Multivariate Cox Proportional Hazards Regression Research Articles

Correlation between environmental DEET exposure and the mortality rate of cancer survivors: a large-sample cross-sectional investigation.

N, N-Diethyl-meta-toluamide (DEET) is the predominant active ingredient found in insect repellents utilized by consumers. Exposure to DEET has been associated with notable risks to human health. Nonetheless, there is a scarcity of extensive cohort studies investigating the precise correlation between DEET exposure and mortality rates among cancer survivors. The objective of this study is to thoroughly evaluate the connection between DEET exposure and mortality rates in cancer survivors. This study employed individual samples obtained from the National Health and Nutrition Examination Survey (NHANES). Utilizing data from NHANES spanning 2007 to 2016, this study incorporated a cohort of 5,859 cancer survivors for subsequent analysis, following the exclusion of incomplete datasets. Through subgroup analysis, the research examined the impact of quartile levels of 3-diethyl-carbamoyl benzoic acid (DCBA), the primary metabolite of DEET, on cancer survivors across various subgroups within the broader population. Furthermore, the research utilized a multivariable Cox proportional hazards regression model and Kaplan-Meier (KM) curves to investigate the relationship between 3-diethyl-carbamoyl benzoic acid (DCBA), a principal metabolite of DEET, and mortality rates in individuals who have survived cancer. The study identified an association between specific quartiles of DCBA concentration and a decreased risk of all-cause mortality among cancer survivors, specifically in the second (Q2: 0.665-1.95) and third quartiles (Q3: 1.95-6.845). Furthermore, a significant correlation was observed between the third quartile and cancer-specific mortality (Q3: 1.95-6.845), as well as between the second quartile and non-cancer mortality (Q2: 0.665-1.95). The quartiles of DCBA concentration exhibit a statistically significant correlation with total deaths (P < 0.001), cancer-specific deaths (P = 0.009), and non-cancer deaths (P < 0.001) among cancer survivors. The correlation between DCBA and reduced mortality risk in cancer survivors is particularly notable among females and individuals of non-Hispanic Black descent. The detection of DCBA in the urine of adult cancer survivors is strongly associated with increased mortality risks, particularly among females and non-Hispanic Black individuals, warranting further investigation and targeted interventions.

Adverse events after nivolumab and ipilimumab combined immunotherapy in advanced renal cell carcinoma: a multicentre experience in Poland.

Immune checkpoint inhibitors (ICIs) have been employed in the adjuvant and metastatic setting of renal cell carcinoma (RCC) treatment. Among ICIs, combined immunotherapy has the highest risk for immune-related adverse events (irAEs). We aimed to document the incidence of irAEs in RCC patients treated with nivolumab and ipilimumab as data from the European population remain limited. We analysed data from 88 RCC patients treated with nivolumab + ipilimumab between May 2022 and June 2024 across six high-volume oncology units in Poland. We reviewed irAEs and estimated their impact on survival parameters via univariate and multivariate Cox proportional hazards regression models, along with log-rank tests. With a median follow-up of 11.3 months, the median overall survival (OS) was not reached, whereas the median progression-free survival (PFS) was 12.8 months (6.3-19.3). A total of 74 irAEs were recorded in 50 patients. The most frequent events were endocrine (n = 20, 27%), hepatic (n = 15, 17%), general (n = 12, 13.6%), and cutaneous (n = 11, 12.5%). The occurrence of irAEs was associated with a 60% lower risk of disease progression (hazard ratio 0.44, 95% confidence interval 0.2-0.87, p = 0.018) without impacting OS and higher disease control rate (n = 45, 90% vs. n = 24, 63.2%, p = 0.004). In contrast, patients with hepatotoxicity had poorer outcomes, with a 2.6-fold greater risk of death (p = 0.05). IrAEs may serve as a predictive factor for the efficacy of the nivolumab + ipilimumab regimen in RCC patients. Special attention is needed for hepatotoxicity, as it can significantly impact survival outcomes.

HIV incidence and recreational drug use among men who have sex with men aged 18-24 years in Tianjin, China: a retrospective cohort study.

Recreational drug use has been identified as a significant risk factor for the transmission of human immunodeficiency virus (HIV). This behavior is particularly prevalent among young men who have sex with men (YMSM). However, limited research has been conducted to investigate the correlation between recreational drug use and HIV incidence within this population. To examine HIV incidence and explore the association between recreational drug use and HIV incidence among YMSM. A retrospective cohort study was conducted by a local non-governmental organization (NGO) among MSM aged 18-24 years from October 2017 to December 2023 in Tianjin, China. Participants were included if they had at least two HIV test records during this period. HIV incidence density and its 95% confidence interval (CI) were calculated using person-years (PYs) with a Poisson distribution. Risk factors for HIV incidence were identified using univariable and multivariable Cox proportional hazards regression models. A total of 56 HIV seroconversions were reported with 2901.9 PYs, resulting in an overall incidence density of 1.9/100 PYs (95% CI: 1.4-2.4). Among YMSM who do not use recreational drugs (YMSM-URD), the incidence density was 1.1/100 PYs (95% CI: 0.5-1.6), while it was 2.8/100 PYs (95% CI: 1.9-3.7) among those who do use recreational drugs (YMSM-RD). Adjusted for confounders, factors associated with HIV infection included recreational drug use (adjusted hazard ratio = 2.6, 95% CI = 1.4-4.7) and unprotected anal intercourse in the past six months (adjusted hazard ratio = 2.3, 95% CI = 1.2-4.4). Recreational drug use and unprotected anal intercourse significantly increase the risk of HIV infection. To effectively mitigate the spread of HIV, interventions should focus on these risk factors by employing HIV counseling and testing clinics, collaborating with NGOs focused on MSM, and establishing peer education programs aimed at YMSM.

Association Between Fatty Liver Index and Incidence of Cataract Surgery in Individuals Aged 50 Years and Older Based on the Korean National Health Insurance Service-Health Screening Cohort (NHIS-HEALS) Data: Longitudinal Retrospective Cohort Study.

Cataract is a leading cause of vision impairment. Obesity-related risk factors, including insulin resistance, increase the risk of cataract. The fatty liver index (FLI) is a biomarker for noninvasive fat layer prediction of nonalcoholic fatty liver disease. The FLI has been used to evaluate the metabolic contribution in other organs besides the eye. However, no study exists on the FLI and eye disease. This retrospective cohort study for the association between the FLI and incidence of cataract surgery in individuals older than 50 years was designed to show that a higher FLI is associated with an increased incidence of cataract surgery in individuals aged 50 years and older. This study was retrospectively designed based on the Korean National Health Insurance Service-Health Screening Cohort (NHIS-HEALS) cohort (median follow-up of 9.8 years). Participants were assigned to 1 of 3 groups based on the FLI: low (FLI<30), intermediate (FLI 30-59), or high (FLI≥60). Kaplan-Meier survival analysis was performed on the cumulative incidence of all-cataract and senile-cataract surgery. Multivariable Cox proportional hazards regression models were used to study the association between the FLI group and cataract surgery after adjusting for potential confounders. Of the 138,347 included participants, the incidence of cataract surgery was 12.49% (4779/38,274), 13.95% (6680/47,875), and 14.16% (7496/52,930) in the low, intermediate, and high FLI groups, respectively. After adjusting for all confounding factors, hazard ratios (HRs; 95% CIs) in the high FLI group for all-cataract surgery were 1.111 (1.028-1.199) and 1.184 (1.101-1.274) in men and women, respectively, when compared with the low FLI group. HRs (95% CIs) in the high FLI group for senile-cataract surgery were 1.106 (1.022-1.197) and 1.147 (1.065-1.237) in men and women, respectively, when compared with the low FLI group. The project was conducted between August 2023 and February 2024 without donations from external bodies. Individuals with a higher FLI had a higher risk of all-cataract surgery. This association was maintained even after limiting the analyses to senile-cataract surgery.

Metabolic phenotype and risk of obesity-related cancers in the Women's Health Initiative.

Body mass index (BMI) may misclassify obesity-related cancer (ORC) risk, as metabolic dysfunction can occur across BMI levels. We hypothesized that metabolic dysfunction at any BMI increases ORC risk compared to normal BMI without metabolic dysfunction. Postmenopausal women (n=20,593) in the Women's Health Initiative with baseline metabolic dysfunction biomarkers (blood pressure, fasting triglycerides, high-density lipoprotein-cholesterol, fasting glucose, Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) and high sensitive C-reactive protein (hs-CRP)) were included. Metabolic phenotype (metabolically healthy normal weight (MHNW), metabolically unhealthy normal weight (MUNW), metabolically healthy overweight/obese (MHO), metabolically unhealthy overweight/obese (MUO)) was classified using four definitions of metabolic dysfunction: (1) Wildman criteria, (2) National Cholesterol Education Program (NCEP) Adult Treatment Panel III (ATP III), (3) HOMA-IR, and (4) hs-CRP. Multivariable Cox proportional hazards regression, with death as a competing risk, was used to assess the association between metabolic phenotype and ORC risk. After a median (IQR) follow-up duration of 21 (IQR 15-22) years, 2,367 women developed an ORC. The risk of any ORC was elevated among MUNW (HR 1.12, 95% CI: 0.90-1.39), MHO (HR 1.15, 95% CI: 1.00-1.32), and MUO (HR 1.35, 95% CI: 1.18-1.54) compared with MHNW using Wildman criteria. Results were similar using ATP III criteria, hs-CRP alone, or HOMA-IR alone to define metabolic phenotype. Individuals with overweight or obesity with or without metabolic dysfunction were at higher risk of ORCs compared with metabolically healthy normal weight individuals. The magnitude of risk was greater among those with metabolic dysfunction, although the confidence intervals of each category overlapped.

Differences in association between hypoalbuminaemia and mortality among younger versus older patients on haemodialysis

Abstract Background Ageing often impacts on biomarker production. Yet, clinical/optimal thresholds to guide clinical decisions do not consider this. Serum albumin decreases with age, but hypoalbuminaemia is defined as serum albumin &amp;lt;4.0 g/dL. This study explores whether age might affect serum albumin levels and its association with mortality in haemodialysis patients. Methods COSMOS (Current management Of Secondary hyperparathyroidism: a Multicentre Observational Study) is a prospective, open cohort, observational study of haemodialysis patients followed for 3 years. Binary logistic and linear regression were used to analyse the association between age and hypoalbuminaemia or serum albumin (continuous). Cox proportional hazard multivariate regression was used to examine the relationship between hypoalbuminaemia and mortality in patients younger and older than 65 years. Time-dependent receiver operating characteristic (ROC) curves were used to assess the discriminatory ability of serum albumin and optimal thresholds for predicting mortality. Results The present analysis included 5,585 patients. The odds of experiencing hypoalbuminaemia increased with age (adjusted odds ratios = 1.56[95%CI: 1.31-1.86], 1.89[95%CI: 1.59-2.24], 2.68[95%CI: 2.22-3.23] for 56-65, 66-75 and &amp;gt; 75 years respectively (reference ≤55 years; p-value for trend: &amp;lt;0.001)). Survival analysis showed that the association between hypoalbuminaemia and mortality was weaker in patients aged ≥65 compared to &amp;lt;65 years (Hazard Ratios: 1.36[95%CI: 1.17-1.57] and 1.81[95%CI:1.42-2.31] respectively; p-value for interaction 0.004). The ability of albumin levels to predict mortality was consistently higher in younger patients. Optimal albumin thresholds for predicting mortality were 3.7 g/dL in patients younger than 65 years and 3.5 g/dL in patients 65 years and older. Conclusions Ageing is accompanied by lower albumin levels, and the association between hypoalbuminaemia and mortality may be modified by age. Different clinical thresholds that consider age may better discriminate risks associated with hypoalbuminaemia.

L-serovar rectal Chlamydia trachomatis in patients who were male-assigned at birth attending two sexual health clinics, Baltimore, Maryland 2009-2016.

ABSTRACT Introduction Lymphogranuloma venereum (LGV) caused by L-serovars of Chlamydia trachomatis (CT) is a sexually transmitted infection (STI) causing asymptomatic infection, and anogenital disease. Epidemiologically, LGV has been strongly associated with HIV infection. Methods Using a retrospective longitudinal study design we first described unadjusted and adjusted associations between demographic and sociobehavioral characteristics and rectal (r) CT (rCT) and rLGV in sexual health clinic attendees in Baltimore, MD between 2009-2016 at baseline visits. Rectal samples that tested positive for CT with the Aptima AC2 assay underwent DNA extraction and in-house L-serovar PCR analysis. Then, patients were followed over 24 months and incident STIs were described using multivariable Cox-proportional hazard regression models. Results In 292/391 (73.4%) patients who were male-assigned at birth (MAB), LGV prevalence was 20/292 (6.8%, 95%CI:4.2%-10.4%). In the final multivariable regression model, LGV was significantly associated with age &gt; 25 years, transgender identity, and a history of syphilis. Baseline LGV was not associated with incident HIV or gonorrhea, but after adjusting for age, race, HIV status, and history of syphilis, LGV was marginally associated with a new syphilis diagnosis [HR 2.35 (95%CI:0.96, 5.73, p = 0.06) over 24 months follow up. Conclusion LGV accounted for almost 7% of rCT in patients MAB attending sexual health clinics in Baltimore between 2009-2016. LGV was not associated with prevalent or incident HIV as in other studies. FDA-cleared tests and better surveillance measures are required to understand changes in the epidemiology of LGV in the U.S.

Survival status and prognostic factors analysis in patients with hereditary hemorrhagic telangiectasia-associated pulmonary arterial hypertension

Objective: To analyze the survival status and prognostic factors of patients with hereditary hemorrhagic telangiectasia-associated pulmonary arterial hypertension (HHT-PAH). Methods: This prospective study included patients diagnosed with HHT-PAH at the Fuwai Hospital of the Chinese Academy of Medical Sciences and Guangdong General Hospital from August 2009 to December 2019. Patients were followed up every 6 months±2 weeks, with all-cause mortality as the study endpoint. Multivariate Cox proportional hazards regression mode was used to further screen and validate the prognostic factors. Survival curves were plotted using the Kaplan-Meier method, and the log-rank test was used to compare the survival time differences between patients with and without hepatic arteriovenous malformations. Results: A total of 18 HHT-PAH patients were included, with 14 females (77.8%) and a median age [M (Q1, Q3)] of 39 (32, 45) years. The median follow-up time was 129 (51, 156) months. During the follow-up period, 12 patients (66.7%) died, with a median survival time of 70 (32, 123) months. The 1-year, 3-year, 5-year, and 10-year survival rates were 100.0%, 70.8%(95%CI: 52.3%-96.0%), 53.1%(95%CI: 34.0%-83.0%), and 26.6%(95%CI: 10.6%-66.4%), respectively. HHT-PAH patients with hepatic arteriovenous malformations had a shorter median survival time than those without hepatic arteriovenous malformations [31.0 months (95%CI: 16.6-45.4 months) vs 84.0 months (95%CI: 54.4-113.6 months), P=0.024]. Cox proportional hazards regression analysis showed that hepatic arteriovenous malformation (HR=4.493, 95%CI: 1.064-18.978) was a risk factor for all-cause mortality in HHT-PAH patients. Conclusions: The 10-year survival rate of HHT-PAH patients is poor. The presence of hepatic arteriovenous malformations is a risk factor for mortality in HHT-PAH patients.

Abstract 4136289: Aortic Valve Calcium as a Predictor of Chronic Kidney Disease in a Multi-Ethnic Cohort: The MESA Study

Background: Aortic valve calcium (AVC) is associated with an increased risk of cardiovascular disease, non-cardiovascular disease such as dementia, and all-cause mortality. Traditional atherosclerotic cardiovascular disease risk factors are associated with both AVC and chronic kidney disease (CKD), but whether there is an association between AVC and CKD is unknown. Objectives: To ascertain whether AVC quantified by cardiac CT scanning is independently associated with the long-term risk of incident CKD among individuals without a previous history of cardiovascular disease. Methods: We examined 6,346 Multi-Ethnic Study of Atherosclerosis (MESA) participants who underwent cardiac CT scanning at Visit 1 (2000-02) and had an eGFR of ≥ 60 mL/min/1.73 m 2 . AVC was quantified using the Agatston method and categorized as 0, 1-99, and ≥100. Incident CKD was defined as an eGFR &lt; 60 mL/min/1.73 m 2 accompanied with an at least 40% decline in eGFR from baseline, and/or a diagnosis of CKD and indicators of end stage renal disease extracted from hospital records using the International Classification of Disease (ICD) codes. We performed Kaplan-Meier survival curve analyses along with multivariable Cox proportional hazard regression models, adjusted for age, gender, race/ethnicity, highest level of education and traditional cardiovascular risk factors along with coronary artery calcium (CAC), lipoprotein (a) (Lp[a]), and the APOE-ε4 genotype to examine the association between AVC (categorical and log-transformed) and incident CKD. Results: Participants had a mean age 62.2±10.1 years, 53% were women, and AVC &gt;0 was present in 795 (12%) participants. During a median follow-up time of 16.9 years, 982 (15%) participants developed incident CKD. AVC examined as a continuous variable was associated with a significantly increased risk of developing CKD (per log-unit [AVC+1] HR 1.06 [95% CI: 1.02-1.10]; p = 0.005). There was a stepwise increased risk for CKD with higher AVC levels ( Figure ). Similarly, in the multivariable adjusted Cox models, participants with AVC ≥100 had a higher risk of incident CKD, compared with the AVC=0 group (HR 1.48 [95% CI: 1.15-1.89]; p = 0.002). The observed associations remained after further adjusting for CAC score ( p = 0.024), Lp (a) ( p = 0.004), and the APOE-ε4 genotype ( p = 0.004). Conclusions: In a multi-ethnic cohort of participants free of CKD at baseline, AVC was independently associated with a higher risk of incident CKD.

Abstract 4138719: Effect of Recombinant Human Brain Natriuretic Peptide on Cardiac Surgery Associated Acute Kidney Injury in Patients Undergoing Coronary Artery Bypass Grafting

Backgrounds: Cardiac surgery associated acute kidney injury (CSA-AKI) is a prevalent and detrimental complication following cardiac surgery, with significant effects on both in-hospital and long-term morbidity and mortality. The effect on renal prognosis of recombinant human brain natriuretic peptide (rhBNP) for patients undergoing cardiac surgery remains unclear. Purpose: This study aims to evaluate the association between postoperative rhBNP and the risk of CSA-AKI following coronary artery bypass grafting (CABG). Methods: This retrospective cohort study included 16096 consecutive patients undergoing CABG between 2017 and 2022. The primary outcome was in-hospital postoperative AKI according to the Kidney Disease: Improving Global Outcomes (KDIGO) criteria. The secondary outcome was the amplitude of postoperative NT-proBNP reduction, defined as a difference value between the highest and last results during hospitalization. Multivariate Cox proportional hazards regression models and linear regression models were constructed to assess the association between perioperative statin and pre-defined outcomes. Results: A total of 9392 (58.3%) patients received postoperative rhBNP therapy, with a total of 1474 (9.2%) patients developing CSA-AKI. For the primary outcome, postoperative rhBNP was associated with a significantly increased risk of CSA-AKI (83.0% vs. 55.9%; adjusted Odds Ratio [OR], 3.615 [95% CI, 3.136-4.166]; p &lt; 0.001). Noticeably, we found that postoperative rhBNP was also related to increased amplitude of postoperative NT-proBNP reduction, with an average of 3193.98 versus 1040.21 pg/mL (p for linear &lt; 0.001). For the subgroup analysis, the association between postoperative rhBNP and reduced CSA-AKI risk was greater among patients with HFpEF (p for interaction = 0.087). Conclusions: Postoperative rhBNP therapy was associated with a significantly higher risk of CSA-AKI following CABG. Meanwhile, rhBNP contributed to NT-proBNP reduction postoperatively, with a more pronounced effect in patients with HFpEF.

Recompensation of Liver Cirrhosis by TIPS Reduces Epithelial Cell Death Markers, Translating Into Improved Clinical Outcome.

Portal hypertension is the main pathophysiological driver of decompensation in patients with liver cirrhosis. Epithelial cell death markers, m30 and m65, correlate with hepatic injury and predict outcomes across various stages of liver disease. We aim (i) to evaluate whether portal hypertension itself contributes to liver outcome-relevant epithelial injury, and (ii) to analyse the capacity of m30/m65 to predict outcome in patients receiving a transjugular intrahepatic portosystemic shunt (TIPS) for refractory ascites. Sixty-six patients undergoing TIPS placement for refractory ascites and 20 patients with compensated cirrhosis as controls were prospectively enrolled in this monocentric cohort study. Epithelial cell death markers were analysed pre-TIPS, as well as 1-3 and 6-9 months post-TIPS. The capacity of baseline levels of m30/m65 in predicting six-month transplant-free survival rates was analysed by multivariable Cox proportional hazards regression. Levels of m30 and m65 were higher in patients with decompensated cirrhosis (pre-TIPS) compared with compensated cirrhosis (controls). Following correction of portal hypertension by TIPS and recompensation, both markers decreased over time, reaching levels comparable to patients with compensated cirrhosis. On multivariable analysis, pre-TIPS baseline levels of m30 and m65 were not predictive for six-month survival. Correction of portal hypertension via TIPS reduces levels of epithelial cell death markers, indicating that portal hypertension is a driver of outcome-relevant, hepatic cell death in patients with decompensated cirrhosis. Baseline m30/m65 values do not affect six-month survival rates, which suggests that TIPS placement overcomes the unfavourable spontaneous prognosis otherwise indicated by elevated baseline m30/65 levels.

Abstract 4138635: The Association of Perioperative Statins and Cardiac Surgery Associated Acute Kidney Injury in Patients Undergoing Coronary Artery Bypass Grafting

Backgrounds: Cardiac surgery associated acute kidney injury (CSA-AKI) is a prevalent and detrimental complication following cardiac surgery, with significant effects on both in-hospital and long-term morbidity and mortality. The renal protective effect of statins for patients undergoing cardiac surgery remains unclear. Purpose: This study aims to evaluate the association between perioperative statin therapy and the risk of CSA-AKI following coronary artery bypass grafting (CABG). Methods: This retrospective cohort study included consecutive patients undergoing CABG between 2013 and 2022, with one year follow-up after hospital discharge. Any usage of statin initiated from admission to 72 hours after surgery was defined as perioperative statin therapy. The primary outcome was in-hospital postoperative AKI according to the Kidney Disease: Improving Global Outcomes (KDIGO) criteria. The secondary outcomes were composite measures including all-cause mortality and dialysis at 30 days and one year. Multivariate Cox proportional hazards regression models were constructed to assess the association between perioperative statin and pre-defined outcomes. Results: Among the included 36288 patients, 22272 (61.3%) patients received perioperative statin therapy, with a total of 19683 (54.2%) patients developing CSA-AKI. For the primary outcome, perioperative statin was associated with a significantly decreased risk of CSA-AKI (52.8% vs. 56.5%; adjusted Odds Ratio [OR], 0.865 [95% CI, 0.829-0.904]; p &lt; 0.001). Additionally, the occurrence of a composite measure including all-cause mortality and dialysis was statistically lower in patients who underwent perioperative statin therapy at 30 days (0.7% vs. 1.6%; OR, 0.485 [95% CI, 0.394-0.597]; p &lt; 0.001), as well as at one year (adjusted Hazard Ratio [HR], 0.632 [95% CI, 0.543-0.737], p &lt; 0.001). For the subgroup analysis, the association between perioperative statin and reduced CSA-AKI risk was greater among patients with chronic heart failure and undergoing on-pump CABG. Conclusions: Perioperative statin therapy was associated with significantly lower risks of CSA-AKI following CABG, and a composite measure including all-cause mortality and dialysis at both 30 days and one year. The preventive effect of perioperative statin was more pronounced in patients with chronic heart failure and undergoing on-pump CABG.

Abstract 4124446: Traditional Risk Factors, Cardiovascular Health, and Elevated Lipoprotein(a): The Multi-Ethnic Study of Atherosclerosis

Introduction: One in five individuals have elevated lipoprotein(a) [Lp(a)], an inheritable risk factor that is causally associated with atherosclerotic cardiovascular disease (ASCVD). Whether individuals with elevated Lp(a) derive similar benefit from control of ASCVD risk factors has not been well-studied. Hypothesis: The magnitude of benefit associated with optimal cardiovascular health will be similar across the spectrum of Lp(a). Aim: To assess the association of traditional risk factor burden and Life’s Simple 7 (LS7) score with incident ASCVD across Lp(a) values. Methods: We studied 6,676 participants from the Multi-Ethnic Study of Atherosclerosis who underwent Lp(a) testing and were followed for incident ASCVD events (coronary heart disease and stroke). Elevated Lp(a) was defined as &gt; 50 mg/dL. As defined by the American Heart Association, LS7 metrics included smoking, physical activity, body mass index, diet, total cholesterol, blood pressure, and glucose. Multivariable Cox proportional hazards regression assessed the association of traditional risk factor burden and LS7 score (poor: 0-8, average: 9-10, optimal: 11-14) with incident ASCVD for individuals with and without elevated Lp(a) during a median follow-up of 17.7 years. Results: The mean age was 62.1 years, 53% were women, and 61% were non-white. The median Lp(a) was 17 mg/dL and 20% had Lp(a) &gt; 50 mg/dL. Individuals with Lp(a) &gt; 50 mg/dL had the highest burden of traditional risk factors except cigarette smoking. Compared to those with a poor LS7 score, those with an optimal LS7 score had a lower ASCVD risk that was significant for participants with Lp(a) &lt;50 mg/dL (HR=0.37, 95% CI: 0.25-0.55), but borderline significant for participants with Lp(a) &gt; 50 mg/dL (HR=0.41, 95% CI: 0.16-1.02). Individuals with Lp(a) &gt; 50 mg/dL had the highest absolute event rates across all LS7 categories, and there was no significant interaction between Lp(a) and LS7 score on incident ASCVD (p-interaction=0.64, Figure ). Conclusions: Participants with an optimal LS7 score had similar reduction in ASCVD risk regardless of their Lp(a) burden. These results emphasize the importance of a healthy lifestyle and ASCVD risk factor control among patients with elevated Lp(a).

Impact of major depressive disorder on breast cancer outcomes: a national retrospective cohort study.

Establishing whether women with major depressive disorder (MDD) who develop breast cancer (BC) have poor outcomes is key to optimizing care for this population. To address this, we examined associations between MDD and BC recurrence and mortality. Using medical record data from the Veterans Affairs Healthcare System, we established a retrospective cohort of women with local or regional stage invasive BC between 2010 and 2019 and followed through 2022. We used a two-year window to identify women diagnosed with MDD prior to BC diagnosis. We used multivariable Cox-proportional hazards regression to estimate associations between MDD and BC recurrence and mortality while accounting for competing-risks and adjusting for sociodemographic, clinical, lifestyle, and tumor characteristics. We identified 6,051 women with BC, of whom 1,754 (29%) had MDD. The mean age at BC diagnosis was 57 years (standard deviation = 11). In multivariable analyses, women with MDD had a 37% (hazard ratio (HR)=1.37; 95% confidence interval (CI): 1.19-1.57) higher risk of recurrence and a 30% (HR = 1.30; 95% CI: 1.02-1.64) higher risk of BC mortality. The association between MDD and recurrence was stronger among women with estrogen receptor-positive BC. In secondary analyses, there were significant interactions between MDD and multiple exposures with respect to recurrence, including current smoking, substance abuse, and non-receipt of screening mammography. Women with MDD had inferior BC outcomes compared to women without a history of MDD. Research is needed to investigate underlying mechanisms linking depression to BC progression and evaluate interventions to improve outcomes in this high-risk population.

Clinical features and prognostic factors of IV combined small cell lung cancer: A propensity score matching analysis.

Nowadays, the characteristics and treatment of combined small-cell lung carcinoma (CSCLC) remain controversial. This study aimed to analyze the features of clinical demographics, survival outcomes and treatment modalities among IV CSCLC, IV SCLC and IV NSCLC, to provide more evidence for the study of IV CSCLC. All CSCLC, SCLC and NSCLC patient data were obtained from the SEER database (2010-2020). Pearson's χ2 test was used to compare the differences in clinical characteristics. Propensity score matching (PSM) was utilized to balance the bias of the variables between patients. Univariate and multivariate Cox proportional hazards regression analyses were performed to identify prognostic factors. KM analysis was used to calculate survival. Adjusted analyses for the primary outcome of different treatment modalities of IV CSCLC, IV SCLC and IV NSCLC were performed using Cox regression models. A total of 493 patients with IV CSCLC, 35503 patients with SCLC, 122807 patients with IV NSCLC were included in this study. The demographic characteristics and tumor characteristics of the three groups were different. Before PSM, there were significant differences in OS and CSS among IV CSCLC, IV SCLC and IV NSCLC, After PSM, there was a significant difference in OS and CSS between the IV CSCLC and IV NSCLC. Risk/protective factors for OS and CSS were different in three groups. Chemotherapy, radiotherapy, and surgery can improve IV CSCLC's survival time. The combination of surgery and chemoradiotherapy treatment group for patients with IV CSCLC demonstrated best OS compared to control treatment groups, and the surgery combined chemotherapy treatment group exhibited the best CSS. Additionally, for select patients with stage IV CSCLC who have missed the window for surgical intervention at the time of initial diagnosis, chemoradiotherapy presents a viable and effective treatment option. The clinical characteristics IV CSCLC, IV SCLC and IV NSCLC were significantly different. The prognosis for IV CSCLC is notably poorer than IV NSCLC, similar to IV SCLC. Surgery combined therapy emerged as the preferred treatment modalities and chemoradiotherapy was a good choice for patients who have lost the indication of surgery for patients diagnosed with IV CSCLC.

Durvalumab Following Chemoradiotherapy for Stage III Non-small Cell Lung Cancer: Differences in Survival Based on Age and Post-Progression Systemic Therapy.

Concurrent chemoradiotherapy (cCRT) followed by 1 year of the immune checkpoint inhibitor (ICI) durvalumab is standard of care for patients with unresectable stage III nonsmall cell lung cancer (NSCLC). The purpose of this study was to evaluate survival outcomes of (1) cCRT followed by durvalumab in patients older versus younger than 75 years of age and (2) post-progression treatment with ICI alone versus chemotherapy alone versus combined ICI and chemotherapy. Patients with unresectable stage III NSCLC treated between January 2018 and July 2023 with cCRT followed by durvalumab were identified retrospectively. Progression-free survival (PFS) and overall survival (OS) from ICI start were analyzed in three cohorts aged < 65, 65-74, and ≥ 75 years. Multivariable Cox proportional hazard regression modelling of factors associated with OS was undertaken. Logistic regression analysis identified risk factors of early durvalumab discontinuation for toxicity. Time from first salvage drug treatment to death (OS-2) was described. A total of 472 patients were analyzed: the proportions aged < 65, 65-74, and ≥ 75 years were 34.3%, 42.8%, and 22.9%, respectively. Odds of early durvalumab discontinuation was 2.2-fold greater in the oldest (versus youngest) cohort. Age associated differences in median PFS (26.7months, 20.3months, and 14.2months; p< 0.001) and OS (60.8months, 44.4 months, and 27.6 months; p< 0.001) were observed. On multivariable analysis, factors associated with shorter OS were age ≥ 75years (versus < 65), performance status 2/3 (versus 0/1), stage IIIC (versus IIIA), neutrophil to lymphocyte ratio (per 7.43 unit increase), Charlson comorbidity index (per 1 unit increase), tumoral PD-L1 expression < 1% (versus ≥ 50%, 1-49%, or unknown), and squamous histology (versus non-squamous). Of 264 patients with disease progression, 48.5% received subsequent drug therapy. Median OS-2 was longer with ICI alone (9.9 months) or ICI-chemotherapy (11.8 months) than platinum doublet chemotherapy (6.7 months.) For recurrences < 6 months from the last durvalumab infusion, OS-2 were similar across treatment groups. In the studied cohort, OS was significantly shorter for patients ≥ 75 years of age treated with cCRT followed by durvalumab compared to those < 65 years. Post-progression systemic therapy was associated with modest efficacy, underscoring the need for new therapies.

Racial disparities in presenting stage and surgical management among octogenarians with breast cancer: a national cancer database analysis.

As the US faces a diverse aging population, racial disparities in breast cancer outcomes among elderly patients remain poorly understood. We evaluate the association of race with presenting stage, treatment, and survival of invasive breast cancer among octogenarians. Women (≥ 80years) with invasive breast cancer were identified in 2004-2020 NCDB. To facilitate comparison, only non-Hispanic Black and non-Hispanic White patients were included; patients of Hispanic ethnicity were excluded. Demographics, tumor characteristics, and treatments were assessed by race. Overall survival was compared using the logrank test. Multivariable logistic and Cox proportional hazard regression models were developed to evaluate the independent association of race with outcomes of interest. Of 222,897 patients, 19,059 (8.6%) were Black. Most patients had stage I ER + HER2- invasive ductal carcinoma. Black patients more frequently had greater comorbidities, low income and education, and advanced stage (p < 0.001 each; ref: White). Following adjustment, Black women had increased likelihood of Stage III/IV over time, as well as increased odds of chemotherapy (AOR 1.22, 95% CI 1.15 - 1.29) and non-operative management (AOR 1.82, 95% CI 1.72 - 1.92; ref: White). Although Black patients had lower survival rates compared to White, race was not associated with 5-year mortality following adjustment for stage, receipt of surgery, and adjuvant treatments (p = 0.34). Inferior survival among elderly Black patients appears be driven by advanced stage at presentation. While such disparities are narrowing in the present era, future work must consider upstream interventions to ensure equitable outcomes for all races.

Laparoscopic versus open surgery for liver resection: a multicenter cohort study

The relative risk and benefits of Laparoscopic liver resection (LLR) are still controversial. This study aimed to evaluate perioperative and survival outcomes for three primary malignant liver tumors related outcomes following LLR. Data from three Homogeneous-High-Volume-Expert-Centers were collected. Multivariable logistic regression analysis was performed for the association between LLR, and major complications defined as Clavien-Dindo Classification grade ≥ II. Multivariable Cox proportional hazards regression was used to explore the impact of LLR on primary malignant liver tumor survival. Overall, 5886 patients underwent liver resection, of which 1991 underwent LLR. After adjusting for covariables, LLR had significantly lower rate of CDC grade ≥ II (OR = 0.56, 95% CI: 0.48–0.67, P < 0.001). Interaction analysis showed that LLR had significant association with sex, drinking status, history of abdominal surgery, and platelet count (all P < 0.05). The overall survival for each primary malignant liver tumor shown potential risk but without significantly different between LLR and OLR (all P > 0.05). LLR was associated with lower rate of major complications, especially in women, non-drinkers, those without a history of abdominal surgery, and those with normal platelet. For primary malignant liver tumors, the survival outcomes did not differ significantly between LLR and OLR.

Establishment and Validation of a Prognostic Nomogram for Predicting Postoperative Overall Survival in Advanced Stage III-IV Colorectal Cancer Patients.

Most colorectal cancer (CRC) patients are at an advanced stage when they are first diagnosed. Risk factors for predicting overall survival (OS) in advanced stage CRC patients are crucial, and constructing a prognostic nomogram model is a scientific method for survival analysis. A total of 2956 advanced stage CRC patients were randomised into training and validation groups at a 7:3 ratio. Univariate and multivariate Cox proportional hazards regression analyses were used to screen risk factors for OS and subsequently construct a prognostic nomogram model for predicting 1-, 3-, 5-, 8- and 10-year OS of advanced stage CRC patients. The performance of the model was demonstrated by the area under the curve (AUC) values, calibration curves and decision curve analysis (DCA). Kaplan-Meier curves were used to plot the survival probabilities for different strata of each risk factor. There was no statistically significant difference (p > 0.05) in the 32 clinical variables between patients in the training and validation groups. Univariate and multivariate Cox proportional hazards regression analyses demonstrated that age, location, TNM, chemotherapy, liver metastasis, lung metastasis, MSH6, CEA, CA199, CA125 and CA724 were risk factors for OS. We estimated the AUC values for the nomogram model to predict 1-, 3-, 5-, 8- and 10-year OS, which in the training group were 0.826 (95% CI: 0.807-0.845), 0.836 (0.819-0.853), 0.839 (0.820-0.859), 0.835 (0.809-0.862) and 0.825 (0.779-0.870) respectively; in the validation group, the corresponding AUC values were 0.819 (0.786-0.852), 0.831 (0.804-0.858), 0.830 (0.799-0.861), 0.815 (0.774-0.857) and 0.802 (0.723-0.882) respectively. Finally, the 1-, 3-, 5-, 8- and 10-year OS rates for advanced stage CRC patients were 73.4 (71.8-75.0), 49.5 (47.8-51.4), 43.3 (41.5-45.2), 40.1 (38.1-41.9) and 38.6 (36.6-40.8) respectively. We constructed and validated an original nomogram for predicting the postoperative OS of advanced stage CRC patients, which can help facilitates physicians to accurately assess the individual survival of postoperative patients and identify high-risk patients.

A positive correlation between serum lactate dehydrogenase level and in-hospital mortality in ICU sepsis patients: evidence from two large databases

BackgroundSepsis presents a significant healthcare challenge, characterized by high morbidity and mortality rates. There is a scarcity of relevant studies investigating the association between serum lactate dehydrogenase level and the prognosis of sepsis in patients from intensive care unit, with smaller sample sizes compared to other studies.MethodsA retrospective analysis was conducted utilizing data from the Second Affiliated Hospital of Guangzhou Medical University and the Medical Information Mart for Intensive Care IV (MIMIC-IV). The primary outcome was the in-hospital mortality. Multivariate Cox proportional hazards regression was adopted to assess the independent association. Receiver operator characteristic (ROC) curve was used to evaluate the predictive value.ResultsWe included a total of 2148 patients in the Guangzhou Sepsis Cohort (GZSC) database and 5830 patients in the MIMIC-IV database. In multivariate Cox proportional hazards regression, high levels of LDH are significantly associated with higher mortality (HR = 1.21, 95% CI 1.13–1.30, p < 0.001 in the GZSC database and HR = 1.19, 95% CI 1.13–1.25, p < 0.001 in the MIMIC-IV database). The ROC curves showed that the AUC of LDH was 0.663 in the GZSC database and 0.660 in the MIMIC-IV database.ConclusionsA lower lactate dehydrogenase level is associated with reduced in-hospital mortality among patients with sepsis, suggesting its potential as a valuable marker for predicting prognosis in this patient population.