The standards of reporting trials in pets (PetSORT): Explanation and elaboration

Well-designed randomized controlled trials (RCTs) provide the best evidence of the primary research designs for evaluating the effectiveness of interventions. However, if RCTs are incompletely reported, the methodological rigor with which they were conducted cannot be reliably evaluated and it may not be possible to replicate the intervention. Missing information also may limit the reader's ability to evaluate the external validity of a trial. Reporting guidelines are available for clinical trials in human healthcare (CONSORT), livestock populations (REFLECT), and preclinical experimental research involving animals (ARRIVE 2.0). The PetSORT guidelines complement these existing guidelines, providing recommendations for reporting controlled trials in pet dogs and cats. The rationale and scientific background are explained for each of the 25 items in the PetSORT reporting recommendations checklist, with examples from well-reported trials

The standards of reporting randomized trials in pets (PetSORT): Methods and development processes

BackgroundReporting of clinical trials conducted in client- and shelter-owned dog and cat populations is not optimal, which inhibits the ability to assess the reliability and validity of trial findings and precludes the ability to include some trials in evidence synthesis.ObjectiveTo develop a reporting guideline for parallel group and crossover trials that addresses the unique features and reporting requirements for trials conducted in client- and shelter-owned dog and cat populations.DesignConsensus statement.SettingVirtual.ParticipantsFifty-six experts from North America, the United Kingdom, Europe, and Australia working in academia, government (research and regulatory agencies), industry, and clinical veterinary practice.MethodsA steering committee created a draft checklist for reporting criteria based upon the CONSORT statement and the CONSORT extensions for reporting of abstracts and crossover trials. Each item was presented to the expert participants and was modified and presented again until >85% of participants were in agreement about the inclusion and wording of each item in the checklist.ResultsThe final PetSORT checklist consists of 25 main items with several sub-items. Most items were modifications of items contained in the CONSORT 2010 checklist or the CONSORT extension for crossover trials, but 1 sub-item pertaining to euthanasia was created de novo.ConclusionThe methods and processes used to develop this guideline represent a novel departure from those used to create other reporting guidelines, by using a virtual format. The use of the PetSORT statement should improve reporting of trials conducted in client- and shelter-owned dogs and cats and published in the veterinary research literature

Primary extraskeletal osteosarcoma of the post-hepatic caudal vena cava in a dog—Case report

Extraskeletal osteosarcoma (EOSA) in dogs is a rare malignant mesenchymal tumor of somatic soft tissues or more commonly visceral organs with a poor prognosis. In dogs, EOSAs have been described as arising from multiple locations, but differently from humans, never from a main vessel. In this report, we describe the first case of an EOSA arising from the post-hepatic caudal vena cava in a 7-year-old male neutered mix breed dog. This report focuses on the description of the diagnostic challenges to obtain a preoperative diagnosis, highlights the importance of histopathology for a correct diagnosis, and introduces a new differential diagnosis for an animal presenting with a suspected thrombus of the vena cava

Genome-wide analysis of canine oral malignant melanoma metastasis-associated gene expression

Abstract Oral malignant melanoma (OMM) is the most common canine melanocytic neoplasm. Overlap between the somatic mutation profiles of canine OMM and human mucosal melanomas suggest a shared UV-independent molecular aetiology. In common with human mucosal melanomas, most canine OMM metastasise. There is no reliable means of predicting canine OMM metastasis, and systemic therapies for metastatic disease are largely palliative. Herein, we employed exon microarrays for comparative expression profiling of FFPE biopsies of 18 primary canine OMM that metastasised and 10 primary OMM that did not metastasise. Genes displaying metastasis-associated expression may be targets for anti-metastasis treatments, and biomarkers of OMM metastasis. Reduced expression of CXCL12 in the metastasising OMMs implies that the CXCR4/CXCL12 axis may be involved in OMM metastasis. Increased expression of APOBEC3A in the metastasising OMMs may indicate APOBEC3A-induced double-strand DNA breaks and pro-metastatic hypermutation. DNA double strand breakage triggers the DNA damage response network and two Fanconi anaemia DNA repair pathway members showed elevated expression in the metastasising OMMs. Cross-validation was employed to test a Linear Discriminant Analysis classifier based upon the RT-qPCR-measured expression levels of CXCL12, APOBEC3A and RPL29. Classification accuracies of 94% (metastasising OMMs) and 86% (non-metastasising OMMs) were estimated

The effect of prophylactic treatment with levetiracetam on the incidence of post-attenuation seizures in dogs undergoing surgical management of single congenital extrahepatic portosystemic shunts

Objectives: To report (1) the incidence of post-attenuation seizures (PAS) in dogs that underwent single congenital extrahepatic portosystemic shunt (cEHPSS) attenuation and (2) to compare incidence of PAS in dogs that either did or did not receive prophylactic treatment with levetiracetam (LEV).Study Design: Multi-institutional retrospective study.Sample Population: Nine-hundred-and-forty dogs.Methods: Medical records were reviewed to identify dogs that underwent surgical attenuation of a single cEHPSS from January 2005 through July 2017 and developed PAS within seven days postoperatively. Dogs were divided into three groups: no LEV (LEV-); LEV at >15mg/kg TID for >24 hours or a 60mg/kg intravenous loading dose preoperatively, followed by >15mg/kg TID postoperatively (LEV1); ); and LEV at less than 15mg/kg TID, for less than 24 hours preoperatively, or continued at less than 15mg/kg TID postoperatively (LEV2).Results: Nine-hundred-and-forty dogs were included. Seventy-five (8.0%) developed PAS. Incidence of PAS was 35/523 (6.7%), 21/188 (11.2%) and 19/228 (8.3%) in groups LEV-, LEV1 and LEV2, respectively. This difference was not statistically significant (p=0.14). No significant differences between groups of dogs that seized with respect to variables investigated were identified.Conclusions: The overall incidence of PAS was low (8%). Prophylactic treatment with LEV according to the protocols investigated in our study was not associated with a reduced incidence of PAS.Clinical Significance: Prophylactic treatment with LEV does not afford protection against development of PAS. Surgically treated dogs should continue to be monitored closely during the first seven days postoperatively for seizures

Prognostic factors for short‐term survival of dogs that experience postattenuation seizures after surgical correction of single congenital extrahepatic portosystemic shunts: 93 cases (2005‐2018)

© 2020 The American College of Veterinary Surgeons Objective: To identify prognostic factors for short-term survival of dogs that experience seizures within 7 days after surgical correction of single congenital extrahepatic portosystemic shunts (cEHPSS). Study design: Multi-institutional retrospective study. Sample population: Ninety-three client-owned dogs. Methods: Medical records at 14 veterinary institutions were reviewed to identify dogs that underwent surgical attenuation of a single cEHPSS from January 1, 2005 through February 28, 2018 and experienced postattenuation seizures (PAS) within 7 days postoperatively. Logistic regression analysis was performed to identify factors associated with 1-month survival. Factors investigated included participating institution, signalment, shunt morphology, concurrent/historical conditions, presence of preoperative neurologic signs, presence of preoperative seizures, aspects of preoperative medical management, surgical details including method and degree of shunt attenuation, type of PAS (focal only or generalized ± focal), drugs administered as part of the treatment of PAS, and development of complications during treatment of PAS. Results: Thirty (32.3%) dogs survived to 30 days. Seventy-six (81.7%) dogs experienced generalized PAS. Factors positively associated with short-term survival included having a history of preoperative seizures (P =.004) and development of focal PAS only (P =.0003). Most nonsurvivors were humanely euthanized because of uncontrolled or recurrent seizures. Conclusion: Dogs that experienced PAS that had a history of preoperative seizures and those that experienced focal PAS only had significantly improved short-term survival. Clinical significance: The results of this study provide information that will help in the counseling of owners who seek treatment for PAS after surgical correction of cEHPSS. © 2020 The American College of Veterinary Surgeons

Demographic characteristics, site and phylogenetic distribution of dogs with appendicular osteosarcoma: 744 dogs (2000-2015).

OBJECTIVE:To report demographic characteristics of a contemporary population of dogs with appendicular osteosarcoma and assess the relationship between demographic characteristics, site distribution, and phylogenetic breed clusters. DESIGN:Retrospective case series. METHODS:A search of the Veterinary Medical Database was performed for dogs with appendicular osteosarcoma as a new diagnosis. Entries were reviewed for the sex, neuter status, age at diagnosis, breed, affected limb, and tumor location. The reported breed for purebred dogs was used to categorize each dog into one of five phylogenetic groups based on microsatellite analysis. RESULTS:744 client-owned dogs were included in the study. Study dogs were represented by a male-to-female ratio of 0.95:1.0, the majority of which (80.9%) were neutered. Most dogs were diagnosed between 7-10 years of age. The majority (77.8%) of dogs were large or giant-breed dogs. Purebred dogs comprised 80.4% of the population. The most common purebred breed affected by OS was the Rottweiler (17.1%). The most common phylogenetic group represented was Mastiff-Terrier (M-T, 26.3%). OS was more commonly located in the forelimb (64.2%) versus the hindlimb (35.8%), and the humerus was the most common site (20.9%). The distribution of age groups and tumor locations were significantly different between phylogenetic clusters. The distribution of age groups and neuter status were significantly different between size groups. CONCLUSIONS AND SIGNIFICANCE:The demographic data of canine appendicular OS are similar to previous reports. The data on phylogenetic associations can guide future studies aimed at evaluating the genomic mutations that contribute to OS development and its biological behavior

Pharmacological Regulation of Tumor Hypoxia in Model Murine Tumors and Spontaneous Canine Tumors

Background: Hypoxia is found in many solid tumors and is associated with increased disease aggressiveness and resistance to therapy. Reducing oxygen demand by targeting mitochondrial oxidative metabolism is an emerging concept in translational cancer research aimed at reducing hypoxia. We have shown that the U.S. Food and Drug Administration (FDA)-approved drug papaverine and its novel derivative SMV-32 are potent mitochondrial complex I inhibitors. Methods: We used a dynamic in vivo luciferase reporter system, pODD-Luc, to evaluate the impact of pharmacological manipulation of mitochondrial metabolism on the levels of tumor hypoxia in transplanted mouse tumors. We also imaged canine patients with blood oxygen level-dependent (BOLD) MRI at baseline and one hour after a dose of 1 or 2 mg/kg papaverine. Results: We showed that the pharmacological suppression of mitochondrial oxygen consumption (OCR) in tumor-bearing mice increases tumor oxygenation, while the stimulation of mitochondrial OCR decreases tumor oxygenation. In parallel experiments in a small series of spontaneous canine sarcomas treated at The Ohio State University (OSU) Veterinary Medical Center, we observed a significant increase in BOLD signals indicative of an increase in tumor oxygenation of up to 10–50 mm HgO2. Conclusion: In both transplanted murine tumors and spontaneous canine tumors we found that decreasing mitochondrial metabolism can decrease tumor hypoxia, potentially offering a therapeutic advantage