Large-scale structure-informed multiple sequence alignment of proteins with SIMSApiper.

SUMMARY: SIMSApiper is a Nextflow pipeline that creates reliable, structure-informed MSAs of thousands of protein sequences faster than standard structure-based alignment methods. Structural information can be provided by the user or collected by the pipeline from online resources. Parallelization with sequence identity-based subsets can be activated to significantly speed up the alignment process. Finally, the number of gaps in the final alignment can be reduced by leveraging the position of conserved secondary structure elements. AVAILABILITY AND IMPLEMENTATION: The pipeline is implemented using Nextflow, Python3, and Bash. It is publicly available on github.com/Bio2Byte/simsapiper.

Private Equity Investment in Surgical Care.

OBJECTIVE: To characterize the extent of private equity investment affecting surgical care. SUMMARY BACKGROUND DATA: Over the last decade, investor-backed, for-profit private equity groups have invested in healthcare at an unprecedented rate, but the breadth of these investments affecting surgical practice remains largely unknown. METHODS: Four nationally representative databases were used to identify all merger/acquisitions involving surgical practices between 2015-2019, determine private equity investment in those transactions, and link the acquisitions with a physician dataset. RESULTS: 1,542 unique transactions were identified, of which 539 were financed by private equity. 58 transactions were then classified into their respective categories within surgical care: digestive disease, orthopedics, urology, vascular surgery, and plastic/cosmetic surgery. These transactions accounted for 199 practice sites and 1,405 physicians, averaging 24.2 physicians per transaction. Acquisition activity peaked in 2017 with a total of 63 practices involved. Digestive disease, urology, and orthopedic surgery accounted for the most activity. General surgeons were involved in a small share of the digestive disease practice acquisitions. Three "surgery-adjacent" categories were also identified: anesthesiology, ambulatory surgery centers, and surgical staffing firms. Among these, anesthesia was the largest category in terms of practices (194) and physicians (2,660) involved in transactions across the study period. Medical Service Organizations (MSOs) were a key mechanism through which private equity firms invested in surgical care. CONCLUSIONS: Private equity has engaged in substantial investment within surgical specialties, creating increased practice consolidation. These investments affect all levels of medical care and have notable implications for patients, practitioners, and policymakers.

The ACPYPE web server for small-molecule MD topology generation.

MOTIVATION: The generation of parameter files for molecular dynamics (MD) simulations of small molecules that are suitable for force fields commonly applied to proteins and nucleic acids is often challenging. The ACPYPE software and website aid the generation of such parameter files. RESULTS: ACPYPE uses OpenBabel and ANTECHAMBER to generate MD input files in Gromacs, AMBER, CHARMM, and CNS formats. It can now take a SMILES string as input, in addition to the original PDB or mol2 coordinate files, with GAFF2 support and GLYCAM force field conversion added. It can be installed locally via Anaconda, PyPI, and Docker distributions, while the web server at https://bio2byte.be/acpype/ was updated with an API, and provides visualization of results for uploaded molecules as well as a pre-generated set of 3738 drug molecules. AVAILABILITY AND IMPLEMENTATION: The web application is freely available at https://www.bio2byte.be/acpype/ and the open-source code can be found at https://github.com/alanwilter/acpype.

Association of ICD-10 Clinical Modification Codes for Social Determinants of Health with Surgical Outcomes and Hospital Charges Among Cancer Patients.

INTRODUCTION: We sought to characterize the impact of social determinants of health (SDOH)-related codes on outcomes among patients with a cancer diagnosis. METHODS: Patients diagnosed with lung, pancreas, colon, or rectal cancer between 2017 and 2020 were identified in the California Department of Healthcare Access and Information Patient Discharge Database. Data on concomitant SDOH-related codes (International Classification of Diseases, Tenth Revision [ICD-10] Z55-Z65) designating health hazards related to socioeconomic and psychosocial circumstances were obtained. The association of these SDOH codes with postoperative outcomes was evaluated. RESULTS: Among 10,421 patients who underwent an operation from 2017 to 2020, median age was 66 years (interquartile range [IQR] 56-75) and nearly half of the cohort was male (n = 551,252.9%). In total, 102 (1%) patients had a concurrent ICD-10 SDOH diagnosis. After controlling for competing risk factors, the risk-adjusted probability of in-hospital death was 4.1% (95% confidence interval [CI] 1.0-7.2) among patients with an SDOH diagnosis compared with 2.9% (95% CI 2.5-3.2) among patients without an SDOH diagnosis (odds ratio [OR] 1.52, 95% CI 0.63-3.66; p = 0.258); postoperative complications were 27.0% (95% CI 20.0-34.1) compared with 24.9% (95% CI 24.1-25.6) among patients without an SDOH diagnosis (OR 1.15, 95% CI 0.73-1.82; p = 0.141), and length of stay was 10.6 days (95% CI 10.0-11.2) compared with 9.4 days (95% CI 9.3-9.5) among patients without an SDOH diagnosis. Patients with an SDOH diagnosis had a 5.19 (95% CI 3.23-8.34; p < 0.005) higher odds of being discharged to a skilled nursing facility versus patients without an SDOH diagnosis. CONCLUSION: Uptake and utilization of ICD-10 SDOH was 1% among California patients with lung, pancreas, colon, or rectal cancer. Patients with a concomitant ICD-10 SDOH code had longer length of stay and had higher odds of being discharged to a skilled nursing facility.

Payer-Negotiated Price Variation and Relationship to Surgical Outcomes for the Most Common Cancers at NCI-Designated Cancer Centers.

BACKGROUND: Federal rules mandate that hospitals publish payer-specific negotiated prices for all services. Little is known about variation in payer-negotiated prices for surgical oncology services or their relationship to clinical outcomes. We assessed variation in payer-negotiated prices associated with surgical care for common cancers at National Cancer Institute (NCI)-designated cancer centers and determined the effect of increasing payer-negotiated prices on the odds of morbidity and mortality. MATERIALS AND METHODS: A cross-sectional analysis of 63 NCI-designated cancer center websites was employed to assess variation in payer-negotiated prices. A retrospective cohort study of 15,013 Medicare beneficiaries undergoing surgery for colon, pancreas, or lung cancers at an NCI-designated cancer center between 2014 and 2018 was conducted to determine the relationship between payer-negotiated prices and clinical outcomes. The primary outcome was the effect of median payer-negotiated price on odds of a composite outcome of 30 days mortality and serious postoperative complications for each cancer cohort. RESULTS: Within-center prices differed by up to 48.8-fold, and between-center prices differed by up to 675-fold after accounting for geographic variation in costs of providing care. Among the 15,013 patients discharged from 20 different NCI-designated cancer centers, the effect of normalized median payer-negotiated price on the composite outcome was clinically negligible, but statistically significantly positive for colon [aOR 1.0094 (95% CI 1.0051-1.0138)], lung [aOR 1.0145 (1.0083-1.0206)], and pancreas [aOR 1.0080 (1.0040-1.0120)] cancer cohorts. CONCLUSIONS: Payer-negotiated prices are statistically significantly but not clinically meaningfully related to morbidity and mortality for the surgical treatment of common cancers. Higher payer-negotiated prices are likely due to factors other than clinical quality.

Association Between Historical Redlining and Access to High-Volume Hospitals Among Patients Undergoing Complex Cancer Surgery in California.

BACKGROUND: We sought to determine the impact of historical redlining on travel patterns and utilization of high-volume hospitals (HVHs) among patients undergoing complex cancer operations. METHODS: The California Department of Health Care Access and Information database was utilized to identify patients who underwent esophagectomy (ES), pneumonectomy (PN), pancreatectomy (PA), or proctectomy (PR) for cancer between 2010 and 2020. Patient ZIP codes were assigned Home Owners' Loan Corporation grades (A: 'Best'; B: 'Still Desirable'; C: 'Definitely Declining'; and D: 'Hazardous/Redlined'). A clustered multivariable regression was used to assess the likelihood of patients undergoing surgery at an HVH, bypassing the nearest HVH, and total real driving time and travel distance. RESULTS: Among 14,944 patients undergoing high-risk cancer surgery (ES: 4.7%, n = 1216; PN: 57.8%, n = 8643; PD: 14.4%, n = 2154; PR: 23.1%, n = 3452), 782 (5.2%) individuals resided in the 'Best', whereas 3393 (22.7%) individuals resided in redlined areas. Median travel distance was 7.8 miles (interquartile range [IQR] 4.1-14.4) and travel time was 16.1 min (IQR 10.7-25.8). Overall, 10,763 (ES: 17.4%; PN: 76.0%; PA: 63.5%; PR: 78.4%) patients underwent surgery at an HVH. On multivariable regression, patients residing in redlined areas were less likely to undergo surgery at an HVH (odds ratio [OR] 0.67, 95% confidence interval [CI] 0.54-0.82) and were more likely to bypass the nearest hospital (OR 1.80, 95% CI 1.44-2.46). Notably, Medicaid insurance, minority status, limited English-language proficiency, and educational level mediated the disparities in access to HVH. CONCLUSION: Surgical disparities in access to HVH among patients from historically redlined areas are largely mediated by social determinants such as insurance and minority status.

Development of Neighborhood Trajectories Employing Historic Redlining and the Area Deprivation Index.

The role of historic residential redlining on health inequities is intertwined with policy changes made before and after the 1930s that influence current neighborhood characteristics and shape ongoing structural racism in the United States (U.S.). We developed Neighborhood Trajectories which combine historic redlining data and the current neighborhood socioeconomic characteristics as a novel approach to studying structural racism. Home Owners' Loan Corporation (HOLC) neighborhoods for the entire U.S. were used to map the HOLC grades to the 2020 U.S. Census block group polygons based on the percentage of HOLC areas in each block group. Each block group was also assigned an Area Deprivation Index (ADI) from the Neighborhood Atlas®. To evaluate changes in neighborhoods from historic HOLC grades to present degree of deprivation, we aggregated block groups into "Neighborhood Trajectories" using historic HOLC grades and current ADI. The Neighborhood Trajectories are "Advantage Stable"; "Advantage Reduced"; "Disadvantage Reduced"; and "Disadvantage Stable." Neighborhood Trajectories were established for 13.3% (32,152) of the block groups in the U.S., encompassing 38,005,799 people. Overall, the Disadvantage-Reduced trajectory had the largest population (16,307,217 people). However, the largest percentage of non-Hispanic/Latino Black residents (34%) fell in the Advantage-Reduced trajectory, while the largest percentage of Non-Hispanic/Latino White residents (60%) fell in the Advantage-Stable trajectory. The development of the Neighborhood Trajectories affords a more nuanced mechanism to investigate dynamic processes from historic policy, socioeconomic development, and ongoing marginalization. This adaptable methodology may enable investigation of ongoing sociopolitical processes including gentrification of neighborhoods (Disadvantage-Reduced trajectory) and "White flight" (Advantage Reduced trajectory).

Assessment of Mayaro virus vector competence of the mosquito Aedes aegypti (Linnaeus, 1762) populations in Argentine using dose-response assays.

Mayaro virus (MAYV; Alphavirus: Togaviridae) is an emerging pathogen in Latin America, causing fever and polyarthritis. Sporadic outbreaks of MAYV have occurred in the region, with reported human cases being imported to Europe and North America. Although primarily a risk for those residing in the Amazon basin's tropical forests, recent reports highlight that urbanization would increase the risk of MAYV transmission in Latin America. Urban emergence depends on human susceptibility and the ability of mosquitos like Aedes aegypti  (Linnaeus, 1762) (Diptera: Culicidae) to transmit MAYV. Despite the absence of active MAYV transmission in Argentine, the risk of introduction is substantial due to human movement and the presence of Ae. aegypti in the region. This study aimed to evaluate the susceptibility of different Argentine Ae. aegypti populations to MAYV genotype L (MAYV-L) using dose-response assays and determine barriers to virus infection, dissemination and transmission. Immature mosquito stages were collected in Buenos Aires, Córdoba and Rosario cities. Female Ae. aegypti (F2) were orally infected by feeding on five concentrations of MAYV-L, ranging from 1.0 to 6.0 log10 PFU/mL. Abdomens, legs and saliva were analysed using viral plaque assays. Results revealed that MAYV-L between infection and dissemination were associated with viral doses rather than the population origin. Infection rates varied between 3% and 65%, with a 50% infectious dose >5.5 log10 PFU/mL. Dissemination occurred at 39%, with a 50% dissemination dose of ~6.0 log10 PFU/mL. Dissemination among infected mosquitoes ranged from 60% to 86%, and transmission from disseminated mosquitoes ranged from 11% to 20%. Argentine Ae. aegypti populations exhibited a need for higher viral doses of MAYV-L than those typically found in humans to become infected. In addition, only a small proportion of infected mosquitoes were capable of transmitting the virus. Understanding MAYV transmission in urban areas is crucial for public health interventions.

Flow in temporally and spatially varying porous media: a model for transport of interstitial fluid in the brain.

Flow in a porous medium can be driven by the deformations of the boundaries of the porous domain. Such boundary deformations locally change the volume fraction accessible by the fluid, creating non-uniform porosity and permeability throughout the medium. In this work, we construct a deformation-driven porous medium transport model with spatially and temporally varying porosity and permeability that are dependent on the boundary deformations imposed on the medium. We use this model to study the transport of interstitial fluid along the basement membranes in the arterial walls of the brain. The basement membrane is modeled as a deforming annular porous channel with the compressible pore space filled with an incompressible, Newtonian fluid. The role of a forward propagating peristaltic heart pulse wave and a reverse smooth muscle contraction wave on the flow within the basement membranes is investigated. Our results identify combinations of wave amplitudes that can induce either forward or reverse transport along these transport pathways in the brain. The magnitude and direction of fluid transport predicted by our model can help in understanding the clearance of fluids and solutes along the Intramural Periarterial Drainage route and the pathology of cerebral amyloid angiopathy.

Diversity and molecular characterization of insect-specific flaviviruses in mosquitoes (Diptera: Culicidae) collected in central and northern Argentina.

The genus Flavivirus comprises approximately 80 different viruses. Phylogenetic relationships among its members indicate a clear ecological separation between those viruses transmitted by mosquitoes, ticks, with no known vector, and insect-specific Flaviviruses. The diversity and phylogenetic relationships among insect-specific flaviviruses circulating in the central and northern regions of Argentina were studied by performing molecular detection and characterization of the NS5 protein gene in mosquitoes collected in Córdoba, Chaco and Tucumán provinces. Overall, 68 out of 1776 pools were positive. CxFV, KRV and CFAV circulate in the 3 studied provinces. Several mosquito species (Aedes aegypti, Culex bidens, Cx. dolosus, Cx. interfor, Cx. quinquefasciatus, Cx. saltanensis, Haemagogus spegazzini) were found infected. A wide circulation of CxFV was observed in the central-northern region of Argentina. CxFV strains detected in our study clustered with strains circulating in Santa Fe and Buenos Aires provinces (Argentina), and other countries such as Indonesia, Mexico, Uganda and Taiwan. The presence of these viruses in mosquitoes could play an important role from the public health perspective, because it has been shown that previous CxFV infection can increase or block the infection of the mosquito by other pathogenic flaviviruses.

Fluorinated Man9 as a High Mannose Mimetic to Unravel Its Recognition by DC-SIGN Using NMR.

Lectins are capable of reading out the structural information contained in carbohydrates through specific recognition processes. Determining the binding epitope of the sugar is fundamental to understanding this recognition event. Nuclear magnetic resonance (NMR) is a powerful tool to obtain this structural information in solution; however, when the sugar involved is a complex oligosaccharide, such as high mannose, the signal overlap found in the NMR spectra precludes an accurate analysis of the interaction. The introduction of tags into these complex oligosaccharides could overcome these problems and facilitate NMR studies. Here, we show the preparation of the Man9 of high mannose with some fluorine tags and the study of the interaction with its receptor, dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin (DC-SIGN). This fluorinated ligand has allowed us to apply heteronuclear two-dimensional (2D) 1H,19F STD-TOCSYreF NMR experiments, using the initial slope approach, which has facilitated the analysis of the Man9/DC-SIGN interaction, unequivocally providing the binding epitope.

Association of Neighborhood Deprivation, Race, and Postoperative Outcomes: Improvement in Neighborhood Deprivation is Associated With Worsening Surgical Disparities.

INTRODUCTION: While there is a broad understanding that patient factors, hospital characteristics, and an individual's neighborhoods all contribute to the observed disparities, the relationship between these factors remains unclear. The purpose of this study was to evaluate the association of neighborhood deprivation improve postoperative outcomes for White and Black Medicare beneficiaries equally. METHODS: We performed a cross-sectional Retrospective cohort study from 2014 to 2018 of 1372,487 White and Black Medicare beneficiaries aged 65 and older who underwent an inpatient colon resection, coronary artery bypass, cholecystectomy, appendectomy, or incisional hernia repair. We compared postoperative complications, readmission, and mortality by race across neighborhood deprivation. Outcomes were risk-adjusted using a multivariable logistical regression model accounting for patient factors (age, sex, Elixhauser comorbidities), admission type (elective, urgent, emergency), type of operation, and each neighborhoods Area Deprivation Index; a modern-day measure of neighborhood disadvantage that includes education, employment, housing quality, and poverty measures. RESULTS: Overall, 1372,487 Medicare beneficiaries with mean age 72.1 years, 50.3% female, 91.2% White, residing in 1107,051 unique neighborhoods underwent 1 of 5 operations. The proportion of Black beneficiaries was 6.5% within the lowest deprivation neighborhoods and increased to 16.9% within the highest deprivation neighborhoods ( P <0.001). The interaction between beneficiary neighborhood and race demonstrated that the association of neighborhood on outcomes varied by race. Specifically, White beneficiaries had 1.5% absolute mortality decrease from the highest to lowest deprivation neighborhoods [odds ratio (OR):1.32, 95% confidence interval (CI): 1.27-1.38; P <0.001], whereas Black beneficiaries had a 0.72% absolute mortality decrease from the highest to lowest deprivation neighborhoods (OR: 1.13, 95% CI: 1.02-1.24; P =0.018). Similarly, White beneficiaries had 3.6% absolute decrease in complication rate from the highest to lowest deprivation neighborhoods (OR: 1.23, 95% CI: 1.21-1.28; P <0.001) while Black beneficiaries had a 1.2%% absolute decrease in complication rate from the highest to lowest deprivation neighborhoods (OR: 1.07, 95% CI: 1.01-1.13; P =0.017). For 30-day readmission rates, White beneficiaries realized a 2.3% absolute decrease from the highest to lowest deprivation neighborhoods (OR: 1.19, 95% CI: 1.02-1.24; P <0.001), whereas Black beneficiaries saw no change (OR: 1.03, 95% CI: 0.97-1.10; P =0.269). CONCLUSIONS AND RELEVANCE: Lower neighborhood deprivation is associated with improved outcomes across both White and Black Medicare beneficiaries; however, improvement in neighborhood deprivation disproportionately favored White beneficiaries. These findings provide a cautionary example of the misperception of the protective effect of higher social class for Black patients and provide a cautionary example that improvements in neighborhoods may have disparate health impact on its members.

Residential Redlining, Neighborhood Trajectory, and Equity of Breast and Colorectal Cancer Care.

OBJECTIVE: This study aimed to determine the influence of structural racism, vis-à-vis neighborhood socioeconomic trajectory, on colorectal and breast cancer diagnosis and treatment. SUMMARY BACKGROUND DATA: Inequities in cancer care are well documented in the United States but less is understood about how historical policies like residential redlining and evolving neighborhood characteristics influence current gaps in care. METHODS: This retrospective cohort study included adult patients diagnosed with colorectal or breast cancer between 2010 and 2015 in 7 Indiana cities with available historic redlining data. Current neighborhood socioeconomic status was determined by the Area Deprivation Index (ADI). Based on historic redlining maps and current ADI, we created four "Neighborhood Trajectory" categories: Advantage Stable, Advantage Reduced, Disadvantage Stable, Disadvantage Reduced. Modified Poisson regression models estimated the relative risks (RR) of Neighborhood Trajectory on cancer stage at diagnosis and receipt of cancer-directed surgery (CDS). RESULTS: A final cohort derivation identified 4,862 cancer patients with colorectal or breast cancer. Compared to Advantage Stable neighborhoods, Disadvantage Stable neighborhood was associated with late-stage diagnosis for both colorectal and breast cancer (RR=1.30 [95% CI=1.05 - 1.59]; RR=1.41 [1.09 - 1.83], respectively). Black patients had lower likelihood of receiving CDS in Disadvantage Reduced neighborhoods (RR=0.92 [0.86 - 0.99]) than White patients. CONCLUSIONS: Disadvantage Stable neighborhoods were associated with late-stage diagnosis for breast and colorectal cancer. Disadvantage Reduced (gentrified) neighborhoods were associated with racial-inequity in CDS. Improved neighborhood socioeconomic conditions may improve timely diagnosis but could contribute to racial inequities in surgical treatment.

Surgical Leadership Competencies for Navigating Hospital Network Expansion.

INTRODUCTION: Today, many hospitals are part of a multihospital network, which changes the context in which surgeons are asked to lead. This study explores key leadership competencies that surgical leaders use to navigate this hospital network expansion. METHODS: In this qualitative study, 30 surgical leaders were interviewed. Interviews were coded and analyzed via thematic analysis. RESULTS: We identified three key competencies that leaders felt were important leadership skills to successfully navigate expanding hospital networks. First, leaders must steer the departmental vision within the evolving hospital network landscape. Second, leaders must align the visions of the department and of the hospital network. Third, leaders must build a network-oriented culture within their department. CONCLUSIONS: As networks expand, leaders are tasked with unifying vision in their department. Leaders identified a unique opportunity to leverage their growing influence across the hospital network and invested in the people and culture of their department.

The Association of Persistent Poverty and Outcomes Among Patients Undergoing Cardiac Surgery.

INTRODUCTION: We sought to evaluate the association of county-level poverty duration and cardiac surgical outcomes. METHODS: Patients who underwent coronary artery bypass graft, surgical aortic valve replacement, and mitral valve repair and replacement between 2016 and 2020 were identified using the Medicare Standard Analytical Files Database. County-level poverty data were acquired from the American Community Survey and US Department of Agriculture (1980-2015). High poverty was defined as ≥19.5% of residents in poverty. Patients were stratified into never-high poverty (NHP), intermittent low poverty, intermittent high poverty, and persistent poverty (PP). A mixed-effect hierarchical generalized linear model and Cox regression models that adjusted for patient-level covariates were used to evaluate outcomes. RESULTS: Among 237,230 patients, 190,659 lived in NHP counties, while 10,273 resided in PP counties. Compared with NHP patients, PP patients were more likely to present at a younger median age (NHP: 75 y versus PP: 74 y), be non-Hispanic Black (5388, 2.9% versus PP: 1030, 10.1%), and live in the south (NHP: 66,012, 34.6% versus PP: 87,815, 76.1%) (all P < 0.001). PP patients also had more nonelective surgical operations (NHP: 58,490, 30.8% versus 3645, 35.6%, P < 0.001). Notably, PP patients had increased odds of 30-d mortality (odds ratio 1.13, 95% confidence interval [CI] 1.02-1.26), 90-d mortality (odds ratio 1.14, 95% CI 1.05-1.24), and risk of long-term mortality (hazard ratio 1.13, 95% CI 1.09-1.19) compared with patients in NHP counties (all P < 0.05). CONCLUSIONS: County-level poverty was associated with a greater risk of short- and long-term mortality among cardiac surgical patients.

Association Between California's State Insurance Gender Nondiscrimination Act and Utilization of Gender-Affirming Surgery.

Importance: Gender-affirming surgery is often beneficial for gender-diverse or -dysphoric patients. Access to gender-affirming surgery is often limited through restrictive legislation and insurance policies. Objective: To investigate the association between California's 2013 implementation of the Insurance Gender Nondiscrimination Act, which prohibits insurers and health plans from limiting benefits based on a patient's sex, gender, gender identity, or gender expression, and utilization of gender-affirming surgery among California residents. Design, Setting, and Participants: Population epidemiology study of transgender and gender-diverse patients undergoing gender-affirming surgery (facial, chest, and genital surgery) between 2005 and 2019. Utilization of gender-affirming surgery in California before and after implementation of the Insurance Gender Nondiscrimination Act in July 2013 was compared with utilization in Washington and Arizona, control states chosen because of geographic similarity and because they expanded Medicaid on the same date as California-January 1, 2014. The date of last follow-up was December 31, 2019. Exposures: California's Insurance Gender Nondiscrimination Act, implemented on July 9, 2013. Main Outcomes and Measures: Receipt of gender-affirming surgery, defined as undergoing at least 1 facial, chest, or genital procedure. Results: A total of 25 252 patients (California: n = 17 934 [71%]; control: n = 7328 [29%]) had a diagnosis of gender dysphoria. Median ages were 34.0 years in California (with or without gender-affirming surgery), 39 years (IQR, 28-49 years) among those undergoing gender-affirming surgery in control states, and 36 years (IQR, 22-56 years) among those not undergoing gender-affirming surgery in control states. Patients underwent at least 1 gender-affirming surgery within the study period in 2918 (11.6%) admissions-2715 (15.1%) in California vs 203 (2.8%) in control states. There was a statistically significant increase in gender-affirming surgery in the third quarter of July 2013 in California vs control states, coinciding with the timing of the Insurance Gender Nondiscrimination Act (P < .001). Implementation of the policy was associated with an absolute 12.1% (95% CI, 10.3%-13.9%; P < .001) increase in the probability of undergoing gender-affirming surgery in California vs control states observed in the subset of insured patients (13.4% [95% CI, 11.5%-15.4%]; P < .001) but not self-pay patients (-22.6% [95% CI, -32.8% to -12.5%]; P < .001). Conclusions and Relevance: Implementation in California of its Insurance Gender Nondiscrimination Act was associated with a significant increase in utilization of gender-affirming surgery in California compared with the control states Washington and Arizona. These data might inform state legislative efforts to craft policies preventing discrimination in health coverage for state residents, including transgender and gender-diverse patients.

Molecular Studies for the Early Detection of Philadelphia-Negative Myeloproliferative Neoplasms.

JAK2 V617F is the predominant driver mutation in patients with Philadelphia-negative myeloproliferative neoplasms (MPN). JAK2 mutations are also frequent in clonal hematopoiesis of indeterminate potential (CHIP) in otherwise "healthy" individuals. However, the period between mutation acquisition and MPN diagnosis (known as latency) varies widely between individuals, with JAK2 mutations detectable several decades before diagnosis and even from birth in some individuals. Here, we will review the current evidence on the biological factors, such as additional mutations and chronic inflammation, which influence clonal expansion and may determine why some JAK2-mutated individuals will progress to an overt neoplasm during their lifetime while others will not. We will also introduce several germline variants that predispose individuals to CHIP (as well as MPN) identified from genome-wide association studies. Finally, we will explore possible mutation screening or interventions that could help to minimize MPN-associated cardiovascular complications or even delay malignant progression.

Effect of Agroecosystems on Seroprevalence of St. Louis Encephalitis and West Nile Viruses in Birds, La Pampa, Argentina, 2017-2019.

In Argentina, the Pampa ecoregion has been almost completely transformed into agroecosystems. To evaluate the environmental (agricultural area, tree coverage, distance to the nearest water body and urban site) and biological (dove, cowbird, and sparrow abundance) effects on free-ranging bird exposure to St. Louis encephalitis virus (SLEV) and West Nile virus (WNV), we used generalized linear mixed models. For 1,019 birds sampled during 2017-2019, neutralizing antibodies were found against SLEV in samples from 60 (5.8%) birds and against WNV for 21 (2.1%). The best variable for explaining SLEV seroprevalence was agricultural area, which had a positive effect; however, for WNV, no model was conclusive. Our results suggest that agroecosystems in the La Pampa ecoregion increase the exposure of avian hosts to SLEV, thus potentially increasing virus activity.

Variation in Surgical Spending Among the Highest Quality Hospitals for Cancer Surgery.

OBJECTIVE: This study evaluates the variation in spending by the highest-quality hospitals performing complex cancer surgery in the United States. SUMMARY BACKGROUND DATA: As mortality rates for high-risk cancer surgery have improved, increased attention has focused on other elements of quality, such as complications. However, high-value surgical care requires both high-quality care and cost savings. Therefore, understanding any residual cost variation among high-quality hospitals is essential to better direct efforts to achieve efficient, high-value care. METHODS: Medicare beneficiaries age 65 to 99 who underwent surgery for pancreas, esophageal, lung, rectal, and colon cancer from 2014 to 2016 were identified. The highest-quality hospitals were identified as those in the quintile with the lowest risk- and reliability-adjusted serious complication rates for each operation. Within this cohort of high-quality hospitals, 30-day total episode, index hospitalization, physician, postacute care, and readmis-sion spending were analyzed. Logistic regression models were utilized to estimate the probability of postoperative outcomes and post-discharge resource utilization. RESULTS: A total of 43,007 Medicare patients underwent either pancreas, esophageal, lung, rectal, or colon resection for cancer at a hospital within the highest-quality quintile. Among the highest quality hospitals, total episode spending ranged from $18,712 for colectomy to $38,054 for esophagectomy. Spending between the lowest- and highest spending hospitals varied from $1207 [confidence intervals (CI 95% ) $1195-$1220] or 6.6% of total episode spending in the lowest tertile for colectomy to $5706 (CI 95% $5,506-$5906) or 16.1% of total episode spending in the lowest tertile for esophagectomy. The largest component of variation was from postacute care spending followed by readmission. For all operations, the risk-adjusted rate of postacute care facility utilization was lower among the lowest spending hospitals compared to the highest spending hospitals. For example, for pancreas the lowest-spending hospitals on average discharged patients to a postacute care facility at a rate of 18,6% (CI 95% 16.2-20.9) compared to 31.0% (CI 95% 28.2-33.9) in the highest-spending hospitals. In all operations, the risk-adjusted readmission rate was lower among the lowest-spending hospitals compared to the highest-spending hospitals. For instance, within the esophagus cohort, the lowest-spending hospitals had an average risk-adjusted readmission rate of 17.3% compared to 29.4% in the highest spending hospitals ( P < .001). CONCLUSIONS AND RELEVANCE: Even among the highest-quality hospitals, significant cost variation persists among cancer operations. Postacute care variation, rather than residual variation in complication rates, explains the majority of this variation and represents an immediately actionable target for increased cost-efficiency.

Challenges and Opportunities for the Academic Mission Within Expanding Health Systems: A Qualitative Study.

OBJECTIVE: To explore challenges and opportunities for surgery departments' academic missions as they become increasingly affiliated with expanding health systems. SUMMARY BACKGROUND DATA: Academic medicine is in the midst of unprecedented change. In addition to facing intense competition, narrower margins, and decreased federal funding, medical schools are becoming increasingly involved with large, expanding health systems. The impact of these health system affiliations on surgical departments' academic missions is unknown. METHODS: Semistructured interviews with 30 surgical leaders at teaching hospitals affiliated with health systems from August - December 2019. Interviews were transcribed verbatim and coded in an iterative process using MaxQDA software. The topic of challenges and opportunities for the academic mission was an emergent theme, analyzed using thematic analysis. RESULTS: Academic health systems typically expanded to support their business goals, rather than their academic mission. Changes in governance sometimes disempowered departmental leadership, shifted traditional compensation models, redirected research programs, and led to cultural conflict. However, at many institutions, health system growth cross-subsidized surgical departments' research and training missions, expanded their clinical footprint, enabled them to improve standards of care, and enhanced opportunities for researchers and trainees. CONCLUSIONS: Although health system expansion generally intended to advance business goals, the accompanying academic and clinical opportunities were not always fully captured. Alignment between medical school and health system goals enabled some surgical department leaders to take advantage of their health systems' reach and resources to support their academic missions.