Increased Risk Of Mortality Research Articles

Independent Association of Individual Lipid Abnormalities with Cardiovascular All-cause Mortality: A Prospective Cohort Study.

Abnormalities in total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TG) are each associated with increased cardiovascular risk, after adjusting for non-lipid risk factors. However, whether and to what extent the association for each lipid measure is confounded by other lipid measures is less understood. This study aims to investigate the association of each lipid measure with cardiovascular and all-cause mortality while precluding the confounding caused by abnormalities in other lipid measures. The study utilized data from the third National Health and Nutrition Examination Survey (NHANES III, 1988-1994) and ten cycles of continuous NHANES (1999-2018). The study cohort included 23,761 participants who were 20 years or older, not pregnant, not receiving lipid-lowering treatment, and had complete data on all four lipid measures and mortality status. Participants were categorized into seven subgroups based on their lipid profiles. Kaplan-Meier survival curves and Cox proportional hazards models were used to examine the association between lipid abnormalities and mortality. During a median follow-up of 140 months, 5,003 participants (14.1%) died, with 1,665 deaths (4.2%) attributable to cardiovascular causes. Compared with the reference group in which the four lipid measures were all normal, the subgroups with isolated high TC, two to three lipid abnormalities, and four lipid abnormalities were associated with increased risks for both cardiovascular and all-cause mortality in univariate analysis. However, only those with isolated high TC (for cardiovascular mortality, HR 1.52, 95% CI 1.13-2.06) and four lipid abnormalities (for all-cause mortality, HR 1.34, 95% CI 1.04-1.72) remained statistically significant after adjusting for non-lipid risk factors. Of note, compared with the reference group, the profile of non-lipid risk factors was apparently less favorable in the subgroup with two to three lipid abnormalities but similar (and some factors even more favorable) in the subgroup with isolated high TC. When the lipid measures were analyzed as continuous variables, a U-shaped relationship between HDL-C and mortality risk was observed for both cardiovascular and all-cause mortality, and very low LDL-C level was associated with increased mortality risk. No statistically significant association was found between TG levels and mortality risk. Isolated high TC, very low LDL-C, and concurrent abnormalities in all four lipid measures were associated with increased mortality risk, whereas isolated high TG was not. A U-shaped relationship may exist between HDL-C level and mortality. Overall, these findings underscore the need for integrated management of dyslipidemia that takes all four lipid measures as well as non-lipid cardiovascular risk factors into account, particularly for those with concurrent abnormalities in two or more lipid measures.

BISAP Beyond Pancreatitis: A New Horizon in Acute Kidney Injury Prediction

Background: Acute kidney injury (AKI) is a common complication in acute pancreatitis (AP), with a significant impact on mortality. The Bedside Index for Severity in Acute Pancreatitis (BISAP) score is well-established for assessing mortality risk in AP, but its utility in predicting AKI is less explored. Methods: We conducted a retrospective chart review of 779 AP patients across two hospitals in New York, USA, from 2016 to 2022. Data on patient demographics, laboratory values, and vital signs were collected. BISAP scores were calculated. The primary outcome was AKI, defined by the KDIGO criteria. Multivariate logistic regression was done to assess the association between the BISAP score and AKI, adjusting for confounders. Secondary outcomes include the association of the BISAP score to hospital length of stay and mortality. Results: There was a significant association between the BISAP score and AKI, with an odds ratio of 2.36 [95% C.I 1.42-4.41, p =0.001], indicating a more than twofold increase in AKI risk for each point increase in BISAP score. The BISAP score was also significantly correlated with longer hospital stays and increased mortality risk. Conclusion: The BISAP score is a strong predictor of AKI in AP patients. This association and relation to hospital stay and mortality highlights the potential of the BISAP score as a comprehensive risk assessment tool in AP, especially for early identification of patients at high risk for AKI. This study paves the way for future research into risk scoring systems for AKI in AP based on significant BISAP components.

Impact of Smokeless Oral Nicotine Products on Cardiovascular Disease: Implications for Policy, Prevention, and Treatment: A Policy Statement From the American Heart Association.

Smokeless oral nicotine products are addictive, and their use has potential adverse effects on some but not all biomarkers of cardiovascular risk. The use of some types of these products, for instance, is associated with an increased mortality risk in those with ischemic heart or cerebrovascular disease. Similarly, smokeless tobacco has the potential to increase the risk of oral cancer, but the risks depend on the chemical composition of the product. The market of smokeless oral nicotine products has transformed since the last American Heart Association smokeless tobacco policy statement. Several varieties of tobacco-free oral nicotine products-including oral nicotine pouches; nontherapeutic nicotine gums, lozenges, and tablets; and nicotine gummies-have rapidly proliferated. The sales of oral nicotine pouches, in particular, have increased substantially; however, no data are available on their cardiovascular or health risks. In addition, synthetic (compared with tobacco-derived) nicotine has been used in some brands of oral nicotine products, but its cardiovascular and health effects have been inadequately studied. Robust public policy levers are identified to support ending addiction to all commercial tobacco products. Critical components and policy initiatives include clinicians emphasizing the prevention of tobacco product initiation and supporting cessation with established pharmacological and behavioral tobacco dependence treatment therapies as primary goals for achieving an end to commercial tobacco and nicotine addiction.

Association between DNA methylation predicted growth differentiation factor 15 and mortality: results from NHANES 1999–2002

BackgroundGrowth differentiation factor 15 (GDF15) is a crucial biomarker in various physiological and pathological processes. While elevated GDF15 levels are linked to increased mortality risk, the role of DNA methylation (DNAm)-predicted GDF15 in predicting mortality has not been extensively studied. The purpose of the study is to investigate the association between DNAm-predicted GDF15 levels and all-cause and cardiovascular disease (CVD) mortality in a nationally representative cohort.MethodsData from NHANES 1999–2002 were analyzed. DNAm-predicted GDF15 levels were estimated using a regression model. Weighted multivariate Cox regressions were employed to assess the relationship between DNAm-predicted GDF15 and mortality outcomes. Restricted cubic splines were used to explore dose-response relationships, and subgroup analyses were conducted to enhance result reliability.ResultsHigher DNAm-predicted GDF15 levels were significantly associated with increased all-cause mortality risk (HR = 1.08, 95% CI: 1.02–1.15). Participants in the highest DNAm-predicted GDF15 tertile showed significantly higher all-cause mortality risk (HR = 1.56, 95% CI: 1.16–2.10) and a 2.52-fold increased risk of cardiovascular mortality (HR = 2.52, 95% CI: 1.22–5.19). Kaplan-Meier curves revealed decreasing survival probability with higher DNAm-predicted GDF15 tertiles. Restricted cubic spline analysis demonstrated a non-linear dose-response relationship between DNAm-predicted GDF15 levels and cardiovascular mortality. The positive correlation between DNAm-predicted GDF15 and mortality remained robust in most of subgroups.ConclusionsDNAm-predicted GDF15 independently predicts all-cause and cardiovascular mortality. This association persists across multiple models and stratified subgroups, supporting GDF15’s value as a biomarker for mortality risk stratification. Future research should elucidate underlying biological mechanisms and evaluate GDF15’s clinical utility in guiding mortality risk reduction interventions.

Vitamin D deficiency in hip fracture patients is associated with an increased mortality risk

PurposeThe aims were to assess whether vitamin D deficiency influenced mortality risk and length of acute hospital stay in patients presenting with a hip fracture.MethodsA retrospective study was undertaken including all patients aged over 50 years that were admitted with a hip fracture to a single centre during a 24-month period. Serum vitamin D levels on admission, patient demographics, perioperative variables and mortality were collected. Cox regression analysis was utilised to determine the independent association between serum vitamin D levels and patient mortality.ResultsThe cohort consisted of 1510 patients with a mean age of 81.3 years and 1107 (71.4%) were female. 876 (58.0%) were vitamin D deficient (< 50 nmol/l). The median follow up was 405 (IQR 249 to 610) days. During follow-up there were 464 deaths (30.7%). Vitamin D deficiency was independently associated with higher mortality risk (hazard ratio [HR] 1.26, 95% confidence interval (CI) 1.03 to 1.53, P = 0.022). Male sex (HR 1.64, 95% CI 1.34 to 2.01, P < 0.001) was also associated with a higher mortality risk. Vitamin D deficiency was not associated with length of hospital stay (median difference 0 days, P = 0.207).ConclusionVitamin D deficiency was independently associated with increased mortality in hip fracture patients, though this finding may be influenced by lack of comprehensive adjustment for comorbidity. While the value of routine serum vitamin D measurement is debated, supplementation during hospital stays is important to reduce falls and fracture risks associated with deficiency.

Prognostic Significance of Recurrence and Timing of Recurrence on Survival Among Patients with Early-Stage Hepatocellular Carcinoma in U.S. Clinical Practice.

Many patients with hepatocellular carcinoma (HCC) experience recurrence after curative-intent resection or ablation, with a poor prognosis. Real-world patterns of recurrence and the prognostic significance of early recurrence in U.S. clinical practice have not been well characterized. This retrospective observational study was designed to evaluate the impact of recurrence on overall survival (OS) among patients with HCC following initial curative-intent resection or ablation. We used the Surveillance, Epidemiology, and End Results cancer registry linked with Medicare claims (January 1, 2010-December 31, 2019). Eligible patients (≥66 years) diagnosed with HCC (2010-2017) had liver resection or ablation within 180 days of diagnosis. Patients were stratified by recurrence status using diagnosis- and treatment-based definitions of recurrence. Early or late recurrence was defined as within 1 year or after 1 year, respectively. Adjusted OS analyses used multivariable Cox regression models. A total of 1,146 patients were included. During a median overall follow-up of 35.2 months, 736 (64%) patients had a recurrence, of whom 380 (52%) had early recurrence (within 1 year). In the adjusted analysis, patients with recurrence had a 2.24-fold higher risk of death (95% confidence interval 1.85, 2.71; P < 0.001). Patients with early recurrence had a 1.39-fold higher risk of death (95% confidence interval 1.14, 1.68; P < 0.001) than those with late recurrence. Recurrence and the timing of recurrence are significant predictors of increased mortality risk for patients with HCC following initial curative-intent resection or ablation, highlighting the need for effective adjuvant therapies that may delay or avoid recurrences.

Toxic epidermal necrolysis: management strategies in burns units.

The most common severe exfoliative condition is toxic epidermal necrolysis (TEN), also known as Lyell's syndrome, for which patients may sometimes require admission to hospital burns units. This study analyses the experience of the authors and results in this condition at the Cruces University Hospital in Bilbao, Spain. Over the last 22 years, the authors carried out a retrospective analytical observational study of TEN cases at the hospital and analysed risk factors including age, associated comorbidities, percentage of body surface area affected, positive bacterial culture, and treatment strategies used to assess their potential influence on prognosis. The results indicated an association between mortality and age (ρ (rho)=0.60, 95% CI [0.29, 0.79], p<0,001), ocular (ρ=0.58, 95% CI [0.28, 0.78], p<0.001), oropharyngeal (ρ=0.64, 95% CI [0.36, 0.81], p<0.001), genitourinary (ρ=0.58 CI [0.28, 0.78], p<0.001) respiratory mucosa involvement (ρ=0.53, 95 % CI [0.28, 0.78], p<0.001) and bacteraemia (ρ=0.44, 95% CI [0.17, 0.64], p=0.020). Bacteraemia also showed a higher incidence in elderly patients (ρ=0.4, 95% CI [0.03, 0.67], p=0.033) and in those with a higher Score for Toxic Epidermal Necrolysis at admission (ρ=0.51, CI [0.17, 0.74], p=0.006). A reduction in mortality was found in patients who received systemic treatment; cyclosporine, etanercept or a combination of both (ρ=-0.44, Cl [-0.70, -0.09], p=0.018). TEN is a rare but serious exfoliative condition. Traditionally, management of denuded skin was seen as the main prognostic factor; yet, systemic damage, especially to the respiratory mucosa, significantly increases mortality risk. While life support is crucial and recovery is possible, preventing long-term sequelae relies on effective care protocols. Current treatments may offer benefits, though their efficacy remains unclear. Clinicians in burns units should develop standardised protocols and collaborate on long-term studies to enhance patient care.

Trends in prevalence and multimorbidity of metabolic, cardiovascular, and chronic kidney diseases among US adults with depression from 2005 to 2020

BackgroundComorbid depression and cardiometabolic diseases are prevalent and increase risk of mortality. However, trends in the prevalence and multimorbidity of cardiometabolic diseases in depression are unclear. MethodsData of adults aged≥20 years with depression from the National Health and Nutrition Examination Survey 2005–2020 were analyzed. Joinpoint regression analysis was used to estimate trends in the prevalence of dyslipidemia, hypertension, diabetes, chronic kidney disease, non-alcoholic fatty liver disease, and cardiovascular disease as well as having≥3 of these diseases. Differences in the prevalence of these diseases in depression vs no depression were assessed using Poisson regressions after applying propensity score weighting. ResultsA total of 3412 adults with depression were included. The prevalence of cardiometabolic diseases as well as having≥3 diseases remained high and stable in the overall sample from 2005 to 2020 (P for trend>0.05). In 2017–2020, the prevalence ranged from 17.1 % (95 % CI, 12.7 %–21.5 %) for cardiovascular disease to 58.4 % (95 % CI, 50.4 %–66.3 %) for dyslipidemia; 40.7 % (95 % CI, 34.4 %–46.9 %) had≥3 diseases. The prevalence of diabetes, cardiovascular disease, and having≥3 diseases was 23 %–85 % higher in adults with depression than those without. LimitationsThe utilization of self-reported data and/or one-time laboratory measurements may misclassify participants. ConclusionsPrevalence of cardiometabolic diseases was high and multimorbidity was common in US adults with depression. Addressing the prevention, treatment, and management of cardiometabolic diseases in depression requires greater public health and clinical attention.

Building a Risk Scoring Model for ARDS in Lung Adenocarcinoma Patients Using Machine Learning Algorithms.

Lung adenocarcinoma (LUAD), the predominant form of non-small-cell lung cancer, is frequently complicated by acute respiratory distress syndrome (ARDS), which increases mortality risks. Investigating the prognostic implications of ARDS-related genes in LUAD is crucial for improving clinical outcomes. Data from TCGA, GEO and GTEx were used to identify 276 ARDS-related genes in LUAD via differential expression analysis. Univariate Cox regression, consensus clustering and machine learning algorithms were used to develop a prognostic risk scoring model. Functional enrichment, immune infiltration analyses, copy number variations and mutational burdens were examined, and the results were validated at the single-cell level. ARDS-related genes significantly impact the prognosis of LUAD patients. A machine learning-based risk scoring model accurately predicted survival rates. Functional enrichment and immune infiltration analyses revealed that these genes are primarily involved in cell cycle regulation and immune cell infiltration. Single-cell expression data supported these findings, and the assessments of copy number variations and mutational burdens highlighted distinct genetic characteristics. This study establishes the prognostic relevance of ARDS-associated genes in LUAD and provides potential biomarkers for personalized therapy and prognosis. Future studies will validate these findings and explore their clinical applications.

Características clínico-epidemiológicas de los pacientes hospitalizados por COVID-19 y enfermedades crónicas durante los primeros siete meses de la pandemia en Paraguay-2020

Introduction: COVID-19, a respiratory infection caused by SARS-CoV-2, has demonstrated varying severity across populations, with approximately 20% of patients developing complications and less than 5% experiencing severe disease requiring hospitalization. The impact of chronic diseases on COVID-19 outcomes remains particularly relevant in developing countries, where healthcare resources and population characteristics differ from well-studied settings. Objective: Describe the clinical and epidemiological characteristics of patients hospitalized with COVID-19 during the first seven months of the pandemic in Paraguay, analyzing how chronic non-communicable diseases (NCDs) influenced disease progression and outcomes. Material and Methods: We conducted a cross-sectional analytical study examining medical records from patients hospitalized with confirmed SARS-CoV-2 infection across five major referral hospitals in Paraguay from March to September 2020. Using bivariate and multivariate logistic regression analyses with likelihood ratio criterion, we identified factors associated with ICU admission and mortality, considering p&lt;0.05 statistically significant. Results: Among 1,690 hospitalized patients, 797 (47.2%) met inclusion criteria, with a median age of 51 years and male predominance (53.8%). Chronic diseases were present in 61.9% of patients, with hypertension (29.6%) and diabetes (25.6%) being most prevalent. Multivariate analysis revealed that age over 80 years (OR=7.70), presence of COPD (OR=2.58), and having three or more NCDs (OR=2.78) significantly increased mortality risk. ICU admission was required for 29.6% of patients, with an overall mortality rate of 29.1%. Conclusion: The severity of COVID-19 outcomes among hospitalized patients in Paraguay showed strong associations with advanced age, multiple chronic conditions, and specific comorbidities like COPD. These findings emphasize the need for targeted preventive strategies and enhanced monitoring of high-risk patients, particularly those with multiple NCDs.

Association of the Inflammatory Burden Index With Increased Mortality Among Cancer Patients: Insights From the NHANES Study.

The systemic inflammatory response significantly influences the progression and prognosis of various cancers. The novel Inflammatory Burden Index (IBI) was recently introduced as a biomarker to gauge systemic inflammation and evaluate cancer patient prognosis. However, studies investigating the relationship between IBI and mortality rates in cancer patients remain limited. This study analyzed data from 2748 cancer patients enrolled in the National Health and Nutrition Examination Surveys between 1999 and 2018. We used weighted Cox regression analysis and restricted cubic spline models to examine the relationship between the IBI and mortality due to all causes, cardiovascular disease (CVD), and cancer. Furthermore, we employed Kaplan-Meier survival curves, subgroup analyses, and receiver operating characteristic curves to elaborate on these associations. Over a median follow-up period of 112 months, the cohort experienced 1067 deaths, including 320 from cancer, 239 attributable to heart disease, and 508 from various other causes. The Kaplan-Meier curve indicated that individuals in the higher quartiles of the IBI faced significantly increased mortality risks compared to those in lower quartiles. Analyses using weighted Cox proportional hazards models demonstrated that subjects in the top IBI quartile were at a substantially higher risk for all-cause mortality (Hazard Ratio [HR] 2.09, 95% Confidence Interval [CI] 1.67-2.62, p < 0.001), CVD mortality (HR = 1.95, 95% CI= 1.18-3.23, p = 0.010), and cancer mortality (HR = 2.06, 95% CI = 1.31-3.26, p = 0.002). Furthermore, stratification and interaction analyses affirmed the uniformity of these initial findings. The areas under the curve for the 3-, 5-, and 10-year survival predictions for all-cause mortality were 0.62, 0.62, and 0.67, respectively; for cardiovascular mortality, they were 0.64, 0.64, and 0.70; and for cancer mortality, they were 0.62, 0.77, and 0.70. In cancer patients, higher IBI levels significantly correlate with increased mortality from all causes, CVD, and cancer-specific deaths. This index could possess considerable diagnostic and prognostic importance, possibly acting as a new biomarker for evaluating outcomes in cancer patients.

Outcomes of Patients with Hepatocellular Carcinoma Undergoing Liver Transplantation Utilizing Extended Criteria Donor Grafts

Background: The deceased donor shortage in the United States has led to increased utilization extended criteria donor (ECD) liver grafts. Centers often utilize ECD grafts in patients with low Model for End-Stage Liver Disease scores, like patients with hepatocellular carcinoma (HCC). However, few studies have directly examined outcomes of using ECD grafts in HCC patients. Methods: Adults receiving liver transplantation (LT) for HCC between 2010-2020 were identified in the Organ Procurement and Transplantation Network database. Recipients were categorized according to donor type: standard criteria (SCD), extended criteria, donation after brain death (ECD-DBD), and donation after circulatory death (DCD). Multivariable Cox regression analysis identified variables associated with overall or graft survival at 3 years post-LT. Results: Most patients received ECD-DBD grafts (51.4%); only 8.3% received DCD grafts. Time on waitlist was similar for ECD and SCD recipients (p=0.79). SCD recipients had higher 5-year overall survival post-LT than ECD-DBD or DCD recipients (79.1%, 77.1%, and 76.8%, respectively, p<0.001). Similarly, 5-year graft survival was also highest in SCD recipients (SCD, 77.8%; ECD-DBD, 75.7%; DCD, 72,.2%; p<0.001). In multivariable analysis, DCD grafts increased mortality risk (HR, 1.33; 95% CI, 1.12-1.57; p=0.001), but ECD-DBD grafts did not (HR, 1.10; 95% CI, 1.00-1.22; p=0.052). Conclusions: DCD and ECD-DBD recipients had significantly lower overall and graft survival. However, the survival benefit of liver transplantation for HCC patients greatly outweighs the small differences in patient and graft survival from using ECD grafts. Further research should investigate whether treatment of ECD grafts with machine perfusion may ameliorate this discrepancy.

Investigating pre-registration podiatry students approaches to identifying dermatology conditions in different skin tones: A mixed methods protocol.

Health inequalities are a well-known and widespread phenomenon throughout health care settings. In particular, people of color experience higher rates of delayed and/or misdiagnosis contributing to poorer outcomes and an increased mortality risk. Research suggests that health care professionals find it more difficult to correctly diagnose dermatological conditions in the non-White patient demographic. Although podiatrists routinely examine and assess skin lesions, there is a paucity of research exploring their accuracy or confidence in recognizing skin pathologies. This study aims to investigate podiatry student's ability, confidence, approaches, and perceptions in diagnosing dermatology pathologies in different skin tones. A mixed methods exploratory sequential design is proposed. In stage one, podiatry students from different higher education institutions will be invited to complete a pictorial survey. We have designed a survey comprising six validated images of inflammatory skin pathology (either eczema or psoriasis) in three different skin tone categories, standardized using the Fitzpatrick scale. Data from the survey in stage one will then be utilized to inform the next stage of the research. In stage two, respondents who completed the initial survey will be invited to participate in focus groups to explore their perceptions surrounding diagnostic approaches, confidence, and perceptions of skin conditions in different skin tone. A process of thematic analysis will be employed to identify emergent themes from these data. A mixed methods exploratory sequential design is proposed. In stage one, podiatry students from different higher education institutions will be invited to complete a pictorial survey. We have designed a survey comprising six validated images of inflammatory skin pathology (either eczema or psoriasis) in three different skin tone categories, standardized using the Fitzpatrick scale. Data from the survey in stage one will then be utilized to inform the next stage of the research. In stage two, respondents who completed the initial survey will be invited to participate in focus groups to explore their perceptions surrounding diagnostic approaches, confidence, and perceptions of skin conditions in different skin tone. A process of thematic analysis will be employed to identify emergent themes from these data.

Analysis of four long non-coding RNAs for hepatocellular carcinoma screening and prognosis by the aid of machine learning techniques

Hepatocellular carcinoma (HCC) represents a significant health burden in Egypt, largely attributable to the endemic prevalence of hepatitis B and C viruses. Early identification of HCC remains a challenge due to the lack of widespread screening among at-risk populations. The objective of this study was to assess the utility of machine learning in predicting HCC by analyzing the combined expression of lncRNAs and conventional laboratory biomarkers. Plasma levels of four lncRNAs (LINC00152, LINC00853, UCA1, and GAS5) were quantified in a cohort of 52 HCC patients and 30 age-matched controls. The individual diagnostic performance of each lncRNA was assessed using ROC curve analysis. Subsequently, a machine learning model was constructed using Python’s Scikit-learn platform to integrate these lncRNAs with additional clinical laboratory parameters for HCC diagnosis. Individual lncRNAs exhibited moderate diagnostic accuracy, with sensitivity and specificity ranging from 60 to 83% and 53–67%, respectively. In contrast, the machine learning model demonstrated superior performance, achieving 100% sensitivity and 97% specificity. Notably, a higher LINC00152 to GAS5 expression ratio significantly correlated with increased mortality risk. The integration of lncRNA biomarkers with conventional laboratory data within a machine learning framework demonstrates significant potential for developing a precise and cost-effective diagnostic tool for HCC. To enhance the model’s robustness and prognostic capabilities, future studies should incorporate larger cohorts and explore a wider array of lncRNAs.

Impact of inappropriate empirical antibiotic therapy on in-hospital mortality: a retrospective multicentre cohort study of patients with bloodstream infections in Chile, 2018–2022

IntroductionEmpirical antibiotic therapy is essential for treating bloodstream infections (BSI), yet there is limited evidence from resource-limited settings. We quantified the association of inappropriate empirical antibiotic therapy (IEAT) with in-hospital...

Association between low-density lipoprotein cholesterol levels and all-cause mortality in patients with coronary artery disease: a real-world analysis using data from an international network

The current cholesterol guidelines recommend maintaining low levels of low-density lipoprotein cholesterol (LDL-C) in patients with coronary artery disease (CAD). However, recent studies have suggested that both very low and very high LDL-C levels may be associated with increased mortality in the general population. We utilized data from TriNetX, a global health research network, to investigate the association between LDL-C levels and all-cause mortality in patients with CAD. CAD patients were identified using the International Classification of Diseases, Tenth Revision (ICD-10) diagnosis code and stratified into six LDL-C categories: <50 mg/dL (cohort 1), 50–69.9 mg/dL (cohort 2), 70–99.9 mg/dL (cohort 3), 100–129.9 mg/dL (cohort 4), 130–159.9 mg/dL (cohort 5), and ≥ 160 mg/dL (cohort 6). Mortality data were obtained by linking patient records to death registries spanning the 15 years prior to the analysis. Weighted Cox proportional hazards regression models were employed to estimate hazard ratios (HRs) for mortality outcomes along with their 95% confidence intervals (CIs). A total of 2,145,732 individuals with CAD (mean age 72 years, SD 13; mean LDL-C 87.7 mg/dL, SD 37.7) were included in the analysis. Over a 15-year follow-up period, 191,779 deaths (8.9%) were recorded. After propensity score matching, patients with LDL-C < 50 mg/dL (37.05% vs. 33.11%, HR 1.144, 95% CI 1.125–1.164, p < 0.0001), LDL-C 130–159.9 mg/dL (26.47% vs. 25.71%, HR 1.032, 95% CI 1.007–1.059, p = 0.0136), and LDL-C ≥ 160 mg/dL (26.29% vs. 24.38%, HR 1.121, 95% CI 1.082–1.163, p < 0.0001) demonstrated a higher risk of all-cause mortality compared to those with LDL-C 100–129.9 mg/dL. Conversely, patients with LDL-C 50–69.9 mg/dL (27.88% vs. 29.68%, HR 0.898, 95% CI 0.883–0.913, p = 0.0002) and LDL-C 70–99.9 mg/dL (26.21% vs. 27.84%, HR 0.908, 95% CI 0.893–0.923, p = 0.0057) exhibited a lower risk of all-cause mortality compared to the reference group (LDL-C 100–129.9 mg/dL). In conclusion, our findings suggest a U-shaped relationship between LDL-C levels and all-cause mortality in patients with CAD, where both very low (< 50 mg/dL) and high (≥ 130 mg/dL) LDL-C levels are associated with increased mortality risk. These results highlight the need for individualized LDL-C targets in managing patients with CAD.

Role of molecular alterations in transplantation decisions for patients with primary myelofibrosis

AbstractThe aim of our study was to analyze the potential survival benefit associated with hematopoietic stem cell transplantation (HSCT) according to clinicobiological scores, which incorporate molecular data (MIPSS70 and MIPSS70+V2) to facilitate decision-making in this context. One transplant (n = 241) and 1 nontransplant cohort (n = 239) were used to test the hypothesis that patients with primary myelofibrosis with higher risk molecular score benefit from HSCT. A weighted propensity score was applied to balance confounding factors with the transplanted cohort as reference. Weighted Cox proportional hazard models and logistic regression analyses were performed. Overall, 105 patients who did not receive transplant could be matched to the 239 patients who did receive transplants. Mean age in matched patients who did and did not undergo transplant was 55.5 and 57.9 years, respectively. Blood cell count and Dynamic International Prognostic Scoring System (DIPSS) score distribution were similar in both groups. HSCT was associated with a higher 6-year overall survival rate in intermediate-2 (60.1% vs 41.5%) and high-risk DIPSS patients (44.4% vs 6.55%), high-risk MIPSS70 (46.5% vs 23.9%), high-risk (73.2% vs 39.7%) or very high-risk MIPSS70+V2 (51.8% vs 24%). Patients with intermediate MIPSS70 scores have an advantage of survival with HSCT only when their myelofibrosis transplant scoring system (MTSS) were low or intermediate. Patients who received transplant had an increased mortality risk the first year, but a significant benefit with HSCT after the 1-year landmark was observed in higher risk patients. This study confirms that, similar to DIPSS, MIPSS70 and MIPSS70+V2 risk score in addition to MTSS can be used to determine which patients with primary myelofibrosis have survival benefit from HSCT over non-HSCT strategies.

Longitudinal changes in plasma Cystatin C and all-cause mortality risk among the middle-aged and elderly Chinese population

ObjectiveElevated plasma Cystatin C levels are associated with an increased mortality risk among middle-aged and elderly Chinese individuals. This study explores whether tracking the longitudinal changes in Cystatin C can improve the prediction of mortality risk and allow better risk stratification, jointly with baseline measurements. Design & MethodsThis analysis includes 3,195 participants from the China Health and Retirement Longitudinal Study who completed plasma Cystatin C measurements in two waves (2011 and 2015) and were followed through 2020. To evaluate the association between Cystatin C levels/changes and mortality risk, multivariate Cox proportional hazard models were employed, adjusting for potential confounders. Survival probabilities were compared using Kaplan-Meier curves and log-rank tests, while restricted cubic splines were utilized to illustrate any nonlinear relationships between Cystatin C levels and hazard ratios. ResultsParticipants in the highest quartile of baseline Cystatin C show an increased risk of mortality compared to those in the lowest quartile (hazard ratio (HR): 1.51, 95 % CI: 1.02–2.24, p = 0.04). Including longitudinal changes in Cystatin C further strengthens this association (HR: 1.81, 95 % CI: 1.20–2.74, p < 0.001). Kaplan-Meier plots show that baseline levels effectively stratify both the entire cohort and gender-specific subgroups (p < 0.001). Moreover, integrating baseline levels with the longitudinal changes in Cystatin C levels provides additional stratification benefits. The predictive performance significantly improves by including longitudinal changes in Cystatin C in baseline-only models, with the concordance index increasing from 0.745 to 0.839 and the area under the receiver operator characteristic curve rising from 0.751 to 0.845. Additionally, significant nonlinear relationships between changes in Cystatin C and HR are observed in the entire population, the males and the females (p = 0.003, 0.018, 0.025). ConclusionsDynamic monitoring of changes in Cystatin C could enhance the prediction of mortality risk among middle-aged and elderly individuals.

Whole-Body Cryotherapy Reduces Systemic Inflammation in Healthy Adults: Pilot Cohort Study.

Chronically elevated inflammation is implicated in many conditions, including obesity, metabolic syndrome, and cardiovascular disease, and has been associated with increased mortality risk. Whole-body cryotherapy (W-BC) is a promising modality to treat inflammation with demonstrated benefits for clinical subpopulations including those with arthritis, obesity, and type 2 diabetes. However, it is unclear whether the benefit from W-BC extends to healthy individuals prior to chronic disease-related inflammation. In addition, the long-term durability of W-BC effect is unknown. This study investigates the inflammatory response to W-BC in healthy adults with a biomarker of inflammation, high-sensitivity C-reactive protein (hsCRP), and clinical biomarkers of metabolism including fasting glucose, hemoglobin A1c (HbA1c), low-density lipoprotein (LDL) and high-density lipoprotein (HDL), and triglycerides. Fifteen individuals (n=9 female) participated in frequent recreational W-BC (3 minutes of cold exposure at -110 ℃) over approximately 9 months and had blood draws at baseline plus follow-up visits. Biomarkers were modeled as linear functions of W-BC sessions received in the month prior to blood draw. The mean amount of W-BC received was 6.78 (SD 4.26) times per month with the cumulative total ranging from 13 to 157 W-BC sessions over the course of the study. On average, participants completed 1-2 sessions per week throughout the intervention. The number of W-BC sessions were associated with decreased hsCRP (-0.14 mg/L in hsCRP per W-BC session; P<.01) and with durability of up to 9 months. Increased W-BC was also associated with a downward trend in fasting glucose. This trend failed to reach significance at 1 month (-0.73 mg/dL in fasting glucose per W-BC session; P<.10) but was significant for 2- and 3-month windows (P<.05). HbA1c was increased significantly after 9 months (P<.01); however, the change occurred within normal ranges (difference=0.13% and <5.7%) and was not clinically significant. There was no association between W-BC and LDL cholesterol, HDL cholesterol, or triglycerides (P>.10), although LDL trended lower over the time period examined (P=.07). These results suggest that W-BC beneficially impacts systemic inflammation by lowering hsCRP levels in healthy individuals and may also have some modulating effect on fasting glucose.

Survival analysis shows tuberculosis patients with silicosis experience earlier mortality and need employer-led care models in occupational settings in India

India’s high tuberculosis (TB) burden is exacerbated by concurrent silicosis, which increases TB susceptibility and worsens treatment outcomes. Limited studies on TB patients with silicosis highlight the need to address this vulnerable group’s specific challenges, particularly to improve diagnosis and management. This retrospective cohort study analyzed survival data from 137 silico-tuberculosis and 2,605 TB-only patients in Khambhat, India, using Kaplan-Meier curves, log-rank tests, and comparisons between Cox proportional hazards and accelerated failure time (AFT) models. The lognormal AFT model, selected for its lowest Akaike Information Criterion (AIC), estimated survival times based on age, gender, HIV status, and prior TB treatment. Among the 2,742 patients, 309 (11%) died within 27 months. Median time from diagnosis to outcome was shorter for deceased patients (1.7 months) than for censored patients (5.6 months, p < 0.001, median test). Kaplan-Meier analysis showed a significantly steeper survival decline for silico-tuberculosis patients (p < 0.001, log-rank test). Silico-tuberculosis was associated with a two-fold increased mortality risk (HR = 2.0, 95% CI: 1.4-3.0, p < 0.001, Cox-proportional hazards regression). The lognormal AFT model indicated silico-tuberculosis patients had 36% of the median survival time compared to TB-only patients (16 vs. 44 months). These findings highlight significantly earlier mortality in silico-tuberculosis patients, underscoring the need for targeted, employer-led care models and TB-silicosis collaborative screening within India’s TB program for high-risk occupational groups.