https://hdl.handle.net/20.500.14178/905 2026-09-07T23:55:26Z https://hdl.handle.net/20.500.14178/3895 Comparable outcomes of BTK inhibitors and fixed-duration venetoclax plus rituximab in second-line treatment of chronic lymphocytic leukaemia: a real-world analysis by the Czech CLL study group Mihályová, Jana; Panovská, Anna; Šimkovič, Martin; Smolej, Lukáš; Špaček, Martin; Shokralla, Tereza; Kubová, Zuzana; Zuchnická, Jana; Arpáš, Tomáš; Vodárek, Pavel; Turcsányi, Peter; Polcerová, Lenka; Chrápavá, Marika; Lysák, Daniel; Brejcha, Martin; Móciková, Heidi; Doubek, Michael In relapsed/refractory (RR) chronic lymphocytic leukaemia (CLL), Bruton tyrosine kinase inhibitors (BTKi) are administered as monotherapy until disease progression. In contrast, venetoclax, a B-cell lymphoma 2 (BCL-2) protein inhibitor, is typically combined with rituximab (VenR) as a time-limited regimen. To date, neither randomized nor retrospective trials have directly compared these approaches in RR CLL, and only limited data are available comparing venetoclax plus obinutuzumab (VenObi) to BTKi in the first-line setting. We retrospectively analysed 352 patients receiving second-line therapy: 93 VenR and 259 BTKi (ibrutinib: n = 222; acalabrutinib: n = 37). Baseline characteristics were well balanced, except for a higher incidence of TP53 mutation and trisomy 12 in BTKi-treated patients. At a median follow-up of 13.8 months (VenR) and 22.1 months (BTKi), 12-month progression-free survival (PFS) and overall survival (OS) were comparable (PFS: 85.1% vs. 82.2%, p = 0.265; OS: 87.6% vs. 88.4%, p = 0.291). Estimated median PFS (45.4 vs. 37.9 months, p = 0.265) and OS (83.6 vs. 74.2 months, p = 0.291) also showed no significant differences between the VenR and BTKi cohorts. Treatment discontinuation due to adverse events before month 24 was more frequent with BTKi (22.5% with VenR vs. 34.3% with BTKi), primarily due to infections (10.6% vs. 28.6%) and disease progression (14.3% vs. 22.5%). These preliminary data suggest comparable outcomes and manageable toxicity profiles for both regimens. 2026-01-01T00:00:00Z https://hdl.handle.net/20.500.14178/3889 Pyrazinamide-derived 1,2,3-triazoles: Antimicrobial evaluation, selective antimycobacterial activity and mechanism of action insights Houngbedji, Priam-Amedeo; Bachtíková, Andrea; Boháčová, Jarmila; Tabarestani, Parinaz; Janďourek, Ondřej; Konečná, Klára; Ősterreicher, Jan; Paterová, Pavla; Novák, Martin; Bárta, Pavel; Záhorszká, Monika; Korduláková, Jana; Mori, Matteo; Meneghetti, Fiorella; Zitko, Jan A series of pyrazinamide-derived 1,2,3-triazoles featuring systematic chlorination of the pyrazine ring and diverse aryl substituents was synthesized and evaluated for antimycobacterial activity. Biological activity screening revealed broad-spectrum antimycobacterial activity and good selectivity toward mycobacteria over other pathogens, with 11 of the prepared compounds showing activity against Mycobacterium tuberculosis (Mtb) H37Ra and/or Mtb H37Rv (MIC <= 62.5 mu g/mL). Structure-activity relationship analysis showed that 5-Cl substitution on the pyrazine ring was associated with improved antimycobacterial activity, with the best MIC values observed for compound 7 against Mtb H37Ra (MIC =1.98 mu g/mL) and compound 37 against Mtb H37Rv (MIC =1.56 mu g/mL). The tested compounds retained activity against drug-resistant Mtb isolates and partially against naturally resistant Mycobacterium abscessus, while showing low in vitro cytotoxicity in the HepG2 cell line and favorable selectivity indices. During advanced cytotoxicity testing, both compounds 7 and 37 displayed substantially lower hemolytic activity than bedaquiline, indicating a favorable erythrocyte safety profile within the tested concentration ranges. In vivo toxicity testing on Galleria mellonella showed low acute toxicity for both compounds. Mechanistic studies on compounds 7, 27, 31, and 37 revealed reduced biosynthesis of fatty acids and derived lipids, a phenotype consistent with interference with the Fatty Acid Synthase I (FAS I) system. 2026-01-01T00:00:00Z https://hdl.handle.net/20.500.14178/3807 Recent developments in salivary gland pathology after the WHO 2024 classification: new developments in existing entities and evolving new entities Skálová, Alena; Laco, Jan; Thompson, Lester D R; Bradová, Martina; Vander Poorten, Vincent; Araújo, Anna Luíza Damaceno; Stenman, Göran; Leivo, Ilmo; Agaimy, Abbas; Ferlito, Alfio Parallel to and after publication of the WHO 2024 classification of head and neck tumors, several developments concerning known existing salivary gland tumor entities, but also proposing new evolving tumor entities have been published. This review article describes the most important new developments in salivary gland pathology published through 2022-2025, that were not included in the 5th edition of the WHO Classification of Head and Neck Tumours 2024. This review summarizes these recent developments in both the benign and the malignant tumor categories. Among the recently proposed entities are palisading adenocarcinoma, microcribriform adenocarcinoma, fenestrating adenocarcinoma and skin-analogue poroid carcinoma. Developments in existing carcinoma entities include recognition of mucoacinar carcinoma as subtype of mucoepidermoid carcinoma (MAML2-fused), mucoepidermoid carcinoma without squamous cell differentiation, metatypical adenoid cystic carcinoma, and adenoid cystic carcinoma with prominent tubular hypereosinophilia. In the benign tumor category, recognition of pleomorphic adenoma with canalicular/trabecular phenotype driven by HMGA2 fusions, triphasic basal cell adenoma with S100 protein-positive "stroma", characterized by CTNNB1 mutations, metaplastic Warthin tumor with KRAS mutations and delineation of thymus-like phenotype in non-sebaceous lymphadenoma with recurrent CYLD mutations are the main highlights. Emerging concepts include benign tumor with ductal and papillary morphology (sialadenopapillary ductal tumor). Finally, new grading schemes have been developed/ proposed for acinic cell carcinoma and secretory carcinoma. 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. 2026-01-01T00:00:00Z