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Opis: The lack of reliable biomarkers in response to anti-TNFα biologicals hinders personalized therapy for Crohn’s disease (CD) patients. The motivation behind our study is to shift the paradigm of anti-TNFα biomarker discovery toward specific immune cell sub-populations using single-cell RNA sequencing and an innovative approach designed to uncover PBMCs gene expression signals, which may be masked due to the treatment or ongoing inflammation; Methods: The singlecell RNA sequencing was performed on PBMC samples from CD patients either naïve to biological therapy, in remission while on adalimumab, or while on ustekinumab but previously non-responsive to adalimumab. Sieves for stringent downstream gene selection consisted of gene ontology and independent cohort genomic profiling. Replication and meta-analyses were performed using publicly available raw RNA sequencing files of sorted immune cells and an association analysis summary. Machine learning, Mendelian randomization, and oligogenic risk score methods were deployed to validate DEGs highly relevant to anti-TNFα therapy response; Results: This study found PLCB1 in CD4+ T cells and CRTAM in double-negative T cells, which met the stringent statistical thresholds throughout the analyses. An additional assessment proved causal inference of both genes in response to anti-TNFα therapy; Conclusions: This study, jointly with an innovative design, uncovered novel candidate genes in the anti-TNFα response landscape of CD, potentially obscured by therapy or inflammation.
Ključne besede: inflammatory bowel diseases, Crohn’s disease, tumor necrosis factor alpha, adalimumab, single-cell gene expression analysis
Objavljeno v DKUM: 10.12.2024; Ogledov: 0; Prenosov: 8
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Opis: Izhodišča. Paliativno zdravljenje bolnikov z neozdravljivim rakom je velik problem. Ko gre za bolnika z razširjenim rakom danke, je cilj zdravljenja preprečiti zaporo črevesa, krvavitev iz tumorja in bolečino in tako izboljšati kakovost preostalega življenja. Namen prikazane študije je bil oceniti vlogo laserja v paliativnem zdravljenju raka danke. Bolniki in metode. Od 1998 do 2005 smo z laserjem zdravili 44 bolnikov z rakom danke, ki ga ni bilo mogoče operativno zdraviti. Indikacija za zdravljenje je bila grozeča zapora, krvavitev in/ali bolečina. Rezultati. Rekanalizacijo in hemostazo smo dosegli pri 37 bolnikih, kar je v 84 %. Neuspešni smo bili pri 7 bolnikih, kar je 16 %. Opazovali smo 4 resne, vendar ne smrtne zaplete, perforacije danke z okolnim vnetjem. Vsi zapleti so bili zdravljeni konzervativno. Zaključki. Endoskopsko lasersko zdravljenje bolniki dobro prenašajo, metoda je učinkovita in varna. Je odlična metoda za paliativno zdravljenje raka danke, ki ga ni mogoče operativno zdraviti.
Objavljeno v DKUM: 21.12.2015; Ogledov: 1651; Prenosov: 42
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