胰腺癌免疫治疗的现状及前景CSCD

胰腺癌(胰腺导管腺癌)是一种恶性程度较高,诊断和治疗都较困难的消化系统恶性肿瘤。近年来,肿瘤免疫治疗在多种肿瘤中如黑色素瘤、膀胱癌、乳腺癌、非小细胞肺癌和肾癌等均取得了令人振奋的治疗效果,但是胰腺癌的免疫治疗策略尚在不断探索中。目前针对胰腺癌独特的肿瘤微环境设计了多种免疫治疗策略,包括强化/提高自身免疫反应(免疫调节剂、单克隆抗体、肿瘤疫苗和细胞治疗)以及抑制肿瘤免疫逃逸(免疫检查点抑制剂和肿瘤微环境)等。本文就胰腺癌免疫治疗的研究进展进行综述,着重探讨PD-1/PD-L1抑制剂在胰腺癌中的应用,并分析免疫治疗联合其他方式治疗胰腺癌的前景。     

Microvascular heart involvement in systemic autoimmune diseases: The purinergic pathway and therapeutic insights from the biology of the diseases

Heart involvement – often asymptomatic – is largely underestimated in patients with systemic autoimmune diseases (SADs). Cardiovascular events are more frequent in patients with SADs compared to the general population, owing to the consequences of inflammation and autoimmunity and to the high prevalence of traditional risk factors. Coronary microvascular disease (CMD) is a form of cardiac involvement that is increasingly recognised yet still largely neglected. CMD, the incapacity of the coronary microvascular tree to dilate when myocardial oxygen demand increases or when there is a microvascular spasm (or subclinical myocarditis), is increasingly reported because of the widespread use of new cardiac imaging tools, even in a subclinical phase. The assessment of myocardial coronary flow reserve (CFR) emerged as the most effective clinical tool to detect microvascular damage. The potential causes of microvascular damage, molecular and cellular inflammation along with a pathological CD39-CD73 axis, need always to be considered because data show that they play a role in the occurrence of acute coronary syndromes, heart failure and arrhythmias, even in the early asymptomatic stage. Data suggest that controlling disease activity by means of methotrexate, biologic drugs, antimalarial medications, statins and aspirin, according to indication, might reduce the cardiovascular risk related to macrovascular and microvascular damage in most patients with SADs, provided that they are used early and timely to control diseases. The need of new biomarkers and a careful assessment of myocardial CFR emerged as the most effective clinical tool to detect microvascular damage.     

Case report of a uniocular topography guided laser-assisted in situ keratomileusis enhancement following an incorrectly treated astigmatic axis

A 23-year-old male presented to us wanting spectacle removal for cosmetic purposes. He underwent bilateral wavefront optimized (WFO) laser-assisted in situ keratomileusis (LASIK) on the Alcon Wavelight^® EX-500 excimer laser with an incorrectly treated astigmatism axis for left eye due to a manual data entry error in the laser. WFO LASIK treats the sphere and cylinder only. LASIK enhancement with topographic-guided ablation resulted in the elimination of all refractive errors and gave excellent results. Wavelight^® topographic-guided treatment can perform two separate layers of correction in the same ablation: The first is to treat the corneal irregularities for the higher order aberration (HOA) removal, the second one meant to treat the sphere and cylinder if indicated.     

囊性小肾癌、复杂性肾囊肿MSCT动态增强影像学表现及其诊断价值

目的研究囊性小肾癌、复杂性肾囊肿MSCT动态增强影像学表现及其诊断价值。方法回顾分析本院2017年6月至2019年6月收治的经病理学检查确诊的41例囊性小肾癌患者的临床资料,为肾癌组;再另选40例同时期入院诊断为囊性小肾癌,病理学检查确诊为复杂性肾囊肿的患者为囊肿组。两组均进行MSCT平扫和动态增强检查,通过对比结果,分析MSCT动态增强的诊断价值。结果CT平扫时可见囊肿组病灶形态规则、边界清晰、密度均匀;肾癌组病灶形态不规则、边界不清晰、密度不均匀;肾癌组囊壁厚度明显大于囊肿组(P<0.05)。增强后,囊肿组在皮质期、皮髓质期、排泄期的CT值显著低于肾癌组(P<0.05)。结合病理学检查,CT增强对囊性小肾癌和复杂性肾囊肿诊断的正确度达到91.36%。结论MSCT动态增强扫描对囊性小肾癌和复杂性肾囊肿具有重要的诊断价值,能有效判断病灶位置、形态、边界、囊壁厚度等,且准确性较高,值得推广应用。     

A genome-wide association study of suicide severity scores in bipolar disorder

BackgroundSuicide claims one million lives worldwide annually, making it a serious public health concern. The risk for suicidal behaviour can be partly explained by genetic factors, as suggested by twin and family studies (reviewed in (Zai et al. 2012)). Recently, genome-wide association studies (GWASs) of suicide attempt on large samples of bipolar disorder (BD) patients from multiple sites have identified a number of novel candidate genes. GWASs of suicide behaviour severity, from suicidal ideation to serious suicide attempt, have not been reported for BD.MethodsWe conducted a GWAS of suicide behaviour severity in three independent BD samples:212 small nuclear families with BD probands from Toronto, Canada, 428 BD cases from Toronto, and 483 BD cases from the UK. We carried out imputation with 1000 Genome Project data as reference using IMPUTE2. Quality control and data analysis was conducted using PLINK and R. We conducted the quantitative analyses of suicide behaviour severity in the three samples separately, and derived an overall significance by a meta-analysis using the METAL software.ResultsWe did not find genome-wide significant association of any tested markers in any of the BD samples, but we found a number of suggestive associations, including regions on chromosomes 8 and 10 (p < 1e-5).ConclusionsOur GWAS findings suggest that likely many gene variants of small effects contribute collectively to the risk for suicidal behaviour severity in BD. Larger independent replications are required to strengthen the findings from the GWAS presented here.     

Thermal enhancement of melphalan and oxaliplatin cytotoxicity in vitro

It has been established that hyperthermia can enhance cytotoxicity of some chemotherapeutic agents. This has led to various clinical trials of thermochemotherapy, although many questions remain unanswered. The effects of various agents have been studied on animal tumours with different histopathology at elevated temperatures. These studies indicated that alkylating agents were most effective to all tumours at a moderately elevated temperature. Cisplatin was also effective to all tumours, but its effectiveness at 41.5°C was less than that of alkylating agents. To quantitatively study these findings, the magnitude of thermal enhancement of melphalan, an alkylating agent, and that of oxaliplatin, a new platinum compound, were studied at 37-44.5°C by the colony formation assay. The dose of each agent was kept constant, and cell survival was determined as a function of treatment time. The cell survival curve was exponentially related with treatment time at all test temperatures, and the T 0 (the time to reduce survival from 1 to 0.37) decreased with an increasing temperature. These results suggested that the cytotoxic effect of these agents occurred with a constant rate at 37°C, and the rate was facilitated with an increasing temperature. This suggests that heat can accelerate the cytotoxic chemical reaction, leading to substantial thermal enhancement. The thermal enhancement ratio (TER, the ratio of the T 0 at 37°C to the T 0 at an elevated temperature) increased with an increase in the temperature. The activation energy for melphalan at moderately elevated temperatures was largest among the agents tested in the laboratory and that for oxaliplatin was approximately half of the melphalan activation energy. This suggests that the thermal enhancement for the cytotoxicity of melphalan or alkylating agents might be the greatest. Potential mechanisms of thermal enhancement of cytotoxicity were discussed.     

DE-CMR在主动脉关闭不全患者手术预后评估中的应用分析

目的探讨造影剂延迟增强心脏磁共振成像(DE-CMR)在主动脉关闭不全(AI)患者手术预后评估中的应用价值。方法回顾性分析行手术治疗的AI患者48例病例资料,根据术前DE-CMR检查是否出现钆对比延迟增强分为增强组和非增强组,比较两组患者的资料特征,随访至2017年3月记录不良预后发生情况,并分析不良预后的预测因子。结果 48例患者中,钆剂延迟增强患者17例(35.42%),非钆剂延迟增强患者31例(64.48%);两组患者性别、年龄、高血压、糖尿病、术前心功能分级比较,差异无统计学意义(P0.05),增强组术前LVESD、LVEDD、左心房前后径、左心室最大横径均大于非增强组,(P0.05),随访期间室性心律失常、心功能进展为Ⅲ-Ⅳ级、死亡的几率分别为23.52%、35.29%、29.41%高于非增强组的3.23%、9.68%、6.45%(P0.05);Cox比例风险模型分析显示LVEDD、LVESD、左心房前后径是AI术后不良预后的独立预测因子。结论 DE-CMR诊断AI可提供更加全面的影像学资料,其中钆对比剂延迟增强识别的心肌纤维化可预测不良预后。     

The Geriatric Workforce Enhancement Program: Review of the Coordinating Center and Examples of the GWEP in Practice

The Health Resources and Services Administration created the Geriatric Workforce Enhancement Program (GWEP) in 2015 to address future geriatric workforce challenges and redefine the delivery of care to older adults. The John A. Hartford Foundation subsequently funded the GWEP Coordinating Center (GWEP-CC) to offer centralized, strategic support to these 44 diverse GWEP sites. This article outlines the last 3 years of GWEP work done at the national and local levels to transform geriatric care. Dissemination of the innovative Geriatric Interprofessional Team Transformation in Primary Care program, created by the Dartmouth GWEP, demonstrates how the GWEP-CC can benefit local initiatives and inform national perspectives. The GWEP-CC is a change agent in this way, scaling and distributing information and implementation support across the country. The GWEP-CC also serves as an essential repository of data, continuously determining what is working and what could be improved. This informs activity of the GWEP-CC, funders and other stakeholders, and provides the most up-to-date resources to GWEP sites and their partners. The GWEP-CC achieves its objectives through several key pillars: networking opportunities, education and training, advocacy, and evaluation. Although many advances have been made, opportunities to continue paving the way are plenty, especially with regards to mental health. This article discusses the work accomplished to date and presents some future considerations for mental health and overall healthcare transformation.