Relationship between pulmonary hypertension and cardiovascular events, all-cause death in maintenance hemodialysis patients

Objective: To determine the impact of pulmonary hypertension (PH) on maintenance hemodialysis (MHD) patients' cardiovascular events and all-cause mortality. Methods: We included 90 MHD patients, divided into group with PH and group without PH. All patients had been followed up for 4 years, and the primary endpoints were all cause mortality and cardiovascular events. We compared the clinical data and the endpoint events between the two groups. Results: We found PH in 37 patients (41.11%). The incidence of previous cardiovascular disease in group with PH was significantly higher than that in group without PH (χ2=2.034, P < 0.05). The left atrial diameter in group with PH was significantly higher than that in group without PH (t = 7.265, P < 0.01). Logistic regression analysis revealed that previous cardiovascular disease and left atrial diameter were the independent determinants of PH. The rate of new cardiovascular events in group with PH(59.5%) was significantly higher than that in group without PH(34%) (χ2=9.203, P < 0.05). The associated variables of cardiovascular events were:systolic pulmonary arterial pressure, age, history cardiovascular disease, hs-CRP, ejection fraction, left ventricular diastolic dysfunction. In a multivariate model, the PH maintained its independent association. The mortality rate in group with PH (48.6%) was significantly higher than that in group without PH (26.4%) (χ2=5.049, P <0.05). In the Cox survival analysis, we found an association between mortality and systolic pulmonary arterial pressure, age, previous cardiovascular disease, Alb, ejection fraction. In a multivariate model the PH remains as independent predictor of mortality. Conclusion:Pulmonary hypertension is common in HD patients and a valuable predictor of mortality and cardiovascular events.

Immune-related adverse events induced by programmed death protein-1 inhibitors from the perspective of lymphoma immunotherapy

Lymphoma,which is highly malignant,stems from lymph nodes and lymphoid tissue.Lymphoma cells express programmed death-ligand 1/2(PD-L1/PD-L2),which binds with programmed cell death 1 protein(PD-1)to establish inhibitory signaling that impedes the normal function of T cells and allows tumor cells to escape immune system surveillance.Recently,immune checkpoint inhibitor immunotherapies such as PD-1 inhibitors(nivolumab and pembrolizumab)have been introduced into the lymphoma treatment algorithm and have shown remarkable clinical efficacy and greatly improve prognosis in lymphoma patients.Accordingly,the number of lymphoma patients who are seeking treatment with PD-1 inhibitors is growing annually,which results in an increasing number of patients developing immune-related adverse events(irAEs).The occurrence of irAEs inevitably affects the benefits provided by immunotherapy,particularly when PD-1 inhibitors are applied.However,the mechanisms and characteristics of irAEs induced by PD-1 inhibitors in lymphoma need further investigation.This review article summarizes the latest research advances in irAEs during treatment of lymphoma with PD-1 inhibitors.A comprehensive understanding of irAEs incurred in immunotherapy can help to achieve better efficacy with PD-1 inhibitors in lymphoma.

The relationships between step count and all-cause mortality and cardiovascular events:A doseresponse meta-analysis

Background:A goal of 10,000 steps per day is widely advocated,but there is little evidence to support that goal.Our purpose was to examine the doseresponse relationships between step count and all-cause mortality and cardiovascular disease risk.Methods:Cochrane Central Register of Controlled Trials,EMBASE,OVID,PubMed,Scopus,and Web of Science databases were systematically searched for studies published before July 9,2021,that evaluated the association between daily steps and at least 1 outcome.Results:Sixteen publications(12 related to all-cause mortality,5 related to cardiovascular disease;and 1 article contained 2 outcomes:both allcause death and cardiovascular events)were eligible for inclusion in the meta-analysis.There was evidence of a nonlinear doseresponse relationship between step count and risk of all-cause mortality or cardiovascular disease(p=0.002 and p=0.014 for nonlinearity,respectively).When we restricted the analyses to accelerometer-based studies,the third quartile had a 40.36%lower risk of all-cause mortality and a 35.05%lower risk of cardiovascular event than the first quartile(all-cause mortality:Q1=4183 steps/day,Q3=8959 steps/day;cardiovascular event:Q1=3500 steps/day,Q3=9500 steps/day;respectively).Conclusion:Our meta-analysis suggests inverse associations between higher step count and risk of premature death and cardiovascular events in middle-aged and older adults,with nonlinear doseresponse patterns.

Predictive Value of Carotid-femoral Pulse Wave Velocity for Major Adverse Cardiovascular Events and All-cause Mortality in Different Age Groups of a Chinese Community

Objective:To investigate the predictive value of carotid-femoral pulse wave velocity(cf-Pw)for assessing major adverse cardiovascular events(MACE)and all-cause mortality in different age groups of a Chinese community.Methods:This is an observational study which enrolled 1,325 individuals from a community in Beijing from September 2007 to October 2018.They were classified based on age into<65-year-old(n=572)and≥65-year-old(n=753)groups,and on cf-PWV into cf-PWV<12 m/s(n=501)and cf-PWV≥12 m/s(n=824)group.The incidence rates of MACE and all-cause mortality were recorded for both the groups during the follow-up period of 9.5 years.The predictive value of cf-PWV for MACE and all-cause mortality in the 2 age groups was estimated using the Cox proportional hazards regression models.Results:The baseline cf-PWV showed positive correlation with age(r=0.462,P<0.001).During the follow-up period,191 MACE and 84 all-cause mortality cases were recorded in the study population.The incidence rates of MACE(χ^(2)=27.196,P<0.001)and all-cause mortality(χ^(2)=9.473,P=0.002)were significantly higher in subjects with cf-PWV≥12 m/s than in subjects with cf-PWV<12 m/s.Cox proportional hazards regression model analyses demonstrated that cf-PWV was an independent risk factor in the<65-year-old group for MACE(hazard ratio:1.310;95%confidence interval:1.007-1.560;P=0.038)and all-cause mortality(hazard ratio:1.412;95%confidence interval:1.133-1.936;P=0.005)after adjusting for several risk factors.However,both univariate and multivariate analyses demonstrated that cf-PWV was not an independent risk factor for MACE or all-cause mortality in the≥65-year-old group(P>0.05).Conclusion:cf-PWV,a measure of arterial stifness,emerged as an independent risk factor for MACE and all-cause mortality insubjectsbelow65yearsofage.

Effectiveness and tolerability of programmed cell death protein-1 inhibitor+chemotherapy compared to chemotherapy for upper gastrointestinal tract cancers

BACKGROUND The combination of programmed cell death protein-1(PD-1)inhibitor and che-motherapy is approved as a standard first-or second-line treatment in patients with advanced oesophageal or gastric cancer.However,it is unclear whether this combination is superior to chemotherapy alone.AIM To assess the comparative effectiveness and tolerability of combining PD-1 inhibitors with chemotherapy vs chemotherapy alone in patients with advanced gastric cancer,gastroesophageal junction(GEJ)cancer,or oesophageal carcinoma.METHODS We searched the PubMed and Embase databases for studies that compared the efficacy and tolerance of PD-1 inhibitors in combination with chemotherapy vs chemotherapy alone in patients with advanced oesophageal or gastric cancer.We employed either random or fixed models to analyze the outcomes of each clinical trial,en-compassing data on overall survival(OS),progression-free survival(PFS),objective response rate,and adverse events(AEs).RESULTS Nine phase 3 clinical trials(7016 advanced oesophageal and gastric cancer patients)met the inclusion criteria.Our meta-analysis demonstrated that the pooled PD-1 inhibitor+chemotherapy group had a significantly longer OS than the chemotherapy-alone group[hazard ratio(HR)=0.76,95%confidence interval(CI):0.71-0.81];the pooled PFS result was consistent with that of OS(HR=0.67,95%CI:0.61-0.74).The count of patients achieving an objective response in the PD-1 inhibitor+chemotherapy group surpassed that of the chemotherapy-alone group[odds ratio(OR)=1.86,95%CI:1.59-2.18].AE incidence was also higher in the combination-therapy group than in the chemotherapy-alone group,regardless of whether≥grade 3 only(OR=1.30,95%CI:1.07-1.57)or all AE grades(OR=1.88,95%CI:1.39-2.54)were examined.We performed a subgroup analysis based on the programmed death-ligand 1(PD-L1)combined positive score(CPS)and noted extended OS and PFS durations within the CPS≥1,CPS≥5,and CPS≥10 subgroups of the PD-1 inhibitor+chemotherapy group.CONCLUSION In contrast to chemotherapy alone,the combination of PD-1 inhibitor and chemotherapy appears to present a more favorable option for initial or subsequent treatment in patients with gastric cancer,GEJ tumor,or oesophageal cancer.This holds true particularly for individuals with PD-L1 CPS scores of≥5 and≥10.

The Use of Lipoprotein-Associated Phospholipase A2 in a Chinese Population to Predict Cardiovascular Events

Objective To explore associations between lipoprotein-associated phospholipase A2(Lp-PLA2)and the risk of cardiovascular events in a Chinese population,with a long-term follow-up.Methods A random sample of 2,031 participants(73.6%males,mean age=60.4 years)was derived from the Asymptomatic Polyvascular Abnormalities Community study(APAC)from 2010 to 2011.Serum Lp-PLA2 levels were determined by enzyme-linked immunosorbent assay(ELISA).The composite endpoint was a combination of first-ever stroke,myocardial infarction(MI)or all-cause death.Lp-PLA2 associations with outcomes were assessed using Cox models.Results The median Lp-PLA2 level was 141.0 ng/m L.Over a median follow-up of 9.1 years,we identified 389 events(19.2%),including 137 stroke incidents,43 MIs,and 244 all-cause deaths.Using multivariate Cox regression,when compared with the lowest Lp-PLA2 quartile,the hazard ratios with95%confidence intervals for developing composite endpoints,stroke,major adverse cardiovascular events,and all-cause death were 1.77(1.24–2.54),1.92(1.03–3.60),1.69(1.003–2.84),and 1.94(1.18–3.18)in the highest quartile,respectively.Composite endpoints in 145(28.6%)patients occurred in the highest quartile where Lp-PLA2(159.0 ng/m L)was much lower than the American Association of Clinical Endocrinologists recommended cut-off point,200 ng/m L.Conclusion Higher Lp-PLA2 levels were associated with an increased risk of cardiovascular event/death in a middle-aged Chinese population.The Lp-PLA2 cut-off point may be lower in the Chinese population when predicting cardiovascular events.

The serum anion gap is associated with disease severity and all-cause mortality in coronary artery disease

Objective To evaluate the associations between the serum anion gap （AG） with the severity and prognosis of coronary artery disease （CAD）. Methods We measured serum electrolytes in 18,115 CAD patients indicated by coronary angiography. The serum AG was calculated according to the equation： AG = Na^＋ [（mmol/L） ＋ K^＋ （mmol/L）] - [Cl^- （mmol/L） ＋ HCO3^- （mmol/L）]. Results A total of 4510 （24.9%） participants had their AG levels greater than 16 mmol/L. The serum AG was independently associated with measures of CAD severity, including more severe clinical types of CAD （P 〈 0.001） and worse cardiac function （P = 0.004）. Patients in the 4th quartile of serum AG （≥ 15.92 mmol/L） had a 5.171-fold increased risk of 30 days all-cause death （P 〈 0.001）. This association was robust, even after adjustment for age, sex, evaluated glomerular filtration rate [hazard ratio （HR）： 4.861, 95% confidence interval （CI）： 2.150–10.993, P 〈 0.001], clinical diagnosis, severity of coronary artery stenosis, cardiac function grades, and other confounders （HR： 3.318, 95% CI： 1.76–2.27, P = 0.009）. Conclusion In this large population-based study, our findings reveal a high percentage of increased serum AG in CAD. Higher AG is associated with more severe clinical types of CAD and worse cardiac function. Furthermore, the increased serum AG is an independent, significant, and strong predictor of all-cause mortality. These findings support a role for the serum AG in the risk-stratification of CAD.

Fatty liver disease:Disparate predictive ability for cardiometabolic risk and all-cause mortality

AIM: To assess the association of a surrogate of fatty liver disease(FLD) with incident type-2 diabetes, coronary heart disease, and all-cause mortality.METHODS: In a prospective population-based study on 1822 middle-aged adults, stratified to gender, we used an algorithm of fatty liver index(FLI) to identify associations with outcomes. An index ≥ 60 indicated the presence of FLD. In Cox regression models, adjusted for age, smoking status, high-density lipoprotein cholesterol, and systolic blood pressure, we assessed the predictive value of FLI for incident diabetes, coronary heart disease(CHD), and all-cause mortality.RESULTS: At a mean 8 year follow-up, 218 and 285 incident cases of diabetes and CHD, respectively, and 193 deaths were recorded. FLD was significantly associated in each gender with blood pressure, total cholesterol, apolipoprotein B, uric acid, and C-reactive protein; weakly with fasting glucose; and inversely with high-density lipoprotein-cholesterol and sex hormonebinding globulin. In adjusted Cox models, FLD was(with a 5-fold HR) the major determinant of diabetes development. Analyses further disclosed significant independent prediction of CHD by FLD in combined gender [hazard ratio(HR) = 1.72, 95% confidence interval(CI): 1.17-2.53] and men(HR = 2.35, 95%CI: 1.25-4.43). Similarly-adjusted models for all-cause mortality proved, however, not to confer risk, except for a tendency in prediabetics and diabetic women.CONCLUSION: A surrogate of FLD conferred significant high risk of diabetes and coronary heart disease, independent of some metabolic syndrome traits. Allcause mortality was not associated with FLD, except likely in the prediabetic state. Such a FLI may reliably be used in epidemiologic studies.

维持性腹膜透析患者外周血双特异性磷酸酶6预测全因死亡及心血管事件死亡的临床研究

目的研究外周血双特异性磷酸酶6(dual-specificity phosphatase 6,Dusp6)联合临床参数对维持性腹膜透析患者全因死亡及心血管事件死亡的预测价值。方法选择行腹膜透析置管并开始进行持续性腹膜透析的患者进行前瞻性队列研究,检测外周血Dusp6水平并收集基线临床资料,随访全因死亡和心血管事件死亡。采用Kaplan-Meier法比较不同Dusp6水平患者的死亡率,采用COX回归模型分析全因死亡和心血管事件死亡的影响因素,采用ROC曲线分析全因死亡和心血管事件死亡的预测指标。结果共纳入138例患者,随访时间19(15,23)月;外周血Dusp6水平的中位数为38.9pg/ml,外周血Dusp6≥38.9 pg/ml患者的全因死亡率和心血管事件死亡率均高于Dusp6<38.9 pg/ml(χ^(2)=17.500,P<0.001,χ^(2)=10.560,P=0.001);年龄、低密度脂蛋白胆固醇、C反应蛋白、Dusp6水平是患者全因死亡的影响因素(HR=1.104、3.105、21.929、1.075,95%CI:1.021~1.193、1.069~9.013、6.280~76.575、1.008~1.147,P=0.013、0.037、<0.001、0.028),4项指标联合预测全因死亡的灵敏度为81.11%、特异度为80.17%;年龄、尿酸、C反应蛋白、Dusp6水平是患者心血管事件死亡的影响因素(HR=1.095、2.985、4.646、1.105,95%CI:1.003~1.195、1.219~8.938、1.597~13.517、1.003~1.184,P=0.042、0.032、0.005、0.004),4项指标联合预测心血管事件死亡的灵敏度为81.25%、特异度为80.77%。结论外周血Dusp6高表达与维持性腹膜透析患者全因死亡及心血管事件死亡有关,Dusp6与不同临床参数联合对全因死亡及心血管事件死亡具有一定预测价值。

氧化平衡评分与哮喘患者全因死亡和心血管事件死亡的关联:NHANES数据分析

目的:探讨氧化平衡评分(OBS)与哮喘患者全因死亡及心血管事件死亡的关联。方法:使用1999至2018年美国全国健康与营养检查调查(NHANES)的数据,选择16种营养素和4种生活方式因素进行OBS评分,并根据三分位数分为3组(Q1、Q2、Q3)组。采用Cox回归分析OBS与哮喘患者全因死亡及心血管事件死亡的关系,并采用亚组分析和交互作用测试评价这种关联在不同群体中是否稳定。结果:研究共纳入6739人。Cox回归分析显示,在调整混杂因素后,以Q1组为参照,Q2组和Q3组个体全因死亡风险降低(HR=0.65,95%CI:0.49~0.86;HR=0.53,95%CI:0.37~0.77),Q3组心血管事件死亡风险降低(HR=0.45,95%CI:0.27~0.76)。性别及是否患有慢性阻塞性肺病、高血压、冠状动脉疾病、卒中、糖尿病在OBS与全因死亡的关联中无交互作用(P>0.05)。结论:高OBS是哮喘人群全因死亡和心血管事件死亡的保护因素。

不同心力衰竭亚型老年患者血清尿酸与预后的关系

背景血清尿酸(serum uric acid,sUA)与炎症和微血管功能障碍有关,对不同的心力衰竭分型可能有不同的影响。目的研究sUA水平与不同左心室射血分数心力衰竭亚型老年患者预后的关系。方法纳入2014年9月—2017年7月解放军总医院第一医学中心和苏州大学附属第一医院心血管内科住院的老年慢性心力衰竭患者,所有患者入院24 h内接受血清尿酸的检测。随访至2017年9月,以心血管死亡事件为终点事件,以多因素Cox回归模型评估sUA水平对预后的影响。结果1355例患者中位随访时间18个月,总体上心血管死亡事件发生率为6.8%(92例),射血分数减低的心力衰竭(heart failure with reduced ejection fraction,HFrEF)、射血分数中间值的心力衰竭(heart failure with mid-range ejection fraction,HFmrEF)和射血分数保留的心力衰竭(heart failure with preserved ejection fraction,HFpEF)三组心血管死亡事件发生率分别为13.9%(47例)、6.1%(24例)和3.4%(21例)。与低sUA组相比,高sUA组患者心血管死亡事件的发生风险更高(HR=2.141,95%CI:1.199~3.824,P=0.01)。亚组分析中,在HFrEF患者中,与低sUA组相比,高sUA组不良事件发生风险也升高(HR=4.151,95%CI:1.866~9.234,P<0.001);在HFmrEF患者中,高sUA组心血管死亡事件发生风险相较低sUA组同样升高(HR=4.724,95%CI:1.664~13.414,P=0.004)。结论sUA水平的升高与老年HFrEF和HFmrEF患者心血管不良预后相关。

Long-term outcomes of titanium-nitride-oxide coated stents and drug-eluting stents in acute coronary syndrome:A systematic review and meta-analysis

BACKGROUND In severe cases of coronary artery disease,percutaneous coronary intervention provide promising results.The stent used could be a drug-eluting stent(DES)or a titanium-nitride-oxide coated stent(TiNOS).AIM To compare the 5-year effectiveness and safety of the two stent types.METHODS The following systematic review and meta-analysis was conducted in accordance with the preferred reporting items for systematic reviews and meta-analysis guidelines,and PubMed/MEDLINE,Scopus,and Cochrane Central were searched from inception till August 2023.Primary outcomes were major adverse cardiac events(MACE),cardiac death,myocardial infarction(MI),cardiac death or MI,and ischemia-driven total lesion revascularization(ID-TLR).RESULTS Four randomized controlled trials(RCT),which analyzed a sum total of 3045 patients with acute coronary syndrome(ACS)after a median follow-up time of 5 years were included.Though statistically insignificant,an increase in the ID-TLR was observed in patients receiving TiNOSs vs DESs.In addition,MI,cardiac death and MI,and definite stent thrombosis(DST)were significantly decreased in the TiNOS arm.Baseline analysis revealed no significant results with meta-regression presenting non-ST elevated MI(NSTEMI)as a statistically significant covariate in the outcome of MACE.CONCLUSION TiNOS was found to be superior to DES in terms of MI,cardiac death or MI,and DST outcomes,however,the effect of the two stent types on ID-TLR and MACE was not significant.A greater number of studies are required to establish an accurate comparison of patient outcomes in TiNOS and DES.

临床衰弱指数对急性心肌梗死患者在院心脏康复后远期预后的预测价值

目的·探讨临床衰弱指数(Clinical Frailty Scale,CFS)对急性心肌梗死(acute myocardial infarction,AMI)患者在院心脏康复(cardiac rehabilitation,CR)后远期预后的预测价值。方法·序贯纳入2020年5月至2022年5月在上海交通大学医学院附属第六人民医院心脏中心接受诊治的501例AMI患者。采集患者基本临床信息,制定分级在院CR方案。根据患者出院前的CFS等级将患者分为3组,即正常(norm)组、脆弱(vulnerable)组和衰弱(frail)组,比较3组患者1年主要心血管事件率,包括全因死亡率及心力衰竭(心衰)再住院率。采用Logistic回归分析研究影响主要心血管事件率的危险因素,通过受试者操作特征(receiver operator characteristic,ROC)曲线分析各危险因素对主要心血管事件率的预测价值,建立最佳风险预测模型。结果·AMI患者在院CR后衰弱程度与高龄、B型利钠肽前体峰值(peak pro-B-type natriuretic peptide,peak proBNP)呈正比,与性别差异呈反比(P<0.05)。随患者衰弱程度增加,两种事件率均增高;其中全因死亡率(分别为2.6%、5.6%、15.2%)的组间差异有统计学意义(P=0.002),心衰再住院率(分别为19.6%、22.2%、24.2%)的组间差异无统计学意义。两两比较,frail组全因死亡率显著高于norm组(P=0.004),但vulnerable组与norm组的差异无统计学意义。CFS分级能够敏感预测AMI患者1年后的全因死亡风险(β=1.89,OR=6.61,P=0.001),且叠加CFS分级的风险模型预测效应最佳(AUC=0.845,P=0.000)。结论·接受在院CR的AMI患者出院前进行CFS分级,有助于识别1年内全因死亡风险较高的人群。

Reconceptualization of immune checkpoint inhibitor-associated gastritis

In recent years,with the extensive application of immunotherapy in clinical practice,it has achieved encouraging therapeutic effects.While enhancing clinical efficacy,however,it can also cause autoimmune damage,triggering immunerelated adverse events(irAEs).Reports of immunotherapy-induced gastritis have been increasing annually,but due to its atypical clinical symptoms,early diagnosis poses a certain challenge.Furthermore,it can lead to severe complications such as gastric bleeding,elevating the risk of adverse outcomes for solid tumor patients if immunotherapy is interrupted.Therefore,gaining a thorough understanding of the pathogenesis,clinical manifestations,diagnostic criteria,and treatment of immune-related gastritis is of utmost importance for early identification,diagnosis,and treatment.Additionally,the treatment of immune-related gastritis should be personalized according to the specific condition of each patient.For patients with grade 2-3 irAEs,restarting immune checkpoint inhibitors(ICIs)therapy may be considered when symptoms subside to grade 0-1.When restarting ICIs therapy,it is often recommended to use different types of ICIs.For grade 4 irAEs,permanent discontinuation of the medication is necessary.

免疫检查点抑制剂相关性肝毒性研究进展

免疫检查点抑制剂(immune checkpoint inhibitors, ICIs)作为肿瘤治疗领域近年来取得的重大进展之一,通过阻断免疫抑制进而重新激活T细胞,恢复其对肿瘤细胞的杀伤发挥抗肿瘤作用,极从而大程度地改善肿瘤患者的生存获益。但ICIs在发挥作用的同时也会非特异性激活免疫系统,导致免疫耐受失衡,损伤正常器官组织,这类不良事件即为免疫相关不良反应(immune-related adverse events, irAEs)。随着ICIs的广泛应用,其引发的irAEs的数量及类型不断增多已成为不容忽视的临床问题。其中,免疫检查点抑制剂相关性肝毒性(ICI-induced immune mediated hepatitis, IMH)作为一种潜在的致命性不良反应,对于其时间及结果尚无透彻的研究。

多因素联合预测维持性血液透析患者心血管疾病风险

目的研究平均血小板体积(mean platelet volume,MPV)及中性粒细胞与淋巴细胞比值(neutrophil-to-lymphocyte ratio,NLR)联合C反应蛋白(CRP)对维持性血液透析(maintenance hemodialysis,MHD)患者心血管疾病(cardiovascular disease,CVD)发生风险的预测价值。方法选取2018年8月—2023年6月在民航总医院肾内科确诊为尿毒症且行规律血液透析的患者,按是否发生心血管死亡事件分为心血管死亡事件组和存活组,收集人口学资料包括年龄、性别、体质量指数(body mass index,BMI)、透析龄及实验室资料(血常规、生化等),用二元Logistic回归分析筛选独立危险因素,采用ROC曲线进行预测效能分析。结果共纳入267例患者,其中存活组228例,心血管死亡事件组39例。①2组患者年龄(t=-1.835,P=0.068)、性别(χ^(2)=3.515,P=0.061)、BMI(t=1.971,P=0.051)、透析龄(t=-1.092,P=0.062)等一般资料比较差异无统计学意义。②心血管死亡事件组MPV、NLR、CRP较存活组高(Z/t分别为-7.456、-5.340、-5.416,均P<0.001)。心血管死亡事件组白蛋白(ALB)、血肌酐(Cr)、钙(Ca)、磷(P)、血红蛋白(Hb)较存活组低(Z/t分别为5.968、5.168、4.375、-3.552、-2.052,P分别为<0.001、<0.001、<0.001、0.040、0.039)。③MPV(OR=7.182,95%CI:2.974~17.348,P<0.001)、NLR(OR=1.203,95%CI:1.015~1.427,P=0.033)、CRP(OR=1.127,95%CI:1.098~1.258,P=0.042)升高及Hb(OR=1.062,95%CI:1.007~1.319,P=0.027)、Ca(OR=0.006,95%CI:0.000~0.184,P=0.003)降低是引起MHD患者并发心血管死亡事件的独立危险因素。④ROC曲线分析结果示MPV(AUC=0.881,95%CI:0.821~0.940,P<0.001)、NLR(AUC=0.764,95%CI:0.668~0.860,P<0.001)、CRP(AUC=0.778,95%CI:0.677~0.878,P<0.001)及三者联合对MHD患者心血管死亡事件均具有预测价值,三者联合的AUC大于单一指标(AUC=0.931,95%CI:0.882~0.980,P<0.001)。结论MPV、NLR、CRP升高及Hb、Ca降低是MHD患者发生心血管死亡事件的独立危险因素。MPV、NLR、CRP及三者联合对MHD患者心血管死亡事件具有预测价值,三者联合的预测价值更具临床指导意义。

血浆N末端脑钠肽前体对高龄左室肥厚病人预后的预测价值

目的探讨N末端脑钠肽前体(N-terminal pro-brain natriuretic peptide,NT-proBNP)对高龄(≥80岁)左室肥厚(LVH)病人预后的预测价值。方法连续纳入在中国人民解放军总医院第二医学中心住院的309例高龄LVH病人,记录病人临床基线资料、生化指标和血浆NT-proBNP水平。对病人全因死亡和主要不良心血管事件(MACEs)进行随访。采用线性回归方法筛选与NT-proBNP相关的临床因素,采用Cox风险比例回归模型评估NT-proBNP水平与终点事件之间的关系,利用ROC曲线评估NT-proBNP对高龄LVH病人预后的预测价值。结果309例高龄LVH病人的NT-proBNP中位水平为325(144,821)pg/mL。血浆NT-proBNP水平与年龄、心房颤动、起搏器植入、左室质量指数(LVMI)和使用β受体阻滞剂呈正相关,与估算的肾小球滤过率(eGFR)、Hb、血浆白蛋白和LVEF呈负相关。中位随访6.7(3.1,9.1)年,239例(77.3%)死亡,117例(37.9%)发生MACEs。多因素Cox回归模型显示,与最低分位组相比,NT-proBNP最高分位组全因死亡(HR=3.029;95%CI:1.918~4.728)和MACEs(HR=3.173;95%CI:1.612~6.244)风险显著增加。ROC曲线分析显示,NT-proBNP预测高龄LVH病人全因死亡和MACEs的AUC分别为0.669和0.594(均P<0.01)。结论血浆NT-proBNP对高龄LVH病人全因死亡和MACEs具有较好的预测价值。

Programmed cell death-1 inhibitor-related sclerosing cholangitis:A systematic review

BACKGROUND Programmed cell death-1(PD-1)inhibitor has been indicated for many types of malignancies.However,these inhibitors also cause immune-related adverse events.Hepatobiliary disorder is a phenotype of immune-related adverse event affecting 0%–4.5%of patients treated with PD-1 inhibitors.Recent studies have reported PD-1 inhibitor-related sclerosing cholangitis(SC);however,the associated clinical and pathological features are unclear.AIM To evaluate the clinical and pathological features of PD-1 inhibitor-related SC through a systematic review of the literature.METHODS The review,conducted using electronic databases in PubMed,was restricted to the period from January 2014 to September 2019 and focused on case reports/series on PD-1 inhibitor-related SC published in English.We scanned the references of the selected literature to identify any further relevant studies.Six cases previously studied by us,including three that have not yet been published,were included in this review.RESULTS Thirty-one PD-1 inhibitor-related SC cases were evaluated.Median age of patients was 67 years(range,43–89),with a male to female ratio of 21:10.The main disease requiring PD-1 inhibitor treatment was non-small cell lung cancer.Agents that caused PD-1 inhibitor-related SC were nivolumab(19 cases),pembrolizumab(10 cases),avelumab(1 case),and durvalumab(1 case).The median number of cycles until PD-1 inhibitor-related SC onset was 5.5(range,1–27).Abdominal pain or discomfort(35.5%,11/31)was the most frequent symptom.Blood serum tests identified liver dysfunction with a notable increase in biliary tract enzymes relative to hepatic enzymes,and a normal level of serum immunoglobulin G4.Biliary dilation without obstruction(76.9%,20/26),diffuse hypertrophy of the extrahepatic biliary tract(90.5%,19/21),and multiple strictures of the intrahepatic biliary tract(30.4%,7/23)were noted.In 11/23(47.8%)cases,pathological examination indicated that CD8+T cells were the dominant inflammatory cells in the bile duct or peribiliary tract.Although corticosteroids were mainly used for PD inhibitor-related SC treatment,the response rate was 11.5%(3/26).CONCLUSION Some clinical and pathological features of PD-1 inhibitor-related SC were revealed.To establish diagnostic criteria for PD-1 inhibitor-related SC,more cases need to be evaluated.

Post-coital death in chronic sildenafil abuser

Sex-related cardiovascular arrest is a rare event occurring typically among middle-aged men with cardiovascular risk.[1,2]The main etiologies of sex-related sudden cardiovascular arrest are acute coronary syndrome and subarachnoid hemorrhage and,to a lesser extent,chronic coronary artery disease and structural non-ischemic heart disease.[3]Coital angina that occurs during the minutes or hours after sexual activity represents<5%of all anginal attacks and it is rare in patients who do not have angina during strenous physical exertion.[4]Moreover,sexual activity is the cause of<1%of all acute myocardial infarctions.[5]Sudden death during sexual intercourse is reported with an incidence of 0.6%–1.7%.[6–8]The investigation of sudden death related to sexual activity may be difficult as it may be regarded as shameful or disgraceful to the family members and,especially to the remaining partner.Because of rarity of epidemiological data,considerable bias in the investigation of sudden death related to sexual activity has to be expected.[9–11]Extramarital sexual activity with younger partner and unfamiliar setting seems to represent risk factor as well as excessive food and alcohol consumption.[7]

外周血基线红细胞体积分布宽度对老年冠心病患者长期预后的预测价值

目的探讨外周血基线红细胞体积分布宽度(RDW)对老年冠心病(冠状动脉粥样硬化性心脏病)患者长期预后的预测价值。方法连续纳入2008年1月至2016年12月在新疆医科大学第一附属医院明确诊断冠心病的老年(年龄≥60岁)患者3024例并对其进行定期随访,中位随访时间为32个月,最长随访时间达10年,终点事件为全因死亡、心源性死亡(CM)、主要不良心脑血管事件(MACCE)、主要不良心血管事件(MACE)。根据受试者工作特征(ROC)曲线分析获得预测长期全因死亡的基线RDW最佳截断值为13.5%,根据RDW最佳截断值将患者分为低RDW组(<13.5%,1915例)和高RDW组(≥13.5%,1109例)。比较2组患者基线资料和终点事件发生率。调整混杂因素后采用多因素Cox比例风险回归模型分析RDW与患者长期不良预后的关系。结果2组患者年龄、冠状动脉慢性完全闭塞病变比例、血尿素氮、血肌酐、血尿酸、脂蛋白a水平比较差异均有统计学意义(均P<0.05)。高RDW组随访期间全因死亡、CM、MACCE、MACE发生率均高于低RDW组,差异均有统计学意义(均P<0.05)。调整多种混杂因素后,多因素Cox回归分析结果显示,RDW≥13.5%显著增加老年冠心病患者全因死亡(风险比=1.592,95%置信区间:1.160~2.185,P=0.004)、CM(风险比=1.759,95%置信区间:1.217~2.542,P=0.003)、MACE(风险比=1.351,95%置信区间:1.078~1.692,P=0.009)的发生风险,而不增加MACCE的发生风险(风险比=1.229,95%置信区间:0.994~1.521,P=0.057)。结论在老年冠心病患者中,基线RDW水平升高可作为长期全因死亡、CM、MACE的独立预测因子。