2018 ACVIM Forum Research Report Program

2018 ACVIM Forum Research Report Program Seattle, Washington, June 14 ‐ 16, 2018 Index of Abstracts THURSDAY, JUNE 14 Time Presenting Author Abstract Title CARDIOLOGY 1:40 PM Lauren Markovic Interventional Management of Central Venous Obstruction in Dogs 2:05 PM Jens Häggström Effect of Signalment Variables and Examiner on Echocardiographic Measurements in 25,472 Normal Pedigree Cats NEUROLOGY 4:10 PM Karen Vernau A Spontaneous Model of Succinic Semialdehyde Dehydrogenase Deficiency in the Saluki Dog 4:35 PM Christopher Mariani Cerebrospinal Fluid Lactate as a Biomarker in Canine Central Nervous System Disorders

UK) is currently used to identify recent infection and to identify exposed animals without signs. This serologic test uses 2 surface protein antigens composed of N-terminal portions of SEQ_2190 (Antigen A) and SeM (Antigen C) and has the capability to differentiate vaccinates from infected animals (DIVA), depending on which vaccine is used. We hypothesize that horses vaccinated for strangles with Pinnacle IN (Zoetis), which is based on a live attenuated, non-encapsulated SeM-2 strain of S. equi, will seroconvert when tested 5 weeks after annual revaccination. Serum samples from 26 horses (mean 15.1 years) in a stable with a strangles outbreak 11 years prior were obtained at the time of annual strangles vaccination (S1) and 5 weeks post vaccination (S2). No horses had a history of strangles and mean medical record history was 4.28 years; mean historical Pinnacle vaccines was 5. For each antigen (Ag), seroconversion was determined as an OD450nm value above 0.5. 5 out of 25 (20%) horses were seroconverted to Ag A prior to vaccination (2 of these 5 were seroconverted to both Ag A and C). 5 weeks post vaccination, 12 out of 25 (48%) were seroconverted to Ag A (mean S2 1.09) and 18 of 25 (72%) to Ag C (mean S2 1.7). With a high rate of seroconversion to both antigens, the DIVA capabilities of this iELISA 1 in horses vaccinated with Pinnacle appears poor. any biologic product administered to each case were tested for EqPV-H by qRT-PCR. Eighteen cases of Theiler';s disease had a history of biologic product administration within the prior 4 months: 12 received tetanus antitoxin, 3 received equine plasma, and 3 received allogenic stem cells. Ten cases occurred with no history of equine biologic product administration. Serum and/or liver was EqPV-H + in 27 of 28 consecutive cases. The biologic product was EqPV-H + in 10/10 cases for which aliquots were obtained. One farm with 4 non-biologicassociated cases was investigated further and 21/40 (52%) mares
Fourteen of 21 (66%) EqPV-H + mares were persistently infected for 1 year without clinical disease. In conclusion, 27/28 consecutive cases of Theiler';s disease were infected with EqPV-H, but infection was also common in horses with subclinical hepatitis and clinically healthy horses. These findings suggest that fulminant hepatitis is an important, but rare, outcome of EqPV-H infection. Further studies should be performed to definitively prove EqPV-H is the cause of Theiler';s disease.
Proportional Morbidity Rate (1990Rate ( -2015 and  6 healthy adult horses received 500 mL 0.9% saline infused IV over 15 minutes containing 2, 3, or 4 mmol/kg BWT (Dose) NaLAC, resulting in a range of 1200 to 2600 mEq total Na and LAC administered. Neuropathic pain, as can occur in laminitis, is largely refractory to standard analgesic drugs but may be controlled with the drug gabapentin. In humans, gabapentin undergoes non-proportional pharmacokinetics which can alter safety and efficacy. There is no information on the pharmacokinetics of escalating dosages or on dose proportionality of gabapentin in horses.
In a single blinded randomized cross-over study using 10 adult horses receiving gabapentin administered by nasogastric tube, 3 horses received 10, 20, 40 mg/kg and 6 horses received 60, 80, 120, 160 mg/kg. Plasma was collected at pre-dose and at 0.25, 0.5, 1, 2, 4, 8, 16, 32 and 64 hours post administration of gabapentin. All horses had a 2-week washout period between doses. Gabapentin was quantified in plasma using a validated chromatographic method. Pharmacokinetic parameters were estimated using non-compartmental analysis.
Pharmacokinetic parameters are presented in table 1. Computer simulation of the disposition of gabapentin following multi-dose oral administration predicts accumulation of gabapentin in plasma when given every 8 or 12 hs. Steady state is likely to be reach after 3 days MEL+CEF improved feed intake at 24 hrs (SE = 0.45, P = 0.01) and increased average daily gain (SE = 0.077, P < 0.001) and feed conversion ratio (SE = 1.50, P < 0.001). Over all lying time was increased for control calves (SE = 2.56, P < 0.01). In conclusion, meloxicam, when combined with antimicrobials, can improve clinical illness behavior and economically relevant performance outcomes and should be considered an important adjunctive therapy.  bacterial antigens (P < 0.05). In addition, PMNs isolated from UNS calves had a greater ability to phagocytose E. coli and S. aureus when compared to STR calves. Serum non-esterified fatty acids (NEFA) were significantly higher in STR calves (P < 0.01). Serum β-hydroxybutyrate (BHB) was significantly lower in STR calves (P < 0.01). These data suggest that immunologic and physiologic differences exist between STR and UNS calves. While the underlying mechanisms for these differences are not clear, it is possible that combinations of energy imbalances, stress-induced immunosuppression, and general immune naiveté, may predispose STR calves to an increased risk of morbidity and mortality due to bovine respiratory disease. of calves sampled at arrival, and from 54.6% sampled at revaccination.

Characterization of cell mediated immune responses in stressed and unstressed beef calves
In calves receiving tulathromycin, M. haemolytica was cultured from 10.8% of calves sampled at arrival, and from 48.7% sampled at revaccination. There was a significant effect of sampling occasion (P < 0.001) with both groups having higher prevalences of M. haemolytica at revaccination than at arrival. All calves in both groups had MDR strains at the time of revaccination, with the prevalence being significantly (P < 0.000) higher than at arrival. Eight dogs were re-imaged 18 to 57 months after initial diagnosis. Seven dogs were managed medically and one surgically with a dorsal laminectomy at two sites (the non-operated stenotic sites were evaluated). The first and follow-up MRIs were reviewed to determine the characteristics of the compressive lesion(s) and spinal cord signal changes.

Pharmacokinetics of Tulathromycin in Healthy Goats and Goats with
The mean age at diagnosis was 1.5 years (  Spinal spreading of brain gliomas is a rare condition in human medicine that was never described in dogs. Further studies could highlight if the stereotactic irradiation could promote the spinal spreading of loosely arranged neoplastic cells of superficial oligodendrogliomas.

Comparison of Serum Phenobarbital Concentrations After Chronic Oral and Transdermal Phenobarbital Administration in Epileptic Cats
Heidi The purpose of this study was to determine the pharmacokinetics and biological effects of cytarabine ocfosfate (CO) in dogs. CO is the orally administered prodrug of cytosine arabinoside (Ara-C), a nucleoside analogue used in the treatment of inflammatory brain disease. Ara-C must be given parenterally, which limits its use.
Three healthy dogs received 200 mg/m 2 of CO orally every 24 hours for 7 doses. Serum was obtained up to 21 days after administration of the first dose. Cerebrospinal fluid (CSF) was obtained at 0, 24, 144 and 180h. CO and Ara-C concentrations were measured using HPLC. Complete blood counts measured leukocyte values up to 21 days. Ara-CTP, an intranuclear metabolite, was measured in leukocyte DNA.
The maximal serum CO concentration was 575.3 ± 109.6 ng/mL at 112 ± 36.7 h. The maximal serum Ara-C concentration was 635.7 ± 140.5 ng/mL at 36.7 ± 58.3 h. CO was not detected in the CSF until 144 hours in one dog, and until 180 hours in two dogs, while Ara-C was detected at 24 hours in all dogs. All dogs became leukopenic after receiving 7 doses of CO (144 h). The maximal concentration of Ara-CTP detected in leukocyte DNA at 168 ± 41.6 h.
Serum Ara-C concentrations following CO administration were lower than those reported following parenteral Ara-C administration. Both CO and Ara-C were able to enter the CSF. Peripheral blood leukocyte concentrations decreased significantly following the administration of CO, and Ara-CTP accumulated within leukocyte DNA. All outcome assessment methods contain inherent variability, owing to errors in measurement and differences within and between individuals. These can be analyzed in untreated animals, using methods derived from laboratory medicine, and then combined to define boundaries of outcome beyond which 'real change'; attributable to the intervention can be inferred.
In both of two recent clinical trials of putative therapies for chronic spinal cord injury in companion dogs there were interventionassociated benefits at a group level. The data from untreated controls were re-analyzed as described above, which identified 2 of 23 recipients of intraspinal olfactory ensheathing cells and 2 of 27 dogs that received intraspinal chondroitinase as unequivocal responders. There were no specific pre-trial clinical characteristics in common amongst these dogs except that all became paralyzed following intervertebral disc herniation (not fracture-luxation).
This responder rate (4/50 cases overall) corresponds to a numberneeded-to-treat (NNT) of 12.5. Although this NNT appears high, it is comparable to those associated with many commonly used drugs and the treated condition is extremely severe and has no other available therapy.
This analysis confirms the efficacy of these two interventions in severe chronic spinal cord injury in dogs, defines a responder rate and, although not successful here, provides a method to identify prognostic factors for response to therapy.

Influence of Duration of Injury on Diffusion Tensor Imaging in Acute Canine Spinal Cord Injury
Melissa Lewis 1 , Natasha J. Olby 2 , Peter J. Early 2 , Christopher L. Mariani 2 , Karen R. Acute thoracolumbar spinal cord injury (TLSCI) is common in dogs. Diffusion tensor imaging (DTI) quantifies microstructural lesion characteristics but optimal timing of examination after injury in dogs is unknown.
Our objective was to investigate the impact of duration of injury on DTI imaging parameters and the association with clinical severity.
Thirty-three dogs with acute TLSCI of variable severity who underwent DTI were included. Fractional anisotropy (FA) and mean diffusivity (MD) were calculated on regions of interest cranial, caudal and within the lesion epicenter. The relationships between FA or MD values and duration (injury to imaging interval) and clinical neurologic grade were determined using regression analysis and Wilcoxon rank sum.

Duration of injury should be considered when interpreting DTI results
in dogs with acute TLSCI. There was a variable relationship between injury severity and DTI indices in the acute setting.

Impact of a Novel Diet on Quality of Life in Dogs Receiving Chemotherapy
Cailin Heinze 1 , Ken Rassnick 2 , Kristine Burgess 1 , Lisa Barber 1 , Julie Bayle 3 1 Cummings School of Veterinary Medicine at Tufts University, North Grafton, MA, USA, 2 VETERINARY MEDICAL CENTER OF CNY, East Syracuse, NY, USA, 3 Royal Canin SAS, Aimargues, Languedoc-Roussillon, France The goal of cancer treatment for dogs is to increase survival while providing good quality of life (QOL). In a prospective, blinded, randomized, controlled study, we investigated whether a novel dry diet with increased protein and antioxidants, a custom fiber blend, and EPA and DHA would improve QOL compared to a typical maintenance diet in dogs undergoing chemotherapy for lymphoma (LSA) and mast cell tumors (MCT).
Twenty-one chemotherapy-naïve client-owned dogs (16 LSA, 5 MCT) were enrolled in the maintenance diet group and 24 (17 LSA, 7 MCT) in the test diet group. The dogs ate the diets for 8 weeks while being treated with standardized chemotherapy protocols specific for each tumor type at five study sites. Dog owners evaluated QOL at baseline and after 8 weeks using a previously published questionnaire designed for dogs with cancer. Data was analyzed using 'intent to treat'; principles.
There were no significant differences in dog or tumor parameters between diet groups at baseline other than body weight; dogs on the test diet weighed more than dogs on the maintenance diet (by 7.51 kg; p = 0.031). Fourteen (10 LSA, 4 MCT) dogs in the maintenance group and 22 dogs (16 LSA, 6 MCT) in the test group completed the study (p = 0.061). From baseline to 8 weeks, 10/12 QOL parameters significantly improved for the dogs on the test diet while only 1/12 improved for dogs eating the maintenance diet. Dogs on the test diet had more improvement in signs of illness than dogs on the maintenance diet (p < 0.009) but there were no other QOL differences between diet groups. Although statistical power was limited by small sample size, this study suggests that diet during chemotherapy could play a role in QOL and that further investigation is warranted. The results of this study suggest that the use of a liquid fiducial to create a planning target volume for SRS delivery is very safe, with minimal acute and delayed toxicity observed. Additionally, all patients injected with fiducial had easily identifiable markers present that could be used both for CTV/PTV creation and for treatment alignment purposes using the cone beam CT of the linear accelerator. Based on these results, the trial has expanded to focus on long-term outcomes and toxicity analysis based on specific tumor types. In conclusion, rabacfosadine administered every three weeks is generally well-tolerated and demonstrates substantial antitumor activity in dogs with previously untreated lymphoma. The anal glad carcinoma patients were treated every 3 weeks in combination with their Carboplatin treatments. Each patient was also pretreated with diphenhydramine. Both dogs and cats were treated in this study using the same administration protocol. Each administration was performed on the same day following standard chemotherapy dosing of one of the following: Vincristine (0.5mg/m2), Doxorubicin (27mg/m2), Dacarbazine (800mg/m2) or Carboplatin (225mg/m2) according to standard treatment protocols.

Safety Evaluation of Multiple Intravenous Administrations of Immunocidin® in Cats and Dogs with Malignancies
Following administration of MCWF, all animals were closely monitored for 2h in the clinic before being sent home with the owner.
Temperature, blood pressure, heart and respiratory rate were assessed every 30-45 min. In addition, whole blood samples were taken every two to four weeks and complete blood counts and clinical chemistry analysis were performed.
Adverse events (AE';s) were observed in 5 animals and were considered minimal. Observed AE';s included mild lethargy (8)  Additional, controlled clinical studies are planned to further demonstrate Immunocidin ® efficacy as conjunctive therapy to standard of care in treatment of hemangiosarcoma and soft tissue sarcoma.
Overall, present data showed that in our clinical setting the MCWF has immunomodulatory potential that can play a role in treating additional neoplasias beyond mammary tumors as an adjunct treatment in combination with standard protocols. Dogs with treatment-naïve appendicular osteosarcoma and no radiographic pulmonary metastasis were prospectively enrolled in a singlearm clinical trial. Following limb amputation, dogs were prescribed oral toceranib 2.5-2.75 mg/kg q48h and famotidine 0.5-1mg/kg q24.

Prospective
Blood and exam parameters were collected weekly for 4 weeks, monthly for 1 year, then q2-3 months. Thoracic radiographs were performed every 3 months. Quality of life and symptoms were measured at each visit using validated questionnaires. Dogs were followed until death and underwent necropsy.
14 dogs (mean age 9.0 ± 1.9 years, mean weight 29.7 ± 6.9 kg) were enrolled. Mean starting toceranib dose was 2.66 ± 0.9 mg/kg; mean The aim of this study was to develop culture protocols for duodenum, jejunum, ileum and colon ENT/COL from healthy dogs (n=23) and dogs with chronic enteropathies (CE) (n=12). In addition, we sought to extensively characterize the cells within ENT/COL using bright field imaging, transmission electron microscopy, immunohistochemistry, RNA in situ hybridization, and RNA microarray. Functional assays were developed using a 2D transwell culture approach for stimulation assays and optical metabolic imaging (OMI) for 3D cultures in matrigel.
Organoids were cryopreserved for the development of a canine ENT/COL bioarchive.
Ten endoscopic biopsies per intestinal region were acquired from healthy or CE dogs. Minced samples were repeatedly washed. Crypts were enriched, using EDTA chelation, released via trituration, embedded in matrigel, and grown in intestinal stem cell media.
Organoid yield was 5 enteroids/biopsy and 30 colonoids/biopsy on average. Optimized intestinal stem cell growth media for proliferation versus differentiation contained rho-associated kinase ROCK inhibitor Y27632, glycogen synthase kinase 3β inhibitor CHIR99021, and wnt- This is the first report of successful propagation ex vivo of canine endoscopically procured ENT/COL from clinical CE patients across the regions of the intestine. This study lies the foundation for future tissue engineering, toxicological and microbial studies, and pre-clinical therapeutic trials. lence of post-treatment azotemia was significantly higher (P < 0.0001) in the cats with overt (50%) and subclinical (36.5%) hypothyroidism than in the cats that remained euthyroid (11.5%) after radioiodine treatment.

Frequency Of Oral Famotidine Administration Determines
In conclusion, our novel algorithm for calculating individual 131 I doses based on serum thyroid hormone concentrations, thyroid scintigraphy (thyroid tumor volume and percent TcTU), and radioiodine uptake by the thyroid tumor resulted in "cure rates" similar to historical rates, but dramatically reduced the incidence of overt and subclinical hypothyroidism. Importantly, the lower calculated radioiodine doses (compared to those currently administered by most other protocols), limit radiation exposure to veterinary staff and owners. Finally, by lowering the incidence of iatrogenic hypothyroidism, this individualized approach also lowers the rate of azotemia that develops after radioiodine treatment. Treatment of hyperthyroidism in cats is frequently associated with unmasking of pre-existing chronic kidney disease. Currently, there is no renal biomarker that can reliably predict the development of azotemia that occurs secondary to decreases in glomerular filtration rates (GFR) following treatment for hyperthyroidism. S-dimethylarginine (SDMA) has been shown to be a sensitive marker of GFR in veterinary medicine that is not influenced by changes in muscle mass. We hypothesized that SDMA could be a cost-effective and useful biomarker for prediction of decreases in total GFR and the onset of azotemia in cats receiving I-131 therapy.
Cats (n=7) diagnosed with hyperthyroidism based on clinical signs and increased serum total T4 (TT4) were included in this prospective clinical trial. Study design included a physical exam, complete blood count, serum chemistry, total T4, urinalysis and SDMA prior to treatment and at 1 and 3 months post-treatment. In addition, GFR was quantified by renal scintigraphy (Tc99mDTPA) immediately prior to and at 3 months post-treatment.
Currently, 6 of 7 cats enrolled in the trial have completed diagnostic evaluation at all three time points. The median age of the cats was 12.6 years (range 11.2 -15.2 years) and comprised 4 neutered males and 3 spayed females. All cats were non-azotemic at enrollment (creatinine < 1.6 mg/dl). The mean TT4 decreased significantly at one and three months post-treatment (p < 0.05). Five cats were euthyroid and 1 cat was hypothyroid at three months post-treatment. Mean total GFR (p < 0.05) and mean serum creatinine (p < 0.01) decreased and increased significantly between time points, respectively. Mean serum SDMA did not differ significantly from baseline at 1 (p = 0.27) or 3 (p = 0.22) months post-treatment. No significant correlation was found between SDMA and either total GFR (r=-0.17, p=0.62) or TT4 (r = -0.06, p = 0.98). Based on these results, we conclude that serum SDMA does not accurately reflect changes in GFR in hyperthyroid cats. The results do not support the use of SDMA in predicting the development of azotemia following I-131 therapy. Hypertensive cats were randomly assigned (2:1 ratio) to receive telmisartan oral solution or placebo. Cats were administered 1.5 mg telmisartan/kg q12h for 14 days, followed by 2 mg telmisartan/kg q24h. SBP was measured on days 0 (baseline), 14 and 28. Change in SBP compared to baseline was calculated for days 14 and 28. Telmisartan efficacy was defined as significant reduction in SBP at day 14 compared to placebo, and a clinically relevant (>20 mmHg) reduction in SBP at day 28. Data are presented as mean (95% CI).
Telmisartan decreased SBP by a statistically significant and clinically relevant magnitude and was well tolerated in hypertensive cats.

Evaluation of a Quantitative Ultrasound Technique for Assessment of Muscle in Normal Cats
Lisa Freeman 1 , James Sutherland-Smith 2 , Charles Cummings 3 , John Rush 1 1 Tufts University, North Grafton, MA, USA, 2 Cummings School of Veterinary Medicine, Tufts University, North Grafton, MA, USA, 3 Cummings School of Veterinary Medicine, North Grafton, MA, USA Muscle loss is common in disease and aging but is difficult to quantitatively assess clinically. Therefore, non-invasive, quantitative methods are needed. The objective of this study was to evaluate an ultrasound technique previously validated in dogs, the Vertebral Epaxial Muscle Score (VEMS), in cats.
Healthy, neutered cats between 1-6 years of age were eligible. Mean epaxial muscle height was calculated from three transverse ultrasound images obtained at the 13 th thoracic vertebra using a 12-5Mhz linear transducer. Fourth thoracic vertebral (T4) length was measured from thoracic radiography, and the ratio of the epaxial muscle height/T4 length (VEMS) was calculated and compared to body weight. Ratios of epaxial muscle height to various zoometric measurements also were compared to body weight as potential alternatives to using T4 length.
Both the VEMS and epaxial muscle height/fore limb circumference are techniques that can normalize muscle size across varying body weights in cats. Studies are warranted to determine whether these techniques can accurately assess muscle in cats of varying adiposity and in those with muscle loss.