Identifying young adults at high risk of cardiometabolic disease using cluster analysis and the Framingham 30-yr risk score

Background and aimsCurrent strategies to reduce cardiovascular disease (CVD) risk in young adults are largely limited to those at extremes of risk. In cohort studies we have shown cluster analysis identified a large sub-group of adolescents with multiple risk factors. This study examined if individuals classified at ‘high-risk’ by cluster analysis could also be identified by their Framingham risk scores.Methods and resultsRaine Study data at 17- (n = 1048) and 20-years (n = 1120) identified high- and low-risk groups by cluster analysis using continuous measures of systolic BP, BMI, triglycerides and insulin resistance. We assessed:- CVD risk at 20-years using the Framingham 30 yr-risk-score in the high- and low-risk clusters, and cluster stability from adolescence to adulthood.Cluster analysis at 17- and 20-years identified a high-risk group comprising, 17.9% and 21.3%, respectively of the cohort. In contrast, only 1.2% and 3.4%, respectively, met the metabolic syndrome criteria, all of whom were within the high-risk cluster. Compared with the low-risk cluster, Framingham scores of the high-risk cluster were elevated in males (9.4%; 99%CI 8.3, 10.6 vs 6.0%; 99%CI 5.7, 6.2) and females (4.9%; 99%CI 4.4, 5.4 vs 3.2%; 99%CI 3.0, 3.3) (both P < 0.0001). A score >8 for males and >4 for females identified those at high CVD risk with 99% confidence.ConclusionCluster analysis using multiple risk factors identified ～20% of young adults at high CVD risk. Application of our Framingham 30 yr-risk cut-offs to individuals allows identification of more young people with multiple risk factors for CVD than conventional metabolic syndrome criteria.     

托特罗定联合奥昔布宁治疗膀胱过度活动症的疗效及对患者焦虑评分的影响

目的：观察托特罗定联合奥昔布宁治疗膀胱过度活动症的疗效,关注治疗后患者焦虑评分,以期为临床工作提供帮助。方法选取医院收治的144例膀胱过度活动症患者作为研究对象,应用随机区组的原则分为观察组和对照组各72例,对照组应用托特罗定进行治疗,观察组应用托特罗定联合奥昔布宁进行治疗,观察治疗效果。同时应用焦虑自评量表评价治疗后患者的焦虑评分。结果观察组总有效率为98．61％明显高于对照组的90．28％,且治疗后焦虑评分明显低于对照组,差异均有统计学意义（P＜0．05）。结论托特罗定联合奥昔布宁治疗膀胱过度活动症患者的疗效明显,同时能更有效地减少患者的焦虑情绪,临床治疗中可以积极应用。     

Forecasting mortality: dynamic assessment of risk in ST-segment elevation acute myocardial infarction.

AIMS: To demonstrate the feasibility and clinical utility of developing dynamic risk assessment models for ST-segment elevation myocardial infarction (STEMI) patients. METHODS AND RESULTS: In 6066 STEMI patients enrolled in the Assessment of the Safety and Efficacy of a New Thrombolytic-3 (ASSENT-3) trial with complete electrocardiographic data, we assessed the probability of 30-day mortality over the following forecasting periods beginning at day 0 (baseline), 3 h, day 2, and day 5 using multiple-logistic regression. These models were validated and simplified in independent samples of 1622 similar fibrinolytic-treated patients from the ASSENT-3 PLUS trial and in 814 STEMI patients undergoing primary percutaneous coronary intervention in the COMplement inhibition in Myocardial infarction treated with Angioplasty (COMMA) trial. The discriminatory power of these predictive models, from baseline to day 5, was excellent (c-statistics 0.80 to 0.87); and their predictive ability was supported by strong gradients in mortality outcomes as the risk score increased. Dynamic modelling also provided information on the change in prognosis over time which may be used to advise more appropriate therapeutic decisions, e.g. the identification of high-risk patients for possible co-interventions. CONCLUSION: Dynamic modelling for STEMI patients enhances the risk assessment and stratification and should provide valuable ongoing guidance for their management.     

Performance of stent thrombosis and bleeding risk scores in out-of-hospital cardiac arrest due to acute coronary syndromes

BackgroundPatients with out-of-hospital cardiac arrest (OHCA) due to acute coronary syndromes (ACS) who undergo percutaneous coronary intervention (PCI) are at high risk of bleeding and thrombosis. While predictive bleeding and stent thrombosis risk scores have been established, their performance in patients with OHCA has not been evaluated.MethodsAll consecutive patients admitted for OHCA due to ACS who underwent PCI between January 2007 and December 2019 were included. The ACTION and CRUSADE bleeding risk scores and the Dangas score for early stent thrombosis risk were calculated for each patient. A C-statistic analysis was performed to assess the performance of these scores.ResultsAmong 386 included patients, 82 patients (21.2%) experienced severe bleeding and 30 patients (7.8%) experienced stent thrombosis. The predictive performance of the ACTION and CRUSADE bleeding risk scores for major bleeding was poor, with areas under the curve (AUCs) of 0.596 and 0.548, respectively. Likewise, the predictive performance of the Dangas stent thrombosis risk score was poor (AUC 0.513). Using multivariable analysis, prolonged low-flow (odds ratio [OR] 1.03, 95% confidence interval [CI] 1.00–1.05; P = 0.025), reduced haematocrit or fibrinogen at admission (OR 0.93, 95% CI 0.88–0.98; P = 0.010 and OR 0.61; 95% CI 0.41–0.89; P = 0.012, respectively) and the use of glycoprotein IIb/IIIa inhibitors (OR 2.10, 95% CI 1.18–3.73; P = 0.011) were independent risk factors for major bleeding.ConclusionThe classic bleeding and stent thrombosis risk scores have poor performance in a population of patients with ACS complicated by OHCA. Other predictive factors might be more pertinent to determine major bleeding and stent thrombosis risks in this specific population.     

克唑替尼联合PC方案治疗非小细胞肺癌的临床研究

目的 探讨克唑替尼联合PC方案治疗非小细胞肺癌的临床疗效。方法 选择2016年1月—2018年12月新疆喀什地区第二人民医院治疗的64例非小细胞肺癌患者作为研究对象。用抽签法随机将患者分为对照组和观察组,每组各32例。对照组每天静脉滴入注射用培美曲塞二钠,500 mg/m²,静滴时间超过10 min,并静脉滴入卡铂注射液,AUC5静滴时间超过30 min。观察组在对照组的基础上口服克唑替尼胶囊,250 mg/次,2次/d。1个周期为21 d,两组共治疗2个周期。观察两组患者的临床疗效,同时比较两组患者治疗前后的血清癌胚抗原（CEA）、神经元特异性烯醇化酶（NSE）、人鳞状细胞癌相关抗原（SCCAg）以及细胞角蛋白19片段（Cyfra21-1）水平和Karnofsky功能状态评分量表（KPS）评分情况。结果 治疗后,观察组总有效率为81.25%,明显高于对照组的59.37%（P<0.05）。两组治疗后的NSE、CEA、SCCAg和CYFRA21-1水平均明显降低（P<0.05）,且观察组上述肿瘤标志物水平明显低于对照组（P<0.05）。治疗后,观察组的生活质量好转率明显高于对照组,恶化率明显低于对照组（P<0.05）。结论 克唑替尼联合PC方案治疗非小细胞肺癌患者的疗效显著,能明显降低肿瘤标志物水平,提高生活质量。     

The pattern and prognostic relevance of immune activity scores and tumor-infiltrating immune cells in metastatic clear cell renal cell carcinoma: Evidence from multiple datasets

PurposeTo investigate the immune activity scores (IAS) and tumor-infiltrating immune cells (TIIC) in metastatic clear cell renal cell carcinoma (mccRCC) patients and to explore their patterns and potential prognostic values.MethodsThe gene expression profiles and clinical information of ccRCC patients from multiple Gene Expression Omnibus (GEO) datasets and TCGA were used as study cohorts. Overall, 3 sets of 69 variables associated with tumor-immune interactions were collected from several tumor immunophenotype analysis websites. Least absolute shrinkage and selection operator (LASSO) and area under receiver operating characteristic (AUC) analyses were performed to establish and evaluate the predictive models.ResultsSeveral TIIC and IAS variables are significantly different between patients and between different sites within the same patient. The AUC of the multivariable logistic models based on IAS and the two TIIC groups is 0.705 (95%CI 0.643–0.766), 0.719 (95%CI 0.650–0.788), and 0.685 (95%CI 0.623–0.747), respectively. The AUC of the LASSO model is 0.715 (95%CI 0.652–0.777). Certain subtypes identified by the consensus clustering method show a favorable OS (log-rank, p < 0.01) in both nonmetastatic and metastatic ccRCC patients.ConclusionIAS and TIIC could vary between patients and different sites within the same patient, and distinct patterns of these variables could correlate with clinical features. Heterogeneity might exist in the biological process of metastasis. LASSO logistic regression reveals that the infiltration of two TIICs would be a predictor of metastatic ccRCC. Last, certain subtypes may have a better prognosis in both ccRCC and mccRCC patients.     

Serum nuclear factor IB as a novel and noninvasive indicator in the diagnosis of secondary hyperparathyroidism

BackgroundChronic renal failure (CRF) referred to chronic progressive renal parenchymal damage caused by various causes, with metabolite retention and imbalance of water, electrolyte, and acid‐base balance as the main clinical manifestations. Secondary hyperparathyroidism (sHPT) was a common complication in maintenance hemodialysis patients with CRF. Nuclear factor IB (NFIB) was a newly found tumor suppressor gene in various cancers. The present study aimed to illustrate the role of NFIB in sHPT clinical diagnosis and treatment response.MethodsA retrospective, case‐control study, including 189 patients with sHPT and 106 CRF patients without sHPT, compared with 95 controls. Serum NFIB and 1,25(OH)₂D₃ levels were measured by RT‐qPCR and ELISAs, respectively. ROC analysis was conducted to verify the diagnostic value of NFIB in sHPT. Spearman''s correlation analysis was conducted to verify the association between NFIB and bone mineral density (BMD) scores. After 6 months of treatment, the variance of NFIB and 1,25(OH)₂D₃ in different groups was recorded.ResultsThe expression of NFIB was significantly lower in serum samples from sHPT and non‐sHPT CRF patients, compared to controls. Clinicopathological information verified sHPT was associated with NFIB, parathyroid hormone (PTH), serum calcium, serum phosphorus, time of dialysis, and serum 1,25(OH)₂D₃ levels. Spearman''s correlation analysis illustrated the positive correlation between NFIB levels and BMD scores. At receiver operator characteristic (ROC) curve analysis, the cutoff of 1.6508 for NFIB was able to identify patients with sHPT from healthy controls; meanwhile, NFIB could also discriminate sHPT among CRF patients as well (cutoff = 1.4741). Furthermore, we found that during 6 months of treatment, NFIB levels were gradually increased, while PTH and serum P levels were decreased.ConclusionsSerum NFIB was a highly accurate tool to identify sHPT from healthy controls and CRF patients. Due to its simplicity, specificity, and sensitivity, this candidate can be proposed as a first‐line examination in the diagnostic workup in sHPT.     

Early detection of intensive care needs and mortality risk by use of five early warning scores in patients with traumatic injuries: An observational study

ObjectiveThe purpose of this research was to evaluate the predictive capacity of five Early Warning Scores in relation to the clinical evolution of adult patients with different types of trauma.Research MethodologyWe conducted a longitudinal, prospective, observational study, calculating the Early Warning Scores [Modified Early Warning Score (MEWS), National Early Warning Score 2 (NEWS-2), VitalPAC Early Warning Score (ViEWS), Modified Rapid Emergency Medicine Score (MREMS), and Rapid Acute Physiology Score (RAPS)] upon arrival of patients to the emergency department.SettingIn total, 445 cases of traumatic injuries were included in the study.Main Outcome MeasuresThe predictive capacity was verified with the data on admission to intensive care units (ICU) and mortality at two, seven and 30 days.Results201 patients were hospitalized and 244 were discharged after being attended in the emergency department. 91 cases (20.4%) required ICU care and 4.7% of patients died (21 patients) within two days, 6.5% (29 patients) within seven days and 9.7% (43 patients) within 30 days. The highest area under the curve for predicting the need for ICU care was obtained by the National Early Warning Score 2 and the VitalPAC Early Warning Score. For predicting mortality, the Modified Rapid Emergency Medicine Score obtained the best scores for two-day mortality, seven-day mortality and 30-day mortality.ConclusionsEvery Early Warning Score analyzed in this study obtained good results in predicting adverse effects in adult patients with traumatic injuries, creating an opportunity for new clinical applications in the emergency department.     

Sortilin receptor 1 predicts longitudinal cognitive change

The gene encoding sortilin receptor 1 (SORL1) has been associated with Alzheimer's disease risk. We examined 15 SORL1 variants and single nucleotide polymorphism (SNP) set risk scores in relation to longitudinal verbal, spatial, memory, and perceptual speed performance, testing for age trends and sex-specific effects. Altogether, 1609 individuals from 3 population-based Swedish twin studies were assessed up to 5 times across 16 years. Controlling for apolipoprotein E genotype (APOE), multiple simple and sex-moderated associations were observed for spatial, episodic memory, and verbal trajectories (p = 1.25E-03 to p = 4.83E-02). Five variants (rs11600875, rs753780, rs7105365, rs11820794, rs2070045) were associated across domains. Notably, in those homozygous for the rs2070045 risk allele, men demonstrated initially favorable performance but accelerating declines, and women showed overall lower performance. SNP set risk scores predicted spatial (Card Rotations, p = 5.92E-03) and episodic memory trajectories (Thurstone Picture Memory, p = 3.34E-02), where higher risk scores benefited men's versus women's performance up to age 75 but with accelerating declines. SORL1 is associated with cognitive aging, and might contribute differentially to change in men and women.