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- Hollo, G, et al.
(författare)
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Referral for first glaucoma surgery in Europe, the ReF-GS study
- 2019
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Ingår i: European journal of ophthalmology. - : SAGE Publications. - 1724-6016 .- 1120-6721. ; 29:4, s. 406-416
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Tidskriftsartikel (refereegranskat)abstract
- To analyze the appropriateness of referrals for incisional glaucoma-surgery in Europe. Methods: Referrals for the first open-angle glaucoma surgery between January and October 2017 were analyzed in 18 countries: 8 “old” European Union, 7 “new” European Union and 3 non-European Union European countries. Results: Most eyes had primary open-angle or exfoliative glaucoma. The average mean deviation was −13.8 dB with split fixation in 44.3%. No structural progression analysis was made before the referrals. The most common medications were the combination of a prostaglandin analog, timolol and a carbonic anhydrase inhibitor (30.0%), and all other combinations comprising ⩾ 3 molecules (33.8%). Laser trabeculoplasty was reported in only 18.4%. Of the 294 referrals, 41.5% were appropriate and timely, 35.0% appropriate but later than optimal, and 17.6% appropriate but too late (minimal vision maintained). The treatment period was significantly longer (median: 7 years) in the “old” European Union countries than in the other groups (3 and 2 years, respectively). No between-group differences were seen in intraocular pressure and mean deviation, but the non-European Union group referred the patients at significantly lower cup/disk ratio and eye drop usage than the other groups. Split fixation was significantly more common in the “old” (60.6%) than the “new” European Union countries (38.7%), and in both EU country-groups than in the non-European Union countries (13.6%). Conclusions: Of 294 European open-angle glaucoma referrals for first glaucoma-surgery, 41.5% were completely satisfactory. The damage was typically advanced, and the care varied considerably among the countries. This suggests that further efforts are necessary to improve glaucoma care in Europe.
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| 2. |
- Flood, Peter, et al.
(författare)
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DNA sensor-associated type I interferon signaling is increased in ulcerative colitis and induces JAK-dependent inflammatory cell death in colonic organoids
- 2022
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Ingår i: American Journal of Physiology - Gastrointestinal and Liver Physiology. - : American Physiological Society. - 0193-1857 .- 1522-1547. ; 323:5, s. G439-G460
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Tidskriftsartikel (refereegranskat)abstract
- DNA sensor pathways can initiate inflammasome, cell death, and type I interferon (IFN) signaling in immune-mediated inflammatory diseases (IMIDs), including type I interferonopathies. We investigated the involvement of these pathways in the pathogenesis of ulcerative colitis (UC) by analyzing the expression of DNA sensor, inflammasome, and type I IFN biomarker genes in colonic mucosal biopsy tissue from control (n = 31), inactive UC (n = 31), active UC (n = 33), and a UC single-cell RNA-Seq dataset. The effects of type I IFN (IFN-β), IFN-γ, and TNF-α on gene expression, cytokine production, and cell death were investigated in human colonic organoids. In organoids treated with cytokines alone, or in combination with NLR family pyrin domain-containing 3 (NLRP3), caspase, or JAK inhibitors, cell death was measured, and supernatants were assayed for IL-1β/IL-18/CXCL10. The expression of DNA sensor pathway genes-PYHIN family members [absent in melanoma 2 (AIM2), IFI16, myeloid cell nuclear differentiation antigen (MNDA), and pyrin and HIN domain family member 1 (PYHIN1)- as well as Z-DNA-binding protein 1 (ZBP1), cyclic GMP-AMP synthase (cGAS), and DDX41 was increased in active UC and expressed in a cell type-restricted pattern. Inflammasome genes (CASP1, IL1B, and IL18), type I IFN inducers [stimulator of interferon response cGAMP interactor 1 (STING), TBK1, and IRF3), IFNB1, and type I IFN biomarker genes (OAS2, IFIT2, and MX2) were also increased in active UC. Cotreatment of organoids with IFN-β or IFN-γ in combination with TNFα increased expression of IFI16, ZBP1, CASP1, cGAS, and STING induced cell death and IL-1β/IL-18 secretion. This inflammatory cell death was blocked by the JAK inhibitor tofacitinib but not by inflammasome or caspase inhibitors. Increased type I IFN activity may drive elevated expression of DNA sensor genes and JAK-dependent but inflammasome-independent inflammatory cell death of colonic epithelial cells in UC.NEW & NOTEWORTHY This study found that patients with active UC have significantly increased colonic gene expression of cytosolic DNA sensor, inflammasome, STING, and type I IFN signaling pathways. The type I IFN, IFN-β, in combination with TNF-α induced JAK-dependent but NLRP3 and inflammasome-independent inflammatory cell death of colonic organoids. This novel inflammatory cell death phenotype is relevant to UC immunopathology and may partially explain the efficacy of the JAKinibs tofacitinib and upadacitinib in patients with UC.
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