TY - JOUR AU - Sándor, Lilla AU - Donka, Tibor AU - Török, László AU - Hartmann, Petra TI - Thrombocyte aggregometry and rotational viscoelastometry function tests in coagulopathy of polytrauma patients JF - EUROPEAN JOURNAL OF TRAUMA AND EMERGENCY SURGERY J2 - EUR J TRAUMA EMERG S VL - 49 PY - 2023 SP - 13 EP - 14 PG - 2 SN - 1863-9933 UR - https://m2.mtmt.hu/api/publication/34555371 ID - 34555371 LA - English DB - MTMT ER - TY - JOUR AU - Jávor, Péter János AU - Donka, Tibor AU - Horváth, Tamara AU - Sándor, Lilla AU - Török, László AU - Szabó, Andrea AU - Hartmann, Petra TI - Impairment of Mesenteric Perfusion as a Marker of Major Bleeding in Trauma Patients JF - JOURNAL OF CLINICAL MEDICINE J2 - J CLIN MED VL - 12 PY - 2023 IS - 10 PG - 18 SN - 2077-0383 DO - 10.3390/jcm12103571 UR - https://m2.mtmt.hu/api/publication/33844366 ID - 33844366 N1 - Funding Agency and Grant Number: National Research Development and Innovation Office OTKA Research Grant [FK138839]; Hungarian Academy of Sciences [BO/00605/21/5] Funding text: The study was funded by the National Research Development and Innovation Office OTKA Research Grant FK138839. Further funding was provided by the Hungarian Academy of Sciences: Janos Bolyai Research Grant BO/00605/21/5. Funders did not influence the design and scientific content of our paper in any way. AB - The majority of potentially preventable mortality in trauma patients is related to bleeding; therefore, early recognition and effective treatment of hemorrhagic shock impose a cardinal challenge for trauma teams worldwide. The reduction in mesenteric perfusion (MP) is among the first compensatory responses to blood loss; however, there is no adequate tool for splanchnic hemodynamic monitoring in emergency patient care. In this narrative review, (i) methods based on flowmetry, CT imaging, video microscopy (VM), measurement of laboratory markers, spectroscopy, and tissue capnometry were critically analyzed with respect to their accessibility, and applicability, sensitivity, and specificity. (ii) Then, we demonstrated that derangement of MP is a promising diagnostic indicator of blood loss. (iii) Finally, we discussed a new diagnostic method for the evaluation of hemorrhage based on exhaled methane (CH4) measurement. Conclusions: Monitoring the MP is a feasible option for the evaluation of blood loss. There are a wide range of experimentally used methodologies; however, due to their practical limitations, only a fraction of them could be integrated into routine emergency trauma care. According to our comprehensive review, breath analysis, including exhaled CH4 measurement, would provide the possibility for continuous, non-invasive monitoring of blood loss. LA - English DB - MTMT ER - TY - JOUR AU - Bozó, Renáta AU - Matiz, E. AU - Flink, Lili Borbála AU - Baráth, Bálint AU - Sándor, Lilla AU - Hartmann, Petra AU - Kemény, Lajos AU - Csörgő Sándorné Bata, Zsuzsanna TI - Mitochondrial abnormalities in the psoriatic uninvolved keratinocytes JF - JOURNAL OF INVESTIGATIVE DERMATOLOGY J2 - J INVEST DERMATOL VL - 143 PY - 2023 IS - Suppl. 5 SP - S24 EP - S24 PG - 1 SN - 0022-202X DO - 10.1016/j.jid.2023.03.143 UR - https://m2.mtmt.hu/api/publication/33827230 ID - 33827230 N1 - HCEMM-USZ Skin Research Group, University of Szeged, Szeged, Hungary LA - English DB - MTMT ER - TY - JOUR AU - Horváth, Tamara AU - Sándor, Lilla AU - Baráth, Bálint AU - Donka, Tibor AU - Baráth, Bence AU - Mohácsi, Árpád AU - Jász, Dávid Kurszán AU - Hartmann, Petra AU - Boros, Mihály TI - Methane Admixture Protects Liver Mitochondria and Improves Graft Function after Static Cold Storage and Reperfusion JF - ANTIOXIDANTS J2 - ANTIOXIDANTS-BASEL VL - 12 PY - 2023 IS - 2 PG - 15 SN - 2076-3921 DO - 10.3390/antiox12020271 UR - https://m2.mtmt.hu/api/publication/33603762 ID - 33603762 AB - Mitochondria are targets of cold ischemia-reperfusion (IR), the major cause of cell damage during static cold preservation of liver allografts. The bioactivity of methane (CH4) has recently been recognized in various hypoxic and IR conditions as having influence on many aspects of mitochondrial biology. We therefore hypothesized that cold storage of liver grafts in CH4-enriched preservation solution can provide an increased defence against organ dysfunction in a preclinical rat model of liver transplantation. Livers were preserved for 24 h in cold histidine–tryptophan–ketoglutarate (HTK) or CH4-enriched HTK solution (HTK-CH4) (n = 24 each); then, viability parameters were monitored for 60 min during normothermic isolated reperfusion and perfusate and liver tissue were collected. The oxidative phosphorylation capacity and extramitochondrial Ca2+ movement were measured by high resolution respirometry. Oxygen and glucose consumption increased significantly while hepatocellular damage was decreased in the HTK-CH4 grafts compared to the HTK group. Mitochondrial oxidative phosphorylation capacity was more preserved (128.8 ± 31.5 pmol/s/mL vs 201.3 ± 54.8 pmol/s/mL) and a significantly higher Ca2+ flux was detected in HTK-CH4 storage (2.9 ± 0.1 mV/s) compared to HTK (2.3 ± 0.09 mV/s). These results demonstrate the direct effect of CH4 on hepatic mitochondrial function and extramitochondrial Ca2+ fluxes, which may have contributed to improved graft functions and a preserved histomorphology after cold IR. LA - English DB - MTMT ER - TY - JOUR AU - Jávor, Péter János AU - Rárosi, Ferenc AU - Horváth, Tamara AU - Török, László AU - Hartmann, Petra TI - Mitochondrial Dysfunction in Trauma-Related Coagulopathy: Is There Causality? Study Protocol for a Prospective Observational Study JF - EUROPEAN SURGICAL RESEARCH J2 - EUR SURG RES VL - 64 PY - 2023 IS - 2 SP - 304 EP - 309 PG - 6 SN - 0014-312X DO - 10.1159/000521670 UR - https://m2.mtmt.hu/api/publication/32714157 ID - 32714157 N1 - Study protocol Besorolása szakcikk a központi MTMT adminisztrátorokkal történt egyeztetés és az MTA V. Osztályának képviselője által végzett tartalmi vizsgálat alapján. (BCS, SZTE admin4, 2023.01.10.) AB - Hemorrhage control often poses a great challenge for clinicians due to trauma-induced coagulopathy (TIC). The pathogenesis of TIC is not completely revealed; however, growing evidence attributes a central role to altered platelet biology. The activation of thrombocytes and subsequent clot formation are highly energetic processes being tied to mitochondrial activity, and the inhibition of the electron transport chain (ETC) impedes on thrombogenesis, suggesting the potential role of mitochondria in TIC. Our present study protocol provides a guide to quantitatively characterize the derangements of mitochondrial functions in TIC. One hundred eleven severely injured (injury severity score ≥16), bleeding trauma patients with an age of 18 or greater will be included in this prospective observational study. Patients receiving oral antiplatelet agents including cyclooxygenase-1 or adenosine diphosphate receptor inhibitors (aspirin, clopidogrel, prasugrel, and ticagrelor) will be excluded from the final analysis. Hemorrhage will be confirmed and assessed with computer tomography. Conventional laboratory markers of hemostasis such as prothrombin time and international normalized ratio will be measured and rotational thromboelastometry (ROTEM) will be performed directly upon patient arrival. Platelets will be isolated from venous blood samples and subjected to high-resolution fluororespirometry (Oxygraph-2k, Oroboros Instruments, Innsbruck, Austria) to evaluate the efficacy of mitochondrial respiration. Oxidative phosphorylation (OxPhos), coupling of the ETC, mitochondrial superoxide formation, mitochondrial membrane potential changes, and extramitochondrial Ca2+-movement will be recorded. The association between OxPhos capacity of platelet mitochondria and numerical parameters of ROTEM aggregometry will constitute our primary outcome. The relation between OxPhos capacity and results of viscoelastic assays and conventional markers of hemostasis will serve as secondary outcomes. The association of the OxPhos capacity of platelet mitochondria upon patient arrival to the need for massive blood transfusion and 24-h mortality will constitute our tertiary outcomes. Mitochondrial dysfunction and its importance in TIC are yet to be assessed for the deeper understanding of this common, life-threatening condition. Disclosure of mitochondria-mediated processes in thrombocytes may reveal new therapeutic targets in the management of hemorrhaging trauma patients, thereby leading to a reduction of potentially preventable mortality. The present protocol was registered to ClinicalTrials.gov on 12 August 2021, under the reference number NCT05004844. LA - English DB - MTMT ER - TY - JOUR AU - Lantos, Judit AU - Furák, József AU - Zombori-Tóth, Noémi AU - Zombori, Tamás AU - Bihari, Katalin AU - Varga, Endre AU - Hartmann, Petra TI - A csecsemőmirigy T-sejtjeinek összetételében létrejövő változások a COVID–19-pandémia alatt [Changes of the T cell composition in the thymus during the COVID-19 pandemic] JF - ORVOSI HETILAP J2 - ORV HETIL VL - 163 PY - 2022 IS - 52 SP - 2062 EP - 2066 PG - 5 SN - 0030-6002 DO - 10.1556/650.2022.32664 UR - https://m2.mtmt.hu/api/publication/33295158 ID - 33295158 AB - Bevezetés: A COVID–19-fertőzés vagy a védőoltás hatását vizsgáltuk a csecsemőmirigyben zajló T-sejtek differenciá- lódására, illetve hogy a T-sejtek számának a fertőzöttek vérében észlelhető csökkenése a thymusban is észlelhető-e. Módszer: Összesen 55, thymectomián átesett beteg adatainak feldolgozása során három csoportot alakítottunk ki: 1) a pre-COVID–19 (PC)-csoportban szerepel 22 beteg, 12 nő és 10 férfi, akiknél 2008 és 2013 között történt thymectomia; a 2) no-COVID–19 (NC)-csoportban (védőoltást nem kapott, fertőzésen át nem esett) 20 betegnél (11 nő és 9 férfi) 2020–2021-ben, a 3) COVID–19-védőoltást kapott vagy -infekción átesett (VIC-) csoportban 13 betegnél (4 nő és 9 férfi) szintén 2020–2021-ben történt thymectomia. A patológiai mintákon CD4, CD8, CD25 és FOXP3 immunhisztokémiai vizsgálatok történtek a ’helper’, a citotoxikus és a regulációs T-sejtek igazolására. Eredmények: A VIC-csoportban a CD4-sejtek előfordulása szignifikánsan alacsonyabb volt a PC- és az NC-csoporthoz képest. A FOXP3 a VIC- és az NC-csoportban szignifikánsan kisebb előfordulást mutatott a PC-csoporthoz képest. A CD8, CD25 esetében szignifikáns különbséget a vizsgált csoportok között nem találtunk. Megbeszélés: A COVID–19-fertőzés vagy a védőoltás hatással van a thymus T-sejtes összetételére. A VIC-csoportban észlelt CD4-expresszió-csökkenés igazolja a T-sejtek számának a thymusban is bekövetkező csökkenését. A COVID– 19-éra alatt az NC-csoportban a PC-csoporthoz képest észlelt alacsony FOXP3-szint a tünetmentes COVID–19-fertőzés nagy arányára utalhat, és az immuntolerancia romlását jelzi. Következtetés: Az általunk hozzáférhető irodalomban először igazoltuk, hogy a COVID–19-fertőzés hatására a csecsemőmirigyben csökken a ’helper’ T-sejtek előfordulása, és tünetmentes betegeknél is csökken az immunvédekezés. LA - Hungarian DB - MTMT ER - TY - JOUR AU - Jávor, Péter János AU - Hanák, Lilla AU - Hegyi, Péter AU - Csonka, Endre AU - Butt, Edina AU - Horváth, Tamara AU - Góg, István AU - Lukács, Anita AU - Soós, Alexandra AU - Rumbus, Zoltán AU - Pákai, Eszter AU - Toldi, János AU - Hartmann, Petra TI - Predictive value of tachycardia for mortality in trauma-related haemorrhagic shock: a systematic review and meta-regression JF - BMJ OPEN J2 - BMJ OPEN VL - 12 PY - 2022 IS - 10 PG - 8 SN - 2044-6055 DO - 10.1136/bmjopen-2021-059271 UR - https://m2.mtmt.hu/api/publication/33192543 ID - 33192543 AB - Objectives Heart rate (HR) is one of the physiological variables in the early assessment of trauma-related haemorrhagic shock, according to Advanced Trauma Life Support (ATLS). However, its efficiency as predictor of mortality is contradicted by several studies. Furthermore, the linear association between HR and the severity of shock and blood loss presented by ATLS is doubtful. This systematic review aims to update current knowledge on the role of HR in the initial haemodynamic assessment of patients who had a trauma. Design This study is a systematic review and meta-regression that follows the Preferred Reporting Items for Systematic Reviews and Meta-Analyses recommendations. Data sources EMBASE, MEDLINE, CENTRAL and Web of Science databases were systematically searched through on 1 September 2020. Eligibility criteria Papers providing early HR and mortality data on bleeding patients who had a trauma were included. Patient cohorts were considered haemorrhagic if the inclusion criteria of the studies contained transfusion and/or positive focused assessment with sonography for trauma and/or postinjury haemodynamical instability and/or abdominal gunshot injury. Studies on burns, traumatic spinal or brain injuries were excluded. Papers published before January 2010 were not considered. Data extraction and synthesis Data extraction and risk of bias were assessed by two independent investigators. The association between HR and mortality of patients who had a trauma was assessed using meta-regression analysis. As subgroup analysis, meta-regression was performed on patients who received blood products. Results From a total of 2017 papers, 19 studies met our eligibility criteria. Our primary meta-regression did not find a significant relation (p=0.847) between HR and mortality in patients who had a trauma with haemorrhage. Our subgroup analysis included 10 studies, and it could not reveal a linear association between HR and mortality rate. Conclusions In accordance with the literature demonstrating the multiphasic response of HR to bleeding, our study presents the lack of linear association between postinjury HR and mortality. Modifying the pattern of HR derangements in the ATLS shock classification may result in a more precise teaching tool for young clinicians. LA - English DB - MTMT ER - TY - JOUR AU - Jávor, Péter János AU - Rárosi, Ferenc AU - Horváth, Tamara AU - Török, László AU - Varga, Endre AU - Hartmann, Petra TI - Detection of exhaled methane levels for monitoring trauma-related haemorrhage following blunt trauma. study protocol for a prospective observational study TS - study protocol for a prospective observational study JF - BMJ OPEN J2 - BMJ OPEN VL - 12 PY - 2022 IS - 7 PG - 7 SN - 2044-6055 DO - 10.1136/bmjopen-2021-057872 UR - https://m2.mtmt.hu/api/publication/32924263 ID - 32924263 N1 - Study protocol Besorolása szakcikk a központi MTMT adminisztrátorokkal történt egyeztetés és az MTA V. Osztályának képviselője által végzett tartalmi vizsgálat alapján. (BCS, SZTE admin4, 2023.01.10.) AB - Early recognition and effective treatment of internal bleeding impose a cardinal challenge for trauma teams. The reduction of the superior mesenteric artery (SMA) blood flow is among the first compensatory responses to blood loss, thus being a promising candidate as a diagnostic tool for occult haemorrhage. Unfortunately, methods for monitoring the SMA flow have not been elaborated to date. Nevertheless, animal experiments suggest that exhaled methane (CH4) levels correspond to the SMA perfusion. We hypothesise that real-time detection of CH4 concentrations in the exhaled air is an applicable technique for the early recognition of haemorrhage in severely injured patients. We also hypothesise that exhaled CH4 levels reflect the volume of blood loss more accurately than conventional markers of blood loss and shock such as shock index, haemoglobin, base deficit, lactate, end-tidal carbon dioxide and sublingual microcirculatory indices.One hundred and eleven severely injured (Injury Severity Score ≥16), intubated, bleeding patients sustaining blunt trauma will be included in this prospective observational study. Blood loss will be detected with CT and estimated with CT-linked radiologic software. Exhaled CH4 concentrations will be monitored by attaching a near-infrared laser technique-based photoacoustic spectroscopy apparatus to the exhalation outlet of the ventilator on patient arrival. The primary outcome is the volume of blood loss. Need for massive transfusion and 24-hour mortality will constitute secondary outcomes. The relation of exhaled CH4 to study outcomes and its performance in predicting blood loss in comparison with conventional shock markers and microcirculatory indices will be tested.Our protocol (ID: 5400/2021-SZTE) has been registered on ClinicalTrials.gov (NCT04987411) and complies with the Declaration of Helsinki and has been approved by the medical ethics committee at the University of Szeged (Ref.nr.:121/2021-SZTE RKEB). It is in data collection phase, theresults will be shared with the scientific community through publication in a peer-reviewed journal.NCT04987411; ClinicalTrials.gov, registered on 27 July 2021. LA - English DB - MTMT ER - TY - JOUR AU - Jávor, Péter János AU - Mácsai, Attila AU - Butt, Edina AU - Baráth, Bálint AU - Jász, Dávid Kurszán AU - Horváth, Tamara AU - Baráth, Bence AU - Csonka, Ákos AU - Török, László AU - Varga, Endre AU - Hartmann, Petra TI - Mitochondrial Dysfunction Affects the Synovium of Patients with Rheumatoid Arthritis and Osteoarthritis Differently JF - INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES J2 - INT J MOL SCI VL - 23 PY - 2022 IS - 14 PG - 14 SN - 1661-6596 DO - 10.3390/ijms23147553 UR - https://m2.mtmt.hu/api/publication/32924179 ID - 32924179 AB - There is growing evidence regarding the role of mitochondrial dysfunction in osteoarthritis (OA) and rheumatoid arthritis (RA). However, quantitative comparison of synovial mitochondrial derangements in these main arthritis forms is missing. A prospective clinical study was conducted on adult patients undergoing knee surgery. Patients were allocated into RA and OA groups based on disease-specific clinical scores, while patients without arthritis served as controls. Synovial samples were subjected to high-resolution respirometry to analyze mitochondrial functions. From the total of 814 patients, 109 cases were enrolled into the study (24 RA, 47 OA, and 38 control patients) between 1 September 2019 and 31 December 2021. The decrease in complex I-linked respiration and dyscoupling of mitochondria were characteristics of RA patients, while both arthritis groups displayed reduced OxPhos activity compared to the control group. However, no significant difference was found in complex II-related activity between the OA and RA groups. The cytochrome C release and H2O2 formation were increased in both arthritis groups. Mitochondrial dysfunction was present in both arthritis groups; however, to a different extent. Consequently, mitochondrial protective agents may have major benefits for arthritis patients. Based on our current study, we recommend focusing on respiratory complex I in rheumatoid arthritis research. LA - English DB - MTMT ER - TY - JOUR AU - Baráth, Bálint AU - Jász, Dávid Kurszán AU - Horváth, Tamara AU - Baráth, Bence AU - Maróti, Gergely AU - Strifler, Gerda AU - Varga, Gabriella AU - Sándor, Lilla AU - Perényi, Domonkos AU - Tallósy, Szabolcs Péter AU - Donka, Tibor AU - Jávor, Péter János AU - Boros, Mihály AU - Hartmann, Petra TI - Mitochondrial Side Effects of Surgical Prophylactic Antibiotics Ceftriaxone and Rifaximin Lead to Bowel Mucosal Damage JF - INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES J2 - INT J MOL SCI VL - 23 PY - 2022 IS - 9 PG - 17 SN - 1661-6596 DO - 10.3390/ijms23095064 UR - https://m2.mtmt.hu/api/publication/32805370 ID - 32805370 N1 - Funding Agency and Grant Number: Hungarian Academy of Sciences; Janos Bolyai Research Scholarship [BO/00605/21/5]; National Research, Development and Innovation Office (NFKIH) [K120232, FK138839]; National Research, Development and Innovation Office (NFKIH) Thematic Program of Excellence [TKP2020 NKFIH-1279-2/2020]; Economic Development and Innovation Operative Programme [GINOP-2.3.2-15-2016-00034] Funding text: Hungarian Academy of Sciences; Janos Bolyai Research Scholarship grant BO/00605/21/5 (P.H.); National Research, Development and Innovation Office (NFKIH) grant FK138839 (P.H.); National Research, Development and Innovation Office (NFKIH) grant K120232 (M.B.); National Research, Development and Innovation Office (NFKIH) Thematic Program of Excellence grant TKP2020 NKFIH-1279-2/2020; Economic Development and Innovation Operative Programme grant GINOP-2.3.2-15-2016-00034. AB - Despite their clinical effectiveness, a growing body of evidence has shown that many classes of antibiotics lead to mitochondrial dysfunction. Ceftriaxone and Rifaximin are first choice perioperative antibiotics in gastrointestinal surgery targeting fundamental processes of intestinal bacteria; however, may also have negative consequences for the host cells. In this study, we investigated their direct effect on mitochondrial functions in vitro, together with their impact on ileum, colon and liver tissue. Additionally, their impact on the gastrointestinal microbiome was studied in vivo, in a rat model. Rifaximin significantly impaired the oxidative phosphorylation capacity (OxPhos) and leak respiration in the ileal mucosa, in line with increased oxidative tissue damage and histological changes following treatment. Ceftriaxone prophylaxis led to similar changes in the colon mucosa. The composition and diversity of bacterial communities differed extensively in response to antibiotic pre-treatment. However, the relative abundances of the toxin producing species were not increased. We have confirmed the harmful effects of prophylactic doses of Rifaximin and Ceftriaxone on the intestinal mucosa and that these effects were related to the mitochondrial dysfunction. These experiments raise awareness of mitochondrial side effects of these antibiotics that may be of clinical importance when evaluating their adverse effects on bowel mucosa. LA - English DB - MTMT ER -