Objective:To explore the safety of restarting immunotherapy in patients with ≥grade 3 immune checkpoint inhibitor-related immune mediated hepatitis (IMH).Methods:The diagnosis and treatment of a patient with grade 4 IMH and restarting immunotherapy who was admitted to Beijing Youan Hospital, Capital Medical University was reported, and the main clinical data of the patient and related cases collected from PubMed, Embase, Cochrane Library, CNKI, and Wanfang databases (as of November 2023) were analyzed statistically from 5 aspects such as the study type, initial immunotherapy, severity of liver toxicity, resumption of immunotherapy, and recurrence rate of IMH after restarting immunotherapy.Results:A total of 17 relevant literature were collected, including 13 retrospective case series studies, 1 prospective study, and 3 case reports. One hundred and eleven patients who experienced ≥grade 3 IMH and restarted treatment with immune checkpoint inhibitors (ICIs) were extracted. Along with one case reported by our hospital, there were totally 112 cases. After restarting ICIs treatment, the recurrence rate of IMH was 22.3% (25/112). The recurrence rate in patients with cytotoxic T lymphocyte associated antigen 4 (CTLA-4) inhibitors in the ICIs treatment regimen was higher than those without CTLA-4 inhibitors, and the difference were not statistically significant [30.0% (6/20) vs. 21.1% (19/90), χ2=0.736, P=0.279]. The recurrence rate of IMH in patients with original treatment regimen was higher than those with adjusted treatments, and the difference were not statistically significant [22.2%(6/27) vs. 17.4%(8/46), χ2=0.256, P=0.613]. Conclusion:Restarting ICIs treatment in patients with ≥grade 3 ICI-related IMH after weighing the pros and cons may benefit some patients.

Objective:To explore the safety of restarting immunotherapy in patients with ≥grade 3 immune checkpoint inhibitor-related immune mediated hepatitis (IMH).Methods:The diagnosis and treatment of a patient with grade 4 IMH and restarting immunotherapy who was admitted to Beijing Youan Hospital, Capital Medical University was reported, and the main clinical data of the patient and related cases collected from PubMed, Embase, Cochrane Library, CNKI, and Wanfang databases (as of November 2023) were analyzed statistically from 5 aspects such as the study type, initial immunotherapy, severity of liver toxicity, resumption of immunotherapy, and recurrence rate of IMH after restarting immunotherapy.Results:A total of 17 relevant literature were collected, including 13 retrospective case series studies, 1 prospective study, and 3 case reports. One hundred and eleven patients who experienced ≥grade 3 IMH and restarted treatment with immune checkpoint inhibitors (ICIs) were extracted. Along with one case reported by our hospital, there were totally 112 cases. After restarting ICIs treatment, the recurrence rate of IMH was 22.3% (25/112). The recurrence rate in patients with cytotoxic T lymphocyte associated antigen 4 (CTLA-4) inhibitors in the ICIs treatment regimen was higher than those without CTLA-4 inhibitors, and the difference were not statistically significant [30.0% (6/20) vs. 21.1% (19/90), χ2=0.736, P=0.279]. The recurrence rate of IMH in patients with original treatment regimen was higher than those with adjusted treatments, and the difference were not statistically significant [22.2%(6/27) vs. 17.4%(8/46), χ2=0.256, P=0.613]. Conclusion:Restarting ICIs treatment in patients with ≥grade 3 ICI-related IMH after weighing the pros and cons may benefit some patients.

Objective To analyze the risk factors of adverse drug reactions related to iodinated contrast medium.Methods All the hospitalized patients,who underwent coronary angiography (CAG) or percutaneous coronary intervention (PCI) from April 20th 2013 to July 20th 2013 in Beijing Hospital,were investigated using a questionnaire on usage of iodinated contrast medium designed by the research group.The investigation included patients' basic information,main discharge diagnosis,information on surgery,combined drugs,the results of laboratory tests before and after using iodinated contrast medium,and information on adverse drug reactions and adverse events.The questionnaire was filled in by the research group according to the patient's subjective feelings one day after surgery and on discharge and the medical records.Using the patient's sex,age,body mass index (BMI),CAG or PCI,usage of iodinated contrast medium,allergic history,history of drinking,coexisting diseases,kinds of iodinated contrast medium used this time,and combined drugs as independent variables,the whole iodinated contrast medium-related adverse reactions and adverse reactions of single system were studied by the single-factor analysis.The significant statistical variables were selected and the logistic regression analysis including odds ratio (OR) and 95％ confidence interval (CI) was performed.Results Totally 581 patients were enrolled into this study; 364 were men (62.7％) and 217 women (38.3％) with an average age of (65 ± 12) years (29-90).The patients' levels of BMI were 15.8-41.0 kg/m2 with an average level of (25.5 ± 3.4) kg/m2.Of them,338 patients (58.2％) underwent CAG and 243 patients (41.8％) underwent PCI.The number of patients receiving iohexol injection (Shuangbei),iohexol injection (Omnipaque),iodixanol injection (Visipaque),and iopromide injection (Ultravist) were 173 (29.8％),160 (27.5％),164 (28.2％),and 84 (14.5％),respectively.And the dosage of iodinated contrast medium was 23-500 ml with an average dose of (136 ± 77) ml.Of the 581 patients,69 patients (11.9％) developed iodinated contrast medium-related adverse reactions.The incidences of Shuangbei,Omnipaque,Visipaque,and Ultravist were respectively 12.7％ (22/173),7.5％ (12/160),18.3％ (30/164),and 6.0％ (5/84)and there were no statistically significant differences among the different kinds (P ＜ 0.05,P ＜ 0.01).The 69 patients experienced 88 adverse reactions in total including 60 mild reactions and 28 moderate reactions.These reactions involved skin and accessories (23 reactions,26.1％),central and peripheral nervous system (17 reactions,19.4％),gastro-intestinal system (14 reactions,15.9％),autonomic nervous system (12 reactions,13.6％),urinary system (12 reactions,13.6％),systemic disorders (8 reactions,9.1％),and musculoskeletal system (2 reactions,2.3％).The logistic regression analysis showed that the risk factors of skin and accessories disorders were duration of hospital stay (OR =1.083,95％ CI:1.024-1.146,P =0.005),history of liver disease (OR =4.483,95％ CI:1.815-11.072,P =0.001),and allergic history (OR =5.686,95％ CI:2.136-15.135,P =0.001) ; the risk factors of gastro-intestinal system disorders were history of liver disease (OR =3.879,95％ CI:1.110-13.552,P =0.034) and insulin use (OR =3.764,95％ CI:1.087-12.027,P =0.036) ; the risk factors of central and peripheral nervous system disorders was allergic history (OR =6.778,95％ CI:1.187-38.685,P =0.031) ; the risk factors of urinary system disorders was anti-infective drug use (OR =6.918,95％ CI:1.425-33.589,P =0.016) ; the risk factors of musculoskeletal system disorders was BMI (OR =0.608,95％ CI:0.376-0.984,P =0.043); the risk factors of the systemic reactions were history of liver disease (OR =2.925,95％ CI:1.412-6.061,P =0.004),having PCI (OR =2.546,95 ％ CI:1.071-6.054,P =0.034),underweight (OR =10.743,95％ CI:2.040-56.572,P =0.005),and allergic history (OR =2.925,95％ CI:1.191-7.183,P =0.019).Conclusions The main risk factors of adverse drug reactions related to iodinated contrast medium to different system were different.The main systemic risk factors of the iodinated contrast medium-related adverse reactions were history of liver disease,underweight,and allergic history.

Objective To analyze the risk factors of adverse drug reactions related to iodinated contrast medium.Methods All the hospitalized patients,who underwent coronary angiography (CAG) or percutaneous coronary intervention (PCI) from April 20th 2013 to July 20th 2013 in Beijing Hospital,were investigated using a questionnaire on usage of iodinated contrast medium designed by the research group.The investigation included patients' basic information,main discharge diagnosis,information on surgery,combined drugs,the results of laboratory tests before and after using iodinated contrast medium,and information on adverse drug reactions and adverse events.The questionnaire was filled in by the research group according to the patient's subjective feelings one day after surgery and on discharge and the medical records.Using the patient's sex,age,body mass index (BMI),CAG or PCI,usage of iodinated contrast medium,allergic history,history of drinking,coexisting diseases,kinds of iodinated contrast medium used this time,and combined drugs as independent variables,the whole iodinated contrast medium-related adverse reactions and adverse reactions of single system were studied by the single-factor analysis.The significant statistical variables were selected and the logistic regression analysis including odds ratio (OR) and 95％ confidence interval (CI) was performed.Results Totally 581 patients were enrolled into this study; 364 were men (62.7％) and 217 women (38.3％) with an average age of (65 ± 12) years (29-90).The patients' levels of BMI were 15.8-41.0 kg/m2 with an average level of (25.5 ± 3.4) kg/m2.Of them,338 patients (58.2％) underwent CAG and 243 patients (41.8％) underwent PCI.The number of patients receiving iohexol injection (Shuangbei),iohexol injection (Omnipaque),iodixanol injection (Visipaque),and iopromide injection (Ultravist) were 173 (29.8％),160 (27.5％),164 (28.2％),and 84 (14.5％),respectively.And the dosage of iodinated contrast medium was 23-500 ml with an average dose of (136 ± 77) ml.Of the 581 patients,69 patients (11.9％) developed iodinated contrast medium-related adverse reactions.The incidences of Shuangbei,Omnipaque,Visipaque,and Ultravist were respectively 12.7％ (22/173),7.5％ (12/160),18.3％ (30/164),and 6.0％ (5/84)and there were no statistically significant differences among the different kinds (P ＜ 0.05,P ＜ 0.01).The 69 patients experienced 88 adverse reactions in total including 60 mild reactions and 28 moderate reactions.These reactions involved skin and accessories (23 reactions,26.1％),central and peripheral nervous system (17 reactions,19.4％),gastro-intestinal system (14 reactions,15.9％),autonomic nervous system (12 reactions,13.6％),urinary system (12 reactions,13.6％),systemic disorders (8 reactions,9.1％),and musculoskeletal system (2 reactions,2.3％).The logistic regression analysis showed that the risk factors of skin and accessories disorders were duration of hospital stay (OR =1.083,95％ CI:1.024-1.146,P =0.005),history of liver disease (OR =4.483,95％ CI:1.815-11.072,P =0.001),and allergic history (OR =5.686,95％ CI:2.136-15.135,P =0.001) ; the risk factors of gastro-intestinal system disorders were history of liver disease (OR =3.879,95％ CI:1.110-13.552,P =0.034) and insulin use (OR =3.764,95％ CI:1.087-12.027,P =0.036) ; the risk factors of central and peripheral nervous system disorders was allergic history (OR =6.778,95％ CI:1.187-38.685,P =0.031) ; the risk factors of urinary system disorders was anti-infective drug use (OR =6.918,95％ CI:1.425-33.589,P =0.016) ; the risk factors of musculoskeletal system disorders was BMI (OR =0.608,95％ CI:0.376-0.984,P =0.043); the risk factors of the systemic reactions were history of liver disease (OR =2.925,95％ CI:1.412-6.061,P =0.004),having PCI (OR =2.546,95 ％ CI:1.071-6.054,P =0.034),underweight (OR =10.743,95％ CI:2.040-56.572,P =0.005),and allergic history (OR =2.925,95％ CI:1.191-7.183,P =0.019).Conclusions The main risk factors of adverse drug reactions related to iodinated contrast medium to different system were different.The main systemic risk factors of the iodinated contrast medium-related adverse reactions were history of liver disease,underweight,and allergic history.

Polymyxin E and polymyxin B were the polypeptide antibiotic which were obtained from the Bacillus polymyxa medium. They were used to treat the resistant bacterial infection with Pseudomonas aeruginosa,Acinetobacter baumannii and Klebsiella pneumonia. The adverse reactions of polymyxin E were renal toxicity and nervous system toxicity. Age,dose and the combination with other drugs are the risk factors of renal toxicity. Combination with antioxidant,free radical scavenger and some Chinese medicine with protective effect on the kidney may reduce the renal toxicity of polymyxin E and improve the curative effect. Patients with renal insufficiency do not need to adjust the dose when they used polymyxin E and polymyxin B. Novel derivatives of polymyxin had lower renal toxicity.

Polymyxin E and polymyxin B were the polypeptide antibiotic which were obtained from the Bacillus polymyxa medium. They were used to treat the resistant bacterial infection with Pseudomonas aeruginosa,Acinetobacter baumannii and Klebsiella pneumonia. The adverse reactions of polymyxin E were renal toxicity and nervous system toxicity. Age,dose and the combination with other drugs are the risk factors of renal toxicity. Combination with antioxidant,free radical scavenger and some Chinese medicine with protective effect on the kidney may reduce the renal toxicity of polymyxin E and improve the curative effect. Patients with renal insufficiency do not need to adjust the dose when they used polymyxin E and polymyxin B. Novel derivatives of polymyxin had lower renal toxicity.