@phdthesis{Notz2019, author = {Notz, Quirin Julius}, title = {Der Einfluss von Fingolimod auf die autoreaktive B-Zell-Antwort in einem B-Zell-abh{\"a}ngigen Mausmodell der Multiplen Sklerose}, doi = {10.25972/OPUS-19154}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-191540}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2019}, abstract = {Die MP4-induzierte experimentelle autoimmune Encephalomyelitis (EAE) erlaubt eine fokussierte Betrachtung von B-Zellen, die eine wichtige Rolle bei der Pathogenese der Multiplen Sklerose (MS) spielen. Es konnte zum Beispiel gezeigt werden, dass das Vorhandensein von B-Zell-Aggregaten im zentralen Nervensystem (ZNS) von MS-Patienten mit einem aggravierten Krankheitsverlauf assoziiert war. Diese Follikel k{\"o}nnten dabei als ektope lymphatische Strukturen den Immunprozess aktiv gestalten und somit ein therapeutisches Ziel darstellen. In der vorliegenden Studie wurde der Effekt des Sphingosin-1-Phosphat-Rezeptor-Modulators Fingolimod (FTY720) auf die autoreaktive B-Zell-Antwort und speziell die Bildung von B-Zell-Aggregaten im Kleinhirn der MP4-EAE-M{\"a}use untersucht.}, subject = {Multiple Sklerose}, language = {de} } @article{DresenLeeHilletal.2023, author = {Dresen, Ellen and Lee, Zheng-Yii and Hill, Aileen and Notz, Quirin and Patel, Jayshil J. and Stoppe, Christian}, title = {History of scurvy and use of vitamin C in critical illness: A narrative review}, series = {Nutrition in Clinical Practice}, volume = {38}, journal = {Nutrition in Clinical Practice}, number = {1}, doi = {10.1002/ncp.10914}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-318176}, pages = {46 -- 54}, year = {2023}, abstract = {In 1747, an important milestone in the history of clinical research was set, as the Scottish surgeon James Lind conducted the first randomized controlled trial. Lind was interested in scurvy, a severe vitamin C deficiency which caused the death of thousands of British seamen. He found that a dietary intervention with oranges and lemons, which are rich in vitamin C by nature, was effective to recover from scurvy. Because of its antioxidative properties and involvement in many biochemical processes, the essential micronutrient vitamin C plays a key role in the human biology. Moreover, the use of vitamin C in critical illness—a condition also resulting in death of thousands in the 21st century—has gained increasing interest, as it may restore vascular responsiveness to vasoactive agents, ameliorate microcirculatory blood flow, preserve endothelial barriers, augment bacterial defense, and prevent apoptosis. Because of its redox potential and powerful antioxidant capacity, vitamin C represents an inexpensive and safe antioxidant, with the potential to modify the inflammatory cascade and improve clinical outcomes of critically ill patients. This narrative review aims to update and provide an overview on the role of vitamin C in the human biology and in critically ill patients, and to summarize current evidence on the use of vitamin C in diverse populations of critically ill patients, in specific focusing on patients with sepsis and coronavirus disease 2019.}, language = {en} } @article{SchmidbauerFerseSalihetal.2022, author = {Schmidbauer, Moritz L. and Ferse, Caroline and Salih, Farid and Klingner, Carsten and Musleh, Rita and Kunst, Stefan and Wittstock, Matthias and Neumann, Bernhard and Schebesch, Karl-Michael and B{\"o}sel, Julian and Godau, Jana and Lochner, Piergiorgio and Adam, Elisabeth H. and Jahnke, Kolja and Knier, Benjamin and Schirotzek, Ingo and M{\"u}llges, Wolfgang and Notz, Quirin and Dengl, Markus and G{\"u}ldner, Andreas and Onur, Oezguer A. and Garcia Borrega, Jorge and Dimitriadis, Konstantinos and G{\"u}nther, Albrecht}, title = {COVID-19 and intracranial hemorrhage: a multicenter case series, systematic review and pooled analysis}, series = {Journal of Clinical Medicine}, volume = {11}, journal = {Journal of Clinical Medicine}, number = {3}, issn = {2077-0383}, doi = {10.3390/jcm11030605}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-255236}, year = {2022}, abstract = {Introduction: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) profoundly impacts hemostasis and microvasculature. In the light of the dilemma between thromboembolic and hemorrhagic complications, in the present paper, we systematically investigate the prevalence, mortality, radiological subtypes, and clinical characteristics of intracranial hemorrhage (ICH) in coronavirus disease (COVID-19) patients. Methods: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we performed a systematic review of the literature by screening the PubMed database and included patients diagnosed with COVID-19 and concomitant ICH. We performed a pooled analysis, including a prospectively collected cohort of critically ill COVID-19 patients with ICH, as part of the PANDEMIC registry (Pooled Analysis of Neurologic Disorders Manifesting in Intensive Care of COVID-19). Results: Our literature review revealed a total of 217 citations. After the selection process, 79 studies and a total of 477 patients were included. The median age was 58.8 years. A total of 23.3\% of patients experienced the critical stage of COVID-19, 62.7\% of patients were on anticoagulation and 27.5\% of the patients received ECMO. The prevalence of ICH was at 0.85\% and the mortality at 52.18\%, respectively. Conclusion: ICH in COVID-19 patients is rare, but it has a very poor prognosis. Different subtypes of ICH seen in COVID-19, support the assumption of heterogeneous and multifaceted pathomechanisms contributing to ICH in COVID-19. Further clinical and pathophysiological investigations are warranted to resolve the conflict between thromboembolic and hemorrhagic complications in the future.}, language = {en} } @article{BailNotzRovitusoetal.2017, author = {Bail, Kathrin and Notz, Quirin and Rovituso, Damiano M. and Schampel, Andrea and Wunsch, Marie and Koeniger, Tobias and Schropp, Verena and Bharti, Richa and Scholz, Claus-Juergen and Foerstner, Konrad U. and Kleinschnitz, Christoph and Kuerten, Stefanie}, title = {Differential effects of FTY720 on the B cell compartment in a mouse model of multiple sclerosis.}, series = {Journal of Neuroinflammation}, volume = {14}, journal = {Journal of Neuroinflammation}, number = {148}, doi = {10.1186/s12974-017-0924-4}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-157869}, year = {2017}, abstract = {Background: MP4-induced experimental autoimmune encephalomyelitis (EAE) is a mouse model of multiple sclerosis (MS), which enables targeted research on B cells, currently much discussed protagonists in MS pathogenesis. Here, we used this model to study the impact of the S1P1 receptor modulator FTY720 (fingolimod) on the autoreactive B cell and antibody response both in the periphery and the central nervous system (CNS). Methods: MP4-immunized mice were treated orally with FTY720 for 30 days at the peak of disease or 50 days after EAE onset. The subsequent disease course was monitored and the MP4-specific B cell/antibody response was measured by ELISPOT and ELISA. RNA sequencing was performed to determine any effects on B cell-relevant gene expression. S1P\(_{1}\) receptor expression by peripheral T and B cells, B cell subset distribution in the spleen and B cell infiltration into the CNS were studied by flow cytometry. The formation of B cell aggregates and of tertiary lymphoid organs (TLOs) was evaluated by histology and immunohistochemistry. Potential direct effects of FTY720 on B cell aggregation were studied in vitro. Results: FTY720 significantly attenuated clinical EAE when treatment was initiated at the peak of EAE. While there was a significant reduction in the number of T cells in the blood after FTY720 treatment, B cells were only slightly diminished. Yet, there was evidence for the modulation of B cell receptor-mediated signaling upon FTY720 treatment. In addition, we detected a significant increase in the percentage of B220\(^{+}\) B cells in the spleen both in acute and chronic EAE. Whereas acute treatment completely abrogated B cell aggregate formation in the CNS, the numbers of infiltrating B cells and plasma cells were comparable between vehicle- and FTY720-treated mice. In addition, there was no effect on already developed aggregates in chronic EAE. In vitro B cell aggregation assays suggested the absence of a direct effect of FTY720 on B cell aggregation. However, FTY720 impacted the evolution of B cell aggregates into TLOs. Conclusions: The data suggest differential effects of FTY720 on the B cell compartment in MP4-induced EAE.}, language = {en} } @article{HerrmannAdamNotzetal.2020, author = {Herrmann, Johannes and Adam, Elisabeth Hannah and Notz, Quirin and Helmer, Philipp and Sonntagbauer, Michael and Ungemach-Papenberg, Peter and Sanns, Andreas and Zausig, York and Steinfeldt, Thorsten and Torje, Iuliu and Schmid, Benedikt and Schlesinger, Tobias and Rolfes, Caroline and Reyher, Christian and Kredel, Markus and Stumpner, Jan and Brack, Alexander and Wurmb, Thomas and Gill-Schuster, Daniel and Kranke, Peter and Weismann, Dirk and Klinker, Hartwig and Heuschmann, Peter and R{\"u}cker, Viktoria and Frantz, Stefan and Ertl, Georg and Muellenbach, Ralf Michael and Mutlak, Haitham and Meybohm, Patrick and Zacharowski, Kai and Lotz, Christopher}, title = {COVID-19 Induced Acute Respiratory Distress Syndrome — A Multicenter Observational Study}, series = {Frontiers in Medicine}, volume = {7}, journal = {Frontiers in Medicine}, issn = {2296-858X}, doi = {10.3389/fmed.2020.599533}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-219834}, year = {2020}, abstract = {Background: Proportions of patients dying from the coronavirus disease-19 (COVID-19) vary between different countries. We report the characteristics; clinical course and outcome of patients requiring intensive care due to COVID-19 induced acute respiratory distress syndrome (ARDS). Methods: This is a retrospective, observational multicentre study in five German secondary or tertiary care hospitals. All patients consecutively admitted to the intensive care unit (ICU) in any of the participating hospitals between March 12 and May 4, 2020 with a COVID-19 induced ARDS were included. Results: A total of 106 ICU patients were treated for COVID-19 induced ARDS, whereas severe ARDS was present in the majority of cases. Survival of ICU treatment was 65.0\%. Median duration of ICU treatment was 11 days; median duration of mechanical ventilation was 9 days. The majority of ICU treated patients (75.5\%) did not receive any antiviral or anti-inflammatory therapies. Venovenous (vv) ECMO was utilized in 16.3\%. ICU triage with population-level decision making was not necessary at any time. Univariate analysis associated older age, diabetes mellitus or a higher SOFA score on admission with non-survival during ICU stay. Conclusions: A high level of care adhering to standard ARDS treatments lead to a good outcome in critically ill COVID-19 patients.}, language = {en} } @article{HerrmannNotzSchlesingeretal.2021, author = {Herrmann, Johannes and Notz, Quirin and Schlesinger, Tobias and Stumpner, Jan and Kredel, Markus and Sitter, Magdalena and Schmid, Benedikt and Kranke, Peter and Schulze, Harald and Meybohm, Patrick and Lotz, Christopher}, title = {Point of care diagnostic of hypercoagulability and platelet function in COVID-19 induced acute respiratory distress syndrome: a retrospective observational study}, series = {Thrombosis Journal}, volume = {19}, journal = {Thrombosis Journal}, number = {1}, doi = {10.1186/s12959-021-00293-8}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-260739}, year = {2021}, abstract = {Background Coronavirus disease 2019 (COVID-19) associated coagulopathy (CAC) leads to thromboembolic events in a high number of critically ill COVID-19 patients. However, specific diagnostic or therapeutic algorithms for CAC have not been established. In the current study, we analyzed coagulation abnormalities with point-of-care testing (POCT) and their relation to hemostatic complications in patients suffering from COVID-19 induced Acute Respiratory Distress Syndrome (ARDS). Our hypothesis was that specific diagnostic patterns can be identified in patients with COVID-19 induced ARDS at risk of thromboembolic complications utilizing POCT. Methods This is a single-center, retrospective observational study. Longitudinal data from 247 rotational thromboelastometries (Rotem®) and 165 impedance aggregometries (Multiplate®) were analysed in 18 patients consecutively admitted to the ICU with a COVID-19 induced ARDS between March 12th to June 30th, 2020. Results Median age was 61 years (IQR: 51-69). Median PaO2/FiO2 on admission was 122 mmHg (IQR: 87-189), indicating moderate to severe ARDS. Any form of hemostatic complication occurred in 78 \% of the patients with deep vein/arm thrombosis in 39 \%, pulmonary embolism in 22 \%, and major bleeding in 17 \%. In Rotem® elevated A10 and maximum clot firmness (MCF) indicated higher clot strength. The delta between EXTEM A10 minus FIBTEM A10 (ΔA10) > 30 mm, depicting the sole platelet-part of clot firmness, was associated with a higher risk of thromboembolic events (OD: 3.7; 95 \%CI 1.3-10.3; p = 0.02). Multiplate® aggregometry showed hypoactive platelet function. There was no correlation between single Rotem® and Multiplate® parameters at intensive care unit (ICU) admission and thromboembolic or bleeding complications. Conclusions Rotem® and Multiplate® results indicate hypercoagulability and hypoactive platelet dysfunction in COVID-19 induced ARDS but were all in all poorly related to hemostatic complications..}, language = {en} } @article{NotzLotzHerrmannetal.2021, author = {Notz, Quirin and Lotz, Christopher and Herrmann, Johannes and Vogt, Marius and Schlesinger, Tobias and Kredel, Markus and Muellges, Wolfgang and Weismann, Dirk and Westermaier, Thomas and Meybohm, Patrick and Kranke, Peter}, title = {Severe neurological complications in critically ill COVID‑19 patients}, series = {Journal of Neurology}, journal = {Journal of Neurology}, issn = {0340-5354}, doi = {10.1007/s00415-020-10152-7}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-232429}, pages = {1576-1579}, year = {2021}, abstract = {No abstract available.}, language = {en} } @article{LotzNotzKrankeetal.2020, author = {Lotz, Christopher and Notz, Quirin and Kranke, Peter and Kredel, Markus and Meybohm, Patrick}, title = {Unconventional approaches to mechanical ventilation - step-by-step through the COVID-19 crisis}, series = {Critical Care}, volume = {24}, journal = {Critical Care}, doi = {10.1186/s13054-020-02954-y}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-229868}, year = {2020}, abstract = {No abstract available.}, language = {en} } @article{SchlesingerWeissbrichWedekinketal.2020, author = {Schlesinger, Tobias and Weißbrich, Benedikt and Wedekink, Florian and Notz, Quirin and Herrmann, Johannes and Krone, Manuel and Sitter, Magdalena and Schmid, Benedikt and Kredel, Markus and Stumpner, Jan and D{\"o}lken, Lars and Wischhusen, J{\"o}rg and Kranke, Peter and Meybohm, Patrick and Lotz, Christpher}, title = {Biodistribution and serologic response in SARS-CoV-2 induced ARDS: A cohort study}, series = {PLoS One}, volume = {15, 2020}, journal = {PLoS One}, number = {11}, doi = {10.1371/journal.pone.0242917}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-231348}, year = {2020}, abstract = {Background The viral load and tissue distribution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remain important questions. The current study investigated SARS-CoV-2 viral load, biodistribution and anti-SARS-CoV-2 antibody formation in patients suffering from severe corona virus disease 2019 (COVID-19) induced acute respiratory distress syndrome (ARDS). Methods This is a retrospective single-center study in 23 patients with COVID-19-induced ARDS. Data were collected within routine intensive care. SARS-CoV-2 viral load was assessed via reverse transcription quantitative polymerase chain reaction (RT-qPCR). Overall, 478 virology samples were taken. Anti-SARS-CoV-2-Spike-receptor binding domain (RBD) antibody detection of blood samples was performed with an enzyme-linked immunosorbent assay. Results Most patients (91\%) suffered from severe ARDS during ICU treatment with a 30-day mortality of 30\%. None of the patients received antiviral treatment. Tracheal aspirates tested positive for SARS-CoV-2 in 100\% of the cases, oropharyngeal swabs only in 77\%. Blood samples were positive in 26\% of the patients. No difference of viral load was found in tracheal or blood samples with regard to 30-day survival or disease severity. SARS-CoV-2 was never found in dialysate. Serologic testing revealed significantly lower concentrations of SARS-CoV-2 neutralizing IgM and IgA antibodies in survivors compared to non-survivors (p = 0.009). Conclusions COVID-19 induced ARDS is accompanied by a high viral load of SARS-CoV-2 in tracheal aspirates, which remained detectable in the majority throughout intensive care treatment. Remarkably, SARS-CoV-2 RNA was never detected in dialysate even in patients with RNAemia. Viral load or the buildup of neutralizing antibodies was not associated with 30-day survival or disease severity.}, language = {en} } @article{MengerLeeNotzetal.2022, author = {Menger, Johannes and Lee, Zheng-Yii and Notz, Quirin and Wallqvist, Julia and Hasan, M. Shahnaz and Elke, Gunnar and Dworschak, Martin and Meybohm, Patrick and Heyland, Daren K. and Stoppe, Christian}, title = {Administration of vitamin D and its metabolites in critically ill adult patients: an updated systematic review with meta-analysis of randomized controlled trials}, series = {Critical Care}, volume = {26}, journal = {Critical Care}, number = {1}, doi = {10.1186/s13054-022-04139-1}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-299700}, year = {2022}, abstract = {Background The clinical significance of vitamin D administration in critically ill patients remains inconclusive. The purpose of this systematic review with meta-analysis was to investigate the effect of vitamin D and its metabolites on major clinical outcomes in critically ill patients, including a subgroup analysis based on vitamin D status and route of vitamin D administration. Methods Major databases were searched through February 9, 2022. Randomized controlled trials of adult critically ill patients with an intervention group receiving vitamin D or its metabolites were included. Random-effect meta-analyses were performed to estimate the pooled risk ratio (dichotomized outcomes) or mean difference (continuous outcomes). Risk of bias assessment included the Cochrane tool for assessing risk of bias in randomized trials. Results Sixteen randomized clinical trials with 2449 patients were included. Vitamin D administration was associated with lower overall mortality (16 studies: risk ratio 0.78, 95\% confidence interval 0.62-0.97, p = 0.03; I2 = 30\%), reduced intensive care unit length of stay (12 studies: mean difference - 3.13 days, 95\% CI - 5.36 to - 0.89, n = 1250, p = 0.006; I2 = 70\%), and shorter duration of mechanical ventilation (9 studies: mean difference - 5.07 days, 95\% CI - 7.42 to - 2.73, n = 572, p < 0.0001; I2 = 54\%). Parenteral administration was associated with a greater effect on overall mortality than enteral administration (test of subgroup differences, p = 0.04), whereas studies of parenteral subgroups had lower quality. There were no subgroup differences based on baseline vitamin D levels. Conclusions Vitamin D supplementation in critically ill patients may reduce mortality. Parenteral administration might be associated with a greater impact on mortality. Heterogeneity and assessed certainty among the studies limits the generalizability of the results.}, language = {en} } @article{NotzSchmalzingWedekinketal.2020, author = {Notz, Quirin and Schmalzing, Marc and Wedekink, Florian and Schlesinger, Tobias and Gernert, Michael and Herrmann, Johannes and Sorger, Lena and Weismann, Dirk and Schmid, Benedikt and Sitter, Magdalena and Schlegel, Nicolas and Kranke, Peter and Wischhusen, J{\"o}rg and Meybohm, Patrick and Lotz, Christopher}, title = {Pro- and Anti-Inflammatory Responses in Severe COVID-19-Induced Acute Respiratory Distress Syndrome—An Observational Pilot Study}, series = {Frontiers in Immunology}, volume = {11}, journal = {Frontiers in Immunology}, issn = {1664-3224}, doi = {10.3389/fimmu.2020.581338}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-212815}, year = {2020}, abstract = {Objectives The severity of Coronavirus Disease 2019 (COVID-19) is largely determined by the immune response. First studies indicate altered lymphocyte counts and function. However, interactions of pro- and anti-inflammatory mechanisms remain elusive. In the current study we characterized the immune responses in patients suffering from severe COVID-19-induced acute respiratory distress syndrome (ARDS). Methods This was a single-center retrospective study in patients admitted to the intensive care unit (ICU) with confirmed COVID-19 between March 14th and May 28th 2020 (n = 39). Longitudinal data were collected within routine clinical care, including flow-cytometry of lymphocyte subsets, cytokine analysis and growth differentiation factor 15 (GDF-15). Antibody responses against the receptor binding domain (RBD) of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Spike protein were analyzed. Results All patients suffered from severe ARDS, 30.8\% died. Interleukin (IL)-6 was massively elevated at every time-point. The anti-inflammatory cytokine IL-10 was concomitantly upregulated with IL-6. The cellular response was characterized by lymphocytopenia with low counts of CD8+ T cells, natural killer (NK) and na{\"i}ve T helper cells. CD8+ T and NK cells recovered after 8 to 14 days. The B cell system was largely unimpeded. This coincided with a slight increase in anti-SARS-CoV-2-Spike-RBD immunoglobulin (Ig) G and a decrease in anti-SARS-CoV-2-Spike-RBD IgM. GDF-15 levels were elevated throughout ICU treatment. Conclusions Massively elevated levels of IL-6 and a delayed cytotoxic immune defense characterized severe COVID-19-induced ARDS. The B cell response and antibody production were largely unimpeded. No obvious imbalance of pro- and anti-inflammatory mechanisms was observed, with elevated GDF-15 levels suggesting increased tissue resilience.}, language = {en} } @article{NotzHerrmannSchlesingeretal.2021, author = {Notz, Quirin and Herrmann, Johannes and Schlesinger, Tobias and Helmer, Philipp and Sudowe, Stephan and Sun, Qian and Hackler, Julian and Roeder, Daniel and Lotz, Christopher and Meybohm, Patrick and Kranke, Peter and Schomburg, Lutz and Stoppe, Christian}, title = {Clinical Significance of Micronutrient Supplementation in Critically Ill COVID-19 Patients with Severe ARDS}, series = {Nutrients}, volume = {13}, journal = {Nutrients}, number = {6}, issn = {2072-6643}, doi = {10.3390/nu13062113}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-241112}, year = {2021}, abstract = {The interplay between inflammation and oxidative stress is a vicious circle, potentially resulting in organ damage. Essential micronutrients such as selenium (Se) and zinc (Zn) support anti-oxidative defense systems and are commonly depleted in severe disease. This single-center retrospective study investigated micronutrient levels under Se and Zn supplementation in critically ill patients with COVID-19 induced acute respiratory distress syndrome (ARDS) and explored potential relationships with immunological and clinical parameters. According to intensive care unit (ICU) standard operating procedures, patients received 1.0 mg of intravenous Se daily on top of artificial nutrition, which contained various amounts of Se and Zn. Micronutrients, inflammatory cytokines, lymphocyte subsets and clinical data were extracted from the patient data management system on admission and after 10 to 14 days of treatment. Forty-six patients were screened for eligibility and 22 patients were included in the study. Twenty-one patients (95\%) suffered from severe ARDS and 14 patients (64\%) survived to ICU discharge. On admission, the majority of patients had low Se status biomarkers and Zn levels, along with elevated inflammatory parameters. Se supplementation significantly elevated Se (p = 0.027) and selenoprotein P levels (SELENOP; p = 0.016) to normal range. Accordingly, glutathione peroxidase 3 (GPx3) activity increased over time (p = 0.021). Se biomarkers, most notably SELENOP, were inversely correlated with CRP (r\(_s\) = -0.495), PCT (r\(_s\) = -0.413), IL-6 (r\(_s\) = -0.429), IL-1β (r\(_s\) = -0.440) and IL-10 (r\(_s\) = -0.461). Positive associations were found for CD8\(^+\) T cells (r(_s\) = 0.636), NK cells (r\(_s\) = 0.772), total IgG (r\(_s\) = 0.493) and PaO\(_2\)/FiO\(_2\) ratios (r\(_s\) = 0.504). In addition, survivors tended to have higher Se levels after 10 to 14 days compared to non-survivors (p = 0.075). Sufficient Se and Zn levels may potentially be of clinical significance for an adequate immune response in critically ill patients with severe COVID-19 ARDS.}, language = {en} } @article{NotzLeeMengeretal.2022, author = {Notz, Quirin and Lee, Zheng-Yii and Menger, Johannes and Elke, Gunnar and Hill, Aileen and Kranke, Peter and Roeder, Daniel and Lotz, Christopher and Meybohm, Patrick and Heyland, Daren K. and Stoppe, Christian}, title = {Omega-6 sparing effects of parenteral lipid emulsions-an updated systematic review and meta-analysis on clinical outcomes in critically ill patients}, series = {Critical Care}, volume = {26}, journal = {Critical Care}, number = {1}, doi = {10.1186/s13054-022-03896-3}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-299710}, year = {2022}, abstract = {Background Parenteral lipid emulsions in critical care are traditionally based on soybean oil (SO) and rich in pro-inflammatory omega-6 fatty acids (FAs). Parenteral nutrition (PN) strategies with the aim of reducing omega-6 FAs may potentially decrease the morbidity and mortality in critically ill patients. Methods A systematic search of MEDLINE, EMBASE, CINAHL and CENTRAL was conducted to identify all randomized controlled trials in critically ill patients published from inception to June 2021, which investigated clinical omega-6 sparing effects. Two independent reviewers extracted bias risk, treatment details, patient characteristics and clinical outcomes. Random effect meta-analysis was performed. Results 1054 studies were identified in our electronic search, 136 trials were assessed for eligibility and 26 trials with 1733 critically ill patients were included. The median methodologic score was 9 out of 14 points (95\% confidence interval [CI] 7, 10). Omega-6 FA sparing PN in comparison with traditional lipid emulsions did not decrease overall mortality (20 studies; risk ratio [RR] 0.91; 95\% CI 0.76, 1.10; p = 0.34) but hospital length of stay was substantially reduced (6 studies; weighted mean difference [WMD] - 6.88; 95\% CI - 11.27, - 2.49; p = 0.002). Among the different lipid emulsions, fish oil (FO) containing PN reduced the length of intensive care (8 studies; WMD - 3.53; 95\% CI - 6.16, - 0.90; p = 0.009) and rate of infectious complications (4 studies; RR 0.65; 95\% CI 0.44, 0.95; p = 0.03). When FO was administered as a stand-alone medication outside PN, potential mortality benefits were observed compared to standard care. Conclusion Overall, these findings highlight distinctive omega-6 sparing effects attributed to PN. Among the different lipid emulsions, FO in combination with PN or as a stand-alone treatment may have the greatest clinical impact.}, language = {en} } @article{LotzHerrmannNotzetal.2021, author = {Lotz, Christopher and Herrmann, Johannes and Notz, Quirin and Meybohm, Patrick and Kehl, Franz}, title = {Mitochondria and pharmacologic cardiac conditioning — At the heart of ischemic injury}, series = {International Journal of Molecular Sciences}, volume = {22}, journal = {International Journal of Molecular Sciences}, number = {6}, issn = {1422-0067}, doi = {10.3390/ijms22063224}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-285368}, year = {2021}, abstract = {Pharmacologic cardiac conditioning increases the intrinsic resistance against ischemia and reperfusion (I/R) injury. The cardiac conditioning response is mediated via complex signaling networks. These networks have been an intriguing research field for decades, largely advancing our knowledge on cardiac signaling beyond the conditioning response. The centerpieces of this system are the mitochondria, a dynamic organelle, almost acting as a cell within the cell. Mitochondria comprise a plethora of functions at the crossroads of cell death or survival. These include the maintenance of aerobic ATP production and redox signaling, closely entwined with mitochondrial calcium handling and mitochondrial permeability transition. Moreover, mitochondria host pathways of programmed cell death impact the inflammatory response and contain their own mechanisms of fusion and fission (division). These act as quality control mechanisms in cellular ageing, release of pro-apoptotic factors and mitophagy. Furthermore, recently identified mechanisms of mitochondrial regeneration can increase the capacity for oxidative phosphorylation, decrease oxidative stress and might help to beneficially impact myocardial remodeling, as well as invigorate the heart against subsequent ischemic insults. The current review highlights different pathways and unresolved questions surrounding mitochondria in myocardial I/R injury and pharmacological cardiac conditioning.}, language = {en} }