Comparison of inhaled nitric oxide with aerosolized prostacyclin or analogues for the postoperative management of pulmonary hypertension: a systematic review and meta-analysis

Abstract

Background: This study aims to compare the effectiveness of inhaled prostacyclin or its analoguesversus nitric oxide (NO) in treating pulmonary hypertension (PH) after cardiac or pulmonary surgery remains unclear.

Methods: PubMed, Cochrane, and Embase databases were searched for literature published prior to December 2019 using the following keywords: inhaled, nitric oxide, prostacyclin, iloprost, treprostinil, epoprostenol, Tyvaso, flolan, and pulmonary hypertension. Randomized controlled trials and multiple-armed prospective studies that evaluated inhaled NO versus prostacyclin (or analogues) in patients for perioperative and/or postoperative PH after either cardiac or pulmonary surgery were included. Retrospective studies, reviews, letters, comments, editorials, and case reports were excluded.

Results: Seven studies with a total of 195 patients were included. No difference in the improvement of mean pulmonary arterial pressure (pooled difference in mean change= ?0.10, 95% CI: ?3.98 to 3.78, p?=?.959) or pulmonary vascular resistance (pooled standardized difference in mean change= ?0.27, 95% CI: ?0.60 to 0.05, p?=?.099) were found between the two treatments. Similarly, no difference was found in other outcomes between the two treatments or subgroup analysis.

Conclusions: Inhaled prostacyclin (or analogues) was comparable to inhaled NO in treating PH after cardiac or pulmonary surgery.

• Key messages

• This study compared the efficacy of inhaled prostacyclin or its analogues versus inhaled NO to treat PH after surgery. The two types of agent exhibited similar efficacy in managing MPAP, PVR, heart rate, and cardiac output was observed.

• Inhaled prostacyclin may serve as an alternative treatment option for PH after cardiac or pulmonary surgery.

     

Pulmonary Carcinosarcoma: A Surveillance,Epidemiology, and End Results (SEER) Analysis

IntroductionPulmonary carcinosarcoma (PC) is a rare malignant neoplasm composed of epithelial and mesenchymal components. It accounts for < 1% of thoracic cancers and is not fully understood. This study examined Surveillance, Epidemiology, and End Results (SEER) data to describe demographic and clinical characteristics of patients with PC and assessed survival outcomes by treatment modality and stage.Patients and MethodsSEER data were reviewed to identify patients diagnosed with primary PC (1973-2012). Overall survival (OS) and disease-specific survival (DSS) were analyzed by univariate/multivariable Cox proportional hazards models and Kaplan-Meier methods.ResultsA total of 411 patients were included. Median age was 67 (range, 24-96) years. Disease stage at the time of initial diagnosis was known for 74.7% of the identified patients (307/411). Of these patients, 23.1% had localized disease. Survival was significantly better for patients with localized disease (OS: 31 vs. 6 months, P < .001; DSS: 54 vs. 8 months, P < .001). Additionally, patients who received surgery alone had significantly improved OS (20 months; P < .001) and DSS (32 months; P < .001) compared to patients who received combined surgery and radiotherapy (OS: 7 months; DSS: 8 months) or radiotherapy alone (OS: 4 months; DSS: 4 months).ConclusionTreatment with surgery alone resulted in superior survival outcomes compared to other treatment modality combinations, regardless of patient age and disease stage. Within the limitations of this study, providers may wish to consider these findings when devising patient treatment plans.     

维纳托克在肝癌细胞中的抗肿瘤活性及其机制

目的探讨维纳托克(Venetoclax)在HepG2、Hep3B 2个肝癌细胞株的抗癌活性。方法对人肝癌细胞株HepG2、Hep3B细胞株进行体外培养,采用不同浓度的Venetoclax(0、3、10、30μmol/L)处理肝癌细胞,以细胞计数试剂盒(CCK-8)检测细胞活性,0,3,10和30μmol/L Venetoclax作用细胞48 h,锥虫蓝拒染法检测细胞的死亡,0,5μmol/L Venetoclax,作用24 h,流式细胞学检测细胞凋亡率,蛋白质印迹法(Western blot)检测Venetoclax诱导半胱氨酰天冬氨酸特异性蛋白酶(Caspase)-3活化,聚腺苷二磷酸核糖聚合酶(PARP)裂解。组间比较采用t检验。结果Venetoclax对HepG2、Hep3B细胞株均有较强活性抑制作用。不同浓度的Venetoclax处理肝癌细胞48、72 h,Venetoclax在HepG2细胞株中取得的半数细胞活性抑制率(IC50)值分别为46.5μmol/L和14.2μmol/L;在Hep3B细胞的IC50值分别为24.6μmol/L和11.2μmol/L。处理24 h,30.0μmol/L的Venetoclax在HepG2和Hep3B细胞株中诱导57%[对照组、实验组凋亡率分别为(4.00±1.00)%、(56.67±8.51)%,t=-10.650,P<0.01]和54%[对照组、实验组凋亡率分别为(5.67±1.53)%、(54.33±9.87)%,t=-8.440,P<0.01]的肝癌细胞发生凋亡,并能诱导肝癌细胞的Caspase-3活化,PARP裂解,差异均有统计学意义。用0、3、10和30μmol/L的Venetoclax处理48 h,在HepG2细胞株中可诱导3%(3.26±1.71)%,12%[(12.36±1.99)%,(t=-12.36,P<0.05)],32%[(32.38±4.57)%,(t=-10.350,P<0.01)]和67%[(66.71±6.29)%,(t=-16.86,P<0.01)]的细胞死亡,差异均有统计学意义;在Hep3B细胞株诱导2%(1.91±0.68)%,16%[(15.72±3.40)%,(t=-6.890,P<0.05)],42%[(42.39±6.86)%,(t=-10.180,P<0.01)]和73%[(73.32±2.69)%,t=-44.490,P<0.01]的细胞死亡,差异均有统计学意义。应用半胱氨酸蛋白酶(Caspase)抑制剂预处理,Venetoclax对HepG2和Hep3B细胞的死亡率分别从56%(56.71±6.29)%降低至11%(10.70±1.43)%,(t=12.350,P<0.01)和68%(68.05±10.16)%至12%(12.7±6.12)%,(t=8.080,P<0.01),差异有统计学意义。结论Venetoclax能够通过诱导Caspase的活化,诱导肝癌细胞发生凋亡,并对肝癌细胞进行杀伤。     

Emodin attenuates acute lung injury in Cecal-ligation and puncture rats

Acute lung injury (ALI) is a major cause of sepsis-induced acute respiratory failure. Emodin has been considered to play a protective role for acute lung edema in cecal ligation and puncture (CLP)-induced sepsis model. In this study we aimed to investigate whether emodin could improve CLP-induced lung sepsis via regulating aquaporin (AQP) and tight junction (TJ), inflammatory factors, and pulmonary apoptosis. The results showed that sepsis-induced pulmonary pathological changes were significantly improved after emodin treatment. Emodin was found to upregulate AQP and TJ expression in the CLP model. Meanwhile, inflammatory cytokine release and pulmonary apoptosis was remarkably reduced after emodin treatment in lung sepsis. Our data demonstrated that emodin could suppresse inflammation, restore pulmonary epithelial barrier and reduce mortality in CLP-induced ALI, suggesting the potential therapeutic application of emodin in sepsis.     

肝细胞核因子-κB异常激活与肝细胞癌变

核因子-κB（nuclear factor-κB，NF-κB）是具有和某些基因上启动子区固定核苷酸序列结合而启动该基因转录的蛋白质。NF-κB是具有多向性调节作用的核转录因子，可调控多种基因（免疫、炎症反应、病毒和原癌基因）的转录表达。激活的NF-κB参与癌症的启动、发生及发展过程，在炎症性相关的肝癌（HCC）发生发展中呈高表达，在肝细胞炎症与癌变间起桥梁作用，其中包括肝脏免疫炎症反应相关基因、肝炎病毒相关基因和原癌基因的转录表达。在肝癌组织中异常激活，可抑制细胞凋亡，促进肝细胞存活，与肝癌的发生发展密切相关。     

经肺动脉与支气管动脉血管造影的CTA观察原发肺癌的血供

目的用支气管动脉(BA)和肺动脉(PA)造影CTA观察肺癌血供情况。方法前瞻性观察6例支气管肺癌患者,分别行体循环动脉和肺动脉数字减影血管造影(DSA)后,留置BA导管与PA导管行CTBA与CTPA,观察BA与PA对肺癌的血供。结果CTPA上,无体动脉与左心强化的图像上肿瘤未见强化,有体动脉或左心强化的图像上见肿瘤边缘强化,CT强化值为10.0~45.6 Hu。CTBA上肿瘤部分明显强化,CT强化值为150.3~320.7 Hu,可见杂乱无章的肿瘤血管影,3例见纵隔淋巴结强化。结论本组病例观察表明原发性肺癌由BA为主的多发体循环动脉供血,未发现PA参与供血。     

异常灌注评分法评价肺血栓栓塞症患者治疗效果的价值

目的 分析异常灌注评分法对肺血栓栓塞症（PTE）疗效的评估价值。方法 选择明确诊断为急性PTE的患者46例，在治疗前及治疗后14d行肺灌注显像，2位核医学科医师分别对肺灌注显像图进行定性分析，随后采用异常灌注评分法和Parker创建的肺段评分法进行肺灌注显像结果判读，比较两者在判读结果方面的一致性及其相关性，并比较2种方法所示的治疗后灌注改善率。结果 2位医师对左肺灌注结果判读的一致性为100％（Kappa值为1．0），对右肺灌注结果判读的一致性为91．3％（Kappa值为0．69）。治疗前后2种灌注评分结果均有较高度的一致性（Kappa值分别为0．657和0．665，P均〈0．001）。在治疗前和治疗后通过2种评分方法所计算的联合评分均呈显著正相关（r值分别为0．770和0．771，P均〈0．001）。肺灌注改善率在2种评分方法之间无显著差异（P=0．128）。结论 异常灌注评分法判读简单，是评价PTE治疗效果的较好方法。