Multivariate Cox Proportional Hazards Regression Research Articles

Combined influence of physical activity and C-reactive protein to albumin ratio on mortality among older cancer survivors in the United States: a prospective cohort study

BackgroundAlthough a high C-reactive protein-to-albumin ratio (CAR) is believed to increase mortality risk, the association between the physical activity (PA), CAR, and mortality among cancer survivors has not been investigated. This study aimed to examine this association among cancer survivors in the United States.MethodsThis cohort study used data from the National Health and Nutrition Examination Survey from 1999 to 2010. PA was self-reported using the Global Physical Activity Questionnaire, and C-reactive protein and albumin levels were obtained from laboratory data files. Mortality data were obtained by linkage of the cohort database to the National Death Index as of December 31, 2019. The analysis was conducted from November 1 to December 31, 2023. We used Cox proportional hazards multivariable regression to assess hazard ratios (HRs) and 95% confidence interval (CIs) for total and cancer-specific mortality risks attributable to PA and CAR.ResultsAmong 2,232 cancer survivors, 325 (14.6%) reported no PA with a high CAR. During a follow-up of up to 20.75 years (median, 12.3 years; 27,453 person-years), 1,174 deaths occurred (cancer, 335; other, 839). A high CAR was observed to be consistently associated with the highest risks of total (HR, 1.59; 95% CI, 1.37–1.85) and cancer-specific (HR, 2.06; 95% CI, 1.55–2.73) mortality compared with a low CAR in a series of adjusted models. Multivariable models showed that PA was associated with a lower risk of all-cause (HR, 0.60; 95% CI, 0.52–0.69) and cancer-specific (HR, 0.64; 95% CI, 0.49–0.84) mortality compared with no PA. In the joint analyses, survivors with PA ≥ 600 metabolic equivalent min/wk and a low CAR were more likely to reduce the risk of total (HR, 0.41; 95% CI, 0.32–0.51) and cancer-specific (HR, 0.32; 95% CI, 0.20–0.50) mortality by 59% and 68% compared with those with no PA and a high CAR.ConclusionThe pairing of adequate PA and a low CAR was significantly associated with reduced all-cause and cancer-related mortality risks.

Association between neutrophil-to-lymphocyte ratio and short-term all-cause mortality in patients with cerebrovascular disease admitted to the intensive care unit-a study based on the MIMIC-IV database.

Inflammation plays a crucial role in cerebrovascular disease (CVD) progression. Neutrophil-to-lymphocyte ratio (NLR) is an important inflammatory marker, though its diagnostic role in CVD is still under investigation. This study evaluates the relationship between NLR and short-term all-cause mortality in patients with CVD admitted to the intensive care unit (ICU). We conducted a retrospective study using data from the Medical Information Mart for Intensive Care (MIMIC-IV) (v2.2) database, including 4,327 adult ICU-admitted CVD patients. NLR values at admission were analyzed alongside various mortality variables. Multivariate Cox proportional hazards regression models and Kaplan-Meier (K-M) survival curves assessed the relationship between NLR and short-term all-cause mortality. Predictive power, sensitivity, specificity, and area under the curve (AUC) of NLR for short-term mortality were investigated using Receiver Operating Characteristic (ROC) analysis. Additionally, restricted cubic spline (RCS) curves and subgroup analyses were conducted. Among the 4,327 patients, 3,600 survived (survival group) and 727 died (non-survival group) within 28 days of admission (mortality rate: 16.8%). A multivariate Cox regression analysis identified NLR as an independent predictor of 28-day all-cause mortality (hazard ratio: 1.013; 95% confidence interval: 1.0086-1.0188; p < 0.001). The predictive model, incorporating NLR, age, gender, BMI, Charlson comorbidity index (CCI), WBC counts, Platelet, INR, and CRP, achieved an AUC of 0.686 (95% confidence interval: 0.665-0.70). While platelet-to-lymphocyte ratio was also analyzed, its predictive efficiency was less pronounced compared to NLR. A best NLR threshold of 6.19 was determined, distinguishing survivors from non-survivors. Kaplan-Meier survival curves showed that patients with NLR ≥ 6.19 had significantly lower survival rates at 7-, 14-, 21-, and 28-days. Subgroup analyses indicated that NLR did not significantly interact with most subgroups. NLR may serve as an independent predictor for short-term all-cause mortality in ICU-admitted CVD patients, enhancing our understanding of the association between inflammatory biomarkers and CVD prognosis.

Genetic variants of LRRC8C, OAS2, and CCL25 in the T cell exhaustion-related genes are associated with non-small cell lung cancer survival.

T cell exhaustion is a state in which T cells become dysfunctional and is associated with a decreased efficacy of immune checkpoint inhibitors. Lung cancer has the highest mortality among all cancers. However, the roles of genetic variants of the T cell exhaustion-related genes in the prognosis of non-small cell lung cancer (NSCLC) patients has not been reported. We conducted a two-stage multivariable Cox proportional hazards regression analysis with two previous genome-wide association study (GWAS) datasets to explore associations between genetic variants in the T cell exhaustion-related genes and survival of NSCLC patients. We also performed expression quantitative trait loci analysis for functional validation of the identified variants. Of all the 52,103 single nucleotide polymorphisms (SNPs) in 672 T cell exhaustion-related genes, 1,721 SNPs were found to be associated with overall survival (OS) of 1185 NSCLC patients of the discovery GWAS dataset from the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial, and 125 of these 1,721 SNPs remained significant after validation in an additional independent replication GWAS dataset of 984 patients from the Harvard Lung Cancer Susceptibility (HLCS) Study. In multivariable stepwise Cox model analysis, three independent SNPs (i.e., LRRC8C rs10493829 T>C, OAS2 rs2239193 A>G, and CCL25 rs3136651 T>A) remained significantly associated with OS with hazards ratios (HRs) of 0.86 (95% confidence interval (CI) = 0.77-0.96, P = 0.008), 1.48 (95% CI = 1.18-1.85, P < 0.0001) and 0.78 (95% CI = 0.66-0.91, P = 0.002), respectively. Further combined analysis for these three SNPs suggested that an unfavorable genotype score was associated with a poor OS and disease-specific survival. Expression quantitative trait loci analysis suggested that the LRRC8C rs10493829 C allele was associated with elevated LRRC8C mRNA expression levels in normal lymphoblastoid cells, lung tissue, and whole blood. Our findings suggested that these functional SNPs in the T cell exhaustion-related genes may be prognostic predictors for survival of NSCLC patients, possibly via a mechanism of modulating corresponding gene expression.

Cardiac MRI Predictors of ArrhythmicSudden Cardiac Events in Patients With Fontan Circulation.

Among patients with congenital heart disease, those with single ventricles have the highest risk of early mortality. Sudden cardiac death is an important cause of death in this population. Understanding the risk factors for sudden cardiac events (SCE) in Fontan patients could improve prediction and prevention. The goal of this study was to determine the prevalence of SCE and risk factors for SCE in the Fontan population. The Fontan Outcomes Registry Using CMR Examinations (FORCE) is an international registry collecting clinical and imaging data on Fontan patients. SCE was defined as: 1) cardiac arrest from a shockable rhythm; 2) need for emergent cardioversion/defibrillation; or 3) documented sustained ventricular tachycardia. Univariate and multivariate Cox proportional hazards regression models estimated hazard ratios for predictors of SCE. Our sample included 3,132 patients (41% female). The median age at first cardiac magnetic resonance was 14.6 years. SCE was experienced by 3.5% (n=109) over a median follow-up time of 4.00 years. Of the 109 patients with SCE, 39 (36%) died. On multivariable analysis, NYHA functional class >II (HR: 4.91; P< 0.0001), history of protein-losing enteropathy/plastic bronchitis (HR: 2.37; P=0.0082), single-ventricle end-diastolic volume index >104mL/m2 (HR: 3.15; P< 0.0001), and ejection fraction<50% (HR: 1.73; P=0.0437) were associated with SCE. Kaplan-Meier analysis demonstrated that in patients with none of the above risk factors, the 4-year freedom from SCE was 99.5%. SCE occurred in 3.5% of the study population, and one-third of patients who experienced SCE died. Mild ventricular dysfunction and dilatation by cardiac magnetic resonance, NYHA functional class, and history of protein-losing enteropathy/plastic bronchitis were associated with SCE.

Relationship between self-reported challenges with social determinants of health and delayed time-to-treatment initiation for gynecologic malignancies.

90 Background: Delays in time to treatment initiation (TTI) for gynecologic malignancies have been associated with worse survival. Worsened outcomes and presentation with more advanced disease are more common for gynecologic cancer patients who come from socioeconomically disadvantaged populations and whose healthcare is negatively impacted by their social determinants of health (SDoH). There is a need to characterize the particular social determinants of health that are associated with delays in treatment initiation in patients with gynecologic malignancy, particularly in underserved urban populations. Methods: Retrospective cohort study at an urban community-based academic center. Participants were 257 patients with primary gynecologic malignancy either of the cervix, ovary, uterus, vulva/vagina or NOS diagnosed between January 2017 and August 2022, identified through the Montefiore Medical Center Cancer Registry. The primary exposure was TTI, defined as the duration between histopathological diagnosis and initial treatment. Univariate and multivariate logistic regression analyses were conducted to examine the association between delays in TTI and SDoH. Multivariate Cox proportional hazard regression was used to obtain hazard ratios and 95% confidence intervals associated with TTI. Results: Among 257 patients with gynecologic malignancy (median [IQR] age 63 [56-72] years), 205 patients were treated within 45 days of diagnosis, and 52 were treated at or after 45 days. Predictors of delayed TTI (defined as ≥45 days) included positive SDoH screening in univariate logistic regression (OR = 3.12, 95% CI 1.39-6.98, p = 0.0061) and in multivariate logistic regression (OR = 3.06, 95% CI 2.62-3.57, p&lt;0.001) as well as increased age in multivariate logistic regression (OR = 1.02, 95% CI 1.02-1.03, p&lt;0.001). Multivariate logistic regression showed that protective factors for delayed TTI were Non-Hispanic Black race/ethnicity (OR = 0.87, 95% CI 0.77-0.99, p = 0.0351), non-Hispanic white race/ethnicity (OR = 0.37, 95% CI 0.30-0.46, p&lt;0.001), inpatient stay within 30 days of diagnosis (OR = 0.74, 95% CI 0.62-0.88, p=0.001) and AJCC clinically late stage (OR = 0.57, 95% CI 0.50-0.66, p&lt;0.001). Conclusions: In patients with gynecologic malignancies, greater SDoH burden increases risk for delays in treatment ≥ 45 days from diagnosis. Non-Hispanic race/ethnicity, inpatient stay within 30 days of diagnosis and clinically late-stage diagnoses are protective factors for expedited treatment initiation. Identification of predictive and protective factors for treatment delay will help identify at-risk patients and facilitate earlier intervention in hospitals with underserved populations.

Gamma-Glutamyl Transpeptidase to Neutrophil Ratio as Prognostic Indicator for Hepatocellular Carcinoma Patients Post-Curative Resection.

The close association between inflammation and the clinical outcomes of hepatocellular carcinoma (HCC) has been extensively documented. This study aims to analyze the association between a novel inflammatory indicator, the gamma-glutamyl transpeptidase to neutrophil ratio (GNR), and HCC prognosis following curative resection. A cohort of 204 eligible HCC cases were included. Based on an optimal cut-off value determined utilizing the X-tile software, patients were categorized into low- and high-GNR groups. The overall survival (OS) and recurrence-free survival (RFS) rates were assessed using the Kaplan-Meier analysis method with Log rank tests. Multivariate Cox proportional hazard regression was used to investigate the independent association between GNR and HCC prognosis. Restricted cubic splines were used to explore the nonlinear relationship between GNR and the risk of death or recurrence. The low GNR group exhibited significantly higher 3-year OS and RFS rates than the high GNR group. Multivariate Cox analysis indicated that a high GNR level was independently associated with poor OS and RFS. A linear correlation between GNR and the risk of death, as well as a nonlinear inverted "U" shape correlation between GNR and the risk of recurrence, were observed. The findings provide evidence supporting the independent association of GNR with HCC prognosis. These results offer promise for enhancing prognosis assessments and guiding active monitoring strategies for patients with HCC post-curative resection.

Association of Physician Certification and Outcomes Among Patients Undergoing Left Atrial Appendage Occlusion.

Percutaneous left atrial appendage occlusion (LAAO) is indicated in patients with atrial fibrillation for whom long-term oral anticoagulation is contraindicated. Whether outcomes are different based on operator certification [interventional cardiology (IC) versus electrophysiology (EP)] is unclear. To compare LAAO outcomes by physician certification (EP versus IC) in the NCDR LAAO Registry. We identified patients from 2020-2022 undergoing implantation of a Watchman FLX or Amulet LAAO device and stratified patients by primary operator certification. Outcomes of interest included: (1) any major adverse event (MAE), 2) mortality, 3) ischemic stroke, and 4) major bleeding during the initial hospitalization and at 45 days. We performed multivariable Cox proportional hazards regression analysis to determine the risk of adverse events by physician certification. A total of 1,638 physicians (57% electrophysiologists) performing 91,711 procedures during the study period were included. EPs were more likely to use intracardiac echocardiography (25.2% vs 9.7%, p<0.001) and had lower radiation total (235 mGy vs 305 mGy, p<0.001). EPs were more likely than ICs to discharge patients on DOAC+aspirin, whereas ICs were more likely to discharge patients on single or dual antiplatelet therapy (all p<0.001). In-hospital death (0.1% vs. 0.1%, p=0.46) and MAE (1.5% vs 1.6%, p=0.42) were similar by physician certification. At 45 days, there was no difference in death [HRdeath 1.03, 95% CI (0.89-1.2)] or MAE [HRMAE 0.97, 95% CI (0.91-1.03)] after multivariable regression. Contemporary LAAO is safe with low rates of procedural complications and no significant differences in procedural outcomes by operator subspecialty after multivariable adjustment. Continued utilization of technology by EPs and ICs is necessary to allow for broad access to this treatment for eligible patients.

Time to COVID-19 Vaccination by Language and Country of Origin

Disparities in COVID-19 vaccination rates by race and ethnicity are well documented. Less is known about primary language and COVID-19 vaccine uptake. To describe the time to COVID-19 primary series vaccination and booster doses by primary language and country of origin. This retrospective cohort study included patients aged 6 months or older with at least 1 health encounter from July 1, 2019, to June 30, 2023, at a single health care system serving patients across Minnesota and western Wisconsin. Primary language and country of origin documented in the electronic health record. Three COVID-19 vaccine coverage outcomes were evaluated: (1) primary series (1 Ad26.COV.S vaccine or 2 mRNA COVID-19 vaccines), (2) first-generation booster (primary series Ad26.COV.S vaccine plus 1 Ad26.COV.S or mRNA COVID-19 vaccine at least 2 months after the second dose or primary series mRNA vaccine plus 1 mRNA vaccine at least 5 months after the second dose), and (3) bivalent booster. Vaccine coverage was described by patient characteristics. Associations of primary language, race and ethnicity, and other patient characteristics with COVID-19 vaccine uptake were evaluated using time-to-event analysis in multivariable Cox proportional hazards regression models, and adjusted hazard ratios (AHRs) with 95% CIs were reported. There were 1 001 235 patients included (53.7% female). Most patients reported English as a primary language (94.1%) and were born in the US (91.8%). Primary series coverage was 63.7%; first-generation booster coverage, 64.4%; and bivalent booster coverage, 39.5%. Coverage for all outcomes was lower among those with a non-English primary language compared with English as the primary language (56.9% vs 64.1% for primary series; 47.5% vs 65.3% for first-generation booster; 26.2% vs 40.3% for bivalent booster). Those with a non-English primary language had lower COVID-19 vaccine uptake for the primary series (AHR, 0.85; 95% CI, 0.84-0.86), first-generation booster (AHR, 0.74; 95% CI, 0.73-0.75), and bivalent booster (AHR, 0.65; 95% CI, 0.64-0.67) compared with patients with English as their primary language. Non-US-born patients had higher primary series uptake compared with US-born patients (AHR, 1.19; 95% CI, 1.18-1.20) but similar first-generation booster (AHR, 1.01; 95% CI, 0.99-1.02) and bivalent booster (AHR, 1.00; 95% CI, 0.98-1.02) uptake. In this retrospective cohort study, patients with a non-English primary language had both lower coverage and delays in receiving COVID-19 vaccines compared with those with English as their primary language. Reporting on language may identify health disparities that can be addressed with language-specific interventions.

Statin Therapy is Associated With Lower Risk of Mortality Among Liver Transplant Candidates With Metabolic Dysfunction-associated Steatohepatitis

BackgroundStatin therapy is historically underutilized in patients with chronic liver disease. There is increasing evidence to support the use of statins in patients with cirrhosis, though data in decompensated patients are limited. The primary aim of this study was to evaluate the association between statin use and mortality in patients with advanced liver disease, comparing MASH and non-MASH cirrhosis. MethodsThis single-center retrospective cohort study included patients undergoing liver transplant (LT) evaluation at a large quaternary care center. Patients were categorized by etiology as metabolic dysfunction-associated steatohepatitis (MASH) or non-MASH cirrhosis. Statin use was defined as having an active prescription at the time of LT evaluation. The association between statin use and mortality was evaluated using multivariable Cox proportional hazard regression. ResultsThe study included 623 patients; 24% had MASH cirrhosis and 20% were prescribed a statin. Statin users were older, had a higher BMI and were more likely to have coronary artery disease. At the end of the study, statin use was associated with lower mortality among MASH patients (16% vs. 35%, p=0.010) and higher mortality among non-MASH patients (31% vs. 19%, p=0.066). After controlling for age (HR 1.05, 95% CI 1.00 – 1.10, p=0.039), MELD-Na (HR 1.07, 95% CI 1.04 – 1.11, p<0.001), BMI (HR 1.09, 95% CI 1.05 – 1.14, p<0.001), and CAD (HR 1.20, 95% CI 0.54 – 2.69, p=0.653), statin use conferred a 53% lower risk of death compared to no statin use in patients with MASH cirrhosis (HR 0.47, 95% CI 0.22 – 0.98, p=0.043). ConclusionsStatin use was associated with reduced mortality in patients with decompensated MASH cirrhosis undergoing LT evaluation, but increased mortality in those with non-MASH cirrhosis, particularly those with high-MELD-Na. These findings underscore the importance of reviewing individual patient characteristics and disease etiology when considering the benefits of statin therapy in patients with cirrhosis.

Prognostic factors and surgical management in pediatric primary lung cancer: a retrospective cohort study using SEER data.

Primary lung cancer (LC) is extremely rare in pediatric patients, making diagnosis and management particularly challenging. Currently, there are no established guidelines for treating LC in this age group, and both prognosis and treatment experiences are scarcely studied. This study aims to evaluate prognostic factors and assess the survival benefits of surgical intervention in pediatric LC patients. Data were obtained from the Surveillance, Epidemiology, and End Results (SEER) database spanning from 1988 to 2019, encompassing 337 children aged 0-19 years diagnosed with primary LC. Clinical characteristics, prognostic factors, and surgical approaches were elucidated. Prognostic markers for overall survival (OS) were evaluated through univariate and multivariate Cox proportional hazards regression models. Survival analysis between groups utilized Kaplan-Meier survival curves. The children indicated a median age of 15 years and the female-to-male ratio was close to 1:1. The most common pathological type was carcinoid tumor (31.45%). Most of the tumors were <5 cm in diameter (63.79%) or confined in situ (46.77%). The 5-year OS rate for the entire cohort was 77.9%, with pathologic classification, SEER stage, surgery, and tumor size identified as independent prognostic factors. Pulmonary/pleuropulmonary blastoma [hazards ratio (HR): 6.41; 95% confidence interval (CI): 1.69-24.35; P=0.006] or adenocarcinoma (HR: 8.82; 95% CI: 2.20-35.25; P=0.002), no surgery (HR: 2.05; 95% CI: 1.13-3.72; P=0.02), and tumor size ≥5 cm (HR: 2.87; 95% CI: 1.20-6.89; P=0.02) were associated with a worse prognosis in pediatric LC patients. In localized of SEER stage (HR: 0.15; 95% CI: 0.04-0.56; P=0.005) was associated with a better prognosis in pediatric LC patients. Common pathological types including carcinoid, pulmonary/pleuropulmonary blastoma, and mucoepidermoid carcinoma demonstrated the most favorable prognosis (P<0.001). Surgery did not significantly benefit patients with American Joint Committee on Cancer (AJCC) stage IV (HR: 0.83; 95% CI: 0.42-1.62; P=0.58) or distant-stage disease (HR: 0.59; 95% CI: 0.33-1.06; P=0.06). Conversely, children with regional lymph node metastasis (HR: 0.23; 95% CI: 0.06-0.88; P=0.02) or AJCC stage III-IV (HR: 0.40; 95% CI: 0.19-0.87; P=0.02) showed improved survival following lymph node dissection. Tumor size also influenced surgical decision-making, with smaller tumors (<5 cm) favoring surgical resection, including lobectomy (P<0.001) or local tumor resection (P=0.03), while larger tumors exhibited advantages with less specificity regarding surgical approach (P=0.15). This study identified pathologic classification, SEER stage, surgery, and tumor size as independent prognostic factors for pediatric LC. For children with advanced-stage LC, surgical intervention may not extend survival time. This study underscores the importance of tailoring therapeutic strategies based on histology, disease stage, and tumor size. These findings offer valuable insights into managing pediatric LC, enabling more informed clinical decisions and potentially enhancing patient outcomes.

Imminent risk of the first and second recurrent osteoporotic fractures in South Korea

BackgroundA history of fractures increases the likelihood of experiencing subsequent and secondary fractures. To prevent further fractures, global guidelines recommend aggressive proactive treatment with medication for patients at an imminent risk of osteoporotic fracture (OF), which is defined as a high likelihood of experiencing subsequent fractures in the near future. However, there is a lack of research focusing on patients with imminent risk of OFs in South Korea. Hence, this study aimed to evaluate the imminent risk of the first and second recurrent OFs among patients with OF in South Korea. MethodsWe conducted a retrospective analysis using the comprehensive Health Insurance Review and Assessment database, which encompasses the entire population of Korea from 2012 to 2017. The study focused on eligible patients aged 55 years and older who experienced an OF in 2013, including fractures in the hip/femur, vertebral, humerus, radius, tibia/fibula, and ankle regions. The first OF occurring in 2013 was considered the index OF. To ensure that the index fracture was the index OFs, we excluded patients who had any OF within 1 year before their index OF. We assessed the incidence of the first recurrent OF within 2 years after the index OF, and the second recurrent OF within 2 years after the occurrence of the first recurrent OF. Additionally, we estimated the risks of experiencing the first and second recurrent OFs according to age and sex using multi-variable Cox proportional hazard regression analysis. ResultsApproximately 17 % of patients with an index OF had the first recurrent OF within 2 years after the index OF. Of those with a first recurrent OF, 28 % experienced a second recurrent OF within 2 years after the first recurrent OF. The two-year incidence rate of the first recurrent OF was 9.6 per 100 person-years (95 % confidence interval [CI], 9.6–9.7). The two-year incidence rate of the second recurrent OF was 22.0 per 100 person-years (95 % CI, 21.6–22.4), which is higher than that of the first recurrent OF. Females had a 31 % higher risk of the first recurrent OF (hazard ratio [HR] = 1.31; 95 % CI, 1.20–1.43) and a 43 % higher risk of the second recurrent OF than males (HR = 1.43; 95 % CI, 1.35–1.51). ConclusionsIn Korea, the imminent risk of a second recurrent OF was higher than that of a first recurrent OF. Consequently, given the elevated risk of subsequent fractures with the number of OFs experienced, a more targeted approach to treatment is recommended for patients with a first recurrent OF considering the risk of subsequent OF.

The relationship between serum uric acid and gastrointestinal bleeding in peritoneal dialysis patients: a propensity score analysis

Purpose Gastrointestinal bleeding is an important gastrointestinal complication among peritoneal dialysis patients and correlated with a higher risk of mortality. Increased uric acid levels are a significant complication for peritoneal dialysis patients and have been associated with an increased risk of hemorrhagic stroke. The objective of the present study was to investigate the relationship between serum uric acid levels and gastrointestinal bleeding in peritoneal dialysis patients. Methods A total of 2498 peritoneal dialysis patients were recruited. Based on the optimal uric acid cutoff value, two groups of patients were divided. We constructed a propensity-score-matched population of 1762 patients by matching sex, age, and body mass index. Survival outcomes between the two groups were compared using adjusted Kaplan–Meier curves. We constructed the restricted cubic splines regression to assess the correlation between levels of uric acid and gastrointestinal bleeding. A multivariate Cox proportional hazards regression was performed to test whether higher levels of uric acid are an independent risk factor for gastrointestinal bleeding. We performed a forest plot to show interaction effects in different subgroups. Results According to restricted cubic splines regression, uric acid levels were positively correlated with the risk of gastrointestinal bleeding events. After adjusted different confounding factors, patients with high levels of uric acid were prone to experience gastrointestinal bleeding (HR 1.868, 95%CI 1.001–3.486). In subgroups, the interaction between higher levels of uric acid and utilizing proton pump inhibitors was significant (P for interaction = 0.034). Further research found that taking proton pump inhibitors could decrease the risk of gastrointestinal bleeding in peritoneal dialysis patients accompanied high levels of uric acid. Conclusion The baseline high levels of uric acid are an independent risk factor for gastrointestinal bleeding in patients undergoing peritoneal dialysis.

Identification of the Prognostic Factors for Synchronous Multiple Primary Lung Cancer Treated With Staged Bilateral Surgery.

Staged bilateral surgery is widely used to treat synchronous multiple primary lung cancer (SMPLC); however, the prognostic factors for survival outcomes remain unclear. This study aimed to identify prognostic factors and construct a predictive model for overall survival (OS) and recurrence-free survival (RFS) in patients with SMPLC who underwent staged bilateral surgery. The study included 256 patients diagnosed with SMPLC and treated with staged bilateral surgery at our hospital between January 2010 and July 2017. Multivariate Cox proportional-hazard regression was used to identify prognostic factors for OS and RFS. Additionally, a predictive model was constructed using time-dependent receiver operating characteristic curves. Among the 256 patients, 10 (3.95%) succumbed to the disease and 24 (9.41%) experienced recurrence. Smoking (hazard ratio [HR]: 5.128; 95% confidence interval [CI]: 1.442-18.233; p = 0.012) and most advanced pathological TNM (pTNM) stage (II + III) (HR: 12.938; 95% CI: 2.650-63.176; p = 0.002) were identified as significant predictors of poor OS. A prognostic model was developed for predicting OS, with a 5-year area under the curve (AUC) of 0.854. Furthermore, most advanced pTNM stage (II + III) was associated with poor RFS (HR: 5.964; 95% CI: 2.669-13.327; p < 0.001), and the predictive model exhibited a 5-year AUC of 0.718 for RFS. This study revealed that smoking and most advanced pTNM stage were independent prognostic factors associated with poor OS in patients with bilateral SMPLC. Moreover, most advanced pTNM stage was also linked to unfavorable RFS. The developed predictive model demonstrated moderate prognostic performance for both OS and RFS.

The impact of socioeconomic status on overall survival in patients at a radiation oncology center: A retrospective study.

147 Background: There are few reports examining the impact of socioeconomic status (SES), as indicated by the Area Deprivation Index (ADI), on overall survival (OS) in radiation oncology patients, making this an important area of investigation. This study aims to investigate the influence of ADI on OS in radiation oncology patients, while controlling for stage and other relevant variables. Methods: This retrospective study analyzed data from radiation oncology patients treated at a large multi-site single-institution center from October 2006 to January 2024. Demographic and treatment information, including age, gender, race, insurance status, comorbidity index (CCI), mental health disorders (MHD), treatment intent, cancer type, and stage, were collected. The ADI was used to measure SES and was gathered from the Neighborhood Atlas. Kaplan-Meier curves were generated for all patients, with separate curves for different cancer types. The impact of demographic, clinical, and socioeconomic factors on OS was assessed using a Cox proportional hazards multivariable (MVA) logistic regression analysis. The model was stratified by treatment intent, cancer type, stage, insurance status, and CCI. Results: In this comprehensive analysis of 7343 patients, the median follow-up was 12.00 months (IQR: 1.8–36.82). Most patients were breast cancer (30.2%), over 65 years old (60.5%), and had an ADI below the mean (55.5%), indicating lower socioeconomic disadvantage. Kaplan-Meier analysis showed that 5-year OS rates were significantly lower for the fourth quartile ADI group (85.1%) compared to the first quartile ADI group (94.0%) (p&lt;0.001). Among different cancer types, significant differences in OS were observed for breast cancer (p=0.002) and miscellaneous (uncategorized) cancers (p=0.005), with lung cancer showing a trend towards significance (p=0.053). The MVA revealed that patients in both the third quartile (hazard ratio (HR)=1.343, 95% CI: 1.029–1.752, p=0.030) and fourth quartile (HR=1.403, 95% CI: 1.075–1.829, p=0.013) of ADI had significantly higher likelihood of mortality compared to those in the first ADI quartile. Conclusions: SES, as measured by ADI, significantly impacts OS in radiation oncology patients. Poorer patients, indicated by higher ADI, exhibited worse survival outcomes despite controlling for cancer type, stage, treatment intent, CCI, MHD, and insurance status. These findings underscore the need for targeted interventions to address socioeconomic disparities in cancer care to improve survival outcomes for disadvantaged populations.

No sex-based differences in odds of starting or time to treatment of generalized myasthenia gravis: A single center cohort study.

Females with generalized myasthenia gravis (gMG) report lower quality of life (QoL) and have more severe disease than males. Sex differences in disease characteristics exist, however whether there are sex differences in the treatment of gMG that may contribute to QoL disparities is unknown. Our objective is to determine whether there are sex differences in the treatment of gMG. We performed a single-center retrospective study of people diagnosed with gMG at the University of Calgary between 1997 and 2021. Primary outcome was proportion starting treatment and secondary outcome was time from diagnosis to treatment initiation. Treatments included pyridostigmine, prednisone, steroid sparing therapies (azathioprine, mycophenolate mofetil [MMF], methotrexate [MTX], or tacrolimus), intravenous immunoglobulin (IVIg), plasmapheresis, rituximab, eculizumab, cyclosporine, stem cell transplantation, and thymectomy. Multivariable logistic and Cox proportional hazards regression models were used to examine treatment associations with sex, adjusted for time from onset to diagnosis, age at diagnosis, presence of thymoma, and antibody status. A total of 179 people with gMG were included (41.9% female). Odds of starting treatment were not statistically associated with sex after adjustment for confounders and correction for multiple testing. Results of the secondary analysis using time to treatment initiation as the outcome were similar. We found no sex differences in odds of starting treatment or time to treatment initiation that might explain previously observed sex-based differences in QoL. Future work should capture physician and patient treatment preferences that may influence disease management.

Infective Endocarditis Among Women Who Inject Drugs

In the US and Canada, women comprise approximately one-third of people who inject drugs (PWID); however, clinical characteristics and outcomes of injection drug use complications in women are poorly described. To identify clinical characteristics and outcomes of infective endocarditis (IE) among women who inject drugs (WWID). This is a retrospective cohort study of PWID with definite IE (per 2023 Duke-International Society for Cardiovascular Infectious Diseases criteria) admitted from April 5, 2007, to March 15, 2018, at 5 tertiary-care hospitals in London, Ontario, and Regina, Saskatchewan, Canada. Data were analyzed from June 1, 2023, to August 2, 2024. Descriptive analyses were conducted for baseline characteristics at index hospitalization and stratified by sex. The primary outcome was the difference in 5-year survival between female and male PWID with IE. The secondary outcome was 1-year survival. Multivariable time-dependent Cox proportional hazards regression analyses were conducted for variables of clinical importance to evaluate 5-year mortality. Of 430 PWID with IE, 220 (51.2%) were women; of 332 non-PWID with IE, 101 (30.4%) were women. WWID with IE were younger than men (median [IQR] age, 31.5 [27.0-38.5] vs 38.5 [31.0-49.0] years), and 11 of 220 (5.0%) were pregnant at index hospitalization, although only 12 of 220 (5.5%) had contraceptive use documented. Women had a larger proportion of right-sided IE than men (158 of 220 women [71.8%] vs 113 of 210 men [53.8%]). WWID living in urban areas had higher mortality than WWID in rural areas (adjusted hazard ratio [aHR], 2.70; 95% CI, 1.15-6.34; P = .02). Overall mortality was lower among PWID referred for substance use disorder counseling in centers with inpatient services compared with centers with only outpatient referrals (aHR, 0.29; 95% CI, 0.17-0.51; P < .001). Overall mortality was lower with right-sided heart disease for both women (aHR, 0.44; 95% CI, 0.27-0.71; P < .001) and men (aHR, 0.22; 95% CI, 0.10-0.50; P < .001) and was higher with congestive heart failure for both women (aHR, 2.32; 95% CI, 1.29-4.18; P = .005) and men (aHR, 1.73; 95% CI, 1.07-2.79; P = .02). In this cohort of PWID with IE, women were overrepresented. Reasons for women's disproportionately high IE incidence need further study. Inpatient substance use disorder services, contraception counseling, and enhanced social support for WWID living in urban areas need to be prioritized.

Application of metabolic phase-specific modified nutrition risk in critically ill score: a prospective observational study in critically ill patients.

The prevalence of malnutrition in intensive care units (ICU) is high and can be caused by poor intake or absorption of nutrients in the digestive track, as well as disease-related inflammation. As strong catabolism restricts nutrient supply and potentially leads to subsequent malnutrition, appropriate nutrition should be provided based on the metabolic status. However, nutritional support strategies for considering the metabolic phase are not well established. Therefore, this study aimed to establish a strategy for nutritional support in each phase by implementing a phase-specific modified Nutrition Risk in Critically Ill (mNUTRIC) score. This prospective observational study was conducted on all adult patients admitted to the medical ICU for at least 36 h at Seoul National University Bundang Hospital between September 2020 and September 2022. Patient nutrition assessment (mNUTRIC score), clinical information, and nutritional supply (calories and proteins) were measured twice, in the acute phase (measured at 2 days) and late phase (measured at 7 days). The relationship between nutritional supply and 28-day mortality was analyzed using multiple logistic regression according to the mNUTRIC score in the acute and late phases. Risk factors related to 28-day mortality were analyzed using univariate and multivariate Cox proportional hazards regressions. Of the 631 patients admitted to the ICU during the study period, 613 were included in the acute phase and 361 patients were included in the late phase. Nutritional supply was associated with 28-day mortality, with high mNUTRIC scores in both the acute and late phases. Cox proportional hazards regression analysis demonstrated that a high mNUTRIC score [hazard ratio (HR) 3.20 and 2.52, respectively], lactate >2.5 mg/dL were independent risk factors in both the acute and late phases. In addition, Albumin <2.5 mg/dL, the presence of neoplasm, and the need for dialysis in the acute phase, calorie adequacy <0.7 in the late phase (HR, 2.19) were identified as additional risk factors. The mNUTRIC score is a suitable tool for identifying critically ill patients who benefit from nutritional support. Nutritional supply should be considered for patients with high mNUTRIC scores in both the acute and late phases; however, careful supply should be provided in the acute phase and sufficient supply should be provided in the late phase.

Weight-adjusted waist index is positively and linearly associated with all-cause and cardiovascular mortality in metabolic dysfunction-associated steatotic liver disease: findings from NHANES 1999-2018.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common chronic liver disease. Body mass index (BMI) is the most used obesity index but has important limitations. The weight-adjusted waist index (WWI) is a novel obesity metric and accurately reflects body composition. We explored the association of WWI with all-cause and cardiovascular disease (CVD) mortality in MASLD. Adult participants with MASLD were included from NHANES 1999-2018. WWI was calculated by dividing the waist circumference (WC) by the square root of body weight. MASLD was diagnosed by the presence of hepatic steatosis and at least one cardiometabolic risk factor in the absence of other causes of steatosis. A fatty liver index ≥60 suggested the presence of hepatic steatosis. Mortality data was obtained by prospectively linking to the National Death Index. Multivariate Cox proportional hazards regression analyses were used to explore these associations and multiple adjustment models were constructed including crude, partial, and fully adjusted models. After adjusting for all covariates including BMI, WWI remained positively and linearly associated with all-cause and CVD mortality in MASLD (hazard ratios [HR] 1.247 and 1.218, respectively). Higher WWI was associated with a significantly increased risk of mortality (both p for trend <0.05). There was an "obesity paradox" between BMI and all-cause mortality in MASLD, with significantly lower all-cause mortality in those with overweight/obesity compared to normal BMI (HR 0.625 and 0.596, respectively, p for trend = 0.024), and no association between BMI and CVD mortality. Interaction analyses indicated that these associations were influenced by several demographic variables and disease status. Time-dependent receiver operating characteristic curves indicated that the predictive value of WWI for mortality in MASLD was higher than that of BMI, WC, and waist-to-height ratio across all follow-up durations. WWI was positively and linearly associated with all-cause and CVD mortality in MASLD, whereas BMI did not accurately reflect mortality risk. WWI provided the optimal predictive value for mortality compared to traditional obesity indicators. These findings emphasize the potential use of WWI as a novel obesity indicator for mortality risk assessment, stratification, and prevention in MASLD.

Occurrence and predictors of laboratory abnormalities during outpatient parenteral antimicrobial therapy – A multicenter cohort study to inform laboratory test monitoring

ObjectivesEvidence on the optimal frequency of laboratory testing during outpatient parenteral antimicrobial therapy (OPAT) is lacking. Therefore, we investigated how often and when laboratory abnormalities occur during OPAT and which factors are associated with these abnormalities. MethodsWe performed a multicenter cohort study in four Dutch hospitals among adult patients receiving OPAT and collected routinely obtained laboratory test results. Incidence and incidence rates were calculated for various laboratory abnormalities. Survival analysis was performed to visualize the time to the first occurrence of laboratory abnormalities and Poisson regression analysis to compare the number of abnormalities in the first and second 30 OPAT days among patients receiving OPAT for ≥60 days. Predictors were identified using a multivariable Cox proportional hazard regression model. Results45.1% of 1152 included patients developed laboratory abnormalities, but only 2% led to OPAT discontinuation. Hepatotoxicity was most common (33.9 events/1000 OPAT days), with a time-dependent decrease in the occurrence of the first hepatotoxic event, while hypokalemia was rare (1.7 events/1000 OPAT days). In the subgroup of patients receiving ≥60 days of OPAT, nephrotoxicity was more common in days 31-60. We observed partly toxicity-specific associations between antibiotic type, concomitant medication, baseline laboratory values, patient characteristics, and the occurrence of laboratory abnormalities. ConclusionsWhile laboratory abnormalities are frequently observed during OPAT, they rarely lead to discontinuation of OPAT. Specific patient, treatment and laboratory characteristics were associated with the occurrence of laboratory abnormalities. Based on our results, we recommend a more personalized laboratory monitoring policy with less blood sampling.

Hsa_circ_0079929 in lung adenocarcinoma and its biological implications in lung adenocarcinoma progression

BackgroundThis report investigated the expression, prognostic and biological implications of hsa_circ_0079929 in lung adenocarcinoma, which was based on clinical and experimental data.MethodsPatients with lung adenocarcinoma were screened and their clinical data and tissues (including cancerous tissues and adjacent normal tissues) were collected. The total RNA in tissues and cell lines was analyzed to obtained hsa_circ_0079929 level. The clinical significance was examined using the Chi-square test, Multi-variate Cox proportional hazards regression, and Kaplan-Meier curve. Cell malignant features were evaluated from three aspects (proliferation, migration, and invasion), detected by CCK-8 and Transwell methods.ResultsHsa_circ_0079929 raised in expression level in lung adenocarcinoma. This upregulation of hsa_circ_0079929 was correlated with adverse clinical parameters and poor outcome in terms of overall survival, resulting in an independent prognostic purpose molecular for overall survival. Overexpression of hsa_circ_0079929 could contribute to cell proliferation/migration/invasion, whereas its knockdown could inhibit these malignant features. Hsa_circ_0079929 was a molecular decoy for miR-1184 in lung adenocarcinoma cells.ConclusionsHsa_circ_0079929 could promote the malignant features of lung adenocarcinoma cells and may aid the follow up and therapeutic target discovery of lung adenocarcinoma.