Risk Of Overall Mortality Research Articles

Abstract 4116714: Macrophage Colony Stimulating Factor as a Causal Metabolic Mediator of Cardiovascular Disease: An Observational and Mendelian Randomization Analysis

Background: Macrophage biology plays a key role in the pathogenesis of atherosclerosis and circulating macrophage colony-stimulating factor (M-CSF) is a marker of macrophage activity. However, there is conflicting evidence regarding its role as a mediator of cardiovascular disease. Methods: We evaluated the association between plasma M-CSF concentration with myocardial infarction, stroke, heart failure and mortality in a large substudy involving 9992 participants drawn from 14 countries and followed for a median period of 9.8 years (Interquartile Range 8.9 years - 11.4 years) utilizing a nested case-cohort design in the Prospective Urban Rural Epidemiology (PURE) study. We then conducted a two-sample Mendelian randomization (MR) analysis to evaluate the upstream determinants (using genome wide association data from the PURE biobank and publicly available consortia) and downstream effects on clinical events.. Results: The strongest causal upstream determinant of M-CSF concentration was body mass index (BMI), which showed a positive association with plasma M-CSF concentration (Beta: 0.17 SD increase; 95% CI: 0.08 - 0.27). In a survival analysis, M-CSF was independently associated with increased incident myocardial infarction (HR: 1.25 per 1 SD M-CSF increase; 95% CI: 1.13-1.38), stroke (HR: 1.17; 95% CI:1.04-1.32), and heart failure (HR: 1.34; 95% CI: 1.15-1.56) and other cardiovascular disease risk factors. Circulating M-CSF concentration also showed a strong association with long-term risk of overall mortality (HR: 1.44; 95% CI: 1.39-1.60). Mendelian randomization analyses confirmed that increased M-CSF was associated with increased risk of MI, heart failure, and ischemic stroke (specifically large artery atherosclerotic and cardioembolic stroke). Conclusions: M-CSF is a strong causal driver of cardiovascular disease morbidity whose concentration is causally influenced by body mass index. Our analysis suggests a role for macrophage activity in mediating the relationship between body mass index and cardiovascular disease outcomes.

Relationship between timing of coffee and tea consumption with mortality (total, cardiovascular disease and diabetes) in people with diabetes: the U.S. National Health and Nutrition Examination Survey, 2003–2014

BackgroundPrevious observational studies have suggested diabetic patients should synchronize their foods and nutrient intake with their biological rhythm; however, the optimal intake time of coffee and tea for reducing all-cause and disease-specific mortality in diabetes is still unknown. This study aims to examine by investigating the association of timing for coffee and tea consumption with long-term survival in people with diabetes.MethodsA total of 5378 people with diabetes who enrolled in the National Health and Nutrition Examination Survey from 2003 to 2014 were recruited for this study. Coffee and tea intakes were measured by a 24-h dietary recall, which were divided by different time intervals across the day, including dawn to forenoon, forenoon to noon, noon to evening, and evening to dawn. Weighted cox proportional hazards regression models were developed to evaluate the survival-relationship of coffee and tea consumption with mortality of all-cause, cardiovascular disease (CVD), stroke, and diabetes.ResultsDuring 47,361 person-year follow up, total 1639 death cases were documented, including 731 CVD deaths, 467 heart disease deaths, 99 stroke deaths, and 462 diabetes deaths. After adjustment for potential confounders, compared with participants without drinking coffee during dawn to forenoon, drinking coffee at this period was associated with increased mortality risk of all-cause (HR 1.25, 95% CI 1.05–1.50), CVD (HR 1.41, 95% CI 1.07–1.86), heart-disease (HR 1.47, 95% CI 1.05–2.07), and diabetes (HR 1.50, 95% CI 1.10–2.04). In contrast, drinking coffee during forenoon to noon had lower mortality risk of all-cause (HR 0.80, 95% CI 0.69–0.92), CVD (HR 0.79, 95% CI 0.63–0.99), and heart disease (HR 0.70, 95% CI 0.52–0.94). Similarly, drinking tea during forenoon to noon had lower risk of CVD mortality (HR = 0.62, 95% CI 0.44–0.87).ConclusionsThis study suggests that drinking coffee in dawn to forenoon is linked to a higher risk of death, but having coffee and tea from forenoon to noon is linked to a lower risk of overall mortality, CVD, and heart disease in individuals with diabetes.Graphical

The change of paradigm: high HDL-c levels could not mean a long lifespan

Abstract Background It is known that a low HDL-c level is associated with a high risk of overall mortality. Consequently, it was presumed that achieving higher levels of high-density lipoprotein cholesterol (HDL-c) would reduce the risk or even extend the lifespan. However, clinical trials with medical intervention failed to find clinical benefits. Aim We aimed to investigate the association between (HDL-c) levels and overall mortality using a prospective cohort from Portugal. Methods A prospective sub-study (2001-2022) was performed in a cohort of 1718 participants without coronary artery disease (CAD) of the control arm of the ongoing GENEMACOR study. The participants <65 years were followed during a mean follow-up of 7.0±5.7 years. All demographic, biochemical, and clinical data were collected. Participants were stratified into six levels of HDL-c. Kaplan-Meier estimated differences in the survival probability of each HDL-c level. Cox proportional analysis models (unadjusted and adjusted) were used to assess the association between HDL-c levels and overall mortality. Results The HDL-c levels with the lowest overall mortality rate were 60 to 70 mg/dl, set as the reference level. Total HDL-c strata were associated with overall mortality with a U-shaped relationship: in the control group, the first level (<40 mg/dl) was independently associated with increased risk of overall mortality (HR of 3.533; 95% CI: 1.738-7.178; p<0.0001). This risk drops and falls to the reference level (the lower risk) and rises again to an HR of 3.875 (95% CI: 1.472-10.201; p=0.006) in the very high HDL-c levels (≥80 mg/dl). Conclusions Our results, based on a large Portuguese cohort, suggest that very high HDL-c levels in the normal population may not represent a good prognosis, especially in women. Future research may confirm these findings and investigate the underlying mechanisms.

Association between self-reported napping and risk of cardiovascular disease and all-cause mortality: A meta-analysis of cohort studies.

This meta-analysis aims to assess the association between adult nap duration and risk of all-cause mortality and cardiovascular diseases (CVD). PubMed, Cochrane Library, Embase and Web of Science databases were searched to identify eligible studies. The quality of observational studies was assessed using the Newcastle-Ottawa Scale. We performed all statistical analyses using Stata software version 14.0. For the meta-analysis, we calculated hazard ratio (HR) and their corresponding 95% confidence intervals (CIs). To assess publication bias, we used a funnel plot and Egger's test. A total of 21 studies involving 371,306 participants revealed varying methodological quality, from moderate to high. Those who indulged in daytime naps faced a significantly higher mortality risk than non-nappers (HR: 1.28; 95% CI: 1.18-1.38; I2 = 38.8%; P<0.001). Napping for less than 1 hour showed no significant association with mortality (HR: 1.00; 95% CI: 0.90-1.11; I2 = 62.6%; P = 0.971). However, napping for 1 hour or more correlated with a 1.22-fold increased risk of mortality (HR: 1.22; 95% CI: 1.12-1.33; I2 = 40.0%; P<0.001). The risk of CVD associated with napping was 1.18 times higher than that of non-nappers (HR: 1.18; 95% CI: 1.02-1.38; I2 = 87.9%; P = 0.031). Napping for less than 1 hour did not significantly impact CVD risk (HR: 1.03; 95% CI: 0.87-1.12; I2 = 86.4%; P = 0.721). However, napping for 1 hour or more was linked to a 1.37-fold increased risk of CVD (HR: 1.37; 95% CI: 1.09-1.71; I2 = 68.3%; P = 0.007). Our meta-analysis indicates that taking a nap increases the risk of overall mortality and CVD mortality. It highlights that the long duration time of the nap can serve as a risk factor for evaluating both overall mortality and cardiovascular mortality.

Application of deep learning-based fuzzy systems to analyze the overall risk of mortality in glioblastoma multiforme

Abstract Glioblastoma multiforme (GBM) is the most aggressive brain cancer in adults, with 3.2-3.4 cases per 100 thousand. In the US, brain cancer does not rank in the top 10 causes of death, but it remains in the top 15. Therefore, this research proposes a fuzzy-based GRUCoxPH model to identify missense variants associated with a high risk of all-cause mortality in GBM. The study combines various models, including fuzzy logic, Gated Recurrent Units (GRUs), and Cox&amp;#xD;Proportional Hazards Regression (CoxPh), to identify potential risk factors. The dataset is derived from TCGA-GBM clinicopathological information and mutations to create four risk score models: GRU, CoxPH, GRUCoxPHAddition, and GRUCoxPHMultiplication, analyzing 9 risk factors of the dataset. The Fuzzy-based GRUCoxPH model achieves an average accuracy of&amp;#xD;86.97%, outperforming other models. This model demonstrates its ability to classify and identify missense variants associated with mortality in GBM, potentially advancing cancer research.&amp;#xD;

Impact of Smoking on Overall and Cancer-Specific Mortality in Prostate Cancer: Elevated Risks in Older and Early-Stage Patients—A Population-Based Study

Prostate cancer (PCa) ranks sixth in cancer mortality among Taiwanese men, with smoking rates remaining high despite the 2009 Tobacco Hazards Prevention Act. This study used the Taiwan Cancer Registry to evaluate smoking’s impact on PCa mortality, providing important information for healthcare strategies and patient management. From 2011 to 2017, 23,107 PCa patients were analyzed, with 7164 smokers and 15,943 non-smokers. The baseline characteristics, clinical stages, comorbidities, and treatment modalities were all included to estimate overall and cancer-specific mortality using the Cox regression model and Kaplan–Meier analysis. The stratified analysis of clinical stage and age group was also estimated. Our study found an association between smoking and increased overall and cancer-specific mortality in PCa patients. Although smokers over 60 had higher risks of overall mortality than non-smokers, cancer-specific mortality did not show significant differences in any age group. Smokers had higher overall mortality than non-smokers across all clinical stages, but cancer-specific mortality was significantly raised only in early-stage cases. In conclusion, smoking is associated with higher overall mortality in PCa patients, with a significant increase in cancer-specific mortality in early-stage cases. Therefore, active smoking management is critical for clinical urologists, particularly in the treatment of early-stage patients.

Higher levels of neighborhood deprivation and risk for incident colorectal cancer and mortality outcomes: A systematic review and meta-analysis.

131 Background: Significant geographic and racial disparities exist for colorectal cancer (CRC) incidence and mortality in the United States (US), which may be caused by neighborhood-level deprivation and limited access to preventative cancer screening. We completed the first systematic review and meta-analysis of neighborhood-level deprivation in relation to CRC incidence, mortality, and screening among individuals from the US. Methods: A systematic literature review was completed to identify original research articles from PubMed, Scopus, and Web of Science. Eligible studies reported associations between deprivation at the census block or tract level using a validated deprivation index (e.g. the Area Deprivation Index or Yost Index) and CRC incidence, mortality, or screening outcomes in a US-based sample. A fixed-effects meta-analysis was completed using inverse-variance weighting to estimated hazard ratios (HRs) or odds ratios (ORs) with 95% confidence intervals (CIs) for CRC incidence, mortality, and screening outcomes, comparing the highest vs. lowest quantiles of neighborhood-level deprivation. All analyses were completed using the meta package in R. Results: In total, 19 studies were included in the meta-analysis. Living in a neighborhood in the highest quantile of deprivation was associated with significantly higher risk for incident CRC (HR 1.37, 95% CI 1.34-1.41, seven studies). In stratified analysis, positive associations with incident CRC were observed for White (HR 1.43, 95% CI 1.39-1.47, three studies), Black (HR 1.18, 95% CI 0.96-1.44, three studies), and Asian/Pacific Islander individuals (HR 1.18, 95% CI 1.08-1.28, two studies). For individuals diagnosed with CRC, higher deprivation was associated with elevated risk for overall mortality (HR 1.11, 95% CI 1.10-1.13, four studies) and CRC-specific mortality (HR 1.17, 95% CI 1.15-1.19, seven studies). Higher deprivation was associated with lower completion of recommended screening for CRC, including colonoscopy, sigmoidoscopy, or fecal occult blood testing (OR 0.76, 95% CI 0.74-0.79, four studies). Conclusions: Individuals who reside in neighborhoods with high levels of deprivation have significantly elevated risk for CRC incidence and mortality compared to individuals from low deprivation neighborhoods. Targeting healthcare resources to highly deprived neighborhoods to increase uptake of preventative screening may help to address racial and geographic disparities for CRC.

Abstract C039: Nativity and breast cancer outcomes by breast cancer subtype in the ENCLAVE Study

Abstract Background: Associations of nativity and breast cancer (BC) mortality are mixed in studies using cancer registry data. We examined associations in diverse women with detailed individual-level data on BC treatment and subtype. Methods: The study population included 5,718 Asian (n=722, 71% foreign-born), Hispanic (n=631, 42% foreign-born), and non-Hispanic White (n=4,365, 9% foreign-born) women from the ENCLAVE Study diagnosed with invasive BC from 1996-2013 using pooled, harmonized data from two (of three) cohorts with data on BC subtype. Data on nativity, reproductive and behavioral factors were self-reported from questionnaires; data on disease severity, BC subtype (luminal A, luminal B, Her2 expressing, triple negative breast cancer), treatment, and mortality were obtained from cancer registries and electronic health records. Recurrences were identified by recurrence algorithms and medical record review. We fit Cox proportional hazards regression models to examine associations between self-reported nativity and recurrence, BC-specific mortality, and overall mortality. Covariates included age, sociodemographic factors, disease severity, and treatment, reproductive and behavioral factors. We also examined associations by race, ethnicity, and BC subtype. Results: Compared to US-born women, foreign-born women had lower total mortality (hazard ratio [HR]=0.75, 95% confidence interval [CI]: 0.64-0.89); lower risks were suggested for recurrence (HR=0.85, 95% CI: 0.68-1.06) and breast cancer-specific mortality (HR=0.87, 95% CI: 0.66-1.14). Stratified by BC subtype, foreign- (vs. US-) born women had a lower risk of overall mortality among those with luminal A (HR=0.72, 95% CI: 0.56-0.92) and luminal B (HR=0.66, 95% CI: 0.48-0.91) but not other subtypes. Among women with luminal B BC, these associations reached statistical significance for recurrence (HR=0.65, 95% CI: 0.45-0.94) and BC-specific mortality (HR=0.53, 95% CI: 0.33-0.84). We noted no associations in other BC subtypes though analyses of less common subtypes were underpowered. Associations did not differ by race or ethnicity. Conclusion: Foreign-born women with BC had lower risk of overall mortality than US-born women. Risks of recurrence and BC-specific mortality were lower in foreign-born vs. US-born women among those with the luminal B BC subtype. Associations were not explained by behavioral or reproductive factors. Citation Format: Candyce Kroenke, Rhonda Aoki, Stacey Alexeeff, Scarlett Gomez, Bette Caan, Brittany Morey, Jacqueline Torres, Larry Kushi. Nativity and breast cancer outcomes by breast cancer subtype in the ENCLAVE Study [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr C039.

Abstract A076: Racial disparities in disease-free and overall survival among colorectal cancer patients in the prospective ColoCare cohort

Abstract Background: Despite improvements in screening and treatment, Black and other underserved colorectal cancer survivors continue to experience poorer clinical outcomes. Multicenter prospective cohorts among large cancer centers in the United States (US) offer the unique opportunity to characterize potential multilevel determinants of disparate outcomes while accounting for known contributions of medical access and treatment. We investigated racial and ethnic disparities in disease-free survival (DFS) and overall survival in the ColoCare study, a prospective cohort study of newly diagnosed colorectal cancer patients across six US cancer centers. Method: The ColoCare study population (n=2,471) from six US sites included n=1,950 non-Hispanic White (NHW), n=238 non-Hispanic Black (NHB), and n=114 Hispanic patients. We estimated racial and ethnic differences in baseline patient characteristics using χ2. We investigated disparities in outcomes by estimating associations of race and ethnicity with DFS (among stage I-III) and overall mortality using Cox Proportional Hazards Models, adjusted for sex, stage at diagnosis, age, study center, and anatomic site. Results: The patients were primarily male (53%), had colon tumors (37.5%), with an average age at diagnosis of 58.6 years. Hispanic individuals were on average younger than their counterparts (P=.03), while NHB individuals were more likely to be overweight and obese (P&amp;lt;.01). NHB individuals had statistically significantly poorer DFS than NHW individuals (HR=1.55, 95% CI=1.03-2.32; P=0.03). NHB individuals also had higher risk for overall mortality (HR=1.45, 95% CI=0.97-2.16; P=0.07), though these findings were not statistically significant. Overall, associations of Hispanic ethnicity with DFS and overall survival were close to null. Discussion: NHB individuals had poorer survivorship outcomes in our study despite all patients receiving care at designated comprehensive cancer centers. Our findings highlight the continued need to address disparities in survivorship using targeted, culturally sensitive intervention strategies. Future research efforts should identify actionable factors, such as adiposity, that may disproportionately impact health outcomes among minority colorectal cancer survivors. Citation Format: Esther Jean-Baptiste, Mmadili Ilozumbo, Gazelle Rouhani, Maria F. Gomez, Stephanie R. Hogue, Sheetal Hardikar, Biljana Gigic, Christopher I Li, Jane C Figueiredo, Adetunji T. Toriola, Cornelia M Ulrich, David Shibata, Erin M Siegel, Doratha A. Byrd. Racial disparities in disease-free and overall survival among colorectal cancer patients in the prospective ColoCare cohort [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr A076.

Serum Erythritol and Risk of Overall and Cause-Specific Mortality in a Cohort of Men.

Erythritol occurs naturally in some fruits and fermented foods, and has also been used as an artificial sweetener since the 1990s. Although there have been questions and some studies regarding its potential adverse health effects, the association between serum erythritol and long-term mortality has not been evaluated. To examine the association between serum erythritol's biochemical status and risk of overall and cause-specific mortality, a prospective cohort analysis was conducted using participants in the ATBC Study (1985-1993) previously selected for metabolomic sub-studies. The analysis included 4468 participants, among whom 3377 deaths occurred during an average of 19.1 years of follow-up. Serum erythritol was assayed using an untargeted, global, high-resolution, accurate-mass platform of ultra-high-performance liquid and gas chromatography. Cause-specific deaths were identified through Statistics Finland and defined by the International Classification of Diseases. After adjustment for potential confounders, serum erythritol was associated with increased risk of overall mortality (HR = 1.50 [95% CI = 1.17-1.92]). We found a positive association between serum erythritol and cardiovascular disease mortality risk (HR = 1.86 [95% CI = 1.18-2.94]), which was stronger for heart disease mortality than for stroke mortality risk (HR = 3.03 [95% CI = 1.00-9.17] and HR = 2.06 [95% CI = 0.72-5.90], respectively). Cancer mortality risk was also positively associated with erythritol (HR = 1.54 [95% CI = 1.09-2.19]). The serum erythritol-overall mortality risk association was stronger in men ≥ 55 years of age and those with diastolic blood pressure ≥ 88 mm Hg (p for interactions 0.045 and 0.01, respectively). Our study suggests that elevated serum erythritol is associated with increased risk of overall, cardiovascular disease, and cancer mortality. Additional studies clarifying the role of endogenous production and dietary/beverage intake of erythritol in human health and mortality are warranted.

Additive impact of diabetes and Helicobacter pylori infection on all-cause mortality, diabetic mortality, and cardiovascular mortality: a longitudinal nationwide population-based study

BackgroundDiabetes mellitus (DM) and Helicobacter pylori infection (HPI) pose increasing public health challenges in aging societies, sharing common pathophysiological mechanisms, and linked to significant health risks. Our study examines their respective impacts on all-cause and cardiovascular mortalities in a comprehensive longitudinal population-based analysis.MethodsThe study analyzed data from the National Health and Nutrition Examination Survey (NHANES) database conducted between 1999 and 2019, which included information on Diabetes mellitus status and Helicobacter pylori infection status. Mortality data were obtained from the same database mentioned above.ResultsAmong the 2719 participants, 1362 (50.1%) were free of both diabetes mellitus (DM) and Helicobacter pylori infection (HP) (DM −/HP −), 140 (5.1%) had DM alone (DM +/HP −), 1011 (37.2%) had HP alone (DM −/HP +), and 206 (7.6%) had both DM and HP (DM +/HP +). Compared to the DM −/HP − group, the DM +/HP − and DM + /HP + groups demonstrated increased all-cause mortality with adjusted hazard ratios (HRs) of 1.40 (95% [CI] 1.07–1.78) and 1.46 (95% CI 1.15–1.84), respectively. For diabetic mortality, DM +/HP– group and DM + /HP + group showed increased HR of 6.30 (95% CI 1.30–30.43) and 8.56 (95% CI 1.98–36.94), respectively. For cardiovascular mortality, the DM + /HP– group and DM + /HP + group exhibited increased HR of 1.75 (95% CI 1.14–2.69) and 1.98 (95% CI 1.40–2.79), respectively. The DM + /HP + cohort displayed the highest risk of overall mortality (p for trend = 0.003), diabetic mortality (p for trend < 0.0001), an6d cardiovascular mortality (p for trend < 0.0001).ConclusionsThe concurrent presence of DM and Helicobacter pylori infection significantly amplifies the risk of all-cause, cardiovascular, and diabetic mortality. Individuals with either condition may necessitate heightened management to prevent the onset of the other ailment and reduce mortality rates.

Can Bisphosphonate Therapy Reduce Overall Mortality in Patients With Osteoporosis? A Meta-analysis of Randomized Controlled Trials.

For patients with osteoporosis, bisphosphonate therapy can reduce the risk of fractures, but its effect on reducing mortality remains unclear. Previous studies on this topic have produced conflicting results and generally have been too small to definitively answer the question of whether bisphosphonate therapy reduces mortality. Therefore, a meta-analysis may help us arrive at a more conclusive answer. In a large meta-analysis of placebo-controlled randomized controlled trials (RCTs), we asked: (1) Does bisphosphonate use reduce mortality? (2) Is there a subgroup effect based on whether different bisphosphonate drugs were used (zoledronate, alendronate, risedronate, and ibandronate), different geographic regions where the study took place (Europe, the Americas, and Asia), whether the study was limited to postmenopausal female patients, or whether the trials lasted 3 years or longer? We conducted a systematic review using multiple databases, including Embase, Web of Science, Medline (via PubMed), Cochrane Library, and ClinicalTrials.gov, with each database searched up to November 20, 2023 (which also was the date of our last search), following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We included randomized, placebo-controlled clinical trials with participants diagnosed with osteoporosis and receiving bisphosphonate treatment. We excluded papers posted to preprint servers, other unpublished work, conference abstracts, and papers that were registered on ClinicalTrials.gov but were not yet published. We collected 2263 records. After excluding records due to study type, study content not meeting the inclusion criteria, and duplicates, our meta-analysis included 47 placebo-controlled RCTs involving 59,437 participants. Data extraction, quality assessment, and statistical analyses were performed. The evaluation of randomized trials for potential bias was conducted using the revised Cochrane Risk of Bias tool. This assessment encompassed factors such as sequence generation, allocation concealment, subject blinding, outcome assessor blinding, incomplete outcome data, and reporting bias. Some studies did not provide explicit details regarding random sequence generation, leading to a high risk of selection bias. A few studies, due to their open-label nature, were unable to achieve double-blind conditions for both the subjects and the researchers, resulting in intermediate performance bias. Nevertheless, the overall study quality was high. Due to the low heterogeneity among the studies, as evidenced by the low statistical heterogeneity (that is, a low I2 statistic), we opted for a fixed-effects model, indicating that the effect size is consistent across the studies. In such cases, the fixed-effects model can provide more precise estimates. According to the results of the funnel plot, we did not find evidence of publication bias. The use of bisphosphonates did not reduce the overall risk of mortality in patients with osteoporosis (risk ratio 0.95 [95% CI 0.88 to 1.03]). Subgroup analyses involving different bisphosphonate drugs (zoledronate, alendronate, risedronate, and ibandronate), regions (Europe, the Americas, and Asia), diverse populations (postmenopausal female patients and other patients), and trials lasting 3 years or longer revealed no associations with reduced overall mortality. Based on our comprehensive meta-analysis, there is high-quality evidence suggesting that bisphosphonate therapy for patients with osteoporosis does not reduce the overall risk of mortality despite its effectiveness in reducing the risk of fractures. The primary consideration for prescribing bisphosphonates to individuals with osteoporosis should continue to be centered on reducing fracture risk, aligning with clinical guidelines. Long-term studies are needed to investigate potential effects on mortality during extended treatment periods. Level I, therapeutic study.

Elevated plasma hepcidin concentrations are associated with an increased risk of mortality and nonfatal cardiovascular events in patients with type 2 diabetes: a prospective study

BackgroundThe effect of plasma hepcidin concentrations on the long-term risk of developing adverse cardiovascular outcomes in people with type 2 diabetes mellitus (T2DM) is unclear.MethodsWe followed for a median of 55.6 months 213 outpatients with established T2DM (45.5% women, mean age 69 ± 10 years; BMI 28.7 ± 4.7 kg/m2; median diabetes duration 11 years). Baseline plasma ferritin and hepcidin concentrations were measured with an electrochemiluminescence immunoassay and mass spectrometry-based assay, respectively. The primary study outcome was a composite of all-cause mortality or incident nonfatal cardiovascular events (inclusive of myocardial infarction, permanent atrial fibrillation, ischemic stroke, or new hospitalization for heart failure).Results42 patients developed the primary composite outcome over a median follow-up of 55.6 months. After stratifying patients by baseline hepcidin tertiles [1st tertile: median hepcidin 1.04 (IQR 0.50–1.95) nmol/L, 2nd tertile: 3.81 (IQR 3.01-4-42) nmol/L and 3rd tertile: 7.72 (IQR 6.37–10.4) nmol/L], the risk of developing the primary composite outcome in patients in the 3rd tertile was double that of patients in the 1st and 2nd tertile combined (unadjusted hazard ratio [HR] 2.32, 95%CI 1.27–4.26; p = 0.007). This risk was not attenuated after adjustment for age, sex, adiposity measures, smoking, hypertension, statin use, antiplatelet medication use, plasma hs-C-reactive protein and ferritin concentrations (adjusted HR 2.53, 95%CI 1.27–5.03; p = 0.008).ConclusionsIn outpatients with T2DM, higher baseline hepcidin concentrations were strongly associated with an increased long-term risk of overall mortality or nonfatal cardiovascular events, even after adjustment for established cardiovascular risk factors, plasma ferritin concentrations, medication use, and other potential confounders.

Overall and cause-specific mortality among patients diagnosed with gastric precancerous lesions in Sweden between 1979 and 2014: an observational cohort study

BackgroundThe Correa’s cascade, encompassing chronic non-atrophic gastritis, atrophic gastritis, intestinal metaplasia, and dysplasia, represents the well-recognized pathway for the development of non-cardia gastric cancer. Population-based studies on all-cause and cause-specific mortalities among patients with gastric lesions in Correa’s cascade are scarce.MethodsWe compiled a cohort of 340 744 eligible patients who had undergone endoscopy with biopsy for non-malignant indications during the period 1979–2011, which was followed up until 2014. Standardized mortality ratios (SMRs) with 95% confidence intervals (CIs) provided estimation of the relative risk, using the general Swedish population as reference. Cox regression model was used to estimate hazard ratios (HRs) of death for internal comparison.ResultsA total of 306 117 patients were included in the final analysis, accumulating 3,049,009 person-years of follow-up. In total 106,625 deaths were observed during the study period. Compared to the general population, excess risks of overall mortality were noted in all subgroups, with SMRs ranging from 1.11 (95% CI 1.08–1.14) for the normal mucosa group to 1.54 (95% CI 1.46–1.62) for the dysplasia group. For cause-specific mortalities, mortality from gastric cancer gradually increased along Correa’s cascade, with excess risk rising from 105% for patients with chronic gastritis to more than 600% for the dysplasia group. These results were confirmed in the comparison with the normal mucosa group. For non-cancer conditions, increased death risks were noted for various diseases compared to the general population, especially among patients with more severe gastric precancerous lesions. But the results were confirmed only for “infectious diseases and parasitic diseases”, “respiratory system diseases”, and “digestive system disease”, when using the normal mucosa group as reference.ConclusionsIncreased mortality from gastric cancer suggests that early recognition and intervention of gastric precancerous lesions probably benefit the patients. Excess mortality due to non-cancer conditions should be interpreted with caution, and future studies are warranted.

Associations of Diet and Lifestyle with Mortality and Stroke: The China Cardiometabolic Disease and Cancer Cohort (4C) Study.

This study aimed to examine the individual and combined associations between dietary habits and lifestyle factors concerning all-cause mortality and stroke in Chinese adults. We conducted a nationwide, multicenter, prospective cohort study involving 10,008 participants, gathering baseline data on lifestyle, metabolic status, dietary habits, and living behaviors. Subsequently, a 10-year follow-up was performed, resulting in the inclusion of 7,612 participants in this study. We employed Spearman correlation analysis, restricted cubic spline regression, and Cox regression analysis to evaluate the connections between outcome events, dietary habits, and lifestyle. For each additional serving of pulses consumed per week, there was a slight decrease in the risk of all-cause mortality (HR: 0.91, 95% CI: 0.83-0.99). The hazard ratios for stroke were 2.24 (1.48, 3.37) for current smokers, in comparison to individuals who had never smoked. Appropriate intake of specific dietary factors and certain lifestyle habits were associated with reduced stroke: fruit drinks at 0.51 (0.34, 0.87), and animal viscera at 0.58 (0.32, 1.04). Weekly consumption of at least 21 servings of vegetables (0.72, 0.53-0.98), 0-1 serving of fried food (0.58, 0.38-0.90), and at least 1 serving of carbonated beverages (0.51, 0.28-0.92) was associated with a reduced risk of stroke. Smoking was found to be linked to an increased risk of stroke. A higher intake of fruit drinks and animal viscera was associated with a reduced risk of stroke. In contrast, a higher intake of beans was associated with a decreased risk of overall mortality. Consuming an appropriate amount of vegetables, fried foods, and carbonated drinks was found to potentially lower the risk of stroke. Collectively, these findings underscore the importance of developing tailored dietary interventions conducive to the Chinese populace's health.

2236 Emergency department attendance stratified by cause and frailty status: a national cohort study of over 155 million patients

Abstract Introduction Data are limited on whether the causes of Emergency Department (ED) attendance and clinical outcomes vary by frailty status. Methods Using data from the Nationwide Emergency Department Sample, all ED attendances from 2016 to 2018 were stratified by the cause of attendance and Hospital Frailty Risk Score (HFRS) category. Logistic regression was used to determine adjusted odds ratios (aOR) and 95% confidence intervals (95% CI) of ED and overall mortality. Results A total of 155,497,048 ED attendances were included, of which 125,809,960 (80.9%) had a low HFRS (&amp;lt;5), 27,205,257 (17.5%) had an intermediate HFRS (5–15) and 2,481,831 (1.6%) had a high HFRS (&amp;gt;15). The most common cause of ED attendance in the high HFRS group was infectious diseases (43.0%), followed by cardiovascular diseases (CVD) (24.0%) and respiratory diseases (10.2%). Musculoskeletal diseases were the most common cause of admission for the low HFRS group (21.2%), followed by respiratory diseases (20.6%), and gastrointestinal diseases (18.5%). On adjusted analysis, high HFRS patients had increased overall mortality (combined ED and in-hospital) across most attendance causes, compared to their low HFRS counterparts (p &amp;lt; 0.001). High HFRS patients with infectious diseases (aOR 23.88 95% CI 23.42–24.34), CVD (aOR 2.58 95% CI 2.55–2.61) and respiratory diseases (aOR 36.90 95% CI 36.18–37.62) had an increased risk of overall mortality, compared to their low-risk counterparts (p &amp;lt; 0.001). Conclusions A significant proportion of patients attending the ED are frail, with the cause of attendance varying by frailty status. Frailty is associated with increased overall mortality across most attendance causes.

Patient-Reported Outcome Measures in Cancer Care

Patient-reported outcome measures (PROMs) come directly from the patient, without clinician interpretation, to provide a patient-centered perspective. To understand the association of PROM integration into cancer care with patient-related, therapy-related, and health care utilization outcomes. Searches included MEDLINE and MEDLINE Epub ahead of print, in-process, and other nonindexed citations; Embase databases (OvidSP); PsychINFO; CENTRAL; and CINAHL from January 1, 2012 to September 26, 2022. Randomized clinical trials (RCTs) that enrolled adult patients (ages 18 years and older) with active cancer receiving anticancer therapy using a PROM as an intervention. Pairs of review authors, using prepiloted forms, independently extracted trial characteristics, disease characteristics, and intervention details. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses reporting guideline was followed. Random-effects analyses were conducted. Overall mortality, health-related quality of life (HRQoL) measures, and hospital utilization outcomes. From 1996 to 2022, 45 RCTs including 13 661 participants addressed the association of PROMs with outcomes considered important to patients. The addition of a PROM likely reduced the risk of overall mortality (HR, 0.84; 95% CI, 0.72-0.98; moderate certainty), improved HRQoL (range 0-100) at 12 weeks (mean difference [MD], 2.45; 95% CI, 0.42-4.48; moderate certainty). Improvements of HRQoL at 24 weeks were not significant (MD, 1.87; 95% CI, -1.21 to 4.96; low certainty). There was no association between the addition of a PROM and HRQoL at 48 weeks. The addition of a PROM was not associated with reduced ED visits (OR, 0.74; 95% CI, 0.54-1.02; low certainty) or hospital admissions (OR, 0.86; 95% CI, 0.73-1.02; low certainty). The findings of this study suggest that the integration of PROMs into cancer care may improve overall survival and quality of life.

Obesity and Colorectal Cancer: A Narrative Review.

Background and Objectives: Cancer is a multicausal disease, and environmental, cultural, socioeconomic, lifestyle, and genetic factors can influence the risk of developing cancer. Colorectal cancer (CRC) stands as the third most common cancer globally. Some countries have observed a rise in the incidence of CRC, especially among young people. This increase is associated with lifestyle changes over the last few decades, including changes in diet patterns, a sedentary lifestyle, and obesity. Currently, obesity and overweight account for approximately 39% of the world's population and increase the risk of overall mortality of certain cancer types. This study aims to conduct a literature review examining the association between obesity and CRC. Materials and Methods: This narrative review explored the pathophysiological mechanisms, treatment strategies, and challenges related to obesity and CRC. Results: Several studies have established a clear causal relationship between obesity and CRC, showing that individuals with morbid obesity are at a higher risk of developing colorectal cancer. The adipose tissue, particularly the visceral, secretes proinflammatory cytokines, such as TNF-alpha, interleukin-6, and C-reactive protein. Chronic inflammation is closely linked to cancer initiation and progression, with a complex interplay of molecular mechanisms underlying this association. Obesity can complicate the treatment of CRC due to several factors, reducing the therapeutic effectiveness and increasing the risk for adverse events during treatment. Dietary modification, calorie restriction, and other types of weight-control strategies can reduce the risk of CRC development and improve treatment outcomes. Conclusions: Obesity is intricately linked to CRC development and progression, making it a crucial target for intervention, whether through diet therapy, physical exercises, medical therapy, or bariatric surgery.

Remission of Obesity-Related Sleep Apnea and Its Effect on Mortality and Cardiovascular Events after Metabolic and Bariatric Surgery: A Propensity-Matched Cohort Study.

Although obstructive sleep apnea (OSA) is common among patients with obesity and linked to cardiovascular disease, there is a lack of studies evaluating the effects of reaching remission from OSA after metabolic and bariatric surgery. A registry-based nationwide study including patients operated with sleeve gastrectomy or Roux-en-Y gastric bypass from 2007 until 2019 in Sweden. Patients who reached remission of OSA were compared with those who did not reach remission and a propensity score-matched control group of patients without OSA at the time of operation. The main outcome was overall mortality, and secondary outcome was major cardiovascular events (MACEs). In total, 5,892 patients with OSA and 11,552 matched patients without OSA completed a 1-year follow-up and were followed for a median of 6.8 years. Remission of OSA was seen for 4,334 patients (74%). Patients in remission had a lower risk for overall mortality (cumulative incidence 6.0% vs 9.1%; p < 0.001) and MACE (cumulative incidence 3.4% vs 5.8%; p < 0.001) at 10 years after operation compared with those who did not reach remission. The risk was similar to that of the control group without OSA at baseline (cumulative incidence for mortality 6%, p = 0.493, for MACE 3.7%, p = 0.251). The remission rate of OSA was high after metabolic and bariatric surgery. This was in turn associated with reduced risk for death and MACE compared with patients who did not achieve remission reaching a similar risk seen among patients without OSA at baseline. A diligent follow-up of patients who do not reach remission remains important.

Surviving the cold: Assessing long-term outcomes among Korean CKD patients exposed to low perceived temperature during winter

Perceived temperature (PT), which encompasses meteorological factors such as wind speed, cloud cover, and humidity, reflects the actual effect of temperature on the human body. However, limited data exist on the health implications of prolonged exposure to low temperatures during winter in individuals with chronic kidney disease (CKD). We investigated the association between winter PT and long-term outcomes among CKD patients. A total of 32,870 CKD patients from three tertiary hospitals in Seoul were enrolled in this retrospective study (2001–2018). PT was calculated using Staiger's equation, integrating temperature data from 29 automated weather stations across Seoul, along with dew point temperature, wind velocity, and cloud cover data. Kriging interpolation was utilized to estimate PT values at the patients' locations. Overall mortality and major adverse cardiovascular events (MACEs) were assessed using a time-varying Cox proportional hazards model. Additionally, the Cox regression model evaluated PT corresponding to temperature thresholds for cold surge watches or warnings. Over a median follow-up of 6.14 ± 3.96 years, 6147 deaths (18.7%) were recorded. We found that as the average or minimum PT and Ta decreased by 1 °C, the risk of overall mortality significantly increased. In multivariable analyses, the hazard ratio (HR) for the average PT was 1.049 (95% confidence interval [CI] 1.028–1.071), and that for the minimum PT was 1.038 (CI 1.027–1.052). Furthermore, a cold surge warning at a PT of −25.63 °C indicated an HR of 1.837 (CI 1.764–1.914) and a C-index of 0.792. The increased risk of mortality was more pronounced in patients with low or middle socioeconomic statuses. For MACEs, lower average and minimum PT and Ta were associated with an increased risk, following a similar trend to overall mortality, although not all results reached statistical significance. These findings emphasize the importance of targeted public health policies to mitigate risks among vulnerable CKD patients.