Background:Recently,several cutting-edge experimental studies have directed chimeric antigen receptor(CAR)-T therapies toward specific renal diseases,revealing substantial renal benefits.Prior to widespread implementa...Background:Recently,several cutting-edge experimental studies have directed chimeric antigen receptor(CAR)-T therapies toward specific renal diseases,revealing substantial renal benefits.Prior to widespread implementation of these animal experiments and potentially clinical trials,it is crucial to assess the renal safety of CAR-T therapies using real-world safety evidence.Methods:Our focus was on utilizing 4 algorithms,including disproportionality analysis,based on the US Food and Drug Administration Adverse Event Reporting System database,to filter positive signals of acute and chronic renal injury associated with 6 CAR-T therapies.Further determination of causality was achieved through Mendelian randomization(MR)for drugs associated with renal injury events showing a correlation.Results:Six therapies were evaluated involving a total of 9,770 patients,with only acute kidney injury(AKI)identified as associated with idecabtagene vicleucel treatment using 4 algorithmic thresholds,including disproportionality analysis.Subsequently,MR revealed no causal relationship between the idecabtagene vicleucel target B cell maturation antigen and the risk of AKI(P=0.576),a finding validated in another independent dataset(P=0.734).Conclusion:CAR-T therapies do not directly cause renal damage and necessitate controlling adverse renal risks during or after treatment,such as cytokine release syndrome.Future research efforts should rigorously optimize these aspects to better cater to nephrologists’requirements.展开更多
Objective To explore the clinical characteristics and prognostic value in hereditary transthyretin amyloidosis cardiomyopathy(hATTR-CM)patients based on cluster analysis,and to explore the risk factors for cardiovascu...Objective To explore the clinical characteristics and prognostic value in hereditary transthyretin amyloidosis cardiomyopathy(hATTR-CM)patients based on cluster analysis,and to explore the risk factors for cardiovascular composite events.Methods This retrospective cohort study included hATTR-CM patients who were admitted to Peking Union Medical College Hospital from January 2000 to January 2024.These patients were divided into two clusters using cluster analysis,based on genetic information,ddemographic information and clinical information.During the follow-up period,cardiovascular composite events were defined as all-cause death and hospitalization for heart failure.Both cardiovascular composite events and all-cause death were the endpoints.Kaplan-Meier survival curves and log-rank method were used to compare the prognostic significance of cluster analysis subgroups.Univariate and multivariate Cox proportional hazardd regression mnodelswere used to analyze the risk factors affecting the incidence of cardiovascular composite events.Results A total of 43 patients were included in this study,30 were male(69.8%).In cluster 1(n=27),whose age of onset was(49.9±13.9)years old,24(88.9%)of them started with neuropathy or gastrointestinal symptoms,and all clinical phenotypes were mixed type(neurological and cardiac).In cluster 2(n=16),whose age of onset was(59.0±10.6)years old,15(93.8%)of them started with heart failure symptoms,and 13(81.3%)were pure cardiomyopathy.During the median follow-up time of 2.6 years,a total of 16 patients(37.2%)experienced composite cardiovascular events,and a total of 12 patients(27.9%)died.Kaplan-Meier survival curves showed a significantly lower cumulative survival rate for cardiovascular composite endpoint events(log-rank P=0.04)and all-cause death(log-rank P=0.04)in cluster 2 was than that in cluster 1.Univariate Cox proportional hazard regression model analysis showed that hATTR-CM patients with reduced estimated glomerular filtration rate,left ventricular ejection fraction≤40%,and moderate to severe mitral regurgitation were risk factors for vascular composite events(all P<0.05).Multivariate Cox proportional hazard regression analysis showed that left ventricular ejection fraction≤40%was an independent risk factor(P<0.O1).Conclusion Cluster analysis is a valuable prediction tool on the prognostic stratification of hATTR-CM.Cluster 2,which is late-onset with onset of heart failure symptoms has a worse prognosis during follow-up period.The occurrence of composite cardiovascular events in hATTR-CM is related to left ventricular ejection fraction≤40%.Cluster analysis is helpful for clinical identification of high-risk groups.展开更多
基金supported by grants from the National Natural Science Foundation of China(82470736,22321005,824B2015,82170711,82070733)Beijing Nova Program(20220484147,20240484677)+4 种基金Beijing Natural Science Foun dation(7242144)the National Key Research and Development Program of China(2024YFC2511000)the Funda mental Research Funds for the Central Universities(Peking University Clinical Scientist Training Program)(BMU2024 PYJH021)the National High Level Hospital Clinical Research Funding(Interdisciplinary Research Project of Peking University First Hospital)(2023IR12)CAMS Innovation Fund for Medical Sciences(2019-I2M-5-046).
文摘Background:Recently,several cutting-edge experimental studies have directed chimeric antigen receptor(CAR)-T therapies toward specific renal diseases,revealing substantial renal benefits.Prior to widespread implementation of these animal experiments and potentially clinical trials,it is crucial to assess the renal safety of CAR-T therapies using real-world safety evidence.Methods:Our focus was on utilizing 4 algorithms,including disproportionality analysis,based on the US Food and Drug Administration Adverse Event Reporting System database,to filter positive signals of acute and chronic renal injury associated with 6 CAR-T therapies.Further determination of causality was achieved through Mendelian randomization(MR)for drugs associated with renal injury events showing a correlation.Results:Six therapies were evaluated involving a total of 9,770 patients,with only acute kidney injury(AKI)identified as associated with idecabtagene vicleucel treatment using 4 algorithmic thresholds,including disproportionality analysis.Subsequently,MR revealed no causal relationship between the idecabtagene vicleucel target B cell maturation antigen and the risk of AKI(P=0.576),a finding validated in another independent dataset(P=0.734).Conclusion:CAR-T therapies do not directly cause renal damage and necessitate controlling adverse renal risks during or after treatment,such as cytokine release syndrome.Future research efforts should rigorously optimize these aspects to better cater to nephrologists’requirements.
文摘Objective To explore the clinical characteristics and prognostic value in hereditary transthyretin amyloidosis cardiomyopathy(hATTR-CM)patients based on cluster analysis,and to explore the risk factors for cardiovascular composite events.Methods This retrospective cohort study included hATTR-CM patients who were admitted to Peking Union Medical College Hospital from January 2000 to January 2024.These patients were divided into two clusters using cluster analysis,based on genetic information,ddemographic information and clinical information.During the follow-up period,cardiovascular composite events were defined as all-cause death and hospitalization for heart failure.Both cardiovascular composite events and all-cause death were the endpoints.Kaplan-Meier survival curves and log-rank method were used to compare the prognostic significance of cluster analysis subgroups.Univariate and multivariate Cox proportional hazardd regression mnodelswere used to analyze the risk factors affecting the incidence of cardiovascular composite events.Results A total of 43 patients were included in this study,30 were male(69.8%).In cluster 1(n=27),whose age of onset was(49.9±13.9)years old,24(88.9%)of them started with neuropathy or gastrointestinal symptoms,and all clinical phenotypes were mixed type(neurological and cardiac).In cluster 2(n=16),whose age of onset was(59.0±10.6)years old,15(93.8%)of them started with heart failure symptoms,and 13(81.3%)were pure cardiomyopathy.During the median follow-up time of 2.6 years,a total of 16 patients(37.2%)experienced composite cardiovascular events,and a total of 12 patients(27.9%)died.Kaplan-Meier survival curves showed a significantly lower cumulative survival rate for cardiovascular composite endpoint events(log-rank P=0.04)and all-cause death(log-rank P=0.04)in cluster 2 was than that in cluster 1.Univariate Cox proportional hazard regression model analysis showed that hATTR-CM patients with reduced estimated glomerular filtration rate,left ventricular ejection fraction≤40%,and moderate to severe mitral regurgitation were risk factors for vascular composite events(all P<0.05).Multivariate Cox proportional hazard regression analysis showed that left ventricular ejection fraction≤40%was an independent risk factor(P<0.O1).Conclusion Cluster analysis is a valuable prediction tool on the prognostic stratification of hATTR-CM.Cluster 2,which is late-onset with onset of heart failure symptoms has a worse prognosis during follow-up period.The occurrence of composite cardiovascular events in hATTR-CM is related to left ventricular ejection fraction≤40%.Cluster analysis is helpful for clinical identification of high-risk groups.
