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...     

免疫相关不良事件报告表在PD-1抑制剂治疗中的应用

目的:观察和分析作者自行编制的免疫相关不良事件病人报告表在PD-1抑制剂治疗中的应用。方法:2017年1月4日至2019年1月31日,作者参加全球或全国多中心PD-1抑制剂治疗肝细胞癌、食管癌的临床研究,使用的治疗药物有纳武利尤单抗、帕博利珠单抗和卡瑞利珠单抗(SHR-1210),其剂量和用法均按药物说明书或研究方案规定的执行。结果:66例病人纳入临床研究,所有病人及其照护者都能准确理解病人报告表中的内容,电子形式的病人报告表通过微信发送给责任护士简单快捷,最为病人及其照护者接受。所发生的不良事件除血清转氨酶、肌酐、蛋白尿等实验室异常外,都能从该表中找到相应的选项。研究过程中病人的依从性良好,仅2例病人发生脱落,其原因分别是由于交通不便、自愿退出。结论:作者自行编制的免疫相关不良事件病人报告表能及时准确地反映PD-1抑制剂治疗过程中发生的不良事件,对保证治疗的顺利进行有较好的应用价值。     

卡瑞丽珠单抗治疗期间发生免疫相关甲状腺不良事件的影响因素分析

目的 探讨应用卡瑞丽珠单抗治疗患者免疫相关甲状腺不良事件的影响因素。方法 选取2019年10月至2021年8月在我科应用卡瑞丽珠单抗治疗的食管癌、肺癌及肝癌患者共131例,均按照规范行卡瑞丽珠单抗单药或联合放、化疗及靶向治疗,回顾性分析患者的临床资料,分析免疫相关甲状腺不良事件的相关影响因素。结果 按治疗期间甲状腺功能情况分为正常组76例(58.0%)及异常组55例(42.0%),免疫相关甲状腺不良事件发生组中女性患者、行靶向治疗、化疗、颈部放疗患者的占比较未发生组高(P<0.05)。Logstic回归分析结果示女性、颈部放疗及靶向治疗是免疫相关甲状腺不良事件的独立危险因素(P<0.05)。免疫相关甲状腺不良事件组的患者促甲状腺激素及抗甲状腺球蛋白抗体的基线水平较高,疾病控制率较高(74.5%vs 51.3%,P=0.011)。结论 女性、联合颈部放疗或靶向治疗的患者,在应用卡瑞丽珠单抗时,更易发生免疫相关甲状腺不良事件。     

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。     

帕博利珠单抗治疗去势抵抗性前列腺癌的研究进展

前列腺癌是欧美国家老年男性最常见恶性肿瘤，早期或局限性前列腺癌可通过根治性手术达到治愈。但随着病程发展，几乎所有初始对雄激素剥夺治疗敏感的前列腺癌患者都将产生激素抵抗，进展为去势抵抗性前列腺癌（castration-resistant prostate cancer,CRPC）。近年，基于程序性死亡受体-1(PD-1)抑制剂帕博利珠单抗（Pembrolizumab）的治疗方案对多种实体瘤效果显著，治疗CRPC也取得初步疗效。本综述旨在总结帕博利珠单抗在CRPC临床试验中的现状及其存在的问题。     

晚期原发性肝癌患者行帕博利珠单抗免疫治疗的护理

目的总结晚期原发性肝癌患者行帕博利珠单抗免疫治疗的护理经验。方法18例晚期原发性肝癌使用帕博利珠单抗进行免疫治疗的患者,实施包括心理舒缓,用药前病情评估、给予抗组胺药预防过敏反应,严格按规范配置药液,药物使用中严密观察副作用的发生和护理等措施。结果18例患者均顺利完成帕博利珠单抗免疫治疗。2例患者在输注药物后30min出现低至中度发热,2例在用药后2~5d出现低度发热,1例用药第2天出现中度疲乏,2例出现轻度皮炎反应,所有患者经对症治疗和及时有效的护理,症状缓解或消失,均顺利出院。结论在晚期原发性肝癌患者行帕博利珠单抗免疫治疗中,加强病情评估、严格按规范配置和输液药液、严密观察药物不良反应和护理,对提高药物治疗效果具有积极的意义。     

免疫检查点抑制剂相关内分泌不良事件

免疫检查点抑制剂（immune checkpoint inhibitors，ICIs）是一类新型抗肿瘤药物，通过增强抗肿瘤免疫应答产生抗肿瘤作用，已经在多种恶性肿瘤治疗中表现出显著疗效。由于免疫检查点抑制剂特定的作用靶点和机制，可引起自身免疫和炎症效应，称为免疫相关不良事件（immune-related adverse events，irAEs）。随着免疫检查点抑制剂的广泛应用，其导致的irAEs也越来越受到重视，其中内分泌相关不良事件（如甲状腺功能障碍、垂体炎、肾上腺功能不全等）起病时表现隐匿，不易被发现，导致治疗延误，往往带来严重不良后果甚至危及患者生命。本文将总结既往文献，对免疫检查点抑制剂相关内分泌不良事件的发生率、可能的发病机制、临床表现、诊断等进行述评。     

既往免疫经治的晚期非小细胞肺癌患者接受安罗替尼联合PD-1单抗的疗效及安全性

目的 旨在探讨既往免疫经治的晚期非小细胞肺癌（non-small cell lung cancer,NSCLC）患者接受安罗替尼联合PD-1单抗治疗方案的疗效和安全性。方法 纳入临床实践中接受安罗替尼联合PD-1单抗治疗的既往免疫经治的52例晚期NSCLC患者。安罗替尼为临床常规用法用量，PD-1单抗为目前已经在中国上市的PD-1单抗，包括信迪利单抗，卡瑞利珠单抗和帕博利珠单抗。回顾性地收集患者治疗过程中的疗效及安全性数据，并对患者进行定期的随访获取长期生存的数据。结果 最佳的疗效结果提示接受安罗替尼联合PD-1单抗治疗的既往免疫经治的晚期NSCLC患者中取得部分缓解患者12例，疾病稳定患者32例，疾病进展患者8例。因此，该方案的客观缓解率为23.1%(95%CI:12.5%～36.8%)，疾病控制率为84.6%(95%CI:71.9%～93.1%)。中位无进展生存期为6.3个月（95%CI:2.64～9.96），中位的总生存期为16.6个月（95%CI:8.08～25.12）。既往免疫相关方案不耐受的患者（10例）接受该方案治疗时具有相对较好的预后（中位OS:23.4个月vs. 11...     

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。     

免疫检查点抑制剂致心肌炎风险分析——基于open FDA数据库的真实世界研究

目的 对免疫检查点抑制剂（ICI）致心肌炎的临床特征进行分析。方法 从美国FDA不良事件报告系统（FAERS）中下载2014年1月1日至2022年9月30日关于ICI（阿替利珠单抗、度伐利尤单抗、帕博利珠单抗和纳武利尤单抗）导致心肌炎的不良反应（ADR）报告。对ICI相关心肌炎患者的性别、年龄、用药剂量、发生时间等进行分析。结果 共提取到ICI相关心肌炎ADR报告1 892例。ICI致心肌炎患者男性多于女性（1.9∶1）。有糖尿病、心脏病等基础疾病以及65～75岁年龄段患者的发病率较高。纳武利尤单抗使用常规剂量30天的发病率较高,其他3种药物常规使用剂量31～90天发病率较高,联合用药较单药使用的发病率更高。结论 不同品种ICI均可导致心肌炎发生,男性、高龄、患有基础疾病和联合用药可能是ICI致心肌炎的风险因素。     

Determination of creatine kinase isoenzyme MB activity in serum using immunological inhibition of creatine kinase M subunit activity. Activity kinetics and diagnostic significance in myocardial infarction.

This is a new method for the determination of creatine kinase isoenzyme MB activity in serum. The method uses direct activity measurement of creatine kinase B subunit activity after blocking of CK-M subunit activity by inhibiting antibodies. The test takes no longer than 15 min. The method yields an intra-serial C.V. of 2.0-12.9%, and a C.V. from day to day of 5.5%. The detection limit is 3.4 U/l creatine kinase MB. In the 95 cases with proven myocardial infarction several types of creatine kinase MB activity kinetics could be determined. The percentage of creatine kinase MB of peak CK-total is 6-25%, with a mean of 11.1%. The amount of creatine kinase MB with respect to total CK activity after reinfarction is higher than the amount after initial infarction.     

俯卧位通气对高海拔地区肺复张治疗无效急性呼吸窘迫综合征患者氧合的影响

目的 探讨俯卧位通气对高海拔地区肺复张术(RM)治疗无效急性呼吸窘迫综合征(ARDS)患者的治疗作用.方法 从海拔2260m的地区医院筛选RM治疗无效的41例ARDS患者[平均氧合指数( PaO2/FiO2)较RM前升高＜20％视为RM无效],依不同病因分为肺内源性ARDS组(ARDSp组)和肺外源性ARDS组(ARDSexp组),每组再按信封法随机分为俯卧位组和仰卧位组,即ARDSp俯卧位组(11例)、ARDSp仰卧位组(9例)、ARDSexp俯卧位组(10例)、ARDSexp仰卧位组(11例).在通气前及通气1、2、3、4h监测动脉血氧分压( PaO2)、PaO2/FiO2、静态顺应性(Cst)、气道阻力(Raw)的变化.结果 通气lh时,ARDSexp俯卧位组PaO2/FiO2( mm Hg,l mm Hg=0.133 kPa)即较通气前显著升高(157.4±40.6比129.3±48.7,P＜0.05),并随通气时间延长呈持续增高趋势,4h达峰值(219.1 ±41.1);且ARDSexp俯卧位组通气3h内PaO2/FiO2较其他3组显著增高,另3组间则差异无统计学意义.ARDSp俯卧位组、ARDSexp俯卧位组通气4h时PaO2/FiO2均较相应仰卧位组显著增高(208.8±39.7比127.4±47.1,219.1±41.1比124.9±50.8,均P＜0.05).4组通气前后Cst无显著改变,各组间差异也无统计学意义.ARDSp俯卧位组通气4h时Raw(cmH2O·L-1·s-1)较通气前显著降低(6.8±1.7比10.7±1.8,P＜0.05),且明显低于其他3组;其他3组各时间点Raw组内及组间比较差异均无统计学意义.结论 俯卧位通气作为ARDS机械通气重要策略之一,可以改善RM无效高原ARDS患者的氧合,为抢救患者赢得宝贵的时间.     

Digital imaging among medical facilities

The Department of Veterans Affairs (VA) in the USA operates a network of 172 medical centres which all utilize a hospital information system (HIS) which has been developed and is currently maintained by the VA. During the past several years, an image management and communication module has been developed, installed and clinically utilized at the Washington DC and Maryland VA Medical Centres. This image management and communication system, referred to as the decentralized hospital computer program (DHCP) imaging system, is fully integrated with a commercial picture archiving and communication system (PACS). The system is utilized to capture, archive, and display all images generated within the hospital including radiology, nuclear medicine, pathology, endoscopy, bronchoscopy, and dermatology, intraoperative photographs, ECG data, and a limited number of paper documents. The ultimate goal of the project is to have all patient text and image data available at any clinical workstation to any authorized user anywhere within the network of medical centres. Clinical requirements for an imaging workstation include ease of use, rapid and reliable access to the complete set of patient information, and images which are of acceptable quality to meet the requirements of the user and the subspecialty. Patient confidentiality and data security must be safeguarded at all times. Integration of the images with the remainder of the patient's database was found to be critical to the success of the project. The experience at the Washington and Maryland facilities suggests that an imaging system that is successfully integrated with a hospital information system can provide substantial clinical and economic benefits both within and among medical centres. Clinical acceptance and utilization of the system has been excellent, particularly in diagnostic radiology where DHCP Imaging has been interfaced to a commercial PAC system. Based upon this initial experience, the VA has begun to deploy the system throughout its large network of medical centres.     

Myocardial elastography at both high temporal and spatial resolution for the detection of infarcts

Myocardial elastography is a novel method for noninvasively assessing regional myocardial function, with the advantages of high spatial and temporal resolution and high signal-to-noise ratio (SNR). In this paper, in-vivo experiments were performed in anesthetized normal and infarcted mice (one day after left anterior descending coronary artery [LAD] ligation) using a high-resolution (30 MHz) ultrasound system (Vevo 770, VisualSonics Inc., Toronto, ON, Canada). Radiofrequency (RF) signals of the left ventricle (LV) in longitudinal (long-axis) view and the associated electrocardiogram (ECG) were simultaneously acquired. Using a retrospective ECG gating technique, 2-D full field-of-view RF frames were acquired at an extremely high frame rate (8 kHz) that resulted in high-quality incremental displacement and strain estimation of the myocardium. The incremental results were further accumulated to obtain the cumulative displacements and strains. Two-dimensional and M-mode displacement images and strain images (elastograms), as well as displacement and strain profiles as a function of time, were compared between normal and infarcted mice. Incremental results clearly depicted cardiac events including LV contraction, LV relaxation and isovolumetric phases in both normal and infarcted mice, and also evidently indicated reduced motion and deformation in the infarcted myocardium. The elastograms indicated that the infarcted regions underwent thinning during systole rather than thickening, as in the normal case. The cumulative elastograms were found to have higher elastographic SNR (SNR(e)) than the incremental elastograms (e.g., 10.6 vs. 4.7 in a normal myocardium, and 6.0 vs. 2.4 in an infarcted myocardium). Finally, preliminary statistical results from nine normal (m = 9) and seven infarcted (n = 7) mice indicated the capability of the cumulative strain in differentiating infracted from normal myocardia. In conclusion, myocardial elastography could provide regional strain information at simultaneously high temporal (>/=0.125 ms) and spatial ( approximately 55 microm) resolution as well as high precision ( approximately 0.05 microm displacement). This technique was thus capable of accurately characterizing normal myocardial function throughout an entire cardiac cycle, at the same high resolution, and detecting and localizing myocardial infarction in vivo.     

手转胎头术失败的原因与分娩结局临床分析

目的 探讨手转胎头术失败的原因与分娩结局.方法 选择2008年1月至2010年12月于我院住院分娩的持续性枕横位、枕后位产妇198例,根据行手转胎头术后结果分为成功组126例、失败组72例.比较两组分娩结局,对比分析失败原因.结果 失败组胎儿体质量≥3500 g的发生率[76.4％(55/72)]明显高于成功组[31.7％(40/126)],差异有统计学意义(x2=30.177,P=0.001)、失败组宫缩乏力发生率[58.3％(42/72)]高于成功组[38.1％ (48/126)],差异有统计学意义(x2=7.569,P=0.006)、失败组骨盆临界或轻度狭窄发生率[38.9％ (28/72)]高于成功组[23.8％(30/126)],差异有统计学意义(x2 =5.030,P=0.002)、失败组手转胎头时机不当(宫口开大＜6 cm、胎头位于坐骨棘上及宫口开大8～10 cm、胎头位于坐骨棘下≥2 cm)发生率[61.1％(44/72)]高于成功组[38.9％(49/126)],差异有统计学意义(x2=9.084,P=0.003).失败组母儿并发症(产后出血、产褥病率、胎儿窘迫、新生儿窒息)发生率高于成功组(x2 =9.586,P=0.002、x2=9.334,P=0.002、x2=5.910,P=0.015、x2=5.240,P=0.022)、失败组剖宫产发生率[72.2％(52/72)]明显高于成功组[34.1 ％(43/126),x2=26.641,P=0.001)].结论 手转胎头术能使难产变顺产,降低剖宫产率,减少母儿并发症,但须积极预防、处理导致手转胎头术失败的原因,对矫正失败后继续矫正及试产应慎重.     

Clinical Pharmacokinetics of Morphine

Morphine, the most widely used mu-opioid analgesic for acute and chronic pain, is the standard against which new analgesics are measured. A thorough understanding of the pharmacokinetics of morphine is required in order to safely and effectively use this analgesic in a wide variety of patients with different levels of organ function. A MEDLINE search was conducted to identify literature published between 1966 and January 2002 relevant to the pharmacokinetics of morphine. These publications were reviewed and the literature summarized regarding unique and clinically important elements of morphine disposition relative to its parenteral administration (including intravenous, intramuscular, subcutaneous, epidural and intrathecal administration), absorption profile (immediate release, controlled release, and sublingual/buccal, and rectal administration), distribution, and its metabolism/ excretion. Special populations, including infants, elderly, and those with renal/liver failure, have a unique morphine pharmacokinetic profile that must be taken into account in order to maximize analgesic efficacy and reduce the risk of adverse events.     

Evidence-Based Pain Management and Palliative Care in Issue Four for 2009 of The Cochrane Library

ABSTRACT

The Cochrane Library of Systematic Reviews is published quarterly. Issue 4 for 2009 contains 4027 complete reviews, 1906 protocols for reviews in production, and 11447 one-page summaries of systematic reviews published in the general medical literature. In addition, there are citations of 600,000 randomized controlled trials, and 12,200 cited papers in the Cochrane methodology register. The health technology assessment database contains over 7500 citations. This edition of the Library contains 90 new reviews, of which 19 have potential relevance for practitioners in pain and palliative medicine.     

Wie zuverlässig sind Angaben zu nichtentzündlichen ausgedehnten Schmerzen?

ZusammenfassungFragestellung Es wurde geprüft, wie sich der Differenziertheitsgrad zweier Schmerzmessmethoden auf Angaben zur Ausgedehntheit klinischer Schmerzen auswirkt. Zugleich wurde der Referenzzeitraum variiert, über den die Patienten berichten sollten.Methode Erfasst wurde der Einfluss zu Lasten der Befragungsdifferenziertheit durch den Vergleich zweier Körperschema-Bildvorlagen. Drei Referenzzeiträume (Schmerz aktuell, letzte Woche, letztes halbes Jahr) wurden vorgegeben.Ergebnisse Patienten mit ausgedehnten Schmerzen gaben bei differenzierter Befragung um so mehr Schmerzen an, je weiter die Schmerzen zurück lagen und je größer der Berichtszeitraum war. Patienten mit gelenknahen Schmerzen gaben bei hoch differenzierter Befragung weniger ausgedehnte Schmerzen in der Vergangenheit an als bei globaler Einschätzung. Patienten mit Rückenschmerzen berichteten bei differenzierter Befragung zum aktuellen Schmerz über weniger ausgedehnte Schmerzen als bei globaler Befragung.Schlussfolgerung Die Angaben zur Schmerzausdehnung variieren vor allem bei Patienten mit ausgedehnten Schmerzen in Abhängigkeit von der Differenziertheit der Befragung. In diesen Fällen ist die Wahrscheinlichkeit erhöht, dass sich die Beschwerdesymptomatik zumindest teilweise erst in der Reaktion auf die situativen Befragungsbedingungen konstituiert und daher nicht auf andere Befragungsbedingungen generalisiert werden kann.