24 research outputs found
Genomic variants associated with primary biliary cirrhosis
Primary biliary cirrhosis (PBC) is an autoimmune hepatobiliary disease characterized by immune-mediated injury of small and medium-sized bile ducts, eventually leading to liver cirrhosis. Several studies have addressed PBC immunopathology, and the data support an immune activation leading to autoantibodies and autoreactive T cells acting against the lipoylated 2-oxoacid dehydrogenase complexes. The causes of the disease remain unknown, but environmental factors and genetic susceptibility both contribute to its onset. Over the past two decades several association studies have addressed the role of genetic polymorphisms in PBC pathogenesis and have reported multiple associations. However, only a few studies had sufficient statistical power, and in most cases results were not independently validated. A genome-wide association study has recently been reported, but this too awaits independent confirmation. The aim of this present work is to critically review the numerous studies dedicated to revealing genetic associations in PBC, and to predict the potential for future studies based on these data
Prevalence and characterization of human mecC methicillin-resistant Staphylococcus aureus isolates in England
Objectives: There are limited data available on the epidemiology and prevalence of methicillin-resistant Staphylococcus aureus (MRSA) in the human population that encode the recently described mecA homologue, mecC. To address this knowledge gap we undertook a prospective prevalence study in England to determine the prevalence of mecC among MRSA isolates.<p></p>
Patients and methods: Three hundred and thirty-five sequential MRSA isolates from individual patients were collected from each of six clinical microbiology laboratories in England during 2011–12. These were tested by PCR or genome sequencing to differentiate those encoding mecA and mecC. mecC-positive isolates were further characterized by multilocus sequence typing, spa typing, antimicrobial susceptibility profile and detection of PBP2a using commercially available kits.<p></p>
Results: Nine out of the 2010 MRSA isolates tested were mecC positive, indicating a prevalence among MRSA in England of 0.45% (95% CI 0.24%–0.85%). The remainder were mecA positive. Eight out of these nine mecC MRSA isolates belonged to clonal complex 130, the other being sequence type 425. Resistance to non-β-lactam antibiotics was rare among these mecC MRSA isolates and all were phenotypically identified as MRSA using oxacillin and cefoxitin according to BSAC disc diffusion methodology. However, all nine mecC isolates gave a negative result using three different commercial PBP2a detection assays.
Conclusions: mecC MRSA are currently rare among MRSA isolated from humans in England and this study provides an important baseline prevalence rate to monitor future changes, which may be important given the increasing prevalence of mecC MRSA reported in Denmark.<p></p>
Robotic magnetic navigation-guided catheter ablation establishes highly effective pulmonary vein isolation in patients with paroxysmal atrial fibrillation when compared to conventional ablation techniques
Introduction: Pulmonary vein isolation (PVI) is a pivotal part of ablative therapy for atrial fibrillation (AF). Currently, there are multiple techniques available to realize PVI, including: manual-guided cryoballoon (MAN-CB), manual-guided radiofrequency (MAN-RF), and robotic magnetic navigation-guided radiofrequency ablation (RMN-RF). There is a lack of large prospective trials comparing contemporary RMN-RF with the more conventional ablation techniques. This study prospectively compared three catheter ablation techniques as treatment of paroxysmal AF. Methods: This multicenter, prospective study included patients with paroxysmal AF who underwent their first ablation procedure. Procedural parameters (including procedural efficiency), complication rates, and freedom of AF during 12-month follow-up, were compared between three study groups which were defined by the utilized ablation technique. Results: A total of 221 patients were included in this study. Total procedure time was significantly shorter in MAN-CB (78 ± 21 min) compared to MAN-RF (115 ± 41 min; p <.001) and compared to RMN-RF (129 ± 32 min; p <.001), whereas it was comparable between the two radiofrequency (RF) groups (p =.062). A 3% complication rate was observed, which was comparable between all groups. At 12-month follow-up, AF recurrence was observed in 40 patients (19%) and was significantly lower in the robotic group (MAN-CB 19 [24%], MAN-RF 16 [23%], RMN-RF 5 [8%] AF recurrences, p =.045) (multivariate hazard ratio of RMN-RF on AF recurrence 0.32, 95% confidence interval: 0.12–0.87, p =.026). Conclusion: RMN-guided PVI results in high freedom of AF in patients with paroxysmal AF, when compared to cryoablation and manual RF ablation. Cryoablation remains the most time-efficient ablation technique, whereas RMN nowadays has comparable efficiency with manual RF ablation.</p
Connecting the data landscape of long-term ecological studies: The SPI-Birds data hub
The integration and synthesis of the data in different areas of science is drastically slowed and hindered by a lack of standards and networking programmes. Long-term studies of individually marked animals are not an exception. These studies are especially important as instrumental for understanding evolutionary and ecological processes in the wild. Furthermore, their number and global distribution provides a unique opportunity to assess the generality of patterns and to address broad-scale global issues (e.g. climate change). To solve data integration issues and enable a new scale of ecological and evolutionary research based on long-term studies of birds, we have created the SPI-Birds Network and Database (www.spibirds.org)\u2014a large-scale initiative that connects data from, and researchers working on, studies of wild populations of individually recognizable (usually ringed) birds. Within year and a half since the establishment, SPI-Birds has recruited over 120 members, and currently hosts data on almost 1.5 million individual birds collected in 80 populations over 2,000 cumulative years, and counting. SPI-Birds acts as a data hub and a catalogue of studied populations. It prevents data loss, secures easy data finding, use and integration and thus facilitates collaboration and synthesis. We provide community-derived data and meta-data standards and improve data integrity guided by the principles of Findable, Accessible, Interoperable and Reusable (FAIR), and aligned with the existing metadata languages (e.g. ecological meta-data language). The encouraging community involvement stems from SPI-Bird's decentralized approach: research groups retain full control over data use and their way of data management, while SPI-Birds creates tailored pipelines to convert each unique data format into a standard format. We outline the lessons learned, so that other communities (e.g. those working on other taxa) can adapt our successful model. Creating community-specific hubs (such as ours, COMADRE for animal demography, etc.) will aid much-needed large-scale ecological data integration
Comparing Presenting Clinical Features in 48 Children With Microscopic Polyangiitis to 183 Children Who Have Granulomatosis With Polyangiitis (Wegener's) : an ARChiVe Cohort Study
OBJECTIVE:
To uniquely classify children with microscopic polyangiitis (MPA), to describe their demographic characteristics, presenting clinical features, and initial treatments in comparison to patients with granulomatosis with polyangiitis (Wegener's) (GPA).
METHODS:
The European Medicines Agency (EMA) classification algorithm was applied by computation to categorical data from patients recruited to the ARChiVe (A Registry for Childhood Vasculitis: e-entry) cohort, with the data censored to November 2015. The EMA algorithm was used to uniquely distinguish children with MPA from children with GPA, whose diagnoses had been classified according to both adult- and pediatric-specific criteria. Descriptive statistics were used for comparisons.
RESULTS:
In total, 231 of 440 patients (64% female) fulfilled the classification criteria for either MPA (n\u2009=\u200948) or GPA (n\u2009=\u2009183). The median time to diagnosis was 1.6 months in the MPA group and 2.1 months in the GPA group (ranging to 39 and 73 months, respectively). Patients with MPA were significantly younger than those with GPA (median age 11 years versus 14 years). Constitutional features were equally common between the groups. In patients with MPA compared to those with GPA, pulmonary manifestations were less frequent (44% versus 74%) and less severe (primarily, hemorrhage, requirement for supplemental oxygen, and pulmonary failure). Renal pathologic features were frequently found in both groups (75% of patients with MPA versus 83% of patients with GPA) but tended toward greater severity in those with MPA (primarily, nephrotic-range proteinuria, requirement for dialysis, and end-stage renal disease). Airway/eye involvement was absent among patients with MPA, because these GPA-defining features preclude a diagnosis of MPA within the EMA algorithm. Similar proportions of patients with MPA and those with GPA received combination therapy with corticosteroids plus cyclophosphamide (69% and 78%, respectively) or both drugs in combination with plasmapheresis (19% and 22%, respectively). Other treatments administered, ranging in decreasing frequency from 13% to 3%, were rituximab, methotrexate, azathioprine, and mycophenolate mofetil.
CONCLUSION:
Younger age at disease onset and, perhaps, both gastrointestinal manifestations and more severe kidney disease seem to characterize the clinical profile in children with MPA compared to those with GPA. Delay in diagnosis suggests that recognition of these systemic vasculitides is suboptimal. Compared with adults, initial treatment regimens in children were comparable, but the complete reversal of female-to-male disease prevalence ratios is a provocative finding
The performance of dipole charge density mapping integrated with robotic magnetic navigation in the treatment of atrial tachycardias
Dipole charge density mapping integrated in remote magnetic navigation: First-in-human feasibility study
Aims: Robotic magnetic navigation (RMN) provides increased catheter precision and stability. Formerly, only the CARTO 3 mapping system was integrated with the RMN system (CARTO-RMN). Recently, a novel high-resolution non-contact mapping system (AcQMap) has been integrated with the RMN system (AcQMap-RMN) for the treatment of atrial fibrillation (AF) and atrial tachycardias (AT). We aim to compare the safety, efficiency, and efficacy of AcQMap-RMN with CARTO-RMN guided catheter ablation (CA) procedures. Material and methods: In this prospective registry, procedural safety efficiency and outcome data from total of 238 consecutive patients (147 AcQMap-RMN and 91 CARTO-RMN patients) were compared. Results: AcQMap-RMN is non-inferior in the primary endpoint of safety as compared to CARTO-RMN across the whole group (overall procedural complications in 5 (3.4%) vs. 3 (3.3%) patients, p = 1.0). Overall procedure durations were longer and associated with more fluoroscopy use with AcQMap-RMN (172.5 vs. 129.6 min, p < 0.01; 181.0 vs. 131.0 mGy, p = 0.02, respectively). Procedure duration and fluoroscopy use decreased significantly between the first 30 and the last 30 AcQMap-RMN procedures. The AcQMap-RMN system had fewer recurrences after persistent AF ablations and was non-inferior in paroxysmal AF patients compared to CARTO-RMN at 12 months (36.6% vs. 75.0%, p = 0.04, PAF 6.6% vs. 12.5%, p = 0.58; respectively). CA of AT outcomes were better using the AcQMap-RMN system (1 year recurrence 17.1% vs. 38.7%, p < 0.05). Conclusion: AcQMap-RMN integration has no negative impact on the excellent safety profile of RMN guided ablations. It improves outcomes of CA procedures for persAF and AT but requires longer procedure times and higher fluoroscopy use during the initial learning phase
New Possibilities in the Treatment of Brief Episodes of Highly Symptomatic Atrial Tachycardia: The Usefulness of Single-Position Single-Beat Charge Density Mapping
Single-beat global atrial mapping facilitates the treatment of short-lived atrial tachycardias and infrequent premature atrial contractions
Background: Short runs of atrial tachycardias (ATs) and infrequent premature atrial contractions (PACs) are difficult to map and ablate using sequential electrophysiology mapping techniques. The AcQMap mapping system allows for highly accurate mapping of a single atrial activation. Objectives: We aimed to test the value of a novel dipole charge density-based high-resolution mapping technique (AcQMap) in the treatment of brief episodes of ATs and PACs. Methods: Data of all patients undergoing catheter ablation (CA) using the AcQMap mapping system were reviewed. Results: Thirty-one out of 219 patients (male n = 8; female n = 23) had short runs of ATs (n = 23) and PACs (n = 8). The mean procedural time was 155.3 ± 46.6 min, with a mean radiation dose of 92.0 (IQR 37.0–121.0) mGy. Total radiofrequency application duration 504.0 (271.0–906.0) s. Left atrial localization of ATs and PACs was identified in 45.1% of the cases, right atrium localization in 45.1%, and septal origins in 9.8% of the cases. Acute success was achieved in 30/31 (96.8%), and recurrence during the follow-up developed in six patients (19.4%), including four patients with PACs and two patients with short-lived ATs. One patient presented procedure-related groin hematoma as minor complication. Conclusion: Brief episodes of highly symptomatic ATs and infrequent PACs can be mapped using charge density mapping and successfully ablated with high acute and long-term success rates
The First Evaluation of Remote Magnetic Navigation-Guided Pediatric Ventricular Arrhythmia Ablation
Catheter ablation (CA) is an important treatment option for ventricular arrhythmias (VA) in pediatric cardiology. Currently, various CA techniques are available, including remote magnetic navigation (RMN)-guided radiofrequency (RF) ablation. However, no studies evaluate RMN-guided ablative therapy outcomes in children with VA yet. This study aimed to compare procedural and long-term outcomes between RMN-guided and manual (MAN)-guided VA ablation in children. This single-center, retrospective study included all CA procedures for VA performed in children with or without structural heart disease from 2008 until 2020. Two study groups were defined by CA technique: RMN or MAN. Primary outcome was recurrence of VA. Baseline clinical, procedural and safety data were also evaluated. This study included 22 patients, who underwent 30 procedures, with a median age of 15 (IQR 14–17; range 1–17) years and a mean weight of 57 ± 20 kg. In total, 14 procedures were performed using RMN and 16 using MAN (22 first and 8 redo procedures). Regarding first procedures, recurrence rates were significantly lower in RMN compared to MAN (20% versus 67%, P = 0.029), at a mean follow-up of 5.2 ± 3.0 years. Moreover, fluoroscopy dosages were significantly lower in RMN compared to MAN [20 (IQR 14–54) versus 48 (IQR 38–62) mGy, P = 0.043]. In total, 20 patients (91%) were free of VA following their final ablation procedure. This is the first study to investigate the use of RMN in pediatric VA ablation. RMN showed improved outcomes compared to MAN, resulting in lower VA recurrence and reduced fluoroscopy exposure