A Phase I Dose Escalation Study of the Safety,Tolerability, and Pharmacokinetics of Ipilimumab in Chinese Patients with Select Advanced Solid Tumors

Lessons Learned

• The overall safety profiles of ipilimumab 3 mg/kg and 10 mg/kg administered every 3 weeks, were consistent between Chinese patients with solid tumors in the current study and patients from previous U.S. ipilimumab monotherapy studies. No new safety signals were identified.
• The mean systemic exposures to ipilimumab (assessed by first dose area under the curve during the dosing interval and maximum serum concentration) were numerically lower in the Chinese patient population than in U.S. patients for both 3 mg/kg and 10 mg/kg doses; however, the range of serum concentrations in the Chinese and U.S. populations overlapped (3 mg/kg and 10 mg/kg), suggesting that ipilimumab pharmacokinetics was ethnically insensitive in this study.

BackgroundThis phase I, open‐label study assessed ipilimumab safety, tolerability, pharmacokinetics (PK), immunogenicity, and antitumor activity in Chinese patients with unresectable, metastatic, recurrent malignant melanoma (MM) or nasopharyngeal carcinoma (NPC).MethodsOf 39 patients enrolled, 25 received ipilimumab (11 patients received 3 mg/kg, and 14 patients received 10 mg/kg). Reasons for not receiving treatment were withdrawal of consent (3 patients), no longer meeting the criteria (10 patients), and one recorded as “other.” During the induction phase, patients received ipilimumab (3 mg/kg, i.v.), on day 1 of a 3‐week cycle, to a maximum of four doses or progressive disease (PD). During the maintenance phase at week 24, patients received ipilimumab (3 mg/kg, i.v.) on day 1 of a 12‐week cycle, to a maximum of 3 years or PD. Considering the co‐primary safety and PK endpoints, the successive dosing required nine patients with two or fewer dose‐limiting toxicities during the 42‐day observation period to proceed with a new cohort of nine patients at 10 mg/kg.ResultsIpilimumab safety and PK profiles were similar in Chinese and predominantly White populations. Ipilimumab was well tolerated. Most adverse events (AEs) were grades 1–2 and experienced by 11 patients treated with 3 mg/kg and 14 patients treated with 10 mg/kg. There were no new safety concerns. Incidence of anti‐ipilimumab antibodies was low (1 of 10 in the 3 mg/kg patients and 2 of 13 in the 10 mg/kg patients) and without safety implications. In the 3 mg/kg group, 8 of 11 patients had PD. In the 10 mg/kg group (all NPC, 0 MM patients), 11 of 14 patients had PD. Three patients had stable disease (one at 3 mg/kg and two at 10 mg/kg).ConclusionIpilimumab was well tolerated in Chinese patients, showing similar safety and PK to previous studies in predominantly White populations.     

关节滑液检测在关节假体周围感染诊断中的研究进展

关节假体周围感染(periprosthetic joint infection,PJI)是人工关节置换术后可能发生的一种严重并发症,其导致的严重后果,无论对于医生还是患者来说,都很难接受。目前,由于多种不确定因素的存在,PJI诊断的准确性较低。传统的血清学检查、影像学检查有一定的价值,但是易受全身情况的影响,导致特异性不高。为了正确诊断关节假体周围感染,不同学科的研究人员采用各种不同的方法进行了大量的诊断研究,并取得了丰富的成果。近年来,关节滑液炎性标志物检测、分子生物学方法等被研究证实具有较高的敏感性和特异性。因此,关节滑液CRP、-防御素、白细胞酯酶、PCR技术等被广泛研究,期望能从中找到诊断关节假体周围感染的特异性指标,提高临床诊断的准确性。     

2014—2018年黄山市淋病疫情流行特征分析

目的分析2014-2018年黄山市淋病的流行特征,为全市的淋病防控工作提供科学依据。方法通过中国疾病预防控制信息系统收集黄山市2014—2018年的淋病数据、人口数据,进行统计分析。结果2014—2018年黄山市累计报告淋病病例761例,年均发病率为11.09/10万,年均增长率为29.14%,发病率呈逐年上升趋势(χ^2趋势=112.29,P<0.05)。淋病的人群分布中,男女报告病例数之比为13.63:1,男女发病率有统计学差异(χ^2=113.18,P<0.05);15~49岁年龄组病例数最多,占85.94%,职业以农民最多,占44.81%;以屯溪区、歙县报告病例数较多,分别占37.45%、23.26%。结论2014—2018年黄山市淋病发病率呈上升趋势,淋病防控形势严峻,需进一步完善各项防控措施。     

雌、孕激素受体和C-erbB-2在原发胆囊癌中的表达及意义

目的　探讨雌、孕激素受体 (ER、PgR)和C erbB 2癌基因蛋白产物在原发胆囊癌发生、发展中的作用及相互关系 ,研究它们的表达与肿瘤的病理类型、分级 ,临床分期及预后的关系 ,并为该病的临床诊治提供参考依据。方法　应用免疫组织化学法 ,检测 3 5例原发胆囊癌 ,2 0例慢性胆囊炎组织中ER、PgR和C erbB 2癌基因蛋白的表达水平。结果　在原发胆囊癌中ER、PgR和C erbB 2阳性表达率分别为 60 %、4 5 .7%和 65 .7%。ER的阳性表达与浸润及淋巴结转移密切相关 (P <0 .0 5 )。C erbB 2过度表达与胆囊癌淋巴结转移有关 (P <0 .0 5 )。ER或PgR阳性患者的累计生存率明显低于阴性者。结论　ER、PgR及C erbB 2在原发胆囊癌中的表达率显著高于其在胆囊良性病变中的表达率。ER或PgR阳性者积累生存率显著低于ER或PgR阴性者。ER可能有希望成为反映胆囊癌恶性程度和预后的一项生物学指标     

腹壁巨大切口疝患者行无张力修补术的护理

对24例采用膨化聚氟乙烯网片行腹壁巨大切口疝无张力修补术患者术前予详细评估、束腹训练、呼吸功能锻炼及肠道准备;术后密切观察呼吸情况,防止腹内压增加和切口感染,给予出院指导.结果 本组病例无并发症发生,切口甲级愈合23例,乙级愈合1例,平均住院13.4 d,随访1～5年,22例无复发,2例术后2～3年复发.提出系统的积极的术前术后护理干预是促进腹壁巨大切口疝无张力修补术患者尽快康复,减少术后并发症和复发率的重要措施.     

经肘外侧入路治疗Gartland Ⅲ型肱骨髁上骨折

1995年1月～2006年6月，我院采用肘外侧纵形切口、交叉克氏针内固定治疗Gartlandm型肱骨髁上骨折96例，取得较好效果。     

2-cyclohexene-1-one-induced hyperglycemia in the mice

2-Cyclohexene-1-one (CHX) dose-dependently caused the elevation of blood glucose levels in both fed and fasted mice. Adrenalectomy considerably prevented the elevated blood glucose with CHX, and plasma adrenaline assays revealed about a three- to fifteen-fold rise after CHX treatment. These findings indicate that the CHX-induced hyperglycemia may be largely mediated by adrenaline released from the adrenal medulla.