Prognostic Value Research Articles

Prognostic Value of Complete Resection of the High-Frequency Oscillation Area in Intracranial EEG: A Systematic Review and Meta-Analysis.

High-frequency oscillations (HFOs; ripples 80-250 Hz; fast ripples [FRs] 250-500 Hz) recorded with intracranial electrodes generated excitement and debate about their potential to localize epileptogenic foci. We performed a systematic review and meta-analysis on the prognostic value of complete resection of the HFOs-area (crHFOs-area) for epilepsy surgical outcome in intracranial EEG (iEEG) accessing multiple subgroups. We searched PubMed, Embase, and Web of Science for original research from inception to October 27, 2022. We defined favorable surgical outcome (FSO) as Engel class I, International League Against Epilepsy class 1, or seizure-free status. The prognostic value of crHFOs-area for FSO was assessed by (1) the pooled FSO proportion after crHFOs-area; (2) FSO for crHFOs-area vs without crHFOs-area; and (3) the predictive performance. We defined high combined prognostic value as FSO proportion >80% + FSO crHFOs-area >without crHFOs-area + area under the curve (AUC) >0.75 and examined this for the clinical subgroups (study design, age, diagnostic type, HFOs-identification method, HFOs-rate thresholding, and iEEG state). Temporal lobe epilepsy (TLE) was compared with extra-TLE through dichotomous variable analysis. Individual patient analysis was performed for sex, affected hemisphere, MRI findings, surgery location, and pathology. Of 1,387 studies screened, 31 studies (703 patients) met our eligibility criteria. Twenty-seven studies (602 patients) analyzed FRs and 20 studies (424 patients) ripples. Pooled FSO proportion after crHFOs-area was 81% (95% CI 76%-86%) for FRs and 82% (73%-89%) for ripples. Patients with crHFOs-area achieved more often FSO than those without crHFOs-area (FRs odds ratio [OR] 6.38, 4.03-10.09, p < 0.001; ripples 4.04, 2.32-7.04, p < 0.001). The pooled AUCs were 0.81 (0.77-0.84) for FRs and 0.76 (0.72-0.79) for ripples. Combined prognostic value was high in 10 subgroups: retrospective, children, long-term iEEG, threshold (FRs and ripples) and automated detection and interictal (FRs). FSO after complete resection of FRs-area (crFRs-area) was achieved less often in people with TLE than extra-TLE (OR 0.37, 0.15-0.89, p = 0.006). Individual patient analyses showed that crFRs-area was seen more in patients with FSO with than without MRI lesions (p = 0.02 after multiple correction). Complete resection of the brain area with HFOs is associated with good postsurgical outcome. Its prognostic value holds, especially for FRs, for various subgroups. The use of HFOs for extra-TLE patients requires further evidence.

Prognostic value and drug sensitivity of F‑box and leucine‑rich repeat protein 6 in glioma

Prognostic value and drug sensitivity of F‑box and leucine‑rich repeat protein 6 in glioma

The clinical significance of PD-1 expression in patients with bladder cancer without lymph node metastasis: a comparative study with drained lymph nodes and tumor tissues

ABSTRACT Objective In light of the increasing importance of immunotherapy in bladder cancer treatment, this study is aim to investigate the expression and clinical significance of programmed cell surface death-1 (PD-1) in bladder cancer patients without lymph node metastasis, and to compare and analyze the difference of PD-1 in draining lymph nodes and tumor tissues. Methods The expression of PD-1 on T cells and the proportion of positive PD-1 + T cells of IFN-γ and CD105a were detected by flow cytometry, and the correlation between PD-1 expression and clinical parameters was analyzed. Results The percentage of PD-1 positive cells in drainage lymph nodes was higher than that in tumor tissues (P < 0.001). PD-1 positive cells accounted for the highest proportion in CD3 + T cells. The proportion of IFN-γ-positive PD-1 + T cells in draining lymph nodes was significantly higher than that in tumor tissues (P < 0.001), while there was no significant difference in CD105a positive PD-1 + T cells between tumor tissues and draining lymph nodes. Pathological grade, tumor size and stage were positively correlated with PD-1 expression level in the lymph nodes. Conclusion The high expression of PD-1 in patients with bladder cancer without lymph node metastasis, especially in draining lymph nodes, suggests that PD-1 may play a key role in the regulation of tumor immune microenvironment. The correlation between PD-1 and clinical parameters indicates its potential prognostic value. These findings provide important clinical implications for PD-1 targeted therapy, but further prospective studies are needed to determine the application value of PD-1 in therapeutic strategies.

Risk factors and prognosis for supraclavicular lymph node metastasis in patients with thoracic esophageal cancer. Distant or regional metastasis?

We aimed to determine the frequency and prognosis of supraclavicular (#104) lymph node (LN) metastasis compared with other LN stations in patients with advanced thoracic esophageal cancer and to identify risk factors for metastasis to delineate the indications for three-field lymphadenectomy (3FL). The study cohort of 567 eligible patients with esophageal cancer had undergone subtotal esophagectomy from 2003 to 2020. LN metastasis was defined as pathologically proven metastasis or positron emission tomography-positive LNs. The efficacy index (EI), calculated from the frequency of LN metastases and survival rates, was used as prognostic value of each LN station dissection for patient survival. Risk factors for #104 LN metastasis were determined by multivariable logistic regression. The frequency of #104 LN metastasis was 11.6% overall, 31.7% in upper and 8.3% in middle/lower third lesion. Neoadjuvant chemotherapy was administered to 71% of patients and chemo-radiation to 11%. The 5-year overall survival was 45.8%. The EI for #104 LNs (5.3) was similar to that for #101 LNs. Risk factors were age < 65years, upper third lesion, clinical N2-3, #101/106rec LN metastasis and poorly differentiated carcinoma. The 5-year overall survival of patients with middle/lower lesions was 38% (EI 3.1), similar to that for #101 and #8/9/11 LNs. The prognosis of patients with #104 LN metastases is similar to that of patients with metastases in other regional LN stations. Therefore, we recommend 3FL exclusively for patients at a high risk of #104 LN metastasis due to the overall metastatic rate not being high.

Prognostic value of skeletal muscle measured by CT at the T4 level in advanced EGFR-positive non-small cell lung cancer patients treated with ecotinib

Objective: To investigate the prognostic value of skeletal muscle measured by CT at the level of the fourth thoracic vertebra (T4) in advanced epidermal growth factor receptor (EGFR)-positive non-small cell lung cancer (NSCLC) patients treated with ecotinib. Methods: The study retrospectively reviewed clinical and pathological characteristics of 176 patients with advanced EGFR-positive NSCLC who received ecotinib and underwent chest CT scans at Wuhan Union Hospital between January 2017 and October 2020. Among them, 70 were male and 106 were female, with ages ranging from 27 to 80 (58.6±10.6) years. As of August 21, 2021, the median follow-up duration was 19.2 months (95%CI: 15.3 to 23.7 months). The optimal cut-off value of skeletal muscle density (T4-SMD) on CT images at the T4 level were determined using X-tile software. Kaplan-Meier analysis and log-rank test were used to plot progression-free survival curves. Cox proportional hazards regression models were employed to analyze factors influencing 1-year progression-free survival (PFS), and a nomogram prognostic model was constructed accordingly. Receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA) were utilized to evaluate the predictive value of the nomogram. Results: The T4-SMD [M (Q1,Q3)] of 176 patients was 42.56 (37.05, 45.93) HU. Patients were divided into low T4-SMD group (n=122) and high T4-SMD group (n=54) based on the cut-off value (The values for males and females were 49.44 and 41.41 HU, respectively) of T4-SMD. The median PFS time and 1-year PFS rate in the low T4-SMD group were significantly lower than those in the high T4-SMD group [10.4 (95%CI: 9.3-11.8) vs 13.7 (95%CI: 11.1-18.5) months, 36.1% vs 59.3%, respectively, P=0.034]. Eastern Cooperative Oncology Group performance status (HR=3.308, 95%CI: 1.183-9.247, P=0.023), lactate dehydrogenase level (HR=1.852, 95%CI: 1.037-3.307, P=0.037), systemic immune-inflammation index (HR=1.772, 95%CI: 1.019-3.080, P=0.043), and T4-SMD (HR=0.563, 95%CI: 0.325-0.974, P=0.040) were prognostic factors for 1-year PFS in advanced EGFR-positive NSCLC patients treated with ecotinib. A nomogram for predicting 1-year PFS of advanced EGFR-positive NSCLC patients treated with ecotinib was constructed based on the four indicators selected by multivariate Cox regression analysis. The area under the ROC curve of the nomogram was 0.775 (95%CI: 0.676-0.874). The calibration curve showed good consistency between the predicted and actual 1-year PFS. DCA demonstrated good clinical prediction effectiveness of the nomogram. Conclusion: Low T4-SMD is a prognostic risk factor for patients with advanced EGFR-positive NSCLC receiving icotinib therapy.

Machine-learning developed an iron, copper, and sulfur-metabolism associated signature predicts lung adenocarcinoma prognosis and therapy response

BackgroundPrevious studies have largely neglected the role of sulfur metabolism in LUAD, and no study has combine iron, copper, and sulfur-metabolism associated genes together to create prognostic signatures.MethodsThis study encompasses 1564 LUAD patients, 1249 NSCLC patients, and over 10,000 patients with various cancer types from diverse cohorts. We employed the R package ConsensusClusterPlus to separate patients into different ICSM (Iron, Copper, and Sulfur-Metabolism) subtypes. Various machine-learning methods were utilized to develop the ICSMI. Enrichment analyses were conducted using ClusterProfiler and GSVA, while IOBR quantified immune cell infiltration. GISTIC2.0 and maftools were utilized for CNV and SNV data analysis. The Oncopredict package predicted drug information based on GDSC1. TIDE algorithm and cohorts GSE91061 and IMvigor210 evaluated patient response to immunotherapy. Single-cell data was processed using the Seurat package, AUCell package calculated cells geneset activity scores, and the Scissor algorithm identified ICSMI-associated cells. In vitro experiments was conducted to explore the role of ICSMRGs in LUAD.ResultsUnsupervised clustering identified two distinct ICSM subtypes of LUAD, each with unique clinical characteristics. The ICSMI, comprising 10 genes, was constructed using integrated machine-learning methods. Its prognostic power was validated in 10 independent datasets, revealing that LUAD patients with higher ICSMI levels had poorer prognoses. Furthermore, ICSMI demonstrated superior predictive abilities compared to 102 previously published signatures. A nomogram incorporating ICSMI and clinical features exhibited high predictive performance. ICSMI positively correlated with patients gene mutations, and integrated analysis of bulk and single-cell transcriptome data revealed its association with TME modulators. Cells representing the high-ICSMI phenotype exhibited more malignant features. LUAD patients with high ICSMI levels exhibited sensitivity to chemotherapy and targeted therapy but displayed resistance to immunotherapy. In a comprehensive analysis across various cancers, ICSMI retained significant prognostic value and emerged as a risk factor for the majority of cancer patients.ConclusionsICSMI provides critical prognostic insights for LUAD patients, offering valuable insights into the tumor microenvironment and predicting treatment responsiveness.

A comprehensive analysis of the oncogenic and prognostic role of TBC1Ds in human hepatocellular carcinoma.

TBC1D family members (TBC1Ds) are a group of proteins that contain the Tre2-Bub2-Cdc16 (TBC) domain. Recent studies have shown that TBC1Ds are involved in tumor growth, but no analysis has been done of expression patterns and prognostic values of TBC1Ds in hepatocellular carcinoma (HCC). The expression levels of TBC1Ds were evaluated in HCC using the TIMER, UALCN and Protein Atlas databases. The correlation between the mRNA levels of TBC1Ds and the prognosis of patients with HCC in the GEPIA database was then analyzed. An enrichment analysis then revealed genes that potentially interact with TBC1Ds. The correlation between levels of TBC1Ds and tumor-infiltrating immune cells (TIICs) in HCC were studied using the TIMER 2.0 database. Finally, a series of in vitro assays verified the role of TBC1Ds in HCC progression. This study revealed the upregulated expression of TBC1Ds in HCC and the strong positive correlation between the mRNA levels of TBC1Ds and poor prognosis of patients with HCC. The functions of TBC1Ds were mainly related to autophagy and the AMPK pathway. There was also a significant correlation between level of TBC1Ds and tumor-infiltrating immune cells (TIICs) in HCC. The promoting role of TBC1Ds in HCC progression was verified in vitro assays. The results of this analysis indicate that TBC1Ds may serve as new biomarkers for early diagnosis and treatment of HCC.

External Validation of the PREdiction of Survival on Extracorporeal Membrane Oxygenation Therapy (PRESET) Score: A Single Center Cohort Experience.

Acute respiratory distress syndrome (ARDS) is a life-threatening condition affecting >10% of intensive care unit (ICU) patients worldwide with a mortality of up to 59% depending on severity. Extracorporeal membrane oxygenation (ECMO) is a potentially life-saving procedure in severe ARDS but is technically and financially challenging. In recent years, various scoring systems have been proposed to select patients most likely to benefit from ECMO, with the PREdiction of Survival on ECMO Therapy (PRESET) score being one of the most used. We collected data from 283 patients with ARDS of various etiology who underwent veno-venous (V-V) ECMO therapy at a German tertiary care ICU from January 2012 to December 2022. Median age in the cohort was 56 years, and 64.31% were males. The in-hospital mortality rate was 50.88% (n = 144). The median (25%; 75% quartile) severity scores were 38 (31; 49) for Simplified Acute Physiology Score (SAPS) II, 12 (10; 13) for Sequential Organ Failure Assessment (SOFA) and 7 (5; 8) for PRESET. Simplified Acute Physiology Score-II displayed the best prognostic value (area under the receiver operating characteristic [AUROC]: 0.665 [confidence interval (CI): 0.574-0.756; p = 0.046]). Prediction performance was weak in all analyzed scores despite good calibration. Simplified Acute Physiology Score-II had the best discrimination after adjustment of our original cohort. The use of scores explored in this study for patient selection for eligibility for V-V ECMO is not recommendable.

Dialysis parameters associated with SARS-CoV-2 infection and prognosis in end-stage kidney disease

Background The Covid-19 pandemic has affected patients with end-stage kidney disease (ESKD). Whether dialysis parameters have a prognostic value in ESKD patients with Covid-19 remains unclear. Materials and Methods We retrospectively evaluated clinical characteristics, blood pressure (BP) and dialysis parameters in ESKD patients undergoing maintenance outpatient hemodialysis, with (Covid-ESKD) and without (No-Covid-ESKD) Covid-19, at four Brazilian hemodialysis facilities. The Covid-ESKD (n = 107; 54% females; 60.8 ± 17.7 years) and No-Covid-ESKD (n = 107; 62% females; 58.4 ± 14.6 years) groups were matched by calendar time. The average BP and dialysis parameters were calculated during the pre-infection, acute infection, and post-infection periods. The main outcomes were Covid-19 hospitalization and all-cause mortality. Results Covid-ESKD patients had greater intradialytic and postdialysis systolic BP and lower predialysis weight, postdialysis weight, ultrafiltration rate, and interdialytic weight gain during acute-illness compared to 1-week-before-illness, while these changes were not observed in No-Covid-ESKD patients. After 286 days of follow-up (range, 276–591), there were 18 Covid-19-related hospitalizations and 28 deaths among Covid-ESKD patients. Multivariable logistic regression analysis showed that increases in predialysis systolic BP from 1-week-before-illness to acute-illness (OR, 95%CI = 1.06, 1.02–1.10; p = .004) and Covid-19 vaccination (OR, 95%CI = 0.16, 0.04–0.69; p = .014) were associated with hospitalization in Covid-ESKD patients. Multivariable Cox-regression analysis showed that Covid-19-related hospitalization (HR, 95%CI = 5.17, 2.07–12.96; p < .001) and age (HR, 95%CI = 1.05, 1.01–1.08; p = .008) were independent predictors of all-cause mortality in Covid-ESKD patients. Conclusion Acute Covid-19 illness is associated with variations in dialysis parameters of volume status in patients with ESKD. Furthermore, increases in predialysis BP during acute Covid-19 illness are associated with an adverse prognosis in Covid-ESKD patients.

Prognostic value of the advanced lung cancer inflammation index in patients with gastric cancer after radical gastrectomy: a propensity-score matching cohort study and meta-analysis

BackgroundInsufficient evidence existed about the prognostic role of the advanced lung cancer inflammation index (ALI) for gastric cancer patients who underwent curative resection. The aim of this study was to identify the predictive ability of ALI for survival after curative gastrectomy.MethodsWe retrospectively analyzed 328 gastric cancer patients who received curative gastrectomy from the database of Chongqing University Cancer Hospital, and investigated the prognostic role of the preoperative ALI compared with clinicopathological variables and other serum biomarkers, such as preoperative neutrophil-to-lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR) and Lymphocyte-monocyte ratio (LMR). To minimize intergroup differences, propensity score matching (PSM) analysis was employed. Additionally, we performed a meta-analysis of four cohort studies published up to October 2023 following the PRISMA guidelines.ResultsIn the overall cohort, patients in the low ALI group had a significantly worse overall survival compared to those in the high ALI group (P < 0.0001). Subgroup analysis identified that ALI maintained its prognostic significance across different subgroups. In addition, ROC analysis showed that ALI had a higher AUC value for 3-year overall survival compared to NLR, PLR, and LMR (0.576 vs. 0.573 vs. 0.557 vs. 0.557). Multivariate analysis indicated that ALI, other than other serum biomarkers, was an independent risk factor for decreased overall survival in GC patients following curative surgery (HR = 1.449; 95%CI: 1.028–2.045; P = 0.034). Consistently, PSM analysis supported all of these findings. The meta-analysis including 4 studies evaluating 2542 patients, confirmed the association between the low ALI and poor survival outcomes.ConclusionThe preoperative ALI was an independent prognostic factor for survival in gastric cancer patients who underwent curative gastrectomy.

Proposed diagnostic and prognostic markers of primary malignant hepatic vascular neoplasms

IntroductionPrimary malignant hepatic vascular tumors with various malignant potentials include epithelioid hemangioendothelioma (EHE) and angiosarcoma (AS), which may overlap pathologically. This study aimed to compare the pathological findings of hepatic EHE with those of AS, in association with patient outcomes.MethodsFifty-nine histologically confirmed patients with 34 EHE and 25 AS were admitted to a tertiary hospital from 2003 to 2020. Their EHE and AS pathological features were compared. Immunohistochemistry for CD31, ERG, CAMTA-1, TFE3, P53, and Ki-67 labeling was performed on paraffin-embedded blocks. Markers, along with histological findings, were analyzed for the purposes of diagnostic and prognostic significance by multivariate analysis.ResultsCAMTA-1 was 91.2% positive in EHE, but negative in AS (p = < 0.001). AS was significantly correlated to an aberrant p53 expression, high Ki-67 labeling, and high mitotic activity, compared to EHE (all, p = < 0.001). EHE can be classified as low grade (LG) and high grade (HG) using the prognostic values of mitotic activity and ki-67 labeling (sensitivity = 1, specificity = 1). Low grade-EHE showed significantly better overall survival than high grade-EHE (p = 0.020).ConclusionsImmunohistochemistry for CAMTA-1, P53, and Ki-67 labeling may help distinguish EHE and AS in histologically ambiguous cases, especially small biopsied tissue. Moreover, the combination of mitotic activity and Ki-67 labeling can be a prognostic factor for EHE with various clinical features.

The Role of Emphysema on Postoperative Prognosis in Early-Stage Nonsmall Cell Lung Cancer.

Emphysema is generally considered a poor prognostic factor for patients with nonsmall cell lung cancer; however, whether the poor prognosis is due to highly malignant tumors or emphysema itself remains unclear. This study was designed to determine the prognostic value of emphysema in patients with early-stage nonsmall cell lung cancer. A total of 721 patients with clinical stage IA nonsmall cell lung cancer who underwent complete resection between April 2007 and December 2018 were retrospectively analyzed regarding clinicopathological findings and prognosis related to emphysema. The emphysematous and normal lung groups comprised 197 and 524 patients, respectively. Compared with the normal lung group, lymphatic invasion (23.9% vs. 14.1%, P = 0.003), vascular invasion (37.6% vs. 17.2%, P < 0.001), and pleural invasion (18.8% vs. 10.9%, P = 0.006) were observed more frequently in the emphysema group. Additionally, the 5-year overall survival rate was lower (77.1% vs. 91.4%, P < 0.001), and the cumulative incidence of other causes of death was higher in the emphysema group (14.0% vs. 3.50%, P < 0.001). Multivariable Cox regression analysis of overall survival revealed that emphysema (vs. normal lung, hazard ratio 2.02, P = 0.0052), age >70 years (vs. <70 years, hazard ratio 4.03, P < 0.001), and SUVmax >1.8 (vs. ≤1.8, hazard ratio 2.20, P = 0.0043) were independent prognostic factors. Early-stage nonsmall cell lung cancer with emphysema has a tendency for the development of highly malignant tumors. Additionally, emphysema itself may have an impact on poor prognosis.

Bioinformatics analysis and validation of mesenchymal stem cells related gene MT1G in osteosarcoma.

Osteosarcoma (OS) is a primary malignant bone tumor arising from mesenchymal cells. The standard clinical treatment for OS involves extensive tumor resection combined with neoadjuvant chemotherapy or radiotherapy. OS's invasiveness, lung metastasis, and drug resistance contribute to a low cure rate and poor prognosis with this treatment. Metallothionein 1G (MT1G), observed in various cancers, may serve as a potential therapeutic target for OS. OS samples in GSE33382 and TARGET datasets were selected as the test cohorts. As the external validation cohort, 13 OS tissues and 13 adjacent cancerous tissues from The Second Affiliated Hospital of Nanchang University were collected. Patients with OS were divided into high and low MT1G mRNA-expression groups; differentially expressed genes (DEGs) were identified as MT1G-related genes. The biological function of MT1G was annotated using Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene Ontology (GO) and gene set enrichment analysis (GSEA). Gene expression correlation analysis and competing endogenous RNA (ceRNA) regulatory network construction were used to determine potential biological regulatory relationships of DEGs. Survival analysis assessed the prognostic value of MT1G. MT1G expression increased in OS samples and presented higher in metastatic OS compared with non-metastatic OS. Functional analyses indicated that MT1G was mainly associated with spliceosome. A ceRNA network with DEGs was constructed. MT1G is an effective biomarker predicting survival and correlated with increased recurrence rates and poorer survival. This research identified MT1G as a potential biomarker for OS prognosis, highlighting its potential as a therapy target.

Prognostic Value of Cardiovascular Biomarkers in the Population

Identification of individuals at high risk for atherosclerotic cardiovascular disease within the population is important to inform primary prevention strategies. To evaluate the prognostic value of routinely available cardiovascular biomarkers when added to established risk factors. Individual-level analysis including data on cardiovascular biomarkers from 28 general population-based cohorts from 12 countries and 4 continents with assessments by participant age. The median follow-up was 11.8 years. Measurement of high-sensitivity cardiac troponin I, high-sensitivity cardiac troponin T, N-terminal pro-B-type natriuretic peptide, B-type natriuretic peptide, or high-sensitivity C-reactive protein. The primary outcome was incident atherosclerotic cardiovascular disease, which included all fatal and nonfatal events. The secondary outcomes were all-cause mortality, heart failure, ischemic stroke, and myocardial infarction. Subdistribution hazard ratios (HRs) for the association of biomarkers and outcomes were calculated after adjustment for established risk factors. The additional predictive value of the biomarkers was assessed using the C statistic and reclassification analyses. The analyses included 164 054 individuals (median age, 53.1 years [IQR, 42.7-62.9 years] and 52.4% were women). There were 17 211 incident atherosclerotic cardiovascular disease events. All biomarkers were significantly associated with incident atherosclerotic cardiovascular disease (subdistribution HR per 1-SD change, 1.13 [95% CI, 1.11-1.16] for high-sensitivity cardiac troponin I; 1.18 [95% CI, 1.12-1.23] for high-sensitivity cardiac troponin T; 1.21 [95% CI, 1.18-1.24] for N-terminal pro-B-type natriuretic peptide; 1.14 [95% CI, 1.08-1.22] for B-type natriuretic peptide; and 1.14 [95% CI, 1.12-1.16] for high-sensitivity C-reactive protein) and all secondary outcomes. The addition of each single biomarker to a model that included established risk factors improved the C statistic. For 10-year incident atherosclerotic cardiovascular disease in younger people (aged <65 years), the combination of high-sensitivity cardiac troponin I, N-terminal pro-B-type natriuretic peptide, and high-sensitivity C-reactive protein resulted in a C statistic improvement from 0.812 (95% CI, 0.8021-0.8208) to 0.8194 (95% CI, 0.8089-0.8277). The combination of these biomarkers also improved reclassification compared with the conventional model. Improvements in risk prediction were most pronounced for the secondary outcomes of heart failure and all-cause mortality. The incremental value of biomarkers was greater in people aged 65 years or older vs younger people. Cardiovascular biomarkers were strongly associated with fatal and nonfatal cardiovascular events and mortality. The addition of biomarkers to established risk factors led to only a small improvement in risk prediction metrics for atherosclerotic cardiovascular disease, but was more favorable for heart failure and mortality.

Review of the Diagnostic and Prognostic Values of Cardiac Markers in Diabetes

Abstract Introduction Cardiovascular disease is a leading cause of mortality in people with diabetes (PWD). We aimed to explore the role of troponin T (TnT) and probrain natriuretic peptide (proBNP) as screening and prognostic indicators of cardiovascular morbidity and mortality in PWD in the existing literature. Methods This review paper is a focused narrative nonsystematic review of the literature which examined relevant publications pertinent to the significance of cardiac biomarkers. We aimed to investigate the diagnostic value of cardiac TnT (cTnT) and cTnI in addition to proBNP in diabetes and the prognostic value of cTnT and proBNP in diabetic and nondiabetic patients. The process of searching through literature was conducted from December 2022 to April 2023. Searches were done across PubMed and Google Scholar databases to identify relevant articles published from January 2001 to April 2023. The selected were entered into EndNote 20 software to extract the title and abstract. Results A total of 75 articles were identified in Google Scholar in addition to 32 articles from PubMed. After a thorough review, only a total of 22 articles were selected, pointing out those which discussed the pathophysiology and diagnostic, prognostic, and screening values of the types of Tn and proBNP markers. The value of TnT in PWD, specifically T2D, is threefold higher than in healthy patients. Individuals with high levels of high-sensitivity (hs) cTnI or cTnT were at the highest mortality risk. Nonetheless, N-terminal (NT)-proBNP and TnT function independently as predictors of unfavorable outcomes. Conclusions TnT is an important early screening tool prognostic indicator. Elevated TnT was associated with an increased risk of cardiovascular events in PWD. hs-cTn may help diabetes-related clinical care for older persons by identifying those at high mortality risk; furthermore, in diabetic individuals, NT-pro-BNP appears to be 92% sensitive and 90% specific for the diagnosis of heart failure.

Effect of chemotherapy on prognosis in patients with primary pancreatic signet ring cell carcinoma: A large real-world study based on machine learning.

Primary pancreatic signet ring cell carcinoma (PSRCC), an extremely rare histologic variant of pancreatic cancer, has a poor prognosis. This study aimed to investigate the prognostic value of chemotherapy in PSRCC. Patients with PSRCC between 2000 and 2019 were identified using the Surveillance Epidemiology and End Results (SEER) database. The main outcomes in this study were cancer-specific survival (CSS) and overall survival (OS). The baseline characteristics of patients were compared using Pearson's Chi-square test. Kaplan-Meier analysis was used to generate the survival curves. Least absolute shrinkage and selection operator (LASSO), univariate and multivariate Cox regression models, and Random Survival Forest model were used to analyze the prognostic variables for OS and CSS. The variance inflation factors (VIFs) were used to analyze whether there was an overfitting problem. A total of 588 patients were identified. Chemotherapy was an independent prognostic factor for OS and CSS, and significantly associated with OS (HR = 0.33, 95% CI = 0.27-0.40, P <0.001) and CSS (HR = 0.32, 95% CI = 0.26-0.39, P <0.001). Chemotherapy showed beneficial effects on OS and CSS in patients with PSRCC and should be recommended in clinical practice.

Clinical value of BRE-AS1 in myocardial infarction and its role in myocardial infarction-induced cardiac muscle cell apoptosis

Objectives. The aim of this study was to investigate the expression of long non-coding RNA (lncRNA) brain and reproductive organ-expressed protein (BRE) antisense RNA 1 (BRE-AS1) in patients with acute myocardial infarction (AMI) and its effect on ischemia/reperfusion (I/R)-induced oxidative stress and apoptosis of cardiomyocytes. Methods. Serum BRE-AS1 levels in patients with AMI was detected using quantitative real-time polymerase chain reaction (qRT-PCR). The diagnostic and prognostic values of BRE-AS1 were evaluated. H9c2 cells were treated with hypoxia/reoxygenation to establish an in vitro myocardial infarction cell model. The levels of inflammatory cytokines such as tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and IL-6 were detected by enzyme-linked immunosorbent assay (ELISA). Levels of lactate dehydrogenase (LDH), malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) were determined by commercial kits. Cell counting kit-8 (CCK-8) and flow cytometry were used to evaluate the cell viability and cell apoptosis. Results. The expression of BRE-AS1 in serum of patients with AMI is upregulated, which shows the clinical diagnostic value for AMI. In the I/R injury cell model, the knockout of BRE-AS1 can significantly alleviate the increase in TNF-α, IL-1β, and IL-6 levels, inhibit the production of LDH and MDA, increase the activities of SOD and GSH-Px, promote the cell viability and suppress cell apoptosis. Conclusions. Abnormally elevated BRE-AS1 has a high diagnostic value for AMI as well as a prognostic value for major adverse cardiovascular events (MACEs). The elevation of BRE-AS1 promoted oxidative stress injury and cell apoptosis in vitro.

The prognostic and predictive significance of perineural invasion in stage I to III colon cancer: a propensity score matching-based analysis

BackgroundColorectal cancer (CRC) presents with varying prognoses, and identifying factors for predicting metastasis and outcomes is crucial. Perineural invasion (PNI) is a debated prognostic factor for CRC, particularly in stage I-III patients, but its role in guiding adjuvant chemotherapy for node-positive colon cancer remains uncertain.MethodsWe conducted a single-center study using data from the Colorectal Section Tumor Registry Database at Chang Gung Memorial Hospital, Taiwan. This prospective study involved 3,327 CRC patients, 1,536 of whom were eligible after application of the exclusion criteria, to investigate the prognostic value of PNI in stage I-III patients and its predictive value for node-positive/negative cancer patients receiving adjuvant chemotherapy. Propensity score matching (PSM) was used to minimize selection bias, and follow-up was performed with standardized procedures.ResultsPNI-positive (PNI+) tumors were associated with higher preoperative CEA levels and more frequent adjuvant chemotherapy. After PSM, PNI + tumors were associated with marginally significantly lower 5-year disease-free survival (DFS) and significantly lower overall survival (OS) rates in stages III CRC. However, no significant differences were observed in stages I and II. Subgroup analysis showed that among PNI + tumors, only poorly differentiated tumors had higher odds of recurrence. PNI did not predict outcomes in node-negative colon cancer. Adjuvant chemotherapy benefited PNI + patients with node-positive but not those with node-negative disease.ConclusionsOur study indicates that PNI is an independent poor prognostic factor in stage III colon cancer but does not predict outcomes in node-negative disease. Given the potential adverse effects of adjuvant chemotherapy, our findings discourage its use in node-negative colon cancer when PNI is present.

Elucidating the impact of parthanatos-related microRNAs on the tumoral immune microenvironment and clinical outcome in low-grade gliomas

Parthanatos, a cell death mechanism triggered by PARP-1 activation, is implicated in oncogenic processes, yet their role in low-grade gliomas (LGG) remains poorly understood. This research investigates Parthanatos-related miRNAs' prognostic and immunomodulatory potential, alongside their influence on therapeutic outcomes in LGGs. Comprehensive miRNA and mRNA profiles of LGG patients were extracted from TCGA and CGGA databases, integrating clinical parameters to identify Parthanatos-associated miRNAs. IHC data validated the expression levels of Parthanatos-related genes in glioma versus normal brain tissues. Protein–protein interaction networks and Spearman correlation analysis facilitated the identification of key miRNAs. Parthanatos-related miRNA indices (PMI) were screened using Lasso and assessed for their accuracy in predicting prognosis, comparing their associated potential molecular functions and heterogeneity of the immune microenvironment. Drug sensitivity was assessed between different groups and optimal therapeutic agents were predicted. Validate the expression levels of key miRNAs by qPCR. Ninety-one miRNAs significantly associated with Parthanatos were screened, through which a PMI prognosis model of nine miRNAs was constructed. The PMI score was able to independently predict the prognosis of patients with LGG, and the nomogram constructed based on the PMI provided a practical tool for clinical prediction of patient prognosis. The proportion of immune response was lower in patients in the high-risk group, and there were significant differences in drug sensitivity between different risk classes, while drugs such as Fasudil were identified as the most promising therapeutic agents for patients in the high-risk group. Our findings highlight the critical role of Parthanatos-associated miRNAs in the progression and treatment of LGG, offering novel insights into their prognostic value and therapeutic potential.

Diagnostic and Prognostic Values of KLF5 and RUNX1 in Acute Kidney Injury in Septic Patients.

Diagnostic and prognostic values of Kruppel-like factor 5 (KLF5) and Runt-related transcription factor 1 (RUNX1) were determined in sepsis-induced acute kidney injury (SI-AKI). The study included 120 septic patients and set two groups: SI-AKI group (n = 60) or non-AKI group (n = 60). Fasting venous blood was drawn, and KLF5 and RUNX1 levels were measured. The receiver operating characteristic curve was plotted for diagnostic evaluation of KLF5 and RUNX1 in SI-AKI. The correlation between KLF5 and RUNX1 and serum creatinine (Scr), cystatin C (Cys-C), and kidney injury molecule 1 (KIM-1) were assessed by Pearson method. Predictive values of KLF5 and RUNX1 in 28-day survival of SI-AKI patients were considered by Kaplan-Meier survival curves and multivariate Cox regression analysis. Serum KLF5 and RUNX1 in SI-AKI patients were upregulated. Serum KLF5 and RUNX1 were of high diagnostic value in distinguishing SI-AKI patients from non-AKI patients. KLF5 and RUNX1 were in a positive correlation with Scr, Cys-C, and KIM-1, respectively. The 28-day survival of SI-AKI patients with high serum KLF5 or RUNX1 expression was poor, and serum KLF5 and RUNX1 expression were independently correlated with SI-AKI patients' survival. KLF5 and RUNX1 have diagnostic and prognostic values in SI-AKI patients.