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Background: Urinary tract infections (UTI) caused by Escherichia coli and Enterococcus spp., which are frequently coisolated in polymicrobial UTI, cause morbidity among dogs and warrant antimicrobial therapy. Objectives: To evaluate clinical features of dogs with polymicrobial E. coli and Enterococcal UTI. Animals: Forty‐four client‐owned dogs with polymicrobial bacteriuria and groups of 100 client‐owned dogs with E. coli and Enterococcal monomicrobial bacteriuria. Methods: Retrospective cohort study of medical records of dogs at a university teaching hospital from 2014 to 2019. Prevalence of recurrent UTI and isolate antimicrobial resistance were determined. Clinical outcomes of dogs with recurrent UTI from groups including cost and hospital visits were compared. Results: Recurrent UTI was more prevalent (P =.05) in dogs with polymicrobial bacteriuria (57%, 95% confidence interval [95% CI]: 42%‐70%) compared to the Enterococcal monomicrobial group (40%, 95% CI: 31%‐50%). Escherichia coli from polymicrobial bacteriuria were more frequently resistant to doxycycline (P <.01, 43%, 95% CI: 29%‐58%) and gentamicin (P =.03, 17%, 95% CI: 9%‐31%) compared to E. coli from monomicrobial bacteriuria (17% and 5%, 95% CI: 11%‐26% and 2%‐11% for doxycycline and gentamicin, respectively). Dogs with recurrent UTI from the polymicrobial UTI group had significantly (P =.05) more hospital visits (mean = 6 visits, 95% CI: 1.7‐9.8) compared to recurrent monomicrobial UTI dogs (mean = 4 and 3 visits, 95% CI: 1.0 to 4.4 and −0.7 to 7.7 for E. coli and Enterococcal monomicrobial UTI, respectively). Conclusions and Clinical Importance: Escherichia coli and Enterococcus spp. polymicrobial UTI had more frequent adverse clinical outcomes for dogs. [ABSTRACT FROM AUTHOR]

Cranial internal hemipelvectomy can be successful for excision of ilial CSA with minimal complications. Iliectomy with adjuvant radiation therapy was well tolerated in a dog with grade II ilial CSA. The dog survived 1,271 days postoperatively and supposedly succumbed to a disease process unrelated to the CSA. [ABSTRACT FROM AUTHOR]

Background: Metabolomics may represent an avenue for diagnosis of equine ascending placentitis. Objectives: To characterise the plasma metabolomic profile in healthy mares and mares with induced ascending placentitis, with the goal of identifying metabolites with potential clinical value for early diagnosis of placentitis. Study design: Controlled in vivo experiment. Methods: Placentitis was induced in 10 late‐term pregnant pony mares via Streptococcal equi subsp. zooepidemicus inoculation in five mares between days 285 and 290 of gestation, while five mares served as healthy controls. Repeated ultrasound examinations and jugular venipuncture were performed to obtain combined thickness of the uterus and placenta (CTUP) and plasma for NMR spectroscopy. Mares with increased CTUP were diagnosed with placentitis and treated in accordance with published therapeutic recommendations. NMR metabolomic analysis was performed to identify and quantify plasma metabolites at each time point. Concentrations were compared using ANOVA with repeated‐measures and PLS‐DA analysis. Results: Four hours post‐inoculation, a significant increase was detected in the metabolites alanine, phenylalanine, histidine, pyruvate, citrate, glucose, creatine, glycolate, lactate and 3‐hydroxyisobutyrate that returned to baseline by 12 hours. On day 4, a significant reduction in the metabolites alanine, phenylalanine, histidine, tyrosine, pyruvate, citrate, glycolate, lactate and dimethylsulfone was seen in infected mares compared with controls. Main limitations: There were small numbers of mares within groups. In addition, this work compares healthy animals with animals treated with multimodal therapeutics following diagnosis of placentitis without an untreated cohort. Conclusions: Two phases of metabolite changes were noted after experimental infection: An immediate rise in metabolite concentration involved in energy, nitrogen, hydrogen and oxygen metabolism within 4 hours after inoculation that was followed by a decrease in metabolite concentrations involved in energy and nitrogen metabolism at 4 days, coinciding with ultrasonographic diagnosis of placentitis. [ABSTRACT FROM AUTHOR]

In this study, we take an important step toward clinical translation by generating the first canine‐induced neural stem cells (iNSCs). We explore key aspects of scale‐up, persistence, and safety of personalized iNSC therapy in autologous canine surgery models. iNSCs are a promising new approach to treat aggressive cancers of the brain, including the deadly glioblastoma. Created by direct transdifferentiation of fibroblasts, iNSCs are known to migrate through the brain, track down invasive cancer foci, and deliver anticancer payloads that significantly reduce tumor burden and extend survival of tumor‐bearing mice. Here, skin biopsies were collected from canines and converted into the first personalized canine iNSCs engineered to carry TNFα‐related apoptosis‐inducing ligand (TRAIL) and thymidine kinase (TK), as well as magnetic resonance imaging (MRI) contrast agents for in vivo tracking. Time‐lapse analysis showed canine iNSCs efficiently migrate to human tumor cells, and cell viability assays showed both TRAIL and TK monotherapy markedly reduced tumor growth. Using intraoperative navigation and two delivery methods to closely mimic human therapy, canines received autologous iNSCs either within postsurgical cavities in a biocompatible matrix or via a catheter placed in the lateral ventricle. Both strategies were well tolerated, and serial MRI showed hypointense regions at the implant sites that remained stable through 86 days postimplant. Serial fluid sample testing following iNSC delivery showed the bimodal personalized therapy was well tolerated, with no iNSC‐induced abnormal tissue pathology. Overall, this study lays an important foundation as this promising personalized cell therapy advances toward human patient testing. [ABSTRACT FROM AUTHOR]

Since William Coley utilized bacterial immunotherapy to treat sarcomas in the late 19th century, an association between infection and improved survival has been reported for human and canine osteosarcoma patients. One of the reasons for this improved survival is likely a reactivation of the host immune system towards an inflammatory anti‐tumour response, and one of the key players is the macrophage. Yet, despite their importance, the response of macrophages to infectious agents in the context of osteosarcoma has not been thoroughly evaluated. The aim of this study was to evaluate how in vitro exposure to a bacterial agent (Staphylococcus aureus) influenced canine and human macrophage differentiation in the presence of osteosarcoma. Our hypothesis was that S. aureus would, in the presence of osteosarcoma, induce a macrophage phenotype with significantly increased inflammatory signatures. Consistent with our hypothesis, human macrophages co‐cultured with osteosarcoma and S. aureus exhibited increased IFN‐γ, TNF‐α and IL‐12p70 cytokine secretion, decreased TGF‐β cytokine secretion and increased mRNA expression of TNF‐α when compared with macrophages co‐cultured with osteosarcoma and to macrophages cultured alone. Canine macrophages similarly exhibited increased IFN‐γ and TNF‐α cytokine secretion, decreased TGF‐β cytokine secretion, increased mRNA expression of TNF‐α and increased surface receptor expression of CD80 when co‐cultured with osteosarcoma and S. aureus. Collectively, the findings of this study suggest that infection upregulates the inflammatory immune response to counteract osteosarcoma‐induced immune suppression. This work informs a potential therapeutic strategy to optimize inflammatory stimuli for triggering an anti‐osteosarcoma macrophage response. [ABSTRACT FROM AUTHOR]

Background: Esophagitis with eosinophilia, inflammation, and fibrosis represent a chronic condition in humans with food allergies. Objective: In this investigation, we asked whether esophagitis with an eosinophilic component is observed in young pigs rendered allergic to hen egg white protein (HEWP). Methods: Food allergy was induced in young pigs using two protocols. In one protocol, sensitized pigs were challenged by gavage with a single dose of HEWP. Clinical signs were monitored for 24 hours, and then, gastrointestinal (GI) tissues were collected for histological examination. The phenotype of circulating, ovalbumin (OVA)‐specific T cells also was examined in HEWP challenged animals. In the second protocol, sensitized animals were fed HEWP for 28 days. Animals were then examined by endoscopy and gastrointestinal tissues collected for histological examination. Results: In pigs challenged by gavage with HEWP, clinical signs were noted in 5/6 pigs including diarrhoea, emesis, and skin rash. Clinical signs were not seen in any control group. Histological analysis revealed significant levels of oesophageal eosinophilic infiltration (P <.05) in 4/6 of these animals, with two also displaying eosinophilic infiltration in the stomach. Eosinophils were not increased in ileum or colon samples. Increased numbers of circulating, OVA‐specific CD4+ T cells also were observed in pigs that received HEWP by gavage. In the group of animals fed HEWP, endoscopy revealed clinical signs of esophagitis including oedema, granularity, white spots, and furrowing, while histology revealed oedema, immune cell infiltration, and basal zone hyperplasia. Conclusions and Clinical Relevance: Food allergy in the pig can be associated with esophagitis based on histological and endoscopic findings, including eosinophilic infiltration. The young pig may, therefore, be a useful large animal model for the study of eosinophilic esophagitis in humans. [ABSTRACT FROM AUTHOR]

An 11-year-old, 443-kg Haflinger mare was presented to the North Carolina State University Veterinary Teaching Hospital with a 2-week history of lethargy and a 3-day duration of anorexia, pyrexia, tachycardia, and ventral edema. Severe pitting edema, peripheral lymphadenopathy, and a caudal abdominal mass were noted on physical examination. An extreme leukocytosis (154.3 × 103/μL) and microscopic hematologic findings suggestive of myelomonocytic leukemia were observed. Serum protein electrophoresis revealed a monoclonal gammopathy and urine protein electrophoresis revealed a monoclonal light chain proteinuria. Necropsy and histopathology confirmed widespread neoplastic infiltration in many organs with a heterogenous population of cells; there was no apparent evidence of bone marrow involvement. Immunohistochemistry confirmed presence of a majority of B cells with a limited antigen expression, admixed with a lower number of T cells. Molecular clonality analysis of IgH2, IgH3, and kappa-deleting element ( KDE, B cell) on whole blood and KDE on infiltrated tissues revealed clonal rearrangements, and the KDE intron clones that amplified in blood and in infiltrated tissue were identical. In contrast, the clonality analysis of T-cell receptor γ revealed no clonality on blood cells and infiltrated tissues. In conjunction with the histopathologic changes, the lesion was interpreted to be composed of neoplastic B cells with a reactive T-cell population. Polymerase chain reaction testing for equine herpes virus 5 was negative. The final diagnosis was diffuse large B-cell lymphoma with a marked hematogenous component. [ABSTRACT FROM AUTHOR]

Objective To evaluate corneal changes associated with chronic, nonhealing, superficial, corneal ulcers in horses via common histopathological stains. Design Retrospective study. Animals Twenty-four horses diagnosed with chronic, nonhealing, superficial, corneal ulceration. Methods The medical records of horses evaluated at North Carolina State University's Veterinary Teaching Hospital ( NCSU- VTH) from 2005 to 2011, diagnosed with a chronic, nonhealing, superficial, corneal ulcer and treated with superficial keratectomy ( SK) were reviewed. Inclusion criteria were superficial corneal ulceration, no cellular infiltration via slit-lamp biomicroscopy, no microorganisms evident on corneal cytology, and acquisition of samples for aerobic bacterial and common fungal cultures. Corneal tissue samples were evaluated histopathologically for the presence or absence of a nonadherent epithelial 'lip', epithelial dysmaturity, intraepithelial inflammatory cells, an acellular hyaline zone in the anterior stroma, and stromal inflammatory cells, fibrosis and vascularization. Results In the majority of analyzed samples, epithelial cells adjacent to the ulcerated site showed nonadherence to the basement membrane and dysmaturity. Intraepithelial inflammatory cell infiltration was uncommon. Histopathological features of an anterior stromal hyaline zone, intrastromal inflammation, fibrosis and vascularization were variably present. Conclusions The most consistent histopathological characteristics of equine chronic, nonhealing, superficial, corneal ulcers include epithelial nonadherence, epithelial dysmaturity and mild to moderate stromal inflammation; however, one set of histopathological characteristics does not definitively define this syndrome in horses. Additionally, the anterior stromal acellular hyaline zone commonly cited in canine spontaneous chronic corneal epithelial defects ( SCCED) is not a consistent finding in equine corneas. [ABSTRACT FROM AUTHOR]

Genetic aberrations linked to tumorigenesis have been identified in both canine and human hematopoietic malignancies. While the response of human patients to cancer treatments is often evaluated using cytogenetic techniques, this approach has not been used for dogs with comparable neoplasias. The aim of this study was to demonstrate the applicability of cytogenetic techniques to evaluate the cytogenetic response of canine leukemia to chemotherapy. Cytology and flow cytometric techniques were used to diagnose chronic myelomonocytic leukemia in a dog. High-resolution oligonucleotide array comparative genomic hybridization (oaCGH) and multicolor fluorescence in situ hybridization (FISH) were performed to identify and characterize DNA copy number aberrations (CNAs) and targeted structural chromosome aberrations in peripheral blood WBC at the time of diagnosis and following one week of chemotherapy. At the time of diagnosis, oaCGH indicated the presence of 22 distinct CNAs, of which trisomy of dog chromosome 7 (CFA 7) was the most evident. FISH analysis revealed that this CNA was present in 42% of leukemic cells; in addition, a breakpoint cluster region-Abelson murine leukemia viral oncogene homolog (BCR-ABL) translocation was evident in 17.3% of cells. After one week of treatment, the percentage of cells affected by trisomy of CFA7 and BCR-ABL translocation was reduced to 2% and 3.3%, respectively. Chromosome aberrations in canine leukemic cells may be monitored by molecular cytogenetic techniques to demonstrate cytogenetic remission following treatment. Further understanding of the genetic aberrations involved in canine leukemia may be crucial to improve treatment protocols. [ABSTRACT FROM AUTHOR]