Overall Risk Of Death Research Articles

Influence of persistent atrial fibrillation on the prognosis of heart failure with preserved, mildly reduced, and reduced ejection fraction in women and men

Abstract Introduction Heart failure (HF) is one of the leading causes of death from cardiovascular disease. Persistent atrial fibrillation (PAF) is associated with a worse prognosis in HF. However, little is known about the influence of AF on mortality in women and men with heart failure with preserved (HFpEF ≥50%), mildly reduced (HFmrEF 41% to 49%), and reduced ejection fraction (HFrEF ≤40%). Purpose to analyze the characteristics and influence of PAF on the prognosis of different HF phenotypes. Methods From February 2017 to September 2020, we analyzed hospitalizations, emergency admissions, and mortality of different HF phenotypes with and without PAF. Baseline data included clinical features and echocardiographic findings. Statistical analyses were performed using the Kaplan-Meier (K-M) and Cox proportional hazards methods to analyze mortality rates. Results We studied 11,543 patients, with a mean of 64.1±14.0 years: 55.1% male, 42% with HFrEF, 12.8% with HFmrEF, and 45.1% with HFpEF. PAF was associated with higher mean age (67.6±14.3 vs. 62.8±13.4 years, p<0.001) and more prevalent in men (21% vs. 19%; p=0.019) and in patients with valvular and Chagas etiologies, chronic kidney disease (CKD), stroke, and anemia. The prevalence of PAF in women and men was, respectively, 12.4% vs. 18.3% (p<0.001) in HFrEF, 18.1% vs. 22.2% (p=0.029) in HFmrEF, and 23.3% vs. 23.9 (p=NS) in HFpEF. The overall mortality was 21.6%, with mortality being 2.4 times higher in patients with PAF (40.9% vs. 16.7%, p<0.001) compared to sinus rhythm but similar in women and men with PAF (39.5% vs. 41.9%; p=NS), respectively. The hospitalization (30.3% vs 19.4%, p<0.001) and emergency admissions (38.4% vs 25.7%, p<0.001) were higher in patients with AF. Cumulative mortality was higher in patients with PAF in all HF phenotypes: HFrEF (36.6%), HFmrEF (16.8%), HFpEF (46.6%; p<0.001). Men had higher cumulative mortality in HFrEF (18.3% vs. 12.4%; p<0.001) and in HFmrEF (22.2% vs. 18.09%; p=0.029), but not for HFpEF (23.9% vs. 23.3%; p=NS). In the multivariate analysis, adjusted for age, sex, previous myocardial infarction and stroke, diabetes, CKD, PAF, Cardiac surgery, and electronic device implantation, PAF was an independent predictor of death in all HF phenotypes: HFrEF [HR=1.78(95%CI:1.57-2.02); p<0.001], HFmrEF [HR=2.14(95%CI:1.74-2.65); p<0.001], HFpEF [HR=2.08(95%CI:1.82-2.37); p<0.001]. Conclusion PAF is a frequent comorbidity in HF and is associated with a worse prognosis in all HF phenotypes. Women with PAF had a better prognosis than men with AF in HFrEF and HFmrEF. Sex-specific strategies to maintain sinus rhythm in HF patients on the overall risk of death are needed.

Association Between Insurance Status and Nonelderly Penile Squamous Cell Carcinoma Survivorship: A National Retrospective Analysis

Background: Penile squamous cell carcinoma is an aggressive malignancy with significant physical and psychological impacts. Socioeconomic factors influence prognosis in genitourinary cancers, making the investigation of insurance status critical for reducing cancer burden and promoting health equity. Materials and Methods: Men diagnosed with primary penile squamous cell carcinoma from 2007 to 2015 were identified from the Surveillance, Epidemiology, and End Results (SEER) national database. Participants were categorized based on insurance status: privately insured, Medicaid, and uninsured. Pearson’s chi-squared test assessed the distribution of observed frequencies between the patient demographics, socioeconomic status, tumor characteristics, and surgical variables across the insurance groups. Overall and cancer-specific survival was estimated using a multivariate Cox hazards proportional model analysis. Results: The multivariate Cox hazards proportional model showed that, compared to privately insured patients, Medicaid patients had an increased risk for overall death (hazard ratio [HR] = HR 1.54; 95% CI, 1.12–2.07). For cancer-specific mortality, Medicaid patients had an increased risk of death compared to privately insured patients (HR 1.58; 95% CI, 1.11–2.25). Conclusions: Medicaid does not mitigate the differences caused by health insurance status due to health insurance disparities for overall or cancer-specific mortality. Lower Medicaid reimbursements and out-of-pocket costs lead to a narrow network of physicians, hospitals, and treatment modalities that compromise health equity. Increasing awareness of health insurance disparities and improving access to care via a clinician–community–governmental partnership can potentially lead to improved predictive outcomes.

Association between serum IgM and all-cause mortality risk in Chinese centenarians: a prospective cohort study

BackgroundWe investigated the associations between IgM, IgG, IgA, and IgE levels and all-cause mortality risk in Chinese centenarians.MethodsAll participants were from the China Hainan Centenarian Cohort Study. Eligible participants were divided into quartiles based on their IgM, IgG, IgA, and IgE levels. We used restricted cubic spline analyses, Cox regression analyses, and Kaplan–Meier survival curves to analyze associations between IgM, IgG, IgA, and IgE and all-cause mortality risk.ResultsA total of 906 centenarian participants were included in this study (81.2% female; median age, 102 years). During a median follow-up of 30.1 months, 838 (92.5%) participants died. Restricted cubic spline analysis revealed a nonlinear relationship (“L” type) between serum IgM level and all-cause mortality. Compared with the higher three quartiles of serum IgM level, the lowest quartile was associated with a higher risk of death (Q1 versus Q2-Q4: HR, 1.365; 95% CI, 1.166–1.598; P < 0.001). Among individuals for whom IgM < 0.708 g/L (Q1), the risk of all-cause mortality was 36.5% higher. Kaplan–Meier analyses showed that centenarians with lower serum IgM levels had significantly shorter median survival time (Q1 versus Q2-Q4: 26 months versus 32 months, log-rank P = 0.001).ConclusionSerum IgM levels in centenarians significantly correlated with the risk of death, suggesting that they are suitable for predicting the overall risk of death in centenarians and can be used as an independent predictor of death.

Racial Inequities in Receiving Neoadjuvant Treatment in Patients With Pancreatic Cancer Are Associated With Worse Outcomes in Louisiana.

Pancreatic ductal adenocarcinoma (PDAC) is the third leading cause of cancer-related deaths. In recent years, the approach to managing this malignancy has evolved toward embracing neoadjuvant treatment (NAT), backed by studies reporting its survival benefit. This study aimed to identify factors that contribute to disparities in NAT utilization and their impact on outcomes in patients with PDAC who underwent resection in Louisiana. Data on diagnosed PDAC cases were obtained from the Louisiana Tumor Registry between 2000 and 2020. We conducted multivariable logistic regression to adjust for potential confounding factors in assessing the covariate relationships with NAT use. Multivariate Cox regression analysis was performed to determine which factors were associated with survival. Chained multiple imputation was performed on covariates with missing data in multivariable regressions. The study encompassed 2121 patients who underwent resection for PDAC. Upon controlling for potential confounding variables, Black patients were on average 5.7% less likely to receive NAT than their White counterparts (ATE = 5.7, aOR= 0.56, 95% CI = 0.40-0.80, p = 0.001). After adjustment for confounding factors, there was a significant decrease in the risk of overall death for patients who received NAT (aHR = 0.82, 95% CI = 0.71-0.94, p = 0.006). There was no significant interaction between race and NAT for the risk of death. Black patients with PDAC were less likely to receive NAT before resection in Louisiana. Overall survival improved in patients who underwent NAT. These differences were independent of insurance status and poverty zip codes, and future investigations should identify modifiable barriers to access and receipt of NAT in patients with PDAC.

The incremental value of left ventricular energy loss in predicting adverse events in chronic kidney disease patients with preserved ejection fraction

BackgroundVector flow mapping (VFM) is a new echocardiographic technology that can effectively evaluate systolic and diastolic hemodynamic function. However, little is known about the prognostic value of VFM-related parameters. In this paper we aimed to investigate whether left ventricular energy loss (EL) parameters as assessed by VFM enhance prediction of adverse events in patients with chronic kidney disease with preserved ejection fraction. MethodsOne hundred thirty-nine prospectively recruited patients (66% male, 58% on dialysis) with CKD stage 3–5 with normal left ventricular ejection fraction (LVEF) made up the study cohort. Global longitudinal strain (GLS) was calculated using 2-dimensional speckle tracking, and the LV EL during one cardiac cycle for each period was measured using VFM technology. Participants were followed for 4.17 ± 1.58 years for the primary end point of overall mortality and major adverse cardiovascular events (MACE). ResultsForty-five (32%) patients had a primary endpoint event. The EL during each period especially during the ejection stage (Ej-EL) was significantly higher in patients with adverse events than in those without, meanwhile the LV GLS were lower. The Ej-EL (HR: 1.11; 95% CI: 1.06–1.15) and LV GLS (HR: 0.87; 95% CI: 0.81–0.94) (all P < .001) were independent predictors for the primary end point. Increased Ej-EL (≥6.13, 10−3 J/m s) and impaired GLS (<15.52, %) were associated with a higher risk of overall mortality death and MACE (log rank χ2 = 26.94, 7.19; P < .001, =0.007), and DeLong tests showed that Ej-EL (AUC = 0.823) has a slight advantage in predicting adverse events compared to GLS (AUC = 0.681). Furthermore, the addition of Ej-EL to a model with conventional parameters did more to improve the model's discrimination compared to GLS. ConclusionsIncreased Ej-EL as determined by VFM is associated with a higher risk of overall death and MACE in CKD patients with preserved EF.

Language barriers in head and neck cancer: Matched pair analysis of outcomes between non-English speaking and English-speaking patients.

As society grows in cultural diversity, an increasing proportion of patients are expected to be from non-English speaking backgrounds. This study sought to compare the clinical outcomes between non-English speakers and English speakers treated by radiation therapy for head and neck cancer. Seventy-five non-English speaking patients with squamous cell carcinoma of the head and neck were matched to English-speaking controls based on patient and disease variables; clinical outcomes were compared. Non-English speaking patients had inferior 3-year overall survival (64% vs. 77%, p = 0.02) and progression-free survival (59% vs. 73%, p = 0.01) compared with the English-speaking cohort. On logistical regression, non-English-speaking status was associated with a significantly increased risk of overall death (OR = 1.41; 95% CI, 1.09-1.92). Prognosis differed significantly between non-English speaking and English-speaking patients. Culturally tailored programs to address language barriers should be considered to ameliorate disparities in outcome.

Fecal Immunochemical Test Screening and Risk of Colorectal Cancer Death

The fecal immunochemical test (FIT) is widely used for colorectal cancer (CRC) screening, but evidence of its effectiveness is limited. To evaluate whether FIT screening is associated with a lower risk of dying from CRC overall, according to cancer location, and within demographic groups. This nested case-control study in a cohort of screening-eligible people was conducted in 2 large, integrated health systems of racially, ethnically, and socioeconomically diverse members with long-term programs of mailed FIT screening outreach. Eligible participants included people aged 52 to 85 years who died from colorectal adenocarcinoma between 2011 and 2017 (cases); cases were matched in a 1:8 ratio based on age, sex, health-plan membership duration, and geographic area to randomly selected persons who were alive and CRC-free on case's diagnosis date (controls). Data analysis was conducted from January 2002 to December 2017. Completing 1 or more FIT screenings in the 5-year period prior to the CRC diagnosis date among cases or the corresponding date among controls; in secondary analyses, 2- to 10-year intervals were evaluated. The primary study outcome was CRC death overall and by tumor location. Secondary analyses were performed to assess CRC death by race and ethnicity. From a cohort of 2 127 128 people, a total of 10 711 participants (3529 aged 60-69 years [32.9%]; 5587 male [52.1%] and 5124 female [47.8%]; 1254 non-Hispanic Asian [11.7%]; 973 non-Hispanic Black [9.1%]; 1929 Hispanic or Latino [18.0%]; 6345 non-Hispanic White [59.2%]) was identified, including 1103 cases and 9608 controls. Among controls during the 10-year period prior to the reference date, 6101 (63.5%) completed 1 or more FITs with a cumulative 12.6% positivity rate (768 controls), of whom 610 (79.4%) had a colonoscopy within 1 year. During the 5-year period, 494 cases (44.8%) and 5345 controls (55.6%) completed 1 or more FITs. In regression analysis, completing 1 or more FIT screening was associated with a 33% lower risk of death from CRC (adjusted odds ratio [aOR], 0.67; 95% CI, 0.59-0.76) and 42% lower risk in the left colon and rectum (aOR, 0.58; 95% CI, 0.48-0.71). There was no association with right colon cancers (aOR, 0.83; 95% CI, 0.69-1.01) but the difference in the estimates between the right colon and left colon or rectum was statistically significant (P = .01). FIT screening was associated with lower CRC mortality risk among non-Hispanic Asian (aOR, 0.37; 95% CI, 0.23-0.59), non-Hispanic Black (aOR, 0.58; 95% CI, 0.39-0.85) and non-Hispanic White individuals (aOR, 0.70; 95% CI, 0.57-0.86) (P for homogeneity = .04 for homogeneity). In this nested case-control study, completing FIT was associated with a lower risk of overall death from CRC, particularly in the left colon, and the associations were observed across racial and ethnic groups. These findings support the use of FIT in population-based screening strategies.

Causes of death in patients with atrial fibrillation anticoagulated with rivaroxaban: a pooled analysis of XANTUS.

Anticoagulation can prevent stroke and prolong lives in patients with atrial fibrillation (AF). However, anticoagulated patients with AF remain at risk of death. The aim of this study was to investigate the causes of death and factors associated with all-cause and cardiovascular death in the XANTUS population. Causes of death occurring within a year after rivaroxaban initiation in patients in the XANTUS programme studies were adjudicated by a central adjudication committee and classified following international guidance. Baseline characteristics associated with all-cause or cardiovascular death were identified. Of 11 040 patients, 187 (1.7%) died. Almost half of these deaths were due to cardiovascular causes other than bleeding (n = 82, 43.9%), particularly heart failure (n = 38, 20.3%) and sudden or unwitnessed death (n = 24, 12.8%). Fatal stroke (n = 8, 4.3%), which was classified as a type of cardiovascular death, and fatal bleeding (n = 17, 9.1%) were less common causes of death. Independent factors associated with all-cause or cardiovascular death included age, AF type, body mass index, left ventricular ejection fraction, hospitalization at baseline, rivaroxaban dose, and anaemia. The overall risk of death due to stroke or bleeding was low in XANTUS. Anticoagulated patients with AF remain at risk of death due to heart failure and sudden death. Potential interventions to reduce cardiovascular deaths in anticoagulated patients with AF require further investigation, e.g. early rhythm control therapy and AF ablation. NCT01606995, NCT01750788, NCT01800006.

Disparities in cause-specific mortality by health insurance type and premium: evidence from Korean NHIS-HEALS cohort study, 2002–2019

BackgroundAlthough one’s socioeconomic status affects health outcomes, limited research explored how South Korea’s National Health Insurance (NHI) system affects mortality rates. This study investigated whether health insurance type and insurance premiums are associated with mortality.MethodsBased on the National Health Insurance Service-Health Screening cohort, 246,172 men and 206,534 women aged ≥ 40 years at baseline (2002–2003) were included and followed until 2019. Health insurance type was categorized as employee-insured (EI) or self-employed-insured (SI). To define low, medium, and high economic status groups, we used insurance premiums at baseline. Death was determined using the date and cause of death included in the cohort. Cox proportional hazard models were used to analyze the association between insurance factors and the overall and cause-specific mortality.ResultsThe SI group had a significantly higher risk of overall death compared to the EI group (adjusted hazard ratio (HR) [95% confidence interval]: 1.13 [1.10–1.15] for men and 1.18 [1.15–1.22] for women), after adjusting for various factors. This trend extended to death from the five major causes of death in South Korea (cancer, cardiovascular disease, cerebrovascular disease, pneumonia, and intentional self-harm) and from external causes, with a higher risk of death in the SI group (vs. the EI group). Further analysis stratified by economic status revealed that individuals with lower economic status faced higher risk of overall death and cause-specific mortality in both sexes, compared to those with high economic status for both health insurance types.ConclusionThis nationwide study found that the SI group and those with lower economic status faced higher risk of overall mortality and death from the five major causes in South Korea. These findings highlight the potential disparities in health outcomes within the NHI system. To address these gaps, strategies should target risk factors for death at the individual level and governments should incorporate such strategies into public health policy development at the population level.Trial registrationThis study was approved by the Institutional Review Board of Chungbuk National University Hospital (CBNUH-202211-HR-0236) and adhered to the principles of the Declaration of Helsinki (1975).

Survival paradox between stage IIB/C and stage IIIA colon cancer: is it time to revise the American Joint Committee on Cancer TNM system?

A survival paradox between T4N0 (Stage IIB/IIC) and Stage IIIA colon cancer exists, even after adjusting for adequate lymph node (LN) retrieval and receipt of adjuvant chemotherapy (C). We conducted a large hospital-based study to re-evaluate this survival paradox based on the newest 8th edition staging system. The National Cancer Data Base was queried to evaluate 35,606 patients diagnosed with Stage IIB, IIC, and IIIA colon cancer between 2010 and 2017. The Kaplan-Meier method and log-rank test were used to compare unadjusted overall survival (OS). Multivariable Cox proportional hazards model was used to determine the association of stage with hazard ratios adjusted for relevant demographic and clinical variables including ≥ 12 LNs retrieved and receipt of adjuvant chemotherapy. P value < 0.05 was considered statistically significant. The 5-year OS for optimally treated stage IIIA colon cancer (receipt of C) was 84.3%, which was significantly higher than stage IIB/C (≥ 12 LNs retrieved + C) (72.8%; P < 0.0001). Stage was an independent predictor of OS. Among optimally treated Stage IIIA patients, T1N1 had the best survival (90.6%) while stage T4bN0 (stage IIC) had the worst (70.9%) (P < 0.0001). Compared to stage IIB, stage IIC had a 17% increased risk of overall death while stage IIIA had a 21% reduction in death (P < 0.0001). Stage IIB/C and Stage IIIA survival paradox persists even after accounting for receipt of adjuvant chemotherapy and adequate lymph node retrieval. Future iteration of the TNM system should take this paradox into consideration.

Spontaneous intestinal perforation among very preterm infants in China: a multicenter cohort study.

Spontaneous intestinal perforation (SIP) is one of the most serious surgical bowel conditions affecting preterm infants. There are limited data on the mortality and morbidities of very preterm infants [VPIs, <32 weeks' gestational age (GA)] with SIP in China. The study aimed to describe the prevalence, treatment, and outcomes of SIP among VPIs in China. This retrospective cohort study included all infants born at 24+0-31+6 weeks GA from January 1, 2019, to December 31, 2020, and admitted within seven days after birth to the neonatal intensive care units in the Chinese Neonatal Network. The primary outcome was survival without major morbidities. The association between SIP and neonatal outcomes was evaluated using multivariate logistic regression controlling for possible confounders. Out of the 15,814 enrolled infants, 150 (1.0%) developed SIP with a median onset age of four (IQR 2-6) days. Infants with GA 24+0-25+6 weeks had the highest incidence of SIP (13/532, 2.4%), followed by those with GA 26+0-27+6 weeks (22/2,005, 1.1%), 28+0-29+6 weeks (44/5,269, 0.8%) and 30+0-31+6 weeks (71/8,008, 0.9%). Ten SIP cases were lost to follow-up with unknown survival status and 41 (29.3%) of the remaining 140 infants with SIP died during hospitalization. Only 29.3% of infants with SIP survived without major morbidities, significantly lower than those without SIP (59.2%; P<0.01). Multivariate analysis revealed SIP was associated with a higher risk of overall death (adjusted OR 3.36; 95% CI: 1.85 to 6.08), late-onset sepsis (adjusted OR 2.10; 95% CI: 1.02 to 4.31), and bronchopulmonary dysplasia (adjusted OR 2.49; 95% CI: 1.44 to 4.30). Among all infants with SIP, 28 (18.7%) did not receive any surgical intervention. Laparotomy was provided to 113 (92.6%) of the remaining 122 infants, solely (84/122, 68.9%) or following peritoneal drainage (29/122, 23.8%), while nine (7.4%) infants underwent peritoneal drainage only. Around 1% of VPIs in China developed SIP, associated with increased risk of mortality and morbidities. Over 90% of VPIs with SIP underwent laparotomy as initial or subsequent surgical treatment. Effective and evidence-based strategies are needed for the prevention and management of SIP.

Abstract P275: Long-Term Mortality Prediction Model for HIV Patients With Heart Failure: Analysis From a Multi-Center Cohort Database in New York City Health + Hospitals

Introduction: Given the intricate interplay of HIV infection and heart failure (HF), conventional mortality prediction models for general heart failure may prove insufficient for this specific population. Our objective is to assess the fitness of current HF death prediction models and develop a prediction model tailored to the unique challenges of long-term mortality risk in HIV patients with heart failure. Method: The statistical models were developed through New York City Health + Hospitals HIV Heart failure (NYC 4H) retrospective cohort. Demographic and medical factors were obtained through chart reviews, while social adversities were assessed via licensed social workers' psychosocial assessment notes. Patients with baseline cancer, no baseline ejection fraction (EF), or those below 18 years of age were excluded from the study. Multivariable logistic regression models were constructed to predict the risk of overall death. Model 1 was derived from the existing MAGGIC Risk prediction model for general heart failure patients. Model 2 employed backward step-wise selection from NYC 4H cohort for HIV HF biologic factors, functional status, medical and interventional treatment to predict mortality risk. Model 3 further adjusted for single significant social factors and insurance. Model comparison was performed using the area under the ROC curve. Result: The study comprised 597 HIV heart failure patients, averaging 61.1 years in age. Over the 4-year follow-up, 102 deaths (17.1%) were recorded. Model 1 (MAGGIC Risk prediction model) had an AUC of 0.72. Model 2, which included backward-selected variables such as age, race, HIV viral load at baseline and follow-up, CD4 count at baseline, EF at baseline, smoking status, chronic obstructive pulmonary disease, pulmonary hypertension, peripheral arterial disease, chronic kidney disease, activities of daily living, obesity, implantable cardioverter-defibrillator implantation, and the total number of guideline-directed medical therapy, significantly improved the AUC to 0.85. Incorporating social factors such as exposure to any lifetime adversities, specific adversities (lack of family support, polysubstance abuse, and mental illness), and insurance status, model 3 raised the AUC to 0.88. In heart failure with reduced EF (HFrEF) subset (n=502), Model 2 and Model 3 achieved AUCs of 0.88 and 0.90, respectively. Conclusion: HIV heart failure patients exhibit unique mortality prediction factors compared to general heart failure patients without HIV infection. Considering the high burden of social adversities, socioeconomic factors can enhance the predictive yield of models within this specific population.

Prognostic factors of renal cell cancer in elderly patients: a population-based cohort study

Mortality in renal cell cancer (RCC) is high in the elderly population. Comorbidities have a greater impact on overall prognosis of RCC among elderly patients than in younger patients. All new RCC cases were collected in people over 74 years of age between 1995 and 2018 from the Finnish cancer registry. The comorbidities were identified from the Care Registry for Healthcare. Charlson Comorbidity Index (CCI) was used to evaluate the risk of death based on comorbidities. The overall risk of death was analyzed using the Cox regression model. The risk for RCC death was analyzed using Fine and Gray regression analysis. Individual prognostic role of CCI components was evaluated by adding each component separately into the multivariable Fine and Gray regression model. Using the most prognostic comorbidities we constructed a nomogram to predict RCC mortality. Statistically significant prognostic factors of RCC death were tumor morphology (clear cell, papillary and chromophobe), sex, operative treatment, age, primary tumor extent and CCI. The strongest prognostic factors for overall mortality were tumor extent, tumor morphology and operative treatment. Among the components of CCI, the most important comorbidities predicting mortality were dementia, heart failure and kidney disease. The limitation of this study is that the comorbidities have only been recorded at inpatient and outpatient hospital contacts, which is why the prevalence of comorbidities is probably underestimated. In addition, physical performance status was not available from registry data, but it significantly affects the treatment decisions. RCC mortality is high in the elderly population. Among comorbidities, dementia and heart failure have the greatest impact on the prognosis. Curative treatment in selected elderly patients is efficient and should be considered in patients who can tolerate it and have only limited comorbidities.

Patient Outcomes by Ventricular Systolic and Diastolic Function.

Left ventricular dysfunction is characterized by systolic and diastolic parameters, leading to heart failure (HF) with reduced or preserved ejection fraction (EF), respectively. The goal of this study is to examine the impact of left ventricular systolic and diastolic dysfunction (DD) on patient outcomes. Two cohorts were used in this analysis: Cohort A included 136 455 patients with EF ≥50%, stratified by the presence and grade of DD. Cohort B included 16 850 patients with EF <50%, stratified by EF quartiles. Patients were followed to the end points of all-cause death and cardiovascular, HF, or cardiac arrest hospitalizations. Over a median follow-up of 3.42 years, 23 946 (16%) patients died and 31 113 (20%), 13 305 (9%), and 1269 (1%) were hospitalized for cardiovascular, HF, or cardiac arrest causes, respectively. With adjustment for comorbidities, the risk of all-cause mortality and of cardiovascular and HF hospitalizations increased steadily with increasing grade of DD in patients with normal EF, and even more so in patients with worsening EF. The risk of hospitalization for cardiac arrest in patients with grade III DD, however, was comparable to that of patients with EF <25% (hazard ratio, 1.00 [95% CI, 0.98-1.01]) and worse than that of patients in better EF quartiles. Although systolic dysfunction is associated with a greater risk of overall death and HF hospitalizations than DD, the risk of cardiac arrest in patients with grade II and III DD is comparable to that of patients with moderate and severe systolic dysfunction, respectively. Future studies are needed to examine treatment strategies than can improve these outcomes.

Evidence of COVID-19 fatalities in Swedish neighborhoods from a full population study

The COVID-19 pandemic has highlighted a debate about whether marginalized communities suffered the disproportionate brunt of the pandemic’s mortality. Empirical studies addressing this question typically suffer from statistical uncertainties and potential biases associated with uneven and incomplete reporting. We use geo-coded micro-level data for the entire population of Sweden to analyze how local neighborhood characteristics affect the likelihood of dying with COVID-19 at individual level, given the individual’s overall risk of death. We control for several individual and regional characteristics to compare the results in specific communities to overall death patterns in Sweden during 2020. When accounting for the probability to die of any cause, we find that individuals residing in socioeconomically disadvantaged neighborhoods were not more likely to die with COVID-19 than individuals residing elsewhere. Importantly, we do find that individuals show a generally higher probability of death in these neighborhoods. Nevertheless, ethnicity is an important explanatory factor for COVID-19 deaths for foreign-born individuals, especially from East Africa, who are more likely to pass away regardless of residential neighborhood.

Genetic Correlates of Biological Aging and the Influence on Prediction of Mortality.

Longevity and disease-free survival are influenced by a combination of genetics and lifestyle. Biological age (BioAge), a measure of aging based on composite biomarkers, may outperform chronological age in predicting health and longevity. This study investigated the relationship between genetic risks, lifestyle factors, and delta age (Δage), estimated as the difference between biological and chronological age. BioAge and Δage were calculated for 52418 participants from the population-based Lifelines cohort. We computed 2 independent polygenic risk scores (PRS) for health span and DNA methylation-based aging clock to characterize genetic risks. The capacity of BioAge to predict all-cause mortality when adjusted for chronological age and genetic risks for aging, was assessed. Obesity, lifestyle, socioeconomic status, sex, and genetic variations in a population contributed to the differences in the rates of accelerated aging. The overall risk of death for a 1-year increase in BioAge for a given chronological age and sex among the genotyped participants was 11% (HR = 1.11; 95% CI: 1.09, 1.13). After adjusting for genetic factors, BioAge maintained its sensitivity for predicting mortality. Findings from this study ascertain that BioAge can be a useful tool for risk stratification in research and aging interventions.

Well-defined survival outcome disparity across age cutoffs at 45 and 60 for medullary thyroid carcinoma: a long-term retrospective cohort study of 3601 patients.

Medullary thyroid cancer (MTC) is a challenging malignancy. The survival outcome of MTC based on AJCC staging system does not render a discriminant classifier among early stages. 3601 MTC patients from 2000 to 2018 were identified from the Surveillance, Epidemiology, and End Results (SEER) database. Smooth curve fitting, Cox proportional hazard regression and competing risk analysis were applied. A linear correlation between age and log RR (relative risk of overall death) was detected. Overlaps were observed between K-M curves representing patients aged 45-50, 50-55, and 55-60. The study cohort was divided into 3 subgroups with 2 age cutoffs set at 45 and 60. Each further advanced age cutoff population resulted in a roughly "5%" increase in MTC-specific death risks and an approximately "3 times" increase in non-MTC-specific death risks. The survival outcome disparity across age cutoffs at 45 and 60 for MTC has been well defined.

Matched-pair long-term survival analysis of male and female patients with breast cancer: a population-based study.

Previous studies found that the long-term survival of male breast cancer patients differed from those of female patients, however, the conclusions were contradictory. We conducted the study to examine the sex disparity in breast cancer survival by carefully controlling demographic and clinical factors using data from the Shanghai Cancer Registry (SCR). Every male breast cancer patient was matched with four female patients by the diagnosis year, age, stage, and histology. We used Kaplan-Meier survival estimates to calculate the cumulative observed overall survival (OS) and cancer-specific survival (CSS) rates and log-rank tests to compare the survival rates by sex. We used Cox proportional-hazards regression models to assess the association between sex and risk of death. A total of 50,958 patients with breast cancer (0.85% male) were registered in the SCR between 2002 and 2013. After matching, 434 male and 1,736 female patients were included in the study. With a median follow-up of 10 years, men with breast cancer showed worse OS (P<0.001) and CSS (P<0.001) than did women. The 5- and 10-year OS rates for male and female patients were 67.27% and 77.75%, and 45.95% and 62.60%, respectively; the 5- and 10-year CSS rates for male and female patients were 70.19% and 79.79%, and 50.57% and 67.20%, respectively. Compared with women, men had 65% increased risk of overall death [95% confidence interval (CI): 1.42-1.92] and 70% increased risk of cancer-specific death (95% CI: 1.44-2.00). This study found male patients with breast cancer had poorer long-term survival than women in China.

Establishing Standard of Care in Predicting Serious Complications for Patients Planned to Undergo Allogenic Hematopeotic Stem Cell Transplantation

Background: There is no reliable way to predict the individual risk of suffering from relevant complications during the course of Hematopoetic Stem Cell Transplantation (HSCT), because the huge amount of multidimensional parameters influencing clinical outcome is impossible for a human to compute accurately. Reliable prediction of complications: supports patients and physicians to make informed decisions, simplifies choosing best matched HSCT donors to avoid complications and enables superior, individualized planning of conditioning and prophylaxis. Up to now prediction is not based on evidence but rather experience, which differs amongst physicians. MatchGraft.AI is an artificial intelligence based machine learning tool that predicts the individual risk of acute Graft versus Host Disease, recurrence of basic disease and overall risk of death, using only pre transplant data (Table 1). The model was trained and tested on retrospective data of an international, multicenter cohort. Aim: Explore standard of care of choosing an HSCT donor and compare choice with real world data and MatchGraft.AI. Method: We developed an electronic questionnaire with 200 short patient histories including all parameters Matchgraft.AI is using. Pediatric and adult, benign and malignant cases with different donor types (matched unrelated, matched sibling, haploidentical family donor) are represented. This real world data is derived from a retrospective cohort of pediatric and adult patients of Charité Universitätsmedizin. 50 international experts in HSCT will: 1. choose a donor 2. predict individual risk of acute Graft versus Host Disease, risk of relapse and overall death for 50 individual patients. Cases are randomly allotted according to the physician's specialty (adult/pediatric treater, both). Questionnaires are anonymized. Answers are not traceable to the expert. Personal results compared with real world outcome and MatchGraft.AI can be provided to participants, if they wish. Results: We compare sensitivity and specificity of MatchGraft.AI to the standard of care, which is expert opinion and real world outcome. We examine: 1. whether the choosing of a donor is dependent on the individual physician or consistent throughout different HSCT experts. 2. how precise HSCT experts can predict the occurrence of severe complications for patients planned to undergo HSCT. 3. how well MatchGraft.AI can predict the occurrence of severe complications for patients planned to undergo HSCT in comparison. Conclusion: This study will provide important data about the standard of care in HSCT donor choosing and for the planned prospective study evaluating MatchGraft.AI.

Trends in mortality risk of patients with congenital heart disease during the COVID-19 pandemic

Cardiovascular conditions are considered risk factors for poor outcomes associated with COVID-19. However, the effect of the COVID-19 pandemic on the mortality of patients with congenital heart disease (CHD) is unclear. Our study aims to examine the trends in mortality risk of CHD patients during the COVID-19 pandemic. This is a retrospective cohort study from the Pediatric Cardiac Care Consortium, a US-based registry of interventions for CHD. We included patients having US residence and direct identifiers; death events were captured by matching with the National Death Index. The observation window (2017-2022) was divided into pre-COVID-19 and COVID-19 era defined around the national onset of COVID-19 disease in 2020. Stratified Cox model was used to assess all-cause mortality between the pre- and the COVID-19 era. Among 45,130 patients with CHD (median age in 2017: 23.3 years, IQR: 19.0-28.4), 503 deaths occurred during the pandemic with 44 deaths (8.7%) attributed to COVID-19 (COVID-19 mortality rate of 0.09%). The overall risk of death for patients with all types of CHD during the pandemic was significantly higher compared to the pre-COVID-19 era (aHR 1.28, 95%CI: 1.08-1.53), with a differential trend towards increased risk in patients with two-ventricle (aHR 1.44, 95% CI: 1.19-1.76) vs unchanged risk for those with single ventricle CHD (aHR=0.83, 95% CI: 0.57-1.21). Adjusted subgroup analysis revealed a higher risk of death during the pandemic for CHD patients with male and chromosomal abnormalities. The excess deaths during the pandemic were attributed to COVID-19 itself rather than CHD or cardiovascular conditions. In this large CHD cohort study, there was a higher risk of death among CHD patients with male and chromosomal abnormalities. A differential trend towards higher risk for those with two vs. unchanged risk for single ventricle CHD was presented. The excess mortality was attributed to the COVID-19 itself and not to conditions potentially related to deferral of care. These results justify targeted protective measures towards the CHD population and may provide guidance for public health and medical care response in future epidemics.