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...     

硼替佐米为主的联合方案治疗多发性骨髓瘤的临床观察

目的观察硼替佐米为主的联合方案治疗多发性骨髓瘤的疗效和安全性。方法多发性骨髓瘤患者15例,其中初治患者9例,复发难治者6例,采用至少2个疗程的硼替佐米(1.3 mg/m2,第l、4、8、11天),同时联合沙利度胺(100～200 mg/d)及地塞米松(20～40 mg/d,第1～4、8～11天)治疗,21 d为1个疗程。疗效判断参照国际骨髓瘤工作组(IMWG)标准,化疗相关不良反应参照WHO标准分级。结果 9例初治患者达完全缓解CR 3例(33.3%),非常好的部分缓解VGPR 4例(44.4%),部分缓解PR 2例(22.2%),总有效率为100%;6例复发难治患者达CR 1例(16.7%),VGPR 1例(16.7%),PR 2例(33.3%),疾病稳定(SD)1例(16.7%),疾病进展(PD)1例(16.7%),总有效率为83.3%。常见不良反应包括血小板下降10例(66.7%),白细胞减少7例(46.7%),胃肠道反应8例(53.3%),周围神经病变6例(40%),严重带状疱疹1例(0.07%),低血压1例(0.07%),经治疗均可耐受。结论硼替佐米为主的联合方案治疗初治及复发难治多发性骨髓瘤患者具有有效率高、耐受性好等优点,为多发性骨髓瘤患者治疗提供了一种全新的治疗方法。     

硼替佐米治疗多发性骨髓瘤10例

目的:观察硼替佐米治疗初治、复发难治多发性骨髓瘤的疗效及不良反应.方法:2007年3月至2008年10月宁波第一医院血液科住院的10例多发性骨髓瘤患者(7例初治,3例复发难治),其中7例初治1例复发难治接受VTD方案:硼替佐米1.0～1.3 mg/m2(d1,d4,d8,d11),地塞米松20～40mg/d(d1～4,d8～11),反应停100mg/d,复发难治者中另2例在此基础上分别加用环磷酰胺0.4mg/d(d1～4)(VTCD方案),或表阿霉素10mg(d1～4)(VTAD方案),21 d为1个周期.每例患者接受1～8疗程化疗.结果:随访1～20个月,10例患者中CR 2例,nCR 3例,PR 3例,MR 1例,NC 1例.总体缓解率(CR+nCR+PR)80%(8/10),总体有效率90%(9/10).10例患者中出现末梢神经炎5例(5/10),白细胞减少4例(4/10),血小板减少4例(4/10),继发感染6例(6/10),33例次化疗中出现白细胞减少6例次(18.1%),血小板减少6例次(18.1%),发生感染13例次(39.4%),其中1例死于感染.结论:硼替佐米治疗初治或复发难治的多发性骨髓瘤是一种可以耐受的、疗效确切的治疗新选择,并发症中感染发生率高,末梢神经炎较多见.     

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。     

中西医结合治疗多发性骨髓瘤的临床疗效观察

目的 观察中药联合硼替佐米为主方案治疗初发或复发难治性多发性骨髓瘤的疗效及不良反应.方法 22例多发性骨髓瘤患者采用中药联合硼替佐米治疗.中医根据临床所见,分为痰瘀互结、肝肾两虚两型予以辨证施治,从化疗之日起,每日一剂,煎取200ml,早晚分服,西药为硼替佐米1.0-1.3mg/m2,静脉注射,第1、4、8、11天,3周为1个疗程,所有患者接受1~5个疗程治疗.根据EBMT疗效标准判断临床疗效并观察不良反应.结果 VGPR/CR 11例(50%),PR 7例(33%),总有效率83%.完成2个疗程可评价的5例中,CR/VGPR2例(40%),PR 3例(60%).20例随访3~21个月(平均8个月),16例(72%)持续CR/VGPR/PR(平均10.6月);4例NR患者接受其他化疗维持.出现的不良反应包括外周神经病变4例、疲乏6例、带状疱疹1例、下肢水肿2例,1例出现轻度皮肤过敏反应,有1例出现小完全性肠梗阻,1例出现血压增高,1例出现血糖增高反应.肾功能不全患者可安全使用,并同样有效.结论 中西陕结合治疗多发性骨髓瘤疗效确切,可缓解症状,起剑减毒增效作用.     

国产硼替佐米（昕泰）治疗初治多发性骨髓瘤的初步研究

目的:初步评价国产硼替佐米(昕泰)治疗初治多发性骨髓瘤(multiple myeloma, MM)的有效性及安全性。方法:纳入确诊活动性MM,并接受昕泰治疗2个周期以上可评估疗效的初治患者。采用昕泰联合地塞米松的两药(BD)方案或两药基础上加用环磷酰胺的三药方案(VCD)。昕泰的起始剂量为每周1.3 mg/m~2。每2周期评价疗效和安全性。结果:2018年6月至2018年11月,共纳入14例MM患者,随访至2019年1月。全部患者可行2周期疗效评估,其中3例为非常好的部分缓解(VGPR)、9例部分缓解(PR)、1例微小缓解(MR)、1例疾病进展(PD),总反应率(ORR)为85.7%。6例患者可行4周期疗效评估,均为VGPR,ORR为100%。不良事件与原研药类似。主要血液学毒性包括血小板及淋巴细胞计数降低;非血液学毒性主要为消化系统不良反应,腹泻与便秘较多见。结论:昕泰治疗初治MM具有良好的疗效及安全性。     

硼替佐米联合地塞米松、环磷酰胺治疗多发性骨髓瘤疗效观察

目的观察硼替佐米联合地塞米松、环磷酰胺（BCD）在治疗多发性骨髓瘤（MM）患者有效率和安全性以及完全缓解（CR）后的持续时间。方法回顾性分析2008年3月至2012年12月34例MM应用BCD方案治疗后的临床资料,总结应用BCD治疗后的缓解率,缓解持续时间及不良反应。结果采用IMWG制定的疗效标准对所有患者进行疗效评价,32例有效,总有效率ORR 94.11%。获得CR 12例（35.2%）、VGPR 15例（44.1%）、PR 5例（14.7%）、SD 1例（2.9%）、PD 1例（2.9%）。结论硼替佐米联合环磷酰胺和地塞米松对初发和复发难治性多发性骨髓瘤有明显的临床疗效,且药物不良反应较轻,耐受性良好。     

硼替佐米联合化疗治疗多发性骨髓瘤10例临床观察

目的 观察硼替佐米联合化疗治疗初发、复发多发性骨髓瘤患者的疗效及不良反应.方法 10例多发性骨髓瘸患者,其中初治7例,复发3例,使用BAD方案(硼替佐米1.3 mg/m2,d1,d4,d8,d11;表阿霉素10 mg,d1～4;地塞米松20～40 mg,d1～4,d8～11)或BD方案(硼替佐米1.3 mg/m2,d1,d4,d8,d11;地塞米松20～40mg,d1～2,d4～5,d8～9,d11～12);每例患者化疗2～4个疗程.结果 10例患者中完全缓解(CR)3例,接近完全缓解(nCR)3例,部分缓解(PR)2例,轻微反应(MR)1例,无变化(NC)1例,总体有效率为CR+nCR+PR:80.0％.主要不良反应包括周围神经炎,消化道反应,白细胞及血小板减少等.结论 硼替佐米联合化疗治疗初治、复发多发性骨髓瘤患者疗效确切,不良反应轻微.     

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。     

硼替佐米联合地塞米松治疗多发性骨髓瘤的临床研究

本研究观察硼替佐米治疗多发性骨髓瘤的疗效及不良反应。7例初治患者均采用硼替佐米联合地塞米松治疗；另3例复发难治患者中2例采用硼替佐米联合地塞米松，1例同时加用米托蒽醌和沙利度胺治疗。结果显示，根据EMBT标准判定疗效，7例初治患者中1例完全缓解（CR），5例部分缓解（PR），1例轻微缓解（MR）；3例复发难治患者中2例部分缓解（PR），1例轻微缓解（MR）。总缓解率（CR＋PR）80％。3例患者在治疗过程中出现血小板减少，1例出现腹泻，1例足部麻木，经对症处理后均恢复。结论：硼替佐米治疗初发及复发难治多发性骨髓瘤均有较好的疗效，对治疗相关的副反应患者可耐受。     

Guns and Knives in New Mexico: Patterns of Penetrating Trauma, 1978–1993

Objective: To identify patterns of nonfatal and fatal penetrating trauma among children and adults in New Mexico using ED and medical examiner data.
Methods: The authors retrospectively sampled in 5-year intervals all victims of penetrating trauma who presented to either the state Level-1 trauma center or the state medical examiner from a 16-year period (1978–1993). Rates of nonfatal and fatal firearm and stabbing injury were compared for children and adults.
Results: Rates of nonfatal injury were similar (firearm, 34.3 per 100,000 person-years; stabbing, 35.1). However, rates of fatal injury were significantly different (firearm, 21.9; stabbing, 2.7; relative risk: 8.2; 95% confidence interval: 5.4, 12.5). From 1978 to 1993, nonfatal injury rates increased for children (p = 0.0043) and adults (p < 0.0001), while fatal penetrating injury remained constant. The increase in nonfatal injury in children resulted from increased firearm injury rates. In adults, both stabbing and firearm nonfatal injury rates increased.
Conclusions: Nonfatal injury data suggest that nonfatal violence has increased; fatal injury data suggest that violent death rates have remained constant. Injury patterns vary by age, mechanism of trauma, and data source. These results suggest that ED and medical examiner data differ and that both are needed to guide injury prevention programs.     

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.     

Interprofessional approaches to creating safe,high quality health care

Three supplementary perspectives are presented arguing that interprofessional collaboration is both necessary and desirable. Nonetheless, there are often too many serious intra-professional barriers and obstacles to interprofessional collaboration to make it successful. Some of these barriers, it is argued and illustrated, are found in the multiple ways in which professional identity is tacitly acquired and embodied in the practitioners' habitual, everyday practice. The paper then explores ways in which reflection, especially Second order reflection, can help to elucidate and overcome these obstacles, as well as increasing professional adaptability and competence.     

Systematic Reviews Published in the January 2011 Issue of The Cochrane Library

ABSTRACT

The Cochrane Library of Systematic Reviews is published quarterly as a DVD and monthly online. The January 2011 issue (first quarterly DVD for 2011) contains 4515 complete reviews, 1985 protocols for reviews in production, and 13,521 one-page summaries of systematic reviews published in the general medical literature. In addition, there are citations of 641,000 randomized controlled trials, and 14,018 cited papers in the Cochrane methodology register. The health technology assessment database contains over 9300 citations. One hundred and seven new reviews have been published in the last 3 months, of which five have potential relevance for practitioners in pain and palliative medicine.     

Modified micro-superior percutaneously-assisted total hip: early experiences & case reports

Because of the extensile nature and familiarity of the standard posterior-lateral approach to the hip, a family of "micro-posterior" approaches has been developed. This family includes the Percutaneously-Assisted Total Hip (PATH) approach, the Supercapsular (SuperCap) approach and a newer hybrid approach, the Supercapsular Percutaneously-Assisted Total Hip (SuperPATH) approach. Such approaches should ideally provide a continuum for the surgeon: from a "micro" (external rotator sparing) posterior approach, to a "mini" (external rotator sacrificing) posterior approach, to a standard posterior approach. This could keep a surgeon within his comfort zone during the learning curve of the procedure, while leaving options for complicated reconstructions for the more practiced micro-posterior surgeons. This paper details one author's experiences utilizing this combined approach, as well as permutations of this entire micro-posterior family of approaches as applied to more complex hip reconstructions.     

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.     

Structure and function of "metalloantibiotics"

Although most antibiotics do not need metal ions for their biological activities, there are a number of antibiotics that require metal ions to function properly, such as bleomycin (BLM), streptonigrin (SN), and bacitracin. The coordinated metal ions in these antibiotics play an important role in maintaining proper structure and/or function of these antibiotics. Removal of the metal ions from these antibiotics can cause changes in structure and/or function of these antibiotics. Similar to the case of "metalloproteins," these antibiotics are dubbed "metalloantibiotics" which are the title subjects of this review. Metalloantibiotics can interact with several different kinds of biomolecules, including DNA, RNA, proteins, receptors, and lipids, rendering their unique and specific bioactivities. In addition to the microbial-originated metalloantibiotics, many metalloantibiotic derivatives and metal complexes of synthetic ligands also show antibacterial, antiviral, and anti-neoplastic activities which are also briefly discussed to provide a broad sense of the term "metalloantibiotics."