This study aimed to obtain data describing the epidemiology and antifungal susceptibility of yeasts isolated from bloodstream infections (BSI) in the Czech Republic (CR). This study presents data from the first year of a national, long-term surveillance program. All microbiologically confirmed candidemia cases in patients hospitalized at 30 Czech centers in 2023 were evaluated. This study assessed BSI incidence per 100,000 inhabitants, species distribution, and antifungal susceptibilities (EUCAST E.Def 7.4 protocol) of strains.aff Whole-genome sequencing was performed on selected isolates with acquired resistance or non-wild-type phenotypes to determine the molecular mechanisms of resistance. In total, 433 isolates from 408 unique BSI episodes in 398 patients were recorded in 2023. Candida albicans was the most frequent species (40.6%), followed by Candida glabrata (24.5%), Candida parapsilosis (14.5%), and Candida tropicalis (5.5%). In pediatric patients, C. albicans (58.8%) was the most common, followed by C. parapsilosis (17.6%). Candida auris BSI was not detected in 2023. The highest rates of acquired fluconazole resistance were detected in C. parapsilosis (16.9%) and C. glabrata (15.4%). Most fluconazole-resistant (FLC-R) C. parapsilosis isolates carried Y132F mutation in ERG11 gene (14/15; 93.3%). One isolate of C. glabrata was resistant to echinocandins (1.3%), but remained susceptible to azoles, mutations in FKS1 (G14S) and FKS2 (S663P, T926P) were identified. This nationwide survey provides the first comprehensive yeast BSI surveillance data from the Czech Republic, which spans the entire country. CR follows trends observed in developed countries, with a decline in C. albicans and a rise in C. glabrata infections. To our knowledge, this is the first report describing FLC-R C. parapsilosis isolates carrying the Y132F ERG11 mutation in CR. These findings highlight several emerging challenges that reflect global trends: a shifting spectrum of Candida species from C. albicans to non-albicans species, and rising levels of acquired azole resistance. Therefore, continuous national monitoring is essential.
This international, multidisciplinary consensus report represents the first effort to systematically define and characterize fatty pancreas. A key outcome of this endeavor was the recommendation to adopt "fatty pancreas" as the standardized and inclusive term to describe all forms of fat accumulation in the pancreas. This terminological consensus provides a critical foundation for unified reporting and clinical communication. Another major contribution of the report is the consensus on diagnostic imaging findings, which was based on radiological and endoscopic modalities. The proposed criteria aim to enhance consistency in clinical assessment and support the development of standardized research protocols. In addition to establishing terminology and diagnostic frameworks, the report also synthesizes current knowledge across a wide range of relevant domains. These include the etiology and epidemiology of fatty pancreas, as well as its associations with alcohol consumption, smoking, acute and chronic pancreatitis, pancreatic exocrine insufficiency, type 2 diabetes mellitus, and surgical outcomes. The potential links between fatty pancreas and neoplastic conditions such as intraductal papillary mucinous neoplasms and pancreatic cancer are also addressed, alongside the current understanding of its metabolic implications (beta-cell function and glucose homeostasis) and treatment strategies. Throughout the consensus process, a consistent theme emerged: the limited availability of high-quality, prospective clinical data. Therefore, many of the recommendations in this report are based on expert consensus rather than strong empirical evidence. As such, the statements require rigorous prospective validation before they can be adopted into routine clinical practice. This underscores a critical need for further research, particularly studies aimed at clarifying causal relationships, validating diagnostic tools, and determining the clinical relevance of fatty pancreas across diverse patient populations. This report serves as both a summary of our current understanding and a roadmap for future investigations, aiming to close existing knowledge gaps and guide evidence-based clinical practice in this emerging field.
Lymphoceles (LCs) are one of the most common complications after robot-assisted radical prostatectomy (RARP). Peritoneal flaps (PF) have shown to possibly decrease the incidence of LCs. This individual patient data meta-analysis (IPD-MA) investigates the efficacy of PF on rates of symptomatic lymphoceles (sLCs) requiring intervention, sLCs, overall lymphoceles and perioperative complications. We conducted a prespecified systematic review and IPD-MA (PROSPERO CRD42024519284). A database search via Medline, Web of Science, Embase, Central, ClinicalTrials.gov and the International Clinical Trials Registry Platform was performed up to December 2023. Six randomized controlled trials (RCTs) comparing PF vs. no PF during RARP with PLND were included and five RCTs provided IPD. MA was conducted using a random-effects model (two-stage model). PF significantly reduced sLCs requiring intervention as well as the rates of sLCs and overall lymphoceles. Additionally, PF significantly reduced overall complications, most likely driven by fewer lymphoceles and associated interventions. Furthermore, BMI and the presence of lymphoceles at discharge were identified as risk factors for sLCs. Subgroup analyses suggested that the protective effect of PF diminishes with increasing BMI, indicating limited benefit in patients with severe obesity. The creation of PF after RARP significantly reduces sLCs without affecting the complication rate or meaningfully prolonging operative time. LCs at the time of discharge represent significant risk factors for occurrence of sLCs, indicating a possibility for closer observation for this subgroup. With the evidence provided by this IPD-MA, creation of PF should be the new standard of care to reduce LC-related morbidity.
The global rise of antimicrobial resistance has renewed interest in fosfomycin (FOS), an old antibiotic with activity against multidrug-resistant Enterobacterales. However, resistance to FOS is increasing, driven by impaired drug uptake, target modification, and by fosA-encoded enzymatic inactivation. This study assessed the prevalence and molecular basis of FOS resistance among Enterobacterales collected in Czech tertiary care hospitals in 2024. A total of 211 preliminary FOS-resistant isolates were obtained from nine hospitals across the Czech Republic, predominantly Proteus mirabilis (n=149) and Escherichia coli (n=57). All isolates showed elevated FOS MICs, and the PPF test identified FosA activity in 34/211 isolates. Carbon-source growth testing demonstrated widespread impairment of GlpT and UhpT transporters (93.8% affecting both). PCR confirmed fosA genes in 14 isolates (9 P. mirabilis, 5 E. coli). WGS revealed fosA3 as the dominant variant (85.7%), followed by fosA4 (14.3%). P. mirabilis isolates primarily belonged to ST185 and ST135, forming two Czech-specific fosA3 clusters with limited relatedness to international genomes. FosA-producing E. coli displayed broader diversity (ST69, ST58, ST550, ST1308). FosA4 was detected exclusively in E. coli. Most fosA-positive strains co-harbored ESBL genes, predominantly blaCTX-M-65. SNP-based phylogenies indicated local clonal circulation of fosA3-positive P. mirabilis ST185, whereas E. coli isolates showed heterogeneous international linkages. Analysis of GlpT/UhpT/MurA identified numerous amino acid substitutions, though only a minority were predicted to affect protein function. This study documents the first broader emergence of plasmid-mediated FOS resistance in Czech Enterobacterales and underscores the importance of continuous genomic surveillance of fosA-mediated resistance.
Environmental exposure to toxic and essential metals can disrupt host immune function through mechanisms involving epigenetic, transcriptional, and post-transcriptional regulation. Although numerous studies have investigated these regulatory layers separately, integrative analyses across molecular levels in relation to metallome is missing. In this study, we performed a targeted multi-omics analysis of six immune-associated genes (NFKB1, CDKN2A, IGF2, H19, ESR1, and APOA5) and corresponding proteins in healthy residents from a long-term mining region (MRR, n = 46) and a non-mining region (NMR, n = 48). Transcriptome data were generated by mRNA sequencing, while DNA methylation data were obtained using targeted bisulfite sequencing by analyzing previously identified differentially methylated positions. Plasma protein levels were measured by enzyme-linked immunosorbent assay, and plasma metal concentrations were quantified using inductively coupled plasma mass spectrometry. We observed significantly higher plasma levels of NFKB1 and CDKN2A proteins, along with lower ESR1 transcript levels, in residents of the mining region compared to the non-mining region. NFKB1 protein levels were associated with both promoter methylation and residence in mining region, suggesting a regulatory cascade from DNA methylation to protein expression. IGF2 protein levels were higher in males and showed positive associations with age and the cumulative Z-score of essential metal mixture burden. Our results show that long-term residence in mining regions is associated with changes in NFKB1 at both the DNA methylation and protein levels, which may serve as a sensitive biomarker of metal exposure.
