Cox Regression Research Articles

Plasma DNA methylation detection for early screening, diagnosis, and monitoring of esophageal adenocarcinoma and squamous cell carcinoma

BACKGROUND The early diagnosis rate of esophageal cancer (EC), one of the most prevalent digestive tract cancers worldwide, remains low. AIM To investigate the utility of plasma SHOX2 , SEPTIN9 , EPO , and RNF180 methylation in the clinical diagnosis and monitoring of EC. METHODS Plasma samples were collected from 210 patients at Hubei Cancer Hospital, and TaqMan polymerase chain reaction was employed to detect plasma SHOX2 , SEPTIN9 , RNF180 , and EPO methylation. The area under the curve was used to estimate their diagnostic value for EC. Cox and logistic regression analyses were used to estimate the independent screening risk factors for patients with EC. RESULTS The sensitivity and specificity of combined assessment of plasma SHOX2 , SEPTIN9 , RNF180 , and EPO methylation for adenocarcinoma, squamous cell carcinoma (SCC), and EC detection were 66.67% and 86.27%, 77.40% and 85.29%, and 76.19% and 86.27%, respectively; the area under the curve values for diagnosing adenocarcinoma, SCC, and EC were 0.737 [95% confidence interval (CI): 0.584–0.89], 0.824 (95%CI: 0.775–0.891), and 0.864 (95%CI: 0.809–0.92), respectively. CONCLUSION According to our findings, plasma SHOX2 , SEPTIN9 , RNF180 , and EPO methylation exhibits appreciated sensitivity for diagnosing EC. The precise measurement of plasma SHOX2 , SEPTIN9 , RNF180 , and EPO methylation can improve EC diagnosis and therapy efficacy monitoring.

Primary Results of NRG-RTOG1106/ECOG-ACRIN 6697: A Randomized Phase II Trial of Individualized Adaptive (chemo)Radiotherapy Using Midtreatment 18F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography in Stage III Non-Small Cell Lung Cancer.

NRG-RTOG0617 demonstrated a detrimental effect of uniform high-dose radiation in stage III non-small cell lung cancer. NRG-RTOG1106/ECOG-ACRIN6697 (ClinicalTrials.gov identifier: NCT01507428), a randomized phase II trial, studied whether midtreatment 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) can guide individualized/adaptive dose-intensified radiotherapy (RT) to improve and predict outcomes in patients with this disease. Patients fit for concurrent chemoradiation were randomly assigned (1:2) to standard (60 Gy/30 fractions) or FDG-PET-guided adaptive treatment, stratified by substage, primary tumor size, and histology. All patients had midtreatment FDG-PET/CT; adaptive arm patients had an individualized, intensified boost RT dose to residual metabolically active areas. The primary therapeutic end point was 2-year centrally reviewed freedom from local-regional progression (FFLP), defined as no progression in or near the planning target volume and/or regional nodes. FFLP was analyzed on a modified intent-to-treat population at a one-sided Z-test significance level of 0.15. The primary imaging end point was centrally reviewed change in SUVpeak from baseline to midtreatment; its association with FFLP was assessed using the two-sided Wald test on the basis of Cox regression. Of 138 patients enrolled, 127 were eligible. Adaptive-arm patients received a mean 71 Gy in 30 fractions, with mean lung dose 17.9 Gy. There was no significant difference in centrally reviewed 2-year FFLP (59.5% and 54.6% in standard and adaptive arms; P = .66). There were no significant differences in protocol-specified grade 3 toxicities, survival, or progression-free survival (P > .4). Median SUVpeak and metabolic tumor volume (MTV) in the adaptive arm decreased 49% and 54%, from pre-RT to mid-RT PET. However, ΔSUVpeak and ΔMTV were not associated with FFLP (hazard ratios, 0.997; P = .395 and .461). Midtreatment PET-adapted RT dose escalation as given in this study was safe and feasible but did not improve efficacy outcomes.

Long-term Outcomes of Surgical Treatment for Pancreatic Neuroendocrine Neoplasm with Synchronous Hepatic Metastasis: A Multicenter Retrospective Cohort Study

Abstract Objectives: To evaluate surgical impact on the overall survival (OS) of pancreatic neuroendocrine neoplasm (pNEN) with synchronous hepatic metastases (sHM). Methods: A total of 163 pNEN-sHM patients were recruited from 3 institutions in China, who were categorized into 3 groups: no resection (NR), resection of the primary lesion (PR) and resection of both primary and hepatic lesions (PHR). Cox regression was employed to evaluate surgical impact on the OS. Results: In the overall cohort analysis, PHR demonstrated a significant protective effect on OS (HR 0.302, 95% CI: 0.127–0.721, p = 0.007). Nevertheless, subgroup analysis revealed PHR conferred a survival advantage in patients with pancreatic neuroendocrine tumor (pNET) located on the pancreatic body/tail (bt-pNET-sHM) (HR 0.287, 95% CI: 0.087–0.946, p = 0.040), whereas surgical treatment did not significantly impact survival in the subgroups of pancreatic neuroendocrine carcinoma (pNEC)-sHM or pancreatic head/neck pNET-sHM (hn-pNET-sHM). Conclusions: In this study, the survival benefit of surgery was only observed in the bt-pNET-sHM subgroup. Considering the multifactorial nature of decision-making, surgical intervention for pNEN-sHM management should be approached with a careful and comprehensive assessment, to prevent excessive surgery strategies.

In a prospective, multicenter study, the 31-GEP identified patients at increased risk of tumor recurrence and added significant prognostic value to AJCC staging

Cutaneous melanoma (CM) guidelines base management decisions on a patient’s American Joint Committee on Cancer (AJCC) tumor stage. However, limitations in staging accuracy suggest additional tools could improve risk-aligned patient management decisions. The 31-gene expression profile (GEP) test identifies patients with CM with low (Class 1A), intermediate (Class 1B/2A), or high (Class 2B) risk for sentinel lymph node (SLN) positivity, recurrence, metastasis, and death. In this multicenter, prospective study, we validated the 31-GEP for risk of recurrence and demonstrated the added value of 31-GEP to AJCC staging. Patients were included in the prospective CONNECTION study if they were tested with the 31-GEP from 2018 to the present (n=876). Survival was estimated using Kaplan-Meier analysis and 31-GEP stratification tested with the log-rank test. Cox regression was performed to identify predictors of recurrence. ANOVA was used to compare Cox models for the most accurate recurrence prediction. Patients with a Class 1A result had significantly higher 3-year recurrence-free survival than those with a Class 1B/2A or Class 2B result (98.5% vs. 80.8% vs. 63.0%, p<0.001). The 31-GEP had higher sensitivity (75.0% vs. 37.5%) and negative predictive value (98.6% vs. 96.9%) than AJCC staging. Multivariable analysis demonstrated that Class 1B/2A (hazard ratio, HR=3.12, p=0.037) and Class 2B (HR=5.91, p=0.002) were significant predictors of recurrence in addition to stage IB (HR=4.02, p=0.02), IIA (HR=6.06, p=0.006), IIC (HR=17.14, p<0.001), and III (HR=8.84, p<0.001). Stage IIB (HR=4.63, p=0.057) was not significant. Comparing a staging-only model to a 31-GEP+staging model showed that adding 31-GEP to staging significantly improved prediction accuracy over staging alone (ANOVA: c2=10.58, p=0.005). In this prospective study, the 31-GEP stratified risk of recurrence, was a significant predictor of recurrence, and added significant predictive value to AJCC staging. The 31-GEP identifies patients at high risk of recurrence who should be managed more intensely, and adding 31-GEP to staging allows better risk-aligned care decisions, which can lead to improved patient outcomes.

Incremental clinical value of intraplaque neovascularization in predicting recurrent ischemic stroke

AbstractObjectiveCarotid intraplaque neovascularization (IPN) detected by contrast‐enhanced ultrasound (CEUS) is a risk factor for recurrent ischemic stroke. However, it is still unclear whether IPN can be used to accurately identify patients with recurrent ischemic stroke in clinical practice. Herein, we investigated the clinical predictive value of IPN for recurrent ischemic stroke in a real‐world setting.MethodsWe enrolled 200 patients with ischemic stroke and atherosclerotic carotid stenosis who were followed up for 2 years. The endpoint was recurrent ischemic stroke. Cox regression and subgroup analyses were employed to assess whether treatment affected the relationship between IPN and recurrent ischemic stroke. The net classification index (NRI) and integrated discriminant improvement index (IDI) were used to validate the additional clinical value of IPN in identifying recurrent ischemic stroke.ResultsDuring the 2‐year follow‐up, 36 patients experienced recurrent ischemic stroke. Cox regression analyses showed that IPN (grade 2), hypoechoic plaque, high homocysteine levels, and smoking were independent risk factors for recurrent ischemic stroke. Additional IPN evaluation may increase the NRI (0.512; 95% confidence interval [CI]: 0.083–0.624) and IDI (0.151; 95% CI: 0.010–0.213) for identifying high‐risk patients with recurrent ischemic stroke. In addition, in the subgroup undergoing revascularization, the proportion of IPN (grade 2) was significantly higher in patients with recurrent ischemic stroke than in patients with nonrecurrent ischemic stroke (p = 0.001).InterpretationIn clinical settings, IPN, assessed by CEUS, may provide additional clinical value for predicting recurrent ischemic stroke, helping to identify patients with ischemic stroke who require close follow‐up.

Integrative pan-cancer analysis reveals a common architecture of dysregulated transcriptional networks characterized by loss of enhancer methylation

Aberrant DNA methylation contributes to gene expression deregulation in cancer. However, these alterations’ precise regulatory role and clinical implications are still not fully understood. In this study, we performed expression-methylation Quantitative Trait Loci (emQTL) analysis to identify deregulated cancer-driving transcriptional networks linked to CpG demethylation pan-cancer. By analyzing 33 cancer types from The Cancer Genome Atlas, we identified and confirmed significant correlations between CpG methylation and gene expression (emQTL) in cis and trans, both across and within cancer types. Bipartite network analysis of the emQTL revealed groups of CpGs and genes related to important biological processes involved in carcinogenesis including proliferation, metabolism and hormone-signaling. These bipartite communities were characterized by loss of enhancer methylation in specific transcription factor binding regions (TFBRs) and the CpGs were topologically linked to upregulated genes through chromatin loops. Penalized Cox regression analysis showed a significant prognostic impact of the pan-cancer emQTL in many cancer types. Taken together, our integrative pan-cancer analysis reveals a common architecture where hallmark cancer-driving functions are affected by the loss of enhancer methylation and may be epigenetically regulated.

Associations of Clinical Characteristics With Sudden Cardiac Arrest in People With Type 2 Diabetes With and Without Cardiovascular Disease: A Longitudinal Case-Control Study Using Routine Primary Care Data

OBJECTIVE To assess longitudinal associations with sudden cardiac arrest (SCA) of clinical characteristics recorded in primary care in people with type 2 diabetes (T2D), both with and without cardiovascular disease (CVD). RESEARCH DESIGN AND METHODS We performed a case-control study, with SCA case subjects with T2D from the Amsterdam Resuscitation Studies (ARREST) registry of out-of-hospital resuscitation attempts in the Dutch Noord-Holland region (2010–2020) and up to five matched (age, sex, T2D, general practitioner [GP] practice) non-SCA control subjects. We collected relevant clinical measurements, medication use, and medical history from GPs’ electronic health care records. We analyzed the associations of clinical characteristics and medication use with SCA in the total sample and in subgroups with or without CVD using multivariable time-dependent Cox regression (hazard ratios, 95% confidence intervals). RESULTS We included 689 SCA case subjects and 3,230 non-SCA control subjects. In multivariable models, low fasting glucose (<4.5 mmol/mol: 1.91 [1.00–3.64]), antihypertensive (1.80 [1.39–2.33]), glucose lowering (oral only: 1.32 [1.06–1.63]; insulin only: 2.31 [1.71–3.12]; oral and insulin: 1.64 [1.21–2.22]), heart failure (1.91 [1.55–2.35]), and QTc-prolonging prokinetic (1.78 [1.27–2.50]), antibiotic (1.35 [1.05–1.73]), and antipsychotic (2.10 [1.42–3.09]) medication were associated with SCA in the total sample. In subgroup effect modification analyses, QTc-prolonging antibiotic (1.82 [1.26–2.63]) and antipsychotic (3.10 [2.09–4.59]) medication use were associated with SCA only in those without CVD. CONCLUSIONS In people with T2D, low fasting glucose and QTc-prolonging prokinetic, antibiotic, or antipsychotic medication use and a history of heart failure are associated with SCA risk. Subgroup analyses indicate antibiotic and antipsychotic medication use increases SCA risk specifically in those without CVD.

Performance of the comprehensive nutrition screening index in predicting mortality after cardiac surgery

AbstractMalnutrition is a significant risk factor for postoperative outcomes in patients undergoing cardiac surgery. The Seoul National University Hospital-Nutrition Screening Index (SNUH-NSI) is an automated screening tool designed to comprehensively assess malnutrition risk. However, its predictive value in patients undergoing cardiac surgery remains unvalidated. This study included adult patients who underwent cardiac surgery at a tertiary teaching hospital between May 2008 and December 2019. Patients were classified as low-, intermediate-, or high-risk for malnutrition based on the SNUH-NSI. The association between malnutrition risk and postoperative cumulative all-cause mortality was evaluated using multivariable Cox regression analysis. The predictive ability of the SNUH-NSI was compared with conventional nutritional indices. Compared to the low-risk group, both the high-risk (adjusted hazard ratio [HR], 2.64; 95% confidence interval [CI], 2.19–3.19; P < 0.001) and intermediate-risk groups (adjusted HR, 1.54; 95% CI, 1.31–1.82; P < 0.001) demonstrated a significantly elevated risk of cumulative all-cause mortality. The multivariable model incorporating SNUH-NSI demonstrated moderate but superior predictive performance compared to that of other conventional nutritional indices. Preoperative malnutrition assessed by the SNUH-NSI was found to be a significant predictor of mortality following cardiac surgery. Implementing the SNUH-NSI for automated preoperative malnutrition screening could be an efficient and cost-effective approach.

Predictors of Recurrence After Curative Surgery for Stage I Colon Cancer: Retrospective Cohort Analysis of the Italian Society of Surgical Oncology Colorectal Cancer Network Collaborative Group

Objective: The aim of this study is to provide solid evidence to update the management of stage I colon cancer (CC) after surgery. Background: Given the low risk of recurrence of stage I CC, some international guidelines do not recommend intensive follow-up after surgery. However, data on the actual incidence, risk factors, and site of recurrences are scarce. Methods: This is a retrospective multicenter cohort study considering patients who underwent surgery at 25 Italian centers between 2010 and 2019, with a minimum follow-up of 24 months. A total of 1883 consecutive adult patients with stage I CC treated with curative surgery were considered, and 1611 fulfilled the inclusion criteria. The primary outcome was the rate of recurrence. Secondary outcomes included survival and risk factors for recurrence. Results: Eighty patients developed cancer recurrence (5.0%), of which 90% was systemic relapse. The event was more frequent in pT2 (6.0% vs 3.2%, P = 0.013), male patients (6.1% vs 3.6%, P = 0.021), in the presence of lymphovascular invasion (7.2% vs 3.6%, P = 0.01), and in cases of partial resection (11.1% vs 4.6%, P = 0.011). Also, preoperative carcinoembryonic antigen (P = 0.007) and tumor diameter (P < 0.001) were higher in the group who relapsed. Most patients had isolated cancer recurrence (90%). Recurrences peaked between 10 and 18 months after surgery and declined over time. Adjusted Cox regression analysis identified tumor diameter, carcinoembryonic antigen level, lymphovascular invasion, male gender, and less than 12 analyzed lymph nodes as significant risk factors for worse recurrence-free survival. Conclusions: This study showed that a not negligible rate of stage I CC recur after curative surgery. Most relapses occur at a single site within the first 3 years after surgery. This evidence could be used to optimize postoperative follow-up.

Chronic systemic inflammation predicts long-term mortality among patients with fatty liver disease: Data from the National Health and Nutrition Examination Survey 2007–2018

Background Low-grade systemic inflammation (SI) in patients with fatty liver disease (FLD) is an important hallmark of disease onset and progression. This study aims to evaluate the prognostic significance of novel SI markers in FLD. Methods This was a retrospective cohort study. We included adult patients with FLD with complete data and analyzed the association between chronic SI and long-term mortality in patients with FLD. Systemic immune-inflammation index (SII), pan-immune-inflammation value (PIV), and systemic inflammation response index (SIRI) were evaluated based on peripheral blood counts and FLD was determined by the Fatty Liver Index. Results A total of 5497 patients with FLD were included in the final analysis. SII and PIV (but not SIRI) were found to be associated with all-cause and cardiovascular mortality in univariate analysis. Multivariate Cox regression analysis and KM analysis demonstrated that SII and PIV were associated with all-cause mortality, with SII showing a nonlinear correlation in RCS. PIV (but not SII) was associated with the cardiovascular-related survival probability over time. Stratified analysis indicated that the positive correlation between SII and PIV and all-cause mortality was not altered by subgroups. Conclusions SII and PIV are strongly and consistently associated with all-cause mortality in patients with FLD, with PIV potentially showing a closer association with cardiovascular mortality.

Somatic co‐alteration signatures are prognostic in high‐grade TP53‐mutated myeloid neoplasms

SummaryTo assess the relevance of co‐occurring somatic mutations in TP53‐mutated myeloid neoplasms with ≥10% blasts, we pooled 325 individuals from 10 centres. We focused on comparing three published somatic co‐alteration signatures comprising (1) nine MDS‐related genes (‘ICC‐MDSR’), (2) ICC‐MDSR + additional secondary mutations‐related genes (‘Tazi signature’) and (3) EPI6 (comprising six genes). Outcomes examined were 24‐month overall survival (OS24) and front‐line complete response (CR1). The median age was 69 years with 77% receiving front‐line hypomethylating agents (HMA). All three signatures ICC‐MDSR (p = 0.009), Tazi signature (p = 0.001) and EPI6 (p = 0.025) predicted inferior CR1. In the low‐intensity (HMA) subgroup, only Tazi signature (p = 0.026) predicted inferior CR1. In OS24 analysis of the HMA‐treated subgroup (N = 200), only Tazi signature was adverse (hazard ratio, HR = 1.6 [1.1–2.2]; p = 0.011). However, a forward stepwise multivariable age‐adjusted Cox model including all three signatures picked EPI6 as the sole significant adverse predictor in the entire cohort (p = 0.0001) as well as within the HMA‐treated subgroup (p = 0.0071). These data confirm the value of testing co‐occurring somatic alterations even within a high‐grade TP53‐mutated myeloid neoplasm cohort.

Association between D-dimer-to-albumin ratio and 28-days all-cause mortality in patients with sepsis.

We aimed to investigate the correlation between the serum D-dimer (D-D) to albumin (ALB) ratio (DAR) and 28-day all-cause mortality in patients with sepsis. Data from sepsis patients admitted to the intensive care unit (ICU) of Wuhan Fourth Hospital from October 2021 to January 2024 were collected. Univariate cox analysis was performed for mortality factors in sepsis patients, and multiple cox regression models were used to analyze independent mortality risk factors. The receiver operating characteristics (ROC) curve was used to analyze the value of DAR in predicting sepsis mortality, and the Kaplan-Meier method was used to plot the survival curve. A total of 833 patients with sepsis in the ICU of our hospital were selected and divided into alive group (n = 574) and death group (n = 171) according to their 28-day survival. In the death group, D-D and DAR levels were higher, while ALB levels was lower than in the alive group. Spearman analysis found that DAR level were positively correlated with APACHE II and SOFA scores. Multivariate cox regression analysis showed that DAR was an independent predictor of all-cause mortality within 28 days of admission for sepsis patients (HR = 17.956, 95% CI 3.435-93.851, p < 0.001). The ROC curve results showed that the cut-off value of DAR was 0.068, with a sensitivity of 78.4% and a Youden index of 0.375, predicting mortality in sepsis patients, with an area under curve (AUC) of 0.767 (95% CI 0.744-0.790, P < 0.001). Further analysis divided patients into low DAR (DAR < 0.068) and high DAR (DA ≥ 0.068) groups based on the optimal cut-off value. Kaplan-Meier analysis found higher mortality in the high DAR group. DAR is an independent predictor of all-cause mortality within 28 days of admission in sepsis patients. Combining these two indicators can improve clinical treatment guidance and reduce the risk of death.

A redox-related lncRNA signature in bladder cancer.

The redox status is intricately linked to the development and progression of cancer, a process that can be modulated by long non-coding RNAs (lncRNAs). Previous studies have demonstrated that redox regulation can be considered a potential therapeutic approach for cancer. However, the redox-related lncRNA predictive signature specific to bladder cancer (BCa) has yet to be fully elucidated. The purpose of our study is to establish a redox-related lncRNA signature to improve the prognostic prediction for BCa patients. To achieve this, we downloaded transcriptome and clinical data from the Cancer Genome Atlas (TCGA) database. Prognostic redox-related lncRNAs were identified through univariate Cox regression, least absolute shrinkage and selection operator (LASSO) regression, and multivariate Cox regression analysis, resulting in the establishment of two risk groups. A comprehensive analysis corresponding to clinical features between high-risk and low-risk groups was conducted. Eight redox-related lncRNAs (AC018653.3, AC090229.1, AL357033.4, AL662844.4, AP003352.1, LINC00649, LINC01138, and MAFG-DT) were selected to construct the risk model. The overall survival (OS) in the high-risk group was worse than that in the low-risk group (p < 0.001). The redox-related lncRNA signature exhibits superior predictive accuracy compared to traditional clinicopathological characteristics. Gene Set Enrichment Analysis (GSEA) showed that the MAPK signaling pathway and Wnt signaling pathway were enriched in the high-risk group. Compared with the low-risk group, patients in the high-risk group demonstrated increased sensitivity to cisplatin, docetaxel, and paclitaxel. Furthermore, IGF2BP2, a potential target gene of MAFG-DT, was found to be overexpressed in tumor tissues and correlated with overall survival (OS). Our study demonstrated that the predictive signature based on eight redox-related lncRNAs can independently and accurately predict the prognosis of BCa patients.

Lower creatinine-to-cystatin c ratio associated with increased risk of incident amyotrophic lateral sclerosis in the prospective UK biobank cohort.

Reduced muscle mass has been associated with the progression and prognosis of amyotrophic lateral sclerosis (ALS). However, it remains unclear whether decreased muscle mass is a risk factor for ALS or a consequence of motor neuron degeneration. Recently, serum creatinine-to-cystatin C ratio (CCR) have emerged as promising biomarkers for assessing muscle mass. We aimed to explore the association between CCR and the incidence of ALS using data from the UK Biobank. Between 2006 and 2010, 446,945 participants were included in the baseline. CCR was calculated as the ratio of serum creatinine to cystatin C. Cox regression models were used to analyze the relationship between CCR and ALS incidence. Furthermore, subgroup analyses were conducted to investigate potential covariates in these relationships. After adjusting for all covariates, the multivariate Cox regression analysis revealed a significant association between decreased CCR and an increased risk of ALS (hazard ratio (HR) = 0.990, 95% confidence interval (CI): 0.982-0.999, P = 0.026). Participants were stratified into groups based on CCR tertiles. Compared with participants in the highest tertiles of CCR, those in the lowest (HR = 1.388, 95% CI: 1.032-1.866, P = 0.030) and medium tertiles (HR = 1.348, 95% CI: 1.045-1.739, P = 0.021) had an increased risk of ALS incidence. Subgroup analysis showed that the relationship between CCR and ALS incidence was particularly significant among participants aged < 65years (CCR tertile 1: HR = 1.916, 95% CI: 1.366-2.688, P < 0.001; CCR tertile 2: HR = 1.699, 95% CI: 1.267-2.278, P < 0.001). The present results demonstrate that lower CCR is significantly associated with a higher risk of ALS.

Association of dietary niacin intake with all-cause and cardiovascular mortality: National Health and Nutrition Examination Survey (NHANES) 2003-2018.

The long-term health impacts of niacin are still debated, and the association between dietary niacin and mortality risk in populations hasn't been extensively explored. This study included 26,746 US adults aged 20 years or older from the National Health and Nutrition Examination Survey 2003-2018, with a median follow-up of 9.17 years. During this period, there were 3,551 all-cause deaths, including 1,096 cardiovascular deaths. Cox models were used to compare hazard ratios (HRs) for mortality among participants grouped into different dietary niacin intake quartiles. Participants with the highest dietary niacin intake had a lower risk of all-cause mortality (HR 0.74, 95%CI 0.63-0.86) compared to those in the lowest intake quartile. For cardiovascular mortality, the HR was 0.73 (95%CI 0.57-0.95) in the highest niacin intake quartile. A dose-response relationship was revealed between dietary niacin intake and mortality by restricted cubic spline. Subgroup analysis showed a significant interaction between dietary niacin intake and diabetes concerning all-cause mortality (P = 0.046). In this population-based cohort study, higher dietary niacin intake correlates with lower risk of all-cause and cardiovascular mortality among US adults. The influence of niacin intake on all-cause mortality appears to be more significant in non-diabetic individuals compared to those with diabetes.

A delphi-based model for prognosis of femoral head collapse in osteonecrosis: a multi-factorial approach.

Osteonecrosis of the femoral head (ONFH) is a progressive and debilitating condition characterized by the death of bone tissue due to inadequate blood supply. Despite advances in diagnostic imaging and treatment strategies, predicting the risk of femoral head collapse remains a significant clinical challenge. This study seeks to address this gap by developing a robust prognostic model that integrates clinical, imaging, and laboratory data to improve early diagnosis and guide therapeutic decision-making. We conducted a qualitative systematic review and employed the Delphi method to select key prognostic factors from clinical data, imaging findings, and laboratory indicators. The study included ONFH patients treated from January 2014 to December 2021. We used univariate and multivariate Cox regression analyses to develop a nomogram for predicting the risk of femoral head collapse. The model's performance was evaluated using the concordance index (C-index), calibration plots, and decision curve analysis (DCA). The study included 297 patients (454 hips) with ONFH. Key prognostic factors identified included pain presence (p < 0.001, RR = 0.185, 95% CI: 0.11-0.31), JIC classification (C1: p < 0.001, RR = 0.096, 95% CI: 0.054-0.171; C2: p < 0.001, RR = 0.323, 95% CI: 0.215-0.487), necrotic area (3 < MNAI < 6: p < 0.001, RR = 0.107, 95% CI: 0.061-0.190; MNAI ≥ 6: p < 0.001, RR = 0.466, 95% CI: 0.314-0.692), weight-bearing reduction (p < 0.001, RR = 0.466, 95% CI: 0.323-0.672), preservation of the anterolateral pillar (p < 0.001, RR = 0.223, 95% CI: 0.223-0.473), and subchondral bone fracture on CT (p < 0.001, RR = 0.32, 95% CI: 0.217-0.472). The nomogram demonstrated a high C-index of 0.88, indicating excellent predictive accuracy. Calibration plots showed good agreement between predicted and observed outcomes, and DCA confirmed the model's clinical utility. The prognostic model developed in this study provides a reliable tool for predicting femoral head collapse in ONFH patients. It allows for early identification of high-risk patients, guiding personalized treatment strategies to improve patient outcomes and reduce the need for invasive surgical procedures.

HLA-G high-expressor 3'UTR markers are linked to gastric cancer development and survival.

Gastric cancer ranks fifth in both world prevalence and lethality, with a 5-year survival of less than 30%. HLA-G, a non-classical class I HLA gene, has emerged as a potential marker for cancer susceptibility and prognosis due to its immunomodulatory properties. Its level of expression is regulated by polymorphisms in the 3' untranslated region (3'UTR) polymorphisms, which form various combined haplotypes (UTR-1 to -9). In this study, we examined HLA-G 3'UTR polymorphisms in paired tissue samples from 111 patients with gastric adenocarcinoma and 119 healthy controls. Polymorphism analysis was performed using PCR and Sanger sequencing, followed by statistical analysis using SNPStats software. Survival analysis was conducted using Kaplan-Meier curves and multivariate Cox regression models. High-expressor HLA-G 3'UTR haplotypes (UTR-1 and UTR-6) were significantly associated with gastric cancer susceptibility, indicating a potential role in tumor immune evasion. Additionally, the 14 base pair insertion/deletion polymorphism (14bp I/D) emerged as a prognostic marker, with D/D genotype carriers showing lower survival rates compared to I/D and I/I genotype carriers. Our study highlights the clinical relevance of HLA-G polymorphisms in gastric cancer, suggesting their potential as prognostic markers and therapeutic targets. Further elucidation of HLA-G-related pathways could lead to personalized treatment strategies and improved patient outcomes in gastric cancer.

Influence of preoperative glaucoma medication on long-term outcomes of trabeculectomy.

This retrospective study evaluated the association between preoperative topical glaucoma medication containing preservatives and long-term trabeculectomy outcomes in 309 eyes from 201 patients with primary open-angle glaucoma, followed for over 10 years. The Glaucoma Medication Intensity Index (GMII) was calculated to quantify the cumulative preoperative exposure to these medications. Kaplan-Meier analysis revealed cumulative success rates of 89.3%, 59.2%, and 46% at 1, 10, and 20 years postoperatively. At 20 years, the success group had a significantly lower GMII (3.28 vs. 8.74, p = 0.004). A GMII threshold of ≥ 4.35 was associated with poorer long-term intraocular pressure (IOP) control and shorter surgical success duration. Cox regression analysis identified advanced age at surgery, higher GMII, and subsequent cataract surgery as significant risk factors for trabeculectomy failure. These findings underscore the adverse impact of prolonged preoperative use of glaucoma medications on long-term surgical outcomes, highlighting GMII as a valuable predictor for guiding preoperative management strategies.

Development and validation of a predictive risk tool for VTE in women with breast cancer under chemotherapy: a cohort study in China.

The incidence of venous thromboembolism (VTE) is significantly elevated in breast cancer patients, with a three-to-fourfold increase, and further escalates to sixfold in those undergoing chemotherapy. This study aims to identify the risk factors for VTE and develop a Nomogram risk prediction model distinct from the traditional Khorana score. Univariate Cox regression analysis assessed the impact of each variable on the occurrence of VTE, while stepwise multivariate Cox regression analysis identified independent predictors. Based on these results, we constructed a Nomogram model. The model's performance was validated using the C-index, receiver-operating characteristic curve (ROC), calibration curves, and decision curve analysis (DCA). Comparisons were made with the Khorana score to evaluate the practical application value. Out of the 903 patients, 108 (11.96%) developed VTE. Cox regression analysis identified that Stage, undergoing surgery, age, white blood cells (WBC), D-dimer, and carcinoembryonic antigen (CEA) were significant risk factors for VTE (P < 0.05). The Nomogram model's C-index was 0.77 (95% CI 0.72-0.83) in the training set and 0.76 (95% CI 0.69-0.84) in the validation set. The model demonstrated excellent predictive accuracy and generalizability on the receiver-operating characteristic (ROC) curves and calibration curves. Compared to the traditional Khorana score, the Nomogram model showed superior predictive accuracy and greater clinical benefit. This study established a VTE risk prediction model for breast cancer patients undergoing chemotherapy. The model is characterized by its intuitive and straightforward application, making it highly suitable for rapid VTE risk assessment in clinical practice.

Trends in Peripheral Artery Disease, Lower Extremity Revascularization, and Lower Extremity Amputation in Incident Type 2 Diabetes: A Danish Population-Based Cohort Study.

To examine trends in peripheral artery disease (PAD), lower-extremity (LE) revascularization, and LE amputation in patients with incident type 2 diabetes. This cohort study included patients in Denmark diagnosed with type 2 diabetes in 1996-2015 and followed until 2020. Patients were age and sex matched with as many as three general population individuals. Outcomes comprised 5-year cumulative incidences of first-time PAD, LE revascularization, and LE amputation. Age- and sex-adjusted hazard ratios (aHRs) were computed using Cox regression. The cohort comprised 349,454 patients with incident type 2 diabetes (53% male; median age 62 years) and 1,025,054 general population individuals. Among patients with diabetes, decreases in 5-year cumulative incidence of PAD (from 6.2 to 3.4%; aHR 0.55 [95% CI 0.52-0.57]), LE revascularization (from 0.8 to 0.6%; aHR 0.80 [95% CI 0.71-0.90]), and LE amputation (from 1.0 to 0.4%; aHR 0.45 [95% CI 0.40-0.51]) occurred from 1996-2000 to 2011-2015. LE amputation decreased at all amputation levels (hip/thigh, knee/lower leg, and ankle/foot/toe) during the study period. In the general population, 5-year cumulative incidence remained stable (1.2-1.5% for PAD, ∼0.4% for LE revascularization, and ∼0.2% for LE amputation). However, the relative rates of all outcomes were two- to threefold higher in patients with diabetes than matched individuals in 2011-2015. In recent decades, the cumulative incidence of LE complications substantially decreased in patients with incident type 2 diabetes while remaining stable in the general population.