Two-center experience comparing the use of the FLOT4 and CROSS schemes for patients with gastric, esophageal, and gastroesophageal junction adenocarcinoma

Introduction. Gastric (GAD), gastroesophageal junction (GEJA), and esophageal adenocarcinoma (EAD) share pathophysiological features. At localized stages, FLOT is used perioperatively for the treatment of GAD and GEJA and CROSS for EAD and some GEJA. Although both therapies have been compared with MAGIC, comparative randomized data on FLOT and CROSS are not yet available. Material andmethods. We retrospectively analyzed and compared 40 patients treated with FLOT and 16 patients treated with CROSS in terms of clinical features and neoadjuvant, surgical, adjuvant, and survival outcomes. Results. At the time of analysis, 65% of patients treated with FLOT4 and 56.3% with CROSS remained in complete remission. Those who progressed after FLOT4 did so mainly at the peritoneal level (25%) and after CROSS at the bone, lymph node, and peritoneal levels (12.5% respectively). Six patients (37.5%) died after CROSS (median OS of 17.5 months; 95% CI 2–41) and 10 (25%) after FLOT4 (median OS 16.5 months; 95% CI 11–22). For the living patients, the median numbers of months from diagnosis to the follow-up cutoff date were 47.5 (95% CI 11–67) and 27 (95% CI 14–44) for CROSS and FLOT4, respectively. There were no significant differences in median OS estimated by Kaplan Meier analysis [FLOT4: 50 ± 4.6 months (95% CI 40.9–59.2); CROSS: 51.2 ± 7 months (95% CI 37.4–65.0; p = 0.79)].  Conclusions. Although we obtained lower pCR rates; TNM downstaging after neoadjuvant therapy, R0 rates, tolerance, PFS, and OS were similar in both groups and comparable with trial results. The adjuvant compliance rate was high with FLOT4. CROSS allows sequencing with nivolumab in PD-L1+ tumors

Detection of intestinal microbiota components in the synovial microenviroment of peripheral spondyloarthritis and its association to immunopathogenic mechanisms

A role for intestinal microbes in arthritis is being considered. We analyzed intra-articular microbiota components and their association with immunopathogenic mechanisms of Spondyloarthritis (SpA). Synovial fluid (SF) of peripheral SpA patients were pooled (n=9): 6 psoriatic arthritis, 2 reactive arthritis, 1 undifferentiated SpA (Protocol approved CE002-2017). IL-17, IL-6, IL-23 and TGF-b levels were quantified in each SF sample by ELISA and compared with SF from osteoarthritis (OA). Moreover, SW982 cells (human synovial fibroblasts) were incubated with the SpA SF pool in absence or presence of polymyxin B (LPS inhibitor) and 48 h later the IL-6 levels in the supernatant were measured by ELISA. Furthermore, intestinal microbiota proteins were analyzed in the SpA SF pool through a Gel-LC bottom-up mass spectrometry-based proteomic study. Higher levels of IL-17, IL-6, IL-23 and TGF-b were detected in SpA compared with OA SF (p<0.001, p<0.01, p<0.001, and p<0.01, respectively). Since segmented filamentous bacteria (SFB) have a cardinal feature to induce Th17 cell differentiation in gut immunity, we searched for SFB peptides in the SF of SpA. We found 54 peptides of SFB with abundance estimated with an exponentially modified Protein Abundance Index (emPAI) from 0.01 to 0.28. In addition, LPS is present in synovial microenvironment of SpA since polymyxin B treatment significantly reduced IL-6 secretion by synovial fibroblasts stimulated with SpA SF (p<0.05). Therefore, we explored the synovial presence of peptides of microbiota Gram-negative bacteria, particularly genus Dialister because it was described as a potential intestinal microbial marker of disease activity in SpA. Accordingly, we found 55 peptides of genus Dialister (emPAI 0.02-0.33). Our findings show the presence of LPS and microbiota bacterial proteins in the synovial microenvironment of peripheral SpA and suggest their potential association with immunopathogenic mechanisms of this inflammatory arthropathy.Fil: Arias, Jose Luis. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; ArgentinaFil: Callegari, Eduardo Alberto. University Of South Dakota. Sanford School Of Medicine.; Estados UnidosFil: Paez, Daniela Veronica. University Of South Dakota. Sanford School Of Medicine.; Estados UnidosFil: Rodrigo, Blas. Centro Médico Medici; ArgentinaFil: Munarriz, Alicia. Centro Médico CENYR; ArgentinaFil: Pardo Hidalgo, Rodolfo. Centro de Rehabilitación Médica CER; ArgentinaFil: Tamashiro, Hector. Centro Médico Bolívar; ArgentinaFil: Di Genaro, Maria Silvia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; ArgentinaLXVI Reunión Anual de la Sociedad Argentina de Investigación Clínica; LXIX Reunión anual de la Sociedad Argentina de Inmunología; LIII Reunión Anual de la Asociación Argentina de Farmacología Experimental y XI Reunión Anual de la Asociación Argentina de NanomedicinasBuenos AiresArgentinaAsociación Argentina de de NanomedicinasSociedad Argentina de Investigación ClinicaSociedad Argentina de InmunologíaAsociación Argentina de Farmacología Experimenta

Association between IL-17 and IgA in the joints of patients with inflammatory arthropathies

Hyperactive secretion and pathogenic effects of interleukin (IL)-17 and IgA have been detected in different arthropathies. Recent evidence has revealed that TH17 cytokines regulate mucosal IgA secretion. However, it is unknown whether and how IL-17 mediates synovial IgA production. Here we aim to investigate the connection of synovial IL-17 with IgA production in the joint. In this study we included synovial fluids (SF) from patients with rheumatoid arthritis (RA; n = 66), spondyloarthritis (SpA; n = 18) and osteoarthritis (OA; n = 36). The levels of IL-17, IL-6, transforming growth factor (TGF)-β1, B-cell-activating factor of the TNF family (BAFF) and anti-lipopolyssacharide (LPS) immunoglobulin (Ig)A were investigated by enzyme-linked immunosorbent assay (ELISA). Total IgA was measured by radial immunodiffusion assay. Synovial fluid-derived mononuclear cells (SFMC) were stimulated with bacterial antigens or SF-conditioned media, and cytokines and IgA were analyzed in the supernatants.Fil: Eliçabe, Ricardo Javier. Universidad Nacional de San Luis; Argentina. Universidad Nacional de San Luis; ArgentinaFil: Silva, Juan Eduardo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidiciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Cs.fisico Matemáticas y Naturales. Instituto Multidiciplinario de Investigaciones Biológicas de San Luis; ArgentinaFil: Dave, Mabel Noemí. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidiciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Cs.fisico Matemáticas y Naturales. Instituto Multidiciplinario de Investigaciones Biológicas de San Luis; ArgentinaFil: Lacoste, Maria Gabriela. Universidad Nacional de San Luis; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidiciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Cs.fisico Matemáticas y Naturales. Instituto Multidiciplinario de Investigaciones Biológicas de San Luis; ArgentinaFil: Tamashiro, Héctor. Centro Privado de Salud Bolivar en San Luis; ArgentinaFil: Blas, Rodrigo. Medici Consultorios Externos en San Luis; ArgentinaFil: Munarriz, Alicia. Centro Médico Privado CENYR Center San Luis; ArgentinaFil: Rabinovich, Gabriel Adrián. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; ArgentinaFil: Di Genaro, Maria Silvia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidiciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Cs.fisico Matemáticas y Naturales. Instituto Multidiciplinario de Investigaciones Biológicas de San Luis; Argentina. Universidad Nacional de San Luis; Argentin