Impact of modified-release opioid use on clinical outcomes following total hip and knee arthroplasty: a propensity score-matched cohort study

Modified-release opioids are often prescribed for the management of moderate to severe acute pain following total hip and knee arthroplasty, despite recommendations against their use due to increasing concerns regarding harm. The primary objective of this multicentre study was to examine the impact of modified-release opioid use on the incidence of opioid-related adverse events compared with immediate-release opioid use, among adult inpatients following total hip or knee arthroplasty. Data for total hip and knee arthroplasty inpatients receiving an opioid analgesic for postoperative analgesia during hospitalisation were collected from electronic medical records of three tertiary metropolitan hospitals in Australia. The primary outcome was the incidence of opioid-related adverse events during hospital admission. Patients who received modified with or without immediate-release opioids were matched to those receiving immediate-release opioids only (1:1) using nearest neighbour propensity score matching with patient and clinical characteristics as covariates. This included total opioid dose received. In the matched cohorts, patients given modified-release opioids (n = 347) experienced a higher incidence of opioid-related adverse events overall, compared with those given immediate-release opioids only (20.5%, 71/347 vs. 12.7%, 44/347; difference in proportions 7.8% [95%CI 2.3–13.3%]). Modified-release opioid use was associated with an increased risk of harm when used for acute pain during hospitalisation after total hip or knee arthroplasty.     

锁骨钩钢板内固定术后钢板钩与肩峰匹配性影像学研究

目的通过测量锁骨钩钢板内固定术后患者影像学资料，分析发生肩峰骨侵蚀的原因是否与钢板钩-肩峰匹配度相关。 方法回顾性分析2015年8月1日至2018年8月31日期间在上海市浦东医院骨科就诊的210例患者的影像学资料，210例患者均因肩锁关节脱位或锁骨远端骨折行锁骨钩钢板内固定治疗，其中男110例、女100例；年龄24~76岁，平均（44.60±8.75）岁；肩锁关节脱位70例，锁骨远端骨折140例。测量术后及终末随访患者肩锁关节正位X线片相关数据，按锁骨钩钢板术后是否发生肩峰骨侵蚀，将纳入患者分为3组：无骨侵蚀组（A组）、伴钢板钩移位骨侵蚀组（B组）、不伴移位的骨侵蚀组（C组），分别测量钢板钩-肩峰的匹配度（β），统计分析术后发生肩峰骨侵蚀与钢板钩-肩峰匹配度之间的关系。 结果纳入研究的210例患者术后随访24~64周，平均（32.0±6.5）周。A组患者115例，B组患者54例，C组患者41例。A组匹配度β（3.72±0.48）mm与B组β¹（6.91±0.84）mm比较差异有统计学意义（P<0.05）；A组匹配度β（3.72±0.48）mm与C组β²（5.88±0.65）mm比较差异有统计学意义（P<0.05）；B组匹配度β¹（6.91±0.84）mm与C组β²（5.88±0.65）mm比较差异有统计学意义（P<0.05）。 结论锁骨钩钢板内固定术后是否发生肩峰骨侵蚀与钢板钩-肩峰匹配度β存在明显相关性，钢板钩与肩峰之间的匹配度越好，β值越小，发生肩峰骨侵蚀的可能性更小。     

IL-10 contributes to gemcitabine resistance in extranodal NK/T-cell lymphoma cells via ABCC4

Investigational New Drugs - Background&nbsp;Chemotherapy resistance is a main reason for treatment failure in extranodal NK/T-cell lymphoma (ENKTL). Interleukin-10 (IL-10) is closely related to...     

Immunotherapy: A new standard in the treatment of metastatic clear cell renal cell carcinoma

Renal cell cancer (RCC) represents 2%-3% of all adulthood cancers and is the most common malignant neoplasm of the kidney (90%). In the mid-nineties of the last century, the standard of treatment for patients with metastatic RCC was cytokines. Sunititib and pazopanib were registered in 2007 and 2009, respectively, and have since been the standard first-line treatment for metastatic clear cell RCC (mccRCC). Renal cell cancer is a highly immunogenic tumor with tumor infiltrating cells, including CD8+ T lymphocytes, dendritic cells, natural killer cells (NK) and macrophages. This observation led to the design of new clinical trials in which patients were treated with immunotherapy. With the growing evidence that proangiogenic factors can have immunomodulatory effects on the host’s immune system, the idea of combining angiogenic drugs with immunotherapy has emerged, and new clinical trials have been designed. In the last few years, several therapeutic options have been approved [immunotherapy and immunotherapy/tyrosine kinase inhibitors (TKI)] for the first-line treatment of mccRCC. Nivolumab/ipilimumab is approved for the treatment of patients with intermediate and poor prognoses. Several checkpoint inhibitors (pembrolizumab, nivolumab, avelumab) in combination with TKI (axitinib, lenvatinib, cabozantinib) are approved for the treatment of patients regardless of their International mRCC Database Consortium prognostic group and PD-L1 expression. There is no specific and ideal biomarker that could help in selecting the ideal patient for the appropriate first-line treatment.     

CNS Maturation Process in Children and Adolescents in the Northern Region of the Russian Federation and Its Reflection in the Dynamics of Integral EEG Parameters

Neuroscience and Behavioral Physiology - We present here results from analysis of the formation of brain bioelectrical activity in children and adolescents living in the northern region of Russia...     

地鳖纤溶蛋白口服时间/pH依赖结肠靶向微囊的开发及评价＊

地鳖中的纤溶活性蛋白是从地鳖中提取的具有抗栓及抗肿瘤作用的有效成分，其口服易被上消化道酶分解从而限制了应用。采用恒流泵滴制法开发地鳖纤溶活性蛋白时间/pH依赖口服结肠靶向微囊（EnpolypHaga fibrinolytic protein oral colon targeting microcapsules， CTM-EFP）。采用单因素实验和正交实验相结合的方法寻找到包封率为60.17 % ± 2.72 %、载药量为15.50 % ± 0.44 % 的最佳配方。扫描电子显微镜（SEM）显示微囊呈球形、表面光滑，在人工肠液中24 h的累积释放度为99.53 % ± 0.69 %，在人工胃液中24 h累积释放度为7.43 ± 1.04 %，通过时间/pH依赖达到结肠靶向作用。CTM-EFP在人工肠液中的体外释放曲线符合Korsmeyer方程，提示地鳖纤溶活性蛋白（EnpolypHaga fibrinolytic protein， EFP）是通过扩散和侵蚀机制结合释放的。CTM-EFP为EFP的口服给药提供了一种新的剂型，为EFP应用于临床提供参考。