Deficit transportu riboflavinu (RTD), známý také jako Brown-Vialetto-van Laere syndrom, je vzácné onemocnění, které na základě poruchy oxidativního metabolizmu vede k úbytku neuronů v jádrech hlavových i periferních nervů. Projevy jsou ztráta svalové síly, ptóza očního víčka, bulbární syndrom a respirační potíže doprovázené těžkou postsynaptickou sluchovou neuropatií. Je-li projeven v dětském věku, vede k úmrtí pro respirační selhání v řádu měsíců až let. Na prezentovaném případu familiárního výskytu u sourozenců je demonstrována nutnost rychlého zahájení substituční léčby riboflavinem, která může předejít rozvoji onemocnění nebo alespoň zmírnit jeho projevy a zvýšit šanci na úspěšnou rehabilitaci sluchu. Při záchytu sluchové neuropatie u dětí doporučujeme vyšetření multigenového NGS/MPS panelu, který zahrnuje i vzácnější příčiny vrozené poruchy sluchu. V případě výskytu jakéhokoli dalšího příznaku onemocnění je třeba neprodleně zahájit substituční léčbu.
Riboflavin transporter deficiency (RTD) is rare disease characterized by progressive loss of cranial and somatic nerve function. Typically ptosis, bulbar syndrome, muscle weakness, and auditory neuropathy are manifested. Without treatment, this leads to death caused by respiratory failure, especially when it starts in childhood. In this paper, we present two siblings with RTD and demonstrate the necessity of early diagnosis and riboflavin substitution treatment. Riboflavin substitution can prevent hearing loss and increase the chance for successful hearing rehabilitation. Comparison with other existing literature is given. We recommend to test every child with captured auditory neuropathy spectrum disorder for a multi-gene NGS/MPS panel and provide substitution treatment before genetic test results, especially when other symptoms are manifested.
Východiská: Z hľadiska epidemiológie predstavuje kolorektálny karcinóm (KRK) celosvetovo jeden z najčastejšie sa vyskytujúcich nádorov. Pokrok vo výskume sa premietol do zníženia úmrtnosti na toto ochorenie, avšak zníženie veku vzniku KRK vytvára obavy vo väčšine rozvinutých krajín. Identifikácia a validácia účinných prognostických biomarkerov sú kľúčové pre zvýšenie presnosti diagnostiky a individualizáciu liečby. Cieľ: Cieľom práce je analyzovať najnovšie údaje o epidemiológii a rizikových faktoroch KRK. Naratívny prehľad sa zameriava aj na zhrnutie súčasných poznatkov o rôznych prognostických biomarkeroch pri liečbe KRK, vrátane ukazovateľov výkonnostného stavu, nutričných a zápalových markerov. Záver: KRK predstavuje závažný zdravotný problém vo väčšine krajín a nádorové biomarkery, ako aj stav pacienta pred liečbou, sú rozhodujúce pre určenie prognózy ochorenia. Ukazovatele nutričného a výkonnostného stavu zohrávajú zásadnú úlohu pri hodnotení stavu pacienta a ovplyvňujú rozhodnutia o liečbe, s potenciálnym dopadom na jej výsledky. Zápalové markery sa javia ako významný prognostický faktor, korelujúc s imunitnou odpoveďou pacienta na nádor a zápalovými procesmi, ktoré môžu viesť k progresii ochorenia. Napriek ich sľubnej prediktívnej sile sa tieto biomarkery zatiaľ bežne nepoužívajú v klinickej praxi z dôvodu potreby ďalšej vedeckej validácie. Integrácia nových biomarkerov do klinickej praxe by však mohla viesť k personalizovanejším liečebným stratégiam a tým k zlepšeniu prežívania pacientov. Pre komplexnejšie posúdenie validity týchto biomarkerov a ich aplikácie v bežnej klinickej praxi je potrebný ďalší výskum.
Background: In terms of epidemiology, colorectal carcinoma (CRC) represents one of the most prevalent tumors worldwide. Progress in research has translated into reduced mortality of the disease, but the trend of early onset CRC troubles most of the developed countries. Identification and validation of effective prognostic biomarkers are crucial for improving diagnostic accuracy and treatment outcomes. Purpose: The objective of the work is to analyze the latest data on the epidemiology and risk factors of CRC. A narrative review also aims to summarize current knowledge about various prognostic biomarkers in the treatment of CRC, including indicators of performance status, nutritional, and inflammatory markers. Conclusion: CRC pose major health problem in most of the countries and the tumor biomarkers as well as patients pre-treatment condition are crucial to establish prognosis of the disease. Nutritional and performance status indicators play an essential role in assessing the patient’s condition and influence treatment decisions, with a potential impact on treatment outcomes. Inflammatory markers have demonstrated significant prognostic value, correlating with the patient’s immune response to the tumor and inflammatory processes that may promote disease progression. Despite promising predictive capabilities, these biomarkers are not yet routinely used in clinical practice due to the need for further research validation. The integration of new biomarkers into clinical practice could lead to more personalized treatment decisions and improved treatment outcomes. For a more comprehensive assessment of the validity of these biomarkers and their application in regular clinical practice, further research is necessary.
- MeSH
- Biomarkers MeSH
- Nutritional Physiological Phenomena MeSH
- Genetic Testing MeSH
- Genes, ras genetics MeSH
- Colorectal Neoplasms * epidemiology MeSH
- Humans MeSH
- Microsatellite Instability MeSH
- Prognosis * MeSH
- Proto-Oncogene Proteins B-raf genetics adverse effects MeSH
- Risk Factors * MeSH
- Neoplasm Staging methods MeSH
- Inflammation complications physiopathology MeSH
- Check Tag
- Humans MeSH
Newborn screening for Phenylketonuria enables early detection and timely treatment with a phenylalanine-restricted diet to prevent severe neurological impairment. Although effective and in use for 60 years, screening, diagnostic, and treatment practices still vary widely across countries and centers. To evaluate the Phenylketonuria newborn screening practices internationally, we designed a survey with questions focusing on the laboratory aspect of the screening system. We analyzed 24 completed surveys from 23 countries. Most participants used the same sampling age range of 48-72 h; they used tandem mass spectrometry and commercial non-derivatized kits to measure phenylalanine (Phe), and had non-negative cut-off values (COV) set mostly at 120 μmol/L of Phe. Participants mostly used genetic analysis of blood and detailed amino acid analysis from blood plasma as their confirmatory methods and set the COV for the initiation of dietary therapy at 360 μmol/L of Phe. There were striking differences in practice as well. While most participants reported a 48-72 h range for age at sampling, that range was overall quite diverse Screening COV varied as well. Additional screening parameters, e.g., the phenylalanine/tyrosine ratio were used by some participants to determine the screening result. Some participants included testing for tetrahydrobiopterin deficiency, or galactosemia in their diagnostic process. Results together showed that there is room to select a best practice from the many practices applied. Such a best practice of PKU-NBS parameters and post-screening parameters could then serve as a generally applicable guideline.
- Publication type
- Journal Article MeSH
Despite improving diagnostic possibilities, the incidence of prostate cancer is increasing, but we are not able to reduce the mortality rate. While PSA, 4K score, PCA3 and other urinary markers, ExoDX, SelectMDX, Confirm MDx or MiPS tests are used to identify potential prostate cancer carriers, Decipher, Prolaris or Oncotype DX tests are used to assess the aggressiveness of proven cancer in order to stratify patients for early or delayed treatment. More modern forms of treatment for advanced disease include second-generation antiandrogens and PARP inhibitors. By assessing genetic mutations (e.g. BRCA1, BRCA2 genes, single nucleotide polymorphism) or the presence of splice variants of the androgen receptor (ARV7), we are able to identify patients in whom the planned treatment may be expected to be ineffective and thus choose other treatment modalities. In the present review article, we offer a comprehensive overview of current diagnostic tests that find application in the diagnosis of early and advanced prostate cancer.
- Publication type
- Journal Article MeSH
- Review MeSH
Background/Objectives: The DIEP flap is among the preferred techniques in autologous breast reconstruction due to better long-term outcomes, including higher satisfaction and more natural breast shape compared to implant-based breast reconstruction. With the rise in genetic testing, bilateral DIEP reconstructions are becoming more common, though they carry a higher risk of complications. This study aims to compare the risks between unilateral and bilateral procedures to improve surgical decision-making. Methods: A retrospective, single-center review was conducted on female patients who underwent DIEP flap breast reconstruction between January 2018 and May 2024. The study included patients with complete medical records and follow-up data, excluding those with incomplete records. Patient characteristics, operative details, and complications were thoroughly analyzed, with donor site complications assessed per patient and recipient site complications per breast. Results: During the study, 141 DIEP flaps were performed on 114 women, with 87 unilateral and 27 bilateral reconstructions. Age and BMI were similar between groups. However, chemotherapy was more common in the bilateral group (85% vs. 47%, p = 0.0011). Operative time was significantly longer in bilateral procedures (650 vs. 460 min, p < 0.0001). There were no statistically significant differences in recipient and donor site complications across groups. The hospital stay was significantly longer in the bilateral group (11 vs. 8.8 days, p = 0.024). Conclusions: Bilateral and unilateral DIEP flap breast reconstructions have similar complication and early take-back rates.
- Publication type
- Journal Article MeSH
Background: The purpose of this study was to assess bone densitometry parameters in patients with classical and hypermobile Ehlers-Danlos syndrome (EDS) and to determine whether the hypermobile subtype increases the risk of low bone mass, which is particularly important in this patient group, since the genetic mutation responsible for this subtype is still unknown. Material and Methods: In order to conduct this study, we collaborated with the EDS society in Poland. A total of 30 females of reproductive age who were included in the study were divided into two groups: Group 1-those with classical EDS (n = 9) and Group 2-those with hypermobile EDS (n = 21). Routine laboratory test results, bone turnover markers, and densitometry parameters were evaluated and compared. Results: The study groups showed no differences in terms of densitometry parameters or markers of calcium-phosphate metabolism. A multivariate logistic analysis demonstrated no increase in the risk of low bone mass (defined as a Z-score lower than -2) in patients with hypermobile EDS (OR 0.067 [95% Cl 0.0-20.927]; p = 0.356). Conclusions: The hypermobile subtype of EDS does not increase the risk of low bone mass; there were no significant differences between patients with hypermobile EDS and those with classical EDS in terms of either densitometry parameters or markers of calcium-phosphate metabolism. Although patients with hypermobile EDS are not at a higher risk of developing low bone mineral density, they should be regularly monitored for any calcium and phosphate metabolism abnormalities.
- Publication type
- Journal Article MeSH
Medical students are exposed to the hospital environment and patients during their studies, increasing the risk of exposure to virulent and antibiotic-resistant isolates of Staphylococcus aureus. The aim of the study is to determine the prevalence of Staphylococcus aureus among medical students who have varying levels of exposure to the hospital environment to provide valuable insights into the risk of colonization and transmission. Nasal swabs and fingerprints were obtained and cultured on a selective medium for staphylococci. The obtained isolates were confirmed as methicillin-sensitive S. aureus (MSSA) or methicillin-resistant (MRSA) using PCR. Antibiotic resistance, the presence of virulence genes including enterotoxin encoding genes, and spa typing were performed. Among pre-clinical students, MSSA was detected on the nose in 45.2% and on the fingerprints in 10.6% of the participants. Among clinical students, MSSA was detected on the nose in 42.0% and on the fingerprints in 25.4%. Only one MRSA isolate was obtained. Genes seg and sei were the most frequently detected in both student groups, with their presence in over 40% of isolates among clinical students. The eta and etb genes were mainly detected from the nose in both student groups. In pre-clinical students, S. aureus carrying eta gene occurred in 6.4% and etb in 8.5%. In clinical students, the occurrence was 5.1% for eta and 8.5% for etb. The tst gene was identified only in the nose and fingerprints of the clinical student group. The most frequently observed resistance was to clindamycin and erythromycin. In total 58 different spa types were identified. High rates of asymptomatic MSSA carriage were observed in both groups of medical students. Detected MSSA strains showed a high degree of genetic variability, with a number of them carrying the virulence and antibiotic resistance genes. Although students do not exhibit increased risk to their patient's, increased hygiene is required in asymptomatic carriage personnel. The overall prevalence of MRSA was low, with a minimal risk of spread.
- MeSH
- Anti-Bacterial Agents pharmacology MeSH
- Adult MeSH
- Virulence Factors * genetics MeSH
- Humans MeSH
- Methicillin-Resistant Staphylococcus aureus genetics isolation & purification drug effects classification MeSH
- Microbial Sensitivity Tests MeSH
- Young Adult MeSH
- Carrier State * microbiology epidemiology MeSH
- Prevalence MeSH
- Staphylococcal Infections * microbiology epidemiology MeSH
- Staphylococcus aureus * genetics isolation & purification drug effects classification MeSH
- Students, Medical * MeSH
- Check Tag
- Adult MeSH
- Humans MeSH
- Young Adult MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
INTRODUCTION: Progressing myelodysplastic syndrome (MDS) into acute myeloid leukemia (AML) is an indication for hypomethylating therapy (HMA, 5-Azacytidine (AZA)) and a BCL2 inhibitor (Venetoclax, VEN) for intensive chemotherapy ineligible patients. Mouse models that engraft primary AML samples may further advance VEN + AZA resistance research. METHODS: We generated a set of transplantable murine PDX models from MDS/AML patients who developed resistance to VEN + AZA and compared the differences in hematopoiesis of the PDX models with primary bone marrow samples at the genetic level. PDX were created in NSGS mice via intraosseal injection of luciferase-encoding Lentivirus-infected MDS/AML primary cells from patient bone marrow. We validated the resistance of PDX-leukemia to VEN and AZA and further tested candidate agents that inhibit the growth of VEN/AZA-resistant AML. RESULTS AND DISCUSSION: Transplantable PDX models for MDS/AML arise with 31 % frequency. The lower frequency of transplantable PDX models is not related to peritransplant lethality of the graft, but rather to the loss of the ability of short-term proliferation of leukemic progenitors after 10 weeks of engraftment. There exist subtle genetic and cytological changes between primary and PDX-AML samples however, the PDX models retain therapy resistance observed in patients. Based on in vitro testing and in vivo validation in PDX models, Panobinostat and Dinaciclib are very promising candidate agents that overcome dual VEN + AZA resistance.
- Publication type
- Journal Article MeSH
Článek na téma Dubinův-Johnsonův syndrom shrnuje základní poznatky tohoto onemocnění. Dále je zmíněn význam genetického vyšetření při podezření na toto onemocnění. Závěrem je uvedeno krátké kazuistické sdělení.
The article on Dubin-Johnson syndrome summarizes the basic knowledge of this condition. It further discusses the significance of genetic testing when there is a suspicion of this disease. In conclusion, a brief case report is presented.
PURPOSE: A new high-resolution next-generation sequencing (NGS)-based method was established to type closely related European type II Toxoplasma gondii strains. METHODS: T. gondii field isolates were collected from different parts of Europe and assessed by whole genome sequencing (WGS). In comparison to ME49 (a type II reference strain), highly polymorphic regions (HPRs) were identified, showing a considerable number of single nucleotide polymorphisms (SNPs). After confirmation by Sanger sequencing, 18 HPRs were used to design a primer panel for multiplex PCR to establish a multilocus Ion AmpliSeq typing method. Toxoplasma gondii isolates and T. gondii present in clinical samples were typed with the new method. The sensitivity of the method was tested with serially diluted reference DNA samples. RESULTS: Among type II specimens, the method could differentiate the same number of haplotypes as the reference standard, microsatellite (MS) typing. Passages of the same isolates and specimens originating from abortion outbreaks were identified as identical. In addition, seven different genotypes, two atypical and two recombinant specimens were clearly distinguished from each other by the method. Furthermore, almost all SNPs detected by the Ion AmpliSeq method corresponded to those expected based on WGS. By testing serially diluted DNA samples, the method exhibited a similar analytical sensitivity as MS typing. CONCLUSION: The new method can distinguish different T. gondii genotypes and detect intra-genotype variability among European type II T. gondii strains. Furthermore, with WGS data additional target regions can be added to the method to potentially increase typing resolution.
- MeSH
- Genetic Variation MeSH
- Genotype MeSH
- Humans MeSH
- Multiplex Polymerase Chain Reaction MeSH
- Polymorphism, Restriction Fragment Length MeSH
- DNA, Protozoan genetics MeSH
- Pregnancy MeSH
- Toxoplasma * genetics MeSH
- High-Throughput Nucleotide Sequencing MeSH
- Check Tag
- Humans MeSH
- Pregnancy MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
