• 【肺静脉解剖对房颤导管消融预后的影响。】 复制标题 收藏 收藏
    DOI:10.3390/medicina55110727 复制DOI
    作者列表:Istratoaie S,Roșu R,Cismaru G,Vesa ȘC,Puiu M,Zdrenghea D,Pop D,Buzoianu AD
    BACKGROUND & AIMS: :Background and Objectives: Prior studies have identified a number of predictors for Atrial fibrillation (AF) ablation success, including comorbidities, the type of AF, and left atrial (LA) size. Ectopic foci in the initiation of paroxysmal AF are frequently found in pulmonary veins. Our aim was to assess how pulmonary vein anatomy influences the recurrence of atrial fibrillation after radiofrequency catheter ablation. Materials and Methods: Eighty patients diagnosed with paroxysmal or persistent AF underwent radiofrequency catheter ablation (RFCA) between November 2016 and December 2017. All of these patients underwent computed tomography before AF ablation. PV anatomy was classified according to the presence of common PVs or accessory PVs. Several clinical and imagistic parameters were recorded. After hospital discharge, all patients were scheduled for check-up in an outpatient clinic at 3, 6, 9, and 12 months after RFCA to detect AF recurrence. Results: A total of 80 consecutive patients, aged 53.8 ± 9.6 years, 54 (67.5%) men and 26 (32.5%) women were enrolled. The majority of patients had paroxysmal AF 53 (66.3%). Regular PV anatomy (2 left PVs, 2 right PVs) was identified in 59 patients (73.7%), a left common trunk (LCT) was detected in 15 patients (18.7%), an accessory right middle pulmonary vein (RMPV) was found in 5 patients (6.25%) and one patient presented both an LCT and an RMPV. The median follow-up duration was 14 (12; 15) months. Sinus rhythm was maintained in 50 (62.5%) patients. Age, gender, antiarrhythmic drugs, and the presence of cardiac comorbidities were not predictive of AF recurrence. The diagnosis of persistent AF before RFCA was more closely associated with an increase in recurrent AF after RFCA than after paroxysmal AF (p = 0.01). Longer procedure times (>265 minutes) were associated with AF recurrence (p = 0.04). Patients with an LA volume index of over 48.5 (mL/m2) were more likely to present AF recurrence (p = 0.006). Multivariate analysis of recurrence risk showed that only the larger LA volume index and variant PV anatomy were independently associated with AF recurrence. Conclusion: The study demonstrated that an increased volume of the left atrium was the most important predictive factor for the risk of AF recurrence after catheter ablation. Variant anatomy of PV was the only other independent predictive factor associated with a higher rate of AF recurrence.
    背景与目标: 背景和目的: 先前的研究已经确定了心房颤动 (AF) 消融成功的许多预测因素,包括合并症,AF的类型和左心房 (LA) 大小。在肺静脉中经常发现阵发性房颤的异位灶。我们的目的是评估肺静脉解剖结构如何影响射频导管消融后房颤的复发。材料和方法: 80例确诊为阵发性或持续性房颤的患者在2016年11月和2017年12月之间进行了射频导管消融 (RFCA)。所有这些患者在AF消融前均接受了计算机断层扫描。根据常见PVs或辅助PVs的存在对PV解剖进行分类。记录了几个临床和影像学参数。出院后,所有患者都计划在RFCA后3、6、9和12个月在门诊进行检查,以检测AF复发。结果: 共纳入80例连续患者,年龄53.8 ± 9.6岁,54 (67.5%) 名男性和26 (32.5%) 名女性。大多数患者有阵发性AF 53 (66.3%)。在59例患者 (73.7%) 中发现了常规的PV解剖 (2个左PVs,2个右PVs),在15例患者 (18.7%) 中发现了左总干 (LCT),在5例患者 (6.25% 例) 中发现了右中肺静脉 (RMPV),一名患者同时出现了LCT和RMPV。中位随访时间为14 (12; 15) 个月。50 (62.5%) 例患者维持窦性心律。年龄,性别,抗心律失常药物和心脏合并症的存在不能预测AF复发。与阵发性房颤相比,RFCA前持续性房颤的诊断与RFCA后复发性房颤的增加更密切相关 (p = 0.01)。较长的手术时间 (>265分钟) 与房颤复发相关 (p = 0.04)。LA体积指数超过48.5 (mL/m2) 的患者更有可能出现AF复发 (p = 0.006)。复发风险的多因素分析表明,只有较大的LA体积指数和变异的PV解剖结构与AF复发独立相关。结论: 研究表明,左心房体积增加是导管消融后房颤复发风险的最重要预测因素。PV的变异解剖结构是与更高的AF复发率相关的唯一其他独立预测因素。
  • 【消融治疗Brugada综合征: 现状和未来前景。】 复制标题 收藏 收藏
    DOI:10.1080/17434440.2020.1719831 复制DOI
    作者列表:Rizzo A,de Asmundis C,Brugada P,La Meir M,Chierchia GB
    BACKGROUND & AIMS: :Introduction: Brugada syndrome (BrS) is an inherited disease characterized by an increased risk of sudden cardiac death (SCD). Therapeutic options in symptomatic patients are limited to implantable cardioverter defibrillator (ICD) and quinidine, but catheter ablation of the right ventricular outflow tract (RVOT) offers a potential cure. Different ablation strategies have been used to treat patients with symptomatic Brugada syndrome. Epicardial radiofrequency substrate ablation of the RVOT/right ventricle (RV) has emerged as a promising tool for the management of the disease.Areas covered: The historical management of BrS, endocardial and epicardial ablation techniques, the use of sodium channel blockers (SCB) and complications are summarized here.Expert opinion: Ventricular fibrillation (VF)-triggering premature ventricular contractions (PVCs) in patients with BrS are unpredictable, spontaneous ones are rarely present to be mapped, making this approach impractical. Furthermore, endocardial mapping for BrS substrates does not seem effective due to the epicardial pathological substrate localization. The size variation of the BrS substrate areas during SCB infusion suggests a dynamic process as arrhythmogenic basis and SCB infusion should guide BrS epicardial ablation of all abnormal potentials areas. If BrS epicardial ablation can truly provide long-term prevention of ventricular arrhythmias it may potentially become an alternative to ICD therapy.
    背景与目标: 简介: Brugada综合征 (BrS) 是一种遗传性疾病,其特征是心脏性猝死 (SCD) 的风险增加。有症状患者的治疗选择仅限于植入式心律转复除颤器 (ICD) 和奎尼丁,但右心室流出道导管消融 (RVOT) 可提供潜在的治愈方法。已使用不同的消融策略来治疗有症状的Brugada综合征患者。心外膜射频基底消融RVOT/右心室 (RV) 已成为治疗该疾病的有前途的工具。涵盖的领域: BrS的历史管理,心内膜和心外膜消融技术,钠通道阻滞剂 (SCB) 的使用和并发症在这里进行总结。专家意见: brS患者的心室纤颤 (VF) 触发室性早搏 (PVCs) 是不可预测的,自发的很少出现,因此这种方法不切实际。此外,由于心外膜病理底物的定位,BrS底物的心内膜定位似乎无效。SCB输注过程中BrS底物区域的大小变化表明动态过程是心律失常的基础,SCB输注应指导BrS心外膜消融所有异常电位区域。如果BrS心外膜消融可以真正提供长期预防室性心律失常,则可能成为ICD疗法的替代方法。
  • 【用电极位移弹性成像描绘手术后消融区域,并与声辐射力冲动成像进行比较。】 复制标题 收藏 收藏
    DOI:10.1016/j.ultrasmedbio.2017.04.021 复制DOI
    作者列表:Yang W,Varghese T,Ziemlewicz T,Alexander M,Lubner M,Hinshaw JL,Wells S,Lee FT Jr
    BACKGROUND & AIMS: :We compared a quasi-static ultrasound elastography technique, referred to as electrode displacement elastography (EDE), with acoustic radiation force impulse imaging (ARFI) for monitoring microwave ablation (MWA) procedures on patients diagnosed with liver neoplasms. Forty-nine patients recruited to this study underwent EDE and ARFI with a Siemens Acuson S2000 system after an MWA procedure. On the basis of visualization results from two observers, the ablated region in ARFI images was recognizable on 20 patients on average in conjunction with B-mode imaging, whereas delineable ablation boundaries could be generated on 4 patients on average. With EDE, the ablated region was delineable on 40 patients on average, with less imaging depth dependence. Study of tissue-mimicking phantoms revealed that the ablation region dimensions measured on EDE and ARFI images were within 8%, whereas the image contrast and contrast-to-noise ratio with EDE was two to three times higher than that obtained with ARFI. This study indicated that EDE provided improved monitoring results for minimally invasive MWA in clinical procedures for liver cancer and metastases.
    背景与目标: : 我们将准静态超声弹性成像技术 (称为电极位移弹性成像 (EDE)) 与声辐射力冲动成像 (ARFI) 进行了比较,以监测诊断为肝肿瘤的患者的微波消融 (MWA) 程序。经过MWA手术后,招募的49名患者使用Siemens Acuson S2000系统接受了EDE和ARFI。根据两名观察者的可视化结果,结合B模式成像,平均可在20例患者中识别ARFI图像中的消融区域,而平均可在4例患者中产生可描绘的消融边界。使用EDE,平均可在40例患者中划定消融区域,且成像深度依赖性较小。对组织模拟体模的研究表明,在EDE和ARFI图像上测量的消融区域尺寸在8% 以内,而EDE的图像对比度和对比度噪声比是ARFI的2至3倍。这项研究表明,EDE在肝癌和转移的临床手术中提供了改进的微创MWA监测结果。
  • 【CT引导下经皮射频消融肾细胞癌的肿瘤学疗效。】 复制标题 收藏 收藏
    DOI:10.2214/AJR.07.2258 复制DOI
    作者列表:Zagoria RJ,Traver MA,Werle DM,Perini M,Hayasaka S,Clark PE
    BACKGROUND & AIMS: OBJECTIVE:A single institution's experience with CT-guided percutaneous radiofrequency ablation of biopsy-proven renal cell carcinomas (RCCs) was studied to determine the disease-free survival and complication rate. MATERIALS AND METHODS:Data from 125 RCCs in 104 patients treated with curative intent was reviewed. Radiofrequency ablation treatments were performed using conscious sedation and local anesthesia. Patients were followed with contrast-enhanced CT or MRI. Tumor control was defined as the absence of contrast enhancement in the tumor on CT or MRI. RESULTS:Tumor size ranged from 0.6 to 8.8 cm (mean, 2.7 cm; SD, 1.5 cm). Of the 125 treated tumors, 116 (93%) were completely ablated (109 in a single ablation session, seven after a second ablation session) with a mean follow-up interval of 13.8 months. All 95 RCCs smaller than 3.7 cm were completely ablated, and 21 (70%) of 30 larger tumors were completely ablated, with nine showing evidence of residual viable tumor on follow-up scans. Tumor size smaller than 3.7 cm was significantly associated with achieving complete tumor eradication (p < 0.001). With each 1-cm increase in tumor diameter over 3.6 cm, the likelihood of tumor-free survival decreased by a factor of 2.19 (p < 0.001). There were 8 (8%) complications, none of which resulted in long-term morbidity. CONCLUSION:CT-guided percutaneous radiofrequency ablation is a safe method to treat small RCCs. This study indicates that radiofrequency ablation can reliably eradicate RCCs smaller than 3.7 cm. Treatment of larger RCCs will result in an increased risk of residual RCC.
    背景与目标:
  • 【心房颤动导管消融过程中激活的凝血时间监测: 抗凝剂是否重要?】 复制标题 收藏 收藏
    DOI:10.3390/jcm9020350 复制DOI
    作者列表:Martin AC,Kyheng M,Foissaud V,Duhamel A,Marijon E,Susen S,Godier A
    BACKGROUND & AIMS: :Atrial fibrillation (AF) catheter ablation is performed in patients receiving direct oral anticoagulants (DOACs) with intra-procedural unfractionated heparin (UFH) administration to achieve activated clotting time (ACT) at 300 s, as for vitamin K antagonist (VKA). We determined whether ACT monitoring might be transposed from VKA to DOAC-treated patients. Blood was taken from 124 patients receiving uninterrupted dabigatran, rivaroxaban, apixaban, or VKA or being untreated. DOAC concentration or INR (VKA) were measured. ACT was determined at baseline, and after spiking with UFH doses equivalent to 1000, 2500, 5000 and 10000 IU in vivo. At baseline, anticoagulants prolonged ACT differently, ACT was longer with dabigatran and shorter with apixaban despite similar concentrations. ACT strongly correlated with INR and dabigatran concentration, but not with apixaban or rivaroxaban concentrations. Moreover, UFH effects on ACT prolongation depended on the anticoagulant: dose-response curves in samples with VKA and dabigatran were parallel whereas ACT prolongation in response to UFH was significantly smaller with rivaroxaban and especially apixaban. Therefore, UFH to achieve ACT at 300 s might be transposed from VKA to uninterrupted dabigatran-treated patients but not to patients receiving FXa-inhibitors, especially apixaban. Targeting 300 s might expose to UFH overdosing and bleeding, questioning the current anticoagulation strategy.
    背景与目标: 心房颤动 (AF) 导管消融是在接受直接口服抗凝剂 (doac) 和程序内普通肝素 (UFH) 给药的患者中进行的,以达到300 s的活化凝血时间 (ACT),如维生素k拮抗剂 (VKA)。我们确定了ACT监测是否可以从VKA转移到DOAC治疗的患者。从124名接受不间断达比加群、利伐沙班、阿哌沙班或VKA或未经治疗的患者中抽取血液。测量DOAC浓度或INR (VKA)。在基线和加入相当于体内1000、2500、5000和10000 IU的UFH剂量后测定ACT。在基线时,抗凝剂的作用时间不同,尽管浓度相似,但达比加群的作用时间较长,而阿哌沙班的作用时间较短。ACT与INR和达比加群浓度密切相关,但与阿哌沙班或利伐沙班浓度无关。此外,UFH对ACT延长的影响取决于抗凝剂: VKA和达比加群样品的剂量反应曲线是平行的,而利伐沙班 (尤其是阿哌沙班) 对UFH的反应的ACT延长明显较小。因此,UFH在300 s时实现ACT可以从VKA转移到不间断的达比加群治疗的患者,但不能转移到接受FXa抑制剂,尤其是阿哌沙班的患者。靶向300可能暴露于UFH过量和出血,质疑当前的抗凝策略。
  • 【使用嵌合噬菌体靶向的金纳米棒,通过光热消融特定细菌种类来控制噬菌体治疗。】 复制标题 收藏 收藏
    DOI:10.1073/pnas.1913234117 复制DOI
    作者列表:Peng H,Borg RE,Dow LP,Pruitt BL,Chen IA
    BACKGROUND & AIMS: :The use of bacteriophages (phages) for antibacterial therapy is under increasing consideration to treat antimicrobial-resistant infections. Phages have evolved multiple mechanisms to target their bacterial hosts, such as high-affinity, environmentally hardy receptor-binding proteins. However, traditional phage therapy suffers from multiple challenges stemming from the use of an exponentially replicating, evolving entity whose biology is not fully characterized (e.g., potential gene transduction). To address this problem, we conjugate the phages to gold nanorods, creating a reagent that can be destroyed upon use (termed "phanorods"). Chimeric phages were engineered to attach specifically to several Gram-negative organisms, including the human pathogens Escherichia coli, Pseudomonas aeruginosa, and Vibrio cholerae, and the plant pathogen Xanthomonas campestris The bioconjugated phanorods could selectively target and kill specific bacterial cells using photothermal ablation. Following excitation by near-infrared light, gold nanorods release energy through nonradiative decay pathways, locally generating heat that efficiently kills targeted bacterial cells. Specificity was highlighted in the context of a P. aeruginosa biofilm, in which phanorod irradiation killed bacterial cells while causing minimal damage to epithelial cells. Local temperature and viscosity measurements revealed highly localized and selective ablation of the bacteria. Irradiation of the phanorods also destroyed the phages, preventing replication and reducing potential risks of traditional phage therapy while enabling control over dosing. The phanorod strategy integrates the highly evolved targeting strategies of phages with the photothermal properties of gold nanorods, creating a well-controlled platform for systematic killing of bacterial cells.
    背景与目标: : 越来越多地考虑使用噬菌体 (噬菌体) 进行抗菌治疗,以治疗抗菌素耐药性感染。噬菌体已经进化出多种机制来靶向其细菌宿主,例如高亲和力,对环境有害的受体结合蛋白。然而,传统的噬菌体疗法遭受多种挑战,这些挑战源于使用指数复制,进化的实体,其生物学尚未完全表征 (例如,潜在的基因转导)。为了解决这个问题,我们将噬菌体与金纳米棒偶联,从而产生一种可以在使用后被破坏的试剂 (称为 “phanorods”)。嵌合噬菌体被设计成特异性附着于几种革兰氏阴性生物,包括人类病原体大肠杆菌,铜绿假单胞菌和霍乱弧菌,以及植物病原体黄单胞菌。生物缀合的phananods可以使用光热消融选择性地靶向并杀死特定的细菌细胞。在近红外光激发后,金纳米棒通过非辐射衰变途径释放能量,局部产生热量,有效杀死目标细菌细胞。在铜绿假单胞菌生物膜的背景下强调了特异性,其中包囊辐射杀死了细菌细胞,同时对上皮细胞造成了最小的损害。局部温度和粘度测量显示细菌高度局部化和选择性消融。辐射的phanorods还破坏了噬菌体,阻止了复制并降低了传统噬菌体疗法的潜在风险,同时可以控制剂量。phanorod策略将高度发展的噬菌体靶向策略与金纳米棒的光热特性相结合,从而为系统杀死细菌细胞创造了一个控制良好的平台。
  • 【8焦耳电击消融房室结疗效的心电图决定因素。】 复制标题 收藏 收藏
    DOI:10.1093/oxfordjournals.eurheartj.a059947 复制DOI
    作者列表:Jordaens L,Van Wassenhove E,Clement L
    BACKGROUND & AIMS: :Factors determining the success of a single, low-energy, direct current-shock to achieve chronic complete heart block were studied in a consecutive group of 14 patients. A shock of 8 J was delivered by a modified device (Sirecust BS1, Siemens). If the first shock did not produce persistent complete block, multiple shocks were given. Standard 6 French U.S.C.I. catheters were used for all procedures. Chronic complete heart block was achieved with a single shock in six cases (43%; Group I); in eight others multiple shocks were needed (Group II). Neither polarity of the bipolar and of the distal His bundle recording nor the presence of sinus rhythm before the first shock were important factors to predict the outcome. The amplitude of the first recording of the bipolar His electrogram was 225 +/- 55 microV in Group I and 138 +/- 105 microV in Group II (P = 0.029). The duration of the HV interval before the first shock was 55 +/- 12 ms in Group I and 45 +/- 11 ms in Group II (NS). It is concluded that complete permanent heart block can be achieved with a single 8-J shock in 43% of the patients. The long-term success (follow-up at least 1 month, with a range of 1 to 8) of a single 8-J shock is predicted by a large amplitude of the bipolar and distal unipolar His bundle deflection, but not by its polarity or the HV interval.
    背景与目标: : 在连续的14名患者中研究了决定单一,低能量,直流休克成功实现慢性完全性心脏传导阻滞的因素。8 J休克是由一个改进的设备 (Sirecust BS1,西门子)。如果第一次休克没有产生持续的完全阻滞,则会给出多休克。标准6法国U.S.C.I. 所有手术均使用导管。在6例 (43%; I组) 中,一次休克即可实现慢性完全性心脏传导阻滞; 在其他八个中,需要多休克 (II组)。双极性和远端His束记录的极性或第一次休克前窦性心律的存在都不是预测结果的重要因素。双极性His电描记图的第一次记录的振幅在I组为225 +/- 55 microV,在II组为138 +/- 105 microV (P = 0.029)。第一次休克前的HV间隔时间在第一组为55/- 12 ms,在第二组 (NS) 为45/- 11 ms。结论是,在43% 患者中,单次8-J休克可以实现完全永久性心脏传导阻滞。单次8-J休克的长期成功 (随访至少1个月,范围为1至8) 是由双极性和远端单极His束偏转的大幅度预测的,但不是由其极性或HV间隔。
  • 【小儿射频消融术后致命恶性肿瘤的长期风险。】 复制标题 收藏 收藏
    DOI:10.1016/j.amjcard.2008.05.033 复制DOI
    作者列表:Clay MA,Campbell RM,Strieper M,Frias PA,Stevens M,Mahle WT
    BACKGROUND & AIMS: :Children undergoing radiofrequency ablation (RFA) are believed to be at increased risk of developing malignancy caused by radiation, although the magnitude of this risk is incompletely understood. We previously reported a strategy to reduce radiation exposure during pediatric RFA. In a cohort of 15 subjects (median age 12 years, range 9 to 17), radiation was measured using dosimeters at 5 sites. The risk of malignancy using measured radiation absorbed dose was calculated. International Council for Radiation Protection 60 risk estimates were applied to calculate absorbed organ doses. Median duration of combined biplane fluoroscopy was 14.4 minutes. Of the 5 dosimeter locations, the right scapular location had the highest median radiation exposure (43 mGy). Incorporating data from the 5 dosimeters, the risk model calculated that the organ with the greatest absorbed dose and at greatest risk of malignancy was the lung, followed by bone marrow, then breast. Thyroid and ovary exposures were negligible. The increased lifetime risk of fatal malignancy was 0.02% per single RFA procedure. In conclusion, with appropriate measures to reduce radiation exposure, the increased risk of malignancy after a single RFA procedure in children is low. These data should be of help counseling families and will contribute to analysis of the relative risk reduction benefits of such novel imaging approaches as a magnetic resonance imaging-based catheterization laboratory.
    背景与目标: : 尽管尚未完全了解这种风险的大小,但接受射频消融 (RFA) 的儿童被认为发展由辐射引起的恶性肿瘤的风险增加。我们之前报道了一种减少儿科RFA期间辐射暴露的策略。在15名受试者 (中位年龄12岁,范围9至17) 的队列中,使用剂量计在5个部位测量了辐射。使用测量的辐射吸收剂量计算了恶性肿瘤的风险。国际辐射防护理事会60风险估计值用于计算吸收器官剂量。联合双平面荧光透视的中位持续时间为14.4分钟。在5个剂量计位置中,右肩胛骨位置的中位辐射暴露量最高 (43 mGy)。结合5个剂量计的数据,风险模型计算出吸收剂量最大且恶性肿瘤风险最大的器官是肺,其次是骨髓,然后是乳房。甲状腺和卵巢暴露可以忽略不计。致命恶性肿瘤的终生风险增加的0.02% 是每个单一的RFA程序。总之,通过采取适当措施减少辐射暴露,儿童单次RFA手术后发生恶性肿瘤的风险较低。这些数据应有助于辅导家庭,并有助于分析基于磁共振成像的导管实验室等新型成像方法的相对风险降低益处。
  • 【静脉内氰基丙烯酸酯粘合剂消融治疗无功能大隐静脉的系统评价和荟萃分析。】 复制标题 收藏 收藏
    DOI:10.1016/j.jvsv.2019.09.010 复制DOI
    作者列表:García-Carpintero E,Carmona M,Chalco-Orrego JP,González-Enríquez J,Imaz-Iglesia I
    BACKGROUND & AIMS: OBJECTIVE:The objective of this study was to assess the effectiveness, safety, and quality of care afforded by cyanoacrylate ablation (CA) vs existing options in treating great saphenous vein incompetence. METHODS:We conducted a systematic review; used the Grading of Recommendations Assessment, Development, and Evaluation framework; assessed the quality of randomized clinical trials using the Cochrane risk of bias tool; and performed a meta-analysis on the available comparative measurements. RESULTS:Three comparative studies, two randomized controlled trials and one observational study comprising 1057 participants, were included for effectiveness assessment purposes. The safety assessment also included 10 case series. Available evidence allowed comparison of CA with radiofrequency ablation (RFA) and endovenous laser ablation (EVLA) but not with other treatments. The comparative effectiveness analysis showed that whereas all three treatments reduced disease severity, none was significantly better than any other in terms of effectiveness. In terms of safety, however, CA devices gave rise to fewer adverse events and less severity at 12 months of follow-up than did EVLA or RFA. Other important advantages of CA over EVLA or RFA were linked to quality of care; patients reported less pain during intervention with CA than with RFA or EVLA devices and registered shorter intervention and recovery times. Furthermore, tumescent anesthesia and compression bandages were not necessary, making this technique more comfortable for the patients than endothermal techniques. CONCLUSIONS:Compared with EVLA and RFA, CA treatments yield comparable effectiveness outcomes and lead to less frequent and fewer mild adverse events, without difference in major adverse events. Furthermore, CA devices have advantages in terms of quality of care indicators, such as pain during intervention, treatment and recovery times, lower use of anesthesia, and zero use of compression bandages after treatment.
    背景与目标:
  • 【未分化人类胚胎干细胞的消融: 利用针对Gal alpha1-3Galbeta1-4GlcNAc-R (α-Gal) 表位的先天免疫。】 复制标题 收藏 收藏
    DOI:10.1634/stemcells.2005-0481 复制DOI
    作者列表:Hewitt Z,Priddle H,Thomson AJ,Wojtacha D,McWhir J
    BACKGROUND & AIMS: :Although undifferentiated human embryonic stem cells (hESCs) are tumorigenic, this capacity is lost after differentiation, and hESCs are being widely investigated for applications in regenerative medicine. To engineer protection against the unintentional transplantation of undifferentiated cells, we generated hESCs carrying a construct in which the alpha1,3-galactosyltransferase (GalT) open reading frame was transcribed from the hTERT promoter (pmGT). Because the endogenous GalT gene is inactive, GalT expression was limited to undifferentiated cells. A second chimeric construct (pmfGT) differed by replacement of the GalT leader sequence for that of the fucosyltransferase gene. Two subclones containing stable integrations of pmGT and pmfGT (M2 and F11, respectively) were assessed for their response to human serum containing antibodies to the Galalpha1-3Galbeta1-4GlcNAc-R (alpha-gal) epitope. The low-variegation line, M2, and to a lesser extent the more variegated line F11, were sensitive to human serum when exposed in the undifferentiated state. However, M2 cells were largely insensitive after differentiation and retained both a normal karyotype and the ability to differentiate into derivatives of the three germ layers in severe combined immunodeficient mice. These data exemplify a method of protection against residual, undifferentiated hESCs prior to engraftment and may provide ongoing immune surveillance after engraftment against dedifferentiation or against de novo tumorigenesis involving hTERT reactivation. Untransfected H9 cells were not sensitive to the human serum used in this study. Hence, in our system, interactions of hESCs with other circulating antibodies, such as anti-Neu5Gc, were not observed.
    背景与目标: : 尽管未分化的人类胚胎干细胞 (hesc) 具有致瘤性,但这种能力在分化后会丧失,并且hesc正在广泛研究其在再生医学中的应用。为了保护未分化细胞的无意移植,我们产生了带有构建体的hesc,其中 α1,3-半乳糖基转移酶 (GalT) 开放阅读框从hTERT启动子 (pmGT) 转录。由于内源性GalT基因无活性,因此GalT表达仅限于未分化细胞。第二个嵌合构建体 (pmfGT) 的区别在于将GalT前导序列替换为岩藻糖基转移酶基因。评估了两个含有pmGT和pmfGT稳定整合的亚克隆 (分别为M2和F11) 对含有Galalpha1-3Galbeta1-4GlcNAc-R (α-gal) 表位抗体的人血清的反应。在未分化状态下暴露时,低杂色系M2和较小程度的杂色系F11对人血清敏感。然而,在严重的联合免疫缺陷小鼠中,M2细胞在分化后基本不敏感,并保留了正常的核型和分化为三个胚层衍生物的能力。这些数据举例说明了在植入前针对残留的,未分化的hesc的保护方法,并且可以在植入后针对去分化或针对涉及hTERT再激活的从头肿瘤发生提供持续的免疫监视。未转染的H9细胞对本研究中使用的人血清不敏感。因此,在我们的系统中,未观察到hesc与其他循环抗体 (例如anti-Neu5Gc) 的相互作用。
  • 【两种心房容积对非瓣膜性房颤射频消融后预后的不同预后影响: 使用多探测器计算机断层扫描的三维成像研究。】 复制标题 收藏 收藏
    DOI:10.1016/j.ijcard.2013.08.045 复制DOI
    作者列表:Moon J,Lee HJ,Shim J,Uhm JS,Kim JY,Pak HN,Lee MH,Kim YJ,Joung B
    BACKGROUND & AIMS: BACKGROUND:Left atrial (LA) enlargement is associated with atrial fibrillation (AF) recurrence after radiofrequency ablation (RFA). However, impact of right atrial (RA) size on outcomes after RFA is unclear. METHODS:Patients who underwent RFA of AF (n=242, 197 men, 57 ± 11 years) were enrolled (159 paroxysmal [PaAF] and 83 persistent [PeAF]). Three-dimensional RA and LA volumes were measured before RFA with multidetector computed tomography and indexed to body surface area (RAVI and LAVI). RESULTS:After a 3-month blanking period, 66 patients (27%) failed to maintain sinus rhythm during follow-up (556 ± 322 days). Despite similar clinical characteristics, LAVI was larger (77 ± 21 vs. 91 ± 27 ml/m(2), P<0.001) and RAVI showed a trend to be greater (85 ± 26 vs. 92 ± 25 ml/m(2), P=0.06) in patients with future recurrence than without recurrence. Additionally, patients with larger RA or LA experienced recurrences more frequently and earlier during follow-up (log rank, P < 0.05 for all). In Cox regression analysis, LAVI was independently associated with outcomes (10 ml/m(2) increase; HR: 1.22, 95% CI: 1.09-1.36, P<0.001), whereas RAVI was not. In subgroup analysis, 25 PaAF patients (16%) experienced recurrence and both atrial volumes failed to predict the outcome independently, despite borderline significance of RAVI (10 ml/m(2) increase; HR: 1.21, 95% CI: 1.00-1.48, P=0.05). Meanwhile, 41 patients (49%) in PeAF group experienced AF recurrence and LAVI was an independent prognosticator (10 ml/m(2) increase; HR: 1.19, 95% CI: 1.03-1.36). CONCLUSIONS:RA size might affect the outcome after RFA in PaAF patients. LA enlargement, rather than RA size, influence outcomes after RFA, especially in PeAF.
    背景与目标:
  • 【心房射频消融介导的间充质基质细胞靶向。】 复制标题 收藏 收藏
    DOI:10.1634/stemcells.2006-0682 复制DOI
    作者列表:Schweizer PA,Krause U,Becker R,Seckinger A,Bauer A,Hardt C,Eckstein V,Ho AD,Koenen M,Katus HA,Zehelein J
    BACKGROUND & AIMS: :Sinus node dysfunction and high-degree heart block are the major causes for electronic pacemaker implantation. Recently, genetically modified mesenchymal stromal cells (MSCs, also known as "mesenchymal stem cells") were demonstrated to generate pacemaker function in vivo. However, experimental approaches typically use open thoracotomy for direct cell injection into the myocardium. Future clinical implementation, however, essentially requires development of more gentle methods to precisely and efficiently apply specified stem cells at specific cardiac locations. In a "proof of concept" study, we performed selective power-controlled radiofrequency catheter ablation (RFCA) with eight ablation pulses (30 W, 60 seconds each) to induce heat-mediated lesions at the auricles of the cardiac right atrium of four healthy foxhounds. The next day, allogeneic MSCs (4.3 x 10(5) cells per kilogram of body weight) labeled with superparamagnetic iron oxide particles (SPIOs) were infused intravenously. Hearts were explanted 8 days later. High numbers of SPIO-labeled cells were identified in areas surrounding the RFCA-induced lesions by Prussian blue staining. Antibody staining revealed SPIO-labeled cells being positive for the typical MSC surface antigen CD44. In contrast, low levels of calprotectin, an antigen found on monocytes and macrophages, indicated negligible infiltration of monocytes in MSC-positive areas. Thus, RFCA allows targeting of MSCs to the cardiac right atrium, adjacent to the sinoatrial node, providing an opportunity to rescue or generate pacemaker function without open thoracotomy and direct injection of MSCs. This method presents a new strategy for cardiac stem cell application leading to an efficient guidance of MSCs into the myocardium. Disclosure of potential conflicts of interest is found at the end of this article.
    背景与目标: : 窦房结功能障碍和高度心脏传导阻滞是植入电子起搏器的主要原因。最近,转基因间充质基质细胞 (MSCs,也称为 “间充质干细胞”) 被证明在体内具有起搏器功能。然而,实验方法通常使用开胸切开术直接将细胞注射到心肌中。然而,未来的临床实施基本上需要开发更温和的方法,以便在特定的心脏位置精确有效地应用特定的干细胞。在一项 “概念验证” 研究中,我们用八个消融脉冲 (30 W,每个60秒) 进行了选择性功率控制的射频导管消融 (RFCA),以在四个心脏右心房的耳廓处诱导热介导的病变健康猎狐犬。第二天,静脉内注入用超顺磁性氧化铁颗粒 (SPIOs) 标记的同种异体msc (每千克体重4.3 × 10(5) 个细胞)。心脏在8天后被移出。通过普鲁士蓝染色,在RFCA诱导的病变周围区域中鉴定出大量SPIO标记的细胞。抗体染色显示SPIO标记的细胞对典型的MSC表面抗原cd44呈阳性。相反,钙卫蛋白 (一种在单核细胞和巨噬细胞上发现的抗原) 的水平较低,表明MSC阳性区域中单核细胞的浸润可忽略不计。因此,RFCA允许将MSCs靶向窦房结附近的心脏右心房,从而提供了挽救或产生起搏器功能的机会,而无需开胸切开术和直接注射MSCs。该方法为心脏干细胞的应用提供了一种新的策略,可有效地将MSCs引导到心肌中。在本文的末尾找到了潜在利益冲突的披露。
  • 【S100B在帕金森氏病中增加,消融通过RAGE和TNF-α 途径保护MPTP诱导的毒性。】 复制标题 收藏 收藏
    DOI:10.1093/brain/aws250 复制DOI
    作者列表:Sathe K,Maetzler W,Lang JD,Mounsey RB,Fleckenstein C,Martin HL,Schulte C,Mustafa S,Synofzik M,Vukovic Z,Itohara S,Berg D,Teismann P
    BACKGROUND & AIMS: :Parkinson's disease is a neurodegenerative disorder that can, at least partly, be mimicked by the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. S100B is a calcium-binding protein expressed in, and secreted by, astrocytes. There is increasing evidence that S100B acts as a cytokine or damage-associated molecular pattern protein not only in inflammatory but also in neurodegenerative diseases. In this study, we show that S100B protein levels were higher in post-mortem substantia nigra of patients with Parkinson's disease compared with control tissue, and cerebrospinal fluid S100B levels were higher in a large cohort of patients with Parkinson's disease compared with controls. Correspondingly, mice treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine showed upregulated S100B messenger RNA and protein levels. In turn, ablation of S100B resulted in neuroprotection, reduced microgliosis and reduced expression of both the receptor for advanced glycation endproducts and tumour necrosis factor-α. Our results demonstrate a role of S100B in the pathophysiology of Parkinson's disease. Targeting S100B may emerge as a potential treatment strategy in this disorder.
    背景与目标: : 帕金森氏病是一种神经退行性疾病,至少部分可以被神经毒素1-甲基-4-苯基-1,2,3,6-四氢吡啶模仿。S100B是在星形胶质细胞中表达并由星形胶质细胞分泌的钙结合蛋白。越来越多的证据表明,S100B不仅在炎症中而且在神经退行性疾病中充当细胞因子或与损伤相关的分子模式蛋白。在这项研究中,我们显示,与对照组织相比,帕金森病患者的死后黑质中S100B蛋白水平较高,与对照组相比,在帕金森病患者的大型队列中,脑脊液S100B水平较高。相应地,用1-甲基-4-苯基-1,2,3,6-四氢吡啶处理的小鼠显示出上调的S100B信使RNA和蛋白质水平。反过来,S100B的消融导致神经保护,小胶质细胞减少,晚期糖基化终产物受体和肿瘤坏死因子-α 的表达降低。我们的结果证明了S100B在帕金森氏病的病理生理中的作用。靶向S100B可能成为该疾病的潜在治疗策略。
  • 【肾肿瘤射频消融: 47例患者的四年随访结果。】 复制标题 收藏 收藏
    DOI:10.3348/kjr.2012.13.5.625 复制DOI
    作者列表:Kim SD,Yoon SG,Sung GT
    BACKGROUND & AIMS: OBJECTIVE:To retrospectively evaluate the intermediate results of radiofrequency ablation (RFA) of small renal masses (SRMs). MATERIALS AND METHODS:Percutaneous or laparoscopic RFA was performed on 48 renal tumors in 47 patients. The follow-up studies included a physical examination, chest radiography, creatinine level, and contrast-enhanced CT or MRI. To confirm the pathologic criteria of complete ablation, 35 patients underwent a follow-up biopsy. Recurrence was defined as contrast enhancement on imaging studies after 3 months, lesion growth at subsequent imaging, or viable cancer cells on follow-up biopsy. RESULTS:Technical success was achieved in 43 (89.6%) of 48 renal tumors. The mean tumor size was 2.3 cm and the mean follow-up period was 49.6 months. Repeated RFA was necessary in 5 tumors due to incomplete ablation. The overall complication rate was 35.8%, of which 96.2% were mild complications. Serum creatinine levels at 12 months after RFA did not differ from those before RFA (1.28 vs. 1.36 mg/dL). Four patients were found to have recurrence at various follow-up intervals, and distant metastasis was not found in any cases. CONCLUSION:RFA appears to be a useful treatment for selected patients with SRMs. Our 4-year follow-up results disclose an excellent therapeutic outcome with RFA, while achieving effective local tumor control.
    背景与目标:
  • 【内镜黏膜下剥离术加射频消融术治疗赘生性Barrett食管。】 复制标题 收藏 收藏
    DOI:10.1055/s-0032-1310155 复制DOI
    作者列表:Neuhaus H,Terheggen G,Rutz EM,Vieth M,Schumacher B
    BACKGROUND & AIMS: BACKGROUND AND STUDY AIMS:Endoscopic submucosal dissection (ESD) of early gastrointestinal tumors has been shown to achieve complete resection rates superior to endoscopic mucosal resection (EMR), but at the cost of higher risk. The aim of this study was to prospectively assess the feasibility and oncological results of ESD in patients with neoplastic Barrett's esophagus in conjunction with subsequent radiofrequency ablation (RFA). METHODS:Patients with Barrett's esophagus who had visible lesions containing high grade intraepithelial neoplasia (HGIN) or mucosal adenocarcinoma (MAC) up to 3 cm in diameter were included in the study. ESD was performed using a new waterjet-assisted system (WESD) with a HybridKnife (Erbe Elektromedizin GmbH, Tübingen, Germany). Primary outcome was the rate of complete tumor resection. RFA of residual intestinal metaplasia was offered to all patients with at least two negative follow-up endoscopies. RESULTS:Of 30 patients (m:f = 21:9; median age 60 years) with biopsy-proven MAC (n = 24) or HGIN (n = 6) with a median diameter of 2 cm, complete resection of the targeted area was achieved in 29 patients (96.7 %; 95 % confidence interval [CI] 82 % - 99 %); en bloc resection was achieved in 27 of these patients (90.0 %; 95 %CI 74 % - 97 %). Minor delayed bleedings occurred in two patients. One patient died due to a sudden cardiac death 7 days after an uneventful WESD. Specimen histology (n = 29) revealed no neoplasia in 3 patients, HGIN in 2, MAC in 21, and submucosal cancer in 3; complete resection was histologically confirmed in only 10 of the 26 patients with HGIN or adenocarcinoma (38.5 %; 95 %CI 22 % - 57 %). However, endoscopic follow-up (median 17 months) showed complete remission of neoplasia in 27 /28 (96.4 %; 95 %CI 81 % - 99 %) patients who underwent successful WESD and were alive at 30 days. One patient underwent EMR of residual tumor. All Barrett's tissue was eradicated by ESD alone in 15 cases and by additional RFA in 8 /10 cases (not done in three patients). CONCLUSIONS:ESD of Barrett's neoplasia is feasible and safe, but does not achieve sufficient R0 resection rates to warrant its recommended use over piecemeal EMR. In combination with RFA it can achieve complete eradication of neoplastic and non-neoplastic Barrett's epithelium. The discrepancy between insufficient oncological resection and good medium-term results needs to be studied further.
    背景与目标:

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