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1.
Clin Res Cardiol ; 2019 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-31667623

RESUMO

INTRODUCTION: It is unknown whether left atrial (LA) roof ablation combined with pulmonary vein isolation (PVI) using a second-generation cryoballoon provides additional benefit beyond that of PVI alone in patients with persistent atrial fibrillation (AF). The aim of this study was to compare arrhythmia recurrence rates after PVI alone versus PVI plus LA roof ablation. METHODS AND RESULTS: In this observational study, we analyzed 399 symptomatic patients with persistent AF treated with cryoballoon ablation. After univariate and multivariate analyses of the entire cohort, propensity score matching resulted in two groups of 86 patients each: (1) PVI plus LA roof ablation (PVI-plus group) and (2) PVI alone (PVI-only group). The primary endpoint was the first documented > 30-s arrhythmia recurrence after a 3-month blanking period. PVI was successful in all patients. A bidirectional conduction block across the LA roof was verified in 91.9% of patients in the PVI-plus group. During a median mid-term follow-up of 33 months, 21 patients (24.4%) in the PVI-plus group and 37 patients (43.0%) in the PVI-only group (P = 0.01) reached the primary endpoint. Multivariate analysis revealed AF history > 2 years (hazard ratio [HR] = 2.04, P < 0.01), LA area > 21 cm2 (HR = 2.36, P < 0.01), female sex (HR = 1.92, P = 0.02), and LA roof ablation (HR = 0.47, P < 0.01) as significant predictors of outcome. CONCLUSIONS: We observed a significant difference in arrhythmia recurrence rates between the two groups. LA roof ablation is an effective adjuvant treatment option that shows improved outcome compared with PVI alone.

2.
Nat Commun ; 10(1): 5120, 2019 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-31719529

RESUMO

Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare inflammatory disease of unknown cause. 30% of patients have anti-neutrophil cytoplasmic antibodies (ANCA) specific for myeloperoxidase (MPO). Here, we describe a genome-wide association study in 676 EGPA cases and 6809 controls, that identifies 4 EGPA-associated loci through conventional case-control analysis, and 4 additional associations through a conditional false discovery rate approach. Many variants are also associated with asthma and six are associated with eosinophil count in the general population. Through Mendelian randomisation, we show that a primary tendency to eosinophilia contributes to EGPA susceptibility. Stratification by ANCA reveals that EGPA comprises two genetically and clinically distinct syndromes. MPO+ ANCA EGPA is an eosinophilic autoimmune disease sharing certain clinical features and an HLA-DQ association with MPO+ ANCA-associated vasculitis, while ANCA-negative EGPA may instead have a mucosal/barrier dysfunction origin. Four candidate genes are targets of therapies in development, supporting their exploration in EGPA.

3.
Nutrients ; 11(11)2019 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-31671589

RESUMO

This prospective observational trial investigated effects and safety of periodic fasting in subjects with and without type 2 diabetes mellitus (T2DM). The primary end point was set as the change of fatty liver index (FLI) as a surrogate parameter of non-alcoholic fatty liver disease (NAFLD). Six-hundred and ninety-seven subjects (38 with T2DM) were enrolled. A baseline FLI ≥ 60 (the threshold for fatty liver) was found in 264 subjects (37.9%). The mean duration of fasting was 8.5 ± 4.0 days (range 6-38). FLI decreased significantly (-14.02 ± 11.67; p < 0.0001), with a larger effect in individuals with T2DM (-19.15 ± 11.0; p < 0.0001; p = 0.002 compared to non-diabetic subjects). Body mass index (BMI) decreased by -1.51 ± 0.82 kg/m2, and 49.9% of the subjects lost ≥5% body weight. After fasting, nearly half of the 264 subjects with FLI ≥ 60 (highest risk category) shifted to a lower category. The improvement of FLI correlated with the number of fasting days (r = -0.20, p < 0.0001) and with the magnitude of BMI reduction (r = 0.14, p = 0.0001). Periodic fasting with concomitant weight reduction leads to significant rapid improvement of FLI in subjects with and without T2DM.

4.
Sci Rep ; 9(1): 16947, 2019 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-31740740

RESUMO

The over-expression and aggregation of α-synuclein (αSyn) are linked to the onset and pathology of Parkinson's disease. Native monomeric αSyn exists in an intrinsically disordered ensemble of interconverting conformations, which has made its therapeutic targeting by small molecules highly challenging. Nonetheless, here we successfully target the monomeric structural ensemble of αSyn and thereby identify novel drug-like small molecules that impact multiple pathogenic processes. Using a surface plasmon resonance high-throughput screen, in which monomeric αSyn is incubated with microchips arrayed with tethered compounds, we identified novel αSyn interacting drug-like compounds. Because these small molecules could impact a variety of αSyn forms present in the ensemble, we tested representative hits for impact on multiple αSyn malfunctions in vitro and in cells including aggregation and perturbation of vesicular dynamics. We thereby identified a compound that inhibits αSyn misfolding and is neuroprotective, multiple compounds that restore phagocytosis impaired by αSyn overexpression, and a compound blocking cellular transmission of αSyn. Our studies demonstrate that drug-like small molecules that interact with native αSyn can impact a variety of its pathological processes. Thus, targeting the intrinsically disordered ensemble of αSyn offers a unique approach to the development of small molecule research tools and therapeutics for Parkinson's disease.

5.
Sci Rep ; 9(1): 14318, 2019 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-31586115

RESUMO

Dietary restriction induces beneficial metabolic changes and prevents age-related deterioration. Mesencephalic astrocyte-derived neurotrophic factor (MANF) shows protective effects on cells in various models of degenerative diseases. Here we studied whether circulating concentrations of MANF are associated with fasting-induced positive effects. We quantified the levels of circulating MANF from 40 human subjects before and after therapeutic fasting. As measured by an enzyme-linked immunosorbent assay (ELISA), the mean concentration of plasma MANF increased after an average fasting of 15 days. Plasma MANF levels correlated inversely with adiponectin, a hormone that regulates metabolism, thus suggesting that MANF levels are related to metabolic homeostasis. To study the effects of dietary intervention on MANF concentrations in mice, we developed an ELISA for mouse MANF and verified its specificity using MANF knock-out (KO) tissue. A switch from high-fat to normal diet increased MANF levels and downregulated the expression of unfolded protein response (UPR) genes in the liver, indicating decreased endoplasmic reticulum (ER) stress. Liver MANF and serum adiponectin concentrations correlated inversely in mice. Our findings demonstrate that MANF expression and secretion increases with dietary intervention. The MANF correlation to adiponectin and its possible involvement in metabolic regulation and overall health warrants further studies.

6.
Clin Neurophysiol ; 130(11): 2076-2087, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31541985

RESUMO

OBJECTIVES: The HOME project is intended to provide evidence of diagnostic and therapeutic yield of a patient-controlled EEG home-monitoring for neurological outpatients. METHODS: This study evaluated the technical and practical usability and efficacy of a new portable dry-electrode EEG recorder in comparison to conventional EEG devices based on technical assessments and inter-rater comparisons of EEG record examinations of office-based practitioners and two experienced neurologists. RESULTS: The technical assessment was based on channel-wise comparisons of band power values derived from power spectra as observed in two recording modalities. Slight yet significant differences were observed only in the Delta-frequency band (1.5-4 Hz). The fraction of automatically detected artifact segments was larger in the new portable recordings than in conventional recordings (20% vs. 11%, median). Overall, 93% of raters' stated diagnostic findings gathered from conventional devices were concordant with stated diagnostic findings gathered from the new portable device. CONCLUSION: The new EEG device was shown to have technical comparability to and a high concordance rate of diagnostic findings with conventional EEG devices. SIGNIFICANCE: The new portable dry-electrode EEG device is suitable to meet the HOME projects' goal of establishing a patient-controlled EEG home-monitoring in the routine care of neurological outpatients. TRIAL REGISTRATION: DRKS DRKS00012685. Registered 09 August 2017, retrospectively registered.

7.
Int J Cardiol ; 292: 112-118, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31103321

RESUMO

INTRODUCTION: There are no data concerning clinical outcome and left atrial (LA) function after LA roof ablation using a second-generation cryoballoon (CB) for treatment of persistent atrial fibrillation (AF). Here, we report the first follow-up results after pulmonary vein isolation (PVI) plus LA roof ablation with the CB technique in patients with symptomatic persistent AF. METHODS AND RESULTS: We enrolled 107 consecutive patients who underwent CB ablation at our institution with the aim of PVI and bidirectional conduction block across the LA roof. Clinical success was defined as freedom from >30-s recurrence of AF, atrial flutter, or atrial tachycardia after a 3-month blanking period. Follow-up data were collected during outpatient clinic visits. LA volume, LA emptying fraction, and LA expansion index (parameters of LA function) were evaluated by echocardiography before and 3 months after ablation. PVI was achieved in all patients, and bidirectional conduction block was verified in 91.6%. Median follow-up duration was 31 (interquartile range 11/44) months. PVI plus LA roof ablation was sufficient to restore and maintain sinus rhythm in 72.9% (n = 78) of patients. The overall complication rate was 1.8%. LA volumes decreased significantly after ablation (P < 0.05), whereas total LA emptying fraction (P = 0.25) and LA expansion index (P = 0.32) were preserved within the 3-month follow-up. CONCLUSIONS: LA roof ablation combined with PVI using the CB technique is a safe and effective adjuvant treatment with a promising midterm outcome and preserved LA function 3 months after ablation.

8.
Environ Sci Process Impacts ; 21(6): 957-969, 2019 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-31081837

RESUMO

Selenium is of special interest in different research fields due to its narrow range between beneficial and toxic effects. On a global scale, Se deficiency is more widespread. Biofortification measures have successfully been applied to specifically increase Se concentrations in food crops. Still not much is known about the behaviour and long-term fate of externally supplied Se. Over many years, natural but external selenate is regularly introduced into the soil-plant system via irrigation at our study sites in Punjab which makes it also an ideal natural analogue to investigate the long term effect of biofortification. For our study, we combined total and species specific analysis of Se in soil and plant material. Selenium is clearly enriched in all investigated topsoils (0-15 cm) with concentrations of 1.5-13.0 mg kg-1 despite similar background Se concentrations (0.5 ± 0.1 mg kg-1) below 15 cm depth. Irrigation is indicated to be the primary source of excess Se. Processes like Se species transformation, uptake by plants and plant material decomposition further influence both the Se speciation and extent of Se enrichment in the soils. The Se concentration in different plants and plant parts is alarmingly high showing concentrations of up to 738 mg kg-1 in wheat. Irrigation induced selenate can be considered as an easily available short term pool of Se for plants and thus strongly controls their total Se concentration and speciation. The long-term pool of Se in the topsoil mainly consists of selenite and organic Se species. These species are readily retained but still sufficiently mobile to be taken up by plants. The formation of elemental Se can be considered as a non-available Se pool and is thus, the major cause of Se immobilization and long-term enrichment of Se in the soils. Our study clearly shows that biofortification with selenate, despite its effectiveness, bears the risk of easily increasing Se levels in plants to toxic levels and producing food with less favourable inorganic Se species if not done with care. Excess selenate is either lost due to biomethylation or immobilized within the soil which has to be considered as highly negative from both an economic and ecological point of few.


Assuntos
Irrigação Agrícola , Água Subterrânea/análise , Plantas/química , Selênio/análise , Poluentes do Solo/análise , Poluentes Químicos da Água/análise , Monitoramento Ambiental , Índia , Ácido Selênico/análise
9.
PLoS One ; 14(4): e0214219, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31002711

RESUMO

Selenium plays an important, but vastly neglected role in human nutrition with a narrow gap between dietary deficiency and toxicity. For a potential biofortification of food with Se, as well as for toxicity-risk assessment in sites contaminated by Se, modelling of local and global Se cycling is essential. As bioavailability of Se for rice plants depends on the speciation of Se and the resulting interactions with mineral surfaces as well as the interaction with Se uptake mechanisms in plants, resulting plant Se content is complex to model. Unfortunately, simple experimental models to estimate Se uptake into plants from substrates have been lacking. Therefore, a mass balance of Se transfer between lithosphere (represented by kaolinite), hydrosphere (represented by a controlled nutrient solution), and biosphere (represented by rice plants) has been established. In a controlled, closed, lab-scale system, rice plants were grown hydroponically in nutrient solution supplemented with 0-10 000 µg L-1 Se of either selenate or selenite. Furthermore, in a series of batch experiments, adsorption and desorption were studied for selenate and selenite in competition with each of the major nutrient oxy-anions, nitrate, sulfate and phosphate. In a third step, the hydroponical plants experiments were coupled with sorption experiments to study synergy effects. These data were used to develop a mass balance fitting model of Se uptake and partitioning. Adsorption was well-described by Langmuir isotherms, despite competing anions, however, a certain percentage of Se always remained bio-unavailable to the plant. Uptake of selenate or selenite by transporters into the rice plant was fitted with the non-time differentiated Michaelis-Menten equation. Subsequent sequestration of Se to the shoot was better described using a substrate-inhibited variation of the Michaelis-Menten equation. These fitted parameters were then integrated into a mass balance model of Se transfer.

10.
Biomed Res Int ; 2019: 8163780, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30956985

RESUMO

Objective: Steroid-resistant graft-versus-host disease (GvHD) is a major challenge after allogeneic stem cell transplantation and associated with significant morbidity and mortality. There is no therapeutic standard defined beyond calcineurin inhibitors (CNI) and steroids. Furthermore, some patients may have contraindications against CNI or high-dose steroids. Efficacy of ruxolitinib against GvHD has been described recently. Methods: Ruxolitinib was used for treatment of acute or chronic GvHD in eight patients. The patients either needed intensification of therapy or had contraindications against use of CNI or high-dose steroids. Results: Supplementation of therapy in acute GvHD with severe diarrhea with ruxolitinib was unsuccessful. All these patients died from acute GvHD. Introduction of ruxolitinib into therapy and relapse prophylaxis in other patients was successful in 4/4 cases (CR=3, PR=1). Indications for ruxolitinib were contraindications against CNI due to aHUS in two cases and the need for steroid sparing in two other cases. None of these patients suffered from diarrhea at the initiation of ruxolitinib. Conclusion: Ruxolitinib was effective for therapy of acute and chronic GvHD in higher lines in patients without severe diarrhea. Ruxolitinib could replace successfully CNI and high-dose steroids. Further investigations are necessary to define the position of ruxolitinib in GvHD-therapy.


Assuntos
Resistência a Medicamentos/efeitos dos fármacos , Doença Enxerto-Hospedeiro/tratamento farmacológico , Pirazóis/administração & dosagem , Doença Aguda , Adulto , Idoso , Doença Crônica , Feminino , Doença Enxerto-Hospedeiro/patologia , Doença Enxerto-Hospedeiro/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Pirazóis/efeitos adversos , Esteroides/administração & dosagem , Esteroides/efeitos adversos
11.
Rofo ; 191(7): 635-642, 2019 Jul.
Artigo em Inglês, Alemão | MEDLINE | ID: mdl-30763963

RESUMO

BACKGROUND: Health technology assessments (HTAs) are an interdisciplinary method to support sustainable, evidence-based healthcare decisions. They systematically assess medical products, procedures, and technologies with respect to medical, economic, legal, social, and ethical aspects. METHOD: This review analyzes the current use of HTAs in radiology in Germany and discusses challenges associated with HTAs. In particular, incentive structures of various players in the healthcare field involved in HTA implementation are considered for both the inpatient and outpatient sectors. Taking into account that the Joint Federal Committee (G-BA) has different authority between sectors ("ban reservation" for inpatients and "authorization right" for outpatients), we focus on the repercussions on reimbursement for new diagnosis or treatment methods by statutory health insurance companies. RESULTS: The G-BA's authority implicitly creates a paradox in terms of incentives to implement and finance HTAs: in the outpatient sector HTAs are considered necessary to evaluate new medical services while players may not have sufficient incentive to implement and finance HTAs in the inpatient sector. CONCLUSION: Characteristics of HTAs differ widely with respect to the items to be assessed. Therefore, an HTA for drug effectiveness is not easily transferable to radiological procedures. Within radiology, each method must be assessed individually (e. g. according to tumor stage). Despite these challenges, systematic compilation and critical assessment (regarding both cost and medical effectiveness) of available evidence should be a basic component of evidence-based radiology. As companies in healthcare fail to invest in studies that advance evidence-based radiology and considering the lack of incentive for such investments, public funding institutions need to accept the challenge to support studies that assess the benefit of radiological procedures. KEY POINTS: · HTAs should be a basic component of evidence-based radiology.. · G-BA's authority implicitly creates a paradox in terms of inventives to implement and finance HTAs.. · University hospitals and public funding institutions need to support studies that assess the benefit of radiological procedures.. CITATION FORMAT: · Winkelmann C, Neumann T, Zeidler J et al. Health Technology Assessments in Radiology in Germany: Lack of Demand, Lack of Supply. Fortschr Röntgenstr 2019; 191: 635 - 642.

12.
Acta Haematol ; 141(2): 65-67, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30605908

RESUMO

BK polyomavirus-associated haemorrhagic cystitis (BKHC) is a complication after allogeneic stem cell transplantation, which can occur in 5-60% of the cases. BK viruria alone can also occur in up to 100%. BKHC can lead to severe morbidity in stem cell-transplanted patients, but data about this disease is limited. Consequently, we conducted a prospective unicentric non-interventional trial on BKHC as well as BK viruria after first adult allogeneic stem cell transplantation with a follow-up time of 1 year after inpatient treatment. Between November 2013 and December 2015, we were able to include 40 adult patients with a mean age of 52.8 years. Twenty-seven (67.5%) of these patients were male and 13 (32.5%) were female. Acute myeloid leukaemia was the most frequent underlying disease (n = 15; 37.5%). Only 1 patient developed BKHC during inpatient treatment (n = 1; 2.5%), but BK viruria was frequent (n = 11; 27.5%) during inpatient treatment as well as in the follow-up time (n = 14; 35%). Interestingly, BK viruria was significantly associated with mucositis (p = 0.038) and number of transfused platelet concentrates (p = 0.001). This unexpected association will be discussed and needs further investigation.


Assuntos
Cistite/diagnóstico , Infecções por Polyomavirus/diagnóstico , Alemtuzumab/uso terapêutico , Cistite/etiologia , Cistite/mortalidade , Feminino , Doença Enxerto-Hospedeiro/prevenção & controle , Humanos , Estimativa de Kaplan-Meier , Leucemia Mieloide Aguda/complicações , Leucemia Mieloide Aguda/diagnóstico , Masculino , Pessoa de Meia-Idade , Infecções por Polyomavirus/complicações , Transplante de Células-Tronco/efeitos adversos , Transplante Homólogo
13.
PLoS One ; 13(12): e0209343, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30586461

RESUMO

BACKGROUND: The TNFSF13B (TNF superfamily member 13b) gene encodes BAFF, a cytokine with a crucial role in the differentiation and activation of B cells. An insertion-deletion variant (GCTGT→A) of this gene, leading to increased levels of BAFF, has been recently implicated in the genetic predisposition to several autoimmune diseases, including multiple sclerosis, systemic lupus erythematosus, and rheumatoid arthritis. Based on the elevated levels of this cytokine found in patients with giant cell arteritis (GCA) and systemic sclerosis (SSc), we aimed to assess whether this functional variant also represents a novel genetic risk factor for these two disorders. METHODS: A total of 1,728 biopsy-proven GCA patients from 4 European cohorts, 4,584 SSc patients from 3 European cohorts and 5,160 ethnically-matched healthy controls were included in the study. The single nucleotide polymorphism (SNP) rs374039502, which colocalizes with the genetic variant previously implicated in autoimmunity, was genotyped using a custom TaqMan assay. First, association analysis was conducted in each independent cohort using χ2 test in Plink (v1.9). Subsequently, different case/control sets were meta-analyzed by the inverse variance method. RESULTS: No statistically significant differences were found when allele distributions were compared between cases and controls for any of the analyzed cohorts. Similarly, combined analysis of the different sets evidenced a lack of association of the rs374039502 variant with GCA (P = 0.421; OR (95% CI) = 0.92 (0.75-1.13)) and SSc (P = 0.500; OR (95% CI) = 1.05 (0.91-1.22)). The stratified analysis considering the main clinical subphenotypes of these diseases yielded similar negative results. CONCLUSION: Our data suggest that the TNFSF13B functional variant does not contribute to the genetic network underlying GCA and SSc.


Assuntos
Fator Ativador de Células B/genética , Predisposição Genética para Doença , Arterite de Células Gigantes/genética , Escleroderma Sistêmico/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia , Estudos de Casos e Controles , Estudos de Coortes , Europa (Continente) , Feminino , Redes Reguladoras de Genes/genética , Técnicas de Genotipagem , Arterite de Células Gigantes/patologia , Humanos , Mutação INDEL , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Escleroderma Sistêmico/patologia
14.
Mol Ther Nucleic Acids ; 13: 256-274, 2018 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-30317165

RESUMO

The recently discovered CRISPR/Cas9 system is widely used in basic research and is a useful tool for disease modeling and gene editing therapies. However, long-term expression of DNA-modifying enzymes can be associated with cytotoxicity and is particularly unwanted in clinical gene editing strategies. Because current transient expression methods may still suffer from cytotoxicity and/or low efficiency, we developed non-integrating retrovirus-based CRISPR/Cas9 all-in-one particles for targeted gene knockout. By redirecting the gammaretroviral packaging machinery, we transiently delivered Streptococcus pyogenes Cas9 (SpCas9) mRNA and single-guide RNA transcripts into various (including primary) cell types. Spatiotemporal co-delivery of CRISPR/Cas9 components resulted in efficient disruption of a surrogate reporter gene, as well as functional knockout of endogenous human genes CXCR4 and TP53. Although acting in a hit-and-run fashion, knockout efficiencies of our transient particles corresponded to 52%-80% of those obtained from constitutively active integrating vectors. Stable SpCas9 overexpression at high doses in murine NIH3T3 cells caused a substantial G0/G1 arrest accompanied by reduced cell growth and metabolic activity, which was prevented by transient SpCas9 transfer. In summary, the non-integrating retrovirus-based vector particles introduced here allow efficient and dose-controlled delivery of CRISPR/Cas9 components into target cells.

15.
J Cardiovasc Electrophysiol ; 29(11): 1500-1507, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30230074

RESUMO

INTRODUCTION: We analyzed the procedural experience and clinical outcome after pulmonary vein isolation (PVI) in patients with persistent atrial fibrillation (AF) gained over 5 years using the second-generation cryoballoon (CB-Adv). METHODS AND RESULTS: For this retrospective study, we enrolled 281 patients undergoing PVI at our institution between 2012 and 2016. The analyzed period was divided into 5 calendar years. Follow-up data, including Holter electrocardiography recordings, were collected during outpatient clinic visits. The impact of several variables on outcome was evaluated by means of univariate and multivariate analyses and Cox proportional hazards regression models. The median procedure and fluoroscopy times over the years were 90 (72 of 114) and 15 (11 of 21) minutes, respectively. A continuous decline in complication rates and fluoroscopy and procedure times was observed in each subsequent year. During mid-term follow-up (33 [25 of 48] months), 178 (63.3%) patients were AF, atrial flutter, or atrial tachycardia free. Multivariate analysis revealed left atrial area (hazard ratio [HR] = 1.05; P < 0.001), female sex (HR = 2.53; P < 0.001), and common ostium (HR = 1.93; P < 0.001) as significant predictors of outcome. The overall 1-year success rate was 76.2%. A gradual decrease in the 1-year success rate (from 90.5% in 2012 to 67.9% in 2016) was mainly related to a steady increase of left atrial area in the entire cohort with successive years of the study. CONCLUSIONS: PVI using CB-Adv in patients with persistent AF is accompanied by a learning curve and facilitates a satisfactory outcome, followed by the proper selection of patients.

16.
Herzschrittmacherther Elektrophysiol ; 29(3): 293-299, 2018 Sep.
Artigo em Alemão | MEDLINE | ID: mdl-30105608

RESUMO

BACKGROUND: CardioInsight™ is a noninvasive three-dimensional mapping system technology which offers a unique method for arrhythmia characterization and localization. With a 252-lead ECG vest on the patient's torso and a noncontrast CT scan, epicardial potentials are detected and by means of reconstruction algorithms activation and phase maps are created, offering a deeper understanding of localization and mechanisms of arrhythmias including atrial fibrillation without the need for an endocardial catheter. MATERIALS AND METHODS: The system has proven to be accurate and applicable in the clinical setting of accessory pathways, premature ventricular contractions (PVC), atrial tachycardias and atrial fibrillation. Beat-to-beat analysis offers detection and thus a therapeutic approach for arrhythmias which occur only paroxysmally such as supraventricular extrasystoles, atrial bursts or PVCs. Another advantage is the simultaneous display of various heart chambers such as the left and right atrium. However, major multicenter prospective randomized data are still lacking. CONCLUSION: If in the future noninvasive mapping could be achieved with MRI and if the technology was compatible with invasive mapping systems so that catheter positioning and noninvasive maps can be merged, the authors believe that this would represent a new dimension of mapping technology and ablation strategy of arrhythmias.

17.
Pacing Clin Electrophysiol ; 41(10): 1279-1285, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30133719

RESUMO

INTRODUCTION: The aim of this study was to evaluate a spatial correlation between active atrial fibrillation (AF) drivers measured by electrocardiographic imaging and complex fractionated atrial electrograms (CFAEs) in patients with persistent AF. METHODS: Sixteen patients with persistent AF were included. A biatrial geometry relative to an array of 252-body-surface-electrodes was obtained from a noncontrast computed tomography scan. The reconstructed unipolar AF electrograms were signal-processed (ECVUE™, CardioInsight Technologies Inc., Cleveland, OH, USA) to identify AF drivers. Before driver ablation, a biatrial mapping using the NavX system (St. Jude Medical, St. Paul, MN, USA) was performed to identify CFAEs. CFAE and driver regions were then quantified and compared. RESULTS: AF was terminated by driver ablation in 11/16 (70%) patients. The mean number of ablated driver regions was 4 ± 1 per patient. The most frequent driver locations were the inferior left atrium and coronary sinus, the right pulmonary veins, and the right atrium. In 49/63 (78%) of the driver locations, more than 75% of the driver site showed CFAEs. The mean ablated driver area was 58 ± 24 cm2 (19 ± 11% of total surface area). The mean CFAE area was 178 ± 59 cm2 (49 ± 16%). The percentage of non-ablated CFAE area was 76 ± 13% of total CFAEs. In 9/11 patients with AF termination, the termination site showed CFAEs. CONCLUSIONS: There is a significant overlap between AF driver regions identified by the ECVUE™ system and CFAE areas identified by the NavX system. AF driver regions are smaller and mostly embedded in larger CFAE areas. Selective ablation of drivers in CFAE areas seems sufficient to terminate persistent AF in the majority of patients.

18.
Dalton Trans ; 47(32): 11002-11015, 2018 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-30022201

RESUMO

Environmental and health hazards associated with the trace element selenium are mainly related to the presence of the highly mobile selenium oxyanions selenite and selenate (oxidation states IV and VI). In this study, we investigated the immobilization of dissolved selenite and selenate during the formation of magnetite in coprecipitation experiments based on the progressive oxidation of an alkaline, anoxic Fe2+ system (pH 9.2). Up to initial selenium concentrations of 10-3 mol L-1 (mass/volume ratio = 3.4 g L-1), distribution coefficient values (log Kd) of 3.7 to 5.1 L kg-1 demonstrate high retention of selenium oxyanions during the mineral formation process. This immobilization is due to the reduction of selenite or selenate, resulting in the precipitation of sparingly soluble selenium compounds. By X-ray diffraction analysis, these selenium compounds were identified as trigonal elemental selenium that formed in all coprecipitation products following magnetite formation. Time-resolved analysis of selenium speciation during magnetite formation and detailed spectroscopic analyses of the solid phases showed that selenium reduction occurred under anoxic conditions during the early phase of the coprecipitation process via interaction with iron(ii) hydroxide and green rust. Both minerals are the initial Fe(ii)-bearing precipitation products and represent the precursor phases of the later formed magnetite. Spectroscopic and electron microscopic analysis showed that this early selenium interaction leads to the formation of a nanoparticulate iron selenide phase [FeSe], which is oxidized and transformed into gray trigonal elemental selenium during the progressive oxidation of the aquatic system. Selenium is retained regardless of whether the oxidation of the unstable iron oxides leads to the formation of pure magnetite or other iron oxide phases, e.g. goethite. This reductive precipitation of selenium induced by interaction with metastable Fe(ii)-containing iron oxide minerals has the potential to influence the mobility of selenium oxyanions in contaminated environments, including the behavior of 79Se in the near-field of nuclear waste repositories.

19.
Artigo em Inglês | MEDLINE | ID: mdl-29994665

RESUMO

Objective assessment in long-term rehabilitation under real-life recording conditions is a challenging task. We propose a data-driven method to evaluate changes in motor function under uncontrolled, long-term conditions with the low-cost Microsoft Kinect Sensor. Instead of using human ratings as ground truth data, we propose kinematic features of hand motion, healthy reference trajectories derived by principal component regression, and methods from machine learning to analyze the progression of motor function. We demonstrate the capability of this approach on datasets with repetitive unrestrained bi-manual drumming movements in 3-dimensional space of stroke survivors, patients suffering of Parkinson's disease, and a healthy control group. We present processing steps to eliminate the influence of varying recording setups under real-life conditions and offer visualization methods to support clinicians in the evaluation of treatment effects.

20.
Int J Cardiol ; 266: 106-111, 2018 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-29887425

RESUMO

INTRODUCTION: Data on long-term outcomes of cryoballoon ablation for treatment of atrial fibrillation (AF) are sparse. Here, we report the first 5-year follow-up results and predictors of outcome for pulmonary vein isolation (PVI) using the second-generation cryoballoon (CB-Adv) in patients with symptomatic AF. METHODS AND RESULTS: For this prospective observational study, we enrolled 178 patients with paroxysmal (132/178 [74.2%] patients) or persistent AF who underwent PVI with CB-Adv at our institution during 2012. Clinical success was defined as freedom from AF, atrial flutter or atrial tachycardia recurrence >30-s following the 3-month blanking period. Follow-up data were collected during outpatient clinic visits and included Holter-ECG recordings. The impacts of several variables on outcome were evaluated by means of univariate and multivariate analyses and Cox proportional hazards regression models. PVI was sufficient in restoring and maintaining sinus rhythm in 59.0% (n = 105) of patients (paroxysmal AF: 81/132 (61.4%) patients; persistent AF: 24/46 (52.2%) patients, P = 0.20). The median procedure and fluoroscopy times were 126 (interquartile range 114/150) and 20 (16/26) min, respectively. Cox regression analysis showed that left atrial area ≤21 cm2 and the absence of diabetes independently predicted outcome. CONCLUSIONS: Sinus rhythm was maintained in a substantial proportion of patients even 5 years after CB-Adv ablation. Patients with a non-enlarged left atrium without diabetes had the best outcome.

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