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.     

Lumbar Lipomeningomyelocele Associated with Multiple Café au Lait Spots: A Case Report

We report on a child with several café au lait spots in association with a lumbar lipomeningomyelocele as an apparently new association. Cutaneous markers, the identification of which plays a crucial role in the early diagnosis and management of spinal malformations, can accompany occult spinal dysraphism. Herein we report a case of lumbar lipomeningomyelocele associated with an overlying café au lait spot that served as a marker of occult spinal dysraphism. The patient also had segmental café au lait spots on the face, making the association unique.     

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。     

Antibody testing in Indian children with celiac disease.

BACKGROUND: We prospectively evaluated the usefulness of IgA tissue transglutaminase antibodies (IgA tTG) in the initial diagnosis of celiac disease (CD) and compared its diagnostic potential with that of IgA anti-endomysial antibodies (IgA EMA) and anti-IgA and IgG gliadin antibodies (AGA and AGG, respectively). METHODS: Sera of 23 untreated children fulfilling the revised ESPGHAN criteria for diagnosis of CD (Group I; mean age 10.8 y); 19 disease controls (Group II; mean age 8.5 y) presenting with chronic diarrhea, short stature or both; and 22 healthy children (Group III; mean age 8.8 y) were studied. These were tested in a blinded manner for AGA, AGG, IgA tTG (guinea pig as antigen) and IgA EMA. RESULTS: In Group I, IgA EMA was positive in 19, IgA tTG in 17, AGA in 14 and AGG in 17 patients. In Group II, these tests were positive in 1, 0, 2 and 14 patients, respectively and in Group III, in 0, 0, 0 and 1 child, respectively. Analyzing data from Group I and II, IgA EMA, IgA tTG, AGA and AGG had sensitivity rates of 83%, 74%, 61% and 74%, respectively; the specificity rates were 95%, 100%, 89% and 26%; positive predictive values were 95%, 100%, 88% and 55% and negative predictive values were 82%, 74%, 65% and 45%, respectively. CONCLUSION: IgA tTG is useful for the diagnosis of CD, with sensitivity and specificity rates comparable to those of EMA and this test is well suited for use in tropical countries like India.     

A ‘Weight‐Listing’ Paradox for Candidates of Renal Transplantation?

Research suggests that end-stage renal disease patients with elevated body mass index (BMI) have superior outcomes on dialysis. In contrast, low and high BMI patients represent the highest risk cohorts for kidney transplant recipients. The important question remains concerning how to manage transplant candidates given the potentially incommensurate impact of BMI by treatment modality. We conducted a retrospective analysis of waitlisted and transplanted patients in the United States from 1990 to 2003. We constructed Cox models to evaluate the effect of BMI on mortality of waitlisted candidates and identified risk factors for rapid weight change. We then assessed the impact of weight change during waitlisting on transplant outcomes. Decline in BMI on the waiting list was not protective for posttransplant mortality or graft loss across BMI strata. Substantial weight loss pretransplantation was associated with rapid gain posttransplantation. The highest risk for death was among listed patients with low BMI (13-20 kg/m(2), adjusted hazard ratio = 1.47, p < 0.01). Approximately one-third of candidates had a change in BMI category prior to transplantation. While observed declines in BMI may be volitional or markers of disease processes, there is no evidence that candidates have improved transplant outcomes attributable to weight loss. Prospective trials are needed to evaluate the efficacy of weight loss protocols for candidates of kidney transplantation.     

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.