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Article ; Online: Microvascular Leakage as Therapeutic Target for Ischemia and Reperfusion Injury.

Kloka, Jan Andreas / Friedrichson, Benjamin / Wülfroth, Petra / Henning, Rainer / Zacharowski, Kai

2023 Volume 12, Issue 10

Abstract: Reperfusion injury is a very common complication of various indicated therapies such as the re-opening of vessels in the myocardium or brain as well as reflow in hemodynamic shutdown (cardiac arrest, severe trauma, aortic cross-clamping). The treatment ... ...

Abstract	Reperfusion injury is a very common complication of various indicated therapies such as the re-opening of vessels in the myocardium or brain as well as reflow in hemodynamic shutdown (cardiac arrest, severe trauma, aortic cross-clamping). The treatment and prevention of reperfusion injury has therefore been a topic of immense interest in terms of mechanistic understanding, the exploration of interventions in animal models and in the clinical setting in major prospective studies. While a wealth of encouraging results has been obtained in the lab, the translation into clinical success has met with mixed outcomes at best. Considering the still very high medical need, progress continues to be urgently needed. Multi-target approaches rationally linking interference with pathophysiological pathways as well as a renewed focus on aspects of microvascular dysfunction, especially on the role of microvascular leakage, are likely to provide new insights.
MeSH term(s)	Animals ; Prospective Studies ; Reperfusion Injury/drug therapy ; Ischemia ; Myocardium ; Models, Animal
Language	English
Publishing date	2023-05-09
Publishing country	Switzerland
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	2661518-6
ISSN	2073-4409 ; 2073-4409
ISSN (online)	2073-4409
ISSN	2073-4409
DOI	10.3390/cells12101345
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Article ; Online: Anaemia and red blood cell transfusion in women with placenta accreta spectrum: an analysis of 38,060 cases.

Kloka, Jan Andreas / Friedrichson, Benjamin / Jasny, Thomas / Blum, Lea Valeska / Choorapoikayil, Suma / Old, Oliver / Zacharowski, Kai / Neef, Vanessa

Scientific reports

2024 Volume 14, Issue 1, Page(s) 4999

Abstract: Placenta accreta spectrum (PAS) has become a significant life-threatening issue due to its increased incidence and associated morbidity and mortality. Pregnancy is often associated with states of anaemia, and severe maternal haemorrhage represents a ... ...

Abstract	Placenta accreta spectrum (PAS) has become a significant life-threatening issue due to its increased incidence and associated morbidity and mortality. Pregnancy is often associated with states of anaemia, and severe maternal haemorrhage represents a major risk factor for red blood cell (RBC) transfusion. The present study retrospectively analyzed the prevalence of anaemia, transfusion requirements and outcome in women with PAS. Using data from the German Statistical Office pregnant patients with deliveries hospitalized between January 2012 and December 2021 were included. Primary outcome was the prevalence of anemia and administration of RBCs. Secondary outcome were complications in women with PAS who received RBC transfusion. In total 6,493,606 pregnant women were analyzed, of which 38,060 (0.59%) were diagnosed with PAS. The rate of anaemia during pregnancy (60.36 vs. 23.25%; p < 0.0001), postpartum haemorrhage (47.08 vs. 4.41%; p < 0.0001) and RBC transfusion rate (14.68% vs. 0.72%; p < 0.0001) were higher in women with PAS compared to women without PAS. Women with PAS who had bleeding and transfusion experienced significantly more peripartum complications than those who did not. A multiple logistic regression revealed that the probability for RBC transfusion in all pregnant women was positively associated with anaemia (OR 21.96 (95% CI 21.36-22.58)). In women with PAS, RBC transfusion was positively associated with the presence of renal failure (OR 11.27 (95% CI 9.35-13.57)) and congestive heart failure (OR 6.02 (95% CI (5.2-7.07)). Early anaemia management prior to delivery as well as blood conservation strategies are crucial in women diagnosed with PAS.
MeSH term(s)	Female ; Humans ; Pregnancy ; Erythrocyte Transfusion/adverse effects ; Placenta Accreta/epidemiology ; Placenta Accreta/therapy ; Placenta Accreta/diagnosis ; Retrospective Studies ; Anemia/complications ; Anemia/epidemiology ; Anemia/therapy ; Blood Transfusion ; Placenta ; Hysterectomy/adverse effects
Language	English
Publishing date	2024-02-29
Publishing country	England
Document type	Journal Article
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-024-55531-6
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Article ; Online: Expectations of Anesthesiology and Intensive Care Professionals Toward Artificial Intelligence: Observational Study.

Kloka, Jan Andreas / Holtmann, Sophie C / Nürenberg-Goloub, Elina / Piekarski, Florian / Zacharowski, Kai / Friedrichson, Benjamin

JMIR formative research

2023 Volume 7, Page(s) e43896

Abstract: Background: Artificial intelligence (AI) applications offer numerous opportunities to improve health care. To be used in the intensive care unit, AI must meet the needs of staff, and potential barriers must be addressed through joint action by all ... ...

Abstract	Background: Artificial intelligence (AI) applications offer numerous opportunities to improve health care. To be used in the intensive care unit, AI must meet the needs of staff, and potential barriers must be addressed through joint action by all stakeholders. It is thus critical to assess the needs and concerns of anesthesiologists and intensive care physicians related to AI in health care throughout Europe. Objective: This Europe-wide, cross-sectional observational study investigates how potential users of AI systems in anesthesiology and intensive care assess the opportunities and risks of the new technology. The web-based questionnaire was based on the established analytic model of acceptance of innovations by Rogers to record 5 stages of innovation acceptance. Methods: The questionnaire was sent twice in 2 months (March 11, 2021, and November 5, 2021) through the European Society of Anaesthesiology and Intensive Care (ESAIC) member email distribution list. A total of 9294 ESAIC members were reached, of whom 728 filled out the questionnaire (response rate 728/9294, 8%). Due to missing data, 27 questionnaires were excluded. The analyses were conducted with 701 participants. Results: A total of 701 questionnaires (female: n=299, 42%) were analyzed. Overall, 265 (37.8%) of the participants have been in contact with AI and evaluated the benefits of this technology higher (mean 3.22, SD 0.39) than participants who stated no previous contact (mean 3.01, SD 0.48). Physicians see the most benefits of AI application in early warning systems (335/701, 48% strongly agreed, and 358/701, 51% agreed). Major potential disadvantages were technical problems (236/701, 34% strongly agreed, and 410/701, 58% agreed) and handling difficulties (126/701, 18% strongly agreed, and 462/701, 66% agreed), both of which could be addressed by Europe-wide digitalization and education. In addition, the lack of a secure legal basis for the research and use of medical AI in the European Union leads doctors to expect problems with legal liability (186/701, 27% strongly agreed, and 374/701, 53% agreed) and data protection (148/701, 21% strongly agreed, and 343/701, 49% agreed). Conclusions: Anesthesiologists and intensive care personnel are open to AI applications in their professional field and expect numerous benefits for staff and patients. Regional differences in the digitalization of the private sector are not reflected in the acceptance of AI among health care professionals. Physicians anticipate technical difficulties and lack a stable legal basis for the use of AI. Training for medical staff could increase the benefits of AI in professional medicine. Therefore, we suggest that the development and implementation of AI in health care require a solid technical, legal, and ethical basis, as well as adequate education and training of users.
Language	English
Publishing date	2023-06-12
Publishing country	Canada
Document type	Journal Article
ISSN	2561-326X
ISSN (online)	2561-326X
DOI	10.2196/43896
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Article ; Online: Characteristics and mortality of 561,379 hospitalized COVID-19 patients in Germany until December 2021 based on real-life data.

Kloka, Jan Andreas / Blum, Lea Valeska / Old, Oliver / Zacharowski, Kai / Friedrichson, Benjamin

Scientific reports

2022 Volume 12, Issue 1, Page(s) 11116

Abstract: The ongoing SARS-CoV-2 pandemic is characterized by poor outcome and a high mortality especially in the older patient cohort. Up to this point there is a lack of data characterising COVID-19 patients in Germany admitted to intensive care (ICU) vs. non- ... ...

Abstract	The ongoing SARS-CoV-2 pandemic is characterized by poor outcome and a high mortality especially in the older patient cohort. Up to this point there is a lack of data characterising COVID-19 patients in Germany admitted to intensive care (ICU) vs. non-ICU patients. German Reimbursement inpatient data covering the period in Germany from January 1st, 2020 to December 31th, 2021 were analyzed. 561,379 patients were hospitalized with COVID-19. 24.54% (n = 137,750) were admitted to ICU. Overall hospital mortality was 16.69% (n = 93,668) and 33.36% (n = 45,947) in the ICU group. 28.66% (n = 160,881) of all patients suffer from Cardiac arrhythmia and 17.98% (n = 100,926) developed renal failure. Obesity showed an odds-ratio ranging from 0.83 (0.79-0.87) for WHO grade I to 1.13 (1.08-1.19) for grade III. Mortality-rates peaked in April 2020 and January 2021 being 21.23% (n = 4539) and 22.99% (n = 15,724). A third peak was observed November and December 2021 (16.82%, n = 7173 and 16.54%, n = 9416). Hospitalized COVID-19 patient mortality in Germany is lower than previously shown in other studies. 24.54% of all patients had to be treated in the ICU with a mortality rate of 33.36%. Congestive heart failure was associated with a higher risk of death whereas low grade obesity might have a protective effect on patient survival. High admission numbers are accompanied by a higher mortality rate.
MeSH term(s)	COVID-19/epidemiology ; Germany/epidemiology ; Humans ; Intensive Care Units ; Obesity ; Retrospective Studies ; SARS-CoV-2
Language	English
Publishing date	2022-07-01
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-022-15287-3
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Article ; Online: Use of cell salvage in obstetrics in Germany: analysis of national database of 305 610 cases with peripartum haemorrhage.

Neef, Vanessa / Friedrichson, Benjamin / Jasny, Thomas / Old, Oliver / Raimann, Florian J / Choorapoikayil, Suma / Steinbicker, Andrea U / Meybohm, Patrick / Zacharowski, Kai / Kloka, Jan Andreas

British journal of anaesthesia

2024

Abstract: Background: One of the leading causes of maternal death worldwide is severe obstetric haemorrhage after childbirth. Use of intraoperative cell salvage is strongly recommended by international guidelines on patient blood management. Recent data provide ... ...

Abstract	Background: One of the leading causes of maternal death worldwide is severe obstetric haemorrhage after childbirth. Use of intraoperative cell salvage is strongly recommended by international guidelines on patient blood management. Recent data provide strong evidence that use of cell salvage in obstetrics is effective and safe in women with postpartum haemorrhage resulting in fewer transfusion-related adverse events and shorter hospital stay. We retrospectively analysed the use of cell salvage in bleeding women during delivery for a period of 10 yr in German hospitals. Methods: Data from the German Federal Statistical Office were used that covers all in-hospital birth deliveries from 2011 to 2020. Prevalence of peripartum haemorrhage (pre-, intra-, and post-partum haemorrhage), comorbidities, peripartum complications, administration of blood products, and use of cell salvage were analysed. Results: Of 6 356 046 deliveries in Germany, 305 610 women (4.8%) suffered from peripartum haemorrhage. Of all women with peripartum haemorrhage, postpartum haemorrhage was the main cause for major obstetric haemorrhage (92.33%). Cell salvage was used in only 228 (0.07%) of all women with peripartum haemorrhage (cell salvage group). In women undergoing Caesarean delivery with postpartum haemorrhage, cell salvage was used in only 216 out of 70 450 women (0.31%). Conclusion: Cell salvage during peripartum haemorrhage is rarely used in Germany. There is tremendous potential for the increased use of cell salvage in peripartum haemorrhage nationwide.
Language	English
Publishing date	2024-01-23
Publishing country	England
Document type	Journal Article
ZDB-ID	80074-0
ISSN	1471-6771 ; 0007-0912
ISSN (online)	1471-6771
ISSN	0007-0912
DOI	10.1016/j.bja.2023.12.014
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Article ; Online: Characteristics and mortality of 561,379 hospitalized COVID-19 patients in Germany until December 2021 based on real-life data

Jan Andreas Kloka / Lea Valeska Blum / Oliver Old / Kai Zacharowski / Benjamin Friedrichson

Scientific Reports, Vol 12, Iss 1, Pp 1-

2022 Volume 9

Abstract: Abstract The ongoing SARS-CoV-2 pandemic is characterized by poor outcome and a high mortality especially in the older patient cohort. Up to this point there is a lack of data characterising COVID-19 patients in Germany admitted to intensive care (ICU) ... ...

Abstract	Abstract The ongoing SARS-CoV-2 pandemic is characterized by poor outcome and a high mortality especially in the older patient cohort. Up to this point there is a lack of data characterising COVID-19 patients in Germany admitted to intensive care (ICU) vs. non-ICU patients. German Reimbursement inpatient data covering the period in Germany from January 1st, 2020 to December 31th, 2021 were analyzed. 561,379 patients were hospitalized with COVID-19. 24.54% (n = 137,750) were admitted to ICU. Overall hospital mortality was 16.69% (n = 93,668) and 33.36% (n = 45,947) in the ICU group. 28.66% (n = 160,881) of all patients suffer from Cardiac arrhythmia and 17.98% (n = 100,926) developed renal failure. Obesity showed an odds-ratio ranging from 0.83 (0.79–0.87) for WHO grade I to 1.13 (1.08–1.19) for grade III. Mortality-rates peaked in April 2020 and January 2021 being 21.23% (n = 4539) and 22.99% (n = 15,724). A third peak was observed November and December 2021 (16.82%, n = 7173 and 16.54%, n = 9416). Hospitalized COVID-19 patient mortality in Germany is lower than previously shown in other studies. 24.54% of all patients had to be treated in the ICU with a mortality rate of 33.36%. Congestive heart failure was associated with a higher risk of death whereas low grade obesity might have a protective effect on patient survival. High admission numbers are accompanied by a higher mortality rate.
Keywords	Medicine ; R ; Science ; Q
Language	English
Publishing date	2022-07-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: The impact of intravenous iron supplementation in elderly patients undergoing major surgery.

Blum, Lea Valeska / Zierentz, Philipp / Hof, Lotta / Kloka, Jan Andreas / Messroghli, Leila / Zacharowski, Kai / Meybohm, Patrick / Choorapoikayil, Suma

BMC geriatrics

2022 Volume 22, Issue 1, Page(s) 293

Abstract: Background: Age and preoperative anaemia are risk factors for poor surgical outcome and blood transfusion. The aim of this study was to examine the effect of iron supplementation in iron-deficient (ID) elderly patients undergoing major surgery.: ... ...

Abstract	Background: Age and preoperative anaemia are risk factors for poor surgical outcome and blood transfusion. The aim of this study was to examine the effect of iron supplementation in iron-deficient (ID) elderly patients undergoing major surgery. Method: In this single-centre observational study, patients ≥ 65 years undergoing major surgery were screened for anaemia and ID. Patients were assigned to the following groups: A Results: Of 4,381 patients screened at the anaemia walk-in clinic, 2,381 (54%) patients were ≥ 65 years old and 2,191 cases were included in analysis. The ID prevalence was 63% in patients with haemoglobin (Hb) < 8 g/dl, 47.2% in patients with Hb from 8.0 to 8.9 g/dl, and 44.3% in patients with Hb from 9 to 9.9 g/dl. In severely anaemic patients, an Hb increase of 0.6 (0.4; 1.2) and 1.2 (0.7; 1.6) g/dl was detected with iron supplementation 6-10 and > 10 days before surgery, respectively. Hb increased by 0 (-0.1; 0) g/dl with iron supplementation 1-5 days before surgery, 0.2 (-0.1; 0.5) g/dl with iron supplementation 6-10 days before surgery, and 0.2 (-0.2; 1.1) g/dl with supplementation > 10 days before surgery (p < 0.001 for 1-5 vs. 6-10 days). Overall, 58% of A Conclusions: Intravenous iron supplementation increases Hb level and thereby reduces blood transfusion rate in elderly surgical patients with ID anaemia.
MeSH term(s)	Aged ; Anemia/diagnosis ; Anemia/drug therapy ; Anemia/epidemiology ; Dietary Supplements ; Erythrocyte Transfusion ; Hemoglobins ; Humans ; Iron
Chemical Substances	Hemoglobins ; Iron (E1UOL152H7)
Language	English
Publishing date	2022-04-07
Publishing country	England
Document type	Journal Article ; Observational Study ; Research Support, Non-U.S. Gov't
ZDB-ID	2059865-8
ISSN	1471-2318 ; 1471-2318
ISSN (online)	1471-2318
ISSN	1471-2318
DOI	10.1186/s12877-022-02983-y
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Book ; Online ; Thesis: Endogene Lipide als neues Behandlungstarget im TRPA1-vermittelten Entzündungsschmerz

Kloka, Jan Andreas [Verfasser] / Rittner, Heike [Gutachter]

2019

Author's details	Jan Andreas Kloka ; Gutachter: Heike Rittner
Keywords	Medizin, Gesundheit ; Medicine, Health
Subject code	sg610
Language	German
Publisher	Universität Würzburg
Publishing place	Würzburg
Document type	Book ; Online ; Thesis
Database	Digital theses on the web

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Article ; Online: Short-term predictor for COVID-19 severity from a longitudinal multi-omics study for practical application in intensive care units.

Kugler, Sabine / Hahnefeld, Lisa / Kloka, Jan Andreas / Ginzel, Sebastian / Nürenberg-Goloub, Elina / Zinn, Sebastian / Vehreschild, Maria Jgt / Zacharowski, Kai / Lindau, Simone / Ullrich, Evelyn / Burmeister, Jan / Kohlhammer, Jörn / Schwäble, Joachim / Gurke, Robert / Dorochow, Erika / Bennett, Alexandre / Dauth, Stephanie / Campe, Julia / Knape, Tilo /

Laux, Volker / Kannt, Aimo / Köhm, Michaela / Geisslinger, Gerd / Resch, Eduard / Behrens, Frank

Talanta

2023 Volume 268, Issue Pt 1, Page(s) 125295

Abstract: Background: The COVID-19 pandemic challenged the management of technical and human resources in intensive care units (ICU) across the world. Several long-term predictors for COVID-19 disease progression have been discovered. However, predictors to ... ...

Abstract	Background: The COVID-19 pandemic challenged the management of technical and human resources in intensive care units (ICU) across the world. Several long-term predictors for COVID-19 disease progression have been discovered. However, predictors to support short-term planning of resources and medication that can be translated to future pandemics are still missing. A workflow was established to identify a predictor for short-term COVID-19 disease progression in the acute phase of intensive care patients to support clinical decision-making. Methods: Thirty-two patients with SARS-CoV-2 infection were recruited on admission to the ICU and clinical data collected. During their hospitalization, plasma samples were acquired from each patient on multiple occasions, excepting one patient for which only one time point was possible, and the proteome (Inflammation, Immune Response and Organ Damage panels from Olink® Target 96), metabolome and lipidome (flow injection analysis and liquid chromatography-mass spectrometry) analyzed for each sample. Patient visits were grouped according to changes in disease severity based on their respiratory and organ function, and evaluated using a combination of statistical analysis and machine learning. The resulting short-term predictor from this multi-omics approach was compared to the human assessment of disease progression. Furthermore, the potential markers were compared to the baseline levels of 50 healthy subjects with no known SARS-CoV-2 or other viral infections. Results: A total of 124 clinical parameters, 271 proteins and 782 unique metabolites and lipids were assessed. The dimensionality of the dataset was reduced, selecting 47 from the 1177 parameters available following down-selection, to build the machine learning model. Subsequently, two proteins (C-C motif chemokine 7 (CCL7) and carbonic anhydrase 14 (CA14)) and one lipid (hexosylceramide 18:2; O2/20:0) were linked to disease progression in the studied SARS-CoV-2 infections. Thus, a predictor delivering the prognosis of an upcoming worsening of the patient's condition up to five days in advance with a reasonable accuracy (79 % three days prior to event, 84 % four to five days prior to event) was found. Interestingly, the predictor's performance was complementary to the clinicians' capabilities to foresee a worsening of a patient. Conclusion: This study presents a workflow to identify omics-based biomarkers to support clinical decision-making and resource management in the ICU. This was successfully applied to develop a short-term predictor for aggravation of COVID-19 symptoms. The applied methods can be adapted for future small cohort studies.
MeSH term(s)	Humans ; COVID-19/diagnosis ; SARS-CoV-2 ; Pandemics ; Multiomics ; Intensive Care Units ; Disease Progression
Language	English
Publishing date	2023-10-09
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	1500969-5
ISSN	1873-3573 ; 0039-9140
ISSN (online)	1873-3573
ISSN	0039-9140
DOI	10.1016/j.talanta.2023.125295
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Article ; Online: Potential of FX06 to prevent disease progression in hospitalized non-intubated COVID-19 patients - the randomized, EU-wide, placebo-controlled, phase II study design of IXION

Kloka, Jan Andreas / Friedrichson, Benjamin / Dauth, Stephanie / Foldenauer, Ann Christina / Bulczak-Schadendorf, Anita / Vehreschild, Maria J.G.T. / Matos, Francisco Maio / Riera-Mestre, Antoni / Asselt, Antoinette D.I. van / Robertis, Edoardo de / Juskeviciene, Vilma Traskaite / Meybohm, Patrick / Tomescu, D. / Lacombe, Karine / Stehouwer, Coen D.A. / Zacharowski, Kai D.

2022

Abstract: Background: More than 2.7 million hospitalizations of COVID-19-infected patients have occurred in Europe alone since the outbreak of the coronavirus in 2020. Interventions against SARS-CoV-2 are still in high need to prevent admissions to ICUs worldwide. ...

Abstract	Background: More than 2.7 million hospitalizations of COVID-19-infected patients have occurred in Europe alone since the outbreak of the coronavirus in 2020. Interventions against SARS-CoV-2 are still in high need to prevent admissions to ICUs worldwide. FX06, a naturally occurring peptide in humans and other mammals, has the potential to reduce capillary leak by improving endothelial dysfunction and thus preventing the deterioration of patients. With IXION, we want to investigate the potential of FX06 to prevent disease progression in hospitalized, non-intubated COVID-19 patients. Methods: IXION is an EU-wide, multicentre, placebo-controlled, double-blinded, parallel, randomized (2:1) phase II clinical study. Patient recruitment will start in September 2022 (to Q2/2023) in Germany, Italy, Lithuania, Spain, Romania, Portugal, and France. A total of 306 hospitalized patients (≥ 18 years and < 75 years) with a positive SARS-CoV-2 PCR test and a COVID-19 severity of 4-6 according to the WHO scale will be enrolled. After randomization to FX06 or placebo, patients will be assessed until day 28 (and followed up until day 60). FX06 (2 × 200 mg per day) or placebo will be administered intravenously for 5 consecutive days. The primary endpoint is to demonstrate a difference in the proportion of patients with progressed/worsened disease state in patients receiving FX06 compared to patients receiving placebo. Secondary endpoints are lung function, oxygen saturation and breathing rate, systemic inflammation, survival, capillary refill time, duration of hospital stay, and drug accountability. Discussion: With IXION, the multidisciplinary consortium aims to deliver a new therapy in addition to standard care against SARS-CoV-2 for the clinical management of COVID-19 during mild and moderate stages. Potential limitations might refer to a lack of recruiting and drop-out due to various possible protocol violations. While we controlled for drop-outs in the same size estimation, recruitment problems may be subject to external ...
Keywords	Capillary leak ; COVID-19 ; Disease progression ; FX06 ; Inflammation
Subject code	610
Language	English
Publishing country	de
Document type	Article ; Online
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