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Article ; Online: Association of telomere length and mitochondrial DNA copy number, two biomarkers of biological aging, with the risk of venous thromboembolism.

Vostatek, Rafaela / Hohensinner, Philipp / Nopp, Stephan / Haider, Patrick / Englisch, Cornelia / Pointner, Julia / Pabinger, Ingrid / Ay, Cihan

Thrombosis research

2023 Volume 223, Page(s) 168–173

Abstract: Background: Venous thromboembolism (VTE) is the third most common cardiovascular disease and occurs in all age groups, albeit the risk increases considerably with age. Previous research indicates mitochondrial dysfunction and telomere shortening in ... ...

Abstract	Background: Venous thromboembolism (VTE) is the third most common cardiovascular disease and occurs in all age groups, albeit the risk increases considerably with age. Previous research indicates mitochondrial dysfunction and telomere shortening in cardiovascular aging. However, in the context of VTE this has not been investigated in detail. Aim: We aimed to explore biomarkers reflecting biological aging (i.e. human mitochondrial DNA copy number (mtDNA) and telomere length) and their association with VTE. Methods: mtDNA and telomere length were measured in a case-control study of 116 patients with a history of VTE and 128 age- and sex-matched healthy individuals from isolated blood using a qPCR-based assay kit. Cases had at least one unprovoked VTE event and were enrolled no earlier than 3 months after the last VTE event. Results: The mtDNA copy number was significantly lower in VTE cases compared to controls (median [IQR]: 663 per diploid cells [78.75-2204.5] vs. 2832 per diploid cells [724-4350]; p < 0.001). After adjustment for age, sex, BMI, and smoking, mtDNA copy number was independently associated with VTE risk (odds ratio per increase in 400 mtDNA per diploid cell: 0.889, 95%CI 0.834-0.947). mtDNA copy numbers were significantly different between women and men (2375 [455-3737] women vs. 893 [152-3154] men; p < 0.001). The analysis of telomere length showed no significant difference between patients and healthy controls. Conclusion: Lower mtDNA levels were found in patients with VTE compared to controls, indicating an association of biological aging with risk of VTE.
MeSH term(s)	Male ; Humans ; Female ; DNA, Mitochondrial/genetics ; Venous Thromboembolism ; DNA Copy Number Variations ; Case-Control Studies ; Telomere ; Aging/genetics ; Mitochondria ; Biomarkers
Chemical Substances	DNA, Mitochondrial ; Biomarkers
Language	English
Publishing date	2023-02-03
Publishing country	United States
Document type	Journal Article
ZDB-ID	121852-9
ISSN	1879-2472 ; 0049-3848
ISSN (online)	1879-2472
ISSN	0049-3848
DOI	10.1016/j.thromres.2023.01.031
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Article ; Online: Quantitative and Functional Assessment of the Influence of Routinely Used Cryopreservation Media on Mononuclear Leukocytes for Medical Research.

Haider, Patrick / Hoberstorfer, Timothy / Salzmann, Manuel / Fischer, Michael B / Speidl, Walter S / Wojta, Johann / Hohensinner, Philipp J

International journal of molecular sciences

2022 Volume 23, Issue 3

Abstract: Quantitative and functional analysis of mononuclear leukocyte populations is an invaluable tool to understand the role of the immune system in the pathogenesis of a disease. Cryopreservation of mononuclear cells (MNCs) is routinely used to guarantee ... ...

Abstract	Quantitative and functional analysis of mononuclear leukocyte populations is an invaluable tool to understand the role of the immune system in the pathogenesis of a disease. Cryopreservation of mononuclear cells (MNCs) is routinely used to guarantee similar experimental conditions. Immune cells react differently to cryopreservation, and populations and functions of immune cells change during the process of freeze-thawing. To allow for a setup that preserves cell number and function optimally, we tested four different cryopreservation media. MNCs from 15 human individuals were analyzed. Before freezing and after thawing, the distribution of leukocytes was quantified by flow cytometry. Cultured cells were stimulated using lipopolysaccharide, and their immune response was quantified by flow cytometry, quantitative polymerase chain reaction (qPCR), and enzyme-linked immunosorbent assay (ELISA). Ultimately, the performance of the cryopreservation media was ranked. Cell recovery and viability were different between the media. Cryopreservation led to changes in the relative number of monocytes, T cells, B cells, and their subsets. The inflammatory response of MNCs was altered by cryopreservation, enhancing the basal production of inflammatory cytokines. Different cryopreservation media induce biases, which needs to be considered when designing a study relying on cryopreservation. Here, we provide an overview of four different cryopreservation media for choosing the optimal medium for a specific task.
MeSH term(s)	Cell Culture Techniques/methods ; Cell Survival ; Cells, Cultured ; Cryopreservation/methods ; Female ; Flow Cytometry ; Humans ; Leukocyte Count ; Leukocytes, Mononuclear/cytology ; Leukocytes, Mononuclear/metabolism ; Male
Language	English
Publishing date	2022-02-07
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms23031881
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Article ; Online: Reduced Monocyte and Neutrophil Infiltration and Activation by P-Selectin/CD62P Inhibition Enhances Thrombus Resolution in Mice.

Kral-Pointner, Julia B / Haider, Patrick / Szabo, Petra L / Salzmann, Manuel / Brekalo, Mira / Schneider, Karl H / Schrottmaier, Waltraud C / Kaun, Christoph / Bleichert, Sonja / Kiss, Attila / Sickha, Romana / Hengstenberg, Christian / Huber, Kurt / Brostjan, Christine / Bergmeister, Helga / Assinger, Alice / Podesser, Bruno K / Wojta, Johann / Hohensinner, Philipp

Arteriosclerosis, thrombosis, and vascular biology

2024 Volume 44, Issue 4, Page(s) 954–968

Abstract: Background: Venous thromboembolism is a major health problem. After thrombus formation, its resolution is essential to re-establish blood flow, which is crucially mediated by infiltrating neutrophils and monocytes in concert with activated platelets and ...

Abstract	Background: Venous thromboembolism is a major health problem. After thrombus formation, its resolution is essential to re-establish blood flow, which is crucially mediated by infiltrating neutrophils and monocytes in concert with activated platelets and endothelial cells. Thus, we aimed to modulate leukocyte function during thrombus resolution post-thrombus formation by blocking P-selectin/CD62P-mediated cell interactions. Methods: Thrombosis was induced by inferior vena cava stenosis through ligation in mice. After 1 day, a P-selectin-blocking antibody or isotype control was administered and thrombus composition and resolution were analyzed. Results: Localizing neutrophils and macrophages in thrombotic lesions of wild-type mice revealed that these cells enter the thrombus and vessel wall from the caudal end. Neutrophils were predominantly present 1 day and monocytes/macrophages 3 days after vessel ligation. Blocking P-selectin reduced circulating platelet-neutrophil and platelet-Ly6C Conclusions: Inhibition of P-selectin-dependent activation of monocytes and neutrophils accelerates venous thrombosis resolution due to reduced infiltration and activation of innate immune cells at the site of thrombus formation, which prevents early thrombus stabilization and facilitates fibrinolysis.
MeSH term(s)	Mice ; Humans ; Animals ; Monocytes/pathology ; P-Selectin ; Endothelial Cells ; Thromboplastin ; Neutrophil Infiltration ; Thrombosis ; Neutrophils
Chemical Substances	P-Selectin ; Thromboplastin (9035-58-9)
Language	English
Publishing date	2024-02-22
Publishing country	United States
Document type	Journal Article
ZDB-ID	1221433-4
ISSN	1524-4636 ; 1079-5642
ISSN (online)	1524-4636
ISSN	1079-5642
DOI	10.1161/ATVBAHA.123.320016
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Article ; Online: Short-term toll-like receptor 9 inhibition leads to left ventricular wall thinning after myocardial infarction.

Lenz, Max / Kiss, Attila / Haider, Patrick / Salzmann, Manuel / Brekalo, Mira / Krychtiuk, Konstantin A / Hamza, Ouafa / Huber, Kurt / Hengstenberg, Christian / Podesser, Bruno K / Wojta, Johann / Hohensinner, Philipp J / Speidl, Walter S

ESC heart failure

2023 Volume 10, Issue 4, Page(s) 2375–2385

Abstract: Aims: Ischaemia-reperfusion injury (IRI) following myocardial infarction remains a challenging topic in acute cardiac care and consecutively arising heart failure represents a severe long-term consequence. The extent of neutrophil infiltration and ... ...

Abstract	Aims: Ischaemia-reperfusion injury (IRI) following myocardial infarction remains a challenging topic in acute cardiac care and consecutively arising heart failure represents a severe long-term consequence. The extent of neutrophil infiltration and neutrophil-mediated cellular damage are thought to be aggravating factors enhancing primary tissue injury. Toll-like receptor 9 was found to be involved in neutrophil activation as well as chemotaxis and may represent a target in modulating IRI, aspects we aimed to illuminate by pharmacological inhibition of the receptor. Methods and results: Forty-nine male adult Sprague-Dawley rats were used. IRI was induced by occlusion of the left coronary artery and subsequent snare removal after 30 min. Oligonucleotide (ODN) 2088, a toll-like receptor 9 (TLR9) antagonist, control-ODN, or DNase, were administered at the time of reperfusion and over 24 h via a mini-osmotic pump. The hearts were harvested 24 h or 4 weeks after left coronary artery occlusion and immunohistochemical staining was performed. Echocardiography was done after 1 and 4 weeks to determine ventricular function. Inhibition of TLR9 by ODN 2088 led to left ventricular wall thinning (P = 0.003) in association with drastically enhanced neutrophil infiltration (P = 0.005) and increased markers of tissue damage. Additionally, an up-regulation of the chemotactic receptor CXCR2 (P = 0.046) was found after TLR9 inhibition. No such effects were observed in control-ODN or DNase-treated animals. We did not observe changes in monocyte content or subset distribution, hinting towards neutrophils as the primary mediators of the exerted tissue injury. Conclusions: Our data indicate a TLR9-dependent, negative regulation of neutrophil infiltration. Blockage of TLR9 appears to prevent the down-regulation of CXCR2, followed by an uncontrolled migration of neutrophils towards the area of infarction and the exertion of disproportional tissue injury resulting in potential aneurysm formation. In comparison with previous studies conducted in TLR
MeSH term(s)	Rats ; Mice ; Male ; Animals ; Toll-Like Receptor 9/therapeutic use ; Rats, Sprague-Dawley ; Myocardial Infarction/drug therapy ; Heart ; Coronary Vessels
Chemical Substances	Toll-Like Receptor 9
Language	English
Publishing date	2023-05-16
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2814355-3
ISSN	2055-5822 ; 2055-5822
ISSN (online)	2055-5822
ISSN	2055-5822
DOI	10.1002/ehf2.14403
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Article ; Online: Neutrophil extracellular traps induce persistent lung tissue damage via thromboinflammation without altering virus resolution in a mouse coronavirus model.

Salzmann, Manuel / Gibler, Patrizia / Haider, Patrick / Brekalo, Mira / Plasenzotti, Roberto / Filip, Thomas / Nistelberger, Rebecca / Hartmann, Boris / Wojta, Johann / Hengstenberg, Christian / Podesser, Bruno K / Kral-Pointner, Julia B / Hohensinner, Philipp J

Journal of thrombosis and haemostasis : JTH

2023 Volume 22, Issue 1, Page(s) 188–198

Abstract: Background: During infection, neutrophil extracellular traps (NETs) are associated with severity of pulmonary diseases such as acute respiratory disease syndrome. NETs induce subsequent immune responses, are directly cytotoxic to pulmonary cells, and ... ...

Abstract	Background: During infection, neutrophil extracellular traps (NETs) are associated with severity of pulmonary diseases such as acute respiratory disease syndrome. NETs induce subsequent immune responses, are directly cytotoxic to pulmonary cells, and are highly procoagulant. Anticoagulation treatment was shown to reduce in-hospital mortality, indicating thromboinflammatory complications. However, data are sparsely available on the involvement of NETs in secondary events after virus clearance, which can lead to persistent lung damage and postacute sequelae with chronic fatigue and dyspnea. Objectives: This study focuses on late-phase events using a murine model of viral lung infection with postacute sequelae after virus resolution. Methods: C57BL/6JRj mice were infected intranasally with the betacoronavirus murine coronavirus (MCoV, strain MHV-A95), and tissue samples were collected after 2, 4, and 10 days. For NET modulation, mice were pretreated with OM-85 or GSK484 and DNase I were administered intraperitoneally between days 2 to 5 and days 4 to 7, respectively. Results: Rapid, platelet-attributed thrombus formation was followed by a second, late phase of thromboinflammation. This phase was characterized by negligible virus titers but pronounced tissue damage, apoptosis, oxidative DNA damage, and presence of NETs. Inhibition of NETs during the acute phase did not impact virus burden but decreased lung cell apoptosis by 67% and oxidative stress by 94%. Prevention of neutrophil activation by immune training before virus infection reduced damage by 75%, NETs by 31%, and pulmonary thrombi by 93%. Conclusion: NETs are detrimental inducers of tissue damage during respiratory virus infection but do not contribute to virus clearance.
MeSH term(s)	Animals ; Mice ; Extracellular Traps ; Neutrophils ; Coronavirus ; Thromboinflammation ; Disease Models, Animal ; Inflammation/complications ; Thrombosis/complications ; Mice, Inbred C57BL ; Lung ; Coronavirus Infections/complications
Language	English
Publishing date	2023-09-23
Publishing country	England
Document type	Journal Article
ZDB-ID	2112661-6
ISSN	1538-7836 ; 1538-7933
ISSN (online)	1538-7836
ISSN	1538-7933
DOI	10.1016/j.jtha.2023.09.014
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Zs.A 5805: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MO 295: Show issues

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Article ; Online: Intrahepatic neutrophil accumulation and extracellular trap formation are associated with posthepatectomy liver failure.

Brunnthaler, Laura / Pereyra, David / Brenner, Miriam / Santol, Jonas / Herrmann, Lukas / Schrottmaier, Waltraud C / Pirabe, Anita / Schmuckenschlager, Anna / Kim, Sarang / Kern, Anna Emilia / Huber, Felix Xaver / Michels, Lisa Emilie / Brostjan, Christine / Salzmann, Manuel / Hohensinner, Philipp / Kain, Renate / Gruenberger, Thomas / Starlinger, Patrick / Assinger, Alice

Hepatology communications

2023 Volume 8, Issue 1

Abstract: Background: Posthepatectomy liver failure (PHLF) represents a life-threatening complication with limited therapeutic options. Neutrophils play a critical and dynamic role during regeneratory processes, but their role in human liver regeneration is ... ...

Abstract	Background: Posthepatectomy liver failure (PHLF) represents a life-threatening complication with limited therapeutic options. Neutrophils play a critical and dynamic role during regeneratory processes, but their role in human liver regeneration is incompletely understood, especially as underlying liver disease, detectable in the majority of patients, critically affects hepatic regeneration. Here we explored intrahepatic neutrophil accumulation and neutrophil extracellular traps (NETs) in patients with PHLF and validated the functional relevance of NETs in a murine partial hepatectomy (PHx) model. Methods: We investigated the influx of neutrophils, macrophages, eosinophils, and mast cells and the presence of their respective extracellular traps in liver biopsies of 35 patients undergoing hepatectomy (10 patients with PHLF) before and after the initiation of liver regeneration by fluorescence microscopy. In addition, NET formation and neutrophil activation were confirmed by plasma analysis of 99 patients (24 patients with PHLF) before and up to 5 days after surgery. Furthermore, we inhibited NETs via DNase I in a murine PHx model of mice with metabolically induced liver disease. Results: We detected rapid intrahepatic neutrophil accumulation, elevated levels of myeloperoxidase release, and NET formation in regenerating human livers, with a significantly higher increase of infiltrating neutrophils and NETs in patients with PHLF. Circulating markers of neutrophil activation, including elastase, myeloperoxidase, and citrullinated histone H3, correlated with markers of liver injury. In a murine PHx model, we showed that the inhibition of NET accelerated hepatocyte proliferation and liver regeneration. Conclusions: Patients with PHLF showed accelerated intrahepatic neutrophil infiltration and NET formation, which were associated with liver damage. Further, we identified postsurgical myeloperoxidase levels as predictive markers for adverse outcomes and observed that blocking NETs in a murine PHx model accelerated tissue regeneration.
MeSH term(s)	Humans ; Animals ; Mice ; Neutrophils ; Extracellular Traps ; Liver Failure/etiology ; Focal Nodular Hyperplasia ; Peroxidase
Chemical Substances	Peroxidase (EC 1.11.1.7)
Language	English
Publishing date	2023-12-15
Publishing country	United States
Document type	Journal Article
ISSN	2471-254X
ISSN (online)	2471-254X
DOI	10.1097/HC9.0000000000000348
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Article ; Online: The pro-inflammatory marker soluble suppression of tumorigenicity-2 (ST2) is reduced especially in diabetic morbidly obese patients undergoing bariatric surgery.

Demyanets, Svitlana / Kaun, Christoph / Kaider, Alexandra / Speidl, Walter / Prager, Manfred / Oravec, Stanislav / Hohensinner, Philipp / Wojta, Johann / Rega-Kaun, Gersina

Cardiovascular diabetology

2020 Volume 19, Issue 1, Page(s) 26

Abstract: Background: High soluble suppression of tumorigenicity-2 (sST2) is a marker of poor prognosis in chronic inflammatory conditions. ST2 and its ligand interleukin (IL)-33 are elevated in adipose tissue of obese individuals. We aimed to evaluate ... ...

Abstract	Background: High soluble suppression of tumorigenicity-2 (sST2) is a marker of poor prognosis in chronic inflammatory conditions. ST2 and its ligand interleukin (IL)-33 are elevated in adipose tissue of obese individuals. We aimed to evaluate circulating sST2 and IL-33 as possible markers of metabolic benefit in morbidly overweight patients after Roux-en-Y gastric bypass (RYGB) bariatric surgery. Methods: sST2, IL-33, high sensitive IL-6, high sensitive C-reactive protein (hsCRP), leptin, cholesterol metabolism and liver parameters were measured in 80 morbidly obese individuals before and 1 year after bariatric surgery. Results: sST2 was higher (P = 0.03) in diabetics as compared to individuals without diabetes. Baseline sST2 was also higher in males than in females (P= 0.0002). One year after bariatric surgery, sST2 levels were decreased (median 120, IQR 59-176 pg/mL) as compared to sST2 before surgery (median 141, IQR 111-181, P = 0.0024), and the diabetic group showed most pronounced reduction in sST2 (P = 0.0016). An association was found between sST2 and liver function parameters before and after bariatric surgery, and between baseline sST2 and total cholesterol, triglyceride, total low density lipoprotein (LDL), small dense LDL, Apolipoprotein B as well as with small dense high density lipoproteins (HDL). In the subgroup of diabetic patients positive correlation between IL-33 and sST2 (r = 0.44, P = 0.05) was noticed. Conclusions: Circulating sST2 is associated with markers of liver functions and lipid metabolism in severely obese patients and a reduction of sST2 was shown after successful bariatric surgery, most prominently in diabetic patients.
MeSH term(s)	Adult ; Biomarkers/blood ; Case-Control Studies ; Diabetes Mellitus/blood ; Diabetes Mellitus/diagnosis ; Down-Regulation ; Female ; Gastric Bypass ; Humans ; Inflammation Mediators/blood ; Interleukin-1 Receptor-Like 1 Protein/blood ; Interleukin-33/blood ; Male ; Middle Aged ; Obesity, Morbid/blood ; Obesity, Morbid/diagnosis ; Obesity, Morbid/surgery ; Time Factors ; Treatment Outcome
Chemical Substances	Biomarkers ; IL1RL1 protein, human ; IL33 protein, human ; Inflammation Mediators ; Interleukin-1 Receptor-Like 1 Protein ; Interleukin-33
Language	English
Publishing date	2020-02-26
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	1475-2840
ISSN (online)	1475-2840
DOI	10.1186/s12933-020-01001-y
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Article ; Online: CD8+CD28null T Lymphocytes are Associated with the Development of Atrial Fibrillation after Elective Cardiac Surgery.

Kazem, Niema / Sulzgruber, Patrick / Thaler, Barbara / Baumgartner, Johanna / Koller, Lorenz / Laufer, Günther / Steinlechner, Barbara / Hohensinner, Philipp / Wojta, Johann / Niessner, Alexander

Thrombosis and haemostasis

2020 Volume 120, Issue 8, Page(s) 1182–1187

Abstract: Background: Postoperative atrial fibrillation (POAF) is assumed as a complex and multifactorial interaction of different pathogenic factors. Data suggests an inflammatory process as the main trigger of this specific type of atrial fibrillation. CD8: ... ...

Abstract	Background: Postoperative atrial fibrillation (POAF) is assumed as a complex and multifactorial interaction of different pathogenic factors. Data suggests an inflammatory process as the main trigger of this specific type of atrial fibrillation. CD8 Methods: A total of 129 patients undergoing elective cardiac valve and/or coronary artery bypass graft surgery were enrolled. Fluorescence-activated cell sorting was performed to investigate lymphocyte subsets. Patients were stratified in two subgroups according to patients developing POAF ( Results: Comparing patients developing POAF to individuals free of POAF, the fraction of CD8 Conclusion: We found that cytotoxic CD8
MeSH term(s)	Aged ; Atrial Fibrillation/etiology ; Atrial Fibrillation/immunology ; C-Reactive Protein/analysis ; CD28 Antigens/analysis ; Comorbidity ; Coronary Artery Bypass ; Cytotoxicity, Immunologic ; Elective Surgical Procedures ; Female ; Heart Valve Prosthesis Implantation ; Humans ; Inflammation ; Male ; Middle Aged ; Postoperative Complications/etiology ; Postoperative Complications/immunology ; Prospective Studies ; T-Lymphocyte Subsets/immunology
Chemical Substances	CD28 Antigens ; C-Reactive Protein (9007-41-4)
Language	English
Publishing date	2020-06-28
Publishing country	Germany
Document type	Journal Article ; Observational Study
ZDB-ID	518294-3
ISSN	2567-689X ; 0340-6245
ISSN (online)	2567-689X
ISSN	0340-6245
DOI	10.1055/s-0040-1713096
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Uh III Zs.192: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Epinephrine treatment but not time to ROSC is associated with intestinal injury in patients with cardiac arrest.

Krychtiuk, Konstantin A / Richter, Bernhard / Lenz, Max / Hohensinner, Philipp J / Huber, Kurt / Hengstenberg, Christian / Wojta, Johann / Heinz, Gottfried / Speidl, Walter S

Resuscitation

2020 Volume 155, Page(s) 32–38

Abstract: Aim: Current guidelines suggest the use of epinephrine in patients with cardiac arrest (CA). However, evidence for increased survival in good neurological condition is lacking. In experimental settings, epinephrine-induced impairment of microvascular ... ...

Abstract	Aim: Current guidelines suggest the use of epinephrine in patients with cardiac arrest (CA). However, evidence for increased survival in good neurological condition is lacking. In experimental settings, epinephrine-induced impairment of microvascular flow was shown. The aim of our study was to analyze the association between epinephrine treatment and intestinal injury in patients after CA. Methods: We have included 52 patients with return of spontaneous circulation (ROSC) after CA admitted to our medical intensive care unit (ICU). Blood was taken on admission and levels of circulating intestinal fatty acid binding protein (iFABP) were analyzed. Results: Patients were 64 (49.8-73.8) years old and predominantly male (76.9%). After six months, 50% of patients died and 38.5% of patients had a cerebral performance category (CPC)-score of 1-2. iFABP levels were lower in survivors (234 IQR 90-399 pg/mL) as compared to non-survivors (283, IQR 86-11500 pg/mL; p < 0.05). Plasma levels of iFABP were not associated with time to ROSC but correlated with epinephrine-dose (R = 0.32; p < 0.05). 40% of patients receiving ≥3 mg of epinephrine as compared to 10.5% of patients treated with <3 mg (p < 0.05) developed iFABP plasma levels >1500 pg/mL, which was associated with dramatically increased mortality (HR4.87, 95%CI 1.95-12.1; p < 0.001). iFABP levels predicted mortality independent from time to ROSC and the disease severity score SAPS II. In contrast to mortality, iFABP plasma levels were not associated with neurological outcome. Conclusions: In this small, single centre study, cumulative dose of epinephrine used in cardiac arrest patients was associated with an increase in biomarker indicative of intestinal injury and 6-month mortality.
MeSH term(s)	Aged ; Biomarkers ; Cardiopulmonary Resuscitation ; Epinephrine ; Heart Arrest ; Humans ; Intensive Care Units ; Male ; Middle Aged ; Out-of-Hospital Cardiac Arrest/drug therapy ; Simplified Acute Physiology Score
Chemical Substances	Biomarkers ; Epinephrine (YKH834O4BH)
Language	English
Publishing date	2020-06-06
Publishing country	Ireland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	189901-6
ISSN	1873-1570 ; 0300-9572
ISSN (online)	1873-1570
ISSN	0300-9572
DOI	10.1016/j.resuscitation.2020.05.046
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Article ; Online: Targets of immune regeneration in rheumatoid arthritis.

Hohensinner, Philipp J / Goronzy, Jörg J / Weyand, Cornelia M

Mayo Clinic proceedings

2014 Volume 89, Issue 4, Page(s) 563–575

Abstract: Many of the aging-related morbidities, including cancer, cardiovascular disease, neurodegenerative disease, and infectious susceptibility, are linked to a decline in immune competence with a concomitant rise in proinflammatory immunity, placing the ... ...

Abstract	Many of the aging-related morbidities, including cancer, cardiovascular disease, neurodegenerative disease, and infectious susceptibility, are linked to a decline in immune competence with a concomitant rise in proinflammatory immunity, placing the process of immune aging at the center of aging biology. Immune aging affects individuals older than 50 years and is accelerated in patients with the autoimmune disease rheumatoid arthritis. Immune aging results in a marked decline in protective immune responses and a parallel increase in tissue inflammatory responses. By studying immune cells in patients with rheumatoid arthritis, several of the molecular underpinnings of the immune aging process have been delineated, such as the loss of telomeres and inefficiencies in the repair of damaged DNA. Aging T cells display a series of abnormalities, including the unopposed up-regulation of cytoplasmic phosphatases and the loss of glycolytic competence, that alter their response to stimulating signals and undermine their longevity. Understanding the connection between accelerated immune aging and autoimmunity remains an area of active research. With increasing knowledge of the molecular pathways that cause immunosenescence, therapeutic interventions can be designed to slow or halt the seemingly inevitable deterioration of protective immunity with aging.
MeSH term(s)	Aged ; Aging/immunology ; Aging/physiology ; Arthritis, Rheumatoid/immunology ; Arthritis, Rheumatoid/physiopathology ; Autoimmune Diseases/immunology ; Autoimmune Diseases/physiopathology ; Cellular Senescence/immunology ; Cellular Senescence/physiology ; DNA Damage/immunology ; DNA Repair/immunology ; DNA Repair/physiology ; Disease Progression ; Female ; Humans ; Male ; Middle Aged ; Regeneration/immunology ; Regeneration/physiology ; Sensitivity and Specificity ; T-Lymphocytes/immunology ; T-Lymphocytes/pathology
Language	English
Publishing date	2014-03-28
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	124027-4
ISSN	1942-5546 ; 0025-6196
ISSN (online)	1942-5546
ISSN	0025-6196
DOI	10.1016/j.mayocp.2014.01.020
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