Objective: To compare uterine tissue concentrations of ethinyl estradiol (EE) and etonogestrel (ENG) after one cycle of use of a contraceptive vaginal ring (NuvaRing;NV Organon, Oss, The Netherlands) or a combined ora...Objective: To compare uterine tissue concentrations of ethinyl estradiol (EE) and etonogestrel (ENG) after one cycle of use of a contraceptive vaginal ring (NuvaRing;NV Organon, Oss, The Netherlands) or a combined oral contraceptive (COC). Design: Randomized, open-label, pharmacokinetic study. Setting: Obstetrics and gynecology unit. Patient(s): Eight premenopausal women about to undergo hysterectomy but otherwise healthy. Intervention(s): One cycle (17-21 days) of NuvaRing or COC treatment that ended with surgical hysterectomy. Main Outcome Measure(s): Tissue concentrations of EE and ENG in uterine tissue samples taken from the upper myometrium and mid-myometrium, the cervical region, and the endometrium. Result(s): In both groups, concentrations of EE and ENG were similar in uterine tissue taken from the upper myometrium and mid-myometrium and the cervical region. However, compared with the COC group, concentrations of both hormones were markedly lower in tissue samples from the endometrium of women who had been treated with NuvaRing. Conclusion(s): Vaginal administration of hormones with NuvaRing did not produce elevated uterine concentrations of EE and ENG, compared with an oral contraceptive.展开更多
Background and Aims:Large-scale data on the hepatitis D virus(HDV)/hepatitis B virus(HBV)co-infection rate is needed to estimate the current epidemiology of HDV in China.This study aimed to estimate the current epidem...Background and Aims:Large-scale data on the hepatitis D virus(HDV)/hepatitis B virus(HBV)co-infection rate is needed to estimate the current epidemiology of HDV in China.This study aimed to estimate the current epidemiology of HDV.Methods:Patients with chronic HBV infection,with documented serum hepatitis B surface antigen(HBsAg)positivity for more than six months,were enrolled across China.Blood samples were collected at baseline for central evaluations of HDV antibody and HBsAg quantification.Assessments for antibodies of hepatitis A virus,hepatitis C virus,hepatitis E virus,and human immunodeficiency virus,as well as HDV RNA quantification,were performed in patients who tested positive for HDV antibodies.Results:Of the 5,044 enrolled patients between September 24,2021,and December 28,2022,4,936 patients were included in the analysis.The mean age(±standard deviation)was 42.9±9.9 years,and 69.8%of patients were male.The mean alanine aminotransferase level was 34±58 U/L,and 1,509(30.6%)patients were hepatitis B e antigen-positive.The mean(standard deviation)HBsAg level at baseline was 3,535±11,292 IU/mL among 4,842 patients who were HBsAg positive.The rate of HBV infection and HDV antibody positivity was 0.24%(95%confidence interval:0.1–0.4%),and only one patient was HDV RNA positive.Conclusions:The prevalence of HDV antibody positivity was 0.24%in Chinese patients with chronic HBV infection,and only one patient with both anti-HDV antibody and HDV RNA positivity was observed in this study.展开更多
Background:The introductions of anti-human epidermal growth factor receptor-2(HER2)agents have significantly improved the treatment outcome of patients with HER2-positive breast cancer.BAT8001 is a novel antibodydrug ...Background:The introductions of anti-human epidermal growth factor receptor-2(HER2)agents have significantly improved the treatment outcome of patients with HER2-positive breast cancer.BAT8001 is a novel antibodydrug conjugate targeting human epidermal growth factor receptor-2(HER2)-expressing cells composed of a trastuzumab biosimilar linked to the drug-linker Batansine.This dose-escalation,phase I study was designed to assess the safety,tolerability,pharmacokinetics,and preliminary anti-tumor activity of BAT8001 in patients with HER2-positive locally advanced or metastatic breast cancer.Methods:This trial was conducted in subjects with histologically confirmed HER2-positive breast cancer(having evaluable lesions and an Eastern Cooperative Oncology Group performance status of 0 or 1)using a 3+3 design of escalating BAT8001 doses.Patients received BAT8001 intravenously in a 21-day cycle,with dose escalation in 5 cohorts:1.2,2.4,3.6,4.8,and 6.0 mg/kg.The primary objective was to evaluate the safety and tolerability of BAT8001.Preliminary activity of BAT8001 was also assessed as a secondary objective.Results:Between March 2017 to May 2018,29 HER2-positive breast cancer patients were enrolled.The observed dose-limiting toxicities were grade 4 thrombocytopenia and grade 3 elevated transaminase.The maximum tolerated dose was determined to be 3.6 mg/kg.Grade 3 or greater adverse events(AEs)occurred in 14(48.3%)of 29 patients,including thrombocytopenia in 12(41.4%)patients,aspartate aminotransferase increased in 4(13.8%)patients,γ-glutamyl transferase increased in 2(6.9%)patients,alanine aminotransferase increased in 2(6.9%)patients,diarrhea in 2(6.9%)patients.Objective response was observed in 12(41.4%,95%confidence interval[CI]=23.5%-61.1%)and disease control(including patients achieving objective response and stable disease)was observed in 24(82.8%,95%CI=64.2%-94.2%)patients.Conclusions:BAT8001 demonstrated favorable safety profiles,with promising anti-tumor activity in patients with HER2-positive locally advanced or metastatic breast cancer.BAT8001 has the potential to provide a new therapeutic option in patients with metastatic HER2-positive breast cancer.展开更多
文摘Objective: To compare uterine tissue concentrations of ethinyl estradiol (EE) and etonogestrel (ENG) after one cycle of use of a contraceptive vaginal ring (NuvaRing;NV Organon, Oss, The Netherlands) or a combined oral contraceptive (COC). Design: Randomized, open-label, pharmacokinetic study. Setting: Obstetrics and gynecology unit. Patient(s): Eight premenopausal women about to undergo hysterectomy but otherwise healthy. Intervention(s): One cycle (17-21 days) of NuvaRing or COC treatment that ended with surgical hysterectomy. Main Outcome Measure(s): Tissue concentrations of EE and ENG in uterine tissue samples taken from the upper myometrium and mid-myometrium, the cervical region, and the endometrium. Result(s): In both groups, concentrations of EE and ENG were similar in uterine tissue taken from the upper myometrium and mid-myometrium and the cervical region. However, compared with the COC group, concentrations of both hormones were markedly lower in tissue samples from the endometrium of women who had been treated with NuvaRing. Conclusion(s): Vaginal administration of hormones with NuvaRing did not produce elevated uterine concentrations of EE and ENG, compared with an oral contraceptive.
文摘Background and Aims:Large-scale data on the hepatitis D virus(HDV)/hepatitis B virus(HBV)co-infection rate is needed to estimate the current epidemiology of HDV in China.This study aimed to estimate the current epidemiology of HDV.Methods:Patients with chronic HBV infection,with documented serum hepatitis B surface antigen(HBsAg)positivity for more than six months,were enrolled across China.Blood samples were collected at baseline for central evaluations of HDV antibody and HBsAg quantification.Assessments for antibodies of hepatitis A virus,hepatitis C virus,hepatitis E virus,and human immunodeficiency virus,as well as HDV RNA quantification,were performed in patients who tested positive for HDV antibodies.Results:Of the 5,044 enrolled patients between September 24,2021,and December 28,2022,4,936 patients were included in the analysis.The mean age(±standard deviation)was 42.9±9.9 years,and 69.8%of patients were male.The mean alanine aminotransferase level was 34±58 U/L,and 1,509(30.6%)patients were hepatitis B e antigen-positive.The mean(standard deviation)HBsAg level at baseline was 3,535±11,292 IU/mL among 4,842 patients who were HBsAg positive.The rate of HBV infection and HDV antibody positivity was 0.24%(95%confidence interval:0.1–0.4%),and only one patient was HDV RNA positive.Conclusions:The prevalence of HDV antibody positivity was 0.24%in Chinese patients with chronic HBV infection,and only one patient with both anti-HDV antibody and HDV RNA positivity was observed in this study.
基金This study was supported by the Natural Science Foundation of Guangdong Province(2020A1515010105)Joint Fund of the National Natural Science Foundation of China and Natural Science Foundation of Guangdong Province(U1601224).
文摘Background:The introductions of anti-human epidermal growth factor receptor-2(HER2)agents have significantly improved the treatment outcome of patients with HER2-positive breast cancer.BAT8001 is a novel antibodydrug conjugate targeting human epidermal growth factor receptor-2(HER2)-expressing cells composed of a trastuzumab biosimilar linked to the drug-linker Batansine.This dose-escalation,phase I study was designed to assess the safety,tolerability,pharmacokinetics,and preliminary anti-tumor activity of BAT8001 in patients with HER2-positive locally advanced or metastatic breast cancer.Methods:This trial was conducted in subjects with histologically confirmed HER2-positive breast cancer(having evaluable lesions and an Eastern Cooperative Oncology Group performance status of 0 or 1)using a 3+3 design of escalating BAT8001 doses.Patients received BAT8001 intravenously in a 21-day cycle,with dose escalation in 5 cohorts:1.2,2.4,3.6,4.8,and 6.0 mg/kg.The primary objective was to evaluate the safety and tolerability of BAT8001.Preliminary activity of BAT8001 was also assessed as a secondary objective.Results:Between March 2017 to May 2018,29 HER2-positive breast cancer patients were enrolled.The observed dose-limiting toxicities were grade 4 thrombocytopenia and grade 3 elevated transaminase.The maximum tolerated dose was determined to be 3.6 mg/kg.Grade 3 or greater adverse events(AEs)occurred in 14(48.3%)of 29 patients,including thrombocytopenia in 12(41.4%)patients,aspartate aminotransferase increased in 4(13.8%)patients,γ-glutamyl transferase increased in 2(6.9%)patients,alanine aminotransferase increased in 2(6.9%)patients,diarrhea in 2(6.9%)patients.Objective response was observed in 12(41.4%,95%confidence interval[CI]=23.5%-61.1%)and disease control(including patients achieving objective response and stable disease)was observed in 24(82.8%,95%CI=64.2%-94.2%)patients.Conclusions:BAT8001 demonstrated favorable safety profiles,with promising anti-tumor activity in patients with HER2-positive locally advanced or metastatic breast cancer.BAT8001 has the potential to provide a new therapeutic option in patients with metastatic HER2-positive breast cancer.
