Oxidative stress in dogs with chronic inflammatory enteropathy treated with allogeneic mesenchymal stem cells.

The search for new biomarkers in patients with chronic inflammatory enteropathy (CIE) is ongoing in the human and veterinary medicine fields. Oxidative stress biomarkers (malondialdehyde [MDA], reduced glutathione [GSH], and albumin) have been studied in humans with chronic enteropathies, but among them, only albumin has been studied in dogs with CIE. Moreover, the effect of mesenchymal stem cell (MSCs) treatment with or without prednisone on these parameters has never been studied in dogs with CIE. These parameters were compared between healthy dogs (n = 12) and dogs with CIE, and before and 1, 3, 6, and 12 months after the treatment with MSCs alone (n = 9) or together with prednisone (n = 11). The relationship between the Canine Inflammatory Bowel Disease Activity Index (CIBDAI) and oxidative stress was evaluated. Albumin was the only parameter that significantly differed between dogs with CIE and healthy dogs (p = 0,037). Differences were observed only in albumin values after combined treatment with MSCs and prednisone. No differences were observed in MDA and GSH after treatment with MSCs with or without prednisone. Albumin could help stage canine CIE, as well as its prognosis, as has already been demonstrated, although it is essential to evaluate this parameter for its antioxidant capacity, and therefore it could be a good biomarker of oxidative stress in this pathology. However, the treatment with MSCs seems unable to modify any of the analyzed oxidative stress parameters.

Urinary cystatin C and N-acetyl-beta-D-glucosaminidase (NAG) as early biomarkers for renal disease in dogs with leishmaniosis.

Canine leishmaniasis (CanL) is a disease caused by Leishmania infantum that can vary from a subclinical infection to a severe disease. Dogs affected with CanL present varying degrees of renal dysfunction. Unfortunately, traditional biomarkers such as urea and creatinine detect renal damage in advanced stages of the disease, so more accurate biomarkers are needed. Hence, we aimed to study how urinary cystatin C (CysC) and N-acetyl-beta-D-glucosaminidase (NAG), behave in dogs with CanL at different stages of the disease. Eighty-six CanL infected dogs were classified according to LeishVet stages: LI (16 dogs), LIIa (12 dogs), LIIb (12 dogs), LIII (16 dogs) and LIV (30 dogs); as a control, 17 healthy dogs were studied. Blood samples were collected for complete haematological and biochemistry analysis including plasma cystatin C. Urine analysis included urine specific gravity (USG), urine protein to creatinine ratio (UPC), CysC and NAG expressed as a ratio with creatinine uCysCc (µg/g) and uNAGc (IU/g). The haematological, biochemical and urinary analysis coincided with the LeishVet guidelines. The statistical study of the uCysCc ratio and the uNAGc, showed significant increase when compared against control starting from group LI (p < 0.05). Interestingly, when the cut-off values were calculated using the ROC curve, uCysCc (258.85 µg/g) and uNAGc (2.25 IU/g) 75 % of the dogs included in LI groups surpassed the threshold. Hence our study indicates that uCysCc and uNAGc, could help to detect early renal damage in CanL affected dogs.

Complete Blood Count-Derived Inflammatory Markers Changes in Dogs with Chronic Inflammatory Enteropathy Treated with Adipose-Derived Mesenchymal Stem Cells.

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.

Effects of Allogeneic Mesenchymal Stem Cell Transplantation in Dogs with Inflammatory Bowel Disease Treated with and without Corticosteroids.

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.

Evaluation of a Bochdalek diaphragmatic hernia rabbit model for pediatric thoracoscopic training.

BACKGROUND/AIM: This study evaluated the usefulness of a Bochdalek hernia rabbit model as a tool for advanced thoracoscopic training, teaching the specific skills required for thoracoscopic repair of congenital diaphragmatic hernia. MATERIALS AND METHODS: An incision was made in the Bochdalek triangle of 25 New Zealand rabbits (weighing 3-3.5 kg) to induce an experimental diaphragmatic hernia. At 72 hours later, a thoracoscopic repair of the hernia as described for newborns was performed by 25 pediatric surgeons divided into two groups: expert and novice. The tasks assessed were organ relocation and diaphragm suture. A visual analog scale was used to evaluate technical performance. The objective performance measure was completion time. Complications were recorded, and suture quality was scored. The surgeons evaluated the model by completing a questionnaire, grading items on a 5-point scale. RESULTS: All 25 animals developed a diaphragmatic hernia with protrusion of the intestine into the thoracic cavity. Expert trainees had significantly shorter completion times and better performance scores than novices. Experts also received higher scores for suture quality. Five novices caused perforations or bleeding, but no experts did. The surgeons rated the model positively, highlighting the similarities between the model and newborn hernias and its usefulness for pediatric training programs. CONCLUSIONS: The Bochdalek hernia rabbit model can be used to detect different levels of experience in pediatric thoracoscopy. This realistic and easily reproducible model can help to perfect thoracoscopic skills in a realistic recreation of a pediatric Bochdalek hernia repair.

[Pyramid training model in laparoscopic surgery]. / Modelo de formación piramidal para la enseñanza de cirugía laparoscópica.

BACKGROUND: Minimally invasive surgery implementation requires a regulated and orderly learning process. METHODS: Jesús Usón Minimally Invasive Surgery Centre promotes a pyramid training model structured into four levels: training of basic and advanced skills in physical simulator (level 1), training of anatomical protocols and advanced skills with animal models (level 2) training advanced procedural skills with tele-surgical applications (level 3), and training in the operating room (level 4). Training provided at levels 1 and 2 is described and evaluated. RESULTS: 4284 participants have been trained in laparoscopy at our institution. 95.5% surgeons: 49% gastroenterologists, 30% urologists, and 14% gynecologist (14%). 77% of celebrated courses consisted of 20 hours training (8 at level 1 and 12 at level 2). 94.37% of participants considered pyramid model as highly suitable, scoring 9.5 on a scale 1-10 for the model and for the simulation quality. 82.7% perceived the improvement in their laparoscopic skills and 99.56% recommend this training program to other surgeons. DISCUSSION: There are no unified criteria between different training programs but most of them measure laparoscopic skills based on time of execution, quality or mistakes of the exercise, and the student satisfaction test. CONCLUSION: The pyramid training model lead to the acquisition of necessary laparoscopic skills to perform safely advanced minimally invasive techniques.

Antecedentes: la práctica de la cirugía de mínima invasión necesita que el aprendizaje sea estructurado y progresivo. Material y métodos: estudio prospectivo efectuado en el Centro de Cirugía de Mínima Invasión Jesús Usón que propone un modelo de formación piramidal con cuatro niveles: adquisición de habilidades básicas en simulador (nivel 1), desarrollo de técnicas quirúrgicas específicas en modelos animales (nivel 2), telemedicina y telementorización (nivel 3), y aplicación al paciente con supervisión experimentada (nivel 4). Objetivo: describir los niveles 1 y 2 que se practican en el Centro y evaluar la formación impartida. Resultados: 4,284 alumnos han recibido formación en cirugía laparoscópica: 95.5% médicos: cirujanos del aparato digestivo (49%), urólogos (30%) y ginecólogos (14%). En 77% de los cursos celebrados disponen de 20 horas de adiestramiento, 8 en el nivel 1, y 12 en el nivel 2. El 94.37% considera altamente apropiado el modelo de formación piramidal, calificándolo con 9.58 sobre 10 y con 9.5 a la calidad de la simulación. El 82.75% percibe que ha avanzado notablemente en sus destrezas y 99.56% recomendaría a otros cirujanos la realización de actividades en el Centro. Conclusión: el modelo de formación propuesto permite alcanzar las habilidades necesarias para efectuar correctamente procedimientos avanzados en cirugía de mínima invasión.