RESUMEN
BACKGROUND: Biliary dilation suggests obstruction and prompts further work up. Our experience with endoscopic ultrasound and endoscopic retrograde cholangiopancreatography in the symptomatic post-bariatric surgery population revealed many patients with radiographically dilated bile ducts, but endoscopically normal studies. It is unclear if this finding is phenomenological or an effect of surgery. Additionally, it is unknown whether the type of bariatric surgery alters biliary pathophysiology. Thus, we studied whether a change occurs in biliary diameter following Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG). METHODS: A single-center retrospective study assessing biliary diameter before and after RYGB or SG based on radiographic imaging. All adult patients undergoing RYGB or SG from January 2010 to December 2013 who had imaging studies before and > 3 months after surgery were included. Those with known obstructive etiologies and those without post-operative imaging were excluded. Common bile duct (CBD) diameter was re-read by a radiologist at the same location in the CBD for pre- and post-operative imaging. Baseline clinical factors and cholecystectomy status were collected. RESULTS: 269 patients met inclusion criteria (193 RYGB;76 SG). Between the groups, there were no significant differences in pre-operative characteristics. Average time from surgery to repeat imaging was 24.1 months. After adjusting for pre-operative factors, subjects who underwent an RYGB had an increase in CBD diameter of 1.4 mm (95% CI 0.096, 0.18), which was greater than the change following SG 0.5 mm(95% CI - 0.007, 0.11). The magnitude of this change did not depend on prior cholecystectomy in the RYGB cohort. Within the SG group, for patients without a prior cholecystectomy, there was a significant increase in post-operative CBD diameter of 0.8 mm(95% CI 0.02, 0.14). CONCLUSION: Bariatric surgery results in CBD dilation, with changes more pronounced after RYGB. Biliary dilation occurs irrespective of cholecystectomy status. Further work is necessary to determine the cause and clinical implications of this phenomenon.
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Enfermedades del Conducto Colédoco/etiología , Conducto Colédoco/patología , Gastrectomía/efectos adversos , Derivación Gástrica/efectos adversos , Complicaciones Posoperatorias , Adulto , Colangiopancreatografia Retrógrada Endoscópica , Conducto Colédoco/diagnóstico por imagen , Enfermedades del Conducto Colédoco/diagnóstico por imagen , Enfermedades del Conducto Colédoco/patología , Dilatación Patológica , Femenino , Gastrectomía/métodos , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/diagnóstico por imagen , Complicaciones Posoperatorias/patología , Periodo Posoperatorio , Estudios Retrospectivos , Tomografía Computarizada por Rayos X , UltrasonografíaRESUMEN
OBJECTIVE: Inflammation in response to oxidized lipoproteins is thought to play a key role in acute coronary syndromes (ACS), but the pattern of immune activation has not been fully characterized. We sought to perform detailed phenotypic and functional analysis of CD8 T lymphocytes from patients presenting with ACS to determine activation patterns and potential immunologic correlates of ACS. APPROACH AND RESULTS: We used polychromatic flow cytometry to analyze the cytokine production profiles of naïve, effector, and memory CD8 T cells in patients with ACS compared with control subjects with stable coronary artery disease. ACS was associated with an altered distribution of circulating CD8(+) T-cell maturation subsets with reduced proportions of naïve cells and expansion of effector memory cells. ACS was also accompanied by impaired interleukin-2 production by phenotypically naïve CD8 T cells. These results were validated in a second replication cohort. Naïve CD8 cells from patients with ACS also had increased expression of programmed cell death-1, which correlated with interleukin-2 hypoproduction. In vitro, stimulation of CD8 T cells with oxidized low-density lipoprotein was sufficient to cause programmed cell death-1 upregulation and diminished interleukin-2 production by naïve CD8 T cells. CONCLUSIONS: In this exploratory analysis, naïve CD8(+) T cells from patients with ACS show phenotypic and functional characteristics of immune exhaustion: impaired interleukin-2 production and programmed cell death-1 upregulation. Exposure to oxidized low-density lipoprotein recapitulates these features in vitro. These data provide evidence that oxidized low-density lipoprotein could play a role in immune exhaustion, and this immunophenotype may be a biomarker for ACS.
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Síndrome Coronario Agudo/inmunología , Linfocitos T CD8-positivos/inmunología , Activación de Linfocitos , Síndrome Coronario Agudo/sangre , Síndrome Coronario Agudo/diagnóstico , Anciano , Biomarcadores/sangre , Linfocitos T CD8-positivos/efectos de los fármacos , Linfocitos T CD8-positivos/metabolismo , Estudios de Casos y Controles , Células Cultivadas , Femenino , Citometría de Flujo , Humanos , Memoria Inmunológica , Inmunofenotipificación/métodos , Interleucina-2/sangre , Lipoproteínas LDL/farmacología , Activación de Linfocitos/efectos de los fármacos , Masculino , Persona de Mediana Edad , Fenotipo , Receptor de Muerte Celular Programada 1/metabolismoRESUMEN
INTRODUCTION: The lymphocyte antigen 6 (Ly-6) supergene family encodes proteins of 12-14 kda in molecular mass that are either secreted or anchored to the plasma membrane through a glycosyl-phosphatidylinisotol (GPI) lipid anchor at the carboxy-terminus. The lipidated GPI-anchor allows localization of Ly-6 proteins to the 10-100 nm cholesterol-rich nano-domains on the membrane, also known as lipid rafts. Ly-6A/Sca-1, a member of Ly-6 gene family is known to transduce signals despite the absence of transmembrane and cytoplasmic domains. It is hypothesized that the localization of Ly-6A/Sca-1 with in lipid rafts allows this protein to transduce signals to the cell interior. METHODS AND RESULTS: In this study, we found that cross-linking mouse Ly-6A/Sca-1 protein with a monoclonal antibody results in functionally distinct responses that occur simultaneously. Ly-6A/Sca-1 triggered a cell stimulatory response as gauged by cytokine production with a concurrent inhibitory response as indicated by growth inhibition and apoptosis. While production of interleukin 2 (IL-2) cytokine by CD4+ T cell line in response to cross-linking Ly-6A/Sca-1 was dependent on the integrity of lipid rafts, the observed cell death occurred independently of it. Growth inhibited CD4+ T cells showed up-regulated expression of the inhibitory cell cycle protein p27kip but not of p53. In addition, Ly-6A/Sca-1 induced translocation of cytochrome C to the cytoplasm along with activated caspase 3 and caspase 9, thereby suggesting an intrinsic apoptotic cell death mechanism. CONCLUSIONS: We conclude that opposing responses with differential dependence on the integrity of lipid rafts are triggered by engaging Ly-6A/Sca-1 protein on the membrane of transformed CD4+ T cells.