https://hdl.handle.net/20.500.14178/905 Fri, 01 May 2026 10:59:13 GMT 2026-05-01T10:59:13Z https://hdl.handle.net/20.500.14178/3743 One-year multicenter surveillance of Fosfomycin resistance Enterobacterales: the rise of FosA3-producing P. mirabilis Chudějová, Kateřina; Mattioni Marchetti, Vittoria; Zaccaria, Vita; Kanova, Stepanka; Šrámková, Anna; Krůtová, Marcela; Ryšková, Lenka; Kroneislová, Gabriela; Horvathova, Beata; Tejkalova, Renata; Krejci, Eva; Vagnerova, Iva; Zemanova, Zuzana; Bitar, Ibrahim 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 bla <inf>CTX-M-65</inf>. 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. Thu, 01 Jan 2026 00:00:00 GMT https://hdl.handle.net/20.500.14178/3743 2026-01-01T00:00:00Z https://hdl.handle.net/20.500.14178/3728 Comparative effectiveness of anti-CD20 therapies and S1P receptor modulators in late-onset multiple sclerosis: real-world evidence from the MSBase registry Surcinelli, Andrea; Kalincik, Tomas; Roos, Izanne; D'amico, Emanuele; Lechner-Scott, Jeannette; Ozakbas, Serkan; Hradilek, Pavel; Horáková, Dana; Vachová, Marta; Panzera, Ivan; Ruzza, Stefano; Piscaglia, Maria Grazia; Gerlach, Oliver; Meca-Lallana, Jose Eustasio; Valero-Lopez, Gabriel; Kermode, Allan G.; Fabis-Pedrini, Marzena J.; Prevost, Julie; Ampapa, Radek; Hodgkinson, Suzanne; Grand'maison, Francois; Khoury, Samia J.; John, Nevin A.; Peterka, Marek; Houskova, Jana; Recmanova, Eva; Rous, Zuzana; Shaygannejad, Vahid; Alroughani, Raed; Kuhle, Jens; Jakob, Gregor Brecl; Grammond, Pierre; Patti, Francesco; Van Der Walt, Anneke; Butzkueven, Helmut; Foschi, Matteo Background: Late-onset multiple sclerosis (LOMS), defined by symptom onset after age 50, is increasingly recognised as a distinct clinical entity. Evidence comparing disease-modifying therapies (DMTs) in this subgroup remains limited. Objectives: To compare clinical outcomes of anti-CD20 monoclonal antibodies and sphingosine-1-phosphate receptor modulators (S1PRMs) in LOMS. Design: Multicentre, observational cohort study based on real-world data from an international multiple sclerosis registry. Methods: We analysed data from the MSBase registry, including relapsing-remitting LOMS patients treated with anti-CD20 therapies (ocrelizumab, ofatumumab, rituximab) or S1PRMs (fingolimod, ozanimod, siponimod, ponesimod) for >= 6 months. Primary outcomes were annualised relapse rate (ARR), Expanded Disability Status Scale (EDSS) change, confirmed disability worsening (CDW), progression independent of relapse activity (PIRA), and PIRA without MRI activity (PIRMA). Analyses used inverse probability of treatment weighting (IPTW). Causal forest and best linear projector (BLP) models explored effect modification. Results: After weighting, 347 patients (median age 53.7 years; 69% female; median follow-up 6.9 years) were included. No significant differences were found for ARR, EDSS change, CDW, PIRA, or PIRMA. Exploratory analyses suggested greater anti-CD20 benefit in patients with earlier onset (<= 55 years), shorter disease duration (<= 2 years from diagnosis), and lower disability (EDSS < 3). Conclusions: In this real-world LOMS cohort, no statistically significant differences were observed between anti-CD20 and S1PRM therapies. Exploratory analyses suggested anti-CD20 may be associated with better outcomes in selected subgroups; these findings are hypothesis-generating. Thu, 01 Jan 2026 00:00:00 GMT https://hdl.handle.net/20.500.14178/3728 2026-01-01T00:00:00Z https://hdl.handle.net/20.500.14178/3530 Basal cell adenoma with S100 protein-positive "stroma": a distinct triphasic salivary gland neoplasm characterized by CTNNB1 mutation Skálová, Alena; Bradová, Martina; Laco, Jan; Vaněček, Tomáš; Hájková, Veronika; Martínek, Petr; Grendár, Marián; Querzoli, Giulia; Leivo, Ilmo; Michal, Michal Basal cell adenoma (BCA) is a benign salivary neoplasm that exhibits a divergent spectrum of growth patterns, including cribriform, tubular, trabecular, membranous, and solid. A subset of BCAs is characterized by the presence of abundant S100 protein-positive stroma, which makes this variant unique and potentially represents a hybrid lesion or an entity intermediate between BCA and pleomorphic adenoma (PA). From the authors' registry, we selected 17 cases of BCA with abundant S100 protein-positive stromal components and compared them with 7 cases of BCA without S100 protein-positive stroma, and 6 cases of myoepithelial cell-rich PAs. All cases were analyzed by immunohistochemistry (IHC) using antibodies to S100 protein, SOX10, PLAG1, HMGA2, p63/p40, cytokeratins, EMA, LEF1, and/or β-catenin. Next-generation sequencing (NGS), fluorescence in situ hybridization (FISH) for the rearrangement of PLAG1, and methylation analysis were performed. The BCA S100 protein stromal cell-rich group consisted of 7 males and 10 females with an average age of 62 years. Their tumors showed typical S100 protein-positive stroma, which was also positive for SOX10 in all cases. The stromal and/or epithelial components showed expression of LEF1 and β-catenin in 17 and 15 cases, respectively. HMGA2 IHC showed nuclear expression in one case while PLAG1 was negative in all cases. In 11 cases, one or more mutations were present, including CTNNB1 mutation (n = 11). The first control cohort of BCA without S100 protein-positive stroma consisted of 1 male and 6 females with an average age of 50 years. This group showed LEF1 and nuclear β-catenin expression in 1 and 2 cases, respectively. The second control group of PA (including 4 spindle-shaped cellular and 2 oncocytic PAs) was devoid of CTNNB1 mutations. Two cases presented with gene fusions, including MEG3::PLAG1 and ACTA2::PLAG1, and an additional two cases showed PLAG1 break. It has been proposed earlier that BCA is related to PA based on a shared biphasic nature and a divergent spectrum of growth patterns. Our findings suggest that BCAs with abundant S100 protein-positive stroma are tumors that morphologically display tricellular differentiation into inner (luminal) ductal epithelial cells, outer (abluminal) basaloid myoepithelial cells, and spindle-shaped stromal S100-positive cells (stromal abluminal). According to our investigation, BCAs with S100 protein-positive stroma represent a distinctive triphasic subset of BCA, which is substantially different from PA, both in immunoprofile and molecular underpinnings. Thu, 01 Jan 2026 00:00:00 GMT https://hdl.handle.net/20.500.14178/3530 2026-01-01T00:00:00Z https://hdl.handle.net/20.500.14178/3529 Sclerosing mucoepidermoid carcinoma of salivary glands Othman, Bacem Abdullah Essam Othman Khalele; Bradová, Martina; Simpson, Roderick H W; Laco, Jan; Agaimy, Abbas; Rito, Miguel; Ihrler, Stephan; Steiner, Petr; Grossmann, Petr; Hájková, Veronika; de Rezende, Gisele; Goma, Montse; Koljenovic, Senada; Fonseca, Isabel; Michal, Michal; Leivo, Ilmo; Skálová, Alena Sclerosing mucoepidermoid carcinoma (SMEC) of the salivary glands is a rare variant of low-grade mucoepidermoid carcinoma with scanty cellular atypia characterized by marked fibrosis/sclerosis and a rich inflammatory infiltrate. Herein, we report 25 unpublished cases of SMEC, two of them with prominent eosinophilia (2/25; 8%) and three with abundant IgG4-positive plasma cells (3/25; 12%). In our series of salivary SMEC, molecular analysis using fluorescence in situ hybridization (FISH) and/or next-generation sequencing (NGS) provided evidence of MAML2 gene rearrangement in 18 cases of the 21 analyzable cases tested (86%), while this gene locus was intact in 3 cases (14%). This study focuses on the diagnostic criteria of salivary SMEC given its challenge of abundant collagenous stroma, minimal residual neoplastic areas, and inconspicuous mucous cells. Follow-up data of our cases indicate that salivary SMECs have favorable outcomes. Molecular analysis for MAML2 gene rearrangement suggests that SMECs of salivary glands represent a rare variant of conventional low-grade MECs of salivary glands. In contrast, SMECs of the thyroid gland are genetically distinct from salivary-type thyroid MECs. Wed, 01 Jan 2025 00:00:00 GMT https://hdl.handle.net/20.500.14178/3529 2025-01-01T00:00:00Z