Cdc73 protects Notch-induced T-cell leukemia cells from DNA damage and mitochondrial stress.

ABSTRACT: Activated Notch signaling is highly prevalent in T-cell acute lymphoblastic leukemia (T-ALL), but pan-Notch inhibitors showed excessive toxicity in clinical trials. To find alternative ways to target Notch signals, we investigated cell division cycle 73 (Cdc73), which is a Notch cofactor and key component of the RNA polymerase-associated transcriptional machinery, an emerging target in T-ALL. Although we confirmed previous work that CDC73 interacts with NOTCH1, we also found that the interaction in T-ALL was context-dependent and facilitated by the transcription factor ETS1. Using mouse models, we showed that Cdc73 is important for Notch-induced T-cell development and T-ALL maintenance. Mechanistically, chromatin and nascent gene expression profiling showed that Cdc73 intersects with Ets1 and Notch at chromatin within enhancers to activate expression of known T-ALL oncogenes through its enhancer functions. Cdc73 also intersects with these factors within promoters to activate transcription of genes that are important for DNA repair and oxidative phosphorylation through its gene body functions. Consistently, Cdc73 deletion induced DNA damage and apoptosis and impaired mitochondrial function. The CDC73-induced DNA repair expression program co-opted by NOTCH1 is more highly expressed in T-ALL than in any other cancer. These data suggest that Cdc73 might induce a gene expression program that was eventually intersected and hijacked by oncogenic Notch to augment proliferation and mitigate the genotoxic and metabolic stresses of elevated Notch signaling. Our report supports studying factors such as CDC73 that intersect with Notch to derive a basic scientific understanding on how to combat Notch-dependent cancers without directly targeting the Notch complex.

Unplanned Surgery in Dually Eligible Beneficiaries for Conditions that Should Be Treated Electively.

OBJECTIVE: To evaluate the rate of unplanned surgery among dually eligible beneficiaries for surgical conditions that should be treated electively. SUMMARY BACKGROUND DATA: Access-sensitive surgical conditions (e.g. abdominal aortic aneurysm repair, colectomy for colon cancer, ventral hernia repair) are ideally treated with elective surgery, but when left untreated have a natural history leading to unplanned surgery. Dually eligible beneficiaries may face systematic barriers to access surgical care. METHODS: Cross-sectional retrospective study of all beneficiaries who were eligible for both Medicare and Medicaid, and underwent surgery for an access-sensitive surgical condition between 2016-2020. We compared the rate of unplanned surgery as well as 30-day mortality, complications and readmissions for dually eligible versus non-dually eligible beneficiaries. Sex, age, race/ethnicity, comorbidities, teaching status, nursing ratio, hospital region and bed size and surgery year were included in the risk-adjustment model. RESULTS: Out of 853,500 beneficiaries, 118,812 were dually eligible with an average age (SD) of 75.2(7.7) years. Compared to non-dually eligible beneficiaries, dually eligible beneficiaries had a higher rates of unplanned surgery for access-sensitive surgical conditions (45.1% vs. 31.8%, P<0.001), 30-day mortality (2.9% vs. 2.6%, aOR=1.10 (1.07-1.14), P<0.001), complications (23.6% vs. 20.1%, aOR=1.23 (1.20-1.25), P<0.001), and 30-day readmissions (15.5% vs. 12.9%, aOR=1.24 (1.22-1.27), P<0.001). These differences narrowed significantly when evaluating elective procedures only. CONCLUSIONS: Dually eligible beneficiaries were more likely to undergo unplanned surgery for access-sensitive surgical conditions, leading to worse rates of mortality, complications and readmissions. Our findings suggest that improving rates of elective surgery for these conditions represents an actionable target to narrow the difference in post-operative outcomes between dually eligible and non-dually eligible beneficiaries.

Rate of Emergency Lower Extremity Amputations in the United States Among Medicare Beneficiaries.

OBJECTIVE: To determine the rate of emergency versus elective lower extremity amputations in the United States. BACKGROUND: Lower extremity amputation is a common endpoint for patients with poorly controlled diabetes and multilevel peripheral vascular disease. Although the procedure is ideally performed electively, patients with limited access may present later and require an emergency operation. To what extent rates of emergency amputation for lower extremities vary across the United States is unknown. METHODS: Evaluation of Medicare beneficiaries who underwent lower extremity amputation between 2015 and 2020. The rate was determined for each zip code and placed into rank order from lowest to highest rate. We merged each beneficiary's place of residence and location of care with the American Hospital Association Annual Survey using Google Maps Application Programming Interface to determine the travel distance for patients to undergo their procedure. RESULTS: Of 233,084 patients, 66.3% (154,597) were men, 69.8% (162,786) were White. The average age (SD) was 74 years (8). There was wide variation in rates of emergency lower extremity amputation. The lowest quintile of zip codes demonstrated an emergency amputation rate of 3.7%, whereas the highest quintile demonstrated 90%. The median travel distance in the lowest emergency surgery rate quintile was 34.6 miles compared with 10.5 miles in the highest quintile of emergency surgery ( P < 0.001). CONCLUSIONS: There is wide variation in the rate of emergency lower extremity amputations among Medicare beneficiaries, suggesting variable access to essential vascular care. Travel distance and rate of amputation have an inverse relationship, suggesting that barriers other than travel distance are playing a role.

Association of Health Professional Shortage Area Hospital Designation With Surgical Outcomes and Expenditures Among Medicare Beneficiaries.

OBJECTIVE: To compare surgical outcomes and expenditures at hospitals located in Health Professional Shortage Areas to nonshortage area designated hospitals among Medicare beneficiaries. BACKGROUND: More than a quarter of Americans live in federally designated Health Professional Shortage Areas. Although there is growing concern that medical outcomes may be worse, far less is known about hospitals providing surgical care in these areas. METHODS: Cross-sectional retrospective study from 2014 to 2018 of 842,787 Medicare beneficiary patient admissions to hospitals with and without Health Professional Shortage Area designations for common operations including appendectomy, cholecystectomy, colectomy, and hernia repair. We assessed risk-adjusted outcomes using multivariable logistic regression accounting for patient factors, admission type, and year were compared for each of the 4 operations. Hospital expenditures were price-standardized, risk-adjusted 30-day surgical episode payments. Primary outcome measures included 30-day mortality, hospital readmissions, and 30-day surgical episode payments. RESULTS: Patients (mean age=75.6 years, males=44.4%) undergoing common surgical procedures in shortage area hospitals were less likely to be White (84.6% vs 88.4%, P <0.001) and less likely to have≥2 Elixhauser comorbidities (75.5% vs 78.2%, P <0.001). Patients undergoing surgery at Health Professional Shortage Area hospitals had lower risk-adjusted rates of 30-day mortality (6.05% vs 6.69%, odds ratio=0.90, CI, 0.90-0.91, P <0.001) and readmission (14.99% vs 15.74%, odds ratio=0.94, CI, 0.94-0.95, P <0.001). Medicare expenditures at Health Professional Shortage Area hospitals were also lower than nonshortage designated hospitals ($28,517 vs $29,685, difference= -$1168, P <0.001). CONCLUSIONS: Patients presenting to Health Professional Shortage Area hospitals obtain safe care for common surgical procedures without evidence of higher expenditures among Medicare beneficiaries. These findings should be taken into account as current legislative proposals to increase funding for care in these underserved communities are considered.

Surgical Procedures at Critical Access Hospitals Within Hospital Networks.

OBJECTIVE: To compare surgical outcomes and expenditures at critical access hospitals that do versus do not participate in a hospital network among Medicare beneficiaries. BACKGROUND: Critical access hospitals provide essential care to more than 80 million Americans. These hospitals, often rural, are located more than 35 miles away from another hospital and are required to maintain patient transfer agreements with other facilities capable of providing higher levels of care. Some critical access hospitals have gone further to formally participate in a hospital network. METHODS: This was a cross-sectional retrospective study from 2014 to 2018 comparing 16,128 Medicare beneficiary admissions for appendectomy, cholecystectomy, colectomy, or hernia repair at critical access hospitals that do versus do not participate in a hospital network. Thirty-day mortality and readmissions were risk adjusted using multivariable logistic regression accounting for patient and hospital factors. Price-standardized, risk-adjusted Medicare expenditures were compared for the 30-day total episode payments consisting of index hospitalization, physician services, readmissions, and postacute care payments. RESULTS: Beneficiaries (average age = 75.7 years, SD = 7.4) who obtained care at critical access hospitals in a hospital network were more likely to carry ≥2 Elixhauser comorbidities (68.7% vs. 62.8%, P < 0.001). Rates of 30-day mortality were higher at critical access hospitals in a hospital network (4.30% vs. 3.81%, OR = 1.11, P < 0.001). Similarly, readmission rates were higher at critical access hospitals that were in a hospital network (15.13% vs. 14.34%, OR = 1.06, P < 0.001). Additionally, total episode payments were found to be $960 higher per patient at critical access hospitals that were in a hospital network ($23,878 vs. $22,918, P < 0.001). CONCLUSIONS: Critical access hospitals within hospital networks provided care to more medically complex patients and were associated with worse clinical outcomes and higher costs among Medicare beneficiaries undergoing common general surgery operations.

Coronary Artery Bypass Surgery Among Medicare Beneficiaries in Health Professional Shortage Areas.

OBJECTIVE: Health professional shortage areas (HPSAs) were created by the Health Resources and Services Administration to identify communities with a shortage of clinical providers. For medical conditions, these designations are associated with worse outcomes. However, far less is known about patients undergoing high-complexity surgical procedures, such as coronary artery bypass grafting (CABG). BACKGROUND: The aim was to compare postoperative surgical outcomes of high-complexity surgery in beneficiaries living in HPSA versus non-HPSA designated areas. METHODS: This study is a retrospective cohort review of Medicare beneficiaries who underwent CABG between 2014 and 2018. The authors compared risk-adjusted 30-day mortality, complication, reoperation, and readmission rates for beneficiaries living in a designated HPSA versus non-HPSA using a multivariable logistic regression model accounting for patient (eg, age, sex, comorbidities, surgery year) and hospital characteristics (eg, patient-to-nurse ratio, teaching status). Patient travel burden was measured based on the time and distance required to travel from the beneficiary's home zip code to the hospital zip code. RESULTS: Of the 370,532 Medicare beneficiaries who underwent CABG, 30,881 (8.3%) lived in a HPSA. Beneficiaries in HPSAs were found to experience comparable 30-day mortality (3.50% vs. 3.65%, P <0.001), complication (32.67% vs. 33.54%, P <0.001), reoperation (1.58% vs. 1.66%, P <0.001), and readmission (14.72% vs. 14.86%, P <0.001) rates. Beneficiaries experienced greater mean travel times (91.2 vs. 64.0 minutes, P <0.001) and mean travel distances (85.0 vs. 59.3 miles, P <0.001). CONCLUSIONS: Medicare beneficiaries living in designated HPSA experienced comparable surgical outcomes after CABG surgery but a significantly greater travel burden. The greater travel burden experienced by patients living in designated shortage areas to obtain comparable surgical care for complex procedures demonstrates important tradeoffs between access and quality.

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.

Emergency Surgery Rates Among Medicare Beneficiaries With Access Sensitive Surgical Conditions.

INTRODUCTION: Access sensitive surgical conditions should be treated electively with optimal access but result in emergency operations when access is limited. However, the rates of emergency procedures for these conditions are unknown. METHODS: Cross-sectional retrospective review of Medicare beneficiaries who underwent access sensitive surgical procedures (abdominal aortic aneurysm repair, colectomy for colorectal cancer, or incisional hernia repair) between 2014 and 2018. Risk-adjusted outcomes using a multivariable logistical regression that adjusted for patient factors (age, sex, race, and Elixhauser comorbidities), hospital characteristics (ownership, size, geographic region, surgical volume) and type of operation were compared between planned and emergency (urgent and emergent) surgical procedures. Outcome measures were rates of emergency procedures as well as associated postoperative outcomes. RESULTS: Of the 744,818 Medicare beneficiaries undergoing access sensitive surgical procedures, 259,541 (34.9%) were done in the emergency setting. Risk-adjusted rates of emergency surgery varied widely across hospital service areas from 23.28% (lowest decile) to 54.88% (highest decile) (Odds Ratio 4.74; P < 0.001). Emergency procedures were associated with significantly higher rates of 30-d mortality (8.15% versus 3.65%, P < 0.001) and readmissions (16.28% versus 12.88%, P < 0.001) compared to elective procedures. Sensitivity analysis with younger and healthier beneficiaries demonstrated persistently high rates (23.3%) of emergency surgery with wide regional variation and worse patient outcomes. CONCLUSIONS: Emergency surgery for access sensitive surgical conditions is extremely common and varied almost fivefold across United States hospital service areas. This suggests there are opportunities to improve access for these common surgical conditions.

Variation in Postoperative Outcomes Across Federally Designated Hospital Star Ratings.

Importance: Despite widespread use to guide patients to hospitals providing the best care, it remains unknown whether Centers for Medicare & Medicaid Services (CMS) hospital star ratings are a reliable measure of hospital surgical quality. Objective: To examine the CMS hospital star ratings and hospital surgical quality measured by 30-day postoperative mortality, serious complications, and readmission rates for Medicare beneficiaries undergoing colectomy, coronary artery bypass graft, cholecystectomy, appendectomy, and incisional hernia repair. Design, Setting, and Participants: This cohort study evaluated 100% Medicare administrative claims for nonfederal acute care hospitals with a CMS hospital star rating for calendar years 2014-2018. Data analysis was performed from January 15, 2022, to April 30, 2023. Participants included fee-for-service Medicare beneficiaries aged 66 to 99 years who underwent colectomy, coronary artery bypass graft, cholecystectomy, appendectomy, or incisional hernia repair with continuous Medicare coverage for 3 months before and 6 months after surgery. Exposure: Centers for Medicare & Medicaid Services hospital star rating. Main Outcomes and Measures: Risk- and reliability-adjusted hospital rates of 30-day postoperative mortality, serious complications, and 30-day readmissions were measured and compared across hospitals and star ratings. Results: A total of 1 898 829 patients underwent colectomy, coronary artery bypass graft, cholecystectomy, appendectomy, or incisional hernia repair at 3240 hospitals with a CMS hospital star rating. Mean (SD) age was 74.8 (7.0) years, 50.6% of the patients were male, and 86.5% identified as White. Risk- and reliability-adjusted 30-day mortality rate decreased in a stepwise fashion from 6.80% (95% CI, 6.79%-6.81%) in 1-star hospitals to 4.93% (95% CI, 4.93%-4.94%) in 5-star hospitals (adjusted odds ratio, 1.86; 95% CI, 1.73-2.00). There was wide variation in the rates of hospital mortality (variation, 1.89%; range, 2.4%-16.2%), serious complications (variation, 1.97%; range, 5.5%-45.1%), and readmission (variation, 1.27%; range, 9.1%-22.5%) across all hospitals. After stratifying hospitals by their star rating, similar patterns of variation were observed within star rating groups for 30-day mortality: 1 star (variation, 1.91%; range, 3.6%-12.0%), 2 star (variation, 1.86%; range, 2.8%-16.2%), 3 star (variation, 1.84%; range, 2.9%-12.3%), 4 star (variation, 1.76%; range, 2.9%-11.5%), and 5 star (variation, 1.79%; range, 2.4%-9.1%). Similar patterns were observed for serious complications and readmissions. Conclusion and Relevance: Although CMS hospital star rating was associated with postoperative mortality, serious complications, and readmissions, there was wide variation in surgical outcomes within each star rating group. These findings highlight the limitations of the CMS hospital star rating system as a measure of surgical quality and should be a call for continued improvement of publicly reported hospital grade measures.

Health Insurance Status and Unplanned Surgery for Access-Sensitive Surgical Conditions.

Importance: Access-sensitive surgical conditions, such as abdominal aortic aneurysm, ventral hernia, and colon cancer, are ideally treated with elective surgery, but when left untreated have a natural history requiring an unplanned operation. Patients' health insurance status may be a barrier to receiving timely elective care, which may be associated with higher rates of unplanned surgery and worse outcomes. Objective: To evaluate the association between patients' insurance status and rates of unplanned surgery for these 3 access-sensitive surgical conditions and postoperative outcomes. Design, Setting, and Participants: This cross-sectional cohort study examined a geographically broad patient sample from the Healthcare Cost and Utilization Project State Inpatient Databases, including data from 8 states (Arizona, Colorado, Florida, Kentucky, Maryland, North Carolina, Washington, and Wisconsin). Participants were younger than 65 years who underwent abdominal aortic aneurysm repair, ventral hernia repair, or colectomy for colon cancer between 2016 and 2020. Patients were stratified into groups by insurance status. Data were analyzed from June 1 to July 1, 2023. Exposure: Health insurance status (private insurance, Medicaid, or no insurance). Main Outcomes and Measures: The primary outcome was the rate of unplanned surgery for these 3 access-sensitive conditions. Secondary outcomes were rates of postoperative outcomes including inpatient mortality, any hospital complications, serious complications (a complication with a hospital length of stay longer than the 75th percentile for that procedure), and hospital length of stay. Results: The study included 146 609 patients (mean [SD] age, 50.9 [10.3] years; 73 871 females [50.4%]). A total of 89 018 patients (60.7%) underwent elective surgery while 57 591 (39.3%) underwent unplanned surgery. Unplanned surgery rates varied significantly across insurance types (33.14% for patients with private insurance, 51.46% for those with Medicaid, and 72.60% for those without insurance; P < .001). Compared with patients with private insurance, patients without insurance had higher rates of inpatient mortality (1.29% [95% CI, 1.04%-1.54%] vs 0.61% [0.57%-0.66%]; P < .001), higher rates of any complications (19.19% [95% CI, 18.33%-20.05%] vs 12.27% [95% CI, 12.07%-12.47%]; P < .001), and longer hospital stays (7.27 [95% CI, 7.09-7.44] days vs 5.56 [95% CI, 5.53-5.60] days, P < .001). Conclusions and Relevance: Findings of this cohort study suggest that uninsured patients more often undergo unplanned surgery for conditions that can be treated electively, with worse outcomes and longer hospital stays compared with their counterparts with private health insurance. As efforts are made to improve insurance coverage, tracking elective vs unplanned surgery rates for access-sensitive surgical conditions may be a useful measure to assess progress.

Higher Rates Of Emergency Surgery, Serious Complications, And Readmissions In Primary Care Shortage Areas, 2015-19.

Primary care physicians are often the first to screen and identify patients with access-sensitive surgical conditions that should be treated electively. These conditions require surgery that is preferably planned (elective), but, when access is limited, treatment may be delayed and worsening symptoms lead to emergency surgery (for example, colectomy for cancer, abdominal aortic aneurysm repair, and incisional hernia repair). We evaluated the rates of elective versus emergency surgery for patients with three access-sensitive surgical conditions living in primary care Health Professional Shortage Areas during 2015-19. Medicare beneficiaries in more severe primary care shortage areas had higher rates of emergency surgery compared with rates in the least severe shortage areas (37.8 percent versus 29.9 percent). They were also more likely to have serious complications (14.9 percent versus 11.7 percent) and readmissions (15.7 percent versus 13.5 percent). When we accounted for areas with a shortage of surgeons, the findings were similar. Taken together, these findings suggest that residents of areas with greater primary care workforce shortages may also face challenges in accessing elective surgical care. As policy makers consider investing in Health Professional Shortage Areas, our findings underscore the importance of primary care access to a broader range of services.

Association of National Accreditation Program for Rectal Cancer Accreditation with Outcomes after Rectal Cancer Surgery.

BACKGROUND: The National Accreditation Program for Rectal Cancer (NAPRC) defined a set of standards in 2017 centered on multidisciplinary program structure, evidence-based care processes, and internal audit to address widely variable rectal cancer practices and outcomes across U.S. hospitals. There have been no studies to-date testing the association between NAPRC accreditation and rectal cancer outcomes. STUDY DESIGN: This was a retrospective, observational study of Medicare beneficiaries aged 65-99 years with rectal cancer who underwent proctectomy from 2017-2020. The primary exposure was NAPRC accreditation and the primary outcomes included mortality (in-hospital, 30-day, 1-year) and 30-day complications, readmissions, and reoperations. Associations between NAPRC accreditation and each outcome were tested using multivariable logistic regression with risk-adjustment for patient and hospital characteristics. RESULTS: Among 1,985 hospitals, 65 were NAPRC accredited (3.3%). Accredited hospitals were more likely to be nonprofit and teaching with ≥ 250 beds. Among 20,202 patients, 2,078 patients (10%) underwent proctectomy at an accredited hospital. Patients at accredited hospitals were more likely to have an elective procedure with a minimally invasive approach and sphincter preservation. Risk-adjusted in-hospital mortality (1.1% vs. 1.3%; p=0.002), 30-day mortality (2.1% vs. 2.9%; p<0.001), 30-day complication (18.3% vs. 19.4%; p=0.01), and 1-year mortality rates (11.0% vs. 12.1%; p<0.001) were significantly lower at accredited compared to non-accredited hospitals. CONCLUSIONS: NAPRC accredited hospitals have lower risk-adjusted morbidity and mortality for major rectal cancer surgery. Although NAPRC standards address variability in practice, without directly addressing surgical safety, our findings suggest that NAPRC accredited hospitals may provide higher quality surgical care.

High-risk surgery among Medicare beneficiaries living in health professional shortage areas.

PURPOSE: Americans who reside in health professional shortage areas currently have less than half of the needed physician workforce. While the shortage designation has been associated with poor outcomes for chronic medical conditions, far less is known about outcomes after high-risk surgical procedures. METHODS: We performed a retrospective review of Medicare beneficiaries living in health professional shortage areas and nonshortage areas who underwent abdominal aortic aneurysm repair, coronary artery bypass graft, esophagectomy, liver resection, pancreatectomy, or rectal resection between 2014 and 2018. Risk-adjusted multivariable logistic regression was used to determine whether rates of postoperative complications and 30-day mortality differed between patient cohorts. Beneficiary and hospital ZIP codes were used to quantify travel time to obtain care. FINDINGS: Compared with patients living in nonshortage areas, patients living in health professional shortage areas traveled longer (median 60.0 vs 28.0 minutes, P<.001). There were no differences in risk-adjusted rates of complications (28.5% vs 28.6%, OR = 1.00, 95% CI 1.00-1.00, P = .59) and small differences in rates of 30-day mortality (4.2% vs 4.4%, OR = 0.95, 95% CI 0.95-0.95, P<.001) between beneficiaries living in shortage areas versus those not in shortage areas, respectively. CONCLUSIONS: Patients living in health professional shortage area undergoing high-risk surgery traveled more than 2 times longer for their care to obtain similar outcomes. While reassuring for clinical outcomes, additional efforts may be needed to mitigate the travel burden experienced by shortage area patients.

Outcomes for High-Risk Surgical Procedures Across High- and Low-Competition Hospital Markets.

Importance: Maintaining competition among hospitals is increasingly seen as important to achieving high-quality outcomes. Whether or not there is an association between hospital market competition and outcomes after high-risk surgery is unknown. Objective: To evaluate whether there is an association between hospital market competition and outcomes after high-risk surgery. Design, Setting, and Participants: We performed a retrospective study of Medicare beneficiaries who received care in US hospitals. Participants were 65 years and older who electively underwent 1 of 10 high-risk surgical procedures from 2015 to 2018: carotid endarterectomy, mitral valve repair, open aortic aneurysm repair, lung resection, esophagectomy, pancreatectomy, rectal resection, hip replacement, knee replacement, and bariatric surgery. Hospitals were categorized into high-competition and low-competition markets based on the hospital market Herfindahl-Hirschman index. Comparisons of 30-day mortality and 30-day readmissions were risk-adjusted using a multivariate logistic regression model adjusting for patient factors (age, sex, comorbidities, and dual eligibility), year of procedure, and hospital characteristics (nurse ratio and teaching status). Data were analyzed from May 2022 to March 2023. Main Outcomes and Measures: Thirty-day postoperative mortality and readmissions. Results: A total of 2 242 438 Medicare beneficiaries were included in the study. The mean (SD) age of the cohort was 74.1 (6.4) years, 1 328 946 were women (59.3%), and 913 492 were men (40.7%). When examined by procedure, compared with low-competition hospitals, high-competition market hospitals demonstrated higher 30-day mortality for 2 of 10 procedures (mitral valve repair: odds ratio [OR], 1.11; 95% CI, 1.07-1.14; and carotid endarterectomy: OR, 1.06; 95% CI, 1.03-1.09) and no difference for 5 of 10 procedures (open aortic aneurysm repair, bariatric surgery, esophagectomy, knee replacement, and hip replacement; ranging from OR, 0.97; 95% CI, 0.94-1.00, for hip replacement to OR, 1.09; 95% CI, 0.94-1.26, for bariatric surgery). High-competition hospitals also demonstrated 30-day readmissions that were higher for 5 of 10 procedures (open aortic aneurysm repair, knee replacement, mitral valve repair, rectal resection, and carotid endarterectomy; ranging from OR, 1.01; 95% CI, 1.00-1.02, for knee replacement to OR, 1.05; 95% CI, 1.02-1.08, for rectal resection) and no difference for 3 procedures (bariatric surgery: OR, 1.03; 95% CI, 0.99-1.07; esophagectomy: OR, 1.02; 95% CI, 0.99-1.06; and pancreatectomy: OR, 1.00; 95% CI, 0.99-1.01). Hospitals in high-competition compared with low-competition markets cared for patients who were older (mean [SD] age of 74.4 [6.6] years vs 74.0 [6.2] years, respectively; P < .001), were more likely to be racial and ethnic minority individuals (77 322/450 404 [17.3%] vs 23 328/444 900 [5.6%], respectively; P < .001), and had more comorbidities (≥2 Elixhauser comorbidities, 302 415/450 404 [67.1%] vs 284 355/444 900 [63.9%], respectively; P < .001). Conclusions and Relevance: This study found that hospital market competition was not consistently associated with improved outcomes after high-risk surgery. Efforts to maintain hospital market competition may not achieve better postoperative outcomes.

Social Vulnerability and Emergency General Surgery among Medicare Beneficiaries.

BACKGROUND: Although the Social Vulnerability Index (SVI) was created to identify vulnerable populations after unexpected natural disasters, its ability to identify similar groups of patients undergoing unexpected emergency surgical procedures is unknown. We sought to examine the association between SVI and outcomes after emergency general surgery. STUDY DESIGN: This study is a cross-sectional review of 887,193 Medicare beneficiaries who underwent 1 of 4 common emergency general surgery procedures (appendectomy, cholecystectomy, colectomy, and ventral hernia repair) performed in the urgent or emergent setting between 2014 and 2018. These data were merged with the SVI at the census-track level of residence. Risk-adjusted outcomes (30-day mortality, serious complications, readmission) were evaluated using a logistic regression model accounting for age, sex, comorbidity, year, procedure type, and hospital characteristics between high and low social vulnerability quintiles and within the 4 SVI subthemes (socioeconomic status; household composition and disability; minority status and language; and housing type and transportation). RESULTS: Compared with beneficiaries with low social vulnerability, Medicare beneficiaries living in areas of high social vulnerability experienced higher rates of 30-day mortality (8.56% vs 8.08%; adjusted odds ratio 1.07; p < 0.001), serious complications (20.71% vs 18.40%; adjusted odds ratio 1.17; p < 0.001), and readmissions (16.09% vs 15.03%; adjusted odds ratio 1.08; p < 0.001). This pattern of differential outcomes was present in subgroup analysis of all 4 SVI subthemes but was greatest in the socioeconomic status and household composition and disability subthemes. CONCLUSIONS: National efforts to support patients with high social vulnerability from natural disasters may be well aligned with efforts to identify communities that are particularly vulnerable to worse postoperative outcomes after emergency general surgery. Policies targeting structural barriers related to household composition and socioeconomic status may help alleviate these disparities.

Disparities in unplanned surgery amongst medicare beneficiaries.

BACKGROUND: While significant efforts have been made to understand surgical disparities for procedures that are performed in either the elective or unplanned settings, far less is known about procedures performed in both settings. METHODS: Cross-sectional study of 1,135,743 Medicare beneficiaries undergoing incisional hernia repair, colectomy, or abdominal aortic aneurysm repair between 2014 and 2018. Risk-adjusted outcomes were assessed using multivariable logistic regression. RESULTS: Compared to White beneficiaries, unplanned surgery rates were higher for Black (44.0%vs38.8%, OR = 1.29,p < 0.001) and Asian beneficiaries(40.4%vs38.8%,OR = 1.09,p < 0.001). While there were minimal differences in 30-day mortality for elective procedures, unplanned procedures demonstrated wider disparities (Black vs White 12.4%vs11.3%,OR = 1.11,p < 0.001; Asian vs White 13.2%vs11.3%,OR = 1.18,p < 0.001). Similar patterns were observed for readmissions. CONCLUSIONS: Unplanned procedures are more common and demonstrate wider disparities in outcomes among minority Medicare beneficiaries. Reducing unplanned surgery rates among these groups may be an effective strategy to limit overall disparities in postoperative outcomes.

Hospital-Level Segregation Among Medicare Beneficiaries Undergoing Lung Cancer Resection.

BACKGROUND: Recent research has raised concern that health care segregation, the high concentration of racial groups within a subset of hospitals, is a key contributor to persistent disparities in surgical care. However, to date the extent and effect of hospital level segregation among patients undergoing resection for lung cancer remains unclear. METHODS: We used 100% Medicare fee-for-service claims to evaluate the degree of hospital-level racial segregation for patients undergoing resection for lung cancer between 2014 and 2018. Hospitals serving a high volume of minority patients were defined as the top decile of hospitals by volume of racial and ethnic minority beneficiaries served. Multivariable logistic regression analysis was used to compare surgical outcomes between hospitals serving high vs low volumes of minority patients. RESULTS: A total of 122,943 patients were included, with racial/ethnic composition of 360 American Indian or Native American (0.3%), 2077 Asian or Pacific Islander (1.7%), 1146 Hispanic or Latino (0.9%), 8707 non-Hispanic Black (7.1%), and 108,665 non-Hispanic White patients. Overall, 31.6%, 15.9%, 15.0%, and 7.8% of all hospitals performed 90% of lung cancer resection for Black, Asian, Hispanic, and Native American patients, respectively. Hospitals performing higher volumes of operations for racial and ethnic minorities had higher mortality (3.9% vs 3.1%; odds ratio [OR], 1.19; 95% CI, 1.15-1.23; P < .001), complications (18.1% vs 15.9%; OR, 1.17; 95% CI, 1.14-1.19; P < .001), and readmissions (11.7% vs 11.2%; OR, 1.04; 95% CI, 1.02-1.05; P < .001) for resections for lung cancer. CONCLUSIONS: Our findings suggest that a small proportion of hospitals provide a disproportionate amount of surgical care for racial and ethnic minorities with lung cancer with inferior surgical outcomes.

Cdc73 protects Notch-induced T-cell leukemia cells from DNA damage and mitochondrial stress.

Activated Notch signaling is highly prevalent in T-cell acute lymphoblastic leukemia (T-ALL) but pan-Notch inhibitors were toxic in clinical trials. To find alternative ways to target Notch signals, we investigated Cell division cycle 73 (Cdc73), which is a Notch cofactor and component of transcriptional machinery, a potential target in T-ALL. While we confirmed previous work that CDC73 interacts with NOTCH1, we also found that the interaction in T-ALL was context-dependent and facilitated by the lymphoid transcription factor ETS1. Using mouse models, we showed that Cdc73 is important for Notch-induced T-cell development and T-ALL maintenance. Mechanistically, Cdc73, Ets1, and Notch intersect chromatin at promoters and enhancers to activate oncogenes and genes that are important for DNA repair and oxidative phosphorylation. Consistently, Cdc73 deletion in T-ALL cells induced DNA damage and impaired mitochondrial function. Our data suggests that Cdc73 might promote a gene expression program that was eventually intersected by Notch to mitigate the genotoxic and metabolic stresses of elevated Notch signaling. We also provide mechanistic support for testing inhibitors of DNA repair, oxidative phosphorylation, and transcriptional machinery. Inhibiting pathways like Cdc73 that intersect with Notch at chromatin might constitute a strategy to weaken Notch signals without directly targeting the Notch complex.

Neighborhood deprivation and Medicare expenditures for common surgical procedures.

INTRODUCTION: The Center of Medicare and Medicaid Services valued based payments for inpatient surgical hospitalizations are adjusted for clinical but not social risk factors. While research has shown that social risk is associated with worse surgical patient outcomes, it is unknown if inpatient surgical episode Medicare payments are affected by social risk factors. METHODS: Retrospective review of Medicare beneficiaries, age 65-99, undergoing appendectomy, colectomy, hernia repair, or cholecystectomy between 2014 and 2018. Neighborhood deprivation measured by Area Deprivation Index for beneficiary census tract. We evaluated Medicare payments for a total episode of surgical care comprised of index hospitalization, physician fees, post-acute care, and readmission by beneficiary neighborhood deprivation. RESULTS: A total of 809,059 patients (Women, 56.0%) and mean (SD) age of 75.7 (7.4 years were included. A total of 145,351 beneficiaries lived in the least deprived neighborhoods and 134,188 who lived in the most deprived neighborhoods. Total surgical episode spending was $2654 higher among beneficiaries from the most deprived neighborhoods compared to those from the least after risk adjustment for clinical and hospital factors. These differences were driven in part by higher rates of readmissions (12.9% vs 10.8%, P < 0.001) and post-acute care (67.8% vs. 61.2%, P < 0.001) among beneficiaries living in the most deprived neighborhoods. CONCLUSION: These findings suggest that value-based payment models with inclusion of social risk adjustment may be needed for surgical cohorts. Moreover, efforts focused on investing in deprived communities may be aligned with surgical quality improvement.