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。     

Variation of resting energy expenditure after the first chemotherapy cycle in acute leukemia patients

Changes in resting energy expenditure (REE) of cancer patients vary depending on type of tumor, treatment time point and kind of treatment. Little is known about REE of acute leukemia adult patients after treatment, especially with results related to body weight or fat free mass (FFM). This study aimed to assess changes in REE of acute leukemia adult patients before and after the first remission induction. Evaluation of REE was performed by indirect calorimetry and predicted REE was calculated by Harris-Benedict equation. Weight and height were measured and compared to a control group of healthy individuals. FFM was assessed by bioelectrical impedance for adjusting REE values. We evaluated 18 patients and 26 healthy individuals. At diagnosis, patients presented REE, REE/weight, and REE/FFM higher than the controls. Reductions of REE, REE/weight, and REE/FFM were also observed in patients after the first cycle of chemotherapy. The predicted REE for the patients group showed significant lower value compared with measured REE. Before the first cycle of chemotherapy REE was increased but undergoes a reduction after treatment, reaching values similar to the controls. For predictive Harris-Benedict equation, stress factors should be added to avoid underestimation of REE before and after chemotherapy.     

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。     

Left pulmonary artery evaluation through transesophageal echocardiography.

INTRODUCTION: Transesophageal echocardiography (TEE) has become increasingly useful in the study of patients with suspected pulmonary thromboembolism. OBJECTIVE: The aim of this study was to prospectively evaluate the usefulness of TEE in the study of the distal part of the left pulmonary artery (LPA) as well as the influence of this procedure on total echocardiographic exam duration. METHODOLOGY: A prospective study in two groups of consecutive patients referred for TEE with a one- year interval between evaluation of Group A: 33 patients, 17 male, mean age 54 +/- 24 years, and Group B: 42 patients, 20 male, mean age 48 +/- 27 years (p = NS). The procedure was considered long when it took more than 3 min to evaluate the distal part of the LPA. RESULTS: In group A we were able to visualize the distal part of the LPA in 24 patients (73%) without significant prolongation of total exam duration in 16 patients (48% of group A). In one of the patients with suspected pulmonary thromboembolism thrombi were only observed in the distal part of the LPA. In group B we were able to visualize the distal part of the LPA in 36 patients (86%) without significant prolongation of total exam duration in 26 patients (61% of group B). CONCLUSIONS: 1. Visualization of the distal part of the LPA was possible in more patients, and with TEE time prolongation in less patients, in group B. These differences can be accounted for by the training of the operator in this technique. 2. The importance of visualization of this part of the LPA in guiding treatment in the subset of patients with pulmonary thromboembolism confirms the usefulness of this specific procedure.