TMB表达水平对EGFR突变晚期NSCLC患者预后分析

目的 探索肿瘤突变负荷（TMB）表达水平对EGFR驱动基因阳性的晚期非小细胞肺癌（NSCLC）患者的预后影响。方法 回顾性分析2015年1月至2021年1月首都医科大学大兴教学医院肿瘤科收治的95例EGFR敏感突变的晚期NSCLC患者的临床资料,所有患者满足诊断时已行TMB检测并可以获得完整的病历资料,一线治疗均接受EGFR-TKIs靶向治疗且至少30d以上。通过三分位法将TMB表达水平分为高TMB组和中、低TMB组,分析TMB与EGFR-TKIs一线治疗客观缓解率（ORR）及无进展生存期（PFS）之间的关系。结果 与高TMB组相比,中、低TMB组患者接受EGFR-TKIs治疗的客观缓解率更高（84.1%vs 59.4%,P=0.008）,中位无进展生存期更长（11.2mvs 7.2m,P=0.001）,具有统计学差异。结论 TMB数值的高低可以预测EGFR驱动基因阳性的晚期非小细胞肺癌（NSCLC）患者的预后,高TMB患者近远期预后不佳。     

埃克替尼治疗EGFR突变型非小细胞肺癌脑转移的预后

目的:探讨埃克替尼治疗EGFR突变型非小细胞肺癌脑转移的临床效果及预后因素。方法:回顾性分析2012年1月至2015年9月诊断肺癌脑转移并接受埃克替尼治疗的116例患者。采用Kaplan-Meier单因素、Cox多因素分析方法,探讨非小细胞肺癌脑转移患者接受埃克替尼治疗的生存情况及影响因素。结果:116例非小细胞肺癌脑转移患者以女性、60岁和不吸烟患者为主。Cox风险比例回归模型显示:病理类型和EGFR基因类型是非小细胞肺癌脑转移患者接受埃克替尼治疗的独立预后因素。结论:非小细胞肺癌脑转移患者接受埃克替尼治疗具有良好的疗效,腺癌亚型患者的PFS和OS均长于非腺癌患者,EGFR常见突变患者PFS和OS均长于少见突变。     

非小细胞肺癌患者表皮生长因子受体突变与血清癌胚抗原和糖类抗原检测的关系

目的研究非小细胞肺癌(NSCLC)患者表皮生长因子受体(EGFR)基因突变与血清癌胚抗原(CEA)、糖类抗原(CA125、CA199)的关系,研究其对靶向治疗的价值。方法选择非小细胞肺癌患者193例,术前行血清CEA、CA125、CA199检测作为备用数据,术后对标本行EGFR检测,分析CEA、CA125、CA199与EGFR基因突变的关系及临床意义。结果全组患者中发生EGFR基因突变者共83例,基因突变率为43.0%;EGFR基因突变在女性、非吸烟及腺癌患者多见(P0.05);EGFR基因突变与CEA值呈正相关(P0.05);EGFR与CA125、CA199无相关性(P0.05)。结论非小细胞肺癌EGFR基因突变在女性、非吸烟及腺癌患者中多见,其突变与血清CEA水平升高有关。     

吉非替尼靶向联合GP化疗方案治疗晚期EGFR阳性非小细胞肺癌的效果

目的 探讨吉非替尼靶向联合吉西他滨+顺铂(GP)化疗方案应用于晚期表皮生长因子受体(EGFR)阳性非小细胞肺癌患者的效果。方法 采用前瞻性随机试验方法,选取2019年1月至2020年6月在郑州市第三人民医院就诊的晚期EGFR阳性非小细胞肺癌患者76例,以随机数字表法分为两组,每组38例。对照组采用GP化疗方案,观察组采用吉非替尼靶向与GP化疗方案联用。比较两组临床疗效及肿瘤标志物水平。结果 观察组临床治疗总有效率为60. 53%(23/38),高于对照组[34. 21%(13/38)],差异有统计学意义(P 0. 05);治疗3个疗程后,两组血清癌胚抗原(CEA)、神经元特异性烯醇化酶(NSE)及细胞角蛋白19片段抗原21-1(CY-FRA21-1)水平均低于治疗前,且观察组上述指标水平均比对照组低,差异有统计学意义(P 0. 05)。结论 吉非替尼靶向联合GP化疗方案应用于晚期EGFR阳性非小细胞肺癌治疗可提升临床治疗总有效率,改善肿瘤标志物水平。     

粟粒型肺癌的肿瘤微环境及其与EGFR-TKI疗效的关系

目的 探讨肿瘤免疫微环境对粟粒型肺癌患者接受靶向治疗疗效的影响.方法 回顾性分析2017年3月至2019年3月广州市胸科医院诊治的147例表皮生长因子受体(EGFR)突变阳性晚期非小细胞肺癌(NSCLC)患者.根据影像学特征将患者分为粟粒型肺癌组(A组,49例)和非粟粒型肺癌组(B组,98例).比较两组患者肿瘤微环境的...     

EGFR-TKI靶向治疗联合放疗对EGFR突变型非小细胞肺癌脑转移的疗效分析

目的分析表皮生长因子受体酪氨酸激酶抑制剂(EGFR-TKI)靶向治疗联合放疗对表皮生长因子受体(EGFR)突变型非小细胞肺癌脑转移的疗效。方法 2016年1月至2018年3月收治的EGFR突变型非小细胞肺癌脑转移患者90例,按随机数表法分为对照组和观察组各45例。对照组给予单纯放疗治疗,观察组在上述基础上,给予EGFR-TKI靶向治疗。治疗3个月。观察两组治疗效果、生存情况及不良反应。结果观察组总有效率高于对照组,差异有统计学意义(P 0. 05)。观察组的无进展生存时间(PFS)及总生存时间(OS)明显长于对照组,且1年生存率和2年生存率显著高于对照组,差异有统计学意义(P 0. 05)。两组不良反应率比较,差异无统计学意义(P 0. 05)。结论 EGFR-TKI靶向治疗联合放疗对EGFR突变型非小细胞肺癌脑转移患者效果显著,可明显提高患者的生存质量,减少不良反应发生率,值得临床推广应用。     

非小细胞肺癌表皮生长因子受体基因突变及其临床背景关系分析

目的探讨非小细胞肺癌患者EGFR基因突变状况以及与各临床背景间的关系。方法采用扩增阻遏突变系统taqman-ARMS法对257例非小细胞肺癌患者肿瘤组织进行了EGFR基因检测,并回顾性分析突变情况与病理类型、TNM分期、患者性别、年龄及生活习惯等临床背景间的关联性。结果 257例非小细胞肺癌样本中,EGFR突变率为38.5%,93例存在单一突变,6例存在两种突变,突变主要集中在19外显子缺失突变和21外显子的点突变。腺癌突变率明显高于鳞癌及其他非腺癌(P0.01)。女性突变率高于男性(P0.01)。≤65岁与65岁两组间差异无统计学意义(P0.05)。非吸烟者突变率明显高于吸烟者(P0.01),突变与吸烟年限关联不明显,与日吸烟量明显相关(P0.01)。根据TNM分期,Ⅰ、Ⅱ、Ⅲ、Ⅳ期各组间比较突变率差异无统计学意义。中、高分化间突变与低分化相比较差异有统计学意义(均P0.01)。结论非小细胞肺癌EGFR基因突变与性别、组织学分型、肿瘤分化程度、吸烟以及日吸烟量等临床特征显著相关,与年龄、淋巴结转移、TNM分期及吸烟年限等无明显相关。     

表皮生长因子受体酪氨酸酶抑制剂一线治疗不同表皮生长因子受体突变阳性晚期非小细胞肺癌疗效关系

目的表皮生长因子受体酪氨酸酶抑制剂(EGFR-TKI)是治疗表皮生长因子受体(EGFR)突变阳性非小细胞肺癌(NSCLC)一线标准治疗方案,但不同EGFR突变状态与疗效的关系报道较少。本研究分析晚期NSCLC不同EGFR突变状态(外显子19缺失、21突变)经EGFR-TKI一线治疗后的疗效。方法收集徐州市肿瘤医院自2008年1月1日至2013年12月31日经组织病理学证实的门诊及住院晚期EGFR突变(19外显子缺失、21外显子突变)的NSCLC患者(ⅢB/Ⅳ期)72例(均进行过EGFR基因检测),分析两个不同EGFR突变状态与一线EGFR-TKI治疗疗效及无病进展生存期(PFS)之间的关系(统计学方法采用χ~2或Fisher's检验)。结果 72例患者中EGFR19外显子缺失的患者37例,EGFR 21外显子突变的患者35例。所有患者均可评价疗效,其中EGFR19外显子缺失的患者一线EGFR-TKI治疗后完全缓解(CR)1例,部分缓解(PR)27例,稳定(SD)5例,进展(PD)4例,客观缓解率(ORR)75.7%,疾病控制率(DCR)89.2%;EGFR 21外显子突变的患者一线EGFR-TKI治疗后CR 1例,PR 17例,SD 6例,PD 11例,ORR 51.4%,DCR 68.6%;两组ORR及DCR差异均有统计学意义(P=0.032,P=0.031)。EGFR 19外显子缺失的患者一线EGFR-TKI治疗后1年PFS率为81.2%(30例),而EGFR 21外显子突变的患者1年PFS为57.1%(20例),两组间统计学有差异(P=0.025)。两组间毒副作用相似。结论 EGFR突变状态是晚期NSCLC患者一线EGFR-TKI治疗PFS和ORR的疗效预测因素。     

肺癌患者血清肿瘤标志物与EGFR突变相关性研究

目的探究肺癌患者血清细胞角蛋白19片段(CYFRA21-1)、神经元特异烯醇化酶(NSE)、鳞状上皮细胞抗原(SCC)浓度与EGFR(表皮生长因子受体)基因突变的关系,为EGFR基因突变提供可靠的预测指标。方法收集174例肺癌患者术前血清及术后肺癌组织;电化学发光法检测血清肿瘤标志物浓度,利用突变扩增阻滞系统(ARMS)检测肺癌组织EGFR基因突变;分析EGFR突变与肺癌患者临床病理特征的关系;分析血清肿瘤标志物与肺癌患者EGFR突变的关系。结果 174例肺癌患者中,78例发生突变,其中以19号外显子缺失(19-del)和21号外显子L858R突变为主;女性肺癌患者EGFR突变率显著高于男性患者(χ2=34.027,P=0.000),腺癌患者EGFR突变率显著高于鳞癌患者(χ2=34.027,P=0.002),非吸烟患者EGFR突变率显著高于吸烟患者(χ2=40.397,P=0.000);EGFR野生型肺癌患者血清CYFR21-1、NSE、SCC浓度显著高于EGFR突变者[4.80(2.50,8.30)ng/mL vs.2.50(1.90,4.60)ng/mL,P=0.000;13.05(10.63,18.35)U/L vs.11.00(9.20,13.10)U/L,P=0.010;1.00(0.70,1.58)ng/mL vs.0.70(0.55,1.00)ng/mL,P=0.000]。结论EGFR突变多发生在非吸烟女性腺癌患者,血清肿瘤标志物作为EGFR基因突变的预测指标具有一定的临床应用价值,值得扩大样本量进一步研究。     

晚期NSCLC中EGFR基因突变状态与PD-L1蛋白表达的相关性分析

目的 探讨晚期非小细胞肺癌(NSCLC)患者中EGFR基因突变状态与PD-L1蛋白表达的关系。方法 收集晚期NSCLC病例74例,采用荧光定量PCR法检测EGFR基因突变,免疫组织化学法检测PD-L1蛋白表达,统计分析病理特征对患者的EGFR突变状态与PD-L1表达的关系。结果 IV期肺癌和腺癌患者的EGFR突变率较高(P=0.02～0.042),肿瘤细胞非低分化的女性脑转移无吸烟史患者更倾向于具有较高的EGFR突变率(P=0.052～0.189),EGFR突变率与患者年龄和骨转移情况均无关;肿瘤细胞低分化患者更倾向于具有较高的PD-L1表达率(P=0.159),PD-L1表达率与患者年龄、性别、吸烟史、肿瘤类型、TNM分期、骨、脑转移均无明显相关性;EGFR突变状态与PD-L1表达存在负相关(r=-0.249,P=0.032),EGFR突变状态与PD-L1阳性表达高低无相关性。结论 患者EGFR突变状态与PD-L1表达存在负相关性,该研究可以给晚期NSCLC患者的临床靶向或免疫治疗及临床药物实验方面提供新思路。     

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.     

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.     

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.     

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.