Browsing by Author "Varela, Nelson M."

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    Comparison between optimized bismuth quadruple therapy and standard clarithromycin-based triple therapy for first-line Helicobacter pylori eradication: a double-blind randomized controlled trial
    (2026) Medel Jara, Patricio Andrés; Latorre Selvat, Gonzalo Ignacio; Fuentes López, Eduardo; Pizarro Rojas, Margarita Alicia; Viviani García, Paola; Chahuán Abde, Javier Nicolás; Maquilón Tamayo, Sara Andrea; Corsi Sotelo, Óscar Felipe; Reyes Placencia, Diego Armando; Espino Espino, Alberto Antonio; Vargas Dominguez, José Ignacio; Wichmann Pérez, Ignacio Alberto; Harris D., Paul R.; Serrano Berrios, Carolina Lourdes; Buruato García, Isabella María; Sandoval, Christopher; Varela, Nelson M.; Cerpa, Leslie; Quiñones, Luis; Megraud Francis; Huang, Robert J.; Shah, Shailja C.; Riquelme Pérez, Arnoldo
    BackgroundHelicobacter pylori eradication reduces the risk of peptic ulcer disease and gastric cancer. In Chile, the effectiveness of standard triple therapy has dropped below 80%. We compared optimized bismuth quadruple therapy: esomeprazole 40 mg three times a day, amoxicillin 1 gr three times a day, metronidazole 500 mg three times a day, and bismuth subsalicylate 369 mg three times a day for 14 days, and standard triple therapy omeprazole 20 mg twice a day, amoxicillin 1 gr twice a day, and clarithromycin 500 mg twice a day for 14 days in a Chilean population.MethodsRandomized double-blind clinical trial. 127 treatment-naïve individuals with confirmed active H. pylori were recruited. The primary outcome was successful H. pylori eradication, at least 4 weeks post-treatment. We assessed H. pylori resistance to clarithromycin and participants’ CYP2C19 genotype/phenotype. We compared eradication success between the groups using intention-to-treat and per-protocol analyses. The trial adhered to CONSORT guidelines. NTC-Number: NCT05664685 (trial completed).Findings127 participants were recruited and randomized (64 standard triple therapy, 63 optimized bismuth quadruple therapy). Men were 44% (56/127), and the mean age was 48 (standard deviation: 14.2) in the sample. Baseline characteristics between the two groups were similar. In intention-to-treat analysis, optimized bismuth quadruple therapy had a significantly higher eradication rate versus standard triple therapy: 95% (60/63) [95% CI 86%–99%] vs. 81% (52/64) [70%–89%], p = 0.033. Adverse events were comparable: optimized bismuth quadruple therapy 67% (42/63) [54%–77%] vs. standard triple therapy 66% (42/64) [53%–76%], p = 1.00. There was no difference in baseline clarithromycin resistance or CYP2C19 polymorphisms.InterpretationOptimized bismuth quadruple therapy eradication is higher than standard triple therapy in treatment-naïve individuals with active H. pylori, without difference in adverse events or adherence. Optimized bismuth quadruple therapy is a reliable and safe empiric eradication therapy, especially in areas with high clarithromycin resistance.
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    Novel Risk Associations between microRNA Polymorphisms and Gastric Cancer in a Chilean Population
    (2022) Landeros, Natalia; Corvalán R., Alejandro; Musleh, Maher; Quinones, Luis A.; Varela, Nelson M.; Gonzalez Hormazabal, Patricio
    Gastric cancer (GC) is the fifth leading cause of cancer deaths in the world, with variations across geographical regions and ethnicities. Emerging evidence indicates that miRNA expression is dysregulated in GC and its polymorphisms may contribute to these variations, which has yet to be explored in Latin American populations. In a case-control study of 310 GC patients and 311 healthy donors from Chile, we assessed the association of 279 polymorphisms in 242 miRNA genes. Two novel polymorphisms were found to be associated with GC: rs4822739:C>G (miR-548j) and rs701213:T>C (miR-4427). Additionally, rs1553867776:T>TCCCCA (miR-4274) and rs12416605:C>T (miR-938) were associated with intestinal-type GC, and rs4822739:C>G (miR-548j) and rs1439619:T>G (miR-3175) with TNM I-II stage. The polymorphisms rs6149511:T> TGAAGGGCTCCA (miR-6891), rs404337:G>A (miR-8084), and rs1439619:T>G (miR-3175) were identified among H.pylori-infected GC patients and rs7500280:T>C (miR-4719) and rs1439619:T>G (miR-3175) were found among H. pylori cagPAI+ infected GC cases. Prediction analysis suggests that seven polymorphisms could alter the secondary structure of the miRNA, and the other one is located in the seed region of miR-938. Targets of miRNAs are enriched in GC pathways, suggesting a possible biological effect. In this study, we identified seven novel associations and replicated one previously described in Caucasian population. These findings contribute to the understanding of miRNA genetic polymorphisms in the GC pathogenesis.