Multivariate Proportional Hazards Regression Analysis Research Articles

Comparison of BCG Tokyo172 Strain Induction Therapy Between Low Dose and Standard Dose for Non-Muscle Invasive Bladder Cancer: Intravesical Instillation of BCG Tokyo172 Strain

Objectives: The aim of this study was to identify factors that predict recurrence by comparing low-dose and standard-dose Bacillus Calmette-Guérin (BCG) induction therapy in patients with non-muscle invasive bladder cancer (NMIBC). Methods: A total of 273 consecutive NMIBC patients who received low-dose (40 mg) or standard-dose (80 mg) BCG intravesical instillation therapy between January 2004 and December 2023 were analyzed. Recurrence-free survival (RFS) rates were assessed using the Kaplan–Meier method with the log-rank test. Univariate and multivariate Cox proportional hazards regression analyses were used to identify independent predictors of recurrence based on the Club Urológico Español de Tratamiento Oncológico (CUETO) criteria. Results: The log-rank test showed that older age, low BCG dose, number of tumors, and a history of recurrence increased the risk of recurrence significantly. Regarding older patients, recurrence rates were similar between the two dose groups. However, younger patients had significantly lower recurrence rates with standard-dose BCG compared to low-dose BCG. Multiple Cox regression analysis confirmed that older age, low-dose BCG, greater than three tumors, and a history of recurrence were significant predictors of recurrence. Conclusions: In this study, we found that low-dose BCG induction therapy was associated with higher relapse rates compared with standard doses, especially in younger patients. Age-related differences in the immune response to BCG may influence these relapse patterns.

Quadrant, necrosis, and infection criteria for the risk stratification of walled-off necrosis: external validation using multi-institutional data.

Endoscopic ultrasound-guided peripancreatic fluid drainage (EUS-PFD) with on-demand endoscopic necrosectomy, increasingly utilized to manage walled-off necrosis (WON), is associated with substantial morbidity and mortality. This multicenter study aimed to externally validate recently developed quadrant (an abdominal quadrant distribution), necrosis, and infection (QNI) criteria for risk stratification in this setting. Of 423 patients with pancreatic fluid collections treated in a large multi-institutional cohort between 2010 and 2020, 212 with available preprocedural computed tomography images were included. Clinical outcomes between high- and low-risk groups defined according to QNI criteria were compared. The clinical success rate did not differ significantly between the QNI-high and QNI-low groups (74.4% vs. 83.5%, respectively; P = 0.12). Time to clinical success was longer in the QNI-high group compared with the QNI-low group (median, 68 vs. 46 days, respectively; P = 0.0016). Compared with the QNI-low group, the QNI-high group was associated with higher rates of percutaneous interventions, direct endoscopic necrosectomy, mortality, and adverse events. The QNI-high group was independently associated with time to clinical success (hazard ratio 0.64, 95% confidence interval 0.46-0.87; P =0.005) in multivariable Cox proportional hazards regression analysis, and with the risk of ≥grade III adverse events (odds ratio 2.93, 95% confidence interval 1.04-8.20; P = 0.04) in multivariable logistic regression analysis. The QNI criteria effectively stratified time to clinical success and the risk of adverse outcomes for patients receiving EUS-PFD of WON. Further investigations could elucidate appropriate management strategies based on QNI-based risk stratification.

Association between stress hyperglycemia ratio and mortality in patients with heart failure complicated by sepsis

Individuals afflicted with heart failure complicated by sepsis often experience a surge in blood glucose levels, a phenomenon known as stress hyperglycemia. However, the correlation between this condition and overall mortality remains unclear. 869 individuals with heart failure complicated by sepsis were identified from the Medical Information Mart for Intensive Care-IV (MIMIC-IV) database and categorized into five cohorts based on their stress hyperglycemia ratio (SHR). The primary endpoints evaluated were mortality within the intensive care unit (ICU), all-cause mortality within 28 days, and all-cause mortality during hospitalization. Cox proportional hazards regression and restricted cubic spline analyses were employed to unravel the association between SHR and mortality. The ICU mortality, in-hospital mortality, and 28-day all-cause mortality were 10.01%, 13.69%, and 16.46%, respectively. Multivariable Cox proportional hazards regression analysis revealed a significant association between elevated SHR and all-cause mortality. After adjusting for confounding variables, elevated SHR was significantly associated with increased risk of ICU mortality (hazard ratio [HR] = 1.67; 95% confidence interval [CI], 1.03–2.70)), in-hospital mortality (HR = 1.53; 95% CI, 1.00-2.33)), and 28-day all-cause mortality (HR = 1.49; 95% CI, 1.02–2.17)). Restricted cubic spline analysis demonstrated a significant U-shaped relationship between SHR and the risk of all-cause mortality. This study revealed that stress hyperglycemia ratio is an independent prognostic factor in patients with heart failure complicated by sepsis. Notably, both very high and very low SHR values were associated with increased mortality risk.

Pre-procedural TMAO as a predictor for recurrence of atrial fibrillation after catheter ablation

BackgroundNumerous studies have demonstrated the significance of trimethylamine-N-oxide (TMAO) in the progression of atrial fibrillation (AF). However, the association between TMAO and AF recurrence (RAF) post-catheter ablation is not yet fully understood. This study aims to elucidate the predictive capability of pre-procedural TMAO levels in determining RAF following catheter ablation (CA).MethodsThis study was conducted as a prospective, single-center observational study. Between June 2021 and June 2022, 152 patients from the Department of Cardiology at The Affiliated Huaian No. 1 People’s Hospital of Nanjing Medical University were enrolled. Baseline characteristics and serum TMAO levels were assessed for all participants. Patients with AF who underwent CA were monitored for recurrences of AF using electrocardiography (ECG) or 24-hour Holter monitoring during the follow-up period.ResultsThe study found that serum TMAO levels were significantly higher in persistent AF (PeAF) patients compared to those in sinus rhythm (SR) and paroxysmal AF (PaAF) patients (3.96 ± 1.69 vs. 1.81 ± 0.59, 3.02 ± 1.50 µM, P < 0.001 and P < 0.01, respectively). After a one-year follow-up, 29 (21.2%) AF patients experienced recurrence after CA. Multivariate Cox proportional hazards regression analysis revealed that pre-procedural serum TMAO was an independent predictor of recurrent AF (HR = 1.78, 95% CI = 1.43–2.21, P < 0.001). The receiver operating characteristic (ROC) curve analysis identified a cut-off value of 4.3µM for serum TMAO levels in predicting recurrent AF (area under the curve: 0.835, P < 0.001). The Kaplan-Meier plot demonstrated that patients with TMAO levels greater than 4.3µM had a significantly higher rate of recurrent AF (HR = 13.53, 95% CI = 6.19–29.56, P < 0.001).ConclusionPatients with AF exhibited elevated levels of circulating TMAO compared to patients with SR. The findings suggest a potential role of TMAO in the development of AF, with pre-procedural serum TMAO levels serving as a reliable predictor of recurrence of AF CA.

Association Between Serum Thyrotropin and Cancer Recurrence in Differentiated Thyroid Cancer: A Population-Based Retrospective Cohort Study.

Background: Levothyroxine to suppress thyrotropin (TSH) to <0.5 mIU/L following thyroidectomy in differentiated thyroid cancer (DTC) may reduce recurrence in higher-risk DTC. However, there is limited evidence to support guideline recommendations to maintain TSH in the low-normal range of 0.5-2 mIU/L to reduce recurrence in patients with lower risk DTC. The primary objective was to assess the association between exposure to high normal serum TSH (2-4 mIU/L) as compared with low normal TSH (0.5-2 mIU/L) target ranges and cancer recurrence in patients with DTC after thyroidectomy. Methods: This population-based retrospective cohort study used linked, administrative health care databases from Ontario, Canada, to follow patients with DTC post-thyroidectomy from 2007 to 2018. The exposure was time updated, serum TSH, treated as a cumulative and instantaneous exposure. Multivariable cause-specific proportional hazard regression analyses were performed to determine time to DTC recurrence from index date, defined as a composite of repeat neck surgery, radioactive iodine (RAI) treatment, and/or DTC-specific death. Results were also stratified by initial treatment as a marker of baseline recurrence risk in a sensitivity analysis. Results: This cohort of 26,336 individuals (78% female) with DTC and a median age of 50 years were followed for a median of 5.9 (interquartile range 3.6-8.6) years; 40.9% were initially treated with a hemi-thyroidectomy only and 38.2% received a total thyroidectomy and RAI. Compared with exposure to TSH 0.5 to ≤2 mIU/L, DTC recurrence rate was similar for each additional 3 months of exposure to TSH >2 to ≤4 mIU/L (adjusted cause specific [cs] hazard ratio [HR] 0.99 [confidence interval or CI 0.97-1.02]) but was significantly increased with each additional 3 months of exposure to TSH >4 mIU/L (adjusted csHR 1.07 [CI 1.04-1.09]). Results were similar across baseline treatment groups. Conclusion: There was no difference in clinically significant recurrence in those with low-risk DTC maintained with a TSH of 0.5-2 mIU/L compared with 2-4 mIU/L. Guidelines should consider liberalizing target TSH level post thyroidectomy in low-risk cohorts. These results cannot be applied to patients with high-risk DTC.

Cluster analysis and analysis of risk factors for hereditary transthyretin amyloidosis cardiomyopathy

Objective: To explore the clinical characteristics and prognostic value in hereditary transthyretin amyloidosis cardiomyopathy (hATTR-CM) patients based on cluster analysis, and to explore the risk factors for cardiovascular composite events. Methods: This retrospective cohort study included hATTR-CM patients who were admitted to Peking Union Medical College Hospital from January 2000 to January 2024. These patients were divided into two clusters using cluster analysis, based on genetic information, demographic information and clinical information. During the follow-up period, cardiovascular composite events were defined as all-cause death and hospitalization for heart failure. Both cardiovascular composite events and all-cause death were the endpoints. Kaplan-Meier survival curves and log-rank method were used to compare the prognostic significance of cluster analysis subgroups. Univariate and multivariate Cox proportional hazard regression models were used to analyze the risk factors affecting the incidence of cardiovascular composite events. Results: A total of 43 patients were included in this study, 30 were male (69.8%). In cluster 1 (n=27), whose age of onset was (49.9±13.9) years old, 24(88.9%) of them started with neuropathy or gastrointestinal symptoms, and all clinical phenotypes were mixed type (neurological and cardiac). In cluster 2 (n=16), whose age of onset was (59.0±10.6) years old, 15(93.8%) of them started with heart failure symptoms, and 13(81.3%) were pure cardiomyopathy. During the median follow-up time of 2.6 years, a total of 16 patients (37.2%) experienced composite cardiovascular events, and a total of 12 patients (27.9%) died. Kaplan-Meier survival curves showed a significantly lower cumulative survival rate for cardiovascular composite endpoint events (log-rank P=0.04) and all-cause death (log-rank P=0.04) in cluster 2 than in cluster 1. Univariate Cox proportional hazard regression model analysis showed that hATTR-CM patients with reduced estimated glomerular filtration rate, left ventricular ejection fraction≤40%, and moderate to severe mitral regurgitation were risk factors for vascular composite events (all P<0.05). Multivariate Cox proportional hazard regression analysis showed that left ventricular ejection fraction≤40% was an independent risk factor (P<0.01). Conclusions: Cluster analysis is a valuable prediction tool on the prognostic stratification of hATTR-CM. Cluster 2, which is late-onset with onset of heart failure symptoms has a worse prognosis during follow-up period. The occurrence of composite cardiovascular events in hATTR-CM is related to left ventricular ejection fraction≤40%. Cluster analysis is helpful for clinical identification of high-risk groups.

The systemic inflammation response index (SIRI) predicts survival in advanced non-small cell lung cancer patients undergoing immunotherapy and the construction of a nomogram model.

Inflammation and immune evasion are associated with tumorigenesis and progression. The Systemic Inflammation Response Index (SIRI) has been proposed as a pre-treatment peripheral blood biomarker. This study aims to compare the relationship between SIRI, various serum biomarkers, and the prognosis of NSCLC patients before and after treatment. A retrospective study was conducted on advanced NSCLC patients treated with anti-PD-1 drugs from December 2018 to September 2021. Peripheral blood markers were measured pre- and post-treatment, and hazard ratios were calculated to assess the association between serum biomarkers and progression-free survival (PFS) and overall survival (OS). Kaplan-Meier curves and Cox proportional hazards models were employed for survival analysis. A nomogram model was built based on multivariate Cox proportional hazards regression analysis using the R survival package, with internal validation via the bootstrap method (1,000 resamples). Predictive performance was expressed using the concordance index (C-index), and calibration plots illustrated predictive accuracy.The application value of the model was evaluated by decision curve analysis (DCA). Among 148 advanced NSCLC patients treated with PD-1 inhibitors, the median PFS was 12.9 months (range: 5.4-29.2 months), and the median OS was 19.9 months (range: 9.6-35.2 months). Univariate analysis identified pre- and post-treatment SIRI, mGRIm-Score, and PNI as independent prognostic factors for both PFS and OS (p < 0.05). Multivariate analysis demonstrated that high post-SIRI and post-mGRIm-Score independently predicted poor PFS (P < 0.001, P = 0.004) and OS (P = 0.048, P = 0.001). The C-index of the nomogram model for OS was 0.720 (95% CI: 0.693-0.747) and for PFS was 0.715 (95% CI: 0.690-0.740). Internal validation via bootstrap resampling (B = 1,000) showed good agreement between predicted and observed OS and PFS at 1, 2, and 3 years, as depicted by calibration plots. SIRI is an important independent predictor of early progression in advanced NSCLC patients treated with PD-1 inhibitors and may assist in identifying patients who will benefit from PD-1 inhibitors therapy in routine clinical practice.

Analysis of prognostic risk factors for patients with locally advanced gastric cancer in the stage ypT0~2N0M0 after neoadjuvant chemotherapy

Objectives: To analyze the long-term prognosis of patients with locally advanced gastric cancer in the stage of ypT0~2N0M0 after neoadjuvant chemotherapy. Methods: The clinical data of 78 patients with locally advanced gastric cancer who underwent neoadjuvant chemotherapy and radical resection at ypT0~2N0M0 stage from January 2012 to December 2019 in the Department of Abdominal Surgery/Pancreatic and Gastric Surgery of the Cancer Hospital of Chinese Academy of Medical Sciences were retrospectively analyzed. Kaplan-Meier method was used to calculate the overall survival and disease-free survival, and the survival difference between patients with postoperative ypT0N0M0 and ypT1~2N0M0 was compared. Multivariate Cox proportional hazards regression analysis was performed on clinical, pathologic and treatment measures that may affect survival. Results: Among the 78 patients, there were 18 cases (23.1%) with ypT0N0M0, 14 cases (17.9%) with ypT1aN0M0, 17 cases (21.8%) with ypT1bN0M0, and 29 cases (37.2%) with ypT2N0M0. Median follow-up time was 74.1 (19.8~132.5) months. Fourteen patients (17.9%) had tumor recurrence and metastasis, and 9 patients died from tumor recurrence and metastasis. The 5-year disease-free survival and overall survival rates were 84.4% and 87.8%, respectively. There was no statistically significant difference in 5-year overall survival (86.9% vs 87.8%) or 5-year disease-free survival (88.9% vs 83.2%) between patients with ypT0N0M0 and ypT1~2N0M0. Analysis of factors that may affect prognosis revealed that signet ring cell carcinoma, nerve invasion, and lymph node dissection of fewer than 16 were significantly associated with prognosis (P＜0.05). Multivariate Cox analysis including these three factors showed that only lymph node dissection of fewer than 16 was an independent risk factor affecting prognosis (OS: HR=10.44 ,95% CI: 2.15-50.72, P=0.004; DFS: HR=11.47, 95% CI: 2.85-46.20, P=0.001). Conclusions: The long-term prognosis of patients with locally advanced gastric cancer at ypT0~2N0M0 stage after neoadjuvant chemotherapy is relatively good, and the long-term survival time of patients with ypT1~2N0M0 and ypT0N0M0 is similar. Lymph node dissection of less than 16 nodes may be an independent risk factor affecting prognosis. During surgery, efforts should be made to increase the number of lymph node dissections. For patients with less than 16 nodes dissected, postoperative treatment and follow-up should be strengthened.

Construction and validation of a regulatory T cells-based classification of renal cell carcinoma: an integrated bioinformatic analysis and clinical cohort study.

Renal cell carcinoma (RCC), exhibiting remarkable heterogeneity, can be highly infiltrated by regulatory T cells (Tregs). However, the relationship between Treg and the heterogeneity of RCC remains to be explored. We acquired single-cell RNA-seq profiles and 537 bulk RNA-seq profiles of TCGA-KIRC cohort. Through clustering, monocle2 pseudotime and prognostic analyses, we identified Treg states-related prognostic genes (TSRPGs), then constructing the RCC Treg states-related prognostic classification (RCC-TSC). We also explored its prognostic significance and multi-omics landmarks. Additionally, we utilized correlation analysis to establish regulatory networks, and predicted candidate inhibitors. More importantly, in Xinhua cohort of 370 patients with kidney neoplasm, we used immunohistochemical (IHC) staining for classification, then employing statistical analyses including Chi-square tests and multivariate Cox proportional hazards regression analysis to explore its clinical relevance. We defined 44 TSRPGs in four different monocle states, and identified high immune infiltration RCC (HIRC, LAG3+, Mki67+) as the highly exhausted subtype with the worst prognosis in RCC-TSC (p < 0.001). BATF-LAG3-immune cells axis might be its underlying metastasis-related mechanism. Immunotherapy and inhibitors including sunitinib potentially conferred best therapeutic effects for HIRC. Furthermore, we successfully validated HIRC subtype as an independent prognostic factor within the Xinhua cohort (OS, HR = 16.68, 95% CI = 1.88-148.1, p = 0.011; PFS, HR = 4.43, 95% CI = 1.55-12.6, p = 0.005). Through integrated bioinformatics analysis and a large-sample retrospective clinical study, we successfully established RCC-TSC and a diagnostic kit, which could stratify RCC patients with different prognosis and to guide personalized treatment.

Prognostic Factors, Predictive Modeling, and Treatment Patterns in Breast Cancer Patients with Bone Metastasis Receiving First-Line Chemotherapy: A Population-Based Study.

The prognostic factors and a nomogram applicable to breast cancer (BC) patients with bone metastasis (BM) who received first-line chemotherapy have not been extensively studied. This study aimed to identify prognostic factors and construct a prognostic nomogram to predict overall survival (OS) in this population. Data for BC patients with BM undergoing first-line chemotherapy were retrieved from the Surveillance, Epidemiology, and End Results (SEER) database from 2010 to 2016. A total of 2996 BC patients with BM undergoing first-line chemotherapy were included. Age, tumor size, race, tumor grade, breast cancer subtype, brain metastasis, liver metastasis, lung metastasis, surgical intervention, and marital status were identified as independent prognostic factors in the training cohort. Patients were randomly assigned into a training cohort (n = 2100) and an internal validation cohort (n = 896). Prognostic variables were identified using univariate and multivariate Cox Proportional Hazards (Cox) regression analysis. A nomogram was constructed and validated in both cohorts. The discrimination and accuracy of the nomogram were evaluated using receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA). The areas under the curves (AUCs) for 1-, 2- and 3-year OS were 0.803 (95% confidence interval (CI): 0.752-0.854), 0.785 (95% CI: 0.756-0.814), and 0.767 (95% CI: 0.701-0.803), respectively, in the training cohort, and 0.793 (95% CI: 0.756-0.830), 0.791 (95% CI: 0.761-0.821), and 0.756 (95% CI: 0.719-0.793), respectively, in the validation cohort. The nomogram demonstrated excellent discrimination, calibration, and clinical utility. This study developed and validated a robust survival prediction model for breast cancer patients with bone metastasis receiving first-line chemotherapy. The nomogram demonstrates strong predictive performance and can aid clinicians in formulating individualized treatment strategies, thereby improving patient outcomes.

Atherosclerotic plaque evolution predicts cerebral ischemic events in patients with intracranial atherosclerosis: a multicentre longitudinal study using high-resolution MRI.

Intracranial atherosclerosis (ICAS) is the leading cause of ischemic stroke in Asians and the recurrent rate remains high despite the optimal medical treatment. This study aimed to confirm that follow-up high-resolution magnetic resonance imaging (hrMRI) provided essential values in predicting subsequent cerebral ischemic events in patients with ICAS. Patients with moderate to severe stenosis in the middle cerebral artery (MCA) defined by magnetic resonance (MRA) or computed tomography angiography (CTA) were recruited from three centers retrospectively. Detailed plaque composition was analyzed on baseline and follow-up hrMRI. Multivariate Cox proportional hazards regression analysis was used to identify the key risk factors for predicting subsequent ischemic events. Among 152 patients, a total of 86 patients with MCA atherosclerotic stenosis underwent follow-up hrMRI exams and ipsilateral cerebral ischemic events occurred in 12 patients during a 1-year follow-up. Analyses showed the predictors of ischemic events were age (adjusted Hazard ratio (HR) = 0.942; 95% Confidence Interval (CI), [0.903, 0.983]; p = 0.006), progression of plaque burden (HR = 3.818; 95% CI [1.117, 13.051]; p = 0.033), vessel expansion (HR = 5.173; 95% CI [1.077, 24.838]; p = 0.040) and enhancement ratio progression (HR = 6.144; 95% CI [1.480, 25.511]; p = 0.012). The combined model achieved a concordance index of 0.804 (95% CI [0.658, 0.950]). Longitudinal hrMRI evaluation improved the accuracy in identifying higher-risk patients with intracranial atherosclerosis. Question Can longitude high-resolution magnetic resonance imaging (hrMRI) help clinicians observe intracranial plaque evolution? Findings Compared with the baseline exam, intracranial plaque evolution distinguished by follow-up hrMRI exam showed a higher accuracy in predicting subsequent ischemic events. Clinical relevance Longitudinal high-resolution magnetic resonance vessel wall imaging enables dynamic observation and evaluation of the changes in plaque characteristics among intracranial atherosclerosis patients. Atherosclerotic plaque evolution revealed by repeated exams can strengthen the risk stratification of patients with intracranial atherosclerosis.

Systematic Intravenous Administration of Autologous Mesenchymal Stem Cells Is Safe.

Background: Mesenchymal stem cells (MSCs) have drawn significant attention for their regenerative potential and therapeutic applicability across a range of conditions, including cardiovascular diseases and age-related frailty. Despite extensive preclinical studies, there remain gaps in understanding the long-term safety and efficacy of MSC therapy in humans. This study aimed to assess the safety of intravenous MSC administration, evaluate the mean major adverse cardiac and cerebrovascular event (MACCE)-free period, and identify potential risk factors for MACCE development in patients receiving MSC therapy for various indications. Methods: A retrospective observational study was conducted on 2504 patients (mean age: 54.09 ± 11.65 years) who received intravenous adipose-derived MSC (AD-MSC) therapy between October 2014 and December 2023 at the Omotesando Helene Clinic, Tokyo, Japan. Patients received MSC doses ranging from 100 million to 2 billion cells, with the majority receiving 1-2 billion cells per treatment. Statistical analyses included multivariate Cox proportional hazards regression and Kaplan-Meier survival analysis to evaluate MACCE risk factors and event-free duration. Results: Over the follow-up period, the MACCE rate was exceptionally low at 0.2%. Multivariate analysis identified age as a significant risk factor for MACCE (hazard ratio: 1.127; 95% CI: 1.0418-1.219; p = 0.0029), while sex and MSC dose showed no significant association. Minor adverse events occurred in 0.8% of patients, with no severe adverse events reported. The study found MSC therapy to be safe, with a low adverse event rate and minimal risk of MACCE. Conclusions: This study demonstrates the safety of intravenous MSC therapy in a large cohort of patients, with a low incidence of MACCE and minimal adverse effects. Age was the only significant predictor of MACCE risk. Further prospective randomized studies are needed to validate these findings and explore the potential of MSC therapy in reducing MACCE risk and improving clinical outcomes across diverse indications.

Association of leukocyte telomere length with the risk of digestive diseases: A large-scale cohort study.

Leukocyte telomere length (LTL) shortening, a biomarker of telomere attrition, has been linked to multiple diseases. However, the relationship between LTL and digestive diseases remains uncertain. This study aimed to investigate the association between LTL and the risk of digestive diseases. A cohort analysis of over 500,000 participants from the UK Biobank (UKB) between 2006 and 2021 was conducted to estimate the associations of LTL with more than 90 common digestive diseases. LTL was quantified using multiplex quantitative polymerase chain reaction, and cases of each disease were determined according to inpatient and primary care data. Multivariable Cox proportional hazards regression analysis was used to evaluate the associations of LTL with the risk of digestive diseases. Furthermore, such associations were also evaluated after stratification by sex and ethnicity. After a mean follow-up time of 11.8years, over 20 the International Classification of Diseases 10th Revision (ICD-10) codes were observed to be associated with telomere attrition. LTL shortening is associated with an increased risk of several digestive diseases, including gastroesophageal reflux disease (K21: hazard ratio [HR]= 1.30, 95% confidence interval [95% CI]: 1.19-1.42), esophageal ulcer (K221: HR= 1.81, 95% CI: 1.22-2.71), Barrett's esophagus (K227: HR= 1.58 95% CI: 1.14-2.17), gastritis (K29: HR= 1.39, 95% CI: 1.26-1.52), duodenal ulcer (K26: HR= 1.55, 95% CI: 1.14-2.12), functional dyspepsia (K30X: HR= 1.36, 95% CI: 1.06-1.69), non-alcoholic fatty liver disease (NAFLD) (K760: HR= 1.39, 95% CI: 1.09-1.78), liver cirrhosis (K74: HR= 4.73, 95% CI: 3.27-6.85), cholangitis (K830: HR= 2.55, 95% CI: 1.30-5.00), and hernia (K43: HR= 1.50, 95% CI: 1.17-1.94; K44: HR= 1.29, 95% CI: 1.17-1.42). The risk of rectal polyps (K621: HR= 0.77, 95% CI: 0.63-0.92) decreased per unit shortening of LTL. This study suggests that LTL shortening is associated with an increased risk of most digestive diseases except for rectal polyps. These findings may provide some clues for understanding the pathogenesis of digestive diseases.

Cardiac Events and Survival in Patients With EGFR-Mutant Non–Small Cell Lung Cancer Treated With Osimertinib

Although it has been reported that osimertinib mesylate provides better survival benefits compared with first- or second-generation epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs), it remains unclear whether osimertinib is associated with more cancer therapy-related cardiac events (CTRCEs) compared with other EGFR TKIs, as does the extent of the association these adverse effects may have with overall survival. This issue is particularly critical due to the high prevalence of EGFR variants within Asian populations, including that of Taiwan. To compare CTRCEs and their association with survival in patients treated with osimertinib vs other EGFR TKIs. This cohort study was conducted at the National Cheng Kung University Hospital, a college hospital and tertiary academic referral center in Taiwan. The median follow-up duration was 23.2 (IQR, 15.2-31.5) months. A total of 401 patients with EGFR-mutant non-small cell lung cancer (NSCLC) beginning treatment with EGFR TKIs from September 1, 2019, to July 31, 2022, were retrospectively analyzed. CTRCEs included newly emerging arrhythmias, valvular heart diseases (moderate and more), myocardial infarction, and heart failure and were analyzed after adjusting for age, sex, smoking, alcohol consumption, body mass index, cardiovascular comorbidities, thoracic radiotherapy, and cardiovascular medications. Follow-up was completed January 31, 2024. Osimertinib. The Cox proportional hazards model was used to estimate CTRCEs in patients treated with osimertinib or other EGFR TKIs. Considering that death can lower the incidence of CTRCEs, the competing risk method was used to calculate CTRCEs after adjusting for potential confounders. Multivariable Cox proportional hazard regression analysis for overall survival was used to explore whether CTRCEs were independently associated with overall survival. Among the 401 patients (253 [63.1%] female; mean [SD] age, 69.2 [11.3] years), 195 (48.6%) treated with osimertinib were matched with 206 (51.4%) treated with other EGFR TKIs. Occurrence of CTRCEs in patients receiving osimertinib was significantly higher compared with patients treated with other EGFR TKIs (29 [14.9%] vs 9 [4.4%]; hazard ratio [HR], 3.37; 95% CI, 1.56-7.26; P = .002). After adjustment for relevant cardiovascular risk factors, the HR of CTRCEs was significantly higher in the group treated with osimertinib (adjusted subdistribution HR, 4.00; 95% CI, 1.81-8.85; P < .001). In addition, CTRCEs were independently associated with overall survival (HR, 4.02; 95% CI, 2.44-6.63; P < .001). In this cohort study of patients with EGFR-mutant NSCLC, osimertinib was associated with a higher incidence of CTRCEs compared with other EGFR TKIs; CTRCEs were independently associated with overall survival. These findings highlight the need for ongoing cardiac monitoring in these patients, regardless of preexisting cardiac risk factors.

Mediation Analysis of Serum Fibroblast Growth Factor 20 and Poor Prognosis After Ischemic Stroke.

We aimed to examine the relationship between serum FGF20 (fibroblast growth factor 20) levels and stroke prognosis in a multicenter cohort study. Patients with ischemic stroke/transient ischemic attack were prospectively recruited from 5 participating centers and followed up at 3 months and 1 year. FGF20 levels were measured using the ELISA method. The primary outcome was poor stroke functional outcome (modified Rankin Scale score of 3-6), and secondary outcomes included death and composite vascular events. Multivariable logistic regression analysis or Cox proportional hazards regression analysis was employed to estimate the relationship between FGF20 and study outcomes. Mediation analysis was conducted to examine the mediating effects of traditional risk factors on the association between FGF20 and stroke outcomes. A total of 1011 patients with ischemic stroke were included in the study. After adjusting for potential confounding factors, an elevated serum FGF20 level was associated with a reduced risk of the poor outcome and death. Multivariable adjusted spline regression analysis demonstrated a linear correlation between serum FGF20 levels and the stroke outcomes. The incorporation of FGF20 alongside conventional risk factors marginally enhanced the reclassification of adverse outcomes. Renal function and white blood cell count partially mediated the relationship between FGF20 and the prognosis of ischemic stroke. Elevated FGF20 level is associated with decreased risks of adverse outcomes after ischemic stroke, which was partially mediated by renal function and white blood cells with a modest amount, indicating that serum FGF20 might serve as a promising biomarker for predicting stroke prognosis. URL: https://www.chictr.org.cn; Unique identifier: ChiCTR2100051104.

The value of assessing deep disease healing by probe-based confocal laser endomicroscopy and histology for long-term prognosis of ulcerative colitis.

The benefits of deep disease healing need evaluation by long-term clinical research in different populations. Confocal laser endomicroscopy (CLE) is a superior method for evaluating deep disease healing. This prospective study enrolled ulcerative colitis (UC) patients in clinical remission who underwent colonoscopy, CLE, and histological assessment. Patients were monitored for relapse by patient-reported outcomes and colonoscopy evaluation of mucosal healing. The ability of different methods of mucosal healing to predict long-term disease recurrence was assessed using Kaplan-Meier estimation and Cox proportional hazard regression. Forty-two patients in clinical remission were assessed by colonoscopy. Those with Mayo endoscopic subscores (MES)≤1 were enrolled. The 48-month recurrence rates in present healing group, assessed by CLE (colonic barrier assessment and ENHANCE index) and by histological examination (Geboes scale), were 20.0%, 26.7%, and 11.1%, respectively, and were significantly lower than absent healing group (P<0.05). Univariate Cox proportional risk regression analysis in absent of healing disease, determined by the ENHANCE index and Geboes scale, indicated an increased risk of recurrent events, with hazard ratios (HR) of 3.87 (95% CI: 1.18, 12.62) and 8.20 (95% CI: 1.06, 63.30), respectively. Multivariate Cox proportional hazard regression analysis adjusted for the extent of inflammation (E3 or not) showed a significant difference only for the ENHANCE index, with an HR of 3.53 (95% CI: 1.03, 12.10), P=0.045. Deep disease healing has a lower recurrence rate. The colonic barrier healing assessment, ENHANCE index, and histological Geboes scale have superior long-term prognostic value for UC patients.

Inflammatory Burden Index: A Superior Prognostic Biomarker of Systemic Inflammation in Patients on Peritoneal Dialysis.

Systemic inflammation biomarkers, derived from routine blood tests, have been demonstrated to be associated with prognosis of patients undergoing peritoneal dialysis (PD). However, studies focusing on the comparisons of their role on predictive efficacy for prognosis of PD patient are limited and results are inconsistent. The purpose of this study was to evaluate the prognostic value of various systemic inflammation biomarkers and to identify the optimal one in PD patients. This longitudinal study involved 3,225 patients undergoing PD across China. The prognostic accuracy of systemic inflammatory biomarkers was evaluated using C-statistics. Independent prognostic biomarkers of outcomes were determined using multivariate Cox proportional hazards regression analysis. During a 46-month follow-up, 829 (25.7%) patients died, with 458 (55.3%) deaths attributed to cardiovascular disease (CVD). The highest C-statistics were observed for the IBI, with 0.619 and 0.621 for all-cause and CVD mortality, respectively. The optimal threshold of the IBI for predicting prognosis in patients undergoing PD was 50.0. An elevated IBI was a significant independent predictor of all-cause mortality, with a 1-SD increase associated with higher risks of all-cause and CVD mortality. Participants in the upper two quartiles of IBI exhibited increased risks of all-cause mortality by 41.2% and 67.6%, respectively, compared to those in the lowest quartile. Similar results were observed for CVD mortality. The IBI is a superior prognostic indicator of survival and could be broadly applied for prognosis of patients undergoing PD. Elevated IBI is an independent risk factor for all-cause and CVD mortality.

Identification of prognostic factors of chronic pulmonary aspergillosis: a retrospective cohort of 106 patients.

The morbidity and mortality of chronic pulmonary aspergillosis (CPA) are very high. We aimed to investigate the prognostic factors of patients with CPA, especially focusing on the underlying pulmonary disease and the probable co-infection of bacterial. We retrospectively analyzed 106 CPA patients from November 2019 to August 2023. We collected the patient's clinical medical records. Kaplan-Meier survival curves were used to analyze patient survival; log-rank tests were utilized to compare survival among groups. Univariate and multivariate Cox proportional hazards regression analyses were applied for identification of potential prognostic factors. The mean age at the time of diagnosis was 60.3±14.8 years; 74 (69.8%) patients were male. There was significant difference between patients with and without lung cancer (P<0.001), and with and without emphysema (P=0.02). Other prognosis factors associated with mortality were as follows: smoking (P=0.04), cough (P=0.01), simultaneous discovery with Gram-negative bacteria (P=0.02), and hypoalbuminemia (P=0.001) in log-rank tests. Multivariate Cox regression analyses showed that emphysema [hazard ratio (HR), 4.107; 95% confidence interval (CI): 1.414-11.933; P=0.009] and lung cancer (HR, 8.511; 95% CI: 2.494-29.047; P<0.001) were identified as independent predictors of mortality. The 1- and 3-year survival rates with emphysema were 75.2% and 64.9%, respectively, whereas those for patients without emphysema were 92.6% and 85.9%, respectively. In the current study, emphysema and lung cancer were independent predictors of mortality. Therefore, we should pay attention to the patients with these underlying lung diseases in order to improve the prognosis.

Construction of an immunogenic cell death-related LncRNA signature to predict the prognosis of patients with lung adenocarcinoma

BackgroundLung adenocarcinoma (LUAD) is one of the most common malignant diseases worldwide. This study aimed to construct an immunogenic cell death (ICD)-related long non-coding RNA (lncRNA) signature to effectively predict the prognosis of LUAD.MethodsThe RNA-sequencing and clinical data of LUAD were downloaded from The Cancer Genome Atlas (TCGA). Least absolute shrinkage and selection operator (LASSO) and stepwise multivariate Cox proportional hazard regression analysis were utilized to construct lncRNA signature. Then, the reliability of the signature was evaluated in the training, validation and whole cohorts. The differences in the immune landscape and drug sensitivity between the low- and high-risk groups were analyzed. Finally, the expression level of the selected ICD-related lncRNAs in LUAD cell lines via reverse transcription quantitative PCR (RT-qPCR). CCK-8 and transwell assays were performed to study biological function of AC245014.3.ResultsA signature consisting of 5 ICD-related lncRNAs was constructed. Kaplan Meier (K-M) survival analysis showed shorter overall survival (OS) in high-risk group. The receiver operating characteristic (ROC) curves and Multivariate Cox regression analysis showed the signature was good predictive and independent prognostic factor in LUAD. Moreover, the high-risk group had a lower level of antitumor immunity and was less sensitive to some chemotherapeutics and targeted drugs. Finally, the expression level of selected ICD-related lncRNAs was validated in LUAD cell lines by RT-qPCR. Knockdown of AC245014.3 significantly suppressed LUAD proliferation, migration and invasion.ConclusionsIn this study, an ICD-related lncRNA signature was constructed, which could accurately predict the prognosis of LUAD patients and guide clinical treatment.

Long non-coding RNA H19 as a prognostic biomarker for oral squamous cell carcinoma.

H19, a 2.3 kb lncRNA, has been linked to tumor metastasis and progression, but its significance in oral squamous cell carcinoma (OSCC) remains unclear. H19 was initially thought to have a tumor-suppressive function, but recent studies have shown that it possesses both tumor-promoting and suppressive functions. The variation in H19 expression may be due to the influence of tobacco or low basal expression levels. However, there are limited studies available on the association between H19 and its role in the prognosis of OSCC. The present study analyzes the expression of H19 correlated with clinicopathological parameters, tobacco habit, loco-regional recurrence, and overall survival. A longitudinal study was undertaken using 96 formalin-fixed paraffin-embedded (FFPE) OSCC tissues and 30 FFPE adjacent normal mucosa (NM) tissues from patients who had surgery between 2015 and 2018. The tissues were subjected to quantitative reverse-transcription PCR (qRT-PCR) to determine H19 expression. The differential expression levels of H19 in OSCC were compared to clinicopathological variables and risk habits using the t-test and ANOVA. H19 expression correlated overall survival was analyzed by drawing the Kaplan-Meier curve followed by the log-rank test. A multivariate Cox proportional hazards regression analysis was performed to determine the ability of H19 to independently predict loco-regional recurrence and overall survival for OSCC. H19 was significantly underexpressed in OSCC compared to NM in both the study cases and the TCGA OSCC database. The lower expression of H19 was significantly associated with the tobacco smoking habit and was not associated with any clinical or pathological features. Multivariate Cox's proportional hazards regression analysis indicated that low H19 expression and positive lymph node metastasis were independent predictors of overall survival for OSCC. Higher age, higher TNM staging, and low H19 expression were independent predictors of loco-regional recurrence. The findings in the present study indicate that H19 is a novel prognostic marker and may provide a therapeutic strategy for the targeted treatment of OSCC, and tobacco may play a role in the expression of H19.