Univariate Cox Proportional Hazards Analyses Research Articles

Factors Associated with Ureteral Stent Failure in Patients with Malignant Ureteral Obstruction.

Introduction: Management of malignant ureteral obstruction (MUO) with ureteral stents remains a clinical challenge, often involving frequent stent exchanges attributable to stent failure or other urological complications. We report our institutional experience with ureteral stents for management of MUO, including analysis of clinical factors associated with stent failure. Methods: We performed a retrospective review of patients treated with indwelling ureteral stents for MUO in nonurothelial malignancies at our tertiary-care institution between 2008 and 2019. Univariate Cox proportional hazards analysis was performed to identify clinical variables associated with stent failure and stent-related complications. Stent failure was defined as need for unplanned stent exchange, placement of percutaneous nephrostomy (PCN), or tandem stents. Results: In our cohort of 78 patients, the median (range) number of stent exchanges was 2 (0-17) during a total stent dwell time of 4.3 (0.1-40.3) months. Thirty-four patients (43.6%) developed a culture-proven urinary tract infection (UTI) during stent dwell time. Thirty-five patients (44.8%) had stent failure. Twenty-two patients (28.2%) underwent unplanned stent exchanges, 23 (29.5%) required PCN after initial stent placement, and 6 (7.7%) required tandem stents. Ten (28.6%) patients with stent failure were treated with upsized stents, which led to resolution in seven patients. Stent failure occurred with 20/44 (45.4%) Percuflex™, 15/27 (55.6%) polyurethane, and 2/3 (66.7%) metal stents. In patients with ≥2 exchanges (N = 45), median time between exchanges was 4.1 (2.0-14.8) months. Bilateral stenting and history of radiation predicted UTI development. Median overall patient survival after initial stent placement was 19.9 months (95% CI 16.5-37.9 months). Conclusions: Ureteral stent failure poses a significant medical burden to patients with MUO. Better methods to minimize stent-related issues and improve patient quality of life are needed. Using a shared decision-making approach, clinicians and patients should consider PCN or tandem stents early in the management of MUO.

Baseline Left Atrial Strain is Predictive of Chemotherapy Induced Cardiotoxicity in High-Risk Cancer Patients

Currently, no baseline imaging biomarkers can predict chemotherapy induced cardiotoxicity (CTx). We aimed to determine if baseline left atrial (LA) reservoir strain (LAS) is predictive of CTx. We performed retrospective analysis of the SUCCOUR study, an international multicentre randomised controlled trial. CTx was defined as an asymptomatic drop of >10% in left ventricular ejection fraction (LVEF) compared to baseline to <55%. After excluding 78 with inadequate images, 229 were included in the analysis. Most participants were female (n=215, 94%), with a mean age of 54±12 years. Breast cancer was the main cancer type (n=205, 90%). The mean baseline 3D LVEF, LV global longitudinal strain (GLS), LAS, and LA volume index (LAVI) were 61±4%, 20.6±2.5%, 28.6±7.9%, and 28±9mL/m2, respectively. At 1-year follow-up, 29 patients (13%) developed CTx. On univariable Cox proportional hazard analysis, lower baseline LAS was associated with a higher risk of CTx (HR 0.95, 95% CI 0.90–0.99; p=0.026) but baseline GLS was not (p=0.17). In nested Cox models (Figure 1), adding LAS significantly improved the model’s predictive accuracy for CTx. Baseline LAS is an independent and incremental predictor of CTx. LAS can be used for baseline risk stratification in oncology patients who receive cardiotoxic chemotherapy.

The prognosis of HPV-associated metastatic pharyngeal patients by primary and distant site

ObjectivesHuman papillomavirus (HPV) positivity is a favorable prognostic factor in the general population of head and neck squamous cell carcinoma (HNSCC) patients. However, its impact on the survival of metastatic HNSCC of pharynx (mHNSC-P) patients is unclear. This study aims to investigate the associations between HPV status and survival in mHNSC-P patients. Methods735 mHNSC-P patients diagnosed at first presentation from 2010 to 2016 were retrieved from the Surveillance, Epidemiology and End Result database (SEER). Chi-Squared test, univariate and multivariate cox proportional hazards model, Kaplan–Meier analysis, and log-rank test were applied to compare HPV-positive and -negative mHNSC-P patients. ResultUsing univariate cox proportional hazards analysis, HPV status, primary site, T stage, treatment and distant metastatic site correlate with the overall survival (OS) and disease-specific survival (DSS) in mHNSC-P patients. Multivariate cox regression analysis shows that HPV-positive mHNSC-P patients experienced significantly better OS (HR: 0.62 CI: 0.51–0.76, p < 0.001) and DSS (HR: 0.73 CI: 0.58–0.91, p < 0.01) as compared to HPV-negative mHNSC-P patients. Subgroup analysis indicates that HPV-associated OS and DSS benefits exist in patients with metastatic HNSCC of oropharynx (mHNSC-OP) but not in patients with metastatic HNSCC of non-oropharynx (mHNSC-non-OP). Among mHNSC-OP patients, HPV positivity confers disease-specific survival benefit in patients with oligometastatic rather than polymetastatic patients. Furthermore, HPV associated OS and DSS advantages in mHNSC-OP with lung metastasis was observed. ConclusionHPV-positive mHNSC-OP patients with lung metastasis show better survival than HPV-negative mHNSC-OP patients, providing key information to guide patient treatment approaches.

Prognostic Value of the Three-Dimensional Right Ventricular Ejection Fraction in Patients With Asymptomatic Aortic Stenosis.

Background: The right ventricular (RV) function is an important prognostic marker of asymptomatic aortic stenosis (AS). However, previous publications have not addressed the additive value of conventional RV parameters over left heart parameters. Whether three-dimensional echocardiography (3DE)-derived RV ejection fraction (RVEF) has prognostic utility independent of 3DE derived left heart parameters is also unknown. We investigated the prognostic utility of 3DE RVEF in patients with asymptomatic AS.Methods: We retrospectively selected 392 asymptomatic AS patients. RVEF, left ventricular ejection fraction (LVEF) and left atrial volumes (LAVs) were measured using 3DE datasets. We determined the association of those parameters, as well as of aortic valve replacement (AVR), and Charlson's comorbidity index with cardiac events. We also analyzed whether RVEF has incremental value over two-dimensional echocardiography (2DE) RV parameters.Results: During a median follow-up of 27 months, 57 patients developed cardiac events, and 68 patients received AVR. Univariate Cox proportional hazard analysis revealed that RVEF was associated with cardiac events (p < 0.001). Multivariate analysis revealed that RVEF was significantly associated with cardiac events (p < 0.001) even after adjusting for AVR, Charlson's comorbidity index, LVEF, LAV, E/e', and indexed aortic valve area (iAVA). An incremental value of RVEF over left heart parameters was also demonstrated using a nested regression model. Classification and regression-tree analysis selected RVEF first with a cut-off value of 41%. RVEF had incremental value over iAVA, LVEF, and 2DE conventional RV parameters for its association with future outcomes.Conclusions: 3DE RVEF had significant prognostic value even after adjusting for comorbidities, left heart parameters, and conventional 2DE RV parameters in asymptomatic aortic stenosis.

Incremental predictive value of echocardiographic indices of right ventricular function in the assessment of long-term prognosis in dogs with myxomatous mitral valve disease

IntroductionFew studies have evaluated the utility of echocardiographic indices of right ventricular (RV) function in predicting prognosis in dogs with myxomatous mitral valve disease (MMVD). AnimalsSixty-seven client-owned dogs were diagnosed with MMVD. Materials and methodsclinical cohort study. Dogs diagnosed with American college of veterinary internal medicine (ACVIM) stage B2, C or D between April 2014 and March 2017 were enrolled. Long-term outcomes were assessed by telephone or from the medical record. The primary end-point was defined as cardiac-related death. Echocardiographic indices of RV function, including the RV Tei index, free wall and septal RV longitudinal strain, were obtained. Univariable and multivariable Cox proportional hazard analyses were used to identify variables predictive of cardiac-related death. ResultsTwenty-four dogs died during the follow-up period. The median follow-up time was 482 days, and the median survival time for dogs with cardiac-related death was 230 days. For cardiac-related death, peak early diastolic mitral inflow velocity, ACVIM stage C or D, tricuspid regurgitation velocity, RV Tei index and RV end-diastolic area were predictors in univariable Cox proportional hazard analysis. In multivariable Cox proportional analysis adjusted for the left atrial to aorta ratio, peak early diastolic mitral inflow velocity and ACVIM stage, an increase in the Tei index by 0.1 increased the hazard ratio of cardiac-related death by 33% (95% confidence interval, 16–70%; P = 0.002). ConclusionsIn dogs with MMVD, RV dysfunction assessed by the Tei index is an independent predictor of cardiac-related death.

Abstract 10471: Prognostic Significance of Soluble Programed Cell Death Ligand-1 on Cardiovascular Outcomes in Patients with Atherosclerotic Cardiovascular Disease

Background: Programmed Death-1(PD-1) and its ligand, PD-L1 regulate T cell proliferation and secretion of cytokines, leading to immunotolerance. A previous experimental study reported increased expression of PD-L1 in myocardium. Hence, PD-L1 could be associated with atherosclerotic cardiovascular disease (ASCVD). We hypothesized that serum soluble PD-L1 (sPD-L1) could be associated with cardiovascular events. We prospectively investigated the association between the serum levels of sPD-L1 and cardiovascular outcomes in patients with ASCVD. Methods: We prospectively measured sPD-L1 in patients with ASCVD admitted to Kumamoto University Hospital using a commercially available enzyme-linked immunosorbent assay kit and observed the occurrence of cardiovascular events between December 2017 and June 2019. The primary outcome was a composite of death from any cause, death from cardiovascular causes, nonfatal myocardial infarction, unstable angina pectoris, stroke, and heart failure hospitalization. We excluded patients complicated with cancer, hemodialysis, active collagen diseases, and inflammatory diseases. Results: Finally, 446 patients with ASCVD were enrolled. Median follow-up period was 322 days. A total of 153 events were recorded. Kaplan-Meier curve revealed that the higher sPD-L1 group (sPD-L1 ≧155pg/dL, median) showed significantly higher rate of cardiovascular events than the lower sPD-L1 group (19.2% vs. 28.1%, log-rank test: P =0.044). Univariate Cox proportional hazards analysis showed that creatinine, low density-lipoprotein cholesterol, B-type natriuretic peptide (BNP), and higher sPD-L1 (≧155pg/dL) were significantly associated with cardiovascular events. Multivariable Cox proportional hazards analysis by significant factors from univariate analysis identified that higher sPD-L1 [hazard ratio (HR): 1.699, 95% confidence interval (CI): 1.023-2.823, P =.041) and BNP (HR: 1.001, 95% CI: 1.000-1.001, P =0.036) were significantly and independently associated with cardiovascular events. Conclusions: The higher levels of sPD-L1 were significantly associated with near future cardiovascular events in patients with ASCVD, suggesting sPD-L1 could be a novel prognostic predictor in patients with ASCVD.

Minimally invasive approach in endometrial cancer with lower uterine segment involvement in stage ≥ II: A retrospective study

ObjectiveTo compare oncological outcomes in women with lower uterine segment involvement (LUSI) in endometrial carcinoma (EC) stage ≥ II - staged by a minimally invasive surgery (MIS) versus laparotomy. Study designA retrospective multi-center cohort study. Univariate analysis, Kaplan-Meier survival and Cox proportional hazard analysis were performed to compare between women staged by MIS and those staged by laparotomy. ResultsOver a median follow-up period of 3 years (interquartile range, 1.5–6 years) 212 women were included, 68 (32.1%) were surgically staged by MIS. Stages of disease did not vary between MIS and laparotomy and were 32.1%, 51.9%, and 16.0%, in stages II, III and IV – respectively. Adjuvant radiation and chemotherapy rate did not differ between groups. Overall recurrence rate was comparable (p = 0.084). Locoregional recurrence rate was higher in the MIS group odds ratio 2.17, 95% confidence interval 1.19–4.20).Overall and progression free survival were similar in both groups (log rank test p = 0.08 and p = 0.912 respectively). In Cox regression model adjusting for age, comorbidities, tumor grade, stage and adjuvant therapy, route of surgery (MIS vs. laparotomy) was not associated with overall survival (p = 0.169). ConclusionsIn women with advanced EC and LUSI, although MIS is associated with locoregional recurrences, survival is comparable to laparotomy.

SURG-08. SARCOPENIA IS A PROGNOSTIC FACTOR OF 90-DAY MORTALITY AND OVERALL SURVIVAL IN ELDERLY PATIENTS WITH GLIOBLASTOMA

Abstract Elderly patients with glioblastoma (GBM) have worse overall prognosis compared to younger patients and are less likely to undergo tumor resection and adjuvant therapy. The goal of this study was to identify patient and treatment factors as well as preoperative imaging features associated with worse overall survival and death within 3 months of surgery in elderly GBM patients. A single-center retrospective study was conducted with patients who met the following inclusion criteria: 1) age ≥ 79 at surgery (past the average age of life expectancy), 2) underwent biopsy or resection of an IDH-wildtype WHO Grade IV GBM at the time of initial diagnosis, and 3) had no prior radiation or chemotherapy. Patient, imaging, and treatment data were collected retrospectively from the electronic medical record. Univariate and multivariate Cox proportional hazard and logistic regression analyses were performed to identify factors associated with overall survival and 90-day mortality. The cohort consisted of 110 patients with a mean age of 82.8 (range 79 to 94.1) at surgery and a median preoperative KPS of 80. Thirty-seven (33.6%) and 73 (66.4%) patients underwent biopsy and resection, respectively. Adjuvant chemo- and/or radiation therapy were used in 72.5% of cases. On multivariate analysis, age (HR 1.13 by year, p=0.01), increased masseter thickness (HR 0.88 by mm, p=0.049), adjuvant therapy (HR 0.05, p&amp;lt; .0001), and surgical resection rather than biopsy (HR 0.38, p=0.0007) were associated with improved survival. Decreased masseter thickness was the only preoperative factor on analysis that predicted 90-day mortality in the cohort (p=0.038). GBM patients past the average age of life expectancy still fare better when undergoing resection followed by adjuvant chemotherapy and radiation therapy. In addition to treatment factors that predict survival, smaller masseter diameter on preoperative imaging, a marker of sarcopenia, is associated with shorter survival and death within 90 days of surgery.

Accelerated fibrin clot degradation is associated with arterial thromboembolism in patients following venous thrombosis: a cohort study

Several lines of evidence have suggested that patients following venous thromboembolism (VTE) are at higher risk of arterial thromboembolism (ATE). Prothrombotic fibrin clot characteristics were reported in individuals with cardiovascular risk factors. We investigated whether specific fibrin clot properties measured after 3–4 months of anticoagulation characterize VTE patients with subsequent ATE. We enrolled 320 patients following VTE aged below 70 years (median age, 46). Ten patients were lost to follow-up. ATE occurred in 21 individuals after a median 54 (31–68) months during a follow-up of 87.5 months (incidence 0.94%; 95% confidence interval [CI], 0.59–1.4 per patient-year). Patients with ATE had faster fibrin clot degradation, reflected by maximum rate of D-dimer increase during plasma clot lysis induced by tissue-type plasminogen activator (D-Drate) at baseline. Clot permeability, turbidimetric variables, clot lysis time, and thrombin generation were unrelated to ATE. Univariable Cox proportional hazards analysis showed that age, diabetes, and D–Drate were risk factors for subsequent ATE. Increased D–Drate (by 0.001 mg/L/min; hazard ratio, 1.08; 95% CI 1.02–1.14) was an independent predictor of ATE after adjustment for potential confounders. Faster fibrin clot degradation at 3 months since VTE may increase the risk of ATE among VTE patients during follow-up.

Prognostic efficacy of the RTN1 gene in patients with diffuse large B-cell lymphoma

Gene expression profiling has been vastly used to extract the genes that can predict the clinical outcome in patients with diverse cancers, including diffuse large B-cell lymphoma (DLBCL). With the aid of bioinformatics and computational analysis on gene expression data, various prognostic gene signatures for DLBCL have been recently developed. The major drawback of the previous signatures is their inability to correctly predict survival in external data sets. In other words, they are not reproducible in other datasets. Hence, in this study, we sought to determine the gene(s) that can reproducibly and robustly predict survival in patients with DLBCL. Gene expression data were extracted from 7 datasets containing 1636 patients (GSE10846 [n = 420], GSE31312 [n = 470], GSE11318 [n = 203], GSE32918 [n = 172], GSE4475 [n = 123], GSE69051 [n = 157], and GSE34171 [n = 91]). Genes significantly associated with overall survival were detected using the univariate Cox proportional hazards analysis with a P value < 0.001 and a false discovery rate (FDR) < 5%. Thereafter, significant genes common between all the datasets were extracted. Additionally, chromosomal aberrations in the corresponding region of the final common gene(s) were evaluated as copy number alterations using the single nucleotide polymorphism (SNP) data of 570 patients with DLBCL (GSE58718 [n = 242], GSE57277 [n = 148], and GSE34171 [n = 180]). Our results indicated that reticulon family gene 1 (RTN1) was the only gene that met our rigorous pipeline criteria and associated with a favorable clinical outcome in all the datasets (P < 0.001, FDR < 5%). In the multivariate Cox proportional hazards analysis, this gene remained independent of the routine international prognostic index components (i.e., age, stage, lactate dehydrogenase level, Eastern Cooperative Oncology Group [ECOG] performance status, and number of extranodal sites) (P < 0.0001). Furthermore, no significant chromosomal aberration was found in the RTN1 genomic region (14q23.1: Start 59,595,976/End 59,870,966).

Survival Is Related to Estrogen Signal Transduction Pathway Activity in Postmenopausal Women Diagnosed with High-Grade Serous Ovarian Carcinoma.

Simple SummaryAll cells have a complex internal network of ‘communication chains’ called signal transduction pathways (STPs). Through interaction of different proteins in STPs, they are partly responsible for the behavior of a cell. In our study, we investigated the activity of six STPs in 85 women with advanced stage high-grade serous ovarian cancer (HGSC). To investigate the relation between and differences in survival and STP activity, women with a short disease-free survival (below 12 months) and a long disease-free survival (above 24 months) were included. We found no differences in mean STP activity between short-term survivors (52 women) and long-term survivors (33 women). However, when we analyzed postmenopausal women, we found that both disease-free and overall survival were related to estrogen receptor (ER) pathway signaling. This indicates that a better survival outcome was related to a more active ER pathway in this subgroup.High-grade serous ovarian carcinoma (HGSC), the most common subtype of ovarian cancer, has a high mortality rate. Although there are some factors associated with survival, such as stage of disease, there are remarkable differences in survival among women diagnosed with advanced stage disease. In this study, we investigate possible relations between survival and signal transduction pathway (STP) activity. We assessed the functional activity of the androgen receptor (AR), estrogen receptor (ER), phosphoinositide-3-kinase (PI3K), Hedgehog (HH), transforming growth factor beta (TGF-β) and canonical wingless-type MMTV integration site (Wnt) pathway in 85 primary tumor samples of patients with FIGO stage IIIC to IVB HGSC and disease-free survival (DFS) below 12 (n = 52) or over 24 months (n = 33). There were no significant differences in median pathway activity between patients with a short and long DFS. In univariate Cox proportional hazards analysis, ER pathway activity was related to a favorable DFS and overall survival (OS) in postmenopausal women (p = 0.033 and p = 0.041, respectively), but not in premenopausal women. We divided the postmenopausal group into subgroups based on ER pathway activity quartiles. Survival analysis revealed that postmenopausal women in the lowest ER quartile had a shorter DFS and OS (log-rank p = 0.006 and p < 0.001, respectively). Furthermore, we were able to form subgroups of patients based on an inverse relation between ER and PI3K pathway activity. In conclusion, in postmenopausal patients with advanced stage HGSC, a poorer survival outcome was associated with low functional ER pathway activity.

Immune checkpoint CD155 promoter methylation profiling reveals cancer-associated behaviors within breast neoplasia.

CD155 immune checkpoint has recently emerged as a compelling immunotherapeutic target. Epigenetic DNA methylation changes are recognized as key molecular mechanisms in cancer development. Hence, the identification of methylation markers that are sensitive and specific for breast cancer may improve early detection and predict prognosis. We speculate that CD155 promotermethylation can be a valuable epigenetic biomarker, based upon strong indications for its immunoregulatory functions. Methylation analyses were conducted on 14 CpGs sites in the CD155 promoter region by bisulfite pyrosequencing. To elucidate the related gene expression changes, a transcriptional study using RT-qPCR was performed. Statistical analyses were performed to evaluate correlations of CD155 methylation profiles with mRNA expression together with clinical-pathological features, prognosis and immune infiltrate. CD155 promoter methylation profile was significantly associated with SBR grade, tumor size, molecular subgroups, HER2 and hormonal receptors expression status. Low CD155 methylation rates correlated with better prognosis in univariate cox proportional hazard analysis and appeared as an independent survival predictor in cox-regression multivariate analysis. Further, methylation changes at CD155 specific CpG sites were consistent with CD155 membranous mRNA isoform expression status. Statistical analyses also showed a significant association with immune Natural Killer cell infiltrate when looking at the CpG7, CpG8, CpG9 and CpG11 sites. Altogether, our results contribute to a better understanding of the impact of CD155 immune checkpoint modality expression in breast tumors, revealing for the first time that specific CpG sites from CD155 promoter may be a potential biomarker in breast cancer monitoring.

Utility of the Modified and High-Sensitivity Modified Glasgow Prognostic Scores for Hypopharyngeal Squamous Cell Carcinoma.

ObjectiveTo determine whether the modified Glasgow prognostic score (mGPS) and high-sensitivity mGPS (HS-mGPS) could predict outcomes among patients with hypopharyngeal squamous cell carcinoma (HSCC).Study DesignRetrospective cohort study.SettingAffiliated university hospital.MethodsWe reviewed the records of 115 patients with histologically confirmed HSCC between March 2007 and December 2019. Univariate and multivariable Cox proportional hazard analyses were performed for overall survival (OS) and disease-free survival (DFS).ResultsThe 5-year OS rates were 84.0% for the mGPS0 group, 47.8% for the mGPS1 group, and 17.9% for the mGPS2 group (P < .0001), while the 5-year OS rates were 86.7% for the HS-mGPS0 group, 69.0% for the HS-mGPS1 group, and 22.2% for the HS-mGPS2 group (P < .001). The mGPS and HS-mGPS were both associated with OS in the univariate analyses, although only the HS-mGPS was independently associated with OS (hazard ratio, 2.68 [95% CI, 1.19-6.05]; P < .05). The 5-year DFS rates were 75.8% for the mGPS0 group, 53.0% for the mGPS1 group, and 13.8% for the mGPS2 group (P < .001), while the 5-year DFS rates were 79.8% for the HS-mGPS0 group, 56.8% for the HS-mGPS1 group, and 11.6% for the HS-mGPS2 group (P < .001). The mGPS and HS-mGPS were both associated with DFS in the univariate analyses, although only the HS-mGPS was independently associated with DFS (hazard ratio, 2.35 [95% CI, 1.03-5.37]; P < .05).ConclusionOur study suggests that the HS-mGPS is useful as prognostic factor in HSCC.

Preoperative transferrin level is a novel indicator of short- and long-term outcomes after esophageal cancer surgery

This study aimed to examine whether preoperative serum transferrin, a rapid-turnover protein, correlates with short- and long-term outcomes after esophagectomy. Preoperative transferrin levels, calculated by summing serum iron and unsaturated iron-binding capacity, were evaluated in 224 patients who underwent esophagectomy for stage I-III esophageal cancer without preoperative treatment. Transferrin levels are directly proportional to total iron-binding capacity (TIBC), and we defined TIBC < 250μg/dL as low transferrin. We evaluated the relationship between preoperative transferrin levels and short- and long-term outcomes after esophagectomy using univariate and multivariate Cox proportional hazards analyses. Of all patients, 25 (11.2%) had low preoperative transferrin levels. Low preoperative transferrin levels were strongly correlated with worse preoperative performance status, advanced pathological T stage, and more open esophagectomy (p = 0.0078, 0.0001, and 0.013, respectively). Patients with low preoperative transferrin levels experienced significantly more frequent postoperative pneumonia in univariate and multivariate analysis [hazard ratio (HR) 3.30, 95% confidence interval (CI) 1.032-10.033, p = 0.0443]. Additionally, these patients were significantly correlated with worse overall survival (OS) in univariate and multivariate analyses (HR 2.75, 95% CI 1.018-7.426, p = 0.0460). Furthermore, we investigated the relationship between OS and postoperative pneumonia to elucidate why low preoperative transferrin, which is an independent risk factor for postoperative pneumonia, leads to poor prognosis. Patients with postoperative pneumonia were strongly associated with a shorter OS (p = 0.0099). Preoperative serum transferrin levels may be a novel indicator of postoperative pneumonia and OS after esophagectomy.

Tumor necrosis factor alpha-an underestimated risk predictor in patients undergoing transcatheter aortic valve replacement (TAVR)?

BackgroundSystemic inflammation has been identified as a major cardiovascular risk factor in patients undergoing transcatheter aortic valve replacement (TAVR), yet currently, it is not adequately portrayed in scores for pre‐interventional risk assessment. The aim of this study was to investigate the predictive ability of TNF‐α in TAVR.MethodsA total of 431 patients undergoing transfemoral TAVR were enrolled in this study. Blood samples were drawn prior to intervention, 24 h post‐intervention, 4, 5, and 7 days post‐intervention, and 1, 3, and 6 months post‐TAVR.ResultsIn a univariate Cox proportional hazard analysis, plasma concentrations of TNF‐α after 24 h and after 5 days were associated with mortality after 12 months (after 24 h: HR 1.002 (1.000–1.004), p = 0.028; after 5d: HR 1.003 (1.001–1.005), p = 0.013). This association remained significant even after correction for confounders in a multivariate Cox regression analysis. Additionally, cut‐offs were calculated. Patients above the cut‐off for TNF‐α after 5d had a significantly worse 12‐month mortality than patients below the cut‐off (18.8% vs. 2.8%, p = 0.046).ConclusionPlasma levels of TNF‐α after 24 h and 5 days were independently associated with 12‐month mortality in patients undergoing TAVR. Thus, TNF‐α could represent a novel biomarker for enhanced risk stratification in these patients.

Total arch replacement in octogenarians.

OBJECTIVESWe investigated the effect of a preoperative age ≥80 years on postoperative outcomes in patients who underwent isolated elective total arch replacement using mild hypothermic lower body circulatory arrest with bilateral antegrade selective cerebral perfusion.METHODSA total of 140 patients who had undergone isolated elective total arch replacement between January 2007 and December 2020 were enrolled in the present study. We compared postoperative outcomes between 30 octogenarian patients (≥80 years old; Octogenarian group) and 110 non-octogenarian patients (≤79 years old; Non-Octogenarian group).RESULTSOverall 30-day mortality and hospital mortality were 0% in both groups, and there was no significant difference in overall survival between the 2 groups (log-rank test, P = 0.108). Univariable Cox proportional hazard analysis showed that age as continuous variable was only the predictor of mid-term all-cause death (hazard ratio 1.08, 95% confidence interval 1.01–1.16; P = 0.037), but not in the Octogenarians subgroup (P = 0.119).CONCLUSIONSPreoperative age ≥80 years is not associated with worse outcomes postoperatively after isolated elective total arch replacement with mild hypothermic lower body circulatory arrest and bilateral antegrade selective cerebral perfusion.

High Visceral Adipose Tissue Density Correlates With Unfavorable Outcomes in Patients With Intermediate-Stage Hepatocellular Carcinoma Undergoing Transarterial Chemoembolization.

Objectives: This study aimed to evaluate the association between different body composition features with prognostic outcomes of intermediate stage hepatocellular carcinoma (HCC) patients treated with transarterial chemoembolization (TACE).Methods: The areas and density of skeletal muscle area (SM) and adipose tissue [subcutaneous (SAT); visceral (VAT)] were calculated on the pre-TACE CT scans. Overall survival (OS) and progression-free survival (PFS) curves were calculated using the Kaplan–Meier method and compared with log-rank test. The discrimination and performance of body composition features were measured by area under time-dependent receiver operating characteristic (ROC) curve. Univariate and multivariate Cox proportional hazard analyses were applied to identify the association between body composition parameters and outcomes.Results: A significant prolonged OS and PFS was displayed by Kaplan–Meier curve analysis for HCC patients with VAT HU below −89.1 (25.1 months, 95% CI: 18.1–32.1 vs. 17.6 months, 95% CI: 16.3–18.8, p < 0.0001, 15.4 months, 95% CI: 10.6–20.2 vs. 6.6 months, 95% CI: 4.9–8.3, p < 0.0001, respectively). The 1-, 2-, 3-, and 5-year OS area under the curve (AUC) values of the VAT HU were higher than the other body composition parameters. Meanwhile, it is also found that 3-, 6-, 9-, and 12-month PFS AUC values of VAT HU were the highest among all the parameters. Univariate and multivariate Cox-regression analysis suggested a significant association between VAT density and outcomes (OS, HR: 1.015, 95% CI: 1.004–1.025, p = 0.005, PFS, HR: 1.026, 95% CI: 1.016–1.036, p < 0.0001, respectively).Conclusion: The VAT density could provide prognostic prediction value and may be helpful to stratify the intermediate stage HCC patients.

Influence of sarcopenia, clinical data, and 2-[18F] FDG PET/CT in outcome prediction of patients with early-stage adenocarcinoma esophageal cancer.

To determine the prognostic value of sarcopenia measurements done on staging 2-[18F] FDG PET/CT together with metabolic activity of the tumor in patients with adenocarcinoma esophagogastric cancer with surgical treatment. Patients with early-stage, surgically treated esophageal adenocarcinoma and available pre-treatment 2-[18F] FDG PET/CT were included. The standard uptake value (SUV) and SUV normalized by lean body mass (SUL) were recorded. Skeletal muscle index (SMI) was measured at the L3 level on the CT component of the PET/CT. Sarcopenia was defined as SMI < 34.4cm2/m2 in women and < 45.4cm2/m2 in men. Of the included 145 patients. 30% were sarcopenic at baseline. On the univariable Cox proportional hazards analysis, ECOG, surgical T and N staging, lymphovascular invasion (LVI) positive lymph nodes, and sarcopenia were significant prognostic factors concerning RFS and OS. On multivariable Cox regression analysis, surgical N staging (p = 0.025) and sarcopenia (p = 0.022) remained significant poor prognostic factors for OS and RFS. Combining the clinical parameters with the imaging-derived nutritional evaluation of the patient but not metabolic parameters of the tumor showed improved predictive ability for OS and RFS. Combining the patients' imaging-derived sarcopenic status with standard clinical data, but not metabolic parameters, offered an overall improved prognostic value concerning OS and RFS.

Nomograms predict survival of patients with lymph node-positive, luminal a breast cancer

BackgroundTo develop nomograms for the prediction of the 1-, 3-, and 5-year overall survival (OS) and breast cancer-specific survival (BCSS) for patients with lymph node positive, luminal A breast cancer.MethodsThirty-nine thousand fifty-one patients from The Surveillance, Epidemiology, and End Results (SEER) database were included in our study and were set into a training group (n = 19,526) and a validation group (n = 19,525). Univariate analysis and Cox proportional hazards analysis were used to select variables and set up nomogram models on the basis of the training group. Kaplan-Meier curves and the log-rank test were adopted in the survival analysis and curves plotting. C-index, calibration plots and ROC curves were used to performed internal and external validation on the training group and validation group.ResultsFollowing independent factors were included in our nomograms: Age, marital status, grade, ethnic group, T stage, positive lymph nodes numbers, Metastasis, surgery, radiotherapy, chemotherapy. In both the training group and testing group, the calibration plots show that the actual and nomogram-predicted survival probabilities are consistent greatly. The C-index values of the nomograms in the training and validation cohorts were 0.782 and 0.806 for OS and 0.783 and 0.804 for BCSS, respectively. The ROC curves show that our nomograms have good discrimination.ConclusionsThe nomograms may assist clinicians predict the 1-, 3-, and 5-year OS and BCSS of patients with lymph node positive, luminal A breast cancer.

Identification of a prognostic ferroptosis-related lncRNA signature in the tumor microenvironment of lung adenocarcinoma

Ferroptosis is closely linked to various cancers, including lung adenocarcinoma (LUAD); however, the factors involved in the regulation of ferroptosis-related genes are not well established. In this study, we identified and characterized ferroptosis-related long noncoding RNAs (lncRNAs) in LUAD. In particular, a coexpression network of ferroptosis-related mRNAs and lncRNAs from The Cancer Genome Atlas (TCGA) was constructed. Univariate and multivariate Cox proportional hazards analyses were performed to establish a prognostic ferroptosis-related lncRNA signature (FerRLSig). We obtained a prognostic risk model consisting of 10 ferroptosis-related lncRNAs: AL606489.1, AC106047.1, LINC02081, AC090559.1, AC026355.1, FAM83A-AS1, AL034397.3, AC092171.5, AC010980.2, and AC123595.1. High risk scores according to the FerRLSig were significantly associated with poor overall survival (hazard ratio (HR) = 1.412, 95% CI = 1.271–1.568; P < 0.001). Receiver operating characteristic (ROC) curves and a principal component analysis further supported the accuracy of the model. Next, a prognostic nomogram combining FerRLSig with clinical features was established and showed favorable predictive efficacy for survival risk stratification. In addition, gene set enrichment analysis (GSEA) revealed that FerRLSig is involved in many malignancy-associated immunoregulatory pathways. Based on the risk model, we found that the immune status and response to immunotherapy, chemotherapy, and targeted therapy differed significantly between the high-risk and low-risk groups. These results offer novel insights into the pathogenesis of LUAD, including the contribution of ferroptosis-related lncRNAs, and reveal a prognostic indicator with the potential to inform immunological research and treatment.