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Masia, Ricard

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Masia

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Ricard

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Masia, Ricard

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2017 - 20182

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Author's Publications: search.filters.isAuthorOfPublication.d6d696ff-beb3-4eaa-840d-3f7dd5508094

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    Prolonged cenicriviroc therapy reduces hepatic fibrosis despite steatohepatitis in a diet‐induced mouse model of nonalcoholic steatohepatitis
    (John Wiley and Sons Inc., 2018) Kruger, Annie; Fuchs, Bryan; Masia, Ricard; Holmes, Jacinta; Salloum, Shadi; Sojoodi, Mozhdeh; Ferreira, Diego S.; Rutledge, Stephanie; Caravan, Peter; Alatrakchi, Nadia; Vig, Pam; Lefebvre, Eric; Chung, Raymond
    Nonalcoholic steatohepatitis (NASH) is a progressive liver disease projected to become the leading cause of cirrhosis and liver transplantation in the next decade. Cenicriviroc (CVC), a dual chemokine receptor 2 and 5 antagonist, prevents macrophage trafficking and is under clinical investigation for the treatment of human NASH fibrosis. We assessed the efficacy and durability of short and prolonged CVC therapy in a diet‐induced mouse model of NASH, the choline deficient, L‐amino acid‐defined, high‐fat diet (CDAHFD) model. C57BL/6 mice received 4 or 14 weeks of standard chow or the CDAHFD. CVC (10 mg/kg/day and 30 mg/kg/day for 4 weeks and 20 mg/kg/day and 30 mg/kg/day for 14 weeks) was initiated simultaneously with the CDAHFD. At 4 and 14 weeks, livers were harvested for histology and flow cytometric analyses of intrahepatic immune cells. High‐dose CVC (30 mg/kg/day) therapy in CDAHFD mice for 4 or 14 weeks inhibited intrahepatic accumulation of Ly6Chigh bone marrow‐derived macrophages. Prolonged CVC therapy (14 weeks) yielded no significant differences in the total intrahepatic macrophage populations among treatment groups but increased the frequency of intrahepatic anti‐inflammatory macrophages in the high‐dose CVC group. Despite ongoing steatohepatitis, there was significantly less fibrosis in CDAHFD mice receiving high‐dose CVC for 14 weeks based on histologic and molecular markers, mirroring observations in human NASH CVC trials. CVC also directly inhibited the profibrotic gene signature of transforming growth factor‐β‐stimulated primary mouse hepatic stellate cells in vitro. Conclusion: CVC is a novel therapeutic agent that is associated with reduced fibrosis despite ongoing steatohepatitis. Its ability to alter intrahepatic macrophage populations and inhibit profibrogenic genes in hepatic stellate cells in NASH livers may contribute to its observed antifibrotic effect. (Hepatology Communications 2018;2:529‐545)
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    Creation and pilot testing of cases for case-based learning: A pedagogical approach for pathology cancer diagnosis
    (AOSIS, 2017) Sayed, Shahin; Lester, Susan; Wilson, Michael; Berney, Daniel; Masia, Ricard; Moloo, Zahir; Stall, Jennifer; Eslan, Alexia; Ayers, Stephanie; Mutuku, Angela; Guarner, Jeannette
    Background: Case-based learning (CBL) is an established pedagogical active learning method used in various disciplines and defined based on the field of study and type of case. The utility of CBL for teaching specific aspects of cancer diagnosis to practising pathologists has not been previously studied in sub-Saharan Africa. Objectives: We aimed to pilot test standardised cancer cases on a group of practising pathologists in sub-Saharan Africa to evaluate case content, clarity of questions and delivery of content. Methods: Expert faculty created cases for the four most commonly diagnosed cancers. The format included mini-cases and bullet cases which were all open-ended. The questions dealt with interpretation of clinical information, gross specimen examination, morphologic characteristics of tumours, ancillary testing, reporting and appropriate communication to clinicians. Results: Cases on breast, cervical, prostate and colorectal cancers were tested on seven practising pathologists. Each case took an average of 45–90 min to complete. Questions that were particularly challenging to testers were on: Specimens they should have been but for some reason were not exposed to in routine practice.Ancillary testing and appropriate tumour staging. New knowledge gained included tumour grading and assessment of radial margins. Revisions to cases were made based on testers’ feedback, which included rewording of questions to reduce ambiguity and adding of tables to clarify concepts. Conclusion: Cases were created for CBL in Kenya, but these are applicable elsewhere in Africa and beyond to teach cancer diagnosis. The pilot testing of cases prepared faculty for the actual CBL course and feedback provided by the testers assisted in improving the questions and impact on day-to-day practice.