Fate of nutrients and trace contaminants in a large shallow soda lake. Spatial gradients and underlying processes from the tributary river to the reed belt.

Shallow lakes provide a multitude of ecosystem functions, but they are particularly vulnerable to natural and anthropogenic disturbances. Understanding the driving factors determining the fate and spatial distribution of nutrients and pollutants in such systems is fundamental to assess the impact of ongoing or future external pressures endangering their ecological integrity. This study investigates the fate of trace contaminants transported into the large shallow Lake Neusiedl, including contaminants representative of different patterns of sources and emission pathways and of environmental behavior, namely metals, pharmaceuticals, an artificial sweetener and perfluoroalkyl substances. Further, it examines the horizontal spatial distribution of nutrients, ions and physico-chemical parameters with an unprecedented detailed focus on the internal variability within the large reed belt. As described in the past e.g. for chloride, evaporation was identified as the process leading to a substantial concentration enrichment of the industrial chemical PFOA and the sweetener acesulfame K from the tributary river into the open lake. This is particularly relevant in view of the predicted future increase of evapotranspiration due to climate change. In contrast, the observed loss of diclofenac, but also of PFOS and carbamazepine suggests that the well-mixed, humic-rich and alkaline Lake Neusiedl offers favorable conditions for the photodegradation of otherwise very persistent chemicals. Another important finding, in the context of possible modifications in lake water levels due to climate change, is the fundamental role played by the connectivity between open lake and reed belt but also by the presence and characteristics of inner water areas within the reed belt region in determining the hydrochemistry of the lake system. By revealing systematic spatial patterns and by focusing on the underlying factors and processes, the understanding offered by this study is of high value for the conservation of shallow lakes.

The combination of supervised and unsupervised learning based risk stratification and phenotyping in pulmonary arterial hypertension-a long-term retrospective multicenter trial.

BACKGROUND: Accurate risk stratification in pulmonary arterial hypertension (PAH), a devastating cardiopulmonary disease, is essential to guide successful therapy. Machine learning may improve risk management and harness clinical variability in PAH. METHODS: We conducted a long-term retrospective observational study (median follow-up: 67 months) including 183 PAH patients from three Austrian PAH expert centers. Clinical, cardiopulmonary function, laboratory, imaging, and hemodynamic parameters were assessed. Cox proportional hazard Elastic Net and partitioning around medoid clustering were applied to establish a multi-parameter PAH mortality risk signature and investigate PAH phenotypes. RESULTS: Seven parameters identified by Elastic Net modeling, namely age, six-minute walking distance, red blood cell distribution width, cardiac index, pulmonary vascular resistance, N-terminal pro-brain natriuretic peptide and right atrial area, constituted a highly predictive mortality risk signature (training cohort: concordance index = 0.82 [95%CI: 0.75 - 0.89], test cohort: 0.77 [0.66 - 0.88]). The Elastic Net signature demonstrated superior prognostic accuracy as compared with five established risk scores. The signature factors defined two clusters of PAH patients with distinct risk profiles. The high-risk/poor prognosis cluster was characterized by advanced age at diagnosis, poor cardiac output, increased red cell distribution width, higher pulmonary vascular resistance, and a poor six-minute walking test performance. CONCLUSION: Supervised and unsupervised learning algorithms such as Elastic Net regression and medoid clustering are powerful tools for automated mortality risk prediction and clinical phenotyping in PAH.

Very High-Power Short-Duration (HPSD) Ablation for Pulmonary Vein Isolation: Short and Long-Term Outcome Data.

BACKGROUND: Circumferential pulmonary vein isolation (PVI) using radiofrequency ablation (RFA) is a standard of care intervention for patients with symptomatic atrial fibrillation (AF). During follow-up, a substantial number of patients need a redo procedure due to reconnections on the basis of insufficient non-transmural ablation lesions. High-power short-duration ablation (HPSD) is expected to create efficient lesions while causing fewer complications than in conventional RFA settings. The aim of this study was to compare one-year outcome data of very HPSD (90 Watt, 4 s) to a strategy using 50 Watt HPSD ablation guided by the CLOSE protocol using the Ablation Index (AI), an arbitrary unit composed of power, contact force and ablation time. METHODS: We retrospectively analyzed short and long-term (median follow-up 23.2 ± 9.9 months) outcome data from 52 patients that were scheduled for first-do-symptomatic PVI. A very HPSD ablation protocol with 90 Watt and a 4 s duration cut-off was compared to an HPSD CLOSE approach (50 Watts; AI 550 at the anterior LA wall; AI 400 at the posterior LA wall, the roof and the floor) in terms of freedom from AF recurrence in a long-term electrocardiogram (ECG) over a five days surveillance period. To gain an impression of the subjective sense of wellbeing, the Atrial Fibrillation Effects on QualiTy-of-Life (AFEQT) score was recorded. RESULTS: Overall freedom from AF was found in 81% (90 W 4 s) vs. 87.5% (50 W), (p = 0.52). There were 3 AF recurrences during the blanking period (90 W 4 s) vs. 1 (50 W). Within each population, one patient was scheduled for a redo-PVI-procedure. The AFEQT score was in favor of the 90 Watt 4 s approach (86.1 vs. 77.5; p = 0.37). CONCLUSION: Within our relatively small studied population, we found hints that in addition to shortening ablation times and radiation exposure without significantly increasing the rate of relevant intraprocedural complications, very high power short-duration ablation (90 W 4 s) provides comparable efficacy rates after one year.

Long-term experience with implantable infusion pumps for intravenous treprostinil in pulmonary arterial hypertension-procedural safety and system-related complications.

Implantable pumps for intravenous treprostinil provide a promising option to overcome drawbacks of parenteral prostanoid administration with external pumps in pulmonary hypertension. We retrospectively analyzed 85 patients undergoing implantation in a single center since 2010. In our cohort, serious complications were rare, and flow rate increase over time warrants careful monitoring.

Feasibility and safety of uninterrupted periprocedural apixaban administration in patients undergoing radiofrequency catheter ablation for atrial fibrillation: Results from a multicenter study.

BACKGROUND: Periprocedural anticoagulation management with uninterrupted warfarin and a "therapeutic" international normalized ratio is the best approach for reducing both thromboembolic and bleeding complications in the setting of catheter ablation for atrial fibrillation (AF). OBJECTIVE: The purpose of this study was to evaluate the safety and feasibility of uninterrupted apixaban in this setting. METHODS: This was a prospective multicenter registry of AF patients undergoing radiofrequency catheter ablation at 4 institutions in United States and Europe with uninterrupted apixaban. These patients were compared with an equal number of patients, matched for age, gender, and type of AF, undergoing AF ablation on uninterrupted warfarin. The apixaban group was comprised of consecutive patients who had taken their last dose of apixaban the morning of the procedure. A subset of 29 patients in the apixaban group underwent diffusion magnetic resonance imaging (dMRI) to detect silent cerebral ischemia. RESULTS: A total of 400 patients (200 patients in each group) were included in the study. The average age was 65.9 ± 9.9 years, 286 (71.5%) were male, and 334 (83.5%) had nonparoxysmal AF. There were no statistical differences with regard to major complications (1% vs 0.5%, P = 1), minor complications (3.5% vs 2.5%, P = .56), or total bleeding complications (4.5% vs 3%, P = .43) between the apixaban and warfarin groups. There were no symptomatic thromboembolic complications. All dMRIs were negative for "new" silent cerebral ischemia in the apixaban group. CONCLUSION: Uninterrupted apixaban administration in patients undergoing AF ablation seems to be feasible and effective in preventing clinical and silent thromboembolic events without increasing the risk of major bleeding.

Optimizing radiofrequency ablation of paroxysmal and persistent atrial fibrillation by direct catheter force measurement-a case-matched comparison in 198 patients.

BACKGROUND: Sufficient electrode-tissue contact is crucial for adequate lesion formation in radiofrequency catheter ablation (RFCA). OBJECTIVE: We assessed the impact of direct catheter force measurement on acute procedural parameters and outcome of RFCA for paroxysmal and persistent atrial fibrillation (AF). METHODS: Ninety-nine consecutive patients (70% men) with paroxysmal (63.6%) or persistent AF underwent left atrial RFCA using a 3.5-mm open-irrigated-tip (OIT) catheter with contact force measurement capabilities (group 1). For comparison a case-matched cohort with standard OIT catheters was used (99 patients; group 2). Case matching included gender, type of AF, number or RFCA procedures, and type of procedure. RESULTS: Procedural data showed a significant decline in radiofrequency ablation time from 52 ± 20 to 44 ± 16 minutes (P = 0.003) with a remarkable mean reduction in overall procedure time of 34 minutes (P = 0.0001; 225.8 ± 53.1 vs 191.9 ± 53.3 minutes). In parallel, the total fluoroscopy time could be significantly reduced from 28.5 ± 11.0 to 19.9 ± 9.3 minutes (P = 0.0001) as well as fluoroscopy dose from 74.1 ± 58.0 to 56.7 ± 38.9 Gy/cm(2) (P = 0.016). Periprocedural complications were similar in both groups. CONCLUSIONS: The use of contact force sensing technology is able to significantly reduce ablation, procedure, and fluoroscopy times as well as dose in RFCA of AF in a mixed case-matched group of paroxysmal and persistent AF. Energy delivery is substantially reduced by avoiding radiofrequency ablation in positions with insufficient surface contact. Additionally 12-month outcome data showed increased efficacy. Such time saving and equally safe technology may have a relevant impact on laboratory management and increased cost effectiveness.

Asymptomatic cerebral lesions during pulmonary vein isolation under uninterrupted oral anticoagulation.

AIMS: Left atrial radiofrequency ablation has been shown to carry a risk of asymptomatic cerebral lesions. No data exist in patients under continued oral anticoagulation during the ablation procedure. The aim of this study was to quantify the amount of silent cerebral lesions assessed by pre-procedural and post-procedural magnetic resonance imaging (MRI) in patients under therapeutic international normalized ratio (INR) and to identify clinical or procedural parameters that correlate with cerebral embolism. METHODS AND RESULTS: A total of 131 consecutive patients undergoing catheter ablation for paroxysmal (n = 80, 61.1%) or persistent (n = 51, 38.9%) atrial fibrillation were included in the study. Pulmonary vein antrum isolation (PVI), roofline, mitral isthmus line, and complex fractionated atrial electrogram (CFAE) ablation using 3.5 mm open-irrigated tip catheters were performed, as needed. All patients underwent pre-procedural and post-procedural cerebral MRI. Post-procedural MRI revealed new embolic lesions in 16 patients (12.2%), all of them asymptomatic. Clinical parameters showing a significant correlation with cerebral embolism in univariate analysis were age (P = 0.027), persistent atrial fibrillation (vs. paroxysmal; P = 0.039), and spontaneous echo contrast in transesophageal echocardiography (P = 0.029). Significant procedural parameters were electric cardioversion (P = 0.041), PVI only (P = 0.008), and ablation of complex atrial electrograms (P = 0.005). Independent risk factors in multivariate analysis were age (P = 0.009), spontaneous echo contrast (P = 0.029) and CFAE ablation (P = 0.006). CONCLUSION: Radiofrequency ablation in patients under continued oral therapeutic anticoagulation is associated with a substantial risk of silent embolism detected by cerebral MRI. Therefore, continuation of oral anticoagulation is not able to prevent cerebral embolism. A variety of different clinical and procedural factors seem to contribute to the risk of cerebral lesions.

Clinical impact of an open-irrigated radiofrequency catheter with direct force measurement on atrial fibrillation ablation.

BACKGROUND: Electrode-tissue contact is crucial for adequate lesion formation in radiofrequency catheter ablation (RFCA). OBJECTIVE: We assessed the impact of direct catheter force measurement on acute procedural parameters during RFCA of atrial fibrillation (AF). METHODS: Fifty consecutive patients (28 male) with paroxysmal AF who underwent their first procedure of circumferential pulmonary vein (PV) isolation (PVI) were assigned to either RFCA using (1) a standard 3.5-mm open-irrigated-tip catheter or (2) a catheter with contact force measurement capabilities. Using the endpoint of PVI with entry and exit block, acute procedural parameters were assessed. RESULTS: Procedural data showed a remarkable decline in ablation time (radiofrequency time needed for PVI) from 50.5 ± 15.9 to 39.0 ± 11.0 minutes (P = 0.007) with a reduction in overall procedure duration from 185 ± 46 to 154 ± 39 minutes (P = 0.022). In parallel, the total energy delivered could be significantly reduced from 70,926 ± 19,470 to 58,511 ± 14,655 Ws (P = 0.019). The number of acute PV reconnections declined from 36% to 12% (P = 0.095). CONCLUSIONS: The use of contact force sensing technology is able to significantly reduce ablation and procedure times in PVI. In addition, energy delivery is substantially reduced by avoiding radiofrequency ablation in positions with insufficient surface contact. Procedural efficacy and safety of this new feature have to be evaluated in larger cohorts.

Polyacetylenes from the Apiaceae vegetables carrot, celery, fennel, parsley, and parsnip and their cytotoxic activities.

A dichloromethane extract of root celery yielded falcarinol, falcarindiol, panaxydiol, and the new polyacetylene 8-O-methylfalcarindiol. The structure of the new compound was established by one- and two-dimensional (1D and 2D) NMR, mass spectrometry, and optical rotation data. Nonpolar extracts of roots and bulbs of carrots, celery, fennel, parsley, and parsnip were investigated for their content of polyacetylenes by high-performance liquid chromatography with diode array detection (HPLC-DAD). All five species contained polyacetylenes, although carrots and fennel only in minor amounts. Additionally, the cytotoxicity of the four polyacetylenes against five different cell lines was evaluated by the annexin V-PI assay. Falcarinol proved to be the most active compound with a pronounced toxicity against acute lymphoblastic leukemia cell line CEM-C7H2, with an IC(50) of 3.5 micromol/L. The possible chemopreventive impact of the presented findings is discussed briefly.