Multivariate Proportional Hazards Regression Analysis Research Articles

Abstract PS10-02: Association between Germline Mutation Status and Overall Survival among Women with Breast Cancer in Population-based Studies in the United States

Abstract Background: The influence of germline pathogenic variants (PVs) in breast cancer predisposition genes on overall survival (OS) after breast cancer diagnosis is not well defined, particularly for PVs in genes other than BRCA1 and BRCA2, and in the context of estrogen-receptor (ER) positive breast cancer. Even for BRCA1/2, OS estimates in women with breast cancer have primarily been derived from high-risk women qualifying for genetic testing due to young age at diagnosis or family history of cancer, and OS estimates by germline PV status from population-based studies are lacking. Methods: The study included 16,797 prospectively followed women with locoregional breast cancer within the population-based CARRIERS study who underwent surgical resection of the primary tumor. OS was compared between germline PV carriers and non-carriers (negative for germline PVs in 12 breast cancer predisposition genes) from the time of breast cancer diagnosis in a multivariable Cox proportional hazard regression analysis adjusting for age and menopausal status at diagnosis, race/ethnicity, ER status, type of surgery, use of adjuvant radiation, chemotherapy and endocrine agents, and prophylactic oophorectomy. Further subset analyses by race/ethnicity ER status of the primary tumor and adjusting for relevant covariates were also performed. Results: Germline PVs in ATM, BRCA1, BRCA2, CHEK2, or PALB2 were detected in 5.6% of the women in the study [ATM: 142 (0.8%), BRCA1: 206 (1.2%), BRCA2: 260 (1.5%), CHEK2:167 (1.0%) and PALB2:116 (0.7%)]. Compared to non-carriers, a significant difference in OS was not observed for germline PV carriers in ATM, BRCA1, BRCA2, or CHEK2 in the overall study population. However, a trend towards worse OS was noted for PALB2 PV carriers compared to non-carriers although this was not statistically significant (Hazard Ratio (HR): 1.36, 95%CI: 0.98 – 1.89, p=0.06). Further subset analysis by race/ethnicity demonstrated that the OS was significantly worse among Black PALB2 PV carriers (HR: 3.11, 95%CI: 1.74 – 5.55, p< 0.001) but not in non-Hispanic White PALB2 PV carriers (HR: 1.00, 95%CI: 0.59 – 1.70, p=0.98) compared to non-carriers within the same race/ethnicity. Among 12,780 women with ER+ breast cancer, compared to non-carriers, OS was significantly worse in BRCA2 PV carriers (HR: 1.51, 95%CI: 1.06 – 2.16, p=0.02) and a trend towards worse OS was observed in BRCA1 PV carriers (HR:1.53, 95%CI:0.93 – 2.51, p=0.09). Among women with ER-negative breast cancer, a significant difference in OS was not observed between PV carriers in each of the five genes and non-carriers. Conclusions: The differences in OS by race/ethnicity in PALB2 PV carriers and by ER status of the tumor in BRCA2 PV carriers warrant further investigation of underlying tumor biology and assessment of endocrine sensitivity of breast cancer in germline PV carriers. Citation Format: Fergus Couch. Association between Germline Mutation Status and Overall Survival among Women with Breast Cancer in Population-based Studies in the United States [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PS10-02.

Abstract PO3-03-02: Effect of Surgery on Breast Cancer-Specific Mortality in Elderly Patients with Hormone Receptor-Positive, HER2-Negative Breast Cancer

Abstract Background: The number of elderly patients with breast cancer has been increasing in Japan. Although standard treatment including surgery is desirable if the expected life expectancy is sufficient, not all elderly patients with breast cancer are eligible for surgery due to frailty and comorbidities. Endocrine therapy (ET) alone is an alternative option if surgery is not considered adequate in patients with hormone receptor-positive breast cancer. We evaluated whether ET alone was associated with inferior overall and breast cancer-specific survival compared to standard treatment including surgery in elderly patients. Methods: This study included all patients aged 75 years and over who were diagnosed with non-metastatic primary invasive hormone receptor-positive, HER2-negative breast cancer and treated at Hiraka General Hospital from July 2006 to March 2022. Patients were divided as those who received ET alone (ET alone group) and those who received surgery with other therapies (Surgery group). Survival status as on March 31, 2023 and cause of death were determined. Overall survival and breast cancer-specific survival were estimated using the Kaplan–Meier method and compared using the log-rank test. Univariate analysis and multivariate Cox proportional hazards regression model including age, Eastern Cooperative Oncology Group performance status (PS) score, clinical stage, and treatment were used to identify survival-associated factors. Propensity score matching was used to reduce the effect of selection bias on treatment type during survival comparison of the groups. Results: The study cohort comprised 128 patients, including 33 and 95 patients in the ET alone group and Surgery group, respectively. The median ages were 84.6 and 80.4 years in the ET alone group and Surgery group, respectively (p < 0.05). Ten patients (30%) in the ET alone group had poor PS (3 or 4), and no patient in the Surgery group had poor PS (p < 0.01). Also, 24.2%, 54.5%, and 21.2% of the patients in the ET alone group and 48.4%, 43.2%, and 8.4% of the patients in the Surgery group had clinical stage I, II, and III disease at diagnosis, respectively (p < 0.05). Survival status was confirmed in all patients, and the cause of death was confirmed in 52 of the 53 patients who died (98%) during the study period, including 24 and 29 patients in the ET alone group and Surgery group, respectively. Breast cancer was the cause of death in 3 patients (13%) in the ET alone group and 5 patients (17%) in the Surgery group. By univariate analysis, overall survival was significantly better in the Surgery group than in the ET alone group (median, 12.5 vs. 4.1 years; p < 0.0001). Similarly, breast cancer-specific survival was better in the Surgery group than in the ET alone group (p < 0.05). By multivariate Cox proportional hazards regression analysis, age was associated with shorter overall survival time (hazard ratio [HR] 1.07, 95% confidence interval [CI] 1.00–1.15; p = 0.04) and surgery was associated with longer overall survival (HR 0.24, 95% CI 0.12–0.47; p < 0.001). Breast cancer-specific survival was associated with age (HR 1.18, 95% CI 1.03–1.36; p = 0.02) and clinical stage (HR 8.89, 95% CI 1.05–75.5; p < 0.05) but not with treatment (HR 0.66, 95% CI 0.73–5.85; p = 0.71). After propensity score matching, overall survival was significantly better in the Surgery group than in the ET alone group (HR 0.26, 95% CI 0.09–0.73; p = 0.01) whereas breast cancer-specific survival was not significantly different between the two groups (HR 0.82, 95% CI 0.08–8.27; p = 0.86). Conclusion: Even in elderly patients, surgery should be considered if sufficient life expectancy is expected. However, most of the deaths were not related to breast cancer in the present study cohort. Therefore, for elderly patients without sufficient life expectancy, endocrine therapy alone would be an appropriate option. Citation Format: Misako Yatsuyanagi, Tomoyuki Shimada, Yuko Takeishi, Yukiko Matsuzaka, Chika ohsawa. Effect of Surgery on Breast Cancer-Specific Mortality in Elderly Patients with Hormone Receptor-Positive, HER2-Negative Breast Cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-03-02.

Prognostic Value of Stress Myocardial Perfusion Imaging Across the Spectrum of Cardiovascular Risk

BackgroundSingle-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) is widely used to identify ischemia. There is limited research to evaluate if there is a risk threshold below which SPECT-MPI may not add significant prognostic value. MethodsBetween January 1, 2012, and December 31, 2018, individuals who underwent SPECT-MPI were stratified into four risk groups. The primary outcome was acute myocardial infarction (MI) or death. Multivariable Cox proportional hazards regression analysis was used to calculated HRs with 95% CIs. ResultsAmong 48,845 patients (52.3% male, median age 67 years), 8.5% were low risk, 4.8% borderline risk, 18.1% intermediate risk, and 68.6% high risk based on the American College of Cardiology pooled cohort equation. Ischemia was more commonly detected in the high-risk cohort (19.4% in high-risk vs. 6.5% in low-risk). SPECT-MPI testing was associated with a significantly increased use of preventive medications such as statin therapy, regardless of stress test results. At a median follow-up of 4.2 years, there was no significant association between ischemia and death or MI in the low-risk cohort (adjusted HR 1.91, 95% CI 0.94-3.92) or the borderline-risk cohort (adjusted HR 1.58, 95% CI 0.79-3.15). Ischemia was associated with a higher risk of death or MI in the intermediate-risk (adjusted HR 1.57, 95% CI 1.24-1.99) and high-risk groups (adjusted HR 1.54, 95% CI 1.44-1.64). ConclusionSPECT-MPI was less useful for risk stratification among low-risk patients due to their low event rates regardless of test result.

A Clinical Nomogram for Predicting Overall Survival in Patients With T1/T2 Penile Squamous Cell Carcinoma

BackgroundTo evaluate the overall survival (OS) and construct a nomogram to predict the OS of patients with penile squamous cell carcinoma (PSCC). MethodsThis retrospective study analyzed data of patients with PSCC from the First Affiliated Hospital of Soochow University between 2012 and 2022. R software was used to explore factors influencing OS in PSCC. Kaplan–Meier method and log-rank test were employed for OS estimation. Univariate and multivariate Cox proportional hazards regression analyses were performed to identify these factors. A nomogram was created to identify the independent prognostic factors. The model was evaluated by concordance index, receiver operating characteristic (ROC) curves, and calibration plots. ResultsA total of 159 patients with T1/T2 PSCC were included in the analysis. Patients with T2/N2 stage, older age, larger tumor size, high preoperative systemic immune-inflammation index (SII), and poor preoperative nutrition had a higher incidence of poor OS. Age, T/N stage, tumor size, and SII were identified as independent prognostic indicators. A prognostic nomogram was formulated, and its predictive accuracy for estimating OS in PSCC patients was validated through ROC curves and calibration plots. ConclusionThe nomograms, based on age, T/N stage, tumor size, and high preoperative SII, provide a valuable tool for predicting 1-, 2-, and 3-year OS in patients with T1/T2 PSCC without distant metastases.

Construction and Validation of a MRI‑Based Radiomic Nomogram to Predict Overall Survival in Patients with Local Advanced Cervical Cancer: A Multicenter Study

BackgroundCervical cancer is the fourth most common cancer among women. Radiomics has emerged as a new approach providing valuable information for cancer management. The aim of this study was to construct a radiomics nomogram to accurately predict survival outcomes in patients with locally advanced cervical cancer. MethodsThis retrospective study enrolled a total of 582 locally advanced cervical cancer patients from three center (training cohort: n=228; internal validation cohort: n=98; external validation cohort: n=256). Radiomic features were extracted from pretreatment MRI images. Least absolute shrinkage and selection operator logistic regression (LASSO) was applied to select radiomic features and calculated the radiomic scores. Univariate and multivariate Cox proportional hazards regression analyses were used to identify the independent prognostic clinic-radiological factors for cervical cancer, which were incorporated into the nomogram. ResultsA total of 6 radiomic features were found to be associated with overall survival of locally advanced cervical cancer patients. The AUC of radiomic scores in the training cohort was 0.634-0.708 for the training cohort, 0.725-0.762 for internal validation cohort and 0.788-0.881 for the external validation cohort. Age, parametrial invasion, and radiomic score were the independent prognostic indicators for cervical cancer patients (Age: HR=1.041, 95% CI=1.012-1.071, p=0.006; Parametrial invasion: HR=4.755, 95% CI=1.493-15.144, p=0.008; HR=2.324, 95% CI=1.050-5.143, p=0.037). The nomogram model incorporating these factors showed favorable discrimination in predicting the overall survival rates of cervical cancer patients, with the AUC values of 0.809, 0.808, and 0.862 for 1-, 2-, and 3-year predictions. The decision curve analysis (DCA) indicated that the nomogram model achieved the highest clinical net benefit across the entire range of reasonable threshold probabilities. ConclusionThe nomogram, incorporating clinicopathological factors and radiomic features derived from MRI images, showed satisfactory discrimination in predicting the overall survival rates of locally advanced cervical cancer patients.

Association between Plasma Interleukin-27 Levels and Cardiovascular Events in Patients Undergoing Coronary Angiography.

Atherosclerotic disease, including coronary heart disease (CHD), is one of the chronic inflammatory conditions, and an imbalance between pro-inflammatory and anti-inflammatory cytokines plays a role in the process of atherosclerosis. Interleukin (IL)-27, one of the IL-12 family members, is recognized to play a dual role in regulating immune responses with both pro-inflammatory and anti-inflammatory properties. IL-27 is secreted from monocytes, T cells, and endothelial cells, and its expression is upregulated in atherosclerotic plaques. We previously reported that no significant difference was observed in plasma IL-27 levels between patients with stable CHD and those without it. However, the prognostic value of IL-27 levels has not been fully elucidated. We studied the relation of plasma IL-27 levels to cardiovascular events in 402 patients undergoing elective coronary angiography for suspected CHD. We defined cardiovascular events as cardiovascular death, myocardial infarction, unstable angina, stroke, or coronary revascularization. Of the 402 study patients, CHD was present in 209 (52%) patients. Plasma IL-27 levels were not markedly different between patients with CHD and those without it (median 0.23 vs. 0.23 ng/mL). During a follow-up of 7.6 ± 4.5 years, cardiovascular events were observed in 70 patients (17%). In comparison to the 332 patients with no event, the 70 patients who had cardiovascular events showed significantly higher IL-27 levels (median 0.29 vs. 0.22 ng/mL) and more frequently had an IL-27 level of >0.25 ng/mL (59% vs. 40%) (p < 0.01). The Kaplan-Meier analysis demonstrated a lower event-free survival rate in patients with an IL-27 level >0.25 ng/mL than in those with an IL-27 level ≤0.25 ng/mL (p < 0.02). The multivariate Cox proportional hazards regression analysis showed that IL-27 level (>0.25 ng/mL) was a significant predictor for cardiovascular events (hazard ratio: 1.82; 95%CI: 1.13-2.93, p < 0.02), independent of CHD. Thus, high IL-27 levels in plasma were related to an increased risk of further cardiovascular events in patients who underwent elective coronary angiography.

The proportion of tumour stroma predicts response to treatment of immune checkpoint inhibitor in combination with chemotherapy in patients with stage IIIB-IV non-small cell lung cancer.

Immunotherapy has brought a new era to cancer treatment, yet we lack dependable predictors for its effectiveness. This study explores the predictive significance of intratumour stroma proportion (iTSP) for treatment success and prognosis in non-small cell lung cancer (NSCLC) patients undergoing treatment with immune check-point inhibitors (ICIs) together with chemotherapy. We retrospectively collected data from patients with unresectable stage IIIB-IV NSCLC who were treated with first-line ICIs and chemotherapy. Each patient received a confirmed pathological diagnosis, and the pathologist evaluated the iTSP on haematoxylin and eosin (H&E)-stained sections of diagnostic tissue slides. Among the 102 H&E-stained biopsy samples, 61 (59.8%) were categorised as stroma-L (less than 50% iTSP), while 41 (40.2%) were classified as stroma-H (more than 50% iTSP). We observed that the stroma-L group exhibited a significantly better objective response rate (ORR) (72.1 versus 51.2%, P = 0.031) and deeper response depth (DpR) (-50.49 ± 28.79% versus -35.83 ± 29.91%, P = 0.015) compared to the stroma-H group. Furthermore, the stroma-L group showed longer median progression-free survival (PFS) (9.6 versus 6.0 months, P = 0.011) and overall survival (OS) (24.0 versus 12.2 months, P = 0.001) compared to the stroma-H group. Multivariate Cox proportional hazards regression analysis indicated that iTSP was a highly significant prognostic factor for both PFS [hazard ratio (HR) = 1.713; P = 0.030] and OS (HR = 2.225; P = 0.003). Our findings indicate that a lower iTSP corresponds to improved clinical outcomes and greater DpR in individuals with stage IIIB-IV NSCLC treated with first-line ICIs and chemotherapy. The iTSP could potentially serve as a predictive biomarker for ICIs therapy response.

Analysis of long-term prognosis and risk factors in patients with dilated cardiomyopathy

Objective: To investigate the risk factors and long-term prognosis of major adverse cardiovascular events(MACEs) in patients with dilated cardiomyopathy (DCM). Methods: This study was a single-center retrospective cohort study. Clinical information from 300 patients with DCM hospitalized in Peking Union Medical College Hospital from April 2013 to April 2023 was collected. Based on echocardiography results, the patients were divided into two groups: isolated DCM and DCM with left ventricular non-compaction cardiomyopathy (LVNC). The MACEs, including major heart failure events, severe ventricular arrhythmias, and cardiovascular death, were recorded by outpatient or telephone follow-up. Univariate and multivariate Cox proportional hazard regression models were used to analyze the risk factors affecting the prognosis of patients with DCM. Kaplan-Meier curve and log-rank were used for survival analysis to compare the difference in the incidence of cardiovascular events between the two groups. Results: The included 300 DCM patients were (47.8±16.8) years old, with 197 males (65.7%), of which 237 (79.0%) were isolated DCM and 63 (21.0%) were DCM with LVNC. The follow-up time was 4.0 (1.9, 6.2) years. A total of 142 (47.3%) MACEs occurred, including 117 (39.0%) major heart failure events, 20 (6.7%) severe ventricular arrhythmia events, and 53 (17.7%) cardiovascular death events. Multivariate Cox proportional hazard regression analysis showed that increased left ventricular end-diastolic diameter (HR=1.21, 95%CI: 1.01-1.44, P=0.042), moderate or severe mitral regurgitation (HR=1.71, 95%CI: 1.19-2.47, P=0.004), increased ln (N-terminal pro-B-type natriuretic peptide) (HR=1.30, 95%CI: 1.10-1.54, P=0.002) were independent risk factors for dverse cardiovascular events in DCM patients, and angiotensin-converting enzyme inhibitor (ACEI)/angiotensin receptor blocker (ARB)/angiotensin receptor neprilysin inhibitor (ARNI) treatment (HR=0.45, 95%CI: 0.26-0.78, P=0.004) was independent protective factor. Kaplan-Meier survival analysis found no significant difference in the risk of MACEs between isolated DCM and DCM with LVNC (P=0.22). Similarly, there were no significant differences in the incidence of major heart failure, severe ventricular arrhythmia, and cardiovascular death between the two groups (all P>0.05). Conclusion: An increase in left ventricular end-diastolic diameter, moderate or severe mitral regurgitation, elevated N-terminal pro-B-type natriuretic peptide, and non use of ACEI/ARB/ARNI are independent predictors of cardiovascular events in DCM patients. There was no significant risk of MACEs in patients with isolated DCM and DCM with LVNC, and suggested that LVNC may be a unique phenotype and should be accurately managed in combination with genetic background.

Treatment patterns and survival in T4b esophageal cancer: a retrospective cohort study.

This study aims to evaluate the efficacy of various treatment approaches in stage T4b esophageal cancer patients. Data were extracted from the Surveillance, Epidemiology, and End Results databases, covering patients diagnosed with esophageal cancer between 2000 and 2020. Kaplan-Meier analysis was used to assess cancer-specific survival (CSS) and overall survival (OS) across different treatment patterns. The study included 482 patients: 222 (46.1%) received chemoradiotherapy, 58 (12.0%) underwent radiotherapy alone, 37 (7.7%) received chemotherapy alone, 50 (10.4%) underwent surgery, and 115 (23.8%) received no treatment. Median CSS were 12, 4, 6, 18, and 1 month for chemoradiotherapy, radiotherapy alone, chemotherapy alone, surgery, and non-treatment groups. Median OS for these groups were 11, 3, 6, 17, and 1 month, respectively. Multivariable proportional hazard regression analysis revealed that patients who underwent surgery experienced significantly improved CSS (hazard ratio [HR] = 0.42, 95% confidence interval [CI]: 0.24-0.72; P = 0.002) and OS (HR = 0.45, 95% CI: 0.28-0.74; P = 0.002) compared to those receiving chemoradiotherapy after propensity score matching. Esophagectomy, with or without radiotherapy and/or chemotherapy, results in better survival outcomes than chemoradiotherapy in patients with stage T4b esophageal cancer.

Convalescent Growth Differentiation Factor-15 and Long-Term Outcomes after an Acute Coronary Syndrome.

Growth differentiation factor-15 (GDF-15) has been shown to be associated with adverse clinical outcomes in patients after an acute coronary syndrome when measured soon after an event. Although dynamic in the acute phase after myocardial injury, GDF-15 has been shown to remain stable during convalescence. In this study, we aimed to assess the value of GDF-15 as a long-term prognostic marker for clinical outcomes when measured in the convalescent phase following an acute coronary syndrome. GDF-15 concentrations were measured in 1945 patients who were recruited between 2002 and 2009 to the Coronary Disease Cohort Study. For this analysis, follow-up was curtailed at 10 years and association of GDF-15 with all-cause death, cardiovascular death, recurrent myocardial infarction, and heart failure hospitalizations were assessed with multivariate Cox proportional hazard regression analysis. After 10 years of follow-up, there were 648 deaths (348 from cardiovascular causes), 500 admissions for myocardial infarction, and 436 for heart failure. Four-month convalescent GDF-15 demonstrated a robust independent association with all endpoints, which remained after adjustment for Global Registry of Acute Coronary Events score and other convalescent biomarkers. When compared to the lowest quartile of GDF-15 concentrations, those in the highest quartile had a 3-fold increased risk of all-cause death. Convalescent plasma GDF-15 is a strong and independent predictor of 10-year all-cause death, cardiovascular death, recurrent myocardial infarction, and heart failure admission following an acute coronary syndrome. ACTRN12605000431628.

Arteriovenous fistula for haemodialysis as a predictor of de novo heart failure in kidney transplant recipients.

The haemodynamic effects of a functioning haemodialysis arteriovenous fistula (AVF) can cause or exacerbate heart failure (HF). We investigated whether the presence of an AVF at the time of kidney transplant (KT) is associated with de novo HF. This was an observational cohort study including adult patients who received a KT in the West of Scotland between 2010 and 2020. We evaluated the risk and associations of pretransplant factors with de novo HF, alone and as a composite cardiovascular (CV) outcome (including non-fatal myocardial infarction, non-fatal stroke, de novo HF and CV death). Multivariable proportional hazards regression and sensitivity analyses were used to identify independent correlates of the outcomes. Among 1330 included patients, the incident rate of de novo HF after transplantation was 58/1000 person-years [95% confidence interval (CI) 50-67] in AVF patients (n=716) compared with 33/1000 person-years (95% CI 27-41) in non-AVF patients (n=614). De novo HF was associated with the presence of an AVF [adjusted hazard ratio (aHR) 2.14 (95% CI 1.40-3.26)], duration of dialysis [aHR 1.03/year increase (95% CI 1.01-1.04)], age at transplant [aHR 1.03/year increase (95% CI 1.02-1.05)], female sex [aHR 1.93 (95% CI 1.40-2.65)] and pretransplant diabetes [aHR 2.43 (95% CI 1.48-4.01)]. The presence of an AVF was also associated with the composite CV outcome [aHR 1.91 (95% CI 1.31-2.78)]. The presence of an AVF may be an underrecognized modifiable predictor of de novo HF posttransplantation.

Incremental value of tricuspid annular enlargement to progressive tricuspid regurgitation in patients with longstanding persistent atrial fibrillation.

Tricuspid annular enlargement in patients with atrial fibrillation (AF) can induce tricuspid regurgitation (TR). However, risk factors associated with TR progression in patients with AF have not been defined. This study aimed to clarify an association between tricuspid annular diameter (TAD) and TR progression in patients with longstanding persistent AF. We retrospectively analyzed data from 228 patients who had longstanding persistent AF for > 1year and mild or less TR on baseline echocardiograms. We defined significant TR as moderate or greater TR, graded according to the jet area and vena contracta. The optimal cut-off value of the TAD index (TADI), based on body surface area for predicting progression to significant TR, was estimated using receiver operating characteristic (ROC) curves. The independence and incremental value of the TADI were evaluated using multivariate Cox proportional hazard regression analysis and likelihood ratio tests. Over a median follow-up of 3.7years, 55 (24.1%) patients developed significant TR. The optimal cut-off value of 21.1mm/m2 for the TADI at baseline and ROC curves predicted TR progression with 70.4% sensitivity and 86% specificity. Furthermore, TADI was an independent predictor of TR progression (hazard ratio, 1.32; 95% confidence interval, 1.17-1.49, P < 0.001) and had a significant incremental value that exceeded that of models constructed using clinical parameters. In conclusion, TADI was significantly associated with TR progression and was an independent predictor of TR progression in longstanding persistent AF.

Risk factors, prognostic factors, and nomograms for distant metastasis in patients with diagnosed duodenal cancer: A population-based study.

Duodenal cancer is one of the most common subtypes of small intestinal cancer, and distant metastasis (DM) in this type of cancer still leads to poor prognosis. Although nomograms have recently been used in tumor areas, no studies have focused on the diagnostic and prognostic evaluation of DM in patients with primary duodenal cancer. To develop and evaluate nomograms for predicting the risk of DM and personalized prognosis in patients with duodenal cancer. Data on duodenal cancer patients diagnosed between 2010 and 2019 were extracted from the Surveillance, Epidemiology, and End Results database. Univariate and multivariate logistic regression analyses were used to identify independent risk factors for DM in patients with duodenal cancer, and univariate and multivariate Cox proportional hazards regression analyses were used to determine independent prognostic factors in duodenal cancer patients with DM. Two novel nomograms were established, and the results were evaluated by receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA). A total of 2603 patients with duodenal cancer were included, of whom 457 cases (17.56%) had DM at the time of diagnosis. Logistic analysis revealed independent risk factors for DM in duodenal cancer patients, including gender, grade, tumor size, T stage, and N stage (P < 0.05). Univariate and multivariate COX analyses further identified independent prognostic factors for duodenal cancer patients with DM, including age, histological type, T stage, tumor grade, tumor size, bone metastasis, chemotherapy, and surgery (P < 0.05). The accuracy of the nomograms was validated in the training set, validation set, and expanded testing set using ROC curves, calibration curves, and DCA curves. The results of Kaplan-Meier survival curves (P < 0.001) indicated that both nomograms accurately predicted the occurrence and prognosis of DM in patients with duodenal cancer. The two nomograms are expected as effective tools for predicting DM risk in duodenal cancer patients and offering personalized prognosis predictions for those with DM, potentially enhancing clinical decision-making.

Long-Term Outcomes After Aortic Valve Replacement for Aortic Valve Regurgitation - Importance of Left Ventricular End-Systolic Diameter.

We determined the left ventricular end-systolic diameter (LVDs) cut-off value for risk of major adverse cardiac and cerebrovascular events (MACCE) in Japanese asymptomatic or mildly symptomatic patients undergoing aortic valve replacement (AVR) for aortic valve regurgitation (AR), and investigated the effect of left ventricular dilation on long-term postoperative outcomes.Methods and Results: The 168 patients who underwent surgical AVR for AR at Shiga University of Medical Science between January 2002 and December 2022 were included in this study. Receiver operating characteristic curve analysis showed that the cut-off value of preoperative LVDs for the incidence of MACCE was 42.8 mm (area under the curve 0.616). Postoperative outcomes were compared between patients with preoperative LVDs >42.8 mm (n=77) and those with preoperative LVDs ≤42.8 mm (n=91) using propensity score matching. The 10-year estimated rates of freedom from MACCE in those with LVDs >42.8 and ≤42.8 mm were 59.9% and 85.7%, respectively; the curves differed significantly (P=0.004). In multivariable Cox proportional hazard regression analyses, preoperative LVDs >42.8 mm was an independent predictor of MACCE (hazard ratio 2.485; 95% confidence interval 1.239-4.984; P=0.010). Preoperative LVDs >42.8 mm is associated with an increased risk of MACCE in Japanese patients undergoing AVR for AR.

Mid-Term Outcome after Extracorporeal Life Support in Postcardiotomy Cardiogenic Shock: Recovery and Quality of Life.

Background: Extracorporeal life support (ECLS) therapy for refractory postcardiotomy cardiogenic shock (rPCS) is associated with high early mortality rates. This study aimed to identify negative predictors of mid-term survival and to assess health-related quality of life (HRQoL) and recovery of the survivors. Methods: Between 2017 and 2020, 142 consecutive patients received ECLS therapy following cardiac surgery. The median age was 66.0 [57.0-73.0] years, 67.6% were male and the median EuroSCORE II was 10.5% [4.2-21.3]. In 48 patients, HRQoL was examined using the 36-Item Short Form Survey (SF-36) and the modified Rankin-Scale (mRS) at a median follow-up time of 2.2 [1.9-3.2] years. Results: Estimated survival rates at 3, 12, 24 and 36 months were 47%, 46%, 43% and 43% (SE: 4%). Multivariable Cox Proportional Hazard regression analysis revealed preoperative EuroSCORE II (p = 0.013), impaired renal function (p = 0.010), cardiopulmonary bypass duration (p = 0.015) and pre-ECLS lactate levels (p = 0.004) as independent predictors of mid-term mortality. At the time of follow-up, 83.3% of the survivors were free of moderate to severe disability (mRS < 3). SF-36 analysis showed a physical component summary of 45.5 ± 10.2 and a mental component summary of 50.6 ± 12.5. Conclusions: Considering the disease to be treated, ECLS for rPCS is associated with acceptable mid-term survival, health-related quality of life and functional status. Preoperative EuroSCORE II, impaired renal function, cardiopulmonary bypass duration and lactate levels prior to ECLS implantation were identified as negative predictors and should be included in the decision-making process.

Frailty Influences the Relationship between the Soluble Receptor for Advanced Glycation-End Products and Mortality in Older Adults with Diabetes Mellitus

Introduction: Frailty is prevalent among older adults with diabetes mellitus. Elevated serum levels of the soluble receptor for advanced glycation-end products (sRAGE) predict mortality in frail older adults. The evidence that sRAGE is also related to higher mortality in older adults with diabetes mellitus is inconsistent. Therefore, this study explored if frailty status influences the relationship between sRAGE and mortality in older adults with this condition. Methods: We analysed data of 391 participants with diabetes mellitus (median age, 76 years) from four European cohorts enrolled in the FRAILOMIC project. Frailty was evaluated at baseline using Fried’s criteria. Serum sRAGE was determined by ELISA. Participants were stratified by frailty status (n = 280 non-frail and 111 frail). Multivariate Cox proportional hazards regression and Kaplan-Meier survival analysis were used to assess the relationship between sRAGE and mortality. Results: During 6 years of follow-up, 98 participants died (46 non-frail and 52 frail). Non-survivors had significantly higher baseline levels of sRAGE than survivors (median [IQR]: 1,392 [962–2,043] pg/mL vs. 1,212 [963–1,514], p = 0.008). High serum sRAGE (>1,617 pg/mL) was associated with increased mortality in the whole diabetes sample after adjustment for relevant confounders (HR 2.06, 95% CI: 1.36–3.11, p < 0.001), and there was an interaction between sRAGE and frailty (p = 0.006). Accordingly, the association between sRAGE and mortality was stronger in the frail group compared to the non-frail group (HR 2.52, 95% CI: 1.30–4.90, p = 0.006 vs. HR 1.71, 95% CI: 0.91–3.23, p = 0.099, respectively). Likewise, Kaplan-Meier curves showed a significant difference in survival rates between frail participants with high sRAGE and those with low sRAGE (p = 0.001), whereas no survival difference was seen in the non-frail group (p = 0.09). Conclusions: Frailty status influences the relationship between sRAGE and mortality in older adults with diabetes mellitus. Determination of sRAGE in this population could be a useful tool for risk stratification.

Surgical options and survival prognosis in geriatric patients beyond average lifespan with locally advanced gastric cancer: a propensity score-matched analysis.

The appropriateness of laparoscopic gastrectomy (LG) for super-geriatric patients with locally advanced gastric cancer (LAGC) is inconclusive, and the prognostic factors are also yet to be elucidated. Herein, we aimed to investigate the surgical and oncological outcomes of LG versus open gastrectomy (OG) for geriatric patients with LAGC who have outlived the average lifespan of the Chinese population (≥ 78years). This is a monocentric, retrospective, comparative study. A 1:1 propensity score matching (PSM) was performed to minimize selection bias and ensure well-balanced characteristics. The primary endpoint of interest was 3-year overall survival, while secondary endpoints included procedure-related variables, postoperative recovery indices, and complications. Univariate and multivariate Cox proportional hazards regression analyses were performed to identify unfavorable prognostic factors. Of 196 eligible individuals, 107 underwent LG and 89 underwent OG, with a median age (interquartile range [IQR]) of 82 [79, 84] years. PSM yielded 61 matched pairs, with comparable demographic and tumor characteristics. The LG group had a significantly lower overall complication rate than the OG group (31.1% vs. 49.2%, P = 0.042), as well as shorter duration of postoperative hospital stay [12 (11, 13) vs. 13 (12, 15.5) d, P < 0. 001], less intraoperative blood loss [95 (75, 150) vs. 230 (195, 290) mL, P < 0.001], but a longer operative time [228 (210, 255.5) vs. 196 (180, 219.5) min, P < 0.001]. The times to first aerofluxus, defecation, liquid diet, and half-liquid diet were comparable. Kaplan-Meier analyses revealed no significant difference in 3-year overall survival between the groups, either in the entire cohort or in subgroups with different TNM staging. Moreover, Age-adjusted Charlson Comorbidity Index scores of > 6 [hazard ratio (HR) 4.003; P = 0.021] and pathologic TNM stage III (HR 3.816, P = 0.023) were independent unfavorable prognostic factors for long-term survival. LG performed by experienced surgeons offers the benefits of comparable or better surgical and oncological safety profiles than OG for super-geriatric patients with LAGC.

Treatment Patterns and Survival Outcomes in Patients With Breast Cancer on Medicaid, Pre- and Post-Expansion.

The objective of this study was to evaluate the impact of Medicaid expansion on breast cancer treatment and survival among Medicaid-insured women in Ohio, accounting for the timing of enrollment in Medicaid relative to their cancer diagnosis and post-expansion heterogeneous Medicaid eligibility criteria, thus addressing important limitations in previous studies. Using 2011-2017 Ohio Cancer Incidence Surveillance System data linked with Medicaid claims data, we identified women aged 18 to 64 years diagnosed with local-stage or regional-stage breast cancer (n=876 and n=1,957 pre-expansion and post-expansion, respectively). We accounted for women's timing of enrollment in Medicaid relative to their cancer diagnosis, and flagged women post-expansion as Affordable Care Act (ACA) versus non-ACA, based on their income eligibility threshold. Study outcomes included standard treatment based on cancer stage and receipt of lumpectomy, mastectomy, chemotherapy, radiation, hormonal treatment, and/or treatment for HER2-positive tumors; time to treatment initiation (TTI); and overall survival. We conducted multivariable robust Poisson and Cox proportional hazards regression analysis to evaluate the independent associations between Medicaid expansion and our outcomes of interest, adjusting for patient-level and area-level characteristics. Receipt of standard treatment increased from 52.6% pre-expansion to 61.0% post-expansion (63.0% and 59.9% post-expansion in the ACA and non-ACA groups, respectively). Adjusting for potential confounders, including timing of enrollment in Medicaid, being diagnosed in the post-expansion period was associated with a higher probability of receiving standard treatment (adjusted risk ratio, 1.14 [95% CI, 1.06-1.22]) and shorter TTI (adjusted hazard ratio, 1.14 [95% CI, 1.04-1.24]), but not with survival benefits (adjusted hazard ratio, 1.00 [0.80-1.26]). Medicaid expansion in Ohio was associated with improvements in receipt of standard treatment of breast cancer and shorter TTI but not with improved survival outcomes. Future studies should elucidate the mechanisms at play.

Association between novel genetic variants of Notch signaling pathway genes and survival of hepatitis B virus-related hepatocellular carcinoma.

Although the Notch pathway plays an important role in formation and progression of hepatocellular carcinoma (HCC), few studies have reported the associations between functional genetic variants and the survival of hepatitis B virus (HBV)-related HCC. In the present study, we performed multivariable Cox proportional hazard regression analysis to evaluate associations between 36,101 SNPs in 264 Notch pathway-related genes and overall survival (OS) of 866 patients with HBV-related HCC. It was found that three independent SNPs (NEURL1B rs4868192, CNTN1 rs444927 and FCER2 rs1990975) were significantly associated with the HBV-related HCC OS. The number of protective genotypes (NPGs) were significantly associated with better survival in a dose-response manner (ptrend <0.001). Compared with the model with sole clinical factors, the addition of protective genotypes to the predict models significantly increased the AUC, i.e., from 72.72% to 75.13% (p = 0.002) and from 72.04% to 74.76 (p = 0.004) for 3-year and 5-year OS, respectively. The expression quantitative trait loci (eQTL) analysis further revealed that the rs4868192 C allele was associated with lower mRNA expression levels of NEURL1B in the whole blood (p = 1.71 × 10-3), while the rs1990975 T allele was correlated with higher mRNA expression levels of FCER2 in the whole blood and normal liver tissues (p = 3.51 × 10-5 and 0.033, respectively). Three potentially functional SNPs of NEURL1B, CNTN1 and FCER2 may serve as potential prognostic biomarkers for HBV-related HCC.

Incidence and predictors of mortality among neonates admitted with birth asphyxia to neonatal intensive care unit of West Shewa Zone Public Hospitals, Central Ethiopia

BackgroundBirth asphyxia is still one of the primary causes of newborn mortality worldwide. Similarly, the risk of newborn asphyxia in Ethiopia remains unacceptably high. Thus, studies on the incidence and...