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Background—Postoperative atrial fibrillation (PoAF) is common after coronary artery bypass grafting. We previously showed that atrial fibrillation susceptibility single nucleotide polymorphisms (SNPs) at the chromosome 4q25 locus are associated with PoAF. Here, we tested the hypothesis that a combined clinical and genetic model incorporating atrial fibrillation risk SNPs would be superior to a clinical-only model. Methods and Results—We developed and externally validated clinical and clinical/genetic risk models for PoAF. The discovery and validation cohorts included 556 and 1164 patients, respectively. Clinical variables previously associated with PoAF and 13 SNPs at loci associated with atrial fibrillation in genome-wide association studies were considered. PoAF occurred in 30% and 29% of patients in the discovery and validation cohorts, respectively. In the discovery cohort, a logistic regression model with clinical factors had good discrimination, with an area under the receiver operator characteristic curve of 0.76. The addition of 10 SNPs to the clinical model did not improve discrimination (area under receiver operator characteristic curve, 0.78; P=0.14 for difference between the 2 models). In the validation cohort, the clinical model had good discrimination (area under the receiver operator characteristic curve, 0.69) and addition of genetic variables resulted in a marginal improvement in discrimination (area under receiver operator characteristic curve, 0.72; P<0.0001). Conclusions—We developed and validated a model for the prediction of PoAF containing common clinical variables. Addition of atrial fibrillation susceptibility SNPs did not improve model performance. Tools to accurately predict PoAF are needed to risk stratify patients undergoing coronary artery bypass grafting and identify candidates for prophylactic therapies.

Background: Systemically administered antibiotics are thought to penetrate the wounds more effectively during negative pressure wound therapy (NPWT).To test this hypothesis total and free antibiotic concentrations were quantified in serum and wound exudate., Methods: UHPLC-MS/MS methods were developed and validated for the determination of ceftazidime, cefepime, cefotaxime, cefuroxime, cefazolin, meropenem, oxacillin, piperacillin with tazobactam, clindamycin, ciprofloxacin, sulfamethoxazole/trimethoprim (cotrimoxazole), gentamicin, vancomycin, and linezolid. The unbound antibiotic fraction was obtained by ultrafiltration using a Millipore Microcon-30kda Centrifugal Filter Unit. Analysis was performed on a 1.7-µm Acquity UPLC BEH C18 2.1 × 100-mm column with a gradient elution., Results: The validation was performed for serum, exudates and free fractions. For all matrices, requirements were met regarding linearity, precision, accuracy, limit of quantitation, and matrix effect. The coefficient of variation was in the range of 1.2-13.6%.and the recovery 87.6-115.6%, respectively. Among the 29 applications of antibiotics thus far, including vancomycin, clindamycin, ciprofloxacin, oxacillin, cefepime, cefotaxime, cotrimoxazole, and gentamicin, total and free antibiotic concentrations in serum and exudate were correlated., Conclusion: This method can accurately quantify the total and free concentrations of 16 antibiotics. Comparison of concentration ratios between serum and exudates allows for monitoring individual antibiotics' penetration capacity in patients receiving NPWT., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Dual-ion batteries (DIBs) offer a great alternative to state-of-the-art lithium-ion batteries, based on their high promises due to the absence of transition metals and the use of low-cost materials, which could make them economically favorable targeting stationary energy storage applications. In addition, they are not limited by certain metal cations, and DIBs with a broad variety of utilized ions could be demonstrated over the last years. Herein, a systematic study of different electrolyte approaches for Mg-ion-based DIBs was conducted. A side-by-side comparison of Li- and Mg-ion-based electrolytes using activated carbon as negative electrode revealed the opportunities but also limitations of Mg-ion-based DIBs. Ethylene sulfite was successfully introduced as electrolyte additive and increased the specific discharge capacity significantly up to 93±2 mAh g -1 with coulombic efficiencies over 99 % and an excellent capacity retention of 88 % after 400 cycles. In addition, and for the first time, highly concentrated carbonate-based electrolytes were employed for Mg-ion-based DIBs, showing adequate discharge capacities and high coulombic efficiencies., (© 2021 The Authors. ChemSusChem published by Wiley-VCH GmbH.)

Organic redox polymers are attractive electrode materials for more sustainable rechargeable batteries. To obtain full-organic cells with high operating voltages, redox polymers with low potentials (<2 V versus Li|Li + ) are required for the negative electrode. Dibenzo[a,e]cyclooctatetraene (DBCOT) is a promising redox-active group in this respect, since it can be reversibly reduced in a two-electron process at potentials below 1 V versus Li|Li + . Upon reduction, its conformation changes from tub-shaped to planar, rendering DBCOT-based polymers also of interest to molecular actuators. Here, the syntheses of three aliphatic DBCOT-polymers and their electrochemical properties are presented. For this, a viable three-step synthetic route to 2-bromo-functionalized DBCOT as polymer precursor is developed. Cyclic voltammetry (CV) measurements in solution and of thin films of the DBCOT-polymers demonstrate their potential as battery electrode materials. Half-cell measurements in batteries show pseudo capacitive behavior with Faradaic contributions, which demonstrate that electrode composition and fabrication will play an important role in the future to release the full redox activity of the DBCOT polymers., (© 2021 The Authors. Macromolecular Rapid Communications published by Wiley-VCH GmbH.)

Background: Association between clinical effect and serum concentration of amiodarone (AMI) and its active metabolite desethylamidarone (DEA) in patients after surgical ablation (SA) of atrial fibrillation (AF) has not yet been studied., Aims: We wanted to find a correlation between AMI and DEA serum concentration and maintaining sinus rhythm (SR) after SA of AF., Methods: Sixty eight patients with AF who had undergone surgical ablation between 2014 and 2017 were included in a single-centre, prospective, observational study. Maintaining of SR was evaluated by standard 12-lead ECG and 24-hour Holter ECG monitoring at months 1, 3, 6 and 12 following surgery. Therapeutic monitoring of AMI and DEA concentrations was done to optimize therapy and adverse effects were followed up., Results: We have noticed a high success rate in maintaining of SR (overall 83%). The median of serum concentration of AMI was 0.81 mg/L (range 0.16-2.35 mg/L) and DEA 0.70 mg/l (range 0.19-2.63 mg/L). No significant differences were found in the serum concentratration of AMI, DEA or DEA/AMI concentratration ratios between patients with SR and persistent supraventricular tachyarrhythmia except on the second outpatient visit. We observed significant correlation between serum concentration of DEA and thyroid-stimulating hormone elevation., Conclusion: We confirmed the efficacy of AMI and DEA at the measured serum concentrations. However, analysis of these concentrations alone cannot replace assessment of the clinical response for treatment. Establishment of individual AMI (and DEA) concentrations at which the optimal therapeutic response is achieved seems to be advantageous. Therapeutic monitoring of AMI and DEA is helpful in personalised pharmacotherapy after SA of AF., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 The Author(s).)

Organic materials are promising candidates for next-generation battery systems. However, many organic battery materials suffer from high solubility in common battery electrolytes. Such solubility can be overcome by introducing tailored high-molecular-weight polymer structures, for example, by cross-linking, requiring enhanced synthetic efforts. We herein propose a different strategy by optimizing the battery electrolyte to obtain insolubility of non-cross-linked poly(3-vinyl- N -methylphenothiazine) ( PVMPT ). Successive investigation and theoretical insights into carbonate-based electrolytes and their interplay with PVMPT led to a strong decrease in the solubility of the redox polymer in ethylene carbonate/ethyl methyl carbonate (3:7) with 1 M LiPF 6 . This allowed accessing its full theoretical specific capacity by changing the charge/discharge mechanism compared to previous reports. Through electrochemical, spectroscopic, and theoretical investigations, we show that changing the constituents of the electrolyte significantly influences the interactions between the electrolyte molecules and the redox polymer PVMPT . Our study demonstrates that choosing the ideal electrolyte composition without chemical modification of the active material is a successful strategy to enhance the performance of organic polymer-based batteries.

Li metal batteries (LMBs) containing cross-linked polymer electrolytes (PEs) are auspicious candidates for next-generation batteries. However, the wetting behavior of PEs on uneven Li metal surfaces has been neglected in most studies. Herein, it is shown that microscale defect sites with curved edges play an important role in a wettability-dependent electrodeposition. The wettability and the viscoelastic properties of PEs are correlated, and the impact of wettability on the nucleation and diffusion near the Li|PE interface is distinguished. It is found that the curvature of the edges is a key factor for the investigation of wetting phenomena. The appearance of microscale defects and phase separation are identified as main causes for erratic nucleation. It is emphasized that the implementation of stable and consistent long-term cycling performance of LMBs using PEs requires a deeper understanding of the "soft-solid"-solid contact between PEs and inherently rough Li metal surfaces., (© 2020 The Authors. Published by Wiley-VCH GmbH.)

Introduction: Although there is a significant utilization gap of biologic medicines in the EU, many studies estimate equity in patient access to biopharmaceuticals only based on their availability on the national list of reimbursed medicines. Hidden access barriers may facilitate financial sustainability of pharmaceuticals in less affluent EU countries; however, they have rarely been documented in scientific publications. Our objective was to explore these access barriers for tumor necrosis factor (TNF) alpha inhibitors in rheumatoid arthritis (RA) in five Central and Eastern European countries., Methods: A detailed interview guide was developed based on multi-stakeholder workshops and a targeted literature review. In each participant country 3-3-3-3 interviews with payers, rheumatologists, patients/patient representatives, and industry representatives were conducted. Responses were aggregated at a country level and validated by primary investigators in each country., Results: Limited number of RA centers and consequently significant travelling time and cost for patients in distant geographical areas, uneven budget allocation among centers, limited capacity of nurses, narrowed patient population in national financial protocols compared to international clinical guidelines in initiating or continuing biologics, high administrative burden in prescribing biologics and limited health literacy of patients were the most relevant barriers to timely patient access in at least three participant countries., Conclusion: Assessing only the availability of TNF alpha inhibitors on the national list of reimbursed medicines provides limited information about real-world patient access to these medicines. Revealing hidden access barriers may contribute to initiate policy actions which could reduce inequity in patient access., (Copyright © 2020 Inotai, Tomek, Niewada, Lorenzovici, Kolek, Weber, Kurrat, Kiss and Kaló.)

Organic cathode materials are handled as promising candidates for new energy-storage solutions based on their transition-metal-free composition. Phenothiazine-based polymers are attractive owing to their redox potential of 3.5 V vs. Li/Li + and high cycling stabilities. Herein, three types of poly(norbornene)s were investigated, functionalized with phenothiazine units through either a direct connection or ester linkages, as well as their crosslinked derivatives. The directly linked poly(3-norbornylphenothiazine)s demonstrated excellent rate capability and cycling stability with a capacity retention of 73 % after 10 000 cycles at a C-rate of 100 C for the crosslinked polymer. The polymer network structure of the crosslinked poly(3-norbornylphenothiazine) was beneficial for its rate performance., (© 2019 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.)

Aims: Limited contemporary data are available on the clinical and echocardiographic outcomes after surgery for cardiac papillary fibroelastoma (CPF). The aim of this study was to review the clinical manifestations, pathological characteristics, surgical management, and prognoses of patients with histologically verified CPF, who underwent surgery at our cardiac surgery center from 2008 to 2018., Methods and Results: Twelve patients of median age 62 years (28 to 77 years) were treated. Embolic stroke or transient ischemic attack (five patients, 42%) were the only CPF clinical manifestations. Eleven (92%) tumors were localized on the valves, with the aortic valve being the most common tumor site (seven patients; 58%). Multiple factor analysis revealed no independent predictor of CPF-related embolization. Simple shave tumor excision was sufficient in most patients (10 patients, 83%). No operative or tumor-related late mortality during the median follow-up period of 4.7 years (1.1 to 10.2 years) was recorded. Asymptomatic metachronous valve tumor recurrence (in a location different from that of the original tumor) was revealed in two patients (17%) by transesophageal echocardiography (TEE), not detected by transthoracic echocardiography (TTE). One of these two patients underwent repeated surgery for CPF but later suffered a recurrent embolic stroke, due to another tumor recurrence., Conclusion: CPF can be safely and effectively treated surgically. TEE is superior to the TTE option in CPF post-operative recurrence detection. There is a clear need for a prospective study to determine criteria for embolization risk stratification and optimum management in patients with CPF.

A major challenge of lithium metal electrodes, in theory a suitable choice for rechargeable high energy density batteries, comprises non-homogeneous lithium deposition and the growth of reactive high surface area lithium, which eventually yields active material losses and safety risks. While it is hard to fully avoid inhomogeneous deposits, the achievable morphology of the occurring lithium deposits critically determines the long-term cycling behaviour of the cells. In this work, we focus on a combined scanning electron microscopy (SEM) and 7 Li nuclear magnetic resonance spectroscopy ( 7 Li-NMR) study to unravel the impact of the choice of conducting salts (LiPF 6 and LiTFSI), solvents (EC : DEC, 3 : 7, DME : DOL, 1 : 1), as well as their respective concentrations (1 M, 3 M) on the electrodeposition process, demonstrating that lithium deposition morphologies may be controlled to a large extent by proper choice of cycling conditions and electrolyte constituents. In addition, the applicability of 7 Li-NMR spectroscopy to assess the resulting morphology is discussed. It was found, that lithium deposition analysis based on the 7 Li chemical shift and intensity should be used carefully, as various morphologies can lead to similar results. Still, our case study reveals that the combination of SEM and NMR data is rather advantageous and offers complementary insights that may provide pathways for the future design of tailored electrolytes.

In many Mg-based battery systems, the reversibility of Mg deposition and dissolution is lowered by parasitic formation processes of the electrolyte. Therefore, high Coulombic efficiencies of Mg deposition and dissolution are only achieved after several "conditioning" cycles. As this phenomenon is especially reported for AlCl 3 -containing solutions, this study focuses on the "conditioning" mechanisms of MgCl 2 /AlCl 3 and MgHMDS 2 /AlCl 3 (HMDS = hexamethyldisilazide) in tetraethylene glycol dimethyl ether (TEGDME)-based electrolytes. Electrochemical (cyclic voltammetry) and spectroscopic investigations ( 27 Al nuclear magnetic resonance spectroscopy, Raman spectroscopy, inductively coupled plasma optical emission spectroscopy, scanning electron microscopy, and energy-dispersive X-ray spectroscopy) reveal that cationic AlCl 2 + species in TEGDME-based electrolytes with an AlCl 3 /MgCl 2 ratio higher than 1:1 corrode the Mg metal. According to a cementation reaction mechanism, the corrosion of Mg is accompanied with Al deposition. In effect, the consumption of Mg results in low Coulombic efficiencies of Mg deposition and dissolution during the electrolyte "conditioning". After understanding the mechanism of this process, we demonstrate that a careful adjustment of the stoichiometry in MgCl 2 /AlCl 3 and MgHMDS 2 /AlCl 3 in TEGDME formulations prevents Mg corrosion and results in "conditioning"-free, highly efficient Mg deposition and dissolution.

Implantable cardioverter defibrillators (ICDs) have been shown to have a significant benefit in reducing sudden cardiac death (SCD) in patients with systolic heart failure. Additionally, cardiac devices as a bridge to transplant or destination therapy are often used in patients with end-stage systolic heart failure. As a result, most patients with left ventricular assist devices (LVADs) also have an ICD. Here, we present an electromagnetic interference (EMI) between HeartMate 3 LVAD and ICD. This issue might be critical for both electrophysiologists and advanced heart failure cardiologists to understand prior to implantation of ICD/LVADs in these patients., (© 2017 Wiley Periodicals, Inc.)

Introduction: The β1 adrenergic receptor blocker metoprolol is often prescribed together with the antiarrhythmic drug propafenone. Both are metabolized by cytochrome P450 2D6 and propafenone is also an inhibitor of this enzyme. We present a pediatric case showing metoprolol and propafenone intoxication in combination., Case: A 14-year-old girl was admitted to a local emergency department after ingestion of metoprolol (probably 1g) and propafenone (probably 1.5-3g) in a suicide attempt. She developed cardiogenic shock with cardiac arrest and was fully resuscitated. Veno-arterial femorofemoral extracorporeal membrane oxygenation was started immediately. High serum levels of both drugs were detected approximately 10h after ingestion (2630ng/mL metoprolol and 2500ng/mL propafenone). Other serial samples for the monitoring of the levels of metoprolol and its metabolite alfa-hydroxymetoprolol were obtained between days 2 and 4 after admission. The metoprolol/alfa-hydroxymetoprolol ratio on the 2nd day was 36.1, indicative of a poor metabolizer phenotype. The elimination half-life of metoprolol was prolonged to 13.2h and the clearance decreased by about 70%. The patient condition gradually worsened, brain edema and intracerebral hemorrhage occurred, and on the 6th day, the patient died., Conclusion: We document a pediatric case report of death due to a mixed drug overdose of metoprolol and propafenone, along with data regarding serum metoprolol, alfa-hydroxymetoprolol, and propafenone levels., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Aims: This study assessed the cost-effectiveness of the subcutaneous RANKL inhibitor, denosumab, vs the intravenous bisphosphonate, zoledronic acid, for the prevention of skeletal-related events (SREs) in patients with prostate cancer, breast cancer, and other solid tumors (OST) in the Czech Republic., Materials and Methods: A lifetime Markov model was developed to compare the effects of denosumab and zoledronic acid on costs (including drug costs and administration, patient management, SREs, and adverse events), quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios from a national payer perspective. Different discount rates, time horizons, SRE rates, distributions, and nature (asymptomatic vs all SREs), and the inclusion of treatment discontinuation were considered in scenario analyses. The robustness of the model was tested using deterministic and probabilistic sensitivity analyses., Results: Across tumor types, denosumab was associated with fewer SREs, improved QALYs, and higher total costs over a lifetime. The incremental cost per QALY gained for denosumab vs zoledronic acid was 382,673 CZK for prostate cancer, 408,450 CZK for breast cancer, and 608,133 CZK for OST. Incremental costs per SRE avoided for the same tumor type were 54,007 CZK, 51,765 CZK, and 94,426 CZK, respectively. In scenario analyses, the results remained similar to baseline, when different discount rates and time horizons were considered. At a non-official willingness-to-pay threshold of 1.2 million CZK, the probabilities of denosumab being cost-effective vs zoledronic acid were 0.64, 0.67, and 0.49 for prostate cancer, breast cancer, and OST, respectively., Limitations: The SRE rates used were obtained from clinical trials; studies suggest rates may be higher in clinical practice. Additional evidence on real-world SRE rates could further improve the accuracy of the modeling., Conclusions: Compared with zoledronic acid, denosumab provides a cost-effective treatment option for the prevention of SREs in patients with prostate cancer, breast cancer, and OST in the Czech Republic.

Background: There are limited contemporary data on the safety and efficacy of echo-guided pericardiocentesis following cardiac surgery in Europe. The aim of the study was to review tertiary cardiac surgery center experience with postoperative pericardial effusion (PE) diagnosis and treatment., Methods: A total of 6830 patients underwent open-heart surgery at our center between December 2004 and November 2016. Of these patients, 208 (3%) required pericardiocentesis for significant PE., Results: There was a significant reduction of the incidence of substantial PE requiring pericardiocentesis by use of alternative surgical pericardial cavity drainage system (the accessory Redon drain positioned along the diaphragmatic surface of the heart) compared to conventional retrosternal chest tube drainage (3.3% vs. 2.1%). The rate/relative risk of pericardiocentesis was significantly higher after valve surgery, aortic root and ascending aorta surgery, and surgical ablation of atrial fibrillation-i.e. among patients who had received postoperative anticoagulation therapy. Clinical manifestations of cardiac tamponade were observed in 36% of patients, while progressive large PE without tamponade was evacuated in 41% of patients. Initial echo-guided pericardiocentesis was therapeutically effective in 98.6% of cases, and the rate of major complications was 1%. There was no mortality related to pericardiocentesis. Eighteen patients (8.7%) required repeated pericardiocenteses due to recurrent effusion. Fifteen patients (7.2%) in the pericardiocentesis group required surgery due to recurrent effusion, persistent bleeding, or clotted hemopericardium., Conclusions: Echo-guided pericardiocentesis was very effective and safe method for primary treatment of postoperative PE. Most patients did not require further intervention after this treatment.

The demand for high energy densities has brought rechargeable lithium metal batteries back into the research focus. Ionic liquids (ILs) are considered as suitable electrolyte components for these systems. In this work, the wetting behavior of 1-ethyl-3-methylimidazolium bis((trifluoromethyl)sulfonyl)imide ([C2MIm]TFSI), 1-butyl-3-methylimidazolium bis-((trifluoromethyl)sulfonyl)imide ([C4MIm]TFSI), 1-hexyl-3-methylimidazolium bis((trifluoromethyl)sulfonyl)imide ([C6MIm]TFSI), and N-butyl-N-methylpyrrolidinium bis((trifluoromethyl)sulfonyl)imide (Pyr 14 TFSI) on mechanically modified lithium electrodes, with and without lithium bis((trifluoromethyl)sulfonyl)imide (LiTFSI) conducting salt, is investigated and is compared to an organic carbonate-based electrolyte. Three different patterns were chosen for the lithium modification, enabling a surface area increase of 12%, 20%, and 56% for the modified lithium electrodes. Especially for pure ILs, the contact angle on lithium was significantly larger with higher surface areas of the lithium electrodes. Since the addition of LiTFSI remarkably decreased the contact angles of the ILs on the modified lithium surfaces, it could be shown that the effect of LiTFSI can be attributed to a decreased surface tension. This observation could be explained by an interruption of the ordering of ionic liquid cations and anions, which is supported by Raman spectroscopy and molecular dynamics (MD) simulations.

The next generation of lithium ion batteries (LIBs) with increased energy density for large-scale applications, such as electric mobility, and also for small electronic devices, such as microbatteries and on-chip batteries, requires advanced electrode active materials with enhanced specific and volumetric capacities. In this regard, silicon as anode material has attracted much attention due to its high specific capacity. However, the enormous volume changes during lithiation/delithiation are still a main obstacle avoiding the broad commercial use of Si-based electrodes. In this work, Si-based thin film electrodes, prepared by magnetron sputtering, are studied. Herein, we present a sophisticated surface design and electrode structure modification by amorphous carbon layers to increase the mechanical integrity and, thus, the electrochemical performance. Therefore, the influence of amorphous C thin film layers, either deposited on top (C/Si) or incorporated between the amorphous Si thin film layers (Si/C/Si), was characterized according to their physical and electrochemical properties. The thin film electrodes were thoroughly studied by means of electrochemical impedance spectroscopy, Raman spectroscopy, X-ray photoelectron spectroscopy, and atomic force microscopy. We can show that the silicon thin film electrodes with an amorphous C layer showed a remarkably improved electrochemical performance in terms of capacity retention and Coulombic efficiency. The C layer is able to mitigate the mechanical stress during lithiation of the Si thin film by buffering the volume changes and to reduce the loss of active lithium during solid electrolyte interphase formation and cycling.