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Article ; Online: Distinct patterns of serum and urine macrophage migration inhibitory factor kinetics predict death in sepsis: a prospective, observational clinical study.

Toldi, Janos / Kelava, Leonardo / Marton, Sandor / Muhl, Diana / Kustan, Peter / Feher, Zsolt / Maar, Klaudia / Garai, Janos / Pakai, Eszter / Garami, Andras

Scientific reports

2023 Volume 13, Issue 1, Page(s) 588

Abstract: Macrophage migration inhibitory factor (MIF) has been considered as a biomarker in sepsis, however the predictive value of the pattern of its kinetics in the serum and in the urine has remained unclarified. It is also unclear whether the kinetics of MIF ... ...

Abstract	Macrophage migration inhibitory factor (MIF) has been considered as a biomarker in sepsis, however the predictive value of the pattern of its kinetics in the serum and in the urine has remained unclarified. It is also unclear whether the kinetics of MIF are different between males and females. We conducted a single-center prospective, observational study with repeated measurements of MIF in serum and urine on days 0, 2, and 4 from admission to the intensive care unit (ICU) in 50 adult septic patients. We found that in patients who died within 90 days, there was an increase in serum MIF level from day 0 to 4, whereas in the survivors there was rather a decrease (p = 0.018). The kinetics were sex-dependent as the same difference in the pattern was present in males (p = 0.014), but not in females (p = 0.418). We also found that urine MIF was markedly lower in patients who died than in survivors of sepsis (p < 0.050). Urine MIF levels did not show temporal changes: there was no meaningful difference between day 0 and 4. These results suggest that kinetics of serum MIF during the initial days from ICU admission can predict death, especially in male patients. Additionally, lower urine MIF levels can also indicate death without showing meaningful temporal kinetics.
MeSH term(s)	Adult ; Female ; Humans ; Male ; Biomarkers ; Intensive Care Units ; Macrophage Migration-Inhibitory Factors/blood ; Macrophage Migration-Inhibitory Factors/chemistry ; Macrophage Migration-Inhibitory Factors/urine ; Prospective Studies ; Sepsis/complications ; Sepsis/diagnosis
Chemical Substances	Biomarkers ; Macrophage Migration-Inhibitory Factors
Language	English
Publishing date	2023-01-11
Publishing country	England
Document type	Observational Study ; 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/s41598-023-27506-6
Database	MEDical Literature Analysis and Retrieval System OnLINE

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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: Nonconventional Markers of Sepsis.

Kustán, Péter / Horváth-Szalai, Zoltán / Mühl, Diána

EJIFCC

2017 Volume 28, Issue 2, Page(s) 122–133

Abstract: Sepsis still remains a challenging healthcare problem with high mortality rate. To improve outcome, early diagnosis and monitoring of sepsis is of utmost importance. In this process objective laboratory parameters are the most helpful. Procalcitonin and ... ...

Abstract	Sepsis still remains a challenging healthcare problem with high mortality rate. To improve outcome, early diagnosis and monitoring of sepsis is of utmost importance. In this process objective laboratory parameters are the most helpful. Procalcitonin and C-reactive protein are the most commonly used and recommended markers of sepsis however, more than 200 sepsis biomarkers have already been published. This mini review focuses on nonconventional novel possibilities for the recognition of sepsis severity. Presepsin, actin and actin scavenger proteins (gelsolin and Gc-globulin) and orosomucoid are discussed. Besides serum parameters, the urinary levels of these markers are also elaborated, since urinary biomarkers of sepsis provide new diagnostic implications and are helpful for monitoring both the kidney function and the septic process. Increasing serum actin levels and decreasing levels of actin binding proteins seem to be associated with sepsis severity and outcome. Actin can be detected in the urine samples of septic patients as well, and strongly elevated levels of it were found in sepsis-related acute kidney injury. Both serum and urinary orosomucoid might be able to indicate sepsis, however urinary orosomucoid is a more sensitive inflammatory marker. Novel laboratory tests can provide rapid help for clinical decision making because the key point in successful treatment lies in the early diagnosis of sepsis.
Language	English
Publishing date	2017-05-01
Publishing country	Italy
Document type	Journal Article
ISSN	1650-3414
ISSN	1650-3414
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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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Article ; Online: Urinary Orosomucoid A Potential Marker Of Inflammation In Psoriasis.

Kustán, Péter / Kőszegi, Tamás / Miseta, Attila / Péter, Iván / Ajtay, Zénó / Kiss, István / Németh, Balázs

International journal of medical sciences

2018 Volume 15, Issue 11, Page(s) 1113–1117

Abstract: ... ...

Abstract	Background
MeSH term(s)	Adult ; Aged ; Biomarkers/urine ; C-Reactive Protein ; Female ; Humans ; Inflammation ; Male ; Middle Aged ; Orosomucoid/urine ; Psoriasis/diagnosis ; Psoriasis/urine ; Quality of Life
Chemical Substances	Biomarkers ; Orosomucoid ; C-Reactive Protein (9007-41-4)
Language	English
Publishing date	2018-07-13
Publishing country	Australia
Document type	Journal Article
ZDB-ID	2151424-0
ISSN	1449-1907 ; 1449-1907
ISSN (online)	1449-1907
ISSN	1449-1907
DOI	10.7150/ijms.25687
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Article ; Online: Role of microparticles derived from monocytes, endothelial cells and platelets in the exacerbation of COPD.

Tőkés-Füzesi, Margit / Ruzsics, István / Rideg, Orsolya / Kustán, Péter / Kovács, Gábor L / Molnár, Tihamér

International journal of chronic obstructive pulmonary disease

2018 Volume 13, Page(s) 3749–3757

Abstract: Background: Microparticles (MPs) are shedding membrane vesicles released from activated blood and endothelial cells under inflammatory conditions. The role of endothelial MPs (EMPs) in pathophysiology of COPD is relatively well known. However, the ... ...

Abstract	Background: Microparticles (MPs) are shedding membrane vesicles released from activated blood and endothelial cells under inflammatory conditions. The role of endothelial MPs (EMPs) in pathophysiology of COPD is relatively well known. However, the release and function of MPs of other cellular origins, eg, platelets, red blood cells and leukocytes, are not clearly evaluated in COPD. Purpose: The aim of this study was to measure EMPs and other cell-derived circulating MPs in stable and exacerbated COPD patients. Patients and methods: A total of 50 patients with COPD and 19 healthy volunteers were enrolled in the study. EMPs (CD31+, CD62E+) and platelet-derived (CD61+, CD41+, CD42a+, PAC1+), red blood cell-derived (GlyA+) and leukocyte-derived (CD45+, CD13+, CD14+, CD56+) MPs were measured. Flow cytometry (FC) was performed on Beckman Coulter FC500 analyzer. MP reference gate was set using 0.3-0.5-0.9 µm microbeads with MP size gates of 0.5-1.0 µm. Results: All the measured MPs were significantly ( Conclusion: In this study, we describe a reliable flow cytometric assay for MP analysis that was successfully applied in COPD. Besides EMPs, COPD is accompanied by an increased concentration of various MPs in the systemic circulation; particularly, platelet- and monocyte-derived MPs seem to be important in exacerbation.
MeSH term(s)	Aged ; Biomarkers/blood ; Blood Platelets/metabolism ; Blood Platelets/pathology ; Case-Control Studies ; Cell Separation/methods ; Cell-Derived Microparticles/metabolism ; Cell-Derived Microparticles/pathology ; Disease Progression ; Endothelial Cells/metabolism ; Endothelial Cells/pathology ; Female ; Flow Cytometry ; Humans ; Male ; Middle Aged ; Monocytes/metabolism ; Monocytes/pathology ; Phenotype ; Prospective Studies ; Pulmonary Disease, Chronic Obstructive/blood ; Pulmonary Disease, Chronic Obstructive/pathology
Chemical Substances	Biomarkers
Language	English
Publishing date	2018-11-15
Publishing country	New Zealand
Document type	Journal Article
ZDB-ID	2212419-6
ISSN	1178-2005 ; 1176-9106
ISSN (online)	1178-2005
ISSN	1176-9106
DOI	10.2147/COPD.S175607
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Article ; Online: Antagonistic sepsis markers: Serum gelsolin and actin/gelsolin ratio.

Horváth-Szalai, Zoltán / Kustán, Péter / Mühl, Diána / Ludány, Andrea / Bugyi, Beáta / Kőszegi, Tamás

Clinical biochemistry

2017 Volume 50, Issue 3, Page(s) 127–133

Abstract: Objectives: For appropriate sepsis care, prognostic laboratory markers are mandatory. The aim of our study was to evaluate the predictive value of serum actin, gelsolin and the recently defined actin/gelsolin ratio during sepsis by comparison it to ... ...

Abstract	Objectives: For appropriate sepsis care, prognostic laboratory markers are mandatory. The aim of our study was to evaluate the predictive value of serum actin, gelsolin and the recently defined actin/gelsolin ratio during sepsis by comparison it to classical clinical and inflammatory laboratory parameters. Design & methods: We analyzed sera of severe septic (n=32) and SIRS (n=12) patients for 5days. Ophthalmologic patients (n=27) served as controls. Besides serum actin, gelsolin and actin/gelsolin ratios classical laboratory parameters (WBC count, serum procalcitonin, hsCRP) and clinical scores (APACHE II, SAPS II, SOFA), were also assessed. Results: Septic patients showed significantly decreased first-day gelsolin levels and increased actin/gelsolin ratios compared to SIRS patients (p<0.05), furthermore, non-survivors had significantly lower gelsolin levels compared to survivors (p<0.05). Non-survivors had 11.4-fold higher 2nd day actin/gelsolin ratios than survivors. Besides procalcitonin (PCT) and hsCRP, gelsolin and actin/gelsolin ratios also proved to be useful in discriminating SIRS from sepsis in the ICU (p<0.05). Gelsolin had similar prognostic value to PCT when assessing 7-day mortality and the predictive capacity of the first-day actin/gelsolin ratios was similar to that of APACHE II score regarding ICU mortality in severe sepsis. Conclusions: Serum gelsolin and actin/gelsolin ratio might serve as efficient complementary prognostic markers in sepsis. However, for daily clinical usage, an automated laboratory assay of actin and gelsolin is still needed to be developed.
MeSH term(s)	Actins/blood ; Aged ; Deoxyguanosine/analogs & derivatives ; Deoxyguanosine/blood ; Female ; Gelsolin/blood ; Glutathione/blood ; Homocysteine/blood ; Humans ; Male ; Metabolic Syndrome/blood ; Metabolic Syndrome/pathology ; Middle Aged ; Oxidative Stress/physiology ; Sepsis/blood
Chemical Substances	Actins ; Gelsolin ; Homocysteine (0LVT1QZ0BA) ; 8-oxo-7-hydrodeoxyguanosine (88847-89-6) ; Deoxyguanosine (G9481N71RO) ; Glutathione (GAN16C9B8O)
Language	English
Publishing date	2017-02
Publishing country	United States
Document type	Journal Article
ZDB-ID	390372-2
ISSN	1873-2933 ; 0009-9120
ISSN (online)	1873-2933
ISSN	0009-9120
DOI	10.1016/j.clinbiochem.2016.10.018
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Article: Microchip gel electrophoretic analysis of perchloric acid‐soluble serum proteins in systemic inflammatory disorders

Makszin, Lilla / Kustán, Péter / Szirmay, Balázs / Páger, Csilla / Mező, Emerencia / Kalács, Krisztina I / Pászthy, Vera / Györgyi, Erzsébet / Kilár, Ferenc / Ludány, Andrea / Kőszegi, Tamás

Electrophoresis. 2019 Feb., v. 40, no. 3

2019

Abstract: Perchloric acid (PCA) precipitation is a well‐known method for the separation of heavily glycosylated proteins and for reducing the masking effect of major serum proteins. The aim of this study is to characterize PCA‐soluble serum proteins in healthy ... ...

Abstract	Perchloric acid (PCA) precipitation is a well‐known method for the separation of heavily glycosylated proteins and for reducing the masking effect of major serum proteins. The aim of this study is to characterize PCA‐soluble serum proteins in healthy individuals and in patients with systemic inflammatory diseases, such as Crohn's disease and sepsis. A PCA precipitation protocol was prepared and adapted to the analytical methods. After PCA treatment of the serum, the soluble proteins in the supernatant were analyzed by SDS‐PAGE and by microchip gel electrophoresis (MGE). Characteristic changes of the electrophoretic patterns of the PCA‐soluble fractions were observed. Four characteristic bands (at ∼11, ∼65, ∼85, and ∼120 kDa) with varying intensity were detected by MGE. The proportion of the ∼65, ∼85, and ∼120 kDa bands were significantly higher in systemic inflammatory conditions than in healthy individuals (p < 0.001), and characteristic patterns were observed in patients with acute inflammation. The marked differences in the acid‐soluble protein patterns, which were observed in patients with ongoing systemic inflammation, might be a good indicator of inflammation. The MGE analysis is a fast screening and quantification method for the detection of characteristic changes among acid‐soluble serum proteins.
Keywords	Crohn disease ; blood proteins ; blood serum ; glycosylation ; inflammation ; microchip technology ; patients ; perchloric acid ; polyacrylamide gel electrophoresis ; protocols ; screening ; sepsis (infection)
Language	English
Dates of publication	2019-02
Size	p. 447-454.
Publishing place	John Wiley & Sons, Ltd
Document type	Article
Note	JOURNAL ARTICLE
ZDB-ID	619001-7
ISSN	1522-2683 ; 0173-0835
ISSN (online)	1522-2683
ISSN	0173-0835
DOI	10.1002/elps.201800378
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Elevated urinary orosomucoid excretion as a novel biomarker in Crohn's disease.

Szirmay, Balázs / Tárnok, András / Sarlós, Patrícia / Szigeti, Nóra / Ludány, Andrea / Kustán, Péter / Horváth-Szalai, Zoltán / Miseta, Attila / Kőszegi, Tamás

European journal of clinical investigation

2018 Volume 49, Issue 3, Page(s) e13054

Abstract: Background: Laboratory markers are essential tools in the follow-up of patients with Crohn's disease (CD). Our aim was to investigate urinary concentrations of orosomucoid in relation to the inflammatory activity of CD and to compare it with clinical ... ...

Abstract	Background: Laboratory markers are essential tools in the follow-up of patients with Crohn's disease (CD). Our aim was to investigate urinary concentrations of orosomucoid in relation to the inflammatory activity of CD and to compare it with clinical indices and conventional laboratory parameters. Materials and methods: Blood and urine samples of 86 patients (55 adults and 31 children) with CD and 68 healthy individuals (38 adults and 30 children) as controls were analysed. Patients were categorized according to their clinical scores (Harvey-Bradshaw Index [HBI] or Pediatric Crohn's Disease Activity Index [PCDAI]). Urinary orosomucoid (u-ORM) was determined by automated immune turbidimetric assay, and values were referred to urinary creatinine (u-ORM/u-CREAT, mg/mmol). Results: U-ORM/u-CREAT values were seven times higher in children with active CD (0.50 vs 0.07 mg/mmol, P < 0.001) and two times higher in adults (0.32 vs 0.14 mg/mmol, P = 0.01) compared with patients with inactive disease. U-ORM/u-CREAT showed good correlation with conventional inflammatory markers (hs-CRP, serum ORM; P < 0.01) and activity indices (HBI, P = 0.018; PCDAI, P < 0.001). U-ORM/u-CREAT had similar discriminative performance to hs-CRP and serum ORM in the differentiation of active from inactive paediatric CD patients. Conclusions: Our findings suggest that u-ORM/u-CREAT might serve as a valuable additional marker in the follow-up of CD patients, especially in children for whom the non-invasive sampling is a further advantage.
MeSH term(s)	Adolescent ; Adult ; Biomarkers/metabolism ; Child ; Crohn Disease/urine ; Cross-Sectional Studies ; Humans ; Middle Aged ; Orosomucoid/metabolism ; ROC Curve ; Young Adult
Chemical Substances	Biomarkers ; Orosomucoid
Language	English
Publishing date	2018-12-13
Publishing country	England
Document type	Journal Article
ZDB-ID	186196-7
ISSN	1365-2362 ; 0014-2972 ; 0960-135X
ISSN (online)	1365-2362
ISSN	0014-2972 ; 0960-135X
DOI	10.1111/eci.13054
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Article ; Online: Balneotherapy in Psoriasis Rehabilitation.

Péter, Iván / Jagicza, Anna / Ajtay, Zénó / Boncz, Imre / Kiss, István / Szendi, Katalin / Kustán, Péter / Németh, Balázs

In vivo (Athens, Greece)

2017 Volume 31, Issue 6, Page(s) 1163–1168

Abstract: Background/aim: This study aimed to report a balneotherapy-based psoriasis rehabilitation protocol and assess its effectivity.: Patients and methods: Eighty psoriatic patients who underwent a 3-week-long inward balneotherapy-based rehabilitation were ...

Abstract	Background/aim: This study aimed to report a balneotherapy-based psoriasis rehabilitation protocol and assess its effectivity. Patients and methods: Eighty psoriatic patients who underwent a 3-week-long inward balneotherapy-based rehabilitation were enrolled. Psoriasis Area and Severity Index (PASI) score and high sensitivity C-reactive protein (CRP) were determined on admission and before discharge. Results: The mean PASI score and CRP level -determined on admission and before discharge-decreased significantly after the 3-week-long rehabilitation 7.15±7.3 vs. 2.62±3.05 (p<0.001) and 4.1±3.8 vs. 3.5±3.1 (p=0.026). A negative correlation was found between PASI delta and the number of spa therapies received (r=-0.228). Conclusion: After completing the 3-week-long spa therapy based rehabilitation, both PASI score and CRP levels showed improvement of psoriasis. The complex spa therapy used during the rehabilitation is an effective tool to reduce the symptoms of psoriasis and improve the patient's well-being.
Language	English
Publishing date	2017-11
Publishing country	Greece
Document type	Journal Article
ZDB-ID	807031-3
ISSN	1791-7549 ; 0258-851X
ISSN (online)	1791-7549
ISSN	0258-851X
DOI	10.21873/invivo.11184
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