Multivariate Cox Proportional Hazards Analysis Research Articles

The Discovery of Oral Cancer Prognostic Factor Ranking Using Association Rule Mining.

A 5-year survival rate is a predictor for the assessment of oral cancer prognosis. The purpose of this study is to analyze oral cancer data to discover and rank the prognostic factors associated with oral cancer 5-year survival using the association rule mining (ARM) technique. This study is a retrospective analysis of 897 oral cancer patients from a regional cancer center between 2011 and 2017. The 5-year survival rate was assessed. The multivariable Cox proportional hazards analysis was performed to determine prognostic factors. ARM was applied to clinicopathologic and treatment modalities data to identify and rank the prognostic factors associated with oral cancer 5-year survival. The 5-year overall survival rate was 35.1%. Multivariable Cox proportional hazards analysis showed that tumor (T) stage, lymph node metastasis, surgical margin, extranodal extension, recurrence, and distant metastasis of tumor were significantly associated with overall survival rate (p < 0.05). The top associated death within 5 years rule was positive extranodal extension, followed by positive perineural and lymphovascular invasion, with confidence levels of 0.808, 0.808, and 0.804, respectively. This study has shown that extranodal extension, and perineural and lymphovascular invasion were the top ranking and major deadly prognostic factors affecting the 5-year survival of oral cancer.

Canine Mammary Tumors as a Potential Model for Human Breast Cancer in Comparative Oncology

Clinical and molecular similarities between canine mammary tumors (CMTs) and human breast cancer (HBC) propel scientists to further study their application in comparative oncology as a model for human breast cancer. In total, 64 canine mammary tumors were selected to study the most common markers, which are applicable for human breast cancer treatment, including estrogen and progesterone receptors (ER and PR), human epidermal growth factor (HER2/neu), Ki67, and cyclooxygenase 2 (Cox2). Immunohistochemistry (IHC) was used to assess the protein expression. The Veterinary Nottingham Prognostic Index (Vet-NPI) was also computed. Moreover, univariate and multivariable Cox proportional hazard analyses were applied to estimate hazard ratios (HRs). The results demonstrated that Ki67 was strongly expressed in the triple-negative tumors, and Ki67 protein expression continuously increased over the increase of Cox2 protein expression (p&lt;0.001). Further analysis revealed a significant difference among canine mammary subtypes and Vet-NPI, in which triple-negative tumors displayed the highest mean score compared to other subtypes (p&lt;0.001). In addition, the multivariable analysis revealed that the regional mastectomy procedure (adjusted HR = 2.78 (1.14–6.8)), the triple-negative tumors (adjusted HR = 48.08 (7.74–298.8)), strong Ki67 protein expression group (adjusted HR = 7.88 (2.02–30.68)), and strong Cox2 protein expression group (adjusted HR = 29.35 (5.18–166.4)) demonstrated significantly lower disease-free survival rates compared to other corresponding groups. Overall, canine mammary tumors showed strong similarities to human breast cancer in terms of clinical and molecular aspects; therefore, they could be suggested as a model for human breast cancer in comparative oncology.

Associations between in-hospital daily protein intake and adverse clinical outcomes in older patients with heart failure.

The adverse effects of low daily protein intake (DPI) on clinical outcomes in patients with heart failure (HF) are known; however, an optimal DPI to predict event adverse outcomes remains undetermined. Moreover, whether protein restriction therapy for chronic kidney disease is applicable in patients with HF and renal dysfunction remains unclear. In this single-centre, ambispective cohort study, we included 405 patients with HF aged ≥65years (mean age, 78.6±7.5years; 50% women). DPI was estimated from consumption over three consecutive days before discharge and normalized relative to the ideal body weight [IBW, 22kg/m2×height (m)2]. The primary outcome was a composite of all-cause mortality and HF-related readmission within the 2year post-discharge period. During an average follow-up period of 1.49±0.74years, 100 patients experienced composite events. Kaplan-Meier survival curves revealed a significantly lower composite event-free rate in patients within the lowest quartile of DPI than in the upper quartiles (log-rank test, P=0.02). A multivariate Cox proportional hazards analysis after adjusting for established prognostic markers and non-proteogenic energy intake revealed that patients in the lowest DPI quartile faced a two-fold higher risk of composite events than those in the highest quartile [hazard ratio (HR), 2.03; 95% confidence interval (CI), 1.08-3.82; P=0.03]. The composite event risk linearly increased as DPI decreased (P for nonlinearity=0.90), with each standard deviation (0.26g/kg IBW/day) decrease in DPI associated with a 32% increase in composite event risk (HR, 1.32; 95% CI, 1.10-1.71; P=0.04). There was significant heterogeneity in the effect of DPI, with the possible disadvantage of lower DPI in patients with HF with cystatin C-based estimated glomerular filtration rate <30mL/min/1.73m2. The cutoff value of DPI for predicting the occurrence of composite events calculated from the Youden index was 1.12g/kg IBW/day. Incorporating a DPI<1.12g/kg IBW/day into the baseline model significantly improved the prediction of post-discharge composite events (continuous net reclassification improvement, 0.294; 95% CI, 0.072-0.516; P=0.01). Lower DPI during hospitalization is associated with an increased risk of mortality and HF readmission independent of non-proteogenic energy intake, and the possible optimal DPI for predicting adverse clinical outcomes is >1.12g/kg IBW/day in older patients with HF. Caution is warranted when protein restriction therapy is administered to older patients with HF and renal dysfunction.

Abstract PO1-07-11: Radiogenomic-based imaging intratumor heterogeneity model predicts breast cancer prognosis and unveils therapeutic targets

Abstract Background: Intratumor heterogeneity (ITH) refers to variations observed among cancer cells within a single tumor, posing significant challenges in clinical practice due to its contribution to treatment resistance and unfavorable outcome. However, the inconvenience of multi-region biopsy and limitations of genomic sequencing based on limited tissue impede the practical detection of ITH. Consequently, there is an urgent need for a non-invasive method that comprehensively captures ITH from a holistic perspective of the entire tumor. Methods: We utilized a large multicenter dataset comprising dynamic contrast-enhanced magnetic resonance images from breast cancer patients (n = 1423) along with matched multiomics data (n = 468) to develop a non-invasive machine learning approach for measuring ITH. We extracted quantitative radiomic features from both the entire tumor and peritumor regions, with a specific focus on features associated with imaging heterogeneity. Using these radiomic features, we established an imaging ITH (IITH) model. The robustness of IITH evaluation was determined by assessing its correlation with genomic ITH (employing the mutant-allele tumor heterogeneity [MATH] algorithm) and pathological cellular ITH (analyzing variation in quantitative nuclear features extracted through digital pathology). Prognostic power was evaluated using Kaplan-Meier and multivariate Cox proportional hazards analyses. Integrated multiomics analyses were performed to investigate the molecular basis of different IITH subgroups. Results: We developed a non-invasive radiomic signature to quantify imaging ITH (IITH) in the FUSCC cohort. Breast cancer patients were retrospectively categorized into high and low IITH groups. Multivariate Cox analysis identified high IITH as an independent predictor of poor prognosis in breast cancer patients, even after adjusting for clinical risk factors such as tumor size, positive lymph nodes, clinical subtype and lymphovascular invasion status. These findings were further validated in the DUKE cohort, confirming the prognostic value of IITH. Moreover, we substantiated the robustness of IITH by demonstrating its association with genomic and pathological ITH. Multiomics analysis revealed the activation of oncogenic pathways and metabolic dysregulation in high-IITH tumors. Intriguingly, our investigation also highlighted ferroptosis as a vulnerability and potential therapeutic target in high-IITH tumors, which was further supported by evidence from the TCGA cohort. Conclusion: Radiomic-based assessment of ITH provides a non-invasive approach to comprehensively capture ITH and predict the prognosis of breast cancer patients. Targeting ferroptosis may hold promise as a treatment strategy for patients with high IITH. Citation Format: Guan-Hua Su, Yi Xiao, Chao You, Ren-Cheng Zheng, Shen Zhao, He Wang, Yi-Zhou Jiang, Ya-Jia Gu, Zhi-Ming Shao. Radiogenomic-based imaging intratumor heterogeneity model predicts breast cancer prognosis and unveils therapeutic targets [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 PO1-07-11.

Abstract PO3-29-05: Clinical risk score to predict overall survival and breast cancer recurrence in phase 3 TAILORx trial and the Surveillance, Epidemiology, and End Results (SEER) Database populations

Abstract Background: Overall survival (OS) is the gold standard and most relevant endpoint in oncology research and patient care. It underscores a need to develop methods to estimate the likelihood of mortality in breast cancer. Methods: We evaluated molecular and clinical measures that predicted mortality risk using multiple logistic regression and developed a clinical risk score (CS) in 8,905 patients from the phase 3 TAILORx trial. Association of CS with mortality in patients at low, intermediate, and high risks was analyzed by Kaplan-Meier and multivariable Cox proportional-hazards regression analyses. The score was validated in an independent population of 148,301 patients with node-negative, hormone-receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer in the SEER database. Likelihood ratio (LR) test and c-index were used to compare prognostic information provided by CS and a 21-gene recurrence score (RS) to OS, invasive disease-free survival (DFS), recurrence-free interval (RFI), and distant recurrence-free interval (dRFI). Results: The 10-year mortality rates in low-risk, intermediate risk, and high-risk groups were 3.9% (95% CI 3.1 to 4.8), 37.2% (95% CI 23.4 to 51.1), and 75.8% (95% CI 54.1 to 97.4), respectively (P&amp;lt; 0.0001). Compared with low-risk score, intermediate (adjusted HR 45.5, 95% CI 32.2 to 64.9) and high-risk scores (HR 2026, 95% CI 1194 to 3483) were associated with risk of mortality, independent of demographics, tumor grade, RS, tumor size, PR, and treatment factors. The algorithm also predicted DFS, dRFI, and RFI outcomes (P&amp;lt; 0.0001 each), outperforming RS by both LR test and c-index estimate. Its validity was corroborated in the SEER population (intermediate risk: HR 9.3, 95% CI 6.7 to 13.3 and high-risk: HR 125.9, 95% CI 85.2 to 189.6). Conclusions: Clinical risk score robustly predicts risk of mortality in early-stage breast cancer populations. It provides more prognostic information than RS to survival and breast cancer recurrences. Citation Format: Sherry Yang, John Yu, Ninet Sinaii. Clinical risk score to predict overall survival and breast cancer recurrence in phase 3 TAILORx trial and the Surveillance, Epidemiology, and End Results (SEER) Database populations [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 PO3-29-05.

Contact Aspiration for Basilar Artery Occlusion Safely Reduces the Puncture-to-recanalization Time

ObjectiveEffective thrombectomies in the posterior circulation remain controversial. Previous reports have demonstrated the superiority of contact aspiration in anterior circulation. Aspiration catheters and stent retrievers are often used alone on a global scale, while combined techniques are commonly used in Japan. This study evaluated the effect of first-line contact aspiration with other strategies for the treatment of basilar artery occlusion. MethodsThe primary outcome was the frequency of the first-pass effect, and the secondary outcome was the time from puncture to the first-pass effect. A multicenter observational registry including 16 Japanese stroke centers was used. Between December 2013 and February 2021, enrolled patients underwent endovascular thrombectomy for basilar artery occlusion. The efficacy of contact aspiration compared to other methods (including stent retrievers and combined techniques) was evaluated. ResultsEighty-four patients were included, all of whom had achieved effective recanalization. Twenty-six patients were treated with contact aspiration, 13 with combined technique, and 45 with stent retrievers. The two groups: contact aspiration and non-contact aspiration, had different backgrounds. Both had similar frequencies of effective recanalization and first-pass effects. The contact aspiration group experienced better functional outcomes without statistical significance, while this strategy was significantly associated with a shorter puncture-to-recanalization time (38 vs. 55minutes, P=0.036). In particular, in the 55 patients with the first-pass effect, multivariate Cox proportional hazard analysis showed that contact aspiration was significantly associated with a shorter time from puncture to first-pass effect, independent of age and etiology of large-artery atherosclerosis (hazard ratio 2.02, 95% confidence intervals 1.10–3.69, P=0.023). ConclusionThis study suggested that contact aspiration for basilar artery occlusion may shorten the puncture-to-first-pass effect, compared to stent retrievers and combined techniques.

Patients with Advanced or Metastasised Non-Small-Cell Lung Cancer with Viscum album L. Therapy in Addition to PD-1/PD-L1 Blockade: A Real-World Data Study.

Immunotherapy with PD-1/PD-L1 inhibitors has significantly improved the survival rates of patients with metastatic non-small-cell lung cancer (NSCLC). Results of a real-world data study investigating add-on VA (Viscum album L.) to chemotherapy have shown an association with the improved overall survival of patients with NSCLC. We sought to investigate whether the addition of VA to PD-1/PD-L1 inhibitors in patients with advanced or metastasised NSCLC would have an additional survival benefit. In the present real-world data study, we enrolled patients from the accredited national registry, Network Oncology, with advanced or metastasised NSCLC. The reporting of data was performed in accordance with the ESMO-GROW criteria for the optimal reporting of oncological real-world evidence (RWE) studies. Overall survival was compared between patients receiving PD-1/PD-L1 inhibitor therapy (control, CTRL group) versus the combination of anti-PD-1/PD-L1 therapy and VA (combination, COMB group). An adjusted multivariate Cox proportional hazard analysis was performed to investigate variables associated with survival. From 31 July 2015 to 9 May 2023, 415 patients with a median age of 68 years and a male/female ratio of 1.2 were treated with anti-PD-1/PD-L1 therapy with or without add-on VA. Survival analyses included 222 (53.5%) patients within the CRTL group and 193 (46.5%) in the COMB group. Patients in the COMB group revealed a median survival of 13.8 months and patients in the CRTL group a median survival of 6.8 months (adjusted hazard ratio, aHR: 0.60, 95% CI: 0.43-0.85, p = 0.004) after adjustment for age, gender, tumour stage, BMI, ECOG status, oncological treatment, and PD-L1 tumour proportion score. A reduction in the adjusted hazard of death by 56% was seen with the addition of VA (aHR 0.44, 95% CI: 0.26-0.74, p = 0.002) in patients with PD-L1-positive tumours (tumour proportion score > 1%) treated with first-line anti-PD-1/PD-L1 therapy. Our findings suggest that add-on VA correlates with improved survival in patients with advanced or metastasised NSCLC who were treated with PD-1/PD-L1 inhibitors irrespective of age, gender, tumour stage, or oncological treatment. The underlying mechanisms may include the synergistic modulation of the immune response. A limitation of this study is the observational non-randomised study design, which only allows limited conclusions to be drawn and prospective randomised trials are warranted.

Adiponectin-to-leptin ratio and incident chronic kidney disease: Sex and body composition-dependent association.

The association between the adiponectin-to-leptin ratio (A/L ratio) and the risk of incident chronic kidney disease (CKD) is poorly understood. This study aimed to investigate the association between A/L ratio and the risk of incident CKD and to examine whether such a relationship varied according to sex and body composition. In this prospective community-based cohort, participants with normal kidney function were analysed (N=5192). The association between the A/L ratio at baseline and the risk of incident CKD, defined as two or more occasions with an estimated glomerular filtration rate of <60mL/min/m2 or proteinuria of ≥1+ on a dipstick test during the follow-up period, was evaluated using multivariable Cox proportional hazards analyses. Subgroup analyses were conducted based on sex, body mass index (BMI) and the presence of sarcopenia. The participants' mean age was 57.2±8.3years, and 53.2% were women. The A/L ratio was higher in men compared with women (1.5 [0.8-3.2] and 0.5 [0.3-0.9] μg/ng, P<0.001). During a median follow-up of 9.8 [9.5-10.0] years, 417 incident CKD events occurred (8.7 per 1000 person-years). Men in the highest quartile of A/L ratio had a lower risk of incident CKD (adjusted hazard ratio [aHR], 0.57; 95% confidence interval [CI], 0.33-0.99) than those in the lowest quartile. Additionally, a 1.0 increase in A/L ratio was associated with a 12% decreased risk of incident CKD in men (aHR, 0.88; 95% CI, 0.80-0.97). However, no significant association was observed in women. In subgroup analysis stratified by BMI and the presence of sarcopenia, the association between a high A/L ratio and a reduced risk of incident CKD was consistent in men with a BMI<23.0kg/m2 and those with sarcopenia. However, no significant association was observed between men with a BMI≥23.0kg/m2 and those without sarcopenia. A high A/L ratio is an independent marker of a reduced risk of incident CKD in men, especially in those with a BMI<23.0kg/m2 and sarcopenia.

The association between body mass index and osteoporosis in a Taiwanese population: a cross-sectional and longitudinal study

This study investigates the correlation between body mass index (BMI) and osteoporosis utilizing data from the Taiwan Biobank. Initially, a comprehensive analysis of 119,009 participants enrolled from 2008 to 2019 was conducted to assess the association between BMI and osteoporosis prevalence. Subsequently, a longitudinal cohort of 24,507 participants, initially free from osteoporosis, underwent regular follow-ups every 2–4 years to analyze the risk of osteoporosis development, which was a subset of the main cohort. Participants were categorized into four BMI groups: underweight (BMI < 18.5 kg/m2), normal weight (18.5 kg/m2 ≤ BMI < 24 kg/m2), overweight (24 kg/m2 ≤ BMI < 27 kg/m2), and obese groups (BMI ≥ 27 kg/m2). A T-score ≤ − 2.5 standard deviations below that of a young adult was defined as osteoporosis. Overall, 556 (14.1%), 5332 (9.1%), 2600 (8.1%) and 1620 (6.7%) of the participants in the underweight, normal weight, overweight and obese groups, respectively, had osteoporosis. A higher prevalence of osteoporosis was noted in the underweight group compared with the normal weight group (odds ratio [OR], 2.20; 95% confidence interval [95% CI], 1.99 to 2.43; p value < 0.001) in multivariable binary logistic regression analysis. Furthermore, in the longitudinal cohort during a mean follow-up of 47 months, incident osteoporosis was found in 61 (9%), 881 (7.2%), 401 (5.8%) and 213 (4.6%) participants in the underweight, normal weight, overweight and obese groups, respectively. Multivariable Cox proportional hazards analysis revealed that the risk of incident osteoporosis was higher in the underweight group than in the normal weight group (hazard ratio [HR], 1.63; 95% CI 1.26 to 2.12; p value < 0.001). Our results suggest that BMI is associated with both the prevalence and the incidence of osteoporosis. In addition, underweight is an independent risk factor for developing osteoporosis. These findings highlight the importance of maintaining normal weight for optimal bone health.

The therapeutic effect of radiotherapy combined with systemic therapy compared to radiotherapy alone in patients with simple brain metastasis after first-line treatment of limited-stage small cell lung cancer: a retrospective study

PurposeWe aimed to compare the therapeutic effect of radiotherapy (RT) plus systemic therapy (ST) with RT alone in patients with simple brain metastasis (BM) after first-line treatment of limited-stage small cell lung cancer (LS-SCLC).MethodsThe patients were treated at a single center from January 2011 to January 2022. BM only without metastases to other organs was defined as simple BM. The eligible patients were divided into RT alone (monotherapy arm) and RT plus ST (combined therapy arm). Univariate and multivariate Cox proportional hazards analyses were used to examine factors associated with increased risk of extracranial progression. After 1:1 propensity score matching analysis, two groups were compared for extracranial progression-free survival (ePFS), PFS, overall survival (OS), and intracranial PFS (iPFS).Results133 patients were identified and 100 were analyzed (monotherapy arm: n = 50, combined therapy arm: n = 50). The ePFS of the combined therapy was significantly longer than that of the monotherapy, with a median ePFS of 13.2 months (95% CI, 6.6–19.8) in combined therapy and 8.2 months (95% CI, 5.7–10.7) in monotherapy (P = 0.04). There were no statistically significant differences in PFS (P = 0.057), OS (P = 0.309), or iPFS (P = 0.448). Multifactorial analysis showed that combined therapy was independently associated with better ePFS compared with monotherapy (HR = 0.617, P = 0.034); more than 5 BMs were associated with worse ePFS compared with 1–5 BMs (HR = 1.808, P = 0.012).ConclusionsCompared with RT alone, combined therapy improves ePFS in patients with simple BM after first-line treatment of LS-SCLC. Combined therapy and 1–5 BMs reduce the risk of extracranial recurrence.

AGE IS NOT A SOLE PREDICTOR OF OUTCOMES IN OCTOGENARIANS UNDERGOING COMPLEX ENDOVASCULAR AORTIC REPAIR

To examine the perioperative, postoperative, and long-term outcomes of fenestrated/branched endovascular aneurysm repair (F/BEVAR) in octogenarians compared with nonoctogenarians. A multicenter, retrospective cohort study was conducted using the Vascular Quality Improvement database, which prospectively captures information on patients who undergo vascular surgery across 1021 academic and community hospitals in North America. All patients who underwent F/BEVAR endovascular aortic repair from 2012 to 2022 were included. Patients were stratified into two groups: those aged<80years and those aged ≥80years at the time of the procedure. The preoperative, intraoperative, and postoperative factors were compared between the two groups. The primary outcome was long-term all-cause mortality; secondary outcomes included aortic-specific mortality and aortic-specific reintervention. A total of 6007 patients (aged<80years, n= 4860; aged ≥80years, n= 1147) who had undergone F/BEVAR procedures were included. No significant difference was found in technical success, postoperative length of stay, length of intensive care unit stay, postoperative bowel ischemia, and spinal cord ischemia. After adjustment for baseline covariates, octogenarians were more likely to suffer from a postoperative complication (odds ratio [OR]: 1.16; [95% confidence interval (CI): 0.98-1.37], P< .001) and be discharged to a rehabilitation center (OR: 1.60; [95% CI: 1.27-2.00], P< .001) or nursing home (OR: 2.23; [95% CI: 1.64-3.01], P< .001). Five-year survival was lower in octogenarians (83% vs 71%, hazard ratio [HR]: 1.70; [95% CI: 1.46-2.0], P< .0001). Multivariate Cox proportional hazard analysis demonstrated that age was associated with increased all-cause mortality (HR: 1.72, [95% CI: 1.39-2.12], P< .001) and aortic-specific mortality (HR: 1.92, [95% CI: 1.04-3.68], P= .038). Crawford extent II aortic disease was associated with an increase in all-cause mortality (HR 1.49; [95% CI: 1.01-2.19], P< .001), aortic-specific mortality (HR: 5.05; [95% CI: 1.35-18.9], P= .016), and aortic-specific reintervention (HR: 1.91; [95% CI: 1.24-2.93], P= .003). Functional dependence was associated with increased all-cause mortality (HR: 2.90; [95% CI: 1.87-4.51], P< .001) and aortic-specific mortality (HR: 4.93; [95% CI: 1.69-14.4], P= .004). Our findings suggest that octogenarians do have a mildly increased mortality rate and rate of adverse events after F/BEVAR procedures. Despite this, when adjusted for other risk factors, on par with other medical comorbidities and therefore age should be strict exclusion criterion for F/BEVAR procedures, rather age should be considered in the global context of patient's aortic anatomy, health, and functional status.

The effect of statins on the risk of anti-tuberculosis drug-induced liver injury among patients with active tuberculosis: A cohort study

BackgroundTuberculosis (TB) remains prevalent worldwide, and anti-TB drugs are associated with drug-induced liver injury (DILI). Statins have pleiotropic effects which may decrease inflammation and achieve immunomodulation. However, few studies have investigated the pleiotropic effects of statins on the risk of DILI. The purpose of this study was to investigate whether statins prevent anti-tuberculosis DILI among active TB patients on standard anti-TB drug therapy. MethodsWe conducted a hospital-based retrospective cohort study using claims data from the Integrated Medical Database of National Taiwan University Hospital (NTUH-iMD). Patients with a positive TB culture were included. The use of statins was defined as a daily equivalent dose >0.5 mg of pitavastatin. Deterioration in liver function was evaluated according to elevated liver enzyme levels. The primary and secondary endpoints were the DILI and the severe DILI. The prognostic value of statins was evaluated by Kaplan–Meier analysis, and Cox proportional hazards models. ResultsA total of 1312 patients with a diagnosis of TB and receiving anti-TB treatment were included. During the study period, 193 patients had the DILI and 140 patients had the severe DILI. Kaplan–Meier analysis showed a significant difference between the usual statin users and controls in the DILI. In multivariable Cox proportional hazards analysis, statins showed a protective effect against the primary and secondary endpoints. In addition, the protective effect of statins showed a dose–response relationship against the DILI. ConclusionStatin treatment had a protective effect against the risk of anti-TB DILI with a positive dose–response relationship.

385 Genomic Alterations Associated With Postoperative Nodular Leptomeningeal Disease After Resection of Brain Metastases

INTRODUCTION: The relationship between brain metastasis resection and risk of nodular leptomeningeal disease (nLMD) is unclear. Prior studies have not explored genomic alterations associated with postoperative nLMD. METHODS: A retrospective, single-center study was conducted with patients who underwent resection of a BM with available clinical and genomic data available. Postoperative nLMD was the primary endpoint of interest. Targeted next-generation sequencing of over 500 oncogenes using a CLIA certified assay was performed in brain metastases. Cox proportional hazards analyses were performed to identify clinical features and genomic alterations associated with nLMD. RESULTS: One hundred and one patients composed the cohort with tumors originating from multiple cancer types. There were 15 cases of nLMD (14.9% of the cohort) with a median time from surgery to nLMD diagnosis of 8.2 months. Two supervised machine learning algorithms consistently identified CDKN2A/B co-deletion and ERBB2 amplification as the top predictors associated with postoperative nLMD across all cancer types. In a multivariate Cox proportional hazard analysis including clinical factors and genomic alterations observed in the cohort, tumor volume (HR 8.8, 95% CI 1.1-69, p = 0.04), CDKN2A/B co-deletion (HR 5.3, 95% CI 1.7-16.9, p = 0.004), and ERBB2 amplification (HR 3.9, 95% CI 1.1-14.4, p = 0.04) were associated with decreased time to postoperative nLMD. CONCLUSIONS: In addition to increased resected tumor volume, ERBB2 amplification and CDKN2A/B deletion were independently associated with an increased risk of postoperative nLMD across multiple cancer types. Additional work is needed to determine if targeted therapy decreases this risk in the postoperative setting.

Late Outcomes of Porcine and Pericardial Bioprostheses after Mitral Valve Replacement in 1162 Patients

Debate continues regarding the superiority of porcine versus pericardial bioprostheses, and data relevant to this comparison are scant. We therefore compare late survival and structural valve deterioration of porcine and pericardial mitral valve prostheses. Adults undergoing mitral valve replacement with one first-generation porcine valve model and one pericardial valve line were reviewed from our prospectively-maintained institutional database between 1976 and 2020. Multivariable regression and Cox proportional hazards analysis were used to compare late outcomes. Of 1162 consecutive patients, 612 (53%) received porcine valves and 550 (47%) received pericardial valves. At 10 years, patient survival (porcine 36±2%, pericardial 38±3%, P=0.5) and cumulative incidence (CI) of mitral valve structural deterioration (porcine 18±2%, pericardial 19±3%, P=0.3) were similar. The structural failure mode was more likely severe mitral stenosis in pericardial valves (35/50(70%) versus 38/106(36%), P<0.001), and more likely severe mitral regurgitation in porcine valves (80/106(75%) versus 19/50(38%), P<0.0001). After adjustment, structural deterioration was associated with younger patient age (P<0.001), but not valve type. At 10 years, porcine valves demonstrated a higher CI of mitral reoperation (19±2% vs 9±2%, P<0.001) and reoperation for structural deterioration (15±1% vs 6±2%, P=0.007). We demonstrate similar rates of 10-year survival and structural deterioration with porcine and pericardial bioprosthetics in mitral valve replacement. This study suggests a lack of major improvement in durability of mitral bioprosthetic valves over time. Failure mode may have greater influence on surgeon decision-making of valve choice.

Impact of lymph node dissection on cancer-specific survival in non-small cell lung cancer patients: a SEER database analysis.

Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related mortality worldwide, and lymph node dissection (LND) is a significant surgical procedure employed in its management. Although some studies suggest benefits of LND, the extent of its impact on survival, the optimal range of lymph nodes to be examined, and the specific patient groups that benefit most remain areas of active debate and investigation. A population-based analysis was conducted using the Surveillance, Epidemiology, and End Results (SEER) database. Patients diagnosed with NSCLC between 2004 and 2017, undergoing primary tumor resection, were included. Descriptive, univariate, and multivariate analyses assessed the effect of LND on survival, and a restricted cubic spline method determined the optimal range for lymph node examination. This study of 37,323 NSCLC patients delved into the impact of LND on lung cancer-specific survival. Key findings revealed a median survival of 19.58 months, with 85% mortality. Baseline characteristics included a majority of White patients (81%), distant stage diagnoses (63%), and 64% with Grade IV tumors. LND emerged as a crucial predictor, influencing survival across age, gender, race, and tumor characteristics. Univariate analysis highlighted its significance, with higher T, N, and M categories, advanced stage, and poorer grade associating with elevated hazard ratios. Multivariate Cox proportional hazards (PH) analysis reinforced LND's impact, showcasing lower hazard ratios post-removal. Hazard ratios for biopsy/aspiration and removal of regional lymph nodes were 0.85 [95% confidence interval (CI): 0.81-0.89; P<0.001] and 0.43 (95% CI: 0.39-0.46; P<0.001), underscoring the protective effect. Visualizations and a U-shaped curve analysis identified an optimal range (24-32 nodes) for examination, emphasizing the nuanced benefits across NSCLC stages. The study findings suggest that LND plays a critical role in improving cancer-specific survival in NSCLC patients, particularly when tailored to the early stages of the disease. The optimal range of lymph nodes examined, between 24 and 32, offers crucial insights for personalized NSCLC treatment strategies and may enhance overall survival. These results underscore the need for refined surgical guidelines that incorporate the extent of LND, supporting the utility of a more personalized approach in NSCLC management.

A signature based on circadian rhythm-associated genes for the evaluation of prognosis and the tumour microenvironment in HNSCC

The morbidity and mortality rates of head and neck squamous cell carcinoma (HNSCC) remain high worldwide. Therefore, there is an urgent need to identify a new prognostic biomarker to guide the personalized treatment of HNSCC patients. Increasing evidence suggests that circadian rhythm genes play an important role in the development and progression of cancer. We aimed to explore the value of circadian rhythm genes in predicting prognosis and guiding the treatment of HNSCC. We first obtained a list of circadian rhythm genes from previous research. The sequencing data were retrieved from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Finally, univariate Cox proportional hazard analysis, least absolute shrinkage and selection operator (LASSO) regression, and multivariate Cox proportional hazard analysis were performed to develop a prognostic signature (Circadian Rhythm-Related Gene Prognostic Index, CRRGPI) consisting of nine circadian rhythm genes. The signature exhibited good performance in predicting overall survival. Patients with low CRRGPI scores had lower metabolic activities and an active antitumour immunity ability. Additionally, a clinical cohort was used to further evaluate the ability of the CRRGPI to predict the efficacy of immune checkpoint inhibitors. In conclusion, the novel circadian rhythm-related gene signature can provide a precise prognostic evaluation with the potential capacity to guide individualized treatment regimens for HNSCC patients.

Impact of atrial fibrillation phenotype and left atrial volume on outcome after pulmonary vein isolation.

Pulmonary vein isolation (PVI) is increasingly performed in patients with atrial fibrillation (AF). Both AF phenotype and left atrial (LA) volume have been shown to influence ablation outcome. The inter-relationship of the two is incompletely understood. We aimed to investigate the impact of AF phenotype vs. LA volume on outcome after PVI. In a retrospective analysis of a prospective registry of patients undergoing a first PVI, the association of AF phenotype and LA volume index (LAVI) was assessed as well as their impact on AF recurrence during follow-up. Overall, 476 patients were enrolled (median age 63 years, 29% females, 65.8% paroxysmal AF). Obesity, hypertension, chronic kidney disease, and heart failure were all significantly more frequent in persistent AF. After 1 year, single-procedure, freedom from arrhythmia recurrence was 61.5%. Patients with paroxysmal AF had better outcomes compared with patients with persistent AF (65.6 vs. 52.7%, P = 0.003), as had patients with no/mild vs. moderate/severe LA dilation (LAVI <42 mL/m2 67.1% vs. LAVI ≥42 mL/m2 53%, P < 0.001). The combination of both parameters refined prediction of 1-year recurrence (P < 0.001). After adjustment for additional clinical risk factors in multivariable Cox proportional hazard analysis, both AF phenotype and LAVI ≥42 mL/m2 contributed significantly towards the prediction of 1-year recurrence. Atrial fibrillation phenotype and LA volume are independent predictors of outcome after PVI. Persistent AF with no/mild LA dilation has a similar risk of recurrence as paroxysmal AF with a moderate/severe LA dilation and should be given similar priority for ablation.

Joint Association of Low Nadir Serum Sodium and Potassium with Worse Outcomes after Ischemic Stroke

Background. Potassium and sodium are inextricably linked to the maintenance of cell potential and electrolyte homeostasis. Few studies have examined their joint relationship with outcomes after stroke. The objective of this study is to ascertain whether combined low nadir serum sodium and potassium levels are correlated with an unfavorable outcome in ischemic stroke. Methods. Retrospective cohort study of 2,920 consecutive patients with first-ever ischemic stroke. Serum sodium and potassium levels were measured at 10 consecutive time points over 10 days poststroke. The Youden Index was performed to identify patients with low nadir sodium (&lt;140 mmol/L) and potassium (&lt;3.65 mmol/L) levels, defined as a NaK score of 2. Multivariable logistic regression and Cox proportional hazard analysis were used to evaluate the independent relationship of sodium and potassium levels with clinical outcomes at three months. Results. A total of 2,920 patients with ischemic stroke were analyzed (mean age 62.14±14.13 years; 60.19% male), of whom 740 (25.3%) with both low nadir sodium and potassium levels had a quintuple 3-month case fatality compared to other patients (10.6% vs. 2.1%). Multivariable analyses identified NaK=2 as an independent predictor of 3-month death (adjusted odds ratio (OR) 2.23; 95% confidence interval (CI) 1.17-4.53; p=0.019) and an unfavorable shift in the distribution of scores on the modified Rankin scale (adjusted OR 1.51, 95% CI 1.12-2.04; p=0.007). Conclusions. Low sodium and potassium levels are common after ischemic stroke and are independent predictors of subsequent death.

Blood urea nitrogen to serum albumin ratio: a novel mortality indicator in intensive care unit patients with coronary heart disease

The blood urea nitrogen to albumin ratio (BAR) has been demonstrated as a prognostic factor in sepsis and respiratory diseases, yet its role in severe coronary heart disease (CHD) remains unexplored. This retrospective study, utilizing data from the Medical Information Mart for Intensive Care-IV database, included 4254 CHD patients, predominantly male (63.54%), with a median age of 74 years (IQR 64–83). Primary outcomes included in-hospital, 28-day and 1-year all-cause mortality after ICU admission. The Kaplan–Meier curves, Cox regression analysis, multivariable restricted cubic spline regression were employed to assess association between BAR index and mortality. In-hospital, within 28-day and 1-year mortality rates were 16.93%, 20.76% and 38.11%, respectively. Multivariable Cox proportional hazards analysis revealed associations between the increased BAR index and higher in-hospital mortality (HR 1.11, 95% CI 1.02–1.21), 28-day mortality (HR 1.17, 95% CI 1.08–1.27) and 1-year mortality (HR 1.23, 95% CI 1.16–1.31). Non-linear relationships were observed for 28-day and 1-year mortality with increasing BAR index (both P for non-linearity < 0.05). Elevated BAR index was a predictor for mortality in ICU patients with CHD, offering potential value for early high-risk patient identification and proactive management by clinicians.

Risk factors for repeated percutaneous transluminal angioplasty of hemodialysis vascular access after initial intervention.

Percutaneous transluminal angioplasty (PTA) is a significant intervention to deal with occlusion and stenosis of vascular access. The study aimed to explore the risk factors of repeated PTA (re-PTA) after the initial intervention in patients undergoing hemodialysis. This retrospective study included 180 patients who underwent successful PTA for the first time between March 2016 and December 2020. Information on demographic, clinical, anatomical, and medication variables was collected. Survival curves were plotted using Kaplan-Meier analysis and the risk factors associated with re-PTA were analyzed using univariate and multivariate Cox proportional hazards analyses. The primary clinical patency rates at 6, 12, and 24months after PTA were found to be 85.2%, 70.7%, and 58.6%, respectively. The univariate Cox proportion hazards analysis revealed the association of non-antiplatelet agents (HR 2.368 95% CI 1.351 to 4.150, p = .003) and arteriovenous graft (AVG) (HR 2.096 95% CI 1.147 to 3.831, p = .016) with re-PTA. However, only non-antiplatelet therapy showed statistical significance (HR 2.368 95% CI 1.351 to 4.150, p = .003) in multivariate Cox proportional hazards analysis. Among the patients undergoing hemodialysis, the use of antiplatelet agents was associated with a lower risk of re-PTA. Therefore, the use of antiplatelet drugs may reduce the rates of re-PTA and help in maintaining the patency of vascular access.