@article{HerrmannHerrmannPasslicketal.2022,
  author    = {Herrmann, Anna and Herrmann, Matthias and Passlick, Bernward and Herth, Felix and Herrmann, Johannes},
  title     = {Cycling-induced recurrent spontaneous pneumomediastinum and pneumopericardium in a young female patient},
  series = {Clinical Case Reports},
  volume    = {10},
  journal   = {Clinical Case Reports},
  number    = {3},
  doi       = {10.1002/ccr3.5587},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-276465},
  year      = {2022},
  abstract  = {We present an exceptional case of recurrent cycling-induced spontaneous pneumomediastinum and pneumopericardium in a female patient without any trauma. Radiological and endoscopic examinations were carried out to exclude other differential diagnoses. Decision for in-hospital observation and conservative treatment was made. No symptoms were reported 12 months after return to sports activity.},
  language  = {en}
}
@article{NotzHeylandLeeetal.2023,
  author    = {Notz, Quirin and Heyland, Daren K. and Lee, Zheng-Yii and Menger, Johannes and Herrmann, Johannes and Chillon, Thilo S. and Fremes, Stephen and Mohammadi, Siamak and Elke, Gunnar and Mazer, C. David and Hill, Aileen and Velten, Markus and Ott, Sascha and Kleine-Brueggeney, Maren and Meybohm, Patrick and Schomburg, Lutz and Stoppe, Christian},
  title     = {Identifying a target group for selenium supplementation in high-risk cardiac surgery: a secondary analysis of the SUSTAIN CSX trial},
  series = {Intensive Care Medicine Experimental},
  volume    = {11},
  journal   = {Intensive Care Medicine Experimental},
  doi       = {10.1186/s40635-023-00574-8},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-357196},
  year      = {2023},
  abstract  = {Background Recent data from the randomized SUSTAIN CSX trial could not confirm clinical benefits from perioperative selenium treatment in high-risk cardiac surgery patients. Underlying reasons may involve inadequate biosynthesis of glutathione peroxidase (GPx3), which is a key mediator of selenium's antioxidant effects. This secondary analysis aimed to identify patients with an increase in GPx3 activity following selenium treatment. We hypothesize that these responders might benefit from perioperative selenium treatment. Methods Patients were selected based on the availability of selenium biomarker information. Four subgroups were defined according to the patient's baseline status, including those with normal kidney function, reduced kidney function, selenium deficiency, and submaximal GPx3 activity. Results Two hundred and forty-four patients were included in this analysis. Overall, higher serum concentrations of selenium, selenoprotein P (SELENOP) and GPx3 were correlated with less organ injury. GPx3 activity at baseline was predictive of 6-month survival (AUC 0.73; p = 0.03). While selenium treatment elevated serum selenium and SELENOP concentrations but not GPx3 activity in the full patient cohort, subgroup analyses revealed that GPx3 activity increased in patients with reduced kidney function, selenium deficiency and low to moderate GPx3 activity. Clinical outcomes did not vary between selenium treatment and placebo in any of these subgroups, though the study was not powered to conclusively detect differences in outcomes. Conclusions The identification of GPx3 responders encourages further refined investigations into the treatment effects of selenium in high-risk cardiac surgery patients.},
  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{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{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{HerrmannLotzKaragiannidisetal.2022,
  author    = {Herrmann, Johannes and Lotz, Christopher and Karagiannidis, Christian and Weber-Carstens, Steffen and Kluge, Stefan and Putensen, Christian and Wehrfritz, Andreas and Schmidt, Karsten and Ellerkmann, Richard K. and Oswald, Daniel and Lotz, G{\"o}sta and Zotzmann, Viviane and Moerer, Onnen and K{\"u}hn, Christian and Kochanek, Matthias and Muellenbach, Ralf and Gaertner, Matthias and Fichtner, Falk and Brettner, Florian and Findeisen, Michael and Heim, Markus and Lahmer, Tobias and Rosenow, Felix and Haake, Nils and Lepper, Philipp M. and Rosenberger, Peter and Braune, Stephan and Kohls, Mirjam and Heuschmann, Peter and Meybohm, Patrick},
  title     = {Key characteristics impacting survival of COVID-19 extracorporeal membrane oxygenation},
  series = {Critical Care},
  volume    = {26},
  journal   = {Critical Care},
  number    = {1},
  doi       = {10.1186/s13054-022-04053-6},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-299686},
  year      = {2022},
  abstract  = {Background Severe COVID-19 induced acute respiratory distress syndrome (ARDS) often requires extracorporeal membrane oxygenation (ECMO). Recent German health insurance data revealed low ICU survival rates. Patient characteristics and experience of the ECMO center may determine intensive care unit (ICU) survival. The current study aimed to identify factors affecting ICU survival of COVID-19 ECMO patients. Methods 673 COVID-19 ARDS ECMO patients treated in 26 centers between January 1st 2020 and March 22nd 2021 were included. Data on clinical characteristics, adjunct therapies, complications, and outcome were documented. Block wise logistic regression analysis was applied to identify variables associated with ICU-survival. Results Most patients were between 50 and 70 years of age. PaO\(_{2}\)/FiO\(_{2}\) ratio prior to ECMO was 72 mmHg (IQR: 58-99). ICU survival was 31.4\%. Survival was significantly lower during the 2nd wave of the COVID-19 pandemic. A subgroup of 284 (42\%) patients fulfilling modified EOLIA criteria had a higher survival (38\%) (p = 0.0014, OR 0.64 (CI 0.41-0.99)). Survival differed between low, intermediate, and high-volume centers with 20\%, 30\%, and 38\%, respectively (p = 0.0024). Treatment in high volume centers resulted in an odds ratio of 0.55 (CI 0.28-1.02) compared to low volume centers. Additional factors associated with survival were younger age, shorter time between intubation and ECMO initiation, BMI > 35 (compared to < 25), absence of renal replacement therapy or major bleeding/thromboembolic events. Conclusions Structural and patient-related factors, including age, comorbidities and ECMO case volume, determined the survival of COVID-19 ECMO. These factors combined with a more liberal ECMO indication during the 2nd wave may explain the reasonably overall low survival rate. Careful selection of patients and treatment in high volume ECMO centers was associated with higher odds of ICU survival.},
  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}
}