Simeprevir added to peginterferon and ribavirin lessens time with fatigue,depressive symptoms and functional limitations in patients with chronic hepatitis C compared with peginterferon and ribavirin: results from 1161 patients in the QUEST‐1, QUEST‐2 and PROMISE studies

The value of adding simeprevir (SMV) vs placebo (PBO) to peginterferon and ribavirin (PR) for treatment of chronic hepatitis C virus infection was examined using patient‐reported outcomes (PROs); further, concordance of PROs with virology endpoints and adverse events (AEs) was explored. Patients (n = 768 SMV/PR, n = 393 PBO/PR) rated fatigue (FSS), depressive symptoms (CES‐D) and functional impairment (WPAI: Hepatitis C Productivity, Daily Activity and Absenteeism) at baseline and throughout treatment in three randomised, double‐blind trials comparing the addition of SMV or PBO during initial 12 weeks of PR. PR was administered for 48 weeks (PBO group) and 24/48 weeks (SMV group) using a response‐guided therapy (RGT) approach. Mean PRO scores (except Absenteeism) worsened from baseline to Week 4 to the same extent in both groups but reverted after Week 24 for SMV/PR and only after Week 48 for PBO/PR. Accordingly, there was a significantly lower area under the curve (baseline–Week 60, AUC₆₀) and fewer weeks with clinically important worsening of scores in the SMV/PR group at any time point. Incidences of patients with fatigue and anaemia AEs were similar in both groups, but FSS scores showed that clinically important increases in fatigue lasted a mean of 6.9 weeks longer with PBO/PR (P < 0.001). PRO score subgroup analysis indicated better outcomes for patients who met the criteria for RGT or achieved sustained virological response 12 weeks post‐treatment (SVR12); differences in mean PRO scores associated with fibrosis level were only observed with PBO/PR. Greater efficacy of SMV/PR enabled reduced treatment duration and reduced time with PR‐related AEs without adding to AE severity.     

血清胱抑素C和尿微量白蛋白联合检测在人类免疫缺陷病毒感染者肾功能损伤检测中的应用价值

目的评估血肌酐和尿常规的常规检测基础上联合血清胱抑素C和尿微量白蛋白检测在人类免疫缺陷病毒（HIV）感染者肾功能损伤检测中的应用价值。 方法以2019年2～5月于首都医科大学附属北京地坛医院感染一科住院的169例HIV感染者为研究对象，完善其尿常规、尿微量白蛋白、血肌酐、血清胱抑素C检测；分析尿蛋白及尿微量白蛋白的阳性检出率及其差异，血肌酐升高及血清胱抑素C升高的比例及其差异。计算应用替诺福韦酯（TDF）及合并丙型肝炎、高血压、糖尿病、肿瘤的肾功能损伤的相对危险度。 结果169例HIV感染者中尿常规示尿蛋白阳性者5例（3.0%），尿微量白蛋白升高者17例（10.1%），两者阳性检出率差异具有统计学意义（χ² = 5.9、P = 0.007）。血肌酐升高者10例（5.9%），血清胱抑素C升高者20例（11.8%），两者阳性检出率差异具有统计学意义（χ² = 3.0、P = 0.042）。在尿常规和血肌酐检测的基础上联合检测尿微量白蛋白和血清胱抑素C的总体阳性检出率为49例（30.0%）。CD4⁺ T淋巴细胞计数< 200个/μl与≥ 200个/μl组患者血清胱抑素C水平分别为0.94（0.83，1.05）mg/L、0.85（0.77，0.95）mg/L，差异具有统计学意义（Z =-3.02、P = 0.003）。应用TDF及合并丙型肝炎、高血压、糖尿病、肿瘤的肾功能损伤的相对危险度分别为1.1、1.5、1.9、2.2和1.4。 结论HIV感染者中，单纯以尿常规为依据评估有无蛋白尿，以血肌酐水平为依据评估肾小球滤过功能会低估肾功能损伤的患病率。在常规检测血肌酐和尿常规的基础上联合检测血清胱抑素C和尿微量白蛋白在提高HIV感染者肾功能损伤检出率方面具有重要的应用价值。低CD4⁺ T淋巴细胞计数、应用TDF及合并丙型肝炎、高血压、糖尿病、肿瘤均为肾功能损伤的危险因素。     

酪氨酸激酶受体RON与E-cadherin在子宫内膜异位症上的表达及意义

目的探讨酪氨酸激酶受体RON及上皮型钙粘蛋白(E-cadherin)在子宫内膜异位症(endometriosis,EMs)上的表达及意义。方法选择2017年7~12月深圳市龙岗区人民医院收治的42例EMs患者,术中分别留取新鲜异位内膜组织和在位内膜组织,随机选取子宫切除或诊断性刮宫治疗的非EMs患者42例,术中留取其正常子宫内膜组织。采用逆转录聚合酶链反应(RT-PCR)检测子宫内膜组织中RON mRNA的表达,采用免疫组织化学方法检测对应42例石蜡组织中RON蛋白和E-cadherin的表达,并分析RON蛋白和E-cadherin的相关性。结果EMs异位内膜组织RON mRNA及RON蛋白阳性表达率显著高于在位内膜组织及正常子宫内膜组织(P<0.001),在位内膜组织及正常内膜组织中E-cadherin阳性表达率显著高于异位内膜组织(P<0.001),且异位内膜组织中RON mRNA及RON蛋白的表达与临床分期有关(P<0.001)。在同一标本中RON蛋白和E-cadherin表达呈负相关关系(r=-0.497,P<0.05)。结论RON的过度表达与EMs的发生发展密切相关,联合检测RON和E-cadherin的异常对判断EMs的发生发展有一定的参考价值,RON可能成为诊断治疗EMs的新靶点。     

Immune Checkpoint Inhibitor Toxicities

Immune checkpoint inhibitors are molecules that increase the endogenous immune response against tumors. They have revolutionized the field of oncology. Since their initial approval for the treatment of advanced melanoma, their use has expanded to the treatment of several other advanced cancers. Unfortunately, immune checkpoint inhibitors have also been associated with the emergence of a new subset of autoimmune-like toxicities, known as immune-related adverse events. These toxicities differ depending on the agent, malignancy, and individual susceptibilities. Although the skin and colon are most commonly involved, any organ may be affected, including the liver, lungs, kidneys, and heart. Most of these toxicities are diagnosed by excluding other secondary infectious or inflammatory causes. Corticosteroids are commonly used for treatment of moderate and severe immune-related adverse events, although additional immunosuppressive therapy may occasionally be required. The occurrence of immune-related toxicities may require discontinuation of immunotherapy, depending on the specific toxicity and its severity. In this article, we provide a focused review to familiarize practicing clinicians with this important topic given that the use of immune checkpoint inhibitors continues to increase.