Cox Regression Research Articles

Correlation between the immune microenvironment and bladder cancer based on a prognostic miRNA risk model

<p class="MsoNormal"><strong><span lang="EN-US" style="mso-bidi-font-size: 10.5pt; font-family: Nunito; mso-bidi-font-family: 'Times New Roman'; mso-bidi-theme-font: minor-bidi; color: #212529; background: white;">Background: </span></strong><span lang="EN-US" style="mso-bidi-font-size: 10.5pt; font-family: Nunito; color: #212529; background: white;">Bladder cancer (BLCA), particularly invasive BLCA, has become a medical burden worldwide as it is associated with recurrence and easy metastasis. There are specific differences in the expression of various miRNAs in tumor and normal tissues. Hence, miRNAs can be used as biomarkers for tumor diagnosis and prognostic evaluation. The current study aimed to predict the downstream target genes of BLCA-related miRNAs and explore their association with immune infiltration. Method: Data on BLCA-related mRNA and miRNA expression levels were downloaded from The Cancer Genome Atlas. Correlation analysis and Cox regression analysis were performed to validate the miRNA risk model. The infiltration of various immune cells should be compared to determine the distinct differences between the immunological microenvironment of the two risk groups. <strong><span style="font-family: Nunito; mso-bidi-font-family: 'Times New Roman'; mso-bidi-theme-font: minor-bidi;">Results: </span></strong>A predictive framework of BLCA was established using the expression levels of two miRNAs. Cox regression analysis showed that the low-risk group had a better prognosis. Then, the target genes of miRNA were predicted, and the target genes were analyzed using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes. Moreover, variations in immune cells and functions between the high- and low-risk groups were assessed. <strong><span style="font-family: Nunito; mso-bidi-font-family: 'Times New Roman'; mso-bidi-theme-font: minor-bidi;">Conclusion:</span></strong> The prognostic features composed of two associated miRNAs (MIR-25, MIR-548AN) may help predict the overall survival of BLCA.</span></p>

Impact of Poverty on Stroke Recurrence: A Population-Based Study.

Poverty is associated with greater stroke incidence. The relationship between poverty and stroke recurrence is less clear. In this population-based study, incident strokes within the Greater Cincinnati/Northern Kentucky region were ascertained during the 2015 study period and followed up for recurrence until December 31, 2018. The primary exposure was neighborhood socioeconomic status (nSES), defined by the percentage of households below the federal poverty line in each census tract in 4 categories (≤5%, >5%-10%, >10%-25%, >25%). Poisson regression models provided recurrence rate estimates per 100,000 residents using population data from the 2015 5-year American Community Survey, adjusting for age, sex, and race. In a secondary analysis, Cox models allowed for the inclusion of vascular risk factors in the assessment of recurrence risk by nSES among those with incident stroke. Of 2,125 patients with incident stroke, 245 had a recurrent stroke during the study period. Poorer nSES was associated with increased stroke recurrence, with rates of 12.5, 17.5, 25.4, and 29.9 per 100,000 in census tracts with ≤5%, >5%-10%, >10%-25%, and >25% below the poverty line, respectively (p < 0.01). The relative risk (95% CI) for recurrent stroke among Black vs White individuals was 2.54 (1.91-3.37) before adjusting for nSES, and 2.00 (1.47-2.74) after adjusting for nSES, a 35.1% decrease. In the secondary analysis, poorer nSES (HR 1.74, 95% CI 1.10-2.76 for lowest vs highest category) and Black race (HR 1.31, 95% CI 1.01-1.70) were both independently associated with recurrence risk, though neither retained significance after full adjustment. Age, diabetes, and left ventricular hypertrophy were associated with increased recurrence risk in fully adjusted models. Residents of poorer neighborhoods had a dose-dependent increase in stroke recurrence risk, and neighborhood poverty accounted for approximately one-third of the excess risk among Black individuals. These results highlight the importance of poverty, race, and the intersection of the 2 as potent drivers of stroke recurrence.

Associations Between Ultra-Processed Food Consumption and Adverse Brain Health Outcomes.

Ultra-processed foods (UPFs) are linked to cardiometabolic diseases and neurologic outcomes, such as cognitive decline and stroke. However, it is unclear whether food processing confers neurologic risk independent of dietary pattern information. We aimed to (1) investigate associations between UPFs and incident cognitive impairment and stroke and (2) compare these associations with other commonly recommended dietary patterns in the REasons for Geographic and Racial Differences in Stroke study. This prospective, observational cohort study enrolled Black and White adults in the United States from 2003 to 2007. The NOVA system was used to categorize items from a baseline food frequency questionnaire according to the level of processing. Participants with incomplete or implausible self-reported dietary data were excluded. Consumption for each category (grams) was normalized to total grams consumed. Scores quantifying adherence to a Mediterranean, Dietary Approaches to Stop Hypertension (DASH), and Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) diet were also calculated. Incident cognitive impairment was defined using performance relative to a normative sample on memory and fluency assessments. Incident stroke was identified through adjudicated review of medical records. The cognitive impairment cohort (n = 14,175) included participants without evidence of impairment at baseline who underwent follow-up testing. The stroke cohort (n = 20,243) included participants without a history of stroke. In multivariable Cox proportional hazards models, a 10% increase in relative intake of UPFs was associated with higher risk of cognitive impairment (hazard ratio [HR] = 1.16, 95% CI 1.09-1.24, p = 1.01 × 10-5) and intake of unprocessed or minimally processed foods with lower risk of cognitive impairment (HR = 0.88, 95% CI 0.83-0.94, p = 1.83 × 10-4). Greater intake of UPFs (HR = 1.08, 95% CI 1.02-1.14, p = 1.12 × 10-2) and unprocessed or minimally processed foods (HR = 0.91, 95% CI 0.86-0.95, p = 2.13 × 10-4) were also associated with risk of stroke in multivariable Cox models. The effect of UPFs on stroke risk was greater among Black than White participants (UPF-by-race interaction HR = 1.15, 95% CI 1.03-1.29, p = 1.50 × 10-2). Associations between UPFs and both cognitive impairment and stroke were independent of adherence to the Mediterranean, DASH, and MIND diets. Food processing may be important to brain health in older adults independent of known risk factors and adherence to recommended dietary patterns.

Prognostic value of body mass index for first-line chemoimmunotherapy combinations in advanced non-small cell lung cancer in Chinese population.

BackgroundFew studies have examined the correlation between body mass index (BMI) and effectiveness of first-line chemoimmunotherapy in patients with advanced non-small cell lung cancer (NSCLC); moreover, the conclusion remains elusive and no such studies have been conducted in the Chinese population. Our study aimed to validate the predictive significance of BMI in Chinese patients with advanced NSCLC receiving first-line chemoimmunotherapy combinations. MethodsData of patients with advanced NSCLC treated with first-line chemoimmunotherapy between June 2018 and February 2022 at three centers were retrieved retrospectively. The association between baseline BMI with progression-free survival (PFS) and overall survival (OS) was evaluated using the Kaplan–Meier method and Cox regression models. BMI was categorized according to the World Health Organization criteria. ResultsOf the included 805 patients, 5.3% were underweight, 63.4% had normal weight, 27.8% were overweight, and 3.5% were obese. Survival analysis showed that patients in the high BMI group had significantly better PFS (p=0.012) and OS (p=0.014) than those in the low BMI group. Further, patients in the overweight subgroup had better PFS (p=0.036) and OS (p=0.043) compared to the normal weight population. The results of Cox regression analysis confirmed the correlations between BMI and prognosis of advanced NSCLC patients receiving first-line chemoimmunotherapy combinations. ConclusionsBaseline BMI affected the clinical outcomes of first-line chemoimmunotherapy combinations in patients with advanced NSCLC, and was especially favorable for the overweight subgroup.

The association of the dietary inflammatory potential with risk of overall and site-specific cancers: A community-based longitudinal study in the UK Biobank

ObjectivesThe association of the dietary inflammatory potential with cancer risk remains uncertain. We examined the relationship of the dietary inflammatory potential with risk of overall and site-specific cancers and explored its sex and age differences. DesignA community-based longitudinal study. SettingParticipants from the UK Biobank completed baseline surveys during 2006–2010 and were followed for up to 15 years to detect incident cancer. Participants170,899 cancer-free participants with dietary data available (mean age: 55.73 ± 7.95, 54.10% female). MeasurementsAt baseline, dietary intake was assessed with a 24-h dietary record for up to 5 times. The inflammatory diet index (IDI) was calculated to assess the dietary inflammatory potential as a weighted sum of 31 food groups (including 14 anti-inflammatory and 17 pro-inflammatory) based on plasma high-sensitivity C-reactive protein (hsCRP) levels, and tertiled as low (indicating low-inflammatory diet), moderate, and high IDI (as reference). Overall and site-specific cancers were ascertained via linkage to routine hospital admission, cancer registry, and death certificate data. Data were analyzed using Cox regression and Laplace regression. ResultsDuring the follow-up (median 10.32 years, interquartile range: 9.95–11.14 years), 18,884 (11.05%) participants developed cancer. In multi-adjusted Cox regression, low IDI scores were associated with decreased risk of rectal cancer (hazard ratio [95% confidence interval, CI] 0.76 [0.61, 0.94]), thyroid cancer [0.45 (0.27, 0.74)], lung cancer [0.73 (0.61, 0.88)]. However, the association between IDI score and the risk of overall cancer was not significant. Laplace regression analysis showed that 10th percentile differences (95% CIs) of cancer onset time for participants with low IDI scores was prolonged by 1.29 (0.32, 2.27), 1.44 (0.58, 2.30), and 2.62 (0.98, 4.27) years for rectal cancer, thyroid cancer, and lung cancer, respectively, compared to those with high IDI scores. Stratified analysis revealed that low IDI scores were associated with a lower risk of rectal cancer (p interaction between IDI score and sex = 0.035) and lung cancer in males, but not in females, and with a reduced risk of thyroid cancer in females, but not in males. Moreover, low IDI scores were associated with a reduced risk of rectal cancer and lung cancer in the participants aged ≥60 years, but not in those <60 years, and with a reduced risk of thyroid cancer in those aged ≥60 years and <60 years. ConclusionsA low-inflammatory diet is associated with decreased risk and prolonged onset time of rectal cancer and lung cancer, especially among males and individuals aged ≥60 years, and thyroid cancer among females.

Identification of PANoptosis-related genes as prognostic indicators of thyroid cancer

BackgroundThyroid cancer (THCA) has become a common malignancy in recent years, with the mortality rate steadily increasing. PANoptosis is a unique kind of programmed cell death (PCD), including pyroptosis, necroptosis, and apoptosis, and is involved in the proliferation and prognosis of numerous cancers. This paper demonstrated the connection between PANoptosis-related genes and THCA based on the analyses of Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases, which have not been evaluated yet. MethodsWe identified PANoptosis-related expression genes (PRDEGs) by multi-analyzing the TCGA-THCA and GEO datasets. To identify the significant PRDEGs, a prognostic model was constructed using least absolute shrinkage and selection operator regression (LASSO). The predictive values of the significant PRDEGs for THCA outcomes were determined using Cox regression analysis and nomograms. Gene enrichment analyses were performed. Finally, immunohistochemistry was carried out using the human protein atlas. ResultsA LASSO regression model based on nine PRDEGs was constructed, and the prognostic value of key PRDEGs was explored via risk score. Univariate and multivariate Cox regression were implemented to identify further three significant PRDEGs closely related to distant metastasis, lymph node metastasis, and tumor stage. Then, a nomogram was constructed, which presented high predictive accuracy for 5 years survival of THCA patients. Gene enrichment analyses in THCA were strongly associated with PCD pathways. CASP6 presented significantly differential expression during clinical T stage, N stage, and PFI events (P<0.05 for all) and demonstrated the highest degree of diagnostic efficacy in PRDEGs (HR: 2.060, 95% CI: 1.170-3.628, P < 0.05). Immunohistochemistry showed CASP6 was more abundant in THCA tumor tissue. ConclusionA potential prognostic role for PRDEGs in THCA was identified, providing a new direction for treatment. CASP6 may be a potential therapeutic target and a novel prognostic biomarker for THCA.

Mapping the Ecological Terrain of Stroke Prehospital Delay: A Nationwide Registry Study.

Delays in hospital presentation limit access to acute stroke treatments. While prior research has focused on patient-level factors, broader ecological and social determinants have not been well studied. We aimed to create a geospatial map of prehospital delay and examine the role of community-level social vulnerability. We studied patients with ischemic stroke who arrived by emergency medical services in 2015 to 2017 from the American Heart Association Get With The Guidelines-Stroke registry. The primary outcome was time to hospital arrival after stroke (in minutes), beginning at last known well in most cases. Using Geographic Information System mapping, we displayed the geography of delay. We then used Cox proportional hazard models to study the relationship between community-level factors and arrival time (adjusted hazard ratios [aHR] <1.0 indicate delay). The primary exposure was the social vulnerability index (SVI), a metric of social vulnerability for every ZIP Code Tabulation Area ranging from 0.0 to 1.0. Of 750 336 patients, 149 145 met inclusion criteria. The mean age was 73 years, and 51% were female. The median time to hospital arrival was 140 minutes (Q1: 60 minutes, Q3: 458 minutes). The geospatial map revealed that many zones of delay overlapped with socially vulnerable areas (https://harvard-cga.maps.arcgis.com/apps/webappviewer/index.html?id=08f6e885c71b457f83cefc71013bcaa7). Cox models (aHR, 95% CI) confirmed that higher SVI, including quartiles 3 (aHR, 0.96 [95% CI, 0.93-0.98]) and 4 (aHR, 0.93 [95% CI, 0.91-0.95]), was associated with delay. Patients from SVI quartile 4 neighborhoods arrived 15.6 minutes [15-16.2] slower than patients from SVI quartile 1. Specific SVI themes associated with delay were a community's socioeconomic status (aHR, 0.80 [95% CI, 0.74-0.85]) and housing type and transportation (aHR, 0.89 [95% CI, 0.84-0.94]). This map of acute stroke presentation times shows areas with a high incidence of delay. Increased social vulnerability characterizes these areas. Such places should be systematically targeted to improve population-level stroke presentation times.

Alemtuzumab induction is associated with decreased hospitalization rates in pediatric kidney transplant: A UNOS data review for safety and outcomes with common induction regimens.

We hypothesized that alemtuzumab use is safe in pediatric kidney transplant recipients (KTRs) with equivalent long-term outcomes compared to other induction agents. Using pediatric kidney transplant recipient data in the UNOS database between January 1, 2000, and June 30, 2022, multivariate logistic regression, multivariable Cox regression, and survival analyses were utilized to estimate the likelihoods of 1st-year and all-time hospitalizations, acute rejection, CMV infection, delayed graft function (DGF), graft loss, and patient mortality among recipients of three common induction regimens (ATG, alemtuzumab, and basiliximab). There were no differences in acute rejection or graft failure among induction or maintenance regimens. Basiliximab was associated with lower odds of DGF in deceased donor recipients (OR 0.77 [0.60-0.99], p = .04). Mortality was increased in patients treated with steroid-containing maintenance (HR 1.3 [1.005-1.7] p = .045). Alemtuzumab induction correlated with less risk of CMV infection than ATG (OR 0.76 [0.59-0.99], p = .039). Steroid-containing maintenance conferred lower rate of PTLD compared to steroid-free maintenance (HR 0.59 [0.4-0.8] p = .001). Alemtuzumab was associated with less risk of hospitalization within 1 year (OR 0.79 [0.67-0.95] p = .012) and 5 years (HR 0.54 [0.46-0.65] p < .001) of transplantation. Steroid maintenance also decreased 5 years hospitalization risk (HR 0.78 [0.69-0.89] p < .001). Pediatric KTRs may be safely treated with alemtuzumab induction without increased risk of acute rejection, DGF, graft loss, or patient mortality. The decreased risk of CMV infections and lower hospitalization rates compared to other agents make alemtuzumab an attractive choice for induction in pediatric KTRs, especially in those who cannot tolerate ATG.

Identification of Stem Cell-related Gene Markers by Comprehensive Transcriptome Analysis to Predict the Prognosis and Immunotherapy of Lung Adenocarcinoma.

Cancer stem cells (CSCs) contribute to metastasis and drug resistance to immunotherapy in lung adenocarcinoma (LUAD), so the stemness evaluation of cancer cells is of great significance. The single-cell RNA sequencing (scRNA-seq) data of the GSE149655 dataset were collected and analyzed. Malignant cells were distinguished by CopyKAT. CytoTRACE score of marker genes in malignant cells was counted by CytoTRACE to construct the stemness score formula. Sample stemness score in TCGA was determined by the formula and divided into high-, medium- and low-stemness score groups. LASSO and COX regression analyses were carried out to screen the key genes related to the prognosis of LUAD from the differentially expressed genes (DEGs) in high- and low-stemness score groups and a risk score model was constructed. Seven types of cells were identified from a total of 4 samples, and 193 marker genes of 3455 malignant cells were identified. There were 1098 DEGs between low- and high-stemness score groups of TCGA, of which CPS1, CENPK, GJB3, and TPSB2 constituted gene signatures. The 4-gene signature could independently evaluate LUAD survival in the training and validation sets and showed an acceptable area under the receiver operator characteristic (ROC) curves (AUCs). This study provides insights into the cellular heterogeneity of LUAD and develops a new cancer stemness evaluation indicator and a 4-gene signature as a potential tool for evaluating the response of LUAD to immune checkpoint blockade (ICB) therapy or antineoplastic therapy.

Low subcutaneous adipose tissue and myosteatosis are prognostic factors after allogeneic hematopoietic stem cell transplantation

ObjectiveAllogeneic hematopoietic stem cell transplantation (allo-HSCT) represents the only curative treatment option for several hematological neoplasms. This study aimed to assess the parameters of body composition as predictors of posttransplant overall survival (OS) and adverse events in patients with leukemia, myelodysplastic syndromes (MDS), and myeloproliferative neoplasms (MPN). MethodsThis was a retrospective study of 122 adult patients who underwent their first allo-HSCT. The CT-based semi-automated measurement of subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT), visceral-to-subcutaneous fat ratio (VSR), sarcopenia in terms of skeletal muscle index (SMI), and myosteatosis based on the skeletal muscle radiation attenuation (SM-RA) was performed. Cox regression analysis was used to assess the association of body composition parameters with OS. ResultsIn the univariate analysis, low SAT and myosteatosis were associated with lower OS (hazard ratio [HR] 2.02, 95% confidence interval [CI] 1.16–3.51, p = 0.01) and (HR 2.50, 95% CI 1.48 – 4.25, p=< 0.001), respectively. This association remained significant after adjusting for relevant covariates, with HR 2.32, 95% CI 1.23 – 4.38, p=0.01 and HR 2.86, 95% CI 1.51 – 5.43, p=< 0.001, respectively. On the contrary, VAT, VSR, sarcopenia, and sarcopenic obesity were not statistically significant in OS. Severe post-transplant adverse events were more common in the low SAT group (odds ratio [OR] 3.12, 95% CI 1.32– 7.40, p=0.01) and OR 3.17, 95% CI 1.31 – 7.70, p=< 0.01 in the age- and sex-adjusted analysis. ConclusionLow SAT and myosteatosis may contribute to an increased risk of mortality, while low SAT appears to increase the risk of severe post-transplant adverse events.

Suppression of N-Glycosylation of Zinc Finger Protein 471 Affects Proliferation, Invasion, and Docetaxel Sensitivity of Tongue Squamous Cell Carcinoma via Regulation of c-Myc

Zinc finger protein 471 (ZNF471) is a member of the Krüppel-related domain zinc finger protein family, and has recently attracted attention because of its anti-cancer effects. N-glycosylation regulates expression and functions of the protein. This study aimed to investigate the effects of ZNF471 N-glycosylation on the proliferation, invasion, and docetaxel sensitivity of tongue squamous cell carcinoma (TSCC). It analyzed the expression, function, and prognostic significance of ZNF471 in TSCC using bioinformatics techniques such as gene differential expression analysis, univariate Cox regression analysis, functional enrichment analysis, and gene set enrichment analysis. Using site-specific mutagenesis, this study generated three mutant sites for ZNF471 N-glycosylation to determine the effect of N-glycosylation on ZNF471 protein levels and function. Quantitative real-time PCR, Western blot analysis, and immunohistochemistry tests confirmed the down-regulation of ZNF471 expression in TSCC. Low expression of ZNF471 is associated with poor prognosis of patients with TSCC. Overexpression of ZNF471 invitro retarded the proliferation of TSCC cells and suppressed cell invasion and migration ability. Asparagine 358 was identified as a N-glycosylation site of ZNF471. Suppressing N-glycosylation of ZNF471 enhanced the protein stability and promoted the translocation of protein to the cell nucleus. ZNF471 binding to c-Myc gene promoter suppressed oncogene c-Myc expression, thereby playing the anti-cancer effect and enhancing TSCC sensitivity to docetaxel. In all, N-glycosylation of ZNF471 affects the proliferation, invasion, and docetaxel sensitivity of TSCC via regulation of c-Myc.

Noninvasive Pressure-Volume Loops Predict Major Adverse Cardiac Events in Heart Failure With Reduced Ejection Fraction

BackgroundHeart failure with reduced ejection fraction (HFrEF) is characterized by ventricular remodeling and impaired myocardial energetics. Left ventricular pressure-volume (PV) loop analysis can be performed noninvasively using cardiovascular magnetic resonance (CMR) imaging to assess cardiac thermodynamic efficiency. ObjectivesThe aim of the study was to investigate whether noninvasive PV loop parameters, derived from CMR, could predict major adverse cardiac events (MACE) in HFrEF patients. MethodsPV loop parameters (stroke work, ventricular efficiency, external power, contractility, and energy per ejected volume) were computed from CMR cine images and brachial blood pressure. The primary end point was MACE (cardiovascular death, heart failure (HF) hospitalization, myocardial infarction, revascularization, ventricular tachycardia/fibrillation, heart transplantation, or left ventricular assist device implantation within 5 years). Associations between PV loop parameters and MACE were evaluated using multivariable Cox regression. ResultsOne hundred and sixty-four HFrEF patients (left ventricular ejection fraction ≤40%, age 63 [IQR: 55-70] years, 79% male) who underwent clinical CMR examination between 2004 and 2014 were included. Eighty-eight patients (54%) experienced at least one MACE after an average of 2.8 years. Unadjusted models demonstrated a significant association between MACE and all PV loop parameters (P < 0.05 for all), HF etiology (P < 0.001), left ventricular ejection fraction (P = 0.003), global longitudinal strain (P < 0.001), and N-terminal prohormone of brain natriuretic peptide level (P = 0.001). In the multivariable Cox regression analysis adjusted for age, sex, hypertension, diabetes, and HF etiology, ventricular efficiency was associated with MACE (HR: 1.04 (95% CI: 1.01-1.08) per-% decrease, P = 0.01). ConclusionsVentricular efficiency, derived from noninvasive PV loop analysis from standard CMR scans, is associated with MACE in patients with HFrEF.

Association between the stress-hyperglycemia ratio and all-cause mortality in community-dwelling populations: An analysis of the National Health and Nutrition Examination Survey (NHANES) 1999-2014.

Reportedly, the stress-hyperglycemia ratio (SHR) is closely associated with poor prognosis in patients with severe acute disease. However, the community-dwelling may also be in a state of stress due to environmental exposure. Our study aimed to explore the association between SHR and all-cause mortality in the community-dwelling population. A total of 18 480 participants were included out of 82 091 from the NHANES 1999-2014 survey. The Kaplan-Meier survival analyses were used to assess the disparities in survival rates based on SHR, and the log-rank test was employed to investigate the distinctions between groups. The multivariate Cox regression analysis and restricted cubic spline (RCS) analysis were performed to assess the association of SHR with all-cause mortality. A subgroup analysis was also conducted. A total of 3188 deaths occurred during a median follow-up period of 11.0 (7.7; 15.4) years. The highest risk for all-cause mortality was observed when SHR≤ 0.843 or SHR ≥0.986 (log-rank p < .001). After adjusting for the confounding factors, compared with subjects in the second SHR quartile (Q2), participants in the highest (Q4, adjusted hazard ratio [HR] 1.49, 95% confidence interval [CI] 1.28-1.73) and lowest quartiles (Q1, adjusted HR 1.37, 95% CI 1.16-1.60) have a higher probability of all-cause death. The RCS observed a dose-response U-shaped association between SHR and all-cause mortality. The U-shaped association between SHR and all-cause mortality was similar across subgroup analysis. The SHR was significantly associated with all-cause mortality in the community-dwelling population, and the relationship was U-shaped.

The prognostic nutritional index as a predictor of efficacy and early recurrence for adjuvant transarterial chemoembolization in hepatocellular carcinoma.

Postoperative adjuvant transcatheter arterial chemoembolization (TACE) can prevent recurrence of hepatocellular carcinoma (HCC) in certain patients. This study aimed to identify the potential beneficiaries of adjuvant TACE. 477 patients who underwent curative resection for HCC were enrolled in this retrospectively cohort study. The trajectory of the prognostic nutritional index (PNI) during the perioperative period was fitted using a latent-class growth mixed model. The association between adjuvant TACE and recurrence-free survival in each PNI group was assessed using the Kaplan-Meier curve. Furthermore, Cox regression analysis was conducted to identify the risk factors for early recurrence after adjuvant TACE and develop a nomogram model. Patients in the PNI group III had a high risk of recurrence and could benefit from adjuvant TACE (P = 0.009). The prognostic prediction model for adjuvant TACE (PAT) incorporated eight variables (PNI, tumor size, tumor number, vascular invasion, sex, aspartate aminotransferase, gamma-glutamyl transferase, and degree of differentiation). Patients with PAT scores > 330 and 235-330 had significantly higher recurrence rates than those with PAT scores < 235 (P < 0.001). PNI may help guide the selection of adjuvant TACE beneficiaries. PAT demonstrated a high accuracy in predicting the prognosis of patients who underwent postoperative TACE.

Circulating metabolic biomarkers and risk of new-onset hypertension: findings from the UK Biobank.

The evidence regarding the associations of circulating metabolic biomarkers with hypertension risk is scarce. We aimed to examine the associations between circulating metabolites and risk of hypertension. We included 49 422 individuals free of hypertension at baseline with a mean (SD) age of 53.5 (8.0) years from the UK Biobank. Nuclear magnetic resonance spectroscopy was used to quantify 143 individual metabolites. Multivariable-adjusted Cox regression models were used to estimate hazard ratios and 95% confidence intervals (CIs). During a mean (SD) follow-up of 11.2 (1.8) years, 2686 incident hypertension cases occurred. Out of 143 metabolites, 76 were associated with incident hypertension, among which phenylalanine (hazard ratio: 1.40; 95% CI: 1.24-1.58) and apolipoprotein A1 (hazard ratio: 0.76; 95% CI: 0.66-0.87) had the strongest association when comparing the highest to the lowest quintile. In general, very-low-density lipoprotein (VLDL) particles were positively, whereas high-density lipoprotein (HDL) particles were inversely associated with risk of hypertension. Similar patterns of cholesterol, phospholipids, and total lipids within VLDL and HDL particles were observed. Triglycerides within all lipoproteins were positively associated with hypertension risk. Other metabolites showed significant associations with risk of hypertension included amino acids, fatty acids, ketone bodies, fluid balance and inflammation markers. Adding 10 selected metabolic biomarkers to the traditional hypertension risk model modestly improved discrimination (C-statistic from 0.745 to 0.752, P < 0.001) for prediction of 10-year hypertension incidence. Among UK adults, disturbances in metabolic biomarkers are associated with incident hypertension. Comprehensive metabolomic profiling may provide potential novel biomarkers to identify high-risk individuals.

Detectable troponin below the 99th percentile predicts survival in patients undergoing coronary angiography

BackgroundCardiac troponin I (cTnI) above the 99th percentile is associated with an increased risk of major adverse events. Patients with detectable cTnI below the 99th percentile are a heterogeneous group with a less well-defined risk profile. The purpose of this study is to investigate the prognostic relevance of detectable cTnI below the 99th percentile in patients undergoing coronary angiography. MethodsThe study included 14,776 consecutive patients (mean age of 65.4 ± 12.7 years, 71.3 % male) from the Essen Coronary Artery Disease (ECAD) registry. Patients with cTnI levels above the 99th percentile and patients with ST-segment elevation acute myocardial infarction were excluded. All-cause mortality was defined as the primary endpoint. ResultsDetectable cTnI below the 99th percentile was present in 2811 (19.0 %) patients, while 11,965 (81.0 %) patients were below detection limit of the employed assay. The mean follow-up was 4.25 ± 3.76 years. All-cause mortality was 20.8 % for patients with detectable cTnI below the 99th percentile and 15.0 % for those without detectable cTnI. In a multivariable Cox regression analysis, detectable cTnI was independently associated with all-cause mortality with a hazard ratio of 1.60 (95 % CI 1.45–1.76; p < 0.001). There was a stepwise relationship with increasing all-cause mortality and tertiles of detectable cTnI levels with hazard ratios of 1.63 (95 % CI 1.39–1.90) for the first tertile to 2.02 (95 % CI 1.74–2.35) for the third tertile. ConclusionsDetectable cTnI below the 99th percentile is an independent predictor of mortality in patients undergoing coronary angiography with the risk of death growing progressively with increasing troponin levels.

The effects of diabetes, hypertension and subsequent health control behavior on the survival of a Taiwan cohort aged over 50 years

PurposeThis study used the Taiwan Longitudinal Study in Aging from 1996 to 2011 to investigate the effects of diabetes, hypertension, and healthy living behaviors of those aged over 50 years on the survival status in Taiwan. MethodsAmong the 5,131 participants aged 50 years and above in the 1996 survey were included in this study. Cox’s proportional hazards model was used to examine the incidence of diabetes, hypertension, and related mortality risk in those aged over 50 years. ResultsAfter adjusting for age, gender, education level, diabetes, hypertension, health behavior, and leisure activity, results from the Cox model show that the elderly without diabetes have a lower mortality risk than those with diabetes. Regular exercise was associated with a lower risk of mortality. The hazard ratios of elderly with regular exercise were 0.78 (95 % CI: 0.64–0.96) for two times a week or less, 0.81 (95 % CI: 0.69–0.96) for 3–5 times a week, and 0.84 (95 % CI: 0.77–0.93) for 6 + times a week, respectively. On the other hand, leisure activity positively reduces mortality risk. For example, the hazard ratios of the elderly with watching TV and reading were 0.63 (95 % CI: 0.55–0.72) and 0.80 (95 % CI: 0.72–0.89), respectively. Moreover, smoking can increase mortality risk 23 % whether the elderly are with diabetes or hypertension or not. ConclusionsRegarding preventing and controlling chronic diseases in the future, continuously encouraging improvement in health behavior and engaging in leisure activities for the middle-aged and over should be considered essential markers.

Association of Life’s Essential 8 and Simple 7 Scores With Mortality: Comparison With Pooled Cohort Equation

BackgroundIn 2022, the Life’s Simple 7 (LS7) score was replaced with the Life’s Essential 8 (LE8) score as a tool to measure cardiovascular health. The risk prediction values of LE8 and LS7 scores for mortality have not been compared. Additionally, the risk prediction value of these scores has not been compared with the pooled cohort equations (PCE) in individuals aged 40 to 79 years. ObjectivesThis study compared the risk prediction value of the: 1) LE8 and LS7 scores in the overall population; and 2) LE8 score, LS7 score, and PCE in the 40- to 79-year-old age group for all-cause and cardiovascular mortality in a nationally representative US population. MethodsThe LS7 and LE8 scores and the PCE were calculated in the National Health and Nutrition Examination Survey cycles 2007 to 2018. All-cause and cardiovascular mortality were identified by linking the participants to the National Death Index. The C-statistics of the respective weighted Cox models were used to compare the risk prediction value of the standardized scores. ResultsAmong 21,721 individuals included, the C-statistics for all-cause mortality were 0.823 (95% CI: 0.803-0.843) and 0.819 (95% CI: 0.799-0.838) in the LE8 and LS7 score-based models, respectively. The C-statistics for cardiovascular mortality were 0.887 (95% CI: 0.857-0.905) for the LE8 score-based model and 0.883 (95% CI: 0.861-0.905) for the LS7 score-based model. Among 12,943 individuals aged 40 to 79 years, the C-statistics for the outcome of all-cause mortality were 0.756 (95% CI: 0.732-0.779), 0.674 (95% CI: 0.646-0.701), and 0.681 (95% CI: 0.656-0.706) for the PCE, LS7 score, and LE8 score-based models, respectively. ConclusionsThe LS7 and LE8 scores had similar risk prediction values for all-cause and cardiovascular mortality. Among 40- to 79-year-old individuals, the PCE had better risk discrimination in the LE8 and LS7 scores in predicting all-cause mortality.

Healthy lifestyle change and all-cause and cancer mortality in the European Prospective Investigation into Cancer and Nutrition cohort

BackgroundHealthy lifestyles are inversely associated with the risk of noncommunicable diseases, which are leading causes of death. However, few studies have used longitudinal data to assess the impact of changing lifestyle behaviours on all-cause and cancer mortality.MethodsWithin the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, lifestyle profiles of 308,497 cancer-free adults (71% female) aged 35–70 years at recruitment across nine countries were assessed with baseline and follow-up questionnaires administered on average of 7 years apart. A healthy lifestyle index (HLI), assessed at two time points, combined information on smoking status, alcohol intake, body mass index, and physical activity, and ranged from 0 to 16 units. A change score was calculated as the difference between HLI at baseline and follow-up. Associations between HLI change and all-cause and cancer mortality were modelled with Cox regression, and the impact of changing HLI on accelerating mortality rate was estimated by rate advancement periods (RAP, in years).ResultsAfter the follow-up questionnaire, participants were followed for an average of 9.9 years, with 21,696 deaths (8407 cancer deaths) documented. Compared to participants whose HLIs remained stable (within one unit), improving HLI by more than one unit was inversely associated with all-cause and cancer mortality (hazard ratio [HR]: 0.84; 95% confidence interval [CI]: 0.81, 0.88; and HR: 0.87; 95% CI: 0.82, 0.92; respectively), while worsening HLI by more than one unit was associated with an increase in mortality (all-cause mortality HR: 1.26; 95% CI: 1.20, 1.33; cancer mortality HR: 1.19; 95% CI: 1.09, 1.29). Participants who worsened HLI by more than one advanced their risk of death by 1.62 (1.44, 1.96) years, while participants who improved HLI by the same amount delayed their risk of death by 1.19 (0.65, 2.32) years, compared to those with stable HLI.ConclusionsMaking healthier lifestyle changes during adulthood was inversely associated with all-cause and cancer mortality and delayed risk of death. Conversely, making unhealthier lifestyle changes was positively associated with mortality and an accelerated risk of death.

Survival benefit of postoperative radioiodine therapy among patients with intermediate-risk differentiated thyroid carcinoma.

The 2015 American Thyroid Association (ATA) guidelines proposed the use of the ATA Risk Stratification System and American Joint Committee on Cancer Tumor-Node-Metastasis (AJCC/TNM) Staging System for postoperative radioiodine decision-making. However, the management of patients with intermediate-risk differentiated thyroid carcinoma (DTC) is not well defined. In this study, we aimed to evaluate the therapeutic efficacy of radioactive iodine therapy (RAIT) among various subgroups of patients with intermediate-risk DTC after surgery. This was a retrospective study based on the Surveillance, Epidemiology, and End Results (SEER) database (2010-2015). The DTC patients with intermediate risk of recurrence were divided into two groups (treated or not treated with radioactive iodine (RAI)). As the treatment was not randomly assigned, stabilized inverse probability treatment weighting (sIPTW) was used to reduce selection bias. We used the Kaplan-Meier method and log-rank test to analyze overall survival (OS) and cancer-specific survival (CSS). Kaplan-Meier analysis after sIPTW found a significant difference in OS and CSS between no RAIT and RAIT (log-rank test, P < 0.0001; P = 0.0019, respectively). The Kaplan-Meier curves of CSS in age cutoff of 55 years showed a significant association between no RAIT and RAIT (log-rank test, P = 0.0045). Univariate and multivariate Cox regression showed RAIT was associated with a reduced risk of mortality compared with no RAIT (hazard ratio [HR] 0.59, 95% confidence interval [95% CI 0.44-0.80]). Age (≥ 55) years showed a worse CSS regardless of whether or not a patient was treated or not treated with RAI ([HR] 8.91, 95% confidence interval [95% CI 6.19-12.84]). RAIT improves OS and CSS in patients with intermediate-risk DTC after surgery. 55 years is a more appropriate prognostic age cutoff for the relevant classification systems and is a crucial consideration in RAI decision-making. Therefore, we need individualized treatment plans.