https://hdl.handle.net/20.500.14178/902 Wed, 29 Apr 2026 11:12:56 GMT 2026-04-29T11:12:56Z 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/20.500.14178/3720 Does motherhood increase the risk of developing subsequent malignant neoplasms after childhood cancer treatment? Blagodárná, Sarah; Hošek, Petr; Jelínková, Kristýna; Korbelová, Lucie; Eckschlager, Tomáš; Lischke, Robert; Šrámková, Lucie; Kruseová, Jarmila BACKGROUND: Most young women who have survived childhood cancer express a desire to have children. Many of them are concerned about the potential adverse impact of pregnancy on their health, which has been affected by prior cancer treatment. The aim of this study was to determine whether motherhood increases the risk of developing subsequent malignant neoplasms. METHODS: The study cohort consisted of 942 female childhood cancer survivors, median age at first cancer diagnosis 10.84 years (IQR 4.29-14.92), who had been treated at the Department of Pediatric Hematology and Oncology, Motol University Hospital, Prague, between 1965 and 2018. In this group, 363 women gave birth to 559 children. RESULTS: Seventy-three female childhood cancer survivors developed 80 subsequent malignant neoplasms. Of these, 40 subsequent malignant neoplasms occurred in women who had children. The median time from the end of primary cancer treatment to first subsequent malignant neoplasm development was 19.93 years (IQR 14.55-26.56). A comprehensive analysis revealed no difference in the risk of subsequent malignant neoplasms between mothers and "non-mothers". Only older age of the cancer survivors in follow-up and previous radiotherapy (p = 0.0133) were significant risk factors for subsequent malignant neoplasm development. CONCLUSIONS: This study revealed that motherhood does not increase the risk of subsequent malignant neoplasms. We confirmed a statistically significant increased risk of subsequent malignant neoplasms only for previous treatment modality, the length of follow-up and the age of the female childhood cancer survivors. These results are important for improving the quality of life of young cured women who are worried about a planned pregnancy. PLAIN LANGUAGE SUMMARY: This study evaluated the long-term cancer risk among women treated for cancer during childhood, with particular focus on those who later gave birth. Among 942 participants, 363 had post-treatment pregnancies. Results indicate that childbearing does not increase the risk of subsequent malignant neoplasms in this population. Instead, elevated risk for subsequent malignant neoplasms was associated with older age at follow-up and prior exposure to radiotherapy. These findings provide evidence that pregnancy is safe for female childhood cancer survivors and support informed reproductive decision-making. Thu, 01 Jan 2026 00:00:00 GMT https://hdl.handle.net/20.500.14178/3720 2026-01-01T00:00:00Z https://hdl.handle.net/20.500.14178/3702 The Prognostic Role of Baseline and Early Dynamics of Peripheral Blood Cell Ratios in Metastatic Renal Cell Carcinoma Patients Treated With Nivolumab Fiala, Ondřej; Tkadlecová, Michaela; Kopecký, Jindřich; Hošek, Petr; Studentova, Hana; Vočka, Michal; Matějů, Martin; Lohynská, Radka; Šiková, Dominika; Stránský, Petr; Kučera, Radek; Zemankova, Anezka; Spisarova, Martina; Priester, Peter; Kouril, Jan; Büchler, Tomáš; Grmelova, Lucie; Melichar, Bohuslav; Poprach, Alexandr BACKGROUND/AIM: Immune checkpoint inhibitors (ICI), including nivolumab, have become the cornerstone of systemic treatment in metastatic renal cell carcinoma (mRCC). Blood-derived biomarkers including neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and lymphocyte-to-monocyte ratio (LMR) have emerged as important indicators of systemic inflammatory and immune status. The aim of this study was to evaluate the prognostic and predictive value of NLR, PLR, and LMR at baseline and their early dynamics during nivolumab monotherapy in mRCC patients. PATIENTS AND METHODS: The associations of baseline NLR, PLR, LMR and their changes (Δ) after one month of nivolumab therapy with patient outcomes including progression-free survival (PFS), overall survival (OS) and objective response rate (ORR) were retrospectively analyzed. RESULTS: In total, 310 patients were included. Baseline NLR >=4 (PFS: HR=2.136, p<0.001; OS: HR=2.442, p<0.001), PLR >=310 (PFS: HR=2.383, p<0.001; HR=3.604, p<0.001), and LMR <1.5 (PFS: HR=1.802, p=0.002; OS: HR=2.273, p<0.001) were independent factors for inferior PFS and OS. Regarding early changes, ΔNLR >=2 (PFS: HR=3.019, p<0.001; OS: HR=3.095, p<0.001) and ΔPLR >=20 (PFS: HR=1.436, p=0.024; OS: HR=1.719, p=0.006) were independent factors for inferior PFS and OS, while ΔLMR <0 was independent factor for inferior PFS (HR=1.458, p=0.030). Lower ORR was associated with baseline NLR >=4 (p=0.020), ΔNLR >=2 (p=0.010), and ΔPLR >=20 (p=0.019). CONCLUSION: The results of the present study suggest a prognostic role for baseline NLR, PLR and LMR. In addition, an early change in NLR and PLR is associated with patient outcome and represents a candidate surrogate biomarker for monitoring the immunotherapy response. Thu, 01 Jan 2026 00:00:00 GMT https://hdl.handle.net/20.500.14178/3702 2026-01-01T00:00:00Z https://hdl.handle.net/20.500.14178/3448 Comparative Evaluation of Single- and Multi-Delay Arterial Spin Labeling MRI in Preterm Neonates Prysiazhniuk, Yeva; Alexander, Sasha; Armindo, Rui Duarte; Tong, Elizabeth; Yeom, Kristen W; Otáhal, Jakub; Kynčl, Martin; Moseley, Michael; Petr, Jan; Zhao, Moss Y; Steinberg, Gary K INTRODUCTION: Preterm neonates are vulnerable to brain injuries from disrupted cerebral blood flow (CBF). Achieving high-quality MRI remains a major challenge in neonatal neuroimaging. Arterial Spin Labeling (ASL) MRI offers non-invasive, quantitative CBF assessment, but is understudied in neonates. This study evaluates the feasibility of ASL in non-sedated preterm neonates. METHODS: Preterm neonates (n=48, 25 male, post-natal age 9.74+-4.96 weeks, gestational age 28.74+-2.6 weeks) underwent T1-weighted (T1w), T2-weighted (T2w), and single- and multi-delay (3 and 7 delays) ASL scans. Image quality was rated as "good", "acceptable", or "unusable" and compared across modalities. Cortical CBF and arterial transit time (ATT) were quantified and analyzed using paired t-tests and Cohen's d. Associations with sex and age were assessed using correlation and regression models. RESULTS: Multi-delay ASL demonstrated the highest rate of acceptable images (<10% "unusable"), T2w scans outperformed T1w in quality (4.2% vs. 25% "unusable", p<0.01). Single-delay ASL yielded significantly lower cortical CBF compared to multi-delay ASL (p<0.001, d>=1.12), with sex differences observed: single-delay CBF was lower in females (p=0.035, d=0.72), and ATT was longer in males (p=0.045, d=0.60). CBF positively correlated with postmenstrual and postnatal age, especially for three-delay ASL. CONCLUSIONS: Multi-delay ASL is the favorable technique for neonatal neuroimaging based on image quality and hemodynamic measurements. Sex- and age-related hemodynamic variations underscore the importance of techniques distinguishing ATT and CBF components for improved neonatal perfusion neuroimaging. Despite frequent motion artifacts, ASL quality was comparable to structural scans. These findings support broader clinical adoption of multi-delay ASL in neonatal imaging protocols. Wed, 01 Jan 2025 00:00:00 GMT https://hdl.handle.net/20.500.14178/3448 2025-01-01T00:00:00Z