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Background: Staphylococcus aureus bloodstream infection is treated with at least 14 days of intravenous antimicrobials. We assessed the efficacy and safety of an early switch to oral therapy in patients at low risk for complications related to S aureus bloodstream infection., Methods: In this international, open-label, randomised, controlled, non-inferiority trial done in 31 tertiary care hospitals in Germany, France, the Netherlands, and Spain, adult patients with low-risk S aureus bloodstream infection were randomly assigned after 5-7 days of intravenous antimicrobial therapy to oral antimicrobial therapy or to continue intravenous standard therapy. Randomisation was done via a central web-based system, using permuted blocks of varying length, and stratified by study centre. The main exclusion criteria were signs and symptoms of complicated S aureus bloodstream infection, non-removable foreign devices, and severe comorbidity. The composite primary endpoint was the occurrence of any complication related to S aureus bloodstream infection (relapsing S aureus bloodstream infection, deep-seated infection, and mortality attributable to infection) within 90 days, assessed in the intention-to-treat population by clinical assessors who were masked to treatment assignment. Adverse events were assessed in all participants who received at least one dose of study medication (safety population). Due to slow recruitment, the scientific advisory committee decided on Jan 15, 2018, to stop the trial after 215 participants were randomly assigned (planned sample size was 430 participants) and to convert the planned interim analysis into the final analysis. The decision was taken without knowledge of outcome data, at a time when 126 participants were enrolled. The new sample size accommodated a non-inferiority margin of 10%; to claim non-inferiority, the upper bound of the 95% CI for the treatment difference (stratified by centre) had to be below 10 percentage points. The trial is closed to recruitment and is registered with ClinicalTrials.gov (NCT01792804), the German Clinical trials register (DRKS00004741), and EudraCT (2013-000577-77)., Findings: Of 5063 patients with S aureus bloodstream infection assessed for eligibility, 213 were randomly assigned to switch to oral therapy (n=108) or to continue intravenous therapy (n=105). Mean age was 63·5 (SD 17·2) years and 148 (69%) participants were male and 65 (31%) were female. In the oral switch group, 14 (13%) participants met the primary endpoint versus 13 (12%) in the intravenous group, with a treatment difference of 0·7 percentage points (95% CI -7·8 to 9·1; p=0·013). In the oral switch group, 36 (34%) of 107 participants in the safety population had at least one serious adverse event compared with 27 (26%) of 103 participants in the intravenous group (p=0·29)., Interpretation: Oral switch antimicrobial therapy was non-inferior to intravenous standard therapy in participants with low-risk S aureus bloodstream infection. However, it is necessary to carefully assess patients for signs and symptoms of complicated S aureus bloodstream infection at the time of presentation and thereafter before considering early oral switch therapy., Funding: Deutsche Forschungsgemeinschaft., Translations: For the German, Spanish, French and Dutch translations of the abstract see Supplementary Materials section., Competing Interests: Declaration of interests AJK received funding for this study from the Deutsche Forschungsgemeinschaft and is Chairperson of the German Sepsis Society. HSe received grants or research support from the Bundesministerium für Bildung und Forschung (BMBF) Germany and the German Center for Infection Research, and has been a consultant for Debiopharm, Gilead, MSD, and Shionogi. AS has received grants from Gilead Sciences (IN-ES-540–6089) and Pfizer, consulting fees and lecture honoraria from Pfizer, MSD, Angelini, Shionogi, Gilead, and Menarini, and travel support from Pfizer. JR-B has received grants or research support from the Spanish Network for Research in Infectious Diseases (REIPI RD16/0016/00001) and Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC, CB21/13/00012), Instituto de Salud Carlos III, Spanish Ministry of Science and Innovation, which are co-financed by the European Development Regional Fund. SH received honoraria and travel support from Shionogi, Pfizer, Infectopharm, and AdvanzPharma. NJ reports receiving honoraria for lectures from AbbVie, Bayer, Infectopharm, and Medacta, travel support from Gilead, Pfizer, and Correvio, participation in paid advisory board meetings for MSD, and membership in the steering committee of the German Society of Internal Medicine. SRi received honoraria for lectures from Falk Foundation, Pfizer, bioMérieux, Akademie für Infektionsmedizin, Med Update, streamedup!, and Deutscher Apotheker-Verlag. TW reports receiving honoraria for presentations from AstraZeneca, Advanz, MSD, Pfizer, and Shionogi, grants or research support from BMBF Germany, and travel support from Pfizer. All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Purpose: We analyzed patients' characteristics and hospital admission in Germany's first and second COVID 19 wave., Methods: We include all patients hospitalized with the proven diagnosis COVID 19 admitted to the HELIOS Hospital Krefeld, Germany, in the first wave (n = 84; from 11.03.2020-30.06.2020) and the second wave (n = 344; from 01.07.2020-31.01.2021)., Results: Patients' age, gender and comorbidities were similar with the exception of venous thrombosis in medical history which was more frequent in the first wave (6 % vs 0.3 %, p = p = 0,001). At admission, there were no differences in the results of the initial lab values (c-reactive protein, leucocytes) and blood gas analyses between both groups. Treatment differed in the application of dexamethasone and anticoagulation. In the first wave, nobody received dexamethasone. However, this changed to 52.6 % of patients in the second wave for a mean length of 3.6 ± 4.1 days. Anticoagulation with double standard prophylaxis (2 × 40 mg low molecular heparin, subcutaneous) was applied in 7.1 % of patients in the first wave but 30.2 % (p = 0.002) in the second wave. In the first wave more thromboembolic events were diagnosed after admission (19.0 % vs 7.0 %, p = 0.001). In-hospital death was 26.2 % in the first wave and 15.4 % in the second wave (p = 0.0234). Most deaths were attributed to acute respiratory distress syndrome (ARDS)., Conclusion: Patients' characteristics did not vary in Germany's first and second COVID 19 wave, but anticoagulation and dexamethasone were applied more frequently in the second wave. In addition, there were fewer thromboembolic complications in the second wave., Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commecial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

Lithium ion batteries are essential power sources for mobile electronic devices like cell phones, tablets and increasingly used in the field of electromobility and energy transition. The commonly applied liquid electrolytes in commercial cells contain a conducting salt at relatively high concentration (LiPF 6 , ≥1 mol/L). For analytical battery electrolyte investigations, it is necessary to protect the column and mass spectrometer from salt precipitation and clogging. Thus, dilution of the sample is necessary which results in higher limits of detection and limits of quantification. In this study, a comprehensive online sample preparation approach for reversed phase liquid chromatography with an online-solid phase extraction was developed, which allows higher injections volumes and lower dilution factors. For the method development of the online-solid phase extraction, pristine electrolytes were used with trimethyl phosphate and triethyl phosphate as model substances for organo(fluoro)phosphates with weak and strong retention on the extraction column. Organo(fluoro)phosphates are potential hazardous decomposition products, due to their structural similarity to chemical warfare agents like sarin, and therefore their quantification is beneficial for toxicological assessment. The optimization of chromatographic parameters was performed using electrochemically aged electrolytes. For substance independent quantification with a plasma-based technique, an isocratic separation method was implemented. Using optimized conditions, LiPF 6 could be removed quantitatively and the injection volume was increased up to a factor of 50, while the dilution factor could be decreased up to a factor of ten. Eleven different organo(fluoro)phosphates with an overall concentration of 133 mg/kg were found. Therefore, limit of detection and limit of quantification were improved significantly (LOQ: ≤100 µg kg -1 phosphorus content, LOD: ≤35 µg kg -1 phosphorus content). In summary, a fast online sample preparation for liquid chromatographic investigations of lithium ion battery electrolytes was implemented, validated on electrochemically aged lithium ion battery electrolyte., Competing Interests: Declaration of competing interest 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., (Copyright © 2021. Published by Elsevier B.V.)

We describe a 43-year-old patient with coronavirus disease 2019 who developed a bullous hemorrhagic rash that progressed to necrotic lesions. Histopathology confirmed a vasculitis of small- and medium-sized cutaneous vessels., (© The Author(s) 2020. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Lithium ion batteries are essential power sources in portable electronics, electric vehicles and as energy storage devices for renewable energies. During harsh battery cell operation as well as at elevated temperatures, the electrolyte decomposes and inter alia organo(fluoro)phosphates are formed due to hydrolysis of the conducting salt lithium hexafluorophosphate (LiPF 6 ). Since these phosphorus-containing decomposition products possess a potential toxicity based on structural similarities compared to chemical warfare agents, quantification is of high interest regarding safety estimates. In this study, two comprehensive approaches for the precipitation of highly concentrated PF 6 ¯ were investigated, allowing the separation from target analytes (organo(fluoro)phosphates) and improving mass spectrometry-based quantification techniques. Trimethyl phosphate was used as a polar, non-acidic organophosphate reference substance for method development via liquid chromatography-mass spectrometry. Six solvents were examined regarding precipitation reaction and selectivity. Thermally degraded electrolytes were analyzed after precipitation by means of gas chromatography-flame ionization detector, demonstrating the applicability of the developed sample preparations. The optimized method was applied successfully without influencing any volatile and non-acidic decomposition products. Using optimized conditions, a precipitation rate of 98% PF 6 ¯ was achieved. Consequently, a fast and easy sample preparation for gas chromatographic investigations on lithium ion battery electrolytes was implemented, applicable for routine analysis., Competing Interests: Declaration of Competing Interest There are no conflicts to declare., (Copyright © 2020. Published by Elsevier B.V.)

Aggressive behavior in our modern, civilized society is often counterproductive and destructive. Identifying specific proteins involved in the disease can serve as therapeutic targets for treating aggression. Here, we found that overexpression of RGS2 in explicitly serotonergic neurons augments male aggression in control mice and rescues male aggression in Rgs2 -/- mice, while anxiety is not affected. The aggressive behavior is directly correlated to the immediate early gene c-fos induction in the dorsal raphe nuclei and ventrolateral part of the ventromedial nucleus hypothalamus, to an increase in spontaneous firing in serotonergic neurons and to a reduction in the modulatory action of G i/o and G q/11 coupled 5HT and adrenergic receptors in serotonergic neurons of Rgs2 -expressing mice. Collectively, these findings specifically identify that RGS2 expression in serotonergic neurons is sufficient to drive male aggression in mice and as a potential therapeutic target for treating aggression., Competing Interests: Competing interestsAll authors declare no competing interests., (© The Author(s) 2019.)