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Systemic administration of mesenchymal stem cells (MSCs) has been shown to be safe and efficacious in humans with Crohn's disease. The aim of this study was to evaluate the safety of an intravenous (IV) infusion of adipose tissue-derived mesenchymal stem cells (ASCs) and to assess macroscopic and histological effects in the digestive tract of dogs with inflammatory bowel disease (IBD). Eleven dogs with confirmed IBD received a single ASC infusion (2 × 10(6) cells/kg bodyweight). Full digestive endoscopic evaluation was performed pre-treatment and between 90 and 120 days post-treatment with mucosal changes being assessed using a fit-for-purpose endoscopic scale. Endoscopic biopsies from each digestive section were evaluated histologically according to the World Small Animal Veterinary Association (WSAVA) Gastrointestinal Standardization Group criteria. The pre- and post-treatment canine IBD endoscopic index (CIBDEI) and histological score (HS) were calculated and compared using the Wilcoxon test. Remission was defined as a reduction of >75% of the CIBDEI and HS compared with pre-treatment. No acute reactions to ASC infusion or side effects were reported in any dog. Significant differences between pre- and post-treatment were found in both the CIBDEI (P = 0.004) and HS (P = 0.004). Endoscopic remission occurred in 4/11 dogs with the remaining dogs showing decreased CIBDEI (44.8% to 73.3%). Histological remission was not achieved in any dog, with an average reduction of the pre-treatment HS of 27.2%. In conclusion, a single IV infusion of allogeneic ASCs improved gastrointestinal lesions as assessed macroscopically and slightly reduced gastrointestinal inflammation as evaluated by histopathology in dogs with IBD.

Mesenchymal stem cells have proven to be a promising alternative to conventional steroids to treat canine inflammatory bowel disease (IBD). However, their administration requires a washout period of immunosuppressive drugs that can lead to an exacerbation of the symptoms. Therefore, the feasibility and effects of the combined application of stem cells and prednisone in IBD-dogs without adequate response to corticosteroids was evaluated for the first time in this study over a long- term follow up. Two groups of dogs with IBD, one without treatment and another with prednisone treatment, received a single infusion of stem cells. The clinical indices, albumin and cobalamin were determined prior to the infusion and after one, three, six and 12 months. In both groups, all parameters significantly improved at each time point. In parallel, the steroid dosage was gradually reduced until it was suppressed in all patients a year after the cell therapy. Therefore, cell therapy can significantly and safely improve the disease condition in dogs with IBD receiving or not receiving prednisone. Furthermore, the steroid dosage can be significantly reduced or cancelled after the stem cell infusion. Their beneficial effects are stable over time and are long lasting.

SummaryGastroesophageal reflux can be a catastrophic illness in small animals during anesthesia since its complications can cause serious pathologies, such as esophagitis, esophageal stenosis and aspiration pneumonia. With an incidence from 12 to 78.5% in anesthetized dogs, gastroesophageal reflux is normally silent during anesthesia and will be notices only if regurgitation occurs and stomach acid is present in the nasal or oral cavities. In humans, gastroesophageal reflux disease (GERD) is a well-defined pathology where the lower esophageal sphincter has a sustained weakness. However, in dogs, gastroesophageal reflux disease as such is not well established, if at all; it has only been described as gastroesophagic reflux, occurring principally in anesthetized animals. There are several factors influencing the presentation of reflux in anesthetized dogs, which may be inherent to the patient (e.g. age, sex, breed, weight, or body condition), medications used prior to and during anesthesia, type of surgery or position of the animal during surgery. The objective of this review is to discuss a series of conditions that could predispose dogs to gastroesophageal reflux during anesthesia and to assist in the prevention and diagnosis of this condition.

This article reports on the face, content, and construct validity of a new realistic composite simulator (Simuldog) used to provide training in canine gastrointestinal flexible endoscopy. The basic endoscopic procedures performed on the simulator were esophagogastroduodenoscopy (EGD), gastric biopsy (GB), and gastric foreign body removal (FBR). Construct validity was assessed by comparing the performance of novices (final-year veterinary students and recent graduates without endoscopic experience, n=30) versus experienced subjects (doctors in veterinary medicine who had performed more than 50 clinical upper gastrointestinal endoscopic procedures as a surgeon, n=15). Tasks were scored based on completion time, and specific rating scales were developed to assess performance. Internal consistency and inter-rater agreement were assessed. Face and content validity were determined using a 5-point Likert-type scale questionnaire. The novices needed considerably more time than the experts to perform EGD, GB, and FBR, and their performance scores were significantly lower (p<.010). Inter-rater agreement and the internal validity of the rating scales were good. Face validity was excellent, and both groups agreed that the endoscopy scenarios were very realistic. The experts highly valued the usefulness of Simuldog for veterinary training and as a tool for assessing endoscopic skills. Simuldog is the first validated model specifically developed to be used as a training tool for endoscopy techniques in small animals.

Adipose-derived mesenchymal stem cells (Ad-MSCs) exhibit anti-inflammatory and immunomodulatory activities. The neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and systemic immune-inflammation index (SII) have been reported as novel biomarkers of the inflammatory state; however, they have never been examined in dogs with chronic inflammatory enteropathy (CIE) treated with Ad-MSCs. This study aimed to compare the clinical evolution and the changes in the NLR, PLR, and SII in dogs with CIE before and after cell therapy. Sixteen dogs with CIE were administered a single intravenous dose of Ad-MSCs. The canine chronic enteropathy clinical activity index (CCECAI), NLR, PLR, and SII were assessed before treatment (T0) and at 2 (T2) and 9 (T9) months post-treatment and compared over time and with the reference values obtained from a group of healthy dogs. NLR, PLR, and SII were significantly increased at T0 compared to the reference values, decreasing significantly over time. At T9, the NLR and SII did not differ from the reference values, but PLR remained above the reference values. A correlation was observed between CCECAI and the three markers. These findings show that the clinical improvement of dogs with CIE treated with Ad-MSCs is accompanied by a normalization of the inflammatory status.

This study aims firstly to assess the most adequate surgical approach for the creation of an ureteropelvic juntion obstruction (UPJO) animal model, and secondly to validate this model for laparoscopic pyeloplasty training among urologists.Thirty six Large White pigs (28.29±5.48 Kg) were used. The left ureteropelvic junction was occluded by means of an endoclip. According to the surgical approach for model creation, pigs were randomized into: laparoscopic conventional surgery (LAP) or single port surgery (LSP). Each group was further divided into transperitoneal (+T) or retroperitoneal (+R) approach. Time needed for access, surgical field preparation, wound closure, and total surgical times were registered. Social behavior, tenderness to the touch and wound inflammation were evaluated in the early postoperative period. After ten days, all animals underwent an Anderson-Hynes pyeloplasty carried out by 9 urologists, who subsequently assessed the model by means of a subjective validation questionnaire.Total operative time was significantly greater in LSP+R (p=0.001). Tenderness to the touch was significantly increased in both retroperitoneal approaches, (p=0.0001). Surgeons rated the UPJO porcine model for training on laparoscopic pyeloplasty with high or very high scores, all above 4 on a 1-5 point Likert scale.Our UPJO animal model is useful for laparoscopic pyeloplasty training. The model created by retroperitoneal single port approach presented the best score in the subjective evaluation, whereas, as a whole, transabdominal laparoscopic approach was preferred.

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