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Article ; Online: Serum KL-6 as a Candidate Predictor of Outcome in Patients with SARS-CoV-2 Pneumonia

Simone Kattner / Sivagurunathan Sutharsan / Marc Moritz Berger / Andreas Limmer / Lutz-Bernhard Jehn / Frank Herbstreit / Thorsten Brenner / Christian Taube / Francesco Bonella

Journal of Clinical Medicine, Vol 12, Iss 21, p

2023 Volume 6772

Abstract: Severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2)-infection is associated with an extremely variable disease course. When interstitial pneumonia (IP) occurs, it can lead to acute respiratory distress syndrome and death. Serum Krebs von ... ...

Abstract	Severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2)-infection is associated with an extremely variable disease course. When interstitial pneumonia (IP) occurs, it can lead to acute respiratory distress syndrome and death. Serum Krebs von den Lungen-6 (KL-6) is an established marker of IP, but its role as a marker of SARS-CoV-2 pneumonia is debated. This bicentric study included 157 patients with SARS-CoV-2 pneumonia. The WHO Ordinal Scale for Clinical Improvement (0–10 points) was used to classify the clinical course. Serum samples were collected at admission, and on days 3 and 7 of hospitalization. KL-6 was measured by using automated chemiluminescence immunoassay. A total of 68 patients developed a severe SARS-CoV-2 pneumonia, 135 of them required oxygen, and 15 died during hospitalization. The patients requiring non-invasive ventilation, invasive ventilation, or extracorporeal membrane oxygenation had significantly higher serum KL-6 levels at admission. The serum KL-6 levels were tendentially higher in patients who died than in those who survived. Logistic regression identified serum KL-6 at a cut-off of 335 U/mL at admission as a significant predictor of severe SARS-CoV-2 pneumonia outcome. Serum KL-6 seems to be a candidate biomarker for the clinical routine to stratify patients with SARS-CoV-2 pneumonia for the risk of a severe disease outcome or death.
Keywords	KL-6 ; COVID-19 ; SARS-CoV-2 pneumonia ; biomarker ; disease outcome ; Medicine ; R
Subject code	610
Language	English
Publishing date	2023-10-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Targeting the Granulocytic Defense against A. fumigatus in Healthy Volunteers and Septic Patients

Stefanie Michel / Lisa Kirchhoff / Peter-Michael Rath / Jansje Schwab / Karsten Schmidt / Thorsten Brenner / Simon Dubler

International Journal of Molecular Sciences, Vol 24, Iss 9911, p

2023 Volume 9911

Abstract: Neutrophil granulocytes (NGs) are among the key players in the defense against Aspergillus fumigatus ( A. fumigatus ). To better elucidate a pathophysiological understanding of their role and functions, we applied a human cell model using NGs from ... ...

Abstract	Neutrophil granulocytes (NGs) are among the key players in the defense against Aspergillus fumigatus ( A. fumigatus ). To better elucidate a pathophysiological understanding of their role and functions, we applied a human cell model using NGs from healthy participants and septic patients to evaluate their inhibitory effects on the growth of A. fumigatus ex vivo. Conidia of A. fumigatus (ATCC ® 204305) were co-incubated with NGs from healthy volunteers or septic patients for 16 h. A. fumigatus growth was measured by XTT assays with a plate reader. The inhibitory effect of NGs on 18 healthy volunteers revealed great heterogeneity. Additionally, growth inhibition was significantly stronger in the afternoon than the morning, due to potentially different cortisol levels. It is particularly interesting that the inhibitory effect of NGs was reduced in patients with sepsis compared to healthy controls. In addition, the magnitude of the NG-driven defense against A. fumigatus was highly variable among healthy volunteers. Moreover, daytime and corresponding cortisol levels also seem to have a strong influence. Most interestingly, preliminary experiments with NGs from septic patients point to a strongly diminished granulocytic defense against Aspergillus spp.
Keywords	invasive pulmonary aspergillosis ; Aspergillus fumigatus ; neutrophil granulocyte ; critically ill ; cortisol ; host-pathogen interactions ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Subject code	610
Language	English
Publishing date	2023-06-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Characteristics of Critically Ill Patients with COVID-19 Compared to Patients with Influenza—A Single Center Experience

Frank Herbstreit / Marvin Overbeck / Marc Moritz Berger / Annabell Skarabis / Thorsten Brenner / Karsten Schmidt

Journal of Clinical Medicine, Vol 10, Iss 2056, p

2021 Volume 2056

Abstract: Infections with SARS-CoV-2 spread worldwide early in 2020. In previous winters, we had been treating patients with seasonal influenza. While creating a larger impact on the health care systems, comparisons regarding the intensive care unit (ICU) courses ... ...

Abstract	Infections with SARS-CoV-2 spread worldwide early in 2020. In previous winters, we had been treating patients with seasonal influenza. While creating a larger impact on the health care systems, comparisons regarding the intensive care unit (ICU) courses of both diseases are lacking. We compared patients with influenza and SARS-CoV-2 infections treated at a tertiary care facility offering treatment for acute respiratory distress syndrome (ARDS) and being a high-volume facility for extracorporeal membrane oxygenation (ECMO). Patients with COVID-19 during the first wave of the pandemic ( n = 64) were compared to 64 patients with severe influenza from 2016 to 2020 at our ICU. All patients were treated using a standardized protocol. ECMO was used in cases of severe ARDS. Both groups had similar comorbidities. Time in ICU and mortality were not significantly different, yet mortality with ECMO was high amongst COVID-19 patients with approximately two-thirds not surviving. This is in contrast to a mortality of less than 40% in influenza patients with ECMO. Mortality was higher than estimated by SAPSII score on admission in both groups. Patients with COVID-19 were more likely to be male and non-smokers than those with influenza. The outcomes for patients with severe disease were similar. The study helps to understand similarities and differences between patients treated for severe influenza infections and COVID-19.
Keywords	COVID-19 ; SARS-CoV-2 ; Influenza ; intensive Care ; ECMO ; Medicine ; R
Subject code	610 ; 616
Language	English
Publishing date	2021-05-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Pre-Liver Transplant ROTEM™ Clot Lysis Index Is Associated with 30-Day Mortality, But Is Not a Measure for Fibrinolysis

Matthias Hartmann / Bogdan Craciun / Andreas Paul / Thorsten Brenner / Fuat H. Saner

Journal of Clinical Medicine, Vol 9, Iss 3298, p

2020 Volume 3298

Abstract: Complex alterations of the coagulation system in end stage liver disease lead to an increased risk of bleeding and mortality. In the present study, we investigated; 1. the association of pre-liver transplant rotational thrombelastometry (ROTEM™) ... ...

Abstract	Complex alterations of the coagulation system in end stage liver disease lead to an increased risk of bleeding and mortality. In the present study, we investigated; 1. the association of pre-liver transplant rotational thrombelastometry (ROTEM™) variables with bleeding as well as 30-day-mortality and 2. the underlying pathophysiology. After approval from the local ethics committee, rotational thrombelastometry variables, conventional laboratory coagulation values, MELD score (model of end-stage liver disease), red blood cell loss, blood product use, coagulation factors, underlying disease, and demographic data were retrospectively analysed. Pre-transplant thrombelastometry clot lysis index (CLI) and MELD were the only variables associated with mortality, bleeding and blood product use, respectively. Mortality was 4.2%, when CLI was <85%, and increased to 25.7% when the CLI was >95%. Multivariate analysis including CLI and MELD score identified the CLI as an independent and the best predictor of 30-day-mortality. Interestingly, the inhibition of fibrinolysis did neither affect CLI nor the association of the variable with mortality. Thus, fibrinolysis can be excluded as the reason for low CLI values. In conclusion, low CLI values measured before the beginning of liver transplantation are associated with reduced bleeding and mortality, but do not indicate fibrinolysis.
Keywords	liver transplantation ; ROTEM™ ; clot lysis index ; fibrinolysis ; Medicine ; R
Subject code	610 ; 310
Language	English
Publishing date	2020-10-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Extracellular Vesicles as Possible Plasma Markers and Mediators in Patients with Sepsis-Associated Delirium—A Pilot Study

Konstanze Plaschke / Thorsten Brenner / Mascha O. Fiedler / Tobias Hölle / Maik von der Forst / Robert Christian Wolf / Jürgen Kopitz / Johannes Gebert / Markus A. Weigand

International Journal of Molecular Sciences, Vol 24, Iss 21, p

2023 Volume 15781

Abstract: Patients with sepsis-associated delirium (SAD) show severe neurological impairment, often require an intensive care unit (ICU) stay and have a high risk of mortality. Hence, useful biomarkers for early detection of SAD are urgently needed. Extracellular ... ...

Abstract	Patients with sepsis-associated delirium (SAD) show severe neurological impairment, often require an intensive care unit (ICU) stay and have a high risk of mortality. Hence, useful biomarkers for early detection of SAD are urgently needed. Extracellular vesicles (EVs) and their cargo are known to maintain normal physiology but also have been linked to numerous disease states. Here, we sought to identify differentially expressed proteins in plasma EVs from SAD patients as potential biomarkers for SAD. Plasma EVs from 11 SAD patients and 11 age-matched septic patients without delirium (non-SAD) were isolated by differential centrifugation, characterized by nanoparticle tracking analysis, transmission electron microscopy and Western blot analysis. Differential EV protein expression was determined by mass spectrometry and the resulting proteomes were characterized by Gene Ontology term and between-group statistics. As preliminary results because of the small group size, five distinct proteins showed significantly different expression pattern between SAD and non-SAD patients ( p ≤ 0.05). In SAD patients, upregulated proteins included paraoxonase-1 (PON1), thrombospondin 1 (THBS1), and full fibrinogen gamma chain (FGG), whereas downregulated proteins comprised immunoglobulin (IgHV3) and complement subcomponent (C1QC). Thus, plasma EVs of SAD patients show significant changes in the expression of distinct proteins involved in immune system regulation and blood coagulation as well as in lipid metabolism in this pilot study. They might be a potential indicator for to the pathogenesis of SAD and thus warrant further examination as potential biomarkers, but further research is needed to expand on these findings in longitudinal study designs with larger samples and comprehensive polymodal data collection.
Keywords	plasma extracellular vesicles (EVs) ; sepsis-associated delirium (SAD) ; intensive care unit ; proteomics ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Subject code	610
Language	English
Publishing date	2023-10-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: COVID-19 Co-infection with Legionella pneumophila in 2 Tertiary-Care Hospitals, Germany

Hedda L. Verhasselt / Jan Buer / Jutta Dedy / Renate Ziegler / Joerg Steinmann / Frank Herbstreit / Thorsten Brenner / Peter-Michael Rath

Emerging Infectious Diseases, Vol 27, Iss 5, Pp 1535-

2021 Volume 1537

Abstract: We describe screening results for detection of co-infections with Legionella pneumophila in patients infected with severe acute respiratory syndrome coronavirus 2. In total, 93 patients were tested; 1 was positive (1.1%) for L. pneumophila serogroup 1. ... ...

Abstract	We describe screening results for detection of co-infections with Legionella pneumophila in patients infected with severe acute respiratory syndrome coronavirus 2. In total, 93 patients were tested; 1 was positive (1.1%) for L. pneumophila serogroup 1. Co-infections with L. pneumophila occur in coronavirus disease patients and should not be missed.
Keywords	SARS-CoV-2 ; COVID-19 ; coronavirus ; 2019 novel coronavirus disease ; severe acute respiratory syndrome coronavirus 2 ; zoonoses ; Medicine ; R ; Infectious and parasitic diseases ; RC109-216
Language	English
Publishing date	2021-05-01T00:00:00Z
Publisher	Centers for Disease Control and Prevention
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Recommendations on the structure, personal, and organization of intensive care units

Christian Waydhas / Reimer Riessen / Andreas Markewitz / Florian Hoffmann / Lorenz Frey / Bernd W. Böttiger / Sebastian Brenner / Thorsten Brenner / Teresa Deffner / Matthias M. Deininger / Uwe Janssens / Stefan Kluge / Gernot Marx / Stefan Schwab / Andreas W. Unterberg / Felix Walcher / Thomas van den Hooven

Frontiers in Medicine, Vol

2023 Volume 10

Abstract: BackgroundIntensive care units (ICU) are central facilities of medical care in hospitals world-wide and pose a significant financial burden on the health care system.ObjectivesTo provide guidance and recommendations for the requirements of (infra) ... ...

Abstract	BackgroundIntensive care units (ICU) are central facilities of medical care in hospitals world-wide and pose a significant financial burden on the health care system.ObjectivesTo provide guidance and recommendations for the requirements of (infra)structure, personal, and organization of intensive care units.Design and settingDevelopment of recommendations based on a systematic literature search and a formal consensus process from a group of multidisciplinary and multiprofessional specialists from the German Interdisciplinary Association of Intensive Care and Emergency Medicine (DIVI). The grading of the recommendation follows the report from an American College of Chest Physicians Task Force.ResultsThe recommendations cover the fields of a 3-staged level of intensive care units, a 3-staged level of care with respect to severity of illness, qualitative and quantitative requirements of physicians and nurses as well as staffing with physiotherapists, pharmacists, psychologists, palliative medicine and other specialists, all adapted to the 3 levels of ICUs. Furthermore, proposals concerning the equipment and the construction of ICUs are supplied.ConclusionThis document provides a detailed framework for organizing and planning the operation and construction/renovation of ICUs.
Keywords	intensive care medicine ; personal ; organization ; structural requirements ; quality of care ; recommendation ; Medicine (General) ; R5-920
Subject code	650
Language	English
Publishing date	2023-06-01T00:00:00Z
Publisher	Frontiers Media S.A.
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Generation of potentially inhibitory autoantibodies to ADAMTS13 in coronavirus disease 2019

Adrian A. N. Doevelaar / Martin Bachmann / Bodo Hölzer / Felix S. Seibert / Benjamin J. Rohn / Panagiota Zgoura / Oliver Witzke / Ulf Dittmer / Thorsten Brenner / Krystallenia Paniskaki / Serap Yilmaz / Rita Dittmer / Sonja Schneppenheim / Jochen Wilhelm / Ulrik Stervbo / Nina Babel / Ulrich Budde / Timm H. Westhoff

Scientific Reports, Vol 13, Iss 1, Pp 1-

2023 Volume 8

Abstract: Abstract It has recently been shown that von Willebrand factor (VWF) multimers contribute to immunothrombosis in Coronavirus disease 2019 (COVID-19). Since COVID-19 is associated with an increased risk of autoreactivity, the present study investigates, ... ...

Abstract	Abstract It has recently been shown that von Willebrand factor (VWF) multimers contribute to immunothrombosis in Coronavirus disease 2019 (COVID-19). Since COVID-19 is associated with an increased risk of autoreactivity, the present study investigates, whether the generation of autoantibodies to ADAMTS13 contributes to this finding. In this observational prospective controlled multicenter study blood samples and clinical data of patients hospitalized for COVID-19 were collected from April to November 2020. The study included 156 individuals with 90 patients having confirmed COVID-19 of mild to critical severity. 30 healthy individuals and 36 critically ill ICU patients without COVID-19 served as controls. ADAMTS13 antibodies occurred in 31 (34.4%) COVID-19 patients. Antibodies occurred more often in critically ill COVID-19 patients (55.9%) than non-COVID-19 ICU patients and healthy controls (5.6% and 6.7%; p < 0.001), respectively. Generation of ADAMTS13 antibodies in COVID-19 was associated with lower ADAMTS13 activity (56.5%, interquartile range (IQR) 21.25 vs. 71.5%, IQR 24.25, p = 0.0041), increased disease severity (severe or critical in 90% vs. 62.3%, p = 0.019), and a trend to higher mortality (35.5% vs. 18.6%, p = 0.077). Median time to antibody development was 11 days after first positive SARS-CoV-2-PCR specimen. Gel analysis of VWF multimers resembled the constellation in patients with TTP. The present study demonstrates for the first time, that generation of ADAMTS13 antibodies is frequent in COVID-19, associated with lower ADAMTS13 activity and increased risk of an adverse disease course. These findings provide a rationale to include ADAMTS13 antibodies in the diagnostic workup of SARS-CoV-2 infections.
Keywords	Medicine ; R ; Science ; Q
Subject code	610
Language	English
Publishing date	2023-06-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Next Generation Sequencing of Free Microbial DNA for Rapid Identification of Pathogens in Critically Ill Children with Systemic Inflammatory Response Syndrome (SIRS)

Sarah C. Goretzki / Miriam Schäfer / Burcin Dogan / Nora Bruns / Eva Tschiedel / Peter-Michael Rath / Sebastian Voigt / Silke Grumaz / Petra Horvatek / Stefan Schönberger / Florian Stehling / Thorsten Brenner / Christian Dohna-Schwake

Frontiers in Bioscience-Landmark, Vol 27, Iss 11, p

2022 Volume 302

Abstract: Background: Infections, major surgeries, and hyperinflammatory syndromes are known to trigger Systemic Inflammatory Response Syndrome (SIRS). Discrimination between infectious and noninfectious inflammation often poses a challenge in chronically ill ... ...

Abstract	Background: Infections, major surgeries, and hyperinflammatory syndromes are known to trigger Systemic Inflammatory Response Syndrome (SIRS). Discrimination between infectious and noninfectious inflammation often poses a challenge in chronically ill patients with multiple comorbidities. These patients are routinely treated with a variety of anti-infective medications before a pathogen is identified. With the goal of improving pathogen detection rates and interventions, we evaluated Next Generation Sequencing (NGS) as a highly sensitive and fast means of detecting free microbial DNA in a small amount of serum samples from children with ongoing SIRS. Methods: We describe seven complex pediatric patients of SIRS or prolonged fever (>38.5 °C) >72 hours in which serum samples analyzed by NGS had a major impact on therapy. One patient was analyzed twice. Results: In eight NGS there were six positive results (two bacterial, three viral, one fungal) which were subsequently confirmed by microbiological culture or polymerase chain reaction (PCR) in five of the six NGS. In five of the eight performed NGS, results led to a change of therapy: antibiotic therapy was discontinued in two, escalated in one, an initiated in another; in one an antiviral was administered. Conclusions: NGS may become a valuable addition to infectious disease diagnostics in cases of pediatric SIRS. However, NGS has not yet been validated as a diagnostic method in pediatric as a diagnostic method in pediatric patients and results should therefore be interpreted with caution. Multi-center NGS evaluation studies are currently being planned.
Keywords	sirs ; children ; next generation sequencing ; Biochemistry ; QD415-436 ; Biology (General) ; QH301-705.5
Subject code	610
Language	English
Publishing date	2022-11-01T00:00:00Z
Publisher	IMR Press
Document type	Article ; Online
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Article ; Online: Anesthetic Management during Robotic-Assisted Minimal Invasive Thymectomy Using the Da Vinci System

Ahmed Mohamed / Sharaf-Eldin Shehada / Clemens Aigner / Till Ploenes / Yazan Alnajdawi / Lena Van Brakel / Arjang Ruhparwar / Marcel Hochreiter / Marc Moritz Berger / Thorsten Brenner / Ali Haddad

Journal of Clinical Medicine, Vol 11, Iss 15, p

A Single Center Experience

2022 Volume 4274

Abstract: Background: Robotic-assisted surgery is gaining more adaption in different surgical specialties. The number of patients undergoing robotic-assisted thymectomy is continuously increasing. Such procedures are accompanied by new challenges for ... ...

Abstract	Background: Robotic-assisted surgery is gaining more adaption in different surgical specialties. The number of patients undergoing robotic-assisted thymectomy is continuously increasing. Such procedures are accompanied by new challenges for anesthesiologists. We are presenting our primary anesthesiologic experience in such patients. Methods: This is a retrospective single center study, evaluating 28 patients who presented with thymoma or myasthenia gravis (MG) and undergone minimal invasive robotic-assisted thoracic thymectomy between 01/2020–01/2022. We present our fast-track anesthesia management as a component of the enhanced recovery program and its primary results. Results: Mean patient’s age was 46.8 ± 18.1 years, and the mean height was 173.1 ± 9.3 cm. Two-thirds of patients were female (n = 18, 64.3%). The preoperative mean forced expiratory volume in the first second (FEV1) was 3.8 ± 0.7 L, forced vital capacity (FVC) was 4.7 ± 1.1 L, and the FEV1/FVC ratio was 80.4 ± 5.3%. After the creation of capnomediastinum, central venous pressure and airway pressure have been significantly increased from the baseline values (16.5 ± 4.9 mmHg versus 13.4 ± 5.1 mmHg, p < 0.001 and 23.4 ± 4.4 cmH 2 O versus 19.3 ± 3.9 cmH 2 O, p < 0.001, respectively). Most patients (n = 21, 75%) developed transient arrhythmias episodes with hypotension. All patients were extubated at the end of surgery and discharged awake to the recovery room. The first 16 (57.1%) patients were admitted to the intensive care unit and the last 12 patients were only observed in intermediate care. Postoperatively, one patient developed atelectasis and was treated with non-invasive ventilation therapy. Pneumonia or reintubation was not observed. Finally, no significant difference was observed between MG and thymoma patients regarding analgesics consumption or incidence of complications. Conclusions: Robotic-assisted surgery is a rapidly growing technology with increased adoption in different specialties. Fast-track anesthesia is an important ...
Keywords	thymoma ; myasthenia gravis ; thymectomy ; minimal invasive robotic-assisted surgery ; Medicine ; R
Subject code	616 ; 610
Language	English
Publishing date	2022-07-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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