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Article ; Online: Novel Damage Biomarkers of Sepsis-Related Acute Kidney Injury.

Ragán, Dániel / Horváth-Szalai, Zoltán / Szirmay, Balázs / Mühl, Diána

EJIFCC

2022 Volume 33, Issue 1, Page(s) 11–22

Abstract: Sepsis-related acute kidney injury (AKI) is one of the most common complications of sepsis at the intensive care unit (ICU) with more adverse mortality rates. The early diagnosis and reliable monitoring of sepsis-related AKI are essential in achieving a ... ...

Abstract	Sepsis-related acute kidney injury (AKI) is one of the most common complications of sepsis at the intensive care unit (ICU) with more adverse mortality rates. The early diagnosis and reliable monitoring of sepsis-related AKI are essential in achieving a favorable outcome. Novel serum and urinary biomarkers could yield valuable information during this process. Regarding the widely used Kidney Disease Improving Global Outcomes (KDIGO) classifications, the diagnosis of AKI is still based on the increase of serum creatinine levels and the decrease of urine output; however, these parameters have limitations in reflecting the extent of kidney damage, therefore more sensitive and specific laboratory biomarkers are needed for the early diagnosis and prognosis of sepsis-related AKI. Regarding this, several serum parameters are discussed in this review including presepsin and the most important actin scavenger proteins (gelsolin, Gc-globulin) while other urinary markers are also examined including cell cycle arrest biomarkers, neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule 1 (KIM-1), Cystatin C and actin. Novel biomarkers of sepsis-related AKI could facilitate the early diagnosis and monitoring of sepsis-related AKI.
Language	English
Publishing date	2022-04-11
Publishing country	Italy
Document type	Journal Article
ISSN	1650-3414
ISSN (online)	1650-3414
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Acute Phase Protein Orosomucoid (Alpha-1-Acid Glycoprotein) Predicts Delayed Cerebral Ischemia and 3-Month Unfavorable Outcome after Aneurysmal Subarachnoid Hemorrhage.

Zavori, Laszlo / Varnai, Reka / Molnar, Tihamer / Szirmay, Balazs / Farkas, Nelli / Schwarcz, Attila / Csecsei, Peter

International journal of molecular sciences

2023 Volume 24, Issue 20

Abstract: The pathophysiology and consequences of early brain injury (EBI) after aneurysmal subarachnoid hemorrhage (aSAH) remain incompletely understood. This study aims to investigate the role of orosomucoid (ORM) in aSAH, its potential as a marker for assessing ...

Abstract	The pathophysiology and consequences of early brain injury (EBI) after aneurysmal subarachnoid hemorrhage (aSAH) remain incompletely understood. This study aims to investigate the role of orosomucoid (ORM) in aSAH, its potential as a marker for assessing the extent of EBI-induced damage, and its correlation with delayed cerebral ischemia (DCI) and functional recovery over a 3-month period. We collected serum specimens 72 h post-aSAH to measure ORM levels. The study included 151 aSAH patients and 105 healthy subjects. The serum ORM levels within the patient cohort significantly exceeded those in the control group (
MeSH term(s)	Humans ; Subarachnoid Hemorrhage ; Orosomucoid ; Acute-Phase Proteins ; Brain Ischemia/complications ; Cerebral Infarction/complications
Chemical Substances	Orosomucoid ; Acute-Phase Proteins
Language	English
Publishing date	2023-10-17
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/ijms242015267
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Article: Absence of Nkx2-3 induces ectopic lymphatic endothelial differentiation associated with impaired extramedullary stress hematopoiesis in the spleen.

Gábris, Fanni / Kiss, Gabriella / Szirmay, Balázs / Szomor, Árpád / Berta, Gergely / Jakus, Zoltán / Kellermayer, Zoltán / Balogh, Péter

Frontiers in cell and developmental biology

2023 Volume 11, Page(s) 1170389

Abstract: The red and white pulps as two main parts of the spleen are arranged around distinct types of vasculature, and perform significantly different functions in both humans and mice. Previous observations indicated a profound alteration of the local vessel ... ...

Abstract	The red and white pulps as two main parts of the spleen are arranged around distinct types of vasculature, and perform significantly different functions in both humans and mice. Previous observations indicated a profound alteration of the local vessel specialization in mice lacking Nkx2-3 homeodomain transcription factor, including contradictory results suggesting presence of an ectopic lymphatic vascular structure. Furthermore, how the absence of Nkx2-3 and the consequential changes in endothelial components affect the extramedullary hematopoietic activity restricted to the splenic red pulp is unknown. In this work, we investigated the role of Nkx2-3 homeodomain transcription factor as a major morphogenic determinant for vascular specification, and its effect in the extramedullary hematopoiesis following acute blood loss and pharmacological stimulation of megakaryocyte differentiation after treatment with thrombopoietin-receptor mimetic Romiplostim. We found that, in mice lacking Nkx2-3, Prox1-positive lymphatic capillaries containing gp38/CD31 double positive lymphatic endothelial cells develop, arranged into an extensive meshwork, while the Clever1-positive venous segments of red pulp blood vasculature are absent. This lymphatic endothelial shift is coupled with a severely compromised splenic erythropoiesis and a significantly reduced splenic megakaryocyte colony formation following Romiplostim treatment in mice lacking Nkx2-3. These findings indicate that the shift of microvascular patterning in the absence of Nkx2-3 includes the emergence of ectopic Prox1-positive lymphatic vessels, and that this pivoting towards lymph node-like vascular patterning is associated with an impaired reserve hematopoietic capacity of the splenic red pulp.
Language	English
Publishing date	2023-04-05
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2737824-X
ISSN	2296-634X
ISSN	2296-634X
DOI	10.3389/fcell.2023.1170389
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Article ; Online: Measurement of Urinary Gc-Globulin by a Fluorescence ELISA Technique: Method Validation and Clinical Evaluation in Septic Patients-A Pilot Study.

Kőszegi, Tamás / Horváth-Szalai, Zoltán / Ragán, Dániel / Kósa, Brigitta / Szirmay, Balázs / Kurdi, Csilla / Kovács, Gábor L / Mühl, Diána

Molecules (Basel, Switzerland)

2023 Volume 28, Issue 19

Abstract: A major complication of sepsis is the development of acute kidney injury (AKI). In case of acute tubular damage, Gc-globulin, a known serum sepsis marker is increasingly filtrated into the urine therefore, urinary Gc-globulin (u-Gc) levels may predict ... ...

Abstract	A major complication of sepsis is the development of acute kidney injury (AKI). In case of acute tubular damage, Gc-globulin, a known serum sepsis marker is increasingly filtrated into the urine therefore, urinary Gc-globulin (u-Gc) levels may predict septic AKI. We developed and validated a competitive fluorescence ELISA method for u-Gc measurement. Serum and urine samples from septic patients were collected in three consecutive days (T1, T2, T3) and data were compared to controls. Intra- and interassay imprecisions were CV < 14% and CV < 20%, respectively, with a recovery close to 100%. Controls and septic patients differed (
MeSH term(s)	Humans ; Pilot Projects ; Creatinine ; Acute Kidney Injury/etiology ; Biomarkers ; Sepsis ; Enzyme-Linked Immunosorbent Assay ; Globulins
Chemical Substances	Creatinine (AYI8EX34EU) ; Biomarkers ; Globulins
Language	English
Publishing date	2023-09-29
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	1413402-0
ISSN	1420-3049 ; 1431-5165 ; 1420-3049
ISSN (online)	1420-3049
ISSN	1431-5165 ; 1420-3049
DOI	10.3390/molecules28196864
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Article: Cystatin-c May Indicate Subclinical Renal Involvement, While Orosomucoid Is Associated with Fatigue in Patients with Long-COVID Syndrome.

Zavori, Laszlo / Molnar, Tihamer / Varnai, Reka / Kanizsai, Andrea / Nagy, Lajos / Vadkerti, Bence / Szirmay, Balazs / Schwarcz, Attila / Csecsei, Peter

Journal of personalized medicine

2023 Volume 13, Issue 2

Abstract: Long-COVID syndrome is associated with high healthcare costs, but its pathophysiology is not yet fully understood. Inflammation, renal impairment or disturbance of the NO system emerge as potential pathogenetic factors. We aimed to investigate the ... ...

Abstract	Long-COVID syndrome is associated with high healthcare costs, but its pathophysiology is not yet fully understood. Inflammation, renal impairment or disturbance of the NO system emerge as potential pathogenetic factors. We aimed to investigate the relationship between symptoms of long-COVID syndrome and serum levels of cystatin-c (CYSC), orosomucoid (ORM), l-arginine, symmetric dimethylarginine (SDMA) and asymmetric dimethylarginine (ADMA). A total of 114 patients suffering from long-COVID syndrome were included in this observational cohort study. We found that serum CYSC was independently associated with the anti-spike immunoglobulin (S-Ig) serum level (OR: 5.377, 95% CI: 1.822-12.361;
Language	English
Publishing date	2023-02-19
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2662248-8
ISSN	2075-4426
ISSN	2075-4426
DOI	10.3390/jpm13020371
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Article: Presepsin: gelsolin ratio, as a promising marker of sepsis-related organ dysfunction: a prospective observational study.

Ragán, Dániel / Kustán, Péter / Horváth-Szalai, Zoltán / Szirmay, Balázs / Miseta, Attila / Woth, Gábor / Kőszegi, Tamás / Mühl, Diána

Frontiers in medicine

2023 Volume 10, Page(s) 1126982

Abstract: Introduction: We aimed to facilitate the diagnosis and prognosis of sepsis-related organ dysfunction through analyzing presepsin (PSEP) and gelsolin (GSN) levels along with a novel marker, the presepsin:gelsolin (PSEP:GSN) ratio.: Methods: Blood ... ...

Abstract	Introduction: We aimed to facilitate the diagnosis and prognosis of sepsis-related organ dysfunction through analyzing presepsin (PSEP) and gelsolin (GSN) levels along with a novel marker, the presepsin:gelsolin (PSEP:GSN) ratio. Methods: Blood samples were collected from septic patients at the intensive care unit (ICU) at three time points (T1-3): T1: within 12 h after admission; T2: second day morning; T3: third day morning. Sampling points for non-septic ICU patients were T1 and T3. PSEP was measured by a chemiluminescence-based POCT method while GSN was determined by an automated immune turbidimetric assay. Data were compared with routine lab and clinical parameters. Patients were categorized by the Sepsis-3 definitions. PSEP:GSN ratio was evaluated in major sepsis-related organ dysfunctions including hemodynamic instability, respiratory insufficiency and acute kidney injury (AKI). Results: In our single center prospective observational study, 126 patients were enrolled (23 control, 38 non-septic and 65 septic patients). In contrast to controls, significantly elevated ( Conclusion: PSEP:GSN ratio could be a useful complementary marker besides the routinely used SOFA score regarding the diagnosis and short term mortality prediction of sepsis. Furthermore, the significant increase of this biomarker may also indicate the need for prolonged vasopressor or mechanical ventilation requirement of septic patients. PSEP:GSN ratio could yield valuable information regarding the extent of inflammation and the simultaneous depletion of the patient's scavenger capacity during sepsis. Clinical trail registration: NIH U.S. National Library of Medicine, ClinicalTrails.gov. Trial identifier: NCT05060679, (https://clinicaltrials.gov/ct2/show/NCT05060679) 23.03.2022, Retrospectively registered.
Language	English
Publishing date	2023-05-05
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2775999-4
ISSN	2296-858X
ISSN	2296-858X
DOI	10.3389/fmed.2023.1126982
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Article ; Online: Cardiovascular risk factors in coeliac disease (ARCTIC): a protocol of multicentre series of studies.

Vereczkei, Zsófia / Imrei, Marcell / Szakács, Zsolt / Kővári, Bálint / Papp, Veronika / Lénárt, Zsuzsanna / Berki, Tímea / Szirmay, Balázs / Farkas, Nelli / Balaskó, Márta / Habon, Tamás / Hegyi, Péter / Bajor, Judit

BMJ open

2023 Volume 13, Issue 9, Page(s) e068989

Abstract: Introduction: There is only limited and controversial information available on the cardiovascular (CV) risk in coeliac disease (CD). In this study, we plan to investigate the body composition and CV risk-related metabolic parameters at the diagnosis of ... ...

Abstract	Introduction: There is only limited and controversial information available on the cardiovascular (CV) risk in coeliac disease (CD). In this study, we plan to investigate the body composition and CV risk-related metabolic parameters at the diagnosis of CD and on a gluten-free diet in a Hungarian cohort of patients with CD. Methods and analysis: This study consists of two case-control studies and a prospective cohort study, involving newly diagnosed and treated patients with CD with age and sex-matched non-CD control subjects with an allocation ratio of 1:1. CD-related symptoms, quality of life, quality of the diet and CV risk will be assessed with questionnaires. Our primary outcomes are body composition parameters, which will be estimated with InBody 770 device. Secondary outcomes are CV-risk related metabolic parameters (eg, serum lipids, haemoglobin A1c, homeostatic model assessment index, liver enzymes, homocysteine, interleukin 6, galectin-3) and enteral hormones (leptin, ghrelin, adiponectin) measured from venous blood samples for all participants. Fatty liver disease will be assessed by transabdominal ultrasonography. In statistical analysis, descriptive and comparative statistics will be performed. With this study, we aim to draw attention to the often neglected metabolic and CV aspect of the management of CD. Findings may help to identify parameters to be optimised and reassessed during follow-up in patients with CD. Ethics and dissemination: The study was approved by the Scientific and Research Ethics Committee of the Hungarian Medical Research Council (27521-5/2022/EÜIG). Findings will be disseminated at research conferences and in peer-reviewed journals. Trial registration number: NCT05530070.
MeSH term(s)	Humans ; Celiac Disease/complications ; Cardiovascular Diseases/etiology ; Prospective Studies ; Quality of Life ; Risk Factors ; Heart Disease Risk Factors ; Multicenter Studies as Topic
Language	English
Publishing date	2023-09-13
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2599832-8
ISSN	2044-6055 ; 2044-6055
ISSN (online)	2044-6055
ISSN	2044-6055
DOI	10.1136/bmjopen-2022-068989
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Article ; Online: Is Balneotherapy Protective Against Oxidative Stress? A Pilot Study.

Szenczi, Agnes / Peter, Ivan / Nusser, Nora / Ajtay, Zeno / Szendi, Katalin / Berenyi, Karoly / Horvath-Szalai, Zoltan / Szirmay, Balazs / Sumegi, Andras / Hanzel, Adrienn / Nemeth, Balazs

In vivo (Athens, Greece)

2023 Volume 37, Issue 2, Page(s) 858–861

Abstract: Background/aim: This study aimed to research the effects of Harkány healing water on oxidative stress. The study was performed in a randomized, placebo-controlled, double-blind setup.: Patients and methods: Twenty patients with psoriasis who ... ...

Abstract	Background/aim: This study aimed to research the effects of Harkány healing water on oxidative stress. The study was performed in a randomized, placebo-controlled, double-blind setup. Patients and methods: Twenty patients with psoriasis who underwent a 3-week-long inward balneotherapy-based rehabilitation were enrolled. Psoriasis Area and Severity Index (PASI) score and Malondialdehyde (MDA) - a marker of oxidative stress - were determined, on admission and before discharge. Patients were treated with dithranol. Results: The mean PASI score - determined on admission and before discharge - decreased significantly after the 3-week-long rehabilitation 8.17 vs. 3.51 (p<0.001). The baseline MDA value of patients with psoriasis was significantly higher compared to controls (3.0±3.5 vs. 8.4±7.4) (p=0.018). MDA levels of patients receiving placebo water increased significantly compared to MDA levels of patients receiving healing water (p=0.049). Conclusion: The effectiveness of dithranol resides in the formation of reactive oxygen species. No increased oxidative stress was found in the patients treated with healing water, thus healing water seems to be protective against oxidative stress. However, further research is needed to confirm these preliminary results.
MeSH term(s)	Humans ; Pilot Projects ; Anthralin ; Oxidative Stress ; Balneology ; Psoriasis/therapy ; Water
Chemical Substances	Anthralin (U8CJK0JH5M) ; Water (059QF0KO0R)
Language	English
Publishing date	2023-03-07
Publishing country	Greece
Document type	Randomized Controlled Trial ; Journal Article
ZDB-ID	807031-3
ISSN	1791-7549 ; 0258-851X
ISSN (online)	1791-7549
ISSN	0258-851X
DOI	10.21873/invivo.13153
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Article ; Online: Serum Total Antioxidant Capacity (TAC) and TAC/Lymphocyte Ratio as Promising Predictive Markers in COVID-19.

Horváth-Szalai, Zoltán / Jakabfi-Csepregi, Rita / Szirmay, Balázs / Ragán, Dániel / Simon, Gerda / Kovács-Ábrahám, Zoltán / Szabó, Péter / Sipos, Dávid / Péterfalvi, Ágnes / Miseta, Attila / Csontos, Csaba / Kőszegi, Tamás / Tóth, Ildikó

International journal of molecular sciences

2023 Volume 24, Issue 16

Abstract: SARS-CoV-2 infection might cause a critical disease, and patients' follow-up is based on multiple parameters. Oxidative stress is one of the key factors in the pathogenesis of COVID-19 suggesting that its level could be a prognostic marker. Therefore, we ...

Abstract	SARS-CoV-2 infection might cause a critical disease, and patients' follow-up is based on multiple parameters. Oxidative stress is one of the key factors in the pathogenesis of COVID-19 suggesting that its level could be a prognostic marker. Therefore, we elucidated the predictive value of the serum non-enzymatic total antioxidant capacity (TAC) and that of the newly introduced TAC/lymphocyte ratio in COVID-19. We included 61 COVID-19 (
MeSH term(s)	Humans ; Antioxidants ; COVID-19/diagnosis ; SARS-CoV-2 ; Oxidative Stress ; Lymphocytes
Chemical Substances	Antioxidants
Language	English
Publishing date	2023-08-18
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/ijms241612935
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Article ; Online: Urinary actin, as a potential marker of sepsis-related acute kidney injury: A pilot study.

Ragán, Dániel / Kustán, Péter / Horváth-Szalai, Zoltán / Szirmay, Balázs / Bugyi, Beáta / Ludány, Andrea / Miseta, Attila / Nagy, Bálint / Mühl, Diána

PloS one

2021 Volume 16, Issue 7, Page(s) e0255266

Abstract: Introduction: A major complication of sepsis is the development of acute kidney injury (AKI). Recently, it was shown that intracellular actin released from damaged tissues appears in the urine of patients with multiple organ dysfunction syndrome. Our ... ...

Abstract	Introduction: A major complication of sepsis is the development of acute kidney injury (AKI). Recently, it was shown that intracellular actin released from damaged tissues appears in the urine of patients with multiple organ dysfunction syndrome. Our aims were to measure urinary actin (u-actin) concentrations of septic and control patients and to test if u-actin levels could predict AKI and mortality. Methods: Blood and urine samples were collected from septic and sepsis-related AKI patients at three time points (T1-3): T1: within 24 hours after admission; T2: second day morning; T3: third day morning of follow-up. Patients with malignancies needing palliative care, end-stage renal disease or kidney transplantation were excluded. Serum and u-actin levels were determined by quantitative Western blot. Patients were categorized by the Sepsis-3 and KDIGO AKI classifications. Results: In our study, 17 septic, 43 sepsis-induced AKI and 24 control patients were enrolled. U-actin levels were higher in septic patients compared with controls during follow-up (p<0.001). At T1, the septic and sepsis-related AKI groups also showed differences (p<0.001), yet this increase was not statistically significant at T2 and T3. We also detected significantly elevated u-actin concentrations in AKI-2 and AKI-3 septic patients compared with AKI-1 septic patients (p<0.05) at T1 and T3, along with a significant increase in AKI-2 septic patients compared with AKI-1 septic patients at T2 (p<0.01). This tendency remained the same when referring u-actin to urine creatinine. Parameters of first-day septic patient samples could discriminate AKI from non-AKI state (AUC ROC, p<0.001): u-actin: 0.876; se-creatinine: 0.875. Derived cut-off value for u-actin was 2.63 μg/L (sensitivity: 86.0%, specificity: 82.4%). Conclusion: U-actin may be a complementary diagnostic biomarker to se-creatinine in sepsis-related AKI while higher u-actin levels also seem to reflect the severity of AKI. Further investigations may elucidate the importance of u-actin release in sepsis-related AKI.
MeSH term(s)	Actins/blood ; Actins/urine ; Acute Kidney Injury/diagnosis ; Acute Kidney Injury/etiology ; Acute Kidney Injury/mortality ; Aged ; Area Under Curve ; Biomarkers/urine ; Case-Control Studies ; Creatinine/blood ; Creatinine/urine ; Female ; Humans ; Male ; Middle Aged ; Pilot Projects ; ROC Curve ; Sepsis/complications ; Sepsis/diagnosis ; Sepsis/mortality ; Sepsis/pathology ; Severity of Illness Index ; Survival Analysis
Chemical Substances	Actins ; Biomarkers ; Creatinine (AYI8EX34EU)
Language	English
Publishing date	2021-07-26
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	1932-6203
ISSN (online)	1932-6203
DOI	10.1371/journal.pone.0255266
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