Abnormal liver function tests associated with severe rhabdomyolysis

Rhabdomyolysis is a syndrome of skeletal muscle injury with release of cellular constituents such as potassium,phosphate,urate and intracellular proteins such as myoglobin into the circulation,which may cause complications including acute kidney injury,electrolyte disturbance and cardiac instability.Abnormal liver function tests are frequently observed in cases of severe rhabdomyolysis.Typically,there is an increase in serum aminotransferases,namely aspartate aminotransferase and alanine aminotransferase.This raises the question of liver injury and often triggers a pathway of investigation which may lead to a liver biopsy.However,muscle can also be a source of the increased aminotransferase activity.This review discusses the dilemma of finding abnormal liver function tests in the setting of muscle injury and the potential implications of such an association.It delves into some of the clinical and experimental evidence for correlating muscle injury to raised aminotransferases,and discusses pathophysiological mechanisms such as oxidative stress which may cause actual liver injury.Serum aminotransferases lack tissue specificity to allow clinicians to distinguish primary liver injury from muscle injury.This review also explores potential approaches to improve the accuracy of our diagnostic tools,so that excessive or unnecessary liver investigations can be avoided.     

Innovative Thinking on Endpoint Selection in Clinical Trials

ABSTRACT

In clinical trials, selection of appropriate study endpoints is critical for an accurate and reliable evaluation of safety and effectiveness of a test treatment under investigation. In practice, however, there are usually multiple endpoints available for measurement of disease status and/or therapeutic effect of the test treatment under study. For example, in cancer clinical trials, overall survival, response rate, and/or time to disease progression are usually considered as primary clinical endpoints for evaluation of safety and effectiveness of the test treatment under investigation. Once the study endpoints have been selected, sample size required for achieving a desired power is then determined. It, however, should be noted that different study endpoints may result in different sample sizes. In practice, it is usually not clear which study endpoint can best inform the disease status and measure the treatment effect. Moreover, different study endpoints may not translate one another although they may be highly correlated one another. In this article, we intend to develop an innovative endpoint namely therapeutic index based on a utility function to combine and utilize information collected from all study endpoints. Statistical properties and performances of the proposed therapeutic index are evaluated theoretically. A numerical example concerning a cancer clinical trial is given to illustrate the use of the proposed therapeutic index.     

神经源性声带运动障碍与喉神经电生理

声带运动障碍的病因和临床表现复杂多变，涉及多学科，从病因上分为神经源性和非神经源性。对于神经源性声带运动障碍的诊治，首先通过喉镜等检查明确有无声带运动障碍及严重程度，值得注意的是声带纵向张力变化障碍也属于运动障碍的范畴；然后采用喉肌电图（LEMG）检查进行定性分析，在确诊神经源性损伤后，进一步对神经损伤部位进行定位诊断并查找导致神经损伤的病因；同时根据喉部神经电生理评估结果，判断预后。最后综合上述的评估结果制定相应的治疗策略。     

VATS解剖性肺段切除术与肺叶切除术治疗Ⅰa期NSCLC患者的手术情 况及对肺功能影响的比较

目的:探讨电视胸腔镜（VATS）解剖性肺段切除术与肺叶切除术治疗Ia 期非小细胞肺癌（NSCLC）患者的手术情况及对患者肺功能的影响。方法:选取我院手术治疗的Ⅰa期NSCLC患者，收集时间2014年1月至2016年12月，根据术式不同分为两组，均采用VATS手术治疗，A组（54例）患者采用解剖性肺段切除术、B组（60例）采用肺叶切除术治疗，对比两组患者的手术效果及术后肺功能变化。结果:A组患者的手术时间、清扫淋巴结数目与B组比较差异无统计学意义（P>0.05）；A组患者的手术出血量、术后胸腔引流量、术后拔管时间、术后住院时间均显著的低于B组患者（P<0.05）；术前，A组和B组患者的FEV1%、FVC%、MVV%测定值差异无统计学意义（P>0.05），术后3个月复查，A组患者的FEV1%、FVC%、MVV%测定值均显著高于B组患者（P<0.05）；手术后，A组患者的并发症发生率（7.41%）低于B组患者（13.33%），但是差异无统计学意义（P>0.05）。结论:VATS解剖性肺段切除术治疗Ⅰa期NSCLC患者具有手术创伤小、术后恢复快、对患者肺功能影响更小的优势。     

A case of purulent pneumococcal pericarditis

Background

Purulent bacterial pericarditis is a rare and potentially fatal disease. The course may be fulminant, and the presentation may pose a diagnostic challenge.

Dexamethasone potentiates in vitro blood-brain barrier recovery after primary blast injury by glucocorticoid receptor-mediated upregulation of ZO-1 tight junction protein

Owing to the frequent incidence of blast-induced traumatic brain injury (bTBI) in recent military conflicts, there is an urgent need to develop effective therapies for bTBI-related pathologies. Blood-brain barrier (BBB) breakdown has been reported to occur after primary blast exposure, making restoration of BBB function and integrity a promising therapeutic target. We tested the hypothesis that treatment with dexamethasone (DEX) after primary blast injury potentiates recovery of an in vitro BBB model consisting of mouse brain endothelial cells (bEnd.3). DEX treatment resulted in complete recovery of transendothelial electrical resistance and hydraulic conductivity 1 day after injury, compared with 3 days for vehicle-treated injured cultures. Administration of RU486 (mifepristone) inhibited effects of DEX, confirming that barrier restoration was mediated by glucocorticoid receptor signaling. Potentiated recovery with DEX treatment was accompanied by stronger zonula occludens (ZO)-1 tight junction immunostaining and expression, suggesting that increased ZO-1 expression was a structural correlate to BBB recovery after blast. Interestingly, augmented ZO-1 protein expression was associated with specific upregulation of the α⁺ isoform but not the α⁻ isoform. This is the first study to provide a mechanistic basis for potentiated functional recovery of an in vitro BBB model because of glucocorticoid treatment after primary blast injury.