Multivariable Competing Risk Models Research Articles

Cardiovascular Mortality Risk among Patients with Liver Cancer: A SEER Database Study.

Data sourced from the Surveillance, Epidemiology, and End Results (SEER) database encompassing liver cancer diagnoses from 2000 to 2017 were utilized. The standardized mortality rate (SMR) was computed using general population reference data, and multivariate competing risk models were employed for analysis. Analysis of 70,733 liver cancer patient records revealed 1,954 instances of CVM. The overall CVM SMR for liver cancer patients was 12.01 (95% CI: 11.48-12.55). Various demographic and clinical factors, including sex, race, age, year of diagnosis, pathological type, general stage, treatment modalities, and matrimonial status, emerged as liver cancer pa-tients` independent predictors of CVM. Liver cancer patients have a notably heightened susceptibility to cardiovascular mortality (CVM) in contrast to the general populace. It is imperative to promptly recognize high-risk subcategories and execute tailored cardiovascular interventions as crucial measures to bolster survival rates within this cohort of patients.

Adverse cardiovascular events in patients with cancer: a biomarker-enhanced clinical risk score

Abstract Background/Introduction Continuously improving cancer-specific survival puts a growing proportion of cancer patients at risk of major adverse cardiovascular events (MACE), but reliable tools for cardiovascular risk prediction remain unavailable (1). Purpose To assess a broad panel of cardiovascular biomarkers and clinical risk factors and to provide a novel risk score for the prediction of MACE in cancer patients. Methods Among 2’192 patients with newly diagnosed or recurrent cancer, a broad panel of cardiovascular biomarkers, including NT-proBNP, P-/E-/L-selectins, ICAM-1, VCAM-1, sLOX-1, CRP, and Lp(a) were measured by blinded study personnel. Patients were followed prospectively for the occurrence of 2-year MACE and 5-year cardiovascular death (2,3). Uni- and multivariable competing risk models were fit to assess independent associations of cardiovascular risk factors and biomarkers with MACE, and a risk score was developed. Results Beyond clinical risk factors, ICAM-1, P-/E-/L-selectins and NT-proBNP levels were independently linked to 2-year MACE risk, though shape of associations differed markedly. A clinical risk score was derived, assigning +1 point for male sex, smoking, and age ≥60 years, and +2 points for ASCVD history, yielding a bootstrapped C-statistic of 0.76 (95%CI:0.71-0.81). Implementation of cardiovascular biomarkers conferred improved performance (0.83, 95%CI:0.78-0.88). A simplified model, solely informed by clinical variables and readily available NT-proBNP (+1 point for NT-proBNP≥230pg/mL), achieved similar performance (0.80, 95%CI:0.74-0.86), with a cumulative 2-year MACE incidence of 0% in low- and 11.0% in high-risk patients. Conclusions Cancer patients are at substantial MACE risk. The herein presented first-of-its-kind risk score, integrating traditional cardiovascular risk factors and biomarkers, including NT-proBNP, effectively predicts 2-year MACE and 5-year cardiovascular death.

Association between PCSK9 inhibitor with cause-specific morality amongst cancer survivors

Abstract Background Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor has emerged as a novel pharmacotherapy for dyslipidemia and been shown to be effective in reducing the risks of atherosclerotic cardiovascular diseases. PCSK9 is aberrantly expressed in a broad spectrum of cancers and has been demonstrated to contribute to cancer prognosis. However, no prior study has investigated the associations between PCSK9 inhibitors (PCSK9i) with cardiovascular and cancer mortality amongst cancer survivors. Purpose This study investigated the effects of PCSK9i on cause-specific mortality amongst cancer survivors. Methods This retrospective study used data from the Tianjin Coronary Artery Disease Cohort, which included medical data from 71 secondary or tertiary hospitals in Tianjin, China. Adult patients with coronary artery disease (CAD) diagnosed with incident cancer between 2017 and 2023 were enrolled in this study. Propensity score matching with a 1:3 ratio for PCSK9i users versus non-users was performed. The primary outcomes included all-cause mortality, cardiovascular mortality, and cancer mortality. Multivariable Cox regression was used to test associations between PCSK9i with outcomes, adjusting for age, gender, cardiovascular and non-cardiovascular comorbidities, lipid-lowing agents and other medication use, lipid level, as well as cancer characteristics. Multivariable competing risk analysis was used as sensitivity analysis. Results A total of 62,341 incident cancer patients were identified. After matching, 424 PCSK9i users and 1,272 non-users were included in this study. During a median follow-up of 1,009 days, 315 patients died, among which 98 died due to cardiovascular cause, 146 died due to cancer cause. Compared to non-users, cancer patients treated with PCSK9i presented with significantly lower risk of all-cause mortality (hazard ratio [HR], 0.33; 95% confidence interval [CI] 0.23-0.47; p <0.001), after adjusting for potential confounders. In addition, PCSK9i therapy was associated with a 63% lower risk of cardiovascular mortality (HR, 0.37; 95%CI 0.20-0.69; p=0.002) and a 75% lower risk of cancer-related mortality (HR, 0.25; 95%CI 0.14-0.45; p<0.001), in relation to non-PCSK9i group. Sensitivity analysis using multivariable competing risk model also suggested a significant association between PCSK9i treatment with reduced risk of cardiovascular mortality (HR, 0.41; 95%CI 0.22-0.76; p=0.005) and cancer mortality (HR, 0.26; 95%CI 0.15-0.48; p<0.001) among cancer survivors. Conclusion The use of PCSK9i was associated lower risks of all-cause, cardiovascular-related, and cancer-related mortality amongst cancer survivors. These findings potentially indicate benefits of PCSK9i beyond adverse cardiovascular events related to atherosclerosis.

Risk of Dementia Diagnosis After Injurious Falls in Older Adults

Emerging evidence suggests that mild cognitive impairment, which is a precursor to Alzheimer disease and related dementias (ADRD), places older adults at increased risk for falls. However, the risk that an older adult develops dementia after experiencing a fall is unknown. To determine the risk of new ADRD diagnosis after a fall in older adults. This retrospective cohort study examined Medicare Fee-for-Service data from 2014 to 2015, with follow-up data available for at least 1 year after the index encounter. Participants included adults aged 66 years and older who experienced a traumatic injury that resulted in an emergency department (ED) or inpatient encounter and did not have a preexisting diagnosis of dementia. Data analysis was performed from August 2023 to July 2024. Experiencing a fall compared with other mechanisms of injury, defined by International Classification of Diseases, Ninth Revision (ICD-9) and ICD-10 external cause of injury codes. The hazard of new ADRD diagnosis within 1 year of a fall, assessed by performing a Cox multivariable competing risk model that controlled for potential confounders while accounting for the competing risk of death. The study included 2 453 655 older adult patients who experienced a traumatic injury; 1 522 656 (62.1%) were female; 124 396 (5.1%) were Black and 2 232 102 (91.0%) were White; and the mean (SD) age was 78.1 (8.1) years. The mechanism of injury was a fall in 1 228 847 incidents (50.1%). ADRD was more frequently diagnosed within 1 year of a fall compared with other injury mechanisms (10.6% [129 910 of 1 228 847] vs 6.1% [74 799 of 1 224 808]; P < .001). The unadjusted hazard ratio (HR) of incident dementia diagnosis after a fall was 1.63 (95% CI, 1.61-1.64; P < .001). On multivariable Cox competing risk analysis, falling was independently associated with an increased risk of dementia diagnosis among older adults (HR, 1.21 [95% CI, 1.20-1.21]; P < .001) after controlling for patient demographics, medical comorbidities, and injury characteristics, while accounting for the competing risk of death. Among the subset of older adults without a recent skilled nursing facility admission, the HR was 1.27 (95% CI, 1.26-1.28; P < .001). In this cohort study, new ADRD diagnoses were more common after falls compared with other mechanisms of injury, with 10.6% of older adults being diagnosed with ADRD in the first year after a fall. To improve the early identification of ADRD, this study's findings suggest support for the implementation of cognitive screening in older adults who experience an injurious fall that results in an ED visit or hospital admission.

Demographic and Clinical Characteristics of Malignant Solitary Fibrous Tumors: A SEER Database Analysis

Background/Objectives: Solitary fibrous tumors (SFTs) represent a rare mesenchymal malignancy that can occur anywhere in the body. Due to the low prevalence of the disease, there is a lack of contemporary data regarding patient demographics and cancer-control outcomes. Methods: Within the SEER database (2000–2019), we identified 1134 patients diagnosed with malignant SFTs. The distributions of patient demographics and tumor characteristics were tabulated. Cumulative incidence plots and competing risks analyses were used to estimate cancer-specific mortality (CSM) after adjustment for other-cause mortality. Results: Of 1134 SFT patients, 87% underwent surgical resection. Most of the tumors were in the chest (28%), central nervous system (22%), head and neck (11%), pelvis (11%), extremities (10%), abdomen (10%) and retroperitoneum (6%), in that order. Stage was distributed as follows: localized (42%) vs. locally advanced (35%) vs. metastatic (13%). In multivariable competing risks models, independent predictors of higher CSM were stage (locally advanced HR: 1.6; metastatic HR: 2.9), non-surgical management (HR: 3.6) and tumor size (9–15.9 cm HR: 1.6; ≥16 cm HR: 1.9). Conclusions: We validated the importance of stage and surgical resection as independent predictors of CSM in malignant SFTs. Moreover, we provide novel observations regarding the independent importance of tumor size, regardless of the site of origin, stage and/or surgical resection status.

Association between serum potassium, risk and prognosis of peritonitis in peritoneal dialysis patients-results from the Peritoneal Dialysis Telemedicine-assisted Platform Cohort (PDTAP) Study.

Hypokalemia has been associatedwith an increased risk of peritoneal dialysis (PD)-associated peritonitis. However, hypokalemia is commonly associated with malnutrition, inflammation, and severe coexisting comorbidities, which thus are suspected of being potential confounders. This study was aimed at testingwhether hypokalemia was independently associated with the occurrence and prognosis of PD-associated peritonitis. A national-level dataset from the Peritoneal Dialysis Telemedicine-assisted Platform Cohort (PDTAP) Study was used to explore the independent association of serum potassium with PD-associated peritonitis. Unmatched and propensity score-adjusted multivariate competing risk models, as well as univariate competing risk models following 1:1 propensity score matching, were conducted to balance potential biases between patients with and without hypokalemia. The association between potassium levels prior to peritonitis and treatment failure due to peritonitis was also investigated. During a median follow-up of 25.7months in 7220 PD patients, there was a higher incidence of peritonitis in patients with serum potassium below 4.0mmol/L compared to those withhigher serum levels (677 [0.114/patient-year] vs. 914 [0.096/patient-year], P = 0.001). After adjusting for demographics, laboratory tests, residual renal function, and medication use, baseline potassium levels below 4.0mmol/L were not linked to an increased risk of peritonitis, with a hazard ratio of 0.983 (95% CI 0.855-1.130, P = 0.810). This result remained consistent in both the propensity score adjusted multivariate competing risk regression (HR = 0.974, 95% CI 0.829-1.145, P = 0.750) and the univariate competing risk regression after 1:1 propensity score matching (Fine-Gray test, P = 0.218). The results were similar when analyzing patients with serum potassium level above or below 3.5mmol/L. Lastly, hypokalemia before the occurrence of peritonitis was not independently associated with treatment failure. Hypokalemia was not found to be an independent risk factor for PD-associated peritonitis or treatment failure of peritonitis in China.

Assessment of prognostic factors in patients with primary ocular adnexal lymphoma when considering competing risk elements.

Accurate prognostic factors for primary ocular adnexal lymphoma (POAL) are scarce. Survival models and prognostic factors derived without considering competing risk factors suffer from major statistical errors. This study aimed to accurately assess prognostic factors in POAL patients using competing risk models, and compare this to the traditional COX proportional hazards model. This retrospective study utilised data from the Surveillance, Epidemiology, and End Results (SEER) program 2010-2015 and included patients with B-cell POAL. The cumulative incidence function and Gray's test for cause-specific survival were calculated as univariate analysis. The competing risk models were a Fine-Gray subdistribution hazard model and a cause-specific model, and a traditional COX model was employed as a multivariate analysis. This study enrolled 846 eligible patients with POAL: 60 patients (7.09%) died from POAL and 123 patients (14.54%) died from other causes. Multivariate competing risk models indicated that age, laterality, histology subtype, the 7th edition of American Joint Committee on Cancer stage T, and radiotherapy were independent predictors for cause-specific survival of patients with POAL. There was high consistency between the two competing risk models. The COX model made several misestimations on the statistical significance and hazard ratios of prognostic factors. This study established competing risk models as a method to assess POAL prognostic factors, which was more accurate than traditional methods that do not consider competing risk elements.

Folic acid supplementation is associated with a decreased mortality and reduced hospital readmission in patients with decompensated alcohol-related liver cirrhosis

Background and AimsThiamine and folic acid malnutrition is highly frequent in patients with decompensated alcohol-related liver cirrhosis (aLC). Current guidelines therefore recommend vitamin supplementation in these patients. However, implementation and its impact on the clinical outcome remains unknown. Therefore, we aimed to analyze the use of thiamine and folic acid and their effects on mortality and morbidity in patients with decompensated aLC. MethodsA number of 289 consecutive patients with decompensated aLC who received a paracentesis at Hannover Medical School between 2011 and 2023 were retrospectively investigated. The use of folic acid and thiamine-containing supplements was assessed in the discharge medication. Patients were followed for up to one year regarding liver transplant (LTx)-free survival and the incidence of hepatic encephalopathy, infections and hepatic decompensation requiring rehospitalization. ResultsMedian baseline MELD was 15, median age 56.6 years. 73.0% (n=211) were male patients. At hospital discharge, thiamine-containing supplements and folic acid were prescribed to 48.1% (n=139) and 18.0% (n=52) patients, respectively. Neither thiamine nor folic acid prescription were linked to improved clinical outcomes within 90 days. However, folic acid intake was associated with a higher one-year LTx-free survival (HR=0.48; p=0.04) in the multivariable analysis. Furthermore, folic acid substitution was linked to a decreased risk of rehospitalization within one year (HR=0.55; p=0.01) in the multivariable competing risk model. In contrast, thiamine prescription did neither affect LTx-free survival nor the here investigated liver-related complications. ConclusionFolic acid, but not thiamine substitution was linked to an improved outcome in patients with decompensated aLC.

Comparable long-term survival outcomes after endoscopic and gastrectomy treatment of pT1acN0M0 gastric adenocarcinomain patients who met the expanded criteria.

Whether the Western pT1acN0M0 gastric cancer (GC) patients who met the Japanese expanded criteria could be the candidates for endoscopic treatment (ET) remains unclear because of unknown long-term survival outcomes. A retrospective cohort study using data from the Surveillance, Epidemiology, and End Results (SEER) program was performed. The survival differences between pT1acN0M0 gastric adenocarcinoma patients who received ET or gastrectomy treatment (GT) were evaluated using multivariate survival analysis. A total of 314 pT1acN0M0 gastric adenocarcinoma patients who met the expanded criteria were included, 46 patients received ET and 268 patients received GT. pT1acN0M0 gastric adenocarcinoma patients met the expanded criteria underwent ET experienced a similar hazard of cancer-specific death compared with those underwent GT both in the multivariate Cox survival analysis (adjusted hazard ratio [HR]; 1.18, 95% confidence interval [CI] 0.40-3.49; P = 0.766) and the multivariate competing risk model (subdistribution HR [SHR], 1.12, 95% CI 0.38-3.29; P = 0.845). The result that pT1acN0M0 gastric adenocarcinoma patients met the expanded criteria underwent ET experienced comparable survival outcomes to those who underwent GT did not change even compared with those who underwent GT with > 15 lymph nodes examined (adjusted HR, 1.55, 95% CI 0.44-5.49; P = 0.499; SHR, 1.47, 95% CI 0.44-4.88; P = 0.532). The ET can be considered in Western pT1acN0M0 gastric adenocarcinoma patients who met the Japanese expanded criteria. However, a prospective study should be warranted.

The hepatocellular carcinoma risk in patients with HBV-related cirrhosis: a competing risk nomogram based on a 4-year retrospective cohort study.

The study aimed to build and validate a competitive risk nomogram to predict the cumulative incidence of hepatocellular carcinoma (HCC) for patients with hepatitis B virus (HBV)-related cirrhosis. A total of 1401 HBV-related cirrhosis patients were retrospectively enrolled from January 1, 2011 to December 31, 2014. Application of 20 times imputation dealt with missing data using multiple imputation by chained equations (MICE). The patients were randomly divided into a training set (n = 1017) and a validation set (n = 384) at a ratio of 3:1. A prediction study was carried out using a competing risk model, where the event of interest was HCC and the competing events were death and liver transplantation, and subdistribution hazard ratios (sHRs) with 95% CIs were reported. The multivariate competing risk model was constructed and validated. There was a negligible difference between the original database and the 20 imputed datasets. At the end of follow-up, the median follow-up time was 69.9 months (interquartile range: 43.8-86.6). There were 31.5% (442/1401) of the patients who developed HCC, with a 5-year cumulative incidence of 22.9 (95%CI, 20.8%-25.2%). The univariate and multivariate competing risk regression and construction of the nomogram were performed in 20 imputed training datasets. Age, sex, antiviral therapy history, hepatitis B e antigen, alcohol drinking history, and alpha-fetoprotein levels were included in the nomogram. The area under receiver operating characteristic curve values at 12, 24, 36, 60, and 96 months were 0.68, 0.69, 0.70, 0.68, and 0.80, and the Brier scores were 0.30, 0.25, 0.23, 0.21, and 0.20 in the validation set. According to the cumulative incidence function, the nomogram effectively screened out high-risk HCC patients from low-risk patients in the presence of competing events (Fine-Gray test p < 0.001). The competitive risk nomogram was allowed to be used for predicting HCC risk in individual patients with liver cirrhosis, taking into account both the association between risk factors and HCC and the modifying effect of competition events on this association.

Development and validation of a nomogram for predicting specific mortality risk: A study of competing risk model based on real endometrial cancer patients.

This study aimed to construct a competing risk prediction model for predicting specific mortality risks in endometrial cancer patients from the SEER database based on their demographic characteristics and tumor information. We collected relevant clinical data on patients with histologically confirmed endometrial cancer in the SEER database between 2010 and 2015. Univariate and multivariate competing risk models were used to analyze the risk factors for endometrial cancer-specific death, and a predictive nomogram was constructed. C-index and receiver operating characteristic curve (ROC) at different time points were used to verify the accuracy of the constructed nomogram. There were 26 109 eligible endometrial cancer patients in the training cohort and 11 189 in the validation cohort. Univariate and multivariate analyses revealed that Age, Marriage, Grade, Behav, FIGO, Size, Surgery, SurgOth, Radiation, ParaAortic_Nodes, Peritonea, N positive, DX_liver, and DX_lung were independent prognostic factors for specific mortality in endometrial cancer patients. Based on these factors, a nomogram was constructed. Internal validation showed that the nomogram had a good discriminative ability (C-index = 0.883 [95% confidence interval [CI]: 0.881-0.884]), and the 1-, 3-, and 5-year AUC values were 0.901, 0.886 and 0.874, respectively. External validation indicated similar results (C-index = 0.883 [95%CI: 0.882-0.883]), and the 1-, 3-, and 5- AUC values were 0.908, 0.885 and 0.870, respectively. We constructed a competing risk model to predict the specific mortality risk among endometrial cancer patients. This model has favorable accuracy and reliability and can provide a reference for the development and update of endometrial cancer prognostic risk assessment tools.

Chronic Obstructive Pulmonary Disease Mortality in Bladder Cancer Patients: A SEER-Based Competing Risk Analysis.

This study was designed to evaluate risk of mortality from chronic obstructive pulmonary disease (COPD) in patients with bladder cancer (BC). Data on patients diagnosed with BC by pathology between 2000 and 2016 were collected from the Surveillance, Epidemiology, and End Results (SEER) database. Based on reference data from the general population, the standardized mortality rate (SMR) is calculated. Nelson-Aalen cumulative hazard curves were used for assessment of the risk of COPD mortality in BC patients. Multivariable competing risk models were conducted. The proportional hazards assumption was tested using Schoenfeld residuals, which were scaled and plotted over time for each risk factor. A total of 237,563 BC patients were identified for further analysis from the SEER database, 5,198 of these patients experienced COPD mortality; the overall SMR for COPD mortality in BC patients was 1.58 (95% CI: 1.54-1.63). Age, race, year of diagnosis, histologic type, summary stage, surgery, marital status, college education level, and median household income independently predicted COPD mortality in BC patients. In comparison to the general population, the risk of COPD mortality is significantly higher in patients with BC. Pre-identification of high-risk groups and respiratory care provisions are important measures to effectively improve survival in this group of patients.

Bleeding complications, coagulation disorders, and their management in acute myocardial infarction-related cardiogenic shock rescued by veno-arterial ECMO: A retrospective cohort study

PurposeManagement of dual antiplatelet therapy (DAPT) in patients on venoarterial-extracorporeal membrane (VA-ECMO) after acute myocardial infarction (AMI) is challenging. Our objective was to describe the frequency, management and outcomes of severe bleeding complications and determine their occurrence risk factors. Material and methodsWe conducted a retrospective observational cohort study including post-AMI cardiogenic shock patients requiring VA-ECMO. Severe bleeding was defined based on the Bleeding Academic Research Consortium classification. We calculated multivariable Fine–Gray models to assess factors associated with risk of severe bleeding. ResultsFrom January 2015 to July 2019, 176 patients received VA-ECMO after AMI and 132 patients were included. Sixty-five (49%) patients died. Severe bleeding occurred in 39% of cases. Severe thrombocytopenia (< 50 G/L) and hypofibrinogenemia (<1,5 g/L) occurred in respectively 31% and 19% of patients. DAPT was stopped in 32% of patients with a 6% rate of stent thrombosis. Anticoagulation was stopped in 39% of patients. Using a multivariate competing risk model, female sex, time on ECMO, troponin at admission and Impella® implantation were independently associated with severe bleeding. ConclusionsBleeding complications and coagulation disorders were frequent and severe in patients on VA-ECMO after AMI, leading of antiplatelet therapy withdrawal in one third of patients.

Prediction of bronchopulmonary dysplasia in very preterm infants: competitive risk model nomogram.

To develop predictive clinical models of bronchopulmonary dysplasia (BPD) through competing risk analysis. Retrospective observational cohort study, including preterm newborns ≤32 weeks gestational age, conducted between January 1, 2013 and September 30, 2022 in a third-level Neonatal Intensive Care Unit in Spain. A prediction study was carried out using competing risk models, where the event of interest was BPD and the competing event was death. A multivariate competing risk model was developed separately for each postnatal day (days 1, 3, 7 and 14). Nomograms to predict BPD risk were developed from the coefficients of the final models and internally validated. A total of 306 patients were included in the study, of which 73 (23.9%) developed BPD and 29 (9.5%) died. On day 1, the model with the greatest predictive capacity was that including birth weight, days since rupture of membranes, and surfactant requirement (area under the receiver operating characteristic (ROC) curve (AUC), 0.896; 95% CI, 0.792-0.999). On day 3, the final predictive model was based on the variables birth weight, surfactant requirement, and Fraction of Inspired Oxygen (FiO2) (AUC, 0.891; 95% CI, 0.792-0.989). Competing risk analysis allowed accurate prediction of BPD, avoiding the potential bias resulting from the exclusion of deceased newborns or the use of combined outcomes. The resulting models are based on clinical variables measured at bedside during the first 3 days of life, can be easily implemented in clinical practice, and can enable earlier identification of patients at high risk of BPD.

Impact of prior cancer history on survival in brain malignancy: A propensity score-adjusted, population-based study.

Individuals with a Prior Cancer History (PCH) are often excluded from clinical trials. However, a growing body of evidence suggests that prior cancer history does not present adverse outcomes on cancer patients. The evidence on the survival of brain cancer patients in this regard remains widely unknown. We conducted a retrospective cohort study to estimate the prevalence and impact of prior cancer on survival of patients diagnosed with brain cancer. Data of patients who were diagnosed with brain cancer as their first or second primary malignancy between 2000 and 2019 were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. Propensity Score Matching (PSM) was used to ensure comparable baseline characteristics among the patients. Survival analysis was conducted using the Kaplan-Meier method, as well as multivariate Cox proportional hazard and multivariate competing risk models. Out of 42 726 patients, 1189 (2.78%) had PCH. Genitourinary (40.4%), Breast (13.6%), Hematologic and Lymphatic (11.4%), and Gastrointestinal malignancies (11.3%) were the most common types of prior cancer. PCH served as a significant risk factor for Overall Survival (OS) (Adjusted Hazard Ratio [AHR] 1.26; 95% CI [1.15-1.39]; p < .001) but did not have a statistically significant impact on Brain Cancer-Specific Survival (BCSS) (AHR 0.97; 95% CI [0.88-1.07]; p = .54). Glioblastoma exhibited the most substantial and statistically significant impact on survival as compared to other histological types. Of all the organs systems, only prior Gastrointestinal and Hematologic and Lymphatic malignancies had a statistically significant impact on OS of patients. Our findings indicate that PCH does not exert a substantial impact on the survival of brain cancer patients, except in cases involving gastrointestinal or hematologic and lymphatic PCH, or when the brain cancer is glioblastoma.

Effect of different treatment modalities on ovarian cancer patients with liver metastases: A retrospective cohort study based on SEER.

To examine the trends in morbidity and mortality among ovarian cancer patients with liver metastases, and investigate the impact of different treatments on both overall survival (OS) and cancer-specific survival (CSS). 2,925 ovarian cancer patients with liver metastases from Surveillance, Epidemiology, and End Results 2010-2019 were included. The primary endpoint was considered as OS and CSS. We conducted trend analysis of the incidence, OS and CSS rates of liver metastases in ovarian cancer. Univariate and multivariate COX proportional risk models were used to investigate the association between different treatment methods and OS, and univariate and multivariate competing risk models were employed to evaluate the impact of treatment methods on CSS. At the end of follow-up, 689 patients remained alive. The OS and CSS rates were 76.44% and 72.99% for all patients, respectively. There was a significant decreasing trend in the incidence [average annual percent change (AAPC) = -2.3, 95% confidence interval (CI): -3.9, -0.7], all-cause mortality (AAPC = -12.8, 95% CI: -15.6, -9.9) and specific mortality (AAPC = -13.0, 95% CI: -16.1, -9.8) rate of liver metastases in ovarian cancer. After adjusting all confounding factor, only receiving surgery was associated with OS [hazard ratio (HR) = 0.39, 95%CI: 0.31-0.48]/CSS (HR = 0.37, 95%CI: 0.30-0.47). Chemotherapy was found to be protective factor for OS (HR = 0.33, 95%CI: 0.30-0.37)/CSS (HR = 0.44, 95%CI: 0.39-0.50) of ovarian cancer patients, while not receiving surgery remained a risk factor. Additionally, the result of subgroup analyses also showed that only receiving surgery and chemotherapy still were significant protective factor of OS and CSS for patients without other distant metastases, with distant metastases to the bone, lung, brain or other organs, with bone metastasis, and with lung metastasis. Our research has elucidated a downward trend in morbidity and mortality rates among patients with liver metastases originating from ovarian cancer. Only receiving surgery and chemotherapy as therapies methods confer survival benefits to patients.

Elevated Fibrinogen-to-Albumin Ratio Correlates with Incident Stroke in Cerebral Small Vessel Disease.

We aimed to explore the association between fibrinogen-to-albumin ratio (FAR) and the risk of incident stroke (IS) in a cohort of cerebral small vessel disease (CSVD) patients. Participants were screened from a prospective CSVD database. Clinical data, hematologic measures and imaging findings were collected. The primary outcome was IS during follow-up, with a secondary outcome of composite vascular events (CVE) including IS, myocardial infarction (MI), and vascular deaths. Univariate and multivariate COX proportional risk models, along with competing risk models, were employed to identify factors associated with outcomes. Restricted cubic spline (RCS) and subgroup analyses were conducted to assess the association between FAR and the risk of IS and CVE in CSVD patients. In the final analysis of 682 CSVD patients over a median observation period of 34.0 [24.0-53.0] months, there were 33 cases of IS (4.84%, 1.55/100 person-years), 4 incidents of MI (0.59%, 0.19/100 person-years), 15 non-vascular deaths (2.20%, 0.70/100 person-years), and 37 occurrences of CVE (5.43%, 1.74/100 person-years). Multivariate Cox regression analysis revealed a significant positive correlation between elevated FAR and both IS (HR 1.146; 95% CI 1.043-1.259; P=0.004) and CVE (HR 1.156; 95% CI 1.063-1.257; P=0.001) in CSVD patients. Multivariate competing risk model showed the similar results (IS: HR 1.16; 95% CI 1.06-1.27; P=0.001, CVE: HR 1.15; 95% CI 1.05-1.26; P=0.003). RCS analysis indicated a linear relationship between FAR and the risks of both IS (P for non-linearity =0.7016) and CVE (P for non-linearity =0.6475), with an optimal cutoff value of 8.69, particularly in individuals over 60 years of age. Elevated FAR demonstrated an independent and linear association with IS and the development of CVE in CSVD patients.

Mortality patterns of patients with tonsillar squamous cell carcinoma: a population-based study.

Tonsillar squamous cell carcinoma (TSCC) and second primary malignancies (SPMs) are the most common causes of mortality in patients with primary TSCC. However, the competing data on TSCC-specific death (TSD) or SPM-related death in patients with TSCC have not been evaluated. This study aimed to analyze the mortality patterns and formulate prediction models of mortality risk caused by TSCC and SPMs. Data on patients with a first diagnosis of TSCC were extracted as the training cohort from the 18 registries comprising the Surveillance, Epidemiology, and End Results (SEER) database. A competing risk approach of cumulation incidence function was used to estimate cumulative incidence curves. Fine and gray proportional sub-distributed hazard model analyses were performed to investigate the risk factors of TSD and SPMs. A nomogram was developed to predict the 5- and 10-year risk probabilities of death caused by TSCC and SPMs. Moreover, data from the 22 registries of the SEER database were also extracted to validate the nomograms. In the training cohort, we identified 14,530 patients with primary TSCC, with TSCC (46.84%) as the leading cause of death, followed by SPMs (26.86%) among all causes of death. In the proportion of SPMs, the lungs and bronchus (22.64%) were the most common sites for SPM-related deaths, followed by the larynx (9.99%), esophagus (8.46%), and Non-Melanoma skin (6.82%). Multivariate competing risk model showed that age, ethnicity, marital status, primary site, summary stage, radiotherapy, and surgery were independently associated with mortality caused by TSCC and SPMs. Such risk factors were selected to formulate prognostic nomograms. The nomograms showed preferable discrimination and calibration in both the training and validation cohorts. Patients with primary TSCC have a high mortality risk of SPMs, and the competing risk nomogram has an ideal performance for predicting TSD and SPMs-related mortality. Routine follow-up care for TSCC survivors should be expanded to monitor SPMs.

Exposure to Agent Orange and Hepatocellular Carcinoma Among US Military Personnel

Hepatocellular carcinoma (HCC) and its mortality are on the rise. Viral hepatitis and alcohol are leading risk factors; however, other risk factors among veterans are less defined, including Agent Orange (AO), an herbicide linked to several cancers. To assess the association of AO exposure and HCC in a national cohort of Vietnam veterans. This retrospective cohort study included Vietnam veterans who served between 1966 and 1975, were male, were older than 18 years at the time of deployment, and had established follow-up in the Veterans Affairs (VA) between 2000 and 2019. Veterans with AO exposure were identified in the disability data via validated clinical surveys. Relevant clinical risk factors for cirrhosis and HCC were collected. Patients were stratified based on cirrhosis status, as defined by consecutive diagnosis found by documented International Classification of Diseases, Ninth Revision and International Statistical Classification of Diseases and Related Health Problems, Tenth Revision scores or calculated Fibrosis-4 scores. Data were collected from January 1, 2019, to December 31, 2020, and analyzed from December 2020 to October 2023. Incident HCC was the primary outcome. AO and HCC association was estimated using a multivariable Cox regression analysis, with death and liver transplant as competing events. Of the 296 505 eligible veterans (222 545 [75.1%] White individuals and 44 342 [15.0%] Black individuals), 170 090 (57%) had AO exposure (mean [SD] age, 21.62 [3.49] years; 131 552 White individuals [83.2%] and 22 767 Black individuals [14.4%]) and 35 877 (12.1%) had cirrhosis. Veterans who were not exposed to AO were more likely to smoke (109 689 of 126 413 [86.8%] vs 146 061 of 170 090 [85.9%]); use alcohol (54 147 of 126 413 [42.8%] vs 71 951 of 170 090 [42.3%]) and have viral hepatitis (47 722 of 126 413 [37.8%] vs 58 942 of 170 090 [34.7%]). In a multivariable competing risk model, AO exposure was not associated with HCC. Among veterans with cirrhosis, self-identification as Hispanic individuals (aHR, 1.51; 95% CI, 1.30-1.75; P <.001) or Black individuals (aHR, 1.18; 95% CI, 1.05-1.32; P = .004), and having a diagnosis of viral hepatitis (aHR, 3.71; 95% CI, 3.26-4.24; P <.001), alcohol-associated liver disease (aHR, 1.32; 95% CI, 1.19-1.46; P <.001), and nonalcoholic fatty liver disease (NAFLD) (aHR, 1.92; 95% CI, 1.72-2.15; P <.001) were associated with HCC. Among veterans without cirrhosis, hypertension (aHR, 1.63; 95% CI, 1.23-2.15; P <.001) and diabetes (aHR, 1.52; 95% CI, 1.13-2.05; P = .005) were also associated with HCC. Early smoking and alcohol use were significant risk factors for HCC. In this large nationwide cohort study of Vietnam veterans, AO exposure was not associated with HCC. Smoking, alcohol, viral hepatitis, and NAFLD were the most important clinical risk factors for HCC.

Competing risk analysis of cardiovascular death in breast cancer: evidence from the SEER database.

Cardiovascular disease (CVD) is the leading cause of death for all non-cancer deaths among breast cancer (BC) patients. The aim of this study was to investigate the risk of cardiovascular mortality (CVM) in patients with BC. Patients diagnosed with primary BC between 2010 and 2018 were identified through the Surveillance, Epidemiology and End Results (SEER) database. The standardized mortality ratio (SMR) for CVD was calculated to compare the CVM of BC patients with that of the general population. Multivariate competing risk models were performed to identify predictors of CVM in BC patients. Overall, 399,014 BC patients were included from the SEER database, of whom 7,023 (1.8%) suffered death from CVD. The significantly higher overall SMR of CVM was observed in BC patients [SMR =4.84, 95% confidence interval (CI): 4.72-4.95]. Multivariate competing risk regression analysis revealed that age, race, American Joint Committee on Cancer (AJCC) stage, year of diagnosis, estrogen receptor (ER) status, progesterone receptor (PR) status, human epidermal growth factor receptor 2 (HER2) status, BC subtype, surgery, chemotherapy, radiation therapy, and median household income as independent predictors of CVM in BC patients. Compared to the general population, BC patients have a higher risk of experiencing CVM during the follow-up period after diagnosis. Early detection and intervention of cardiovascular risk factors would improve overall survival (OS) of BC patients.