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- European Registry on Helicobacter pylori management: Single‐capsule bismuth quadruple therapy is effective in real‐world clinical practicePublication . Nyssen, Olga P.; Perez‐Aisa, Angeles; Castro‐Fernandez, Manuel; Pellicano, Rinaldo; Huguet, Jose M.; Rodrigo, Luis; Ortuñ, Juan; o, null; Gomez‐Rodriguez, Blas J.; Marcos-Pinto, Ricardo; Areia, Miguel; Perona, Monica; Nuñez, Oscar; Romano, Marco; Gravina, Antonietta G.; Pozzati, Liliana; Fernandez‐Bermejo, Miguel; Venerito, Marino; Malfertheiner, Peter; Fernanadez‐Salazar, Luis; Gasbarrini, Antonio; Vaira, Dino; Puig, Ignasi; Megraud, Francis; O'Morain, Colm; Gisbert, Javier P.Background: There has been resurgence in the use of bismuth quadruple therapy (proton pump inhibitor, bismuth, tetracycline and metronidazole) for treating Helicobacter pylori infection thanks to a three-in-one single-capsule formulation. Objective: To evaluate the effectiveness and safety of the single-capsule bismuth quadruple therapy. Methods: Data were collected in a multicentre, prospective registry of the clinical practice of gastroenterologists on the management of H. pylori infection, where patients were registered at the Asociación Española de Gastroenterologia REDCap database on an electronic case report form until January 2020. Effectiveness by modified intention-to-treat and per-protocol as well as multivariable analysis were performed. Independent factors evaluated were: age, gender, indication, compliance, proton pump inhibitor dose and treatment line. Results: Finally, 2100 patients were prescribed single-capsule bismuth quadruple therapy following the technical sheet (i.e., three capsules every 6 h for 10 days). The majority of these patients were naive (64%), with an average age of 50 years, 64% women and 16% with peptic ulcer. An overall modified intention-to-treat effectiveness of 92% was achieved. Eradication was over 90% in first-line treatment (95% modified intention-to-treat, n = 1166), and this was maintained as a rescue therapy, both in second (89% modified intention-to-treat, n = 375) and subsequent lines of therapy (third to sixth line: 92% modified intention-to-treat, n = 236). Compliance was the factor most closely associated with treatment effectiveness. Adverse events were generally mild to moderate, and 3% of patients reported a severe adverse event, leading to discontinuation of treatment in 1.7% of cases. Conclusions: Single-capsule bismuth quadruple therapy achieved H. pylori eradication in approximately 90% of patients in real-world clinical practice, both as a first-line and rescue treatment, with good compliance and a favourable safety profile.
- Genetic Variants of the MGAT5 Gene Are Functionally Implicated in the Modulation of T Cells Glycosylation and Plasma IgG Glycome Composition in Ulcerative ColitisPublication . Pereira, Márcia S.; Durães, Cecília; Catarino, Telmo A.; Costa, José L.; Cleynen, Isabelle; Novokmet, Mislav; Krištić, Jasminka; Štambuk, Jerko; Conceição-Neto, Nádia; Machado, José C.; Marcos-Pinto, Ricardo; Magro, Fernando; Vermeire, Séverine; Lauc, Gordan; Lago, Paula; Pinho, Salomé S.Objectives: The impact of genetic variants (single nucleotide polymorphisms [SNPs]) in the clinical heterogeneity of ulcerative colitis (UC) remains unclear. We showed that patients with UC exhibit a deficiency in MGAT5 glycogene transcription in intestinal T cells associated with a hyperimmune response. Herein, we evaluated whether MGAT5 SNPs might functionally impact on T cells glycosylation and plasma IgG glycome in patients with UC, as well as in UC clinical outcomes. Methods: Three selected MGAT5 SNPs (rs3814022, rs4953911, and rs1257220), previously associated with severity of autoimmune disease or with plasma glycome composition in healthy individuals, were functionally evaluated in patients with UC through analysis of MGAT5 mRNA levels in colonic (n = 14) and circulating (n = 24) T cells and through profiling the plasma IgG Fc glycosylation (n = 152). MGAT5 SNPs were genotyped in 931 patients with UC from 2 European cohorts and further associated with patients' prognosis. Targeted next-generation sequencing for MGAT5 coding and regulatory regions was also performed. Results: MGAT5 SNPs were shown to be functionally associated with low transcription levels of MGAT5 in colonic and circulating T cells from patients with UC and with agalactosylation of IgGs, often associated with a proinflammatory phenotype. The SNPs rs3814022 and rs4953911 were further associated with the need of biologics. Next-generation sequencing data further revealed a combination of MGAT5 SNPs that stratify patients with UC according to their severity. Discussion: Our results revealed that MGAT5 SNPs have a phenotypic impact on T cells glycosylation and in plasma IgG glycome composition associated with UC pathogenesis. MGAT5 SNPs display a tendency in the association with a worse disease course in patients with UC.