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Histopathological evaluation of tumours is a subjective process, but studies of inter‐pathologist agreement are uncommon in veterinary medicine. The Comparative Brain Tumour Consortium (CBTC) recently published diagnostic criteria for canine gliomas. Our objective was to assess the degree of inter‐pathologist agreement on intracranial canine gliomas, utilising the CBTC diagnostic criteria in a cohort of eighty‐five samples from dogs with an archival diagnosis of intracranial glioma. Five pathologists independently reviewed H&E and immunohistochemistry sections and provided a diagnosis and grade. Percentage agreement and kappa statistics were calculated to measure inter‐pathologist agreement between pairs and amongst the entire group. A consensus diagnosis of glioma subtype and grade was achieved for 71/85 (84%) cases. For these cases, percentage agreement on combined diagnosis (subtype and grade), subtype only and grade only were 66%, 80% and 82%, respectively. Kappa statistics for the same were 0.466, 0.542 and 0.516, respectively. Kappa statistics for oligodendroglioma, astrocytoma and undefined glioma were 0.585, 0.566 and 0.280 and were 0.516 for both low‐grade and high‐grade tumours. Kappa statistics amongst pairs of pathologists for combined diagnosis varied from 0.352 to 0.839. 8 % of archival oligodendrogliomas and 61% of archival astrocytomas were reclassified as another entity after review. Inter‐pathologist agreement utilising CBTC guidelines for canine glioma was moderate overall but varied from fair to almost perfect between pairs of pathologists. Agreement was similar for oligodendrogliomas and astrocytomas but lower for undefined gliomas. These results are similar to pathologist agreement in human glioma studies and with other tumour entities in veterinary medicine. [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]

Background: Cerebrospinal fluid (CSF) lactate concentrations increase after seizure activity in many human patients independent of the underlying disease process. The effect of seizure activity on CSF lactate concentration in dogs is unknown. Hypothesis/Objectives: Cerebrospinal fluid lactate concentration is unaffected by seizure activity in dogs and is more dependent on the underlying disease process causing the seizures. Animals One‐hundred eighteen client‐owned dogs with seizure disorders. Methods: Case series. Cerebrospinal fluid lactate concentration was determined using a commercially available lactate monitor. Seizure semiology, time from last seizure to CSF collection, number of seizures within the 72 hours preceding CSF collection, and clinical diagnosis were recorded. Results: Dogs with focal seizures had higher CSF lactate concentrations than did those with generalized seizures (P =.03). No differences in lactate concentrations were found among dogs with single seizures, cluster seizures or status epilepticus (P =.12), among dogs with CSF collection at different time points after the last seizure activity (P =.39) or among dogs having different numbers of seizures within the 72 hours preceding CSF collection (P =.42). A significant difference (P =.001) was found in CSF lactate concentrations among diagnostic groups, and dogs with inflammatory and neoplastic disease had higher concentrations than did dogs with idiopathic or unknown epilepsy. Conclusions and Clinical Importance: Cerebrospinal fluid lactate concentration is minimally affected by seizure activity in dogs and increased concentrations are more likely associated with the underlying disease process. [ABSTRACT FROM AUTHOR]

Background: Cerebrospinal fluid (CSF) lactate is frequently used as a biomarker in humans with inflammatory central nervous system (CNS) disorders including bacterial meningitis and autoimmune disorders such as multiple sclerosis. Hypothesis: Cerebrospinal fluid lactate concentrations are increased in a subset of dogs with inflammatory CNS disorders. Animals: One hundred two client‐owned dogs diagnosed with inflammatory CNS disease. Methods: Case series. Cases were identified both prospectively at the time of diagnosis and retrospectively by review of a CSF biorepository. Cerebrospinal fluid lactate was analyzed with a commercially available, handheld lactate monitor. Subcategories of inflammatory disease were created for comparison (eg, steroid‐responsive meningitis arteritis, meningoencephalitis of unknown etiology). Results: Cerebrospinal fluid lactate concentrations were above reference range in 47% of dogs (median, 2.5 mmol/L; range, 1.0‐11.7 mmol/L). There was no significant difference in lactate concentrations between disease subcategories (P =.48). Significant but weak correlations were noted between CSF lactate concentration and nucleated cell count (r =.33, P < .001), absolute large mononuclear cell count (r =.44, P < .001), absolute small mononuclear cell count (r =.39, P < .001), absolute neutrophil cell count (r =.24, P =.01), and protein (r =.44, P < .001). No correlation was found between CSF lactate concentration and CSF red blood cell count (P =.58). There was no significant association of CSF lactate concentration with survival (P =.27). Conclusions and Clinical Importance: Cerebrospinal fluid lactate concentrations could serve as a rapid biomarker of inflammatory CNS disease in dogs. [ABSTRACT FROM AUTHOR]

Background: We aimed to identify mutations associated with osteochondromatosis in a litter of American Staffordshire Terrier puppies. Hypothesis: We hypothesized that the associated mutation would be located in a gene that causes osteochondromatosis in humans. Animals: A litter of 9 American Staffordshire puppies, their sire and dam, 3 of 4 grandparents, 26 healthy unrelated American Staffordshire Terriers, and 154 dogs of 27 different breeds. Methods: Whole genome sequencing was performed on the proband, and variants were compared against polymorphisms derived from 154 additional dogs across 27 breeds, as well as single nucleotide polymorphism database 146. One variant was selected for follow-up sequencing. Parentage and genetic mosaicism were evaluated across the litter. Results: We found 56,301 genetic variants unique to the proband. Eleven variants were located in or near the gene exostosin 2 (EXT2), which is strongly associated with osteochondromatosis in humans. One heterozygous variant (c.969C>A) is predicted to result in a stop codon in exon 5 of the gene. Sanger sequencing identified the identical mutation in all affected offspring. The mutation was absent in the unaffected offspring, both parents, all available grandparents, and 26 healthy unrelated American Staffordshire Terriers. Conclusions and Clinical Importance: These findings represent the first reported mutation associated with osteochondromatosis in dogs. Because this mutation arose de novo, the identical mutation is unlikely to be the cause of osteochondromatosis in other dogs. However, de novo mutations in EXT2 are common in humans with osteochondromatosis, and by extension, it is possible that dogs with osteochondromatosis could be identified by sequencing the entire EXT2 gene. [ABSTRACT FROM AUTHOR]