Association Between Metastatic Pattern and Prognosis in Stage IV Gastric Cancer: Potential for Stage Classification Reform.

PURPOSE: This study aims to clarify the association between metastatic pattern and prognosis in stage IV gastric cancer, with a focus on patients presenting with metastases limited to nonregional lymph nodes. METHODS: In this retrospective cohort study, the National Cancer Database was used to identify patients ≥ 18 years of age diagnosed with stage IV gastric cancer between 2016 and 2019. Patients were stratified according to pattern of metastatic disease at diagnosis: nonregional lymph nodes only ("stage IV-nodal"), single systemic organ ("stage IV-single organ"), or multiple organs ("stage IV-multi-organ"). Survival was assessed by Kaplan-Meier curves and multivariable Cox models in unadjusted and propensity score-matched samples. RESULTS: Overall, 15,050 patients were identified, including 1,349 (8.7%) stage IV-nodal patients. Most patients in each group received chemotherapy [68.6% of stage IV-nodal patients, 65.2% of stage IV-single organ patients, and 63.5% of stage IV-multi-organ patients (p = 0.003)]. Stage IV-nodal patients exhibited better median survival (10.5 months, 95% CI 9.7-11.9, p < 0.001) than single organ (8.0, 95% CI 7.6-8.2) and multi-organ (5.7, 95% CI 5.4-6.0) patients. In the multivariable Cox model, stage IV-nodal patients also exhibited better survival (HR 0.79, 95% CI 0.73-0.85, p < 0.001) than single organ (reference) and multi-organ (HR 1.27, 95% CI 1.22-1.33, p < 0.001) patients. CONCLUSIONS: Nearly 9% of clinical stage IV gastric cancer patients have their distant disease confined to nonregional lymph nodes. These patients were managed similarly to other stage IV patients but experienced a better prognosis, suggesting opportunities to introduce M1 staging subclassifications.

Indoor Versus Outdoor: Does Occupational Sunlight Exposure Increase Melanoma Risk? A Systematic Review.

INTRODUCTION: Melanoma is the fifth most common cancer diagnosed in the United States, representing 5.6% of all new cancer cases. There are conflicting reports correlating a relationship between primarily outdoor occupations, associated with increased exposure to direct sunlight, and the incidence of cutaneous melanoma. Our objective was to outline and critically evaluate the relevant literature related to chronic occupational exposure to sunlight and risk of developing cutaneous melanoma. METHODS: The study protocol for this systematic review was submitted to the International Prospective Register of Systematic Reviews and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed. For each relevant study included, the following information was extracted: author names, publication year, study name, study design, age, exposure assessment, outcome, comparison, number of cases, case ascertainment, and descriptive and adjusted statistics. Study quality and evidence certainty was assessed using the Grading of Recommendations, Assessment, Development and Evaluations model. RESULTS: The initial database search yielded 1629 articles for review and following full-text screening, a total of 14 articles were included for final analysis. Of the studies included, seven articles were retrospective case control and seven were cohort studies. The studies did not report any differences in the likelihood of cutaneous melanoma development based upon membership in the outdoor versus indoor occupation groups included in each study. CONCLUSIONS: Overall, the articles included in this systematic review did not report an increased risk of developing cutaneous melanoma among individuals with outdoor occupations. Further investigation is required to determine if other occupational or life-style-related risk factors exist, to help support the development of individualized skin screening recommendations and improve the early detection of melanoma in all populations.

The Unintended Consequences of Nonoperative Management of Acute Appendicitis.

BACKGROUND: Appendicitis has traditionally been treated surgically. Recently, nonoperative management is emerging as a viable alternative to the traditional operative approach. This raises the question of what are the unintended consequences of nonoperative management of appendicitis with respect to cost and patient burden. METHODS: National Readmissions Database was queried between 2010 and 2014. Patients who were admitted with acute appendicitis between January and June of each year were identified. Patients who underwent appendectomy were compared with those treated nonoperatively. Six-month all-cause readmission rates and aggregate costs between index hospitalization and readmissions were calculated. RESULTS: We identified 438,995 adult admissions for acute appendicitis. Most cases were managed with appendectomy (93.2%). There was a significant increase in the rate of nonoperative management, from 3.6% in 2010 to 6.8% in 2014 (P value for trend <0.01). Discharges receiving nonoperative management tended to be older and have more comorbidities. There was a 59% decreased adjusted odds of readmission within 6 mo among patients receiving appendectomy in comparison to those managed nonoperatively. Despite this, in multivariable linear regression, there was an adjusted $2900 cost increase associated with surgical management (P < 0.01). CONCLUSIONS: This study shows that nonoperative management is increasing. Patients treated nonoperatively may have an increased risk of readmission within 6 mo but incur a decreased average adjusted total cost. Given this, it is important that surgeons critically assess patients who are being considered for nonoperative management of appendicitis.

Training Disparities of Our Future Workforce: A Survey of Trauma Fellowship Candidates.

BACKGROUND: Training in Acute Care Surgery (ACS) is an integral component of general surgery residency and serves as a critical base experience for the added educational qualifications of fellowship. How this training varies between programs is not well characterized. We sought to describe the variation in clinical exposure between residencies in a sample of residents applying to an ACS fellowship. We hypothesized that applicants have significant variations in clinical exposure as well as unique and specific expectations for educational experiences. MATERIALS AND METHODS: We offered an anonymous 82-question survey focused on residency clinical exposure and self-perceived confidence in key areas of ACS training, as well as fellowship training and career expectations to all applicants interviewed at a single trauma, critical care, and emergency surgery fellowship program. Responses were assessed via absolute numbers and confidence via a 5-point Likert scale; data are reported using descriptive statistics and linear regression models. RESULTS: Forty-two interviewing applicants completed the survey, for a 96% response rate. Applicants reported heterogeneous levels of comfort across most ACS domains. There was good correlation between experience and comfort in most procedural areas. During fellowship training, respondents placed highest priority on operative experience, with 43% rating this as their highest priority, followed by penetrating trauma experience (33%). CONCLUSIONS: We found significant variations in both experience and comfort within key ACS domains among fellowship applicants. Despite training variability, there was good correlation between experience and self-reported comfort. Collaboration between residency and fellowship governing bodies may help address areas of limited exposure before entry into clinical practice.

Use of model for end-stage liver disease exceptions for donation after cardiac death graft recipients relisted for liver transplantation.

Donation after cardiac death (DCD) liver transplantation is associated with increased biliary complications and graft failure. Yet for unclear reasons, DCD recipients relisted for transplantation have lower wait-list mortality than other retransplant candidates. We used Organ Procurement and Transplantation Network and United Network for Organ Sharing data from 2002 to 2011 to evaluate all DCD recipients relisted for transplantation to evaluate the impact of the utilization of Model for End-Stage Liver Disease (MELD) exception points on wait-list outcomes. Of 262 DCD recipients relisted for liver transplantation >2 weeks after initial transplantation, 82 (31.3%) applied for a nonstandardized MELD exception, and 68 (82.9%) had ≥1 exception approved. Of the relisted DCD recipients, 187 (71.4%) underwent retransplantation; among those with an approved MELD exception, 85.2% underwent retransplantation versus 57.1% of those with an exception denied and 69.4% of those not applying for an exception (P=0.02). In contrast, those receiving MELD exception points were significantly less likely to be removed from the wait list for death or clinical deterioration in comparison with those not applying for an exception (7.1% versus 19.4%, P=0.02). In multivariate models, patients with an approved exception were 3.3 times more likely to undergo retransplantation than those not applying for an exception. Standardized criteria for exception points among DCD recipients should be established to ensure uniform access to retransplantation.

Respect the Middle Lobe: Perioperative Risk of Bilobectomy Compared With Lobectomy and Pneumonectomy.

BACKGROUND: In some cases of right-sided lung cancer, tumor extension, bronchial involvement, or pulmonary artery infiltration may necessitate bilobectomy. Although the middle lobe is believed to represent a fraction of total lung function, the morbidity and mortality associated with bilobectomy is not well described. METHODS: We retrospectively identified patients in The Society of Thoracic Surgeons Database who underwent lobectomy, bilobectomy, or pneumonectomy for lung cancer from 2009 to 2017. The primary outcome was 30-day perioperative mortality. We performed propensity matching by patient demographics, comorbidities, and perioperative variables for each surgical type against bilobectomy and ran Cox proportional hazard models. Secondary outcomes of 30-day morbidity and mortality of upper vs lower bilobectomy were also compared. RESULTS: Within the study period 2911 bilobectomy, 65,506 lobectomy, and 3370 pneumonectomy patients met the inclusion criteria. Patients undergoing pneumonectomy and bilobectomy had fewer comorbidities than lobectomy patients. After propensity matching 30-day mortality of bilobectomy was comparable with left pneumonectomy (hazard ratio [HR], 1.35; 95% CI, 0.95-1.91; P = .09) and significantly worse than left (HR, 0.40; 95% CI, 0.29-0.56; P < .0001) or right (HR, 0.43; 95% CI, 0.31-0.59; P < .0001) lobectomy. Bilobectomy was associated with a survival advantage compared with right pneumonectomy (HR, 2.54; 95% CI, 1.72-3.74; P < .0001). Thirty-day morbidity was higher for bilobectomy compared with lobectomy, and upper bilobectomy had a significant unadjusted 30-day mortality advantage compared with lower bilobectomy (98.3% vs 97%, P = .04). CONCLUSIONS: The morbidity and mortality of bilobectomy is significantly worse than lobectomy and is comparable with left pneumonectomy. The addition of middle lobectomy to a pulmonary resection is not without risk and should be carefully considered during preoperative risk stratification.

Association of patient socioeconomic status with outcomes after palliative treatment for disseminated cancer.

BACKGROUND: Palliative treatment has been associated with improved quality of life and survival for a wide variety of metastatic cancers. However, it is unclear whether the benefits of palliative treatment are uniformly experienced across the US cancer population. We evaluated patterns and outcomes of palliative treatment based on socioeconomic, sociodemographic and treating facility characteristics. METHODS: Patients diagnosed between 2008 and 2019 with Stage IV primary cancer of nine organ sites were analyzed in the National Cancer Database. The association between identified variables, and outcomes concerning the administration of palliative treatment were analyzed with multivariable logistic regression and Cox proportional hazard models. RESULTS: Overall 238,995 (23.6%) of Stage IV patients received palliative treatment, which increased over time for all cancers (from 20.7% in 2008 to 25.6% in 2019). Palliative treatment utilization differed significantly by region (West less than Northeast, OR: 0.55 [0.54-0.56], p < 0.001) and insurance payer status (uninsured greater than private insurance, OR: 1.35 [1.32-1.39], p < 0.001). Black race and Hispanic ethnicity were also associated with lower rates of palliative treatment compared to White and non-Hispanics respectively (OR for Blacks: 0.91 [0.90-0.93], p < 0.001 and OR for Hispanics: 0.79 [0.77-0.81] p < 0.001). CONCLUSIONS: There are important differences in the utilization of palliative treatment across different populations in the United States. A better understanding of variability in palliative treatment use and outcomes may identify opportunities to improve informed decision making and optimize quality of care at the end-of-life.

Nonregional Lymph Nodes as the Only Metastatic Site in Stage IV Esophageal Cancer.

Introduction: Metastatic involvement of at least one nonregional lymph node currently renders patients with esophageal cancer as having stage IV disease. However, the management and outcomes of patients whose sole determinant of stage IV status is nonregional lymph nodes (abbreviated as "stage IV-nodal" disease) have not been fully characterized. Methods: In this retrospective cohort study, the National Cancer Database was queried to identify patients 18 years of age or older who were diagnosed with stage IV esophageal cancer between 2016 and 2019. Survival was assessed by Kaplan-Meier analysis and Cox models in the overall sample and a propensity-matched sample. Patients with "stage IV-nodal" disease were compared with patients with systemic metastases involving a single organ or multiple organs. Results: Overall, 11,589 patients with clinical stage IV esophageal cancer were identified, including 1331 (11.5%) patients with stage IV-nodal disease. Patients with stage IV-nodal disease were more likely to receive chemotherapy (77%) than those with single systemic organ metastases (64%) and multiorgan metastases (63%) (p < 0.0001); patients with stage IV-nodal disease were also more likely to receive radiation (49%) than those with single systemic organ metastases (40%) and multiorgan metastases (39%) (p < 0.0001). Squamous cell carcinoma (OR = 1.58, 95% confidence interval [CI]: 1.34-1.86, p < 0.0001) and academic facility type (OR = 1.24, 95% CI: 1.09-1.4, p = 0.0009) were associated with higher likelihood of the stage IV-nodal presentation. Patients with stage IV-nodal disease experienced superior survival (hazard ratio = 0.72, 95% CI: 0.66-0.78, p < 0.0001) than those with stage IV-single systemic metastases (reference group) and stage IV-multiorgan disease (hazard ratio = 1.30, 95% CI: 1.24-1.37). Conclusions: Approximately 12% of patients with stage IV esophageal cancer lack systemic metastases at presentation. These patients with stage IV-nodal disease are more likely to receive treatment and experience superior survival. Further study of the stage IV-nodal population and consideration of a potential stage IV subclassification system is justified.

Evaluation of gastroesophageal reflux disease and hiatal hernia as risk factors for lobectomy complications.

Objective: Up to 40% of lobectomies are complicated by adverse events. Gastroesophageal reflux disease (GERD) and hiatal hernia have been associated with morbidity across a range of clinical scenarios, yet their relation to recovery from pulmonary resection is understudied. We evaluated GERD and hiatal hernia as predictors of complications after lobectomy for lung cancer. Methods: Lobectomy patients at Yale-New Haven Hospital between January 2014 and April 2021 were evaluated for predictors of 30-day postoperative complications, pneumonia, atrial arrhythmia, readmission, and mortality. Multivariable regression models included sociodemographic characteristics, body mass index, surgical approach, cardiopulmonary comorbidities, hiatal hernia, GERD, and preoperative acid-suppressive therapy as predictors. Results: Overall, 824 patients underwent lobectomy, including 50.5% with a hiatal hernia and 38.7% with GERD. The median age was 68 [interquartile range, 61-74] years, and the majority were female (58.4%). At least 1 postoperative complication developed in 39.6% of patients, including atrial arrhythmia (11.7%) and pneumonia (4.1%). Male sex (odds ratio [OR], 1.51; 95% confidence interval [CI], 1.11-2.06, P = .01), age ≥70 years (OR, 1.55; 95% CI, 1.13-2.11, P = .01), hiatal hernia (OR, 1.40; 95% CI, 1.03-1.90, P = .03), and intraoperative packed red blood cells (OR, 4.80; 95% CI, 1.51-15.20, P = .01) were significant risk factors for developing at least 1 postoperative complication. Hiatal hernia was also a significant predictor of atrial arrhythmia (OR, 1.64; 95% CI, 1.02-2.62, P = .04) but was not associated with other adverse events. Conclusions: Our findings indicate that hiatal hernia may be a novel risk factor for complications, especially atrial arrhythmia, following lobectomy that should be considered in the preoperative evaluation of lung cancer patients.

Utilization and Outcomes of Radiation in Stage IV Esophageal Cancer.

Introduction: For patients with stage IV esophageal cancer, esophageal radiation may be used selectively for local control and palliation. We aimed to understand patterns of radiation administration among patients with stage IV esophageal cancer and any potential survival associations. Methods: In this retrospective cohort study, the National Cancer Database was queried for patients with metastatic stage IV esophageal cancer diagnosed between 2016 and 2019. Patterns of radiation use were identified. Survival was determined through Kaplan-Meier analysis of propensity score-matched pairs of patients who did and did not receive radiotherapy and time-to-event models. Results: Overall, 12,088 patients with stage IV esophageal cancer were identified, including 32.7% who received esophageal radiation. The median age was 65 (interquartile range [IQR]: 58-73) years, and 82.6% were male. Among the irradiated patients, the median total radiation dose was 35 (IQR: 30-50) Gy administered in a median of 14 (IQR: 10-25) fractions given in 22 (IQR: 14-39) days. Overall, esophageal radiation was not associated with better survival (log-rank p = 0.41). When stratified by radiation dose, a survival advantage (over no radiation) was found in the 1144 patients (29% of the irradiated patients) who received 45 to 59.9 Gy (time ratio = 1.28, 95% confidence interval: 1.20-1.37, p < 0.001) and the 88 patients (2.2%) who received 60 to 80 Gy (time ratio = 1.37, 95% confidence interval: 1.11-1.69, p = 0.003). Conclusions: One-third of the patients with metastatic stage IV esophageal cancer in the National Cancer Database received esophageal radiation. Most received a radiation dose that, although consistent with palliative regimens, was not associated with a survival advantage. Further study is warranted to understand the indications for radiation in stage IV esophageal cancer and potentially reevaluate the most appropriate radiation dose for palliation.

Immunotherapy After Chemotherapy and Radiation for Clinical Stage III Lung Cancer.

Importance: The 2017 international PACIFIC trial established a role for immunotherapy after chemoradiation for unresectable stage III non-small cell lung cancer (NSCLC). However, in the US, patients with NSCLC commonly differ from clinical trial populations in terms of age, health, access to care, and treatment course, which may all factor into the efficacy of immunotherapy. Objective: To determine the outcomes of immunotherapy use in unresectable stage III NSCLC in the general US population. Design, Setting, and Participants: This cohort study analyzed the National Cancer Database for patients diagnosed with clinical stage III NSCLC between 2015 and 2017 with follow-up through the end of 2018 who were treated with chemotherapy and radiation. Data were analyzed January 2022. Main Outcomes and Measures: Mortality hazard in a multivariable Cox proportional hazards model and survival among a propensity-matched sample treated with chemotherapy and radiation, with and without immunotherapy. Results: A total of 23 811 patients with clinical stage III NSCLC with median (IQR) age 66 (59-72) years met inclusion criteria (10 454 [43.9%] women; 564 [2.4%] Asian, 2930 [12.3%] Black, 20 077 [84.3%] White patients), including 209 (16.1%) patients with multiple comorbidities and 1297 (5.4%) immunotherapy recipients. Immunotherapy after chemotherapy and radiation was associated with reduced mortality (hazard ratio [HR], 0.74; 95% CI, 0.67-0.82; P < .001). Among a propensity-matched sample, immunotherapy was associated with superior 3-year survival (52% [1297 patients at 0 months, 56 patients at 36 months] vs 44% [2594 patients at 0 months, 173 patients at 36 months]; P < .001). The treatment of 833 patients who received immunotherapy (64.2%) differed from the PACIFIC trial protocol, including 221 patients (17.0%) who received radiation doses outside of the protocol range and 731 patients (56.4%) who started immunotherapy more than 6 weeks after radiation was completed. The survival advantage of immunotherapy persisted when initiated up to 12 weeks after radiation was completed (HR, 0.75; 95% CI, 0.61-0.92). Among patients who received radiation outside the PACIFIC protocol range, the survival advantage of immunotherapy was not significant (HR, 0.87; 95% CI, 0.69-1.01). Conclusions and Relevance: In this cohort study, immunotherapy after chemotherapy and radiation for stage III NSCLC was associated with a survival advantage in the general US population despite two-thirds of patients treated differently than the PACIFIC protocol. The findings suggest there may be flexibility in the timing of immunotherapy initiation after radiation; further study is warranted to clarify the clinical benefits of immunotherapy.

Association Between Food and Drug Administration Approval and Disparities in Immunotherapy Use Among Patients With Cancer in the US.

Importance: Clinical trials and compassionate use agreements provide selected patients with access to potentially life-saving treatments before approval by the Food and Drug Administration (FDA). Approval from the FDA decreases a number of access barriers; however, it is unknown whether FDA approval is associated with increases in the equitable use of novel therapies and reductions in disparities in use among patients with cancer in the US. Objective: To assess the association between FDA drug approval and disparities in the use of immunotherapy across health, sociodemographic, and socioeconomic strata before and after approval of the first checkpoint inhibitors for the treatment of patients with cancer in the US. Design, Setting, and Participants: This cohort study used data from the National Cancer Database to examine the use of immunotherapy across health, sociodemographic, and socioeconomic strata before and after FDA approval of the first checkpoint inhibitor therapies. A total of 402 689 patients 20 years or older who were diagnosed with stage IV non-small cell lung cancer (NSCLC), renal cell carcinoma (RCC), or melanoma of the skin between January 1, 2007, and December 31, 2018 (specific years varied by tumor type), were included. Exposures: Patient health (Charlson-Deyo comorbidity score and age), sociodemographic characteristics (sex, race, and ethnicity), and socioeconomic (insurance status and household income based on zip code of residence) characteristics. Main Outcomes and Measures: The association of patient characteristics with receipt of immunotherapy was evaluated in the 4 years before and the 3 years immediately after FDA approval using multivariable logistic regression modeling. Results: Among 402 689 patients (median [IQR] age, 68 [60-76 years]; 225 081 men [55.9%]), 347 233 had NSCLC, 43 714 had RCC, and 11 742 patients had melanoma. A total of 47 527 patients (11.8%) were Black, 15 763 (3.9%) were Hispanic, 375 874 (93.3%) were non-Hispanic, 335 833 (83.4%) were White, and 16 553 (4.1%) were of other races. Before FDA approval, 6271 patients (3.2%) with NSCLC, 1155 patients (4.8%) with RCC, and 504 patients (8.6%) with melanoma received immunotherapy compared with 23 908 patients (15.6%) with NSCLC, 3890 patients (19.7%) with RCC, and 1143 patients (19.3%) with melanoma after FDA approval. Before FDA approval, sociodemographic and socioeconomic characteristics were associated with variable immunotherapy administration by tumor type. For example, among those with NSCLC, Black patients were less likely to receive immunotherapy than White patients (odds ratio [OR], 0.78; 95% CI ,0.71-0.85; P < .001); among those with RCC, uninsured patients were less likely to receive immunotherapy than privately insured patients (OR, 0.31; 95% CI, 0.20-0.48; P < .001). After FDA approval, most disparities persisted, but several narrowed (eg, Black patients with NSCLC: OR, 0.87 [95% CI, 0.83-0.91; P < .001]; uninsured patients with RCC: OR, 0.60 [95% CI, 0.48-0.75; P < .001]). Although many disparities remained, some gaps across socioeconomic characteristics appeared to widen (eg, patients with NSCLC in the lowest vs highest income quartile: OR, 0.80; 95% CI, 0.76-0.83; P < .001), and new gaps emerged (eg, Black patients with RCC: OR, 0.82; 95% CI, 0.72-0.93; P = .003). Conclusions and Relevance: In this cohort study, disparities in immunotherapy use existed across a number of sociodemographic and socioeconomic characteristics among patients with NSCLC, RCC, and melanoma before FDA approval, including during the important period when clinical trials were accruing patients. Although FDA approval was associated with a significant increase in the use of immunotherapy, gaps persisted, suggesting that FDA approval may not eliminate disparities in the use of novel therapies.

Revisiting Indications for Brain Imaging During the Clinical Staging Evaluation of Lung Cancer.

Introduction: Available guidelines are inconsistent as to whether patients with newly diagnosed clinical stage II NSCLC should receive routine brain imaging. Methods: The National Cancer Database was queried for the prevalence of isolated brain metastases among patients with newly diagnosed NSCLC in 2016 and 2017. Patients with metastases in locations other than the brain were excluded. The prevalences were then stratified by clinical T and N classifications and further stratified into a summary stage, which was calculated based on T and N classifications. The summary stage represents the clinical stage that would have been available at the time of decision for brain imaging. Results: A total of 6,949 of 149,958 patients (4.6%) with clinical stages I, II, III, or brain-limited stage IV NSCLC had dissemination limited to the brain. As T and N stages increased, prevalence of brain metastases generally increased. Among patients with node-negative (N0) NSCLC, the prevalence of brain-only metastases increased from 1.2% in patients with T1a to 3.8% among patients with T4 (p < 0.001). Among patients with T1a, the prevalence of brain-only metastases increased from 1.2% for patients with N0 to 7.9% for patients with N3 (p < 0.001). The prevalence of brain-limited metastases generally increased with increasing summary stage. The prevalence of brain-only metastases among patients with stage IA was 1.7% whereas that among patients with stage IIIA was 6.7% (p < 0.001). Of note, the prevalence of brain-limited metastases was approximately 6% for both summary stages II and III. Conclusions: Considering the similarity in prevalence of isolated brain metastases and the potential hazards associated with brain imaging in early stage NSCLC, practitioners may consider a more liberal use of brain imaging when interpreting conflicting guidelines.

Affinity of Cu+ for the copper-binding domain of the amyloid-ß peptide of Alzheimer's disease.

The role of metal ions in Alzheimer's disease etiology is unresolved. For the redox-active metal ions iron and copper, the formation of reactive oxygen species by metal amyloid complexes has been proposed to contribute to Alzheimer's disease neurodegeneration. For copper, reactive oxygen species are generated by copper redox cycling between its 1+ and 2+ oxidation states. Thus, the AßCu(I) complex is potentially a critical reactant associated with Alzheimer's disease etiology. Through competitive chelation, we have measured the affinity of the soluble copper-binding domain of the amyloid-ß peptide for Cu(I). The dissociation constants are in the femtomolar range for both wild-type and histidine-to-alanine mutants. These results indicate that Cu(I) binds more tightly to monomeric amyloid-ß than Cu(II) does, which leads us to propose that Cu(I) is a relevant in vivo oxidation state.

The Reporting of Race and Ethnicity in Surgery Literature.

Importance: The reporting of race provides transparency to the representativeness of data and helps inform health care disparities. The International Committee of Medical Journal Editors (ICMJE) developed recommendations to promote quality reporting of race; however, the frequency of reporting continues to be low among most medical journals. Objective: To assess the frequency as well as quality of race reporting among publications from high-ranking broad-focused surgical research journals. Design, Setting, and Participants: A literature review and bibliometric analysis was performed examining all human-based primary research articles published in 2019 from 7 surgical journals: JAMA Surgery, Journal of the American College of Surgeons, Annals of Surgery, Surgery, American Journal of Surgery, Journal of Surgical Research, and Journal of Surgical Education. The 5 journals that stated they follow the ICMJE recommendations were analyzed against the 2 journals that did not explicitly claim adherence. Main Outcomes and Measures: Measured study outcomes included race reporting frequency and use of the ICMJE recommendations for quality reporting of race. Results: A total of 2485 publications were included in the study. The mean (SD) frequency of reporting of race and ethnicity in publications of ICMJE vs non-ICMJE journals was 32.8% (8.4) and 32.0% (20.9), respectively (P = .72). Adherence to ICMJE recommendations for reporting race was more frequent in ICMJE journals than non-ICMJE journals (mean [SD] of 73.1% [17.8] vs 37.0% [10.2]; P < .001). Conclusions and Relevance: The frequency of race and ethnicity reporting among surgical journals is low. A journal's statement of adherence to ICMJE recommendations did not affect the frequency of race and ethnicity reporting; however, there was an increase in the use of ICMJE quality metrics. These findings suggest the need for increased and more standardized reporting of racial and ethnic demographic data among surgical journals.

Surgical research journals - Under review: An assessment of diversity among editorial boards and outcomes of peer review.

BACKGROUND: The COVID-19 pandemic exposed racism as a public health crisis embedded in structural processes. Editors of surgical research journals pledged their commitment to improve structure and process through increasing diversity in the peer review and editorial process; however, little benchmarking data are available. METHODS: A survey of editorial board members from high impact surgical research journals captured self-identified demographics. Analysis of manuscript submissions from 2016 to 2020 compared acceptance for diversity, equity, and inclusion (DEI)-focused manuscripts to overall rates. RESULTS: 25.6% of respondents were female, 2.9% Black, and 3.3% Hispanic. There was variation in the diversity among journals and in the proportion of DEI submissions they attract, but no clear correlation between DEI acceptance rates and board diversity. CONCLUSIONS: Diversity among board members reflects underrepresentation of minorities seen among surgeons nationally. Recruitment and retention of younger individuals, representing more diverse backgrounds, may be a strategy for change. DEI publication rates may benefit from calls for increasing DEI scholarship more so than changes to the peer review process.

Racial disparities in surgical outcomes for benign thyroid disease.

INTRODUCTION: Previous studies have shown racial disparities in surgical outcomes in malignant thyroid disease. We hypothesize that minority groups have a higher incidence of postoperative complications following surgery for benign thyroid disease. METHODS: Using NSQIP (2016-2017), patients (>17 years) undergoing thyroid surgery for benign disease were identified. Outcomes included neck hematoma, recurrent laryngeal nerve (RLN) injury, and hypocalcemia. Multivariate analysis was performed controlling for patient factors. RESULTS: 6817 patients were identified. Postoperative outcomes were neck hematoma (2.0%), RLN injury (5.2%), and significant hypocalcemia (4.9%). Compared to White patients, Black patients had higher chance of neck hematoma (OR 2.32, 95% CI 1.51-3.55) and RLN injury (OR 1.97, 95% CI 1.53-2.55) while Asian patients had significantly greater odds of RLN injury (OR 1.88, 95% CI 1.15-3.06). CONCLUSION: Minority compared to White patients are more likely to have significant postoperative complications which indicates racial disparities in the surgical treatment for benign thyroid disease.