口服蛋白酶体抑制剂伊沙佐米治疗多发性骨髓瘤的疗效和安全性研究

目的:评价口服蛋白酶体抑制剂伊沙佐米治疗多发性骨髓瘤的有效性及安全性。方法:选择2018年7月1日至2019年4月4日于复旦大学附属中山医院接受2周期或以上伊沙佐米治疗的多发性骨髓瘤患者(排除轻链淀粉样变性及浆细胞白血病患者)。治疗方案包括伊沙佐米单药以及联合其他药物(来那度胺、沙利度胺或地塞米松等)的两药或三药方案。伊沙佐米的起始剂量为4 mg,第1、8、15天口服,28 d为1个周期。治疗第2周期及第4周期后进行疗效和安全性评估。结果:共27例多发性骨髓瘤患者符合入选标准,包括复发/难治15例、初发12例。复发/难治患者总体反应率(ORR)为53.3%,其中2例完全缓解(CR)、1例非常好的部分缓解(VGPR)、5例部分缓解(PR);中位获得反应时间为53 d。其中,既往硼替佐米治疗难治者ORR为54.5%(6/11)。可评估初发患者9例,ORR 100.0%,2例CR、3例VGPR、4例PR;中位获得反应时间为38 d。伊沙佐米治疗3～4级不良事件发生率为29.6%。主要血液学毒性为淋巴细胞、血小板及中性粒细胞计数降低和贫血;其他常见不良反应包括乏力和胃肠道反应。所有患者未出现3～4级外周神经毒性。结论:在中国真实世界中,伊沙佐米对初诊及复发/难治的多发性骨髓瘤患者具有良好的疗效及安全性。     

来那度胺联合小剂量地塞米松治疗多发性骨髓瘤的疗效观察

目的:探讨来那度胺联合小剂量地塞米松(Rd)治疗多发性骨髓瘤(multiple myloma,MM)的临床疗效及安全性。方法:回顾性分析2013年5月至2015年6月我院收治的19例MM患者,采用以来那度胺联合地塞米松为主的治疗方案,来那度胺口服治疗剂量为25 mg/d,连续服用21 d,所有患者分别在化疗周期的第1-4,7-10和13-16天每日口服地塞米松10 mg治疗,28 d为1个化疗周期,其中有7例患者接受RCd方案化疗(联合异环磷酰胺化疗)。结果:19例患者接受初次诱导治疗后有3例达到CR,3例达到VGPR,10例达到PR,3例SD,总有效率(ORR=CR+VGPR+PR)为84%,2个疗程后ORR为89%,5例合并肾功能损害患者有4例在治疗早期(第1个疗程)肾功能得到明显改善,4例患者发生血液学毒性,5例患者出现Ⅰ度皮疹,4例患者出现消化道副反应。结论:以来那度胺为主的联合化疗方案具有良好的抗骨髓瘤疗效,能够迅速控制病情,并具有克服MM耐药性的能力,同时能改善肾功能不全患者的不良预后,在硼替佐米治疗过的患者中,仍有较高的缓解率,且副作用低,安全性高。     

苯达莫司汀联合泊马度胺、地塞米松治疗伴髓外病变的复发多发性骨髓瘤：多中心研究

目的评估苯达莫司汀联合泊马度胺、地塞米松(BPD方案)治疗伴髓外病变的复发多发性骨髓瘤(MM)的疗效和安全性。方法本项开放、单臂、多中心前瞻性研究纳入2021年2月至2022年11月在青岛市市立医院等7所医院诊断并接受BPD方案治疗的30例伴髓外病变的复发MM患者, 分析其疗效及不良反应。结果 30例患者中位年龄62(47～72)岁, 其中18例(60.0%)为首次复发, 首次复发的18例患者的总体反应率(ORR)为100%, 其中完全缓解3例(16.7%), 非常好的部分缓解(VGPR)10例(55.5%), 部分缓解(PR)5例(27.8%)。12例二线以上治疗后复发患者的ORR为50%, 其中≥VGPR 0例, PR 6例(50%), 疾病稳定3例(25%), 疾病进展3例(25%)。所有患者的1年无进展生存率为65.2%(95%CI 37.2%～83.1%), 1年总生存率为90.0%(95%CI 76.2%～95.4%)。常见的3～4级血液学不良反应包括中性粒细胞减少2例(6.7%), 血小板减少1例(3.3%), 总体不良反应可控。结论 BPD方案在伴髓外病变的复发MM患者...     

国产仿制硼替佐米治疗多发性骨髓瘤的近期疗效及安全性观察

目的:探讨国产仿制蛋白酶体抑制剂硼替佐米治疗多发性骨髓瘤(MM)的近期疗效及安全性。方法:回顾性分析本中心2017年12月-2019年7月采用以国产仿制硼替佐米为基础的化疗方案并至少完成了2个周期化疗的MM患者共62例,其中初诊患者47例,疾病复发/进展的患者15例,中位年龄62岁。结果:诱导治疗后患者的贫血、肾功能、白蛋白及β2-微球蛋白水平迅速得到改善;至少完成4个周期化疗的患者共56例,总体有效率(ORR)为85.7%,达到非常好的部分缓解(VGPR)及以上治疗反应的患者为64.3%,完全缓解(CR)率为28.6%;完成全部诱导及巩固治疗的患者(9个周期化疗或4-6周期化疗+自体造血干细胞移植)共19例,其中疗效达VGPR以上的患者为84.2%,CR或者严格意义的完全缓解(sCR)的患者为57.9%。截止至2019年9月20日,本研究患者中位随访时间为300d,18个月的无进展生存(PFS)率和总生存(OS)率分别为62.1%和85.3%。与硼替佐米可能有关的不良反应以1-2级为主,最常见的血液学不良反应为血小板减少(27.4%),最常见的非血液学不良反应为周围神经病变(43.5%),其次为乏力(37.1%)。结论:以国产仿制硼替佐米为基础的联合化疗治疗多发性骨髓瘤,疾病缓解迅速,近期疗效、生存情况及安全性总体良好,远期疗效及生存情况将进一步随访观察。     

布鲁顿酪氨酸激酶抑制剂单药治疗初诊华氏巨球蛋白血症患者的疗效和安全性北大核心CSCD

目的探索布鲁顿酪氨酸激酶抑制剂(BTKi)伊布替尼或泽布替尼单药治疗初诊华氏巨球蛋白血症(WM)患者的疗效和安全性。方法回顾性分析2018年1月至2022年8月于上海交通大学医学院附属瑞金医院接受BTKi单药治疗的58例初诊WM患者的疗效和安全性。结果55例患者可评估疗效,40例患者接受伊布替尼单药治疗,中位治疗时间15个月,总缓解率(ORR)为85%,主要缓解率(MRR)为70%,非常好的部分缓解(VGPR)率为10%。15例患者接受泽布替尼单药治疗,中位治疗时间13个月,ORR为93%,MRR为73%,VGPR率为0%。10例患者由于各种原因由伊布替尼转换为泽布替尼治疗,转换前伊布替尼中位用药时间7.5个月,转换后泽布替尼中位用药时间3.5个月,转换前、后的ORR分别为90%和100%,MRR分别为80%和80%,VGPR率分别为10%和50%。中位随访时间为16个月,接受两种BTKi治疗患者预期24个月PFS率均为86%,ISS评分低、中、高危患者PFS的差异无统计学意义(P=0.998),所有患者均存活。BTKi不良反应主要表现为中性粒细胞减少和血小板减少,发生率分别为12%和10%。伊布替尼组心房颤动的发生率为5%,泽布替尼组出血的发生率为7%。结论伊布替尼或泽布替尼单药治疗WM均有良好的疗效和可耐受的不良反应。     

DC-CIK细胞联合化疗治疗初发多发性骨髓瘤疗效及其对Treg细胞影响的分析

目的:研究树突细胞(DC)与细胞因子诱导的杀伤细胞(CIK)为效应细胞的过继免疫联合化疗治疗初发多发性骨髓瘤(MM)的临床疗效和免疫机制。方法:选取22例初发MM患者并将他们分为2组:单纯化疗组12例,给予适合的化疗方案;联合治疗组10例,除接受合适的化疗外,还给予DC-CIK细胞免疫治疗。记录所有患者在治疗前后外周血中的调节性T细胞(Tregs)的比例变化,并比较治疗后两组患者的临床疗效。结果:治疗后,单纯化疗组12例MM患者的总有效率(ORR)50.00%(6/12),其中完全缓解(CR)2例(16.67%),非常好的部分缓解(VGPR)2例(16.67%),部分缓解(PR)2例(16.67%)。联合治疗组MM患者ORR 70.00%(7/10),其中CR3例(30.00%),VGPR 2例(20.00%),PR 2例(20.00%)。与健康者相比,治疗前单纯化疗组及联合治疗组MM患者外周血中Treg细胞比例均明显升高(P0.05),而治疗后,单纯化疗组及联合治疗组MM患者外周血中Tregs比例均明显下降(P0.05),且联合治疗组患者相比单纯化疗组患者Tregs比例下降更明显,差异有统计学意义(P0.05)。进一步分析发现,两组中临床无效的MM患者外周血中Tregs比例治疗前后均无明显变化(P0.05),而临床有效(至少达PR)的MM患者Tregs明显下降(P0.05)。结论:DC-CIK细胞免疫治疗能够协同或增强化疗药物缓解MM患者免疫功能紊乱,DC-CIK细胞免疫治疗与化疗联合有望提高初发MM患者的临床疗效。     

不同化疗方案治疗初治多发性骨髓病患者的近期疗效、生存时间及毒副作用

目的:探讨TCD方案和BCD方案对新诊多发性骨髓病(初治MM)患者近期疗效、生存时间及毒副作用。方法:收集我院2011年1月-2018年1月收治的初治患者106例临床资料。106例患者分为2组:1组53例用沙利度胺(Thalidomide)、环磷酰胺(Cyclophosphamide)和地塞米松(Dexamethasone)组成的化疗方案治疗(TCD组),另1组53例用硼替佐米(Bortezomib)、环磷酰胺和地塞米松组成的化疗方案治疗(BCD组)。比较2组的疗效、中位PFS、中位OS时间及毒副作用发生率,同时分析缓解程度、亚组因素与疗效间的相关性。结果:2组患者≥MR率比较差异无显著性(P0.05);BCD组患者≥PR率、≥VGPR率及CR率均显著高于TCD组(P0.05);BCD组患者中位PFS显著长于TCD组(P0.05);2组患者中位OS比较差异无显著性(P0.05)。TCD组疗效≥MR患者的中位OS时间显著长于MR患者(P0.05);TCD组患者中疗效≥PR患者的中位OS显著长于PR患者(P0.05);BCD组疗效≥VGPR患者中的中位OS时间显著长于VGPR的患者(P0.05);BCD组患者中疗效≥PR与PR的中位OS比较差异无显著性(P0.05)。BCD组患者中ISS分期III期、R-ISS分期II期及肾功能正常者的ORR显著高于TCD组(P0.05)。2组感染、乏力、消化道反应及骨髓抑制发生率比较差异无显著性(P0.05);BCD组末梢神经麻木和带状疱疹发生率均显著高于TCD组(P0.05)。结论:TCD方案和BCD方案治疗初治MM的总体疗效接近,其中BCD方案的应用有助于提高缓解程度,延长PFS时间;而TCD方案应用在降低毒副作用发生风险,提高患者治疗耐受性方面具有优势。     

含伊沙佐米的联合方案治疗多发性骨髓瘤患者的临床疗效及安全性分析

目的:观察含伊沙佐米的联合方案治疗多发性骨髓瘤(MM)的临床疗效及安全性。方法:回顾性分析2020年1月至2022年2月连云港市第一人民医院血液科32例MM患者应用含伊沙佐米联合方案治疗的临床疗效及相关不良反应。32例患者包括复发难治多发性骨髓瘤患者15例(R/RMM组)和硼替佐米诱导有效但因不良反应(AE)或其他原因转换为含伊沙佐米方案治疗的MM患者17例(转换治疗组)。治疗方案包括IPD (伊沙佐米+泊马度胺+地塞米松)方案,IRD (伊沙佐米+来那度胺+地塞米松)方案,ICD (伊沙佐米+环磷酰胺+地塞米松)方案,ID (伊沙佐米+地塞米松)方案。结果:R/RMM患者总有效率(ORR)为53.3%(8/15),其中完全缓解(CR) 1例,非常好的部分缓解(VGPR) 2例,部分缓解(PR) 5例。IPD方案组、IRD方案组、ICD方案组、ID方案组R/R MM患者的ORR分别为100%(3/3)、42.9%(3/7)、33.3%(1/3)、50%(1/2),4组间差异无统计学意义(χ²=3.375,P=0.452)。既往接受1线治疗后的患者ORR为50%(2...     

治疗后达VGPR及以上的初治MM患者MRD状态对临床预后的影响

目的 :探讨治疗后达非常好的部分缓解(VGPR)及以上初治多发性骨髓瘤(MM)患者微小残留病变(MRD)状态对临床预后的影响。方法 :回顾性分析2010年1月-2018年1月于成都市第五人民医院治疗后达VGPR及以上的初治MM患者共210例临床资料,其中MRD-152例设为A组, MRD+58例设为B组,分析患者无进展生存和总生存影响因素,评价MRD状态与高危细胞遗传学异常、治疗方案及疗效反应间的相关性。结果:2组患者临床特征资料比较无显著性差异(P0.05)。单因素分析结果显示, ASCT和MRD状态与初治MM患者无进展生存时间有关(P0.05);Cox回归模型多因素分析结果显示, MRD持续阳性是初治MM患者无进展生存时间的独立危险因素(P0.05);A组患者随访2年累积无进展生存率显著高于B组患者(P0.05)。持续MRD-患者中位无进展生存时间和总生存时间均显著长于MRD转阳患者(P0.05)。单因素分析显示, MRD-持续时间是初治MM患者无进展生存时间和总生存时间的影响因素(P0.05);MRD-维持达6个月患者随访2年累积总生存率显著高于MRD-维持未达6个月患者(P0.05);MRD-维持时间≥12个月患者随访2年累积无进展生存率和总生存率均显著高于MRD-维持未达12个月患者(P0.05)。存在≥1个高危细胞遗传学异常人群中, MRD-患者中位无进展生存时间显著长于MRD+患者(P0.05)。接受ASCT治疗的患者中, MRD-率显著高于未接受ASCT治疗患者(P0.05);未接受ASCT人群中, MRD-患者中位无进展生存时间显著长于MRD+患者(P0.05);MRD-人群中接受硼替佐米治疗患者中位MRD-维持时间显著长于未接受硼替佐米治疗的患者(P0.05);同时硼替佐米治疗患者中位无进展生存时间显著长于未接受硼替佐米治疗的患者(P0.05)。结论:治疗后达VGPR及以上的初治MM患者治疗后持续MRD+与远期预后不良密切相关,其中MRD-维持时间可用于患者预后评估;而MRD+则提示早期复发可能,治疗过程中通过动态监测MRD状态能够帮助临床上确定复发MM治疗时机。     

白蛋白结合型紫杉醇单药作为三线及以上方案治疗晚期非小细胞肺癌的临床研究

目的 观察白蛋白结合型紫杉醇单药三线及以上治疗晚期非小细胞肺癌的近期疗效及不良反应. 方法 选取2013年10月至2015年3月在福建省肿瘤医院已接受过二线治疗的晚期非小细胞肺癌患者46例,予以白蛋白结合型紫杉醇260 mg/m2 D1,每21天为一周期,每个周期复查CT评价疗效,观察其疗效及不良反应. 结果 完全缓解(CR)0例,部分缓解(PR)6例,疾病稳定(SD)26例,疾病进展(PD)14例,客观缓解率(ORR) 13％,疾病控制率(DCR) 70％,中位无进展生存期(PFS) 4.7月,主要不良反应为血液学毒性、肝功能损害,外周神经毒性,无毒性相关死亡病例. 结论 白蛋白结合型紫杉醇用于三线及以上治疗晚期非小细胞肺癌,ORR及DCR高,不良反应可以耐受.     

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.     

Dissociable correlates of two classes of retrieval processing in prefrontal cortex

Although substantial evidence suggests that the prefrontal cortex (PFC) implements processes that are critical for accurate episodic memory judgments, the specific roles of different PFC subregions remain unclear. Here, we used event-related functional magnetic resonance imaging to distinguish between prefrontal activity related to operations that (1) influence processing of retrieval cues based on current task demands, or (2) are involved in monitoring the outputs of retrieval. Fourteen participants studied auditory words spoken by a male or female speaker and completed memory tests in which the stimuli were unstudied foil words and studied words spoken by either the same speaker at study, or the alternate speaker. On "general" test trials, participants were to determine whether each word was studied, regardless of the voice of the speaker, whereas on "specific" test trials, participants were to additionally distinguish between studied words that were spoken in the same voice or a different voice at study. Thus, on specific test trials, participants were explicitly required to attend to voice information in order to evaluate each test item. Anterior (right BA 10), dorsolateral prefrontal (right BA 46), and inferior frontal (bilateral BA 47/12) regions were more active during specific than during general trials. Activation in anterior and dorsolateral PFC was enhanced during specific test trials even in response to unstudied items, suggesting that activation in these regions was related to the differential processing of retrieval cues in the two tasks. In contrast, differences between specific and general test trials in inferior frontal regions (bilateral BA 47/12) were seen only for studied items, suggesting a role for these regions in post-retrieval monitoring processes. Results from this study are consistent with the idea that different PFC subregions implement distinct, but complementary processes that collectively support accurate episodic memory judgments.     

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.