The Cardiovascular Event Risk Associated with Tyrosine Kinase Inhibitors and the Lipid Profile in Patients with Chronic Myeloid Leukemia.

BACKGROUND: Second- and third-generation tyrosine kinase inhibitors (TKIs) are now available to treat chronic-phase chronic myeloid leukemia (CP-CML) in the first and second line. However, vascular adverse events (VAEs) have been reported for patients with CML treated with some TKIs. METHODS: We retrospectively evaluated the cumulative incidence (CI) and cardiovascular risk for 210 patients included in the Canarian Registry of CML. RESULT: With a mean follow up of 6 years, 19/210 (9.1%) patients developed VAEs, all of whom presented at least one cardiovascular risk factor at diagnosis. The mean time to VAE presentation was 54 months from the start of TKI treatment. We found a statistically significant difference between the CI for nilotinib-naïve vs. nilotinib-treated patients (p = 0.005), between dasatinib-naïve and dasatinib-treated patients (p = 0.039), and for patients who received three lines of treatment with first-line imatinib vs. first-line imatinib (p < 0.001). From the multivariable logistic regression analyses, the Framingham risk score (FRS) and patients with three lines of TKI with first-line imatinib were the only variables with statistically significant hazard ratios for VAE development. Significant increases in HDL-C and total cholesterol may also be predictive for VAE. CONCLUSIONS: In conclusion, it is important to estimate the cardiovascular risk at the diagnosis of CML as it can help determine whether a patient is likely to develop a VAE during TKI treatment.

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.

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.

DNMT3A/TET2/ASXL1 Mutations are an Age-independent Thrombotic Risk Factor in Polycythemia Vera Patients: An Observational Study.

BACKGROUND: Polycythemia vera (PV) patients are classified as high or low thrombotic risk based on age and prior history of thrombosis. Despite adherence to treatment recommendations, vascular events remain frequent, leading us to question whether thrombotic risk stratification could be improved. We previously reported an association between thrombotic events and mutations in DTA genes (DNMT3A, TET2, and ASXL1). The objective of this study was to confirm this observation in a larger series of PV patients. METHODS: PV patients with a minimum follow-up of 3 years were recruited from 8 European centers. Medical history was searched for thrombotic event recorded at any time and next-generation sequencing carried out with a myeloid panel. Multivariable logistic regression evaluated the impact of variables on thrombotic risk. Kaplan-Meier thrombosis-free survival curves were compared by the log rank test. Associations in the total cohort were confirmed in a case-control study to exclude selection bias. RESULTS: Of the 136 patients recruited, 74 (56.1%) had a thrombotic event, with an incidence density of 2.83/100 person-years. In multivariable analysis, DTA mutation was a risk factor for thrombotic event, being predictive for shorter thrombosis-free survival in the whole cohort (p = 0.007), as well as in low-risk patients (p = 0.039) and older patients (p = 0.009), but not for patients with a prediagnostic event. A gender- and age-matched case-control study confirmed the increased risk of thrombotic event for PV patients with a DTA mutation. CONCLUSION: Our results support the use of molecular testing at diagnosis to help predict which PV patients are at higher risk of developing thrombosis.

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.

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.

Expanding Access to High-Quality Cancer Care Through Policy-California Cancer Care Equity Act.

This Viewpoint describes key domains in which the California Cancer Care Equity Act may benefit patients, recommends potential improvements to further expand access and reduce disparities, and suggests possible safeguards to monitor and minimize unintended consequences.

Association of social determinants of health International Classification of Disease, Tenth Edition clinical modification codes with outcomes for emergency general surgery and trauma admissions.

BACKGROUND: Patients with Acute Care Surgery needs (ie, emergency general surgery diagnosis or trauma admission) are at particularly high risk for nonmedical patient-related factors that can be important drivers of healthcare outcomes. These social determinants of health are typically ascertained at the geographic area level (ie, county or neighborhood) rather than at the individual patient level. Recently, the International Classification of Diseases Tenth Revision, Tenth Edition created codes to capture health hazards related to patient socioeconomic and psychosocial circumstances. We sought to characterize the impact of these social determinants of health-related codes on perioperative outcomes among patients with acute care surgery needs. METHODS: Patients diagnosed between 2017 and 2020 with acute care surgery needs (ie, emergency general surgery diagnosis or a trauma admission) were identified in the California Department of Healthcare Access and information Patient Discharge database. Data on concomitant social determinants of health-related codes (International Classification of Diseases Tenth Revision, Tenth Edition Z55-Z65), which designated health hazards related to socioeconomic and psychosocial (socioeconomic and psychosocial, respectively) circumstances, were obtained. After controlling for patient factors, including age, sex, race, payer type, and admitting hospital, the association of socioeconomic and psychosocial codes with perioperative outcomes and hospital disposition was analyzed. RESULTS: Among 483,280 with an acute care surgery admission (emergency general surgery: n = 289,530, 59.9%; trauma: n = 193,705, 40.1%) mean age was 56.5 years (standard deviation: 21.5) and 271,911 (56.3%) individuals were male. Overall, 16,263 (3.4%) patients had a concomitant socioeconomic and psychosocial diagnosis code. The percentage of patients with a concurrent social determinants of health International Classification of Diseases Tenth Revision, Tenth Edition diagnosis increased throughout the study period from 2.6% in 2017 to 4.4% in 2020. Patients that were male (odds ratio 1.89; 95% confidence interval 1.82, 1.96), insured by Medicaid (odds ratio 5.43; 95% confidence interval 5.15, 5.72) or self-pay (odds ratio 3.04; 95% confidence interval 2.75, 3.36) all had higher odds of having an social determinants of health International Classification of Diseases Tenth Revision, Tenth Edition diagnosis. Black race did not have a significant association with an social determinants of health International Classification of Diseases Tenth Revision, Tenth Edition diagnosis (odds ratio 0.99; 95% confidence interval 0.94, 1.04); however, Hispanic (odds ratio 0.44; 95% confidence interval 0.43, 0.46) and Asian (odds ratio 0.40; 95% confidence interval 0.36, 0.44) race/ethnicity was associated with a lower odds of having an social determinants of health International Classification of Diseases Tenth Revision, Tenth Edition diagnosis. After controlling for competing risk factors on multivariable analyses, the risk-adjusted probability of hospital postoperative death was 3.1% (95% confidence interval 2.8, 3.4) among patients with a social determinants of health diagnosis versus 5.9% (95% confidence interval 5.9, 6.0) (odds ratio 0.48; 95% confidence interval 0.44, 0.54) among patients without a social determinants of health diagnosis. Risk-adjusted complications were 26.7% (95% confidence interval 26.1, 37.3) among patients with a social determinants of health diagnosis compared with 31.9% (95% confidence interval 31.7, 32.0) (odds ratio 0.74; 95% confidence interval 0.71, 0.77) among patients without a social determinants of health diagnosis. CONCLUSION: International Classification of Diseases Tenth Revision, Tenth Edition social determinants of health code use was low, with only 3.4% of patients having documentation of a socioeconomic and psychosocial circumstance. The presence of an International Classification of Diseases Tenth Revision, Tenth Edition social determinants of health code was not associated with greater odds of complications or death; however, it was associated with longer length of stay and higher odds of being discharged to a skilled nursing facility.

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.

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.

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.

Presence of Myeloid Mutations in Patients with Chronic Myeloid Leukemia Increases Risk of Cardiovascular Event on Tyrosine Kinase Inhibitor Treatment.

For chronic myeloid leukemia (CML) patients with a known risk of cardiovascular events (CVE), imatinib is often recommended for first-line tyrosine kinase inhibitor (TKI) treatment rather than a second-generation TKI (2G-TKI) such as nilotinib or dasatinib. To date, very few studies have evaluated the genetic predisposition associated with CVE development on TKI treatment. In this retrospective study of 102 CML patients, 26 CVEs were reported during an average follow-up of over 10 years. Next-generation sequencing identified pathogenic/likely pathogenic mutations in genes associated with myeloid malignancies in 24.5% of the diagnostic samples analyzed. Patients with a recorded CVE had more myeloid mutations (0.48 vs. 0.14, p = 0.019) and were older (65.1 vs. 55.7 years, p = 0.016). Age ≥ 60 years and receiving a 2G-TKI in first-line were CVE risk factors. The presence of a pathogenic somatic myeloid mutation was an independent risk factor for CVE on any TKI (HR 2.79, p = 0.01), and significantly shortened the CV event-free survival of patients who received first-line imatinib (by 70 months, p = 0.011). Indeed, 62% of patients on imatinib with mutations had a CVE vs. the 19% on imatinib with a mutation and no CVE. In conclusion, myeloid mutations detectable at diagnosis increase CVE risk, particularly for patients on imatinib, and might be considered for first-line TKI choice.

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.

Toxicity of Asciminib in Real Clinical Practice: Analysis of Side Effects and Cross-Toxicity with Tyrosine Kinase Inhibitors.

(1) Background: Despite the prognostic improvements achieved with tyrosine kinase inhibitors (TKIs) in chronic myeloid leukemia (CML), a minority of patients still fail TKIs. The recent introduction of asciminib may be a promising option in intolerant patients, as it is a first-in-class inhibitor with a more selective mechanism of action different from the ATP-competitive inhibition that occurs with TKIs. Therefore, our goal was to analyze toxicities shown with asciminib as well as to study cross-toxicity with previous TKIs. (2) Methods: An observational, multicenter, retrospective study was performed with data from 77 patients with CML with therapeutic failure to second-generation TKIs who received asciminib through a managed-access program (MAP) (3) Results: With a median follow-up of 13.7 months, 22 patients (28.5%) discontinued treatment: 32% (7/22) due to intolerance and 45% (10/22) due to resistance. Fifty-five percent of the patients reported adverse effects (AEs) with asciminib and eighteen percent grade 3-4. Most frequent AEs were: fatigue (18%), thrombocytopenia (17%), anemia (12%), and arthralgias (12%). None of the patients experienced cardiovascular events or occlusive arterial disease. Further, 26%, 25%, and 9% of patients required dose adjustment, temporary suspension, or definitive discontinuation of treatment, respectively. Toxicities under asciminib seemed lower than with prior TKIs for anemia, cardiovascular events, pleural/pericardial effusion, diarrhea, and edema. Cross-toxicity risk was statistically significant for thrombocytopenia, anemia, neutropenia, fatigue, vomiting, and pancreatitis. (4) Conclusion: Asciminib is a molecule with a good safety profile and with a low rate of AEs. However, despite its new mechanism of action, asciminib presents a risk of cross-toxicity with classical TKIs for some AEs.