Changing Strategy Between Bridge to Transplant and Destination LVAD Therapy After the First 3 Months: Analysis of the STS-INTERMACS Database.

BACKGROUND: Left ventricular assist devices (LVADs) have been implanted as bridge to transplantation (BTT), bridge to candidacy (BTC) or destination therapy (DT) on the basis of relative and absolute contraindications to transplantation. Multiple factors may lead to changes in the strategy of support after LVAD implantation. METHODS: Based on INTERMACS (Interagency Registry for Mechanically Assisted Circulatory Support) 2012-2020 data, 11,262 patients survived to 3 months on continuous-flow LVADs with intent of BTT or DT. Preimplant characteristics and early events post-LVAD were analyzed in relation to changes in BTT or DT strategy during the next 12 months. RESULTS: Among 3216 BTT patients at 3 months, later transplant delisting or death without transplant occurred in 536 (16.7%) and was more common with age, profiles 1-2, renal dysfunction, and independently for prior cardiac surgery (HR 1.25, 95% CI 1.04-1.51; P = 0.02). Post-LVAD events of infections, gastrointestinal bleeding, stroke, and right heart failure as defined by inotropic therapy, predicted delisting and death, as did in-hospital location at 3 months (HR 1.67, 95% CI 1.20-2.33; P = 0.0024). Of 8046 patients surviving to 3 months with the intent of destination therapy, 750 (9.3%) subsequently underwent listing or transplantation, often with initial histories of acute HF (HR 1.70, 95% CI 1.27-2.27; P = 0.0012) or malnutrition-cachexia (1.73, 95% CI 1.14-2.63; P = 0.0099). Multiple gastrointestinal bleeding events (≥ 4) with LVAD increased transition from BTT to DT (HR 4.22, 95% CI 1.46-12.275; P = 0.0078) but also from DT to BTT (HR 5.17, 95% CI 1.92-13.9; P = 0.0011). CONCLUSIONS: Implant strategies change over time in relation to preimplant characteristics and adverse events post implant. Preimplant recognition of factors predicting later change in implant strategy will refine initial triage, whereas further reduction of post-LVAD complications will expand options, including eventual consideration of heart transplantation.

Pediatric Burn Injuries: Risk Factors for Increased Mortality.

INTRODUCTION: Burn injuries are among the top ten leading causes of unintentional death in pediatric patients and are encountered by pediatric surgeons in all practice settings. There is a lack of literature evaluating mortality in pediatric burn injuries in regard to nonaccidental burns and potential disparities. Our study aims to determine the risk factors associated with mortality in pediatric burn injuries and highlight the characteristics of this patient population. METHODS: We utilized the Trauma Quality Improvement Program database from 2017 to 2019 to identify primary burn injuries in children ≤14 y old. Physical abuse descriptors were used to identify patients with suspected nonaccidental injuries. Further demographics, including age, race, ethnicity, and insurance type, were evaluated. Descriptive statistics were generated and a multivariable logistic regression analysis was utilized to evaluate risk factors for mortality. RESULTS: 13,472 pediatric burn patients (≤14 y old) were identified. The overall mortality was low (<1%). Children with burns to multiple body regions had the highest independent risk of mortality in this cohort. All older age groups had an independent risk of mortality compared to the youngest patients, but those from ages 5 to <10 y old had the highest risk of mortality (OR = 11.40; 95% confidence interval: 4.41-29.43, P < 0.001). Black children had a significantly higher mortality compared to White children. Nonaccidental burns carried a mortality that was twice that of accidental burns. Government insurance type was the primary insurance type for a majority of patients who died. CONCLUSIONS: Risk factors for mortality in pediatric burn include Black race, multiple affected body regions, and nonaccidental burns. This study identified an increased mortality risk in the older age groups in contrast to previous studies that showed increased mortality in younger patients suffering from burn injuries.

Associations Between Rehabilitation Utilization and Out-of-Pocket Costs Among Older Adults With Breast Cancer in the United States.

OBJECTIVE: To examine the association between rehabilitation utilization within 12 months of breast cancer diagnosis and out-of-pocket costs in the second year (12-24mo after diagnosis). DESIGN: Secondary analysis of the 2009-2019 Surveillance, Epidemiology and End Results-Medicare linked database. Individuals who received rehabilitation services were propensity-score matched to individuals who did not receive services. Overall and health care service-specific models were examined using generalized linear models with a gamma distribution. SETTING: Inpatient and outpatient medical facilities. PARTICIPANTS: A total of 35,212 individuals diagnosed with nonmetastatic breast cancer and were continuously enrolled in Medicare Fee-For Service (parts A, B, and D) in the 12 months before and 24 months postdiagnosis. INTERVENTION: Not applicable. MAIN OUTCOME MEASURES: Individual cost responsibility, a proxy for out-of-pocket costs, which was defined as deductibles, coinsurance, and copayments during the second year after diagnosis (12-24mo postdiagnosis). RESULTS: The mean individual cost responsibility was higher in individuals who used rehabilitation than those who did not ($4013 vs $3783), although it was not a clinically meaningful difference (d=0.06). Individuals who received rehabilitative services had significantly higher costs attributed to individual provider care ($1634 vs $1476), institutional outpatient costs ($886 vs $812), and prescription drugs ($959 vs $906), and significantly lower costs attributed to institutional inpatient costs ($455 vs $504), and durable medical equipment ($81 vs $86). CONCLUSIONS: Older adults with breast cancer who received rehabilitation services had higher cost responsibility during the second year after diagnosis than those who did not. Future work is needed to examine the relationship between rehabilitation and out-of-pocket costs across longer periods of time and in conjunction with perceived benefit.

The Disturbing Findings of Pediatric Firearm Injuries From the National Trauma Data Bank: 2010-2016.

BACKGROUND: Trauma is the leading cause of pediatric and adolescent morbidity and mortality. Firearm-related injuries and deaths contribute substantially to the overall disease burden. This study described the intent, location, demographics, and outcomes of a nationally representative pediatric population with firearm injuries. We hypothesized that younger patients would have a higher percentage of unintentional and self-inflicted injuries with associated higher mortality rates. MATERIALS AND METHODS: The National Trauma Data Bank, maintained by the American College of Surgeons, from 2010 to 2016 was utilized. All pediatric patients (0-19 y) with firearm injuries who had complete data were analyzed for mechanism, location, demographics, and outcomes. Basic descriptive statistics were used to compare subgroups. Multivariable logistic regression analysis was applied to investigate risk factors for firearm injury-caused mortality. RESULTS: In the study period, 46,039 pediatric patients sustained firearm injuries (median age = 17 y). Males, Blacks, ages 15-19, and the Southern region were the most common injured demographics. However, subgroup analysis showed the demographics differ for self-inflicted and unintentional firearm injuries, which had significantly higher White patients (66.6% and 47.9%, respectively; P < 0.001). Nearly 76% of injuries were related to assaults, 14% were unintentional, 5% were self-inflicted, and 5% were undetermined. The overall mortality was nearly 12%. The youngest population had higher proportion of unintentional injuries and highest mortality rate when compared with other classifications of intent (P < 0.001). CONCLUSIONS: Pediatric firearm injuries have high mortality, especially in the youngest populations. Age-tailored prevention strategies, such as strict child access prevention laws and enforced gun storage violations, may help in reducing firearm injuries and improving health outcomes.

Prevalence of Activity Limitations and Association with Multimorbidity Among US Adults 50 to 64 Years Old.

BACKGROUND: Functional limitations may be more common in middle-aged adults than previously recognized. However, there are few published data on the prevalence of activity limitations, and their association with multimorbidity, among adults 50 to 64 years old. OBJECTIVE: To describe the prevalence of activity limitations and the association with multimorbidity in middle-aged adults. DESIGN: Cross-sectional analysis of US population-based National Health and Nutrition Examination Survey (NHANES) 2011-2016. PARTICIPANTS: The total number of community-dwelling NHANES participants aged 50-64 years old is 4217. MAIN MEASURES: Chronic conditions included hypertension, high cholesterol, diabetes mellitus, obesity, chronic kidney disease, cancer, stroke, coronary heart disease, heart failure, chronic obstructive pulmonary disease/asthma, arthritis, and depression. Activity limitations were defined as any difficulty within each of four International Classification of Functioning (ICF) domains: functional limitations (kneeling, carrying, standing, sitting, reaching, grasping, pulling), mobility (walking » mile, climbing 10 steps), basic activities of daily living (BADLs; walking, transferring, eating, dressing), and instrumental activities of daily living (IADLs; finances, chores, cooking). We calculated prevalence ratios for activity limitations using generalized estimating equations. KEY RESULTS: The prevalence of functional limitations, mobility limitations, BADL difficulty, and IADL difficulty was 34%, 11%, 15%, and 17%, respectively. Seventy-two percent of participants had two or more chronic conditions; 23% had two, 18% had three, 15% had four, and 16% had five or more. Multivariable adjusted prevalence ratios (95% CI) for functional limitations among those with 2, 3, 4, and 5 or more chronic conditions, compared with 0-1 conditions, were 1.94 (1.43-2.63), 2.50 (1.93-3.23), 3.26 (2.48-4.27), and 4.54 (3.48-5.93), respectively (p trend < 0.001). Larger prevalence ratios at a higher number of chronic conditions were present for mobility limitations, BADL difficulty, and IADL difficulty. CONCLUSIONS: Problems with function are not limited to older adults and multimorbidity may be helpful for identifying middle-aged adults with a high prevalence of activity limitations.

Medical Expenditures Among Medicare Beneficiaries with Statin-Associated Adverse Effects Following Myocardial Infarction.

PURPOSE: Compare medical expenditures among adults with statin-associated adverse effects (SAAE) and high statin adherence (HSA) following myocardial infarction (MI). METHODS: We analyzed expenditures in 2016 US dollars among Medicare beneficiaries with SAAE (n = 1741) and HSA (n = 55,567) who were ≥ 66 years of age and initiated moderate/high-intensity statins following an MI in 2007-2013. SAAE were identified through a claims-based algorithm, which included down-titrating statins and initiating ezetimibe, switching to ezetimibe monotherapy, having a rhabdomyolysis or antihyperlipidemic adverse event followed by statin down-titration or discontinuation, or switching between ≥ 3 statin types within 365 days following MI. HSA was defined by having a statin available to take for ≥ 80% of the days in the 365 days following MI. RESULTS: Expenditures among beneficiaries with SAAE and HSA were $40,776 (95% CI $38,329-$43,223) and $26,728 ($26,482-$26,974), respectively, in the 365 days following MI, and $34,238 ($31,396-$37,080) and $29,053 ($28,605-$29,500), respectively, for every year after the first 365 days. Multivariable-adjusted ratios comparing expenditures among beneficiaries with SAAE versus HSA in the first 365 days and after the first 365 days following MI were 1.51 (95% CI 1.43-1.59) and 1.23 (1.12-1.34), respectively. Inpatient and outpatient expenditures were higher among beneficiaries with SAAE versus HSA during and after the first 365 days following MI. Compared to beneficiaries with HSA, medication expenditures among those with SAAE were similar in the 365 days following MI, but higher afterwards. Other medical expenditures were higher among beneficiaries with SAAE versus HSA. CONCLUSION: SAAE are associated with increased expenditures following MI compared with HSA.

National patterns in intensity and frequency of outpatient care for apparent treatment-resistant hypertension.

BACKGROUND: Apparent treatment-resistant hypertension (aTRH) is associated with an increased risk of adverse cardiovascular outcomes. We studied the frequency and intensity of care for aTRH among participants aged 65 years and older in the US-based REGARDS study linked with Medicare claims. METHODS: Blood pressure (BP) was measured twice and averaged. aTRH was defined by the use of ≥3 classes of antihypertensive medication and uncontrolled BP (UaTRH, systolic/diastolic BP ≥140/90 mmHg), or ≥4 classes with controlled BP (CaTRH). Participants were categorized as not having aTRH (no aTRH), CaTRH or UaTRH. RESULTS: Among 4650 participants with hypertension, 468 (10.1%) had UaTRH, 247 (5.3%) had CaTRH, and 3935 (84.6%) had hypertension but did not have aTRH. For hypertension-related visits, those with UaTRH saw primary care physicians and cardiologists more frequently than those without aTRH (mean primary care visits per year: 2.77 vs 2.27, P<.001; cardiologists: 0.50 vs 0.35, P=.014). Among those with UaTRH, CaTRH, and no aTRH, respectively 73.5%, 68.0%, and 67.5% had >1 hypertension-related visit per year. Among those with UaTRH, males vs females (prevalence ratio=0.78; 95% CI 0.69-0.89), whites vs blacks (0.88; 95% CI 0.78-0.99), and current smokers vs non-smokers (0.66; 95% CI 0.48-0.89) were less likely to receive >1 hypertension-related visit per year. Diagnostic intensity, measured by testing for end organ damage and secondary hypertension, was similar between groups. CONCLUSIONS: Many people with UaTRH are not seen more than once per year for hypertension and may benefit from increased care.

Burden of Coronary Heart Disease Rehospitalizations Following Acute Myocardial Infarction in Older Adults.

PURPOSE: Studies of prognosis following acute myocardial infarction (AMI) conventionally examine the first recurrent coronary heart disease (CHD) event which may not adequately characterize the full burden of CHD hospitalizations. We therefore examined the cumulative number of CHD rehospitalizations following AMI among older adults in the United States. METHODS: We conducted a retrospective cohort study of 78,085 Medicare beneficiaries aged ≥66 years without recent CHD history who were hospitalized for AMI in 2000-2010. Counts of CHD rehospitalizations over a maximum of 10 years of follow-up were calculated. Characteristics were assessed through claims and enrollment information and associations with CHD rehospitalizations were evaluated using Poisson models. RESULTS: Over 25 % of beneficiaries were aged ≥85 years, 55 % were women, and 89 % were white. Comorbidities were common, including diabetes (22.9 %), hypertension (46.7 %), heart failure (10.3 %), and chronic obstructive pulmonary disease (19.2 %). Following AMI, 16,078 beneficiaries (20.6 %) were hospitalized for CHD a total of 23,132 times. Among those who experienced at least one CHD rehospitalization, 35.9 % had ≥2 CHD rehospitalizations (n = 5773, 7.4 % of all beneficiaries with AMI) in the ensuing decade. Associations of demographics, comorbidities, and index hospitalization characteristics with rates of first and total CHD rehospitalizations were largely similar. Age ≥85 years versus 66-69 years was more strongly associated with first (rate ratio [RR] 1.43) than total (RR 1.35) CHD rehospitalization (p < 0.05), as was male versus female sex (RR 1.13 and 1.07). CONCLUSIONS: Emphasizing the first recurrent CHD rehospitalization underestimates the burden of disease experienced among older adults with AMI.

Trends in mortality and recurrent coronary heart disease events after an acute myocardial infarction among Medicare beneficiaries, 2001-2009.

BACKGROUND: Few contemporary studies examine trends in recurrent coronary heart disease (CHD) events and mortality after acute myocardial infarction (AMI) and whether these trends vary by race or sex. METHODS: We used data from the national 5% random sample of Medicare fee-for-service beneficiaries for 1999 to 2010. We included beneficiaries who experienced an AMI (International Classification of Disease [ICD] 9 410.xx, except 410.x2) between January 1, 2001, and December 31, 2009. Each beneficiary's first AMI was included as their index event. Outcomes included all-cause mortality, recurrent AMI, and recurrent CHD events during the 365days after discharge for the index AMI. To examine secular trends, we pooled calendar years into 3 periods (2001-2003, 2004-2006, and 2007-2009). RESULTS: Among 48,688 beneficiaries with index AMIs from 2001 to 2009, we observed decreases in the age-adjusted rates for mortality (-3.8% for each 3-year period, 95% CI -6.1% to -1.6%, P trend = .001), recurrent AMI (-15.0%, 95% CI -18.6% to -11.2%, P trend < .001), and recurrent CHD events (-11.1%, 95% CI -14.0% to -8.0%, P trend < .001) in the 365days after the index AMI. In 2007 to 2009, blacks had excess risk relative to whites for mortality and recurrent AMI (black/white incidence rate ratio of 1.38 for mortality [95% CI 1.21-1.57] and 1.38 for recurrent AMI [95% CI 1.07-1.79]). CONCLUSIONS: Despite overall favorable trends in lower mortality and recurrent events after AMI, efforts are needed to reduce racial disparities.

Sociodemographic and clinical characteristics associated with rehabilitation services utilization in older women with early-stage breast cancer from SEER-Medicare 2009-2018.

PURPOSE: Rehabilitation services are recommended by clinical practice guidelines following breast cancer treatment, yet little is known about how utilization may vary by patient-level characteristics which we aimed to study using SEER-Medicare data. METHODS: Data from the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database was used to identify non-metastatic breast cancer survivors aged ≥ 66 years diagnosed between 2011 and 2016. Rehabilitation services delivered 0-11 months post-diagnosis were identified via outpatient or physician visit claims. Descriptive statistics and associations between patient characteristics and rehabilitation services were calculated using modified Poisson models estimating relative risk (RR) and corresponding 95% confidence intervals (CIs). RESULTS: Of 55,539 breast cancer survivors, 33% (n = 18,244) had received any type of rehabilitative services. Survivors were a mean age of 75 years (SD 6.7), 88% White, 86% urban-dwelling, and 21% Medicare/Medicaid dually enrolled. In adjusted models, patients aged > 75 vs. ≤ 75 were 6% (RR 0.94, 95% CI 0.92-0.96) less likely to have received rehabilitative services. Survivors in an area with greater educational attainment vs. less educational attainment, White vs. non-White, or living in a rural vs. urban area were 26% (1.26, CI 1.22-1.30), 6% (1.06, CI 1.02-1.11), and 6% (1.06, CI 1.02-1.10) more likely to have received rehabilitative services, respectively. CONCLUSION: The largest differences in rehabilitation utilization were observed for survivors of differing educational and treatment statuses. IMPLICATIONS FOR CANCER SURVIVORS: Further research is needed on barriers, access, and delivery of rehabilitation services, specifically for breast cancer survivors who are older-aged, non-White, or Medicare/Medicaid dual eligible.

Understanding the financial cost of cancer clinical trial participation.

BACKGROUND: Though financial hardship is a well-documented adverse effect of standard-of-care cancer treatment, little is known about out-of-pocket costs and their impact on patients participating in cancer clinical trials. This study explored the financial effects of cancer clinical trial participation. METHODS: This cross-sectional analysis used survey data collected in December 2022 and May 2023 from individuals with cancer previously served by Patient Advocate Foundation, a nonprofit organization providing social needs navigation and financial assistance to US adults with a chronic illness. Surveys included questions on cancer clinical trial participation, trial-related financial hardship, and sociodemographic data. Descriptive and bivariate analyses were conducted using Cramer's V to estimate the in-sample magnitude of association. Associations between trial-related financial hardship and sociodemographics were estimated using adjusted relative risks (aRR) and corresponding 95% confidence intervals (CI) from modified Poisson regression models with robust standard errors. RESULTS: Of 650 survey respondents, 18% (N = 118) reported ever participating in a cancer clinical trial. Of those, 47% (n = 55) reported financial hardship as a result of their trial participation. Respondents reporting trial-related financial hardship were more often unemployed or disabled (58% vs. 43%; V = 0.15), Medicare enrolled (53% vs. 40%; V = 0.15), and traveled >1 h to their cancer provider (45% vs. 17%; V = 0.33) compared to respondents reporting no hardship. Respondents who experienced trial-related financial hardship most often reported expenses from travel (reported by 71% of respondents), medical bills (58%), dining out (40%), or housing needs (40%). Modeling results indicated that respondents traveling >1 h vs. ≤30 min to their cancer provider had a 2.2× higher risk of financial hardship, even after adjusting for respondent race, income, employment, and insurance status (aRR = 2.2, 95% CI 1.3-3.8). Most respondents (53%) reported needing $200-$1000 per month to compensate for trial-related expenses. Over half (51%) of respondents reported less willingness to participate in future clinical trials due to incurred financial hardship. Notably, of patients who did not participate in a cancer clinical trial (n = 532), 13% declined participation due to cost. CONCLUSION: Cancer clinical trial-related financial hardship, most often stemming from travel expenses, affected almost half of trial-enrolled patients. Interventions are needed to reduce adverse financial participation effects and potentially improve cancer clinical trial participation.

Primary or Delayed Repair for Complete Atrioventricular Septal Defect, Tetralogy of Fallot, and Ventricular Septal Defect: Relationship to Country Economic Status.

OBJECTIVE: Primary repair in the first six months of life is routine for tetralogy of Fallot, complete atrioventricular septal defect, and ventricular septal defect in high-income countries. The objective of this analysis was to understand the utilization and outcomes of palliative and reparative procedures in high versus middle-income countries. METHODS: The World Database of Pediatric and Congenital Heart Surgery identified patients who underwent surgery for: tetralogy of Fallot, complete atrioventricular septal defect, and ventricular septal defect. Patients were categorized as undergoing primary repair, repair after prior palliation, or palliation only. Country economic status was categorized as lower middle, upper middle, and high, defined by the World Bank. Multiple logistic regression models were utilized to identify independent predictors of hospital mortality. RESULTS: Economic categories included high (n = 571, 5.3%), upper middle (n = 5,342, 50%), and lower middle (n = 4,793, 49.7%). The proportion of patients and median age with primary repair were: tetralogy of Fallot, 88.6%, 17.7 months; complete atrioventricular septal defect, 83.4%, 7.7 months; and ventricular septal defect, 97.1%, ten months. Age at repair was younger in high income countries (P < .0001). Overall mortality after repair was lowest in high income countries. Risk factors for hospital mortality included prematurity, genetic syndromes, and urgent or emergent operations (all P < .05). CONCLUSIONS: Primary repair was selected in >90% of patients, but definitive repair was delayed in lower and upper middle income countries compared with high-income countries. Repair after prior palliation versus primary repair was not a risk factor for hospital mortality. Initial palliation continues to have a small but important role in the management of these three specific congenital heart defects.

Defining optimal left ventricular assist device short-term outcomes may provide insight into programmatic quality assessment.

BACKGROUND: Patients have substantial variability in perioperative outcomes after left ventricular assist device (LVAD) implant. A perioperative multidimensional tool integrating mortality, adverse events (AEs), and patient-reported outcomes to assist in quality improvement initiatives is needed. METHODS: Patients undergoing HeartMate 3 LVAD implant (January 1, 2017 to January 31, 2024) in the Society of Thoracic Surgeons' Intermacs registry were studied. Cox proportional hazard multivariable analyses incorporating AEs as time-varying covariates for mortality out to 180 days was used to generate the INtermacs Short term composITE quality score (INSITE score derivation), reflecting the adjusted hazard ratio (HR) for mortality contributed by each AE, applying the global ranking methodology. In those alive and on support at 6 months, multivariable logistic regression (odds ratio) was used to examine the impact of AEs on health-related quality of life (QOL) at 180 days, captured through the INSITE-QOL score. Failure to achieve ≥1 point increase in visual analog scale from baseline was the event. RESULTS: Of 13,148 patients, 4,389 (33.4%) suffered at least 1 AE or death through 180 days. Stroke (survival: HR 13.1; QOL: HR 1.7), dialysis (survival: HR 31.4; QOL: HR 4.2), prolonged respiratory failure (survival: HR 5.7; QOL: HR 2.3), reoperation (survival: HR 3.4; QOL: HR 1.6), and right heart failure (survival: 5.0; QOL: HR 1.4), contributed to both mortality and failure to improve QOL at 180 days (all p < 0.05). The median INSITE and INSITE-QOL scores were 0.0 [0.0, 1.6] and 0.0 [0.0, 0.0], respectively. At 9.4% (n = 17) of centers, a high INSITE score (≥13) was present in 15% of patients, while the top 25% of centers had perfect INSITE-QOL scores in at least 75% of patients. CONCLUSIONS: AEs after LVAD confer differential impact on mortality and QOL, enabling the development of global rank outcome scores. Given the high mortality hazard conferred by 180-day AEs, center-specific quality interventions aimed at reducing early complications provide the greatest opportunity to improve long-term survival and QOL.

Engagement Among Diverse Patient Backgrounds in a Remote Symptom Monitoring Program.

PURPOSE: Previous randomized controlled trials have demonstrated benefit from remote symptom monitoring (RSM) with electronic patient-reported outcomes. However, the racial diversity of enrolled patients was low and did not reflect the real-world racial proportions for individuals with cancer. METHODS: This secondary, cross-sectional analysis evaluated engagement of patients with cancer in a RSM program. Patient-reported race was grouped as Black, Other, or White. Patient address was used to map patient residence to determine rurality using Rural-Urban Commuting Area Codes and neighborhood disadvantage using Area Deprivation Index. Key outcomes included (1) being approached for RSM enrollment, (2) declining enrollment, (3) adherence with RSM via continuous completion of symptom surveys, and (4) withdrawal from RSM participation. Risk ratios (RR) and 95% CI were estimated from modified Poisson models with robust SEs. RESULTS: Between May 2021 and May 2023, 883 patients were approached to participate, of which 56 (6%) declined RSM. Of those who enrolled in RSM, a total of 27% of patients were Black or African American and 67% were White. In adjusted models, all patient population subgroups of interest had similar likelihoods of being approached for RSM participation; however, Black or African American patients were more than 3× more likely to decline participation than White participants (RR, 3.09 [95% CI, 1.73 to 5.53]). Patients living in more disadvantaged neighborhoods were less likely to decline (RR, 0.49 [95% CI, 0.24 to 1.02]), but less likely to adhere to surveys (RR, 0.81 [95% CI, 0.68 to 0.97]). All patient populations had a similar likelihood of withdrawing. CONCLUSION: Black patients and individuals living in more disadvantaged neighborhoods are at risk for lower engagement in RSM. Further work is needed to identify and overcome barriers to equitable participation.

A CK2-dependent mechanism for activation of the JAK-STAT signaling pathway.

JAK-STAT signaling is involved in the regulation of cell survival, proliferation, and differentiation. JAK tyrosine kinases can be transiently activated by cytokines or growth factors in normal cells, whereas they become constitutively activated as a result of mutations that affect their function in tumors. Specifically, the JAK2V617F mutation is present in the majority of patients with myeloproliferative disorders (MPDs) and is implicated in the pathogenesis of these diseases. In the present study, we report that the kinase CK2 is a novel interaction partner of JAKs and is essential for JAK-STAT activation. We demonstrate that cytokine-induced activation of JAKs and STATs and the expression of suppressor of cytokine signaling 3 (SOCS-3), a downstream target, are inhibited by CK2 small interfering RNAs or pharmacologic inhibitors. Endogenous CK2 is associated with JAK2 and JAK1 and phosphorylates JAK2 in vitro. To extend these findings, we demonstrate that CK2 interacts with JAK2V617F and that CK2 inhibitors suppress JAK2V617F autophosphorylation and downstream signaling in HEL92.1.7 cells (HEL) and primary cells from polycythemia vera (PV) patients. Furthermore, CK2 inhibitors potently induce apoptosis of HEL cells and PV cells. Our data provide evidence for novel cross-talk between CK2 and JAK-STAT signaling, with implications for therapeutic intervention in JAK2V617F-positive MPDs.

The effect of obesity on fecal incontinence symptom distress, quality of life, and diagnostic testing measures in women.

INTRODUCTION AND HYPOTHESIS: Weight-loss has been demonstrated to result in an improvement in fecal incontinence (FI) severity; however, there is a paucity of data addressing the differential impact of FI on the quality of life (QOL) and results of diagnostic testing across BMI categories. We wished to evaluate symptom distress, QOL, and diagnostic testing parameters among normal, overweight, and obese women with fecal incontinence. METHODS: Women undergoing evaluation for FI between 2003 and 2012 were identified. Participants completed validated, symptom-specific distress, impact, and general QOL measures including the Modified Manchester Questionnaire (MMHQ), which includes the Fecal Incontinence Severity Index (FISI), and the mental and physical component summary scores, MCS and PCS, respectively, of the Short Form-12. Anorectal manometry measures were also included. Multivariate regression analyses were performed. RESULTS: Participants included 407 women with a mean age ± SD of 56 ± 13. Multivariate analyses revealed no differences in symptom-specific distress and impact as measured by MMHQ, MCS, and PCS across BMI groups; however, obese women had increased resting and squeeze pressures compared with normal and overweight BMI women (p < 0.0001 and p < 0.0001; p = 0.007 and p = 0.004 respectively). CONCLUSIONS: Obese women with FI did not have more general impact and symptom-specific distress and impact on quality of life compared with normal and overweight women. Obese women with FI had higher baseline anal resting and squeeze pressures suggesting a lower threshold to leakage with pressure increases.

The impact of obesity and LVAD-bridging on heart transplant candidate outcomes: a linked STS INTERMACS - OPTN/UNOS data analysis.

BACKGROUND: Limited data integrating waitlist and postheart transplant (HT) mortality have evaluated outcomes of left ventricular assist device (LVAD)-bridged strategy vs no LVAD according to patient characteristics. We evaluated waitlist and post-HT mortality in LVAD-bridged vs nonbridged patients based on body mass index (BMI). METHODS: We included linked adults listed for HT in Organ Procurement and Transplant Network/United Network for Organ Sharing and patients receiving durable LVAD as bridge to HT or candidacy in Society of Thoracic Surgeons/Interagency Mechanical Circulatory Support databases (2010-2019). Using BMI at listing or LVAD implant, we categorized patients as underweight (<18.5 kg/m2), normal weight (18.5-24.99 kg/m2), overweight (25-29.99 kg/m2), and obese (≥30 kg/m2). Kaplan-Meier analysis and multivariable Cox proportional hazards models informed the effect of LVAD-bridged and nonbridged strategy by BMI on waitlist, post-HT, and overall mortality (including waitlist and post-HT mortality). RESULTS: Among 11,216 LVAD-bridged and 17,122 nonbridged candidates, bridged candidates were more frequently obese (37.3% vs 28.6%) (p < 0.001). Multivariable analysis indicated increased waitlist mortality in LVAD-bridged vs nonbridged with overweight (Hazard ratio (HR) 1.18, 95% confidence interval (CI) 1.02-1.36) or obesity (HR 1.35, 95%CI 1.17-1.56) in comparison to normal weight candidates (HR 1.02, 95%CI 0.88-1.19) (p-interaction < 0.001). Post-transplant mortality was not statistically different in LVAD-bridged vs nonbridged patients across BMI categories (p-interaction = 0.26). There was a nonsignificant graded increase in overall mortality in LVAD-bridged with overweight (HR 1.53, 95%CI 1.39-1.68) or obesity (HR 1.61, 95%CI 1.46-1.78) compared to nonbridged patients (p-interaction = 0.13). CONCLUSIONS: LVAD-bridged candidates with obesity had higher waitlist mortality compared to nonbridged candidates with obesity. Post-transplant mortality was similar in LVAD-bridged and nonbridged patients, but obesity remained associated with increased mortality in both groups. This study may aid clinicians and advanced heart failure patients with obesity in decision-making.

Heart Transplant Outcomes After Total Artificial Heart.

BACKGROUND: We sought to compare heart transplant (HTX) outcomes from patients with a total artificial heart (TAH), biventricular assist device (BiVAD), or left ventricular assist device (LVAD) as a bridge to transplant (BTT). Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS)-Scientific Registry of Transplant Recipients (SRTR) created a dataset with TAH or durable mechanical circulatory support (MCS) who reached HTX between 2006 and 2015. METHODS: The retrospective analysis compared TAH outcomes with those with a BiVAD or LVAD before HTX. The primary outcome was posttransplant survival at 1, 36, and 60 months. Secondary outcomes included simultaneous heart-kidney transplants, donor characteristics, and mortality risk factors. INTERMACS-SRTR cohort had, at the time of HTX, 2762 patients with LVAD; 205 BiVAD (139 durable and 66 temporary RVAD); 176 TAH (6 prior HeartMate II). RESULTS: Sixty months after HTX, mortality rates were 16.5% in the total group: LVAD 15.2%, BiVAD 22.4%, and TAH 29%. Survival differed between the LVAD, the TAH, and BiVAD but not between the BiVAD and TAH groups. One-year survival and complication rates were similar across groups-there was no difference in survival by donor age in the overall cohort. There was a difference in TTD based on recipient age in the LVAD group but not in BiVAD or TAH groups. Occurrence of HTX-kidney and post-transplant dialysis were higher in the TAH versus LVAD and BiVAD groups. CONCLUSIONS: The TAH is an efficacious BTT. Refinements in technology and patient selection may improve outcomes.

Hospital Mortality and Adverse Events Following Repair of Congenital Heart Defects in Developing Countries.

BACKGROUND: Mortality associated with the correction of congenital heart disease has decreased to approximately 2% in developed countries and major adverse events are uncommon. Outcomes in developing countries are less well defined. The World Database for Pediatric and Congenital Heart Surgery was utilized to compare mortality and adverse events in developed and developing countries. METHODS: A total of 16,040 primary procedures were identified over a two-year period. Centers that submitted procedures were dichotomized to low/middle income (LMI) and high income (HI) by the Gross National Income per capita categorization. Mortality was defined as any death following the primary procedure to discharge or 90 days inpatient. Multiple logistic regression models were utilized to identify independent predictors of mortality. RESULTS: Of the total number of procedures analyzed, 83% (n = 13,294) were from LMI centers. Among all centers, the mean age at operation was 2.2 years, with 36% (n = 5,743) less than six months; 85% (n = 11,307) of procedures were STAT I/II for LMI centers compared with 77% (n = 2127) for HI centers (P < .0001). Overall mortality across the cohort was 2.27%. There was a statistical difference in mortality between HI centers (0.55%) versus LMI centers (2.64%) (P < .0001). After adjustment for other risk factors, the risk of death remained significantly higher in LMI centers (odds ratio: 2.36, 95% confidence interval: 1.707-3.27). CONCLUSION: Although surgical expertise has increased across the globe, there remains a disparity with some outcomes associated with the correction of congenital heart disease between developing and developed countries. Further studies are needed to identify specific opportunities for improvement.

Excretion of anti-angiogenic proteins in patients with chronic allograft dysfunction.

BACKGROUND: We have recently documented the appearance of an anti-angiogenic peptide, endorepellin, in the urine of patients with chronic allograft dysfunction (CAD). METHODS: Here, we analyzed using enzyme-linked immunosorbent assay the excretion of anti-angiogenic peptides endostatin, pigment epithelium-derived factor (PEDF) and Kruppel-like factor-2 (KLF-2), in healthy individuals, patients with stable graft function and patients with various degrees of CAD. RESULTS: In healthy subjects and patients with CAD-0, endostatin, PEDF and KLF-2 excretions were at the level of detection. In contrast, there were significant differences between the patients with CAD-3 and CAD-0, CAD-1 and healthy controls for endostatin and CAD-0 versus CAD-3 for PEDF, but no differences in KLF-2 excretion. Receiver operating characteristic (ROC) curve analyses demonstrated a highly discriminative profile for all three biomarkers: the combination of these parameters offered 83% sensitivity and 90% specificity in distinguishing CAD-0 from CAD-1-3. The quality of these potential biomarkers of CAD was, however, highest in discriminating CAD status in biopsy-proven cases and dropped when CAD-0 was diagnosed based on clinical criteria. CONCLUSIONS: In conclusion, these findings indicate the diagnostic potential of urinary detection of endostatin, PEDF and to lesser degree KLF-2 and suggest a mechanistic role played by anti-angiogenic substances in the developing vasculopathy and vascular rarefaction in patients with CAD.