Stepwise Multivariate Cox Regression Analysis Research Articles

A nomogram based on a three pyroptosis gene model and clinical parameters for predicting prognosis of hepatocellular carcinoma

Globally, hepatocellular carcinoma (HCC) has a dismal prognosis and studies have shown that accurate prognostic risk assessment can have clinically significant benefits for patients with HCC patients. After successively performing univariate Cox regression, Lasso regression, and stepwise multivariate Cox regression analysis, three pyroptosis gene (GPX4, NLRP1, and NLRP6) were selected to construct and validate the prognostic model of HCC based on public data. The expression pattern and prognostic implication of GPX4 in HCC was validated by immunohistochemistry staining in HCC specimens collected from Affiliated Hospital of Jining Medical University. A nomogram combined model and clinical characteristics was plotted after the prognostic predictive value of model was validated with receiver operating characteristic curves and Kaplan–Meier survival analysis. Our results indicate that assessing pyroptosis gene expression may be useful to predict the prognosis of HCC patients by enhancing antitumor immunity.

A Novel Pyroptosis-Related Prognostic Signature for Cervical Squamous Cell Carcinoma.

PurposePyroptosis has vital roles in tumorigenesis and cancer development; however, its relationship with cervical squamous cell cancer (CSCC) remains unexplored. In this study, we aimed to develop a CSCC prediction signature related to pyroptosis.Patients and MethodsConsensus clustering analysis was conducted to detect pyroptosis-related subclusters for CSCC. Next, differentially expressed genes (DEGs) between subclusters were identified. Univariate, least absolute shrinkage and selection operator, and stepwise multivariate Cox regression analyses were applied to establish a prognostic model and a nomogram drawn. Additionally, functional enrichment analysis, tumor mutation burden, and immune characteristics associated with this signature were investigated.ResultsWe constructed a seven-gene signature that functions as an independent predictor of prognosis in CSCC using data from The Cancer Genome Atlas. Patients with CSCC were divided into two groups based on median risk score, and patients in the low-risk group had significantly longer survival time than those in the high-risk group. Our findings were validated using Gene Expression Omnibus cohort data. We also established a nomogram, to expand the clinical applicability of our findings. The seven gene signature was associated with various molecular pathways, tumor mutation status, and immune microenvironment.ConclusionThe pyroptosis-related risk signature consisting of seven genes developed here represents a potential robust biomarker for predicting prognosis and immunotherapy response in patients with CSCC.

Severe Pulmonary Hypertension in COPD: Impact on Survival and Diagnostic Approach

Severe pulmonary hypertension (PH) is prognostically highly relevant in patients with COPD. The criteria for severe PH have been defined based on hemodynamic thresholds in right heart catheterization. Can noninvasive clinical tools predict severe PH in patients with COPD? How does the mortality risk change with increasing severity of airflow limitation and pulmonary vascular disease? We retrospectively analyzed all consecutive patients with COPD with suspected PH undergoing in-depth clinical evaluation, including right heart catheterization, in our PH clinic between 2005 and 2018. Clinical variables potentially indicative of severe PH or death were analyzed using univariate and stepwise multivariate logistic regression and Cox regression analysis adjusted for age and sex. We included 142 patients with median FEV1 of 55.0%predicted (interquartile range [IQR], 42.4%-69.4%predicted) and mean pulmonary arterial pressure of 35mmHg (IQR, 27-43mmHg). A multivariate model combining echocardiographic systolic pulmonary arterial pressure of≥ 56mmHg, N-terminal pro-brain natriuretic peptide (NT-proBNP) plasma levels of≥ 650 pg/mL, and pulmonary artery (PA) to ascending aorta (Ao) diameter ratio on chest CT scan of≥ 0.93 predicted severe PH with high positive and negative predictive values (both 94%). After correction for age and sex, both airflow limitation (P= .002; Global Initiative for Chronic Obstructive Lung Disease [GOLD] stages 1-2 vsstage 3: hazard ratio [HR], 1.56 [95%CI, 0.90-2.71]; GOLD stages 1-2 vsstage 4: HR, 3.45 [95%CI, 1.75-6.79]) and PH severity (P= .012; HR, 1.85 [95%CI, 1.15-2.99]) remained associated independently with survival. The combination of GOLD stages 3 and 4 airflow limitation and severe PH showed the poorest survival (HR for death, 3.26 [95%CI, 1.62-6.57; P= .001] vsGOLD stages 1-2 combined with nonsevere PH). In patients with COPD, the combination of echocardiography, NT-proBNP level, and PA to Ao diameter ratio predicts severe PH with high sensitivity and specificity. The contribution of severe PH and severe airflow limitation to impaired survival is comparable.

Construction and Validation of a Novel Ferroptosis-Related Prognostic Model for Acute Myeloid Leukemia.

Acute myeloid leukemia (AML) is a clonal malignant proliferative blood disorder with a poor prognosis. Ferroptosis, a novel form of programmed cell death, holds great promise for oncology treatment, and has been demonstrated to interfere with the development of various diseases. A range of genes are involved in regulating ferroptosis and can serve as markers of it. Nevertheless, the prognostic significance of these genes in AML remains poorly understood. Transcriptomic and clinical data for AML patients were acquired from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO). Univariate Cox analysis was performed to identify ferroptosis-related genes with prognostic value, and the least absolute shrinkage and selection operator (LASSO) algorithm and stepwise multivariate Cox regression analysis were utilized to optimize gene selection from the TCGA cohort (132 samples) for model construction. Tumor samples from the GEO database (136 samples and 104 samples) were used as validation groups to estimate the predictive performance of the risk model. Finally, an eight-gene prognostic signature (including CHAC1, CISD1, DPP4, GPX4, AIFM2, SQLE, PGD, and ACSF2) was identified for the prediction of survival probability and was used to stratify AML patients into high- and low-risk groups. Survival analysis illustrated significantly prolonged overall survival and lower mortality in the low-risk group. The area under the receiver operating characteristic curve demonstrated good results for the training set (1-year: 0.846, 2-years: 0.826, and 3-years: 0.837), which verified the accuracy of the model for predicting patient survival. Independent prognostic analysis indicated that the model could be used as a prognostic factor (p ≤ 0.001). Functional enrichment analyses revealed underlying mechanisms and notable differences in the immune status of the two risk groups. In brief, we conducted and validated a novel ferroptosis-related prognostic model for outcome prediction and risk stratification in AML, with great potential to guide individualized treatment strategies in the future.

Temporal muscle thickness as an independent prognostic imaging marker in newly diagnosed glioblastoma patients: A validation study.

BackgroundPrevious studies have recognized temporal muscle thickness (TMT) as a prognostic marker in glioblastoma, but clinical implementation is hampered due to studies’ heterogeneity and lack of established cutoff values. The aim of this study was to assess the validity of recent proposed sex-specific TMT cutoff values in a real-world population of genotyped primary glioblastoma patients.MethodsWe measured TMT in preoperative MR images of 328 patients. Sex-specific TMT cutoff values were used to divide patients into “at risk of sarcopenia” or “normal muscle status”. Kaplan-Meier analyses and stepwise multivariate Cox-Regression analyses were used to assess the association with overall survival (OS) and progression-free survival (PFS). The association with occurrence of complications and discontinuation of glioblastoma treatment was investigated using odds ratios (OR).ResultsPatients at risk of sarcopenia had a significantly higher risk of progression and death than patients with normal muscle status, which remained significant in the multivariate analyses (OS HR = 1.437; 95%CI: 1.046–1.973; P = .025 and PFS HR = 1.453; 95%CI: 1.037–2.036; P = .030). Patients at risk of sarcopenia also had a significantly higher risk of early discontinuation of treatment (OR = 2.45; 95%CI: 1.011–5.952; P = .042) and a significantly lower chance of receiving second-line treatment (OR = 0.23; 95%CI: 0.09–0.60; P = .001). There was no association with the occurrence of complications.ConclusionsOur study confirms external validity of the use of proposed sex-specific TMT cutoff values as an independent prognostic marker in newly diagnosed glioblastoma patients. This simple, noninvasive marker could improve patient counseling and aid in treatment decision processes or trial stratification.

Ferroptosis-Related Long Non-Coding RNA Signature Contributes to the Prediction of Prognosis Outcomes in Head and Neck Squamous Cell Carcinomas.

Background: Head and neck squamous cell carcinoma (HNSCC) is a malignant tumor, which makes the prognosis prediction challenging. Ferroptosis is an iron-dependent form of non-apoptotic regulated cell death, which could affect cancer development. However, the prognostic value of ferroptosis-related long non-coding RNA (lncRNA) in HNSCC is still limited. Methods: In the current study, we employed the DESeq2 method to characterize the differentially expressed ferroptosis-related genes (FEGs) between cancer and normal samples. Next, the FEG-related lncRNAs (FElncRNAs) were identified using Spearman’s correlation analysis and multiple permutation hypotheses. Subsequently, LASSO and stepwise multivariate Cox regression analyses were undertaken to recognize the prognosis-related FElncRNA signature (PFLS) and risk scores. Results: Herein, we first identified 60 dysregulated FEGs and their co-expressed FElncRNAs in HNSCC. Then, we recognized a set of six FElncRNAs PFLS (SLCO4A1-AS1, C1RL-AS1, PCED1B-AS1, HOXB-AS3, MIR9-3HG, and SFTA1P) for predicting patients’ prognostic risks and survival outcomes. We also assessed the efficiency of PFLS in the test set and an external validation cohort. Further parsing of the tumor immune microenvironment showed the PFLS was closely associated with immune cell infiltration abundances. Notably, the low-risk group of the PFLS showed a higher MHC score and cytolytic activity (CYT) score than the high-risk group, implying the low-risk group may have greater tumor surveillance and killing ability. In addition, we observed that the expression levels of two immune checkpoints (ICPs), i.e., programmed cell death protein 1 (PD-1) and programmed cell death 1 ligand 1 (PD-L1), showed significant associations with patients’ risk score, prompting the role of the PFLS in ICP blockade therapy. Finally, we also constructed a drug–PFLS network to reinforce the clinical utilities of the PFLS. Conclusion: In summary, our study indicated that FElncRNAs played an important role in HNSCC survival prediction. Identification of PFLS will contribute to the development of novel anticancer therapeutic strategies.

Identification of a 3-gene signature for predicting the prognosis of stage II colon cancer based on microsatellite status.

Though colon cancer (CC) is one of the most malignant tumors across the world, CC patients with microsatellite instability-high (MSI-H) in stage II seem to have a better prognosis. However, the molecular mechanisms underlying the phenomena haven't been elucidated yet. This study enrolled 322 CCs with known microsatellite status from GSE143985, GSE39582 and GSE92921 in the Gene Expression Omnibus (GEO) database. Robust rank aggregation (RRA) analysis, univariate Cox regression analysis and multivariate Cox stepwise regression analysis were performed to identify genes and construct risk score signature. Kaplan-Meier and receiver operating characteristic (ROC) curves analyses were used to evaluate the prognostic value of the signature. The potential mechanisms underlying this signature were assessed in the Metascape database, gene set enrichment analysis (GSEA) and immune infiltration analysis. RRA analysis identified 40 differently expressed genes (DEGs). A 3-gene risk score signature (MKQ signature) associated with disease-free survival (DFS) was generated. DFS was significantly longer in CC patients with lower than higher scores (P=0.0046). The areas under curves (AUCs) of the time-dependent ROC curves of MKQ signature at 1-, 3- and 5-year DFS were 1, 0.963 and 0.961 respectively. Recurrence-free survival (RFS) was significantly longer in patients in GSE39582 with lower than higher risk scores (P=0.032). The AUCs for 1-, 3- and 5-year RFS in GSE39582 were 0.63, 0.618 and 0.583, respectively, validating the value of the MKQ signature. Functional annotation and GSEA revealed that the MKQ signature was associated with multiple immune-related pathways. Immune cell infiltration was found to differ in patients differing in the MKQ signature. Gene expression and microsatellite status identified a 3-gene signature (MKQ signature) that could facilitate risk-stratified management in patients with stage II CC. Dysregulation of MSMB, KRT23, and QPRT can serve as prognostic markers in stage II CC.

Length of hospital stay following hip fracture and risk of 30 and 90 day mortality in a United Kingdom cohort.

A recent study identified a length of stay (LOS) of 10 days or less following hip fracture is associated with increased risk of 30-day mortality. This effect has not been previously studied for 90-day mortality or in the United Kingdom (UK). Our aim was to investigate the effect of LOS on 30-day and 90-day mortality following hip fracture in a UK population. In this single-centre study, we retrospectively identified consecutive patients with a hip fracture from the National Hip Fracture Database over 3 years. We excluded patients who died as inpatient during their index admission. The main end-points were 30-day and 90-day mortalities and risk factors for these were examined using stepwise univariate and multivariate Cox regression analyses. Of 1228 patients, mortality at 30-days was 1.2% (15 patients) and 7.8% (96 patients) at 90-days. Mean LOS was 24 days and a total of 206 patients had a LOS of 10 days or less. Following cariate analysis, the highest risk factor for 30-day mortality was a LOS of 10 days or less with a hazard ratio of 7.26 (95% confidence interval 2.56-20.51). Other risk factors for 30-day mortality included increasing age, male gender and chest infection. A LOS of 10 days or less was not associated with increased mortality at 90-days. A short LOS was associated with higher risk of early mortality. We recommend that hip fracture patients be fully rehabilitated prior to discharge to reduce the risk of early mortality.

Prognostic relevance of peri-infarct zone measured by cardiovascular magnetic resonance in patients with ST-segment elevation myocardial infarction

BackgroundCardiac magnetic resonance (CMR) imaging provides valuable prognostic information in patients with ST-elevation myocardial infarction (STEMI). The peri-infarct zone (PIZ) is a potential marker for post-infarction risk stratification. The aim of this study was to assess the prognostic impact of PIZ in a large multicenter STEMI-trial. MethodsThe study population consisted of 704 consecutive patients undergoing CMR within 10 days after STEMI to assess established parameters of myocardial injury and additionally the extent of PIZ. The primary clinical endpoint was major adverse cardiac events (MACE) consisting of death, re-infarction and new congestive heart failure within 1 year after infarction. ResultsThe median heterogeneous PIZ-volume in the overall population was 14 ml (interquartile range [IQR] 7 to 24 ml). Male sex, infarct size, and left ventricular ejection fraction were identified as independent predictors of larger PIZ alterations. Patients with MACE had a significantly larger PIZ volume compared to patients without adverse events (21 ml [IQR 12 to 35 ml] versus 14 ml [IQR 7 to 23 ml]; p = 0.001). In stepwise multivariable Cox regression analysis, PIZ > median (>14 ml) emerged as an independent predictor of MACE (hazard ratio [HR] 2.84; 95% confidence interval [CI] 1.34 to 6.00; p = 0.006) in addition to the Thrombolysis In Myocardial Infarction (TIMI) risk score (HR 1.53; 95% CI 1.19 to 1.53; p < 0.001). Addition of PIZ to a CMR risk model comprising LVEF, infarct size and microvascular obstruction resulted in net reclassification improvement of 0.46 (0.19–0.73, p < 0.001). ConclusionIn this currently largest prospective, multicenter CMR study assessing PIZ, the extent of PIZ emerged as an independent predictor of MACE and a potential novel marker for optimized risk stratification in STEMI patients.ClinicalTrials.gov: NCT00712101

Identification of an Immune-Related Signature Predicting Survival Risk and Immune Microenvironment in Gastric Cancer.

Background: Tumor immune microenvironment plays a vital role in tumorigenesis and progression of gastric cancer (GC), but potent immune biomarkers for predicting the prognosis have not been identified yet.Methods: At first, RNA-sequencing and clinical data from The Cancer Genome Atlas (TCGA) were mined to identify an immune-risk signature using least absolute shrinkage and selection operator (LASSO) regression and multivariate stepwise Cox regression analyses. Furthermore, the risk score of each sample was calculated, and GC patients were divided into high-risk group and low-risk group based on their risk scores. Subsequently, the performance of this signature, including the correlation with overall survival (OS), clinical features, immune cell infiltration, and immune response, has been tested in GC data from TCGA database and Gene Expression Omnibus (GSE84437), respectively.Results: An immune signature composed of four genes (MAGED1, ACKR3, FZD2, and CTLA4) was constructed. The single sample gene set enrichment analysis (ssGSEA) indicated that activated CD4+/CD8+ T cell, activated dendritic cell, and effector memory CD8+ T cell prominently increased in the low-risk group, showing relatively high immune scores and low stromal scores. Further GSEA analysis indicated that TGF-β, Ras, and Rap1 pathways were activated in the high-risk group, while Th17/Th1/Th2 differentiation, T cell receptor and PD-1/PD-L1 checkpoint pathways were activated in the low-risk group. Low-risk patients presented higher tumor mutation burden (TMB) and expression of HLA-related genes. The immune-associated signature showed an excellent predictive ability for 2-, 3-, and 5-year OS in GC.Conclusion: The immune-related prognosis model contributes to predicting the prognosis of GC patients and providing valuable information about their response to immunotherapy using integrated bioinformatics methods.

Admission Blood Glucose Is Associated With the 30-Days Mortality in Septic Patients: A Retrospective Cohort Study.

Background: Sepsis, as one of the severe diseases, is frequently observed in critically ill patients, especially concurrent with diabetes. Whether admission blood glucose is associated with the prognosis, and outcome of septic patients is still debatable.Methods: We retrospectively reviewed and analyzed the demographic characteristics of septic patients in the Medical Information Mart for Intensive Care III (MIMIC III, version 1.4) between June 2001 and October 2012. The Chi-square and Fisher's exact tests were used for the comparison of qualitative variables among septic patients with different glucose levels and the 30-day mortality in septic patients with diabetes or not. Univariate and stepwise multivariate Cox regression analyses were used to determine the risk factors for 30-day mortality. Kaplan-Meier analysis was conducted to reveal the different 30-day survival probabilities in each subgroup.Results: A total of 2,948 septic patients (910 cases with diabetes, 2,038 cases without diabetes) were ultimately included in the study. The 30-day mortality was 32.4% (956/2,948 cases) in the overall population without any difference among diabetic and non-diabetic septic patients (p = 1.000). Admission blood glucose levels <70 mg/dl were only observed to be significantly associated with the 30-day mortality of septic patients without diabetes (hazard ratio (HR) = 2.48, p < 0.001). After adjusting for confounders, age >65 years (HR = 1.53, p = 0.001), the Sequential Organ Failure Assessment (SOFA) score >5 (HR = 2.26, p < 0.001), lactic acid >2 mmol/L (Lac, HR = 1.35, p = 0.024), and platelet abnormality (<100 k/ul: HR = 1.49; >300 k/ul: HR = 1.36, p < 0.001) were the independent risk factors for 30-day mortality in septic patients with diabetes. In non-diabetes population, age >65 years (HR = 1.53, p < 0.001), non-White or non-Black patients (HR = 1.30, p = 0.004), SOFA score >5 (HR = 1.56, p < 0.001), blood glucose <70 mg/dl (HR = 1.91, p = 0.003), anion gap (AG) >2 mmol/L (HR = 1.60, p < 0.001), Lac (HR = 1.61, p < 0.001), urea nitrogen >21 mg/dl (HR = 1.45, p = 0.001), alanine aminotransferase (ALT, HR = 1.31, p = 0.009), total bilirubin >1.2 mg/dl (HR = 1.20, p = 0.033), and low hemoglobin (HR = 1.34, p = 0.001) were the independent risk factors for 30-day mortality.Conclusions: Our results indicate admission blood glucose, especially in terms of <70 mg/dl, is the key signaling in predicting the worse 30-day survival probability of septic patients without diabetes, which could help clinicians to make a more suitable and precise treatment modality in dealing with septic patients.

Mild Malnutrition Contributes the Greatest to the Poor Prognosis in Coronary Artery Disease With Well-Controlled Low-Density Lipoprotein Cholesterol Levels: A 4,863 Chinese Cohort Study.

Background: Previous studies reported that patients with coronary artery disease (CAD) and well-controlled baseline LDL-C (<1.8 mmol/L) still had higher long-term all-cause mortality. However, no study has been conducted to explore the independent risk factors for long-term mortality. In addition, there also was no study evaluating the population attributable risk (PAR) of independent risk factors in combination with their prevalence and relative risk. Therefore, we aimed to identify the independent risk factors and estimate their PAR in patients with CAD and well-controlled baseline LDL-C (<1.8 mmol/L).Methods: We analyzed 4,863 consecutive CAD patients with well-controlled baseline LDL-C admitted to Guangdong Provincial People's Hospital in China from January 2007 to December 2018. Independent risk factors for long-term all-cause death were evaluated through stepwise approach and multivariable Cox regression analysis. PAR of independent risk factors was calculated with their hazard ratio and prevalence among our cohort.Results: The overall mortality was 16.00% (n = 778) over a median follow-up period of 5.93 years. Independent risk factors for all-cause death included malnutrition, age ≥75 years, congestive heart failure (CHF), chronic kidney disease (CKD) and atrial fibrillation. Among these risk factors of interest, the hazard ratio (HR) of severe malnutrition was the highest (HR 2.82, 95% CI: 1.86–4.26), and the PAR of mild malnutrition was the highest (19.49%, 95% CI: 0.65–36.01%).Conclusion: Malnutrition, age ≥75 years, CHF, CKD and atrial fibrillation were independent predictors for long-term all-cause mortality in CAD patients with well-controlled LDL-C levels. Considering prevalence of these risk factors, more attention should be paid to the occurrence of mild malnutrition for these patients.Clinical Trial Registration: ClinicalTrials.gov, identifier: NCT04407936.

The influence of equitable access policies and socioeconomic factors on post-liver transplant survival

BackgroundSurvival following liver transplant (LT) is influenced by a variety of factors, including donor risk factors and recipient disease burden and co-morbidities. It is difficult to separate these effects from those of socioeconomic factors, such as income or insurance. The United Network for Organ Sharing (UNOS) created equitable access policies, such as Share 35, to ensure that organs are distributed to individuals with greatest medical need; however, the effect of Share 35 on disparities in post-LT survival is not clear. This study aimed to (1) characterize associations between post-transplant survival and race and ethnicity, income, insurance, and citizenship status, when adjusted for other clinical and demographic factors that may influence survival, and (2) determine if the direction of associations changed after Share 35.MethodsA retrospective, cohort study of adult LT recipients (n = 83,254) from the UNOS database from 2005 to 2019 was conducted. Kaplan-Meier survival graphs and stepwise multivariate cox-regression analyses were performed to characterize the effects of socioeconomic status on post-LT survival, adjusted for recipient and donor characteristics, across the time period and after Share 35.FindingsMale sex (HR: 0.93 (95% CI: 0.90–0.96)), private insurance (0.91 (0.88–0.94)), income (0.82 (0.79–0.85)), U.S. citizenship, and Asian (0.81 (0.75–0.88)) or Hispanic (0.82 (0.79–0.86)) race and ethnicity were associated with higher post-transplant survival, after adjustment for clinical and demographic factors (Table 3). These associations were found across the entire time period studied and many persisted after the implementation of Share 35 in 2013 (Table 3; male sex (0.84 (0.79–0.90)), private insurance (0.94 (0.89–1.00)), income (0.82 (0.77–0.89)), and Asian (0.87 (0.73–1.02)) or Hispanic (0.88 (0.81–0.96)) race and ethnicity).InterpretationRecipients’ socioeconomic factors at time of transplant may impact long-term post-transplant survival, and a single policy may not significantly alter these structural health inequalities.FundingNone

MicroRNA-183-3p Is a Predictor of Worsening Heart Failure in Adult Patients With Transposition of the Great Arteries and a Systemic Right Ventricle.

Aim: MicroRNAs (miRNAs) have been shown to play an important role in the progression of heart failure (HF). The aim of our study was to analyze miRNAs in the blood of patients with transposition of the great arteries and a systemic right ventricle (TGA-RV) in order to identify those that predict worsening HF.Materials and Methods: In 36 patients with TGA-RV, SurePrint™ 8 × 60K Human v21 miRNA microarrays were used to determine the miRNA abundance profiles and compared to 35 age- and gender-matched healthy volunteers (HVs). MiRNAs that were most significantly abundant or best related to worsening HF were further validated by RT-qPCR.Results: Using miRNA array analysis, a total of 50 down-regulated and 56 up-regulated miRNAs were found to be differentially abundant in TGA-RV patients compared to HVs. Six of these 106 miRNAs were significantly related to worsening HF. After validation by RT-qPCR, four miRNAs turned out to be significantly associated with worsening HF, namely miR-150-5p, miR-1255b-5p, miR-423-3p, and miR-183-3p. In the stepwise multivariable Cox regression analysis, ejection fraction of the systemic RV, high sensitive TNT and miR-183-3p were found to be independent predictors of worsening HF (P = 0.001, P = 0.002, and P = 0.001, respectively).Conclusions: In patients with TGA-RV, miR-183-3p is an independent predictor of worsening HF and thus may be used as additional biomarker in the risk assessment of these patients.

Novel immune-related signature for risk stratification and prognosis in prostatic adenocarcinoma.

A substantial proportion of prostatic adenocarcinoma (PRAD) patients experience biochemical failure (BCF) after radical prostatectomy (RP). The immune microenvironment plays a vital role in carcinogenesis and the development of PRAD. This study aimed to identify a novel immune‐related gene (IRG)‐based signature for risk stratification and prognosis of BCF in PRAD. Weighted gene coexpression network analysis was carried out to identify a BCF‐related module in a discovery cohort of patients who underwent RP at the Massachusetts General Hospital. The median follow‐up time was 70.32 months. Random forest and multivariate stepwise Cox regression analyses were used to identify an IRG‐based signature from the specific module. Risk plot analyses, Kaplan‐Meier curves, receiver operating characteristic curves, univariate and multivariate Cox regression analyses, stratified analysis, and Harrell’s concordance index were used to assess the prognostic value and predictive accuracy of the IRG‐based signature in the internal discovery cohort; The Cancer Genome Atlas database was used as a validation cohort. Tumor immune estimation resource database analysis and CIBERSORT algorithm were used to assess the immunophenotype of PRAD. A novel IRG‐based signature was identified from the specific module. Five IRGs (BUB1B, NDN, NID1, COL4A6, and FLRT2) were verified as components of the risk signature. The IRG‐based signature showed good prognostic value and predictive accuracy in both the discovery and validation cohorts. Infiltrations of various immune cells were significantly different between low‐risk and high‐risk groups in PRAD. We identified a novel IRG‐based signature that could function as an index for assessing tumor immune status and risk stratification in PRAD.

Diabetes type 2: conventional, social and some genetic predictors of cardiovascular death

Aim of the study was to investigate the associations of metabolic, behavioral, socio-economic risk factors and some molecular genetic markers with the risk of cardiovascular death (CVD) in persons with type 2 diabetes (T2DM) aged 45–69 years. Material and methods . The analysis included survey data from 681 participants with T2DM. The baseline survey was carried out within the framework of the HAPIEE project. The observation period lasted from 2003– 2005 to December 31, 2018 and averaged 14.7 ± 0.7 years. Persons who at the time of the baseline examination had an indication of a previous myocardial infarction and/or cerebral stroke were excluded from the analysis. The causes of CVD were determined according to the code International Classification of Diseases 10th revision – I (0–99). Within the framework of the study, 2 groups were formed: the main group, which included persons with T2DM who «developed fatal CV events» 2 207 people (107 men and 100 women) and a comparison group – persons with T2DM who «did not develop fatal CV events» for observation period – 474 people (177 men and 297 women). Indicators of anthropometry, blood pressure, socio-demographic data, some biochemical parameters and molecular genetic markers were determined. To analyze the association of the studied factors with the risk of CVD, multivariate stepwise Cox regression analysis was used. Results. The risk factors for CVD common for men and women were determined: age, increased SBP, current smoking, non-working status, fasting blood plasma glucose ≥ 7.5 mmol/L. For men, significant risk factors for CVD were also – heart rate ≥ 75 per minute, lonely status; for women – verified diabetes before the baseline examination. Carriage of the heterozygous AG genotype against the AA + GG rs2464196 HNF1A is associated with a reduced risk of fatal CV events in men, OR = 0.488 (95 % CI 0.254–0.941). Carriage of the heterozygous genotype AC rs11212617 ATM is associated with an increased risk of fatal CV events in both sexes. OR = 1.561 (95 % CI = 1.022–2.384). Conclusion . In men and women with T2DM over a 15-year follow-up, associations were found between the risk of fatal CV events with the level of both «traditional» and «diabetes-related» risk factors, as well as with the HNF1A rs2464196 and ATM rs11212617.

Salami-Tactics: when is it time for a major cut after multiple minor amputations?

IntroductionRepetitive minor amputations carry the concomitant risks of multiple surgical procedures, major amputations have physical and economical major drawbacks. The aim of this study was to evaluate whether there is a distinct number of minor amputations predicting a major amputation in the same leg and to determine risk factors for major amputation in multiple minor amputations.Materials and methodsA retrospective chart review including 429 patients with 534 index minor amputations between 07/1984 and 06/2019 was conducted. Patient demographics and clinical data including number and level of re-amputations were extracted from medical records and statistically analyzed.Results290 legs (54.3%) had one or multiple re-amputations after index minor amputation. 89 (16.7%) legs needed major amputation during follow up. Major amputation was performed at a mean of 32.5 (range 0 –275.2) months after index minor amputation. No particular re-amputation demonstrated statistically significant elevated odds ratio (a.) to be a major amputation compared to the preceding amputation and (b.) tolead to a major amputation at any point during follow up. Stepwise multivariate Cox regression analysis revealed minor re-amputation within 90 days (HR 3.8, 95% CI 2.0-7.3, p <0.001) as the only risk factor formajor amputation if at least one re-amputation had to be performed.ConclusionsThere is no distinct number of prior minor amputations in one leg that would justify a major amputation on its own. If a re-amputation has to be done, the timepoint needs to be considered as re-amputations within 90 days carry a fourfold risk for major amputation.Level of evidenceRetrospective comparative study (Level III).

Immune-Related lncRNA Signature for Predicting the Immune Landscape of Head and Neck Squamous Cell Carcinoma.

Background: Long non-coding RNA (lncRNA) plays a significant role in the development, establishment, and progression of head and neck squamous cell carcinoma (HNSCC). This article aims to develop an immune-related lncRNA (irlncRNA) model, regardless of expression levels, for risk assessment and prognosis prediction in HNSCC patients. Methods: We obtained clinical data and corresponding full transcriptome expression of HNSCC patients from TCGA, downloaded GTF files to distinguish lncRNAs from Ensembl, discerned irlncRNAs based on co-expression analysis, distinguished differentially expressed irlncRNAs (DEirlncRNAs), and paired these DEirlncRNAs. Univariate Cox regression analysis, LASSO regression analysis, and stepwise multivariate Cox regression analysis were then performed to screen lncRNA pairs, calculate the risk coefficient, and establish a prognosis model. Finally, the predictive power of this model was validated through the AUC and the ROC curves, and the AIC values of each point on the five-year ROC curve were calculated to select the maximum inflection point, which was applied as a cut-off point to divide patients into low- or high-risk groups. Based on this methodology, we were able to more effectively differentiate between these groups in terms of survival, clinico-pathological characteristics, tumor immune infiltrating status, chemotherapeutics sensitivity, and immunosuppressive molecules. Results: A 13-irlncRNA-pair signature was built, and the ROC analysis demonstrated high sensitivity and specificity of this signature for survival prediction. The Kaplan–Meier analysis indicated that the high-risk group had a significantly shorter survival rate than the low-risk group, and the chi-squared test certified that the signature was highly related to survival status, clinical stage, T stage, and N stage. Additionally, the signature was further proven to be an independent prognostic risk factor via the Cox regression analyses, and immune infiltrating analyses showed that the high-risk group had significant negative relationships with various immune infiltrations. Finally, the chemotherapeutics sensitivity and the expression level of molecular markers were also significantly different between high- and low-risk groups. Conclusion: The signature established by paring irlncRNAs, with regard to specific expression levels, can be utilized for survival prediction and to guide clinical therapy in HNSCC.

Identification and Validation of Immune-Related LncRNA Prognostic Signature for Lung Adenocarcinoma.

This study aimed to establish a prognostic risk model for lung adenocarcinoma (LUAD). We firstly divided 535 LUAD samples in TCGA-LUAD into high-, medium-, and low-immune infiltration groups by consensus clustering analysis according to immunological competence assessment by single-sample gene set enrichment analysis (ssGSEA). Profile of long non-coding RNAs (lncRNAs) in normal samples and LUAD samples in TCGA was used for a differential expression analysis in the high- and low-immune infiltration groups. A total of 1,570 immune-related differential lncRNAs in LUAD were obtained by intersecting the above results. Afterward, univariate COX regression analysis and multivariate stepwise COX regression analysis were conducted to screen prognosis-related lncRNAs, and an eight-immune-related-lncRNA prognostic signature was finally acquired (AL365181.2, AC012213.4, DRAIC, MRGPRG-AS1, AP002478.1, AC092168.2, FAM30A, and LINC02412). Kaplan–Meier analysis and ROC analysis indicated that the eight-lncRNA-based model was accurate to predict the prognosis of LUAD patients. Simultaneously, univariate COX regression analysis and multivariate COX regression analysis were undertaken on clinical features and risk scores. It was illustrated that the risk score was a prognostic factor independent from clinical features. Moreover, immune data of LUAD in the TIMER database were analyzed. The eight-immune-related-lncRNA prognostic signature was related to the infiltration of B cells, CD4+ T cells, and dendritic cells. GSEA enrichment analysis revealed significant differences in high- and low-risk groups in pathways like pentose phosphate pathway, ubiquitin mediated proteolysis, and P53 signaling pathway. This study helps to treat LUAD patients and explore molecules related to LUAD immune infiltration to deeply understand the specific mechanism.

Comparison of Surgical Outcomes Between Ab Interno Suture Trabeculotomy and Ab Externo Metal Trabeculotomy in Adult Patients with Glaucoma

PurposeTo compare the outcomes of ab interno suture trabeculotomy (AbI-TLO) and ab externo metal trabeculotomy (AbE-TLO) in adult patients with glaucoma aged over 40 years.Patients and MethodsA retrospective chart review was conducted, including adult patients with glaucoma who underwent AbI-TLO or AbE-TLO between January 2015 and June 2019. A single surgeon (YO) performed all the operations. Eighty-one patients (81 eyes) were included in this study. Surgical success was defined as a postoperative intraocular pressure (IOP) of ≤18 mmHg and an IOP reduction of ≥20% from the preoperative IOP, without requiring additional glaucoma surgery. Success rates were assessed using Kaplan–Meier survival curves and log-rank (Mantel–Cox) tests, while risk factors were analyzed using the Cox proportional hazards model.ResultsForty-nine patients who underwent AbI-TLO and 32 patients who underwent AbE-TLO were studied; the preoperative IOPs were 27.9 ± 7.3 (mean ± standard deviation) mmHg and 25.6 ± 8.1 mmHg in the AbI-TLO and AbE-TLO groups, respectively (p=0.217). The 12-month postoperative IOPs were 15.8 ± 4.0 mmHg and 16.3 ± 4.2 mmHg in the AbI-TLO and AbE-TLO groups, respectively (p=0.724). The surgical success rates at 12 months were 77.6% and 62.5% in the AbI-TLO and AbE-TLO groups, respectively (p=0.144). Postoperative hyphema with level formation and ocular hypertension over 30 mmHg were observed in 22.4% and 26.5% of patients in the AbI-TLO group and 18.8% and 12.5% of those in the AbE-TLO group, respectively. Stepwise multivariate Cox regression analysis showed that a longer axial length was a risk factor for surgical failure (hazard ratio: 2.030; p=0.042).ConclusionAbI-TLO and AbE-TLO had similar surgical outcomes and postoperative complications. A longer axial length was associated with an insufficient IOP reduction.