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Povzetek: Background In patients who require venom immunotherapy (VIT), there is a need to identify underlying mast cell (MC) disorders since these may affect the risk and severity of future sting reactions and the long-term effectiveness of VIT. Methods 1319 individuals with Hymenoptera venom allergy (HVA) who needed VIT from referral centers in Slovenia, Austria, Croatia, and Poland underwent examination for KIT p.D816V in peripheral blood leukocytes (PBL) using a highly sensitive PCR test and tryptase genotyping by digital droplet PCR. We also included 183 control individuals with large local reactions (LLRs) to Hymenoptera stings and with asymptomatic sensitization to Hymenoptera venoms. Results 285 of 1319 individuals recommended for VIT (21.6%) were positive for KIT p.D816V in PBL, preferably those who present with severe reaction (33.9% [n = 207 of 610] with Ring-Messmer grade 3–4 vs. 11% [n = 78 of 709] with Grade 1–2; p < .0001), whereas only 1.3% (n = 2 of 152) of controls with LLR and none with asymptomatic sensitization (n = 31) had KIT p.D816V. KIT p.D816V allelic burden was higher in those with severe reaction (median 0.018% [n = 207] in Grade 3–4 vs. 0.001% [n = 78] in Grade 1–2; p < .0001), and the majority had normal baseline serum tryptase levels (69% [n = 196 of 285]). All KIT p.D816V-positive individuals (n = 41) who underwent bone marrow (BM) biopsy were found to have underlying clonal diseases, principally BM mastocytosis. HαT was also associated with severe HVA and symptoms (p < .01), and remarkably, 31.0% (n = 31 of 100) were found to have concomitant KIT p.D816V. Concomitant HαT and KIT p.D816V showed an additive effect, and having both was associated with the highest risk for severe HVA, even higher than having either HαT or KIT p.D816V alone (OR = 3.8; p < .01). Conclusions By employing prospective universal tryptase genotyping and examination for KIT p.D816V in PBL in large HVA populations, we have demonstrated a high burden of clonal MC disorders and HαT in patients who require VIT.
Ključne besede: anaphylaxis, hereditary α-tryptasemia, hypersensitivity, immunotherapy, mast cell, mastocytosis, venom
Objavljeno v DiRROS: 17.06.2024; Ogledov: 341; Prenosov: 237
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Povzetek: High-grade B-cell lymphomas with MYC and BCL2 and/or BCL6 rearrangements are known for their aggressive clinical course and so are the ones with MYC and BCL2 protein overexpression. The optimal therapy for these lymphomas remains to be elucidated. A retrospective analysis of all diffuse large B-cell lymphomas and high-grade B-cell lymphomas with MYC and BCL2 and/or BCL6 rearrangements diagnosed between 2017 and 2021 at the Institute of Oncology Ljubljana, Slovenia, has been performed. Only patients with double-expressor lymphoma (DEL), double-hit lymphoma (DHL), or triple-hit lymphoma (THL) were included. Demographic and clinical parameters were assessed, as well as progression-free survival (PFS) and overall survival (OS). In total, 161 cases out of 309 (161/309; 52,1%) were classified as DEL. Sixteen patients had DHL, MYC/BCL2 rearrangement was observed in eleven patients, and MYC/BCL6 rearrangement was observed in five patients. Five patients were diagnosed with THL. Out of 154 patients (according to inclusion/exclusion criteria) included in further evaluation, one-hundred and thirty-five patients had double-expressor lymphoma (DEL), sixteen patients had DHL, and three patients had THL. In total, 169 patients were treated with R-CHOP, 10 with R-CHOP and intermediate-dose methotrexate, 19 with R-DA-EPOCH, and 16 with other regimens. The median follow-up was 22 months. The 5-year OS for the whole DEL group was 57.1% (95% CI 45.9–68.3%) and the 5-year PFS was 76.5% (95% CI 72.6–80.4%). The log-rank test disclosed no differences in survival between treatment groups (p = 0.712) while the high-risk international prognostic index (IPI) carried a significantly higher risk of death (HR 7.68, 95% CI 2.32–25.49, p = 0.001). The 5-year OS for DHL patients was 32.4% (95% CI 16.6–48.2%) while all three TH patients were deceased or lost to follow-up. Our analyses of real-life data disclose that the R-CHOP protocol with CNS prophylaxis is a successful and curative treatment for a substantial proportion of DEL patients.
Ključne besede: lymphoma, double-expressor lymphoma, oncology
Objavljeno v DiRROS: 18.04.2024; Ogledov: 385; Prenosov: 200
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Povzetek: Background. The immune response to Helicobacter pylori importantly determines the outcome of infection as well as the success of eradication therapy. We demonstrate the role of a cysteine protease cathepsin X in the immune response to H. pylori infection. Materials and methods. We analysed how the inhibition of cathepsin X influenced the immune response in experiments when THP-1 cells or dendritic cells isolated from patients were stimulated with 48 strains of H. pylori isolated from gastric biopsy samples of patients which had problems with the eradication of bacteria. Results. The experiments, performed with the help of a flow cytometer, showed that the expression of Toll-like receptors (TLRs), especially TLR-4 molecules, on the membranes of THP-1 cells or dendritic cells was higher when we stimulated cells with H. pylori together with inhibitor of cathepsin X 2F12 compared to THP-1 cells or dendritic cells stimulated with H. pylori only, and also in comparison with negative control samples. We also demonstrated that when we inhibited the action of cathepsin X in THP-1 cells, the concentrations of pro-inflammatory cytokines were lower than when THP-1 cell were stimulated with H. pylori only. Conclusions. We demonstrated that inhibition of cathepsin X influences the internalization of TLR-2 and TLR-4. TLR-2 and TLR-4 redistribution to intra-cytoplasmic compartments is hampered if cathepsin X is blocked. The beginning of a successful immune response against H. pylori in the case of cathepsin X inhibition is delayed.
Ključne besede: cathepsin X, macrophage, dendritic cells
Objavljeno v DiRROS: 22.03.2024; Ogledov: 345; Prenosov: 195
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Povzetek: Szeged, Padmakar-Ivan (PI), and Mostar indices are some of the most investigated distance-based Szeged-like topological indices. On the other hand, the polynomials related to these topological indices were also introduced, for example the Szeged polynomial, the edge- Szeged polynomial, the PI polynomial, the Mostar polynomial, etc. In this paper, we introduce a concept of the general Szeged-like polynomial for a connected strength-weighted graph. It turns out that this concept includes all the above mentioned polynomials and also infinitely many other graph polynomials. As the main result of the paper, we prove a cut method which enables us to efficiently calculate a Szeged-like polynomial by using the corresponding polynomials of strength-weighted quotient graphs obtained by a partition of the edge set that is coarser than ▫$\Theta^*$▫-partition. To the best of our knowledge, this represents the first implementation of the famous cut method to graph polynomials. Finally, we show how the deduced cut method can be applied to calculate some Szeged-like polynomials and corresponding topological indices of para-polyphenyl chains and carbon nanocones.
Ključne besede: graph theory, carbon nanocone, topological indices
Objavljeno v DiRROS: 20.03.2024; Ogledov: 380; Prenosov: 121
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Povzetek: We present novel results related to isomorphic resonance graphs of 2-connected outerplane bipartite graphs. As the main result, we provide a structure characterization for 2-connected outerplane bipartite graphs with isomorphic resonance graphs. Three additional characterizations are expressed in terms of resonance digraphs, via local structures of inner duals, as well as using distributive lattices on the set of order ideals of posets defined on inner faces of 2-connected outerplane bipartite graphs.
Ključne besede: distributive lattice, inner dual, isomorphic resonance graphs, order ideal, 2-connected outerplane bipartite graph
Objavljeno v DiRROS: 13.03.2024; Ogledov: 428; Prenosov: 216
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