Cox's Hazards Regression Model Research Articles

Initiation of Alcohol Consumption Among the Tribal Male Adolescents in Dooars Region of West Bengal: A Failure Event Analysis Approach.

Alcohol consumption is a significant social and health problem among tribal male adolescents. The Dooars region of West Bengal has the highest concentration of the tribal population. This study aimed to examine the role of various factors in the early initiation of alcohol consumption among tribal male adolescents. This study relied on primary data and included 600 tribal adolescents. To fulfil the objective, the Cox regression hazard model was employed. Additionally, hazard rates were calculated to identify the changing hazard rates over a specific age. The Kaplan-Meier failure graph was also used to illustrate the occurrence of alcohol consumption events among different groups of tribal adolescents. The risk of alcohol consumption was higher among tribal adolescents who dropped out of the educational system (HR: 2.94), did not participate in outdoor games (HR: 3.10), worked for pay (HR: 3.23), smoked (HR: 12.55), drank traditional liquor (HR: 3.61), and had siblings (HR: 4.27) or peers (HR: 3.60) who used substances or fathers who consumed alcohol (HR: 3.80). Unsupervised time with peers (HR: 3.61) and stress (HR: 3.61) also increased the risk of alcohol consumption. In contrast, self-esteem was found to be protective (HR: 0.93). The government has introduced various interventions and schemes to reduce alcohol consumption, but more targeted actions are needed at the household and individual levels. In the tea gardens of the Dooars region, NGOs and the government should promote education, organize extracurricular activities for adolescents' holistic development, and raise awareness in tribal communities about the harmful effects of alcohol consumption.

Interaction between Extreme Temperature Events and Fine Particulate Matter on Cardiometabolic Multimorbidity: Evidence from Four National Cohort Studies.

Accumulating evidence linked extreme temperature events (ETEs) and fine particulate matter (PM2.5) to cardiometabolic multimorbidity (CMM); however, it remained unknown if and how ETEs and PM2.5 interact to trigger CMM occurrence. Merging four Chinese national cohorts with 64,140 free-CMM adults, we provided strong evidence among ETEs, PM2.5 exposure, and CMM occurrence. Performing Cox hazards regression models along with additive interaction analyses, we found that the hazards ratio (HRs) of CMM occurrence associated with heatwave and cold spell were 1.006-1.019 and 1.063-1.091, respectively. Each 10 μg/m3 increment of PM2.5 concentration was associated with 17.9% (95% confidence interval: 13.9-22.0%) increased risk of CMM. Similar adverse effects were also found among PM2.5 constituents of nitrate, organic matter, sulfate, ammonium, and black carbon. We observed a synergetic interaction of heatwave and PM2.5 pollution on CMM occurrence with relative excess risk due to the interaction of 0.999 (0.663-1.334). Our study provides novel evidence that both ETEs and PM2.5 exposure were positively associated with CMM occurrence, and the heatwave interacts synergistically with PM2.5 to trigger CMM.

Predictive value of C reactive protein (CRP) and D-dimer in patients with advanced cervical cancer treated with sintilimab and anlotinib.

e17525 Background: The Sintilimab plus Anlotinib in patients with advanced cervical cancer trial was a single-arm, phase II study that showed promising activity of the programmed death-1 (PD-1) inhibitor sintilimab plus the vascular endothelial growth factor receptor inhibitor Anlotinib in patients with advanced cervical cancer. We aimed to identify prognostic values of inflammation biomarkers and coagulation biomarkers in advanced cervical cancer treated with Sintilimab and Anlotinib. Methods: We conducted a post-hoc analysis of the data from the ALTER-C201 study (Clinical trial information: ChiCTR1900023015). The predictive value of coagulation variables and inflammation variables was evaluated by receiver operating characteristic (ROC) curves. Through Cox hazards regression models, prognostic factors were determined for overall survival (OS). Survival curves were visualized by Kaplan–Meier method and compared through Log-rank analysis. Results: We involved 41 patients and followed up for 38.0 (range, 0.6–44.0) months. According to the ROC curve, the predictive values of baseline CRP and D-dimer are better than other indicators, with area under the curve (AUC) values of 0.748 and 0.848, respectively. The cut-off values for D-dimer and CRP are 1.75ug/ml and 10.9mg/L, respectively. Through regression analysis, we demonstrated that CRP (HR 2.591; 95%CI 1.099–6.106; P = 0.030) and D-dimer (HR 2.669; 95%CI 1.154–6.173; P = 0.022) were independent prognostic factors. Compared to patients with CRP ≥ 10.9mg/L, those with CRP < 10.9mg/L have a longer OS (28.93 months, 95% CI, 15.23 to not reached v 10.57 months, 95% CI, 6.14 to not reached; log-rank test, P = 0.007). Compared to patients with D-dimer ≥ 1.75ug/ml, those with D-dimer < 1.75ug/ml have a longer OS (28.93 months, 95% CI, 17.09 to not reached v 10.73 months, 95% CI, 4.63 to not reached; log-rank test, P = 0.005). Conclusions: CRP and D-dimer predict survival in advanced cervical cancer patients undergoing combined ICI/ VEGF-TKI therapy. We advocate further work to validate utilisation of CRP and D-dimer as prognostic biomarkers for advanced cervical cancer in clinical practice.

Association between red cell distribution width and all-cause mortality in patients with breast cancer: A retrospective analysis using MIMIC-IV 2.0.

Investigating the association between red cell distribution width (RDW) and all-cause mortality in patients with breast cancer, to evaluate the potential clinical prognostic value of RDW. Based on the RDW index, patients with breast cancer in the Medical Information Mart for Intensive Care (MIMIC-IV) database were categorized into quartiles. The primary outcomes included in-hospital mortality from all causes during the first six months, the first year, and the first three years. Cox hazards regression and restricted cubic spline (RCS) models were developed to investigate the effects of RDW on primary outcomes. The study included 939 patients (female). The 6-month, 1-year, and 3-year mortality rates were 14.0%, 21.4%, and 28.4%, respectively. Multivariate Cox proportional hazards analyses demonstrated that RDW exhibited an autonomous association with an increased risk of all-cause mortality. After adjusting for confounders, higher RDW quartiles were significantly associated with 6-month mortality (adjusted hazard ratio (HR), 3.197; 95% confidence interval (CI), 1.745-5.762; P < 0.001), 1-year mortality (adjusted HR, 2.978; 95% CI, 1.867-4.748; P < 0.001), and 3-year mortality (adjusted HR, 2.526; 95% CI, 1.701-3.750; P < 0.001). The RCS curves demonstrated that high RDW (> 14.6) was associated with a greater risk of all-cause mortality. Subgroup analyses revealed no statistically significant differences in the interactions between the subgroups. The study revealed a highly pronounced relationship between RDW and overall mortality, indicating its potential as an autonomous prognostic factor for increased mortality among patients with breast cancer.

NDC80 Kinetochore Complex Serves as a Potential Prognostic Predictor and Correlates with Immune Infiltrates in Epithelial OvarianCancer Patients.

This study focuses on evaluating the prognostic value of the NDC80 kinetochore complex in ovarian cancer (OC) using the Gene Expression Omnibus (GEO) database and the Cancer Genome Atlas (TCGA) database and reveals the relationship between the NDC80 complex and immune infiltrates in OC. We collected data on NDC80 complex expression levels in both OC tissues and non-OC ovarian tissues from the University of California Santa Cruz Xena and GEO databases. The clinicopathological characteristics correlated with overall survival were analyzed using Cox regression and the Kaplan-Meier method. Gene Ontology analysis, Kyoto Encyclopedia of Genes and Genomes analysis, gene set enrichment analysis and CIBERSORT were performed using data from TCGA database. Immunohistochemical staining was used to verify the higher expression level of NUF2 protein in OC in vitro. Meanwhile, we utilized the Tumor Immune Estimation Resource to analyze the correlation between the NDC80 complex and immunocyte infiltration. The NDC80 complex expression level was prominently higher in OC tissues than in non-OC ovarian tissues and correlated with advanced histologic grade characteristics. Gene expression profiling interactive analysis and the Kaplan-Meier survival curve uncovered a close relationship between high expression of the NDC80 complex and poor overall survival in OC patients. The univariate Cox regression hazard model produced age, pathologic stage, tumor status, primary therapy outcome, SPC24 expression level, and Karnofsky performance score as prognostic factors for OC patients. NDC80 complex expression levels were highly associated with immune cell infiltration, showing NK CD56 bright cells and NK cells with a negative correlation and T helper 2 cells with a positive correlation (P<0.05). These findings provide evidence that an increased expression level of the NDC80 complex is closely associated with the progression of OC and could also serve as a novel target of immunotherapy in OC.

Significance of NKX2-1 as a biomarker for clinical prognosis, immune infiltration, and drug therapy in lung squamous cell carcinoma.

This study was performed to determine the biological processes in which NKX2-1 is involved and thus its role in the development of lung squamous cell carcinoma (LUSC) toward improving the prognosis and treatment of LUSC. Raw RNA sequencing (RNA-seq) data of LUSC from The Cancer Genome Atlas (TCGA) were used in bioinformatics analysis to characterize NKX2-1 expression levels in tumor and normal tissues. Survival analysis of Kaplan-Meier curve, the time-dependent receiver operating characteristic (ROC) curve, and a nomogram were used to analyze the prognosis value of NKX2-1 for LUSC in terms of overall survival (OS) and progression-free survival (PFS). Then, differentially expressed genes (DEGs) were identified, and Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene Ontology (GO), and Gene Set Enrichment Analysis (GSEA) were used to clarify the biological mechanisms potentially involved in the development of LUSC. Moreover, the correlation between the NKX2-1 expression level and tumor mutation burden (TMB), tumor microenvironment (TME), and immune cell infiltration revealed that NKX2-1 participates in the development of LUSC. Finally, we studied the effects of NKX2-1 on drug therapy. To validate the protein and gene expression levels of NKX2-1 in LUSC, we employed immunohistochemistry(IHC) datasets, The Gene Expression Omnibus (GEO) database, and qRT-PCR analysis. NKX2-1 expression levels were significantly lower in LUSC than in normal lung tissue. It significantly differed in gender, stage and N classification. The survival analysis revealed that high expression of NKX2-1 had shorter OS and PFS in LUSC. The multivariate Cox regression hazard model showed the NKX2-1 expression as an independent prognostic factor. Then, the nomogram predicted LUSC prognosis. There are 51 upregulated DEGs and 49 downregulated DEGs in the NKX2-1 high-level groups. GO, KEGG and GSEA analysis revealed that DEGs were enriched in cell cycle and DNA replication.The TME results show that NKX2-1 expression was positively associated with mast cells resting, neutrophils, monocytes, T cells CD4 memory resting, and M2 macrophages but negatively associated with M1 macrophages. The TMB correlated negatively with NKX2-1 expression. The pharmacotherapy had great sensitivity in the NKX2-1 low-level group, the immunotherapy is no significant difference in the NKX2-1 low-level and high-level groups. The analysis of GEO data demonstrated concurrence with TCGA results. IHC revealed NKX2-1 protein expression in tumor tissues of both LUAD and LUSC. Meanwhile qRT-PCR analysis indicated a significantly lower NKX2-1 expression level in LUSC compared to LUAD. These qRT-PCR findings were consistent with co-expression analysis of NKX2-1. We conclude that NKX2-1 is a potential biomarker for prognosis and treatment LUSC. A new insights of NKX2-1 in LUSC is still needed further research.

Waistline to thigh circumference ratio as a predictor of MAFLD: a health care worker study with 2-year follow-up

BackgroundThis study aimed to determine whether the waist-to-thigh ratio (WTTR) is associated with the incidence of metabolic-associated fatty liver disease (MAFLD) in health care workers.MethodsThere were 4517 health care workers with baseline data and results from 2 follow-up examinations. We divided the subjects into 3 groups according to baseline WTTR and used the Cox hazard regression model to estimate MAFLD risk.ResultsThe WTTRs were categorized by tertiles at baseline using the values 1.58 and 1.66. Patients with higher WTTR tended to have significantly greater values for the following factors, body mass index (BMI), fasting blood glucose (FPG), systolic blood pressure, diastolic blood pressure, total cholesterol (TC), triglycerides (TG), low-density lipoprotein-cholesterol (LDL-C) and neck circumference. The incidence of MAFLD significantly increased with increasing WTTR tertiles (5.74%, 12.75% and 22.25% for the first, second and third tertiles, respectively, P < 0.05 for trend). Kaplan-Meier(K-M) survival analysis revealed a significant tendency towards increased MAFLD risk with increasing WTTR tertile. In the fully adjusted model, the hazard ratios (95% CIs) for MAFLD in the second, third WTTR tertiles compared with the first quartile were 2.17(1.58,2.98), 3.63(2.70,4.89), respectively, third neck circumference tertiles compared with the first quartile were 2.84(1.89,4.25), 8.95(6.00,13.35), respectively. Compared with those of individuals with a BMI > 23 kg/m2, the associations between WTTR and MAFLD incidence were more pronounced in subjects with a BMI < 23 kg/m2. Similarly, the difference in neck circumference was more pronounced in these patients with a BMI < 23 kg/m2.ConclusionsOur results revealed that the WTTR is an independent risk factor for MAFLD, and there was a dose‒response relationship between the WTTR and MAFLD risk. The neck circumference was significantly different in subjects with a BMI < 23 kg/m2. This approach provides a new way to predict the incidence rate of MAFLD.

Pan‑immune‑inflammation value as a novel prognostic biomarker in nasopharyngeal carcinoma.

The pan-immune-inflammation-value (PIV) is a comprehensive biomarker that integrates different peripheral blood cell subsets. The present study aimed to evaluate the prognostic ability of PIV in patients with nasopharyngeal carcinoma (NPC) undergoing chemoradiotherapy. PIV was assessed using the following equation: (Neutrophil count × platelet count × monocyte count)/lymphocyte count. The Kaplan-Meier method and Cox hazards regression models were used for survival analyses. The optimal cut-off values for PIV and systemic immune-inflammation index (SII) were determined using receiver operating characteristic analysis to be 428.0 and 1032.7, respectively. A total of 319 patients were recruited. Patients with a low baseline PIV (≤428.0) accounted for 69.9% (n=223) and patients with a high baseline PIV (>428.0) accounted for 30.1% (n=96). Compared with patients with low PIV, patients with a high PIV had significantly worse 5-year progression-free survival [PFS; 66.8 vs. 77.1%; hazard ratio (HR), 1.97; 95% confidence interval (CI), 1.22-3.23); P=0.005] and 5-year overall survival (OS; 68.7 vs. 86.9%, HR, 2.71; 95% CI, 1.45-5.03; P=0.001). PIV was also a significant independent prognostic indicator for OS (HR, 2.19; 95% CI, 1.16-4.12; P=0.016) and PFS (HR, 1.86; 95% CI, 1.14-3.04; P=0.013) and outperformed the SII in multivariate analysis. In conclusion, the PIV was a powerful predictor of survival outcomes and outperformed the SII in patients with NPC treated with chemoradiotherapy. Prospective validation of the PIV should be performed to better stratify radical treatment of patients with NPC.

Comprehensive prognostic and immune analysis of sterol O-acyltransferase 1 in patients with hepatocellular carcinoma.

Sterol O-acyltransferase 1 (SOAT1) is an important target in the diagnosis and treatment of liver cancer. However, the prognostic value of SOAT1 in patients with hepatocellular carcinoma (HCC) is still not clear. To investigate the correlation of SOAT1 expression with HCC, using RNA-seq and gene expression data of The Cancer Genome Atlas (TCGA)-liver hepatocellular carcinoma (LIHC) and pan-cancer. The correlation between SOAT1 expression and HCC was analyzed. Cox hazard regression models were conducted to investigate the prognostic value of SOAT1 in HCC. Overall survival and disease-specific survival were explored based on TCGA-LIHC data. Biological processes and functional pathways mediated by SOAT1 were characterized by gene ontology (GO) analysis and the Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis of differentially expressed genes. In addition, the protein-protein interaction network and co-expression analyses of SOAT1 in HCC were performed to better understand the regulatory mechanisms of SOAT1 in this malignancy. SOAT1 and SOAT2 were highly expressed in unpaired samples, while only SOAT1 was highly expressed in paired samples. The area under the receiver operating characteristic curve of SOAT1 expression in tumor samples from LIHC patients compared with para-carcinoma tissues was 0.748, while the area under the curve of SOAT1 expression in tumor samples from LIHC patients compared with GTEx was 0.676. Patients with higher SOAT1 expression had lower survival rates. Results from GO/KEGG and gene set enrichment analyses suggested that the PI3K/AKT signaling pathway, the IL-18 signaling pathway, the calcium signaling pathway, secreted factors, the Wnt signaling pathway, the Jak/STAT signaling pathway, the MAPK family signaling pathway, and cell-cell communication were involved in such association. SOAT1 expression was positively associated with the abundance of macrophages, Th2 cells, T helper cells, CD56bright natural killer cells, and Th1 cells, and negatively linked to the abundance of Th17 cells, dendritic cells, and cytotoxic cells. Our findings demonstrate that SOAT1 may serve as a novel target for HCC treatment, which is helpful for the development of new strategies for immunotherapy and metabolic therapy.

Abstract 6151: Relationship between polygenic risk score, lifestyle factors, and colorectal cancer risk

Abstract Although heritable factors are estimated to explain up to 35% of colorectal cancers (CRC), most are diagnosed in people without a family history of CRC suggesting that inherited genetic variants, environmental factors, or a combination of both, contribute to CRC risk. We explored the relationship between a polygenic risk score (PRS) for CRC risk and lifestyle risk factors to understand whether individuals with higher genetic risk, who do not develop CRC, engage in healthier lifestyle behaviors, or conversely, whether those with lower genetic risk, who do develop CRC, engage in riskier behaviors in the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. Using summary statistics obtained from a large independent GWAS meta-analysis of CRC by the GECCO consortium, we developed a genome-wide PRS for CRC using SBayesR and applied it to participants of European ancestry genotyped in the PLCO Trial (n=74,396). For all subjects, we computed an environmental (E) score based on 19 lifestyle risk factors for CRC, a WCRF/AICR score that measured adherence to the 2018 Cancer Prevention recommendations, and a 2015 healthy eating index (HEI) with higher values indicating healthier lifestyle profiles. We used t-tests to evaluate differences in lifestyle scores between CRC-free participants in the highest quartile of PRS and incident CRC cases in the lowest quartile of PRS. To examine the correlations between the PRS and lifestyle scores, we performed multivariable linear regression models regressing PRS on each lifestyle score. We used multivariable Cox hazards regression models to compute hazard ratios and 95% confidence intervals for CRC risk; multiplicative interactions between PRS and lifestyle scores were evaluated using the Wald test for the interaction terms. During the 15 years follow-up period, a total of 1,052 CRC cases were diagnosed. Individuals in the highest quartile of PRS who remained cancer-free were more likely to engage in healthier behaviors than those in the lowest quartile of PRS who were diagnosed with incident CRC (E-score: -0.01 vs. -0.18, WCRF/AICR score: -0.05 vs. -0.32, HEI score: 0.06 vs. -0.13); however, differences were not statistically significant (P value: 0.1 to 0.4). PRS and lifestyle scores were significantly (all P &amp;lt;0.0001), albeit weakly (β: -0.02 to -0.03), associated among participants who remained CRC-free but not among CRC cases (P: 0.1 to 0.3). PRS-lifestyle score interactions were not statistically significant (P: 0.2 to 0.4). Although the differences and multiplicative interaction models were not statistically significant, we found that individuals with a higher PRS who remained CRC-free were slightly more likely to engage in healthier behaviors than those at a lower genetic score who developed CRC. Additional studies with larger sample size are warranted to further explore the interplay between genetic risk and lifestyle factors related to CRC risk. Citation Format: Wen-Yi Huang, Erikka Loftfield, Rebecca Landy, Difei Wang, Hormuzd A. Katki, Jianxin Shi, Lingxiao Wang, Mitchell J. Machiela, Neal D. Freedman, Sonja I. Berndt. Relationship between polygenic risk score, lifestyle factors, and colorectal cancer risk [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6151.

Association of serum magnesium levels with renal prognosis in patients with chronic kidney disease.

Magnesium deficiency is associated with various health conditions, but its impact on the progression of chronic kidney disease (CKD) remains unclear. This study aimed to investigate the association between serum magnesium levels and prognosis of renal function in CKD patients. This is an analysis of the Japan Chronic Kidney Disease Database Ex (J-CKD-DB-Ex), which is a multicenter prospective cohort including CKD patients enrolled from January 1, 2014 to December 31, 2020. We included adult outpatients with CKD stage G3 and G4 at the time of initial magnesium measurement. Patients were classified by magnesium levels as low (<1.7mg/dl), normal (1.7-2.6mg/dl), or high (>2.6mg/dl). The primary outcomes were the composite of an eGFR<15ml/min/1.73m2 or a ≥30% reduction in eGFR from the initial measurement, which was defined as CKD progression. We applied the Kaplan-Meier analysis and Cox regression hazard model to examine the association between magnesium levels and CKD progression. The analysis included 9868 outpatients during the follow-up period. The low magnesium group was significantly more likely to reach CKD progression. Cox regression, adjusting for covariates and using the normal magnesium group as the reference, showed that the hazard ratio for the low magnesium group was 1.20 (1.08-1.34). High magnesium was not significantly associated with poor renal outcomes compared with normal magnesium. Based on large real-world data, this study demonstrated that low magnesium levels are associated with poorer renal outcomes.

Association between comorbidities and survival in patients with metastatic urothelial carcinoma treated with pembrolizumab.

This study aims to investigate the relationship between comorbidities and survival in patients with mUC treated with pembrolizumab as a second-line treatment. From February 2018 to October 2021, we analyzed the data of 185 consecutive patients with metastatic UC who received pembrolizumab as second-line therapy at The Jikei University Hospital and five affiliated hospitals. We used the Charlson Comorbidity Index (CCI) to assess the comorbidities. The outcomes of interest were progression-free survival (PFS) and overall survival (OS). To compare the survival differences, inverse probability of treatment weighting (IPTW)-adjusted Kaplan-Meier curves and the IPTW-adjusted Cox regression hazards model were used. After IPTW adjustment, patient characteristics were well-balanced between patients with high CCI and those with low CCI. The IPTW-adjusted Kaplan-Meier curves of PFS and OS based on CCI revealed that the patients with high CCI (2 or more) had a shorter PFS (median, 1.6 vs. 2.8months) and a shorter OS (median, 12.4 vs. 18.8months) (0-1). Similarly, in the IPTW-adjusted Cox regression hazards model, patients with high CCI had significantly shorter PFS [HR, 1.84 (95% CI 1.26-2.68; p = 0.002)] and OS [HR, 1.98 (95% CI 1.20-3.27; p = 0.008)] than those with lower CCI. High CCI was associated with a higher risk of disease progression as well as overall mortality in mUC patients treated with second-line pembrolizumab.

Cox proportional hazard-model application: time to cervical cancer screening among women living with HIV in South Africa

BackgroundThere is an increased risk of cervical cancer among women living with HIV. While studies have long examined the association between cervical cancer among women with HIV, no study has examined the time taken for women with HIV to undergo cervical cancer screening as well as the hazard thereof in South Africa.MethodsThe study used cross-sectional data from the 2016 South Africa Demographic and Health Survey. To allow for longitudinal analysis and to address the issue of right-censoring, the data were reformatted to a person-data file. The selection criteria were limited to women living with HIV (WLHIV) who had also responded to the question on cervical cancer screening. Descriptive statistics were employed to show the levels of HIV among women aged 15 and older in South Africa. Additionally, Kaplan‒Meier curves were employed to investigate the time to CCS by WLHIV in South Africa. Thereafter, an unadjusted Cox hazards regression model was employed to examine the hazard of undergoing CCS among WLHIV. Finally, it employed an adjusted model to examine the hazard of CCS among WLHIV while adjusting for other factors.ResultsNineteen percent (n = 1,159) of the women who participated in the study tested positive for HIV. Herein, it was found that the risk of CCS among WLHIV began at the age of approximately 19 years. Thereafter, the hazard of undergoing CCS among WLHIV began to decrease at 58 years. There was a significant association between CCS and WLHIV. Additionally, several covariates were found to be significantly associated with HIV. These were race, province, area of residence, marriage, educational attainment, employment, alcohol consumption, perceived health perception, and health insurance.ConclusionThe hazard of CCS was lower among WLHIV compared to WLHIV who did not undergo CCS in South Africa. This puts HIV-positive women at risk of increased morbidity and mortality from potential cervical cancer and HIV comorbidity due to CCS deficits within this group. This is because they are susceptible to HPV and subsequent cervical cancer due to a compromised immune system. HIV-positive women need to routinely undergo CCS every 12 months from baseline for 3 years. Thereafter, they should undergo CCS once every 3 years to reduce their risk of developing the disease.

Association between age-related macular degeneration and risk of incident cancer

Background/aimsAge-related macular degeneration (AMD) and cancer may share similar risk factors, indicating possible common pathogenic pathways. We aimed to describe the site-specific cancer risk based on the relationship of AMD...

A293 PREVALENCE OF METABOLIC ASSOCIATED STEATOTIC LIVER DISEASE AND ITS IMPACT ON ADVERSE OUTCOMES IN PRIMARY BILIARY CHOLANGITIS PATIENTS

Abstract Background Metabolic associated steatotic liver disease (MASLD) is highly prevalent among Canadians, thus making coexistence with other liver diseases inevitable. Primary biliary cholangitis (PBC) is the most common autoimmune liver disease diagnosed in one out of 1,000 women above 40. The impact of concomitant MASLD on liver outcomes in patients with PBC is unclear. Aims We aimed to determine the prevalence of MASLD among patients with PBC and the association between concomitant liver disease and adverse liver outcomes. Methods PBC patients diagnosed between 1984 and 2023 and followed up at the University of Alberta with vibration-controlled transient elastography data available were included. MASLD was diagnosed if the Controlled Attenuation Parameter ≥288 dB/min with at least one cardio-metabolic criteria, based on elevated body mass index, blood pressure, and abnormal glycemic and lipid tests. Proportions were compared using chi-square, medians – Mann-Whitney test. We utilized a Cox hazards regression model to calculate hazard ratios and determine associations between MASLD and the development of cirrhosis or decompensation, need for liver transplant, or death. Results A total of 115 patients (87.0% females, age at diagnosis 52.3±11.5 years) followed over a median duration of 11.0 [range 0.1-39.7] years) were included. The prevalence of MASLD (33.0% [n=38]) was higher in females than males (35.0%[n=35] vs. 20.0%[n=3]; p=0.249). The prevalence of cirrhosis at diagnosis was twice as high among PBC patients with MASLD than those without (26.3%[n=10] vs. 13.0%[n=10]; p=0.076). No difference was observed in the frequency of decompensation at diagnosis (8.8%[n=3] vs. 6.3%[n=4]; p=0.638). Cirrhosis frequency (50.0% vs. 50.6%; p=0.948) and decompensation (38.2% vs.37.1%; p=0.912) over the course of the disease were similar between PBC patients with and without MASLD. There was no association between MASLD and development of cirrhosis (HR0.51, 95%CI 0.23-1.13; p=0.095), decompensation (HR0.81, 95%CI 0.37-1.76; p=0.596), liver transplantation (HR0.72, 95%CI 0.19-2.72; p=0.628), or death (HR0.69, 95%CI 0.22-2.16; p=0.519). PBC patients with MASLD have comparable event-free (median 10.7 [3.1-30.8] vs. 10.7 [0.1-23.3] years; p=0.684) and overall survival (median 11.3 [3.2-39.7 vs. 10.7 [0.1-23.3] years; p=0.456). Conclusions Every third patient with PBC had MASLD, which tended to be more prevalent among females. We did not observe any significant differences in the development of adverse liver outcomes between patients with PBC and concurrent MASLD in comparison to those without. Studies with larger sample sizes are necessary to further explore the potential impact of MASLD on liver outcomes. Funding Agencies None

Nomogram to Predict the Prognosis of Oligodendroglioma Patients Undergoing Postoperative Adjuvant Chemoradiotherapy

ObjectiveThe aim of this study was to develop a prognostic nomogram for predicting the prognosis of oligodendroglioma patients receiving combined chemoradiotherapy (CRT) after surgery. MethodsThe study used data from the Surveillance, Epidemiology, and End Results (SEER) database between 2000 and 2019. The patients were randomly divided into a development cohort (700 patients) and a validation cohort (244 patients) in a 7:3 ratio. The Cox hazards regression model was used to identify predictors, and a nomogram was constructed to visualize the prognosis. The performance of the prognostic nomogram was evaluated using the consistency index (C-index), clinical net benefit, and calibration. ResultsThe nomogram included five variables: age, marital status, tumor size, site of lesions, and surgery type. The C-index of the training set and validation set were 0.77 and 0.68, respectively. The calibration plots showed that the nomogram was in good agreement with the actual observation. The clinical decision curve indicated that the nomogram had a good clinical net benefit in oligodendroglioma patients receiving CRT after surgery. ConclusionsThis study established and verified a prognostic nomogram for a large cohort of oligodendroglioma patients receiving CRT after surgery based on the SEER database. The nomogram may help clinicians provide personalized treatment services and clinical decisions for patients.

Abstract TP279: Atrial Cardiopathy and Intracerebral Hemorrhage in Patients With Acute Ischemic Stroke

Background and Purpose: Atrial cardiopathy is recognized as a potential contributor to cardiovascular events. Whether atrial cardiopathy is associated with the risk of intracranial hemorrhage in acute ischemic stroke (AIS) remains uncertain. We aimed to investigate the relationship between atrial cardiopathy and intracerebral hemorrhage risk in patients with AIS. Methods: This single-center observational study included 631AIS patients (median age: 70 years [IQR] 61-78; 31.5% female). Atrial cardiopathy was defined as any presence of ≥1: left atrial diameter ≥ 52 mm (males) or ≥ 47 mm (females), elevated P-wave terminal force in V1 (PTFV1) &gt; 5000 μV·ms, or serum NT-proBNP &gt;250 pg/ml. Our primary outcomes included any intracranial hemorrhage (ICH) and symptomatic ICH (sICH) during follow-up. Our secondary outcome was ischemic stroke recurrence. The association between atrial cardiopathy and outcomes was analyzed using Cox hazards regression models. Results: During a median of 1.57 years follow-up, 67 (10.6%) AIS patients experienced any ICH, and 18 (2.9%) patients developed sICH. In Kaplan-Meier analysis, the rate of any ICH or sICH during follow-up was more frequent in patients with atrial cardiopathy compared to those without (log-rank test, p &lt; 0.001, respectively; Figure 1 ). After adjustment for CHA 2 DS 2 -VAS C , atrial cardiopathy was significantly associated with the risk of any ICH (HR 3.99, 95% CI 2.20-7.22, p &lt; 0.001) or sICH (HR 7.93, 95% CI 1.77-35.51, p = 0.007). There was no significant association of ischemic stroke recurrence with atrial cardiopathy. Conclusions: This investigation suggests a potential link between atrial cardiopathy and an increased risk of intracranial hemorrhage in patients with acute ischemic stroke.

Neighborhood social vulnerability and disparities in time to kidney cancer surgical treatment and survival in Arizona.

Hispanics and American Indians (AI) have high kidney cancer incidence and mortality rates in Arizona. This study assessed: (1) whether racial and ethnic minority patients and patients from neighborhoods with high social vulnerability index (SVI) experience a longer time to surgery after clinical diagnosis, and (2) whether time to surgery, race and ethnicity, and SVI are associated with upstaging to pT3/pT4, disease-free survival (DFS), and overall survival (OS). Arizona Cancer Registry (2009-2018) kidney and renal pelvis cases (n = 4592) were analyzed using logistic regression models to assess longer time to surgery and upstaging. Cox-regression hazard models were used to test DFS and OS. Hispanic and AI patients with T1 tumors had a longer time to surgery than non-Hispanic White patients (median time of 56, 55, and 45 days, respectively). Living in neighborhoods with high (≥75) overall SVI increased odds of a longer time to surgery for cT1a (OR 1.54, 95% CI: 1.02-2.31) and cT2 (OR 2.32, 95% CI: 1.13-4.73). Race and ethnicity were not associated with time to surgery. Among cT1a patients, a longer time to surgery increased odds of upstaging to pT3/pT4 (OR 1.95, 95% CI: 0.99-3.84). A longer time to surgery was associated with PFS (HR 1.52, 95% CI: 1.17-1.99) and OS (HR 1.63, 95% CI: 1.26-2.11). Among patients with cT2 tumor, living in high SVI neighborhoods was associated with worse OS (HR 1.66, 95% CI: 1.07-2.57). High social vulnerability was associated with increased time to surgery and poor survival after surgery.

Enhanced exclusive enteral nutrition delivery during the first 7 days is associated with decreased 28-day mortality in critically ill patients with normal lactate level: a post hoc analysis of a multicenter randomized trial

Background and aimsExclusive enteral nutrition (EN) is often observed during the first week of ICU admission because of the extra costs and safety considerations for early parenteral nutrition. This study aimed to assess the association between nutrition intake and 28-day mortality in critically ill patients receiving exclusive EN.MethodsThis is a post hoc analysis of a cluster-randomized clinical trial that assesses the effect of implementing a feeding protocol on mortality in critically ill patients. Patients who stayed in the ICUs for at least 7 days and received exclusive EN were included in this analysis. Multivariable Cox hazard regression models and restricted cubic spline models were used to assess the relationship between the different doses of EN delivery and 28-day mortality. Subgroups with varying lactate levels at enrollment were additionally analyzed to address the potential confounding effect brought in by the presence of shock-related hypoperfusion.ResultsOverall, 1322 patients were included in the analysis. The median (interquartile range) daily energy and protein delivery during the first week of enrollment were 14.6 (10.3–19.6) kcal/kg and 0.6 (0.4–0.8) g/kg, respectively. An increase of 5 kcal/kg energy delivery was associated with a significant reduction (approximately 14%) in 28-day mortality (adjusted hazard ratio [HR] = 0.865, 95% confidence interval [CI]: 0.768–0.974, P = 0.016). For protein intake, a 0.2 g/kg increase was associated with a similar mortality reduction with an adjusted HR of 0.868 (95% CI 0.770–0.979). However, the benefits associated with enhanced nutrition delivery could be observed in patients with lactate concentration ≤ 2 mmol/L (adjusted HR = 0.804 (95% CI 0.674–0.960) for energy delivery and adjusted HR = 0.804 (95% CI 0.672–0.962) for protein delivery, respectively), but not in those > 2 mmol/L.ConclusionsDuring the first week of critical illness, enhanced nutrition delivery is associated with reduced mortality in critically ill patients receiving exclusive EN, only for those with lactate concentration ≤ 2 mmol/L.Trial registration: ISRCTN12233792, registered on November 24, 2017.

Circulating IL-6 and not its circulating signaling components sIL-6R and sgp130 demonstrate clinical significance in NSCLC patients treated with immune checkpoint inhibitors.

Introduction: Clinical roles of plasma IL-6 levels have been reported in patients with various cancers, including non-small cell lung cancer (NSCLC), treated with immune checkpoint inhibitors (ICIs). However, the roles of other IL-6 signaling components, soluble IL-6 receptor (sIL-6R) and soluble gp130 (sgp130), in the plasma have not been elucidated. Methods: Blood was collected from 106 patients with NSCLC before initiation of ICI treatment (anti-PD-1 or anti-PD-L1 antibody). Plasma levels of IL-6, sIL-6R, sgp130, and their complexes were assessed by Cox regression hazard model to evaluate their clinical significance. The clinical role of IL-6 or IL-6R genetic polymorphisms was also analyzed. Results: Cox regression analysis showed that higher plasma IL-6 levels significantly predicted unfavorable overall survival (OS; hazard ratio [HR] 1.34, 95% confidence interval [CI] 1.05-1.68, p = 0.012) in NSCLC patients treated with ICIs. However, plasma sIL-6R and sgp130 levels showed no prognostic significance (p = 0.882 and p = 0.934, respectively). In addition, the estimated concentrations of binary IL-6:sIL-6R and ternary IL-6:sIL-6R:sgp130 complexes and their ratios (binary/ternary complex) were not significantly associated with OS (p = 0.647, p = 0.727, and p = 0.273, respectively). Furthermore, the genetic polymorphisms of IL-6 (-634G>C) and IL-6R (48892A>C) showed no clinical role by Kaplan-Meier survival analysis (p = 0.908 and p = 0.639, respectively). Discussion: These findings demonstrated the clinical significance of plasma levels of IL-6, but not of other IL-6 signaling components, sIL-6R and sgp130, suggesting that classical IL-6 signaling, but not trans-signaling, may be related to anti-tumor immune responses in cancer patients treated with ICIs.