免疫检查点抑制剂相关心肌炎临床诊疗实施建议

免疫检查点抑制剂（immune-checkpoint inhibitors，ICIs）现已应用于多种恶性肿瘤的治疗，为肿瘤患者带来获益的同时，其严重ICIs相关心肌炎日益为临床带来新挑战。本临床诊疗实施建议聚焦ICIs相关心肌炎的危险因素、诊断与鉴别诊断、临床分型及治疗、监测转归和治疗重启等关键临床问题，参考国内外相关共识或指南和新近发表的循证证据，结合实际临床经验，为ICIs相关心肌炎的诊疗提供具有实践性的指导意见和建议。     

免疫检查点抑制剂治疗的肝脏毒性管理

免疫检查点抑制剂（immune checkpoint inhibitors，ICIs）在肿瘤领域取得了令人瞩目的疗效，使肿瘤治疗进入免疫治疗的新时代。但随着ICIs的广泛使用，免疫相关不良事件（immune-related adverse events，irAEs）也随之而来。肝脏是人体重要的代谢和消化器官，ICIs引起的肝脏不良事件应引起临床医师的关注。早发现、早诊断、规范治疗是改善预后的关键。本文简述irAEs的发病现状和可能机制，对现有的免疫相关肝脏毒性管理进行总结。     

肿瘤免疫检查点抑制剂相关肺炎的管理

以免疫检查点程序性死亡因子-1（programmed death 1，PD-1）抑制剂、程序性死亡因子配体-1（programmed death ligand 1，PD-L1）抑制剂及细胞毒性T淋巴细胞相关蛋白4（cytotoxic T lymphocyte antigen 4，CTLA-4）抑制剂为代表的肿瘤免疫治疗，近年来在肿瘤治疗中广泛开展，有效延长了肿瘤患者的生存期，但也可能导致免疫治疗相关不良事件（immune-related adverse events，irAEs）。免疫检查点抑制剂（immune checkpoint inhibitor，ICIs）相关肺炎是常见的irAEs之一，可导致部分肿瘤患者治疗暂停、治疗失败、甚至威胁生命。正确了解ICIs相关肺炎的临床特点，早期诊断并恰当治疗，对影响肿瘤患者的预后、延长生命有重要意义。     

免疫检查点抑制剂的抗肿瘤临床实践与展望

基于靶向免疫检查点抑制剂(immune checkpoint inhibitors,ICIs)的肿瘤免疫治疗在近10年取得了重要进展,程序性死亡因子-1(PD-1)/程序性死亡因子配体-1(PD-L1)抗体治疗则成为肿瘤治疗领域最具潜力的新型疗法。中国肿瘤学者与发达国家学者基本同步开展的肿瘤免疫疗法的临床实践,进一步验证了肿瘤免疫治疗的效果。伴随临床应用数据的积累,ICIs抗肿瘤疗法逐渐暴露出很多不足,如总体治疗应答率偏低、获得性耐药机制复杂以及免疫相关不良反应(irAEs)多有发生等。这些问题都值得引起相关领域专家重视。本文总结了近年来国内外ICIs的临床实践成果,深入分析了当前ICIs疗法面临的挑战,探讨并提出了改善患者获益的策略。     

免疫检查点抑制剂相关甲状腺毒症

免疫检查点抑制剂(immune checkpoint inhibitors, ICIs)是近年来恶性肿瘤治疗领域的一项重大突破。其通过针对T细胞的调节作用，增强抗肿瘤免疫反应，改善恶性肿瘤患者的预后，延长患者生存期，现已获批用于治疗多种肿瘤，但ICIs在应用过程中产生的甲状腺毒症是不容忽视的临床问题。本文对ICIs相关甲状腺毒症的发生机制、临床表现、处理对策等进行综述。     

帕博利珠单抗相关爆发性心肌炎一例

免疫检查点抑制剂（ICIs）是近年来肿瘤治疗领域的最重要进展之一。随着ICIs适应证的不断拓展及国内原研药相继进入临床,ICIs将用于越来越多的肿瘤患者,然而ICIs的严重不良反应尚未引起临床医师的广泛关注。该文报道1例肝癌术后复发接受帕博利珠单抗治疗引起爆发性心肌炎的病例,患者主要表现为心肌酶升高,难治性心律失常,伴有肝损伤,呼吸衰竭等,虽经积极抢救最终死亡。该例提示ICIs相关免疫性心肌炎早期症状不典型,但疾病呈爆发性进展,需要临床医师早期识别,及早干预。     

肿瘤免疫检查点抑制剂联合治疗策略及临床应用

目的：免疫检查点抑制剂（immune checkpoint inhibitions，ICIs）的应用显著改善了多种肿瘤的预后，是当前肿瘤治疗中备受重视的手段。以程序性死亡因子-1（programmed death 1，PD-1）、程序性死亡因子配体-1（programmed death ligand 1，PD-L1）和细胞毒性T淋巴细胞相关抗原4（cytotoxic T lymphocyte antigen 4，CTLA-4）单克隆抗体为主的免疫检查点的临床研究结果显示，单一ICIs临床效果有限。不同ICIs的联合治疗、联合化疗及联合抗肿瘤血管生成药物可明显提高疗效，新发现的免疫检查点淋巴细胞激活基因-3（lymphocyte activation gene-3，LAG-3）、T细胞免疫球蛋白黏液素3（T cell immunoglobulin mucin-3，TIM-3）、T细胞免疫球蛋白和ITIM域（T cell immunoglobulin and ITIM domain，TIGIT）等抑制剂的转化和联合应用，对难治性或ICIs耐药患者的疗效值得期待。     

肿瘤免疫检查点抑制剂治疗患者生活质量现状的调查研究

目的：了解肿瘤免疫检查点抑制剂（ICIs）治疗患者生活质量现状及影响因素，为改善肿瘤ICIs治疗患者生活质量提供依据。方法：采用方便抽样的方法，选取2021年9月至2022年2月接受肿瘤ICIs治疗的216例患者为研究对象，采用一般资料调查表、ECOG评分、欧洲癌症研究与治疗组织生命质量核心量表30及肿瘤患者ICIs治疗症状评估量表进行横断面调查。结果：肿瘤ICIs治疗患者总体健康状况评分最低，为66.67(50.00,83.33)分；多元线性回归分析结果显示，治疗方式、症状负担与ECOG评分是躯体功能及角色功能2个维度的影响因素（△R2=0.485,0.383），年龄、性别、症状负担及ECOG评分是情绪功能维度的影响因素（△R2=0.350），年龄、症状负担及ECOG评分是认知功能维度的影响因素（△R2=0.250），症状负担及ECOG评分是社会功能维度及总体健康状况维度的影响因素（△R2=0.201,0.314）。结论：肿瘤ICIs治疗患者自评总体健康状况不佳，应重视年轻、女性、联合治疗、ECOG评分高及症状负担重的患者，制定和实施有效的个体化护理方案以改善其生活质量。     

疗效预测生物标志物在去势抵抗性前列腺癌中的研究进展

免疫检查点抑制剂(ICIs)疗法在治疗多种晚期实体瘤中取得了革命性的突破,其中包括了去势抵抗性前列腺癌(CRPC)。在过去几年中,已有多种ICIs应用于CRPC,并证明可改善患者的总生存期(OS),但是由于适用人群受限以及毒副作用大,大部分药物的临床获益很少是持久的。目前可预测ICIs在CRPC疗效的生物标志物仍欠缺可靠性和临床实用性,因此寻找相关生物标志物对指导治疗至关重要。本文主要就疗效预测生物标志物在去势抵抗性前列腺癌中的研究进展进行综述。     

信迪利单抗治疗胃癌致1型糖尿病1例

免疫检查点抑制剂(immune checkpoint inhibitors, ICIs)目前应用于多种肿瘤的治疗中, 在肿瘤治疗中扮演着重要角色, 随之而来的也有许多与免疫系统相关的不良反应。1型糖尿病(type diabetes mellitus, T1DM)是比较罕见的内分泌系统并发症, 目前报道较少。我们报道1例使用ICIs治疗胃癌后出现T1DM的病例。患者男, 34岁, 使用信迪利单抗206 d后出现糖尿病酮症酸中毒, 空腹血糖15.78 mmol/L, 糖化血红蛋白8.6%。胰岛相关抗体:谷氨酸脱羧酶抗体:119.2 kU/L;胰岛素抗体:<2 U/L。空腹胰岛素:0.21 mU/L;空腹C肽:0.12 μg/L。通过对患者临床资料的分析, 旨在提高临床医师对免疫相关性1型糖尿病的认识, 同时为正确的诊治提供思路。     

Current management of Helicobacter pylori infections in the elderly

Helicobacter pylori infection is a chronic gastric gram-negative infection that increases with age worldwide. However, the percentage age of H. pylori-positive elderly patients who are tested and treated for their infection remains very low. It is now demonstrated that H. pylori infection induces a whole cascade of events leading to gastric pathologies, such as peptic ulcer diseases, gastric precancerous lesions and gastric cancer. Recent data also demonstrated that H. pylori chronic infection can play a role in gastric aging, appetite regulation and extradigestive diseases, such as Alzheimer's disease, in the elderly. The diagnosis of H. pylori infection remains difficult to realize in the very old population, and the urea breath test obtains the best performance in this population. 1-week proton pump inhibitor-based triple therapy regimens are highly effective and well tolerated in elderly patients, and antibiotic resistance remains very low. Low compliance is the main factor related to treatment failure in this population.     

基于选择、优化和补偿模型理论的老年慢性病患者健康素养、社会支持与成功老龄化的关系研究

目的旨在了解老年慢性病患者成功老龄化现状的基础上,探究健康素养、社会支持、选择、优化和补偿模型(the model of selective optimization with compensation,SOC)与成功老龄关系模型,为护理领域成功老龄化相关研究提供参考依据.方法采用一般资料问卷、慢性病病人健康素养量表、社会支持评定量表、SOC策略问卷、成功老龄量表,于2018年6-7月对延吉市328名老年慢性病患者进行调查.结果研究对象成功老龄化得分为(50.08±12.12)分,处于中等水平,男性、汉族、有配偶的老年慢性病患者其健康素养、社会支持、SOC与成功老龄化得分较高(均P<0.01),健康素养、社会支持、SOC与成功老龄化两两呈正相关(r=0.125~0.919,均P<0.01),社会支持对成功老龄化有正向影响,并通过SOC间接对成功老龄化产生正向影响(P<0.01),健康素养通过社会支持和SOC影响成功老龄化(P<0.01).结论提高健康素养和社会支持水平,可为老年慢性病患者采取SOC策略提供资源,进而促进其成功老龄化;护理人员对老年慢性病患者的健康干预策略的研究和实践,必须要重视健康素养和社会支持水平及其相关因素的影响.     

Current management of Helicobacter pylori infections in the elderly

Helicobacter pylori infection is a chronic gastric Gram-negative infection that increases with age worldwide. However, the percentage age of H. pylori-positive elderly patients who are tested and treated for their infection remains very low. It is now demonstrated that H. pylori infection induces a whole cascade of events leading to gastric pathologies, such as peptic ulcer diseases, gastric precancerous lesions and gastric cancer. Recent data also demonstrated that H. pylori chronic infection can play a role in gastric aging, appetite regulation and extradigestive diseases, such as Alzheimer’s disease, in the elderly. The diagnosis of H. pylori infection remains difficult to realize in the very old population, and the urea breath test obtains the best performance in this population. 1-week proton pump inhibitor-based triple therapy regimens are highly effective and well tolerated in elderly patients, and antibiotic resistance remains very low. Low compliance is the main factor related to treatment failure in this population.     

高度重视老年结肠癌合并肠梗阻的诊断和外科治疗

近年来,随着结直肠癌发病率的逐渐上升和人口老龄化,以肠梗阻为首发症状的结直肠癌在临床上也愈来愈多见。因老年人机体反应性较差,常并发多系统疾病,使得此类结直肠癌经常被误诊。结肠镜检查是诊断结肠癌的金标准,但对于急诊危重患者可能无法行肠镜检查,此时CT等影像学检查亦具有极高的诊断价值。本文将从老年急性肠梗阻的临床特点,结肠癌伴发肠梗阻的诊断等方面逐一阐述,并结合笔者多年的临床经验,分析总结结肠癌合并肠梗阻的误诊及原因,旨在提高早期诊断率,为此类患者的手术治疗赢得宝贵的时机。     

Treatment considerations for the elderly person with cancer

In an aging population, the number of patients with cancer continues to rise. Little research has focused on the treatment of cancer in the elderly. Therefore, the treatment for various cancers differs across the healthcare system. A uniform approach in assessing the elderly person with cancer is lacking. This article describes two case studies in the elderly population, focusing on two common cancers: acute myelogenous leukemia and breast cancer. Common side effects of treatment and determinants of treatment options are discussed. It is important that the elderly receive appropriate screening, early detection, treatment, and management of comorbidities.     

Non–Small Cell Lung Cancer: Epidemiology,Screening, Diagnosis,and Treatment

Lung cancer remains the leading cause of cancer deaths in the United States. In the past decade, significant advances have been made in the science of non–small cell lung cancer (NSCLC). Screening has been introduced with the goal of early detection. The National Lung Screening Trial found a lung cancer mortality benefit of 20% and a 6.7% decrease in all-cause mortality with the use of low-dose chest computed tomography in high-risk individuals. The treatment of lung cancer has also evolved with the introduction of several lines of tyrosine kinase inhibitors in patients with EGFR, ALK, ROS1, and NTRK mutations. Similarly, immune checkpoint inhibitors (ICIs) have dramatically changed the landscape of NSCLC treatment. Furthermore, the results of new trials continue to help us understand the role of these novel agents and which patients are more likely to benefit; ICIs are now part of the first-line NSCLC treatment armamentarium as monotherapy, combined with chemotherapy, or after definite chemoradiotherapy in patients with stage III unresectable NSCLC. Expression of programmed cell death protein-ligand 1 in malignant cells has been studied as a potential biomarker for response to ICIs. However, important drawbacks exist that limit its discriminatory potential. Identification of accurate predictive biomarkers beyond programmed cell death protein-ligand 1 expression remains essential to select the most appropriate candidates for ICI therapy. Many questions remain unanswered regarding the proper sequence and combinations of these new agents; however, the field is moving rapidly, and the overall direction is optimistic.     

Immune checkpoint blockade as a potential therapeutic target in non-small cell lung cancer

ABSTRACT

Introduction: The recent emergence of immune checkpoint blockade therapy and the progression of immunobiology in cancer have spurred an increasing interest in the immunotherapy for advanced non-small cell lung cancer (NSCLC). Immune checkpoint inhibitors (ICIs), designed to directly target immune inhibitory molecules, have demonstrated efficacy in the treatment of patients with advanced NSCLC.

Areas covered: In the present article, the authors summarize the mechanism, efficacy and safety of major ICIs for the treatment of advanced or metastatic NSCLC. Combinations of different ICIs or conventional therapy and/or targeted agents for NSCLC treatment in clinical trials are also updated. In addition, immune-related adverse events and the roles of inhibitory immune checkpoint molecules as potential biomarkers in the immune checkpoint blockade therapy for NSCLC are emphatically elucidated.

Expert opinion: Immunotherapies targeting the immune checkpoint pathways have shown potential to generate durable responses and improve survival for NSCLC patients. Although the toxicity profile of this immunotherapy is manageable, immune-related adverse events and drug resistance may cause therapeutic failure. Therefore, a better understanding of the mechanisms underpinning its function and the potential side effects of ICIs, as well as the identification of predictive biomarkers for patient selection are essential.     

Hematological toxicities of immune checkpoint inhibitors and the impact of blood transfusion and its microbiome on therapeutic efficacy and recipient’s safety and survival outcome:A systematic narrative appraisal of where we are now!

Classically, patients with solid and hematologic malignancies have been treated with a combination of chemotherapy with or without a holistic targeted strategy using approved conventional therapy. While the evidence-based use of Immunomodulatory drugs and Immune checkpoint inhibitors (ICIs), including those targeting the PD-1, PD-L1 and CTLA-4, have reshaped the treatment paradigm for many malignant tumors and significantly stretched the life expectancy of patients, as for any interventional therapy, the rise in ICI applications, was associated with the observation of more immune-related hematological adverse events. Many of these patients require transfusion support during their treatment in line with precision transfusion. It has been presumed that transfusion-related immunomodulation (TRIM) and the microbiome can pose immunosuppressive effects on the recipients. Looking to the past and beyond and translating available data into practice in the evolving role of pharmaceutical therapy to ICI-receiving patients, we performed a narrative review of the literature on the immune-related hematological adverse events of ICIs, immunosuppressive mechanisms linked to blood product transfusions, as well as the detrimental impact of transfusions and its related microbiome on the sustained efficacy of ICIs and the patients’ survival outcomes. Recent reports are pointing to the negative impact of transfusion on ICI response. Studies have concluded that packed RBC [PRBC] transfusions lead to an inferior progression-free and overall survival in patients with advanced cancer receiving ICIs, even after adjustments for other prognostic variables. The attenuation of the effectiveness of immunotherapy likely results from the immunosuppressive effects of PRBC transfusions. It is, therefore, wise to look retrospectively and prospectively at the impact of transfusion on ICI effects and adopt, in the interim, a restrictive transfusion strategy, if applicable, for those patients.     

Characteristics of elderly fall patients with baseline mental status: high-risk features for intracranial injury

Background

Falls are a major cause of morbidity in the elderly.

Objectives

We describe the low-acuity elderly fall population and study which historical and clinical features predict traumatic intracranial injuries (ICIs).

Methods

This is a prospective observational study of patients at least 65 years old presenting with fall to a tertiary care facility. Patients were eligible if they were at baseline mental status and were not triaged to the trauma bay. At presentation, a data form was completed by treating physicians regarding mechanism and position of fall, history of head strike, headache, loss of consciousness (LOC), and signs of head trauma. Radiographic imaging was obtained at the discretion of treating physicians. Medical records were subsequently reviewed to determine imaging results. All patients were called in follow-up at 30 days to determine outcome in those not imaged. The study was institutional review board approved.

Results

A total of 799 patients were enrolled; 79.5% of patients underwent imaging. Twenty-seven had ICIs (3.4%). Fourteen had subdural hematoma, 7 had subarachnoid hemorrhage, 3 had cerebral contusion, and 3 had a combination of injuries. Logistic regression demonstrated 2 study variables that were associated with ICIs: LOC (odds ratio, 2.8; confidence interval, 1.2-6.3) and signs of head trauma (odds ratio, 13.2; confidence interval, 2.7-64.1). History of head strike, mechanism and position, headache, and anticoagulant and antiplatelet use were not associated with ICIs.

Conclusion

Elderly fall patients who are at their baseline mental status have a low incidence of ICIs. The best predictors of ICIs are physical findings of trauma to the head and history of LOC.     

手术治疗老年胃癌的疗效观察

目的：探讨老年进展期胃癌外科手术治疗的疗效。方法：回顾分析2003年—2010年134例60岁以上老年进展期胃癌患者的临床资料。结果：老年胃癌起病隐匿,常伴有出血、梗阻及贫血;绝大多数患者合并有其他疾病。手术证实绝大多数为中晚期胃癌。术后并发症发生率为50.7%,围手术期病死率为3.7%。结论：老年胃癌患者经术前充分准备,术后积极处理多能耐受手术。对早期和中期胃癌力争行根治性切除术（D2）,可以获得较满意的长期疗效。