Cox Regression Analysis Research Articles

Abstract 4138686: Impact of Ejection Fraction on Incidence of Atrial Fibrillation Following Admission for Heart Failure

Introduction: Though the prevalence of atrial fibrillation (AF) is similar amongst heart failure (HF) with reduced, mildly reduced, and preserved ejection fractions, population-level data suggests a modestly increased prevalence in patients with HFpEF compared to those HFrEF. The development of atrial fibrillation is associated with increased risk of stroke, hospitalization, and cardiovascular death in all types of heart failure, though some data suggests morbidity and mortality is worse amongst those with HFpEF. Whether ejection fraction plays a role in development of AF following a HF hospitalization is unclear. Hypothesis: We hypothesized incidence of AF following heart failure hospitalization is increased in patients with preserved ejection fractions. Aim: The goal of this study is to assess the impact of ejection fraction on development of new atrial fibrillation following heart failure exacerbation. Methods: Patients admitted to an academic tertiary care hospital with a primary diagnosis of HF without a previous diagnosis of AF were identified and followed for up to one year for this retrospective study. Demographic, comorbidity, medications, and echocardiography of these patients were obtained from the medical record and analyzed. Consistent with the American Heart Association heart failure guidelines, we defined HFrEF as an EF less than 40%, HFmrEF as an EF between 40-50%, and HFpEF as an EF greater than 50%. This data was analyzed on SPSS using cox-regression and Kaplan-Meier survival analysis. Results: Of the 3,953 patients included in our study, 22.2% had HFrEF, 13.5% had HFmrEF, and 64.3% had HFpEF. At the end of one year 23.5% of those with HFrEF, 20.1% of those with HFmrEF, and 15.9% of those with HFpEF, developed atrial fibrillation. The difference in AF incidence was noted to be statistically significantly lower in HFpEF compared to HFrEF (p<0.001) and HFmrEF (p=0.019). The difference between HFmrEF and HFrEF did not reach statistical significance (p=0.144). Conclusion: In patients without atrial fibrillation, a reduced ejection fraction is associated with an increased incidence of atrial fibrillation one year following a hospitalization for heart failure compared to a preserved ejection fraction.

Abstract 4137900: Differences in Echocardiographic Findings Between Epicardial Vasospastic Angina Phenotypes Affect Response to Medical Therapy

Background: The phenotype of epicardial vasospasm is classified as focal or diffuse. However, its echocardiographic characteristics are unknown. Furthermore, patients with diffuse vasospasms have poorer responses to medical therapy than patients with focal spasms because of more extensive areas of endothelial dysfunction. We hypothesized that there are differences in echocardiographic findings between the patients with diffuse and focal vasospasm, which might affect response to medical therapy. Methods: The present study was a single-center retrospective cohort study that included 77 consecutive patients diagnosed with vasospastic angina (VSA) undergoing coronary spasm provocation test using acetylcholine from 2014 to 2024. The patients with a history of cardiomyopathy and significant obstructive coronary artery disease were excluded. Diffuse VSA was defined as vasospasm in 2≧ adjacent coronary segments, and focal VSA was defined as vasospasm in one isolated coronary segment. Patients were divided into diffuse VSA group (n=45) and focal VSA group (n=32). Left ventricular function was assessed using 2D speckle tracking echocardiography. After the diagnosis of VSA and the administration of medical treatment for VSA, an emergency room (ER) visit with a chest pain attack was recorded as the event of poor response to medical therapy. Results: There was no significant difference in the follow-up period and baseline characteristics (Table). LVEF was similar between the two groups (63.1±5.8% vs. 62.9±7.6%, p =0.87). In contrast, the left ventricular global longitudinal strain (LV-GLS) was significantly lower in the diffuse VSA group than in the focal VSA group (17.4±2.8% vs. 20.2±2.4% p <0.001). There is no difference in medical therapy for VSA (Table). Observation of ER visits with a chest was more frequent in the diffuse VSA group [diffuse VSA group (20/45, 44.4%) vs. focal VSA group (3/29, 9.3%), p <0.001]. Kaplan-Meier curves showed that the diffuse VSA group had a higher cumulative rate of ER visits with a chest pain attack (Log-rank p <0.001). On multivariable Cox regression analysis, diffuse VSA (HR=4.2, 95% CI: 1.10-16.06, p =0.030) and low LV-GLS (HR =1.16, 95%CI: 1.01-1.34, p =0.031) were an independent risk factor for poor response to medical therapy. Conclusion: Patients with diffuse VSA had lower LV-GLS than patients with focal VSA. Moreover, diffuse VSA and lower LV-GLS were associated with poor response to medical therapy after diagnosis of VSA.

Interleukin-1 Blockade in Patients With ST-Segment Elevation Myocardial Infarction Across the Spectrum of Coronary Artery Disease Complexity.

Patients with ST-segment elevation myocardial infarction (STEMI) and complex coronary artery disease (CAD) face a poor prognosis, including increased heart failure (HF) risk. Phase 2 clinical trials of anakinra have shown inhibition of the acute inflammatory response and prevention of HF after STEMI, but data on its effects based on CAD complexity are lacking. We performed a pooled secondary analysis of 139 patients with STEMI. The SYNTAX (Synergy Between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery), SYNTAX II and Gensini scores were calculated, and patients were divided into two groups below and above the median. We evaluated the effect of anakinra on the area-under-the-curve of high-sensitivity C-reactive protein (hsCRP-AUC) at 14 days, and the composite endpoint of new-onset HF, HF hospitalization, or all-cause death at 1-year follow-up using Kaplan-Meier survival curves, Cox regression analysis for Hazard Ratios (HR), and tested interactions between subgroups. All three CAD complexity scores (SYNTAX, SYNTAX II and Gensini) were associated with an increased risk of adverse events (HR 1.02 to 1.06, all p-values ≤0.025). We found no statistically significant interactions between CAD extent, measured as single-vessel or multi-vessel CAD, SYNTAX score ≤9 or >9, SYNTAX II score ≤24 or >24, Gensini score ≤32 or >32, and treatment effect of anakinra on hsCRP-AUC or the composite clinical endpoint (all p-values for interaction >0.05). In conclusion, among patients with STEMI, IL-1 blockade with anakinra significantly attenuated the acute inflammatory response and reduced the risk of HF-related events regardless of the spectrum of CAD complexity.

A prognostic nomogram for patients with III-IV nasopharyngeal carcinoma based on dynamic changes in the inflammatory and nutrition index.

The purpose of the study was to explore the value of dynamic changes in inflammatory and nutritional index after comprehensive treatment in patients with stage III-IVA nasopharyngeal carcinoma (NPC). A prognostic model was also established and validated for progression-free survival (PFS) of patients. We retrospectively selected 279 NPC patients with stage III-IVA. Their general clinical data and hematological index were collected and then calculated the changes during treatment. X-tile software was used to determine the optimal cut-off value. COX regression, Lasso method, and Boruta method were used to variable selection and model establishment. Using the bootstrap internal validation method, concordance index (C-index), calibration plot, and Kaplan-Meier curves were used to evaluate the model. To test the prognostic value of the model, we have also evaluated the performance of the nomogram against a conventional tumor metastasis staging system (TNM). Multivariable COX regression analysis demonstrated that clinical staging, delta lymphocyte, delta monocyte, delta albumin, delta platelet-to-lymphocyte ratio and delta systemic immune inflammation index were related to the PFS of NPC patients. The C-index of the model was 0.712, and the calibration curve indicated that the model had good consistency. The C-index of the TNM staging system was 0.597, which was considerably lower compared to our model (P = 0.015). We demonstrated the predictive value of dynamic changes in inflammatory and nutritional indices for the prognosis of NPC by successfully establishing and validating a prognostic model for predicting 1- and 3-year PFS after comprehensive treatment in patients with stage III-IVA NPC.

Prognostic significance of collagen content in solitary fibrous tumors of the central nervous system

PurposeWe aimed to explore the prognostic significance of collagen content in solitary fibrous tumors (SFTs) of the central nervous system (CNS) and preliminarily investigate its relationship with magnetic resonance imaging (MRI) features of SFTs.MethodsCollagen content was identified using Masson’s trichrome staining, and quantitatively assessed. Radiomic methods were applied to extract quantitative MRI features of SFTs, which were then analyzed in relation to collagen content.ResultsThe collagen content in CNS SFTs was categorized into high- and low-content groups, with a cutoff value of 6%. Survival analysis indicated a positive correlation between collagen content and overall survival (OS). In multivariate Cox regression analysis, incorporating factors such as mitosis, necrosis, Ki67, and collagen content and other indicators, collagen content emerged as an independent prognostic factor. Collagen content demonstrated a negative correlation with tumor histological phenotype, Ki67, WHO grade, mitosis, necrosis, and brain invasion. Additionally, the signal intensity of SFTs on T2-weighted imaging (T2WI) decreased with increasing collagen content. Radiomics analysis identified 1,702 features from each patient’s region of interest, with 12 features showing significant differences between the high and low collagen content groups. Among the quantitative parameters and radiomic models, the combined T1- and T2WI models exhibited the highest diagnostic performance.ConclusionThese findings suggest that collagen content is an independent prognostic risk factor for OS. Furthermore, combined radiomic models based on T1-and T2WI sequences may offer a more comprehensive, objective, and accurate assessment of collagen content in CNS SFTs.

Abstract 4137964: Electrical Gaps and Outcomes After Redo AF Ablation: Comparative Analysis from the EARNEST-PVI Trial

Introduction: The efficacy of extensive ablation strategies in addition to pulmonary vein (PV) isolation is still controversial in persistent atrial fibrillation (AF) ablation. Gaps in previously ablated lesions can induce arrhythmias, potentially decreasing the effectiveness of extensive ablation. Purpose: To evaluate the incidence of gaps, gap-related reentry, and subsequent recurrence following redo AF ablation in the EARNEST-PVI trial (NCT03514693). Methods: The analysis was performed using the extended data of the EARNEST-PVI trial (N=512), a randomized controlled trial evaluating ablation strategies for persistent AF. Patients were randomized 1:1 to either the PVI-plus or PVI-alone group. During a median follow-up of 47 months, 126 (25%) patients underwent redo AF ablation. Among them, we enrolled patients who underwent PVI-alone (N=69), or PVI-plus left atrial (LA) linear ablations (LA roof and mitral isthmus) (N=46) during the index ablation. Results: In the previous PVI-alone group, electrical PV gaps were observed in 38 (57%) patients. In the previous PVI-plus group, 19 (41%), 10 (22%), and 11 (24%) patients had electrical gaps in the PVs, LA linear lines, or both, respectively. During the redo session, 19 atrial tachycardias (ATs) were observed/induced in 15 patients. ATs were more frequently observed in the PVI-plus group than in the PVI-alone group (23.9% vs. 5.8%, p=0.005). While 7 ATs were not associated with gaps, 2 were related to PV gaps, and 10 were related to gaps in the linear lesions. In the redo AF ablation, PVI was re-completed in all patients, and any induced ATs were eliminated by additional ablation. During a median follow-up of 32 months post-redo, patients with gaps had a lower clinical recurrence rate than those without (44.3 vs. 47.2%, log-rank p=0.033). However, the Cox regression analysis revealed that AF recurrence post-redo was associated only with PV gaps, and not with linear ablation gaps (hazard ratio, 0.57; 95% confidence interval, 0.32–0.99; p = 0.049). Conclusions: In redo AF ablations, electrical gaps were more prevalent in patients who underwent extensive ablation during the index procedure. While all gaps during redo were potentially arrhythmogenic, PV gaps alone were associated with AF recurrence after redo AF ablation.

Abstract 4112652: Impact of metabolic overweight/obesity phenotypes on clinical outcomes of patients with resectable non-small cell lung cancer in an Asian population

Background: Metabolic syndrome and obesity are known to increase the incidence of lung cancer. We investigated the association between metabolic health and overweight/obesity phenotypes and clinical outcomes in patients with resectable non-small cell lung cancer (NSCLC). Methods: This large retrospective cohort study included adult patients who underwent curative upfront surgery for their stage IA-IIIB NSCLC at a tertiary university hospital from January 2010 to December 2020. They were classified into four phenotypes based on the combination of metabolic health status and body mass index categories: metabolically healthy normal weight (MHNW), metabolically unhealthy normal weight (MUNW), metabolically healthy overweight/obesity (MHO), metabolically unhealthy overweight/obesity (MUO). The primary outcomes were disease recurrence and death. Results: Of the 1,513 patients (342 with MHNW, 585 with MUNW, 122 with MHO, and 464 with MUO), patients with the phenotype of MHO were less likely to experience recurrence (MHO [13.1%] vs. MHNW [16.1%] vs. MUNW [22.9%] vs. MUO [19.2%], p = 0.018) and death (MHO [15.6%] vs. MHNW [24.6%] vs. MHUW [31.3%] vs. MUO [24.8%], p < 0.001) compared to those with other 3 phenotypes. Similar results were observed in Kaplan-Meier curves for the primary outcomes according to the four phenotypes (all log-rank P < 0.05). In multivariate Cox regression analyses, both MHO and MUO phenotypes did not increase the risk of recurrence compared to the MHNW phenotype and were associated with improved survival (MHO: adjusted hazard ratio [HR] 0.60, 95% confidence interval [CI] 0.36-0.98, p = 0.040; MUO: adjusted HR 0.76, 95% CI 0.60-0.96, p = 0.022). Conclusions: After curative resection for NSCLC, regardless of metabolic health, patients with overweight/obesity were not at an increased risk of recurrence and paradoxically, had favorable overall survival.

Abstract 4144554: Revascularization of Patients with Low-Density Non-Calcified Plaque was Associated with Lower Occurrence of Acute Coronary Syndrome

INTRODUCTION: Coronary CT angiography (CCTA) is a powerful noninvasive tool for identifying high-risk plaque, such as low-density non-calcified plaque (LD-NCP). Though, the optimal treatment of patients with LD-NCP remains unclear. This study explored the association of revascularization in the setting of LD-NCP with the occurrence of acute coronary syndrome (ACS). Methods: This was a post-hoc analysis of the ICONIC study. A subset of 234 patients that underwent CCTA with subsequent ACS were matched to 234 control patients who also underwent CCTA but did not have ACS during follow-up. Patients were also followed for occurrence of revascularization, either coronary artery bypass graft or percutaneous coronary intervention. Atherosclerosis imaging-enabled quantitative CT (AI-QCT) was used to measure diameter stenosis, and LD-NCP, non-calcified plaque, and calcified plaque volumes from each CCTA. LD-NCP was defined as plaque with -190 to 30 Hounsfield Units. Patients were stratified based on the presence of LD-NCP. Subgroup analysis was conducted to compare the occurrence of ACS with the rate of revascularization. Kaplan-Meier survival curves and extended Cox regression analysis were used to evaluate the effect size of revascularization and LD-NCP on occurrence of ACS. Results: AI-QCT was completed in 448/468 subjects (follow-up time [MEAN±SD] 2.44±2.48 years). The median of LD-NCP was 1.2 mm 3 for patients with >0 mm 3 LD-NCP. There were 85 patients with LD-NCP >1.2 mm 3 and 363 patients with LD-NCP ≤1.2 mm 3 . In patients with LD-NCP >1.2 mm 3 , the rate of revascularization in patients with and without ACS was 3/52 (5.8%) versus 14/33 (42.4%) (p<0.001). In patients with LD-NCP ≤1.2 mm 3 , the rate of revascularization in patients with and without ACS was 36/170 (21.2%) versus 39/193 (20.2%) (p=0.897). In comparison to patients without revascularization and LD-NCP ≤1.2 mm 3 , patients with LD-NCP >1.2 mm 3 and revascularization were less likely to have ACS during follow-up (adjusted HR: 0.20 [0.07, 0.61]; p=0.005). Additionally, patients with LD-NCP >1.2 mm 3 who did not undergo revascularization were more likely to have ACS (adjusted HR: 1.47 [1.03, 2.12]; p=0.036). Hazard ratios were adjusted for diameter stenosis, and non-calcified and calcified plaque volume. Time-dependent coefficients were included for diameter stenosis. Conclusion: Revascularization of patients with LD-NCP >1.2 mm 3 identified on CCTA with AI-QCT was associated with less risk for ACS.

Abstract 4117731: Interleukin-1 Blockade in Patients With ST-Segment Elevation Myocardial Infarction Across the Spectrum of Coronary Artery Disease Complexity.

Background: Patients with ST-segment elevation myocardial infarction (STEMI) and complex coronary artery disease (CAD) face a poor prognosis, including increased heart failure (HF) risk. Interleukin-1 (IL-1) blockade with Anakinra inhibits the acute inflammatory response and prevent HF after STEMI, but data on its effects based on CAD complexity are lacking. Aims: To assess the effects of Anakinra in patients with STEMI, across the spectrum of CAD complexity. Methods: We performed a pooled secondary analysis of 139 patients with STEMI from three randomized clinical trials (VCUART studies) comparing Anakinra (N=84) versus placebo (N=55). Multivessel CAD was defined as the presence of at least one ≥70% stenosis in a non-culprit vessel of >2.5 mm diameter, not stented during index coronary intervention. The SYNTAX (Synergy Between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery), SYNTAX II and Gensini scores were calculated, and patients were divided by the median. We evaluated a composite endpoint of new-onset HF, HF hospitalization, or all-cause death at 1-year follow-up using Kaplan-Meier survival curves, Cox regression analysis for Hazard Ratios, and calculated interactions between groups. Results: We included 139 patients with STEMI, 85 (61%) with single vessel CAD and 54 (39%) with multivessel CAD. According to the spectrum of CAD complexity, 60 (43%) presented a SYNTAX score >9, 59 (42%) a SYNTAX II score >24 and 65 (47%) a Gensini score >32. New-onset HF, HF hospitalization, or all-cause death occurred in a total of 23 patients: 7 among the 84 subjects in the Anakinra group and 16 within the 55 patients in the placebo group. We found no statistically significant interactions between CAD complexity and allocation to Anakinra or placebo for the composite endpoint (Figure). Conclusions: Among patients with STEMI, IL-1 blockade with Anakinra significantly reduced the risk of new-onset HF, HF hospitalization, or all-cause death compared to placebo, regardless of the number of vessels affected and the spectrum of CAD complexity.

Abstract 4125719: Efficacy of Prodromal Symptom Assessment in Prognostic Stratification of Acute Myocarditis

Introduction: The outcomes of acute myocarditis are heterogeneous and can lead to clinically significant consequences. However, the patient characteristics associated with adverse outcomes at presentation are not fully understood. Objection: To investigate the association between the presence or absence of prodromal symptoms and in-hospital mortality in patients admitted with acute myocarditis. Methods: We analyzed multicenter data registry (Tokyo CCU Network Database, comprising 76 institutions in the Tokyo metropolitan area). The study included 261 cases with acute myocarditis from January 2017 to December 2020, among which 260 required hospitalization from the emergency department. Patients were grouped based on the presence or absence of prodromal symptoms prior to hospitalization. Prodromal symptoms include the following: (a) chest pain; (b) dyspnea; (c) fever; (d) ful-like symptoms; and (e) others.The primary outcome was in-hospital death. Results: Among the 261 patients with acute myocarditis, 187 patients (71.6%) exhibited prodromal symptoms, and 74 patients (28.3%) did not. The primary outcome occurred in 19 patients (25.6%) without prodromal symptoms and in 20 patients (10.6%) with prodromal symptoms (hazard ratio, 2.87; 95% CI, 1.34 to 6.13; P=0.004, Figure 1A). A multivariable-adjusted Cox regression analysis confirmed that the absence of prodromal symptoms was an independent predictor of poor prognosis, even after adjusting for age, sex and the history of diabetes and hypertension. Notably, this trend was pronounced among patients with Killip classes 2-4, revealing higher in-hospital mortality rate in the patients without prodromal symptoms compared to those with prodromal symptoms (48.6% vs 11.7%; P < 0.001, Figure 1B). Conclusions: This study demonstrates that the absence of prodromal symptoms in patients with acute myocarditis is an independent predictor of poor prognosis, especially for patients presented with Killip classes 2-4.

Abstract 4141437: Identification of Mitochondrial-related Diagnostic Biomarkers of Acute Type A Aortic Dissection and Pan-Cancer Analysis

Background: Acute Type A Aortic Dissection (ATAAD) is a lethal disease with limited predictability globally. Cancer, a severe public health issue worldwide, has now become the second leading cause of death in America. In this study, we aimed to explore potential common mechanisms and therapeutic targets between ATAAD and cancer. Aims: Identify mitochondrial-related diagnostic biomarkers of ATAAD and their roles in various cancers. Methods: ATAAD-related datasets GSE52093, GSE98770, GSE190635 were downloaded from GEO and merged after removing batch effects. We verified 119 mitochondrial-related differentially expressed genes (DEGs), followed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Using five machine learning methods (LASSO, SVM, Decision Tree, Random Forest, and Boruta algorithm), we identified two mitochondrial-related diagnostic biomarkers of ATAAD: PPIF and CASQ1. The diagnostic accuracy was performed using receiver operating characteristic (ROC) curves. RT-qPCR was used to detect PPIF and CASQ1 expression. Immune infiltration analysis suggested that PPIF may play a key role in tumor immune microenvironment. We utilized TCGA and GTEx databases, Kaplan-Meier analyses and Cox regression analyses to assess PPIF expression and survival analysis in 33 cancer types. qPCR and Western Blot (WB) assays verified PPIF overexpression in lung adenocarcinoma (LUAD) and uterine corpus endometrial carcinoma (UCEC). CCK-8, wound-healing and transwell assays further verified PPIF’s proliferative, migratory and invasive abilities in LUAD and UCEC. Results: Our study identified PPIF and CASQ1 as hub mitochondrial-related diagnostic biomarkers of ATAAD. Besides its close association with tumor immune infiltration, PPIF also overexpressed in multiple cancer types. Survival analysis suggested the prognostic value of PPIF in most cancers. Experimental results further verified that PPIF promotes the proliferation, migration, and invasion of LUAD and UCEC. Conclusions: PPIF and CASQ1 are potential mitochondrial-related diagnostic biomarkers of ATAAD, not previously reported. Pan-cancer analysis implies that PPIF may serve as a key prognostic and therapeutic target in multiple cancers. PPIF may act as a hub gene linking ATAAD and cancer, offering new insights to reduce ATAAD incidence in cancer patients.

Abstract 4135327: Long-term Bleeding Events after Percutaneous Coronary Intervention in Patients with Malignancy with and without Anticoagulant Therapy

Background: With the aging population, the prevalence of malignancies in patients undergoing percutaneous coronary intervention (PCI) is increasing. Active malignancy is increasingly recognized as a significant contributor to high bleeding risks. In cases where anticoagulant (AC) therapy is required, it becomes crucial to determine which is the optimal choice for cancer patients, direct oral anticoagulants (DOACs) or warfarin. The aim of this study was to investigate long-term bleeding events in patients with malignancy undergoing PCI. Methods: CLIDAS (Clinical Deep Data Accumulation System) is a multicenter database with 7 tertiary medical hospitals in Japan. This retrospective analysis using CLIDAS database included 6838 patients who underwent PCI during April 2014 and March 2020 and also who have completed 3-year follow-up were divided into two groups; No malignancy group (n=6155) and malignancy group (n=683). Malignancy was defined as patients with treatment history of malignancy. Furthermore, these patients were categorized into six groups based on the presence of malignancy and the type of AC therapy; 1) No malignancy without AC (n=5369), 2) No malignancy with DOAC (n=294), 3) No malignancy with warfarin (n=492), 4) Malignancy without AC (n=586), 5) Malignancy with DOAC (n=44), and 6) Malignancy with warfarin (n=53). The primary outcome was the incidence of bleeding events, defined according to the Global Use of Streptokinase and t-PA for Occluded Coronary Arteries classification of moderate and severe bleeding. Results: During the 3-year follow-up period, 260 (3.8%) patients experienced major bleeding events after PCI. Among these patients, 180 (3.4%) were in group 1, 9 (3.1%) in group 2, 33 (6.7%) in group 3, 27 (4.6%) in group 4, 2 (4.5%) in group 5, and 9 (17.0%) in group 6. Multivariate Cox regression analysis showed that patients in the malignancy group had a significantly higher rate of bleeding events (HR, 1.50; 95% CI, 1.03-2.18). Furthermore, only the malignancy with warfarin group showed a significantly higher rate of bleeding events compared to the no malignancy without AC group (HR, 4.03; 95% CI, 1.94-8.37). Conclusions: Patients with malignancies receiving warfarin were associated with a higher risk of bleeding events. DOACs may be a safer alternative to warfarin in reducing bleeding risk in this population.

Predictive and prognostic factors in patients with Anaplastic Lymphoma Kinase: rearranged early-stage lung adenocarcinoma.

This study aimed to evaluate the predictive and prognostic factors in clinical stage I, ALK-rearranged lung adenocarcinoma following radical surgery. Additionally, it sought to compare these factors with an external cohort of ALK wild-type patients. A multicentric, retrospective, case control analysis was conducted on patients with clinical T1-2 N0 ALK-rearranged lung adenocarcinoma who underwent anatomical resection and radical lymphadenectomy. Data were collected from five high-volume oncological centers. An external cohort of ALK wild type patients was also analyzed for comparison. Survival analyses were performed using the Kaplan-Meier method, and multivariable Cox regression analysis was used to identify prognostic factors. From January 2016 to December 2022, 63 patients with ALK-rearranged lung adenocarcinoma were included. High-grade tumors (G3) significantly associated with upstaging (OR = 3.904, p = 0.04). DFS and OS were significantly improved in upstaged patients receiving adjuvant treatment (HR = 0.18, p = 0.0042; HR = 0.24, p = 0.0004, respectively). The solid or micropapillary histological subtypes were independently associated with worse DFS (HR = 3.41, p = 0.022). Comparison with 435 ALK WT patients showed worse DFS in the ALK-rearranged group (HR = 2.09, p = 0.0003). ALK-rearranged patients had higher rates of nodal upstaging, systemic, and brain recurrences. Clinical T1-2 N0 ALK-rearranged lung adenocarcinoma is an aggressive disease with a specific tropism for lymph nodes and the brain. High-grade tumors are predictive of nodal upstaging. Adjuvant treatment significantly improves DFS and OS in upstaged patients, highlighting the need for personalized preoperative staging and post-surgical management in this cohort.

RNF213 p.Arg4810Lys Variant Is Associated with Higher Stenosis Progression in Asymptomatic Intracranial Artery Stenosis.

Intracranial artery stenosis (ICAS) is a significant contributor to ischemic stroke, with the RNF213 p.Arg4810Lys variant identified as a related genetic factor. We explored the clinical outcomes of the RNF213 genotype in patients with asymptomatic ICAS. Between November 2011 and March 2019, 139 patients with asymptomatic ICAS were enrolled in this study. Genotyping for RNF213 p.Arg4810Lys was performed using Sanger sequencing. A comprehensive analysis was conducted to compare the RNF213 genotype with background characteristics and clinical outcomes such as ipsilateral ischemic cerebrovascular events and stenosis progression. RNF213 p.Arg4810Lys was found in 25% of cases, revealing distinct clinical features between carriers and non-carriers. The incidence of ipsilateral ischemic cerebrovascular events was 4.3% (6/139 cases), and stenosis progression was observed in 13% (18/139 cases) during a mean follow-up period of 58months. Stenosis progression rates were notably higher in the RNF213 variant group (25.7%; 9/35 cases) than in the RNF213 wild-type group (8.7%; 9/104 cases). Cumulative stenosis progression rate was significantly higher in the RNF213 variant group than in the RNF213 wild-type group (log-rank test, P = 0.0004). Multivariate Cox regression analysis indicated a significant association between the RNF213 p.Arg4810Lys variant and an increased risk of stenosis progression (P = 0.03, odds ratio 3.2; 95% confidence interval, 1.1-9.0). The RNF213 p.Arg4810Lys variant exhibits clinical disparities in asymptomatic ICAS and is notably linked to a heightened risk of stenosis progression. These results suggest a distinct difference in the vascular stenosis mechanism associated with this variant, warranting further investigation into its clinical implications and potential mechanistic insights.

Abstract 4129945: Risk of stroke for AMI treated with temporary mechanical circulatory support: ten-year data from National Inpatient Sample

Objectives: The aim of this study was to assess the risk of stroke for temporary mechanical circulatory support (tMCS) device treated acute myocardial infarction (AMI). Background: Data are limited regarding risk of stroke for temporary mechanical circulatory support (tMCS) device treated acute myocardial infarction (AMI). Methods: The national inpatient sample database was analyzed to identify adults who were hospitalized for AMI between 2012 and 2021, hospitalizations were grouped based on the temporary mechanical circulatory support device. Study design: In the final cohort, there are 8,272,163 (96.0%) weighted hospitalizations treated without tMCS, 265,870 (3.1%) with Intra-Aortic Balloon Pump (IABP) alone, 59,240 (0.7%) with Impella alone, and 16,225 (0.2%) with Extracorporeal Membrane Oxygenation (ECMO) used during the hospitalization. Results: The overall stroke rates for patients who treated without tMCS, IABP alone, Impella alone, and ECMO group were 3.41%, 3.46%, 4.51%, and 13.34% respectively. Specifically, the rates of ischemic stroke for these groups were 2.95%, 3.12%, 3.96% and 10.11% respectively. The rates for hemorrhagic stroke were 0.68%, 0.55%, 0.81%, and 4.90% for the same groups. In the stepwise forward Cox regression analysis, the adjusted OR (aOR) of ECMO use for overall stroke was 3.04 (95%CI [2.66-3.48]), followed by Impella only use with an aOR of 1.79 (95%CI [1.61-2.00]), and atrial fibrillation (aOR 1.34, 95%CI [1.31-1.38]). The subgroup analysis revealed that hospitalization with age younger than 50 years old, those without hypertension, and those presented with ST-elevation myocardial infarction are at particularly high risk of stroke for ECMO treated AMI. Conclusion: This ten years AMI hospitalizations analysis revealed that ECMO and Impella treatment associated with increased risk of both ischemic and hemorrhagic stroke. Particularly for those younger than 50, those without hypertension, and those presented with ST-elevation myocardial infarction. However, treatment with IABP alone does not increase the risk of stroke.

A comprehensive genome-based analysis identifies the anti-cancerous role of the anoikis-related gene ADH1A in modulating the pathogenesis of breast cancer.

Breast cancer (BC), a widespread and lethal neoplasm, is irrespective of the subtype of BC. Metastasis remains a crucial determinant for unfavorable outcome. The identification of novel diagnostic markers is instrumental in optimizing the treatment regime for BC. The direct correlation between anoikis and the progression/outcome of BC is well established. Nevertheless, the contribution of anoikis-related genes (ARGs) in BC remains obscure at present. We implemented the METABRIC dataset to scrutinize and assess differentially expressed ARGs in BC versus healthy breast tissues. An unsupervised consensus clustering approach for ARGs was employed to classify patients into diverse subtypes. ESTIMATE algorithms were utilized to assess immune infiltrative patterns. Prognostic gene expression patterns were derived from LASSO regression and univariate COX regression analysis. Subsequently, these signatures underwent examination via use of the Kaplan-Meier survival curve. 6 pairs of fresh tissue specimens (tumor and adjacent non-tumor) were employed to assess the expression of 7 ARGs genes via qPCR. Notably, DCN and FOS were not expressed in BC tissue, which had been excluded in our subsequent experiments. Also, among remaining 5 ARGs, solely the expression of ADH1A demonstrated a statistically remarkable disparity between freshly collected cancer tissues and the adjacent ones. ADH1A-overexpressed and ADH1A-sh vectors were transfected into MCF-7 and MCF-7-AR cell lines, respectively. The expression status of FABP4, CALML5, ADH1A, C1orf106, CIDEC, β-catenin, N-cadherin, and Vimentin in the clinical samples were scrutinized using RT-qPCR and western blotting techniques. Migration and invasion through transwell chambers were employed to assess the migratory and invasive potential of the cells. Detailed evaluation of cell proliferation was conducted utilizing a Cell Counting Kit-8 (CCK-8) assay. The apoptotic index of the cells was determined by flow cytometry analysis. An innovative anoikis-associated signature consisting of seven genes, namely ADH1A, DCN, CIEDC, FABP4, FOS, CALML5, and C1orf106, was devised to stratify BC patients into high- and low-risk cohorts. This unique risk assessment model, formulated via the distinctive signature approach, has been validated as an independent prognostic indicator. Additional analysis demonstrated that distinct risk subtypes manifested variances in the tumor microenvironment and drug sensitivities. Suppression of ADH1A enhanced the migratory and invasive capacities and reduced these tumorigenesis-related protein levels, underscoring the prognostic role of ADH1A in the progression of BC. Through our meticulous study, we have elucidated the possible molecular markers and clinical implications of ARGs in BC. Our model, which incorporate seven ARGs, has proven to accurately forecast the survival outcomes of BC patients. Moreover, the thorough molecular study of ADH1A has augmented our comprehension of ARGs in BC and opened a novel avenue for guiding personalized and precise therapeutic interventions for BC patients.

Abstract 4136755: Associations of Pulmonary Hypertension and Lung Cancer: A Prospective Cohort Study of Half a Million UK Biobank Participants

Background: Pulmonary hypertension (PH) and lung cancer (LC) are both significant public health issues with substantial morbidity and mortality. Recent studies suggest potential associations between pulmonary vascular diseases and LC due to shared risk factors and pathophysiological mechanisms, yet comprehensive research in large populations is scarce. Methods: This prospective cohort study utilized data from the UK Biobank, with baseline assessment between 2006 and 2010 and follow-up until November 30, 2023, for England and Scotland, and May 31, 2022, for Wales. We included 6,425 participants with LC, identified using linked cancer registry data, and followed them for the incidence of PH over a period of 10 years. We adjusted for potential confounders including age, ethnics, sex, smoking status, BMI, and histologic subtypes of LC. Statistical analyses were performed using Time-dependent Cox proportional hazards models to estimate the associations between PH and LC. Results: Of 502,173 participants in this prospective cohort, 6,425 were diagnosed with LC, while 494,451 did not receive the LC diagnosis. The prevalence of PH in the LC cohort and the no-LC cohort were 0.64% (1,494 of 3,142 women [47.55%]) and 2.40% (59 of 154 women [38.31%]), respectively, with significant difference between the two groups (p<0.001). In the LC cohort, the mortality rates of patients without PH and with PH were 69.18% and 77.92% (p=0.020). Among the patients diagnosed with LC and PH, 33.12% were diagnosed with LC after PH (PH-LC), while 66.88% were diagnosed with LC before PH (LC-PH). And the mortality rates of the PH-LC group and the LC-PH group were 78.43% and 77.67%, respectively, with no significant difference between the two groups (p=0.915). Time-dependent Cox regression analysis showed that PH shows an increasing trend in risk (5th year HR: 3.22, 95% CI: 2.09-4.99, p-value < 0.001), highlighting its significant impact on LC long-term prognosis. Conclusion: To conclude, the presence of PH significantly increased the risk of mortality in participants with LC, especially for the long-term LC survivors. And certain percentage of patients were diagnosed with LC before PH, but they had no significant difference between the patients with LC after PH.

Abstract 4138446: Ceramides Surpass LDL-Cholesterol in Predicting Cardiovascular Mortality in Diabetic and Non-Diabetic Patients

The power of cardiovascular risk prediction is biased by comorbidities (including T2DM), medical treatment, and age, which impact cholesterol levels. Consequently, when applying LDL-C, the true cardiovascular risk of such confounded patients is often underestimated. However, it is not clear whether this constraint for risk prediction may likewise apply to other lipid risk markers in particular ceramides. In this observational cohort study, we recorded cardiovascular mortality for 16 years in 1195 patients. Their median age was 67 years, all of them had a high preexisting cardiovascular risk, 51% were taking statins, and 30% had T2DM. We found a U-shaped association between cardiovascular mortality and LDL-C. We thus stratified the population according to the vertex into high (≥150mg/dL) and lower LDL-C (<150mg/dL) and also according to the T2DM status. A Cox regression analysis revealed that LDL-C failed to predict cardiovascular mortality in any subgroup. In contrast, no U-shaped but a linear association was found for ceramide-based markers. They were able to significantly predict cardiovascular mortality after stratification and even after multivariate adjustment. We thus propose that ceramide-based predictors rather than LDL-C should be applied for a more accurate cardiovascular risk prediction in diabetic and other high-risk patients.

Abstract 4145842: The Incidence, Predictors and Impact of 30-day Readmission of Takotsubo Cardiomyopathy Hospitalization: A Retrospective Nationwide Analysis

Objective: This study aimed to describe the recent readmission and mortality rates of unplanned 30-day all cause readmission after takotsubo cardiomyopathy hospitalization. Methods: We conducted an analysis of the 2020 Nationwide Readmission Database. Using the ICD-10 code, we identified hospitalizations for takotsubo cardiomyopathy. We excluded hospitalizations for age<18years and planned or elective readmissions. To compare baseline characteristics between readmissions and index hospitalizations, Pearson χ2 tests were employed. We utilized multivariate Cox regression analyses to identify independent predictors of readmissions. Results: A total of 7554 patients were hospitalized for index admission for takotsubo cardiomyopathy, and 633 of them were readmitted. The 30-day all-cause readmission rate was 8.5% while specific takotsubo readmission rate was 0.4%. The mortality rate in the index admission was 1.9% and 5.5% in readmitted patients. The mean age of index admission was 67.6years vs 70.7 years in readmission, about 89.0% were female in index admission vs 85.0% in readmission cohorts. The most common reasons for readmission were hypertensive heart disease with heart failure, hypertensive heart disease and chronic kidney disease with heart failure, takotsubo syndrome, sepsis, NSTEMI, COPD exacerbation, acute kidney failure, pneumonia, atrial fibrillation. Readmissions had more acute kidney injury (20.6% vs 11.3%, p-value <0.001) and atrial fibrillation (23.0% vs 13.0%, p <0.001) compared to the index admission, however the index admission had more ventricular tachycardia (4.6% versus 1.8%, p=0.02) compared to readmission cohorts. Readmission had longer length of hospital stay (4.9 days vs 3.7 days, p< 0.001), but less mean total hospital charge of (US$51039 vs US$60617, P =0.008). Older age, acute renal failure, pulmonary disease, coronary dissection, longer length of hospital stays and transfer to rehabilitation facility after discharge were identified as statistically significant predictors of readmissions. Conclusion: About one in twelve patients hospitalized with takotsubo cardiomyopathy were readmitted within 30days. Readmissions had a higher mortality rate; acute renal failure, pulmonary disease, coronary dissection were notable reasons for readmission. Understanding the predictors for readmission highlighted in this study would enable clinicians implement preventive strategies to improve the rate of takotsubo cardiomyopathy readmission

Abstract 4117640: Thirty-Year Prevalence and Prognosis of the Cardiovascular-Kidney-Metabolic Syndrome in U.S. Females and Males

Background: The American Heart Association recently published guidelines on how to clinically identify and categorize individuals with cardiovascular-kidney-metabolic (CKM) syndrome. The extent to which CKM syndrome prevalence and prognosis differ by sex remain unknown. This study aimed to examine the impact of sex on trends in prevalence over 30 years and long-term prognosis of the CKM syndrome in the US. Methods: We analyzed nationally representative NHANES 1988-2018 data collected from 33,868 US adults (age ≥20 years) who were under surveillance for all-cause mortality through December 31, 2019. We examined sex-specific prevalence of CKM syndrome, and sex-specific CKM associations with all-cause mortality. Results: Of the 33,868 adults studied, the mean±SD age was 48.4±18.3 years with 52% female and 56% non-White. Overall prevalence of CKM syndrome increased steadily from 1988 to 2018 in both sexes, with a larger temporal rise in prevalent Stage 3 CKM seen for males (from 18.9% to 22.4%) compared to females (from 13.9% to 15.2%) ( Figure 1 ). Over a median follow-up of 13.3 years, there were 8745 deaths. In multivariable cox-regression analysis, worsening CKM severity was associated with all-cause mortality (P<0.001 for both sexes), with greater magnitudes of risk seen in females (HR=1.24 to 3.33) compared to males (HR=0.85 to 2.60) across all stages (LRT χ 2 =19.0, P interaction <0.001); results were similar for cardiovascular mortality (LRT χ 2 =22.3, P interaction <0.001) ( Table 1 ). Conclusions: Females, compared with males, exhibited a lower prevalence of CKM stage 3 but experienced excess mortality risk across the spectrum of multi-system CKM dysfunction. These findings underscore the importance of identifying mechanisms underlying joint cardiovascular, renal, and metabolic systems pathophysiology to close a potentially widening sex disparities gap in multi-organ disease risk.