3D Non-Fluoroscopic Cryoablation of Right-Sided Accessory Pathways in Children: Monocentric Study and Literature Review

Background: Cryoablation of accessory pathways (APs) is effective and very safe in children, as previously reported by our group. The aim of this retrospective study was to evaluate the current efficacy of 3D non-fluoroscopic cryoablation of right sided APs in children, comparing results obtained with the Ensite Velocity^TM and the more recent Ensite Precision^TM 3D mapping systems. Methods and Results: From January 2016 to December 2019, 102 pediatric patients [mean age 12.5 ± 2.8, 62 males (61% of total cohort)] with right APs underwent 3D non-fluoroscopic transcatheter cryoablation at our Institution. Fifteen (14.7%) patients had previously undergone catheter ablation. Acute procedural success rate was 95.1% (n = 97). No significant differences were detected in acute success rates achieved with Ensite Velocity^TM or Ensite PrecisionTM systems nor between manifest (94%) and concealed APs (100%). No permanent complications occurred. During follow-up (428 ± 286 days, median 396 days [interquartile range 179-713]), 19 patients (19.6%) had recurrences. Recurrences were more frequent for parahissian/anterior APs compared to midseptal/posterior and lateral APs (p = 0.043). Recurrences were not related to the Ensite system used. A redo ablation procedure was attempted in 13 cases, 11 cryoablation and 2 radiofrequency ablations: the former was successful in 10 cases out of 11 (90.9%). Conclusion: 3D cryoablation of right-sided APs is associated with a very high acute success rate with limited use of fluoroscopy, resulting in great benefit to the children. Recurrence rates are not high and patients can be retreated with cryo-energy with higher success rates.     

Interesting case of narrow QRS tachycardia. What is the mechanism?

A 67‐year‐old female presented with history of recurrent palpitations. During one of the episodes of palpitation, a narrow QRS tachycardia was recorded and it was reported to be terminated with intravenous adenosine. The 12‐lead electrocardiogram (ECG) showed no manifest ventricular preexcitation. ECG was within normal limits. The patient underwent an electrophysiology study after informed consent. She was taking calcium channel blockers and that was stopped five half‐lives prior to the procedure. As catheters were being placed, a narrow QRS tachycardia got induced. During the study, there was development of right bundle branch block during the tachycardia. What is the mechanism of the tachycardia?     

Management of MUTYH-associated neoplasia in Australia

Background: Mutations in the MUTYH gene,which codes for a base excision repair protein, have recently been found to cause an autosomal recessive syndrome characterized by multiple colorectal adenomas and increased risk of colorectal cancer. To identify key areas for clinical research, it is necessary to understand the current management of MUTYH‐associated neoplasia. Methods: Twelve questionnaires were sent to experts from familial colorectal cancer services throughout Australia, including representatives from all Australian states. The questionnaire was designed to clarify the practical management of MUTYH‐associated neoplasia in the patient and their family. Results: All 12 questionnaires were returned. For patients with fewer than 100 colorectal adenomas, and no dominant family history of colorectal neoplasia, most respondents carried out MUTYH testing before or concomitantly with APC. Australian laboratories generally carried out an intial directed analysis of the MUTYH gene for the two common mutations Y165C and G382D. For patients with biallelic MUTYH mutations all respondents endorsed regular colonoscopy surveillance with an interval of 1–2 years, whereas the recommended surveillance for monoallelic mutation carriers varied. Conclusion: This is the first study to document current management practices for MUTYH‐associated neoplasia and forms a basis for the development of evidence‐based recommendations as further research becomes available. Current guidelines for testing and management of MUTYH‐associated neoplasia are discussed.     

Wnt信号转导通路与肝纤维化

Wnt信号通路包括经典通路和非经典通路,其参与调控细胞的分化、癌变、凋亡及机体免疫、应激等生理病理过程。最近有研究表明Wnt信号通路与肝星状细胞的活化及肝纤维化的发生相关,深入研究Wnt信号通路在肝纤维化发生中的作用,将有助于进一步揭示肝纤维化的发生机制,为肝纤维化的防治提供新的可能途径及干预靶点。     

钙调神经磷酸信号通路参与心肌成纤维细胞的增殖

目的 :探讨钙调神经磷酸酶 （Ca N）依赖的信号通路在三磷酸肌醇 （IP3 ）刺激的乳鼠心肌成纤维细胞 （FBs）增殖中的作用。方法 :以培养的 FBs为模型 ,用 IP3 刺激 FBs内 Ca2 +释放 ,环孢素 A（Cs A）阻断 Ca N,维拉帕米 （Ver）阻断 FBs钙通道 ,检测 FBs Ca N、丝裂素活化蛋白激酶 （MAPK ）、蛋白激酶 C（PKC）活性 ,用 3 H-亮氨酸及 3 H-胸腺嘧啶掺入量作为反映 FBs增殖的指标。结果 :IP3 刺激组 FBs蛋白核酸合成速率明显增高 ,与对照组相比差异显著 （P<0 .0 1） ;Cs A及 Ver能明显抑制 IP3 介导的 FBs蛋白核酸合成速率增高 ,与 IP3 刺激组相比差异显著 （P<0 .0 1）。同时发现 IP3 刺激组 Ca N、PKC活性与对照 FBs相比差异显著 （P<0 .0 5或 P<0 .0 1）。 Cs A和 Ver抑制 IP3 介导的FBs Ca N活性增高 ,Ver抑制 IP3 介导的 FBs PKC活性的增高。结论 :Ca N在 IP3 刺激的 FBs增殖中起重要作用 ,其它信号通路可能也参与了 IP3 刺激的 FBs增殖     

丙型肝炎病毒核心蛋白细胞内信号传导途径的探讨

目的：研究丙型肝炎病毒核心蛋白致病作用的细胞内信号传导途径（STPs)。方法：在前期工作已证实HCV核心蛋白激活NF－κB介导的细胞内STPs这一结论的基础上，对核心蛋白活化NF－κB的机制和作用位点进行了测定。用0．4μg pCXN2-core与pNF-κB共转染Hela细胞3h后分别加入5mmol IKKβ的抑制剂乙酰水杨酸和25μmol消炎痛（作为对照）各0．5ml，继续转染33h，测定荧光素酶比活性，以此检测乙酰水杨酸对NF－κB介导的STPs的抑制作用。以pCXN2-core转染Cos-7细胞36h，收获细胞溶解液，用Western印迹分析检测IκBα表达，确定IκBα的降解情况。用pCXN2-core、pMEKKΔ（表达非活性MEKK的质粒）、pNF-κB共转Hela细胞36h，测定荧光素酶比活性，确定HCV核心蛋白是否通过MEKK活化NF－κB介导的STPs。结果：（1）HCV核心蛋白活化NF－κB介导的STPs被乙酰水杨酸抑制；（2）pCXN2-core转染后的细胞溶 解液中IκBα的量较pCXN2转染后的少；（3）HCV核心蛋白活化NF－κB介导的STPs的作用不被MEKKΔ阻断。结论：（1）乙酰水杨酸通过抑制KK的IκBα磷酸化作用，抑制IκB降解，阻断NF－κB的活化，表明核心蛋白作用位点可能在IKK或其上游某个部位；（2）在表达HCV核心蛋白的细胞存在IκBα降解的增加，造成NF－κB的活化；（3）核心蛋白的作用位点处于MEKK作用点下游。（4）HCV核心蛋白可能的细胞内信号传导途径是：HCV核心蛋白直接作用于IKK→IKK磷酸化IκBα→IκBα降解→NF－κB脱离抑制从胞浆转入胞核，与DNA结合发挥作用。     

Impact of a pediatric asthma clinical pathway on hospital cost and length of stay

This study sought to determine if a clinical pathway developed and executed by specialists in pediatric asthma would reduce hospital costs and length of stay (LOS). The study design was a retrospective, nonrandomized, controlled trial. Subjects were children aged 2-18 years (N = 1,004) with a history of recurrent wheezing, hospitalized with a diagnosis of acute asthma exacerbation between 1995-1998 at the New York Hospital-Weill Cornell Medical Center and treated via the pathway, as well as a control group of 206 children ages 2-18 hospitalized for acute asthma exacerbation in 1994, the year prior to pathway implementation. Patients were treated via the pathway under the supervision of an asthma specialist. The pathway provided guidelines for: 1) frequency of patient assessment; 2) bronchodilator usage; 3) corticosteroid use; 4) laboratory evaluation; 5) vital signs, oxygen saturation, and peak flow measurements; 6) chest x-rays; 7) social work intervention; and 8) discharge planning. The main outcome measures were hospital length of stay, cost per hospitalization, nursing, medication, laboratory and radiology costs, and relapse rate. Total charges for admission and average LOS for 1995-1998 were calculated, and compared with 1994, the year preceding implementation of the pathway. LOS decreased from 4.2 days to 2.7 days (P < 0.0001). The annual total charges for pediatric asthma admissions decreased from 2 million dollars to 1.4 million dollars (P < 0.005). Nursing and laboratory costs showed a statistically significant decrease. Follow-up study at 8 months showed a readmission rate of 0.02%. The implementation of a pediatric asthma clinical pathway, directed by specialists, resulted in significantly decreased length of stay and overall cost, without an increased rate of readmission.