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Abstract: zhodišča: Totalno neoadjuvantno zdravljenje (angl. total neoadjuvant therapy, TNT) je uveljavljen standard pri bolnikih z lokalno napredovalim rakom danke (LNRD; angl. locally advanced rectal cancer, LARC) z magnetnoresonančno (angl. magnetic resonance imaging, MRI) opredeljenimi dejavniki visokega tveganja. Kljub vse večji uporabi TNT pa optimalno zaporedje posameznih terapevtskih komponent ter dolgoročni izidi neoperativnega pristopa watch and wait (W&W) ostajajo nepopolno opredeljeni. Prav tako vpliv izbrane radioterapevtske tehnike na uspešnost zdravljenja, lokalno kontrolo bolezni in dol-goročne izide v vsakodnevni klinični praksi še ni jasno razmejen.Bolniki in metode: V primerjalno analizo sta bili vključeni dve zaporedni kohorti bolnikov z LNRD in vsaj enim MRI oprede-ljenim dejavnikom visokega tveganja, zdravljenih na Onkolo-škem inštitutu Ljubljana po institucionalnem »sendvič« TNT protokolu. Študijska populacija je obsegala bolnike zdravljenih s 3D konformno tehniko obsevanja (angl. three dimensional conformal radiotherapy, 3D CRT kohorta), in zdravljenih z intenzitetno moduliranim in volumetrično moduliranim ločnim obsevanjem s simultanim integriranim dodatkom doze (angl. intensity modulated radiotherapy / volumetric modulated arc therapy with simultaneous integrated boost, IMRT/VMAT SIB kohorta). Primarni opazovani izid je bil skupni popolni odgovor, opredeljen kot patohistološko popolni odgovor (angl. pathological complete response, pCR) in klinični popolni odgovor (angl. clinical complete response, cCR) ob vključitvi v skrbno spremljanje po strategiji W&W. Sekundarni izidi so bili pCR, večji patološki odgovor (MPR; angl. major pathological response, MPR), delež R0 resekcij, znižanje stadija, lokalna ponovitev, preživetje brez bolezni (PBB; angl. disease free survival, DFS) in celokupno preživetje (CP; angl. overall survival, OS). Za primarni in ključne sekundarne izide smo izvedli neprilagojene formalne primerjave deležev ter eksploratorne prilagojene analize s Firthovo logistič-no regresijo, za CP do 36 mesecev smo izvedli še uteženi Coxov model.Rezultati: Skupno je bilo vključenih 240 bolnikov, 35 v 3D CRT kohorti in 205 v IMRT/VMAT SIB kohorti. Skupni popolni odgovor je bil v 3D CRT kohorti dosežen pri 14,3% bolnikov, v IMRT/VMAT SIB kohorti pa pri 29,5% bolnikov, pCR pri 9,4% bolnikov v 3D CRT kohorti in pri 19,3% v IMRT/VMAT SIB kohorti, MPR pa pri 30,8% v 3D CRT kohorti oziroma 37,6% bolnikov v IMRT/VMAT SIB kohorti. R0 resekcijo smo beležili pri vseh operiranih bolnikih v 3D CRT kohorti ter pri 94,5% operiranih bolnikov v IMRT/VMAT SIB kohorti. V Firthovem modelu je bil za IMRT/VMAT-SIB nakazan trend k višjemu ONKOLOGIJA | ISSN 1408-1741 | IZVIRNI ZNANSTVENI ČLANEK | LETO XXX | ŠT. 1 | JUNIJ 2026 | 45 skupnemu popolnemu odgovoru (OR 2,39; 95 % CI 0,95 – 7,08; p = 0,064), medtem ko pri pCR statistično značilnega učinka nismo potrdili (OR 2,20; 95 % CI 0,73–8,75; p = 0,171).Zaključki: Obe radioterapevtski tehniki omogočata izvedljivo in onkološko učinkovito izvajanje institucionalnega »sendvič« TNT protokola pri bolnikih z MRI opredeljenimi dejavniki visokega tveganja. V naši enoinstitucionalni izkušnji so bili v IMRT/VMAT-SIB kohorti doseženi numerično ugodnejši lokalni odzivni izidi kot v 3D-CRT kohorti, vendar formalne primerjave teh razlik statistično niso potrdile. Zaradi retrospek-tivne zasnove, deloma prekrivajočih se zgodovinskih kohort in omejenega števila dogodkov dokončnih sklepov o superiornosti ene tehnike ni mogoče podati.
Keywords: lokalno napredovali rak danke, totalno neoadjuvantno zdravljenje, radiokemoterapija
Published in DiRROS: 30.07.2026; Views: 212; Downloads: 90
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Abstract: Determining the genetic contribution of susceptibility to severe SARS-CoV-2 infection outcomes is important for public health measures and individualized treatment. Through intense research on this topic, several hundred genes have been implicated as possibly contributing to the severe infection phenotype(s); however, the findings are complex and appear to be population- dependent. We aimed to determine the contribution of human rare genetic variants associated with a severe outcome of SARS-CoV-2 infections and their burden in the Slovenian population. A panel of 517 genes associated with severe SARS-CoV-2 infection were obtained by combining an extensive review of the literature, target genes identified by the COVID-19 Host Genetic Initiative, and the curated Research COVID-19 associated genes from PanelApp, England Genomics. Whole genome sequencing was performed using PCR-free WGS on DNA from 60 patients hospitalized due to severe COVID-19 disease, and the identified rare genomic variants were analyzed and classified according to the ACMG criteria. Background prevalence in the general Slovenian population was determined by comparison with sequencing data from 8025 individuals included in the Slovenian genomic database (SGDB). Results show that several rare pathogenic/likely pathogenic genomic variants in genes CFTR, MASP2, MEFV, TNFRSF13B, and RNASEL likely contribute to the severe infection outcomes in our patient cohort. These results represent an insight into the Slovenian genomic diversity associated with a severe COVID-19 outcome.
Keywords: severe COVID-19, severe outcome of SARS-CoV-2 infection, whole-genome sequencing, genetic susceptibility, rare variants, human rare genomic variants
Published in DiRROS: 11.06.2026; Views: 358; Downloads: 262
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Abstract: Introduction Diamine oxidase (DAO) degrades histamine, the key mediator in anaphylaxis, yet its relationship with clonal mast cell disorder (CMD) in the context of anaphylaxis is unclear. We evaluated whether DAO during anaphylaxis differs by CMD status. Methods We enrolled 35 emergency-department patients with acute anaphylaxis to drugs (7 patients), food (2 patients), or Hymenoptera venom (26 patients). Tryptase, DAO, and histamine degradation were measured during anaphylaxis and convalescence. CMD was defined by detecting KIT p.D816V in peripheral blood leukocytes using highly sensitive qPCR. Post-mortem DAO and tryptase were also compared in two fatal Hymenoptera venom-triggered anaphylaxis (HVA) cases with CMD versus 13 non-anaphylaxis controls. Results KIT p.D816V was detected in 6 (17%); all had severe HVA and normal basal tryptase. During anaphylaxis, DAO increased markedly in CMD (median 1142%), but only modestly in KIT p.D816V-negative patients (median 20%; p < 0.0001), independent of trigger or severity. Acute DAO was ~5-fold higher in CMD (median 101 vs. 18 U/mL), while convalescent DAO was similar (both 14 U/mL). Despite markedly elevated DAO, we observed impaired histamine degradation in acute anaphylaxis plasma. Receiver-operating-characteristic analyses showed strong discrimination for CMD using acute DAO (AUC 0.92; cut-off 53 U/mL; sensitivity 83%; specificity 97%) and percentage increase from convalescence (AUC 0.97; cut-off 223%; sensitivity 83%; specificity 100%). Post-mortem DAO lacked specificity, whereas post-mortem tryptase supported the diagnosis of fatal anaphylaxis and CMD. Conclusion DAO concentrations rise markedly during anaphylaxis in CMD and may help identify individuals at the highest risk. Further studies should refine the diagnostic utility and elucidate the mechanisms by which DAO may amplify anaphylaxis in CMD.
Keywords: anaphylaxis, clonal mast cell disorder, diamine oxidase, KIT p.D816V, tryptase
Published in DiRROS: 06.05.2026; Views: 258; Downloads: 318
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Abstract: Background: The recommended booster third dose of vaccination against COVID-19 in cancer patients seems reasonable to protect them against a severe disease course. A prospective study was designed to assess the immunogenicity, efficacy, and safety of COVID-19 vaccination in this cohort. Methods: Patients with solid malignancies on active treatment were followed up after the primary course and booster third dose of vaccination to assess their anti-SARS-CoV-2 S1 IgG levels, efficacy in the case of SARS-CoV-2 infection, and safety. Results: Out of 125 patients receiving the primary course of vaccination, 66 patients received a booster third dose of mRNA vaccine, with a 20-fold increase in median anti-SARS-CoV-2 S1 IgG levels compared to Ab levels six months post-primary course of vaccination (p < 0.0001). After the booster third dose, anti-SARS-CoV-2 S1 IgG levels were comparable to healthy controls (p = 0.113). There was a decline in Ab levels 3 (p = 0.0003) and 6 months (p < 0.0001) post-third booster dose. No patients had either a severe disease course or a lethal outcome in the case of SARS-CoV-2 infection after the third booster dose. Conclusion: The third booster vaccination dose against COVID-19 in solid cancer patients triggers substantial immunogenicity and is safe and effective for preventing a severe COVID-19 disease course.
Keywords: solid cancer, COVID-19 vaccination, booster third dose
Published in DiRROS: 25.02.2026; Views: 657; Downloads: 338
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Abstract: Diagnosing and prognosing immune-mediated airway diseases, like hypersensitivity pneumonitis (HP) and sarcoidosis, is complicated due to their overlapping symptoms and the lack of definitive biomarkers. Hence, we wanted to compare bronchoalveolar lavage (BAL) cytokine and chemokine profiles from 92 patients with different immune-mediated and inflammatory airway diseases, namely, HP, sarcoidosis, non-allergic asthma, amiodarone lung, and EGPA. We also compared pulmonary function parameters, BAL’s cellularity, and lymphocyte immunophenotypes. We found significant differences across all measured lung functions (VC, VC%, FEV1, FEV1%, and Tiff%) and in the number of macrophages, lymphocytes, neutrophils, and eosinophils. Furthermore, we showed significant differences in CD4, CD8, and CD4/8 across all included ILDs and OLDs; however, no significant differences were found in CD3, CD19, NK, or NKT. We identified nine biomarkers (IL-1β, IL-6, IL-8, IL-13, VEGF, angiogenin, C4a, RANTES, and MCP-1) that significantly differ in the BAL of patients with HP and sarcoidosis and showed that RANTES and IL-6 are associated with fibrotic outcome. We have demonstrated that interstitial and obstructive lung diseases differ in cytokine and cellular lung imprint, which may, in the future, enable the determination of the disease subtype and thus the identification of targets for the treatment of individuals or subgroups within diseases.
Keywords: hypersensitivity pneumonitis, sarcoidosis, non-allergic asthma, amiodarone lung, EGPA, cytokines, bronchoalveolar lavage, chemokines, complement anaphylatoxins, angiogenesis-related factors
Published in DiRROS: 05.08.2025; Views: 1023; Downloads: 597
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