Biomedical Papers-Olomouc最新文献

Background and aims: In patients with atrial fibrillation, oral anticoagulation therapy is indicated for both primary and secondary prevention of stroke/systemic embolism. Though direct oral anticoagulants with greater safety and efficacy than warfarin were introduced into clinical practice at the beginning of the last decade, even now not all patients with AF have adequate preventative anticoagulant treatment. The primary goal of this study was to evaluate the impact of prior use of oral anticoagulants on admission stroke severity in those with AF. Other aims were, inter alia, to assess the trend in atrial fibrillation prevalence in the years of the HISTORY trials 2012-2021 carried out in the Czech Republic and use of oral anticoagulants (OAC) in ischemic stroke (IS) patients.

Methods: We analyzed consecutive ischemic stroke patients who had been enrolled in the HISTORY (Heart and Ischemic STrOke Relationship studY) study registered on ClinicalTrials.gov (identifier NCT01541163) in the year 2012 and carried out a yearly comparison (detailed in the text).

Results: In total, there were 1059 patients (55.9% males, mean age 71.7±12.8). There was no significant difference over the time period in rate of known (18.3 vs. 16.5%, P=0.442) or newly detected AF (17.0 vs. 16.0%, P=0.665), but sigificantly more patients with known AF were treated with oral anticoagulants before IS in the year 2021 (32.1 vs. 70.7%, P<0.0001), and direct oral anticoagulants (3.6 vs. 35.4%, P<0.0001). The number of patients with atrial fibrillation had not changed significantly over the years (26.2 vs. 31.3%). Patients on OAC had a lower median admission score on the National Institutes of Health Stroke Scale (NIHSS) than those not using an oral anticoagulant (6 vs. 16, P=0.0004) in 2021.

Conclusions: There was no significant upward trend in atrial fibrillation in stroke patients admitted between 2012 and 2021, but patients with known AF were significantly more frequently treated with oral anticoagulants and direct oral anticoagulants (DOAC) in 2021. Patients on OAC had lower admission NIHSS scores than those not using any anticoagulent in the year 2021. The difference in the median admission NIHSS between the patients on OAC and those without OAC treatment was not significant in the year 2012 (6 vs. 12, P=0.066). This might be related to the fact that substantially fewer patients in 2012 were on DOACs, which are considered more effective than warfarin.

Atrial fibrillation (AF), the most common cardiac arrhythmia globally, contributes significantly to morbidity and mortality. With advancements in implantable devices like pacemakers, defibrillators, and loop recorders, incidental detection of AF as device-detected AF (DDAF) or subclinical AF (SCAF) has become common. This asymptomatic AF presents unique management challenges, particularly in anticoagulation decisions for stroke prevention. Evidence from recent trials, notably NOAH-AFNET 6 and ARTESiA, indicates a complex risk-benefit profile for anticoagulation in DDAF. In ARTESiA, anticoagulation modestly reduced stroke and systemic embolism rates, though this effect did not reach statistical significance. The NOAH-AFNET 6 trial found no significant reduction in a composite of cardiovascular death, stroke, or systemic embolism with anticoagulation compared to placebo. Both trials revealed an increased bleeding risk, underscoring the need to carefully weigh stroke prevention against bleeding risks in DDAF. The 2024 European Society of Cardiology guidelines reflect this nuanced approach by advocating a tailored, risk-based strategy. Emerging evidence also shows that AF burden impacts heart failure (HF) outcomes, with a five-fold increase in HF hospitalizations associated with higher AF burden. This highlights the importance of rhythm or rate control to reduce HF progression, particularly in patients with both AF and HF, where reducing AF burden is associated with better prognosis and fewer hospitalizations. Future research should focus on refining anticoagulation strategies, especially for patients with low AF burden, and exploring novel approaches like intermittent anticoagulation and advanced monitoring to support personalized DDAF management.

Background and aim: Vibrio parahaemolyticus a gram-negative, rod-shaped bacterium with salinophilic properties is found mainly in rivers, oceans, and coastal environments. With the expanding scale of aquaculture in coastal regions of China, the contamination of seafoods with Vibrio parahaemolyticus is becoming a significant cause of food poisoning with symptoms including gastroenteritis, wound infection and sepsis. Current methods for detecting this microorganism are unsuitable in the present context. We developed a rapid LAMP-LFD method-by combining the loop-mediated isothermal amplification technique (LAMP) and lateral flow device (LFD).

Methods: The thermolabile hemolysin tlh gene of Vibrio parahaemolyticus was used as the target, and we designed five specific primers in its conserved region. The primers were used to carry LAMP reaction with biotin labelling, the products completed hybridisation with the FAM-labelled primers, and the hybridisation products were tested for results on LFD.

Results: The results showed that the LAMP-LFD method specifically detected Vibrio parahaemolyticus and was negative for proximate strains such as Vibrio vulnificus and other Vibrio pathogens as well as common pathogens such as Escherichia coli. The optimised reaction conditions for LAMP were 40 min at 60 °C, plus 5 min of probe hybridisation and 3-5 min of LFD color development. The lowest concentration of Vibrio parahaemolyticus pure culture bacterial fluid of 1.5×10² cfu/mL could be detected, and the pathogen could be detected from tissue samples with a contamination concentration of 0.75×10³ cfu/mL. The method has higher specificity and sensitivity, and the pathogen can be detected within 1.5 h.

Conclusion: The LAMP-LFD method for Vibrio parahaemolyticus established in this study has the advantages of convenient operation, low dependence on equipment, high sensitivity and rapid detection, all of make it ideally suited to the detection of Vibrio parahaemolyticus at the grass-roots level.

Background: Minimally-invasive extracorporeal circulation (MiECC) is confirmed to mitigate the post-perfusion syndrome resulting in better outcomes in operated patients compared to the conventional cardiopulmonary bypass (ECC).

Aims: To determine whether there is a clinical benefit of lower blood loss in patients operated on MiECC compared to ECC. To provide a detailed construction of modified MiECC and its perfusion management.

Methods: Retrospective analysis of the clinical data of 60 patients undergoing coronary artery bypass grafting on MiECC or ECC. The primary outcome was to compare the following variables in the 2 groups: intraoperative and 30-day mortality and cardiovascular death, myocardial infarction and cerebral stroke (MACCE). Secondary outcomes included surgical revision for bleeding or tamponade, intraoperative and postoperative blood loss and the consumption of packed red blood cell units. We modified our MiECC by connecting a cardiotomy suction.

Results: There was no mortality, major adverse events or surgical revisions in either group. No difference was found for intraoperative blood loss. The MiECC group had significantly lower overall postoperative blood loss (660 mL vs 765 mL, P=0.037). Total consumption of packed red blood cell units was insignificantly higher in the ECC group (n=30 vs n=20, P=0.490).

Conclusion: MiECC is a safe alternative to conventional ECC in routine procedures such as CABG. Its improved biocompatibility was reflected by better preservation of hemostasis in this study.

Background: The tumor microenvironment is a significant mediator enabling tumor growth and progression. Tumor-infiltrating lymphocytes (TILs) are an important component of this but tumor cells develop mechanisms by which they can escape the action of the immune system. Immunosuppressive mechanisms cooperate with each other and involve cells of the immune system, the tumor microenvironment itself, chemokines and cytokines. In this study, we examined the FOXP3+, IL-35+, and PD-L1+ lymphocytes in tumor tissues as they are contributing to immunosuppression in some tumors, including melanoma. Such cells are also associated with tumor progression, early metastasis, and prognosis.

Methods and results: In this study, 95 cutaneous melanomas and 25 melanocytic nevi as a control group were examined by immunohistochemistry for FOXP3+, IL-35+, and PD-L1+ lymphocytes. Melanomas were divided into four groups according to the TNM classification: pT1 (35), pT2 (21), pT3 (21), and pT4 (18). PD-L1+ lymphocytes were enriched in pT3- and pT4-stage melanomas, especially in the periphery of the lesions (P<0.001). The number of FOXP3+ lymphocytes was positively correlated with the stage of the disease, especially in the center of the tumors (P<0.001). Likewise, IL-35+ lymphocytes (P<0.001) were enriched with the stage of the tumor.

Conclusion: This article demonstrates that the immunosuppressive environment develops in proportion to the stage of the melanoma. The most significant changes are found at the tumor periphery, confirming the heterogeneity of the tumor stroma which is more pronounced in more advanced tumors and which may contribute to the greater aggressiveness in these peripheral zones.

Rhegmatogenous retinal detachment (RRD) is a serious ophthalmic condition that, if untreated, can result in significant vision loss. Proliferative vitreoretinopathy (PVR) often complicates RRD and is the leading cause of surgical failure. Proteomic analysis of the vitreous has emerged as a powerful tool for elucidating the molecular mechanisms underlying RRD and PVR. This article reviews proteomic findings related to these conditions. A comprehensive literature search on PubMed was conducted, focusing on studies of vitreous proteomics in RRD and PVR published between 1988 and August 2024. Relevant findings on protein expression, metabolic pathways, and therapeutic targets were synthesized. Proteomic studies reveal significant alterations in photoreceptor-specific proteins, such as rhodopsin and Monocyte Chemoattractant Protein-1 (MCP-1), associated with apoptosis and inflammation during RRD. Metabolic dysregulation is evidenced by changes in glycolytic enzymes and antioxidants, including downregulation of peroxiredoxin-2 and ascorbic acid, suggesting impaired energy production and oxidative stress. Elevated cytokines, complement proteins, and matrix metalloproteinases highlight the role of inflammation and extracellular matrix remodelling in disease progression. Cytokine expression in PVR demonstrates distinct temporal patterns, with early stages marked by T-cell activation and mTOR pathway-related cytokines, and advanced stages characterized by monocyte chemoattractants associated with chronic inflammation. Currently, the potential of pharmacologic interventions in RRD and PVR remains limited. In contrast, proteomics offers critical insights into molecular mechanisms, identifying potential biomarkers and therapeutic pathways. The adoption of single-molecule and top-down proteomics, along with the integration of advanced technologies with artificial intelligence and bioinformatics, holds promise for accelerating progress toward precision medicine. These developments represent a promising avenue for future research and clinical application.

Background: Prostate cancer (PC) is one of the most frequently diagnosed non-skin solid cancers and is a leading cause of cancer-related death and the incidence increasing. Early diagnosis of the disease improves the outcomes. There is an urgent need for new biomarkers with greater discriminative precision for diagnosis, risk-stratification and treatment. The aim of our study was to evaluate the diagnostic and prognostic potential of Fetuin-A and LRG1 in patients with PC.

Methods: Serum levels of Fetuin-A and LRG1 were compared in patients with PC (n=46), a control group 1 including young, healthy subjects (n=26) and control group 2 including patients with negative prostate biopsy (n=46). In PC patients, the levels of both biomarkers were compared in subgroups with different tumour characteristics.

Results: We demonstrated a statistically significant higher concentrations of Fetuin-A in PC patients compared to control group 2 (439 mg/L vs. 372 mg/L), P<0.001. No statistically significant difference was found between PC patients and control group 1, nor for LRG1 levels between the three groups. In PC patients, higher serum levels of LRG1 were found in M1 patients compared to M0 (98 mg/L vs. 42 mg/L), P=0.059.

Conclusion: Fetuin-A levels are significantly higher in patients with prostate cancer than in patients without malignancy but LRG1 levels do not differ between patients with PC and controls.

Neurofibromatosis type 1 (NF1) is an autosomal dominant disorder caused by mutations in the NF1 gene. The most important signs are café-au-lait spots, intertriginous freckling, and neurofibromas. The disease has a progressive course, the penetrance is almost complete, and reduces life expectancy by approximately 15%. This review examines the current literature, including NIH (National Institute of Health) diagnostic criteria, genetic testing, genotype-phenotype correlations, and emerging therapies. Genetic testing has improved diagnostic accuracy, particularly for age-dependent clinical features. The genotype-phenotype correlation in NF1 underscores that specific genetic alterations, such as large deletions in the NF1 gene, are frequently linked to more severe clinical outcomes. These deletions often result in early onset of symptoms, a higher frequency of tumor development, and increased tumor burden, all of which contribute to a more complex clinical course. Consequently, individuals with these genetic changes require intensive and continuous monitoring to manage potential complications and prevent further health deterioration. Advances in therapies such as MEK inhibitors offer hope for inoperable plexiform neurofibromas, while surgery remains the primary option for localized tumors, despite the risk of recurrence. Multidisciplinary care and genetic advancements are crucial for improving the prognosis and quality of life of patients with NF1.

Mitochondria, double-membraned organelles within all eukaryotic cells, are essential for the proper functioning of the human organism. The frequently used phrase "powerhouses of the cell" fails to adequately capture their multifaceted roles. In addition to producing energy in the form of adenosine triphosphate through oxidative phosphorylation, mitochondria are also involved in apoptosis (programmed cell death), calcium regulation, and signaling through reactive oxygen species. Recent research suggests that they can communicate with one another and influence cellular processes. Impaired mitochondrial function on the one hand, can have widespread and profound effects on cellular and organismal health, contributing to various diseases and age-related conditions. Regular exercise on the other hand, promotes mitochondrial health by enhancing their volume, density, and functionality. Although research has made significant progress in the last few decades, mainly through the use of modern technologies, there is still a need to intensify research efforts in this field. Exploring new approaches to enhance mitochondrial health could potentially impact longevity. In this review, we focus on mitochondrial research and discoveries, examine the structure and diverse roles of mitochondria in the human body, explore their influence on energy metabolism and cellular signaling and emphasize their importance in maintaining overall health.

Aims: To present a case of primary ventriculitis in a 53-year-old patient caused by Streptococcus intermedius, emphasizing the rarity of the condition and the challenges in achieving clinical improvement despite targeted therapy.

Methods: The patient underwent clinical evaluation, including CT and MRI imaging, as well as CSF analysis. Empirical antibiotic therapy was initiated with cefotaxime and metronidazole, followed by targeted therapy based on CSF culture results. External ventricular drainage was performed surgically.

Results: No predisposing factors were identified in the patient. Initial imaging showed no acute changes, but follow-up imaging revealed significant ventricular inflammation. CSF analysis confirmed the presence of Streptococcus intermedius. Despite early and targeted antibiotic therapy, and surgical intervention, the patient's clinical condition did not improve.

Conclusion: This case highlights the rarity of primary ventriculitis caused by Streptococcus intermedius and the challenges in managing it. The lack of clinical improvement despite prompt and targeted treatment underscores the need for further research to develop more effective therapeutic strategies for such infections.