信迪利单抗致免疫相关肺炎的临床特征及案例分析

目的 总结4例信迪利单抗致免疫相关肺炎患者的临床症状、影像学、实验室检验指标、治疗方案和随访情况,为此类患者的治疗提供参考。方法 回顾4例免疫相关肺炎患者的治疗过程,结合文献分析该类患者的治疗特点。结果 4例患者发生免疫相关肺炎之前使用信迪利单抗治疗的时间依次为6.4、10.5、5.3、3.9个月,中位时间5.85个月。3例患者初始临床症状为胸闷、气短、咳嗽及乏力,1例无明显临床症状。4例患者胸部电子计算机断层扫描（CT）呈斑片状高密度影,其中1例患者行电子支气管镜检查,发现有肉芽样新生物增生,其余3例未行电子支气管镜检查。4例患者初始中性粒细胞比率轻度升高,超敏C反应蛋白升高,降钙素原基本正常,痰细菌和真菌培养、G/GM试验结果均呈阴性。治疗方案中,4例免疫相关肺炎患者停用信迪利单抗,初始使用甲泼尼龙琥珀酸钠或联合吗替麦考酚酯治疗有效。患者出院序贯口服糖皮质激素,在逐渐减量并停药后或治疗过程中出现了免疫相关肺炎复发,合并肺部感染,其中3例治疗无效,死于免疫相关肺炎合并感染性肺炎导致的呼吸衰竭,1例患者病情缓解。结论 糖皮质激素或联合吗替麦考酚酯可有效治疗信迪利单抗致免疫相关肺炎,但再...     

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。     

免疫检查点抑制剂治疗晚期恶性肿瘤所致免疫相关不良反应

目的 观察晚期恶性肿瘤患者免疫检查点抑制剂(ICIs)治疗中免疫相关不良反应(irAEs)的发生情况,以期提高对irAEs的诊治水平。方法 回顾性分析2019年1月至2021年5月在安徽医科大学第三附属医院进行ICIs(信迪利单抗)治疗的80例晚期恶性肿瘤患者,观察治疗期间患者发生的irAEs,包括不良反应的种类、分级、发生时间、处理措施、预后等。结果 80例患者中,32例患者发生irAEs,总体发生率40.0%,不良反应中位发生时间4.857周,其中14例免疫性输注反应,7例免疫性皮炎,5例免疫性甲状腺功能异常,5例免疫性胃肠道毒性,1例免疫性肺炎;1、2级不良反应发生率为96.9%;31例患者经对症治疗、激素冲击治疗和维持治疗后不良反应完全缓解,1例患者因免疫性肺炎死亡。结论 irAEs发生率较高,大部分为1、2级不良反应,总体安全性较高,不良反应可耐受。     

信迪利单抗联合化疗对晚期非小细胞肺癌肿瘤标志物及免疫功能的影响

目的 探讨信迪利单抗联合化疗对晚期非小细胞肺癌(NSCLC)肿瘤标志物及免疫功能的影响.方法 选取2019年11月至2020年11月于该院接受治疗的180例晚期NSCLC患者,依据随机抽签法将患者分为观察组(90例)与对照组(90例).观察组在常规GP(吉西他滨+顺铂)方案化疗的基础上静脉注射信迪利单抗,对照组行常规G...     

1例肝癌患者应用信迪利单抗致红皮病的护理

总结1例肝癌患者应用信迪利单抗致红皮病的护理经验,包括严格消毒隔离,预防感染;做好皮损严重期、好转期及愈合期不同时期的皮肤护理,有效促进皮损的愈合;做好口腔护理;科学合理安排饮食,提高患者免疫力;同时及时向患者介绍红皮病的发病原因、正确皮肤护理与自我管理的方法,减轻患者的心理负担,提高患者治疗的依从性。经过精心护理,患者皮损愈合较好,面部及胸部皮损完全愈合,四肢皮肤破溃处结痂,仅臀部皮肤破损未完全愈合,转至烧伤科继续治疗。     

信迪利单抗联合化疗对晚期非小细胞肺癌患者免疫功能、肿瘤标志物水平的影响分析

目的 研究信迪利单抗联合化疗治疗晚期非小细胞肺癌(non-small cell lung cancer,NSCLC)的临床效果。方法选取2018年7月至2021年6月在我院诊治的52例NSCLC患者,按随机对照原则分为对照组和观察组各26例。对照组给予GP方案(吉西他滨+顺铂)化疗,观察组在GP方案化疗基础上增加信迪利单抗治疗。比较两组临床疗效、血清肿瘤标志物[癌胚抗原(CEA)、糖类抗原125(CA125)]、免疫功能指标(CD3⁺、CD4⁺、CD8⁺、CD4⁺/CD8⁺)及不良反应。结果 观察组治疗总有效率为73.08%,高于对照组的42.31%,差异有统计学意义(P<0.05)。观察组治疗后血清CEA、CA125水平低于对照组,差异有统计学意义(P<0.05)。观察组治疗后CD3⁺、CD4⁺水平及CD4⁺/CD8⁺均高于对照组,差异有统计学意义(P<0.05);两组治...     

信迪利单抗联合白蛋白紫杉醇对晚期胃癌血清肿瘤标志物水平及免疫功能的影响

目的 探究信迪利单抗联合白蛋白紫杉醇对晚期胃癌血清肿瘤标志物水平及免疫功能的影响。方法 前瞻性选取2021年6月至2023年2月在长治医学院附属和平医院接受治疗的89例晚期胃癌患者为研究对象,按照随机数字表法分为对照组(n=44)和观察组(n=45)。对照组患者采取白蛋白紫杉醇治疗,观察组患者采取信迪利单抗联合白蛋白紫杉醇进行治疗。比较两组治疗效果、肿瘤标志物[糖类抗原(CA)125、CA19-9、癌胚抗原、甲胎蛋白及组织多肽特异性抗原(TPS)]水平、免疫功能指标(CD3⁺、CD4⁺、CD8⁺、CD4⁺/CD8⁺)水平,记录患者治疗期间发生的不良反应。结果 治疗后,观察组患者的客观缓解率及疾病控制率分别为55.56%、77.78%,均高于对照组(34.09%、 47.73%),差异均有统计学意义(P<0.05)。治疗后,两组患者的各肿瘤标志物水平均较治疗前降低,且观察组CA125、CA19-9、癌胚抗原、甲胎蛋白、TPS水平分别为(16.77±2.77)U/mL、(15...     

信迪利单抗治疗非小细胞肺癌后患者甲状腺功能减退的危险因素

目的 观察分析非小细胞肺癌（NSCLC）患者经信迪利单抗治疗后甲状腺功能减退的相关因素。方法 选取宿迁市第一人民医院2021年7月至2023年8月收治的99例接受信迪利单抗治疗的NSCLC患者为研究对象,将其中随访甲状腺功能减退的16例患者作为甲状腺功能减退组,非甲状腺功能减退的83例患者为对照组。采用单因素分析及多因素logistic回归模型分析影响甲状腺功能减退的相关因素。结果 单因素分析结果显示,两组患者在性别、体重指数、基线甲状腺过氧化物酶抗体（TPO-Ab）、手术史、化疗史、放疗史、病程、治疗线数等方面差异有统计学意义（P<0.05）。多因素logistic回归结果显示,女性、体重指数、TPO-Ab阳性为NSCLC患者经信迪利单抗治疗后甲状腺功能减退的危险因素（P<0.05）。结论 NSCLC患者经信迪利单抗治疗后甲状腺功能减退发生风险较高,女性、体重指数、基线TPO-Ab阳性为甲状腺功能减退的危险因素。     

信迪利单抗联合改良DCF方案治疗晚期胃癌的临床研究

目的：探讨信迪利单抗联合改良DCF(多西他赛+奥沙利铂+替吉奥)方案对晚期胃癌患者血清肿瘤标志物水平的影响。方法：将巨野县人民医院2020年5月至2022年6月收治的晚期胃癌患者80例按随机双盲法进行分组。对照组40例采用改良DCF方案,研究组40例在对照组基础上联合信迪利单抗治疗。比较两组临床疗效[客观有效率(ORR)、疾病控制率(DCR)],治疗前后血清肿瘤标志物[糖类抗原(CA)125、CA199、CA724、癌胚抗原(CEA)]水平、肿瘤细胞迁移能力(CD9、CD63、CD151、CD168)、免疫功能(T淋巴细胞亚群)及不良反应发生情况。结果：研究组ORR、DCR分别为62.50%、87.50%,高于对照组的40.00%、67.50%(P<0.05)。治疗后研究组CA125、CA724、CA199、CEA、CD151、CD168水平均低于对照组,CD9、CD63、CD3⁺、CD4⁺、CD8⁺、CD4⁺/CD8⁺水平均高于对照组(P<0.05)。研究组肝功能...     

帕博利珠单抗致剥脱性皮炎1例的临床诊治并同期应用帕博利珠单抗44例皮肤毒性分析

目的 随着免疫治疗在临床的推广及使用,免疫相关不良反应的伴随发生获得越来越多的关注.控制免疫相关皮肤不良反应可有效改善治疗耐受性,提高疗效.方法 本文报道了近期1例严重免疫相关不良皮肤毒性患者的临床诊治经过,同时对同期本院应用帕博利珠单抗的44例患者进行皮肤毒性分析及相关文献复习.结果 44例应用帕博利珠单抗治疗患者中...     

Ventilator-associated pneumonia in paediatric intensive care: a literature review

Background: Ventilator‐associated pneumonia (VAP) has been identified as the most common nosocomial infection in intensive care units (ICUs) with associated health and financial costs. To date, more research has been carried out in adult ICUs than in paediatric units, thus prompting a review and investigation of the implications for paediatric practice. Aims: To identify relevant paediatric literature surrounding VAP and use this in association with research carried out in the adult environment to establish the implications of VAP and possible management strategies. Search strategies: A literature search was undertaken using databases within DialogDatastar to identify the extent to which VAP has been researched in both paediatric and adult centres. This information was used to try and gain a clearer concept of the impact and management of VAP in the paediatric setting. Key words and combinations included VAP, intensive care, paediatric, antibiotics, positioning, suction, economics, management, nosocomial and morbidity and mortality. Results of analysis: Despite the documented significance of VAP in terms of its financial and health implications, discrepancies and inconsistencies exist surrounding the identification and treatment of VAP. This is reflected in paediatric centres by a dearth of literature on the subject and the lack of a national standard as to the management and prevention of VAP. Inappropriate management of VAP plays an important role in the development and spread of multiresistant bacteria within hospitals. Conclusions: While inadequate paediatric research exists, extrapolating from adult research suggests that the financial and health costs of VAP are substantial and can be reduced by introducing simple low‐cost measures. Such measures include improving education surrounding VAP and its implications and making small changes in practice to improve and maintain oral hygiene standards. Implications: With a growing cohort of paediatric patients requiring short‐ and long‐term ventilation, progress must be made in identifying the extent and impact of VAP in paediatric ICUs and among the community ventilated patients. This will require changes in practice and attitudes towards VAP for which an appropriate knowledge base would need to be established using audit and research. These issues are particularly relevant in the current environment given the links with multiresistant strains of bacteria within hospitals and the community.     

免疫检查点抑制剂相关垂体功能减退临床特征

目的 探讨免疫检查点抑制剂（immune checkpoint inhibitors,ICIs）诱发的垂体功能减退的临床特征。方法 回顾性纳入2019年1月至2022年6月在复旦大学附属中山医院内分泌科诊治的使用ICIs后出现垂体功能减退的各类肿瘤患者，分析ICIs相关垂体功能减退的临床表现、实验室检查结果、影像学特征。结果 共纳入23例患者，其中男性13例（53.5%）、女性10例（43.5%），平均年龄（59.5±11.8）岁。ICIs包括程序性死亡受体1(PD-1)单抗和细胞毒T淋巴细胞相关抗原4(CTLA-4)单抗。23例患者均出现继发性肾上腺皮质功能减退，均未出现中枢性尿崩症。累及垂体-甲状腺轴者3例（13.0%）；甲状腺功能正常者11例（47.8%）；出现ICIs相关原发性甲状腺功能减退9例（39.1%）。累及垂体-性腺轴者4例（17.4%）。结论 ICIs相关垂体功能减退主要表现为继发性肾上腺皮质功能减退，部分累及垂体-甲状腺轴、垂体-性腺轴，也可同时出现甲状腺腺体损伤，表明及时评估ICIs治疗中患者的垂体及靶腺功能有助于提高免疫治疗的安全性。     

COVID-19 pneumonia and immune-related pneumonitis: critical issues on differential diagnosis,potential interactions,and management

ABSTRACT

Introduction

The COVID-19 pandemic occurred amid the cancer immunotherapy revolution. Immune checkpoint inhibitors (ICIs) have become the standard of care for several solid cancers and are associated with peculiar toxicities, including pneumonitis which has similar features to COVID-19 pneumonia.     

免疫检查点抑制剂相关心肌炎的诊治进展

免疫调节是控制恶性肿瘤进展的重要决定因素,免疫检查点抑制剂(ICIs)的应用为恶性肿瘤治疗带来突破性进展,很大程度上改善了患者的生存时间和生活质量,然而不可避免的是,其也带来免疫相关不良反应(irAE)毒性风险.本文就ICIs相关心肌炎的发病机制、发病率、诊断和治疗策略进行综述.     

Immunotherapy for non-small-cell lung cancer

Activation of the host immune system represents an attractive treatment approach for cancers. In non-small-cell lung cancer (NSCLC), a variety of immunotherapies, including nonspecific immune stimulants, vaccines and checkpoint inhibitors, have been evaluated in clinical trials. Several randomized Phase III trials have failed to demonstrate clinical benefit from nonspecific immune stimulants and vaccines in the overall trial populations. Activity of vaccines in subsets of patients in these trials needs further evaluation. Unlike vaccines aimed at stimulating a cellular immune response to antigens differentially expressed in cancers, checkpoint inhibitors aim at overcoming immune inhibitory signals in the tumor microenvironment via pharmacological inhibition of immune checkpoints – a crucial tumoral immune escape mechanism. Early clinical trials of checkpoint inhibitors showed promising results with some durable responses. Better understanding of the mechanisms of immunosuppression specific to NSCLC will be crucial for successful patient selection for immunotherapy.     

Predictive molecular markers for the treatment with immune checkpoint inhibitors in colorectal cancer

Colorectal cancer is one of the most common malignant tumors and, hence, has become one of the most important public health issues in the world. Treatment with immune checkpoint inhibitors (ICIs) successfully improves the survival rate of patients with melanoma, non‐small‐cell lung cancer, and other malignancies, and its application in metastatic colorectal cancer is being actively explored. However, a few patients develop drug resistance. Predictive molecular markers are important tools to precisely screen patient groups that can benefit from treatment with ICIs. The current article focused on certain important predictive molecular markers for ICI treatment in colorectal cancer, including not only some of the mature molecular markers, such as deficient mismatch repair (d‐MMR), microsatellite instability‐high (MSI‐H), tumor mutational burden (TMB), programmed death‐ligand‐1 (PD‐L1), tumor immune microenvironment (TiME), and tumor‐infiltrating lymphocytes (TILs), but also some of the novel molecular markers, such as DNA polymerase epsilon (POLE), polymerase delta 1 (POLD1), circulating tumor DNA (ctDNA), and consensus molecular subtypes (CMS). We have reviewed these markers in‐depth and presented the results from certain important studies, which suggest their applicability in CRC and indicate their advantages and disadvantages. We hope this article is helpful for clinicians and researchers to systematically understand these markers and can guide the treatment of colorectal cancer.     

肌减少症对实体瘤患者免疫检查点抑制剂治疗影响的meta分析

目的 探究肌减少症对免疫检查点抑制剂(immune checkpoint Inhibitor,ICIs)的短期疗效、远期预后和免疫相关不良反应的影响。方法 对PubMed、EMBASE和Cochrane数据库中在2021年6月前发表的关于肌减少症对免疫治疗的实体瘤患者短期疗效、远期预后和免疫相关不良反应影响的文献进行检索。采用Review Manager 5.3软件和Stata14.0软件进行统计分析。结果 共有27篇文献被纳入荟萃分析,Meta分析结果显示合并肌减少症可降低肿瘤患者免疫治疗的客观反应率(RR=0.11,95%CI:0.02～0.54)和疾病控制率(RR=0.55,95%CI:0.39～0.78)。同时,治疗前合并肌减少症是肿瘤患者预后不良的危险因素(OS:HR=1.60,95%CI:1.30～1.97;PFS:HR=2.81,95%CI:1.88～4.22),甚至在治疗期间肌减少也是患者预后不良的危险因素。合并肌减少症会增加患者发生严重免疫相关不良事件的风险(RR=1.27;95%CI:0.74～2.19)。结论 肌减少症是肿瘤患者免疫治疗效果和预后不佳的危险因素。     

Results and challenges of immune checkpoint inhibitors in colorectal cancer

Introduction: Colorectal cancer (CRC) is the third most commonly diagnosed cancer worldwide and clinical outcome has improved substantially during the last two decades with targeted therapies. The immune system has a major role in cancers, especially the CD8 + T cells specific to tumor antigens. However, tumors can escape immune response by different mechanisms including upregulation of inhibitory immune checkpoint receptors, such as well-known Programmed cell Death protein-1 (PD-1)/Programmed cell Death Ligand 1 (PD-L1) interaction, leading CD8 + T cells to a state of anergy. Immunotherapy, with the so-called immune checkpoint inhibitors (CPIs), has recently been approved in treatment of multiple cancers due to its prolonged disease control and acceptable toxicities. The recent groundbreaking success involving anti-PD-1 CPIs in metastatic CRC with deficient mismatch repair system (dMMR) is promising, with several trials ongoing. Major challenges are ahead in order to determine how, when and for which patients we should use these CPIs in CRC.

Areas covered: This review highlights some promises and challenges concerning personalized immunotherapy in CRC. First results and ongoing breakthrough trials are presented. The crucial role of biomarkers in selecting patient is also discussed.

Expert opinion: As of now, dMMR and POLE mutations (DNA polymerase ε) with ultramutator phenotype are the most powerful predictive biomarkers of CPI efficacy. The most challenging issue is pMMR mCRC and determination of how to convert a ‘nonimmunogenic’ neoplasm into an ‘immunogenic’ neoplasm, a combination of CPIs with radiation or MEK inhibitor probably being the most relevant strategy. Next-generation sequencing (NGS) assays to quantify mutational load could be more reliable predictive biomarkers of CPIs efficacy than PD-L1 expression or immune scores.     

Efficacy of artificial liver support system in severe immune-associated hepatitis caused by camrelizumab: A case report and review of the literature

BACKGROUNDImmune checkpoint inhibitors (ICIs) can lead to immune-related hepatitis (IRH) and severe liver damage, which is life-threatening in the absence of specific treatment.CASE SUMMARYA 75-year-old man was admitted to our hospital complaining of loss of appetite, yellow urine, and abnormal liver function for the past 2 wk. Three months prior to admission, he was treated with two rounds of capecitabine in combination with camrelizumab for lymph node metastasis of esophageal cancer. Although liver function was normal before treatment, abnormal liver function appeared at week 5. Capecitabine and camrelizumab were discontinued. Ursodeoxycholic acid and methylprednisolone 40 mg daily were administered. Liver function continued to deteriorate. Prothrombin time and international normalized ratio were 19 s and 1.8, respectively. The patient was diagnosed with acute liver failure. A pathological analysis of liver biopsy indicated a strongly positive immunohistochemical staining of T8⁺ cells, thereby suggesting that drug-induced liver injury was related to IRH caused by camrelizumab. Subsequently, we performed sequential dual-molecule plasma adsorption system (DPMAS) treatment with plasma exchange (PE). After two rounds of treatment, the patient''s appetite significantly improved, the yellow color of urine reduced, and liver function improved (total bilirubin level decreased) after five rounds of treatment. Liver function normalized 4 wk after discharge.CONCLUSIONThe use of sequential DPMAS with PE can reduce liver injury and systemic toxic reactions by clearing inflammatory mediators and harmful substances from blood, and regulate immune cell activity, which may be effective in the treatment of severe ICI-induced IRH.