BACKGROUND With the widespread application of immune checkpoint inhibitor(ICI)therapy,the number of immune-related adverse effects(irAEs)has increased over the years.Autoimmune diabetes mellitus(DM)is a rare irAEs of ...BACKGROUND With the widespread application of immune checkpoint inhibitor(ICI)therapy,the number of immune-related adverse effects(irAEs)has increased over the years.Autoimmune diabetes mellitus(DM)is a rare irAEs of ICIs and can be troublesome and life threatening.CASE SUMMARY We report a 78-year-old woman with no history of diabetes who presented with hyperglycemia up to 23.4 mmol/L(random blood glucose level)after 14 courses of sintilimab.Hemoglobin A1c was 8.2%,fasting insulin was 0.29 mIU/mL,and fasting C-peptide was decreased to a level with negative autoantibodies.Combing her medical history and laboratory examination,she was diagnosed with programmed cell death(PD)-1-inhibitor-induced,new-onset autoimmune DM.After controlling her blood glucose,she was treated with daily insulin by subcutaneous injection.She was allowed to continue anti-PD-1 therapy and she still obtained some therapeutic efficacy.We also reviewed some published cases(n=36)of PD-1/PD-ligand 1(PD-L1)inhibitor-induced DM.We also discuss potential pathogenic mechanisms,clinical features,prognostic markers(βcell antibodies,human leukocyte antigen type,PD-L1 Level)of this rare adverse effect.CONCLUSION It is important for all clinicians to be aware of DM as an irAEs of ICIs.展开更多
OBJECTIVE: To assess the effectiveness and safety of Kuntai capsule and hormone replacement therapy in treatment of perimenopausal syndrome.METHODS: Articles were retrieved from the databases Cochrane Database of Syst...OBJECTIVE: To assess the effectiveness and safety of Kuntai capsule and hormone replacement therapy in treatment of perimenopausal syndrome.METHODS: Articles were retrieved from the databases Cochrane Database of Systematic Reviews,Pub Med, Chinese National Knowledge Infrastructure, China Science and Technology Journal Database, and Wanfang Database. Only randomized controlled trials were included; 15 trials involving1243 patients were identified from January 2005 to April 2015. A systemic review and Meta-analysis of publications was performed. The review was limit-ed to randomized controlled trials that compared Kuntai capsule and hormone replacement therapy to treat perimenopausal syndrome for at least 3months. The primary outcome assessed was the treatment efficacy at 3 months, including effective rate of Kupperman menopausal scores, Kupperman menopausal scores, and blood estradiol(E2) or blood follicle stimulating hormone(FSH) levels.Other outcomes assessed were safety or adverse events, such as gastrointestinal complaints, breast distending pain, or vaginal bleeding.RESULTS: Kupperman menopausal scores showed no significant difference in effective rate [odds ratio(OR): 1.05, 95% confidence intervals(CI): 0.71 to1.55] and changes in FSH level [mean difference(MD): 2.14, 95% CI:-2.36 to 6.65]. There was a significant statistical difference in Kupperman menopausal scores(MD:-1.14, 95% CI:-2.03 to-0.25)and changes in E2level(MD:-16.41, 95% CI:-18.83to-13.69). There were fewer adverse events in the Kuntai capsule group than in the hormone replacement therapy group(OR: = 0.35, 95% CI: 0.25 to0.48, P < 0.01).CONCLUSION: Compared with hormone replacement therapy, Kuntai capsule can improve perimenopausal symptoms and blood E2 levels, and reduce the incidence of adverse events.展开更多
Immune checkpoint inhibitors have been a recent major breakthrough in the management of tumors.They have broadened the scope of management in medical oncology,which has been heavily dependent on chemotherapy.Immune ch...Immune checkpoint inhibitors have been a recent major breakthrough in the management of tumors.They have broadened the scope of management in medical oncology,which has been heavily dependent on chemotherapy.Immune checkpoint inhibitors have renewed the hope of many patients for a more effective treatment.However,Immune checkpoint inhibitors are also associated with a variety of adverse effects,most commonly immunerelated adverse events,and these are often different from the known chemotherapy-induced toxicities.Hence,there is a need to identify specific biomarkers which are able to predict or diagnose these immune-related adverse events.展开更多
Immune checkpoint inhibitors(ICIs)have revolutionized the treatment landscape for various malignancies by demonstrating exceptional antitumor effects and significant improvement in patient survival.Despite their overt...Immune checkpoint inhibitors(ICIs)have revolutionized the treatment landscape for various malignancies by demonstrating exceptional antitumor effects and significant improvement in patient survival.Despite their overt therapeutic advantages,ICIs also induce immune-related adverse events(irAEs).Of these,checkpoint inhibitor pneumonitis(CIP)represents a prominent manifestation of pulmonary toxicity following ICI therapy,with inci-dence rates ranging from 2.7%to 20.0%.Notably,a substantial proportion of CIP cases show severe manifesta-tions,often leading to life-threatening complications,which emphasizes its clinical significance.Understanding the risk factors and potential pathogenetic mechanisms of CIP,combined with vigilant monitoring during im-munotherapy,is pivotal for early detection and management of this condition.Proactive strategies for the timely identification,accurate diagnosis,and effective management of CIP are essential to optimize patient outcomes.However,several challenges persist in CIP management,including management of severe and refractory cases,determining the timing of ICI rechallenge after CIP,management of long-term chronic CIP,and mitigating sec-ondary infections.In order to manage this potentially life-threatening irAE effectively,it is urgent to establish multi-disciplinary treatment(MDT)management,precision CIP management,and practical surveillance systems for CIP monitoring,diagnosis,and management and to call for prospective multi-center clinical trials.展开更多
CONSPECTUS:Immunotherapy has become a crucial strategy for cancer and infectious diseases due to its ability to leverage the power of the immune system to combat diseases,particularly when conventional therapeutic opt...CONSPECTUS:Immunotherapy has become a crucial strategy for cancer and infectious diseases due to its ability to leverage the power of the immune system to combat diseases,particularly when conventional therapeutic options have been ineffective.Nonetheless,low immune response rates and immune-related adverse events(irAEs)remain significant challenges for immunotherapeutics.Therefore,there is an urgent need to develop new strategies for improving the immunotherapy.Extracellular vesicles(EVs),secreted by living cells,are small membrane-bound vesicles.展开更多
Objective To develop a nomogram based on the monocyte-to-lymphocyte ratio(MLR)for predicting the risk of aortic-related adverse events within 30 days in patients with acute uncomplicated type B aortic intramural hemat...Objective To develop a nomogram based on the monocyte-to-lymphocyte ratio(MLR)for predicting the risk of aortic-related adverse events within 30 days in patients with acute uncomplicated type B aortic intramural hematoma.Methods This single-center retrospective cohort study screened consecutive patients with acute uncomplicated type B aortic intramural hematoma treated at the EmergencyyandCardiovascular Medicine Departments of the General Hospital of the Northern Theater Command from April 2018 to April 2024.Patients were divided into two groups based on the optimal MLR cut-off value for predicting aortic-related adverse events:low MLR and high MLR group.MLR was defined as the ratio of monocytes to lymphocytes.Aortic-related adverse events were defined as a composite of aortic-related death or aortic intramural hematoma progression(including aortic dissection and penetrating aortic ulcers)within 30 days.The receiver operating characteristic(ROC)curve identified the optimal MLR cut-off value.Multivariate logistic regression was used to identify independent predictors of aortic-related adverse events within 30 days,based on which nomogram models were constructed:the clinical characteristics model and the clinical characteristics-MLR model.The DeLong test was used to evaluate the diagnostic performance of different risk models.The additional predictive value of MLR was assessed using the net reclassification index(NRI)and integrated discrimination improvement(IDI).Results A total of 332 patients were included,of whom 217 were male(65.4%),with an average age of(64.3±9.4)years.A total of 107 aortic-related adverse events occurred during the 30-day follow-up period.The optimal cut-off value for MLR was 0.529.There were 189 cases in the low MLR group(MLR<0.529)and 143 cases in the high MLR group(MLR≥0.529).The rate of aortic-related adverse events was higher in the high MLR group compared to.the low MLR group(44.1%(63/143)vs.23.3%(44/189),P<0.001),mainly due to a higher rate of progression to aortic dissection(9.8%(14/143)vs.1.1%(2/189),P<0.001)and penetrating aortic ulcers(31.5%(45/143)vs.20.6%(39/189),P=0.025).Multivariate analysis identified diabetes(OR=0.25,95%CI 0.08-0.78,P=0.017),anemia(0R=3.45,95%CI 1.28-9.27,P=0.014),maximum descending aorta diameter(0R=1.08,95%CI 1.02-1.15,P=0.007),ulcerlike projections(OR=4.04,95%CI 2.26-7.24,P<0.001),and MLR(0R=6.61,95%CI 2.50-17.46,P<0.001)as independent predictors of aortic-related adverse events during the 30-day follow-up period.The clinical characteristics model includes diabetes,anemia,ulcer-like projections and maximum diameter of the descending aorta,and the clinical characteristics-MLR model includes the above clinical characteristics and MLR.The results of the DeLong test showed that the clinical characteristic-MLR model demonstrated a higher area under the ROC curve compared to the clinical characteristic model alone(0.784(95%CI 0.736-0.841)vs.0.742(95%CI0.691-0.788),P=0.031).The continuous NRI was 0.461(95%CI 0.237-0.685,P<0.001)and the IDI was 0.077(95%CI 0.043-0.112,P<0.001),indicating that the inclusion of the MLR in the model significantly improved the predictive accuracy.Conclusion The integration of MLR with other clinical characteristics improves the early identification ofhigh-risk patients with acute uncomplicated type B aortic intramural hematoma,optimizing clinical decisions and improving patient outcomes.展开更多
In a recent study published in Cancer Cell,Braun et al.introduced extracorporeal photopheresis(ECP)as a novel immunomodulatory approach to mitigate immune-related adverse events(irAEs)associated with immune checkpoint...In a recent study published in Cancer Cell,Braun et al.introduced extracorporeal photopheresis(ECP)as a novel immunomodulatory approach to mitigate immune-related adverse events(irAEs)associated with immune checkpoint inhibitors(ICIs)without compromising anti-tumor immunity.1 ECP suppressed Th1/Trm cell activation and neutrophil infiltration while enhancing an antiinflammatory macrophage phenotype through adiponectin,facilitating the resolution of steroid-refractory irAEs.展开更多
基金Supported by Key Research and Development Project of Science and Technology Department of Zhejiang Province,No.2019C03038.
文摘BACKGROUND With the widespread application of immune checkpoint inhibitor(ICI)therapy,the number of immune-related adverse effects(irAEs)has increased over the years.Autoimmune diabetes mellitus(DM)is a rare irAEs of ICIs and can be troublesome and life threatening.CASE SUMMARY We report a 78-year-old woman with no history of diabetes who presented with hyperglycemia up to 23.4 mmol/L(random blood glucose level)after 14 courses of sintilimab.Hemoglobin A1c was 8.2%,fasting insulin was 0.29 mIU/mL,and fasting C-peptide was decreased to a level with negative autoantibodies.Combing her medical history and laboratory examination,she was diagnosed with programmed cell death(PD)-1-inhibitor-induced,new-onset autoimmune DM.After controlling her blood glucose,she was treated with daily insulin by subcutaneous injection.She was allowed to continue anti-PD-1 therapy and she still obtained some therapeutic efficacy.We also reviewed some published cases(n=36)of PD-1/PD-ligand 1(PD-L1)inhibitor-induced DM.We also discuss potential pathogenic mechanisms,clinical features,prognostic markers(βcell antibodies,human leukocyte antigen type,PD-L1 Level)of this rare adverse effect.CONCLUSION It is important for all clinicians to be aware of DM as an irAEs of ICIs.
文摘OBJECTIVE: To assess the effectiveness and safety of Kuntai capsule and hormone replacement therapy in treatment of perimenopausal syndrome.METHODS: Articles were retrieved from the databases Cochrane Database of Systematic Reviews,Pub Med, Chinese National Knowledge Infrastructure, China Science and Technology Journal Database, and Wanfang Database. Only randomized controlled trials were included; 15 trials involving1243 patients were identified from January 2005 to April 2015. A systemic review and Meta-analysis of publications was performed. The review was limit-ed to randomized controlled trials that compared Kuntai capsule and hormone replacement therapy to treat perimenopausal syndrome for at least 3months. The primary outcome assessed was the treatment efficacy at 3 months, including effective rate of Kupperman menopausal scores, Kupperman menopausal scores, and blood estradiol(E2) or blood follicle stimulating hormone(FSH) levels.Other outcomes assessed were safety or adverse events, such as gastrointestinal complaints, breast distending pain, or vaginal bleeding.RESULTS: Kupperman menopausal scores showed no significant difference in effective rate [odds ratio(OR): 1.05, 95% confidence intervals(CI): 0.71 to1.55] and changes in FSH level [mean difference(MD): 2.14, 95% CI:-2.36 to 6.65]. There was a significant statistical difference in Kupperman menopausal scores(MD:-1.14, 95% CI:-2.03 to-0.25)and changes in E2level(MD:-16.41, 95% CI:-18.83to-13.69). There were fewer adverse events in the Kuntai capsule group than in the hormone replacement therapy group(OR: = 0.35, 95% CI: 0.25 to0.48, P < 0.01).CONCLUSION: Compared with hormone replacement therapy, Kuntai capsule can improve perimenopausal symptoms and blood E2 levels, and reduce the incidence of adverse events.
基金supported by the National Natural Science Foundation of China[No.81472782]Natural Science Foundation of Jiangsu Province[BK20141491].
文摘Immune checkpoint inhibitors have been a recent major breakthrough in the management of tumors.They have broadened the scope of management in medical oncology,which has been heavily dependent on chemotherapy.Immune checkpoint inhibitors have renewed the hope of many patients for a more effective treatment.However,Immune checkpoint inhibitors are also associated with a variety of adverse effects,most commonly immunerelated adverse events,and these are often different from the known chemotherapy-induced toxicities.Hence,there is a need to identify specific biomarkers which are able to predict or diagnose these immune-related adverse events.
基金support from the National High Level Hospital Clinical Research(No.2022-PUMCH–C-054).
文摘Immune checkpoint inhibitors(ICIs)have revolutionized the treatment landscape for various malignancies by demonstrating exceptional antitumor effects and significant improvement in patient survival.Despite their overt therapeutic advantages,ICIs also induce immune-related adverse events(irAEs).Of these,checkpoint inhibitor pneumonitis(CIP)represents a prominent manifestation of pulmonary toxicity following ICI therapy,with inci-dence rates ranging from 2.7%to 20.0%.Notably,a substantial proportion of CIP cases show severe manifesta-tions,often leading to life-threatening complications,which emphasizes its clinical significance.Understanding the risk factors and potential pathogenetic mechanisms of CIP,combined with vigilant monitoring during im-munotherapy,is pivotal for early detection and management of this condition.Proactive strategies for the timely identification,accurate diagnosis,and effective management of CIP are essential to optimize patient outcomes.However,several challenges persist in CIP management,including management of severe and refractory cases,determining the timing of ICI rechallenge after CIP,management of long-term chronic CIP,and mitigating sec-ondary infections.In order to manage this potentially life-threatening irAE effectively,it is urgent to establish multi-disciplinary treatment(MDT)management,precision CIP management,and practical surveillance systems for CIP monitoring,diagnosis,and management and to call for prospective multi-center clinical trials.
基金supported by the National Natural Science Foundation of China(No.82222035)the Shenzhen Medical Research Fund(No.B2302041).
文摘CONSPECTUS:Immunotherapy has become a crucial strategy for cancer and infectious diseases due to its ability to leverage the power of the immune system to combat diseases,particularly when conventional therapeutic options have been ineffective.Nonetheless,low immune response rates and immune-related adverse events(irAEs)remain significant challenges for immunotherapeutics.Therefore,there is an urgent need to develop new strategies for improving the immunotherapy.Extracellular vesicles(EVs),secreted by living cells,are small membrane-bound vesicles.
文摘Objective To develop a nomogram based on the monocyte-to-lymphocyte ratio(MLR)for predicting the risk of aortic-related adverse events within 30 days in patients with acute uncomplicated type B aortic intramural hematoma.Methods This single-center retrospective cohort study screened consecutive patients with acute uncomplicated type B aortic intramural hematoma treated at the EmergencyyandCardiovascular Medicine Departments of the General Hospital of the Northern Theater Command from April 2018 to April 2024.Patients were divided into two groups based on the optimal MLR cut-off value for predicting aortic-related adverse events:low MLR and high MLR group.MLR was defined as the ratio of monocytes to lymphocytes.Aortic-related adverse events were defined as a composite of aortic-related death or aortic intramural hematoma progression(including aortic dissection and penetrating aortic ulcers)within 30 days.The receiver operating characteristic(ROC)curve identified the optimal MLR cut-off value.Multivariate logistic regression was used to identify independent predictors of aortic-related adverse events within 30 days,based on which nomogram models were constructed:the clinical characteristics model and the clinical characteristics-MLR model.The DeLong test was used to evaluate the diagnostic performance of different risk models.The additional predictive value of MLR was assessed using the net reclassification index(NRI)and integrated discrimination improvement(IDI).Results A total of 332 patients were included,of whom 217 were male(65.4%),with an average age of(64.3±9.4)years.A total of 107 aortic-related adverse events occurred during the 30-day follow-up period.The optimal cut-off value for MLR was 0.529.There were 189 cases in the low MLR group(MLR<0.529)and 143 cases in the high MLR group(MLR≥0.529).The rate of aortic-related adverse events was higher in the high MLR group compared to.the low MLR group(44.1%(63/143)vs.23.3%(44/189),P<0.001),mainly due to a higher rate of progression to aortic dissection(9.8%(14/143)vs.1.1%(2/189),P<0.001)and penetrating aortic ulcers(31.5%(45/143)vs.20.6%(39/189),P=0.025).Multivariate analysis identified diabetes(OR=0.25,95%CI 0.08-0.78,P=0.017),anemia(0R=3.45,95%CI 1.28-9.27,P=0.014),maximum descending aorta diameter(0R=1.08,95%CI 1.02-1.15,P=0.007),ulcerlike projections(OR=4.04,95%CI 2.26-7.24,P<0.001),and MLR(0R=6.61,95%CI 2.50-17.46,P<0.001)as independent predictors of aortic-related adverse events during the 30-day follow-up period.The clinical characteristics model includes diabetes,anemia,ulcer-like projections and maximum diameter of the descending aorta,and the clinical characteristics-MLR model includes the above clinical characteristics and MLR.The results of the DeLong test showed that the clinical characteristic-MLR model demonstrated a higher area under the ROC curve compared to the clinical characteristic model alone(0.784(95%CI 0.736-0.841)vs.0.742(95%CI0.691-0.788),P=0.031).The continuous NRI was 0.461(95%CI 0.237-0.685,P<0.001)and the IDI was 0.077(95%CI 0.043-0.112,P<0.001),indicating that the inclusion of the MLR in the model significantly improved the predictive accuracy.Conclusion The integration of MLR with other clinical characteristics improves the early identification ofhigh-risk patients with acute uncomplicated type B aortic intramural hematoma,optimizing clinical decisions and improving patient outcomes.
基金German Cancer Aid(Max-Eder Junior Research Group,ref.70115384)'funded by the Clinician Scientist Program of Heidelberg University,Faculty of Medicine and is part of the Cancer Core Europe(CCE)Training program of Young leaders in TRAnslational Cancer research(TRYTRAC).
文摘In a recent study published in Cancer Cell,Braun et al.introduced extracorporeal photopheresis(ECP)as a novel immunomodulatory approach to mitigate immune-related adverse events(irAEs)associated with immune checkpoint inhibitors(ICIs)without compromising anti-tumor immunity.1 ECP suppressed Th1/Trm cell activation and neutrophil infiltration while enhancing an antiinflammatory macrophage phenotype through adiponectin,facilitating the resolution of steroid-refractory irAEs.
