Hazard Of All-cause Mortality Research Articles

#840 Kidney cancer, treatment with nephrectomy and survival in chronic kidney disease (CKD)

Abstract Background and Aims People with chronic kidney disease (CKD) have increased incidence of kidney cancer and poorer survival post-diagnosis compared to people without CKD. Nephrectomy, either partial or radical is the primary treatment for many kidney cancers and can be curative even in cases with locally advanced disease or single metastasis. We hypothesised that nephrectomy may be less frequently undertaken in people with kidney cancer and pre-existing CKD and that this might contribute to poorer survival in this group. Method Using data from the prospective research cohort UK Biobank (n = 502,536) linked to cancer registry, participants with available biochemistry and a new diagnosis of kidney cancer during follow-up were identified. Occurrence of nephrectomy was extracted from linked hospital data and all-cause mortality data from death certification records. Estimated glomerular filtration rate (eGFRCr) was calculated by CKD-EPI 2009 formula with race coefficient, as this was the formula recommended for use in the UK at the time of recruitment to UK Biobank. Cox proportional hazards models tested associations between eGFRCr and i) undergoing nephrectomy and ii) all-cause mortality by 10 ml/min/1.73 m2 decline from a reference value of 90 ml/min/1.73 m2. We additionally conducted subgroup analyses for nephrectomy and all-cause mortality within eGFRCr categories >105, 90-105, 75-90 (reference), 60-75, 45-60, 30-45 and <30 ml/min/1.73 m2. Both models were adjusted for age, sex, diabetes mellitus, hypertension, stroke, ischaemic heart disease, body mass index and socioeconomic deprivation. The all-cause mortality model was additionally adjusted for undergoing nephrectomy. Results There were 2053 participants with a new diagnosis of kidney cancer and sufficient biochemical data for inclusion. Of these, 935 (46%) had eGFRCr 60-90 ml/min/1.73 m2 and 139 (7%) had eGFRCr <60 ml/min/1.73 m2. Median time from baseline to kidney cancer diagnosis was 5.8 (IQR 0.9, 8.8) years. Median follow-up time after a diagnosis of kidney cancer was 3.4 (IQR 0.9, 6.6) years. For each 10 ml/min/1.73 m2 decline in eGFRCr below 90 ml/min/1.73 m2, there was no significant difference in likelihood of receiving nephrectomy (HR 1.05, p = 0.08) and no significant difference in likelihood of all-cause mortality (HR 1.03, p = 0.23). People with moderate-advanced CKD had increased hazards of all-cause mortality compared to the reference group (eGFRCr 75-90 ml/min/1.73 m2) when models were run by eGFRCr category (eGFRCr 30-45—HR 1.9 95% CI 1.3-3.0; eGFRCr <30—HR 2.0 95% CI 1.0-4.0). Conclusion In UK Biobank participants with kidney cancer and mild CKD, there was no significant difference in likelihood of nephrectomy or in hazards of all-cause mortality associated with declining eGFRCr as a continuous variable. Moderate to advanced CKD (eGFR <45) was associated with increased all-cause mortality despite adjustment for nephrectomy, suggesting that this finding is not explained by reduced access to surgical treatment.

#1415 The association between social isolation and all-cause mortality in patients with chronic kidney disease: a prospective cohort study

Abstract Background and Aims Social isolation has been linked to several diseases and adverse outcomes, such as type 2 diabetes and cardiovascular events. The current study aimed to evaluate the association between social isolation and all-cause mortality in patients with chronic kidney disease (CKD). Method From the UK Biobank, a population-based cohort study, we included 16,250 participants that were diagnosed with CKD and with decreased estimated glomerular filtration rate (eGFR <60 ml/min/1.73 m2) at baseline. Participants were classified as socially isolated if they met at least two of the following criteria: (1) living alone; (2) having close contact with others less than once per month; or (3) lacking leisure or social activities involving interpersonal interaction. The outcome was all-cause mortality obtained from death registries. We performed Cox proportional hazards model to estimate the hazard ratio of social isolation for all-cause death in CKD patients. Results Over a median follow-up of 13.5 years (interquartile range (IQR): 12.6-14.4 years), 3,498 deaths were recorded. The all-cause mortality was 21.5% in the whole cohort, and 20.2%, 55.3% and 62.4% in CKD stage 3, stage 4 and stage 5 respectively. A total of 11.1% of participants were considered to be socially isolated. The results showed that social isolation was independently associated with increased risk for all-cause mortality when compared with no isolation (HR 1.22, 95% CI 1.11 to 1.34) (Fig. 1), after adjusting for age, sex, Townsend deprivation index, education levels, income levels, BMI, smoking status, diet habit, status of physical activity, consumption of alcohol, hypertension, diabetes, Charlson comorbidity index and CKD stages. Subgroup analyses showed that the significant association was only observed in men (HR 1.28, 95% CI 1.14 to 1.45) and in patients with CKD stage 3 (HR 1.23, 95% CI 1.11 to 1.36), but not in women or in those with more advanced renal failure (Fig. 1). Conclusion Social isolation was independently associated with a higher hazard of all-cause mortality in patients with CKD. The association was more significant in men and in patients with mildly decreased renal function.

Contemporary Outcomes of Acute Coronary Syndromes in Indigenous Compared with Non-Indigenous Patients: A Northern Saskatchewan Perspective

In patients presenting with an acute coronary syndrome (ACS), the impact of efforts leveraged at bridging historical care gaps between Indigenous and non-Indigenous patients remains limited. For consecutive ACS presentations (STEMI and NSTEMI/UA, respectively) at the Royal University Hospital, Saskatoon, we compared between self-identified Indigenous and non-Indigenous patients their demographics, treatments and all-cause mortality (in-hospital and 3-years). We used propensity score-inverse probability weighting to mitigate confounding, and Cox regression models to estimate the adjusted hazard (aHR, 95% confidence intervals) for all-cause mortality. Of 3946 ACS patients, 37.2% (n=1468) were STEMI of whom 11.3% (n=166) were Indigenous. Of the NSTEMI/UA (n=2478), 12.6% (n=311) were Indigenous. Overall, Indigenous compared with non-Indigenous patients were likely to be younger, female, have higher risk burden, and lived more remotely; Indigenous STEMI patients triaged to primary PCI had longer first medical contact-to-device times, while Indigenous NSTEMI/UA patients more likely to present with heart failure, cardiac arrest and/or cardiogenic shock. No significant differences were noted for in-hospital mortality (STEMI 8.4% vs 5.7%, p= 0.16; NSTEMI/UA 1.9% vs 1.6%, p=0.68), however, in follow-up, Indigenous STEMI patients associated with a higher all-cause mortality risk (aHR 1.98, 95% CI 1.19, 3.31, p=0.009) with no between-group differences evident for NSTEMI/UA (aHR 1.03, 95% CI 0.63 1.69, p=0.91). Indigenous compared with non-Indigenous patients presenting with an ACS had higher cardiovascular risk profiles, and consequently residual mortality risk. Improving primary care and intensifying secondary risk reduction, and particularly so for Indigenous patients, will substantially modify ACS outcomes in Saskatchewan.

Outcome-based Definition of the Lower Limit of Normal in Spirometry: A Study of 26,000 Young Adult Men.

Rationale The definition of the lower limit of normal (LLN) of spirometric variables is not well established. Objectives To investigate the relationship between spirometric abnormalities defined with different thresholds of the LLN and clinical outcomes, and to explore the possibility of using different LLN thresholds according to the pre-test probability of disease. Methods We studied the associations between pre-bronchodilator spirometric abnormalities (FEV1 < LLN, FVC < LLN, airflow obstruction, spirometric restriction) defined with different thresholds of the LLN (10th, 5th, 2.5th, 1st percentile) and multiple outcomes (prevalence of spirometric abnormalities, respiratory symptoms, all-cause and respiratory mortality) in 26,091 30-46 years old men who participated in a general population survey in Norway in 1988-1990 and were followed for 26 years. Analyses were performed with both local and GLI-2012 reference equations, stratified by pre-test risk (presence or absence of respiratory symptoms), and adjusted for age, BMI, smoking, and education. Results In the total population, the prevalence of airflow obstruction was 11.6% with GLI-LLN10, 11.0% with Local-LLN5, 6.1% with GLI-LLN5, 7.6% with Local-LLN2.5, and 3.5% with GLI-LLN2.5. The prevalence of spirometric restriction was 5.9% with GLI-LLN10, 5.2% with Local-LLN5, and 2.8% with GLI-LLN5. Increasingly lower thresholds of the LLN were associated with increasingly higher odds of respiratory symptoms and hazard of mortality for all spirometric abnormalities with both reference equations. Spirometric abnormalities defined with Local-LLN2.5 in asymptomatic subjects were associated with lower hazard of all-cause mortality (hazard ratio 1.50 (1.15, 1.95, 95% confidence intervals) for FEV1 < LLN) than those defined with Local-LLN5 in the general population (1.67 (1.50, 1.87) for FEV1 < LLN) and symptomatic subjects (1.67 (1.46, 1.91) for FEV1 < LLN). Overall, prevalence of spirometric abnormalities and associations with outcomes obtained with Local-LLN5 were comparable to those obtained with GLI-LLN10, and those obtained with Local-LLN2.5 to GLI-LLN5. Conclusions There is a relationship between statistically-based thresholds of the LLN of spirometric variables and clinical outcomes. Different thresholds of the LLN may be used in different risk subgroups of subjects, but the choice of the threshold needs to be evaluated together with the choice of reference equations.

Frequency, characteristics and risk assessment of pulmonary arterial hypertension with a left heart disease phenotype.

To obtain real-world evidence about the features and risk stratification of pulmonary arterial hypertension (PAH) with a left heart disease (LHD) phenotype (PAH-LHD). By reviewing the records of consecutive incident PAH patients at 7 tertiary centers from 2001 to 2021, we selected 286 subjects with all parameters needed to determine risk of death at baseline and at first follow-up with COMPERA and COMPERA 2.0 scores. Fifty seven (20%) had PAH-LHD according to the AMBITION definition. Compared with no-LHD ones, they were older, had higher BMI, more cardiovascular comorbidities, higher E/e' ratio and left atrial area, but lower BNP concentrations and better right ventricular function and pulmonary hemodynamics. Survival was comparable between PAH-LHD and no-LHD patients, although the former were less commonly treated with dual PAH therapy. Both COMPERA and COMPERA 2.0 discriminated all-cause mortality risk of PAH-LHD at follow-up, but not at baseline. Risk profile significantly improved during follow-up only when assessed by COMPERA 2.0. At multivariable analysis with low-risk status as reference, intermediate-high and high-risk, but not LHD phenotype, were associated with higher hazard of all-cause mortality. Results were comparable in secondary analyses including patients in the last 10years and atrial fibrillation and echocardiographic abnormalities as additional criteria for PAH-LHD. In real life, PAH-LHD patients are frequent, have less severe disease and are less likely treated with PAH drug combinations than no-LHD. TheCOMPERA 2.0 model may be more appropriate to evaluate their mortality risk during follow-up and how it is modulated by therapy.

Klotho exerts protection in chronic kidney disease associated with regulating inflammatory response and lipid metabolism.

The anti-aging protein Klotho plays a protective role in kidney disease, but its potential as a biomarker for chronic kidney disease (CKD) is controversial. Additionally, the main pathways through which Klotho exerts its effects on CKD remain unclear. Therefore, we used bioinformatics and clinical data analysis to determine its role in CKD. We analyzed the transcriptomic and clinical data from the Nephroseq v5 database and found that the Klotho gene was mainly expressed in the tubulointerstitium, and its expression was significantly positively correlated with estimated glomerular filtration rate (eGFR) and negatively correlated with blood urea nitrogen (BUN) in CKD. We further found that Klotho gene expression was mainly negatively associated with inflammatory response and positively associated with lipid metabolism in CKD tubulointerstitium by analyzing two large sample-size CKD tubulointerstitial transcriptome datasets. By analyzing 10-year clinical data from the National Health and Nutrition Examination Survey (NHANES) 2007-2016, we also found that Klotho negatively correlated with inflammatory biomarkers and triglyceride and positively correlated with eGFR in the CKD population. Mediation analysis showed that Klotho could improve renal function in the general population by modulating the inflammatory response and lipid metabolism, while in the CKD population, it primarily manifested by mediating the inflammatory response. Restricted cubic spline (RCS) analysis showed that the optimal concentration range for Klotho to exert its biological function was around 1000pg/ml. Kaplan-Meier curves showed that lower cumulative hazards of all-cause mortality in participants with higher levels of Klotho. We also demonstrated that Klotho could reduce cellular inflammatory response and improve cellular lipid metabolism by establishing an in vitro model similar to CKD. Our results suggest that Klotho exerts protection in CKD, which may be mainly related to the regulation of inflammatory response and lipid metabolism, and it can serve as a potential biomarker for CKD.

Pre-frailty after blood or marrow transplantation and the risk of subsequent mortality.

We examined the prevalence, risk factors, and association between pre-frailty and subsequent mortality after blood or marrow transplantation (BMT). Study participants were drawn from the BMT Survivor Study (BMTSS) and included 3346 individuals who underwent BMT between 1974 and 2014 at one of three transplant centers and survived ≥2 years post-BMT. Participants completed the BMTSS survey at a median of 9 years from BMT and were followed for subsequent mortality for a median of 5 years after survey completion. Closest-age and same-sex biological siblings also completed the survey. Previously published self-reported indices (exhaustion, weakness, low energy expenditure, slowness, unintentional weight loss) classified participants as non-frail (0-1 indices) or pre-frail (2 indices). National Death Index was used to determine vital status and cause of death. Overall, 626 (18.7%) BMT survivors were pre-frail. BMT survivors had a 3.2-fold higher odds of being pre-frail (95% CI = 1.9-5.3) compared to siblings. Compared to non-frail survivors, pre-frail survivors had higher hazards of all-cause mortality (adjusted hazard ratio [aHR] = 1.6, 95% CI = 1.4-2.0). Female sex, pre-BMT radiation, smoking, lack of exercise, anxiety, and severe/life-threatening chronic health conditions were associated with pre-frailty. The novel association between pre-frailty and subsequent mortality provides evidence for interventions as pre-frail individuals may transition back to their robust state.

Impact of Tracheostomy Timing Within the National Veterans Affairs Population.

There is a lack of a definitive study in the literature comparing early versus late tracheostomy and exploring the impact of tracheostomy timing on patient outcomes. This study may help guide treatment paradigms and contribute to a consensus for optimal tracheostomy timing. A retrospective review was performed comparing early versus late timing of tracheostomy placement and their respective outcomes. The authors used data provided by VA Informatics and Computing Infrastructure (VINCI) to find patients who received a tracheostomy at any VA Medical Center in the United States. There were a total of 25,334 tracheostomies in the database which satisfied our criteria. These occurred between the years 1999 and 2022. Propensity score matching assessed 17,074 tracheostomies, 8537 in either group. The median age of patients in the matched groups was 66 years, and approximately 97.4% of patients were male. Early tracheostomy timing was defined as the placement of the tracheostomy within 10 days of intubation. Outcomes included post-tracheostomy intensive care unit (ICU) days, post-tracheostomy hospital days, successful ventilator weaning, and all-cause mortality. Early tracheostomy was associated with significantly fewer ICU days and hospital days, and the early group experienced higher rates of successful ventilator weaning. Survival analysis of data within 5 years of tracheostomy showed that early tracheostomy was associated with significantly lower hazard for all-cause mortality. Our results add to the body of evidence that an earlier transition to mechanical ventilation by tracheostomy confers benefits in patient morbidity and mortality as well as resource utilization. 3 Laryngoscope, 2024.

Abstract P166: Social Isolation and Social Support Are Associated With Self-Rated Health and Heart Failure Outcomes in the Atherosclerosis Risk in Communities (ARIC) Study

Introduction: Social isolation (SI) and social support (SS) are associated with incidence of heart failure (HF). Few studies investigate how SI, SS, and subtypes of SS (appraisal, belonging, self-esteem, and tangible) measured before HF are related to morbidity and mortality after HF. Objective: Assess whether SI, SS, and subtypes of SS are associated with self-rated health trajectories and HF outcomes among participants with incident HF hospitalizations, and if results differ by sex or race. Methods: We included 2967 ARIC participants (51% female, 27% Black, mean age 59 (SD 6) years) with incident HF hospitalization after Visit 2 (1990-1992). We identified incident HF hospitalization as ICD-9 code 428 in any position and physician adjudicated events; on average HF occurred 17 (SD 8) years after Visit 2. We measured predefined SI categories and tertiles of SS at Visit 2 using the 10-item Lubben Social Network Scale and the 16-item Interpersonal Support Evaluation List, which were assessed as separate exposures. We assessed associations with trajectories of annually measured self-rated health in the 4 years prior to and after incident HF hospitalization, measured by the probability of being in excellent/good self-rated health (0-100% scale), using linear mixed effects models. We calculated hazard ratios (HR) and 95% confidence intervals (CIs) for associations with time to first all-cause rehospitalization and all-cause mortality using Cox proportional hazard models. Models were adjusted for age, sex, race-center, employment status, years of education, prior use of mental health medications, and time between Visit 2 and HF. Results: Over mean follow-up of 5 (SD 5) years after initial HF hospitalization, 90% of participants experienced rehospitalization and there were 2378 deaths. Low overall SS had a 5.8% (95% CI 7.8%, 3.8%) lower probability of excellent/good self-rated health over time than high SS; associations of subtypes of SS with this outcome were similar. Low belonging SS was associated with greater days to first rehospitalization (HR 0.85; 95% CI 0.79, 0.96) compared to the highest tertile, however belonging SS was not associated with mortality (HR 1.05; 95% CI 0.95, 1.17). Low tangible SS was associated with greater mortality among White (HR 1.14; 95% CI 1.01, 1.28) but not Black participants (HR 0.95; 95% CI 0.78, 1.16), compared to the highest tertile. Being socially isolated/high risk for SI was associated with greater hazard of all-cause mortality among females (HR 1.57; 95% CI 1.20, 2.06) but not males (HR 0.95; 95% CI 0.75, 1.19), compared to low SI. Conclusions: SI and SS measured before HF were relevant to HF outcomes, but relevance may vary by sex and race. In particular, greater SI was only associated with greater mortality among females, and lower tangible SS with greater mortality among White participants only. Belonging support was associated with some HF outcomes but not others.

Sex differences in cancer outcomes across the range of eGFR.

People with chronic kidney disease (CKD) have increased incidence and mortality from most cancer types. We hypothesised that odds of presenting with advanced cancer may vary according to differences in eGFR, that this could contribute to increased all-cause mortality and that sex differences may exist. Data were from Secure Anonymised Information Linkage Databank, including people with de-novo cancer diagnosis (2011-2017) and two kidney function tests within two years prior to diagnosis to determine baseline eGFR (mL/min/1.73m2). Logistic regression models determined odds of presenting with advanced cancer by baseline eGFR. Cox proportional hazards models tested associations between baseline eGFRcr and all-cause mortality. eGFR<30 was associated with higher odds of presenting with advanced cancer of prostate, breast and female genital organs, but not other cancer sites. Compared to eGFR>75-90, eGFR<30 was associated with greater hazards of all-cause mortality in both sexes, but the association was stronger in females (female: HR 1.71, 95%CI 1.56-1.88; male versus female comparison HR 0.88, 95%CI 0.78-0.90). Lower or higher eGFR was not associated with substantially higher odds of presenting with advanced cancer across most cancer sites, but was associated with reduced survival. A stronger assocation with all-cause mortality in females compared to males with eGFR<30 is concerning and warrants further scrutiny.

Heterogeneity of aging and mortality risk among individuals with hypertension: Insights from phenotypic age and phenotypic age acceleration

ObjectivesHypertension, a key contributor to mortality, is impacted by biological aging. We investigated the relationship between novel biological aging metrics - Phenotypic Age (PA) and Phenotypic Age Acceleration (PAA) - and mortality in individuals with hypertension, exploring the mediating effects of arterial stiffness (estimated Pulse Wave Velocity, ePWV), and Heart/Vascular Age (HVA). MethodsUsing data from 62,160 National Health and Nutrition Examination Survey (NHANES) participants (1999–2010), we selected 4,228 individuals with hypertension and computed PA, PAA, HVA, and ePWV. Weighted, multivariable Cox regression analysis yielded Hazard Ratios (HRs) relating PA, PAA to mortality, and mediation roles of ePWV, PAA, HVA were evaluated. Mendelian randomization (MR) analysis was employed to investigate causality between genetically inferred PAA and hypertension. ResultsOver a 12-year median follow-up, PA and PAA were tied to increased mortality risks in individuals with hypertension. All-cause mortality hazard ratios per 10-year PA and PAA increments were 1.96 (95% CI, 1.81–2.11) and 1.67 (95% CI, 1.52–1.85), respectively. Cardiovascular mortality HRs were 2.32 (95% CI, 1.97–2.73) and 1.93 (95% CI, 1.65–2.26) for PA and PAA, respectively. ePWV, PAA, and HVA mediated 42%, 30.3%, and 6.9% of PA’s impact on mortality, respectively. Mendelian randomization highlighted a causal link between PAA genetics and hypertension (OR = 1.002; 95% CI, 1.000–1.003). ConclusionPA and PAA, enhancing cardiovascular risk scores by integrating diverse biomarkers, offer vital insights for aging and mortality evaluation in individuals with hypertension, suggesting avenues for intensified aging mitigation and cardiovascular issue prevention. Validations in varied populations and explorations of underlying mechanisms are warranted.

Geriatric Nutritional Risk Index and First-Year Mortality in Incident Hemodialysis Patients.

The Geriatric Nutritional Risk Index is a simple nutritional screening method, and this study aimed to investigate the association between the initial Geriatric Nutritional Risk Index and all-cause mortality in incident patients in the first year after the initiation of hemodialysis. This study is a retrospective cohort study and used the Korean Renal Data System database. Patients who were eligible for Geriatric Nutritional Risk Index assessment and underwent hemodialysis from January 2016 to December 2019 were included. The primary outcome was all-cause mortality, and outcome evaluation was performed in December 2020. A Cox proportional hazard model was used to analyze the association between the Geriatric Nutritional Risk Index and mortality. A total of 10,545 patients were included, and the mean age was 63.9 ± 3.7 years. The patients were divided into four groups by the quartile of the Geriatric Nutritional Risk Index with a mean value of 96.2 ± 8.2. During the study period, 545 (5.2%) deaths occurred. The surviving patients had higher Geriatric Nutritional Risk Index values than ones who died in the first year of hemodialysis initiation (96.6 ± 7.5 vs. 88.2 ± 9.3, p < 0.001). Quartile 1 (Geriatric Nutritional Risk Index < 91.8) showed a significantly increased risk of all-cause (Hazard Ratio: 2.56; 95% Confidence Interval: 2.13-3.09; p < 0.001) and cardiovascular mortality (Hazard Ratio: 22.29; 95% Confidence Interval: 1.71- 3.08; p < 0.001) at the first year in comparison with Quartile 4 (Geriatric Nutritional Risk Index ≥ 101.3). In areas under the receiver-operating characteristic curves of all-cause mortality, the Geriatric Nutritional Risk Index model improved predictive values, compared to the baseline model. The area with the Geriatric Nutritional Risk Index model was significantly higher than the one with a model including albumin or body mass index (p < 0.001). These findings suggest that a low Geriatric Nutritional Risk Index (<91.8) is associated with first-year all-cause and cardiovascular mortality in patients who start hemodialysis and may be a useful and reproducible tool for assessing prognoses in this population.

The Association of Stair Climbing Behaviors With Hazard of All-Cause Mortality in Adults With or At Risk of Knee Osteoarthritis.

To investigate the association of stair climbing difficulty and stair climbing frequency with the risk of all-cause mortality over 13 years in adults with or at high risk for knee OA. We used data from the Osteoarthritis Initiative (OAI), a prospective cohort study of community-dwelling adults with or at high risk for symptomatic knee OA. The exposures were stair climbing difficulty and frequency, assessed at baseline using self-report questionnaires. The outcome was all-cause mortality, assessed from baseline through 13 years of follow-up. Kaplan-Meier survival curves and Cox proportional hazards regression were used to investigate the association between stair climbing exposures and all-cause mortality. Three hundred seven (6.81%) and 310 (6.84%) participants in the difficulty and frequency samples, respectively, died during 13 years of follow-up. Those who were limited in any capacity in terms of their stair climbing ability had 54% to 84% greater hazard of all-cause mortality, and those who climbed at least 7 flights of stairs per week had 38% lower hazard of all-cause mortality. Adults with or at high risk for knee OA who report difficulty with climbing stairs or who infrequently use stairs are at greater hazard of all-cause mortality. Stair climbing difficulty and frequency are simple to collect and changes may occur early in OA progression, allowing for early intervention. Brief questions about stair climbing behaviors can serve as a functional vital sign within the clinician's toolbox.

High-sensitivity C-reactive protein is a predictor of all-cause mortality in a rural Japanese population.

High-sensitivity C-reactive protein (hsCRP) is a sensitive marker of inflammation. This study aimed to determine whether increased hsCRP levels are associated with all-cause mortality rate. We examined data for participants from the 2002 Nomura Cohort Study who attended follow-ups for 20 years (follow-up rate: 93.3%). Of these, 793 were male (aged 61 ± 14 years) and 1040 were female (aged 63 ± 11 years). The Japanese Basic Resident Registry provided data on adjusted relative hazards for all-cause mortality. The data were subjected to a Cox regression analysis using a time variable of age and confounding risk factors. The median (interquartile range) follow-up period was 6548 days (6094-7452 days). The follow-up confirmed that there were 632 (34.8%) deaths, of which 319 were male (40.2% of all males) and 313 were female (30.6% of all females). Multivariable-adjusted hazard ratio(1.27; 95% confidence interval, 1.01-1.59) in the highest hsCRP category was also significantly higher compared with reference. A higher hsCRP was associated with a greater risk of all-cause mortality in male participants aged ≥65 years, a BMI < 25 kg/m2 , and no history of CVD or diabetes, and this association was particularly significant among participants with both of the latter two risk factors (p = 0.004 and 0.022 for interaction, respectively). Our results indicate a significant association between hsCRP levels and all-cause mortality in a rural Japanese population. Specifically, hsCRP appears to be a crucial biomarker for predicting long-term survival, particularly among older persons.

Evaluation of guideline-concordant treatment and clinical outcomes in non-small cell lung cancer: A study at a National-Referral Hospital in Indonesia

Non-adherence to guidelines has been demonstrated to affect clinical outcomes. With more than half of the global incidence of lung cancer occurring in Asia, this study aims to evaluate the guideline-concordant treatment (GCT) among Asian patients based on the 2018 NCCN-Asia consensus statements on NSCLC. Patients diagnosed with NSCLC between December 2018 and 2019 were identified from electronic medical records. Patients with complete data were divided into GCT-positive and negative groups. Statistical analyses were performed to analyze survival distributions and the associations between covariates and GCT status. Out of 50 patients, 90% were in stage IV. No patients underwent PET scans nor stereotactic radiotherapy due to the absence of facilities. Overall, 44% of patients were GCT-positive. Most GCT-negative patients did not receive chemotherapy due to poor performance scores. There was a significant difference in the survival distribution between groups (72.7% vs 39.3%, p=0.006). Age and sex were not significantly associated with GCT status (p&gt;0.05). After accounting for other covariates including histology, GCT-negative was still associated with an increased hazard of all-cause mortality (HR 3.07 [1.15-8.12]; p=0.025). Despite limitations, concordance with Asian-specific guidelines independently and significantly improved OS among patients at a national-referral hospital in Indonesia.

Association between cytomegalovirus seropositivity and all-cause mortality: An original cohort study.

To examine the association between cytomegalovirus (CMV) seropositivity and all-cause mortality in a nationwide cohort of US adults. We obtained data from the National Health and Nutrition Examination Survey III (1988-1994), including 16,547 participants aged 18-90 years old with CMV serology assessments. Mortality status was ascertained until December 2019 using the National Death Index linkage data. The Cox proportional hazard model was applied to estimate the association between CMV seropositivity and mortality. During a median follow-up of 26.3 years, 6,930 deaths were recorded. CMV seropositivity was associated with a higher hazard of all-cause mortality after adjusting for attained age, sex, and ethnicity (HR: 1.22, 95% CI: 1.10, 1.36, p < 0.001). The magnitude of the association attenuated slightly after adjusting further for body mass index, family income, smoking status, diabetes, and self-reported cancer history (HR = 1.11, 95% CI: 1.00, 1.23, p = 0.04). While the association was observed for both men and women, it was only statistically significant among non-Hispanic white people (HR: 1.16, 95% CI: 1.06, 1.26, p = 0.001) but not among other ethnic populations. CMV seropositivity might be an independent risk factor for all-cause mortality among US adults. If the findings are validated in an independent population, further research is needed to unveil the biological mechanisms driving the increased mortality with CMV seropositivity.

Racial disparities in breast cancer survival after treatment initiation in Brazil: a nationwide cohort study

Breast cancer is a public health priority in Brazil and ensuring equity in health care is one of the cancer control plan goals. Our aim was to present the first assessment on the influence of race or skin colour on breast cancer survival at the national level. In this nationwide cohort study, data on women who initiated treatment for breast cancer in the public health-care system (Sistema Unico de Saúde), Brazil, were assembled through record linkage of administrative and mortality information systems. The administrative information systems were the Outpatient Information System (data from high complexity procedure authorisations) and the Hospital Information System (data from hospitalisation authorisations). We included women aged 19 years or older who started treatment between Jan 1, 2008, and Nov 30, 2010; self-identified as having White, Black, or Brown race or skin colour; had tumour stage I-IV; and were treated with chemotherapy or radiotherapy, or both. Patients were followed up until Dec 31, 2015. Patients with only hormone therapy records or who underwent only surgery were excluded. The Kaplan-Meier method was used to estimate crude overall survival for race or skin colour by time since treatment initiation, and Cox regression to estimate all-cause mortality hazard ratios (HRs) before and after adjustment for other covariates. We identified 59 811 women treated for stage I-IV breast cancer. 37 318 (62·4%) women identified themselves as White, 18 779 (31·4%) as Brown, and 3714 (6·2%) as Black. 5-year overall survival probability was higher for White women (74% [95% CI 73-74]) than Black women (64% [62-65]; p<0·0001). In adjusted regression models stratified by the absence of hormone therapy, Black women had a 24% (HR 1·24 [95% CI 1·16-1·34]; p<0·0001) higher risk of all-cause death than White women, and in the presence of hormone therapy Black women had a 25% (1·25 [1·14-1·38]; p<0·0001) higher risk of all-cause death than White women. Black skin colour was identified as a statistically significant risk marker for lower 5-year survival probability and higher risk of all-cause death among women treated for breast cancer by the Sistema Unico de Saúde. Actions to understand and mitigate this unfair difference in health results are urgently needed. Conselho Nacional de Desenvolvimento Científico e Tecnológico and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior and Pró-Reitoria de Pesquisa da Universidade Federal de Minas Gerais.

Survival outcomes of malignant peripheral nerve sheath tumors (MPNSTs) with and without neurofibromatosis type I (NF1): a meta-analysis

IntroductionMalignant peripheral nerve sheath tumors (MPNSTs) are malignancies that demonstrate nerve sheath differentiation in the peripheral nervous system. They can occur sporadically or be associated with neurofibromatosis type 1 (NF1), an autosomal dominant neurocutaneous disorder, with up to 13% of patients developing MPNSTs in their lifetimes. Previous studies have suggested conflicting findings regarding the prognosis of NF1 for patients with MPNSTs. The elucidation of NF1 as an independent prognostic factor on mortality has implications for clinical management. We aim to investigate the role of NF1 status as an independent prognostic factor of overall survival (OS) and disease-specific survival (DSS) in MPNSTs.MethodsAn electronic literature search of PubMed and MEDLINE was performed on studies reporting OS or DSS outcomes of MPNSTs with and without NF1. A grey literature search by reviewing bibliographies of included studies and review articles was performed to find pertinent studies. Data was extracted and assessed in accordance with the PRISMA guidelines. A meta-analysis was performed to calculate hazard ratios (HRs) using a random-effects model. The primary and secondary outcomes were all-cause and disease-specific mortality, respectively, with NF1 as an independent prognostic factor of interest.ResultsA total of 59 retrospective studies involving 3602 patients fulfilled the inclusion criteria for OS analysis, and 23 studies involving 704 MPNST patients were included to evaluate DSS outcomes. There was a significant increase in the hazard of all-cause mortality (HR 1.63, 95% CI 1.45 to 1.84) and disease-specific mortality (HR 1.52, 95% CI 1.24 to 1.88) among NF1 as compared to sporadic cases. Subgroup analyses and meta-regression showed that this result was consistent regardless of the quality of the study and year of publication.ConclusionNF1 is associated with a substantially higher risk of all-cause and disease-specific mortality. This finding suggests that closer surveillance is required for NF1 patients at risk of developing MPNSTs.

Patient years lost due to cytomegalovirus serostatus mismatching in the scientific registry of transplant recipients.

The cytomegalovirus (CMV) mismatch rate in deceased donor kidney transplant (DDKT) recipients in the US remains above 40%. Since CMV mismatching is common in DDKT recipients, the cumulative effects may be significant in the context of overall patient and graft survival. Our primary objective was to describe the short- and long-term risks associated with high-risk CMV donor positive/recipient negative (D+/R-) mismatching among DDKT recipients with the explicit goal of deriving a mathematical mismatching penalty. We conducted a retrospective, secondary analysis of the Scientific Registry of Transplant Recipients (SRTR) database using donor-matched DDKT recipient pairs (N=105,608) transplanted between 2011-2022. All-cause mortality and graft failure hazard ratios were calculated from one year to ten years post-DDKT. All-cause graft failure included death events. Survival curves were calculated using the Kaplan-Meier estimation at 10 years post-DDKT and extrapolated to 20 years to provide the average graft days lost (aGDL) and average patient days lost (aPDL) due to CMV D+/R- serostatus mismatching. We also performed an age-based stratification analysis to compare the relative risk of CMV D+ mismatching by age. Among 31,518 CMV D+/R- recipients, at 1 year post-DDKT, the relative risk of death increased by 29% (p<0.001), and graft failure increased by 17% (p<0.001) as compared to matched CMV D+/R+ group (N=31,518). Age stratification demonstrated a significant increase in the risk associated with CMV mismatching in patients 40 years of age and greater. The aGDL per patient due to mismatching was 125 days and the aPDL per patient was 100 days. The risks of CMV D+/R- mismatching are seen both at 1 year post-DDKT period and accumulated throughout the lifespan of the patient, with the average CMV D+/R- recipient losing more than three months of post-DDKT survival time. CMV D+/R- mismatching poses a more significant risk and a greater health burden than previously reported, thus obviating the need for better preventive strategies including CMV serodirected organ allocation to prolong lifespans and graft survival in high-risk patients.

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.