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DNA methylation plays a critical role in the regulation of gene expression in the human leukocyte antigen (HLA) system which is a key component of immune function. This article reviews the molecular mechanisms by which DNA methylation influences HLA gene regulation, highlighting its impact on their antigen presentation and immune tolerance functions. We describe how methylation patterns vary in HLA class I and II genes, affecting their expression in a tissue- and allele-specific manner. In addition, we examine the interplay of DNA methylation in shaping immune responses. A focus is on the role of methylation in immune-mediated, namely autoimmune diseases, where aberrant epigenetic modifications at HLA loci contribute to disease susceptibility and progression. We also explore how single nucleotide polymorphisms (SNPs) within CpG sites can alter methylation patterns and gene expression, providing insights into genetic-epigenetic interactions. These findings may contribute to the development of new diagnostic and therapeutic strategies for immune-mediated diseases.

This study aspired to provide comprehensive real-world data on a population with heart failure in the Moravian region of the Czech Republic. The authors compared local clinically relevant data with those from the ground-breaking Paradigm-HF trial and they found that local patients had a more advanced state of heart failure. The high prevalence of implantable cardioverter-defibrillators (ICD) and cardiac resynchronization therapy (CRT) confirms access to advanced and financially demanding treatment options in this region.

An observational study evaluating the safety and efficacy of thoracoscopic ablation of atrial fibrillation in the single-center experience. The cohort consisted of 81 patients suffering from some form of atrial fibrillation, undergoing thoracoscopic ablation either as a single method of treatment or as a part of the hybrid protocol where catheter ablation was suplemented later.

Aims. Angiogenesis is activated in the retina of diabetic patients with retinopathy complications. Vascular endothelial growth factor (VEGF) plays an essential role as a mediator of the retinal induced neovascularization. VEGF levels are increased significantly in the vitreous and aqueous ocular fluids in the patients with proliferative diabetic retinopathy. The aim of this study is to investigate whether VEGF promoter/5'UTR polymorphisms are associated with diabetic retinopathy (DR) development and/or severity. Methods. In this case-control study, Type 2 diabetic patients with or without DR, and normal controls were recruited. DR was classified based on the presence or absence of proliferative changes. The genotyping was analysed by polymerase chain reaction followed by restriction fragment length polymorphism. Results. A total of 259 subjects (172 with diabetes+DR, 87 healthy controls; male:female, 125:134) were recruited. The average age was 59.5+9.6 years, diabetes duration was 8.5+4.5 years, body mass index was 30.6+6.0 kg/m2, and HbA1c was 7.37+1.2% (57 mmol/mol). Significant differences in the distribution of genotypes in T(-1,498)C, G(-1,190)A and G(-1,154)A polymorphism in diabetic patients versus controls, and DR patients versus DM without DR patients were shown. No association between DR severity and polymorphisms was detected. Non-significant differences in allele frequency were found. The haplotypes TGAGC, TGACT and CAGCT were significantly increased in DM patients, whereas CGGCC was the most common haplotype in DR patients. Conclusions. Multiple VEGF polymorphisms and CGGCC haplotype are significantly correlated with a higher DR risk in Type 2 diabetic patients.

The Measles-Rubella-Zoster (MRZ) reaction is a test for the intrathecal synthesis of IgG antibodies against measles, rubella and varicella zoster viruses. Since the 1990s, it has been used as an adjunctive test to support the diagnosis of multiple sclerosis (MS), although it has no formal role in current McDonald diagnostic criteria and its clinical relevance remains debated. While early studies considered a single elevated antibody index (M, R or Z) as a positive result, the practice today requires at least two elevated antibody indices (M+R, M+Z, or R+Z), referred to as a polyspecific MRZ reaction (MRZ-2). MRZ-2 is the most specific laboratory marker for MS, with reported specificity exceeding 90%. However, sensitivity varies widely across studies, ranging from approximately 30% to over 70%. In the Czech adult MS population, MRZ-2 sensitivity was recently reported at 32%, markedly lower than the 67% pooled sensitivity reported in a meta-analysis of predominantly German cohorts. Broadening the panel of anti-viral antibodies (MRZ+) has been proposed to improve sensitivity, with parvovirus B19 and mumps virus being the most promising candidates. Further studies are required to determine whether an extended panel can increase sensitivity while maintaining high diagnostic specificity.

Objective. To evaluate transperitoneal laparoscopic adrenalectomies performed at the University Hospital, Olomouc over a period of 20 years. Introduction. Thanks to the increased availability of imaging, the detection of adrenal disease is increasing. Laparoscopic adrenalectomy is now regarded as the gold standard for the treatment of adrenal disease due to its safety and efficacy despite the increasing popularity of robotic-assisted surgery. Methods. Over a period of 20 years, from 2002 to 2021, we retrospectively evaluated a cohort of 405 patients who had undergone laparoscopic adrenalectomy. The indication criteria for laparoscopic adrenalectomy were hormonally active symptomatic tumours (pheochromocytoma, Conn's syndrome, Cushing's syndrome, etc.), symptomatic cysts or myelolipomas, carcinomas, metastatic disabling or incidentalomas, growing at a rate >1 cm or more per year. Data collected focused on sex, age, medical classification, imaging, operative time, side dominance, hormonal activity, complications associated with surgery, length of hospital stay, and histopathologic verification. No patient who had undergone laparoscopic adrenalectomy was excluded from the cohort. Patients in our cohort were not operated by a single surgeon. Results. Women accounted for 52.1% (211) and men 47.9% (194). The mean age was 55.6 years, BMI 28.7, and median ASA score was 2. Preoperative imaging included abdominal CT in 352 (86.9%) patients, abdominal MRI with contrast agent in 8 (2.0%), and PET/CT in 45 (11.1%) patients. More frequent findings were on the right side in 223 (54.39%) patients. Hormonal activity was found in 271 patients (67 %). Hormone overproduction from the right adrenal gland was found in 120 (44.3%) patients, and from the left in 151 (55.7%). Adenoma was the most frequent histological finding, followed by hyperplasia. Conversion to open surgery was due to bleeding in 2 patients. There was no perioperative or postoperative mortality. According to the Clavien-Dindo classification, minor complications (Grade I) occurred in 375 patients (92.6%). Grade II complications were reported in 17 patients (4.2%). Grade III complications were identified in 13 patients (3.2%) due to operative field bleeding; in three cases (0.7%), surgical revision of the adrenalectomy bed was required. Conclusion. Laparoscopic adrenalectomy is a safe surgical method for the management of adrenal disease and our retrospective follow-up confirmed that it remains the gold standard.

Aims. This study evaluates the feasibility of an artificial intelligence (AI)-assisted software tool for early identification and classification of chronic wounds and for supporting decisions on whether professional clinical review is needed. Methods. A pilot assistive software solution was developed by integrating wound image analysis with patient-reported metadata. The system combines You Only Look Once (YOLO) for wound localization and U-Net for tissue segmentation. A standardized wound imaging and annotation protocol was designed in collaboration with the University Hospital Bulovka. Diagnostic performance will be evaluated using sensitivity, specificity, positive predictive value and negative predictive value. Results. A Python-based prototype and a multimodal software architecture were developed. More than 500 standardized wound images have been collected to date, and the dataset is being expanded iteratively according to model performance, class balance, annotation quality and validation requirements. A regulatory certification strategy was outlined under the Medical Device Regulation and the AI Act. Conclusion. The study establishes a technical and regulatory foundation for future AI-based wound care tools intended to support earlier triage and professional assessment of chronic wounds.

Introduction. Ovarian tumours represent a highly malignant disease that is often diagnosed at an advanced stage and is associated with a poor prognosis. The most common histological type is high-grade serous carcinoma, characterized by significant genomic instability and homologous recombination defects, particularly due to pathogenic variants in the BRCA1 and BRCA2 genes. The introduction of high throughput sequencing methods has enabled the identification of a broader spectrum of predisposing genes and further emphasised the importance of genetic testing for targeted prevention and individualised treatment. Methods. The aim of our study was to determine the frequency of germline mutations in 117 unrelated patients diagnosed with ovarian, tubal, or primary peritoneal cancer. We also assessed epidemiological and tumor pathogenesis data. The patients were examined with the "CZECANCA" gene panel sequenced by next-generation sequencing (NGS) on an Illumina platform. Results. Pathogenic variants were found in 29% of patients, most commonly mutations in the BRCA1 and BRCA2 genes. The median age of patients with high-grade serous ovarian cancer was 61 years. The median age of BRCA1/2-positive women was 54 years, and all had a positive family history of cancer. Conclusion. Identifying carriers of pathogenic variants enables targeted prevention, earlier detection, and personalized therapy. Despite significant advances in treatment, early diagnosis and screening of at-risk individuals remain a major challenge.

Integrin alpha-6 (α6ITG, CD49f) has long been considered one of the most reliable markers of stemness, yet emerging evidence challenges this view by revealing its broader role in niche accessibility and survival. As a laminin receptor, α6ITG mediates cellular interactions and participates in signal transduction pathways that help maintain cellular phenotype. Its expression allows for the identification and purification of stem cells from heterogeneous populations. Because α6ITG expression is highly sensitive to environmental cues, it also serves as a sensor of culture conditions and cryopreservation stress, with potential use in biobanking and regenerative medicine. This marker holds significant potential; it may be one of the few markers consistently expressed in all stem cells, potentially qualifying it as a common "stemness" marker. Additionally, the therapeutic implications of α6ITG knockdown using antibodies may greatly influence future cancer treatments. Elevated expression in cancer correlates with growth, invasion, and poor prognosis. The aim of this review is to explore the biological and translational importance of α6ITG in stem cell and cancer biology.

Aim. The recurrence rate of colorectal cancer remains high even after radical surgery. Existing criteria for administering adjuvant treatment lack sufficient precision, often leading to undertreatment or overtreatment. This study investigates circulating tumour cells (CTCs) as a potential prognostic biomarker to improve the accuracy of patient selection. Methods. Forty-six colorectal cancer patients without distant metastases who underwent radical surgery were enrolled in this prospective study conducted at Tomas Bata Hospital in Zlín. The study protocol was approved by the hospital's Ethics Committee. Circulating tumour cells (CTCs) were measured in peripheral blood samples collected preoperatively, on the second postoperative day, and one month after surgery. CTCs were detected and characterized using semiautomated microscopy. Comprehensive clinicopathological data were recorded as part of standardized perioperative care. The prognostic significance of CTCs was evaluated based on the time to recurrence (TTR) parameter. Results and Conclusion. Growing evidence from circulating tumour cell (CTC) research supports their potential role as a valuable biomarker in cancer management. In this study involving stage I-III colorectal cancer patients, a recurrence rate of 20% was observed among individuals with detectable CTCs, whereas no recurrence occurred in patients with a sustained absence of CTCs. Despite this apparent difference, the time to recurrence (TTR) did not differ significantly between the groups (log-rank test, P=0.175). Although the result was not statistically significant, the observed trend suggests a possible prognostic value of CTCs that merits investigation in a larger cohort. Furthermore, neither individual time-point measurements nor dynamic changes in CTC levels demonstrated a significant correlation with TTR.

A prosthetic arteriovenous graft (AVG) represents a type of vascular access for haemodialysis (HD), employing a synthetic conduit that replaces a native vessel and permits repeated cannulation. Due to their associated complications, particularly thrombosis and infection, arteriovenous grafts (AVGs) have long been regarded as a secondary option. Current recommendations advocate an individualized approach to vascular access planning based on patient´s anatomy, life expectancy, anticipated dialysis duration, and personal preferences, leading to a broader and more flexible use of AVGs. Their key advantage is the potential for early initiation of HD, while minimizing the need for central venous catheters. However, a major disadvantage of AVGs is their tendency to develop stenotic lesions, predominantly at the venous anastomosis, which adversely affects graft patency. If left untreated, this may lead to graft thrombosis. Regular evaluation of AVG function is essential for early detection of stenosis and maintenance of graft patency. Despite its widespread use in clinical practice, the role of AVG surveillance in vascular access management remains a subject of considerable debate, as current evidence regarding its effectiveness in preventing thrombosis and prolonging graft patency is inconclusive.

Background and Aim. Vitamin D deficiency is linked to increased cancer risk and death but the effect of vitamin D substitution on the prognosis of patients with malignant disease is debatable. We aimed to investigate the value of serum vitamin D3 levels in patients with a history of malignancy and confirmed lung metastases. Materials and Method. Serum Vitamin D2 (25-hydroxyergokalciferol) and D3 (25‑hydroxycholekalciferol) levels were measured in 38 patients (28 with and 10 without lung metastases) using high performance liquid chromatography (HPLC). Serum Vitamin D2 + D3 levels of patients with lung metastases were analysed with respect to season, number of metastases, number of malignancies in the history, value according to the ASA (The American Society of Anaesthesiologists) physical status classification, and compared to patients with a history of malignancy without confirmed lung metastasis. Results. Overall, mean serum vitamin D3 levels were significantly higher in summer (summer vs. winter; 85.06 nmol/L vs. 61.01 nmol/L; P=0.013). There was no significant difference in vitamin D3 levels in summer or winter between patients with or without lung metastases. There was also no significant difference in vitamin D3 levels in the summer months between patients with a history of one malignancy versus those with two or more. In winter however, patients with a history of one malignancy had significantly higher vitamin D3 levels (mean, 75.25 nmol/L) than those with two or more malignancies (mean 44.6 nmol/L) (P=0.027). The differences between vitamin D3 levels in patients with ASA 2 and 3 were not statistically significant. Conclusion. Vitamin D supplementation may be advisable for patients with a history of multiple malignancies, particularly during the winter months. However, confirmation in a clinical trial with a larger patient cohort is warranted before firm recommendations can be made.

Amyloidosis represents a clinically and molecularly heterogeneous group of serious, potentially life-threatening disorders characterized by the extracellular deposition of insoluble amyloid fibrils derived from misfolded precursor proteins. These deposits disrupt tissue architecture and function, often affecting vital organs such as the heart and kidneys. Accurate diagnosis and subtyping of amyloidosis are essential for effective clinical management and personalized therapeutic interventions. This review provides an integrated overview of modern approaches to the laboratory diagnosis of amyloidosis, divided into three main areas: (1) histological and immunological methods (including Congo red staining, immunohistochemistry, immunofluorescence, and immunoelectron microscopy) for the initial detection and characterization of amyloid deposition, (2) electrophoretic techniques (capillary electrophoresis, isoelectric focusing, immunofixation electrophoresis) used primarily for the analysis of amyloid-associated proteins in serum and urine, and (3) mass spectrometry-based proteomic analyses that have significantly improved subtype specificity and clinical decision-making. By emphasizing the complementary roles of these techniques, the review aims to support timely, accurate, and subtype-specific diagnosis, ultimately improving clinical outcomes and treatment strategies for patients affected by amyloidosis.

Congenital hypofibrinogenemia (CH) and congenital dysfibrinogenemia (CD) are rare coagulation disorders caused by quantitative or qualitative defects in the fibrinogen gene. In this study, the authors, working to identify genetic variants and expanding knowledge about genetic variants in Slovak patients with congenital fibrinogen disorders registered at the National Haemophilia Centre. Molecular-genetic analysis have revealed six novel variants in 36 patients - FGA c.923_968dup p.(Gly324Lysfs*44) and FGG c.1105C>T p.(His369Tyr) were identified in CD patients. In CH patients, in the FGG gene c.8G>A p.(Trp3*), c.823G>T p.(Glu275*) and c.323C>A p.(Ala108Asp) variants were detected. In the FGB gene c.1427C>T p.(Ser476Leu) was identified.

More and more articles suggest that warfarin may be involved in the progression of systemic atherosclerosis. It inhibits the synthesis and activity of Matrix-Gla-Protein, which is the major vitamin K-dependent inhibitor of arterial calcification – an active process associated with atherosclerosis, stimulated by inflammatory mechanisms. Warfarin administered in experimental animal models increased the number of aortic calcifications and in clinical trials – the coronary atheroma calcification. Some NOAC reduce the inflammatory process in the vascular walls and stabilize the coronary atherosclerotic process.

The manuscript describes the protocol for a prospective study evaluating the relationship between carotid stenosis and retinal oxygen metabolism. Carotid stenosis is a major cause of ischaemic stroke worldwide. Retinal oximetry imaging of retinal blood vessels is noninvasive and capable of direct examination of the post-stenotic blood flow. It may be useful in differentiating high and low risk stenosis of the same severity. The results will yield more information about adaptive changes in the post-stenotic basin and may reveal mechanisms behind larger ischaemic deficits in some stroke patients. Previous studies have demonstrated that retinal blood flow is affected in a variety of eye and systemic diseases, including diabetic retinopathy, age-related macular degeneration, and glaucoma.

The aim of the study was to evaluate the association of cardiac biomarkers levels with the parameters of cardiac structure and function in the patients with arterial hypertension. Patients with arterial hypertension, normal left ventricular ejection fraction and absence of signs of heart failure were included in the study. Biomarker of cardiac remodeling (NT-proBNP) correlated with the parameters of left ventricular diastolic function and biomarkers involved in myocardial fibrosis (sST2) correlated with parameters of cardiac structure and were associated with left ventricular hypertrophy (sST2 and TIMP-1).

Proteomic analysis of the vitreous has unveiled critical molecular mechanisms underlying retinal pathologies, highlighting novel therapeutic opportunities. This study explores the dynamic protein changes associated with detachment-induced photoreceptor degeneration, metabolic stress, and inflammation. Key findings reveal altered glycolytic enzymes, antioxidant depletion, and cytokine dysregulation, underscoring their roles in cellular damage and repair. The review emphasizes the transformative potential of advanced proteomics, such as data-independent acquisition and exosome profiling, in identifying biomarkers and therapeutic targets, paving the way for precision medicine in combating vision-threatening conditions.

The authors confirmed Johanson-Blizzard syndrome in a Czech proband by identification and characterization of two novel causal variants in the UBR1 gene (NM_174916.3), c.3482A>C and c.3509+6T>C. Using RNA and in silico analysis, they revealed that the splice site variant c.3509+6T>C induced the removal of a very rare non-canonical GC-AG intron and that the missense variant c.3482A>C altered a highly conserved zinc-coordinating histidine in the zinc-stabilized domain RING-H2. Although the variants were found in trans, neither was detected in the parents. To the best of their knowledge, the authors report the first molecular confirmation of JBS in the Czech Republic and the first identification of two de novo causal variants in two alleles.

This study aimed to investigate changes in fundus autofluorescence in patients taking daily lutein oral supplements and to develop image processing methods for follow-up evaluations of the images. Dual wavelength fundus autofluorescence is a valuable technique for macular pigment evaluation in follow-up examinations, utilizing software image post-processing with commonly available hardware.

This work provides an in-depth exploration of mitochondrial functions beyond energy production, highlighting their essential roles in cellular processes, signaling, and health maintenance. By emphasizing recent advances in mitochondrial research, the manuscript underscores the impact of mitochondria in aging, disease, and exercise, offering valuable insights that could guide therapeutic strategies for enhancing mitochondrial health and longevity

This study evaluated the amount of TREC in a group of risk newborns and found a significant association between low TREC values and the occurrence of sepsis. The authors identified an association between mortality in preterm neonates with sepsis in patients with TREC < 5th percentile and they hypothesize that low TREC values may be a surrogate marker for mortality in preterm neonates.

This research study was focused on changes in DNA methylation in specific tumor supressor genes in endometrial hyperplasia. The authors performed a retrospective study of endometrial tissue of 164 patients treated in their department from 2007 to 2014 dividing them into three subsets: atypical hyperplasia, hyperplasia without atypia and a control group with normal endometrial tissue. 25 selected genes using the methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) probe set were tested. Differences in DNA methylation among the groups were found in PTEN, CDH13, and MSH6 promoters. These genes appear to be involved in different stages of the development of endometrial hyperplasia.

Heart failure is one of the critical and most costly medical challenges of the 21st century. It is a chronic debilitating condition and adherence to medication, a precondition for successful treatment is often poor. There are various interventions for improving adherence. Depending on the goal of the intervention, these are roughly patient centric, healthcare provider centric and system centric. The authors provide an overview of these interventions with a focus on effectiveness and appropriateness in different clinical situations. Their use can lead to improved patient outcomes and reduced economic burden of the disease.

Detection of drug or its metabolite in a blood sample without evaluation of serum concentration does not fully enable uncovering instances of improper drug use or white-coat adherence. Considering pharmacokinetic properties of the drug helps us to recognize if measured concentration refers to steady state, i. e. regular use, or is markedly reduced and therefore originates from irregular or single dose ingestion before sampling. Application of pharmacokinetic principles in the interpretation of serum concentrations of antihypertensive drugs leads to a more precise evaluation of a patient's behaviour.

This is a retrospective one tertiary centre study which investigated the humoral and cellular immunity reconstitution and clinical impact of chemotherapeutic protocols that included a single rituximab dose in children and adolescents treated for non-Hodgkin Lymphoma. The proportion of IgG, IgM, and IgA hypogammaglobulinemia decreased over the follow-up period. The median for B cell reconstitution was 3 months after the end of lymphoma treatment. Transitional B lymphocyte subsets dominated at the time of B cell subset reconstitution. No secondary antibody deficiency needing immunoglobulin replacement therapy was found.

The possibility of using deep-frozen corneal stromal lenticules could significantly help in the treatment of corneal ulcers or even perforations, which is currently difficult due to the relative unavailability of corneal tissue donors, especially in developing countries.

Six multiple sclerosis (MS) patients with a rapid progression of disability underwent immunoablative therapy followed by autologous hematopoietic stem cell transplantation (AHSCT) as the first-line disease-modifying therapy, between 2018 and 2021. Four out of six patients showed disability progression after AHSCT, so the rapid progression of MS was just slowed down by AHSCT. One patient developed activity on magnetic resonance imaging and two patients experienced mild relapses after AHSCT. None of the patients developed grade 4 non-hematological toxicity.

Two cases of BCG pneumonitis described in this study highlight the necessity to consider systemic BCG infection in patients after intravesical BCG therapy. Uncommon complications of bacillus Calmette-Guérin administration could be very serious and threaten the life of patients treated with this modality. Treatment with specific antituberculotic medication underlines the importance of correct diagnosis.

Aims: Brittle cornea syndrome (BCS) is a rare autosomal recessive disorder. The aim of this study was to review ZNF469 mutations associated with BCS type 1 to date and to describe an additional case of Czech/Polish background. Methods: Whole genome sequencing was undertaken to identify the molecular genetic cause of disease in the proband. Sequence variants in ZNF469 previously reported as BCS type 1-causing were searched in the literature, manually curated and aligned to the reference sequence NM_001127464.2. Results: The proband has been reviewed since childhood with progressive myopia and hearing loss. Aged 13 years had been diagnosed with Stickler syndrome. Aged 16.5 years, he developed acute hydrops in the left eye managed by corneal transplantation. At the age of 26, he experienced right corneal rupture after blunt trauma, also managed by grafting. He had a number of secondary complications and despite regular follow-up and timely management, the right eye became totally blind and the left eye had light perception at the last follow-up visit, aged 42. He was found to be a compound heterozygote for two novel mutations c.1705C>T; p.(Gln569*) and c.1402_1411del; p.(Pro468Alafs*31) in ZNF469. In total 22 disease-causing variants in ZNF469 have been identified, mainly in consanguineous families or endogamous populations. Only four probands, including the case described in the current study, harboured compound heterozygous mutations. Conclusion: BCS occurs very rarely in outbred populations which may cause diagnostic errors due to poor awareness of the disease. Investigation into the underlying molecular genetic cause in patients with connective tissue disorders may lead to a re-evaluation of their clinical diagnosis.