Multielectrode Pulmonary Vein Ablation Catheter (PVAC®)

Electrical isolation of pulmonary veins is the cornerstone of catheter ablation for patients with symptomatic atrial fibrillation. However, uncertainty surrounds the choice of energy source in pulmonary vein isolation (PVI). Various alternative techniques such as the Pulmonary Vein Ablation Catheter (PVAC^®, Medtronic Inc., Minneapolis, MN, USA) have been developed to facilitate PVI. This over-the-wire multielectrode catheter is delivering duty-cycled bipolar and unipolar radiofrequency (RF) energy at relatively low power. PVI with this “one-shot” PVACatheter can shorten the procedure duration and lower fluoroscopy time compared to irrigated RF. It enables mapping and ablation with the same array, but fails to show signals during RF energy delivery. The effectiveness of PVAC is comparable to other technologies in randomized studies. The overall complication rate of PVAC PVI is comparable to irrigated RF and possibly slightly higher for cryoballoon PVI. Special attention has to be paid to an effective anticoagulation throughout the ablation procedure, avoidance of embolic events and pulmonary venous stenosis. The novel catheter design of the PVAC Gold^® array may improve safety by reducing embolic events through avoidance of electrode 1-to-10 interaction and by better tissue contact due to the 20° forward tilt. Although clinical data with this new array are lacking so far, the PVAC system has been shown to be a promising tool for PVI. However, prospective studies especially with the novel array are required to determine its true role for catheter ablation of atrial fibrillation in the future.     

Bendamustine and rituximab (BR) versus dexamethasone,rituximab, and cyclophosphamide (DRC) in patients with Waldenström macroglobulinemia

The treatment approaches for Waldenstrom macroglobulinemia (WM) are largely based upon information from single-arm phase II trials, without comparative data. We compared the efficacy of two commonly used regimens in routine practice (bendamustine-rituximab (BR) and dexamethasone, rituximab plus cyclophosphamide (DRC)) and evaluated their activity with respect to the patients’ MYD88^L265P mutation status. Of 160 consecutive patients, 60 received BR (43 with relapsed/refractory WM) and 100 received DRC (50 had relapsed/refractory WM). In the treatment-naïve setting, overall response rate (ORR) was 93% with BR versus 96% with DRC (p?=?0.55). Two-year progression-free survival (PFS) with BR and DRC was 88 and 61%, respectively (p?=?0.07). In salvage setting, ORR was 95% with BR versus 87% with DRC, p?=?0.45; median PFS with BR was 58 versus 32 months with DRC (2-year PFS was 66 versus 53%; p?=?0.08). Median disease-specific survival was not reached with BR versus 166 months with DRC (p?=?0.51). The time-to-event endpoints and depth of response were independent of the MYD88 mutation status. Grade ≥?3 adverse events of both regimens were comparable. A trend for longer PFS was observed with BR although the regimens have comparable toxicities. The activity of BR and DRC appears to be unaffected by patients’ MYD88 mutation status.     

Association between waist circumference (WC) values and hypertension,heart disease (HD) and diabetes,reported by the elderly – SABE survey: Health,wellness and aging, 2000 and 2006

The positive association between WC and systemic arterial hypertension (SAH), diabetes mellitus (DM) and HD calls for investigation in the elderly. The objective of the present study was to identify WC values, so as better to determine the risk of these diseases. This was a longitudinal study using the data of 405 elderly participants of the SABE Survey: Health, Well-being and Aging, undertaken in São Paulo, in 2000 and 2006. The study variables were WC, sex, age group, ethnicity, and body mass index (BMI) (2000) and SAH, DM and HD (2006). The area under the Receiver Operating Caracteristics (ROC) curve (AUC) and confidence intervals of 95% was used to estimate the performance of WC values in correctly discriminating among the elderly, according to the reference or not to diseases associated with WC. WC critical values were identified by the highest positive likelihood ratio (PLR), and negative likelihood ratio (NLR) equal to zero. The AUC showed the satisfactory performance of WC critical values in discriminating between reports of DM in individuals of 60–74 years of age. The WC critical values identified were ≥87 cm for women and ≥99 cm for men, which presented a better performance in relation to the AUC value than to the WC values commonly used. The WC critical values identified in this study showed better discriminatory power of foretelling reference to DM than did the WC values commonly used.     

High-sensitivity Troponin I and Ablation Effectiveness Quotient after Ablation Index-guided pulmonary vein isolation—markers of arrhythmia recurrence?

Journal of Interventional Cardiac Electrophysiology - To elucidate the electrophysiological predictors of the intramural origins of left ventricular outflow tract-ventricular tachyarrhythmias...     

Dipeptidyl peptidase-4 (DPP-4) inhibitor and mortality in coronavirus disease 2019 (COVID-19) – A systematic review,meta-analysis,and meta-regression

Background and aimsThis study aims to synthesize evidence on dipeptidyl peptidase-4 (DPP-4) inhibitor and mortality in COVID-19 patients and factors affecting it.MethodsWe performed a systematic literature search from PubMed, Scopus, and Embase databases from inception of databases up until 7 March 2021. Studies that met all of the following criteria were included: 1) observational studies or randomized controlled trials that report COVID-19 patients, 2) reporting DPP-4 inhibitor use, 3) mortality, and 4) mortality based on DPP-4 inhibitor use. The exposure was DPP-4 inhibitor, defined as DPP-4 inhibitor use that started prior to COVID-19 hospitalization. The control group was patients with no exposure to DPP-4 inhibitor. The outcome was mortality. The pooled effect estimate was reported as risk ratio (RR).ResultsThere were 4,477 patients from 9 studies in this systematic review and meta-analysis. 31% of (15%, 46%) the patients use DPP-4 inhibitor. Mortality occurs in 23% (15%, 31%) of the patients. DPP-4 inhibitor was associated with lower mortality in patients with COVID-19 (RR 0.76 [0.60, 0.97], p = 0.030, I2: 44.5%, p = 0.072). Meta-regression analysis showed that the association between DPP-4 inhibitor and mortality was significantly affected by metformin (RR 1.02 [1.00, 1.04], p = 0.048) and angiotensin converting enzyme inhibitor or angiotensin receptor blocker (ACEI/ARB) use (RR 1.04 [1.01, 1.07], p = 0.006), but not age (p = 0.759), sex (reference: male, p = 0.148), and hypertension (p = 0.218).ConclusionDPP-4 inhibitor use was associated with lower mortality in COVID-19 patients, and the association was weaker in patients who were also taking metformin and/or ACE inhibitors.     

Ablation of triadin causes loss of cardiac Ca2+ release units,impaired excitation–contraction coupling,and cardiac arrhythmias

Heart muscle excitation–contraction (E-C) coupling is governed by Ca²⁺ release units (CRUs) whereby Ca²⁺ influx via L-type Ca²⁺ channels (Cav1.2) triggers Ca²⁺ release from juxtaposed Ca²⁺ release channels (RyR2) located in junctional sarcoplasmic reticulum (jSR). Although studies suggest that the jSR protein triadin anchors cardiac calsequestrin (Casq2) to RyR2, its contribution to E-C coupling remains unclear. Here, we identify the role of triadin using mice with ablation of the Trdn gene (Trdn^−/−). The structure and protein composition of the cardiac CRU is significantly altered in Trdn^−/− hearts. jSR proteins (RyR2, Casq2, junctin, and junctophilin 1 and 2) are significantly reduced in Trdn^−/− hearts, whereas Cav1.2 and SERCA2a remain unchanged. Electron microscopy shows fragmentation and an overall 50% reduction in the contacts between jSR and T-tubules. Immunolabeling experiments show reduced colocalization of Cav1.2 with RyR2 and substantial Casq2 labeling outside of the jSR in Trdn^−/− myocytes. CRU function is impaired in Trdn^−/− myocytes, with reduced SR Ca²⁺ release and impaired negative feedback of SR Ca²⁺ release on Cav1.2 Ca²⁺ currents (I_Ca). Uninhibited Ca²⁺ influx via I_Ca likely contributes to Ca²⁺ overload and results in spontaneous SR Ca²⁺ releases upon β-adrenergic receptor stimulation with isoproterenol in Trdn^−/− myocytes, and ventricular arrhythmias in Trdn^−/− mice. We conclude that triadin is critically important for maintaining the structural and functional integrity of the cardiac CRU; triadin loss and the resulting alterations in CRU structure and protein composition impairs E-C coupling and renders hearts susceptible to ventricular arrhythmias.     

Is It Safe (and When) to Stop Oral Anticoagulation After Ablation for Atrial fibrillation? (Do We Have Enough Evidence to Solve the Dilemma?)

Cardiovascular Drugs and Therapy -     

Incidence and Predictors of Adenocarcinoma Following Endoscopic Ablation of Barrett’s Esophagus

Background

The rate and risk factors of recurrent or metachronous adenocarcinoma following endoscopic ablation therapy in patients with Barrett’s esophagus (BE) have not been specifically reported.

Aim

The aim of this study was to determine the incidence and predictors of adenocarcinoma after ablation therapy for BE high-grade dysplasia (HGD) or intramucosal carcinoma (IMC).

Methods

This is a single center, retrospective review of prospectively collected data on consecutive cases of endoscopic ablation for BE. A total of 223 patients with BE (HGD or IMC) were treated by ablation between 1996 and 2011. Primary outcome measures were recurrence and new development of adenocarcinoma after ablation. Recurrence was defined as the presence of adenocarcinoma following the absence of adenocarcinoma in biopsy samples from two consecutive surveillance endoscopies. Logistic regression analysis was performed to assess predictors of adenocarcinoma after ablation.

Results

One hundred and eighty-three patients were included in the final analysis, and 40 patients were excluded: 22 for palliative ablation, eight lost to follow-up, five for residual carcinoma and five for postoperative state. Median follow-up was 39 months. Recurrence or new development of adenocarcinoma was found in 20 patients (11 %) and the median time to recurrence/development of adenocarcinoma was 11.5 months. Independent predictors of recurrent or metachronous adenocarcinoma were hiatal hernia size ≥ 4 cm (odds ratio 3.649, P = 0.0233) and histology (HGD/adenocarcinoma) after first ablation (odds ratio 4.141, P = 0.0065).

Conclusions

Adenocarcinoma after endoscopic therapy for HGD or IMC in BE is associated with large hiatal hernia and histology status after initial ablation therapy.     

Effects of diabetes and hypoxia on gene markers of angiogenesis (HGF, cMET, uPA and uPAR, TGF-α, TGF-β, bFGF and Vimentin) in cultured and transplanted rat islets

Aims/hypothesis. The vascularisation of newly transplanted islets originates from the recipients. Because islets transplanted into a diabetic do less well than those transplanted into a euglycaemic environment, we examined the hypothesis that gene expression of angiogenic factors in grafts is delayed in diabetes. These factors include hepatocyte growth factor (HGF) and its receptor c-MET, and urokinase plasminogen activator (uPA) and its receptor uPAR, basic fibroblast growth factor (bFGF), TGF-α and TGFβ-1.¶Methods. Isolated rat islets were studied in vitro under normoxic and hypoxic culture conditions and gene expression was determined with semi-quantitative multiplex RT-PCR. We found that HGF but not c-MET expression was induced by hypoxia in vitro. Using syngeneic Lewis rats, gene expression was also studied in grafts on days 1, 3, 5, 7 and 14 after transplantation.¶Results. In grafts of normoglycaemic rats, HGF expression was enhanced on day 3 and maintained whereas expression of c-MET fell and remained down until day 14. Expression of uPA was up at day 3 and remained high; expression of uPAR was also up at day 3 but then fell to control levels at day 14. Expression of bFGF, TGF-α and TGFβ-1 persisted throughout. Vimentin, a marker of fibroblasts, had increased expression at day 1 which was further enhanced in subsequent days. In the grafts of diabetic recipients the expression of HGF, uPA and uPAR were delayed, being clearly expressed at day 5 rather than day 3. Vimentin expression was similarly delayed.¶Conclusion/interpretation. This apparent delay in angiogenesis provides a potential mechanism for the less favourable outcomes of islets transplanted into diabetic recipients. [Diabetologia (2000) 43: 763–772]     

Bendamustine, vincristine and prednisone (BOP) versus cyclophosphamide, vincristine and prednisone (COP) in advanced indolent non-Hodgkin’s lymphoma and mantle cell lymphoma: results of a randomised phase III trial (OSHO# 19)

Purpose: The purpose of this study was to compare the efficacy and toxicity of bendamustine, vincristine + prednisone (BOP) with a standard regimen of cyclophosphamide, vincristine + prednisone (COP) in patients with previously untreated advanced indolent non-Hodgkin’s lymphoma (NHL) and mantle cell lymphoma. Methods: A total of 164 patients with follicular lymphoma (grade 1/2), mantle cell lymphoma or lymphoplasmacytic lymphoma (immunocytoma) was randomised to treatment with vincristine 2 mg (day 1) and prednisone 100 mg/m² (days 1–5) + bendamustine 60 mg/m² (days 1–5) or + cyclophosphamide 400 mg/m² (days 1–5) for a total of eight 21-day cycles. Results: The rate of complete remission was 22% with BOP and 20% with COP. The projected 5-year survival rate was 61% with BOP and 46% with COP. The BOP-associated 5-year survival advantage almost reached significance in the subgroup of patients who responded to therapy (74% vs. 56%; P=0.05), and did reach significance in responders who did not receive interferon maintenance therapy (70% vs. 47%; P=0.03). Toxicity was acceptable in both treatment groups, although alopecia and leucopenia were more severe with COP. Conclusions: Bendamustine can efficaciously and safely replace cyclophosphamide, as used in standard COP therapy, for the treatment of patients with indolent NHL and mantle cell lymphoma. Long-term survival data suggest a clinically significant benefit for patients treated with BOP Funding support: Supported by a grant from ribosepharm GmbH, Clinical Research, Munich.     

生物安全培训课程(Biosafety and Biosecurity Training Course,BBTC)简介

<正>美国生物安全培训课程(Biosafety and Biosecurity Training Course,BBTC)是在美国科罗拉多州柯林斯堡举办的为期八天的一个密集培训班。BBTC由科罗拉多州立大学生物安全主任Robert Ellis博士发起并担任主任。Ellis博士同时兼任兽医和生物医学学院教授,是在美国颇有影响的生物安全专家,具有多年的生物安全实践和管理经验。他曾担任美国生物安全学会的主席,并因他在生物安全领域的杰出贡献,于