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Title => Equine asthma: Integrative biologic relevance of a recently proposed nomenclature Abstract => Authors => Stephanie Bond | Renaud Léguillette | Eric A. Richard | Laurent Couetil | Jean-Pierre Lavoie | James G. Martin | R. Scott Pirie published => First published: 07 October 2018 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.15302

Title => Hepatic copper concentrations in 546 dogs (1982–2015) Abstract => Background: Copper associated hepatitis (CAH) has been increasingly recognized in dogs, and speculation exists that hereditary defects in copper metabolism have been exacerbated by increased environmental copper exposure. However, no broad epidemiological investigations have been performed to investigate quantitative hepatic copper concentrations ([Cu]H) over time in both dogs that are (predisposed breed [PB]), and are not (non-predisposed breed [NPB]), considered at-risk for CAH. Objectives: To investigate [Cu]H in dogs and explore temporal, demographic, and histologic associations spanning 34 years. Animals: 546 archived liver specimens. Methods: Retrospective study. Searches of the Michigan State University Veterinary Diagnostic Laboratory database identified dogs that had undergone hepatic histopathologic assessment. Cases with archived tissue were reviewed and classified by breed, time period, and presence or absence of hepatitis. Inductively coupled plasma mass spectrometry was used to determine [Cu]H. Results: In time period 2009–2015, median [Cu]H were 101 μg/g and 313 μg/g greater than median [Cu]H in time period 1982–1988 for NPB and PB dogs, respectively (P < .001 for both comparisons). The proportion of dogs with [CU]H > 300 μg/g increased in NPB (28% to 49%) and PB dogs (48% to 71%) during these periods (P = .002 for both comparisons). Median [Cu]H in dogs with hepatitis increased 3-fold over time in both NPB (P = .004) and PB populations (P < .001). Conclusions and Clinical Importance: The frequent recognition of CAH in recent years is likely due to the observed increases in [Cu]H over time. Importantly, effects are not limited to PB dogs. Authors => Jaimie M. Strickland DVM | John P. Buchweitz PhD | Rebecca C. Smedley DVM, MS, DACVP | Katherine J. Olstad DVM, DACVP | Ryan S. Schultz DVM | N. Bari Oliver DVM, PhD, DACVIM | Daniel K. Langlois DVM, DACVIM published => First published: 07 October 2018 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.15308

Title => Association of Sphingosine-1-phosphate (S1P)/S1P Receptor-1 Pathway with Cell Proliferation and Survival in Canine Hemangiosarcoma Abstract => None Abstract Authors => published => First published: 07 October 2018 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.15309

Title => Assessment of eosinophils in gastrointestinal inflammatory disease of dogs Abstract => Background: Accurate identification of eosinophils in the gastrointestinal (GI) tract of dogs with eosinophilic GI disease (EGID) by histological evaluation is challenging. The currently used hematoxylin and eosin (H&E) staining method detects intact eosinophils but does not detect degranulated eosinophils, thus potentially underrepresenting the number of infiltrating eosinophils. Objective: To develop a more sensitive method for identifying and quantifying both intact and degranulated eosinophils to diagnose EGID more accurately. Methods: Endoscopically obtained paraffin-embedded intestinal biopsy specimens from dogs with GI signs were examined. The study groups were dogs with eosinophilic enteritis (EE), lymphoplasmacytic and mixed enteritis, and control dogs with GI signs but no histologic changes on tissue sections. Consecutive sections were immunolabeled with monoclonal antibodies (mAbs) against the eosinophil granule protein eosinophil peroxidase (Epx) and stained by H&E, respectively. The number of eosinophils was manually quantified and classified as intact or degranulated. Results: The number of intact eosinophils detected in Epx mAb-labeled duodenal sections was significantly higher compared with that in H&E-stained sections, with a similar relationship noted in the colon and stomach. The Epx mAb allowed the unique assessment of eosinophil degranulation. The number of intact and degranulated eosinophils was significantly higher in duodenal lamina propria of the EE and mixed group compared to the control group. Conclusion: Immunohistochemical detection of Epx provides a more precise method to detect GI tract eosinophils compared to H&E staining and could be used as an alternative and reliable diagnostic tool for assessment of biopsy tissues from dogs with EGID. Authors => Idil Bastan | Aaron K. Rendahl | Davis Seelig | Michael J. Day | Edward J. Hall | Savita P. Rao | Robert J. Washabau | P. Sriramarao published => First published: 07 October 2018 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.15310

Title => Comparison of surgical and conservative treatment of hydrated nucleus pulposus extrusion in dogs Abstract => Background: Whether compressive cervical myelopathy caused by hydrated nucleus pulposus extrusion (HNPE) in dogs should be treated surgically or conservatively has been debated. Only 1 recent study has contradicted the former predominant reports of surgical treatment for HNPE. Hypothesis and method: Single center retrospective study to compare the outcome of client-owned dogs with HNPE after decompressive surgery or conservative treatment. Animals: Thirty-six dogs diagnosed with HNPE confirmed by magnetic resonance imaging (MRI). Results: Eighteen of 36 dogs underwent surgery whereas 18 dogs were managed conservatively including cage rest and physiotherapy. The most common affected intervertebral disc space was C4-5. In 3 dogs, HNPE was diagnosed at the level of T13-L1. Median time to regain ambulation was 6.6 days (range, 0-28 days) after surgery and 5.9 days (range, 0-15 days) with conservative management (P = .37). Conclusions and clinical importance: Conservative management of HNPE in the cervical as well as in the thoracolumbar region represents a reasonable alternative to surgery, showing similar favorable outcome. Authors => Jasmin Nessler | Cornelia Flieshardt | Julia Tünsmeyer | Ricarda Dening | Andrea Tipold published => First published: 29 September 2018 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.15304

Title => Comparison of the mitral valve morphologies of Cavalier King Charles Spaniels and dogs of other breeds using 3D transthoracic echocardiography Abstract => Background: Myxomatous mitral valve disease (MMVD) is more prevalent in Cavalier King Charles Spaniels (CKCSs) compared to dogs of other breeds at a given age. Abnormal valvular stress is thought to contribute to the development and progression of MMVD, and a relationship exists between mitral valve (MV) morphology and stress acting on the valve. Objectives: To determine whether the MV morphology of healthy adult CKCSs differs from the morphology of healthy adult dogs of other breeds determined by RT-3DTTE. Animals: Thirty-five healthy CKCSs and 41 healthy dogs of other breeds. Methods: Prospective cross-sectional study. Dogs underwent physical examination, conventional echocardiography, and RT-3DTTE. RT–3DTTE datasets were analyzed using dedicated software for MV morphologic analysis. Morphologic variables were compared between CKCSs and dogs of other breeds. Results: The MV of healthy CKCSs had a smaller annulus height (0.46 ± 0.11 vs. 0.56 ± 0.17; P = .0021), tenting height (0.26 ± 0.12 vs. 0.42 ± 0.18; P < .001), tenting area (0.42 ± 0.15 vs. 0.79 ± 0.34; P < .001), normalized tenting volume (0.09 [0.05–0.13] vs. 0.14 [0.10–0.20]; P < .001), and normalized area of the posterior leaflet (0.57 ± 0.15 vs. 0.66 ± 0.18; P = .016) compared to healthy dogs of other breeds; this results in CKCSs having a flatter MV with reduced tenting, compared to the MV of other breeds. Conclusions and Clinical Importance: These morphologic features could confer a mechanical disadvantage and play a role in the predisposition of CKCSs to the early development of MMVD. Authors => Giulio Menciotti | Michele Borgarelli | Michael Aherne | Paula Camacho | Jens Häggström | Ingrid Ljungvall | Sunshine M. Lahmers | Jonathan A. Abbott published => First published: 20 September 2018 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.15252

Title => Population pharmacokinetics of extended-release levetiracetam in epileptic dogs when administered alone, with phenobarbital or zonisamide Abstract => Background: Extended-release levetiracetam (LEV-XR) has gained acceptance as an antiepileptic drug in dogs. No studies have evaluated its disposition in dogs with epilepsy. Hypothesis/Objectives: To evaluate the pharmacokinetics of LEV-XR in epileptic dogs when administered alone or with phenobarbital or zonisamide. Animals: Eighteen client-owned dogs on steady-state maintenance treatment with LEV-XR (Group L, n = 6), LEV-XR and phenobarbital (Group LP, n = 6), or LEV-XR and zonisamide (Group LZ, n = 6). Methods: Pharmacokinetic study. Blood samples were collected at 0, 2, 4, 8, and 12 hours after LEV-XR was administered with food. Plasma LEV concentrations were determined by high-pressure liquid chromatography. A population pharmacokinetic approach and nonlinear mixed effects modeling were used to analyze the data. Results: Treatment group accounted for most of the interindividual variation. The LP group had lower CMAX (13.38 μg/mL) compared to the L group (33.01 μg/mL) and LZ group (34.13 μg/mL), lower AUC (134.86 versus 352.95 and 452.76 hours·μg/mL, respectively), and higher CL/F (0.17 versus 0.08 and 0.07 L/kg/hr, respectively). The half-life that defined the terminal slope of the plasma concentration versus time curve (~5 hours) was similar to values previously reported for healthy dogs. Conclusions and Clinical Importance: Considerable variation exists in the pharmacokinetics of LEV-XR in dogs with epilepsy being treated with a common dose regimen. Concurrent administration of phenobarbital contributed significantly to the variation. Other factors evaluated, including co-administration of zonisamide, were not shown to contribute to the variability. Drug monitoring may be beneficial to determine the most appropriate dose of LEV-XR in individual dogs. Authors => Karen R. Muñana | Arturo J. Otamendi | Julie A. Nettifee | Mark G. Papich published => First published: 20 September 2018 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.15298

Title => Low-dose ACTH stimulation testing in dogs suspected of hypoadrenocorticism Abstract => Background: Low-dose ACTH stimulation testing would lower cost and may increase sensitivity for identification of partial ACTH deficiency. Hypothesis: (1) The low-dose ACTH stimulation test will provide comparable results to the standard-dose ACTH stimulation test in dogs suspected of hypoadrenocorticism and (2) partial ACTH deficiency exists in dogs and can result in chronic, intermittent gastrointestinal signs. Animals: Thirty-one client-owned dogs suspected of having hypoadrenocorticism. Methods: Prospective study. Dogs suspected of having hypoadrenocorticism received 1 μg/kg cosyntropin IV for the first ACTH stimulation test; the second test was performed 4 h later and dogs received 5 μg/kg cosyntropin IV. Blood samples were obtained pre-ACTH and 1 hour post-ACTH for each dose (4 measurements total). Samples for endogenous ACTH measurement were obtained at the time of initial blood collection. Results: No significant difference was observed in the basal cortisol concentration before administration of a 1 μg/kg versus before a 5 μg/kg dose of cosyntropin (P = .544). For dogs suspected of having hypoadrenocorticism, the ACTH-stimulated cortisol concentrations in response to both doses of ACTH were equivalent (90% confidence interval [CI], 80.5-97.2%; P = .04). No cases with partial ACTH deficiency were identified conclusively. Conclusions and Clinical Importance: A 1 μg/kg dose of cosyntropin is equivalent to a 5 μg/kg dose of cosyntropin for screening dogs suspected of hypoadrenocorticism. The existence of partial ACTH deficiency was not identified in this small group of dogs. Authors => Annabel Botsford | Ellen N. Behrend | Robert J. Kemppainen | Philippe R. Gaillard | Frank Oprandy | Hollie P. Lee published => First published: 19 September 2018 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.15256

Title => An observational study of environmental exposures, airway cytology, and performance in racing thoroughbreds Abstract => Background: Mild equine asthma is presumed to arise in response to environmental exposures but the relative impact of differing inflammatory phenotypes upon performance are largely unexplored. Animals: Thoroughbred racehorses in active training and racing. Methods: Thoroughbreds were recruited 24-48 hours before racing. Each horse was eligible for re-enrollment with each race entry. Within one hour of race completion, physical examination, respiratory endoscopy, and BAL were performed. Respirable and inhalable dust, respirable endotoxin, and respirable β-glucan exposures were measured at the breathing zone within one week after racing. Controlling for age, trainer, and pulmonary hemorrhage, the relationship between performance, bronchoalveolar lavage fluid (BALF) cytology, and measures of exposure were modeled. Results: Performance and BALF data were collected on 64 individual horses from 8 stables for a total of 98 race performances and 79 dust exposure assessments. Evidence of mild equine asthma was found in 80% (78/98) of BALF samples from 52/64 horses. For each percent increase in BALF mast cell and neutrophil proportions, speed figures were reduced by 2.9 (P = .012) and 1.4 (P = .046) points, respectively. Respirable dust concentration was associated with BALF neutrophil proportions (P = .015). Bronchoalveolar lavage fluid mast cell proportions were only associated with respirable β-glucan exposures (P = .030). Authors => Kathleen M. Ivester | Laurent L. Couëtil | George E. Moore published => First published: 17 September 2018 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.15226

Title => Effect of valacyclovir on EHV-5 viral kinetics in horses with equine multinodular pulmonary fibrosis Abstract => Background: Equine herpesvirus-5 is commonly isolated from the lungs of horses with EMPF, suggesting an etiological link. Valacyclovir is used empirically to treat EMPF; however, no data is available concerning its impact on EHV-5 viral kinetics. Objectives: To determine the effect of oral administration of valacyclovir on EHV-5 viral load measured by qPCR in blood, nasal secretions (NS) and BALF in horses with EMPF. Animals: Six horses diagnosed with EMPF. Methods: A prospective clinical trial was performed. Horses received 10 days of PO administered valacyclovir (loading dose 30 mg/kg, maintenance dose 20 mg/kg). Blood, NS, and BALF were collected for EHV-5 viral kinetics analyses during treatment. Blood and NS were collected every other day. BALF was collected on day 0 and day 10. Results: There was no statistical difference in median EHV-5 viral load between day 0 and day 10 for all samples tested. In blood median EHV-5 viral load was 7676 (range 575-39 781) on day 0 and 6822 (range 1136-18 635) glycoprotein B (gB) gene copies per million cells on day 10. For NS median EHV-5 viral load was 2.944 × 106 (range 184 691-3.394 × 109) on day 0 and 8.803 × 106 (range 251 186-9.868 × 108) gB gene copies per million cells on day 10. For BALF median EHV-5 viral load was 59,842 (range 61-315 655) on day 0 and 185 083 (range 3562-542 417) gB gene copies per million cells on day 10. Conclusions and Clinical Importance: Valacyclovir might not be an effective short-term antiviral treatment but efficacy in treatment of EMPF is unknown. Authors => Charlotte A. Easton-Jones | John E. Madigan | Samantha Barnum | Lara K. Maxwell | Sandra D. Taylor | Terry Arnesen | Nicola Pusterla published => First published: 17 September 2018 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.15230

Title => Effect of common storage temperatures and container types on urine protein : creatinine ratios in urine samples of proteinuric dogs Abstract => Background: Preanalytic protein adsorption to polymer and glass container surfaces may decrease urine protein concentration measurements and urine protein: creatinine ratios (UPC). Hypothesis/Objectives: Urine stored in PC or glass containers will have lower UPC than urine stored in HP containers. The specific objective was to determine whether clinically relevant differences in UPC would be detected after storage in glass, PC, or HP containers using common storage times and temperatures. Animals: Twelve client-owned dogs with proteinuria. Methods: Prospective, nonmasked study, divided into 2 phases. The first phase was a pilot study involving multiple (n = 5) measurements at each storage condition using 24-hours urine samples from 2 dogs with persistent renal proteinuria of different magnitude. The second phase used urine samples from 10 dogs with proteinuria of variable magnitude. Sample aliquots were stored in HP, PC, and glass containers at 24°C for 4 hours, 4°C for 12 hours, and −20°C for 72 hours. The UPC of each was measured after storage and compared with baseline. Results: Statistically significant but clinically irrelevant differences were found in phase 1. In phase 2, storage conditions did not affect urinary protein or creatinine concentrations or UPC. Conclusions and Clinical Importance: Collection and storage of canine urine samples in clean HP, PC, or glass containers at 24°C for 4 hours, 4°C for 12 hours, or −20°C for 72 hours is unlikely to result in clinically relevant decreases in measured UPC values. Authors => Patrick S. Moyle | Andrew Specht | Richard Hill published => First published: 17 September 2018 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.15232

Title => Risk factors associated with fecal shedding of Listeria monocytogenes by dairy cows and calves Abstract => Background: Listeria monocytogenes (LM) is an important foodborne pathogen affecting animals and humans. Listeriosis outbreaks in humans caused by consumption of unpasteurized dairy products are of serious concern. Objective: To determine risk factors associated with fecal shedding of LM in family dairy farms. Animals: Fecal samples were collected from cows and calves on 20 family dairy farms in 2-week intervals for a period of 1 year. Methods: Longitudinal study. LM was detected using qPCR. Univariate mixed effect model and multivariate analyses were performed to associate risk factors (dietary change, breed, mastitis, other diseases, antibiotic treatment, other treatments, heat index, and meteorological season) with fecal shedding of LM. Results: LM was isolated from all farms on at least 1 sampling day. The average yearly prevalence was 18.2% (98/540) and 8.4% (43/511) in cows and calves, respectively. Heat index (P = .05) and meteorological season (P = .04) affected fecal shedding of LM on a farm level. Meteorological season only influenced fecal shedding of LM in cows (P = .04), whereas heat index (P = .01) influenced fecal shedding of LM in calves. Spring season was identified as the major risk factor associated fecal shedding of LM on a farm level (P = .01) and in cows (P = .01). Dietary changes were associated with lower odds for fecal shedding of LM in calves (P < .01). Conclusions and Clinical Importance: Fecal shedding of LM is associated with environmental temperatures and the meteorological season. Farmers and veterinarians should use this information when implementing strategies to reduce risks for LM dissemination in animals and in the community. Authors => Petra Bandelj | Urska Jamnikar-Ciglenecki | Matjaz Ocepek | Rok Blagus | Modest Vengust published => First published: 17 September 2018 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.15234

Title => Randomized placebo controlled clinical trial of an enteric coated micro-pelleted formulation of a pancreatic enzyme supplement in dogs with exocrine pancreatic insufficiency Abstract => Background: Pancreatic enzyme supplements for the treatment of exocrine pancreatic insufficiency (EPI) in dogs can be uncoated or enteric coated. Enteric coated supplements might be advantageous. Hypothesis/Objectives: Enteric coated enzyme supplements are superior to uncoated supplements in dogs with clinical EPI. Animals: Eleven dogs with naturally occurring EPI that were apparently free from other diseases. Methods: Randomized, blinded, controlled cross-over clinical trial comparing a novel micro-encapsulated enteric coated enzyme supplement to a commercially available uncoated product in dogs with clinical EPI. Search of serum canine serum trypsin-like immunoreactivity concentration ≤ 2.5 µg/L in the Gastrointestinal Laboratory database was used to identify dogs with EPI. Results: There was no difference −4.46% (95% CI: −7.97%-–0.96%; P = .15) in the % acid hydrolysis fecal fat (primary outcome) between the enteric coated formulation (median: 11.8%; range 6.4%-17.0%) and the uncoated pancreatic enzyme replacement product (median: 17.5%; range: 5.2%-24.9%) in the 11 dogs that completed the study. Other variables did not differ between treatments. Conclusions and Clinical Importance: This study, which had low statistical power, did not detect a difference between formulations. Authors => Joseph Cyrus Parambeth | Geoffrey T. Fosgate | Jan S. Suchodolski | Jonathan A. Lidbury | Jörg M. Steiner published => First published: 17 September 2018 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.15235

Title => Clinical utility of currently available biomarkers in inflammatory enteropathies of dogs Abstract => Authors => Romy M. Heilmann | Jörg M. Steiner published => First published: 17 September 2018 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.15247

Title => Effect of prespecified therapy escalation on plasma NT-proBNP concentrations in dogs with stable congestive heart failure due to myxomatous mitral valve disease Abstract => Background: Treatment targeted to achieve reduction in N-terminal pro-B-type natriuretic peptide (NT-proBNP) improves outcomes in human congestive heart failure (CHF) patients. Hypothesis: A pre-specified therapeutic algorithm that increased diuretic or pimobendan usage will reduce plasma NT-proBNP concentrations in dogs with CHF secondary to myxomatous mitral valve disease (MMVD). Animals: Twenty-six dogs with clinically stable CHF secondary to MMVD. Methods: Prospective, controlled before-and-after study. Dogs were examined up to 3 times over 21 days. Treatment was prescribed based on NT-proBNP as follows: <1500 pmol/L at baseline, no treatment adjustment at any point during the study (group 1); ≥1500 pmol/L and creatinine ≤3.0 mg/dL at baseline or SC visits, treatment escalated according to the algorithm (group 2); ≥1500 pmol/L at baseline, no treatment adjustment (group 3). Results: N-terminal pro-B-type natriuretic peptide decreased significantly in group 2 (mean change = −1736 pmol/L (95% CI, −804 to −2668), P < .001) but not in groups 1 or 3 (623 pmol/L [–631 to 1877 pmol/L], P = .14 and 685 pmol/L [–304 to 1068 pmol/L], P = .46, respectively). Serum BUN and creatinine did not change significantly between visit 0 and visit 2 in group 1 (median = 23 mg/dL [range 13-32] versus 19 mg/dL [12-38], P = .72 and 1.15 mg/dL [0.70-1.40] versus 0.95 mg/dL [0.70-1.10], P = .10, respectively) or group 2 (28 mg/dL [18-87] versus 43.5 mg/dL [21-160], P = .092 and 1.10 mg/dL [0.90-2.50] versus 1.55 mg/dL [0.90-3.30], P = .062, respectively). Conclusions and Clinical Importance: Use of this treatment escalation algorithm allows effective targeting of treatment for CHF in dogs against an objective criterion. Authors => Melanie J. Hezzell | Chloë L. Block | Danielle S. Laughlin | Mark A. Oyama published => First published: 14 September 2018 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.15228

Title => Newborn foal with atypical myopathy Abstract => Authors => Radana Karlíková | Jitka Široká | Marek Mech | David Friedecký | Hana Janečková | Lucie Mádrová | Františka Hrdinová | Zuzana Drábková | Olga Dobešová | Tomáš Adam | Petr Jahn published => First published: 14 September 2018 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.15236

Title => Evaluation of point-of-care thoracic ultrasound and NT-proBNP for the diagnosis of congestive heart failure in cats with respiratory distress Abstract => Background: The diagnosis of congestive heart failure (CHF) in cats is challenging. Point-of-care (POC) thoracic ultrasound and NT-proBNP testing are emerging tools that may aid in diagnosis. Hypothesis/Objectives: To assess the diagnostic accuracy of POC lung ultrasound (LUS), focused cardiac ultrasound (FCU), and NT-proBNP in predicting a final diagnosis of CHF. Animals: Fifty-one cats in respiratory distress. Methods: Blood NT-proBNP, LUS, and FCU evaluating left atrial (LA) size and presence of pericardial effusion (PCEFF) were performed in all cats. Lung ultrasound findings including pleural effusion (PLEFF), number of B-lines, and sub-pleural abnormalities were noted. Medical records were evaluated for final diagnosis. Results: Thirty-three of 51 (65%) cats were diagnosed with CHF. Lung ultrasound and blood NT-proBNP were significant predictors of CHF in a multivariate model. The LUS criterion that maximized accuracy for CHF diagnosis was presence of >1 site strongly positive for B-lines (>3 B-lines per site), resulting in sensitivity of 78.8%, specificity of 83.3%, and area under the curve (AUC) of 0.833. Subjective LA enlargement was 97.0% sensitive and 100% specific for CHF (AUC 0.985). Presence of PCEFF also was 100% specific, but only 60.6% sensitive, for CHF (AUC 0.803). A positive blood NT-proBNP test was 93.9% sensitive and 72.2% specific for the diagnosis of CHF (AUC 0.831). Conclusions and Clinical Importance: Point-of-care diagnostic techniques of LUS, FCU, and NT-proBNP are useful to diagnose CHF in cats with respiratory distress. Authors => Jessica L. Ward | Gregory R. Lisciandro | Wendy A. Ware | Austin K. Viall | Brent D. Aona | Kari A. Kurtz | Yamir Reina-Doreste | Teresa C. DeFrancesco published => First published: 14 September 2018 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.15246

Title => Atrioventricular accessory pathways in 89 dogs: Clinical features and outcome after radiofrequency catheter ablation Abstract => Background: Atrioventricular accessory pathways (APs) in dogs have been reported rarely. Data regarding clinical presentation and long-term outcome after radiofrequency catheter ablation (RFCA) are limited. Hypothesis/Objectives: To study clinical features, electrophysiologic characteristics, and outcome of RFCA in dogs with APs. Animals: Eighty-nine dogs presented consecutively for RFCA of APs. Methods: Case series. Results: Labrador retrievers (47.2% of dogs) and male dogs (67.4% of dogs) were most commonly affected. Labrador retrievers were more likely to be male than non-Labrador breeds (P = .043). Clinical signs were nonspecific and most commonly included lethargy and gastrointestinal signs. Concealed APs were more prevalent in Labrador retrievers than other breeds (P = .001). Right-sided APs (91.7%) predominated over left-sided (8.3%). Tachycardia-induced cardiomyopathy (TICM) occurred in 46.1% of dogs, with complete resolution or substantial improvement noted on one-month postablation echocardiograms. Radiofrequency catheter ablation successfully eliminated AP conduction long term in 98.8% of dogs in which it was performed. Complications occurred in 5/89 dogs. Recurrence in 3 dogs was eliminated long term with a second procedure. Clinical Importance/Conclusions: Accessory pathways are challenging to recognize in dogs because of nonspecific clinical signs, frequency of concealed APs that show no evidence of their presence during sinus rhythm, and intermittent occurrence of tachyarrhythmias resulting from APs. Tachycardia-induced cardiomyopathy commonly occurs with AP-mediated tachycardias and should be considered in any dog presenting with a dilated cardiomyopathic phenotype because of its good long-term prognosis with rhythm control. Radiofrequency catheter ablation is a highly effective method for eliminating AP conduction and providing long-term resolution. Authors => Kathy N. Wright | Chad E. Connor | Holly M. Irvin | Timothy K. Knilans | Dawn Webber | Philip H. Kass published => First published: 14 September 2018 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.15248

Title => Echocardiographic evaluation of the right ventricular dimension and systolic function in dogs with pulmonary hypertension Abstract => Background: Right ventricular (RV) enlargement and dysfunction are associated with prognosis in humans with pulmonary hypertension (PH). Hypothesis/Objectives: To assess RV size and systolic function in dogs with PH and to determine if they are associated with disease severity and right-sided congestive heart failure (R-CHF). Animals: 89 dogs with PH and 74 healthy dogs. Methods: Prospective observational study. PH was classified according to the tricuspid regurgitation pressure gradient. RV end-diastolic area (RVEDA) index was calculated as RVEDA divided by body surface area. RV systolic function was assessed with the tricuspid annular plane systolic excursion (TAPSE) and the RV fractional area change (FAC) normalized for body weight (TAPSEn and FACn, respectively). Results: RVEDA index was higher in dogs with moderate PH (10.8 cm2/m2; range, 6.2-14.4 cm2/m2) and severe PH (12.4 cm2/m2; range, 7.7-21.4 cm2/m2) than in those with mild PH (8.4 cm2/m2; range, 4.8-11.6 cm2/m2) and control dogs (8.5 cm2/m2; range, 2.8-11.6 cm2/m2; P < .001). RVEDA index was significantly higher in dogs with R-CHF (13.7 cm2/m2; range, 11.0-21.4 cm2/m2) than in dogs without R-CHF (9.4 cm2/m2; range, 4.8-17.1 cm2/m2; P < .001). The severity of tricuspid regurgitation (TR) was the only independent predictor of the RVEDA index (P < .001). TAPSEn and FACn were not significantly different among varying degrees of PH severity and between dogs with and without R-CHF. Conclusions and Clinical Importance: The RVEDA index can be used to evaluate RV size in dogs. It can provide additional information in dogs with PH and predict R-CHF. Severity of TR is the main determinant of RV enlargement in dogs with PH. Authors => Tommaso Vezzosi | Oriol Domenech | Giulia Costa | Federica Marchesotti | Luigi Venco | Eric Zini | Maria Josefa Fernández del Palacio | Rosalba Tognetti published => First published: 14 September 2018 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.15253

Title => Utility of C-reactive protein and serum amyloid A in the diagnosis of equine protozoal myeloencephalitis Abstract => Background: Accurate antemortem EPM diagnosis requires evidence of intrathecal antibody production. Some advocate the use of acute phase proteins in addition to serology, which alone results in substantial false positives. Hypothesis/Objectives: The purpose of this study was to determine if serum C-reactive protein (CRP) or serum amyloid A (SAA) concentrations were elevated in cases of equine protozoal myeloencephalitis (EPM) compared to other neurological diseases. Animals: 25 clinical cases of equine neurological disease: EPM (10), cervical vertebral stenotic myelopathy (CVSM) (10), neuroborreliosis (2), equine motor neuron disease (1), degenerative myelopathy (1), and leukoencephalomalacia (1). Methods: Serum and CSF CRP and SAA were measured. Selection criteria included neurologic disease, antemortem diagnosis of EPM or CVSM, or postmortem diagnosis of EPM, CVSM, or other neurologic disease, and availability of serological results and archived samples for testing. Results: Serum SAA and serum CRP levels were generally undetectable or low in horses with EPM (median CRP ≤0.1 mg/L, ≤0.1-14.4 mg/L; median SAA ≤0.1 mg/L, ≤0.1-6.11 mg/L) and CVSM (median CRP ≤0.1, ≤0.1-2.41 mg/L; median SAA ≤0.1mg/L, ≤0.1-13.88 mg/L). CSF CRP and SAA for horses with EPM (median CRP 3.35 mg/l, 0.19-13.43 mg/l; median SAA ≤0.1 mg/L, ≤0.1-2.4 mg/L) and CVSM (median CRP 4.015 mg/L, 0.16-9.62 mg/L; median SAA 0.62 mg/L, ≤0.1-2.91 mg/L) were also undetectable or low. Kruskal–Wallis test showed no statistically significant differences between serum CRP (P = .14), serum SAA (P = .79), spinal fluid CRP (P = .65), or spinal fluid SAA between horses with EPM and CVSM (P = .52). Conclusion: Neither SAA nor CRP in serum or CSF aid diagnosis of EPM. Authors => Neil S. Mittelman | Darko Stefanovski | Amy L. Johnson published => First published: 14 September 2018 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.15254

Title => Seizure occurrence in dogs under primary veterinary care in the UK: prevalence and risk factors Abstract => Background: Primary-care veterinary clinical records can offer data to determine generalizable epidemiological data on seizures occurrence in the dog population. Objectives: To identify and examine epidemiologic characteristics of seizure occurrence in dogs under primary veterinary care in the UK participating in the VetCompass™ Programme. Animals: 455,553 dogs in VetCompass™’. Methods: A cross-sectional analysis estimated the 1-year period prevalence and risk factors for dogs with seizures during 2013. Results: The overall 1-year period prevalence for dogs having at least one seizure during 2013 was 0.82% (95% CI 0.79-0.84). Multivariable modelling identified breeds with elevated odd ratios [OR] compared with the Labrador Retriever (e.g. Pug OR: 3.41 95% CI 2.71-4.28, P < 0.001). Males had higher risk for seizures (Male/Entire OR: 1.47 95% CI 1.30–1.66; Male/Neutered OR: 1.34 95% CI 1.19–1.51) compared to entire females. Age (3.00 - ≤ 6.00 OR: 2.13 95% CI 1.90-2.39, P < 0.001, compared to animals aged 0.50–≤ 3.00 years), and bodyweight (≥ 40.00kg, OR: 1.24 95% CI 1.08–1.41, P = 0.002, compared to animals weighing < 10.0 kg) were identified as risk factors for seizures. Conclusion and clinical Importance: Seizures are a relatively common clinical finding in dogs. The results for breed, age, sex and bodyweight as risk factors can assist veterinarians in refining differential diagnosis lists for dogs reported with behaviors that may have been seizures. In addition, the prevalence values reported here can support pharmacovigilance with baseline data from the overall population. Authors => Alexander Erlen | Heidrun Potschka | Holger A. Volk | Carola Sauter-Louis | Dan G. O'Neill published => First published: 14 September 2018 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.15290

Title => Variability of serum concentrations of cystatin C and urinary retinol-binding protein, neutrophil gelatinase-associated lipocalin, immunoglobulin G, and C-reactive protein in dogs Abstract => Background: Markers of kidney dysfunction and damage have potential to detect chronic kidney disease (CKD) in early stages. However, data on long-term variation of these markers in healthy dogs is lacking and is crucial for the interpretation of results. Hypothesis/Objectives: To determine temporal variations of serum cystatin C (sCysC) and urinary retinol-binding protein (uRBP), neutrophil gelatinase-associated lipocalin (uNGAL), immunoglobulin G (uIgG), and C-reactive protein (uCRP) in healthy dogs. Animals: Eight clinically healthy adult Beagles were evaluated. Methods: Longitudinal observational study. Serum cystatin C was determined by particle-enhanced nephelometric immunoassay. Urinary retinol-binding protein, uNGAL, uIgG and uCRP were determined by ELISA and concentrations were indexed to urinary creatinine. Within- and between-dog variance components (VC) and within-dog coefficients of variation (CV) were determined from blood and urine collected at eight time points over 1.5 years. Results: Urinary C-reactive protein (uCRP) concentrations were consistently below the detection limit (5.28 ng/mL). Mean ± within-dog standard deviation for sCysC, uRBP/c, uNGAL/c and uIgG/c was 0.15 ± 0.01 mg/L, 0.09 ± 0.03 mg/g, 2.32 ± 2.03 μg/g and 12.47 ± 10.98 mg/g, respectively. Within-dog CV for sCysC, uRBP/c, uNGAL/c and uIgG/c was 8.1%, 33.7%, 87.2% and 88.1%, respectively. Conclusions and clinical importance: Serum cystatin C, uRBP/c, uNGAL/c and uIgG/c exhibit a wide range of long-term within-dog variability. Researchers and veterinarians might need to take this into account when interpreting their results. To assess their diagnostic and predictive ability, future studies need to establish reference ranges for healthy dogs and dogs with CKD. Authors => D.J.X. Liu | E. Meyer | B.J.G. Broeckx | S. Daminet | J.R. Delanghe | E. Stock | E. Bogaerts | M. Hesta | K. Vanderperren published => First published: 14 September 2018 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.15293

Title => Presumptive non-cirrhotic bleeding esophageal varices in a dog Abstract => Authors => Marc Myers | Peter V. Scrivani | Kenneth W. Simpson published => First published: 14 September 2018 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.15303

Title => Survival associated with cerebrospinal fluid analysis in downer adult dairy cows: A retrospective study (2006-2014) Abstract => Background: Threshold values for total nucleated cell count (TNCC) and protein concentration in cerebrospinal fluid (CSF) of downer dairy cows suggestive of a spinal cord lesion were recently published. Objectives: Determine short- and long-term survival of downer cows that underwent CSF analysis using the reported threshold values. Evaluate the prognostic value of these threshold values to predict short- and long-term survival. Animals: Two hundred and fourteen downer adult dairy cows that underwent CSF analysis during hospitalization at the Centre Hospitalier Universitaire Vétérinaire (CHUV) of the Université de Montréal. Methods: Retrospective study. Medical records of downer adult dairy cows presented to the hospital between January 2006 and October 2014 for which CSF analysis results were available were studied. Short-term (discharge from hospital) and long-term (completion of lactation) survival were determined and compared in accordance with CSF TNCC and protein concentration, using a Chi-square test. Results: Cows with CSF TNCC and/or protein concentration above the threshold values had a significantly lower short-term survival rate (P = .02). The odds of nonsurvival of cows with one or both CSF values above the threshold values was 2.16 times higher than the odds for cows with values under the threshold values. CSF TNCC >4.5 cells/μL had sensitivity and specificity of 17.3% (95% CI: 10.7%-25.7%) and 92.3% (95% CI: 85.4%-96.6%), respectively, for predicting short-term nonsurvival. CSF protein concentration >0.39 g/L had sensitivity and specificity of 20.9% (95% CI: 13.7%-29.7%) and 91.4% (95% CI: 84.2%-96.0%), respectively. Conclusions: CSF analysis above threshold values used in this study is associated with increased odds of short-term nonsurvival. Authors => Marie-Ève Bilodeau | Damien Achard | David Francoz | Carolyn Grimes | André Desrochers | Sylvain Nichols | Marie Babkine | Gilles Fecteau published => First published: 14 September 2018 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.15305

Title => Hepatocyte expression and prognostic importance of senescence marker p21 in liver histopathology samples from dogs with chronic hepatitis Abstract => Background: Chronic hepatitis (CH) occurs commonly in dogs but is associated with a variable and largely unpredictable prognosis. p21, a cell-cycle inhibitor and marker of cellular senescence, is upregulated in human liver disease and is a better prognostic marker than histological or clinical scoring systems. Objective: To quantify hepatocyte p21 immunopositivity in histopathology samples from dogs with CH and determine its association with outcome. Animals: Twenty-six client-owned dogs with histologically confirmed CH, and 15 dogs with normal liver histology. Methods: Medical records and liver histopathology samples were retrospectively reviewed to identify cases of CH. Immunohistochemistry for p21 was performed on all samples and hepatocyte immunopositivity was visually quantified. Relationships between p21 and dog age and dog survival time were statistically evaluated. Results: Hepatocyte p21 immunopositivity in dogs with CH was high (median percentage of positive hepatocytes: 90%, range: 20%-98%) and exceeded 70% in 23/26 cases with no association with age. In control dogs, p21 immunopositivity was low (≤15% positive hepatocytes in 12/15 cases) and was positively correlated with age (rs = 0.63; P = .011). Dogs with p21 immunopositivity exceeding 91.8% (upper tercile) had significantly shorter survival compared to dogs with less than 88.9% immunopositivity (lowest tercile; 218 versus 874 days, P = .006). Increasing hepatocyte p21 immunopositivity was significantly negatively associated with survival time (HR 4.12; 95% CI 1.34-12.63; P = .013). Conclusions and Clinical Importance: Marked p21 immunopositivity in dogs with CH might be indicative of widespread hepatocellular senescence. A significant association with survival time also suggests a potential value for p21 quantification in determining prognosis. Authors => Andre J. Kortum | Emilie A. Cloup | Tim L. Williams | Fernendo Constantino-Casas | Penny J. Watson published => First published: 22 August 2018 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.15238

Title => Lipid peroxidation biomarkers for evaluating oxidative stress in equine neuroaxonal dystrophy Abstract => Background: Equine neuroaxonal dystrophy/equine degenerative myeloencephalopathy (eNAD/EDM) is a neurodegenerative disorder affecting genetically predisposed foals maintained on an α-tocopherol (α-TOH) deficient diet. Currently no antemortem diagnostic test for eNAD/EDM is available. Hypothesis: Because α-TOH deficiency is associated with increased lipid peroxidation, it was hypothesized that F2-isoprostanes (F2IsoP), F4-neuroprostanes (F4NP) and oxysterols derived from free radical oxidation would be increased in the cerebrospinal fluid (CSF) and neural tissue of eNAD/EDM affected horses and could serve as potential biomarkers for disease. Animals: Isoprostane Study A: 14 Quarter horse foals (10 healthy foals and 4 eNAD/EDM affected foals) at 1 and 6 months of age. Isoprostane Study B: 17 eNAD/EDM affected and 10 unaffected horses ≥ 1-4 years of age. Oxysterol study: eNAD/EDM affected (n = 14, serum; n = 11, CSF; n = 10, spinal cord [SC]) and unaffected horses 1-4 years of age (n = 12, serum; n = 10, CSF; n = 7, SC). Procedures: Cerebrospinal fluid [F2IsoP] and [F4NP] were assessed using gas chromatography-negative ion chemical ionization mass spectrometry. Serum, CSF, and cervical SC [oxysterols] were quantified using high performance liquid chromatography mass spectrometry. Results were compared with respective α-TOH concentrations. Results: Spinal cord [7-ketocholesterol], [7-hydroxycholesterol], and [7-keto-27-hydrocholesterol] were higher in eNAD/EDM horses whereas [24-ketocholesterol] was lower. No significant difference was found in CSF [F2IsoP] and [F4NP], serum [oxysterols] and CSF [oxysterols] between eNAD/EDM affected and unaffected horses. No correlation was found between [F2IsoP], [F4NP], or [oxysterols] and respective [α-TOH]. Conclusions and Clinical Importance: In the SC, targeted markers of cholesterol oxidation were significantly increased in horses with eNAD/EDM. Authors => Carrie J. Finno | Krista E. Estell | Laramie Winfield | Scott Katzman | Matthew H. Bordbari | Erin N. Burns | Andrew D. Miller | Birgit Puschner | Cecilia K. Tran | Libin Xu published => First published: 22 August 2018 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.15241

Title => Inter-rater agreement and reliability of thoracic ultrasonographic findings in feedlot calves, with or without naturally occurring bronchopneumonia Abstract => Background: Thoracic ultrasonography (TUS) can be used to assess the extent and severity of lung lesions associated with bronchopneumonia (BP) in feedlot cattle. Hypothesis/Objectives: To assess inter-rater agreement and reliability of TUS findings in feedlot cattle, with or without naturally occurring BP. Animals: Feedlot steers with (n = 210) or without (n = 107) clinical signs of BP that were assessed by TUS in a previous case-control study. Methods: A random sample of 50 TUS videos (16-s duration) were scored by 6 raters with various levels of TUS expertise. Lung consolidation, comet tail artifacts, pleural irregularity and effusion were scored. Inter-rater agreement was assessed using raw percentage of agreement (Pa), Cohen's and Fleiss’ Kappa (κ), and Gwet agreement coefficient (AC1). Intra-class correlation (ICC) was determined for variables with continuous measurements (mixed factorial design). Results: Median (interquartile range [IQR]) Pa were 0.84 (0.80-0.89), 0.82 (0.80-0.87), 0.62 (0.53-0.67), and 0.82 (0.75-0.86) for presence of lung consolidation, comet tails, pleural irregularity, and pleural effusion, respectively. For the same lesions, Fleiss κ (95% confidence intervals [CI]) were 0.67 (0.49-0.86), 0.56 (0.33-0.80), 0.20 (−0.05 to 0.44), and 0.36 (0.10-0.61), respectively. AC1 were 0.68 (0.51-0.86), 0.73 (0.58-0.89), 0.21 (−0.01 to 0.44), and 0.71 (0.51-0.92), respectively. Moderate reliability was found among raters for all quantitative variables (ICC ranged from 0.52 to 0.70). Conclusions and Clinical Importance: Inter-rater agreement was good for presence of lung consolidation, comet tails and pleural effusion (based on Pa and AC1) but was slight to poor for pleural irregularity. Authors => S. Buczinski | C. Buathier | A.M. Bélanger | H. Michaux | N. Tison | E. Timsit published => First published: 22 August 2018 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.15257

Title => Erratum Abstract => None Abstract Authors => published => First published: 22 August 2018 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.15286

Title => Time-dependent antiarrhythmic effects of flecainide on induced atrial fibrillation in horses Abstract => Background: Pharmacological treatment of atrial fibrillation (AF) in horses can be challenging because of low efficacy and adverse effects. Flecainide has been tested with variable efficacy. Objective: To test whether the efficacy of flecainide is dependent on AF duration. Animals: Nine Standardbred mares. Methods: Factorial study design. All horses were instrumented with a pacemaker and assigned to a control or an AF group. On day 0, all horses were in sinus rhythm and received 2 mg/kg flecainide IV. Atrial fibrillation subsequently was induced in the AF group by pacemaker stimulation. On days 3, 9, 27, and 55, flecainide was administered to all horses, regardless of heart rhythm. Results: All horses in AF cardioverted to sinus rhythm on days 3 and 9. On day 27, 5/6 horses cardioverted, whereas only 2/6 cardioverted on day 55. The time from the start of flecainide infusion to cardioversion (range, 3–185 min, log transformed) showed linear correlation with the cumulative duration of AF (r2 = .80, P < .0001). Flecainide induced abnormal QRS complexes in 4/6 AF horses and 1/3 controls. A positive correlation was found between heart rate before flecainide infusion and number of abnormal QRS complexes (0.14, P < .05). One horse suffered from cardiac arrest and died after flecainide infusion. Conclusions and Clinical Importance: Flecainide is effective for cardioversion of short-term induced AF, but the effect decreases with AF duration. Controlling heart rate may minimize adverse effects caused by flecainide, but the drug should be used with great caution. Authors => Helena Carstensen | Eva Z. Hesselkilde | Merle Fenner | Ameli V. Loft-Andersen | Mette Flethøj | Jørgen K. Kanters | Stefan M. Sattler | Jacob Tfelt-Hansen | Steen Pehrson | Thomas Jespersen | Rikke Buhl published => First published: 22 August 2018 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.15287

Title => Serum concentrations of lipid-soluble vitamins in dogs with exocrine pancreatic insufficiency treated with pancreatic enzymes Abstract => Background: In humans, exocrine pancreatic insufficiency (EPI) is associated with deficiencies in lipid-soluble vitamins. Little is reported regarding lipid-soluble vitamin status in dogs with EPI. Hypothesis/Objectives: Compare serum concentrations of retinol, 25-hydrocholecalciferol (25OHD), and α-tocopherol among dogs with EPI, those with subclinical EPI (sEPI), and healthy dogs. Detect associations between serum concentrations of lipid-soluble vitamins and residual clinical signs in treated dogs with EPI and sEPI. Animals: Twenty dogs with EPI and five dogs with sEPI receiving pancreatic enzyme replacement therapy. Ten healthy dogs sampled before and after 10 days of pancreatic enzyme supplementation. Methods: Case-control study. Serum retinol and α-tocopherol concentrations were measured by high-performance liquid chromatography. Serum 25OHD concentrations were measured by radioimmunoassay. Results: Serum retinol concentration was significantly lower in dogs with EPI (median, 490 ng/mL; range, 322-990 ng/mL) and serum α-tocopherol concentration was significantly lower in dogs with EPI (median, 11.51 μg/L; range, 4.8-27.1 μg/L) and sEPI (median, 12.66 μg/L; range, 10.21-21.03 μg/L) compared with healthy dogs (median, 1203 ng/mL; range, 637-1768 ng/mL and median, 43.54 μg/L; range, 34.26-53.97 μg/L, respectively). Dogs with weight loss had significantly lower 25OHD (mean, 243.50 nmol/L; standard deviation [SD], 3.54 nmol/L) than dogs with stable weight (314.0 nmol/L; SD, 138.38 nmol/L). Conclusions and Clinical Importance: Altered homeostasis of lipid-soluble vitamins is present in dogs with EPI and sEPI, despite enzyme replacement therapy. Additional studies are needed to determine the clinical relevance of these findings and the therapeutic potential of lipid-soluble vitamin supplementation in dogs with EPI and sEPI. Authors => Patrick C. Barko | David A. Williams published => First published: 22 August 2018 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.15292

Title => Effect of insulin treatment on circulating insulin-like growth factor I and IGF-binding proteins in cats with diabetes mellitus Abstract => Background: Insulin-like growth factor-I (IGF-I) is used to screen for acromegaly in diabetic cats. In humans, most circulating IGF-I forms ternary complexes (TC) with IGF-binding protein (IGFBP-3) and an acid-labile subunit. Compared to humans, the amount of TC in cats is more variable. Insulin-like growth factor-I concentrations are reported to increase during insulin treatment, more rapidly in cats achieving remission. Objectives: To investigate (i) factors associated with circulating IGF-I concentrations, including IGFBP-profiles (ii) effect of insulin treatment on IGF-I concentrations and (iii) IGF-I as prognostic marker of diabetes mellitus remission. Animals: Thirty-one privately owned diabetic cats of which 24 were followed 1 year, and 13 healthy cats. Methods: Prospective study. Serum insulin, IGF-I, glucose, and fructosamine concentrations were measured. IGF-binding forms were determined by chromatography in 14 diabetic and 13 healthy cats; and IGF-I, IGF-II, IGFBP-3, and IGFBP-5 by mass spectrometry in 3 cats achieving remission. Results: Insulin-like growth factor-I median (interquartile range) before start of insulin treatment was 300 (160-556) ng/mL. Insulin-like growth factor-I was positively associated with TC (P < .0001) and endogenous insulin (P = .005) and negatively associated with fructosamine (P < .0001). Median IGF-I was higher 2-4 weeks after start of insulin treatment compared with baseline (300 versus 670 ng/mL, P = .0001) and predicted future remission (P = .046). In cats that went into remission, the amount of TC and IGFBP-3 increased, suggesting increase in IGF-I is dependent on TC formation. Conclusions: Insulin treatment should be accounted for when interpreting IGF-I in diabetic cats. Insulin-like growth factor-I 2-4 weeks after initiation of insulin treatment shows promise as prognostic marker for remission in diabetic cats. Authors => Emma M. Strage | Mårten Sundberg | Bodil S. Holst | Mikael Andersson Franko | Margareta Ramström | Tove Fall | Moira Lewitt published => First published: 16 August 2018 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.15243

Title => Characteristics of Dogs with Biofilm-Forming Escherichia Coli Urinary Tract Infections Abstract => Background: Bacterial urinary tract infections (UTIs) are common in companion animals. Increasing awareness of biofilm-forming bacteria raises concern regarding the appropriate diagnosis, treatment, and prognosis of UTIs associated with these organisms. Hypothesis/Objectives: To (1) describe the population of dogs with UTIs associated with biofilm-forming Escherichia coli and (2) determine whether or not clinical differences exist between dogs with biofilm-forming E. coli UTIs and dogs with nonbiofilm-forming E. coli UTIs. We hypothesized that there would be no difference in the population characteristics, but that biofilm-formation would be more prevalent in dogs with chronic, complicated, and asymptomatic UTIs. Animals: Seventy-six client-owned dogs with E. coli UTIs, divided into 2 groups based on the biofilm-forming capability of stored bacterial isolates as assessed by the crystal violet assay. Methods: Retrospective cross-sectional study. Medical records of the affected dogs were reviewed and their population and infection characteristics were compared. Results: Most (52.6%) E. coli isolates were capable of forming biofilms. Biofilm-forming E. coli had a lower likelihood (P < .001) of multidrug resistance than did nonbiofilm-forming E. coli. No statistically significant differences were identified between the population or infection characteristics of the 2 groups of dogs. Conclusions and Clinical Importance: Escherichia coli isolated from canine urinary tracts are frequently capable of forming biofilms. Because no reliable clinical features allowed exclusion of biofilm formation, the potential for biofilm formation should be considered whenever E. coli UTI is diagnosed. The association of antibiotic resistance and biofilm potential may affect treatment of UTIs, but additional investigation is warranted. Authors => Zachary T. Kern | Megan E. Jacob | Jessica M. Gilbertie | Shelly L. Vaden | Sara K. Lyle published => First published: 07 August 2018 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.15231

Title => A prospective, randomized, double-blind, placebo-controlled pilot study of sacubitril/valsartan (Entresto) in dogs with cardiomegaly secondary to myxomatous mitral valve disease Abstract => Background: The effects of sacubitril/valsartan (S/V) on the renin-angiotensin-aldosterone system (RAAS) in dogs with cardiomegaly secondary to myxomatous mitral valve disease (MMVD) are currently unknown. Objectives: To determine the pharmacodynamic effects of S/V on the RAAS, natriuretic peptide concentrations, systolic arterial pressure (SAP), tests of renal function, and serum electrolyte concentrations in dogs with cardiomegaly secondary to MMVD. Animals: Thirteen client-owned dogs weighing 4-15 kg with American College of Veterinary Internal Medicine (ACVIM) Stage B2 MMVD. Methods: Prospective, randomized, double-blind, placebo-controlled pilot study of S/V in dogs with ACVIM Stage B2 MMVD. Results: Thirteen dogs were recruited: S/V (n = 7) and placebo (n = 6). The median percentage increase in urinary aldosterone to creatinine ratio (UAldo : C) between day 0 and day 30 was significantly lower in the S/V group (12%; P = .032) as compared with the placebo group (195%). The median percentage decrease of NT-proBNP concentration from day 0 to day 30 was not statistically different between groups (P = .68). No statistical differences were seen in echocardiographic, thoracic radiographic, SAP, or serum biochemical test results measured at any time point between groups. No adverse events were observed for dogs in either group. Conclusion and Clinical Importance: Sacubitril/valsartan may provide a new pharmaceutical method to effectively inhibit the RAAS in dogs with ACVIM Stage B2 MMVD. Authors => Daniel K. Newhard | SeungWoo Jung | Randolph L. Winter | Sue H. Duran published => First published: 07 August 2018 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.15240

Title => Presumed Neuroglycopenia Caused by Severe Hypoglycemia in Horses Abstract => Background: Neuroglycopenia refers to a shortage of glucose in the brain resulting in neuronal dysfunction and death if left untreated. Presumed neuroglycopenia has not been described in horses. Objective: To report neurological signs in horses with presumed neuroglycopenia as the result of severe hypoglycemia. Animals: Ninety horses (hours to 28 years of age) diagnosed with hypoglycemia (blood glucose concentration < 75 mg/dL [< 4.2 mmol/L]). Methods: Retrospective study. Electronic medical records were searched. Signalment, history, complaint, clinical signs, laboratory findings including CSF analysis, electroencephalogram, clinical or definitive diagnosis, and outcome were recorded. Kruskal-Wallis analysis of variance and logistic regression were used to investigate association between blood glucose concentration and data extracted. Statistical significance was set at P < 0.05. Results: Thirty-eight and 52 horses had mild (50-74 mg/dL [2.8-4.1 mmol/L]), and severe hypoglycemia (< 50 mg/dL [< 2.8 mmol/L]), respectively. Most common causes of hypoglycemia included liver and gastrointestinal (40%) disease, sepsis (33%), neoplasia (7%), and insulin-induced (4%). Most common neurologic deficits included obtundation (100%), seizures (42%), and disorientation (22%). CSF-glucose was severely low (mean 2.5 mg/dL [0.1 mmol/L], median 0 mg/dL). Paroxysmal discharges in support of seizures were identified in the occipital (visual) and parietal (closest to temporal-auditory) cortical regions upon EEG examination (8/8 horses). Conclusions and clinical importance: Neuroglycopenia is presumed to occur in horses as the result of severe hypoglycemia. Subclinical seizures, and intermittent blindness and deafness of cortical origin can occur. Severe altered state of consciousness and seizures can be observed at a blood glucose cut-off value of < 42 mg/dL (< 2.3 mmol/L). Authors => M. Aleman | L. R. R. Costa | C. Crowe | P. H. Kass published => First published: 07 August 2018 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.15245

Title => Efficacy of tamoxifen for the treatment of severe equine asthma Abstract => Background: Tamoxifen, a selective estrogen receptor modulator, decreased airway neutrophilia and improved clinical signs in an experimental model of equine asthma, and induced neutrophilic apoptosis in vitro. Hypothesis/Objectives: Tamoxifen reduces airway neutrophilia and improves lung function in severe asthmatic horses. Animals: Twelve severe asthmatic horses from a research herd. Methods: Randomized controlled blinded study design. The effects of a 12-day oral treatment with tamoxifen (0.22 mg/kg, q24h) or dexamethasone (0.06 mg/kg, q24h) on lung function, endoscopic tracheal mucus score and bronchoalveolar lavage fluid cytology were compared. Results: Tamoxifen significantly improved the pulmonary resistance (RL; mean reduction of 1.15 cm H2O/L/s [CI: 0.29-2.01, P = .007] on day 13), but had no effect on the other variables evaluated. Dexamethasone normalized lung function (mean reduction of RL of 2.48 cm H2O/L/s [CI: 1.54-3.43, P < .0001] on day 13), without affecting airway neutrophilia. Conclusions and Clinical Importance: Results of this study do not support the use of tamoxifen at the dose studied as an antineutrophilic medication in the treatment of asthmatic horses in chronic exacerbation. Authors => Sophie Mainguy-Seers | Khristine Picotte | Jean-Pierre Lavoie published => First published: 07 August 2018 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.15289

Title => Relationship of the mucosal microbiota to gastrointestinal inflammation and small cell intestinal lymphoma in cats Abstract => Background: The gastrointestinal (GI) microbiota in healthy cats is altered in IBD. Little research has been performed to identify whether specific bacterial groups are associated with small cell GI lymphoma (LSA). Hypothesis: Mucosal bacteria, including Enterobacteriaceae and Fusobacterium spp., are abundant in intestinal biopsies of cats with small cell GI LSA compared to cats with IBD. Animals: Fourteen cats with IBD and 14 cats with small cell GI LSA. Methods: Retrospective case control study. A search of the medical records was performed to identify cats diagnosed with IBD and with GI LSA. Bacterial groups identified by FISH in GI biopsies were compared between cohorts and correlated to CD11b+ and NF-κB expression. Results: Fusobacterium spp. (median; IQR bacteria/region) were higher in cats with small cell GI LSA in ileal (527; 455.5 – 661.5; P = .046) and colonic (404.5; 328.8 – 455.5; P = .016) adherent mucus, and combined colonic compartments (free mucus, adherent mucus, attaching to epithelium) (8; 0 – 336; P = .017) compared to cats with IBD (ileum: 67; 31.5 – 259; colon: 142.5; 82.3 – 434.5; combined: 3; 0 – 34). Bacteroides spp. were higher in ileal adherent mucus (P = .036) and 3 combined ileal compartments (P = .034) of cats with small cell GI LSA. There were significant correlations between Fusobacterium spp. totals and CD11b+ cell (P = .009; rs .476) and NF-κB expression (P = .004; rs .523). Conclusions: The bacterial alterations appreciated might be influential in development of small cell GI LSA, and should drive further studies to elucidate the effects of microbial-mediated inflammation on GI cancer progression. Authors => Kayode Garraway | Chad M. Johannes | Angela Bryan | John Peauroi | Giacomo Rossi | Min Zhang | Chong Wang | Karin Allenspach | Albert E. Jergens published => First published: 07 August 2018 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.15291

Title => Management of Coxiella burnetii infection in livestock populations and the associated zoonotic risk: A consensus statement Abstract => Authors => Paul J. Plummer | J.Trenton McClure | Paula Menzies | Paul S. Morley | René Van den Brom | David C. Van Metre published => First published: 06 August 2018 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.15229

Title => Efficacy of pentamidine analogue 6 in dogs with chronic atrial fibrillation Abstract => Background: The inward rectifier inhibitor pentamidine analogue 6 (PA-6) is effective in cardioversion of goats with persistent rapid pacing induced atrial fibrillation (AF) and is not proarrhythmic in dogs with experimental chronic 3rd-degree AV block. Efficacy and safety in the clinical setting are unknown. Hypothesis: That PA-6 would be effective in converting AF to sinus rhythm (SR) in dogs with naturally occurring AF, without the presence of overt adverse effects. Animals: Ten client-owned large and giant breed dogs. Methods: Animals with persistent or permanent AF were recruited for our prospective study. PA-6 was administered IV as a bolus of 2.5 mg/kg 10 min−1 followed by a maintenance infusion of 0.04 mg/kg min−1 for a maximum of 50 minutes in conscious dogs. Standard 6 lead limb ECG was recorded during the infusion. Visible and audible signs of adverse effects were scored during the entire procedure. Results: PA-6 did not induce changes in QRS duration (54.7 ± 4.6 versus 56.7 ± 6.1 ms, P = .42), QTc interval (241.1 ± 19.5 versus 258.7 ± 19.8 ms, P = .061) or RR interval (363.4 ± 84.6 versus 440.8 ± 96.3 ms, P = .072) at the end of the bolus. No cardioversion to SR was observed in any dog. Three dogs displayed no adverse effects. Five dogs had premature ventricular depolarizations during PA-6 infusion on the ECG. Respiratory distress with laryngeal stridor, subtle muscle twitching, and mild generalized muscular weakness were noncardiac adverse effects observed in 5 dogs. Adverse effects resolved spontaneously. Conclusions and Clinical importance: Chronic naturally occurring AF in large and giant breed dogs could not be cardioverted to SR by PA-6. Authors => Viktor Szatmári | Yuan Ji | Bianca van Herwijnen | Mei Feng | Michael Zhou Wang | Alexandre Bossu | Marcel A. G. van der Heyden published => First published: 05 August 2018 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.15242

Title => Echocardiographic evaluation of velocity ratio, velocity time integral ratio, and pulmonary valve area in dogs with pulmonary valve stenosis Abstract => Background: Velocity ratio, velocity time integral (VTI) ratio, and pulmonary valve area indexed to body surface area (iPVA) are methods of assessment of pulmonary valve stenosis (PS) severity that are less dependent on blood flow. Studies evaluating these methods are limited. Objectives: To determine the effects of butorphanol, atenolol, and balloon valvuloplasty (BV) on velocity ratio, VTI ratio, iPVA, mean PG, and max PG. Animals: Twenty-seven dogs with PS (max PG >50 mm Hg). Methods: Prospective study. All dogs underwent an echocardiogram at baseline, 5-minutes after administration of butorphanol (0.2-0.25 mg/kg IV), and 2-to-4 weeks after atenolol (1-1.5 mg/kg q12h). Twenty-one of these were evaluated 24-hours after BV. Results: There were no significant differences (P > .05) amongst any of the methods of assessment of PS severity after butorphanol. After atenolol, mean (SD) of mean (57.0 [21.0] mm Hg) and max PG (93.1 [33.8] mm Hg) were significantly decreased (P ≤ .047) compared with baseline (65.2 [26.2] mm Hg and 108 [44.4] mm Hg, respectively). After atenolol, there were no significant (P ≥ .12) differences in velocity ratio (0.29 [0.09]), VTI ratio (0.18 [0.05]), or iPVA (0.43 [0.16] cm2/m2) compared with baseline (0.30 [0.09], 0.19 [0.09], 0.44 [0.17] cm2/m2, respectively). Conclusions and Clinical Importance: Atenolol might reduce mean and max PG but does not alter less flow-dependent methods of assessment of PS severity (velocity ratio, VTI ratio, and iPVA) in dogs with PS. Results support an integrative approach to assessment of PS severity that includes less flow-dependent methods, particularly in states of altered flow or right ventricular function. Authors => Satoko Nishimura | Lance C. Visser | Catherine Bélanger | Maureen S. Oldach | Catherine T. Gunther-Harrington | Joshua A. Stern published => First published: 05 August 2018 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.15244

Title => Gall bladder mucoceles in Border terriers Abstract => Background: Gall bladder mucoceles (GBM) are a leading cause of biliary disease in dogs with several breeds, including the Shetland Sheepdog, American Cocker Spaniel, Chihuahua, Pomeranian, and Miniature Schnauzer apparently predisposed. Objective: To determine risk factors, clinical features, and response to treatment of GBM in Border terriers (BT). Animals: Medical records of 99 dogs (including 51 BT) with an ultrasonographic (±histopathologic) diagnosis of GBM from three referral centers in the United Kingdom were collected. A control group of 87 similar-aged BT with no ultrasonographic evidence of gall bladder disease was selected for comparison. Method: Retrospective case-control study. Odds ratios were calculated to establish breed predisposition. Signalment, presence of endocrine disease, clinicopathologic results, and outcome were compared between the BT, other breeds, and control BTs. Results: The odds of identifying a GBM in a BT in this hospital population was 85 times that of all other breeds (95% confidence interval 56.9-126.8). BT had similar clinical signs and clinicopathologic changes to other breeds with GBM. There was no evidence that endocrinopathies were associated with GBM in BT. Clinical Significance: A robust breed predisposition to GBM is established for the BT. Authors => F. Allerton | F. Swinbourne | L. Barker | V. Black | A. Kathrani | M. Tivers | T. Henriques | C. Kisielewicz | M. Dunning | A. Kent published => First published: 05 August 2018 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.15249

Title => 25-Hydroxyvitamin D concentrations in dogs with naturally acquired blastomycosis Abstract => Background: Hypovitaminosis D is common in humans with tuberculosis, and adequate serum 25-hydroxyvitamin D [25(OH)D] concentrations may improve response to therapy. The pathomechanism of Blastomyces dermatitidis is similar to that of Mycobacterium tuberculosis, but the 25(OH)D status of dogs with blastomycosis has not been investigated. Objectives: To determine if dogs with blastomycosis have lower 25(OH)D concentrations compared with healthy controls and to explore the prognostic value of 25(OH)D concentrations in blastomycosis. Animals: 35 control dogs (16 client-owned, healthy dogs and 19 healthy, random-source hound mixes) and 22 dogs with blastomycosis. Methods: Prospective study. Serum concentrations of 25(OH)D, parathyroid hormone (PTH), ionized calcium were measured, and biochemistry and hematology profiles were performed. The 25-hydroxyvitamin D concentrations were compared between groups, and factors associated with 25(OH)D variation were investigated in dogs with blastomycosis. Dogs with blastomycosis were followed for up to 5 years after discharge and factors associated with survival were investigated. Results: Dogs with blastomycosis had significantly lower concentrations of 25(OH)D and PTH and higher concentrations of ionized calcium than did control dogs. In dogs with blastomycosis, 25(OH)D concentrations were independently associated with neutrophil count, pCO2, and with bone and skin involvement. The 25-hydroxyvitamin D concentration was not associated with survival in dogs with blastomycosis, whereas lactate concentrations; bone, skin, and lymph node involvement; number of affected sites; and, presence of respiratory signs were associated with survival. Conclusions and Clinical Importance: Dogs with blastomycosis had lower 25(OH)D concentrations than did healthy controls. Despite no impact on survival, investigating the effect of 25(OH)D supplementation on recovery is warranted. Authors => M.A. O'Brien | M.A. McMichael | K. Le Boedec published => First published: 05 August 2018 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.15255

Title => An E321G MYH1 mutation is strongly associated with nonexertional rhabdomyolysis in Quarter Horses Abstract => Background: An E321G mutation in MYH1 was recently identified in Quarter Horses (QH) with immune-mediated myositis (IMM) defined by a phenotype of gross muscle atrophy and myofiber lymphocytic infiltrates. Hypothesis/Objectives: We hypothesized that the MYH1 mutation also was associated with a phenotype of nonexertional rhabdomyolysis. The objective of this study was to determine the prevalence of the MYH1 mutation in QH with exertional (ER) and nonexertional (nonER) rhabdomyolysis. Animals: Quarter Horses: 72 healthy controls, 85 ER-no atrophy, 56 ER-atrophy, 167 nonER horses selected regardless of muscle atrophy. Methods: Clinical and histopathologic information and DNA was obtained from a database for (1) ER > 2 years of age, with or without atrophy and (2) nonER creatine kinase (CK) ≥ 5000 U/L, <5 years of age. Horses were genotyped for E321G MYH1 by pyrosequencing. Results: The MYH1 mutation was present in a similar proportion of ER-no atrophy (1/56; 2%) and in a higher proportion of ER-atrophy (25/85; 29%) versus controls (4/72; 5%). The MYH1 mutation was present in a significantly higher proportion of nonER (113/165; 68%) than controls either in the presence (39/42; 93%) or in absence (72/123; 59%) of gross atrophy. Lymphocytes were present in <18% of muscle samples with the MYH1 mutation. Conclusions and Clinical Importance: Although not associated with ER, the MYH1 mutation is associated with atrophy after ER. The MYH1 mutation is highly associated with nonER regardless of whether muscle atrophy or lymphocytic infiltrates are present. Genetic testing will enhance the ability to diagnose MYH1 myopathies (MYHM) in QH. Authors => Stephanie J. Valberg | Marisa L. Henry | Sudeep Perumbakkam | Keri L. Gardner | Carrie J. Finno published => First published: 05 August 2018 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.15299

Title => Sensitivity and specificity of microRNA-122 for liver disease in dogs Abstract => Background: Current tests for diagnosing liver disease in dogs are sub-optimal. MicroRNA-122 (miR-122) is a sensitive and specific biomarker of liver injury in humans and rodents. Circulating miR-122 could have utility in identifying dogs with liver disease. Objective: Establish the reference interval for miR-122 in healthy dogs and determine performance in a range of dog breeds with liver disease and control animals with non-liver disease. Animals: Stored serum from 120 healthy dogs, 100 dogs with non-liver diseases, and 30 dogs with histologically confirmed liver disease was analyzed. Methods: Retrospective study. Medical records of dogs with liver disease, non-liver disease and healthy dogs were reviewed. Serum miR-122 concentrations were measured by PCR and compared with the characteristics of the dogs and their conventional clinical measurements. Results: In healthy dogs the 2.5th, 50th, and 97.5th quartiles of miR-122 were 110 (90% CI 80-114), 594 (505-682), and 3312 (2925-5144) copies/μL, respectively. There was no difference between healthy dogs and dogs with non-liver disease (median ± IQR: healthy dogs 609 [327-1014] copies/μL; non-liver disease 607 [300-1351] copies/μL). miR-122 was higher in dogs with liver disease (11 332 [4418-20 520] copies/μL, P < .001 compared to healthy dogs). miR-122 identified dogs with liver disease with high accuracy (receiver operating characteristic area under curve for comparison with healthy dogs: 0.93 [95% CI 0.86-0.99]). The upper limit of normal for healthy dogs (3312 copies/μL) had a sensitivity of 77% and specificity of 97% for identifying liver disease. Conclusion and Clinical Importance: Liver disease can be sensitively and specifically diagnosed in dogs by measurement of miR-122. Authors => W. Oosthuyzen | P.W.L. Ten Berg | B. Francis | S. Campbell | V. Macklin | E. Milne | A. G. Gow | C. Fisher | R.J. Mellanby | J.W. Dear published => First published: 02 August 2018 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.15250

Title => Response from Dr. Cridge, et al. to Dr. Steiner, et al. letter to editor regarding JVIM_15039 Abstract => None Abstract Authors => published => First published: 26 July 2018 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.15221

Title => Letter to Editor from Dr. Steiner, et al. regarding JVIM_15039 Abstract => None Abstract Authors => published => First published: 26 July 2018 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.15222

Title => Use of a national identification database to determine the lifetime prognosis in cattle with necrotic laryngitis and the predictive value of venous pCO2 Abstract => Background: Necrotic laryngitis, caused by Fusobacterium necrophorum, frequently requires surgical intervention (laryngostomy) in the chronic stage. Hypothesis/Objectives: To determine survival until slaughter of cattle surgically treated for necrotic laryngitis and to identify predictors of mortality. Animals: A total of 221 cattle diagnosed with necrotic laryngitis by laryngoscopy and surgically treated Methods: Retrospective cohort study. Clinical records were matched with the national cattle identification, registration, and movement database. Information on possible predictors including clinical examination, biochemistry, and surgery was collected. A multivariable Cox proportional hazard model was used to identify predictors of mortality. Results: The overall survival rate was 65.2% and 58.6% of the animals with a completed life cycle could be slaughtered. Animals <6 months old experienced significantly higher mortality risk (hazard ratio [HR], 2.0; 95% confidence interval [CI], 1.1-3.5). The venous partial pressure of carbon dioxide (pCO2; HR, 2.4; 95% CI, 1.4-4.2) at a 64.5 mm Hg cut-off was most significantly associated with mortality. Sensitivity and specificity of the final model consisting of age and pCO2 were 49.1 and 86.4%, respectively. Instead of pCO2, total carbon dioxide (TCO2) could also be used, with similar diagnostic accuracy. Conclusions and Clinical Relevance: The lifetime prognosis for chronic necrotic laryngitis in cattle with surgical intervention appears fair. Age, venous pCO2 and TCO2 are easily accessible predictors of survival to support owners and veterinarians in their decision process of whether or not to operate and to identify high risk animals that require more intensive follow-up. Authors => Bart Pardon | Stefaan Ribbens | Lien Van Damme | Lieven Vlaminck | Ann Martens | Piet Deprez published => First published: 03 July 2018 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.15223

Title => Acute echocardiographic effects of sotalol on ventricular systolic function in dogs with ventricular arrhythmias Abstract => Background: Sotalol is a commonly used antiarrhythmic drug that may alter ventricular function. Objective: To determine the effect of sotalol on echocardiographic indices of ventricular systolic function in dogs with ventricular arrhythmias. Animals: Thirty-five client-owned dogs with ventricular arrhythmias. Methods: Dogs with ventricular arrhythmias (n = 27) had an echocardiogram and 5-minute ECG performed at baseline and 2-4 hours post-sotalol (2-2.5 mg/kg PO once). Eight additional dogs underwent the same protocol but did not receive sotalol (within-day variability controls). Left ventricular (LV) internal dimension at end-systole normalized to bodyweight (LVIDs_N), LV ejection fraction (LV EF), LV shortening area, LV fractional shortening, tricuspid annular plane systolic excursion (TAPSE), and right ventricular systolic myocardial velocity were evaluated as indices of systolic function. Results: All indices except TAPSE had mild decreases in systolic function post-sotalol (all P ≤ .0007) compared with baseline but only the percent change in LVIDs_N and LV EF were significantly (P ≤ .0079) different from the percent change of the same indices in control dogs. Sinus heart rate, ventricular premature complexes/5-minutes, and arrhythmia grade also were decreased post-sotalol (all P ≤ .01) compared with baseline when assessed by a 5-minutes ECG. No dog experienced an adverse event post-sotalol, including dogs with systolic dysfunction or atrial enlargement. Conclusions and Clinical Importance: A single dose of sotalol may cause a mild decrease in LV systolic function in dogs with ventricular arrhythmias. Sotalol appears to be well tolerated, even in dogs with atrial enlargement or systolic dysfunction. Authors => Lance C. Visser | Joanna L. Kaplan | Satoko Nishimura | Catherine T. Gunther-Harrington | Catherine Bélanger | Maureen S. Oldach | Joshua A. Stern | Mikaela S. Mueller published => First published: 03 July 2018 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.15224

Title => Persistent hypoglycemia associated with lipid storage myopathy in a paint foal Abstract => Authors => Toby L. Pinn | Thomas J. Divers | Teresa Southard | Nikhita P. De Bernardis | Joe J. Wakshlag | Stephanie Valberg published => First published: 29 June 2018 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.15218

Title => Sinonasal aspergillosis: Outcome after topical treatment in dogs with cribriform plate lysis Abstract => Background: Cribriform lysis has been considered a contraindication for topical treatment of sinonasal aspergillosis (SNA) because of concerns about drug extravasation with resultant neurologic signs or death. Objective/Hypothesis: To describe dogs with SNA and cribriform plate lysis treated with topical antifungal medications. Our hypothesis was that the conventional dogma that topical therapy should be avoided in these cases is incorrect. Animals: Nine client-owned dogs with SNA and lysis of the cribriform plate, lysis of the floor of a frontal sinus or both detected by computed tomography (CT). Methods: A retrospective review of medical records was performed. Dogs that met inclusion criteria (ie, SNA confirmed by at least 1 laboratory test, braincase affected on CT, and topical treatment applied) were included. Size of lesions, ancillary diagnostic test results, topical therapy, and adjuvant PO treatments were recorded. Outcome was determined by phone calls. Results: Four dogs were alive at the time of the manuscript submission with follow-up ranging from 188 to 684 days without neurological signs observed. All dogs were discharged without major complication 1-7 days postoperatively. One dog that had presented with a history of seizures experienced seizure activity 2 months after treatment. Conclusions and Clinical Importance: Topical therapy did not result in complications in these dogs in which lytic regions as large as 16 × 22 mm2 were noted. Sinonasal aspergillosis associated lysis of the cribriform plate; lysis of the floor of a frontal sinus or both detected on CT is not necessarily a contraindication to topical therapy. Authors => Beatriz Belda | Nicholas Petrovitch | Kyle G. Mathews published => First published: 29 June 2018 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.15219

Title => Electrocardiographic findings in 130 hospitalized neonatal calves with diarrhea and associated potassium balance disorders Abstract => Background: Hyperkalemia in neonatal diarrheic calves can potentially result in serious cardiac conduction abnormalities and arrhythmias. Objectives: To document electrocardiographic (ECG) findings and the sequence of ECG changes that are associated with increasing plasma potassium concentrations (cK+) in a large population of neonatal diarrheic calves. Animals: One hundred and thirty neonatal diarrheic calves (age ≤21 days). Methods: Prospective observational study involving calves admitted to a veterinary teaching hospital. Results: Hyperkalemic calves (cK+: 5.8-10.2, blood pH: 6.55-7.47) had significantly (P < .05) longer QRS durations as well as deeper S wave, higher T wave, and higher ST segment amplitudes in lead II than calves, which had both venous blood pH and cK+ within the reference range. The first ECG changes in response to an increase in cK+ were an increase in voltages of P, Ta, S, and T wave amplitudes. Segmented linear regression indicated that P wave amplitude decreased when cK+ >6.5 mmol/L, S wave amplitude voltage decreased when cK+ >7.4 mmol/L, QRS duration increased when cK+ >7.8 mmol/L, J point amplitude increased when cK+ >7.9 mmol/L, and ST segment angle increased when cK+ >9.1 mmol/L. P wave amplitude was characterized by a second common break point at cK+ = 8.2 mmol/L, above which value the amplitude was 0. Conclusions and Clinical Importance: Hyperkalemia in neonatal diarrheic calves is associated with serious cardiac conduction abnormalities. In addition to increased S and T wave amplitude voltages, alterations of P and Ta wave amplitudes are early signs of hyperkalemia, which is consistent with the known sensitivity of atrial myocytes to increased cK+. Authors => Florian M. Trefz | Ingrid Lorenz | Peter D. Constable published => First published: 26 June 2018 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.15220

Title => Stereotactic radiation therapy for the treatment of functional pituitary adenomas associated with feline acromegaly Abstract => Background: Conventional fractionated radiotherapy has been shown to be partially effective for management of pituitary tumors in cats that cause acromegaly and diabetes mellitus (DM), but, the efficacy and safety of stereotactic radiation therapy (SRT) as a treatment for acromegalic cats has not been described. Hypothesis: Stereotactic radiation therapy is an effective and safe treatment for controlling acromegaly associated with pituitary adenomas in cats. Additionally, SRT-treated acromegalic cats with DM will experience a decrease in insulin requirements after radiation therapy. Animals: Fifty-three client-owned cats referred to Colorado State University for SRT to treat pituitary tumors causing poorly controlled DM secondary to acromegaly. Methods: Retrospective study of cats treated for acromegaly with SRT between 2008 and 2016 at Colorado State University. Diagnosis of acromegaly was based on history, physical examination, laboratory results, and cross-sectional imaging of the pituitary. Signalment, radiation protocol, insulin requirements over time, adverse effects, and survival were recorded. Results: Median survival time was 1072 days. Of the 41 cats for which insulin dosage information was available, 95% (39/41) experienced a decrease in required insulin dose, with 32% (13/41) achieving diabetic remission. Remission was permanent in 62% (8/13) and temporary in 38% (5/13) cats. Median duration to lowest insulin dose was 9.5 months. Of the treated cats, 14% developed hypothyroidism and required supplementation after SRT. Conclusions: Stereotactic radiation therapy is safe and effective for treating cats with acromegaly. Cats treated with SRT have improved survival time and control of their DM when compared to previously reported patients treated with non-SRT. Authors => Tiffany L. Wormhoudt | Mary-Keara Boss | Katharine Lunn | Lynn Griffin | Del Leary | Kristy Dowers | Sangeeta Rao | Susan M. LaRue published => First published: 21 May 2018 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.15212

Title => Genome-wide based model predicting recovery from portosystemic shunting after liver shunt attenuation in dogs Abstract => Background: In dogs with congenital portosystemic shunt (CPSS), recovery after surgical CPSS attenuation is difficult to predict. Objectives: Our aim was to build a model with plasma albumin concentration and mRNA expression levels of hepatic gene products as predictors of recovery from portosystemic shunting after surgery. Animals: Seventy-three client-owned dogs referred for surgical attenuation of CPSS. Methods: A prediction model was constructed using 2 case-control studies of recovered and nonrecovered dogs after surgical CPSS attenuation. In the 1st study, a dog-specific gene expression microarray analysis was used to compare mRNA expression in intraoperatively collected liver tissue between 23 recovered and 23 nonrecovered dogs. In the 2nd study, preoperative plasma albumin concentration and the expression of microarray-selected genes were confirmed by RT-qPCR in intraoperatively collected liver samples of 31 recovered and 31 nonrecovered dogs, including 35 dogs from the 1st study. Results: In the 1st study, 43 genes were differently expressed in recovered and nonrecovered dogs. The mean preoperative plasma albumin concentration in recovered dogs was higher compared to nonrecovered dogs (23 and 19 g/L, respectively; P = .004). The best fitting prediction model in the 2nd study included preoperative plasma albumin concentration and intraoperative DHDH, ERLEC1, and LYSMD2 gene expression levels. Conclusion and Clinical Importance: A preclinical model was constructed using preoperative plasma albumin concentration and intraoperative hepatic mRNA expression of 3 genes that were unbiasedly selected from the genome to predict recovery from portosystemic shunting after shunt ligation. Further development is essential for clinical application. Authors => Lindsay Van den Bossche | Frank G. van Steenbeek | Maarten F. Weber | Bart Spee | Louis C. Penning | Freek J. van Sluijs | Flin Zomerdijk | Marian J. A. Groot Koerkamp | Jan Rothuizen | Iwan A. Burgener | Anne Kummeling published => First published: 17 May 2018 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.15140

Title => Fractional excretion of electrolytes in volume-responsive and intrinsic acute kidney injury in dogs: Diagnostic and prognostic implications Abstract => Background: The value of fractional excretion (FE) of electrolytes to characterize and prognosticate acute kidney injury (AKI) is poorly documented in dogs. Objectives: To evaluate the diagnostic and prognostic roles of FE of electrolytes in dogs with AKI. Animals: Dogs (n = 135) with AKI treated with standard care (February 2014-December 2016). Methods: Prospective study. Clinical and laboratory variables including FE of electrolytes, were measured upon admission. Dogs were graded according to the AKI-IRIS guidelines and grouped according to AKI features (volume-responsive, VR-AKI; intrinsic, I-AKI) and outcome (survivors/non-survivors). Group comparison and regression analyses with hazard ratios (HR) evaluation for I-AKI and mortality were performed. P < .05 was considered significant. Results: Fifty-two of 135 (39%) dogs had VR-AKI, 69/135 (51%) I-AKI and 14/135 (10%) were unclassified. I-AKI dogs had significantly higher FE of electrolytes, for example, FE of sodium (FENa, %) 2.39 (range 0.04-75.81) than VR-AKI ones 0.24 (range 0.01-2.21; P < .001). Overall, case fatality was 41% (55/135). Increased FE of electrolytes were detected in nonsurvivors, for example, FENa 1.60 (range 0.03-75.81) compared with survivors 0.60 (range 0.01-50.45; P = .004). Several risk factors for death were identified, including AKI-IRIS grade (HR = 1.39, P = .002), FE of electrolytes, for example, FENa (HR = 1.03, P < .001), and urinary output (HR = 5.06, P < .001). Conclusions and Clinical Importance: Fractional excretion of electrolytes performed well in the early differentiation between VR-AKI and I-AKI, were related to outcome, and could be useful tools to manage AKI dogs in clinical practice. Authors => Roberta Troìa | Marta Gruarin | Chiara Grisetti | Federica Serafini | Luca Magna | Erika Monari | Massimo Giunti | Francesco Dondi published => First published: 17 May 2018 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.15146

Title => Pharmacokinetic and pharmacodynamic properties of orally administered torsemide in healthy horses Abstract => Background: Diuretic treatment is the mainstay for management of congestive heart failure in horses, and its use has been restricted to injectable medications because no currently data supports the use of PO administered loop diuretics. Objectives: To determine the pharmacokinetic and pharmacodynamic properties of PO administered torsemide and, determine if PO administered torsemide, could be used as an alternative to injectable diuretics in the horse. Animals: Six healthy adult mares. Methods: A 2-phase, prospective study, that consisted of pharmacokinetic profiling of a single dose (6 mg/kg PO) and pharmacodynamic effects of long-term torsemide administration (2 mg/kg PO q12h) for 6 days in healthy horses. Results: Pharmacokinetic analysis identified a peak concentration (Cmax) of 10.14 µg/mL (range, 6.79–14.69 µg/mL) and elimination half-life (T1/2) 9.2 hours (range, 8.4–10.4 hours). The area under the plasma drug concentration over time curve (AUC) was 80.7 µg × h/mL (range, 56.5–117.2 µg × h/mL). A statistically significant increase in urine volume and decrease in urine specific gravity were found from day 0 (baseline) to day 6 (P < .0001). Significant alterations in biochemical variables included hyponatremia, hypokalemia, hypochloremia, and increased serum creatinine concentration. Mean arterial blood pressure significantly decreased on day 6 (57.7 ± 8.8 mm Hg, P = .001) as compared with baseline (78 ± 6.1 mm Hg). Serum aldosterone concentrations significantly increased after 6 days of torsemide administration (P = .0006). Conclusions and Clinical Importance: PO administered torsemide (4 mg/kg/day) successfully reached therapeutic concentrations in blood, induced clinically relevant diuresis, and resulted in moderate pre-renal azotemia and electrolyte disturbances. Authors => Gustavo F. Agne | Seung Woo Jung | Anne A. Wooldridge | Susan H. Duran | William Ravis | Ramiro Toribio published => First published: 17 May 2018 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.15213

Title => Frequency of shedding of respiratory pathogens in horses recently imported to the United States Abstract => Background: Imported horses that have undergone recent long distance transport might represent a serious risk for spreading infectious respiratory pathogens into populations of horses. Objective: To investigate the frequency of shedding of respiratory pathogens in recently imported horses. Animals: All imported horses with signed owner consent (n = 167) entering a USDA quarantine for contagious equine metritis from October 2014 to June 2016 were enrolled in the study. Methods: Prospective observational study. Enrolled horses had a physical examination performed and nasal secretions collected at the time of entry and subsequently if any horse developed signs of respiratory disease during quarantine. Samples were assayed for equine influenza virus (EIV), equine herpesvirus type-1, −2, −4, and −5 (EHV-1, −2, −4, −5), equine rhinitis virus A (ERAV), and B (ERBV) and Streptococcus equi subspecies equi (S. equi) using quantitative PCR (qPCR). Results: Equine herpesviruses were detected by qPCR in 52% of the study horses including EHV-2 (28.7%), EHV-5 (40.7%), EHV-1 (1.2%), and EHV-4 (3.0%). Clinical signs were not correlated with being qPCR-positive for EHV-4, EHV-2, or EHV-5. None of the samples were qPCR-positive for EIV, ERAV, ERBV, and S. equi. The qPCR assay failed quality control for RNA viruses in 25% (46/167) of samples. Conclusions and Clinical Importance: Clinical signs of respiratory disease were poorly correlated with qPCR positive status for EHV-2, −4, and −5. The importance of γ-herpesviruses (EHV-2 and 5) in respiratory disease is poorly understood. Equine herpesvirus type-1 or 4 (EHV-1 or EHV-4) were detected in 4.2% of horses, which could have serious consequences if shedding animals entered a population of susceptible horses. Biosecurity measures are important when introducing recently imported horses into resident US populations of horses. Authors => Fauna Leah Smith | Johanna L. Watson | Sharon J. Spier | Isabelle Kilcoyne | Samantha Mapes | Claudia Sonder | Nicola Pusterla published => First published: 15 May 2018 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.15145

Title => Effects of immunosuppressive agents on the hemostatic system in normal dogs Abstract => Background: In dogs, the effects of immunosuppressive medications on hemostasis are not well known. Hypothesis/Objectives: The objective was to determine the effects of immunosuppressive medications on primary and secondary hemostasis. Our hypothesis was that cyclosporine and prednisone would increase markers of hypercoagulability and thromboxane synthesis, while azathioprine, mycophenolate mofetil, and leflunomide would have minimal effects on hemostasis. Animals: Eight healthy dogs. Methods: A randomized, cross-over study used aggregometry, the PFA-100 platelet function analyzer, viscoelastometry, platelet count, and prothrombin and activated partial thromboplastin times to evaluate hemostasis during the administration of prednisone, azathioprine, cyclosporine, mycophenolate mofetil, and leflunomide for 1 week each at standard oral doses. Urine 11-dehydro-thromboxane-B2 (11-dTXB2) and 6-keto-prostaglandin-F1α (6-keto-PGF1α) concentrations, normalized to urine creatinine concentration, were measured. Results: The aggregometry amplitude decreased from 51 ± 21 to 27 ± 14 (P = .002) during leflunomide treatment (ADP activation), but there were no differences in amplitude (P = .240) for any medications when platelets were activated with collagen. For all medications, there were no significant differences in viscoelastometry indices (ACT, P = .666; ClotRate, P = .340; and platelet function, P = .411) and platelet count (P = .552). Compared with pretreatment values, urinary 11-dTXB2-to-creatinine ratio increased (P = .001) after drug administration (from 3.7 ± 0.6 to 5.6 ± 1.1). Cyclosporine was associated with an increase (P < .001) in the 6-keto-PGF1α-to-creatinine ratio (from 10.3 ± 4.6 to 22.1 ± 5.3). Conclusions and Clinical Importance: Most immunosuppressive drugs do not enhance platelet function or coagulation in healthy dogs, suggesting that these medications might not predispose hypercoagulable dogs to thromboembolism. The results of our study need to be correlated with the clinical outcomes of hypercoagulable dogs. Authors => John M. Thomason | Todd M. Archer | Robert W. Wills | Andrew J. Mackin published => First published: 10 May 2018 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.15132

Title => Establishment of reference values of the caudal vena cava by fast-ultrasonography through different views in healthy dogs Abstract => Background: Clinical assessment of intravascular volume status is challenging. In humans, ultrasonographic assessment of the inferior vena cava diameter, directly or as a ratio to the aortic diameter is used to estimate intravascular volume status. Objectives: To ultrasonographically obtain reference values (RV) for caudal vena cava diameter (CVCD), area (CVCa) and aortic ratios using 3 views in awake healthy dogs. Animals: One hundred and twenty-six healthy adult dogs from clients, students, faculty, or staff. Methods: Prospective, multicenter, observational study. Two observer pairs evaluated CVCD by a longitudinal subxiphoid view (SV), a transverse 11th-13th right hepatic intercostal view (HV), and a longitudinal right paralumbar view (PV). Inter-rater agreements were estimated using concordance correlation coefficients (CCC). For body weight (BW)-dependent variables, RVs were calculated using allometric scaling for variables with a CCC ≥ 0.7. Results: The CCC was ≤0.43 for the CVC/aorta ratio at the PV and ≤0.43 in both inspiration and expiration for CVC at the SV. The RVs using allometric scaling for CVCa at the HV for inspiration, expiration, and for CVCD at the PV were 6.16 × BW0.762, 7.24 × BW0.787, 2.79 × BW0.390, respectively. Conclusions and Clinical Importance: The CVCD, measured at the HV and PV in healthy awake dogs of various breeds has good inter-rater agreement suggesting these sites are reliable in measuring CVCD. Established RVs for CVCD for these sites need further comparison to results obtained in hypovolemic and hypervolemic dogs to determine their usefulness to evaluate volume status in dogs. Authors => Elodie Darnis | Soren Boysen | Anne-Christine Merveille | Loïc Desquilbet | Serge Chalhoub | Kris Gommeren published => First published: 10 May 2018 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.15136

Title => Effect of induced chronic atrial fibrillation on exercise performance in Standardbred trotters Abstract => None Abstract Authors => Rikke Buhl | Helena Carstensen | Eva Zander Hesselkilde | Bjørg Zinkernagel Klein | Karen Margrethe Hougaard | Kirsten Bomberg Ravn | Ameli Victoria Loft-Andersen | Merle Friederike Fenner | Christian Pipper | Thomas Jespersen published => First published: 10 May 2018 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.15137

Title => Insulin dysregulation in horses with systemic inflammatory response syndrome Abstract => Background: Systemic inflammation is a cause of insulin dysregulation in many species, but the insulin and glucose dynamics in adult horses diagnosed with systemic inflammatory response syndrome (SIRS) are poorly documented. Hypothesis/Objectives: In SIRS in horses, insulin and glucose dynamics will be altered and associated with survival. Animals: Adult horses diagnosed with SIRS admitted to a referral hospital. Methods: Prospective study enrolling horses diagnosed with SIRS in which serum insulin and glucose concentrations were measured. Horses were grouped by outcome (survival, hyperinsulinemia, and hyperglycemia) and compared with P < .05 considered significant. Results: Fifty-eight horses were included in the study and 36 (62%) survived. At admission, 21 horses (36%) were hyperinsulinemic and 44 horses (88%) were hyperglycemic, with survivors having significantly higher serum insulin and a significantly lower serum glucose concentration. Horses diagnosed with hyperinsulinemia at any time during hospitalization were 4 times more likely to survive whereas horses that were hyperglycemic at any time during hospitalization were 5 times less likely to survive. Serum glucose concentration and presence of hyperglycemia both were associated with severity of disease. Insulin/glucose ratio, reflecting insulin secretion, was significantly higher in survivors whereas glucose/insulin ratio, reflecting peripheral tissue insulin resistance, was significantly lower in nonsurvivors. Only in survivors was there a significant correlation between serum insulin and glucose concentrations. Conclusions and Clinical Importance: Hyperinsulinemia and hyperglycemia are common features of SIRS in horses, but those presenting with relative hypoinsulinemia and corresponding hyperglycemia suggestive of endocrine pancreatic dysfunction have a worse prognosis. Authors => François-René Bertin | Debra Ruffin-Taylor | Allison Jean Stewart published => First published: 10 May 2018 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.15138

Title => Erratum Abstract => None Abstract Authors => published => First published: 10 May 2018 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.15211

Title => Use of basal and TRH-stimulated plasma growth hormone concentrations to differentiate between primary hypothyroidism and nonthyroidal illness in dogs Abstract => Background: A low plasma total thyroxine (TT4) concentration in combination with a plasma TSH concentration within reference range does not distinguish between hypothyroidism and nonthyroidal illness (NTI) in dogs. Hypothyroidism is associated with TSH-releasing hormone (TRH)-induced increased release of growth hormone (GH). Hypothesis: Basal and TRH-induced plasma GH concentrations can be used to distinguish hypothyroid dogs from NTI dogs. Animals: Twenty-one dogs with signs consistent with hypothyroidism, a low plasma TT4 concentration, and a plasma TSH concentration within reference interval. Methods: Case control study. Thyroid scintigraphy was performed to classify dogs as having hypothyroidism or NTI. All dogs underwent a TRH stimulation test with measurement of plasma concentrations of GH and TSH before and 30 and 45 minutes after IV administration of TRH. Results: Eleven of the dogs were classified as hypothyroid and 10 as having NTI. Basal plasma GH concentration in the hypothyroid dogs (3.2 μg/l; range, 2.0 to 12.5 μg/l) was significantly higher (p<0.001) than that in the NTI dogs (.73 μg/l; range, .45 to 2.3 μg/l), with minimal overlap, and increased (p=.009) after TRH administration in hypothyroid dogs, whereas it did not change in NTI dogs. At T=45, plasma GH concentrations in hypothyroid dogs and NTI dogs did not overlap. The plasma TSH concentration did not change significantly after TRH administration in hypothyroid dogs, whereas it increased (p<.001) in NTI dogs. At T=45, there was no overlap in percentage TSH increase from baseline between hypothyroid dogs. Conclusions and Clinical Importance: Measurement of basal plasma GH concentration and concentrations of GH and TSH after TRH stimulation can distinguish between hypothyroidism and NTI in dogs. Authors => Tera Pijnacker | Hans S. Kooistra | Cathelijne F. Vermeulen | Merel van der Vinne | Marrit Prins | Sara Galac | Jan A. Mol published => First published: 07 May 2018 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.15139

Title => Characteristics of hemostasis during experimental Ehrlichia canis infection Abstract => Background: Ehrlichia canis infection in dogs can cause thrombocytopenia and clinical evidence of bleeding. It is unknown why some dogs show signs of bleeding whereas others do not despite clinically relevant thrombocytopenia. Hypothesis/Objectives: Activated platelets, decreased fibrinolysis or both mitigate bleeding tendency. Assess standard hemostatic variables, platelet dynamics, and specialized coagulation testing in dogs experimentally infected with E. canis to evaluate this clinical discrepancy. Animals: Four healthy laboratory beagles. Methods: Dogs were given blood infected with E. canis IV. Platelet indices of activation, platelet aggregometry, antiplatelet antibodies (percent IgG), complete coagulation panel, and thromboelastography (TEG) were measured before inoculation and on weeks 1-8. Dogs were treated with doxycycline at approximately 5 mg/kg PO q12h between weeks 3 and 4 (day 24). For each variable, 1-way repeated measures analysis (1-way ANOVA) with post-hoc analysis was performed with statistical significance set at P < .05. Results: Dogs had significantly lower platelet counts, evidence of activated platelets, and antiplatelet antibodies during E. canis infection. Dogs also appeared hypercoagulable and hypofibrinolytic using TEG as compared with baseline, changes that persisted for variable amounts of time after doxycycline administration. No overt signs of bleeding were noted during the study. Conclusions and Clinical Importance: Activated platelets and a hypercoagulable, hypofibrinolytic state could explain the lack of a bleeding phenotype in some dogs despite clinically relevant thrombocytopenia. Findings from our pilot study indicate that additional studies are warranted. Authors => Sarah Shropshire | Christine Olver | Michael Lappin published => First published: 27 April 2018 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.15130

Title => Prognostic importance of plasma total magnesium in a cohort of cats with azotemic chronic kidney disease Abstract => Background: Hypomagnesemia is associated with increased mortality and renal function decline in humans with chronic kidney disease (CKD). Magnesium is furthermore inversely associated with fibroblast growth factor 23 (FGF23), an important prognostic factor in CKD in cats. However, the prognostic significance of plasma magnesium in cats with CKD is unknown. Objectives: To explore associations of plasma total magnesium concentration (tMg) with plasma FGF23 concentration, all-cause mortality, and disease progression in cats with azotemic CKD. Animals: Records of 174 client-owned cats with IRIS stage 2-4 CKD. Methods: Cohort study. Cats with azotemic CKD were identified from the records of two London-based first opinion practices (1999–2013). Possible associations of baseline plasma tMg with FGF23 concentration and risks of death and progression were explored using, respectively, linear, Cox, and logistic regression. Results: Plasma tMg (reference interval, 1.73–2.57 mg/dL) was inversely associated with plasma FGF23 when controlling for plasma creatinine and phosphate concentrations (partial correlation coefficient, −0.50; P < .001). Hypomagnesemia was observed in 12% (20/174) of cats, and independently associated with increased risk of death (adjusted hazard ratio, 2.74; 95% confidence interval [CI], 1.35–5.55; P = .005). The unadjusted associations of hypermagnesemia (prevalence, 6%; 11/174 cats) with survival (hazard ratio, 2.88; 95% CI, 1.54–5.38; P = .001), and hypomagnesemia with progressive CKD (odds ratio, 17.7; 95% CI, 2.04–154; P = .009) lost significance in multivariable analysis. Conclusions and Clinical Importance: Hypomagnesemia was associated with higher plasma FGF23 concentrations and increased risk of death. Measurement of plasma tMg augments prognostic information in cats with CKD, but whether these observations are associations or causations warrants further investigation. Authors => D. Hendrik N. van den Broek | Yu-Mei Chang | Jonathan Elliott | Rosanne E. Jepson published => First published: 27 April 2018 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.15141

Title => Saccadic oscillations in 4 dogs and 1 cat Abstract => Authors => Edward J. Ives | Edward MacKillop | Natasha J. Olby published => First published: 27 April 2018 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.15144

Title => Pathological classification of equine recurrent laryngeal neuropathy Abstract => Authors => Alexandra C. E. Draper | Richard J. Piercy published => First published: 24 April 2018 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.15142

Title => Development and implementation of a novel immune thrombocytopenia bleeding score for dogs Abstract => Background: A method of quantifying clinical bleeding in dogs with immune thrombocytopenia (ITP) is needed because ITP patients have variable bleeding tendencies that inconsistently correlate with platelet count. A scoring system will facilitate patient comparisons and allow stratification based on bleeding severity in clinical trials. Hypothesis/Objectives: To develop and evaluate a bleeding assessment tool for dogs, and a training course for improving its consistent implementation. Animals: Client-owned dogs (n = 61) with platelet counts <50,000/μL; 34 classified as primary ITP, 17 as secondary ITP, and 10 as non-ITP. Methods: A novel bleeding assessment tool, DOGiBAT, comprising bleeding grades from 0 (none) to 2 (severe) at 9 anatomic sites, was developed. Clinicians and technicians completed a training course and quiz before scoring thrombocytopenic patients. The training course was assessed by randomizing student volunteers to take the quiz with or without prior training. A logistic regression model assessed the association between training and quiz performance. The correlation of DOGiBAT score with platelet count and outcome measures was assessed in the thrombocytopenic dogs. Results: Clinicians and technicians consistently applied the DOGiBAT, correctly scoring all quiz cases. The odds of trained students answering correctly were higher than those of untrained students (P < .0001). In clinical cases, DOGiBAT score and platelet count were inversely correlated (rs = −0.527, P < .0001), and DOGiBAT directly correlated with transfusion requirements (rs = 0.512, P < .0001) and hospitalization duration (rs = 0.35, P = .006). Conclusions and Clinical Importance: The DOGiBAT and assessment quiz are simple tools to standardize evaluation of bleeding severity. With further validation, the DOGiBAT may provide a clinically relevant metric to characterize ITP severity and monitor response in treatment trials. Authors => Kelly M. Makielski | Marjory B. Brooks | Chong Wang | Jonah N. Cullen | Annette M. O'Connor | Dana N. LeVine published => First published: 21 April 2018 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.15089

Title => Association between indoor air pollution and respiratory disease in companion dogs and cats Abstract => Background: Indoor air pollution (IAP) leads to important respiratory morbidity and mortality in humans. Companion dogs and cats share the same household environment with their owners and are exposed to IAP. Hypothesis: Pets with respiratory disease are more commonly exposed to indoor air pollutants in their homes and to worse air quality than pets without respiratory disease. Animals: Three hundred and forty-eight animals (230 dogs and 118 cats) were recruited. Methods: Dogs and cats attending the National Taiwan University Veterinary Hospital were prospectively enrolled over a 12-month period. Questionnaires were collected from pet owners regarding the status of signs of respiratory problem of animals and air pollutants in their homes. Clinical assessment was performed by veterinarians on all animals included in the case-control study and the presence/absence of respiratory disease and diagnoses were recorded. Individual exposure to particulate matter of 2.5 μm or less (PM2.5) was estimated in the domestic microenvironment of the animals. Results: Dogs with respiratory disease were more commonly exposed to incense burning than control dogs (30 versus 13%, P = .045), but household PM2.5 level was not different between dogs with and without respiratory disease [median 30.8 μg/m3, range 10.8-214.2 versus median 38.2 μg/m3, range 5.4-69.4, P = .57]. Signalment factors (age, body weight, and body condition score) instead of IAP factors were associated with respiratory disease in dogs using multivariable logistic regression. In contrast, household PM2.5 level was significantly higher in cats with respiratory disease than in control cats [median 38.6 μg/m3, range 17.8-131.2 versus median 27.4 μg/m3, range 15.4-70.0, P = .017]. Cats living in households with PM2.5 > 35 μg/m3 were more likely to have respiratory disease than those living in households with acceptable levels of PM2.5 (OR = 4.13, 95% CI 1.12-15.27, P = .03). Conclusions and Clinical Importance: The link between IAP and respiratory disease in dogs is complicated. An unacceptable level of household PM2.5 (>35 μg/m3) is significantly associated with respiratory disease in cats. The effect of IAP on the respiratory health of companion animals warrants further attention. Authors => Chung-Hui Lin | Pei-Ying Lo | Huey-Dong Wu | Chinhao Chang | Lih-Chiann Wang published => First published: 21 April 2018 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.15143

Title => Serum levetiracetam concentrations and adverse events after multiple dose extended release levetiracetam administration to healthy cats Abstract => Background: Multiple dose administration of antiepileptic drugs to cats presents a challenge for owners. Extended release levetiracetam (XRL) has once daily recommended dosing interval, but multiple dose administration of XRL has not been evaluated in cats. Objective: Evaluate serum levetiracetam concentrations and adverse clinical effects after 11 days of once daily XRL administration to healthy cats. Animals: Nine healthy privately owned cats, body weight ≥ 5 kg Methods: Extended release levetiracetam (500 mg/cat) was administered PO q24h for 10 days. On day 11, blood was collected at trough, 4, 6, and 8 hours after tablet administration. Owners maintained records of adverse effects throughout study. Levetiracetam was quantitated in serum using immunoassay validated in cats. Results: Median dose 94.3 mg/kg q24h. Median (range) trough, 4, 6, and 8 hour serum levetiracetam concentrations were 7.0 (2.3-14.1), 82.6 (7.8-125.3), 92.3 (13.3-97.3), and 72 (22.8-96.4) μg/mL, respectively. Peak was not observed in 4 cats because of missed samples (n = 2) and failure to reach maximal concentration (Cmax) by 8 hours (n = 2). Median time of maximal concentration (Tmax) for the remaining 5 cats 5.2 (range 4-6) hours. Adverse effects were minimal and included ataxia (n = 1), sedation (n = 1), and vomiting or regurgitation (n = 1). All signs resolved without dose adjustment or additional treatment. Conclusions and Clinical Importance: Mean trough serum levetiracetam concentrations were ≥5 μg/mL and adverse effects were minimal throughout dosing period, indicating that the drug was well tolerated. Once daily XRL (500 mg/cat) administration may provide an easier alternative to 3 times daily dosing of intermediate-release levetiracetam for epileptic cats. Authors => Heidi Barnes Heller | Martin Granick | Mathew Van Hesteren | Dawn M. Boothe published => First published: 19 April 2018 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.15129

Title => A review of mycoplasma diagnostics in cattle Abstract => Authors => Alysia M. Parker | Paul A. Sheehy | Mark S. Hazelton | Katrina L. Bosward | John K. House published => First published: 19 April 2018 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.15135

Title => International collaborative study to assess cardiovascular risk and evaluate long-term health in cats with preclinical hypertrophic cardiomyopathy and apparently healthy cats: The REVEAL Study Abstract => Background: Hypertrophic cardiomyopathy is the most prevalent heart disorder in cats and principal cause of cardiovascular morbidity and mortality. Yet, the impact of preclinical disease is unresolved. Hypothesis/Objectives: Observational study to characterize cardiovascular morbidity and survival in cats with preclinical nonobstructive (HCM) and obstructive (HOCM) hypertrophic cardiomyopathy and in apparently healthy cats (AH). Animals: One thousand seven hundred and thirty client-owned cats (430 preclinical HCM; 578 preclinical HOCM; 722 AH). Methods: Retrospective multicenter, longitudinal, cohort study. Cats from 21 countries were followed through medical record review and owner or referring veterinarian interviews. Data were analyzed to compare long-term outcomes, incidence, and risk for congestive heart failure (CHF), arterial thromboembolism (ATE), and cardiovascular death. Results: During the study period, CHF, ATE, or both occurred in 30.5% and cardiovascular death in 27.9% of 1008 HCM/HOCM cats. Risk assessed at 1, 5, and 10 years after study entry was 7.0%/3.5%, 19.9%/9.7%, and 23.9%/11.3% for CHF/ATE, and 6.7%, 22.8%, and 28.3% for cardiovascular death, respectively. There were no statistically significant differences between HOCM compared with HCM for cardiovascular morbidity or mortality, time from diagnosis to development of morbidity, or cardiovascular survival. Cats that developed cardiovascular morbidity had short survival (mean ± standard deviation, 1.3 ± 1.7 years). Overall, prolonged longevity was recorded in a minority of preclinical HCM/HOCM cats with 10% reaching 9-15 years. Conclusions and Clinical Importance: Preclinical HCM/HOCM is a global health problem of cats that carries substantial risk for CHF, ATE, and cardiovascular death. This finding underscores the need to identify therapies and monitoring strategies that decrease morbidity and mortality. Authors => Philip R. Fox | Bruce W. Keene | Kenneth Lamb | Karsten A. Schober | Valerie Chetboul | Virginia Luis Fuentes | Gerhard Wess | Jessie Rose Payne | Daniel F. Hogan | Alison Motsinger-Reif | Jens Häggström | Emilie Trehiou-Sechi | Deborah M. Fine-Ferreira | Reid K. Nakamura | Pamela M. Lee | Manreet K. Singh | Wendy A. Ware | Jonathan A. Abbott | Geoffrey Culshaw | Sabine Riesen | Michele Borgarelli | Michael B. Lesser | Nicole Van Israël | Etienne Côté | John E. Rush | Barret Bulmer | Roberto A. Santilli | Andrea C. Vollmar | Maribeth J. Bossbaly | Nadine Quick | Claudio Bussadori | Janice M. Bright | Amara H. Estrada | Dan G. Ohad | Maria Josefa Fernández-Del Palacio | Jenifer Lunney Brayley | Denise S. Schwartz | Christina M. Bové | Sonya G. Gordon | Seung Woo Jung | Paola Brambilla | N. Sydney Moïse | Christopher D. Stauthammer | Rebecca L. Stepien | Cecilia Quintavalla | Christophe Amberger | Ferenc Manczur | Yong-Wei Hung | Remo Lobetti | Marie De Swarte | Alice Tamborini | Carmel T. Mooney | Mark A. Oyama | Andrey Komolov | Yoko Fujii | Romain Pariaut | Masami Uechi | Victoria Yukie Tachika Ohara published => First published: 16 April 2018 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.15122

Title => Determining optimal therapy of dogs with chronic enteropathy by measurement of serum citrulline Abstract => Background: Serum concentration of citrulline is a useful biomarker in human intestinal disease and indicates globally reduced enterocyte mass and absorptive function in various disease states. Objectives: To determine whether serum citrulline concentration is a biomarker in chronic enteropathy (CE) in dogs, to provide useful information regarding optimal treatment or to predict outcome. Animals: Seventy-four dogs with CE and 83 breed- and age-matched hospital controls with no clinical signs of intestinal disease. Methods: Retrospective study. Outcome was determined and dogs were categorized by response to treatment as having food-responsive enteropathy (FRE), antibiotic-responsive diarrhea (ARD), or idiopathic inflammatory bowel disease (IBD). Disease severity was quantified by the CIBDAI scoring index. Results: Serum citrulline concentration did not differ between dogs with CE (median, 8.4 µg/mL, 5th-95th percentile 2.0-19.6) and controls (median, 8.1 µg/mL, 5th-95th percentile 2.2-19.7, P = .91). Serum citrulline concentration was similar between dogs with FRE (median, 9.1 µg/mL, 5th-95th percentile 2.0-18.9), ARD (median, 13.0 µg/mL, 5th-95th percentile 1.6-19.2), IBD (median, 8.4 µg/mL, 5th-95th percentile 2.1-21.0; P = .91). Serum citrulline did not correlate to CIBDAI or to serum albumin concentration. Conclusions and Clinical Importance: In our study, serum citrulline concentration was not associated with efficacy of treatment or outcome in dogs with CE. Authors => Magda Gerou-Ferriani | Rhiannon Allen | Peter-John M. Noble | Alexander J. German | Marco Caldin | Daniel J. Batchelor published => First published: 16 April 2018 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.15124

Title => Clinical findings and diagnostic procedures in 270 small ruminants with obstructive urolithiasis Abstract => Background: Details of the clinical signs of obstructive urolithiasis in male small ruminants have not been documented in a large population. Objective: To describe the clinical presentation and diagnostic procedures in a large group of small ruminants with urolithiasis. Animals: Two hundred and seventy small ruminants (158 sheep and 112 goats). Methods: Retrospective study of 270 cases identified based on clinical records. Results: 81.2% affected goats were castrated and 91.7% sheep were intact males; 65.5% of the animals had been sick ≤2 days before referral. Common abnormalities included dysuria (93.6%), indigestion (84.4%), reduced general state of health (79.5%), signs of pain (73%), increased heart and respiratory rates (53.6% and 39.1%), and azotemia (89.4%). Blood urea nitrogen (BUN) and creatinine concentrations were strongly correlated (r2 = 0.81). Hypochloremia (52.2%), hyponatremia (43.3%), hypophosphatemia (52.4%), and abnormal potassium concentrations (26.2% hypokalemia and 24.5% hyperkalemia) were the most common serum electrolyte imbalances. Packed cell volume (PCV), plasma proteins, potassium, BUN, and creatinine concentrations were significantly increased in animals with uroperitoneum. Ultrasonography allowed for confirmation of diagnosis in 83.9% of the cases (135/161 with sufficient available information), uroliths were visible on 34 of 56 plain radiographs. Conclusions and Clinical Importance: Our study confirmed that clinical and ultrasonographic examinations are sufficient to diagnose urolithiasis. Clinical signs can be divided into an early stage with discrete unspecific clinical signs, a painful stage with frequent straining, expression of pain and moderately reduced general condition, and an advanced stage with a markedly reduced general condition and eventually recumbency. Authors => Anna-Katharina Riedi | Gabriela Knubben-Schweizer | Mireille Meylan published => First published: 16 April 2018 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.15128

Title => Diagnostic utility of cardiac troponin I in cats with hypertrophic cardiomyopathy Abstract => Background: Cardiac troponin I (cTnI) is useful for assessing hypertrophic cardiomyopathy (HCM) in cats. Objective: To measure plasma cTnI concentrations in healthy cats and evaluate the clinical utility of cTnI in determining the severity of HCM. Animals: Clinically healthy cats (n = 88) and cats with HCM (n = 93). Methods: Multicenter prospective study. Cats with HCM, including hypertrophic obstructive cardiomyopathy at various stages, were diagnosed using echocardiography. Plasma cTnI concentrations were analyzed by a commercial laboratory. Receiver-operating characteristic curve analysis was used to evaluate the accuracy of plasma cTnI concentrations to detect HCM. Results: The median cTnI concentration was 0.027 ng/mL (interquartile range, 0.012-0.048 ng/mL) in healthy cats. Concentrations were significantly higher in diseased cats than in healthy controls, and concentrations were significantly higher in cats with heart failure than in asymptomatic cats. A plasma cTnI concentration of 0.163 ng/mL had a sensitivity of 62.0% and specificity of 100% when used to distinguish normal cats from asymptomatic HCM cats without left atrial dilatation. A cutoff of 0.234 ng/mL had high sensitivity (95.0%) and specificity (77.8%) for assessing heart failure. The areas under the receiver-operating characteristic curves were 0.85 and 0.93, respectively. Conclusions and Clinical Importance: Increased cTnI concentrations reflect the severity of HCM. If other causes of cardiac injury are ruled out, plasma cTnI concentration may be useful for predicting the severity of HCM in cats. Authors => Yasutomo Hori | Masayuki Iguchi | Yasuhiro Heishima | Yohei Yamashita | Kensuke Nakamura | Atsushi Hirakawa | Akihito Kitade | Toshiki Ibaragi | Michio Katagi | Tamotsu Sawada | Masashi Yuki | Nobuyuki Kanno | Haruki Inaba | Noriko Isayama | Hideyuki Onodera | Naoki Iwasa | Mikio Kino | Mikihiro Narukawa | Syuhei Uchida published => First published: 16 April 2018 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.15131

Title => In vitro assessment of quality of citrate-phosphate-dextrose-adenine-1 preserved feline blood collected by a commercial closed system Abstract => Background: Optimal procedure for storage of feline blood is needed. Open-collection systems have been employed in feline medicine, thus limiting the possibility for storage. Objectives: To evaluate indicators of quality of feline blood stored for 35 days at +4°C in a closed-collection system specifically designed for cats. Animals: Eight healthy adult European domestic shorthair cats with a weight of 5-6.8 kg. Methods: This is a case series study. A bacteriological test, CBC, blood smear, pH, osmotic fragility, 2,3-diphosphoglycerate (2,3-DPG), and adenosine triphosphate (ATP) measurement were performed weekly on whole blood (WB) units from day 1 to day 35 after donation. The hemolysis index, lactate and potassium concentrations, prothrombin time (PT), activated partial thromboplastin time (aPTT), and fibrinogen were measured on plasma aliquots. Results: One out of eight blood units (BUs) had bacterial growth (Serratia marcescens) at day 35. No significant differences were found regarding CBC, morphology, pH, and osmotic fragility. Despite high inter-individual variability and low starting levels, significant decreases in the mean concentrations of 2,3-DPG (T0 1.99 mmol/g Hb, SD 0.52, T35 1.25 mmol/g Hb, SD 1.43; P = .003) and ATP (T0 1.45 mmol/g Hb, SD 0.71, T35 0.62 mmol/g Hb, SD 0.51; P < .001) were detected during the study, as opposed to an increase in hemolysis (T0 0.11 mmol/L, SD 0.07, T35 0.84 mmol/L, SD 0.19; P < .001), lactate (T0 3.30 mmol/L, SD 0.86, T35 13.36 mmol/L, SD 2.90; P < .001), and potassium (T0 3.10 mmol/L, SD 0.21, T35 4.12 mmol/L, SD 0.35; P < .001) concentrations. Conclusions and Clinical Importance: The commercial BU kit is appropriate for blood collection and conservation of WB in cats. The maintenance of WB quality indicators during storage is essential for future improvements of feline transfusion medicine. Authors => Chiara Crestani | Annalisa Stefani | Antonio Carminato | Angelica Cro | Katia Capello | Michela Corrò | Elisa Bozzato | Franco Mutinelli | Marta Vascellari published => First published: 10 April 2018 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.15056

Title => A randomized, blinded, prospective clinical trial of postoperative rehabilitation in dogs after surgical decompression of acute thoracolumbar intervertebral disc herniation Abstract => Background: Experimental evidence shows benefit of rehabilitation after spinal cord injury (SCI) but there are limited objective data on the effect of rehabilitation on recovery of dogs after surgery for acute thoracolumbar intervertebral disc herniations (TL-IVDH). Objective: Compare the effect of basic and intensive post-operative rehabilitation programs on recovery of locomotion in dogs with acute TL-IVDH in a randomized, blinded, prospective clinical trial. Animals: Thirty non-ambulatory paraparetic or paraplegic (with pain perception) dogs after decompressive surgery for TL-IVDH. Methods: Blinded, prospective clinical trial. Dogs were randomized (1:1) to a basic or intensive 14-day in-house rehabilitation protocol. Fourteen-day open field gait score (OFS) and coordination (regulatory index, RI) were primary outcomes. Secondary measures of gait, post-operative pain, and weight were compared at 14 and 42 days. Results: Of 50 dogs assessed, 32 met inclusion criteria and 30 completed the protocol. There were no adverse events associated with rehabilitation. Median time to walking was 7.5 (2 – 37) days. Mean change in OFS by day 14 was 6.13 (confidence intervals: 4.88, 7.39, basic) versus 5.73 (4.94, 6.53, intensive) representing a treatment effect of −0.4 (−1.82, 1.02) which was not significant, P=.57. RI on day 14 was 55.13 (36.88, 73.38, basic) versus 51.65 (30.98, 72.33, intensive), a non-significant treatment effect of −3.47 (−29.81, 22.87), P = .79. There were no differences in secondary outcomes between groups. Conclusions: Early postoperative rehabilitation after surgery for TL-IVDH is safe but doesn't improve rate or level of recovery in dogs with incomplete SCI. Authors => Natalia Zidan | Cory Sims | Joe Fenn | Kim Williams | Emily Griffith | Peter J. Early | Chris L. Mariani | Karen R. Munana | Julien Guevar | Natasha J. Olby published => First published: 10 April 2018 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.15086

Title => Clinical findings and survival time in dogs with advanced heart failure Abstract => Background: Dogs with advanced heart failure are a clinical challenge for veterinarians but there are no studies reporting clinical features and outcome of this population. Hypothesis/Objectives: To describe clinical findings and outcome of dogs with advanced heart failure caused by degenerative mitral valve disease (DMVD). Animals: Fifty-four dogs with advanced heart failure because of DMVD. Methods: For study purposes, advanced heart failure was defined as recurrence of congestive heart failure signs despite receiving the initially prescribed dose of pimobendan, angiotensin-converting-enzyme inhibitor (ACEI), and furosemide >4 mg/kg/day. Data were collected for the time of diagnosis of Stage C heart failure and time of diagnosis of advanced heart failure. Date of death was recorded. Results: At the diagnosis of advanced heart failure, doses of pimobendan (n = 30), furosemide (n = 28), ACEI (n = 13), and spironolactone (n = 4) were increased, with ≥1 new medications added in most dogs. After initial diagnosis of advanced heart failure, 38 (70%) dogs had additional medications adjustments (median = 2 [range, 0-27]), with the final total medication number ranging from 2-10 (median = 5). Median survival time after diagnosis of advanced heart failure was 281 days (range, 3-885 days). Dogs receiving a furosemide dose >6.70 mg/kg/day had significantly longer median survival times (402 days [range, 3-885 days] versus 129 days [range 9-853 days]; P = .017). Conclusions and Clinical Importance: Dogs with advanced heart failure can have relatively long survival times. Higher furosemide dose and non-hospitalization were associated with longer survival. Authors => Amelie Beaumier | John E. Rush | Vicky K. Yang | Lisa M. Freeman published => First published: 10 April 2018 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.15126

Title => Protozoal coinfection in horses with equine protozoal myeloencephalitis in the eastern United States Abstract => Background: Infection by 2 or more protozoa is linked with increased severity of disease in marine mammals with protozoan encephalitis. Hypothesis/Objectives: To assess whether horses with equine protozoal myeloencephalitis (EPM) caused by Sarcocystis neurona also have evidence of infection with Neospora hughesi or Toxoplasma gondii. We hypothesized that horses with EPM would be more likely than horses with cervical vertebral stenotic myelopathy (CVSM) to be positive for antibodies to multiple protozoan parasites. Animals: One hundred one horses with neurologic disease: 49 with EPM and 52 with CVSM. Methods: Case review. Archived serum and cerebrospinal fluid (CSF) from 101 horses were examined. Inclusion criteria included neurologic disease, antemortem or postmortem diagnosis of EPM or CVSM, and availability of serological results or archived samples for testing. Additional testing for antibodies was performed on serum for T. gondii, as well as serum and CSF for N. hughesi. Results: Horses with EPM were more likely than horses with CVSM to have positive immunologic results for S. neurona on serum (95.9% versus 76.9%, P = .0058), CSF (98.0% versus 44.2%, P < .00001), and serum : CSF titer ratio (91.8% versus 0%, P < .00001). Positive results for Neospora and Toxoplasma were uncommon, with total seroprevalence rates of 12.9% and 14.9%, respectively. The proportions of EPM cases testing positive for Neospora and Toxoplasma (16% and 12%) were not different from the proportions of CVSM cases testing positive (10% and 17%, P = .31 and .47, respectively). Conclusion: Results do not indicate an important role for protozoal coinfection in EPM in the eastern United States. Authors => Sarah Schale | Daniel Howe | Michelle Yeargan | Jennifer K. Morrow | Amy Graves | Amy L. Johnson published => First published: 10 April 2018 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.15127

Title => Serologic and fecal markers to predict response to induction therapy in dogs with idiopathic inflammatory bowel disease Abstract => Background: Little information is available of markers that assess the disease course in dogs with idiopathic inflammatory bowel disease (IBD). Objectives: Evaluate relationship between disease severity and serum and fecal biomarkers in dogs with idiopathic IBD before and after treatment. Animals: Sixteen dogs with idioptahic IBD and 13 healthy dogs. Methods: Prospective case control study. Canine IBD activity index (CIBDAI) clinical score, serum concentrations of C-reactive protein (CRP), perinuclear antineutrophil cytoplasmic antibodies (pANCA), and serum and fecal canine calprotectin (cCP) were measured before and after 21 days of treatment. Results: Serum CRP (median 3.5 mg/L; range: 0.1-52.4 mg/L), fecal cCP (median 92.3 μg/g; range: 0.03-637.5 μg/g), and CIBDAI scores significantly increased in dogs with IBD before treatment compared with serum CRP (median 0.2 mg/L; range: 0.1-11.8 mg/L; P < .001), fecal cCP (median 0.67 μg/g; range: 0.03-27.9 μg/g; P < .001) and CIBDAI (P < .001) after treatment. No significant associations between CIBDAI scores and before or after treatment serum biomarkers. There was a significant association between fecal cCP and CIBDAI scores before treatment (rho = 0.60, P = .01). CRP and fecal cCP significantly decreased after treatment (median 3.5 mg/L v. 0.2 mg/L; P < .001 and 92.3 μg/g v. 0.67 μg/g; P = .001, respectively). Conclusions and Clinical Importance: Our data indicate that measurement of fecal cCP concentration is a useful biomarker for noninvasive evaluation of intestinal inflammation. Dogs with severe signs of GI disease more often have abnormal markers than dogs having less severe disease. Authors => Cristiane C. Otoni | Romy M. Heilmann | Mercedes García-Sancho | Angel Sainz | Mark R. Ackermann | Jan S. Suchodolski | Jörg M. Steiner | Albert E. Jergens published => First published: 06 April 2018 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.15123

Title => Alterations in serum amino acid concentrations in dogs with protein-losing enteropathy Abstract => Background: Certain amino acids are decreased in humans with inflammatory bowel disease (IBD) and supplementation with the same amino acids has shown beneficial effects in animal models of IBD. Currently, the amino acid status of dogs with protein-losing enteropathy (PLE) is unknown. Hypothesis/Objective: To determine if serum amino acid concentrations are abnormal in dogs with PLE and correlated with clinical and laboratory variables and outcome. Animals: Thirty client-owned dogs diagnosed with PLE and 12 apparently healthy dogs seen at Bristol Veterinary School. Methods: Retrospective study using stored residual serum from fasted dogs with PLE, collected at the time of diagnostic investigation and from apparently healthy dogs. Serum was analyzed for 30 amino acids using an automated high-performance liquid chromatography amino acid analyzer. Results: Serum tryptophan concentrations were significantly decreased in dogs with PLE (median, 22 nmol/mL; range, 1–80 nmol/mL) compared with apparently healthy control dogs (median, 77.5 nmol/mL; range, 42–135 nmol/mL, P < .001). There were no significant differences in the remaining 29 serum amino acids between dogs with PLE and apparently healthy. Serum tryptophan concentrations were also significantly correlated with serum albumin concentrations in dogs with PLE (P = .001, R2 = 0.506). Conclusions and Clinical Importance: Decreased serum tryptophan concentration might play a role in the pathogenesis of canine PLE or be a consequence of the disease. Authors => Aarti Kathrani | Karin Allenspach | Andrea J. Fascetti | Jennifer A. Larsen | Edward J. Hall published => First published: 31 March 2018 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.15116

Title => Equine idiopathic hemorrhagic cystitis: Clinical features and comparison with bladder neoplasia Abstract => Background: A new syndrome of hematuria in horses has been documented. Hypothesis/Objectives: Hemorrhagic cystitis is a novel cause of stranguria and hematuria in horses. This syndrome may be difficult to differentiate from bladder neoplasia because they share several clinical features. Animals: Eleven horses with idiopathic hemorrhagic cystitis and 7 horses with bladder neoplasia. Methods: Retrospective cohort study. Results: Hemorrhagic cystitis was detected on cystoscopy of affected horses, with hemorrhagic and thickened apical bladder mucosa. Clinical signs and endoscopic appearance of the bladder resolved within 3-8 weeks. Histopathology of bladder mucosal biopsy specimens featured neutrophilic and hemorrhagic cystitis. Histopathology was suggestive of dysplasia or neoplasia in 3 horses with hemorrhagic cystitis, yet the horses experienced complete resolution, suggesting that small biopsy specimens obtained by endoscopy can be difficult to interpret. Horses with bladder neoplasia had lower hematocrits, were older, more likely to be female, and more likely to have a mass detected on ultrasonographic examination of the bladder than horses with hemorrhagic cystitis syndrome. Conclusions and Clinical Importance: Hemorrhagic cystitis represents a novel differential diagnosis for horses with hematuria, and is associated with a favorable prognosis. Although histopathology may suggest a neoplastic process, affected horses should be monitored cystoscopically, because complete resolution of hemorrhagic cystitis occurs. The cause of this disease is unknown, and warrants investigation. Authors => Fauna L. Smith | K. Gary Magdesian | Adam O. Michel | Betsy Vaughan | Christopher M. Reilly published => First published: 31 March 2018 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.15121

Title => Computer tomographic imaging in 4 dogs with primary nasal canine transmissible venereal tumor and differing cellular phenotype Abstract => Authors => Javier Ojeda | Marcelo Mieres | Francisco Soto | Verónica Arnes | Enrique Paredes | María Navarrete published => First published: 31 March 2018 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.15125

Title => ACVIM small animal consensus statement on safe use of cytotoxic chemotherapeutics in veterinary practice Abstract => Authors => Annette N. Smith | Shawna Klahn | Brenda Phillips | Lisa Parshley | Peter Bennett | Andi Flory | Rosemary Calderon published => First published: 30 March 2018 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.15077

Title => Angiostrongylosis in dogs with negative fecal and in-clinic rapid serological tests: 7 Cases (2013-2017) Abstract => Background: Angiostrongylosis is considered as emerging disease in dogs in Belgium. Detection of first-stage larvae in feces using the Baermann method has an imperfect sensitivity. Objectives: Investigation of efficacy of noninvasive blood and fecal diagnostic tests in comparison with PCR on bronchoalveolar lavage (BAL) material in a small series of coughing or dyspnoeic dogs naturally infected with Angiostrongylus vasorum. Animals: Seven dogs with angiostrongylosis. Methods: Retrospective study. Dogs with cough, exercise intolerance and dyspnea of 2- to 8-week duration. Diagnostic methods used included Baermann analysis, AngioDetect rapid assay, ELISAs for detection of circulating antigen and specific antibodies and qPCR on BAL material. Results: Baermann analysis, AngioDetect rapid assay, antigen ELISA, antibody ELISA, and qPCR on BAL material were positive in 3/7, 2/7, 3/6, 6/6, and 7/7 dogs, respectively. ELISA for antibodies or qPCR on BAL material were essential for definitive diagnosis in 3 dogs. Relative sensitivities of AngioDetect rapid assay, Baermann analysis, and ELISA for antigen detection were lower than 50% compared with ELISA for antibodies or qPCR on BAL material. Conclusion and Clinical Importance: In this small clinical series, Baermann analysis and AngioDetect rapid assay failed to confirm the diagnosis in some dogs. Therefore, ELISA for antibody detection and qPCR on BAL material should strongly be considered in clinically suspected dogs when antigen detection methods (AngioDetect or ELISA) and Baermann analysis are negative. Authors => A. Morgane Canonne | F. Billen | B. Losson | I. Peters | M. Schnyder | C. Clercx published => First published: 30 March 2018 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.15092

Title => Incidence of and associated factors for bacterial colonization of intravenous catheters removed from dogs in response to clinical complications Abstract => Background: Infection rate associated with intravenous (IV) catheter placement is emerging as an important issue in small animal veterinary medicine, mostly because of the economic costs associated with these infections. Identification of possible associated factors may provide useful information for the surveillance and prevention of such infections. Objectives: To determine the incidence of positive bacterial cultures obtained from IV catheters used in dogs hospitalized for at least 48 hours and removed because of clinical complication. To identify the bacteria involved and factors associated with bacterial colonization. Animals: One-hundred eighty-two dogs that underwent IV catheterization from January 2015 to July 2015 at the Veterinary Teaching Hospital of Alfonso X el Sabio University of Madrid were enrolled in the study. Results: The bacterial colonization rate of all IV catheters removed in response to clinical complications was 39.6%, the cumulative proportion of catheters that remained in place at 24, 48, and 72 hours after placement was 89.5, 78, and 59.4%, respectively. Multivariable Cox proportional hazards regression indicated significant associations for staff who performed catheterization (junior, P = .002; student, P = .034) and use of steroidal anti-inflammatory drugs (P = .036). The most frequently isolated bacterium was Acinetobacter spp. (21.7%). Conclusions and Clinical Importance: The bacterial colonization incidence related to IV catheter placement was slightly higher than the incidence described in other veterinary studies. Associated factors not previously described in veterinary medicine were found. The most frequently isolated organism was Acinetobacter spp., indicating its importance as an emerging pathogen in catheter colonization. Authors => Pedro Jose Guzmán Ramos | Cristina Fernández Pérez | Tania Ayllón Santiago | M. Rosario Baquero Artigao | Gustavo Ortiz-Díez published => First published: 30 March 2018 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.15118

Title => Glucose concentrations after insulin-induced hypoglycemia and glycemic variability in healthy and diabetic cats Abstract => Background: Little information is available about posthypoglycemic hyperglycemia (PHH) in diabetic cats, and a causal link between hypoglycemia and subsequent hyperglycemia is not clear. Fluctuations in blood glucose concentrations might only represent high glycemic variability. Hypothesis: Insulin induces PHH in healthy cats, and PHH is associated with poorly regulated diabetes and increased glycemic variability in diabetic cats. Animals: Six healthy cats, 133 diabetic cats. Methods: Insulin (protamine-zinc and degludec; 0.1-0.3 IU/kg) administered to healthy cats. Blood glucose curves were generated with portable glucose meter to determine the percentage of curves with PHH. Data from insulin-treated diabetic cats with blood glucose curves showing hypoglycemia included data of cats with and without PHH. Post-hypoglycemic hyperglycemia was defined as blood glucose concentrations <4 mmol/L followed by blood glucose concentrations >15 mmol/L within 12 hours. Glycemic variability was calculated as the standard deviation of the blood glucose concentrations. Results: In healthy cats, all insulin doses caused hypoglycemia but PHH was not observed; glycemic variability did not differ between insulin preparations. Among diabetic cats with hypoglycemia, 33 (25%) had PHH. Compared with cats without PHH, their daily insulin dose was higher (1.09 ± 0.55 versus 0.65 ± 0.56 IU/kg; P < .001), serum fructosamine concentration was higher (565 ± 113 versus 430 ± 112 µmol/L; P < .001), remission was less frequent (10% versus 56%; P < .001), and glycemic variability was larger (8.1 ± 2.4 mmol/L versus 2.9 ± 2.2 mmol/L; P < .001). Conclusions and Clinical Importance: Insulin-induced hypoglycemia did not cause PHH in healthy cats but it occurred in 25% of diabetic cats with hypoglycemia, particularly when diabetes was poorly controlled. Glycemic variability was increased in cats with PHH. Authors => Eric Zini | Elena Salesov | Perrine Dupont | Laura Moretto | Barbara Contiero | Thomas A. Lutz | Claudia E. Reusch published => First published: 30 March 2018 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.15134

Title => Evaluation of updated sepsis scoring systems and systemic inflammatory response syndrome criteria and their association with sepsis in equine neonates Abstract => Background: The original equine sepsis score provided a method of identifying foals with sepsis. New variables associated with sepsis have been evaluated, but the sepsis score has not been updated. Objectives: To evaluate the sensitivity and specificity of 2 updated sepsis scores and the systemic inflammatory response syndrome (SIRS) criteria in regard to detecting sepsis in foals. Animals: Two-hundred and seventy-three ill foals and 25 healthy control foals. Methods: Historical, physical examination, and clinicopathologic findings were used to calculate the original sepsis score and 2 updated sepsis scores. SIRS criteria were also evaluated. Sepsis scores and positive SIRS scores were statistically compared to foals with sepsis. Results: One-hundred and twenty-six foals were septic and 147 sick-nonseptic. The original and updated sepsis scores were significantly higher in septic foals as compared to sick-nonseptic and healthy foals. The sensitivity and specificity of the updated sepsis scores to predict sepsis were not significantly better than those of the original sepsis score. One-hundred and twenty-seven of 273 (46.5%) foals met the original SIRS criteria and 88/273 (32%) foals met the equine neonatal SIRS criteria. The original SIRS criteria had similar sensitivity and specificity for predicting sepsis as did the 3 sepsis scores in our study. Conclusions and Clinical Importance: The updated sepsis scores did not provide improved ability in predicting sepsis. Fulfilling the original SIRS criteria provided similar sensitivity and specificity in predicting sepsis as the modified sepsis score and might serve as a diagnostic aid in identifying foals at risk for sepsis. Authors => D. M. Wong | R. E. Ruby | K. A. Dembek | B. S. Barr | S. M. Reuss | K. G. Magdesian | E. Olsen | T. Burns | N. M. Slovis | P. A. Wilkins published => First published: 26 March 2018 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.15087

Title => An evaluation of serum gentamicin concentrations and bacterial susceptibility to gentamicin in equine practice Abstract => Background: Therapeutic drug monitoring and minimum inhibitory concentration (MIC) data allow more informed use of gentamicin. Hypothesis/Objectives: To measure peak and trough serum gentamicin concentrations in horses after a 6.6 mg/kg dose of gentamicin given IV and the MIC of gentamicin of bacteria for which gentamicin might be selected. Methods: Retrospective analysis of hospital records. Peak and trough plasma gentamicin concentrations were measured after 6.6 mg/kg gentamicin IV in 339 hospitalized horses. The MIC of gentamicin was measured for 503 isolates from ambulatory practice and 33 from hospital practice. The distribution of gentamicin concentrations and MIC results were compared to current recommendations for MIC breakpoints. Results: The median serum gentamicin concentration at 60 minutes after administration (C60min) was 21.4 μg/mL with a distribution indicating that bacteria with MIC ≥2 μg/mL were unlikely to be exposed to sufficient gentamicin for effective killing. Approximately 90% of isolates from ambulatory practice and 36% of hospital isolates had MICs at or below breakpoints for susceptibility with most of the remainder unlikely to be responsive, even to higher IV doses. Conclusions and Clinical Importance: Gentamicin at a dosage of 6.6 mg/kg IV is likely to be effective against the majority of infections encountered in ambulatory practice, but less effective in an equine hospital. Because there was a dichotomy of most bacteria as being clearly susceptible or clearly resistant to gentamicin, it appears unlikely that higher doses would have been more efficacious, especially in the hospitalized population in our study. Authors => Andy E. Durham published => First published: 25 March 2018 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.15078

Title => Effects of fenoldopam on kidney function parameters and its therapeutic efficacy in the management of acute kidney injury in dogs with heatstroke Abstract => Background: Acute kidney injury (AKI) is common in dogs, but evidence of efficacy of its treatment is lacking. Objective: To evaluate the efficacy of fenoldopam in the management of AKI. Animals: Forty dogs with naturally occurring heatstroke. Methods: Dogs were prospectively enrolled and divided into treatment and the placebo groups (fenoldopam, constant rate infusion [CRI] of 0.1 µg/kg/min or saline, respectively). Urine production (UP) was measured using a closed system. Urinary clearances were performed at 4, 12, and 24 hours after presentation to estimate the effect of fenoldopam on UP, glomerular filtration rate (GFR) and sodium fractional excretion (NaFE). Results: At presentation, severity of heatstroke, based on a previously developed scoring system, was similar between the study groups, but was significantly worse in nonsurvivors compared with survivors. Fenoldopam administration was not associated with hypotension. Overt AKI was diagnosed, based on the International Renal Interest Society guidelines in 22/40 (55%) of the dogs. Overall, 14/40 dogs (35%) died, with no significant (P = .507) mortality rate difference between the fenoldopam (6/20 dogs; 30%) and placebo (8/20; 40%) groups. The proportion of dogs with AKI did not differ between the fenoldopam and the placebo groups (9/20; 45% versus 13/20; 65%, respectively; P = .204). There were no differences in UP, GFR, and NaFE between the fenoldopam and the placebo groups. Conclusion and Clinical Importance: Fenoldopam CRI at 0.1 µg/kg/min did not have a clinically relevant effect on kidney function parameters in dogs with severe heatstroke-associated AKI. Authors => Gilad Segev | Yaron Bruchim | Noga Berl | Adar Cohen | Itamar Aroch published => First published: 25 March 2018 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.15081

Title => Pharmacokinetics and efficacy of intravenous famotidine in adult cattle Abstract => Background: Abomasal ulceration is recognized in neonatal and adult cattle, but research regarding treatment is limited. Histamine-2 receptor antagonists (H2RA), such as famotidine, are used clinically with little evidence-based research about efficacy in adult cattle. Hypothesis and Objectives: Intravenous famotidine administered at 0.4 mg/kg will increase the pH of abomasal outflow digesta compared to saline control in adult cattle. The objectives were to assess the effect of famotidine, administered as a single dose and as multiple doses, on abomasal outflow fluid pH in adult cattle. A third objective was to describe the pharmacokinetic parameters of IV famotidine in cattle. Animals: Four clinically healthy adult Angus-cross steers previously fitted with duodenal cannulae placed orad to the biliary and pancreatic ducts. Methods: Randomized, 2-way cross-over clinical trial. Steers received IV famotidine (0.4 mg/kg) as a single and 3-dose regimen (every 8 hours) versus saline control. Blood for analysis of serum famotidine concentration was collected intermittently for 12 hours, and abomasal outflow fluid pH was measured at intervals for a 24-hour period. After a 34-hour washout period, the opposite treatments were administered and the sampling repeated. Results: Abomasal outflow fluid pH was higher in steers treated with famotidine for up to 4 hours after a single dose but the effect decreased with subsequent doses. The median (range) elimination half-life was 3.33 (3.21-3.54) hours. Conclusions and Clinical Importance: Famotidine may be useful for treatment or prevention of abomasal ulceration in adult cattle, but the duration of effect may decrease with time. Authors => Christie C. Balcomb | Meera C. Heller | Munashe Chigerwe | Heather K. Knych | Allison M. Meyer published => First published: 23 March 2018 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.15080

Title => Barriers to and enablers of implementing antimicrobial stewardship programs in veterinary practices Abstract => Background: Antimicrobial stewardship (AMS) programs are yet to be widely implemented in veterinary practice and medical programs are unlikely to be directly applicable to veterinary settings. Objective: To gain an in-depth understanding of the factors that influence effective AMS in veterinary practices in Australia. Methods: A concurrent explanatory mixed methods design was used. The quantitative phase of the study consisted of an online questionnaire to assess veterinarians’ attitudes to antimicrobial resistance (AMR) and antimicrobial use in animals, and the extent to which AMS currently is implemented (knowingly or unknowingly). The qualitative phase used semi-structured interviews to gain an understanding of the barriers to and enablers of AMS in veterinary practices. Data were collected and entered into NVivo v.11, openly coded and analyzed according to mixed methods data analysis principles. Results: Companion animal, equine, and bovine veterinarians participated in the study. Veterinary practices rarely had antimicrobial prescribing policies. The key barriers were a lack of AMS governance structures, client expectations and competition between practices, cost of microbiological testing, and lack of access to education, training and AMS resources. The enablers were concern for the role of veterinary antimicrobial use in development of AMR in humans, a sense of pride in the service provided, and preparedness to change prescribing practices. Conclusion and Clinical Importance: Our study can guide development and establishment of AMS programs in veterinary practices by defining the major issues that influence the prescribing behavior of veterinarians. Authors => Laura Y. Hardefeldt | J. R. Gilkerson | H. Billman-Jacobe | M. A. Stevenson | K. Thursky | K. E. Bailey | G. F. Browning published => First published: 23 March 2018 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.15083

Title => Computed tomographic appearance of abdominal lymph nodes in healthy cats Abstract => Background: Computed tomography (CT) is commonly used in veterinary medicine and plays an important role in disease identification and cancer staging. Identification of abnormal abdominal lymph nodes is important for clinical, therapeutic, and prognostic decision making. No published study describes the CT appearance of abdominal lymph nodes in healthy cats. Hypothesis/Objectives: All abdominal lymph centers will be identified on CT with the majority of lymph nodes being elongated and homogenously contrast enhancing. Animals: Sixteen healthy cats without clinical or biochemical evidence of disease. Methods: Precontrast and postcontrast CT images of sedated healthy cats were used to identify the presence and descriptive characteristics of intra-abdominal lymph nodes. These assessments then were compared with patient characteristics to identify possible correlations. Results: Abdominal lymph nodes were readily identified on CT with caudal mesenteric, colic, hepatic, inguinal, and pancreaticoduodenal lymph nodes identified in 16/16 cats. Lymph node size and shape varied among lymph centers with nearly all lymph nodes homogeneously contrast enhancing in 515/525. Significant negative correlations were identified between age and length (P = .0166) and width (P = .0387) of abdominal lymph nodes as well as age and number of sacral lymph nodes (P = .0493). Intranodal fat was present in 18/525 lymph nodes. Conclusions and Clinical Importance: CT readily permitted identification and characterization of feline abdominal lymph nodes. This study provides subjective and objective data on the CT characteristics of abdominal lymph nodes in 16 healthy cats, with younger cats having larger abdominal lymph nodes and a higher number of sacral lymph nodes. Authors => Michael Perlini | Andrew Bugbee | Scott Secrest published => First published: 23 March 2018 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.15088

Title => Prospective long-term evaluation of parenteral hydroxocobalamin supplementation in juvenile beagles with selective intestinal cobalamin malabsorption (Imerslund-Gräsbeck syndrome) Abstract => Background: Prospective studies on maintenance treatment for Beagles with hereditary selective cobalamin (Cbl) malabsorption (Imerslund-Gräsbeck syndrome, IGS) are lacking. In our experience, measurement of methylmalonic acid (MMA), a Cbl-dependent metabolite, seems more helpful to monitor Cbl status as compared with serum Cbl concentrations. Objectives: To evaluate a standardized Cbl supplementation scheme in Beagles with IGS. We hypothesized that a single parenteral dose of 1 mg hydroxocobalamin (OH-Cbl) would maintain clinical and metabolic remission for up to 2 months. Animals: Six client-owned juvenile Beagles with genetically confirmed IGS and 28 healthy control dogs. Methods: Prospective study. Monthly IM OH-Cbl (1 mg) supplementation was done over a median of 9 months (range, 6-13) in 6 dogs, followed by bimonthly (every 2 months) injections in 5 dogs over a median of 6 months (range, 3-10). Health status was assessed by routine clinical examinations at injection time points and owner observations. Voided urine samples were collected immediately before OH-Cbl injections for measurement of MMA-to-creatinine concentrations using a gas-liquid chromatography-tandem mass spectrometry (GC-MS) method. Results: All dogs were clinically healthy while receiving monthly and bimonthly OH-Cbl supplementation. Urinary MMA results in healthy dogs ranged from 1.3 to 76.5 mmol/mol creatinine (median, 2.9). Median urinary MMA concentrations did not differ between dogs with IGS receiving monthly (n = 49; 5.3 mmol/mol creatinine; range, 2.3-50.4) and bimonthly (n = 31; 5.3 mmol/mol creatinine; range, 1.6-50) injections. Conclusions and Clinical Importance: A maintenance parenteral dose of 1 mg OH-Cbl monthly or bimonthly appears adequate in Beagles with IGS monitored by metabolic testing. Authors => Peter Hendrik Kook | C. E. Reusch | M. Hersberger published => First published: 23 March 2018 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.15090

Title => Water requirements of canine athletes during multi-day exercise Abstract => Background: Exercise increases water requirements, but there is little information regarding water loss in dogs performing multi-day exercise Objectives: Quantify the daily water turnover of working dogs during multi-day exercise and establish the suitability of SC administration of tracer to determine water turnover. Animals: Fifteen privately owned Labrador retrievers trained for explosive detection duties and 16 privately owned Alaskan Huskies conditioned for mid-distance racing. Methods: All dogs received 0.3 g D2O/kg body weight by IV infusion, gavage, or SC injection before the start of a multi-day exercise challenge. Explosive detection dogs conducted 5 days of simulated off-leash explosive detection activity. Alaskan sled dogs completed a mid-distance stage race totaling 222 km in 2 days. Total body water (TBW) and daily water turnover were calculated using both indicator dilution and elimination regression techniques. Results: Total body water (% of body weight) varied from 60% ± 8.6% in minimally conditioned Labrador retrievers to 74% ± 4.5% in highly conditioned Labrador retrievers. Daily water turnover was as high as 45% of TBW during exercise in cold conditions. There was no effect of sex or speed on daily water turnover. There was good agreement between results calculated using the indicator dilution approach and those calculated using a semilog linear regression approach when indicator isotope was administered IV or SC. Conclusions and Clinical Importance: Water requirements are influenced primarily by the amount of work done. SC administration of isotope-labeled water offers a simple and accurate alternative method for metabolic studies. Authors => Lara Stephens-Brown | Michael Davis published => First published: 23 March 2018 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.15091

Title => Prognostic value of echocardiographic indices of left atrial morphology and function in dogs with myxomatous mitral valve disease Abstract => Background: The prognostic relevance of left atrial (LA) morphological and functional variables, including those derived from speckle tracking echocardiography (STE), has been little investigated in veterinary medicine. Objectives: To assess the prognostic value of several echocardiographic variables, with a focus on LA morphological and functional variables in dogs with myxomatous mitral valve disease (MMVD). Animals: One-hundred and fifteen dogs of different breeds with MMVD. Methods: Prospective cohort study. Conventional morphologic and echo-Doppler variables, LA areas and volumes, and STE-based LA strain analysis were performed in all dogs. A survival analysis was performed to test for the best echocardiographic predictors of cardiac-related death. Results: Most of the tested variables, including all LA STE-derived variables were univariate predictors of cardiac death in Cox proportional hazard analysis. Because of strong correlation between many variables, only left atrium to aorta ratio (LA/Ao > 1.7), mitral valve E wave velocity (MV E vel > 1.3 m/s), LA maximal volume (LAVmax > 3.53 mL/kg), peak atrial longitudinal strain (PALS < 30%), and contraction strain index (CSI per 1% increase) were entered in the univariate analysis, and all were predictors of cardiac death. However, only the MV E vel (hazard ratio [HR], 4.45; confidence interval [CI], 1.76-11.24; P < .001) and LAVmax (HR, 2.32; CI, 1.10-4.89; P = .024) remained statistically significant in the multivariable analysis. Conclusions and Clinical Importance: The assessment of LA dimension and function provides useful prognostic information in dogs with MMVD. Considering all the LA variables, LAVmax appears the strongest predictor of cardiac death, being superior to LA/Ao and STE-derived variables. Authors => Marco Baron Toaldo | Giovanni Romito | Carlo Guglielmini | Alessia Diana | Nazzareno G. Pelle | Barbara Contiero | Mario Cipone published => First published: 23 March 2018 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.15093

Title => Suitability of oral administration of monosodium phosphate, disodium phosphate, and magnesium phosphate for the rapid correction of hypophosphatemia in cattle Abstract => Background: Hypophosphatemia is commonly associated with disease and decreased productivity in dairy cows particularly in early lactation. Oral supplementation with phosphate salts is recognized as suitable for the rapid correction of hypophosphatemia. Little information is available about the differences in efficacy between salts used for oral phosphorus supplementation. Objectives: Comparison of efficacy of oral administration of NaH2PO4, Na2HPO4, and MgHPO4 in treating hypophosphatemia in cattle. Animals: 12 healthy dairy cows in the fourth week of lactation in their second to fifth lactation. Methods: Randomized clinical study. Phosphorus deficient, hypophosphatemic cows underwent a sham treatment and were afterwards assigned to 1 of 3 treatments—NaH2PO4, Na2HPO4, or MgHPO4 (each provided the equivalent of 60 g of phosphorus). Blood samples were obtained immediately before and repeatedly after treatment. Results: Treatment with NaH2PO4 and Na2HPO4 resulted in rapid and sustained increases of plasma phosphate concentrations ([Pi]). Significant effects were apparent within 1 hour (NaH2PO4: P = .0044; Na2HPO4: P = .0077). Peak increments of plasma [Pi] of 5.33 mg/dL [5.26–5.36] and 4.30 mg/dL [3.59–4.68] (median and interquartile range) were reached after 7 and 6 hours in animals treated with NaPH2PO4 and Na2HPO4, respectively, whereas treatment with MgHPO4 led to peak increments 14 hours after treatment (3.19 mg/dL [2.11–4.04]). Conclusions and Clinical Importance: NaH2PO4 and Na2HPO4 are suitable to rapidly correct hypophosphatemia in cattle. Because of the protracted and weaker effect, MgHPO4 cannot be recommended for this purpose. Despite important differences in solubility of NaH2PO4 and Na2HPO4 only small plasma [Pi] differences were observed after treatment. Authors => Imke Cohrs | Walter Grünberg published => First published: 23 March 2018 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.15094

Title => Metabolic perturbations in Welsh Ponies with insulin dysregulation, obesity, and laminitis Abstract => Background: Metabolomics, the study of small-molecule metabolites, has increased understanding of human metabolic diseases, but has not been used to study equine metabolic syndrome (EMS). Objectives: (1) To examine the serum metabolome of Welsh Ponies with and without insulin dysregulation before and during an oral sugar test (OST). (2) To identify differences in metabolites in ponies with insulin dysregulation, obesity, or history of laminitis. Animals: Twenty Welsh Ponies (mean ± SD; 13.8 ± 9.0 years) classified as non-insulin dysregulated [CON] (n = 10, insulin < 30 mU/L) or insulin dysregulated [ID] (n = 10, insulin > 60 mU/L) at 75 minutes after administration of Karo syrup, obese (n = 6) or nonobese (n = 14), and history of laminitis (n = 9) or no history of laminitis (n = 11). Methods: Case-control study. Metabolomic analysis was performed on serum obtained at 0 minutes (baseline) and 75 minutes during the OST. Data were analyzed with multivariable mixed linear models with significance set at P ≤ .05. Results: Metabolomic analysis of 646 metabolites (506 known) detected significant metabolite differences. At baseline, 55 metabolites (insulin response), 91 metabolites (obesity status), and 136 metabolites (laminitis history) were different. At 75 minutes, 51 metabolites (insulin response), 102 metabolites (obesity status), and 124 metabolites (laminitis history) were different. Conclusions and Clinical Importance: Use of metabolomics could have diagnostic utility for early detection of EMS and provide new knowledge regarding the pathophysiology of metabolic perturbations associated with this condition that might lead to improved clinical management. Authors => Sarah I. Jacob | Kevin J. Murray | Aaron K. Rendahl | Raymond J. Geor | Nichol E. Schultz | Molly E. McCue published => First published: 23 March 2018 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.15095

Title => Kinetic and kinematic follow-up gait analysis in Doberman Pinschers with cervical spondylomyelopathy treated medically and surgically Abstract => Background: The efficacy of treatment of dogs with cervical spondylomyelopathy (CSM) is commonly based on the owner's and clinician's perception of the gait, which is highly subjective and suffers from observer bias. Hypothesis/Objectives: To compare selected kinetic and kinematic parameters before and after treatments and to correlate the findings of gait analysis to clinical outcome. Animals: Eight Doberman Pinschers with CSM confirmed by magnetic resonsance imaging. Methods: Patients were prospectively studied and treated with either medical management (n = 5) or surgery (n = 3). Force plate analysis and 3-D kinematic motion capture were performed at initial presentation and approximately 8 weeks later. Force plate parameters evaluated included peak vertical force (PVF). Kinematic parameters measured included number of pelvic limb strides, stifle flexion and extension, maximum and minimum thoracic limb distance, truncal sway, and thoracic limb stride duration. Results: Kinematic analysis showed that deviation of the spine to the right (truncal sway) was significantly smaller (P < .001) and the degree of right stifle flexion was significantly larger (P = .029) after treatment. Force plate analysis indicated that PVF was significantly different after treatment (P = .049) and the difference of the PVF also was significantly larger (P = .027). However, no correlation was found with either method of gait analysis and clinical recovery. Conclusions and Clinical Importance: Kinetic and kinematic gait analysis were able to detect differences in dogs with CSM before and after treatment. A correlation of gait analysis to clinical improvement could not be determined. Authors => Kari D. Foss | Rebecca L. Smith | Ronaldo C. da Costa published => First published: 23 March 2018 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.15096

Title => Detection and seroprevalence of morbillivirus and other paramyxoviruses in geriatric cats with and without evidence of azotemic chronic kidney disease Abstract => Background: Feline morbillivirus (FeMV) is associated with the presence of tubulo-interstitial nephritis (TIN) in cats, however the seroprevalence of FeMV in the UK and the association between the presence of FeMV and renal azotemia is unknown Hypothesis/Objectives: To identify whether paramyxoviruses are present in urine samples of geriatric cats and to develop an assay to assess FeMV seroprevalence. To investigate the relationship between both urinary paramyxovirus (including FeMV) excretion and FeMV seroprevalence and azotemic chronic kidney disease (CKD). Animals: Seventy-nine cats (40 for FeMV detection; 72 for seroprevalence). Methods: Retrospective cross-sectional, case control study. Viral RNA was extracted from urine for RT-PCR. PCR products were sequenced for virus identification and comparison. The FeMV N protein gene was cloned and partially purified for use as an antigen to screen cat sera for anti-FeMV antibodies by Western Blot. Results: Feline morbillivirus RNA from five distinct morbilliviruses were identified. Detection was not significantly different between azotemic CKD (1/16) and nonazotemic groups (4/24; P = .36). Three distinct, non-FeMV paramyxoviruses were present in the nonazotemic group but their absence from the azotemic group was not statistically significant (P = .15). 6/14 (43%) azotemic cats and 40/55 (73%) nonazotemic cats were seropositive (P = .06). Conclusions and Clinical Importance: Feline morbillivirus was detected in cats in the UK for the First time. However, there was no association between virus prevalence or seropositivity and azotemic CKD. These data do not support the hypothesis that FeMV infection is associated with the development of azotemic CKD in cats in the UK. Authors => Katie Elizabeth McCallum | Sam Stubbs | Nicholas Hope | Ian Mickleburgh | Dave Dight | Laurence Tiley | Tim L. Williams published => First published: 23 March 2018 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.15097

Title => Sonographic features of peritoneal lymphomatosis in 4 cats Abstract => Background: The metastatic spread of feline lymphoma to the peritoneum (“lymphomatosis”) has been rarely reported in the literature. The sonographic features specific to this rare disease manifestation have not been described and have important treatment and prognostic considerations prompting definitive diagnosis. Objectives: To describe the ultrasonic features of feline peritoneal lymphomatosis. Animals: Four cats with alimentary lymphoma and peritoneal metastasis confirmed using cytology, histology, or both. Results: The sonographic features described include either a nonobstructive, focally diffuse, and circumferential intestinal mass, or an eccentric, focally diffuse, gastric mass. The intestinal and gastric lesions exhibited hypo-to-anechoic transmural wall thickening with loss of wall layering in association with discrete-to-coalescing plaques or sheets of thickened, hypoechoic tissue throughout the mesentery or omenta. All cases exhibited only small volumes of anechoic free peritoneal fluid. Three of the 4 cats also had multiple small hypoechoic nodular foci on the parietal and/or visceral peritoneal surfaces. Two cats had bilateral renomegaly because of lymphoma invasion (2/4) and 1 cat had local lymphadenopathy secondary to lymphoma invasion (1/4). Conclusions and Clinical Importance: Peritoneal lymphomatosis is a rare manifestation of lymphoma metastasis and to date appears to be associated specifically with B-cell alimentary lymphoma. Authors => Keaton R. S. Morgan | Courtney E. North | Devon J. Thompson published => First published: 23 March 2018 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.15099

Title => Effect of interleukin-1β on occludin mRNA expression in the duodenal and colonic mucosa of dogs with inflammatory bowel disease Abstract => Background: Mucosal imbalance of interleukin (IL)-1β and IL-1 receptor antagonist (Ra) has been reported in the duodenal mucosa of dogs with inflammatory bowel disease (IBD). However, the imbalance in the colonic mucosa and its role in duodenitis and colitis in IBD of dogs remain unclear. Objectives: To measure the expression of IL-1β and IL-1Ra proteins in the colonic mucosa of dogs with IBD, and to determine the effect of IL-1β on expression of occludin (ocln) mRNA, a tight junction component, in the duodenal and colonic mucosa of dogs with IBD. Animals: Twelve dogs with IBD and 6 healthy dogs. Methods: IL-1β and IL-1 Ra proteins in the colonic mucosa were quantified by ELISA in 7 of the 12 dogs with IBD. Expression of ocln mRNA in the duodenal and colonic mucosa was examined in the 12 dogs by real-time PCR. Results: The ratio of IL-1β to IL-1Ra in the colonic mucosa was significantly higher in dogs with IBD than in healthy dogs. The ex vivo experiment determined that IL-1β suppressed expression of ocln mRNA in the colonic mucosa, but not in the duodenal mucosa, of healthy dogs. Expression of ocln mRNA in the colonic mucosa, but not in the duodenal mucosa, was significantly lower in dogs with IBD than in healthy dogs. Conclusions and Clinical Importance: A relative increase in IL-1β may attenuate ocln expression, leading to intestinal barrier dysfunction and promotion of intestinal inflammation in the colonic mucosa, but not in the duodenal mucosa, of dogs with IBD. Authors => Misato Ogawa | Hironari Osada | Ayana Hasegawa | Hikaru Ohno | Nanako Yanuma | Kazuaki Sasaki | Minoru Shimoda | Junsuke Shirai | Hirotaka Kondo | Keitaro Ohmori published => First published: 23 March 2018 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.15117