Multivariate Cox Regression Analysis Research Articles

An anoikis-related signature predicts prognosis and immunotherapy response in gastrointestinal cancers

BackgroundGastrointestinal (GI) cancers have high incidence rates and mortality rates. Anoikis is a special type of cell apoptosis, and anoikis resistance has been reported to be associated with tumor malignancy. We aimed to explore the roles of anoikis-related genes (ARGs) in the GI cancer prognosis.MethodsWe extracted RNA sequencing and clinical data from The Cancer Genome Atlas and Gene Expression Omnibu databases for patients with esophageal cancer, gastric cancer, colon cancer and rectal cancer and identified ARGs from GeneCards and Harmonizome. Anoikis-related patterns were identified via unsupervised clustering analysis. We constructed a prognostic signature (Anoscore) based on prognostic ARGs through univariate, LASSO, and multivariate Cox regression analyses. The model was validated and evaluated using Kaplan–Meier analysis, receiver operating characteristic curves, univariate Cox regression analysis, multivariate Cox regression analysis, column charts, and calibration curves. We also performed a single-cell sequencing analysis of candidate genes via TISCH2. A correlation analysis between the Anoscore, the tumor microenvironment and drug sensitivity was conducted in GI cancers. The expression and function of some candidate genes were validated in vitro.ResultsIn terms of prognostic ARGs, two anoikis-related patterns, ARG clusters A and B, were identified. ARG cluster B had a worse prognosis than did ARG cluster A. Subsequently, the Anoscore was developed as an independent prognostic factor. It demonstrated the robust predictive capability for the prognosis of patients with GI cancers. Notably, patients with high Anoscores exhibited poor outcomes. In addition, we established a nomogram (Ano-nomogram) based on the Anoscore and clinicopathological factors of patients to predict the 3-year and 5-year survival probabilities. Moreover, patients with high Anoscores had higher levels of immune cell infiltration and higher immune checkpoint expression. The drug sensitivity analysis revealed that patients with high or low Anoscores were sensitive to different chemotherapies and targeted drugs. S100A11 and TLR3, representative candidate genes, exhibited different expression patterns and biological functions.ConclusionThis study highlighted the significant potential of the Anoscore in predicting prognosis and guiding the selection of personalized therapeutic regimens for patients with GI cancers.

A new signature associated with anoikis predicts the outcome and immune infiltration in nasopharyngeal carcinoma.

Previous studies have confirmed the phenomenon of anoikis resistance in nasopharyngeal carcinoma (NPC). Nevertheless, the prognostic significance of anoikis-related genes (ARGs) in NPC remains incompletely understood. This study aimed to create a predictive risk score using an ARGs signature for NPC patients and to investigate how this score relates to clinicopathologic features and immune infiltration in the tumor microenvironment. By using data from the Gene Expression Omnibus (GEO) database, we employed machine learning methods to discover prognostic ARGs and create a risk score. Key gene expression levels were validated through real-time PCR and immunohistochemical staining. Three differentially expressed ARGs (CDC25C, E2F1 and RBL2) with prognostic value were identified by the intersection of multiple machine learning algorithms. A risk score based on t 3-ARG feature was developed to stratify NPC patients into two distinct risk groups using the optimal model, Random Survival Forest. NPC patients with high-risk scores experienced notably shorter progression-free survival in comparison to those with low-risk scores. Multivariate Cox regression analysis indicated that the risk score served as an independent prognostic factor. The time-dependent ROC and decision curve analyses demonstrated the risk model's strong predictive accuracy and clinical utility. The low-risk score group exhibited features indicative of early clinical stage, immune activation, high immune checkpoint gene's expression, and low Epstein-Barr virus gene's expression. Functional analysis revealed enrichment of immune-related pathways in the low-risk group. Patients with high-risk scores were discovered to be unlikely to benefit from immune checkpoint inhibitor treatment. Moreover, the expression of RBL2, E2F1, and CDC25C were significantly correlated with the expression of caspase family genes. Finally, the lower mRNA and protein expression of RBL2 were validated in NPC cell lines and tissues. Our ARGs-based signature model shows promising results in predicting the prognosis of NPC patients and might be associated with immune cell infiltration.

Construction and evaluation of a prognostic model for cervical cancer based on dynamic hematological and clinical features

ObjectivesThis study aims to investigate the prognostic significance of dynamic hematological and clinical characteristics and to construct nomograms to predict overall survival (OS) in patients with cervical carcinoma who underwent radical radiotherapy.MethodsThe study analyzed patients with cervical cancer who underwent radical radiotherapy at The University of Hong Kong-Shenzhen Hospital between January 2015 and June 2022 and were staged as IB1 to IVA according to the International Federation of Gynecology and Obstetrics (FIGO) 2018 staging system. We identified predictive factors through univariate and multivariate cox regression analyses. Two multivariate analyses integrating different groups of variables were conducted independently. Concordance index (C-index), receiver operating characteristic (ROC), and Kaplan-Meier curves were used to evaluate the nomograms. Bootstrap validation was performed to determine the accuracy of the nomogram using 1000 resamples. The performances of proposed nomograms and FIGO 2018 staging system were compared to assess the prognostic value of hematological and inflammatory markers.ResultsOne hundred fifty-nine patients were included in this retrospective analysis. The median follow-up time was 41.37 months, and the 3-year OS rate was 82.6%. The first multivariate analysis of pre-treatment clinical factors and all hematological variables showed that FIGO2018 staging, and pre-treatment albumin levels were associated with 3-year OS. The final multivariate analysis incorporating all clinical factors, hematological variables, and inflammatory markers identified the following prognostic factors: FIGO2018 staging, rate of tumor shrinkage before brachytherapy, pre-treatment albumin levels, treatment times, minimum neutrophils during treatment, concurrent chemotherapy cycles, and lymphopenia grade. Calibration plots showed agreement between the OS predicted by the nomograms and actual OS. Kaplan–Meier curves demonstrated that patients in the high-risk group had shorter OS than those in the low-risk group (P ≤ 0.001). The C-index for the two nomograms was superior to that of the current FIGO2018 staging system, with values of 0.709 (95% Confidence Interval [CI], 0.622–0.795) and 0.803 (95% CI, 0.729–0.877), compared to 0.593 (95% CI, 0.508–0.678) for the FIGO system.ConclusionWe developed and validated nomograms to predict OS in cervical cancer patients staged IB1 to IVA who underwent radical radiotherapy RT. The prognostic significance of dynamic changes in blood and inflammatory markers has been confirmed. The proposed nomogram exhibits robust predictive capabilities for estimating OS in these patients, facilitating risk stratification and individualized treatment.

Endothelial cell pY397-FAK expression predicts risk of breast cancer recurrences after radiotherapy in SweBCG91-RT cohort.

Identifying biomarkers of radiotherapy (RT) response is important for optimising the treatment of early breast cancer (BC). Here we tested the interaction between endothelial cell (EC) expression of phospho-Tyr397-FAK (pY397-FAK) and adjuvant-RT on clinical outcomes after breast-conserving surgery (BCS) within a randomised study. Preclinical data suggests an enhanced effect of RT with low EC_ pY397-FAK expression. We analysed tissue microarrays (TMAs) from the SweBCG91-RT (stage I-II, lymph node-negative) BC cohort, consisting of 1,178 patients randomly assigned to receive either BCS alone or BCS plus adjuvant-RT. TMA sections were immunostained for pY397-FAK, CD31, α-smooth-muscle-actin (αSMA) and pan-cytokeratin (panCK). HALO analysis scored mean pY397-FAK intensity in CD31+ ECs, panCK+ tumour epithelial cells (TCs) and αSMA+ mural/stromal cells per core. For 822 patients, multivariable Cox regression analysis was performed for the primary and secondary 5-year endpoints, locoregional recurrence (LRR) and 'all recurrence', respectively, as dependent variables, and RT and EC_pY397-FAK as independent variables. EC_ pY397-FAK expression was not predictive for the primary endpoint, LRR (p=0.098), but the direction of the RT effect was in line with preclinical findings. For the secondary endpoint, all recurrence, there was a significant interaction (p=0.026) between EC_ pY397-FAK and RT. Without RT, higher EC_ pY397-FAK expression resulted in lower risk for all recurrence (HR 0.74 per SD, CI 95% 0.57-0.96, p=0.026). Within the first 5-years post-BCS, patients with low EC_pY397-FAK expression derive greater benefit from RT than patients with high EC_pY397-FAK expression. However, without RT low EC_pY397-FAK expression is associated with a higher risk of recurrence.

Antiviral effectiveness and safety of azvudine in hospitalized SARS‐CoV‐2 patients with pre‐existing chronic respiratory diseases: A multicenter, retrospective cohort study

AbstractAlthough azvudine has become a priority in the treatment of SARS‐CoV‐2, its effectiveness and safety among COVID‐19 patients who already have chronic respiratory diseases (CRDs) have not been sufficiently validated. A retrospective, multicenter cohort study involving 10 hospitals in Henan Province was performed to assess inpatients with COVID‐19 and CRDs (Clinical Trial Registration Number: NCT06349655). Azvudine recipients and the control group were matched at a 1:1 ratio using propensity scores. The clinical outcomes (all‐cause death and composite disease progression) were analyzed using Kaplan‒Meier and Cox regression analyses, with additional subgroup and sensitivity analyses performed. Eighteen clinical features were included to construct a nomogram for predicting the survival of inpatients with COVID‐19 and CRDs. Out of 37,606 hospitalized COVID‐19 patients, 1462 azvudine recipients and 1462 matched controls were included in the analysis. The results of Kaplan‒Meier and multivariate Cox regression analyses demonstrated that in contrast to the controls, azvudine use was associated with a decreased risk of all‐cause death in patients with COVID‐19 and pre‐existing CRDs (log‐rank: p = .012; HR: 0.73; 95% CI: 0.553‒0.956); but was not significantly different in terms of composite disease progression (log‐rank: p = .82; HR: 1.15; 95% CI: 0.948‒1.383). An analysis of subgroups and three sensitivity appraisals validate the above outcomes. The number and type of adverse events associated with azvudine treatment were acceptable. The concordance index (0.8499, 0.8497) and area under the curve (86.1%, 80.4%) of the nomogram showed satisfactory discriminative ability in the training and test sets. Azvudine could be effective in reducing all‐cause death among inpatients with COVID‐19 and CRDs and had few serious adverse events.

Association between the triglyceride–glucose index and the risk of acute kidney injury in critically ill patients with acute pancreatitis: a retrospective study

BackgroundThe triglyceride–glucose (TyG) index is increasingly recognized for its ability to predict cardiovascular and metabolic risks. This study investigated the correlation between the TyG index and the risk of acute kidney injury(AKI) in critical ill patients with acute pancreatitis(AP).MethodsThe Medical Information Mart for Intensive Care IV database was retrospectively searched to identify AP patients hospitalized in the intensive care unit. The primary outcome measure was the incidence of AKI. The secondary endpoint was in-hospital mortality and the rate of renal replacement therapy(RRT) use. Cox regression analysis and restricted cubic spline were used to analyze TyG index association with AKI risk. Kaplan–Meier survival analysis was performed to assess the incidence of endpoints in the different groups.ResultsA total of 848 patients were enrolled. The incidence of AKI was 61.56%.The in-hospital mortality was 11.69%. Kaplan–Meier analysis showed that the TyG index ≥ 8.78 group has a high incidence of AKI and high risk of requiring RRT (P < 0.001). Multivariable Cox regression analysis showed whether TyG index was a continuous variable (HR, 1.65 [95% CI 1.10–2.48], P = 0.015) or a categorical variable (HR, 1.72 [95% CI 1.09–2.79], P = 0.028), and the TyG index was independently associated with the risk of AKI in AP patients. The restricted cubic splines model illustrated the linear relationship between higher TyG index and increased risk of AKI in this specific patient population.ConclusionsHigh TyG index is an independent risk factor for AKI in critical ill patients with AP. Assessing the TyG index may be beneficial for early stratification and interventions to improve prognosis.

Dual-Time-Point Radiomics for Prognosis Prediction in Colorectal Liver Metastasis Treated with Neoadjuvant Therapy Before Radical Resection: A Two-Center Study.

Optimal prognostic stratification for colorectal liver metastases (CRLM) patients undergoing surgery with neoadjuvant therapy (NAT) remains elusive. This study aimed to develop and validate dual-time-point radiomic models for CRLM prognosis prediction using pre- and post-NAT imaging features. Radiomic features were extracted from four MRI sequences in 100 cases of CRLM patients who underwent NAT and radical resection. RAD scores were generated, and clinical/pathologic variables were incorporated into uni- and multivariate Cox regression analyses to construct prognosis models. Time-ROC, time-C index, decision curve analysis (DCA), and calibration curves assessed the predictive performance of Fong score and pre- and post-NAT models for overall survival (OS) and disease-free survival (DFS) in a testing set. The final models included four variables for OS and three variables for DFS. The post-NAT models outperformed the pre-NAT models in time-ROC, time-C index, calibration, and DCA analysis, except for the 1-year DFS area under the curve (AUC). The Fong score models underperformed. The post-NAT OS RAD score effectively stratified patients into prognostic subgroups. The radiomic models incorporating pre- and post-NAT MRI features and clinical/pathologic variables effectively stratified CRLM patients prognositically. The post-NAT models demonstrated superior performance.

The value of inflammation-related indicators in chemotherapy efficacy and disease-free survival of triple-negative breast cancer.

Systemic inflammation is closely correlated with the progression of cancer. Inflammation-related indicators has been recognized as outcome predictors in triple-negative breast cancer (TNBC). Our study aimed to investigate the predictive value of several inflammation-related indicators in TNBC patients underwent chemotherapy (NAC). 100 TNBC patients were enrolled in the study. Levels of interleukin-6 (IL-6) were detected by enzyme-linked immunosorbent assays (ELISAs). Platelet-to-lymphocyte ratio (PLR) and immune inflammatory index (SII) were obtained from blood routine. Levels of Ki-67 expression were detected by immunohistochemistry (IHC). Mentioned indicators were divided into two groups based on their median values. The correlation between these indicators and NAC efficacy was analyzed using t tests. Prognostic risk scores were calculated by univariate Cox regression analysis and Lasso-penalized Cox regression. The patients were divided into low- and high-risk groups based on the median risk score. Survival curves were obtained by Kaplan-Meier method. Models for univariate and multivariate Cox regression analyses were performed to determine the independent risk factors. A nomogram was used for the prediction of 1-, 2-, and 3-year disease-free survival (DFS). Accuracy of the prognostic model was validated by receiver operating characteristic curve (ROC). IL-6, PLR, SII, and Ki-67 levels were associated with neoadjuvant efficacy. IL-6, PLR, SII, Ki-67, and lymphocyte count were associated with DFS. The risk score for each TNBC patient was obtained using LASSO regression analysis to construct a prognostic model. In the prognostic model, patients in the high-risk score group showed worse DFS than those in the low-risk group. Risk score and tumor size were independently correlated with outcomes in multivariate Cox regression analysis. A nomogram was constructed using IL-6, PLR, SII, Ki-67, and Miller-Payne (MP) scores. Calibration curves demonstrated good consistency between the actual and predictive values of the nomogram. A prognostic model was established by combining four prognosis-related indicators in TNBC patients who underwent NAC.

Cytoreductive Surgery with Hyperthermic Intraperitoneal Chemotherapy (CRS-HIPEC) of Extraperitoneal Abdominal Disease, is it Appropriate?

Cytoreductive surgery-hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) candidates often have extraperitoneal abdominal disease. Current expert peritoneal surface malignancy (PSM) guidelines recommend that the presence of extraperitoneal disease is a contraindication to CRS-HIPEC. We conducted a retrospective review of our institutional appendiceal and colorectal CRS-HIPEC registries. Two study cohorts were constructed: (1) cytoreduction with extraperitoneal abdominal disease, and (2) cytoreductions limited to peritoneal structures alone. The primary study outcome was survival. Subgroup analysis was based on the primary tumor and completeness of cytoreduction. Overall, 864 CRS-HIPEC cases were evaluated, consisting of 578 appendiceal primaries and 286 colorectal cancers. The extraperitoneal cohort included 101 patients, with 763 patients in the non-extraperitoneal group. The median follow-up time was 13.18 years. The main analysis showed no significant differences in survival times. Foroverallsurvival (OS) there was amean OS timeof 5.87years and a median OS timeof 4.43 years for extraperitoneal cytoreductions compared with a mean of 5.90years and a median of 4.76 years for non-extraperitoneal cytoreductions (p=0.955). Five-year OS rates did not differ at 49.1% versus 49.5% (odds ratio [OR] 1.036, 95% confidence interval [CI] 0.671-1.597, p=0.874). Disease-free survival (DFS) times showed a mean of 4.40 years and a median of 1.93 years for extraperitoneal cases versus a mean of 5.44years and a median of 3.05 years for non-extraperitoneal cases (p=0.210). Five-year DFS rates also showed no differences (OR 0.894, 95% CI 0.476-1.681, p=0.728). No significant differences in progression-free survival(PFS)Pp times (p=0.061) were reported. Multivariate Cox regression analysis indicated that extraperitoneal CRS was not an independent predictor of OS (hazard ratio [HR] 1.281, 95% CI 0.885-1.854, p=0.190), DFS (HR 1.087, 95% CI 0.694-1.701, p=0.716), or PFS (HR 0.650, 95% CI 0.243-1.738). We conducted the largest analysis evaluating extraperitoneal cytoreductions, with no significant differences in almost all survival outcomes. We propose that the presence of extraperitoneal abdominal disease is not a contraindication to proceeding with CRS-HIPEC.

Patterns of failure and prognosis in nasopharyngeal carcinoma according to Epstein-Barr virus DNA status.

To investigate the patterns of failure and prognosis in recurrent or metastatic nasopharyngeal carcinoma (rmNPC) according to Epstein-Barr virus-DNA (EBV-DNA) status. We included NPC patients who were diagnosed with locoregional recurrence (LRR) and/(or) distant metastasis (DM) between January 2017 and June 2024. Receiver operating characteristic analysis, Chi-square test, Wilcoxon rank sum test, Kaplan-Meier method, and Multivariate Cox regression analyses were used for statistical analysis. This study involved 108 patients, including 105 (97.2%) who had EBV-DNA detectable at the initial diagnosis of NPC. Regarding progression patterns, 34 patients (31.5%) experienced only LRR, while 60 patients (55.6%) had only DM. LRR followed by DM was observed in 5 (4.6%) patients, DM followed by LRR occurred in 2 (1.8%) patients, and both LRR and DM were presented simultaneously in 7 (6.5%) patients. EBV-DNA positivity rates significantly differed between LRR and DM patients, at 76.9% and 97.1% respectively (P = 0.003). A significant difference was also observed in EBV-DNA levels, with a median level of 413 copies/mL for LRR and 6,550 copies/mL for DM (P < 0.001). While the EBV-DNA positivity rate did not differ significantly between oligometastatic disease and polymetastatic disease (P = 0.493), the levels were significantly elevated in the polymetastatic disease group than the oligometastatic disease group (P < 0.001). Multivariate analysis showed that liver metastasis (P = 0.012) and EBV-DNA levels ≥ 3,525 copies/mL at progression (P = 0.009) independently correlated with poorer overall survival. Our study provides substantial evidence linking higher EBV-DNA levels with disease failure patterns and identifies liver metastasis and EBV-DNA levels at disease progression as independent prognostic factors for poorer overall survival in rmNPC patients.

The Reversibility of Cardiac Damage After Transcatheter Aortic Valve Implantation and Short-Term Outcomes in a Real-World Setting.

This study aims to assess the changes in cardiac damage stage in a real-world cohort of patients undergoing transcatheter aortic valve implantation (TAVI) and to investigate the prognostic value of cardiac damage stage evolution. Patients with severe AS undergoing TAVI were retrospectively analyzed. A 5-stage system based on the presence and extent of cardiac damage assessed by echocardiography was applied before and 6 months after TAVI. Multivariable Cox regression analyses were used to examine independent prognostic value of the changes in cardiac damage after TAVI. A total of 734 patients with severe AS (mean age 79.8±7.4 years, 55% male) were included. Before TAVI, 32 (4%) patients did not show any sign of extra-valvular cardiac damage (Stage 0), 85 (12%) had left ventricular damage (Stage 1), 220 (30%) left atrial and/or mitral valve damage (Stage 2), 227 (31%) pulmonary vasculature and/or tricuspid valve damage (Stage 3), and 170 (23%) right ventricular damage (Stage 4). Six months after TAVI, 39% of the patients improved at least 1 stage in cardiac damage. Staging of cardiac damage at 6 months after TAVI (HR per 1-stage increase 1.391; P = 0.035) as well as worsening in the stage of cardiac damage (HR 3.729, P = 0.005) were independently associated with 2-year all-cause mortality. More than one third of patients with severe AS showed an improvement in cardiac damage 6 months after TAVI. Staging cardiac damage at baseline and follow-up may improve risk stratification in patients undergoing TAVI.

Cardiac magnetic resonance left atrioventricular coupling index as a prognostic tool in hypertrophic cardiomyopathy.

A novel marker left atrioventricular coupling index (LACI) has been proved to be associated with cardiovascular events in patients without history of cardiovascular disease. However, the studies on cardiac magnetic resonance-derived LACI in hypertrophic cardiomyopathy (HCM) patients are limited, and the prognostic value of LACI has still not been studied thoroughly, so we aimed to explore the association between LACI and adverse clinical outcomes in HCM patients. A total of 206 HCM patients underwent cardiac magnetic resonance examination were retrospectively enrolled. LACI is defined by the ratio between the left atrial (LA) volume and the left ventricular (LV) volume in LV end-diastolic phase. The composite endpoint was categorized into death-related, heart failure-related, and arrhythmia-related events, reflecting mortality risk, heart failure progression, and arrhythmia burden, respectively. Receiver operating characteristics curve analysis was used to determine the optimal cut-off value for LACI to distinguish HCM patients at high risk of adverse clinical outcome. Multivariable Cox regression models were built including significant clinical variables, LA ejection fraction (LAEF), LA volume index (LAVI), late gadolinium enhancement (LGE) extent and LACI. The improvement of discrimination by adding LACI to a clinical model was assessed using C-statistic, net reclassification improvement (NRI) and integrated discrimination improvement (IDI). Thirty-four HCM patients reached the endpoint during a median follow-up time of 60 [interquartile range (50-68)] months. In the multivariate Cox regression analysis, LACI [hazard ratio 1.054, 95% confidence interval (CI): 1.037, 1.071; P<0.001] was an independent predictor of the composite events after adjustment for age and atrial fibrillation. Then 40.09% was identified as an optimal cut-off for LACI in the risk stratification. Integrating LACI to the clinical model yielded higher C-statistic 0.892 with 95% CI (0.861, 0.922) compared with LA diameter, LAEF, LAVI and LGE extent, providing an improvement in prediction of high-risk patients (NRI=0.627, 95% CI: 0.112-0.934; IDI=0.295, 95% CI: 0.016-0.709). LACI is an independent risk factor for clinical adverse outcome and is superior to conventional LA parameters and LGE extent for the identification of high-risk HCM patients.

Association between blood–urea–nitrogen-to-albumin ratio and in-hospital mortality in patients diagnosed with coronavirus disease 2019: a retrospective cohort study

BackgroundThe blood–urea–nitrogen-to-albumin ratio (BAR) is recognized as a novel prognostic indicator; however, there is a limited number of studies investigating the relationship between BAR and in-hospital mortality associated with coronavirus disease 2019 (COVID-19). Therefore, the present investigation aims to explore the correlation between BAR and in-hospital mortality in patients with COVID-19 in China.MethodsThis retrospective observational study enrolled a cohort of 1027 patients diagnosed with COVID-19 between December 2022 and March 2023. Multivariate Cox regression analyses were used to ascertain the independent association between BAR and in-hospital mortality among patients with COVID-19. Furthermore, stratified analyses were used to investigate potential interaction effects with variables, such as age, sex, COVID-19 Severity, hypertension, coronary artery disease, and diabetes mellitus.ResultsA total of 117 patients (11.4%) died from various causes during hospitalization. Subsequent to adjustment for confounding variables, patients in the highest BAR tertile exhibited an elevated risk for in-hospital mortality relative to those in the lowest tertile (hazard ratio [HR] 2.44 [95% confidence interval CI 1.24–4.79]) when BAR was treated as a categorical variable. When considering BAR as a continuous variable, a 6% increase in the prevalence of in-hospital mortality was observed for each 1-unit increase in BAR (adjusted HR 1.06 [95% CI 1.03–1.08]; P < 0.001). Stratified analyses revealed a consistent association between BAR and in-hospital mortality due to COVID-19.ConclusionsBAR exhibited a significant relationship with in-hospital mortality in patients with COVID-19, suggesting that a higher BAR is associated with a poorer prognosis. However, further research is required to confirm these findings.

Serum uric acid/creatinine ratio and 1-year stroke recurrence in patient with acute ischemic stroke and abnormal renal function: results from the Xi'an stroke registry study of China

BackgroundThe relationship between abnormal renal function and serum uric acid levels in patients with acute ischemic stroke (AIS) remains insufficiently explored. Although uric acid is associated with cardiovascular and cerebrovascular risk, the specific link between normalized serum uric acid (SUA/SCr) and stroke recurrence in patients with impaired renal function has not been well studied. This study aims to fill this gap by investigating the association between SUA/SCr and 1-year stroke recurrence in patients with AIS and abnormal renal function.MethodsThis study utilized the ratio of serum uric acid (SUA) to serum creatinine (SCr) to represent SUA levels normalized for renal function. Abnormal Renal function was defined by the estimated glomerular filtration rate (eGFR) &amp;lt; 90 mL/min/1.73 m2. Multivariable Cox regression, curve fitting, and stratified analyses were employed to assess the relationship between SUA/SCr and 1-year stroke recurrence in patients with AIS and abnormal renal function, considering SUA/SCr as both a continuous variable and in quartiles (Q1–Q4).ResultsOf 1,932 enrolled patients (65.3% male; mean age 66.7 ± 11.3 years), each unit of increase in SUA/SCr was associated with a 17% decrease in 1-year stroke recurrence (HR = 0.83, 95% CI 0.73 to 0.96, P = 0.009). Compared to Q1, the Q2 and Q4 groups showed significantly reduced risk in 1-year stroke recurrence (Q2: HR = 0.46, 95% CI 0.27 to 0.79, P = 0.005; Q4: HR = 0.47, 95% CI 0.27 to 0.81, P = 0.007), with a significant trend across all quartiles (P = 0.01 for trend tests). Curve fitting revealed a negative but non-linear correlation. Subgroup analyses showed that in patients with eGFR &amp;lt; 60 ml/min/1.73 m2, Q4 had significantly lower 1-year stroke recurrence risk than Q1 (HR = 0.19, 95% CI 0.04 to 0.86, P = 0.031).ConclusionLow SUA/SCr independently predicts 1-year stroke recurrence in patients with AIS and abnormal renal function, particularly in those with eGFR &amp;lt; 60 mL/min/1.73 m2.

Elevated POSTN expression predicts poor prognosis and is associated with radioresistance in cervical cancer patients treated with radical radiotherapy

Cervical cancer (CC) is a significant global health issue and remains one of the leading causes of cancer-related mortality in women. Radiotherapy is a crucial treatment modality for CC; however, tumor heterogeneity and resistance to radiotherapy often result in suboptimal outcomes for some patients, including recurrence and metastasis. Periostin (POSTN), a matricellular protein within the tumor microenvironment, has been implicated in the promotion of tumor progression and treatment resistance, particularly through mechanisms such as epithelial-mesenchymal transition (EMT). Despite this, the role of POSTN in radiotherapy resistance in CC patients remains underexplored. Therefore, in this study, we investigated the prognostic significance of POSTN expression in CC patients undergoing radical radiotherapy and explored potential mechanisms underlying radiotherapy resistance. We analyzed data from 92 CC patients in The Cancer Genome Atlas (TCGA) and 153 patients from our institution, assessing POSTN expression levels through mRNA analysis and immunohistochemistry (IHC). Our findings revealed that high POSTN expression was significantly associated with advanced tumor stages, poorer radiotherapy outcomes, and worse overall survival (OS). Additionally, multivariate Cox regression analysis identified POSTN as an independent prognostic factor for CC patients undergoing radical radiotherapy. A prognostic nomogram integrating POSTN expression and clinicopathological features demonstrated superior predictive accuracy for OS. Drug sensitivity analysis suggested that high POSTN expression may be linked to resistance to multiple chemotherapeutic agents. Furthermore, weighted correlation network analysis (WGCNA) and gene set enrichment analysis (GSEA) identified EMT as a top enriched pathway in patients with high POSTN expression, suggesting it may play a critical role in radiotherapy resistance. Subsequently, in vitro experiments confirmed that POSTN knockdown significantly inhibited HeLa cell proliferation, invasion, and enhanced radiosensitivity, while promoting apoptosis. These findings indicate that high POSTN expression is a risk factor for poor prognosis in CC patients undergoing radical radiotherapy, and targeting POSTN may improve radiotherapy efficacy by reducing tumor proliferation and resistance.

Efficacy and safety of aumolertinib in EGFR-mutated non-small cell lung cancer with leptomeningeal metastasis: a single‑center retrospective study.

To evaluate the efficacy and safety of aumolertinib in treating non-small cell lung cancer (NSCLC) patients with leptomeningeal metastasis (LM) and epidermal growth factor receptor (EGFR) mutations. We conducted a retrospective analysis of clinical data from 79 patients with EGFR-mutated advanced NSCLC treated with aumolertinib after being diagnosed with LM at Shandong Cancer Hospital and Institute between April 2020 and July 2023. We evaluated overall survival (OS), progression-free survival (PFS), LM-PFS, and safety. Patient prognosis was assessed using Kaplan-Meier and Cox regression analyses. The median follow-up duration was 19.8 months (95% CI: 16.2-23.4), and 16 (20.3%) patients had previously used third-generation EGFR-TKI. The median LM-PFS was 10.6 months (95% CI: 8.6-12.5). The overall response rate (ORR) for LM was 53.2%, while the disease control rate (DCR) reached 91.1%. Among the 67 (84.8%) patients presenting with symptoms attributable to LM, 60 reported improved or stable symptoms. The median OS was 17.7 months (95% CI: 13.7-21.7), while the median PFS was 9.7 months (95% CI: 7.5-11.9). The systemic ORR and DCR were 38.0% and 87.3%, respectively. Multivariate Cox regression analysis identified L858R mutations (hazard ratio [HR] = 2.22, P = 0.030), prior systemic therapy (HR = 3.89, P < 0.001), ECOG PS ≥ 2 (HR = 4.06, P < 0.001) and ≥ 3 extracranial organ metastases (HR = 2.20, P = 0.025) as independent negative predictors of OS. Creatine kinase elevation (HR = 0.41, P = 0.018) was an independent predictor of better OS. Treatment-related adverse events occurred in 61 patients (77.2%), predominantly as grade 1 or 2. Aumolertinib showed potential in treating EGFR-mutated NSCLC patients with LM, with a tolerable safety profile.

Analysis of prognostic factors and establishment of a recurrence risk prediction model for papillary thyroid carcinoma based on BRAF stratification.

Predicting the likelihood of papillary thyroid carcinoma (PTC) recurrence is crucial for improving patient outcomes. The association between the BRAF V600E (BRAF) mutation and PTC recurrence remains controversial. Our goal was to determine prognostic features of PTC patients and construct models for predicting recurrence risk according to BRAF mutation status. A total of 811 PTC patients whose clinical information and survival data were available were included in this study. Independent prognostic variables of PTC identified by screening via LASSO-Cox regression analysis were then used to construct nomograms. The performance of the predictive models was assessed according to the C-index, ROC curve, validation curve, and decision curve analyses. Kaplan-Meier curves were used to analyze differences between patients grouped according to prognostic factors and relapse risk. Multivariate Cox regression analysis demonstrated that extrathyroidal extension (ETE), vascular tumor thrombus, and lymph node yield (LNY) were correlated with recurrence-free survival (RFS) in the BRAF mutation-negative group, while extranodal extension (ENE), number of metastatic lymph node (NMLN), pathological stage, and vascular tumor thrombus were correlated with RFS in the BRAF mutation-positive group. The mutation-stratified predictive models demonstrated better performance than the model without stratification, as indicated by the greater C-index values (0.880 vs. 0.859 vs. 0.753), AUC values (1-year AUC: 0.946 vs. 0.947 vs. 0.758; 3-year AUC: 0.889 vs. 0.871 vs. 0.760; 5-year AUC: 0.845 vs. 0.793 vs. 0.758), and net clinical benefit. The calibration curves at 1 year, 3 years, and 5 years showed good consistency. The bootstrap internal validation had good AUC values exceeding 0.8 and showed a well-fitting calibration curve. Significant differences in RFS were observed between the low-risk and high-risk groups (P < 0.001). Stratifying patients based on their BRAF mutation status can facilitate the development of better and more targeted postoperative management strategies. Nomograms for BRAF mutation positive and negative patients were developed to precisely and consistently predict recurrence risk in PTC patients.

Efficacy of first-line radiofrequency ablation combined with systemic chemotherapy plus targeted therapy for initially unresectable colorectal liver metastases

Background/Objective The optimal strategy for patients with colorectal liver metastases is still controversially discussed. This study aimed to evaluate the efficacy of radiofrequency ablation (RFA) combined with systemic chemotherapy plus targeted therapy as first-line treatment in patients with initially unresectable colorectal liver metastases (CRLM), to identify prognostic factors and construct nomograms predicting survival. Methods This retrospective study included patients with initially unresectable CRLM treated with (study group n = 74) or without (control group n = 83) RFA at the National Cancer Center from January 2018 to January 2021. Survival curves were assessed using the Kaplan-Meier method and log-rank test. Univariate and multivariate Cox regression analyses were used to determine prognostic factors and include these factors in the nomograms to predict progression-free survival (PFS) and overall survival (OS). Results The study group had significantly better median PFS (17.16 months vs. 8.35 months, p < 0.01) and OS (34.9 months vs. 21.1 months, p < 0.01) than the control group after propensity score matching. Cox regression analyses identified RFA treatment and clinical risk score (CRS) as independent prognostic factors for PFS. The largest diameter of liver metastases, RFA treatment, and CRS were independent prognostic factors for OS. Based on this finding, nomograms with good discrimination and calibration were constructed. Conclusion RFA combined with systemic chemotherapy plus targeted therapy as first-line treatment could significantly prolong PFS and OS in patients with initially unresectable CRLM compared with systemic chemotherapy plus targeted therapy. The nomograms predicting PFS and OS might help clinicians select personalized treatment.

Prediction of postoperative disease-free survival in colorectal cancer patients using CT radiomics nomogram: a multicenter study.

Radiomics analysis is widely used to assess tumor prognosis. To explore the value of computed tomography (CT) radiomics nomogram in predicting disease-free survival (DFS) of patients with colorectal cancer (CRC) after operation. A total of 522 CRC patients from three centers were retrospectively included. Radiomics features were extracted from CT images, and the least absolute shrinkage and selection operator Cox regression algorithm was employed to select radiomics features. Clinical risk factors associated with DFS were selected through univariate and multivariate Cox regression analysis to build the clinical model. A predictive nomogram was developed by amalgamating pertinent clinical risk factors and radiomics features. The predictive performance of the nomogram was evaluated using the C-index, calibration curve, and decision curve. DFS probabilities were estimated using the Kaplan-Meier method. Integrating the retained eight radiomics features and three clinical risk factors (pathological N stage, microsatellite instability, perineural invasion), a nomogram was constructed. The C-index for the nomogram were 0.819 (95% CI=0.794-0.844), 0.782 (95% CI=0.740-0.824), 0.786 (95% CI=0.753-0.819), and 0.803 (95% CI=0.765-0.841) in the training set, internal validation set, external validation set 1, and external validation set 2, respectively. The calibration curves demonstrated a favorable congruence between the predicted and observed values as depicted by the nomogram. The decision curve analysis underscored that the nomogram yielded a heightened clinical net benefit. The constructed radiomics nomogram, amalgamating the radiomics features and clinical risk factors, exhibited commendable performance in the individualized prediction of postoperative DFS in CRC patients.

Prognosis of Fragment Reattachment in Anterior Crown Fractures: A Retrospective Study.

Although several studies have compared fragment attachment with resin build-ups in anterior crown fractures, none have specifically investigated the outcome of reattached fragments. This retrospective study aimed to evaluate long-term outcomes of fragment reattachment in anterior crown fractures and determine the prognostic affecting their success. We retrospectively analyzed clinical records of patients who underwent fragment reattachment for crown fractures in anterior teeth (maxillary and mandibular central and lateral incisors) between 2008 and 2023. All procedures were performed by experienced professors and residents following a standardized protocol. Kaplan-Meier survival curves and Cox proportional hazards regression analyses were performed to evaluate fragment retention outcomes and identify potential prognostic factors. Among 75 anterior crown fractures, the estimated fragment retention rates were 83.7% at 2 years, 75.2% at 5 years, and 56.4% at 10 years. Multivariate Cox regression analyses identified patient age and extent of crown fracture as significant factors affecting outcomes. The 5-year estimated fragment retention rates were 82.8% and 67.0% for uncomplicated and complicated crown fractures, respectively. Fragment reattachment remains a viable treatment option for anterior crown fractures. Treatment success decreased with patient age, and complicated crown fractures demonstrated lower retention rates than uncomplicated ones. Fragment reattachment can provide predictable outcomes in anterior crown fractures when cases are carefully selected, particularly considering the patient's age and the type of crown fracture.