI 1.21–4.08]). Post-discharge VTE risk ranged from 0.3% to 30.2%. Twenty iterations of 10-fold cross validation identified internal validity. Conclusions Risk factors from all phases of care, including inpatient complications, are associated with post-discharge VTE following hepatectomy. Identifying high-risk patients may allow for personalized risk-based post-discharge chemoprophylaxis prescribing.

Surgical site infection after pancreaticoduodenectomy is often caused by pathogens resistant to standard prophylactic antibiotics, suggesting that broad-spectrum antibiotics may be more effective prophylactic agents. This article describes the rationale and methodology underlying a multicenter randomized trial evaluating piperacillin-tazobactam compared with cefoxitin for surgical site infection prevention following pancreaticoduodenectomy. As the first U.S. randomized surgical trial to utilize a clinical registry for data collection, this study serves as proof of concept for registry-based clinical trials.

BACKGROUND: Prophylactic drainage following hepatectomy is frequently performed despite evidence that drainage is unnecessary. It is unknown to what extent drain use is influenced by hospital practice patterns. The objectives of this study were to identify factors associated with the use of prophylactic drains following hepatectomy and assess hospital variation in drain use. METHODS: Retrospective cohort study of patients following hepatectomy without concomitant bowel resection or biliary reconstruction from the ACS NSQIP Hepatectomy Targeted Dataset. Factors associated with the use of prophylactic drains were identified using multivariable logistic regression and hospital-level variation in drain use was assessed. RESULTS: Analysis included 10,530 patients at 130 hospitals. Overall, 42.3% of patients had a prophylactic drain placed following hepatectomy. Patients were more likely to receive prophylactic drains if they were ≥65 years old (adjusted odds ratio [aOR]: 1.34, 95%CI: 1.16–1.56), underwent major hepatectomy (aOR: 1.42, 95%CI 1.15–1.74), or had an open resection (aOR 1.94, 95%CI 1.49–2.53). There was notable hospital variability in drain use (range: 0% to 100% of patients), and 77.5% of measured variation in drain placement was at the hospital level. CONCLUSION: Prophylactic drains are commonly placed in both major and minor hepatectomy. While some patient factors are associated with drain use, hospital-specific patterns appear to be a major driver and represent a target for improvement.

BACKGROUND Patient utilization of public reporting has been suboptimal despite attempts to encourage use. Lack of utilization may be due to discordance between reported metrics and what patients want to know when making health care choices. OBJECTIVE The objective of this study was to identify measures of quality that individuals want to be presented in public reporting and explore factors associated with researching health care. RESEARCH DESIGN Patient interviews and focus groups were conducted to develop a survey exploring the relative importance of various health care measures. SUBJECTS Interviews and focus groups conducted at local outpatient clinics. A survey administered nationally on an anonymous digital platform. MEASURES Likert scale responses were compared using tests of central tendency. Rank-order responses were compared using analysis of variance testing. Associations with binary outcomes were analyzed using multivariable logistic regression. RESULTS Overall, 4672 responses were received (42.0% response rate). Census balancing yielded 2004 surveys for analysis. Measures identified as most important were hospital reputation (considered important by 61.9%), physician experience (51.5%), and primary care recommendations (43.2%). Unimportant factors included guideline adherence (17.6%) and hospital academic affiliation (13.3%, P

BACKGROUND: Endoscopic biliary stenting (EBS) and percutaneous transhepatic biliary drainage (PTBD) are two techniques used for preoperative biliary drainage prior to hepatobiliary resection. The objectives of this study were to determine predictors of the drainage technique selection and to evaluate the association between drainage technique and postoperative outcomes. METHODS: Using ACS NSQIP data (2014–2017), patients who underwent preoperative biliary drainage prior to hepatobiliary resection for malignancy were identified. Separate multivariable-adjusted, propensity score (PS) adjusted, and PS matched logistic regression models were constructed to evaluate the association between drainage technique and postoperative outcomes. RESULTS: Of 527 patients identified, 431 (81.8%) received EBS and 96 (18.2%) received PTBD. Patients who underwent PTBD had more preoperative co-morbidities, including higher ASA class, recent weight loss, and hypoalbuminemia (all p

Perihilar cholangiocarcinoma is a rare hepatobiliary malignancy that requires thoughtful, multidisciplinary evaluation in the preoperative setting to ensure optimal patient outcomes. Comprehensive preoperative imaging, including multiphase CT angiography and some form of cholangiographic assessment, is key to assessing resectability. While many staging systems exist, the Blumgart staging system provides the most useful combination of resectability assessment and prognostic information for use in the preoperative setting. Once resectability is confirmed, volumetric analysis should be performed. Upfront resection without biliary drainage or portal venous embolization may be considered in patients without cholangitis and an estimated functional liver remnant (FLR) > 40%. In patients with FLR < 40%, judicious use of biliary drainage is advised, with the goal of selective biliary drainage of the functional liver remnant. Percutaneous biliary drainage may avoid inadvertent contamination of the contralateral biliary tree and associated infectious complications, though the relative effectiveness of percutaneous and endoscopic techniques is an ongoing area of study and debate. Patients with low FLR also require intervention to induce hypertrophy, most commonly portal venous embolization, in an effort to reduce the rate of postoperative liver failure. Even with extensive preoperative workup, many patients will be found to have metastatic disease at exploration and diagnostic laparoscopy may reduce the rate of non-therapeutic laparotomy. Management of perihilar cholangiocarcinoma continues to evolve, with ongoing efforts to improve preoperative liver hypertrophy and to further define the role of transplantation in disease management.

Randomized controlled trials (RCTs) represent the gold standard for evidence in clinical medicine because of their ability to account for the effects of unmeasured confounders and selection bias by indication. However, their complexity and immense costs limit their application, and thus the availability of high-quality data to guide clinical care. Registry-based RCTs are a type of pragmatic trial that leverages existing registries as a platform for data collection, providing a low-cost alternative for randomized studies. Herein, we describe the tenets of registry RCTs and the development of the first AHPBA/ACS-NSQIP-based registry trial.

IMPORTANCE: Previous studies have shown high rates of mistreatment among US general surgery residents, leading to poor well-being. Lesbian, gay, bisexual, transgender, queer, and other sexual and gender minority (LGBTQ+) residents represent a high-risk group for mistreatment; however, their experience in general surgery programs is largely unexplored. OBJECTIVE: To determine the national prevalence of mistreatment and poor well-being for LGBTQ+ surgery residents compared with their non-LGBTQ+ peers. DESIGN, SETTING, AND PARTICIPANTS: A voluntary, anonymous survey adapting validated survey instruments was administered to all clinically active general surgery residents training in Accreditation Council for Graduate Medical Education–accredited general surgery programs following the 2019 American Board of Surgery In-Training Examination. MAIN OUTCOMES AND MEASURES: Self-reported mistreatment, sources of mistreatment, perceptions of learning environment, career satisfaction, burnout, thoughts of attrition, and suicidality. The associations between LGBTQ+ status and (1) mistreatment, (2) burnout, (3) thoughts of attrition, and (4) suicidality were examined using multivariable regression models, accounting for interactions between gender and LGBTQ+ identity. RESULTS: A total of 6956 clinically active residents completed the survey (85.6% response rate). Of 6381 respondents included in this analysis, 305 respondents (4.8%) identified as LGBTQ+ and 6076 (95.2%) as non-LGBTQ+. Discrimination was reported among 161 LGBTQ+ respondents (59.2%) vs 2187 non-LGBTQ+ respondents (42.3%; P

Key Points Question Is the presence of a resident labor union associated with improved well-being at US surgical training programs? Findings In this cross-sectional survey study of 5701 residents, unionized programs were more likely to offer housing stipends and 4 weeks (instead of 2-3 weeks) of vacation time to residents; however, no difference in burnout, suicidality, job satisfaction, duty hour violations, mistreatment, salary, or the educational environment were found between residents at unionized and nonunionized programs. Meaning These findings suggest that resident labor unions do not appear to improve resident well-being., This survey study evaluates the association of resident physician unions with burnout, suicidality, job satisfaction, duty hour violations, mistreatment, educational environment, salary, and benefits among surgical residents in the US., Importance Labor unions are purported to improve working conditions; however, little evidence exists regarding the effect of resident physician unions. Objective To evaluate the association of resident unions with well-being, educational environment, salary, and benefits among surgical residents in the US. Design, Setting, and Participants This national cross-sectional survey study was based on a survey administered in January 2019 after the American Board of Surgery In-Training Examination (ABSITE). Clinically active residents at all nonmilitary US general surgery residency programs accredited by the American Council of Graduate Medical Education who completed the 2019 ABSITE were eligible for participation. Data were analyzed from December 5, 2020, to March 16, 2021. Exposures Presence of a general surgery resident labor union. Rates of labor union coverage among non–health care employees within a region were used as an instrumental variable (IV) for the presence of a labor union at a residency program. Main Outcomes and Measures The primary outcome was burnout, which was assessed using a modified version of the abbreviated Maslach Burnout Inventory and was defined as experiencing any symptom of depersonalization or emotional exhaustion at least weekly. Secondary outcomes included suicidality, measures of job satisfaction, duty hour violations, mistreatment, educational environment, salary, and benefits. Results A total of 5701 residents at 285 programs completed the pertinent survey questions (response rate, 85.6%), of whom 3219 (56.5%) were male, 3779 (66.3%) were White individuals, 449 (7.9%) were of Hispanic ethnicity, 4239 (74.4%) were married or in a relationship, and 1304 (22.9%) had or were expecting children. Among respondents, 690 residents were from 30 unionized programs (10.5% of programs). There was no difference in burnout for residents at unionized vs nonunionized programs (297 [43.0%] vs 2175 [43.4%]; odds ratio [OR], 0.92 [95% CI, 0.75-1.13]; IV difference in probability, 0.15 [95% CI, −0.11 to 0.42]). There were no significant differences in suicidality, job satisfaction, duty hour violations, mistreatment, educational environment, salary, or benefits except that unionized programs more frequently offered 4 weeks instead of 2 to 3 weeks of vacation (27 [93.1%] vs 52 [30.6%]; OR, 19.18 [95% CI, 3.92-93.81]; IV difference in probability, 0.77 [95% CI, 0.09-1.45]) and more frequently offered housing stipends (10 [38.5%] vs 9 [16.1%]; OR, 2.15 [95% CI, 0.58-7.95]; IV difference in probability, 0.62 [95% CI 0.04-1.20]). Conclusions and Relevance In this evaluation of surgical residency programs in the US, unionized programs offered improved vacation and housing stipend benefits, but resident unions were not associated with improved burnout, suicidality, job satisfaction, duty hour violations, mistreatment, educational environment, or salary.

BACKGROUND: Minimally invasive distal pancreatectomy (MIDP) for localized neoplasms has been demonstrated to be feasible and safe. However, national adoption of the technique is poorly understood. Objectives of this study were to identify factors associated with use of minimally invasive distal pancreatectomy for localized neoplasms and assess hospital variation in MIDP utilization. METHODS: Retrospective cohort study of patients with pancreatic cysts, stage I pancreatic ductal adenocarcinoma, and stage I pancreatic neuroendocrine tumors undergoing distal pancreatectomy from the ACS NSQIP Pancreas Targeted Dataset. Factors associated with use of MIDP were identified using multivariable logistic regression and hospital-level variation was assessed. RESULTS: Analysis included 3,059 patients at 139 hospitals. Overall, 64.5% of patients underwent minimally invasive distal pancreatectomy. Patients were more likely to undergo MIDP if they had lower ASA classification (P = 0.004) or BMI ≥ 30 (P < 0.001) and less likely if they had pancreatic adenocarcinoma (P < 0.001). There was notable hospital variability in utilization (range 0 to 100% of cases). Hospital-level utilization of minimally invasive distal pancreatectomy did not appear to be driven by patient selection, as hierarchical analysis demonstrated that only 1.8% of observed hospital variation was attributable to measured patient selection factors. CONCLUSION: Utilization of MIDP for localized pancreatic neoplasms is highly variable. While some patient-level factors are associated with MIDP use, hospital adoption of MIDP appears to be the primary driver of utilization. Monitoring hospital-level use of MIDP may be a useful quality measure to monitor uptake of emerging techniques in pancreatic surgery.

BACKGROUND: Pancreatic fistula remains common, with limited ability to risk stratify patients preoperatively. The objective of this study was to identify risk factors for clinically-relevant postoperative pancreatic fistula (CR-POPF) that are routinely available in the preoperative setting. METHODS: Preoperatively available variables for all pancreaticoduodenectomies from 2014–2017 were examined using a national clinical registry. The cohort was separated into risk factor identification and internal validation subgroups. RESULTS: Among 15 033 pancreaticoduodenectomies, the CR-POPF rate was 16.7%. CR-POPF was more likely in patients that were male (odds ratio [OR], 1.51), obese (body mass index [BMI] > 30, OR, 1.97), had minimal preoperative weight loss (OR, 1.25), had a nondilated pancreatic duct (OR, 1.81), did not have diabetes, (OR, 1.80), did not receive neoadjuvant therapy (OR, 1.78), had no evidence of biliary obstruction (OR, 1.18), or had nonadenocarcinoma pathology (OR, 1.96; all P

BACKGROUND AND OBJECTIVES: Delayed gastric emptying (DGE) occurs commonly following pancreaticoduodenectomy (PD), but the rate of DGE in the absence of other intra-abdominal complications is poorly understood. The objectives of this study were to define the incidence of DGE and identify risk factors for DGE in patients without pancreatic fistula or other intra-abdominal infections. METHODS: Retrospective cohort study utilizing the American College of Surgeons National Surgical Quality Improvement Program pancreatectomy variables to identify patients with DGE following PD without evidence of fistula or intra-abdominal infection. Multivariable models were developed to assess preoperative, intraoperative, and technical factors associated with DGE. RESULTS: The rate of DGE was 11.7% in 10502 cases without pancreatic fistula or intra-abdominal infection. Patients were more likely to develop DGE if age ≥75 (odds ratio [OR], 1.22; P = 0.003), male (OR, 1.29; P < 0.001), underwent pylorus-sparing PD (OR, 1.27; P = 0.004), or had a prolonged operative time (OR, 1.38 if greater than seven vs less than 5 hours; P = 0.005). Factors not associated with DGE included BMI, pathologic indication, and surgical approach. CONCLUSION: The incidence of DGE after PD is notable even in patients without other abdominal complications. Identification of patients at increased risk for DGE may aid patient counseling as well as decisions regarding surgical technique, enteral feeding access, and enhanced-recovery pathways.

We assess the availability of four names proposed by Wells & Wellington (1985) for Australian death adders (Acanthophis). In agreement with previous literature, A. hawkei is an available name, whereas A. armstrongi, A. lancasteri, and A. schistos are not described in conformity with the requirements of Articles 13.1.1 or 13.1.2 of the International Code of Zoological Nomenclature and are therefore considered nomina nuda. Consequently, A. cryptamydros Maddock et al., 2015, is confirmed as the valid name for the Kimberley death adder of Western Australia. We comment on the need for greater clarity in the Code, and emphasise that the responsibility for establishing the availability of new nomina rests with their authors, not subsequent researchers.

Our knowledge of the conservation status of reptiles, the most diverse class of terrestrial vertebrates, has improved dramatically over the past decade, but still lags behind that of the other tetrapod groups. Here, we conduct the first comprehensive evaluation (~92% of the world’s ~1,714 described species) of the conservation status of skinks (Scincidae), a speciose reptile family with a worldwide distribution. Using International Union for Conservation of Nature (IUCN) criteria, we report that ~20% of species are threatened with extinction, and nine species are Extinct or Extinct in the Wild. The highest levels of threat are evident in Madagascar and the Neotropics, and in the subfamilies Mabuyinae, Eugongylinae and Scincinae. The vast majority of threatened skink species were listed based primarily on their small geographic ranges (Criterion B, 83%; Criterion D2, 13%). Although the population trend of 42% of species was stable, 14% have declining populations. The key threats to skinks are habitat loss due to agriculture, invasive species, and biological resource use (e.g., hunting, timber harvesting). The distributions of 61% of species do not overlap with protected areas. Despite our improved knowledge of the conservation status of the world’s skinks, 8% of species remain to be assessed, and 14% are listed as Data Deficient. The conservation status of almost a quarter of the world’s skink species thus remains unknown. We use our updated knowledge of the conservation status of the group to develop and outline the priorities for the conservation assessment and management of the world’s skink species.

IntroductionAlthough antibiotic prophylaxis is established in reducing postoperative surgical site infections (SSIs), the optimal antibiotic for prophylaxis in pancreatoduodenectomy (PD) remains unclear. The study objective is to evaluate if administration of piperacillin–tazobactam as antibiotic prophylaxis results in decreased 30-day SSI rate compared with cefoxitin in patients undergoing elective PD.Methods and analysisThis study will be a multi-institution, double-arm, non-blinded randomised controlled superiority trial. Adults ≥18 years consented to undergo PD for all indications who present to institutions participating in the National Surgical Quality Improvement Program Hepato-Pancreato-Biliary (NSQIP HPB) Collaborative will be included. Data collection will use the NSQIP HPB Collaborative Surgical Clinical Reviewers. Patients will be randomised to either 1–2 g intravenous cefoxitin or 3.375–4.5 g intravenous piperacillin–tazobactam within 60 min of surgical incision. The primary outcome will be 30-day postoperative SSI rate following PD. Secondary outcomes will include 30-day postoperative mortality; specific postoperative complication rate; and unplanned reoperation, length of stay, and hospital readmission. A subset of patients will have bacterial isolates and sensitivities of intraoperative bile cultures and SSIs. Postoperative SSIs and secondary outcomes will be analysed using logistic regression models with the primary predictor as the randomised treatment group. Additional adjustment will be made for preoperative biliary stent presence. Additionally, bacterial cultures and isolates will be summarised by presence of bacterial species and antibiotic sensitivities.Ethics and disseminationThis study is approved by the Institutional Review Board at Memorial Sloan Kettering Cancer Center. This trial will evaluate the effect of piperacillin–tazobactam compared with cefoxitin as antibiotic prophylaxis on the hazard of postoperative SSIs. The results will be disseminated regardless of the effect of the intervention on study outcomes. The manuscript describing the effect of the intervention will be submitted to a peer-reviewed journal when data collection and analyses are complete.Trial registration numberNCT03269994.

Importance Differences in medical school experiences may affect how prepared residents feel themselves to be as they enter general surgery residency and may contribute to resident burnout. Objectives To assess preparedness for surgical residency, to identify factors associated with preparedness, to examine the association between preparedness and burnout, and to explore resident and faculty perspectives on resident preparedness. Design, Setting, and Participants This cross-sectional study used convergent mixed-methods analysis of data from a survey of US general surgery residents delivered at the time of the 2017 American Board of Surgery In-Training Examination (January 26 to 31, 2017) in conjunction with qualitative interviews of residents and program directors conducted as part of the Flexibility in Duty Hour Requirements for Surgical Trainees (FIRST) trial. A total of 262 Accreditation Council for Graduate Medical Education–approved US general surgery residency programs participated. Survey data were collected from 3693 postgraduate year (PGY) 1 and PGY2 surgical residents (response rate, 99%) and 98 interviews were conducted with residents and faculty from September 1 to December 15, 2018. Data were analyzed from June 1, 2017, to February 15, 2018. Main Outcomes and Measures Hierarchical regression models were developed to examine factors associated with preparedness and to assess the association between preparedness and resident burnout. Qualitative interviews were conducted to identify themes associated with preparation for residency. Results Of the 3693 PGY1 and PGY2 residents who participated (2258 male [61.1%]), 1775 (48.1%) reported feeling unprepared for residency. Approximately half of surgery residents took overnight call infrequently (≤2 per month) during their core medical student clerkship (1904 [51.6%]) or their subinternship (1600 [43.3%]); 524 (14.2%) took no call during their core clerkship. In multivariable analysis, residents were more likely to report feeling unprepared for residency if they were female (odds ratio [OR], 1.34; 95% CI, 1.15-1.57) or did not take call as a medical student (OR for 0 vs >4 calls, 2.72; 95% CI, 2.10-3.52). Residents who did not complete a subinternship were less likely to report feeling prepared for residency (OR, 0.68; 95% CI, 0.48-0.96). Feeling adequately prepared for residency was associated with a nearly 2-fold lower risk of experiencing burnout symptoms (OR, 0.57; 95% CI, 0.48-0.68). In interviews, the dominant themes associated with preparedness included the following: (1) various regulations limit the medical school experience, (2) overnight call facilitates preparation and selection of a specialty compatible with their preferences, and (3) adequate perceptions of residency improve expectations, resulting in improved preparedness, lower burnout rates, and lower risk of attrition. Conclusions and Relevance In this cross-sectional study, the perception of feeling unprepared was associated with inadequate exposure to resident responsibilities while in medical school. These findings suggest that effective preparation of medical students for residency may result in lower rates of subsequent burnout.

OBJECTIVES: Evaluate the frequency of self-reported, post-call hazardous driving events in a national cohort of general surgery residents and determine the associations between duty hour policy violations, psychiatric well-being, and hazardous driving events. SUMMARY OF BACKGROUND DATA: MVCs are a leading cause of resident mortality. Extended work shifts and poor psychiatric well-being are risk factors for MVCs, placing general surgery residents at risk. METHODS: General surgery residents from US programs were surveyed after the 2017 American Board of Surgery In-Training Examination. Outcomes included self-reported nodding off while driving, near-miss MVCs, and MVCs. Group-adjusted cluster Chi-square and hierarchical regression models with program-level intercepts measured associations between resident- and program-level factors and outcomes. RESULTS: Among 7391 general surgery residents from 260 programs (response rate 99.3%), 34.7% reported nodding off while driving, 26.6% a near-miss MVC, and 5.0% an MVC over the preceding 6 months. More frequent 80-hour rule violations were associated with all hazardous driving events: nodding off while driving {59.8% with ≥5 months with violations vs 27.2% with 0, adjusted odds ratio (AOR) 2.86 [95% confidence interval (CI) 2.21–3.69]}, near-miss MVCs, [53.6% vs 19.2%, AOR 3.28 (95% CI 2.53–4.24)], and MVCs [14.0% vs 3.5%, AOR 2.46 (95% CI 1.65–3.67)]. Similarly, poor psychiatric well-being was associated with all 3 outcomes [eg, 8.0% with poor psychiatric well-being reported MVCs vs 2.6% without, odds ratio 2.55 (95% CI 2.00–3.24)]. CONCLUSIONS: Hazardous driving events are prevalent among general surgery residents and associated with frequent duty hour violations and poor psychiatric well-being. Greater adherence to duty hour standards and efforts to improve well-being may improve driving safety.

Aim: Clutch size is a key life-history trait. In lizards, it ranges over two orders of mag-nitude. The global drivers of spatial and phylogenetic variation in clutch have been extensively studied in birds, but such tests in other organisms are lacking. To test the generality of latitudinal gradients in clutch size, and their putative drivers, we present the first global-scale analysis of clutch sizes across lizard taxa.Location: Global.Time period: Recent.Major taxa studied: Lizards (Reptilia, Squamata, Sauria).Methods: We analysed clutch-size data for over 3,900 lizard species, using phyloge-netic generalized least-square regression to study the relationships between clutch sizes and environmental (temperature, precipitation, seasonality, primary productiv-ity, insularity) and ecological factors (body mass, insularity, activity times, and micro-habitat use).Results: Larger clutches are laid at higher latitudes and in more productive and seasonal environments. Insular taxa lay smaller clutches on average. Temperature and precipitation per se are unrelated to clutch sizes. In Africa, patterns differ from those on other continents. Lineages laying small fixed clutches are restricted to low latitudes.Main conclusions: We suggest that the constraint imposed by a short activity season, coupled with abundant resources, is the main driver of large-clutch evolution at high latitudes and in highly seasonal regions. We hypothesize that such conditions – which are unsuitable for species constrained to laying multiple small clutches – may limit the distribution of fixed-clutch taxa Fil: Meiri, Shai. Universitat Tel Aviv; Israel Fil: Avila, Luciano Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Centro Nacional Patagónico. Instituto Patagónico para el Estudio de los Ecosistemas Continentales; Argentina Fil: Bauer, Aaron M.. Villanova University; Estados Unidos Fil: Chapple, David G.. Monash University. Faculty Of Science. School Of Biological Sciences; Australia Fil: Das, Indraneil. Universiti Malaysia Sarawak; Malasia Fil: Doan, Tiffany M.. New College of Florida; Estados Unidos Fil: Doughty, Paul. Western Australian Museum; Australia Fil: Ellis, Ryan. Western Australian Museum; Australia Fil: Grismer, Lee. La Sierra University; Estados Unidos Fil: Kraus, Fred. University of Michigan; Estados Unidos Fil: Morando, Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Centro Nacional Patagónico. Instituto Patagónico para el Estudio de los Ecosistemas Continentales; Argentina Fil: Oliver, Paul. Griffith University; Australia Fil: Pincheira Donoso, Daniel. Nottingham Trent University; Reino Unido Fil: Ribeiro Junior, Marco Antonio. Universitat Tel Aviv; Israel Fil: Shea, Glenn. University of Sydney; Australia Fil: Torres Carvajal, Omar. Pontificia Universidad Católica del Ecuador; Ecuador Fil: Slavenko, Alex. Universitat Tel Aviv; Israel Fil: Roll, Uri. Ben Gurion University of the Negev; Israel

IMPORTANCE: Mistreatment is a common experience among surgical residents and is associated with burnout. Women have been found to experience mistreatment at higher rates than men. Further characterization of surgical residents’ experiences with gender discrimination and sexual harassment may inform solutions. OBJECTIVE: To describe the types, sources, and factors associated with (1) discrimination based on gender, gender identity, or sexual orientation and (2) sexual harassment experienced by residents in general surgery programs across the US. DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional national survey study was conducted after the 2019 American Board of Surgery In-Training Examination (ABSITE). The survey asked respondents about their experiences with gender discrimination and sexual harassment during the academic year starting July 1, 2018, through the testing date in January 2019. All clinical residents enrolled in general surgery programs accredited by the Accreditation Council for Graduate Medical Education were eligible. EXPOSURES: Specific types, sources, and factors associated with gender-based discrimination and sexual harassment. MAIN OUTCOMES AND MEASURES: Primary outcome was the prevalence of gender discrimination and sexual harassment. Secondary outcomes included sources of discrimination and harassment and associated individual- and program-level factors using gender-stratified multivariable logistic regression models. RESULTS: The survey was administered to 8129 eligible residents; 6956 responded (85.6% response rate)from 301 general surgery programs. Of those, 6764 residents had gender data available (3968 [58.7%] were male and 2796 [41.3%] were female individuals). In total, 1878 of 2352 female residents (79.8%) vs 562 of 3288 male residents (17.1%) reported experiencing gender discrimination (P

We present information on primary type specimens for 13,282 species and subspecies of reptiles compiled in the Reptile Database, that is, holotypes, neotypes, lectotypes, and syntypes. These represent 99.4% of all 13,361 currently recognized taxa (11,050 species and 2311 subspecies). Type specimens of 653 taxa (4.9%) are either lost or not located, were never designated, or we did not find any information about them. 51 species are based on iconotypes. To map all types to physical collections we have consolidated all synonymous and ambiguous collection acronyms into an unambiguous list of 364 collections holding these primary types. The 10 largest collections possess more than 50% of all (primary) reptile types, the 36 largest collections possess more than 10,000 types and the largest 73 collections possess over 90% of all types. Of the 364 collections, 107 hold type specimens of only 1 species or subspecies. Dozens of types are still in private collections. In order to increase their utility, we recommend that the description of type specimens be supplemented with data from high-resolution images and CT-scans, and clear links to tissue samples and DNA sequence data (when available). We request members of the herpetological community provide us with any missing type information to complete the list.

This study examines the associations of program characteristics with pass rates on the qualifying examination and certifying examination of the American Board of Surgery.

Physicians, particularly trainees and those in surgical subspecialties, are at risk for burnout. Mistreatment (i.e., discrimination, verbal or physical abuse, and sexual harassment) may contribute to burnout and suicidal thoughts.A cross-sectional national survey of general surgery residents administered with the 2018 American Board of Surgery In-Training Examination assessed mistreatment, burnout (evaluated with the use of the modified Maslach Burnout Inventory), and suicidal thoughts during the past year. We used multivariable logistic-regression models to assess the association of mistreatment with burnout and suicidal thoughts. The survey asked residents to report their gender.Among 7409 residents (99.3% of the eligible residents) from all 262 surgical residency programs, 31.9% reported discrimination based on their self-identified gender, 16.6% reported racial discrimination, 30.3% reported verbal or physical abuse (or both), and 10.3% reported sexual harassment. Rates of all mistreatment measures were higher among women; 65.1% of the women reported gender discrimination and 19.9% reported sexual harassment. Patients and patients' families were the most frequent sources of gender discrimination (as reported by 43.6% of residents) and racial discrimination (47.4%), whereas attending surgeons were the most frequent sources of sexual harassment (27.2%) and abuse (51.9%). Proportion of residents reporting mistreatment varied considerably among residency programs (e.g., ranging from 0 to 66.7% for verbal abuse). Weekly burnout symptoms were reported by 38.5% of residents, and 4.5% reported having had suicidal thoughts during the past year. Residents who reported exposure to discrimination, abuse, or harassment at least a few times per month were more likely than residents with no reported mistreatment exposures to have symptoms of burnout (odds ratio, 2.94; 95% confidence interval [CI], 2.58 to 3.36) and suicidal thoughts (odds ratio, 3.07; 95% CI, 2.25 to 4.19). Although models that were not adjusted for mistreatment showed that women were more likely than men to report burnout symptoms (42.4% vs. 35.9%; odds ratio, 1.33; 95% CI, 1.20 to 1.48), the difference was no longer evident after the models were adjusted for mistreatment (odds ratio, 0.90; 95% CI, 0.80 to 1.00).Mistreatment occurs frequently among general surgery residents, especially women, and is associated with burnout and suicidal thoughts.

BACKGROUND AND OBJECTIVES: Recent studies demonstrating decreased survival following minimally invasive surgery (MIS) for cervical cancer have generated concern regarding oncologic efficacy of MIS. Our objective was to evaluate the association between surgical approach and 5-year survival following resection of abdominopelvic malignancies. METHODS: Patients with stage I or II adenocarcinoma of the prostate, colon, rectum, and stage IA2 or IB1 cervical cancer from 2010-2015 were identified from the National Cancer Data Base. The association between surgical approach and 5-year survival was assessed using propensity-score-matched cohorts. Distributions were compared using logistic regression. Hazard ratio for death was estimated using Cox proportional-hazard models. RESULTS: The rate of deaths at 5 years was 3.4% following radical prostatectomy, 22.9% following colectomy, 18.6% following proctectomy, and 6.8% following radical hysterectomy. Open surgery was associated with worse survival following radical prostatectomy (HR, 1.18; 95% CI, 1.05-1.33; P = .005), colectomy (HR, 1.45; 95% CI, 1.39-1.51; P < .001), and proctectomy (HR, 1.28; 95% CI, 1.10-1.50; P = .002); however, open surgery was associated with improved survival following radical hysterectomy (HR, 0.61; 95% CI, 0.44-0.82; P = .003). CONCLUSIONS: These results suggest that MIS is an acceptable approach in selected patients with prostate, colon, and rectal cancers, while concerns regarding MIS resection of cervical cancer appear warranted.

OBJECTIVES: To empirically describe surgical residency program culture and assess program characteristics associated with program culture. SUMMARY BACKGROUND DATA: Despite concerns about the impact of the learning environment on trainees, empirical data have not been available to examine and compare program-level differences in residency culture. METHODS: Following the 2018 American Board of Surgery In-Training Examination, a cross-sectional survey was administered to all US general surgery residents. Survey items were analyzed using principal component analysis to derive composite measures of program culture. Associations between program characteristics and composite measures of culture were assessed. RESULTS: Analysis included 7387 residents at 260 training programs (99.3% response rate). Principal component analysis suggested that program culture may be described by 2 components: Wellness and Negative Exposures. Twenty-six programs (10.0%) were in the worst quartile for both Wellness and Negative Exposure components. These programs had significantly higher rates of duty hour violations (23.3% vs 11.1%), verbal/physical abuse (41.6% vs 28.6%), gender discrimination (78.7% vs 64.5%), sexual harassment (30.8% vs 16.7%), burnout (54.9% vs 35.0%), and thoughts of attrition (21.6% vs 10.8%; all P < 0.001). Being in the worst quartile of both components was associated with percentage of female residents in the program (P = 0.011), but not program location, academic affiliation, size, or faculty demographics. CONCLUSIONS: Residency culture was characterized by poor resident wellness and frequent negative exposures and was generally not associated with structural program characteristics. Additional qualitative and quantitative studies are needed to explore unmeasured local social dynamics that may underlie measured differences in program culture.

INTRODUCTION: Traditionally, laparoscopic Nissen fundoplication (LNF) has been considered an inpatient procedure. Advances in surgical and anesthetic techniques have led to a shift towards outpatient LNF procedures. However, differences in surgical outcomes between outpatient and inpatient LNF are poorly understood. The objectives of this study were (1) to describe the frequency of outpatient LNF in a national cohort and (2) to identify any differences in complications or readmission rates between outpatient and inpatient LNF. METHODS: The American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database was used to identify elective LNF cases from 2012 to 2016. Patients discharged on the day of surgery were compared to those discharged 24–48 h post-operatively. Outcomes included 30-day readmission and death or serious morbidity (DSM). Bivariate analyses were completed with Chi squared testing for categorical variables and two sided t tests for continuous variables. Associations between outpatient surgery and outcomes were assessed using multivariable logistic regression. Differences in readmission were analyzed using Kaplan–Meier failure estimates and log-rank tests. RESULTS: Of 7734 patients who underwent elective LNF, 568 (7.3%) were discharged on the day of surgery. The overall 30-day readmission rate was 4.1% (n = 316) and the overall rate of DSM was 1.0% (n = 79). The most common 30-day readmission diagnoses overall were infectious complications (16.1%), dysphagia (12.9%), and abdominal pain (11.7%). On multivariable analysis, there was no association between outpatient surgery and 30-day readmission (3.9% vs. 4.1%; aOR 0.97, 95% CI 0.62–1.52, p = 0.908) or DSM (1.1% vs. 1.0%; aOR 0.91, 95%CI 0.36–2.29, p = 0.848). Kaplan–Meier analysis showed no difference in rates of hospital readmission between groups at 30-days from discharge (3.9% vs. 4.1%, p = 0.325). CONCLUSIONS: Among patients undergoing elective LNF, there were no significant differences in post-operative complications and 30-day readmission when compared to traditional inpatient postoperative care. Further consideration should be given to transitioning LNF to an outpatient procedure.

For over two decades, assessments of geographic variation in mtDNA and small numbers of nuclear loci have revealed morphologically similar, but genetically divergent, intraspecific lineages in lizards from around the world. Subsequent morphological analyses often find subtle corresponding diagnostic characters to support the distinctiveness of lineages, but occasionally do not. In recent years it has become increasingly possible to survey geographic variation by sequencing thousands of loci, enabling more rigorous assessment of species boundaries across morphologically similar lineages. Here we take this approach, adding new, geographically extensive SNP data to existing mtDNA and exon capture datasets for the Gehyra australis and G. koira species complexes of gecko from northern Australia. The combination of exon-based phylogenetics with dense spatial sampling of mitochondrial DNA sequencing, SNP-based tests for introgression at lineage boundaries and newly-collected morphological evidence supports the recognition of nine species, six of which are newly described here. Detection of discrete genetic clusters using new SNP data was especially convincing where candidate taxa were continuously sampled across their distributions up to and across geographic boundaries with analyses revealing no admixture. Some species defined herein appear to be truly cryptic, showing little, if any, diagnostic morphological variation. As these SNP-based approaches are progressively applied, and with all due conservatism, we can expect to see a substantial improvement in our ability to delineate and name cryptic species, especially in taxa for which previous approaches have struggled to resolve taxonomic boundaries.

INTRODUCTION. Chemotherapy is increasingly administered prior to resection in patients with early-stage pancreatic adenocarcinoma, but the national prevalence of this practice is poorly understood. Our objectives were to (1) describe the utilization of upfront chemotherapy management of stage I pancreatic cancer; (2) define factors associated with the use of upfront chemotherapy and subsequent resection; and (3) assess hospital-level variability in upfront chemotherapy and subsequent resection. METHODS. The National Cancer Database was used to identify patients treated for clinical stage I pancreatic adenocarcinoma. Outcomes were receipt of upfront chemotherapy and surgical resection after upfront chemotherapy. Associations between patient/hospital factors and both initial management and subsequent resection were assessed by multivariable logistic regression. RESULTS. A total of 17,495 patients were included, with 26.6% receiving upfront chemotherapy. Upfront chemotherapy was more likely in patients who were ≥ 80 years of age (odds ratio [OR] 1.64, 95% confidence interval [CI] 1.39–1.93), had T2 tumors (OR 2.56, 95% CI 2.36–2.78), or were treated at a low-volume center (OR 2.10, 95% CI 1.63–2.71). Among patients receiving upfront chemotherapy, only 33.5% underwent subsequent resection. Resection was more likely in patients with T1 tumors (OR 1.22, 95% CI 1.04–1.43) and in those treated at high-volume centers (OR 4.03, 95% CI 2.90–5.60). Only 20.4% of hospitals performed resection in > 50% of patients after upfront chemotherapy. CONCLUSION. Rates of surgical resection after upfront chemotherapy are relatively low, and the proportion of patients who eventually undergo resection varies considerably between hospitals. The use of surgery after upfront chemotherapy in resectable pancreatic cancer should be considered as an internal quality-of-cancer-care measure.

Background General surgery residencies continue to experience high levels of attrition. Methods Survey of general surgery residents administered with the 2018 American Board of Surgery In-Training Examination. Outcomes were consideration of leaving residency, potential alternative career paths, and reasons for staying in residency. Results Among 7,409 residents, 930 (12.6%) reported considering leaving residency over the last year. Residents were more likely to consider other general surgery programs (46.2%) if PGY 2/3 (OR: 1.93, 95%CI 1.34–2.77) or reporting frequent duty hour violations (OR: 1.58, 95%CI 1.12–2.24). Consideration of other specialties (47.0%) was more likely if dissatisfied with being a surgeon (OR 2.86, 95%CI 1.92–4.26). Residents were more likely to consider leaving medicine (49.7%) if female (OR: 1.54, 95%CI 1.16–2.06) or dissatisfied with a surgical career (OR: 2.81, 95%CI 1.85–4.27). Common reasons for remaining in residency included a sense of too much invested to leave (65.3%) and career satisfaction (55.5%). Conclusion Profiles of trainees considering leaving residency exist based on factors associated with alternative careers. This may be a target for future interventions to reduce attrition.

BackgroundChemotherapy quality measures consider hospitals compliant when chemotherapy is recommended, even if it is not received. This may mask shortcomings in cancer care delivery. Objectives of this study were to (1) identify patient factors associated with failure to receive recommended chemotherapy without a documented contraindication and (2) assess hospital variation in failure to administer recommended chemotherapy.MethodsPatients from 2005 to 2015 with breast, colon and lung cancers who failed to receive recommended chemotherapy were identified using the National Cancer Database. Hospital-level rates of failure to administer recommended chemotherapy were calculated, and patient and hospital factors associated with failure to receive recommended chemotherapy were identified by multivariable logistic regression.ResultsA total of 183 148 patients at 1281 hospitals were analysed. Overall, 3.5% of patients with breast, 6.6% with colon and 10.7% with lung cancers failed to receive recommended chemotherapy. Patients were less likely to receive recommended chemotherapy in all cancers if uninsured or on Medicaid (pConclusions and relevanceThough overall rates are low, failure to receive recommended chemotherapy is associated with sociodemographic factors. Hospital variation in failure to administer recommended chemotherapy is masked by current quality measure definitions and may define a significant and unmeasured difference in hospital quality.

Global biodiversity loss is a profound consequence of human activity. Disturbingly, biodiversity loss is greater than realized because of the unknown number of undocumented species. Conservation fundamentally relies on taxonomic recognition of species, but only a fraction of biodiversity is described. Here, we provide a new quantitative approach for prioritizing rigorous taxonomic research for conservation. We implement this approach in a highly diverse vertebrate group—Australian lizards and snakes. Of 870 species assessed, we identified 282 (32.4%) with taxonomic uncertainty, of which 17.6% likely comprise undescribed species of conservation concern. We identify 24 species in need of immediate taxonomic attention to facilitate conservation. Using a broadly applicable return-on-investment framework, we demonstrate the importance of prioritizing the fundamental work of identifying species before they are lost., In order to inform conservation effort, there is urgent need for rigorous taxonomic research to describe species under threat of extinction. Implementation of a new prioritization method identified 282 Australian reptile species needing taxonomic research, of which 17.6% represent undescribed species of conservation concern; this approach could be readily implemented across many faunal groups.

Importance Physician burnout is a serious issue, given its associations with physician attrition, mental and physical health, and self-reported medical errors. Burnout is typically measured in health care by assessing the frequency of symptoms in 2 domains, emotional exhaustion and depersonalization. However, the lack of a clinically diagnostic threshold to define burnout has led to considerable variability in reported burnout rates. Objective To estimate the prevalence of burnout using a range of definitions (ie, requiring symptoms in both domains or just 1) and thresholds (ie, requiring symptoms to occur weekly vs a few times per year) and examine the strength of the association of various definitions of burnout with suicidal thoughts and thoughts of attrition among general surgery residents. Design, Setting, and Participants A cross-sectional national survey of clinically active US general surgery residents administered in conjunction with the 2019 American Board of Surgery In-Training Examination assessed burnout symptoms, thoughts of attrition, and suicidal thoughts during the past year. Multivariable logistic regression models were used to assess the association of burnout symptoms with thoughts of attrition and suicidal thoughts. Values ofR2and C statistic were used to evaluate multivariable model performance. Exposures Burnout was evaluated with a 6-item, modified, abbreviated Maslach Burnout Inventory for 2 burnout domains: emotional exhaustion and depersonalization. Main Outcomes and Measures The primary outcome was prevalence of burnout. Secondary outcomes were thoughts of attrition and suicidal thoughts within the past year. Results Among 6956 residents (a 85.6% response rate; including 3968 men [57.0%] and 4041 non-Hispanic White individuals [58.1%]) from 301 surgical residency programs, 2329 (38.6%) reported at least weekly symptoms of emotional exhaustion, and 1389 (23.1%) reported at least weekly depersonalization symptoms. Using the most common definition, 2607 general surgery residents (43.2%) reported weekly burnout symptoms on either subscale. Subtle changes in the definition of burnout selected resulted in prevalence estimates varying widely from 3.2% (159 residents; most stringent: daily symptoms on both subscales) to 91.4% (5521 residents; least stringent: symptoms a few times per year on either subscale). In multivariable models, all measures of higher burnout symptoms were associated with increased thoughts of attrition (depersonalization:R2, 0.097; C statistic, 0.717; emotional exhaustion:R2, 0.137; C statistic, 0.758; both:R2, 0.138; C statistic, 0.761) and suicidal thoughts (depersonalization:R2, 0.077; C statistic, 0.718; emotional exhaustion:R2, 0.102; C statistic, 0.750; both:R2, 0.106; C statistic, 0.751) among general surgery residents (allP Conclusions and Relevance In a national evaluation of general surgery residents, prevalence estimates of burnout varied considerably, depending on the burnout definition selected. Frequent burnout symptoms were strongly associated with both thoughts of attrition and suicide, regardless of the threshold selected. Future research on burnout should explicitly include a clear description and rationale for the burnout definition used.

This survey study describes surgical trainees’ self-reported experiences of bullying and symptoms of burnout and suicidality assessed at the time of their board certification examination.

For over two decades, assessments of geographic variation in mtDNA and small numbers of nuclear loci have revealed morphologically similar, but genetically divergent, intraspecific lineages in lizards from around the world. Subsequent morphological analyses often find subtle corresponding diagnostic characters to support the distinctiveness of lineages, but occasionally do not. In recent years it has become increasingly possible to survey geographic variation by sequencing thousands of loci, enabling more rigorous assessment of species boundaries across morphologically similar lineages. Here we take this approach, adding new, geographically extensive SNP data to existing mtDNA and exon capture datasets for the Gehyra australis and G. koira species complexes of gecko from northern Australia. The combination of exon-based phylogenetics with dense spatial sampling of mitochondrial DNA sequencing, SNP-based tests for introgression at lineage boundaries and newly-collected morphological evidence supports the recognition of nine species, six of which are newly described here. Detection of discrete genetic clusters using new SNP data was especially convincing where candidate taxa were continuously sampled across their distributions up to and across geographic boundaries with analyses revealing no admixture. Some species defined herein appear to be truly cryptic, showing little, if any, diagnostic morphological variation. As these SNP-based approaches are progressively applied, and with all due conservatism, we can expect to see a substantial improvement in our ability to delineate and name cryptic species, especially in taxa for which previous approaches have struggled to resolve taxonomic boundaries.

Background Hyperparathyroidism-jaw tumor syndrome (HPT-JT) is a rare autosomal dominant disease secondary to germline inactivating mutations of the tumor suppressor gene HRPT2/CDC73. The aim of the present study is to determine the optimal surgical approach to parathyroid disease in patients with HPT-JT.

OBJECTIVE: The aim of this study was to determine whether the genetic background of the disease should be incorporated into treatment decision making. BACKGROUND: Carotid body paragangliomas are rare tumors that often affect patients with genetic mutations of the succinate dehydrogenase complex (SDHx). Despite growing evidence that germ line genetic mutations alter the aggressiveness of paragangliomas, treatment decisions are currently based only on clinical symptoms and tumor size in patients with carotid body paragangliomas. METHODS: Retrospective analysis of 34 patients with carotid body paragangliomas who underwent genetic testing and surgical treatment. Recurrence was defined by the return of locoregional disease and/or development of distant metastases. Clinical characteristics and genetic testing results were analyzed as predictors of patient outcomes. RESULTS: Thirty-four patients underwent 41 primary carotid body paraganglioma resections (median follow-up time of 42 months, range: 1–293). Overall survival was 91.2%. Twelve patients had germ line mutations in SDHB, 17 in SDHD, and 5 carried no known mutation. Surgical resection of larger tumors was associated with higher operative complications (odds ratio: 5.4, P = 0.05). Tumor size at resection was significantly smaller in patients with SDHB mutations than in patients with non-SDHB mutations (2.1 vs 3.3 cm, P = 0.02). Patients with a mutation in the SDHB gene also had significantly worse disease-free survival compared with patients without an SDHB gene mutation (P = 0.03). CONCLUSIONS: Mutations in the SDHB gene are associated with worse disease- free survival after resection in patients with carotid body paragangliomas despite earlier intervention. This suggests that a more aggressive surgical approach is warranted in patients with SDHB mutations.

Aberrant DNA methylation is known to be a major factor in oncogenesis and cancer progression, but effects of methylation in papillary thyroid cancer (PTC) are not well defined.The objective of the study was to identify altered methylation patterns, which may be associated with PTC disease behavior.This study was a genome-wide methylation analysis of PTC.The study was conducted at the National Institutes of Health Clinical Center.PTC tissue from 51 patients were analyzed and compared with normal thyroid tissue from seven patients.CpG methylation status was assessed using advanced genome-wide methylation bead chips.Altered methylation patterns in PTC were analyzed by stage, recurrence, histological subtype of tumor, and tumor genotype.PTC is globally hypomethylated compared with normal thyroid with 2837 differentially methylated CpG sites. The follicular variant of PTC demonstrated less differential methylation with only 569 differentially methylated CpG sites. Tumors with mutations in BRAF, RET/PTC, and RAS demonstrated a 3.6-fold increase in the number of differentially methylated sites compared with wild-type tumors. The differentially methylated genes were associated with oncological pathways including cellular movement, growth, and proliferation.PTC is epigenetically distinct from the follicular variant of PTC and by gene mutation status (BRAF, RET/PTC, and RAS).

Australia is a global hotspot of reptile diversity, hosting similar to 10% of the world's squamate (snake and lizard) species. Yet the conservation status of the Australian squamate fauna has not been assessed for >25 years; a period during which the described fauna has risen by similar to 40%. Here we provide the first comprehensive conservation assessment of Australian terrestrial squamates using IUCN Red List Categories and Criteria. Most (86.4%; n = 819/948) Australian squamates were categorised as Least Concern, 4.5% were Data Deficient, and 7.1% (range 6.8%-11.3%, depending on the treatment of Data Deficient species) were threatened (3.0% Vulnerable, 2.7% Endangered, 1.1% Critically Endangered). This level of threat is low relative to the global average (similar to 18%). One species (Emoia nativitatis) was assessed as Extinct, and two species (Lepidodactylus listeri and Cryptoblepharus egeriae) are considered Extinct in the Wild: all three were endemic to Christmas Island. Most (75.1%) threat assessments were based on geographic range attributes, due to limited data on population trends or relevant proxies. Agriculture, fire, and invasive species were the threats that affected the most species, and there was substantial geographic variation in the number of species affected by each threat. Threatened species richness peaked on islands, in the Southern Alps, and across northern Australia. Data deficiency was greatest in northern Australia and in coastal Queensland. Approximately one-in-five threatened species were not represented in a single protected area. Our analyses shed light on the species, regions, and threats in most urgent need of conservation intervention.

Aggressive surgical resection with intent to cure and surgical debulking procedures are commonly recommended in patients with metastatic pheochromocytoma and paraganglioma. To date there are no data on operative outcomes of patients after surgical resection of metastatic pheochromocytoma and paraganglioma to determine if such an approach is appropriate and what factors may be associated with a favorable outcome.We performed a retrospective analysis of 30 patients with metastatic pheochromocytoma/paraganglioma who underwent surgical treatment. Clinical characteristics and genetic factors were analyzed as predictors of biochemical response to surgery.Thirty patients underwent a total of 42 operations, with a median follow-up time of 24 months (range 1 to 114 months). Complete disease resection (R0/R1) was achieved in 18 (42.9%) cases; 24 cases (57.1%) were debulking (R2) procedures without intent to cure. Complete biochemical remission was achieved in 10 (23.8%) cases and partial biochemical response was achieved in 23 (54.8%) cases. Patients with disease confined to the abdomen were more likely to achieve and maintain a biochemical response postoperatively than those with extra-abdominal disease (p = 0.0003). Debulking operations were significantly less likely to achieve or maintain biochemical palliation, with only 1 patient maintaining a biochemical response 12 months postoperatively (p0.0001). Patients were less likely to obtain pharmacologic independence after debulking (p = 0.0003), with only 2 (8.3%) not requiring pharmacotherapy 6 months after the intervention. Factors not associated with biochemical response to surgery include sex, family history, SDHB mutation status, systemic therapy, and preoperative biochemical profile.Depending on the extent of disease, patients with metastatic pheochromocytoma/paraganglioma can benefit from aggressive operative intervention and resection with intent to cure. Debulking procedures are unlikely to achieve clinically significant biochemical response, with any biochemical response achieved being very short-lived.

Patients with Cushing's Syndrome (CS) and Conn's Syndrome with bilateral adrenal masses pose a dilemma. Uptake of 18F-FDG by hyperfunctioning adrenal glands has not been previously reported and may help lateralize. The aim was to determine if 18F-FDG PET/CT scan could identify hyperfunctioning adrenal masses and determine a biological basis for uptake.Patients with nonfunctional adenomas (n = 9), CS (n = 11), and Conn's syndrome (n = 4) underwent an 18F-FDG PET/CT scan with a volume of interest circumscribing each mass to obtain a maximal standardized uptake value (SUVmax). Thirty-two adrenal masses were analyzed. Genome-wide expression data from an independent cohort were analyzed in nonfunctioning adenomas (n = 20), Conn's syndrome (n = 29), and CS (n = 24) focusing on GLUT genes. For genes differentially expressed, immunohistochemistry was performed on tissue samples.Cortisol-secreting masses (n = 16) had a higher average SUVmax of 5.9 compared to nonfunctioning masses (n = 11, average SUVmax 4.2) and aldosterone-hypersecreting masses (n = 5, average SUVmax 3.2) (p = 0.007). SUVmax cut-off of 5.33 had 50.0% sensitivity and 81.8% specificity in localizing a cortisol-secreting mass. GLUT3 expression was 2.19-fold higher in patients with CS compared to patients with nonfunctioning adenomas (p = 0.003) and 2.16-fold higher in patients with CS compared to Conn's syndrome (p = 0.006). GLUT3 immunohistochemistry showed 2.2-fold higher staining in CS tumor samples compared to nonfunctioning adenomas.Differential 18F-FDG PET/CT uptake was observed in patients with nonfunctioning, aldosterone-hypersecreting, and cortisol-secreting masses. GLUT3 overexpression in cortisol-secreting tumor likely accounts for the differential uptake. Future larger cohort studies will need to be conducted to determine if 18F-FDG PET/CT uptake can lateralize cortisol-secreting adrenal masses in patients with bilateral adrenal masses.