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。     

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。     

免疫检查点抑制剂相关心肌炎分子机制研究进展

免疫检查点抑制剂（immune checkpoint inhibitors, ICIs）已成为目前应用最广的恶性肿瘤免疫疗法，主要包括CTLA-4（cytotoxic T lymphocyte associated antigen-4）抑制剂、PD-1/PD-L1（programmed death protein-1/ligand-1）抑制剂和LAG-3（lymphocyte activation gene-3）抑制剂。ICIs导致的最致命的免疫相关不良反应（immune-related adverse events, irAE）之一为免疫检查点抑制剂相关的心肌炎（immune checkpoint inhibitor-associated myocarditis, ICIAM）。ICIs联合治疗时ICIAM的发病率多高于单药治疗。其分子机制主要包括免疫检查点作为新抗原、肿瘤同源抗原的异位识别、免疫检查点心脏保护的阻断、自身抗体和炎症因子的产生以及微生物的调节作用等。目前已有多种治疗ICIAM药物及非药物性方案。对于ICIAM分子机制的探索和治疗管理方案的进步仍需多学科共同努力。     

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。     

免疫检查点抑制剂联合方案治疗转移性尿路上皮癌的研究进展

转移性尿路上皮癌（mUC）预后差且治疗难度大。近年免疫治疗策略快速发展，mUC患者的预后得到明显改善，但单一的免疫检查点抑制剂（ICIs）疗效有限，部分ICIs单药治疗mUC的适应证也在近年被撤销。因此基于ICIs的联合方案成为治疗mUC的研究热点。目前多项ICIs联合化学治疗、抗体偶联药物以及双免疫治疗多线治疗mUC的临床研究证明了联合方案有较好的发展前景。该文总结了近期ICIs联合方案治疗mUC的相关研究进展，供临床医师实践参考。     

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。     

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。     

70例非小细胞肺癌患者免疫检查点抑制剂不良反应分析及护理对策

目的 观察非小细胞肺癌患者免疫检查点抑制剂治疗时发生不良反应的情况,探讨预防护理对策。方法 70例非小细胞肺癌患者,均接受免疫检查点抑制剂联合培美曲塞/卡铂为主的一线治疗方案,观察其治疗期间随访6个月的不良反应发生情况。并提出护理预防对策。结果 70例患者中,治疗期间,每21 d为1周期,每周期治疗后1周内进行电话随访,随访满6个月67例,随访率达95%。70例患者中发生不良反应共20例（28%）,甲状腺功能减退2例（2%）,皮疹4例（5%）,发热4例（5%）,肝功能损伤4例（5%）,间质性肺炎4例（5%）,神经不良反应1例（1%）,心脏不良反应1例（1%）;70例患者均伴有不同程度的食欲减退及乏力症状,其中,2例患者因不良反应导致终止用药,1例患者死亡,其余50例患者继续治疗。结论 6个月随访发现,皮肤、内分泌、肝、肺、食欲减退及乏力是常见不良反应,神经系统不良反应及心脏不良反应发生率不高,但是比较严重的不良反应,致死率高,并且有90%不良反应发生在治疗早期。并制定了皮肤、内分泌、肝、肺、发热、食欲减退及乏力、神经系统及心脏不良反应的护理对策。     

免疫检查点抑制剂相关性肺炎的研究进展

免疫检查点抑制剂(ICIs)被广泛应用于多种恶性肿瘤的治疗,但由ICIs诱导的免疫系统过度激活也会导致T细胞对自身抗原进行攻击,临床上出现一系列免疫相关不良事件(IRAEs)。免疫检查点抑制剂相关性肺炎(CIP)是一类少见但有潜在致命危险的免疫相关不良反应,发生在肿瘤免疫治疗任何时间。临床医生应了解CIP的机制及特征,及早识别并正确处理。本文就CIP的流行病学、生物学机制、临床特征、诊断及治疗等进行综述。     

信迪利单抗导致免疫相关性肺炎1例并文献复习

目的目前国内报道免疫检查点抑制剂(ICIs)所致的免疫相关性肺炎的病例较少,本文将结合病例对免疫相关性肺炎的诊断、治疗及预后进行分析、探讨。方法回顾性分析兵器工业五二一医院肿瘤内科1例肺鳞癌经过信迪利单抗免疫治疗后导致的免疫相关性肺炎患者的临床表现、诊治思路、治疗结局,并进行相关文献复习。结果经过糖皮质激素治疗后,患者症状消失,胸部CT示炎症吸收。结论免疫相关性肺炎临床表现不典型,但是如果不及时处理可能导致生命危险,医生应根据临床症状及相关检查及时发现免疫相关性肺炎,早期治疗预防严重不良反应。     

Anticoagulation therapy in older adults newly diagnosed with atrial fibrillation

Atrial fibrillation (AF) is the most common chronic arrhythmia and the most serious heart rhythm irregularity in individuals older than 70. It is usually not life threatening in and of itself, but it can lead to serious medical problems, including stroke, additional heart rhythm problems, and heart failure. Symptoms of AF vary considerably. Some patients are asymptomatic and have a self-limiting arrhythmia of short duration that converts to normal sinus without any intervention. Symptomatic patients may experience minor palpitations, severe palpitations, or even more vague symptoms such as lightheadedness, shortness of breath, or fatigue. More serious symptoms, such as syncope, new or worsening heart failure, or a cerebral vascular accident, may occur. The initial goals of treatment include controlling ventricular rate and addressing anticoagulation status. New guidelines help clinicians effectively manage anticoagulant therapy for older adults newly diagnosed with AF.     

Inhaled treprostinil for the treatment of pulmonary arterial hypertension

Pulmonary arterial hypertension is a progressive disease characterized by vascular proliferation and vasoconstriction of the small pulmonary arteries that eventually leads to right-sided heart failure and death. Patients often initially have symptoms such as shortness of breath, fatigue, and edema; later in the disease, presyncope and syncope are common. Patients with progressive pulmonary arterial hypertension despite oral therapy and/or with severe disease typically require treatment with a prostanoid. Inhaled treprostinil (Tyvaso) is a prostacyclin analog indicated for the treatment of pulmonary arterial hypertension to increase walk distance in patients with symptoms classified as New York Heart Association functional class III. Inhaled treprostinil was approved by the Food and Drug Administration in July 2009. This article provides a brief overview of the pathophysiology of pulmonary arterial hypertension and reviews the mechanism of action, key clinical data, and the practical management of inhaled treprostinil in patients with pulmonary arterial hypertension.     

氟尿嘧啶治疗致急性冠状动脉综合征的诊断学特征并文献复习

目的探讨氟尿嘧啶治疗致急性冠状动脉综合征的诊断学特征。 方法回顾性分析1例因结肠癌于复旦大学附属中山医院肿瘤科治疗,氟尿嘧啶化疗后出现急性冠状动脉综合征患者的临床资料,并复习相关文献。 结果患者男性,60岁,为合并冠心病行经皮冠状动脉介入治疗的结肠癌患者,行辅助化疗FOLFOX(氟尿嘧啶、亚叶酸钙、奥沙利铂)方案,第1周期第14天出现胸闷、持续性胸部隐痛,平卧不能,端坐呼吸,气稍促。血清心肌肌钙蛋白T(cTnT)(0.687 μg/L),氨基末端利钠肽前体(NT-proBNP)(7 128 ng/L)水平均显著升高;心电图呈持续性心肌缺血改变;肺动脉CT血管造影未见明确栓塞征象。排除其他病理因素和药物因素可能,考虑为氟尿嘧啶治疗致急性冠状动脉综合征。经对症支持治疗后心肌细胞损伤标志物水平逐渐下降,患者未再诉胸闷、胸痛症状。改予TOMOX(奥沙利铂、雷替曲塞)方案,化疗期间和化疗后定期随访,心电图、经胸超声心动图较之前无明显变化,cTnT水平逐渐降低至正常值。 结论氟尿嘧啶化疗患者应密切监测其心脏毒性如急性冠状动脉综合征的发生,保障患者化疗顺利进行。     

Do you know them when you see them? Women's prodromal and acute symptoms of myocardial infarction

This study described women's prodromal and acute symptoms associated with myocardial infarction (MI) based on interviews with 76 women who had experienced an MI in the previous year. Sixty-eight women experienced prodromal symptoms including unusual fatigue (70%), shortness of breath (53%), and pain in the shoulder blade/upper back (47%). All women experienced acute symptoms including chest pain/discomfort (90%), unusual fatigue (59%), shortness of breath (59%), and shoulder blade/upper back discomfort (42%). Although women in this study reported numerous prodromal symptoms, none had received a new diagnosis of coronary heart disease (CHD) prior to MI. Practitioners must develop an awareness of and a more comprehensive approach to treating women at risk for CHD. Further research to elucidate prodromal and acute symptom clusters is needed to assist practitioners in early diagnosis of CHD in women.     

NT-前端B型脑钠肽对肺心病合并左心功能不全的诊断价值

目的探讨NT-前端B型脑钠肽（NT-proBNP）对老年慢性肺源性心脏病（肺心病）是否合并左心功能不全患者的诊断价值。方法有胸闷气逼的老年慢性肺心病及其合并左心功能障碍的患者40例,按病情将其分为3组：肺心病组16例（A组）;肺心病合并左心收缩功能障碍组12例（B组）;肺心病合并左心舒张功能障碍组12例（C组）。3组均测定血浆NT-proBNP,并行心脏彩超、肺功能等检查。结果与A组比较,B、C组患者血浆NT-proB-NP明显升高（P〈0.05）,B、C组间比较血浆NT-proBNP差异有统计学意义（P〈0.05）。3组肺功能检查差异无统计学意义（P〉0.05）。结论血浆NT-proBNP的高低对于鉴别老年慢性肺心病患者是否合并左心功能障碍有重要的价值。     

Association between symptom distress and survival in outpatients seen in a palliative care cancer center

Clinical observation and preliminary reports suggest that higher scores for symptoms such as pain may be associated with shorter survival. We undertook a survival analysis to determine whether symptom expression in outpatients with complex cancer is related to the duration of their survival. Participants were 225 outpatients with cancer evaluated in our comprehensive cancer center for pain management or palliative care over a 10-week period ending June 2000. In addition to age and other clinical and demographic information, the patients completed the Anderson Symptom Assessment System (ASAS), which assesses pain, fatigue, nausea, depression, anxiety, drowsiness, shortness of breath (dyspnea), appetite, sleep, and feeling of well-being on a 0–10 scale. Univariate analyses showed that higher symptoms of dyspnea, drowsiness, problems with appetite, and nausea were significantly associated with shorter survival whereas pain, depression and other ASAS items were not. In multivariate analyses, only higher levels of dyspnea and drowsiness showed a significant association (P = 0.01 and P = 0.02, respectively) with shorter survival. Knowledge about these symptoms may be important in formulating adaptive randomization techniques for clinical trials and for research concerning estimates of survival.     

Occult gastric cancer manifested by progressive shortness of breath in a young adult

We have reported a case of occult, diffuse gastric cancer in a young adult with progressive shortness of breath and bilateral pulmonary interstitial infiltrates. Progressive shortness of breath may be the first or only manifestation of occult gastric cancer caused by either lymphangitic carcinomatosis or microscopic tumor emboli to the lungs. Widespread recognition of this syndrome, a high index of suspicion, and prompt lung biopsy are necessary to make the correct diagnosis. With progress in chemotherapy for malignant diseases, early diagnosis and specific treatment may improve the prognosis of this condition.     

Symptom burden in the last week of life

In order to investigate symptom burden in the last week of life, we conducted after-death interviews with close relatives of deceased older persons from a population-based sample of older people in The Netherlands (n=270). Results show that fatigue, pain, and shortness of breath were common (83%, 48% and 50%, respectively). Other symptoms were confusion (36%), anxiety (31%), depression (28%), and nausea and/or vomiting (25%). Cancer patients and patients with chronic obstructive pulmonary disease were clearly at a disadvantage with respect to pain and shortness of breath, respectively. Furthermore, cognitive decline turned out to be predictive of specific symptom burden. Persons with cognitive decline in the last three months had a higher symptom burden and different symptoms compared to patients with no cognitive decline. It is suggested that older persons with cognitive decline require specific attention.     

The association of symptoms with health outcomes in chronically ill adults

Persons with chronic disease experience multiple symptoms. Understanding the association between these symptoms and health outcomes would facilitate a targeted approach to symptom assessment and treatment. Our objectives were to determine the association of a range of symptoms with quality of life, self-rated health, and functional status among chronically ill adults, and to assess methods for evaluating the independent associations of symptoms that may be interrelated. We consecutively enrolled 226 cognitively intact, community-dwelling adults, aged 60 years or older with chronic obstructive pulmonary disease, heart failure, or cancer. Seven symptoms (physical discomfort, pain, fatigue, problems with appetite, feelings of depression, anxiety, and shortness of breath) assessed using the Edmonton Symptom Assessment Scale were examined for their association with self-rated quality of life, self-rated health, and functional status. Principal component analysis and logistic regression revealed similar results. The latter demonstrated that physical discomfort was associated with lower self-rated health (adjusted odds ratio [OR] 1.9; 95% confidence interval 1.2-2.9) and functional disability (adjusted OR 1.8; 95% confidence interval 1.2-2.7). Feelings of depression were associated with poorer quality of life (adjusted OR 1.7; 95% confidence interval 1.1-2.6), and shortness of breath was associated with lower self-rated health (adjusted OR 1.5; 95% confidence interval 1.1-2.0). The association between a range of symptoms and quality of life, self-rated health, and functional status differed across outcomes, but only three symptoms-physical discomfort, feelings of depression, and shortness of breath-maintained their associations when multiple symptoms were examined concurrently. These findings suggest that interventions targeting these symptoms could improve several health-related outcomes.     

Assessing the Symptoms of Cancer Using Patient-Reported Outcomes (ASCPRO): Searching for Standards

The U.S. Food and Drug Administration (FDA) 2006 draft guidance on “Patient-Reported Outcome Measures: Use in Medical Product Development to Support Labeling Claims” has engendered wide discussion about patient-reported outcome (PRO) domains that should be endpoints in clinical trials. Reducing the severity and impact of symptoms is a natural intervention endpoint for cancer, a condition associated with considerable symptom burden. Because symptoms are best described by patients who have them, including PROs as measures of treatment effectiveness or the differences among treatments provides essential information about the efficacy and toxicity of a treatment and its effects on function. The FDA guidance provides a framework for addressing such issues as clinical significance, study design, and statistical methods as they relate to applications for labeling claims; however, no set of recommended approaches for assessing specific symptoms by patient report in clinical trials exists, other than for pain. Accordingly, an interdisciplinary workgroup, Assessing the Symptoms of Cancer using Patient-Reported Outcomes (ASCPRO), has been formed to generate evidence-based recommendations for the assessment of patient-reported cancer-related symptoms and the use of that information to facilitate clinical research and decision making. ASCPRO is among the first working groups to focus primarily on nonpain symptoms, including fatigue, sleep disturbance, appetite loss, depression, cognitive impairment, and shortness of breath. ASCPRO members are stakeholders in optimal symptom assessment, including patient advocates, academics, clinicians, those who pay for symptom control and monitor quality of care, and those who produce products that palliate cancer-related symptoms but that may also engender treatment-related symptoms.