Higher Mortality Hazard Research Articles

Ambient Air Pollution Exposure and Outcomes in Patients Receiving Lung Transplant

Elevated ambient fine particulate matter (PM2.5) air pollution exposure has been associated with poor health outcomes across several domains, but its associated outcomes among lung transplant recipients are poorly understood. To investigate whether greater PM2.5 exposure at the zip code of residence is associated with a higher hazard for mortality and graft failure in patients with lung transplants. This retrospective cohort study used panel data provided by the United Network for Organ Sharing, which includes patients receiving transplants across all active US lung transplant programs. Adult patients who received lung transplants between May 2005 and December 2016 were included, with a last follow-up of September 10, 2020. Data were analyzed from September 2022 to May 2023. Zip code-level annual PM2.5 exposure was constructed using previously published North American estimates. The primary outcome was time to death or lung allograft failure after lung transplant. A gamma shared frailty Cox proportional hazards model was used to produce unadjusted and adjusted hazard ratios (HRs) to estimate the association of zip code PM2.5 exposure at the time of transplant with graft failure or mortality. Among 18 265 lung transplant recipients (mean [SD] age, 55.3 [13.2] years; 7328 female [40.2%]), the resident zip code's annual PM2.5 exposure level was greater than or equal to the Environmental Protection Agency (EPA) standard of 12μg/m3 for 1790 patients (9.8%) and less than the standard for 16 475 patients (90.2%). In unadjusted analysis, median graft survival was 4.87 years (95% CI, 4.57-5.23 years) for recipients living in high PM2.5 areas and 5.84 years (95% CI, 5.71-5.96 years) for recipients in the low PM2.5 group. Having an annual PM2.5 exposure level greater than or equal to the EPA standard 12 μg/m3 was associated with an increase in the hazard of death or graft failure (HR, 1.11; 95% CI, 1.05-1.18; P < .001) in the unadjusted analysis and after adjusting for covariates (HR, 1.08; 95% CI, 1.01-1.15; P = .02). Each 1 μg/m3 increase in exposure was associated with an increase in the hazard of death or graft failure (adjusted HR, 1.01; 95% CI, 1.00-1.02; P = .004) when treating PM2.5 exposure as a continuous variable. In this study, elevated zip code-level ambient PM2.5 exposure was associated with an increased hazard of death or graft failure in lung transplant recipients. Further study is needed to better understand this association, which may help guide risk modification strategies at individual and population levels.

Long-term cause-specific mortality in adolescent and young adult Hodgkin lymphoma patients treated with contemporary regimens-A nationwide Danish cohort study.

The documented treatment-induced excess mortality in Hodgkin lymphoma (HL) has spurred important treatment changes over recent decades. This study aimed to examine mortality among young HL patients treated with contemporary strategies, including historical data comparison. This nationwide study included 1348 HL patients, diagnosed in 1995-2015 and aged 15-40 at diagnosis. Among the patients, 66.5% had Ann Arbor stage I-II and 33.5% had stage III-IV disease. With a median follow-up of 14.76 years, 139 deaths occurred, yielding a 5-year overall survival of 94.6%. Older age, advanced disease, earlier treatment periods and extensive regimens were associated with higher overall mortality risk. The cumulative risk of HL-related death showed an initial sharp rise, with a plateau at 5.3% 10-year post-diagnosis. Deaths due to cardiovascular or pulmonary diseases and second cancers initially had minimal risk, gradually reaching 1.2% and 2.0% at the 20-year mark respectively. HL cases had a 7.5-fold higher mortality hazard than the background population. This study suggests that contemporary HL treatment still poses excess mortality risk, but recent changes have notably reduced overall and cause-specific mortality compared to earlier eras. Balancing treatment efficacy and toxicity remains crucial, but our findings highlight improved outcomes with modern treatment approaches.

Sex, Atrial Fibrillation, and Long-Term Mortality After Cardiac Surgery

There are limited data on the association of sex with the incidence of postoperative atrial fibrillation (poAF) and subsequent long-term mortality after cardiac surgery. To evaluate whether the incidence of poAF and associated long-term mortality after cardiac surgery differ by sex. This retrospective cohort study was conducted at 2 tertiary care centers in Massachusetts from January 1, 2002, until October 1, 2016, with follow-up until December 1, 2022. Adult (aged >20 years) women and men undergoing coronary artery bypass graft surgery, aortic valve surgery, mitral valve surgery, and combined procedures with cardiopulmonary bypass were examined using medical records. Patients who had data on poAF were included in data analyses. Sex and poAF. Primary outcomes were the incidence of poAF and all-cause mortality. poAF was defined as any atrial fibrillation detected on electrocardiogram (EKG) during the index hospitalization in patients presenting for surgery in normal sinus rhythm. Data on poAF were obtained from EKG reports and supplemented by information from the Society of Thoracic Surgeons Adult Cardiac Surgery Database. All-cause mortality was assessed via hospital records. The hypotheses were formulated prior to data analysis. Among 21 568 patients with poAF data (mean [SD] age, 66.5 [12.4] years), 2694 of 6601 women (40.8%) and 5805 of 14 967 men (38.8%) developed poAF. In a multivariable logistic regression model, women had lower risk of poAF (odds ratio [OR], 0.85; 95% CI, 0.79-0.91; P < .001). During the follow-up study period, 1294 women (50.4%) and 2376 men (48.9%) in the poAF group as well as 1273 women (49.6%) and 2484 men (51.1%) in the non-poAF group died. Cox proportional hazards analysis found that the association between poAF and mortality was significantly moderated (ie, effect modified) by sex. Compared with same-sex individuals without poAF, men with poAF had a 17% higher mortality hazard (hazard ratio [HR], 1.17; 95% CI, 1.11-1.25; P < .001), and women with poAF had a 31% higher mortality hazard (HR, 1.31; 95% CI, 1.21-1.42; P < .001). In this retrospective cohort study of 21 568 patients who underwent cardiac surgery, women were less likely to develop poAF than men when controlling for other relevant characteristics; however, women who did develop poAF had a higher risk of long-term mortality than men who developed poAF. This observed elevated risk calls for a tailored approach to perioperative care in women undergoing cardiac surgery.

Association Between Intraoperative Cataract Surgical Complications and Mortality

ABSTRACT Purpose To evaluate the association between intraoperative complications of cataract surgery and postoperative mortality. Methods A retrospective review of patients who underwent cataract surgery at our institution from 2014 to 2020 was conducted. Intraoperative complications included choroidal hemorrhage, posterior capsule rupture, vitreous loss, retained lens, and/or severe zonular dialysis in either eye. All-cause mortality statistics were obtained through a collaborative agreement with the Colorado Department of Public Health and Environment. Hazard ratios (HRs) from Cox proportional hazard models were used to estimate survival following cataract surgery. Results Among 8,054 patients, the mean follow-up time was 4.4 (SD = 2.3) years and the mortality rate was 15% (n = 1,175). The overall complication rate was 2.2% (n = 181), and the rate of retained lens was 0.7% (n = 58). In univariate analysis, retained lens (HR: 1.86, 95% CI: 1.08–3.21, p = 0.026), severe zonular dialysis (HR: 2.00, 95% CI: 1.29–3.12, p = 0.002), and any intraoperative complication (HR: 1.51, 95% CI: 1.09–2.11, p = 0.015) were associated with higher hazard of mortality. When adjusted for demographic factors, comorbid medical conditions, and pre-operative visual acuity, intraoperative complications were not associated with mortality. Conclusion Intraoperative cataract surgery complications were associated with mortality in univariate analysis. However, this association was not significant in the multivariable analysis as it is confounded by other factors such as pre-operative visual acuity.

The impact of COVID-19 on the clinical course and outcome of patients with cirrhosis: An observational study.

Severe outcomes of COVID-19 are associated with advancing age and comorbidities. The specific aim of our study was to determine the impact of COVID-19 on the clinical course and outcome of patients with cirrhosis. We retrieved data from VA national repository and identified patients tested for SARS-CoV-2 RNA who had cirrhosis. Each virus positive patient was propensity-matched with virus negative subjects by demographics and comorbidities. Primary endpoint was death within 30 days of COVID-19 diagnosis and secondary endpoint was hospitalization within 14 days. Among 1,115,037 individuals tested for SARS-CoV-2 RNA, 31,680 had cirrhosis. Of those patients, 4456 virus positive patients were propensity-matched with 8752 virus negative subjects. In this cohort of 13,208, median age was 67 years and 95% were male. Most had multiple comorbidities. Alcohol use, hepatitis C and MASH were the dominant etiologies of cirrhosis. At baseline, median MELD was 6% and 21% had hepatic decompensation. Advanced age was the most significant determinant of hospitalization and mortality. Comorbidities, alcohol use and MELD increased the likelihood of hospitalization whereas SARS-CoV-2 positivity had lower Day-14 hospitalization hazard. MELD was associated with higher mortality hazard whereas vaccination reduced the hazard of hospitalization and death. SARS-CoV-2 positivity increased the hazard of death at Day-30 by 72% and at Day-90 by 26%. Although patients with cirrhosis who developed COVID-19 were less likely to be hospitalized, they were more likely to die within 30 days compared to their virus negative counterparts. Vaccination was effective in reducing both hospitalization and death.

Systemic Immune-Inflammation Index (SII) as a Predictor of Short-Term Mortality Risk in Sepsis-Associated Acute Kidney Injury: A Retrospective Cohort Study.

BACKGROUND Sepsis-associated acute kidney injury (SA-AKI) is linked to high mortality rates and an unfavorable prognosis. Early identification of patients with poor prognosis is crucial. This study aimed to investigate the relationship between the systemic immune-inflammation index (SII) and mortality in this specific patient population. MATERIAL AND METHODS This retrospective cohort study used data from the Medical Information Mart for Intensive Care IV database. Data on patient demographics, comorbidities, vital signs, laboratory parameters, treatment usage, acute kidney injury staging, and renal replacement therapy were collected within 48 h of intensive care unit admission. Restricted cubic splines, Kaplan-Meier curves, and Cox regression models were used for analysis. Stratified analyses were performed on the basis of various factors. RESULTS In total, 7856 patients were included, with a median age of 66.9 years and a male-to-female ratio of 57.7%-42.3%. A J-shaped relationship was observed between SII and mortality risk. The lowest mortality risk occurred at an SII of 760.078×10⁹/L. Compared to the reference group (second quartile of SII), the highest and third quartiles had increased 28-day mortality risk, with adjusted hazard ratios (HRs) of 1.33 (1.16-1.52) and 1.55 (1.36-1.77), respectively. Although a trend towards higher mortality hazard was observed in the lowest SII group (Q1), it was not statistically significant, with an adjusted HR of 1.15 (1-1.32). CONCLUSIONS In patients with SA-AKI, both low and high SII were associated with increased short-term mortality risk. The lowest mortality risk was observed at an SII of 760.078×10⁹/L within a 28-day period.

Percutaneous cholecystostomy in acute complicated versus uncomplicated cholecystitis; is there a difference in outcomes? A single-center experience.

Percutaneous cholecystostomy (PC) is a therapeutic intervention for acute cholecystitis. The benefits of cholecystostomy have been demonstrated in the medical literature, with up to 90% of acute cholecystitis cases shown to resolve postoperatively, and only 40% of patients subsequently undergoing an interval cholecystectomy. To compare the survival outcomes between acute complicated and uncomplicated cholecystitis in patients undergoing PC as an initial intervention, as there is a paucity of evidence in the literature on this perspective. A retrospective search was conducted of all patients who underwent PC for acute cholecystitis between August 2016 and December 2020 at a tertiary institution. A total of 100 patients were included in this study. The outcome, in the form of 30-day mortality, 90-day mortality, being alive after six months, and reintervention, was compared between complicated and uncomplicated cases using the chi-square test or Fisher's exact test. There was no statistically significant difference in any of the compared outcomes. The only variable that showed a statistically significant association with the risk of mortality was acute kidney injury (AKI) at admission. Patients who had stage 1, 2, or 3 AKI had a higher hazard for mortality as compared to patients with no kidney disease. Our results demonstrate that PC is a safe and effective procedure. Mortality is not affected by the presence of complications. The results have, however, highlighted the importance of recognizing and treating AKI, an independent risk factor affecting mortality.

Collective Weakness Is Associated With Time to Mortality in Americans.

McGrath, R, McGrath, BM, Jurivich, D, Knutson, P, Mastrud, M, Singh, B, and Tomkinson, GR. Collective weakness is associated with time to mortality in Americans. J Strength Cond Res 38(7): e398-e404, 2024-Using new weakness cutpoints individually may help estimate time to mortality, but their collective use could improve value. We sought to determine the associations of (a) each absolute and body size normalized cut point and (b) collective weakness on time to mortality in Americans. The analytic sample included 14,178 subjects aged ≥50 years from the 2006-2018 waves of the Health and Retirement Study. Date of death was confirmed from the National Death Index. Handgrip dynamometry measured handgrip strength (HGS). Men were categorized as weak if their HGS was <35.5 kg (absolute), <0.45 kg·kg -1 (body mass normalized), or <1.05 kg·kg -1 ·m -2 (body mass index [BMI] normalized). Women were classified as weak if their HGS was <20.0 kg, <0.337 kg·kg -1 , or <0.79 kg·kg -1 ·m -2 . Collective weakness categorized persons as below 1, 2, or all 3 cutpoints. Cox proportional hazard regression models were used for analyses. Subject values below each absolute and normalized cutpoint for the 3 weakness parameters had a higher hazard ratio for early all-cause mortality: 1.45 (95% confidence interval [CI]: 1.36-1.55) for absolute weakness, 1.39 (CI: 1.30-1.49) for BMI normalized weakness, and 1.33 (CI: 1.24-1.43) for body mass normalized weakness. Those below 1, 2, or all 3 weakness cut points had a 1.37 (CI: 1.26-1.50), 1.47 (CI: 1.35-1.61), and 1.69 (CI: 1.55-1.84) higher hazard for mortality, respectively. Weakness determined by a composite measure of absolute and body size adjusted strength capacity provides robust prediction of time to mortality, thus potentially informing sports medicine and health practitioner discussions about the importance of muscle strength during aging.

All-cause mortality before and after DAA availability among people living with HIV and HCV: An international comparison between 2010 and 2019

BackgroundAmong people living with HIV and hepatitis C virus (HCV), people who inject drugs (PWID) have historically experienced higher mortality rates. Direct-acting antivirals (DAA), which have led to a 90 % HCV cure rate independently of HIV co-infection, have improved mortality rates. However, DAA era mortality trends among PWID with HIV/HCV remain unknown. Using data from the International Collaboration on Hepatitis C Elimination in HIV Cohorts (InCHEHC), we compared pre/post-DAA availability mortality changes in three groups: PWID, men who have sex with men (MSM), and all other participants. MethodsWe included InCHEHC participants with HIV/HCV followed between 2010 and 2019 in Canada, France, the Netherlands, Spain, and Switzerland. All-cause mortality hazard was compared in the three groups, using Cox proportional hazards regression models adjusted for sex, age, advanced fibrosis/cirrhosis, and pre/post DAA availability. ResultsOf the 11,029 participants, 76 % were men, 46 % were PWID, baseline median age was 46 years (interquartile range [IQR] = 40;51), and median CD4 T-cell count was 490 cells/mm3 (IQR = 327;689). Over the study period (median follow-up = 7.2 years (IQR = 3.7;10.0)), 6143 (56 %) participants received HCV treatment, 4880 (44 %) were cured, and 1322 participants died (mortality rate = 1.81/100 person-years (PY) [95 % confidence interval (CI)=1.72–1.91]).Overall, PWID had higher mortality rates than MSM (2.5/100 PY [95 % CI = 2.3–2.6] vs. 0.8/100 PY [95 % CI = 0.7–0.9], respectively). Unlike women with other transmission modes, those who injected drugs had a higher mortality hazard than men who did not inject drugs and men who were not MSM (adjusted Hazard-Ratio (aHR) [95 % CI] = 1.3[1.0–1.6]). Post-DAA availability, mortality decreased among MSM in the Netherlands, Spain, and Switzerland and increased among PWID in Canada (aHR [95 % CI] = 1.73 [1.15–2.61]). ConclusionPost-DAA availability, all-cause mortality did not decrease in PWID. Determinants of cause-specific deaths (drug-related, HIV-related, or HCV-related) need to be identified to explain persistently high mortality among PWID in the DAA era.

Renal Biomarkers in Heart Failure: Systematic Review and Meta-Analysis

BackgroundCystatin C, neutrophil gelatinase-associated lipocalin (NGAL), and kidney injury molecule (KIM)-1 are renal biomarkers increasingly appreciated for their role in the risk stratification and prognostication of heart failure (HF) patients. However, very few have been adopted clinically, owing to the lack of consistency. ObjectivesThe authors aimed to study the association between cystatin C, NGAL, and KIM-1 and outcomes, mortality, hospitalizations, and worsening renal function (WRF) in patients with acute and chronic HF. MethodsWe included peer-reviewed English-language articles from PubMed and EMBASE published up to December 2021. We analyzed the above associations using random-effects meta-analysis. Publication bias was assessed using funnel plots. ResultsAmong 2,631 articles, 100 articles, including 45,428 patients, met the inclusion criteria. Top-tertile of serum cystatin C, when compared to the bottom-tertile, carried a higher pooled hazard ratio (pHR) for mortality (pHR: 1.59, 95% CI: 1.42-1.77) and for the composite outcome of mortality and HF hospitalizations (pHR: 1.49, 95% CI: 1.23-1.75). Top-tertile of serum NGAL had a higher hazard for mortality (pHR: 2.91, 95% CI: 1.49-5.67) and composite outcome (HR: 4.11, 95% CI: 2.69-6.30). Serum and urine NGAL were significantly associated with WRF, with pHRs of 2.40 (95% CI: 1.48-3.90) and 2.01 (95% CI: 1.21-3.35). Urine KIM-1 was significantly associated with WRF (pHR: 1.60, 95% CI: 1.24-2.07) but not with other outcomes. High heterogeneity was noted between studies without an obvious explanation based on meta-regression. ConclusionsSerum cystatin C and serum NGAL are independent predictors of adverse outcomes in HF. Serum and urine NGAL are important predictors of WRF in HF.

Tumor infiltrating lymphocytes (TILs) are a prognosis biomarker in Colombian patients with triple negative breast cancer

Triple negative breast cancer (TNBC) is highly immunogenic and high levels of tumor infiltrating lymphocytes (TILs) have been associated with a better prognosis and higher probability to achieve pathological complete response. Here, we explore the potential role of stromal TILs level and composition as a prognostic and predictive biomarker in TNBC. 195 Tumor biospecimens from patients diagnosed with TNBC were included. Stromal TILs (sTILs), positive CD4/CD8 cells were evaluated. Differences in clinic-pathological characteristics according to immune infiltration were assessed. The predictive and prognostic value of immune infiltration was analyzed by multivariate models. Higher immune infiltration was observed in patients with favorable clinical–pathological features. Survival analysis showed that longer overall survival times were observed in patients with a higher infiltration of sTILs (p = 0.00043), CD4 + (p = 0.0074) and CD8 + (p = 0.008). In the multivariate analysis, low levels of sTILs were found to be associated with a higher mortality hazard (HR: 1.59, 95% CI 1.01–2.48). CD4 and CD8 immune infiltration were associated with higher odds for pathological complete response (OR: 1.20, 95% CI 1.00–1.46, OR: 1.28, 1.02–1.65, respectively). Our results suggest that immune infiltration could be used as a prognostic marker for overall survival in TNBC patients.

Associations of orthostatic hypotension and frailty with dementia and mortality in older adults: a cohort study

AbstractBackgroundOrthostatic hypotension (OH) has been considered a frailty marker and is associated with a higher risk of dementia and mortality. We sought to assess whether OH is associated with dementia and mortality in older adults while taking onto account frailty.MethodWe conducted a population‐based cohort study of 2703 dementia‐free individuals (mean age: 73.7; 63.3% females) from the Swedish National Study on Aging and Care in Kungsholmen, regularly followed from 2001‐2004 to 2016‐2019. OH was defined as systolic/diastolic blood pressure drops ≥20/10 mmHg one minute after standing up from a supine position. Fried’s frailty phenotype was used to assess frailty/pre‐frailty. Dementia was diagnosed following the DSM‐IV criteria. Individuals were cross‐classified into four groups based on their OH and frailty status and followed until dementia diagnosis, death, or dropout, whichever came first. Flexible parametric survival models with follow‐up time as the time scale were applied to estimate the associations of OH and frailty with dementia and mortality, adjusting for age, sex, education, vascular risk factors, and comorbidities. We also tested the interaction between OH and frailty on dementia or mortality risk on the multiplicative and additive scales.ResultDuring the follow‐up period, 418 (15.5%) individuals developed dementia, and 933 (34.5%) died without dementia. Compared with OH‐free and robust people, robust people with OH (adjusted HR = 1.90; 95% CI = 1.27‐2.86) had a higher risk of developing dementia. Pre‐frail/frail people without OH (HR = 1.67; 95% CI = 1.22‐2.28) and pre‐frail/frail people with OH (HR = 2.36; 95% CI = 1.62‐3.42) also had a higher dementia risk. Robust people with OH did not have a higher mortality hazard (HR = 1.11; 95% CI = 0.83‐1.48), but pre‐frail/frail people without OH (HR = 1.25; 95% CI = 1.04‐1.51) and pre‐frail/frail people with OH (HR = 1.55; 95% CI = 1.23‐1.94) had a higher mortality hazard than robust and OH‐free people. There was no evident interaction between OH and frailty on dementia or mortality risk on either the multiplicative or additive scale.ConclusionOlder adults with OH, whether robust or frail, may have a higher dementia risk than those without OH. Robust older adults with OH do not seem to have a higher mortality rate than robust older adults without OH.

Individual- and Community-Level Socioeconomic Status and Deceased Donor Renal Transplant Outcomes.

This study examined the relationship between socioeconomic status (SES), race, and ethnicity and clinical outcomes following deceased donor kidney transplant (DDKT) at a high-volume transplant center. This retrospective cohort study used regression models and survival analyses to examine the relationship between individual- and community-level SES, race, and ethnicity and DDKT outcomes (i.e., delayed graft function, graft failure, mortality) adjusting for potential confounders. The analytic sample included 3366 patients; 40.7% (n = 1370) were female, the mean age was 54.7 (SD = 13.3) years, 49.3% were non-Hispanic White, and the median follow-up time was 39.5 months (IQR = 24.2-68.1). Patients living in the most disadvantaged communities (using the US Census data) had a higher likelihood of delayed graft function (adjusted relative risk [RR] = 1.12, p = 0.042) and a higher hazard of mortality (adjusted hazard ratio [HR] = 1.32, p = 0.025) compared to patients living in the least disadvantaged communities. Patients without a high school diploma had a higher risk of delayed graft function compared to patients with an associate degree or more (RR = 1.37, p < 0.001). Patients with public insurance coverage had a higher risk of delayed graft function (RR = 1.24, p < 0.001) and a higher hazard of mortality (HR = 1.37, p < 0.001) and graft failure (HR = 1.71, p < 0.001) compared to patients without public insurance. There were no differences in graft failure or mortality by race and ethnicity. SES was not consistently associated with outcomes following DDKT; however, many of the predictors were associated with delayed graft function. With a large and diverse sample size, these findings further the heterogeneity of the present renal transplant research suggesting the need for further investigation to guide implementation of innovative strategies and interventions.

Abstract 13721: Coronary Artery Calcium for Risk Stratification Among Persons With Very-High High-Density Lipoprotein Cholesterol

Introduction: Persons with very-high high-density lipoprotein-cholesterol (HDL-C) may experience an increased mortality risk. However, the predictors of mortality among those with very-high HDL-C remain unknown. Hypothesis: Compared to traditional risk factors, coronary artery calcium (CAC) will more strongly stratify risk among individuals with very-high HDL-C. Aims: Among individuals with very-high HDL-C, to 1) calculate crude all-cause mortality rates across the burden of traditional risk factors and CAC, and 2) identify independent risk factors associated with all-cause mortality. Methods: There were 335 primary prevention patients from the CAC Consortium who had very-high HDL-C ( &gt; 80 mg/dL in men, &gt; 100 mg/dL in women) and available information on traditional CVD risk factors. Crude all-cause mortality rates were calculated per 1,000 person-years. Multivariable Cox proportional hazards regression assessed the association of traditional risk factors and CAC with mortality. Results: The mean age was 58.6 years old, 51.0% were women, 51.3% had prevalent CAC, and the median HDL-C was 100 mg/dL. There were 20 deaths (6.0%) over a median follow-up of 10.5 years, 7 (2.1%) of which were attributable to CVD. There was a stepwise higher crude mortality rate per 1,000 person-years across increasing CAC burden ( Central Illustration ). Independent of traditional risk factors, each 100 Agatston Unit increase in CAC score was associated with a 7% higher hazard of all-cause mortality (HR: 1.07, 95% CI: 1.01-1.12) and individuals with CAC &gt; 1000 experienced a 5.75-fold higher hazard of mortality when compared to CAC=0 (HR: 5.75, 95% CI: 1.26-26.24). Beyond age, no traditional risk factor was associated with mortality in multivariable analyses. Conclusion: Measurement of CAC on non-contrast cardiac computed tomography may facilitate risk assessment among individuals with very-high HDL-C.

Comparative Safety of Antidepressants in Adults with CKD.

Depression is prevalent in patients with CKD and is related to poor prognosis. Despite the widespread use of antidepressants in the CKD population, their safety remains unclear. We identified adults with CKD stages G3-5 (eGFR <60 ml/min per 1.73 m 2 not treated with dialysis) and incident depression diagnosis during 2007-2019 from the Stockholm Creatinine Measurements project. Using the target trial emulation framework, we compared the following treatment strategies: ( 1 ) initiating versus not initiating antidepressants, ( 2 ) initiating mirtazapine versus selective serotonin reuptake inhibitors (SSRIs), and ( 3 ) initiating SSRIs with a lower dose versus a standard dose. Of 7798 eligible individuals, 5743 (74%) initiated antidepressant treatment. Compared with noninitiation, initiation of antidepressants was associated with higher hazards of short-term outcomes, including hip fracture (hazard ratio [HR], 1.23; 95% confidence interval [CI], 0.88 to 1.74) and upper gastrointestinal bleeding (HR, 1.38; 95% CI, 0.82 to 2.31), although not statistically significant. Initiation of antidepressants was not associated with long-term outcomes, including all-cause mortality, major adverse cardiovascular event, CKD progression, and suicidal behavior. Compared with SSRIs, initiation of mirtazapine was associated with a lower hazard of upper gastrointestinal bleeding (HR, 0.52; 95% CI, 0.29 to 0.96), but a higher hazard of mortality (HR, 1.11; 95% CI, 1.00 to 1.22). Compared with the standard dose, initiation of SSRIs with a lower dose was associated with nonstatistically significantly lower hazards of upper gastrointestinal bleeding (HR, 0.68; 95% CI, 0.35 to 1.34) and CKD progression (HR, 0.80; 95% CI, 0.63 to 1.02), but a higher hazard of cardiac arrest (HR, 2.34; 95% CI, 1.02 to 5.40). Antidepressant treatment was associated with short-term adverse outcomes but not long-term outcomes in people with CKD and depression.

Socioeconomic status is associated with greater hazard of post-discharge mortality than race, gender, and ballistic injury mechanism in a young, healthy, orthopedic trauma population

ObjectivesTo explore the utility of legacy demographic factors and ballistic injury mechanism relative to popular markers of socioeconomic status as prognostic indicators of 10-year mortality following hospital discharge in a young, healthy patient population with isolated orthopedic trauma injuries. MethodsA retrospective cohort study was performed to evaluate patients treated at an urban Level I trauma center from January 1, 2003, through December 31, 2016. Current Procedure Terminology (CPT) codes were used to identify upper and lower extremity fracture patients undergoing operative fixation. Exclusion criteria were selected to yield a patient population of isolated extremity trauma in young, otherwise healthy individuals between the ages of 18 and 65 years. Variables collected included injury mechanism, age, race, gender, behavior risk factors, Area Deprivation Index (ADI), and insurance status. The primary outcome was post-discharge mortality, occurring at any point during the study period. ResultsWe identified 2539 patients with operatively treated isolated extremity fractures. The lowest two quartiles of socioeconomic status (SES) were associated with higher hazard of mortality than the highest SES quartile in multivariable analysis (Quartile 3 HR: 2.2, 95% CI: 1.2–4.1, p = 0.01; Quartile 4 HR: 2.2, 95% CI: 1.1–4.3, p = 0.02). Not having private insurance was associated with higher mortality hazard in multivariable analysis (HR 2.0, 95% CI: 1.3–3.2, p = 0.002). The presence of any behavioral risk factor was associated with higher mortality hazard in univariable analysis (HR: 1.8, p < 0.05), but this difference did not reach statistical significance in multivariable analysis (HR: 1.4, 95%: 0.8–2.3, p = 0.20). Injury mechanism (ballistic versus blunt), gender, and race were not associated with increased hazard of mortality (p > 0.20). ConclusionLow SES is associated with a greater hazard of long-term mortality than ballistic injury mechanism, race, gender, and medically diagnosable behavioral risk factors in a young, healthy orthopedic trauma population with isolated extremity injury.

Prognostic significance of extramedullary disease (EMD) detected on pre-transplant 18F-FDG PET/CT in patients with multiple myeloma: Results of PIPET-M trial

BackgroundIt is difficult to prognosticate the post-Autologous Stem Cell Transplant (ASCT) responses in multiple myeloma (MM) with the currently available prognostication models. 18F-FDGPET/CT has numerous advantages to prognosticate the post-transplant responses by assessing extramedullary disease (EMD) in addition to the extent of active disease. We aimed at identifying the prognostic value of EMD in predicting progression-free survival (PFS) and overall survival (OS). MethodsThis is a single centre prospective study from western India during a study period of 2014–2022 (with a median follow-up of patients of 6 years). All ASCT patients underwent 18F-FDG-PET/CT as part of pre-transplant workup. The conditioning and treatment protocols were not modified based on PET/CT findings. EMD on PET/CT was correlated with pre-transplant biochemical markers and post-ASCT survival/ progression (as defined by revised IMWG criteria). Statistical analysis was done using SPSS ver. 20. ResultsPatients with pre-ASCT EMD had a hazard-ratio for post-transplant all-cause mortality of 5.46 (p-0.045). Pre-transplant β2M and LDH were significantly higher in patients with EMD (p-0.036). The 6-year median OS in patients with and without EMD were 57.1%, and 80.6% respectively. Kaplan-Meier analysis showed poorer OS in patients with EMD χ2 (1–0.496, p-0.481). There was no significant difference in clinical or biochemical EFS among patients with EMD. ConclusionEMD detected on 18F-FDG-PET/CT has a higher hazard for mortality and is significantly correlated with pre-transplant higher β2M and LDH levels. Thus, EMD by pre-transplant 18F-FDG-PET/CT has a significant prognostic role.

Association of individual low-income status and area deprivation with mortality in multiple myeloma

IntroductionLower individual-level socioeconomic status (SES) and area-level SES have each been associated with poor survival outcomes among patients with multiple myeloma (MM). A body of literature suggests that individual-level SES may be differentially associated with mortality depending on area-level SES, and vice versa. This study assessed the effect of the cross-level interaction between individual low-income status and area deprivation on mortality among patients with MM. Materials and MethodsThis retrospective cohort study used the Surveillance, Epidemiology, and End Results (SEER)—Medicare data (2006–2016). Individuals were defined as having low income if they were dually eligible for Medicare and Medicaid and/or if they received the Low-Income Subsidy. The county-level Social Deprivation Index (SDI) was linked to individual-level SEER-Medicare data and categorized into quintiles, from the least deprived (Quintile 1) to the most deprived (Quintile 5). Adjusted hazard ratios (HRs) for the associations between low-income status, area deprivation, and all-cause mortality were estimated from a mixed-effects Cox proportional-hazards (PH) model. ResultsThe mortality hazard was higher for individuals with low income than individuals without low income in all quintiles of area deprivation, with the exception of Quintile 5 (Quintile 1: HR 1.53 [95% confidence interval [CI]: 1.32–1.77]; Quintile 2: HR 1.17 [95%CI: 1.01–1.36]; Quintile 3: HR 1.34 [95%CI: 1.18–1.53]; Quintile 4: HR 1.33 [95%CI: 1.17–1.52]; Quintile 5: HR 1.09 [95%CI: 0.96–1.23]). Among individuals without low income, individuals residing in the most deprived area had a higher mortality hazard than individuals residing in the least deprived area (HR: 1.22 [95%CI: 1.03–1.45]). In contrast, among individuals with low income, residing in a more deprived area, Quintile 2, was associated with a lower hazard of death than residing in the least deprived area, Quintile 1 (HR: 0.82 [95%CI: 0.67–0.99]), and there was no statistically significant difference between Quintile 1 and Quintiles 3, 4, and 5. DiscussionIn this analysis, there was a statistically significant cross-level interaction between individual low-income status and area deprivation on mortality. More research is needed to fully understand the mechanism behind these associations, but the findings show that patients and their health should be considered in the context of where they live.

Long-term variability in physiological measures in relation to mortality and epigenetic aging: prospective studies in the USA and China

BackgroundVisit-to-visit body weight variability (BWV), pulse rate variability (PRV), and blood pressure variability (BPV) have been respectively linked to multiple health outcomes. The associations of the combination of long-term variability in physiological measures with mortality and epigenetic age acceleration (EAA) remain largely unknown.MethodsWe constructed a composite score of physiological variability (0-3) of large variability in BWV, PRV, and BPV (the top tertiles) in 2006/2008–2014/2016 in the Health and Retirement Study (HRS) and 2011–2015 in the China Health and Retirement Longitudinal Study (CHARLS). All-cause mortality was documented through 2018. EAA was calculated using thirteen DNA methylation-based epigenetic clocks among 1047 participants in a substudy of the HRS. We assessed the relation of the composite score to the risk of mortality among 6566 participants in the HRS and 6906 participants in the CHARLS by Cox proportional models and then investigated its association with EAA using linear regression models.ResultsA higher score of variability was associated with higher mortality risk in both cohorts (pooled hazard ratio [HR] per one-point increment, 1.27; 95% confidence interval [CI], 1.18, 1.39; P-heterogeneity = 0.344), after adjustment for multiple confounders and baseline physiological measures. Specifically, each SD increment in BWV, PRV, and BPV was related to 21% (95% CI: 15%, 28%), 6% (0%, 13%), and 12% (4%, 19%) higher hazard of mortality, respectively. The composite score was significantly related to EAA in second-generation clocks trained on health outcomes (e.g., standardized coefficient = 0.126 in the Levine clock, 95% CI: 0.055, 0.196) but not in most first-generation clocks trained on chronological age.ConclusionsLarger variability in physiological measures was associated with a higher risk of mortality and faster EAA.

Using blood test parameters to define biological age among older adults: association with morbidity and mortality independent of chronological age validated in two separate birth cohorts

Biomarkers defining biological age are typically laborious or expensive to assess. Instead, in the current study, we identified parameters based on standard laboratory blood tests across metabolic, cardiovascular, inflammatory, and kidney functioning that had been assessed in the Berlin Aging Study (BASE) (n = 384) and Berlin Aging Study II (BASE-II) (n = 1517). We calculated biological age using those 12 parameters that individually predicted mortality hazards over 26 years in BASE. In BASE, older biological age was associated with more physician-observed morbidity and higher mortality hazards, over and above the effects of chronological age, sex, and education. Similarly, in BASE-II, biological age was associated with physician-observed morbidity and subjective health, over and above the effects of chronological age, sex, and education as well as alternative biomarkers including telomere length, DNA methylation age, skin age, and subjective age but not PhenoAge. We discuss the importance of biological age as one indicator of aging.