Consenso multidisciplinar para el manejo de la tromboembolia de pulmón

We have updated recommendations on 12 controversial topics that were published in the 2013 National Consensus on the diagnosis, risk stratification and treatment of patients with pulmonary embolism (PE). A comprehensive review of the literature was performed for each topic, and each recommendation was evaluated in two teleconferences. For diagnosis, we recommend against using the Pulmonary Embolism Rule Out Criteria (PERC) rule as the only test to rule out PE, and we recommend using a D-dimer cutoff adjusted to age to rule out PE. We suggest using computed tomography pulmonary angiogram as the imaging test of choice for the majority of patients with suspected PE. We recommend using direct oral anticoagulants (over vitamin K antagonists) for the vast majority of patients with acute PE, and we suggest using anticoagulation for patients with isolated subsegmental PE. We recommend against inserting an inferior cava filter for the majority of patients with PE, and we recommend using full-dose systemic thrombolytic therapy for PE patients requiring reperfusion. The decision to stop anticoagulants at 3 months or to treat indefinitely mainly depends on the presence (or absence) and type of risk factor for venous thromboembolism, and we recommend against thrombophilia testing to decide duration of anticoagulation. Finally, we suggest against extensive screening for occult cancer in patients with PE.     

血液系统肿瘤患者的营养治疗专家共识

血液系统肿瘤患者诊治过程中普遍存在营养不良，化疗作为血液系统肿瘤最重要的治疗手段，进一步加剧患者的营养不 良，其最主要的原因是化疗引起的恶心、呕吐及摄食减少。诱导治疗后C反应蛋白的显著升高，提示感染发生率及炎症水平均较高， 这在一定程度上可能干扰机体代谢、加剧营养状态的恶化。血液系统肿瘤患者的营养不良表现为体质指数异常、人体成分异常、整体/ 综合评估异常和生化指标异常。血液系统肿瘤患者营养治疗的原则与其他肿瘤类似，肠内营养为主，肠外营养为辅。但是，需要注意 补充特殊营养剂：①谷氨酰胺；②针对“粒细胞减少”的饮食；③ω‐3多不饱和脂肪酸；④牛初乳及大豆饮食。通过营养筛查和评估，为 处于不同治疗阶段的血液系统肿瘤患者制定营养治疗方案，及时、恰当地进行个体化营养治疗，可显著改善血液系统肿瘤患者营养状 况、预防营养不良及相关并发症，降低治疗相关不良反应风险，提高耐受性、疗效及生活质量。     

Gender differences in genotypic distribution of endothelin-1 gene and endothelin receptor A gene in pulmonary hypertension associated with rheumatic mitral valve disease

IntroductionThe female gender is a risk factor for idiopathic pulmonary arterial hypertension. However, it is unknown whether females with rheumatic mitral valve disease are more predisposed to develop pulmonary hypertension compared to males.AimWe aimed to investigate whether there was a difference in genotypic distribution of endothelin-1 (ET-1) and endothelin receptor A (ET_A) genes between female and male patients of pulmonary hypertension associated with rheumatic mitral valve disease (PH-MVD).MethodsWe compared prevalence of ET-1 gene (Lys198Asn) and ET_A gene (His323His) polymorphisms according to gender in 123 PH-MVD subjects and 123 healthy controls.ResultsThe presence of mutant Asn/Asn and either mutant Asn/Asn or heterozygous Lys/Asn genotypes of Lys198Asn polymorphism when compared to Lys/Lys in females showed significant association with higher risk (odds ratio [OR] 4.5; p =0.007 and OR 2.39; p =0.02, respectively). The presence of heterozygous C/T and either mutant T/T or heterozygous C/T genotypes of His323His polymorphism when compared to wild C/C genotype in females showed a significant association with higher risk (OR 1.96; p =0.047 and OR 2.26; p =0.01, respectively). No significant difference was seen in genotypic frequencies in males between PH-MVD subjects and controls. Logistic regression analysis showed that mutant genotype Asn/Asn (p =0.007) and heterozygous genotype Lys/Asn of Lys198Asn polymorphism (p =0.018) were independent predictors of development of PH in females.ConclusionsET-1 and ET_A gene polymorphisms were more prevalent in females than males in PH-MVD signifying that females with rheumatic heart disease may be more susceptible to develop PH.     

Immune microenvironment of hepatocellular carcinoma,intrahepatic cholangiocarcinoma and liver metastasis of colorectal adenocarcinoma: Relationship with histopathological and molecular classifications

Tumor tissue is composed of tumor cells and tumor stroma. Tumor stroma contains various immune cells and non-immune stromal cells, forming a complex tumor microenvironment which plays pivotal roles in regulating tumor growth. Recent successes in immunotherapies against tumors, including immune checkpoint inhibitors, have further raised interests in the immune microenvironment of liver carcinoma. The immune microenvironment of tumors is formed because of interactions among tumor cells, immune cells and non-immune stromal cells, including fibroblasts and endothelial cells. Different patterns of immune microenvironment are observed among different tumor subtypes, and their clinicopathological significance and intertumor/intratumor heterogeneity are being intensively studied. Here, we review the immune microenvironment of hepatocellular carcinoma, intrahepatic cholangiocarcinoma and liver metastasis of colorectal adenocarcinoma, focusing on its histopathological appearance, clinicopathological significance, and relationship with histological and molecular classifications. Understanding the comprehensive histopathological picture of a tumor immune microenvironment, in addition to molecular and genetic approaches, will further potentiate the effort for precision medicine in the era of tumor-targeting immunotherapy.     

Phase I Dose-Escalation Study of SCB01A,a Microtubule Inhibitor with Vascular Disrupting Activity,in Patients with Advanced Solid Tumors

Lessons Learned

• SCB01A is a novel microtubule inhibitor with vascular disrupting activity.
• This first‐in‐human study demonstrated SCB01A safety, pharmacokinetics, and preliminary antitumor activity.
• SCB01A is safe and well tolerated in patients with advanced solid malignancies with manageable neurotoxicity.

BackgroundSCB01A, a novel microtubule inhibitor, has vascular disrupting activity.MethodsIn this phase I dose‐escalation and extension study, patients with advanced solid tumors were administered intravenous SCB01A infusions for 3 hours once every 21 days. Rapid titration and a 3 + 3 design escalated the dose from 2 mg/m² to the maximum tolerated dose (MTD) based on dose‐limiting toxicity (DLT). SCB01A‐induced cellular neurotoxicity was evaluated in dorsal root ganglion cells. The primary endpoint was MTD. Safety, pharmacokinetics (PK), and tumor response were secondary endpoints.ResultsTreatment‐related adverse events included anemia, nausea, vomiting, fatigue, fever, and peripheral sensorimotor neuropathy. DLTs included grade 4 elevated creatine phosphokinase (CPK) in the 4 mg/m² cohort; grade 3 gastric hemorrhage in the 6.5 mg/m² cohort; grade 2 thromboembolic event in the 24 mg/m² cohort; and grade 3 peripheral sensorimotor neuropathy, grade 3 elevated aspartate aminotransferase, and grade 3 hypertension in the 32 mg/m² cohort. The MTD was 24 mg/m², and average half‐life was ~2.5 hours. The area under the curve‐dose response relationship was linear. Nineteen subjects were stable after two cycles. The longest treatment lasted 24 cycles. SCB01A‐induced neurotoxicity was reversible in vitro.ConclusionThe MTD of SCB01A was 24 mg/m² every 21 days; it is safe and tolerable in patients with solid tumors.     

术中目标导向液体治疗在腹膜后巨大恶性肿瘤切除术患儿中的应用

目的:探讨基于脉压变异度（PPV）的目标导向液体治疗（GDFT）在腹膜后巨大恶性肿瘤切除术患儿中的应用。方法:择期行腹膜后巨大恶性肿瘤切除术患儿64例，年龄0.5~3岁，ASA Ⅱ-Ⅲ级。随机将患儿分为目标导向液体治疗组（G组）和常规液体治疗组（C组），每组32例。G组以PPV为指导，根据GDFT方案进行液体管理，C组采用常规液体管理。记录手术开始（T1）、手术开始后1 h（T2）、手术结束（T3）的MAP、CVP、PPV、Lac值、TNF-α、IL-6浓度。记录术中输注晶体液量、胶体液量、液体总量、出血量、尿量、手术时间、多巴胺使用率以及排气时间、术后住院时间和恶心呕吐发生率。结果:G组输注晶体液量显著少于C组（P＜0.05），而输注胶体液量显著多于C组（P＜0.05）。两组术中输注液体总量、出血量、尿量与多巴胺使用率方面差异无统计学意义。T2、T3时刻，G组PPV、TNF-α、IL-6显著低于C组（P＜0.05），而两组间MAP、CVP、Lac在各时点差异无统计学意义。G组术后排气时间明显短于C组（P＜0.05），而在术后恶心呕吐发生率和住院时间方面两组差异无统计学意义。结论:PPV指导的GDFT可以应用于腹膜后巨大恶性肿瘤切除术患儿，能维持其血流动力学稳定，减少炎症因子IL-6、TNF-α释放，促进胃肠功能恢复，但对术后转归无明显影响。