放疗后心脏损伤的早期影像检出

放射性治疗（radiotherapy，RT）是肿瘤的重要治疗手段之一，增加了患者的生存率。但是在胸部放射治疗过程中，心脏不可避免地受到影响，引起放射性心脏损伤（rdiation-induced heart disease，RIHD）。RIHD可涉及心脏的任何结构，已成为威胁癌症患者生存的主要并发症之一，近年来越来越受到临床关注。RIHD的早期检出对于癌症患者尤其年轻癌症患者具有重要的临床意义。目前尚无关于RIHD统一明确的早期诊断标准，而影像学检查能够早期、准确地检出RIHD，不同的影像学检查在RIHD的检测中有着不同的意义。本文就RIHD早期的影像检出作一简要综述。     

Starvation in cancer cells: circulating arginine is good for cancer but bad for patients

Introduction: Currently, basic understanding of heterogeneity and complexity of tumors is depicted at molecular, cellular, genetic, epigenetic and metabolic adaptations levels.

Areas covered: There are appreciable numbers of views to pinpoint signaling axis that support metabolic adaptations of cancer cells in response to environmental pressures including nutritional factors and drug treatments. Specifically, nutritional deprivation and autophagy in certain types of cancer are linked to the abilities of cancer cells to use arginine in an auxotrophic or prototrophic manner.

Expert opinion: Hence, this paper highlights the current scope of arginine- and autophagy-centered metabolic adaptations across tumor types and possible avenues to bring tumors towards cytotoxic or cytostatic death.     

二尖瓣成形术的手术临床运用疗效分析

目的通过对行手术治疗的二尖瓣关闭不全的患者进行临床分析,探讨二尖瓣成形术在心脏患者手术中的临床疗效。方法回顾性分析2016年1-2019年1月在昆明医科大学附属曲靖市第一人民医院因"二尖瓣关闭不全"住院的患者,以行二尖瓣手术的患者为研究对象,其中行二尖瓣置换术的患者设为对照组,男性23例,女性15例,年龄40~65岁,平均年龄(53.71±10.67)岁。行二尖瓣成形术的患者设为实验组,男性15例,女性8例,年龄39~63岁,平均年龄(53.21±6.63)岁。术中记录阻断时间、辅助循环时间、食道超声测量术后返流量等数据。术后一周左右复查心脏超声、胸片,观察手术前后左心房、左心室舒张末期内径大小及EF值变化,术后并发症、恢复时间等情况,另通过门诊复查随访等观察,评价手术效果。测定结果采用多样本t检验、χ~2检验。结果实验组体外循环时间、阻断时间、术后出院时间、ICU住院时间均明显优于对照组,且差异具有统计学意义(P<0.05),两组围手术期并发症、二次转机、死亡、术后中度以上返流患者例数差异均无统计学意义(P>0.05)。结论二尖瓣成形术与二尖瓣置换术手术效果相当,且可以很好的缩短体外循环和阻断时间、缩短ICU住院时间,从长期的手术效果看,尚需观察随访。     

稳心颗粒联合尼可地尔治疗缺血性心肌病房性心律失常临床观察

目的探讨缺血性心肌病伴房性心律失常采用稳心颗粒联合尼可地尔治疗的临床效果。方法选择2017年1月—2019年1月收治的缺血性心肌病伴房性心律失常患者114例,遵照不同治疗原则分组标准分为对照组和研究组,各57例,2组入院后均采用常规基础治疗,对照组在基础治疗的基础上给予稳心颗粒进行治疗。研究组在对照组的基础上联合应用尼可地尔进行治疗,比较2组治疗效果、心功能情况、P波离散程度、6 min步行试验距离以及不良反应。结果研究组治疗总有效率为96.49%,显著高于对照组(80.70%),差异有显著性意义(P<0.05)。研究组心功能、P波离散程度、6 min步行距离以及脑钠素水平均显著好于对照组,差异均存在统计学意义(P<0.05),但2组患者用药后不良反应发生率比较,差异无统计学意义(P>0.05)。结论稳心颗粒联合尼可地尔应用于缺血性心肌病伴房性心律失常患者的治疗中,能够显著提高治疗效果,改善心脏功能,且未见明显不良反应,好于单一用药,值得推广。     

Association Between Clinical Tumor Burden and Efficacy of Immune Checkpoint Inhibitor Monotherapy for Advanced Non–Small-Cell Lung Cancer

BackgroundProgrammed cell death 1 (PD-1) inhibitors have become a standard treatment, albeit not completely effective, for patients with advanced non–small-cell lung cancer (NSCLC). Previous studies of advanced melanoma have revealed that the tumor burden predicted the response to PD-1 inhibitors, although this relationship has remained unclear for NSCLC.Patients and MethodsThe present single-center retrospective study evaluated 163 patients with advanced NSCLC who had received PD-1/programmed cell death ligand 1 (PD-L1) inhibitor monotherapy from December 2015 to December 2018. The clinical tumor burden was estimated using the baseline sum of the target lesions’ longest diameters (BSLDs), measured according to the Response Evaluation Criteria for Solid Tumors, and the baseline number of metastatic lesions (BNMLs).ResultsThe optimal cutoff values for predicting progression-free survival (PFS) were 5 for the BNMLs and 76 mm for the BSLDs, using the minimum P value method. The low-BNML group included 73 patients (44.8%). The median PFS was 12.2 months in the low-BNML group and 2.8 months in the high-BNML group (hazard ratio, 0.51; P = .0005). The low-BSLD group included 92 patients (56.4%). The median PFS was 9.6 months in the low-BSLD group and 3.4 months in the high-BSLD group (hazard ratio, 0.52; P = .0006). Multivariable analysis revealed that low-BSLD, low-BNML, nonsquamous histologic type and a PD-L1 tumor proportion score of ≥ 50% were independently associated with prolonged PFS.ConclusionsPD-L1 expression and the clinical tumor burden can predict the efficacy of PD-1/PD-L1 inhibitor monotherapy for NSCLC.     

Cost–Utility Analysis of Pembrolizumab Versus Chemotherapy as First-Line Treatment for Metastatic Non-Small Cell Lung Cancer With Different PD-L1 Expression Levels

To evaluate the cost–utility of pembrolizumab versus chemotherapy as the first-line setting for metastatic nonsmall cell lung cancer (NSCLC) from the US health care system perspective, a Markov model was developed to compare the lifetime cost and effectiveness of pembrolizumab versus chemotherapy for untreated metastatic NSCLC, based on the clinical data derived from phase III randomized controlled trial (KEYNOTE- 042; ClinicalTrials.gov; NCT02220894). Weibull distribution was fitted to simulate the parametric survival functions. Drug costs were collected from official websites, and utility values were obtained from published literature. Total costs, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios (ICERs) were computed as primary output indicators. The impact of different PD-L1 expression levels on ICER was also evaluated. One-way and probabilistic sensitivity analyses were performed to assess the model uncertainty. Compared with chemotherapy, patients treated with pembrolizumab provided an additional 1.13, 1.01, and 0.59 QALYs in patients with PD-L1 expression levels of ≥50%, ≥20%, and ≥1%, with corresponding incremental cost of $53,784, $47,479, and $39,827, respectively. The resultant ICERs of pembrolizumab versus chemotherapy were $47,596, $47,184, and $68,061/QALY, in three expression levels of PD-L1, respectively, all of which did not exceed the WTP threshold of 180,000/QALY. Probability sensitivity analysis outcome supported that pembrolizumab exhibited evident advantage over chemotherapy to be cost-effective. One-way sensitivity analysis found that ICERs were most sensitive to utility value of pembrolizumab in progression survival state. All the adjustment of parameters did not qualitatively change the result. For treatment-naive, metastatic NSCLC patients with PD-L1+, pembrolizumab was estimated to be cost-effective compared with chemotherapy for all PD-L1 expression levels at a WTP threshold of $180,000/QALY in the context of the US health care system.     

Effectivity and safety of PD-1/PD-L1 inhibitors for different level of PD-L1-positive,advanced NSCLC: A meta-analysis of 4939 patients from randomized controlled trials

BackgroundEffective improvement for the programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1) inhibitors had been shown in advanced non-small cell lung cancer (NSCLC) patients compared with traditional therapy. However, we do not have ample evidences to demonstrate the safety and effectivity in the treatment of PD-L1-positive, advanced NSCLC. The relation was controversial about the expression of PD-L1 and survival outcomes of PD-1/PD-L1 inhibitors.Materials and methodsElectronic databases (PubMed, EMBASE, and the Cochrane library) and major conference proceedings were systematically searched for all clinical trials in NSCLC using PD-1/PD-L1 inhibitors. Randomized controlled trials (RCTs) were included to compare PD-1/PD-L1 inhibitors with chemotherapy in advanced NSCLC patients reporting adverse events (AEs) and immune-related AEs (irAEs). The incidence, Hazard Ratio (HR), Odds Ratio (OR), and corresponding 95% confidence interval (CI) of outcomes were calculated.ResultsA total of 4939 patients from 10RCTs were included. In the group of PD-L1 ≥ 1%, PD-L1 ≥ 5%, PD-L1 ≥ 10%, PD-L1 ≥ 50%, the HR of OS is 0.31(95%CI 0.38–0.23; p < 0.0001), 0.47(95%CI 0.82–0.12; p = 0.008), 0.85(95%CI 1.17–0.53; p < 0.0001), 0.47(95%CI 0.59–0.36; p < 0.0001) respectively. The HR of PFS is 0.13(95%CI 0.01–0.24; p = 0.027), 0.31(95%CI 0.00–0.62; p < 0.0001), 0.62(95%CI 0.30–0.93; p < 0.0001), 0.40(95% CI 0.20–0.59; p < 0.0001) respectively. In terms of summary adverse events, PD-1/PD-L1 inhibitors groups had a significant lower risks in any treat-realated AEs than chemotherapy. About irAEs, PD-1/PD-L1 inhibitors groups had a significant higher risks in irAEs than chemotherapy.ConclusionPD-1/PD-L1 inhibitors are generally effected and safer than chemotherapy for patients with PD-L1-positive, advanced NSCLC. However, PD-1/PD-L1 inhibitors can generate a unique spectrum of irAEs, and even life-threatening.     

癫痫持续状态后小鼠海马组织神经元中微管蛋白和内体-溶酶体系统表达的变化及其意义

目的：探讨癫痫持续状态（SE）后小鼠海马组织神经元中微管蛋白β-tubulin和内体-溶酶体系统表达的变化，阐明神经元迟发性死亡过程中微管和内体-溶酶体系统的变化规律。方法：40只雄性ICR小鼠分为对照组（n=7，给予生理盐水）和实验组（n=33，给予匹鲁卡品），实验组中达到SE标准的SE小鼠根据SE后时间分为SE1d、SE2d、SE3d和SE7d组（n=5）。Nissl和Fluoro-Jade B （F-JB）染色检测各组小鼠海马组织神经元损伤情况，免疫荧光法检测各组小鼠海马组织神经元中微管蛋白β-tubulin、内体蛋白Rab5和溶酶体结构蛋白LAMP1表达强度及β-tubulin、Rab5和LAMP1阳性面积百分比；双重荧光法检测各组小鼠海马组织CA1区β-tubulin与Rab5和LAMP1表达的关系。结果：与对照组比较，SE1d组小鼠海马CA1和CA3区神经元数减少（P<0.01），F-JB阳性细胞数增加（P<0.01）；SE2d、SE3d和SE7d组小鼠海马组织中Nissl阳性神经元数明显减少（P<0.01）。与对照组比较，SE2d、SE3d和SE7d组小鼠海马组织中F-JB阳性神经元数增加（P<0.01）。与对照组比较，SE2d、SE3d和SE7d组小鼠海马CA1和CA3区神经元树突中β-tubulin阳性面积百分比明显降低（P<0.05），其变化趋势与神经元损伤相似。与对照组比较，SE1d、SE 2d、SE 3d和SE 7d组小鼠海马组织神经元中Rab5和LAMP1表达强度随着时间延长呈下降趋势；Rab5阳性面积百分比明显降低（P<0.05或P<0.01）；LAMP1阳性面积百分比在SE后第1天出现一过性增多，之后逐渐减少（P<0.05或P<0.01）。双重荧光染色检测，SE后1 d是早期内体减少和溶酶体一过性增多的关键点，并与神经元微管损伤的出现时间极为一致。结论：SE引起神经元迟发性死亡的同时神经元微管骨架受损，内体-溶酶体系统的定位和功能也发生异常改变。     

四川省危重型新型冠状病毒肺炎3例死亡病例分析

目的 分析危重型新型冠状病毒肺炎死亡病例的临床特征,提高对重症病例诊治的认识。方法 收集2020年1月—5月成都市公共卫生临床医疗中心接诊的危重型新型冠状病毒肺炎死亡病例资料,回顾性分析其临床资料和影像学特征。结果 3例危重型COVID-19死亡病例均有冠心病、伴或不伴肺部疾病、肾功能障碍等基础疾病,均有发热、咳嗽、咳痰症状,入院APACHEⅡ评分和PSI评分均为高危,实验室检查结果提示肌酸激酶、肌钙蛋白、脑钠肽、C-反应蛋白及血清淀粉样蛋白A明显升高,而T淋巴细胞计数明显下降,胸部影像学提示双肺磨玻璃斑片影。入院后给予积极的抗病毒、抗细菌、增强免疫治疗及有创机械通气呼吸支持。3例患者均并发脓毒性休克及多器官功能衰竭综合征等严重并发症,起病到死亡的平均时间为13.7 d。结论 高龄、合并心脏病等基础疾病、免疫功能低下者是危重型新型冠状病毒肺炎死亡的高危人群。