The post-hoc analysis of the PERSEO registry by Minardi,et al.[1]offers critical insights into antithrombotic management for elderly patients(≥80 years)on oral anticoagulation undergoing percutaneous coronary interve...The post-hoc analysis of the PERSEO registry by Minardi,et al.[1]offers critical insights into antithrombotic management for elderly patients(≥80 years)on oral anticoagulation undergoing percutaneous coronary intervention.While the authors effectively demonstrate the vulnerability of this population,characterized by substantial comorbidity burden and markedly elevated rates of mortality,ischemic events,and bleeding at one year compared with younger cohorts,their findings raise important questions about contemporary practice patterns and their alignment with evidence-based guidelines.展开更多
Objective Limited evidence is available regarding the risk-benefit ratio of thrombolytic therapy in patients with stroke and renal impairment complications,particularly for the drug tenecteplase.Therefore,we examined ...Objective Limited evidence is available regarding the risk-benefit ratio of thrombolytic therapy in patients with stroke and renal impairment complications,particularly for the drug tenecteplase.Therefore,we examined the association of impaired renal function with the safety and efficacy of intravenous thrombolytic treatment(IVT)in patients with acute ischaemic stroke(AIS).Methods A post hoc analysis of a randomised controlled trial(ClinicalTrials gov.NCT04797013)was conducted.Participants who received IVT with tenecteplase and alteplase(0.25 and 0.9 mg/kg,respectively)within 4.5 hours of symptoms onset were categorised based on their estimated glomerular filtration rate as follows:(1)≥90 mL/min/1.73 m2,normal renal function;(2)60-89 mL/min/1.73 m2,mildly decreased renal function;and(3)<60 mL/min/1.73 m2,moderately to severely decreased renal function.Patients stratified based on the normal renal function were used as the references.The primary efficacy and safety outcome were the percentage of patients achieving a modified Rankin Scale score of 0-1 at 90 days and the symptomatic intracranial haemorrhage(sICH)occurrence within 36 hours,respectively.Results In intravenous tenecteplase-treated patients,mildly decreased renal function(OR 3.10;95%CI:1.41 to 6.78)and moderately to severely decreased renal function(OR:8.03;95%CI:2.76 to 23.38)showed an association with a higher risk of all-cause mortality but not with sICH incidence compared with normal renal function.Among patients administered intravenous alteplase,those with a moderate-to severe decrease in renal function exhibited an elevated risk of sICH(adjusted OR:10.01;95%CI:1.61 to 62.15)and all-cause mortality(adjusted OR:4.54;95%CI:1.48 to 13.91).Comparative treatment effects between tenecteplase and alteplase according to renal function grades showed no heterogeneity.Conclusions A significant correlation was noted between kidney dysfunction and unfavourable outcomes in individuals with AIS who received treatment with either tenecteplase or alteplase.展开更多
Background and purpose Symptomatic internal carotid artery stenosis(sCAS)is an essential cause of transient ischaemic attack(TIA)or minor stroke.We aimed to evaluate whether the superiority of aspirin-ticagrelor over ...Background and purpose Symptomatic internal carotid artery stenosis(sCAS)is an essential cause of transient ischaemic attack(TIA)or minor stroke.We aimed to evaluate whether the superiority of aspirin-ticagrelor over aspirin-clopidogrel varies between patients with sCAS or not.Methods This was a post-hoc analysis of the High-Risk Patients with Acute Nondisabling Cerebrovascular Events-II(CHANCE-2)trial,all of which were CYP2C19 loss-of function alleles carriers.The primary exposures of interest were the treatment group and sCAS status.The primary efficacy endpoint was the new stroke assessed within 90 days.Results A total of 5920(92.3%)from 6412 were analysed,including 197(3.3%)with sCAS and 5723(96.7%)without sCAS.Stroke recurrence occurred in 13(12.15%)and 11(12.22%)patients with sCAS who received aspirin-ticagrelor and aspirin-clopidogrel,respectively(adjusted HR,1.04;95%CI,0.46 to 2.36;p=0.930).Among patients without sCAS,there were 158 cases(5.52%)of new strokes in the aspirin-ticagrelor group and 222 cases(7.76%)in the aspirin-clopidogrel group(HR,0.70;95%CI,0.57 to 0.86;p=0.0006).The treatment-by sCAS subtype was not significant(p=0.405).Conclusions Genotype-guided dual antiplatelet treatment with aspirin-ticagrelor may be beneficial for preventing recurrent strokes in patients without sCAS;however,it appears less effective in those with sCAS.No significant interaction was found between the treatment and sCAS subtypes.展开更多
Background The benefit-risk profile of tenecteplase in the elderly patients with acute ischaemic stroke(AIS)is uncertain.We sought to investigate the efficacy and safety of 0.25 mg/kg tenecteplase compared with altepl...Background The benefit-risk profile of tenecteplase in the elderly patients with acute ischaemic stroke(AIS)is uncertain.We sought to investigate the efficacy and safety of 0.25 mg/kg tenecteplase compared with alteplase for AIS patients aged≥80 years.Methods We performed a post hoc analysis of the Tenecteplase Reperfusion Therapy in Acute Ischaemic Cerebrovascular Events-2 Trial,a randomised,phase 3,non-inferiority clinical trial.Disabling AIS patients aged≥80 years who initiated intravenous thrombolytics within 4.5 hours of symptom onset were enrolled from June 2021 to May 2022 across 53 centres in China and were randomly allocated to receive 0.25 mg/kg tenecteplase or 0.9 mg/kg alteplase.The primary efficacy outcome was the proportion of participants with a modified Rankin Scale(mRS)score of 0-1 at 90 days.Symptomatic intracranial haemorrhage(sICH)within 36 hours was the safety outcome.Results Of 137 participants,mRS 0-1 at 90 days occurred in 37(49.3%)of 75 in the tenecteplase group vs 20(33.9%)of 59 in the alteplase group(risk ratio(RR)1.47,95%CI 0.96 to 2.23).sICH within 36 hours was observed in 3(4.0%)of 76 in the tenecteplase group and two(3.3%)of 61 in the alteplase group(RR 1.30,95%CI 0.20 to 8.41).Conclusions The risk-benefit profile of tenecteplase thrombolysis was preserved in the elderly patients,which lends further support to intravenous 0.25 mg/kg tenecteplase as an alternative to alteplase in these patients.展开更多
To the Editor:Upadacitinib,an oral janus kinase(JAK)inhibitor,exhibits a higher inhibitory potency for JAK1 compared to JAK2,JAK3,or tyrosine kinase 2,making it a promising candidate for the treatment of atopic dermat...To the Editor:Upadacitinib,an oral janus kinase(JAK)inhibitor,exhibits a higher inhibitory potency for JAK1 compared to JAK2,JAK3,or tyrosine kinase 2,making it a promising candidate for the treatment of atopic dermatitis(AD).Global trials Measure Up 1,Measure Up 2,and AD Up have demonstrated efficacy and safety data for moderate-to-severe AD,both as monotherapy and in combination with topical corticosteroids(TCS).[1,2]The updated 52-week results preliminarily reported sustained clinical benefits over 52 weeks,[3,4]but data on long-term outcomes in Chinese patients remain limited.Ethnic differences in AD pathophysiology,including variations in immune signatures,underscore the need for region-specific evidence.[5]This post hoc analysis of Measure Up 1 and AD Up trials evaluates the 140-week efficacy and safety of upadacitinib in Chinese patients.展开更多
To the Editor,Cough is an essential protective reflex that facilitates the clearance of airway secretions and foreign material.Among the many etiologies of cough,respiratory virus infections(RVIs)represent the most fr...To the Editor,Cough is an essential protective reflex that facilitates the clearance of airway secretions and foreign material.Among the many etiologies of cough,respiratory virus infections(RVIs)represent the most frequent cause globally.1 Although cough is often regarded as a nonspecific and self-limited symptom,marked heterogeneity exists in its severity and duration across individuals.In a subset of patients,cough persists beyond the period of acute illness,resulting in postinfectious cough(PIC),which is clinically defined as a subacute cough lasting 3–8 weeks following RVIs.展开更多
Objective: To assess the effects of Shenfu Injection(参附注射液, SFI) on blood lactate, and secondarily its effect on the lactate clearance(LC) in patients with post cardiac arrest syndrome(PCAS). Methods: The present...Objective: To assess the effects of Shenfu Injection(参附注射液, SFI) on blood lactate, and secondarily its effect on the lactate clearance(LC) in patients with post cardiac arrest syndrome(PCAS). Methods: The present study is a post hoc study of a randomized, assessor-blinded, controlled trial. Patients experienced in-hospital cardiac arrest between 2012 and 2015 were included in the predefined post hoc analyses. Of 1,022 patients enrolled, a total of 978 patients were allocated to the control group(486 cases) and SFI(492 cases) group, receiving standardized post-resuscitation care bundle(PRCB) treatment or PRCB combined with SFI(100 mL/d), respectively. Patients’ serum lactate was measured simutaneously with artery blood gas, lactate clearance(LC) was calculated on days 1, 3, and 7 after admission and compared between groups. Lactate and LC were also compared between the survivors and non-survivors according to the 28-d mortality, as well as the survivors and non-survivors subgroups both in the SFI and control groups. Results: In both groups, compared with pre-treatment levels, mean arterial pressure(MAP) and PaOwere significantly improved on 1, 3, 7 d after treatment(P<0.05), while heart rate(HR) and blood glucose levels were significantly decreased on 1, 3 and 7 d after treatment(P<0.05). compared with control group, SFI treatment improved the values of MAP and PaO(P<0.05), and significantly decreased the levels of HR and the blood glucose level on 3 and 7 d after treatment(P<0.05). Compared with the control group, lactate levels decreased faster in the SFI group versus the control group on 3 and 7 d(P<0.05). From initiation of treatment and the following 3 and 7 d, SFI treatment greatly increased the LC compared with that in the control group(P<0.05). Compared with survivors, non-survivors had higher admission lactate levels(7.3±1.1 mmol/L vs. 5.5±2.3 mmol/L;P <0.01), higher lactate levels on days 1, 3 and 7(P <0.05), and LC were decreased significantly on 3 and 7 d after treatment(P<0.05). Similar results were also found both in the SFI and control groups between survivors and non-survivors subgroups. Conclusion: SFI in combination with PRCB treatment is effective at lowering lactate level and resulted in increasing LC in a targeted population of PCAS patients.展开更多
文摘The post-hoc analysis of the PERSEO registry by Minardi,et al.[1]offers critical insights into antithrombotic management for elderly patients(≥80 years)on oral anticoagulation undergoing percutaneous coronary intervention.While the authors effectively demonstrate the vulnerability of this population,characterized by substantial comorbidity burden and markedly elevated rates of mortality,ischemic events,and bleeding at one year compared with younger cohorts,their findings raise important questions about contemporary practice patterns and their alignment with evidence-based guidelines.
基金funded by Key R&D Program of China(2017YFC1308204)This study was funded by Key R&D Program of China(2017YFC1308204),。
文摘Objective Limited evidence is available regarding the risk-benefit ratio of thrombolytic therapy in patients with stroke and renal impairment complications,particularly for the drug tenecteplase.Therefore,we examined the association of impaired renal function with the safety and efficacy of intravenous thrombolytic treatment(IVT)in patients with acute ischaemic stroke(AIS).Methods A post hoc analysis of a randomised controlled trial(ClinicalTrials gov.NCT04797013)was conducted.Participants who received IVT with tenecteplase and alteplase(0.25 and 0.9 mg/kg,respectively)within 4.5 hours of symptoms onset were categorised based on their estimated glomerular filtration rate as follows:(1)≥90 mL/min/1.73 m2,normal renal function;(2)60-89 mL/min/1.73 m2,mildly decreased renal function;and(3)<60 mL/min/1.73 m2,moderately to severely decreased renal function.Patients stratified based on the normal renal function were used as the references.The primary efficacy and safety outcome were the percentage of patients achieving a modified Rankin Scale score of 0-1 at 90 days and the symptomatic intracranial haemorrhage(sICH)occurrence within 36 hours,respectively.Results In intravenous tenecteplase-treated patients,mildly decreased renal function(OR 3.10;95%CI:1.41 to 6.78)and moderately to severely decreased renal function(OR:8.03;95%CI:2.76 to 23.38)showed an association with a higher risk of all-cause mortality but not with sICH incidence compared with normal renal function.Among patients administered intravenous alteplase,those with a moderate-to severe decrease in renal function exhibited an elevated risk of sICH(adjusted OR:10.01;95%CI:1.61 to 62.15)and all-cause mortality(adjusted OR:4.54;95%CI:1.48 to 13.91).Comparative treatment effects between tenecteplase and alteplase according to renal function grades showed no heterogeneity.Conclusions A significant correlation was noted between kidney dysfunction and unfavourable outcomes in individuals with AIS who received treatment with either tenecteplase or alteplase.
基金supported by grants from the National Natural Science Foundation of China(U20A20358,82471356)CAMS Innovation Fund for Medical Sciences(2019-2M 5-029).
文摘Background and purpose Symptomatic internal carotid artery stenosis(sCAS)is an essential cause of transient ischaemic attack(TIA)or minor stroke.We aimed to evaluate whether the superiority of aspirin-ticagrelor over aspirin-clopidogrel varies between patients with sCAS or not.Methods This was a post-hoc analysis of the High-Risk Patients with Acute Nondisabling Cerebrovascular Events-II(CHANCE-2)trial,all of which were CYP2C19 loss-of function alleles carriers.The primary exposures of interest were the treatment group and sCAS status.The primary efficacy endpoint was the new stroke assessed within 90 days.Results A total of 5920(92.3%)from 6412 were analysed,including 197(3.3%)with sCAS and 5723(96.7%)without sCAS.Stroke recurrence occurred in 13(12.15%)and 11(12.22%)patients with sCAS who received aspirin-ticagrelor and aspirin-clopidogrel,respectively(adjusted HR,1.04;95%CI,0.46 to 2.36;p=0.930).Among patients without sCAS,there were 158 cases(5.52%)of new strokes in the aspirin-ticagrelor group and 222 cases(7.76%)in the aspirin-clopidogrel group(HR,0.70;95%CI,0.57 to 0.86;p=0.0006).The treatment-by sCAS subtype was not significant(p=0.405).Conclusions Genotype-guided dual antiplatelet treatment with aspirin-ticagrelor may be beneficial for preventing recurrent strokes in patients without sCAS;however,it appears less effective in those with sCAS.No significant interaction was found between the treatment and sCAS subtypes.
基金funded by Beijing Municipal Science&Technology Committee(Z211100003521019)China Shijiazhuang Pharmaceutical Company Recomgen Pharmaceutical(Guangzhou)Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences(2019-I2M 5-029)National Natural Science Foundation(82111530203,82171272).
文摘Background The benefit-risk profile of tenecteplase in the elderly patients with acute ischaemic stroke(AIS)is uncertain.We sought to investigate the efficacy and safety of 0.25 mg/kg tenecteplase compared with alteplase for AIS patients aged≥80 years.Methods We performed a post hoc analysis of the Tenecteplase Reperfusion Therapy in Acute Ischaemic Cerebrovascular Events-2 Trial,a randomised,phase 3,non-inferiority clinical trial.Disabling AIS patients aged≥80 years who initiated intravenous thrombolytics within 4.5 hours of symptom onset were enrolled from June 2021 to May 2022 across 53 centres in China and were randomly allocated to receive 0.25 mg/kg tenecteplase or 0.9 mg/kg alteplase.The primary efficacy outcome was the proportion of participants with a modified Rankin Scale(mRS)score of 0-1 at 90 days.Symptomatic intracranial haemorrhage(sICH)within 36 hours was the safety outcome.Results Of 137 participants,mRS 0-1 at 90 days occurred in 37(49.3%)of 75 in the tenecteplase group vs 20(33.9%)of 59 in the alteplase group(risk ratio(RR)1.47,95%CI 0.96 to 2.23).sICH within 36 hours was observed in 3(4.0%)of 76 in the tenecteplase group and two(3.3%)of 61 in the alteplase group(RR 1.30,95%CI 0.20 to 8.41).Conclusions The risk-benefit profile of tenecteplase thrombolysis was preserved in the elderly patients,which lends further support to intravenous 0.25 mg/kg tenecteplase as an alternative to alteplase in these patients.
文摘To the Editor:Upadacitinib,an oral janus kinase(JAK)inhibitor,exhibits a higher inhibitory potency for JAK1 compared to JAK2,JAK3,or tyrosine kinase 2,making it a promising candidate for the treatment of atopic dermatitis(AD).Global trials Measure Up 1,Measure Up 2,and AD Up have demonstrated efficacy and safety data for moderate-to-severe AD,both as monotherapy and in combination with topical corticosteroids(TCS).[1,2]The updated 52-week results preliminarily reported sustained clinical benefits over 52 weeks,[3,4]but data on long-term outcomes in Chinese patients remain limited.Ethnic differences in AD pathophysiology,including variations in immune signatures,underscore the need for region-specific evidence.[5]This post hoc analysis of Measure Up 1 and AD Up trials evaluates the 140-week efficacy and safety of upadacitinib in Chinese patients.
基金supported by Beijing Municipal Health Commission Research Ward Excellence Clinical Research Program(No.BRWEP2024W114060100)Beijing Nova Program(No.20230484343)+1 种基金Chinese Academy of Medical Sciences(CAMS)Innovation Fund for Medical Sciences(No.2023-I2M-C&T-B-119)New Cornerstone Science Foundation to B.C.
文摘To the Editor,Cough is an essential protective reflex that facilitates the clearance of airway secretions and foreign material.Among the many etiologies of cough,respiratory virus infections(RVIs)represent the most frequent cause globally.1 Although cough is often regarded as a nonspecific and self-limited symptom,marked heterogeneity exists in its severity and duration across individuals.In a subset of patients,cough persists beyond the period of acute illness,resulting in postinfectious cough(PIC),which is clinically defined as a subacute cough lasting 3–8 weeks following RVIs.
基金Supported by the Beijing Municipal Administration of Hospitals’Youth Programme (No.QML20170301)。
文摘Objective: To assess the effects of Shenfu Injection(参附注射液, SFI) on blood lactate, and secondarily its effect on the lactate clearance(LC) in patients with post cardiac arrest syndrome(PCAS). Methods: The present study is a post hoc study of a randomized, assessor-blinded, controlled trial. Patients experienced in-hospital cardiac arrest between 2012 and 2015 were included in the predefined post hoc analyses. Of 1,022 patients enrolled, a total of 978 patients were allocated to the control group(486 cases) and SFI(492 cases) group, receiving standardized post-resuscitation care bundle(PRCB) treatment or PRCB combined with SFI(100 mL/d), respectively. Patients’ serum lactate was measured simutaneously with artery blood gas, lactate clearance(LC) was calculated on days 1, 3, and 7 after admission and compared between groups. Lactate and LC were also compared between the survivors and non-survivors according to the 28-d mortality, as well as the survivors and non-survivors subgroups both in the SFI and control groups. Results: In both groups, compared with pre-treatment levels, mean arterial pressure(MAP) and PaOwere significantly improved on 1, 3, 7 d after treatment(P<0.05), while heart rate(HR) and blood glucose levels were significantly decreased on 1, 3 and 7 d after treatment(P<0.05). compared with control group, SFI treatment improved the values of MAP and PaO(P<0.05), and significantly decreased the levels of HR and the blood glucose level on 3 and 7 d after treatment(P<0.05). Compared with the control group, lactate levels decreased faster in the SFI group versus the control group on 3 and 7 d(P<0.05). From initiation of treatment and the following 3 and 7 d, SFI treatment greatly increased the LC compared with that in the control group(P<0.05). Compared with survivors, non-survivors had higher admission lactate levels(7.3±1.1 mmol/L vs. 5.5±2.3 mmol/L;P <0.01), higher lactate levels on days 1, 3 and 7(P <0.05), and LC were decreased significantly on 3 and 7 d after treatment(P<0.05). Similar results were also found both in the SFI and control groups between survivors and non-survivors subgroups. Conclusion: SFI in combination with PRCB treatment is effective at lowering lactate level and resulted in increasing LC in a targeted population of PCAS patients.
