Hypothesis: Certain variables that are routinely measured during the diagnostic evaluation of dogs with chronic enteropathies will be predictive for outcome and a new clinical disease activity index incorporating these variables can be applied to predict outcome of disease.Animals: Seventy dogs were entered into a sequential treatment trial with elimination diet (FR, food-responsive group) followed by immunosuppressive treatment with steroids if no response was seen with the dietary trial alone (ST, steroidtreatment group). A 3rd group consisted of dogs with panhypoproteinemia and ascites (PLE, protein-losing enteropathy) that were treated with immunosuppressive doses of steroids.Methods: Three years of follow-up information was available for all dogs. Clinicopathologic variables were tested for their ability to predict negative outcome, defined as euthanasia due to refractoriness to treatment. Different scoring systems including different combinations of these variables were evaluated using receiver operating characteristic (ROC) curves.Results: Thirteen of 70 (18%) dogs were euthanized because of intractable disease. Univariate analysis identified a high clinical activity index, high endoscopic score in the duodenum, hypocobalaminemia (,200 ng/L) and hypoalbuminemia (,20 g/L) as risk factors for negative outcome.Conclusions and clinical importance: Based on the factors identified by logistic regression and ROC curve analysis, a new clinical scoring index (CCECAI) was defined that predicts negative outcome in dogs suffering from chronic enteropathies.
Hypothesis: Certain variables that are routinely measured during the diagnostic evaluation of dogs with chronic enteropathies will be predictive for outcome and a new clinical disease activity index incorporating these variables can be applied to predict outcome of disease. Animals: Seventy dogs were entered into a sequential treatment trial with elimination diet (FR, food-responsive group) followed by immunosuppressive treatment with steroids if no response was seen with the dietary trial alone (ST, steroid-treatment group). A 3rd group consisted of dogs with panhypoproteinemia and ascites (PLE, protein-losing enteropathy) that were treated with immunosuppressive doses of steroids. Methods: Three years of follow-up information was available for all dogs. Clinicopathologic variables were tested for their ability to predict negative outcome, defined as euthanasia due to refractoriness to treatment. Different scoring systems including different combinations of these variables were evaluated using receiver operating characteristic (ROC) curves. Results: Thirteen of 70 (18%) dogs were euthanized because of intractable disease. Univariate analysis identified a high clinical activity index, high endoscopic score in the duodenum, hypocobalaminemia (,200 ng/L) and hypoalbuminemia (,20 g/L) as risk factors for negative outcome. Conclusions and clinical importance: Based on the factors identified by logistic regression and ROC curve analysis, a new clinical scoring index (CCECAI) was defined that predicts negative outcome in dogs suffering from chronic enteropathies.
An association between luminal commensal bacteria and inflammatory bowel disease (IBD) has been suggested in humans, but studies investigating the intestinal microbial communities of dogs with IBD have not been published. The aim of this study was to characterize differences of the small intestinal microbial communities between dogs with IBD and healthy control dogs. Duodenal brush cytology samples were endoscopically collected from 10 dogs with IBD and nine healthy control dogs. DNA was extracted and 16S rRNA gene was amplified using universal bacterial primers. Constructed 16S rRNA gene clone libraries were compared between groups. From a total of 1240 selected clones, 156 unique 16S rRNA gene sequences were identified, belonging to six phyla: Firmicutes (53.4%), Proteobacteria (28.4%), Bacteroidetes (7.0%), Spirochaetes (5.2%), Fusobacteria (3.4%), Actinobacteria (1.1%), and Incertae sedis (1.5%). Species richness was significantly lower in the IBD group (P=0.038). Principal component analysis indicated that the small intestinal microbial communities of IBD and control dogs are composed of distinct microbial communities. The most profound difference involved enrichment of the IBD dogs with members of the Enterobacteriaceae family. However, differences involving members of other families, such as Clostridiaceae, Bacteroidetes and Spirochaetes, were also identified. In conclusion, canine IBD is associated with altered duodenal microbial communities compared with healthy controls.
Background: Dogs with protein-losing enteropathy (PLE) have previously been reported to present with thromboembolism; however, the prevalence and pathogenesis of hypercoagulability in dogs with PLE have not been investigated so far.Hypothesis: Dogs with PLE are hypercoagulable compared with healthy control dogs. Animals: Fifteen dogs with PLE. Thirty healthy dogs served as controls (HC). Methods: A prospective study was performed including 15 dogs with PLE. All dogs were scored using the canine chronic enteropathy activity index (CCECAI). Thromboelastography (TEG) and other measures of coagulation were evaluated. Recalcified, unactivated TEG was performed and reaction time (R), kinetic time (K), alpha angle (a), and maximum amplitude (M A ) values were recorded. Nine dogs were reassessed after initiation of immunosuppressive treatment.Results: All dogs with PLE in the study were hypercoagulable with decreased R ( [33.5-49]) (all P o .001). Median antithrombin (AT) concentration was borderline low in PLE dogs; however, mean serum albumin concentration was severely decreased (mean 1.67 g/dL AE 5.1, reference range 2.8-3.5 g/dL). Despite a significant improvement in serum albumin and CCECAI, all 9 dogs with PLE were hypercoagulable at re-examination.Conclusions and Clinical Importance: The hypercoagulable state in dogs with PLE cannot be solely attributed to loss of AT. Despite good clinical response to treatment, dogs remained hypercoagulable and could therefore be predisposed to thromboembolic complications.
When investigating dogs with chronic upper gastrointestinal signs, the collection of concurrent duodenal and ileal endoscopic biopsies is recommended.
Background Large animal models, such as the dog, are increasingly being used for studying diseases including gastrointestinal (GI) disorders. Dogs share similar environmental, genomic, anatomical, and intestinal physiologic features with humans. To bridge the gap between commonly used animal models, such as rodents, and humans, and expand the translational potential of the dog model, we developed a three-dimensional (3D) canine GI organoid (enteroid and colonoid) system. Organoids have recently gained interest in translational research as this model system better recapitulates the physiological and molecular features of the tissue environment in comparison with two-dimensional cultures. Results Organoids were derived from tissue of more than 40 healthy dogs and dogs with GI conditions, including inflammatory bowel disease (IBD) and intestinal carcinomas. Adult intestinal stem cells (ISC) were isolated from whole jejunal tissue as well as endoscopically obtained duodenal, ileal, and colonic biopsy samples using an optimized culture protocol. Intestinal organoids were comprehensively characterized using histology, immunohistochemistry, RNA in situ hybridization, and transmission electron microscopy, to determine the extent to which they recapitulated the in vivo tissue characteristics. Physiological relevance of the enteroid system was defined using functional assays such as optical metabolic imaging (OMI), the cystic fibrosis transmembrane conductance regulator (CFTR) function assay, and Exosome-Like Vesicles (EV) uptake assay, as a basis for wider applications of this technology in basic, preclinical and translational GI research. We have furthermore created a collection of cryopreserved organoids to facilitate future research. Conclusions We establish the canine GI organoid systems as a model to study naturally occurring intestinal diseases in dogs and humans, and that can be used for toxicology studies, for analysis of host-pathogen interactions, and for other translational applications. Electronic supplementary material The online version of this article (10.1186/s12915-019-0652-6) contains supplementary material, which is available to authorized users.
BackgroundGastrointestinal stromal tumors (GISTs) are uncommon intestinal neoplasms in the dog. Literature regarding adjunctive therapy for GISTs in dogs is sparse. High‐risk GISTs in humans respond to tyrosine kinase inhibition in the adjuvant setting.ObjectivesTo review cases of toceranib phosphate use in dogs with GISTs and provide initial assessment of possible biological activity. A secondary aim was to evaluate patient and tumor characteristics for possible prognostic value.AnimalsTwenty‐seven dogs with confirmed GISTs based on histopathology and immunohistochemistry treated with toceranib.MethodsRetrospective study in which cases of toceranib use in dogs with GIST were solicited using the American College of Veterinary Internal Medicine Oncology and Small Animal Internal Medicine listservs.ResultsFive of 7 dogs with gross disease experienced clinical benefit (71%; 3 complete responses, 1 partial response, 1 stable disease). These included 2 dogs with durable responses after toceranib discontinuation. Median progression‐free interval (PFI) in dogs with gross disease was 110 weeks (range, 36‐155 weeks). Median PFI in dogs with microscopic disease was 67 weeks (range, 9‐257 weeks). Metastasis at diagnosis (P = 0.04) and high mitotic index (P < 0.001) were associated with shorter PFI in toceranib‐treated dogs.Conclusions and Clinical ImportanceBiological activity of toceranib is evident in dogs with gross disease. Metastasis of GIST at diagnosis, as well as high tumor mitotic index, was associated with shorter PFI in toceranib‐treated dogs. Larger studies are needed to define postsurgical risk and refine the use of toceranib in dogs with gross and microscopic GIST.
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