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Article: Biomedical research brings mTBI biomarkers a step closer to the bedside - implementation in clinical practice.

Martinikova, Martina / Ruzinak, Robert / Kurca, Egon / Grey, Michael Teodor / Sivak, Stefan

2023 Volume 42, Issue 4, Page(s) 323–338

Abstract: Research in the field of TBI (traumatic brain injury) has long been focused on severe brain injury, while the number of mild injuries far overweigh severe injuries. Mild head injuries constitute up to 95% of all traumatic head injuries. The purpose of ... ...

Abstract	Research in the field of TBI (traumatic brain injury) has long been focused on severe brain injury, while the number of mild injuries far overweigh severe injuries. Mild head injuries constitute up to 95% of all traumatic head injuries. The purpose of this work is to identify mTBI (mild traumatic brain injury) patients who are unlikely to benefit from CT (computed tomography) scanning. Biomarkers capable of clearly discriminating between CT-positive and CT-negative subjects are needed. Biomarkers hold the potential to document whether a concussion occurred, especially when the history is unclear and neurocognitive sequelae persist. Recently, following advances in proteomics analysis, investigators have introduced ubiquitin C-terminal hydrolase-L1 (UCH-L1) and glial fibrillary acidic protein (GFAP) as two promising brain injury biomarkers. The authors provide an update on the current knowledge of TBI biomarkers, especially protein biomarkers for neuronal cell body injury (UCH-L1) and astroglial injury (GFAP, S100B), and a focused literature review dealing with implementation of mTBI biomarkers in clinical practice.
MeSH term(s)	Humans ; Ubiquitin Thiolesterase ; Brain Injuries, Traumatic/diagnosis ; Brain Injuries ; Biomedical Research ; Biomarkers ; Glial Fibrillary Acidic Protein
Chemical Substances	Ubiquitin Thiolesterase (EC 3.4.19.12) ; Biomarkers ; Glial Fibrillary Acidic Protein
Language	English
Publishing date	2023-06-17
Publishing country	Slovakia
Document type	Journal Article ; Review
ZDB-ID	791184-1
ISSN	0231-5882
ISSN	0231-5882
DOI	10.4149/gpb_2023013
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Article: Embolization of Ruptured Infratentorial Pial AVM in Pregnancy.

Zeleňák, Kamil / Šalát, Dušan / Kolarovszki, Branislav / Kurča, Egon / Zeleňáková, Jana / Koçer, Naci

Life (Basel, Switzerland)

2023 Volume 13, Issue 4

Abstract: A primigravida 22-year-old woman, at a gestation of 23 weeks, experienced bleeding from a pial arteriovenous malformation (AVM) located in the right cerebellum. After interdisciplinary consensus and with the informed consent of the patient and her family, ...

Abstract	A primigravida 22-year-old woman, at a gestation of 23 weeks, experienced bleeding from a pial arteriovenous malformation (AVM) located in the right cerebellum. After interdisciplinary consensus and with the informed consent of the patient and her family, AVM embolization was performed. Complete occlusion of the AVM was achieved by embolization with PHIL (precipitating hydrophobic injectable liquid). The calculated dose in the uterus was less than 1 µSv, which represents a negligible risk of harmful effects on the fetus. She delivered a baby at 37 weeks of gestation by cesarean section without complications. No congenital disorders were diagnosed by standard screening methods until the age of the newborn was two years. The angiography protocol must be optimized to minimize the radiation dose. Adequate shielding protection of the uterus is important. Premature termination of pregnancy is not necessary. Multidisciplinary care of neurologists, neurosurgeons, interventional radiologists, anesthesiologists, neonatologists, and obstetricians is necessary.
Language	English
Publishing date	2023-03-28
Publishing country	Switzerland
Document type	Case Reports
ZDB-ID	2662250-6
ISSN	2075-1729
ISSN	2075-1729
DOI	10.3390/life13040896
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Article: Predictors of Outcome after Direct Aspiration of Basilar Artery Occlusion.

Mako, Miroslav / Krastev, Georgi / Nosáľ, Vladimír / Haring, Jozef / Jakubcová, Denisa / Daniš, Martin / Klepanec, Andrej / Haršány, Ján / Sivák, Štefan / Kurča, Egon

Journal of clinical medicine

2024 Volume 13, Issue 6

Abstract: ... ...

Abstract	Background
Language	English
Publishing date	2024-03-09
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2662592-1
ISSN	2077-0383
ISSN	2077-0383
DOI	10.3390/jcm13061576
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Article ; Online: Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) syndrome: Treatment approach depends on disease course.

Kovacova, Slavomira / Hnilicova, Petra / Grossmann, Jan / Hajas, Gabriel / Kantorova, Ema / Kurca, Egon

Biomedical papers of the Medical Faculty of the University Palacky, Olomouc, Czechoslovakia

2022 Volume 167, Issue 3, Page(s) 303–308

Abstract: Introduction: Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) is a rare inflammatory central nervous system (CNS) disorder, chiefly involving the brainstem, especially the pons. The diagnosis is ... ...

Abstract	Introduction: Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) is a rare inflammatory central nervous system (CNS) disorder, chiefly involving the brainstem, especially the pons. The diagnosis is challenging, requires careful exclusion of alternative diagnoses and a targeted therapeutic approach. CLIPPERS is known to respond well to corticosteroids, but the treatment needs to be long-term and can cause significant side-effects. Moreover, subsequent corticosteroid withdrawal often leads to a relapse. It has been suggested that anti-CD20 molecules could benefit several antibody-mediated CNS inflammatory diseases, including CLIPPERS. Case report: This paper describes two cases of CLIPPERS. The first demonstrates the benefit of early introduction of corticosteroids with side effects in cases of long-term use. The second demonstrates the efficacy of ocrelizumab (anti-CD20 molecule) in a severe course of CLIPPERS. Conclusion: These two cases bring attention to this rare, often misdiagnosed but treatable disease.
MeSH term(s)	Humans ; Magnetic Resonance Imaging ; Inflammation ; Steroids/therapeutic use ; Adrenal Cortex Hormones/therapeutic use ; Pons ; Central Nervous System Diseases/complications ; Central Nervous System Diseases/diagnosis ; Central Nervous System Diseases/drug therapy ; Disease Progression
Chemical Substances	Steroids ; Adrenal Cortex Hormones
Language	English
Publishing date	2022-03-21
Publishing country	Czech Republic
Document type	Case Reports
ZDB-ID	17196-7
ISSN	1804-7521 ; 1213-8118 ; 0231-5599 ; 0862-481X
ISSN (online)	1804-7521
ISSN	1213-8118 ; 0231-5599 ; 0862-481X
DOI	10.5507/bp.2022.013
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Article: Information-processing speed in mildly disabled relapsing-remitting multiple sclerosis patients correlates with volumetry of optic chiasma and subcortical grey matter nuclei.

Kovacova, Slavomira / Hnilicova, Petra / Cierny, Daniel / Babalova, Lucia / Grossmann, Jan / Kurca, Egon / Kantorova, Ema

Bratislavske lekarske listy

2022 Volume 123, Issue 9, Page(s) 678–684

Abstract: Introduction: Multiple sclerosis (MS) is an inflammatory demyelinating disease leading not only to physical disability but also to cognitive dysfunction. The aim of our study was to test cognitive functions of MS patients with mild relapsing-remitting ... ...

Abstract	Introduction: Multiple sclerosis (MS) is an inflammatory demyelinating disease leading not only to physical disability but also to cognitive dysfunction. The aim of our study was to test cognitive functions of MS patients with mild relapsing-remitting form and to find out the relationship between cognitive functions and brain volumetry. Methods: 52 patients (RRMSp) and 23 age-related healthy participants (CON) were enrolled. Mild disability was defined by mean EDSS 2.4 (≤ 4.0), and by median of disease duration 5.2 years. Cognitive status was tested using Single Digit Modality Test (SDMT). Brain volumetry was processed in FreeSurfer 2.0.0. Results: RRMSp patients showed significantly lower SDMT score than CON. SDMT results correlated positively with volume of thalamus, putamen and nc. caudate, and negatively with optic chiasma volume. Compared with CON, RRMSp presented with significantly lower volume in left and right nc. accumbent, cuneus and insular GM, right putamen, total brain cortical grey matter (GM), white matters hypointensities, and 3rd ventricular widths. Conclusion: To our best knowledge, this is the first study that presents results showing a correlation of lower SDMT with higher optic chiasma volume, due to its subclinical chronic demyelination. We confirmed that GM atrophy is involved in cognitive functions in MS (Tab. 3, Fig. 2, Ref. 73).
MeSH term(s)	Brain/diagnostic imaging ; Case-Control Studies ; Cognition ; Gray Matter/diagnostic imaging ; Humans ; Magnetic Resonance Imaging/methods ; Multiple Sclerosis ; Multiple Sclerosis, Relapsing-Remitting/complications ; Multiple Sclerosis, Relapsing-Remitting/diagnostic imaging ; Optic Chiasm
Language	English
Publishing date	2022-08-30
Publishing country	Slovakia
Document type	Journal Article
ZDB-ID	127421-1
ISSN	0006-9248
ISSN	0006-9248
DOI	10.4149/BLL_2022_108
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Article ; Online: Analysis of Cdx2 VDR gene polymorphism rs11568820 in association with multiple sclerosis in Slovaks.

Čierny, Daniel / Dobrota, Dušan / Kantorová, Ema / Malicherová, Bibiana / Škereňová, Mária / Javor, Juraj / Kurča, Egon / Lehotský, Ján

Neurological research

2023 Volume 45, Issue 10, Page(s) 912–918

Abstract: Vitamin D deficiency is involved in the pathogenesis of multiple sclerosis (MS), a severe autoimmune demyelinating disease of the central nervous system. The gene polymorphism Cdx-2 (rs11568820, G/A) seriously influences the trancriptional activity of ... ...

Abstract	Vitamin D deficiency is involved in the pathogenesis of multiple sclerosis (MS), a severe autoimmune demyelinating disease of the central nervous system. The gene polymorphism Cdx-2 (rs11568820, G/A) seriously influences the trancriptional activity of the vitamin D receptor (VDR) that binds the vitamin D responsive elements of target genes including HLA-DRB115. The aim of the present study in Slovaks was to analyse the association of Cdx-2 variants with the risk of MS and disability progression, and to assess the DRB115:01 allele as a possible confounding factor. In total, 493 MS patients and 417 healthy controls were involved in this study. The genotyping of Cdx-2 was performed using restriction analysis; DRB1*15:01 positivity was determined by a high-resolution melting analysis of its surrogate marker rs3135388 (G/A). Our results did not prove any allelic association between Cdx-2 and a risk of MS (minor allele A - 0.181 in patients vs. 0.161 in controls, OR = 1.15, .95 CI = 0.90-1.47,
MeSH term(s)	Humans ; Genetic Predisposition to Disease/genetics ; HLA-DRB1 Chains/genetics ; Multiple Sclerosis/genetics ; Gene Frequency ; Polymorphism, Single Nucleotide/genetics ; Genotype ; Alleles ; Receptors, Calcitriol
Chemical Substances	HLA-DRB1 Chains ; VDR protein, human ; Receptors, Calcitriol
Language	English
Publishing date	2023-08-15
Publishing country	England
Document type	Journal Article
ZDB-ID	424428-x
ISSN	1743-1328 ; 0161-6412
ISSN (online)	1743-1328
ISSN	0161-6412
DOI	10.1080/01616412.2023.2247195
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Article ; Online: Imaging Methods Applicable in the Diagnostics of Alzheimer's Disease, Considering the Involvement of Insulin Resistance.

Hnilicova, Petra / Kantorova, Ema / Sutovsky, Stanislav / Grofik, Milan / Zelenak, Kamil / Kurca, Egon / Zilka, Norbert / Parvanovova, Petra / Kolisek, Martin

International journal of molecular sciences

2023 Volume 24, Issue 4

Abstract: Alzheimer's disease (AD) is an incurable neurodegenerative disease and the most frequently diagnosed type of dementia, characterized by (1) perturbed cerebral perfusion, vasculature, and cortical metabolism; (2) induced proinflammatory processes; and (3) ...

Abstract	Alzheimer's disease (AD) is an incurable neurodegenerative disease and the most frequently diagnosed type of dementia, characterized by (1) perturbed cerebral perfusion, vasculature, and cortical metabolism; (2) induced proinflammatory processes; and (3) the aggregation of amyloid beta and hyperphosphorylated Tau proteins. Subclinical AD changes are commonly detectable by using radiological and nuclear neuroimaging methods such as magnetic resonance imaging (MRI), computed tomography (CT), positron emission tomography (PET), and single-photon emission computed tomography (SPECT). Furthermore, other valuable modalities exist (in particular, structural volumetric, diffusion, perfusion, functional, and metabolic magnetic resonance methods) that can advance the diagnostic algorithm of AD and our understanding of its pathogenesis. Recently, new insights into AD pathoetiology revealed that deranged insulin homeostasis in the brain may play a role in the onset and progression of the disease. AD-related brain insulin resistance is closely linked to systemic insulin homeostasis disorders caused by pancreas and/or liver dysfunction. Indeed, in recent studies, linkages between the development and onset of AD and the liver and/or pancreas have been established. Aside from standard radiological and nuclear neuroimaging methods and clinically fewer common methods of magnetic resonance, this article also discusses the use of new suggestive non-neuronal imaging modalities to assess AD-associated structural changes in the liver and pancreas. Studying these changes might be of great clinical importance because of their possible involvement in AD pathogenesis during the prodromal phase of the disease.
MeSH term(s)	Humans ; Alzheimer Disease/metabolism ; Amyloid beta-Peptides/metabolism ; Insulin Resistance ; Neurodegenerative Diseases/metabolism ; Positron-Emission Tomography/methods ; Neuroimaging/methods ; Magnetic Resonance Imaging/methods ; Brain/metabolism ; Insulins/metabolism
Chemical Substances	Amyloid beta-Peptides ; Insulins
Language	English
Publishing date	2023-02-07
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms24043325
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Article: Dyskinesia and Pain in Advanced Parkinson's Disease: Post Hoc Analysis from the Phase 3b, Open-Label, Randomized DYSCOVER Study.

Freire-Alvarez, Eric / Vanni, Paola / Kurča, Egon / Lopez-Manzanares, Lydia / Kovács, Norbert / Spanaki, Cleanthe / Gao, Tianming / Bergmann, Lars / Sánchez-Soliño, Olga

Neurology and therapy

2024 Volume 13, Issue 2, Page(s) 437–447

Abstract: Introduction: The DYSCOVER study was a phase 3b, open-label, randomized trial (NCT02799381) that evaluated levodopa-carbidopa intestinal gel (LCIG) versus optimized medical treatment (OMT) in patients with Parkinson's disease (PD) and a high burden of ... ...

Abstract	Introduction: The DYSCOVER study was a phase 3b, open-label, randomized trial (NCT02799381) that evaluated levodopa-carbidopa intestinal gel (LCIG) versus optimized medical treatment (OMT) in patients with Parkinson's disease (PD) and a high burden of dyskinesia at baseline (defined as Unified Dyskinesia Rating Scale [UDysRS] total score ≥ 30). At week 12, patients receiving LCIG versus OMT experienced significant improvements in dyskinesia, pain, and health-related outcomes. The objective of this analysis was to examine correlations between dyskinesia, pain, and health-related outcomes in PD. Methods: This post hoc analysis assessed correlations between UDysRS, King's Parkinson's Disease Pain Scale (KPPS), 8-item Parkinson's Disease Questionnaire (PDQ-8), Unified Parkinson's Disease Rating Scale part II, Clinical Global Impression of Severity (CGI-S) or Change (CGI-C), and "On" time without troublesome dyskinesia at baseline and after 12 weeks of LCIG or OMT. Correlations were assessed by Pearson correlation coefficients (categorization: weak, r = 0.20-0.39; moderate, r = 0.40-0.59; strong, r ≥ 0.60). Results: Among 61 patients, moderate-to-strong positive and significant correlations were observed between UDysRS and KPPS scores (baseline, r = 0.47; week 12 change from baseline [CFB], r = 0.63; all p < 0.001). UDysRS and KPPS scores had moderate-to-strong positive and highly significant correlations with PDQ-8 scores (baseline, r = 0.45 and 0.46, respectively; CFB, r = 0.54 and 0.64, respectively; all p < 0.001). Moderate positive and significant correlations were observed between UDysRS and CGI-S/CGI-C scores (baseline, r = 0.41; CFB, r = 0.47; all p < 0.001). Conclusions: In patients with high dyskinesia burden, positive correlations were observed between dyskinesia, pain, and health-related quality of life (HRQoL) at baseline. Improvements in dyskinesia and pain were associated with improvements in HRQoL, demonstrating the clinical burden of troublesome dyskinesia. Trial registration number: Clinicaltrials.gov identifier NCT02799381.
Language	English
Publishing date	2024-02-12
Publishing country	New Zealand
Document type	Journal Article
ISSN	2193-8253
ISSN	2193-8253
DOI	10.1007/s40120-024-00583-z
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Article ; Online: A high‐throughput liquid chromatography‐tandem mass spectrometry method for simultaneous determination of direct oral anticoagulants in human plasma

Žideková, Nela / Pršo, Kristián / Brisudová, Kristína / Babálová, Lucia / Bolek, Tomáš / Sivák, Štefan / Kurča, Egon / Mokry, Juraj / Samoš, Matej / Nosáľ, Vladimír / Kertys, Martin

Journal of Separation Science. 2023 July, v. 46, no. 13 p.e2300084-

2023

Abstract: Direct oral anticoagulants are widely used in many indications to prevent thromboembolic events. Routine therapeutic monitoring is not required; however, there is increasing evidence suggesting the benefit of plasma level measurement in some situations. ... ...

Abstract	Direct oral anticoagulants are widely used in many indications to prevent thromboembolic events. Routine therapeutic monitoring is not required; however, there is increasing evidence suggesting the benefit of plasma level measurement in some situations. In addition, laboratory monitoring might help improve patient and drug non‐compliance and thus individualize therapy. In the present study, we developed a sensitive and high throughput ultra‐high‐performance liquid chromatography‐tandem mass spectrometry method for simultaneous quantification of apixaban, dabigatran, edoxaban, and rivaroxaban in human plasma. A one‐step extraction procedure in 96‐well formate for phospholipid and protein removal was used for sample pre‐treatment, and analytes were separated using gradient elution over 4.2 min. Analytes were detected on a triple quadrupole tandem mass spectrometer by multiple reaction monitoring mode. The method was validated according to the European Medicine Agency guideline for the selectivity, linearity, and lower limit of detection, precision and accuracy, matrix effects, extraction recovery, carryover, dilution integrity, and stability over a concentration range of 3.0–1000 ng/ml for all analytes. The validated method was applied to real clinical samples of patients treated with one of the drugs. Therefore, we can conclude that our method is suitable for therapeutic drug monitoring of direct oral anticoagulants.
Keywords	chemical species ; detection limit ; drugs ; formates ; guidelines ; humans ; liquid chromatography ; medicine ; patients ; phospholipids ; separation ; spectrometers ; tandem mass spectrometry ; therapeutics
Language	English
Dates of publication	2023-07
Publishing place	John Wiley & Sons, Ltd
Document type	Article ; Online
Note	JOURNAL ARTICLE
ZDB-ID	2047990-6
ISSN	1615-9314 ; 1615-9306
ISSN (online)	1615-9314
ISSN	1615-9306
DOI	10.1002/jssc.202300084
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Article: Oxidative stress parameters and their relation to motor subtype of Parkinson's disease and levodopa treatment status.

Grofik, Milan / Cibulka, Michal / Oleksakova, Jana / Sivak, Stefan / Cierny, Daniel / Tatarkova, Zuzana / Grendar, Marian / Nosal, Vladimir / Ruzinak, Robert / Kurca, Egon / Kolisek, Martin

General physiology and biophysics

2023 Volume 42, Issue 1, Page(s) 77–85

Abstract: Parkinson's disease (PD) is an oxidative stress-linked neurodegenerative disorder, with the highest prevalence among seniors. The objective of this study were: (1) to analyse levels of following oxidative stress parameters: total antioxidant capacity ( ... ...

Abstract	Parkinson's disease (PD) is an oxidative stress-linked neurodegenerative disorder, with the highest prevalence among seniors. The objective of this study were: (1) to analyse levels of following oxidative stress parameters: total antioxidant capacity (TAC), uric acid (UA), total glutathione (tGSH), bilirubin (Bil) and albumin (Alb), in blood of PD patients and healthy controls; (2) to find possible associations of examined oxidative stress parameters with PD subtypes and levodopa treatment status; and (3) to evaluate power and relevance of the aforementioned oxidative stress parameter for the prediction of onset and progression of PD by utilizing Random Forest machine learning (RFML). Oxidative stress parameters were determined in 125 PD patients and 55 healthy controls. Evaluated with frequentist statistics, our data revealed that UA is the only oxidative stress parameter associated with PD. However, when the PD cohort was divided in gender-dependent manner, tGSH and Bil were also significantly associated with PD in subgroup of female patients. RFML rendered no predictive power of any of the tested oxidative stress parameters in respect to PD, its subtypes, and/or status of levodopa treatment. In conclusion, despite the positive association of UA with PD (in complete cohort of PD patients) and of tGSH and Bil with PD but only in female patients, these oxidative stress parameters are of no use in clinical practice due to the lack of the predictive/diagnostic power.
MeSH term(s)	Humans ; Female ; Parkinson Disease/drug therapy ; Levodopa/therapeutic use ; Antioxidants/metabolism ; Oxidative Stress ; Uric Acid ; Glutathione
Chemical Substances	Levodopa (46627O600J) ; Antioxidants ; Uric Acid (268B43MJ25) ; Glutathione (GAN16C9B8O)
Language	English
Publishing date	2023-01-27
Publishing country	Slovakia
Document type	Journal Article
ZDB-ID	791184-1
ISSN	0231-5882
ISSN	0231-5882
DOI	10.4149/gpb_2022051
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