托珠单抗在新型冠状病毒肺炎的应用研究探讨

2019年12月以来,新型冠状病毒肺炎(Coronavirus Disease 2019,COVID-19)在武汉暴发并蔓延至全国,给整个社会带来巨大的挑战。部分COVID-19感染者早期发病并不十分凶险,但后期会突然加速进展,病人很快进入多脏器功能衰竭的状态,李兰娟院士等提出了"细胞因子风暴"概念。但目前并没有特效药物,认为IL-6是诱发细胞因子风暴的重要通路,本文结合相关文献的复习和分析,旨在综述IL-6受体阻断剂托珠单抗在新型冠状病毒肺炎危重患者使用的可行性。     

快速康复在不同方式胃癌根治手术中的应用

目的:评价快速康复（fast track,FT）模式在不同方式胃癌根治手术患者术后康复中的有效性及安全性。方法:收集我科2016年1月至2017年6月期间行开放(OS)及腹腔镜(LS)胃癌根治手术患者各40例，随机分为FT处理组（OS+FT组、LS+FT组）和常规处理（NT）对照组（OS+NT组、LS+NT组），比较不同处理模式对术后疼痛评分、恢复情况和术后并发症发生率的影响。结果:OS+FT组、LS+FT组术后1、2、3、4和5 d疼痛评分均低于NT对照组，各观察时点差异均有统计学意义（P＜0.005）；OS+FT组、LS+FT组术后首次排气时间、首次离床时间以及住院时间均短于NT对照组（P＜0.05）；术后OS+FT组、LS+FT组总体并发症发生率均为10%，与NT对照组（OS+NT组20%，LS+NT组15%）相比，差异无统计学意义（P＞0.05）。结论:FT模式有利于减少患者痛苦，加速术后恢复，未增加术后并发症风险，在不同方式胃切除手术患者围术期处理过程中安全、有效。     

Liver dysfunction as a cytokine storm manifestation and prognostic factor for severe COVID-19

Liver damage in severe acute respiratory coronavirus 2 infection occurs in patients with or without preexisting liver disorders, posing a significant complication and mortality risk. During coronavirus disease 2019 (COVID-19), abnormal liver function is typically observed. However, liver injury may occur because of the treatment as well. Ischemia, cytokine storm, and hypoxia were identified as the three major factors contributing to liver damage during COVID-19. Indeed, raised liver enzymes during hospitalizations may be attributed to medications used, as well as sepsis and shock. As a result, the proportion of hospitalized patients afflicted with COVID-19 and pathological liver biomarkers varies from 14% to 53%. Aminotransferases and bilirubin are found most often elevated. Usually, increased gamma-glutamyltransferase, alkaline phosphatase, and decreased serum albumin levels are demonstrated. Additionally, although there is no specific treatment for COVID-19, many of the drugs used to treat the infection are hepatotoxic. In this mini-review, we focus on how liver dysfunction can be one of the features associated with the COVID-19 cytokine storm. Furthermore, data show that liver injury can be an independent predictor of severe COVID-19, the need for hospitalization, and death.     

Catastrophic antiphospholipid syndrome and pregnancy. Clinical report

We have observed the development of a catastrophic antiphospholipid syndrome (CAPS) in a pregnant woman hospitalized at 28 weeks of gestation with a severe preeclampsia. On the same day, an eclampsia attack developed, and an emergency surgical delivery was performed. On the third day, multiorgan failure developed. Examination showed a persistent circulation of lupus anticoagulant, high level of antibodies to cardiolipin, b2-glycoprotein I, and prothrombin. The usual diagnosis of the severe preeclampsia masked a catastrophic antiphospholipid syndrome, exacerbated by the coincident presence of several types of antiphospholipid antibodies. The first pregnancy resulted in a premature birth at 25 weeks, possibly also due to the circulation of antiphospholipid antibodies. The trigger of the catastrophic form development was the pregnancy itself, surgical intervention, and hyperhomocysteinemia. CAPS is the most severe form of antiphospholipid syndrome, manifested in multiple microthrombosis of microcirculation of vital organs and in the development of multiorgan failure against the background of the high level of antiphospholipid antibodies. CAPS is characterized by renal, cerebral, gastrointestinal, adrenal, ovarian, skin, and other forms of microthrombosis. Thrombosis recurrence is typical. Thrombotic microvasculopathy lies at the heart of multiorgan failure and manifests clinically in central nervous system lesions, adrenal insufficiency, and ARDS development. CAPS is a life-threatening condition, therefore, requires an urgent treatment. Optimal treatment of CAPS is not developed. CAPS represent a general medical multidisciplinary problem.     

Aging in COVID-19: Vulnerability,immunity and intervention

The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic was first reported in Wuhan, China in December 2019, moved across the globe at an unprecedented speed, and is having a profound and yet still unfolding health and socioeconomic impacts. SARS-CoV-2, a β-coronavirus, is a highly contagious respiratory pathogen that causes a disease that has been termed the 2019 coronavirus disease (COVID-19). Clinical experience thus far indicates that COVID-19 is highly heterogeneous, ranging from being asymptomatic and mild to severe and causing death. Host factors including age, sex, and comorbid conditions are key determinants of disease severity and progression. Aging itself is a prominent risk factor for severe disease and death from COVID-19. We hypothesize that age-related decline and dysregulation of immune function, i.e., immunosenescence and inflammaging play a major role in contributing to heightened vulnerability to severe COVID-19 outcomes in older adults. Much remains to be learned about the immune responses to SARS-CoV-2 infection. We need to begin partitioning all immunological outcome data by age to better understand disease heterogeneity and aging. Such knowledge is critical not only for understanding of COVID-19 pathogenesis but also for COVID-19 vaccine development.     

CAR-T治疗后细胞因子释放综合征的发生机制与临床治疗

[摘要] 靶向CD19 的嵌合抗原受体修饰T 细胞（CAR-T）疗法在B 细胞肿瘤治疗中取了重大进展，美国FDA 已批准了2 项CD19 CAR-T治疗产品上市。随着CAR-T、双特异性T细胞衔接器（BiTE）和双重高亲靶向蛋白（DART）以及基因修饰的T细胞受体疗法（TCR-T）等免疫治疗临床及机制研究的开展，其潜在风险及副作用得到更广泛的认识，尤其是细胞因子释放综合征（CRS）。CRS是目前CAR-T治疗后最常见的并发症，重者可能危及生命。CRS病理生理学机制复杂，涉及多种免疫细胞及非免疫细胞，并可累及全身各脏器，研究CRS发生发展机制对提高CAR-T治疗安全性有重要意义。近年来，研究者们在动物模型中对CRS机制进行了更深入的研究。本文论述CRS的发生、病理生理学机制、动物模型、临床特征以及分级治疗等研究进展，旨在为更深入地从机制层面了解CRS，更安全地开展CAR-T临床应用提供指导。     

Nano-curcumin therapy,a promising method in modulating inflammatory cytokines in COVID-19 patients

BackgroundAs an ongoing worldwide health issue, Coronavirus disease 2019 (COVID–19) has been causing serious complications, including pneumonia, acute respiratory distress syndrome (ARDS), and multi-organ failure. However, there is no decisive treatment approach available for this disorder, which is primarily attributed to the large amount of inflammatory cytokine production. We aimed to identify the effects of Nano-curcumin on the modulation of inflammatory cytokines in COVID-19 patients.MethodForty COVID-19 patients and 40 healthy controls were recruited and evaluated for inflammatory cytokine expression and secretion. Subsequently, COVID-19 patients were divided into two groups: 20 patients receiving Nano-curcumin and 20 patients as the placebo group. The mRNA expression and cytokine secretion levels of IL-1β, IL-6, TNF-α and IL‐18 were assessed by Real‐time PCR and ELISA, respectively.ResultOur primary results indicated that the mRNA expression and cytokine secretion of IL-1β, IL-6, TNF-α, and IL-18 were increased significantly in COVID-19 patients compared with healthy control group. After treatment with Nano-curcumin, a significant decrease in IL-6 expression and secretion in serum and in supernatant (P = 0.0003, 0.0038, and 0.0001, respectively) and IL-1β gene expression and secretion level in serum and supernatant (P = 0.0017, 0.0082, and 0.0041, respectively) was observed. However, IL-18 mRNA expression and TNF-α concentration were not influenced by Nano-curcumin.ConclusionNano-curcumin, as an anti-inflammatory herbal based agent, may be able to modulate the increased rate of inflammatory cytokines especially IL-1β and IL-6 mRNA expression and cytokine secretion in COVID-19 patients, which may cause an improvement in clinical manifestation and overall recovery.     

Enhanced recovery (fast-track surgery) after total ankle replacement: The state of the art

The post-operative results of a total ankle replacement are not determined solely by an optimal surgical technique, but by an appropriate anesthesiological and rehabilitative post-operative approach. Enhanced functional recovery often depends on a multidisciplinary approach based on a correct framework of the patient and his needs, requests, and characteristics.Extensive bibliographical research has been performed on Pubmed, Google Scholar, Scopus.This comprehensive and inclusive review of the literature aims to examine the state of the art of “fast-track” protocols employed in total ankle replacement (TAR), considering pre-operative preparation, anesthetic management, intraoperative and surgical factors, post-operative rehabilitative care and reduction of hospitalization time.