Publications by authors named "Jochen Schneider"

156 Publications

Convalescent plasma therapy in B-cell-depleted and B-cell sufficient patients with life-threatening COVID-19 - A case series.

Transfus Apher Sci 2021 Sep 17:103278. Epub 2021 Sep 17.

Technical University of Munich, School of Medicine, University Hospital rechts der Isar, Department of Internal Medicine II, 81675 Munich, Germany. Electronic address:

Objective: To investigate the effect of convalescent plasma therapy (CPT) on clinical courses of B-cell-sufficient and B-cell-depleted patients with life-threatening COVID-19.

Patients And Methods: In this case series, we retrospectively analysed clinical, laboratory and cardiopulmonary parameters of six patients with life-threatening COVID-19 receiving convalescent plasma (CP) as rescue therapy between April 11, 2020 to October 10, 2020. Clinical and laboratory parameters before and after transfusion were compared in two B-cell-depleted patients and four B-cell sufficient patients (control group).

Results: Both B-cell-depleted patients cleared SARS-CoV-2 virus and survived, while all other patients died within 14 days from intervention despite maximal therapeutic efforts. D-dimer levels increased in both cohorts subsequent to CPT. In control patients, mean Interleukin-6 increased and platelet levels decreased as opposed to decreasing and stable levels in B-cell-depleted patients, respectively. Control patients required increased doses of vasopressor compared to decreasing doses in B-cell depleted patients subsequent to CPT. PO/FiO decrease was more pronounced and respiratory deterioration required postinterventional extracorporeal membrane oxygenation in two control patients. Transpulmonary thermodilution revealed a further increase of the Extravascular Lung Water Index upon CPT in control patients.

Conclusion: Use of CP in late stages of life-threatening COVID-19 should be used with caution but may be beneficial in B-cell-depleted patients. Further studies are necessary to assess factors predicting potential therapeutic benefits as well as possible hazards.
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http://dx.doi.org/10.1016/j.transci.2021.103278DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8447834PMC
September 2021

Pre-medication with oral anticoagulants is associated with better outcomes in a large multinational COVID-19 cohort with cardiovascular comorbidities.

Clin Res Cardiol 2021 Sep 21. Epub 2021 Sep 21.

Department of Medicine III (Interdisciplinary Medical Intensive Care), Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany.

Aims: Coagulopathy and venous thromboembolism are common findings in coronavirus disease 2019 (COVID-19) and are associated with poor outcome. Timely initiation of anticoagulation after hospital admission was shown to be beneficial. In this study we aim to examine the association of pre-existing oral anticoagulation (OAC) with outcome among a cohort of SARS-CoV-2 infected patients.

Methods And Results: We analysed the data from the large multi-national Lean European Open Survey on SARS-CoV-2 infected patients (LEOSS) from March to August 2020. Patients with SARS-CoV-2 infection were eligible for inclusion. We retrospectively analysed the association of pre-existing OAC with all-cause mortality. Secondary outcome measures included COVID-19-related mortality, recovery and composite endpoints combining death and/or thrombotic event and death and/or bleeding event. We restricted bleeding events to intracerebral bleeding in this analysis to ensure clinical relevance and to limit reporting errors. A total of 1 433 SARS-CoV-2 infected patients were analysed, while 334 patients (23.3%) had an existing premedication with OAC and 1 099 patients (79.7%) had no OAC. After risk adjustment for comorbidities, pre-existing OAC showed a protective influence on the endpoint death (OR 0.62, P = 0.013) as well as the secondary endpoints COVID-19-related death (OR 0.64, P = 0.023) and non-recovery (OR 0.66, P = 0.014). The combined endpoint death or thrombotic event tended to be less frequent in patients on OAC (OR 0.71, P = 0.056).

Conclusions: Pre-existing OAC is protective in COVID-19, irrespective of anticoagulation regime during hospital stay and independent of the stage and course of disease.
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http://dx.doi.org/10.1007/s00392-021-01939-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8453472PMC
September 2021

Virologic outcomes of switching to boosted darunavir plus dolutegravir with respect to history of drug resistance.

AIDS Res Ther 2021 09 8;18(1):58. Epub 2021 Sep 8.

School of Medicine, University Hospital Rechts Der Isar, Technical University of Munich, Ismaninger Str. 22, 81675, Munich, Germany.

Objective: The DUALIS study showed that switching to boosted darunavir (bDRV) plus dolutegravir (DTG; 2DR) was non-inferior to continuous bDRV plus 2 nucleoside/nucleotide reverse-transcriptase inhibitors (NRTIs; 3DR) in treatment-experienced virologically suppressed people living with HIV (PLWH). We analyzed virologic outcomes with respect to treatment history and HIV drug resistance.

Design: Post hoc analysis of a randomized trial.

Methods: Main inclusion criteria were an HIV RNA level < 50 copies/mL for ≥ 24 weeks and no resistance to integrase strand transfer inhibitors or bDRV. Resistance-associated mutations (RAMs) were interpreted using the Stanford HIVdb mutation list. Outcomes measures were 48-week virologic response (HIV RNA < 50 copies/mL, FDA snapshot) and HIV RNA ≥ 50 copies/mL (including discontinuation due to a lack of efficacy or reasons other than adverse events and HIV RNA ≥ 50 copies/mL, referred to as snapshot non-response).

Results: The analysis population included 263 patients (2DR: 131, 3DR: 132): 90.1% males; median age, 48 years; CD4 + T-cell nadir < 200/µl, 47.0%; ≥ 2 treatment changes, 27.4%; NRTI, non-NRTI (NNRTI), and major protease inhibitor (PI) RAMs in 9.5%, 14.4%, and 3.4%, respectively. In patients with RAMs in the 2DR and 3DR groups, virologic response rates were 87.8% and 96.0%, respectively; the corresponding rates in those without RAMs were 85.7% and 81.8%. RAMs were unrelated to virologic non-response in either group. No treatment-emergent RAMs were observed.

Conclusions: DTG + bDRV is an effective treatment option without the risk of treatment-emergent resistance for PLWH on suppressive first- or further-line treatment with or without evidence of pre-existing NRTI, NNRTI, or PI RAMs.

Trial Registration: EUDRA-CT Number 2015-000360-34; registered 07 April 2015; https://www.clinicaltrialsregister.eu/ctr-search/trial/2015-000360-34/DE .
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http://dx.doi.org/10.1186/s12981-021-00384-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8425038PMC
September 2021

Opportunities of combinatorial thin film materials design for the sustainable development of magnesium-based alloys.

Sci Rep 2021 Aug 31;11(1):17454. Epub 2021 Aug 31.

Materials Chemistry, RWTH Aachen University, Aachen, Germany.

Magnesium-based lightweight structural materials exhibit potential for energy savings. However, the state-of-the-art quest for novel compositions with improved properties through conventional bulk metallurgy is time, energy, and material intensive. Here, the opportunities provided by combinatorial thin film materials design for the sustainable development of magnesium alloys are evaluated. To characterise the impurity level of (Mg,Ca) solid solution thin films within grains and grain boundaries, scanning transmission electron microscopy and atom probe tomography are correlatively employed. It is demonstrated that control of the microstructure enables impurity levels similar to bulk-processed alloys. In order to substantially reduce time, energy, and material requirements for the sustainable development of magnesium alloys, we propose a three-stage materials design strategy: (1) Efficient and systematic investigation of composition-dependent phase formation by combinatorial film growth. (2) Correlation of microstructural features and mechanical properties for selected composition ranges by rapid alloy prototyping. (3) Establishment of synthesis-microstructure-property relationships by conventional bulk metallurgy.
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http://dx.doi.org/10.1038/s41598-021-97036-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8408169PMC
August 2021

Patient-specific effects of soluble factors from Staphylococcus aureus and Staphylococcus epidermidis biofilms on osteogenic differentiation of primary human osteoblasts.

Sci Rep 2021 Aug 26;11(1):17282. Epub 2021 Aug 26.

School of Medicine, Klinikum rechts der Isar, Klinik für Orthopädie und Sportorthopädie, Technische Universität München, Munchen, Germany.

Due to the frequency of biofilm-forming Staphylococcus aureus and Staphylococcus epidermidis in orthopedics, it is crucial to understand the interaction between the soluble factors produced by prokaryotes and their effects on eukaryotes. Our knowledge concerning the effect of soluble biofilm factors (SBF) and their virulence potential on osteogenic differentiation is limited to few studies, particularly when there is no direct contact between prokaryotic and eukaryotic cells. SBF were produced by incubating biofilm from S. aureus and S. epidermidis in osteogenic media. Osteoblasts of seven donors were included in this study. Our results demonstrate that the detrimental effects of these pathogens do not require direct contact between prokaryotic and eukaryotic cells. SBF produced by S. aureus and S. epidermidis affect the metabolic activity of osteoblasts. However, the effect of SBF derived from S. aureus seems to be more pronounced compared to that of S. epidermidis. The influence of SBF of S. aureus and S. epidermidis on gene expression of COL1A1, ALPL, BGLAP, SPP1, RUNX2 is bacteria-, patient-, concentration-, and incubation time dependent. Mineralization was monitored by staining the calcium and phosphate deposition and revealed that the SBF of S. epidermidis markedly inhibits calcium deposition; however, S. aureus shows a less inhibitory effect. Therefore, these new findings support the hypotheses that soluble biofilm factors affect the osteogenic processes substantially, particularly when there is no direct interaction between bacteria and osteoblast.
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http://dx.doi.org/10.1038/s41598-021-96719-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8390505PMC
August 2021

Osteocalcin Is Independently Associated with C-Reactive Protein during Lifestyle-Induced Weight Loss in Metabolic Syndrome.

Metabolites 2021 Aug 9;11(8). Epub 2021 Aug 9.

Institute of Laboratory Medicine, Clinical Chemistry and Molecular Diagnostics, University of Leipzig, 04103 Leipzig, Germany.

Bone-derived osteocalcin has been suggested to be a metabolic regulator. To scrutinize the relation between osteocalcin and peripheral insulin sensitivity, we analyzed changes in serum osteocalcin relative to changes in insulin sensitivity, low-grade inflammation, and bone mineral density following lifestyle-induced weight loss in individuals with metabolic syndrome (MetS). Participants with MetS were randomized to a weight loss program or to a control group. Before and after the 6-month intervention period, clinical and laboratory parameters and serum osteocalcin levels were determined. Changes in body composition were analyzed by dual-energy X-ray absorptiometry (DXA). In participants of the intervention group, weight loss resulted in improved insulin sensitivity and amelioration of inflammation. Increased serum levels of osteocalcin correlated inversely with BMI (r = -0.63; 0.001), total fat mass (r = -0.58, < 0.001), total lean mass (r = -0.45, < 0.001), C-reactive protein (CRP) (r = -0.37; < 0.01), insulin (r = -0.4; < 0.001), leptin (r = -0.53; < 0.001), triglycerides (r = -0.42; < 0.001), and alanine aminotransferase (ALAT) (r = -0.52; < 0.001). Regression analysis revealed that osteocalcin was independently associated with changes in CRP but not with changes in insulin concentration, fat mass, or bone mineral density, suggesting that weight loss-induced higher serum osteocalcin is primarily associated with reduced inflammation.
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http://dx.doi.org/10.3390/metabo11080526DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8400285PMC
August 2021

Efficacy of therapeutic fasting and plant-based diet in patients with rheumatoid arthritis (NutriFast): study protocol for a randomised controlled clinical trial.

BMJ Open 2021 08 11;11(8):e047758. Epub 2021 Aug 11.

Institute of Social Medicine, Epidemiology and Health Economics, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.

Background: Previous studies have shown beneficial effects of therapeutic fasting and plant-based dietary interventions on disease activity in patients with rheumatoid arthritis (RA) for a duration of up to 1 year. To date, the effects of such interventions on the gut microbiome and on modern diagnostic markers in patients with RA have not been studied. This trial aims to investigate the clinical effects of therapeutic fasting and a plant-based diet in patients with RA, additionally considering current immunological diagnostic tools and microbiome analyses.

Methods/design: This trial is an open-label, single-centre, randomised, controlled, parallel-group clinical trial. We will randomly assign 84 patients with RA under a stable standard therapy to either (1) therapeutic fasting followed by a plant-based dietary intervention or (2) to a conventional nutritional counselling focusing on an anti-inflammatory dietary pattern according to the recommendations of the Deutsche Gesellschaft für Ernährung (German society for nutrition). Primary outcome parameter is the group difference from baseline to 12 weeks on the Health Assessment Questionnaire (HAQ). Other secondary outcomes include established clinical criteria for disease activity and treatment response in RA (Disease Activity Score 28, Simple Disease Activity Index, ACR-Response Criteria), changes in self-reported health and physical functional ability, mood, stress, quality of life, dietary behaviour via 3-day food records and a modified Food Frequency Questionnaire, body composition, changes in the gut microbiome, metabolomics and cytometric parameters. Outcomes will be assessed at baseline and day 7, after 6 weeks, 12 weeks and after 6 months.

Ethics And Dissemination: Ethical approval to process and analyse data, and to publish the results was obtained through the institutional review board of Charité-Universitätsmedizin Berlin. Results of this trial will be disseminated through peer-reviewed publications and scientific presentations.

Trial Registration Number: NCT03856190.
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http://dx.doi.org/10.1136/bmjopen-2020-047758DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8359474PMC
August 2021

Development and validation of a simplified risk score for the prediction of critical COVID-19 illness in newly diagnosed patients.

J Med Virol 2021 Jul 31. Epub 2021 Jul 31.

Department of Nephrology, School of Medicine, Technical University of Munich, Klinikum rechts der Isar, Munich, Germany.

Scores to identify patients at high risk of progression of coronavirus disease (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), may become instrumental for clinical decision-making and patient management. We used patient data from the multicentre Lean European Open Survey on SARS-CoV-2-Infected Patients (LEOSS) and applied variable selection to develop a simplified scoring system to identify patients at increased risk of critical illness or death. A total of 1946 patients who tested positive for SARS-CoV-2 were included in the initial analysis and assigned to derivation and validation cohorts (n = 1297 and n = 649, respectively). Stability selection from over 100 baseline predictors for the combined endpoint of progression to the critical phase or COVID-19-related death enabled the development of a simplified score consisting of five predictors: C-reactive protein (CRP), age, clinical disease phase (uncomplicated vs. complicated), serum urea, and D-dimer (abbreviated as CAPS-D score). This score yielded an area under the curve (AUC) of 0.81 (95% confidence interval [CI]: 0.77-0.85) in the validation cohort for predicting the combined endpoint within 7 days of diagnosis and 0.81 (95% CI: 0.77-0.85) during full follow-up. We used an additional prospective cohort of 682 patients, diagnosed largely after the "first wave" of the pandemic to validate the predictive accuracy of the score and observed similar results (AUC for the event within 7 days: 0.83 [95% CI: 0.78-0.87]; for full follow-up: 0.82 [95% CI: 0.78-0.86]). An easily applicable score to calculate the risk of COVID-19 progression to critical illness or death was thus established and validated.
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http://dx.doi.org/10.1002/jmv.27252DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8426905PMC
July 2021

Use of monoclonal antibody therapy for nosocomial SARS-CoV-2 infection in patients at high risk for severe COVID-19: experience from a tertiary-care hospital in Germany.

Infection 2021 Jul 9. Epub 2021 Jul 9.

Department of Internal Medicine II, School of Medicine, University Hospital Rechts der Isar, Technical University of Munich, Munich, Germany.

Additional treatment options for coronavirus disease (COVID-19) are urgently needed, particularly for populations at high risk of severe disease. This cross-sectional, retrospective study characterized the outcomes of 43 patients with nosocomial severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection with and without treatment using monoclonal SARS-CoV-2 spike antibodies (bamlanivimab or casirivimab/imdevimab). Our results indicate that treatment with monoclonal antibodies results in a significant decrease in disease progression and mortality when used for asymptomatic patients with early SARS-CoV-2 infection.
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http://dx.doi.org/10.1007/s15010-021-01657-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8269399PMC
July 2021

COVID-19 in Patients Receiving CD20-depleting Immunochemotherapy for B-cell Lymphoma.

Hemasphere 2021 Jul 28;5(7):e603. Epub 2021 Jun 28.

Technical University of Munich, School of Medicine, University Hospital Rechts der Isar, Department of Internal Medicine II, Munich, Germany.

The clinical and immunological impact of B-cell depletion in the context of coronavirus disease 2019 (COVID-19) is unclear. We conducted a prospectively planned analysis of COVID-19 in patients who received B-cell depleting anti-CD20 antibodies and chemotherapy for B-cell lymphomas. The control cohort consisted of age- and sex-matched patients without lymphoma who were hospitalized because of COVID-19. We performed detailed clinical analyses, in-depth cellular and molecular immune profiling, and comprehensive virological studies in 12 patients with available biospecimens. B-cell depleted lymphoma patients had more severe and protracted clinical course (median hospitalization 88 versus 17 d). All patients actively receiving immunochemotherapy (n = 5) required ICU support including long-term mechanical ventilation. Neutrophil recovery following granulocyte colony stimulating factor stimulation coincided with hyperinflammation and clinical deterioration in 4 of the 5 patients. Immune cell profiling and gene expression analysis of peripheral blood mononuclear cells revealed early activation of monocytes/macrophages, neutrophils, and the complement system in B-cell depleted lymphoma patients, with subsequent exacerbation of the inflammatory response and dysfunctional interferon signaling at the time of clinical deterioration of COVID-19. Longitudinal immune cell profiling and functional in vitro assays showed SARS-CoV-2-specific CD8 and CD4 T-effector cell responses. Finally, we observed long-term detection of SARS-CoV-2 in respiratory specimens (median 84 versus 12 d) and an inability to mount lasting SARS-CoV-2 antibody responses in B-cell depleted lymphoma patients. In summary, we identified clinically relevant particularities of COVID-19 in lymphoma patients receiving B-cell depleting immunochemotherapies.
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http://dx.doi.org/10.1097/HS9.0000000000000603DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8240782PMC
July 2021

β3-integrin Leu33Pro gain of function variant does not modulate inflammatory activity in human derived macrophages in diabetes.

Int J Med Sci 2021 13;18(12):2661-2665. Epub 2021 May 13.

Saarland University, Medical Center, Dpt. of Internal Medicine II, Homburg, Saar, Germany.

: We aimed to investigate the association between the Leu33Pro (rs5918) polymorphism in β3-integrin with diabetic complications and inflammatory function of macrophages depending on the genotype in subjects with diabetes mellitus. We determined the Leu33Pro polymorphism in 186 diabetic subjects and collected laboratory data. Monocytes from 24 patients were collected for macrophage differentiation to determine the inflammatory activity by treating with different stimulants. We could demonstrate that human derived differentiated macrophages expressed β3‑integrin. Their secretory capacity upon inflammatory stimulation did not reveal any differences depending on the Leu33Pro variant. We found trends for an association of the polymorphism with the presence of diabetic nephropathy (), as well as with creatinine [1.32 mg/dL (1) vs. 0.98 mg/dL (0)] ( in recessive model) and glomerular filtration rate [75.6 ml/min ± 22 vs. 62.3 ml/min ± 25] () as quantitative markers of kidney function. : Despite the expression of β3‑integrin in human macrophages, the Leu33Pro polymorphism in β3‑integrin does not modify the inflammatory response upon stimulation but might play a role in the progression of diabetic nephropathy. Further studies are necessary to substantiate such a hypothesis.
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http://dx.doi.org/10.7150/ijms.55648DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8176178PMC
May 2021

Increased extravascular lung water index (EVLWI) reflects rapid non-cardiogenic oedema and mortality in COVID-19 associated ARDS.

Sci Rep 2021 06 1;11(1):11524. Epub 2021 Jun 1.

Department of Internal Medicine II, School of Medicine, University Hospital Rechts Der Isar, Technical University of Munich, Ismaninger Straße 22, 81675, Munich, Germany.

Nearly 5% of patients suffering from COVID-19 develop acute respiratory distress syndrome (ARDS). Extravascular lung water index (EVLWI) is a marker of pulmonary oedema which is associated with mortality in ARDS. In this study, we evaluate whether EVLWI is higher in patients with COVID-19 associated ARDS as compared to COVID-19 negative, ventilated patients with ARDS and whether EVLWI has the potential to monitor disease progression. EVLWI and cardiac function were monitored by transpulmonary thermodilution in 25 patients with COVID-19 ARDS subsequent to intubation and compared to a control group of 49 non-COVID-19 ARDS patients. At intubation, EVLWI was noticeably elevated and significantly higher in COVID-19 patients than in the control group (17 (11-38) vs. 11 (6-26) mL/kg; p < 0.001). High pulmonary vascular permeability index values (2.9 (1.0-5.2) versus 1.9 (1.0-5.2); p = 0.003) suggested a non-cardiogenic pulmonary oedema. By contrast, the cardiac parameters SVI, GEF and GEDVI were comparable in both cohorts. High EVLWI values were associated with viral persistence, prolonged intensive care treatment and in-hospital mortality (23.2 ± 6.7% vs. 30.3 ± 6.0%, p = 0.025). Also, EVLWI showed a significant between-subjects (r = - 0.60; p = 0.001) and within-subjects correlation (r = - 0.27; p = 0.028) to Horowitz index. Compared to non COVID-19 ARDS, COVID-19 results in markedly elevated EVLWI-values in patients with ARDS. High EVLWI reflects a non-cardiogenic pulmonary oedema in COVID-19 ARDS and could serve as parameter to monitor ARDS progression on ICU.
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http://dx.doi.org/10.1038/s41598-021-91043-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8169693PMC
June 2021

Fecal Metaproteomics Reveals Reduced Gut Inflammation and Changed Microbial Metabolism Following Lifestyle-Induced Weight Loss.

Biomolecules 2021 05 12;11(5). Epub 2021 May 12.

Bioprocess Engineering, Otto von Guericke University, Universitätsplatz 2, 39106 Magdeburg, Germany.

Gut microbiota-mediated inflammation promotes obesity-associated low-grade inflammation, which represents a hallmark of metabolic syndrome. To investigate if lifestyle-induced weight loss (WL) may modulate the gut microbiome composition and its interaction with the host on a functional level, we analyzed the fecal metaproteome of 33 individuals with metabolic syndrome in a longitudinal study before and after lifestyle-induced WL in a well-defined cohort. The 6-month WL intervention resulted in reduced BMI (-13.7%), improved insulin sensitivity (HOMA-IR, -46.1%), and reduced levels of circulating hsCRP (-39.9%), indicating metabolic syndrome reversal. The metaprotein spectra revealed a decrease of human proteins associated with gut inflammation. Taxonomic analysis revealed only minor changes in the bacterial composition with an increase of the families Desulfovibrionaceae, Leptospiraceae, Syntrophomonadaceae, Thermotogaceae and Verrucomicrobiaceae. Yet we detected an increased abundance of microbial metaprotein spectra that suggest an enhanced hydrolysis of complex carbohydrates. Hence, lifestyle-induced WL was associated with reduced gut inflammation and functional changes of human and microbial enzymes for carbohydrate hydrolysis while the taxonomic composition of the gut microbiome remained almost stable. The metaproteomics workflow has proven to be a suitable method for monitoring inflammatory changes in the fecal metaproteome.
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http://dx.doi.org/10.3390/biom11050726DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8150863PMC
May 2021

Reconvalescent plasma/camostat mesylate in early SARS-CoV-2 Q-PCR positive high-risk individuals (RES-Q-HR): a structured summary of a study protocol for a randomized controlled trial.

Trials 2021 May 17;22(1):343. Epub 2021 May 17.

Department of Gastroenterology, Hepatology and Infectious Diseases, University Hospital Duesseldorf, Medical Faculty Heinrich-Heine-University Duesseldorf, Moorenstr. 5, D-40225, Duesseldorf, Germany.

Objectives: Currently, there are no approved treatments for early disease stages of COVID-19 and few strategies to prevent disease progression after infection with SARS-CoV-2. The objective of this study is to evaluate the safety and efficacy of convalescent plasma (CP) or camostat mesylate administered within 72 h of diagnosis of SARS-CoV-2 infection in adult individuals with pre-existing risk factors at higher risk of getting seriously ill with COVID-19. Camostat mesylate acts as an inhibitor of the host cell serine protease TMPRSS2 and prevents the virus from entering the cell. CP represents another antiviral strategy in terms of passive immunization. The working hypothesis to be tested in the RES-Q-HR study is that the early use of CP or camostat mesylate reduces the likelihood of disease progression to (modified) WHO stages 4b-8 in SARS-CoV-2-positive adult patients at high risk of moderate or severe COVID-19 progression.

Trial Design: This study is a 4-arm (parallel group), multicenter, randomized (2:2:1:1 ratio), partly double-blind, controlled trial to evaluate the safety and efficacy of convalescent plasma (CP) or camostat mesylate with control or placebo in adult patients diagnosed with SARS-CoV-2 infection and high risk for progression to moderate/severe COVID-19. Superiority of the intervention arms will be tested.

Participants: The trial is conducted at 10-15 tertiary care centers in Germany. Individuals aged 18 years or above with ability to provide written informed consent with SARS-CoV-2 infection, confirmed by PCR within 3 days or less before enrolment and the presence of at least one SARS-CoV-2 symptom (such as fever, cough, shortness of breath, sore throat, headache, fatigue, smell/and or taste disorder, diarrhea, abdominal symptoms, exanthema) and symptom duration of not more than 3 days. Further inclusion criteria comprise: Presence of at least one of the following criteria indicating increased risk for severe COVID-19: Age > 75 years Chronic obstructive pulmonary disease (COPD) and/or pulmonary fibrosis BMI > 40 kg/m Age > 65 years with at least one other risk factor (BMI > 35 kg/m, coronary artery disease (CAD), chronic kidney disease (CKD) with GFR < 60 ml/min but ≥ 30 ml/min, diabetes mellitus, active tumor disease) BMI > 35 kg/m with at least one other risk factor (CAD, CKD with GFR < 60 ml/min but ≥ 30 ml/min, diabetes mellitus, active tumor disease) Exclusion criteria: 1. Age < 18 years 2. Unable to give informed consent 3. Pregnant women or breastfeeding mothers 4. Previous transfusion reaction or other contraindication to a plasma transfusion 5. Known hypersensitivity to camostat mesylate and/or severe pancreatitis 6. Volume stress due to CP administration would be intolerable 7. Known IgA deficiency 8. Life expectancy < 6 months 9. Duration SARS-CoV-2 typical symptoms > 3 days 10. SARS-CoV-2 PCR detection older than 3 days 11. SARS-CoV-2 associated clinical condition ≥ WHO stage 3 (patients hospitalized for other reasons than COVID-19 may be included if they fulfill all inclusion and none of the exclusion criteria) 12. Previously or currently hospitalized due to SARS-CoV-2 13. Previous antiviral therapy for SARS-CoV-2 14. ALT or AST > 5 x ULN at screening 15. Liver cirrhosis > Child A (patients with Child B/C cirrhosis are excluded from the trial) 16. Chronic kidney disease with GFR < 30 ml/min 17. Concurrent or planned anticancer treatment during trial period 18. Accommodation in an institution due to legal orders (§40(4) AMG). 19. Any psycho-social condition hampering compliance with the study protocol. 20. Evidence of current drug or alcohol abuse 21. Use of other investigational treatment within 5 half-lives of enrolment is prohibited 22. Previous use of convalescent plasma for COVID-19 23. Concomitant proven influenza A infection 24. Patients with organ or bone marrow transplant in the three months prior to screening visit INTERVENTION AND COMPARATOR: Participants will be randomized to the following 4 groups: 1) Convalescent plasma (CP), 2 units at screening/baseline visit (day 0) or day 1; CP is defined by the presence of neutralizing anti-SARS-CoV-2 antibodies with titers ≥ 1:160; individuals with body weight ≥ 150 kg will receive a third unit of plasma on day 3 2) Camostat mesylate (200 mg per capsule, one capsule taken each in the morning, afternoon and evening on days 1-7) 3) Standard of care (SOC, control for CP) 4) Placebo (identical in appearance to camostat mesylate capsules, one capsule taken each morning, afternoon and evening on days 1-7; for camostat mesylate control group) Participants will be monitored after screening/baseline on day 3, day 5, day 8, and day 14. On day 28 and day 56, telephone visits and on day 90, another outpatient visit are scheduled. Adverse events and serious adverse events will be monitored and reported until the end of the study. An independent data safety monitoring committee will review trial progression and safety.

Main Outcomes: The primary endpoint of the study is the cumulative number of individuals who progress to or beyond category 4b on the modified WHO COVID-19 ordinal scale (defined as hospitalization with COVID-19 pneumonia and additional oxygen demand via nasal cannula or mask) within 28 days after randomization.

Randomization: Participants will be randomized using the Alea-Tool ( aleaclinical.com ) in a 2:2:1:1 ratio to the treatment arms (1) CP, (2) camostat mesylate, (3) standard of care (SoC), and (4) placebo matching camostat mesylate. Randomization will be stratified by study center.

Blinding (masking): The camostat mesylate treatment arm and the respective placebo will be blinded for participants, caregivers, and those assessing outcomes. The treatment arms convalescent plasma and standard of care will not be blinded and thus are open-labeled, unblinded.

Numbers To Be Randomized (sample Size): Overall, n = 994 participants will be randomized to the following groups: n = 331 to convalescent plasma (CP), n = 331 to camostat mesylate, n = 166 to standard of care (SoC), and n = 166 to placebo matching camostat mesylate.

Trial Status: The RES-Q-HR protocol (V04F) was approved on the 18 December 2020 by the local ethics committee and by the regulatory institutions PEI/BfARM on the 2 December 2020. The trial was opened for recruitment on 26 December 2020; the first patient was enrolled on 7 January 2021 and randomized on 8 January 2021. Recruitment shall be completed by June 2021. The current protocol version RES-Q HR V05F is from 4 January 2021, which was approved on the 18 January 2021.

Trial Registration: EudraCT Number 2020-004695-18 . Registered on September 29, 2020. ClinicalTrial.gov NCT04681430 . Registered on December 23, 2020, prior to the start of the enrollment (which was opened on December 26, 2020).

Full Protocol: The full protocol (V05F) is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this letter serves as a summary of the key elements of the full protocol. The study protocol has been reported in accordance with the Standard Protocol Items: Recommendations for Clinical Interventional Trials (SPIRIT) guidelines (Additional file 2).
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http://dx.doi.org/10.1186/s13063-021-05181-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8127198PMC
May 2021

Self-sampling versus health care professional-guided swab collection for SARS-CoV-2 testing.

Infection 2021 May 10. Epub 2021 May 10.

Department of Internal Medicine II, School of Medicine, University Hospital Rechts der Isar, Technical University of Munich, Ismaninger Str. 22, 81675, Munich, Germany.

Purpose: To evaluate the diagnostic reliability and practicability of self-collected oropharyngeal swab samples for the detection of SARS-CoV-2 infection as self-sampling could enable broader testing availability and reduce both personal protective equipment and potential exposure.

Methods: Hospitalized SARS-CoV-2-infected patients were asked to collect two oropharyngeal swabs (SC-OPS1/2), and an additional oropharyngeal swab was collected by a health care professional (HCP-OPS). SARS-CoV-2 PCR testing for samples from 58 participants was performed, with a 48-h delay in half of the self-collected samples (SC-OPS2). The sensitivity, probability of concordance, and interrater reliability were calculated. Univariate and multivariate analyses were performed to assess predictive factors. Practicability was evaluated through a questionnaire.

Results: The test sensitivity for HCP-OPS, SC-OPS1, and SC-OPS2 was 88%, 78%, and 77%, respectively. Combining both SC-OPS results increased the estimated sensitivity to 88%. The concordance probability between HCP-OPS and SC-OPS1 was 77.6% and 82.5% between SC-OPS1 and SC-OPS2, respectively. Of the participants, 69% affirmed performing future self-sampling at home, and 34% preferred self-sampling over HCP-guided testing. Participants with both positive HCP-OPS1 and SC-OPS1 indicating no challenges during self-sampling had more differences in viral load levels between HCP-OPS1 and SC-OPS1 than those who indicated challenges. Increasing disease duration and the presence of anti-SARS-CoV-2-IgG correlated with negative test results in self-collected samples of previously confirmed SARS-CoV-2 positive individuals.

Conclusion: Oropharyngeal self-sampling is an applicable testing approach for SARS-CoV-2 diagnostics. Self-sampling tends to be more effective in early versus late infection and symptom onset, and the collection of two distinct samples is recommended to maintain high test sensitivity.
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http://dx.doi.org/10.1007/s15010-021-01614-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8107404PMC
May 2021

Health-related quality-of-life in people living with HIV after switching to dual therapy with ritonavir-boosted darunavir + dolutegravir: a DUALIS sub-study.

AIDS Care 2021 Apr 25:1-10. Epub 2021 Apr 25.

Department of Psychosomatic Medicine and Psychotherapy, Klinik Barmelweid AG, Barmelweid, Switzerland.

The DUALIS study demonstrated efficacy and safety of switching to dolutegravir plus ritonavir-boosted darunavir (DRV/r) (2DR) as compared to standard-of-care-therapy with two nucleoside reverse transcriptase inhibitors + DRV/r (3DR) in pretreated people living with HIV (PLWH), 48 weeks after switching. This DUALIS sub-study investigates health-related-quality-of-life (HrQoL) in this study-population. The Hospital Anxiety and Depression Scale (HADS) and the Medical Outcome Survey-HIV (MOS-HIV) were used assessing anxiety and depression symptoms, respectively HrQoL. Data were collected at baseline, 4, 24, and 48 weeks after randomization. Outcome scores were dichotomized and used as criteria in longitudinal models identifying differential developments. Odds ratios (ORs) with 95% confidence intervals (CIs) were computed as main measures of effects. ORs<1 indicate better results for HADS, and worse for MOS-HIV scores in the 2DR compared to 3DR group. In total, 263 subjects were randomized and treated (2DR n=131, 3DR n=132; median age 48 years). Significant different progressions could only be found for HADS-Depression scores (OR=.87, 95% CI: .78, .98, =.02). While HADS-Depression scores decreased in the 2DR group, they increased in 3DR group. This sub-study showed no disadvantages regarding HrQoL in PLWH after switching to DTG+DRV/r. Considering lifelong requirements for antiretroviral medication, close attention to HrQL is required.
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http://dx.doi.org/10.1080/09540121.2021.1916873DOI Listing
April 2021

SARS-CoV-2 serology increases diagnostic accuracy in CT-suspected, PCR-negative COVID-19 patients during pandemic.

Respir Res 2021 Apr 23;22(1):119. Epub 2021 Apr 23.

Department of Internal Medicine II, School of Medicine, Technical University of Munich, Munich, Germany.

Background: In the absence of PCR detection of SARS-CoV-2 RNA, accurate diagnosis of COVID-19 is challenging. Low-dose computed tomography (CT) detects pulmonary infiltrates with high sensitivity, but findings may be non-specific. This study assesses the diagnostic value of SARS-CoV-2 serology for patients with distinct CT features but negative PCR.

Methods: IgM/IgG chemiluminescent immunoassay was performed for 107 patients with confirmed (group A: PCR + ; CT ±) and 46 patients with suspected (group B: repetitive PCR-; CT +) COVID-19, admitted to a German university hospital during the pandemic's first wave. A standardized, in-house CT classification of radiological signs of a viral pneumonia was used to assess the probability of COVID-19.

Results: Seroconversion rates (SR) determined on day 5, 10, 15, 20 and 25 after symptom onset (SO) were 8%, 25%, 65%, 76% and 91% for group A, and 0%, 10%, 19%, 37% and 46% for group B, respectively; (p < 0.01). Compared to hospitalized patients with a non-complicated course (non-ICU patients), seroconversion tended to occur at lower frequency and delayed in patients on intensive care units. SR of patients with CT findings classified as high certainty for COVID-19 were 8%, 22%, 68%, 79% and 93% in group A, compared with 0%, 15%, 28%, 50% and 50% in group B (p < 0.01). SARS-CoV-2 serology established a definite diagnosis in 12/46 group B patients. In 88% (8/9) of patients with negative serology > 14 days after symptom onset (group B), clinico-radiological consensus reassessment revealed probable diagnoses other than COVID-19. Sensitivity of SARS-CoV-2 serology was superior to PCR > 17d after symptom onset.

Conclusions: Approximately one-third of patients with distinct COVID-19 CT findings are tested negative for SARS-CoV-2 RNA by PCR rendering correct diagnosis difficult. Implementation of SARS-CoV-2 serology testing alongside current CT/PCR-based diagnostic algorithms improves discrimination between COVID-19-related and non-related pulmonary infiltrates in PCR negative patients. However, sensitivity of SARS-CoV-2 serology strongly depends on the time of testing and becomes superior to PCR after the 2 week following symptom onset.
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http://dx.doi.org/10.1186/s12931-021-01717-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8062836PMC
April 2021

An Eschar-like souvenir from a journey to Colombia: Ecthyma gangrenosum as a differential diagnosis of tropical diseases in immunocompromised patients - a case report.

BMC Infect Dis 2021 Apr 12;21(1):344. Epub 2021 Apr 12.

German Center for Infection Research (DZIF), partner site Munich, Munich, Germany.

Background: Ecthyma gangrenosum (EG) is a cutaneous infectious disease characterized by eschar-like skin ulcers typically caused by Pseudomonas aeruginosa. Here, we report a case of relapsing EG in a patient who had returned from a trip to Colombia, thus establishing EG as an important differential diagnosis of tropical diseases, and demonstrating that even long-term antibiotic treatment can result in only partial remission of EG.

Case Presentation: A 77-year-old man with underlying chronic lymphocytic leukemia (CLL) on ibrutinib treatment was admitted because of a superinfected mosquito bite on the left ear and multiple partially necrotic skin lesions disseminated all over the entire body five days after returning from a trip to Colombia. The initial clinical suspicion of a tropical disease (leishmaniosis, systemic mycosis, or others) could not be confirmed. During the diagnostic workup, microbiological cultures of the skin biopsies and bronchoalveolar lavage revealed Pseudomonas aeruginosa, leading to a diagnosis of EG. Initial antibiotic treatment resulted in partial remission. However, the patient had to be re-admitted due to a relapse 3-4 weeks after the first episode. Finally, the patient was successfully treated with a combined approach consisting of antibiotics, recurrent surgical incisions, and administration of immunoglobulins.

Conclusions: In conclusion, EG should be considered as a differential diagnosis in immunosuppressed patients presenting with eschar-like skin ulcers. A combined treatment approach seems to be the best choice to achieve clinical cure and avoid relapse.
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http://dx.doi.org/10.1186/s12879-021-05998-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8042936PMC
April 2021

Treatment of intestinal tuberculosis with small bowel perforation: a case report.

J Med Case Rep 2021 Mar 31;15(1):144. Epub 2021 Mar 31.

Department of Internal Medicine II, School of Medicine, University Hospital rechts der Isar, Technical University of Munich, Munich, Germany.

Background: Diagnosis of intestinal tuberculosis poses a dilemma to physicians due to nonspecific symptoms like abdominal pain, fever, nausea, and a change in bowel habit. In particular, the distinction between inflammatory bowel disease and intestinal tuberculosis remains challenging.

Case Presentation: A 27-year-old man from Colombia presented with fever, night sweats, and progressive lower abdominal pain. Computed tomography revealed a thickening of the bowel wall with a mesenterial lymphadenopathy, ascites ,and a pleural tumor mass. Histology of intestinal and pleural biopsy specimens showed a granulomatous inflammation. Although microscopy and polymerase chain reaction (PCR) for Mycobacterium tuberculosis (MTB) were negative, empirical MTB treatment was initiated on suspicion. Due to a massive post-stenotic atrophied intestinal bowel, MTB medications were administered parenterally in the initial phase of treatment to guarantee adequate systemic resorption. The complicated and critical further course included an intra-abdominal abscess and bowel perforation requiring a split stoma, before the patient could be discharged in good condition after 3 months of in-hospital care.

Conclusions: This case highlights the clinical complexity and diagnostic challenges of intestinal MTB infection. A multidisciplinary team of physicians should be sensitized to a timely diagnosis of this disease, which often mimics inflammation similar to inflammatory bowel disease, other infections, or malignancies. In our case, radiological findings, histological results, and migratory background underpinned the suspected diagnosis and allowed early initiation of tuberculostatic treatment.
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http://dx.doi.org/10.1186/s13256-021-02752-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8011140PMC
March 2021

Invasive pulmonary aspergillosis in critically ill patients with severe COVID-19 pneumonia: Results from the prospective AspCOVID-19 study.

PLoS One 2021 17;16(3):e0238825. Epub 2021 Mar 17.

Klinik und Poliklinik für Innere Medizin II, Klinikum rechts der Isar der Technischen Universität München, Munich, Germany.

Background: Superinfections, including invasive pulmonary aspergillosis (IPA), are well-known complications of critically ill patients with severe viral pneumonia. Aim of this study was to evaluate the incidence, risk factors and outcome of IPA in critically ill patients with severe COVID-19 pneumonia.

Methods: We prospectively screened 32 critically ill patients with severe COVID-19 pneumonia for a time period of 28 days using a standardized study protocol for oberservation of developement of COVID-19 associated invasive pulmonary aspergillosis (CAPA). We collected laboratory, microbiological, virological and clinical parameters at defined timepoints in combination with galactomannan-antigen-detection from nondirected bronchial lavage (NBL). We used logistic regression analyses to assess if COVID-19 was independently associated with IPA and compared it with matched controls.

Findings: CAPA was diagnosed at a median of 4 days after ICU admission in 11/32 (34%) of critically ill patients with severe COVID-19 pneumonia as compared to 8% in the control cohort. In the COVID-19 cohort, mean age, APACHE II score and ICU mortality were higher in patients with CAPA than in patients without CAPA (36% versus 9.5%; p<0.001). ICU stay (21 versus 17 days; p = 0.340) and days of mechanical ventilation (20 versus 15 days; p = 0.570) were not different between both groups. In regression analysis COVID-19 and APACHE II score were independently associated with IPA.

Interpretation: CAPA is highly prevalent and associated with a high mortality rate. COVID-19 is independently associated with invasive pulmonary aspergillosis. A standardized screening and diagnostic approach as presented in our study can help to identify affected patients at an early stage.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0238825PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7968651PMC
March 2021

Mucosal-Associated Invariant T (MAIT) Cells Are Highly Activated and Functionally Impaired in COVID-19 Patients.

Viruses 2021 02 3;13(2). Epub 2021 Feb 3.

Department of Internal Medicine II, University Hospital Rechts der Isar, School of Medicine, Technical University of Munich (TUM), 81675 Munich, Germany.

Coronavirus disease 2019 (COVID-19), caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), comprises mild courses of disease as well as progression to severe disease, characterised by lung and other organ failure. The immune system is considered to play a crucial role for the pathogenesis of COVID-19, although especially the contribution of innate-like T cells remains poorly understood. Here, we analysed the phenotype and function of mucosal-associated invariant T (MAIT) cells, innate-like T cells with potent antimicrobial effector function, in patients with mild and severe COVID-19 by multicolour flow cytometry. Our data indicate that MAIT cells are highly activated in patients with COVID-19, irrespective of the course of disease, and express high levels of proinflammatory cytokines such as IL-17A and TNFα ex vivo. Of note, expression of the activation marker HLA-DR positively correlated with SAPS II score, a measure of disease severity. Upon MAIT cell-specific in vitro stimulation, MAIT cells however failed to upregulate expression of the cytokines IL-17A and TNFα, as well as cytolytic proteins, that is, granzyme B and perforin. Thus, our data point towards an altered cytokine expression profile alongside an impaired antibacterial and antiviral function of MAIT cells in COVID-19 and thereby contribute to the understanding of COVID-19 immunopathogenesis.
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http://dx.doi.org/10.3390/v13020241DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7913667PMC
February 2021

Degree Adjusted Large-Scale Network Analysis Reveals Novel Putative Metabolic Disease Genes.

Biology (Basel) 2021 Feb 3;10(2). Epub 2021 Feb 3.

Systems Biology Group, Department of Life Sciences and Medicine, University of Luxembourg, L-4365 Esch-sur-Alzette, Luxembourg.

A large percentage of the global population is currently afflicted by metabolic diseases (MD), and the incidence is likely to double in the next decades. MD associated co-morbidities such as non-alcoholic fatty liver disease (NAFLD) and cardiomyopathy contribute significantly to impaired health. MD are complex, polygenic, with many genes involved in its aetiology. A popular approach to investigate genetic contributions to disease aetiology is biological network analysis. However, data dependence introduces a bias (noise, false positives, over-publication) in the outcome. While several approaches have been proposed to overcome these biases, many of them have constraints, including data integration issues, dependence on arbitrary parameters, database dependent outcomes, and computational complexity. Network topology is also a critical factor affecting the outcomes. Here, we propose a simple, parameter-free method, that takes into account database dependence and network topology, to identify central genes in the MD network. Among them, we infer novel candidates that have not yet been annotated as MD genes and show their relevance by highlighting their differential expression in public datasets and carefully examining the literature. The method contributes to uncovering connections in the MD mechanisms and highlights several candidates for in-depth study of their contribution to MD and its co-morbidities.
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http://dx.doi.org/10.3390/biology10020107DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7913176PMC
February 2021

Phase Formation and Thermal Stability of Reactively Sputtered YTaO-ZrO Coatings.

Materials (Basel) 2021 Feb 2;14(3). Epub 2021 Feb 2.

Materials Chemistry, RWTH Aachen University, 52074 Aachen, Germany.

YTaZrO coatings with 0 to 44 mol% ZrO were synthesized by sputtering. Phase-pure -YTaO coatings were obtained at a substrate temperature of 900 °C. Alloying with ZrO resulted in the growth of along with -Zr(Y,Ta)O for ≤15 mol%, while for ≥28 mol%, ZrO X-ray diffraction (XRD) phase-pure metastable was formed, which may be caused by small grain sizes and/or kinetic limitations. The former phase region transformed into and and the latter to an and phase region upon annealing to 1300 and 1650 °C, respectively. In addition to and , -YTa(Zr)O phase fractions were observed at room temperature for ZrO contents ≥28 mol% after annealing to 1650 °C. phase fractions increased during in situ heating XRD at 80 °C. At 1650 °C, a reaction with the -AlO substrate resulted in the formation of AlTaO and an Al-Ta-Y-O compound.
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http://dx.doi.org/10.3390/ma14030692DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7867362PMC
February 2021

[Steroids in infection medicine].

Dtsch Med Wochenschr 2021 Feb 29;146(3):162-166. Epub 2021 Jan 29.

Universitätsklinikum Freiburg, Abteilung Infektiologie, Klinik für Innere Medizin II, Freiburg.

Corticosteroids have been found as useful adjunctive therapy in patients with various infections and hyperinflammation-associated disease. They are recommended in practice guidelines for patients with tuberculous and pneumococcal meningitis and patients with immune reconstitution syndrome associated with antiretroviral therapy. A new indication is severe COVID-19. Evidence from clinical trials is insufficient to allow the routine use of steroids among patients with septic shock, community-acquired pneumonia or tuberculous pericarditis.
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http://dx.doi.org/10.1055/a-1302-3530DOI Listing
February 2021

A Proposal for a Composite with Temperature-Independent Thermophysical Properties: HfV-HfVO.

Materials (Basel) 2020 Nov 7;13(21). Epub 2020 Nov 7.

Materials Chemistry, RWTH Aachen University, Kopernikusstr. 10, 52074 Aachen, Germany.

The HfV-HfVO composite is proposed as a material with potentially temperature-independent thermophysical properties due to the combination of anomalously increasing thermoelastic constants of HfV with the negative thermal expansion of HfVO. Based on literature data, the coexistence of both a near-zero temperature coefficient of elasticity and a coefficient of thermal expansion is suggested for a composite with a phase fraction of approximately 30 vol.% HfV and 70 vol.% HfVO. To produce HfV-HfVO composites, two synthesis pathways were investigated: (1) annealing of sputtered HfV films in air to form HfVO oxide on the surface and (2) sputtering of HfVO/HfV bilayers. The high oxygen mobility in HfV is suggested to inhibit the formation of crystalline HfV-HfVO composites by annealing HfV in air due to oxygen-incorporation-induced amorphization of HfV. Reducing the formation temperature of crystalline HfVO from 550 °C, as obtained upon annealing, to 300 °C using reactive sputtering enables the synthesis of crystalline bilayered HfV-HfVO.
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http://dx.doi.org/10.3390/ma13215021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7664386PMC
November 2020

Clinical and Ophthalmological Characteristics of Ocular Syphilis in a Retrospective Tertiary Hospital Cohort.

Sex Transm Dis 2021 06;48(6):436-442

Department of Ophthalmology.

Background: Data on ocular syphilis (OS) and its clinical presentation are currently insufficient. This study aimed to investigate the characteristics of a cohort with a high OS incidence at a university hospital in Germany, focusing on the clinical presentation of OS.

Methods: This single-center cohort study retrospectively analyzed data on 90 patients with 109 episodes of syphilis between 2008 and 2018. Cases of OS were identified and additionally reevaluated through a study-specific secondary assessment by an ophthalmologist specializing in uveitis.

Results: Twenty-three patients (26%) were diagnosed with OS, 16 (70%) of whom were with binocular involvement. Uveitis, especially that of the posterior segment, showed a high prevalence. Lumbar puncture was performed in 20 OS patients (87%), of whom 17 (85% of those with lumbar puncture/74% in total) met the 2018 Centers for Disease Control and Prevention criteria for likely neurosyphilis. Five (22%) of 23 patients had HIV infection, of whom 2 did not receive antiretroviral therapy. The preferred syphilis treatment regimens were benzylpenicillin and ceftriaxone, which yielded favorable serological, clinical, and ophthalmological outcomes.

Conclusions: A high incidence of OS was identified, and physicians should be aware of uveitis as a manifestation of syphilis. Most patients presented with uveitis and syphilis in an early or late latent stage and showed central nervous system involvement.
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http://dx.doi.org/10.1097/OLQ.0000000000001329DOI Listing
June 2021

Effect of the Free Volume on the Electronic Structure of CuZr Metallic Glasses.

Materials (Basel) 2020 Oct 31;13(21). Epub 2020 Oct 31.

Materials Chemistry, RWTH Aachen University, Kopernikusstr 10, D-52074 Aachen, Germany.

While it is accepted that the plastic behavior of metallic glasses is affected by their free volume content, the effect on chemical bonding has not been investigated systematically. According to electronic structure analysis, the overall bond strength is not significantly affected by the free volume content. However, with an increasing free volume content, the average coordination number decreases. Furthermore, the volume fraction of regions containing atoms with a lower coordination number increases. As the local bonding character changes from bonding to anti-bonding with a decreasing coordination number, bonding is weakened in the volume fraction of a lower coordination number. During deformation, the number of strong, short-distance bonds decreases more for free volume-containing samples than for samples without free volume, resulting in additional bond weakening. Therefore, we show that the introduction of free volume causes the formation of volume fractions of a lower coordination number, resulting in weaker bonding, and propose that this is the electronic structure origin of the enhanced plastic behavior reported for glasses containing free volume.
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http://dx.doi.org/10.3390/ma13214911DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7672583PMC
October 2020

Rates of bacterial co-infections and antimicrobial use in COVID-19 patients: a retrospective cohort study in light of antibiotic stewardship.

Eur J Clin Microbiol Infect Dis 2021 Apr 2;40(4):859-869. Epub 2020 Nov 2.

Department of Internal Medicine II, Technical University of Munich, School of Medicine, Munich, Germany.

The coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread worldwide. Bacterial co-infections are associated with unfavourable outcomes in respiratory viral infections; however, microbiological and antibiotic data related to COVID-19 are sparse. Adequate use of antibiotics in line with antibiotic stewardship (ABS) principles is warranted during the pandemic. We performed a retrospective study of clinical and microbiological characteristics of 140 COVID-19 patients admitted between February and April 2020 to a German University hospital, with a focus on bacterial co-infections and antimicrobial therapy. The final date of follow-up was 6 May 2020. Clinical data of 140 COVID-19 patients were recorded: The median age was 63.5 (range 17-99) years; 64% were males. According to the implemented local ABS guidelines, the most commonly used antibiotic regimen was ampicillin/sulbactam (41.5%) with a median duration of 6 (range 1-13) days. Urinary antigen tests for Legionella pneumophila and Streptococcus peumoniae were negative in all cases. In critically ill patients admitted to intensive care units (n = 50), co-infections with Enterobacterales (34.0%) and Aspergillus fumigatus (18.0%) were detected. Blood cultures collected at admission showed a diagnostic yield of 4.2%. Bacterial and fungal co-infections are rare in COVID-19 patients and are mainly prevalent in critically ill patients. Further studies are needed to assess the impact of antimicrobial therapy on therapeutic outcome in COVID-19 patients to prevent antimicrobial overuse. ABS guidelines could help in optimising the management of COVID-19. Investigation of microbial patterns of infectious complications in critically ill COVID-19 patients is also required.
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http://dx.doi.org/10.1007/s10096-020-04063-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7605734PMC
April 2021

A diagnostic algorithm for detection of urinary tract infections in hospitalized patients with bacteriuria: The "Triple F" approach supported by Procalcitonin and paired blood and urine cultures.

PLoS One 2020 22;15(10):e0240981. Epub 2020 Oct 22.

Department of Internal Medicine II, School of Medicine, Technical University of Munich, Munich, Germany.

For acute medicine physicians, distinguishing between asymptomatic bacteriuria (ABU) and clinically relevant urinary tract infections (UTI) is challenging, resulting in overtreatment of ABU and under-recognition of urinary-source bacteraemia without genitourinary symptoms (USB). We conducted a retrospective analysis of ED encounters in a university hospital between October 2013 and September 2018 who met the following inclusion criteria: Suspected UTI with simultaneous collection of paired urinary cultures and blood cultures (PUB) and determination of Procalcitonin (PCT). We sought to develop a simple algorithm based on clinical signs and PCT for the management of suspected UTI. Individual patient presentations were retrospectively evaluated by a clinical "triple F" algorithm (F1 ="fever", F2 ="failure", F3 ="focus") supported by PCT and PUB. We identified 183 ED patients meeting the inclusion criteria. We introduced the term UTI with systemic involvement (SUTI) with three degrees of diagnostic certainty: bacteremic UTI (24.0%; 44/183), probable SUTI (14.2%; 26/183) and possible SUTI (27.9%; 51/183). In bacteremic UTI, half of patients (54.5%; 24/44) presented without genitourinary symptoms. Discordant bacteraemia was diagnosed in 16 patients (24.6% of all bacteremic patients). An alternative focus was identified in 67 patients, five patients presented with S. aureus bacteremia. 62 patients were diagnosed with possible UTI (n = 20) or ABU (n = 42). Using the proposed "triple F" algorithm, dichotomised PCT of < 0.25 pg/ml had a negative predictive value of 88.7% and 96.2% for bacteraemia und accordant bacteraemia respectively. The application of the algorithm to our cohort could have resulted in 33.3% reduction of BCs. Using the diagnostic categories "possible" or "probable" SUTI as a trigger for initiation of antimicrobial treatment would have reduced or streamlined antimicrobial use in 30.6% and 58.5% of cases, respectively. In conclusion, the "3F" algorithm supported by PCT and PUB is a promising diagnostic and antimicrobial stewardship tool.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0240981PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7580978PMC
December 2020

Gene expression profile of CD14 blood monocytes following lifestyle-induced weight loss in individuals with metabolic syndrome.

Sci Rep 2020 10 20;10(1):17855. Epub 2020 Oct 20.

Institute of Laboratory Medicine, Clinical Chemistry and Molecular Diagnostics, University of Leipzig, Leipzig, Germany.

Lifestyle-induced weight loss is regarded as an efficient therapy to reverse metabolic syndrome (MetS) and to prevent disease progression. The objective of this study was to investigate whether lifestyle-induced weight loss modulates gene expression in circulating monocytes. We analyzed and compared gene expression in monocytes (CD14 cells) and subcutaneous adipose tissue biopsies by unbiased mRNA profiling. Samples were obtained before and after diet-induced weight loss in well-defined male individuals in a prospective controlled clinical trial (ICTRP Trial Number: U1111-1158-3672). The BMI declined significantly (- 12.6%) in the treatment arm (N = 39) during the 6-month weight loss intervention. This was associated with a significant reduction in hsCRP (- 45.84%) and circulating CD14 cells (- 21.0%). Four genes were differentially expressed (DEG's) in CD14 cells following weight loss (ZRANB1, RNF25, RB1CC1 and KMT2C). Comparative analyses of paired CD14 monocytes and subcutaneous adipose tissue samples before and after weight loss did not identify common genes differentially regulated in both sample types. Lifestyle-induced weight loss is associated with specific changes in gene expression in circulating CD14 monocytes, which may affect ubiquitination, histone methylation and autophagy.
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http://dx.doi.org/10.1038/s41598-020-74973-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7576128PMC
October 2020
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