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。     

GALLSTONE CIRRHOSIS: ARE WE ONLY SEEING THE TIP OF THE ICEBERG?

Gallstones are common and their incidence increases with age.¹ Fifty per cent of these stones are in the common bile duct (CBD) in the elderly.² Most of them are silent but with time there is an increasing chance of developing symptoms which are more likely to be serious in the elderly.³ Failure to relieve mechanical obstruction of bile flow may lead to secondary biliary cirrhosis.⁴ It has been estimated that on average secondary biliary cirrhosis develops some seven years after the onset of obstruction from a stricture, four and half years after gallstone obstruction and 10 months after the onset of malignant stricture.⁵ The characteristic features are the pathological findings of portal-portal linkages, with a pattern of monolobular cirrhosis and the preservation of normal vascular relationships.⁶ Secondary biliary cirrhosis may lead to hepatic insufficiency and portal hypertension with the resultant complications, such as bleeding oesophageal varices, hypersplenism with pancytopenia, ascites and encephalopathy. We describe a patient in whom the diagnosis was not suspected until laparotomy and confirmed only at autopsy.     

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.     

Expression of alpha-melanocyte stimulating hormone and the invasive ability of the B16 murine melanoma.

The expression of alpha melanocyte stimulating hormone (MSH) has been investigated in two variants of the B16 murine melanoma. The presence of MSH was demonstrated by immunohistochemical methods using anti-MSH antibodies. The low metastasis variant B16-F1, which grows as an encapsulated non-invasive tumour, showed no alpha-MSH immunoreactivity. In contrast, the high metastasis variant BL6 was found to be alpha-MSH positive and the immunoreactivity was found predominantly in the peripheral invading zones of the tumour.