Univariate Cox Regression Research Articles

Association of inflammatory markers based on routine blood with prognosis in patients underwent percutaneous coronary intervention.

Inflammation contributes to the pathophysiological processes of coronary artery disease. We evaluated the association between inflammatory biomarkers, neutrophil-to-lymphocyte ratio (NLR), red cell distribution width (RDW), systemic inflammatory index, platelet-lymphocyte ratio, and 1-year all-cause mortality in patients underwent percutaneous coronary intervention (PCI). In this retrospective cohort, we consecutively enrolled 4651 patients who underwent PCI. Baseline demographic details, clinical data, and laboratory parameters on admission were analyzed. The primary outcome was 1-year all-cause mortality after PCI. We performed Cox regression and restricted cubic spline analysis to assessed the association between the inflammatory biomarkers and the clinical outcome. The area under the curve from receiver operating characteristic analysis was determined for the ability to classify mortality outcomes. A total of 4651 patients were included. Of these, 198 (4.26%) died on follow-up. Univariate Cox regression showed that NLR (heart rate [HR]: 1.070, 95% confidence interval [CI]: 1.060-1.082, P < .001), RDW (HR: 1.441, 95% CI 1.368-1.518, P < .001), systemic inflammatory index (HR: 1.000, 95% CI 1.000-3.180, P < .001), platelet-lymphocyte ratio (HR: 3.812, 95% CI 1.901-3.364, P < .001) were significant predictors of 1-year all-cause mortality. After adjusting for other confounders in multivariate analysis, NLR (HR: 01.038, 95% CI 1.022-1.054, P < .001) and RDW (HR: 1.437, 95% CI 1.346-1.535, P < .001) remained significant predictors. Restricted cubic spline analysis showed the relationship between RDW, NLR, and 1-year all-cause mortality was linear after adjusting for the covariables (P for non-linearity < 0.001). The multivariable adjusted model led to improvement in the area under the curve to 0.83 (P < .05). Nomogram was created to predict the probability of 1 year mortality. Among the laboratory indices, RDW and NLR showed the best performance for mortality risk prediction. Multivariate predictive models significantly improved risk stratification.

Serum albumin is associated with the inherent property of acute myeloid leukemia and correlates with patient outcomes.

An accurate prognostic model for acute myeloid leukemia (AML) can guide personalized treatment. In our prospective cohort of 591 patients newly diagnosed with AML, we evaluated the prognostic significance of serum albumin levels. We recognized baseline serum albumin as a prognostic factor by univariate Cox regression analysis (albumin-high vs albumin-low: overall survival [OS]: hazard ratio [HR]: 0.679, 95% confidence interval [CI]: 0.529-0.870, P = .002; cumulative incidence of relapse [CIR]: HR: 0.705, 95% CI: 0.530-0.938, P = .017) and multivariate Cox regression analysis (OS: HR per g/L: 0.966, 95% CI: 0.940-0.993, P = .014; CIR: HR per g/L: 0.959, 95% CI: 0.927-0.993, P = .017). In the subgroup analysis, serum albumin was prognostic significant in patients who received intermediate-dose cytarabine combined with daunorubicin and omacetaxine mepesuccinate induction (albumin-high vs albumin-low: OS: HR: 0.585, 95% CI: 0.397-0.863, P = .007; CIR: HR: 0.551, 95% CI: 0.353-0.861, P = .009) rather than those receiving conventional-dose induction regimens. In addition, the impact of baseline serum albumin level was evident in patients with intermediate European LeukemiaNet risk (albumin-high vs albumin-low: OS: HR: 0.617, 95% CI: 0.424-0.896, P = .011; CIR: HR: 0.617, 95% CI: 0.388-0.979, P = .040). Gene set enrichment analysis revealed that leukemia stem cell signatures were enriched in patients with low serum albumin levels. Our study suggested that baseline serum albumin level was associated with the inherent properties of AML and correlated with patient outcomes.

The predictive value of γ-glutamyl transferase to serum albumin ratio in hepatocellular carcinoma patients after liver transplantation.

Elevated preoperative γ-glutamyl transferase (GGT) levels or reduced serum albumin levels have been established as negative prognostic factors for patients with hepatocellular carcinoma (HCC) and various other tumors. Nonetheless, the prognostic significance of the GGT to serum albumin ratio (GAR) in liver transplantation (LT) therapy for HCC is still not well-defined. A retrospective analysis was conducted on the clinical data of 141 HCC patients who underwent LT at Shulan (Hangzhou) Hospital from June 2017 to November 2020. Using the receiver operating characteristic (ROC) curve, the optimal GAR cutoff value to predict outcomes following LT was assessed. Univariate and multivariate Cox proportional hazards regression analyses were used to identify independent risk factors associated with both overall survival (OS) and recurrence-free survival (RFS). A GAR value of 2.04 was identified as the optimal cutoff for predicting both OS and RFS, with a sensitivity of 63.2% and a specificity of 74.8%. Among these patients, 80 (56.7%) and 90 (63.8%) met the Milan and the University of California San Francisco (UCSF) criteria, respectively. Univariate Cox regression analysis showed that microvascular invasion (MVI), maximum tumor size (>5 cm), total tumor size (>8 cm), liver cirrhosis, TNM stage (III), and GAR (≥2.04) were significantly associated with both postoperative OS and RFS in patients with HCC (all p < 0.05). Multivariate Cox regression analysis indicated that GAR (≥2.04) was independently linked with RFS and OS. Pre-transplant GAR ≥2.04 is an independent correlate of prognosis and survival outcomes after LT for HCC and can be used as a prognostic indicator for both mortality and tumor recurrence following LT.

Cancer-associated fibroblast-derived gene signature discriminates distinct prognoses by integrated single-cell and bulk RNA-seq analyses in breast cancer.

Cancer-associated fibroblasts (CAFs) are one of the most predominant cellular subpopulations in the tumor stroma and play an integral role in cancer occurrence and progression. However, the prognostic role of CAFs in breast cancer remains poorly understood. We identified a number of CAF-related biomarkers in breast cancer by combining single-cell and bulk RNA-seq analyses. Based on univariate Cox regression as well as Least Absolute Shrinkage and Selection Operator (LASSO) regression analysis, a novel CAF-associated prognostic model was developed. Breast cancer patients were grouped according to the median risk score and further analyzed for outcome, clinical characteristic, pathway activity, genomic feature, immune landscape, and drug sensitivity. A total of 341 CAF-related biomarkers were identified from single-cell and bulk RNA-seq analyses. We eventually screened eight candidate prognostic genes, including CERCAM, EMP1, SDC1, PRKG1, XG, TNN, WLS, and PDLIM4, and constructed the novel CAF-related prognostic model. Grouped by the median risk score, high-risk patients showed a significantly worse prognosis and exhibited distinct pathway activities such as uncontrolled cell cycle progression, angiogenesis, and activation of glycolysis. In addition, the combined risk score and tumor mutation burden significantly improved the ability to predict patient prognosis. Importantly, patients in the high-risk group had a higher infiltration of M2 macrophages and a lower infiltration of CD8+ T cells and activated NK cells. Finally, we calculated the IC50 for a range of anticancer drugs and personalized the treatment regimen for each patient. Integrating single-cell and bulk RNA-seq analyses, we identified a list of compositive CAF-associated biomarkers and developed a novel CAF-related prognostic model for breast cancer. This robust CAF-derived gene signature acts as an excellent predictor of patient outcomes and treatment responses in breast cancer.

RRP8, associated with immune infiltration, is a prospective therapeutic target in hepatocellular carcinoma

BackgroundRibosomal RNA Processing 8 (RRP8) is a nucleolar Rossman fold-like methyltransferase that exhibits increased expression in many malignant tumours. However, the role of RRP8 in hepatocellular carcinoma (HCC) is still uncertain. We explored the relationships between RRP8 and prognosis and immune infiltration, as well as the putative pathological function and mechanism of RRP8 in HCC.MethodsAnalysis of RRP8 expression across cancers was performed by using multiple databases. Associations between RRP8 expression and clinicopathological factors were further examined. Gene enrichment analysis was used to identify various putative biological activities and regulatory networks of RRP8 in HCC. The relationship between RRP8 expression and immune infiltration was confirmed by single-sample gene set enrichment analysis (ssGSEA). Univariate and multivariate Cox regression analyses were conducted to assess the impact of clinical variables on patient outcomes. Furthermore, a nomogram was constructed to estimate survival probability based on multivariate Cox regression analysis. Functional validation of RRP8 in HCC was performed with two different systems: doxycycline-inducible shRNA knockdown and CRISPR-Cas9 knockout.ResultsRRP8 was markedly overexpressed in HCC clinical specimens compared to adjacent normal tissues. Further analysis demonstrated that RRP8 was directly connected to multiple clinical characteristics and strongly associated with various immune markers in HCC. Moreover, elevated RRP8 expression indicated an unfavourable prognosis. Our functional studies revealed that both knockdown and knockout of RRP8 dramatically attenuated liver cancer cells to proliferate and migrate. Knockout of RRP8 decreased the phosphorylation of MEK1/2 and β-catenin-(Y654) signalling pathway components; downregulated downstream signalling effectors, including Cyclin D1 and N-cadherin; and upregulated E-cadherin.ConclusionsRRP8 is strongly implicated in immune infiltration and could be a potential therapeutic target in HCC.

Epiretinal Membrane Formation Following Rhegmatogenous Retinal Detachment Repair: A Retrospective Cohort Study.

This study aimed to investigate the incidence of and risk factors for epiretinal membrane (ERM) formation following primary rhegmatogenous retinal detachment (RRD) repair. This comparative, retrospective, single center cohort study included eyes with primary RRD treated between 2011 and 2023 at Massachusetts Eye and Ear, Boston, Massachusetts, with pars plana vitrectomy (PPV), scleral buckle (SB), PPV+SB, or pneumatic retinopexy (PnR). Demographic, clinical, and surgical parameters were collected from medical records. The primary outcome was the risk of ERM formation, while the secondary outcome was the risk of ERM requiring surgery. Univariable and multivariable Cox regression was performed, and a hazard ratio (HR) and 95% confidence interval (95%CI) were reported. Overall, 394 eyes were included. The mean age was 58.49±12.8 years and most patients were male. There was a significantly lower risk of ERM formation following SB compared to PPV in the univariable analysis (HR=0.22, 95%CI=0.08-0.60, p=0.003); however, there was no significant association between treatment modality and ERM formation on multivariable Cox regression controlling for confounding factors (p=0.24). ERM formation was found more commonly in patients who were older (HR=1.03 per 1 year increase in age, 95%CI=1.01-1.04, p=0.001), those with worse baseline visual acuity (HR=1.36, 95%CI=1.09-1.71, p=0.008), and those with macula-off RRDs (HR=2.16, 95%CI=1.41-3.32, p<0.001). Surgical modality does not have a significant impact on the risk of ERM following retinal detachment repair. However, age, baseline visual acuity, and macular status are important predictors of ERM formation after RRD repair.

Hemorrhoids are associated with an increased risk of depression in Germany: A retrospective cohort study in primary care outpatients

BackgroundThe aim of the present study was to analyze the cumulative incidence of depression diagnosis in patients with hemorrhoids and to evaluate the association between hemorrhoids and subsequent depression diagnosis. MethodsThis retrospective cohort study was based on electronic medical records from the Disease Analyzer database (IQVIA) and included 87,264 individuals with hemorrhoids (mean age: 54.2 years; 42% women) and 87,264 propensity score-matched individuals without hemorrhoids in 1284 general practices in Germany between January 2005 and December 2021. Univariable Cox regression analysis was conducted to assess the association between hemorrhoids and depression. ResultsAfter up to 10 years of follow-up, 21.4% of patients with hemorrhoids versus 16.3% of the matched cohort (p < 0.001) were diagnosed with depression. There was a significant association between hemorrhoids and a subsequent diagnosis of depression (HR: 1.32; 95% CI: 1.28–1.37), which was confirmed in age- and sex-stratified analyses. The association was stronger with increasing degree of hemorrhoids, from HR: 1.29 (95% CI: 1.15–1.45) for Grade 1 to HR: 1.73 (95% CI: 1.11–2.69) for Grade 4 compared to no hemorrhoids. ConclusionsThe present study provides compelling evidence of an association between hemorrhoids and subsequent depression. Addressing the mental health of individuals with hemorrhoids may not only improve their overall well-being but could also lead to better treatment outcomes for the primary condition.

Use of the combination of spirometry, arterial blood gas analysis and overnight oximetry to predict the outcomes of patients affected by motor neuron disease: The Milan-Torin respiratory score (Mi-To-RS).

The use of multiple tests, including spirometry, arterial blood gas (ABG) analysis and overnight oximetry (OvOx), is highly recommended to monitor the respiratory function of patients with motor neuron disease (MND). In this study, we propose a composite score to simplify the respiratory management of MND patients and better stratify their prognosis. We screened the clinical charts of 471 non-ventilated MND patients referred to the Neuro-rehabilitation Unit of the San Raffaele Scientific Institute of Milan (January 2001-December 2019), collecting spirometric, ABG and OvOx parameters. To evaluate the prognostic role of each measurement, univariate Cox regression for death/tracheostomy was performed, and the variables associated with survival were selected to design a scoring system. Univariate and multivariate Cox regression analyses were then carried out to evaluate the prognostic role of the score. Finally, results were replicated in an independent cohort from the Turin ALS Center. The study population included 450 patients. Six measurements were found to be significantly associated with survival and were selected to design a scoring system (maximum score = 8 points). Kaplan-Meier analysis showed significant stratification of survival and time to non-invasive mechanical ventilation adaptation according to score values, and multivariate analysis confirmed the independent effect of the respiratory score on survival of each cohort. Forced vital capacity, ABG and OvOx parameters provide complementary information for the respiratory management and prognosis of MND patients and the combination of these parameters into a single score might help neurologists predict prognosis and guide decisions on the timing of the implementation of different diagnostic or therapeutic approaches.

Outcomes of Y90 Radioembolization for Hepatocellular Carcinoma in Patients Previously Treated with Transarterial Embolization.

The aim of this study was to evaluate outcomes of transarterial radioembolization (TARE) for hepatocellular carcinoma (HCC) in patients previously treated with transarterial embolization (TAE). In this retrospective study, all HCC patients who received TARE from 1/2012 to 12/2022 for treatment of residual or recurrent disease after TAE were identified. Overall survival (OS) was estimated using the Kaplan-Meier method. Univariate Cox regression was performed to determine significant predictors of OS after TARE. Twenty-one patients (median age 73.4 years, 18 male, 3 female) were included. Median dose to the perfused liver volume was 121 Gy (112-444, range), and 18/21 (85.7%) patients received 112-140 Gy. Median OS from time of HCC diagnosis was 32.9 months (19.4-61.4, 95% CI). Median OS after first TAE was 29.3 months (15.3-58.9, 95% CI). Median OS after first TARE was 10.6 months (6.8-27.0, 95% CI). ECOG performance status of 0 (p = 0.038), index tumor diameter < 4 cm (p = 0.022), and hepatic tumor burden < 25% (p = 0.018) were significant predictors of longer OS after TARE. TARE may provide a survival benefit for appropriately selected patients with HCC who have been previously treated with TAE.

Factors Affecting Survival Outcomes in Neuroendocrine Tumor of the Appendix over the Past Two Decades.

Appendiceal neuroendocrine tumors (NETs) rank as the third most frequent neoplasm affecting the appendix, originating from enterochromaffin cells. This study aims to evaluate the influence of various prognostic factors on the mortality rates of patients diagnosed with NETs of the appendix. Conducted retrospectively, the study involved 3346 patients, utilizing data sourced from the Surveillance, Epidemiology, and End Results (SEER) database. Our analysis centered on investigating demographic characteristics, clinical features, overall mortality (OM), and cancer-specific mortality (CSM) among the cohort. Variables showing a p-value < 0.1 in the univariate Cox regression were incorporated into the multivariate Cox regression analysis. A Hazard Ratio (HR) > 1 indicated an unfavorable prognosis. In the multivariate analysis, higher OM and CSM were observed in males, older age groups, tumors with distant metastasis, poorly differentiated tumors, and those who underwent chemotherapy. Non-Hispanic Black individuals showed elevated mortality rates. Delayed diagnosis may contribute to the increased mortality in this community. Improved access to healthcare and treatment is crucial for addressing these disparities. Larger prospective studies are needed to pinpoint the underlying causes of elevated mortality in non-Hispanic Black populations, and randomized controlled trials (RCTs) are warranted to evaluate therapies for advanced-stage appendix NETs.

Construction and validation of an innovative prognostic nomogram for overall survival in cervical cancer patients with lung metastasis: an analysis utilizing the SEER database.

To facilitate patient consultation and assist in clinical decision-making, we developed a predictive model to analyze the overall survival (OS) rate of cervical cancer patients with concurrent lung metastasis for 6 months, 1 year, or 2 years. We extracted data on patients diagnosed with cervical cancer and concurrent lung metastasis between 2010 and 2020 from the Surveillance, Epidemiology, and End Results (SEER) database. Through a random assignment process, these patients were allocated to either a training cohort or a validation cohort, maintaining a 7:3 ratio. Utilizing both univariate and multivariate Cox regression analyses, we determined the independent prognostic factors influencing OS. To enhance predictive accuracy, we developed a nomogram model incorporating these identified independent prognostic variables. Model effectiveness was subsequently assessed using various metrics, including receiver operating characteristic (ROC) curves, calibration plots, and decision curve analysis (DCA). We gathered data on 1330 patients diagnosed with cervical cancer with lung metastases. An OS nomogram was developed, accounting for factors such as histological type, presence of metastases in other organs (brain, liver), surgical interventions, radiation therapy, and chemotherapy. The ROC curves, calibration plots, and DCA curves demonstrated the commendable predictive performance of the nomogram in assessing the prognosis of cervical cancer patients with lung metastases in both the training and validation cohorts. By utilizing clinical data from the SEER database, we have effectively devised a nomogram capable of predicting the 6-month, 1-year, and 2-year survival rates of cervical cancer patients with lung metastases. The nomogram boasts high accuracy, offering precise prognostic predictions. Its implementation can guide the formulation of individualized follow-up and treatment plans for enhanced patient care.

Nomogram for predicting survival in T1–T2 stage patients with supraglottic squamous cell carcinoma

BackgroundSupraglottic squamous cell carcinoma (SGSCC) is characterized by low differentiation, rapid growth, and inconspicuous initial manifestations. Early detection and prompt treatment can significantly improve survival rates. The main focus of treatment is to maintain optimal laryngeal function.MethodsUsing the Surveillance, Epidemiology, and End Results (SEER) database, we conducted univariate and multivariate Cox regression analyses to identify independent prognostic factors for T1–T2 SGSCC. We also enrolled 109 patients with T1–T2 SGSCC from the First Affiliated Hospital of Xinjiang Medical University as an external validation set. In addition, we developed a nomogram to predict the prognosis of T1–T2 SGSCC, assessed the predictive accuracy and discriminatory ability of the nomogram using the area under the curve (AUC), C-index, receiver operating characteristic (ROC) curve and calibration curve, and confirmed the clinical validity of the nomogram using decision curve analysis (DCA).ResultsOur investigation identified nine prognostic indicators for T1–T2 SGSCC: age (≥ 65 years), marital status, American Joint Committee on Cancer (AJCC) stage (II–IV), grade (III–IV), M stage (M1), radiotherapy, chemotherapy, sex (female), and surgery. These variables were used to create accurate nomograms that predict overall and specific survival rates at 1, 3, and 5 years. The nomograms demonstrated superior prognostic value and accuracy compared to AJCC staging. Laryngectomy with partial laryngectomy is the preferred treatment option for T1–T2 SGSCC cases, providing superior overall survival (OS) and cancer-specific survival (CSS). Radiotherapy also improves OS and CSS. Our results were based on a comprehensive analysis of various indicators, including the C-index, ROC curve, calibration curve, and DCA curve.ConclusionNomograms provide significant advantages in treatment decision making and diagnosis. Laryngectomy with partial laryngectomy is the most appropriate method for T1–T2 SGSCC cases. However, radiotherapy can also be used. Thus, patients with T1–T2 SGSCC should be evaluated to determine if combination therapy is the optimal treatment approach. Nevertheless, further research is needed to understand the role of chemotherapy. Overall, this study identified nine key predictors of future outcomes, aiding healthcare professionals in assessing risks and making treatment decisions for T1–T2 SGSCC patients.

Revealing prognostic insights of programmed cell death (PCD)-associated genes in advanced non-small cell lung cancer.

The management of patients with advanced non-small cell lung cancer (NSCLC) presents significant challenges due to cancer cells' intricate and heterogeneous nature. Programmed cell death (PCD) pathways are crucial in diverse biological processes. Nevertheless, the prognostic significance of cell death in NSCLC remains incompletely understood. Our study aims to investigate the prognostic importance of PCD genes and their ability to precisely stratify and evaluate the survival outcomes of patients with advanced NSCLC. We employed Weighted Gene Co-expression Network Analysis (WGCNA), Least Absolute Shrinkage and Selection Operator (LASSO), univariate and multivariate Cox regression analyses for prognostic gene screening. Ultimately, we identified seven PCD-related genes to establish the PCD-related risk score for the advanced NSCLC model (PRAN), effectively stratifying overall survival (OS) in patients with advanced NSCLC. Multivariate Cox regression analysis revealed that the PRAN was the independent prognostic factor than clinical baseline factors. It was positively related to specific metabolic pathways, including hexosamine biosynthesis pathways, which play crucial roles in reprogramming cancer cell metabolism. Furthermore, drug prediction for different PRAN risk groups identified several sensitive drugs explicitly targeting the cell death pathway. Molecular docking analysis suggested the potential therapeutic efficacy of navitoclax in NSCLC, as it demonstrated strong binding with the amino acid residues of C-C motif chemokine ligand 14 (CCL14), carboxypeptidase A3 (CPA3), and C-X3-C motif chemokine receptor 1 (CX3CR1) proteins. The PRAN provides a robust personalized treatment and survival assessment tool in advanced NSCLC patients. Furthermore, identifying sensitive drugs for distinct PRAN risk groups holds promise for advancing targeted therapies in NSCLC.

Exploring genes within the glutathione peroxidase family as potential predictors of prognosis in papillary renal cell carcinoma

Abstract Objectives This research aims to explore the relationship between glutathione peroxidase (GPX) expression variations in papillary renal cell carcinoma (pRCC) and patient survival, while also developing and evaluating a customized survival prediction model based on GPX. Methods The transcriptomic dataset, including clinical parameters and GPX expression levels, is sourced from The Cancer Genome Atlas (TCGA) database, comprising 290 individuals diagnosed with pRCC. We utilized a univariate Cox regression model to select differentially expressed genes. Subsequently, we calculated risk scores through the least absolute shrinkage and selection operator (LASSO) regression. Based on the median risk score, patients were categorized into high and low-risk groups, establishing a prognostic risk model. Following this, the relationship between the risk model and the survival of pRCC patients was revealed through Kaplan–Meier survival curve analysis. The sensitivity and specificity of the predictive model were evaluated using receiver operating characteristic (ROC) curve analysis. Furthermore, chemotherapy drug sensitivity analysis was conducted on patients in the high and low-risk groups. Results A risk-scoring model was built by selecting GPX7 and GPX8. Compared to the low-risk group, individuals in the high-risk category showed significantly reduced overall survival rates (p=0.018). Additionally, validation results demonstrated the model’s good predictive accuracy. Conclusions The risk-scoring model constructed based on GPX family genes provides an innovative biomarker for forecasting the prognosis of pRCC and serves as a reference for individualized therapy in pRCC.

Intertumoral Heterogeneity Based on MRI Radiomic Features Estimates Recurrence in Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) heterogeneity impacts prognosis, and imaging is a potential indicator. To characterize HCC image subtypes in MRI and correlate subtypes with recurrence. Retrospective. A total of 440 patients (training cohort = 213, internal test cohort = 140, external test cohort = 87) from three centers. 1.5-T/3.0-T, fast/turbo spin-echo T2-weighted, spin-echo echo-planar diffusion-weighted, contrast-enhanced three-dimensional gradient-recalled-echo T1-weighted with extracellular agents (Gd-DTPA, Gd-DTPA-BMA, and Gd-BOPTA). Three-dimensional volume-of-interest of HCC was contoured on portal venous phase, then coregistered with precontrast and late arterial phases. Subtypes were identified using non-negative matrix factorization by analyzing radiomics features from volume-of-interests, and correlated with recurrence. Clinical (demographic and laboratory data), pathological, and radiologic features were compared across subtypes. Among clinical, radiologic features and subtypes, variables with variance inflation factor above 10 were excluded. Variables (P < 0.10) in univariate Cox regression were included in stepwise multivariate analysis. Three recurrence estimation models were built: clinical-radiologic model, subtype model, hybrid model integrating clinical-radiologic characteristics, and subtypes. Mann-Whitney U test, Kruskal-Wallis H test, chi-square test, Fisher's exact test, Kaplan-Meier curves, log-rank test, concordance index (C-index). Significance level: P < 0.05. Two subtypes were identified across three cohorts (subtype 1:subtype 2 of 86:127, 60:80, and 36:51, respectively). Subtype 1 showed higher microvascular invasion (MVI)-positive rates (53%-57% vs. 26%-31%), and worse recurrence-free survival. Hazard ratio (HR) for the subtype is 6.10 in subtype model. Clinical-radiologic model included alpha-fetoprotein (HR: 3.01), macrovascular invasion (HR: 2.32), nonsmooth tumor margin (HR: 1.81), rim enhancement (HR: 3.13), and intratumoral artery (HR: 2.21). Hybrid model included alpha-fetoprotein (HR: 2.70), nonsmooth tumor margin (HR: 1.51), rim enhancement (HR: 3.25), and subtypes (HR: 5.34). Subtype model was comparable to clinical-radiologic model (C-index: 0.71-0.73 vs. 0.71-0.73), but hybrid model outperformed both (C-index: 0.77-0.79). MRI radiomics-based clustering identified two HCC subtypes with distinct MVI status and recurrence-free survival. Hybrid model showed superior capability to estimate recurrence. 3 TECHNICAL EFFICACY STAGE: 2.

Access to early diagnosis for attention-deficit/hyperactivity disorder among children and adolescents in Mexico City at specialized mental health services

BackgroundIn Mexico, this pioneering research was undertaken to assess the accessibility of timely diagnosis of Dyads [Children and adolescents with Attention Deficit Hyperactivity Disorder (ADHD) and their primary caregivers] at specialized mental health services. The study was conducted in two phases. The first phase involved designing an “Access Pathway” aimed to identify barriers and facilitators for ADHD diagnosis; several barriers, with only the teacher being identified as a facilitator. In the second phase, the study aimed to determine the time taken for dyads, to obtain a timely diagnosis at each stage of the Access Pathway. As well as identify any disparities based on gender and socioeconomic factors that might affect the age at which children can access a timely diagnosis.MethodIn a retrospective cohort study, 177 dyads participated. To collect data, the Acceda Survey was used, based on the robust Conceptual Model Levesque, 2013. The survey consisted of 48 questions that were both dichotomous and polytomous allowing the creation of an Access Pathway that included five stages: the age of perception, the age of search, the age of first contact with a mental health professional, the age of arrival at the host hospital, and the age of diagnosis. The data was meticulously analyzed using a comprehensive descriptive approach and a nonparametric multivariate approach by sex, followed by post-hoc Mann-Whitney’s U tests. Demographic factors were evaluated using univariable and multivariable Cox regression analyses.Results71% of dyads experienced a late, significantly late, or highly late diagnosis of ADHD. Girls were detected one year later than boys. Both boys and girls took a year to seek specialized mental health care and an additional year to receive a formal specialized diagnosis. Children with more siblings had longer delays in diagnosis, while caregivers with formal employment were found to help obtain timely diagnoses.ConclusionsOur findings suggest starting the Access Pathway where signs and symptoms of ADHD are detected, particularly at school, to prevent children from suffering consequences. Mental health school-based service models have been successfully tested in other latitudes, making them a viable option to shorten the time to obtain a timely diagnosis.

Chemoradiotherapy versus surgery after neoadjuvant chemoimmunotherapy in patients with stage III NSCLC: a real-world multicenter retrospective study

PurposeThe optimal treatment after neoadjuvant chemoimmunotherapy for patients with stage III non-small cell lung cancer (NSCLC) is unclear. This study aimed at comparing the efficacy and safety of chemoradiotherapy and surgery after neoadjuvant chemoimmunotherapy in stage III NSCLC.Materials and methodsWe conducted a real-world multicenter retrospective study on patients with stage III NSCLC who received surgery or chemoradiotherapy after neoadjuvant chemoimmunotherapy between October 2018 and December 2022. Progression-free survival (PFS) and overall survival (OS) were assessed from the initiation of neoadjuvant treatment and estimated by the Kaplan‒Meier method. Univariate and multivariate Cox regression models were used to examine potential prognostic factors. One-to-one propensity score matching (PSM) was used to further minimize confounding.ResultsA total of 239 eligible patients were enrolled, with 104 (43.5%) receiving surgery and 135 (56.5%) receiving CRT. After 1:1 PSM, 1- and 2-year PFS rates in patients receiving radical surgery (rSurgery group) vs. patients receiving definitive cCRT (dCCRT group) were 80.0% vs. 79.2% and 67.2% vs. 53.1%, respectively (P = 0.774). One- and 2-year OS rates were 97.5% vs. 97.4% and 87.3% vs. 89.9%, respectively (P = 0.558). Patients in the dCCRT group had a numerically lower incidence of distant metastases compared to those in the rSurgery group (42.9% vs. 70.6%, P = 0.119). The incidence of treatment-related adverse events was similar in both groups, except that the incidence of grade 3/4 hematological toxicity was significantly higher in the dCCRT group (30.0% vs. 10.0%, P = 0.025).ConclusionFollowing neoadjuvant chemoimmunotherapy, definitive concurrent chemoradiotherapy may achieve noninferior outcomes to radical surgery in stage III NSCLC.

Comprehensive pan-cancer analysis of inflammatory age-clock-related genes as prognostic and immunity markers based on multi-omics data

Inflammatory age (iAge) is a vital concept for understanding the intricate interplay between chronic inflammation and aging in the context of cancer. However, the importance of iAge-clock-related genes (iAge-CRGs) across cancers remains unexplored. This study aimed to explore the mechanisms and applications of these genes across diverse cancer types. We analyzed profiling data from over 10,000 individuals, covering 33 cancer types, 750 small molecule drugs, and 24 immune cell types. We focused on DCBLD2’s function at the single-cell level and computed an iAge-CRG score using GSVA. This score was correlated with cancer pathways, immune infiltration, and survival. A signature was then derived using univariate Cox and LASSO regression, followed by ROC curve analysis, nomogram construction, decision curve analysis, and immunocytochemistry. Our comprehensive analysis revealed epigenetic, genomic, and immunogenomic alterations in iAge-CRGs, especially DCBLD2, leading to abnormal expression. Aberrant DCBLD2 expression strongly correlated with cancer-associated fibroblast infiltration and prognosis in multiple cancers. Based on GSVA results, we developed a risk model using five iAge-CRGs, which proved to be an independent prognostic index for uveal melanoma (UVM) patients. We also systematically evaluated the correlation between the iAge-related signature risk score and immune cell infiltration. iAge-CRGs, particularly DCBLD2, emerge as potential targets for enhancing immunotherapy outcomes. The strong correlation between abnormal DCBLD2 expression, cancer-associated fibroblast infiltration, and patient survival across various cancers underscores their significance. Our five-gene risk signature offers an independent prognostic tool for UVM patients, highlighting the crucial role of these genes in suppressing the immune response in UVM.Kindly check and confirm whether the corresponding affiliation is correctly identified.I identified the affiliation is correctly.thank you.Per style, a structured abstract is not allowed so we have changed the structured abstract to an unstructured abstract. Please check and confirm.I confirm the abstract is correctly ,thank you.

Construction of exosome-related genes risk model in kidney cell carcinoma predicts prognosis and immune therapy response.

Renal cell carcinoma (RCC) is one of the most prevalent types of urological cancer. Exosomes are vesicles derived from cells and have been found to promote the development of RCC, but the potential biomarker and molecular mechanism of exosomes on RCC remain ambiguous. Here, we first screened differentially expressed exosome-related genes (ERGs) by analyzing The Cancer Genome Atlas (TCGA) database and exoRBase 2.0 database. We then determined prognosis-related ERGs (PRERGs) by univariate Cox regression analysis. Gene Dependency Score (gDS), target development level, and pathway correlation analysis were utilized to examine the importance of PRERGs. Machine learning and lasso-cox regression were utilized to screen and construct a 5-gene risk model. The risk model showed high predictive accuracy for the prognosis of patients and proved to be an independent prognostic factor in three RCC datasets, including TCGA-KIRC, E-MTAB-1980, and TCGA-KIRP datasets. Patients with high-risk scores showed worse outcomes in different clinical subgroups, revealing that the risk score is robust. In addition, we found that immune-related pathways are highly enriched in the high-risk group. Activities of immune cells were distinct in high-/low-risk groups. In independent immune therapeutic cohorts, high-risk patients show worse immune therapy responses. In summary, we identified several exosome-derived genes that might play essential roles in RCC and constructed a 5-gene risk signature to predict the prognosis of RCC and immune therapy response.

Development and Validation of a Prognostic Nomogram for Breast Cancer Patients With Multi-Organ Metastases: An Analysis of the Surveillance, Epidemiology, and End Results Program Database.

Multi-organ metastases represent a substantial life-threatening risk for breast cancer (BC) patients. Nonetheless, the current dearth of assessment tools for patients with multi-organ metastatic BC adversely impacts their evaluation. We conducted a retrospective analysis of BC patients with multi-organ metastases using data from the SEER database from 2010 to 2019. The patients were randomly allocated into a training cohort and a validation cohort in a 7:3 ratio. Univariate COX regression analysis, the LASSO, and multivariate Cox regression analyses were performed to identify independent prognostic factors in the training set. Based on these factors, a nomogram was constructed to estimate overall survival (OS) probability for BC patients with multi-organ metastases. The performance of the nomogram was evaluated using C-indexes, ROC curves, calibration curves, decision curve analysis (DCA) curves, and the risk classification system for validation. A total of 3626 BC patients with multi-organ metastases were included in the study, with 2538 patients in the training cohort and 1088 patients in the validation cohort. Age, grade, metastasis location, surgery, chemotherapy, and subtype were identified as significant independent prognostic factors for OS in BC patients with multi-organ metastases. A nomogram for predicting 1-year, 3-year, and 5-year OS was constructed. The evaluation metrics, including C-indexes, ROC curves, calibration curves, and DCA curves, demonstrated the excellent predictive performance of the nomogram. Additionally, the risk grouping system effectively stratified BC patients with multi-organ metastases into distinct prognostic categories. The developed nomogram showed high accuracy in predicting the survival probability of BC patients with multi-organ metastases, providing valuable information for patient counseling and treatment decision making.