Objective Immune checkpoint inhibitor(ICI)plus angiogenesis inhibitor(AI)combination therapy is a novel treatment model for multiple cancers that normalizes vascular-immune crosstalk to potentiate cancer immunity.In t...Objective Immune checkpoint inhibitor(ICI)plus angiogenesis inhibitor(AI)combination therapy is a novel treatment model for multiple cancers that normalizes vascular-immune crosstalk to potentiate cancer immunity.In this review,we summarize the characteristics of adverse effects(AEs)and all fatal cases reported in clinical studies involing ICI+AI therapy.Methods Four databases were systematically searched for eligible studies,and 28 relevant studies were selected for inclusion.Results Of the patients included,58.1%developed grade≥3 AEs.The most common fatal AEs were cardiovascular events,severe infections,and hemorrhage.Compared with AI alone,ICI+AI therapy resulted in more cases of grade≥3 proteinuria,liver injury,and fatal AEs(2.49%vs.1.28%,P=0.0041),especially respiratory toxicities and severe infections;however,ICI+AI therapy reduced hematological toxicity.Conclusion We shared comprehensive and practical safety data to review the adverse events associated with ICI+AI treatment.展开更多
The application of immune checkpoint inhibitors(ICI)in advanced cancer has been a major development in the last decade.The indications for ICIs are constantly expanding into new territory across different cancers,dise...The application of immune checkpoint inhibitors(ICI)in advanced cancer has been a major development in the last decade.The indications for ICIs are constantly expanding into new territory across different cancers,disease stages and lines of therapy.With this increased use,adverse events including immune checkpoint inhibitor-related hepatotoxicity(ICH)have emerged as an important clinical problem.This along with the introduction of ICI as first-and second-line treatments for advanced hepatocellular carcinoma makes ICH very relevant to gastroenterologists and hepatologists.The incidence of ICH varies between 1%-20%depending on the number,type and dose of ICI received.Investigation and management generally involve excluding differential diagnoses and following a stepwise escalation of withholding or ceasing ICI,corticosteroid treatment and adding other immunosuppressive agents depending on the severity of toxicity.The majority of patients with ICH recover and some may even safely recommence ICI therapy.Guideline recommendations are largely based on evidence derived from retrospective case series which highlights a priority for future research.展开更多
Immune-mediated hepatitis(IMH)induced by immune checkpoint inhibitors(ICIs)is an immune-related adverse event(irAE).IMH usually occurs 8-12 weeks after the first dose of ICI therapy.We report an unusual case of a lung...Immune-mediated hepatitis(IMH)induced by immune checkpoint inhibitors(ICIs)is an immune-related adverse event(irAE).IMH usually occurs 8-12 weeks after the first dose of ICI therapy.We report an unusual case of a lung cancer patient who developed IMH 2 years after initial ICI treatment and relapsed during corticosteroid therapy.A 55-year-old male with stageⅣB lung cancer received ICIs(for over 2 years)and chemotherapy as a second-line therapy.Grade 4 IMH occurred 2 years after initial immunotherapy and was diagnosed as hepatitis via laboratory and imaging tests with the simultaneous exclusion of other causes.The patient responded well to the corticosteroids;however,he decided to discontinue treatment prematurely,meaning that the total treatment period was less than 4 weeks.This led to IMH reoccurrence and the need to readminister corticosteroids at a higher dose than before.Ultimately,the patient's IMH was controlled and did not reoccur.This case illustrates that immune-related toxicity needs to be monitored in patients undergoing long-term ICI therapy.Improving patient education is also essential for the management and treatment of irAEs.展开更多
目的分析接种乙型肝炎(乙肝)疫苗(Hepatitis B Vaccine,HepB)后发生死亡的病例,评价HepB的安全性。方法对2006年1月～2007年3月,中国疾病预防控制系统突发公共卫生事件监测报告的接种HepB后死亡的病例及其个案调查资料进行分析。结果报...目的分析接种乙型肝炎(乙肝)疫苗(Hepatitis B Vaccine,HepB)后发生死亡的病例,评价HepB的安全性。方法对2006年1月～2007年3月,中国疾病预防控制系统突发公共卫生事件监测报告的接种HepB后死亡的病例及其个案调查资料进行分析。结果报告的10例接种HepB后婴儿死亡病例中,2例可能为接种HepB所致急性过敏性休克,其余8例为其它疾病所致死亡,根本死因均与接种HepB无关。结论国产HepB安全性良好,存在个别因过敏反应导致死亡的病例。应进一步规范预防接种,减少疑似预防接种异常反应的发生。展开更多
目的了解海南省甲型病毒性肝炎(甲肝)的发病动态及流行特征,评价2008年甲肝疫苗纳入免疫规划后,在海南省使用的甲肝疫苗预防接种的安全性和有效性,为预防接种实施和控制提供策略依据。方法收集2005年以来不同时期海南省甲肝疫情、人口...目的了解海南省甲型病毒性肝炎(甲肝)的发病动态及流行特征,评价2008年甲肝疫苗纳入免疫规划后,在海南省使用的甲肝疫苗预防接种的安全性和有效性,为预防接种实施和控制提供策略依据。方法收集2005年以来不同时期海南省甲肝疫情、人口统计和接种资料及2010—2014年甲肝疫苗接种后疑似预防接种异常反应(adverseevents following immunization;AEFI)监测资料,从甲肝发病率、疫苗保护率、异常反应发生率、临床类型等流行病学指标评价其有效性和安全性。结果海南省2005—2014年甲肝发病率为1.04/10万~11.35/10万,年均发病率为4.20/10万;2005—2007年甲肝疫苗未纳入扩大免疫规划(Expanded Programme on Immunization,EPI)时期,共报告甲肝2 173例,总报告发病率8.69/10万;2008—2010年甲肝减毒活疫苗分地区纳入EPI过渡时期,共报告甲肝893例,总报告发病率为3.38/10万;2011—2014年甲肝减毒活疫苗完全纳入EPI期,共报告甲肝538例,总报告发病率为1.48/10万;2010—2014年甲肝疫苗年均接种率为99.67%,年均保护率为99.97%;2008—2014年海南省5岁以下儿童甲肝发病率与甲肝疫苗接种率呈高度负相关(r=-0.862)。接种甲肝疫苗后报告AEFI病例179例,其中减毒活疫苗169例,总发生率为2.65/万;灭活疫苗10例,总发生率为1.52/万;两者以一般反应(发热/红肿/硬结),绝大多数反应均为一过性;异常反应主要表现为过敏性皮疹,严重异常反应如过敏性休克和过敏性紫癜发生率等发生率均为0.03/万~0.06/万。结论海南省将甲肝减毒活疫苗纳入儿童计划免疫推广应用效果显著,两种工艺甲肝疫苗安全性均较高,可继续推广应用。展开更多
目的分析吉林省2009-2014年乙型肝炎疫苗（hepatitis B vaccines,Hep B）疑似预防接种异常反应（adverse events following immunization,AEFI）的发生特征,评价Hep B安全性及吉林省AEFI监测工作。方法通过全国AEFI监测信息管理系统,收...目的分析吉林省2009-2014年乙型肝炎疫苗（hepatitis B vaccines,Hep B）疑似预防接种异常反应（adverse events following immunization,AEFI）的发生特征,评价Hep B安全性及吉林省AEFI监测工作。方法通过全国AEFI监测信息管理系统,收集吉林省2009-2014年报告Hep B AEFI数据,采用描述性流行病学方法对相关数据进行分析。结果吉林省2009-2014年共报告Hep B AEFI 897例,报告发生率为159.11/100万剂次;男女性别比为1.09∶1;〈1岁婴儿占88.85%;一般反应报告发生率为154.50/100万剂次,异常反应报告发生率为3.37/100万剂次;Hep B AEFI主要集中在接种后≤1 d。结论 Hep B具有较好的安全性,AEFI以一般反应和过敏反应为主。展开更多
目的了解乙型肝炎疫苗（Hepatitis B Vaccine,HepB）预防接种异常反应（Adverse Events Following Immu-nization,AEFI）发生的特点和规律,为异常反应的鉴定和处理提供参考。方法采用系统评价的方法,全面检索中国医院知识数据库（1994-2...目的了解乙型肝炎疫苗（Hepatitis B Vaccine,HepB）预防接种异常反应（Adverse Events Following Immu-nization,AEFI）发生的特点和规律,为异常反应的鉴定和处理提供参考。方法采用系统评价的方法,全面检索中国医院知识数据库（1994-2007年）和万方数据库（1993-2007年）,对获得文献进行质量评价,从合格文献中提取相关信息进行分析。结果共纳入36种杂志的文献48篇,58例。66.67%的文献来自县、市级医院和疾病预防控制中心。报道的HepB异常反应中,居前4位的是过敏性休克、过敏性皮疹、过敏性紫癜、局部过敏反应。接种HepB后〈24h发生的异常反应占案例总数的75.86%,第1剂接种后发生的异常反应占案例总数的58.62%。结论HepB性质稳定,异常反应发生的概率低。报道的相关文献中,属于异常反应的文献占57.14%。临床医生在异常反应处理中意义重大,应在医生群体中加强培训,以便及时发现并合理处理HepB预防接种异常反应。展开更多
文摘Objective Immune checkpoint inhibitor(ICI)plus angiogenesis inhibitor(AI)combination therapy is a novel treatment model for multiple cancers that normalizes vascular-immune crosstalk to potentiate cancer immunity.In this review,we summarize the characteristics of adverse effects(AEs)and all fatal cases reported in clinical studies involing ICI+AI therapy.Methods Four databases were systematically searched for eligible studies,and 28 relevant studies were selected for inclusion.Results Of the patients included,58.1%developed grade≥3 AEs.The most common fatal AEs were cardiovascular events,severe infections,and hemorrhage.Compared with AI alone,ICI+AI therapy resulted in more cases of grade≥3 proteinuria,liver injury,and fatal AEs(2.49%vs.1.28%,P=0.0041),especially respiratory toxicities and severe infections;however,ICI+AI therapy reduced hematological toxicity.Conclusion We shared comprehensive and practical safety data to review the adverse events associated with ICI+AI treatment.
文摘The application of immune checkpoint inhibitors(ICI)in advanced cancer has been a major development in the last decade.The indications for ICIs are constantly expanding into new territory across different cancers,disease stages and lines of therapy.With this increased use,adverse events including immune checkpoint inhibitor-related hepatotoxicity(ICH)have emerged as an important clinical problem.This along with the introduction of ICI as first-and second-line treatments for advanced hepatocellular carcinoma makes ICH very relevant to gastroenterologists and hepatologists.The incidence of ICH varies between 1%-20%depending on the number,type and dose of ICI received.Investigation and management generally involve excluding differential diagnoses and following a stepwise escalation of withholding or ceasing ICI,corticosteroid treatment and adding other immunosuppressive agents depending on the severity of toxicity.The majority of patients with ICH recover and some may even safely recommence ICI therapy.Guideline recommendations are largely based on evidence derived from retrospective case series which highlights a priority for future research.
文摘Immune-mediated hepatitis(IMH)induced by immune checkpoint inhibitors(ICIs)is an immune-related adverse event(irAE).IMH usually occurs 8-12 weeks after the first dose of ICI therapy.We report an unusual case of a lung cancer patient who developed IMH 2 years after initial ICI treatment and relapsed during corticosteroid therapy.A 55-year-old male with stageⅣB lung cancer received ICIs(for over 2 years)and chemotherapy as a second-line therapy.Grade 4 IMH occurred 2 years after initial immunotherapy and was diagnosed as hepatitis via laboratory and imaging tests with the simultaneous exclusion of other causes.The patient responded well to the corticosteroids;however,he decided to discontinue treatment prematurely,meaning that the total treatment period was less than 4 weeks.This led to IMH reoccurrence and the need to readminister corticosteroids at a higher dose than before.Ultimately,the patient's IMH was controlled and did not reoccur.This case illustrates that immune-related toxicity needs to be monitored in patients undergoing long-term ICI therapy.Improving patient education is also essential for the management and treatment of irAEs.
文摘目的分析接种乙型肝炎(乙肝)疫苗(Hepatitis B Vaccine,HepB)后发生死亡的病例,评价HepB的安全性。方法对2006年1月～2007年3月,中国疾病预防控制系统突发公共卫生事件监测报告的接种HepB后死亡的病例及其个案调查资料进行分析。结果报告的10例接种HepB后婴儿死亡病例中,2例可能为接种HepB所致急性过敏性休克,其余8例为其它疾病所致死亡,根本死因均与接种HepB无关。结论国产HepB安全性良好,存在个别因过敏反应导致死亡的病例。应进一步规范预防接种,减少疑似预防接种异常反应的发生。
文摘目的了解海南省甲型病毒性肝炎(甲肝)的发病动态及流行特征,评价2008年甲肝疫苗纳入免疫规划后,在海南省使用的甲肝疫苗预防接种的安全性和有效性,为预防接种实施和控制提供策略依据。方法收集2005年以来不同时期海南省甲肝疫情、人口统计和接种资料及2010—2014年甲肝疫苗接种后疑似预防接种异常反应(adverseevents following immunization;AEFI)监测资料,从甲肝发病率、疫苗保护率、异常反应发生率、临床类型等流行病学指标评价其有效性和安全性。结果海南省2005—2014年甲肝发病率为1.04/10万~11.35/10万,年均发病率为4.20/10万;2005—2007年甲肝疫苗未纳入扩大免疫规划(Expanded Programme on Immunization,EPI)时期,共报告甲肝2 173例,总报告发病率8.69/10万;2008—2010年甲肝减毒活疫苗分地区纳入EPI过渡时期,共报告甲肝893例,总报告发病率为3.38/10万;2011—2014年甲肝减毒活疫苗完全纳入EPI期,共报告甲肝538例,总报告发病率为1.48/10万;2010—2014年甲肝疫苗年均接种率为99.67%,年均保护率为99.97%;2008—2014年海南省5岁以下儿童甲肝发病率与甲肝疫苗接种率呈高度负相关(r=-0.862)。接种甲肝疫苗后报告AEFI病例179例,其中减毒活疫苗169例,总发生率为2.65/万;灭活疫苗10例,总发生率为1.52/万;两者以一般反应(发热/红肿/硬结),绝大多数反应均为一过性;异常反应主要表现为过敏性皮疹,严重异常反应如过敏性休克和过敏性紫癜发生率等发生率均为0.03/万~0.06/万。结论海南省将甲肝减毒活疫苗纳入儿童计划免疫推广应用效果显著,两种工艺甲肝疫苗安全性均较高,可继续推广应用。
文摘目的分析吉林省2009-2014年乙型肝炎疫苗（hepatitis B vaccines,Hep B）疑似预防接种异常反应（adverse events following immunization,AEFI）的发生特征,评价Hep B安全性及吉林省AEFI监测工作。方法通过全国AEFI监测信息管理系统,收集吉林省2009-2014年报告Hep B AEFI数据,采用描述性流行病学方法对相关数据进行分析。结果吉林省2009-2014年共报告Hep B AEFI 897例,报告发生率为159.11/100万剂次;男女性别比为1.09∶1;〈1岁婴儿占88.85%;一般反应报告发生率为154.50/100万剂次,异常反应报告发生率为3.37/100万剂次;Hep B AEFI主要集中在接种后≤1 d。结论 Hep B具有较好的安全性,AEFI以一般反应和过敏反应为主。
文摘目的了解乙型肝炎疫苗（Hepatitis B Vaccine,HepB）预防接种异常反应（Adverse Events Following Immu-nization,AEFI）发生的特点和规律,为异常反应的鉴定和处理提供参考。方法采用系统评价的方法,全面检索中国医院知识数据库（1994-2007年）和万方数据库（1993-2007年）,对获得文献进行质量评价,从合格文献中提取相关信息进行分析。结果共纳入36种杂志的文献48篇,58例。66.67%的文献来自县、市级医院和疾病预防控制中心。报道的HepB异常反应中,居前4位的是过敏性休克、过敏性皮疹、过敏性紫癜、局部过敏反应。接种HepB后〈24h发生的异常反应占案例总数的75.86%,第1剂接种后发生的异常反应占案例总数的58.62%。结论HepB性质稳定,异常反应发生的概率低。报道的相关文献中,属于异常反应的文献占57.14%。临床医生在异常反应处理中意义重大,应在医生群体中加强培训,以便及时发现并合理处理HepB预防接种异常反应。
