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Title => Urogenital anomalies and urinary incontinence in an English Cocker Spaniel dog with XX sex reversal Abstract => Authors => Hakyoung Yoon | Sung-Hee Han | Jaehwan Kim | Kihoon Kim | Kidong Eom published => First published: 23 March 2018 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.15119

Title => Effect of cross-match on packed cell volume after transfusion of packed red blood cells in transfusion-naïve anemic cats Abstract => Background: Novel feline RBC antigens might contribute to decreased efficacy of RBC transfusion and increased incidence of acute transfusion reactions (ATR). Objectives: To examine the effect of major cross-match in transfusion-naïve anemic cats on the incidence of acute immunologic transfusion reaction and transfusion efficacy for up to 24 hours after transfusion. Animals: Forty-eight client owned transfusion-naïve anemic cats. Methods: Prospective, randomized, controlled study. All transfusion-naïve cats receiving packed red blood cells (pRBC) transfusions from January 2016 to August 2017 were eligible for inclusion. Cats in the study group received cross-match and blood type compatible pRBCs and cats in the control group received noncross-matched blood type compatible pRBCs. Incidence of ATR and change in PCV after transfusion was recorded. Results: No significant difference in incidence of transfusion reactions between cross-matched and noncross-matched groups (CM+ 4/24; 17%, CM– 7/24; 29%, P = .16). No significant difference between groups in mean change in PCV after transfusion scaled to dose of pRBCs administered at any time point after transfusion (immediate: CM+ 0.62 ± 0.59, CM– 0.75 ± 0.48, P = .41; 1 hour: CM+ 0.60 ± 0.66, CM– 0.74 ± 0.53, P = .43; 12 hours: CM+ 0.70 ± 0.55, CM– 0.66 ± 0.60, P = .81; 24 hours: CM+ 0.64 ± 0.71, CM– 0.55 ± 0.48, P = .70). Conclusions and Clinical Importance: Our results do not support use of the major cross-match test to increase efficacy of, and to decrease adverse events associated with, RBC transfusion in AB blood typed transfusion-naïve cats. Authors => Brittany Sylvane | Jennifer Prittie | Ann E. Hohenhaus | Erik Tozier published => First published: 23 March 2018 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.15120

Title => Transcranial magnetic motor evoked potentials and magnetic resonance imaging findings in paraplegic dogs with recovery of motor function Abstract => Background: Transcranial magnetic motor evoked potentials (TMMEP) are associated with severity of clinical signs and magnetic resonance imaging (MRI) findings in dogs with spinal cord disease. Hypothesis: That in initially paraplegic dogs with thoracolumbar intervertebral disc herniation (IVDH), MRI findings before surgery and TMMEPs obtained after decompressive surgery are associated with long-term neurological status and correlate with each other. Animals: Seventeen client-owned paraplegic dogs with acute thoracolumbar IVDH. Methods: Prospective observational study. TMMEPs were obtained from pelvic limbs and MRI (3T) of the spinal cord was performed at initial clinical presentation. Follow-up studies were performed ≤ 2 days after reappearance of motor function and 3 months later. Ratios of compression length, intramedullary hyperintensities' length (T2-weighted hyperintensity length ratio [T2WLR]), and lesion extension (T2-weighted-lesion extension ratio) in relation to the length of the 2nd lumbar vertebral body were calculated. Results: TMMEPs could be elicited in 10/17 (59%) dogs at 1st and in 16/17 (94%) dogs at 2nd follow-up. Comparison of TMMEPs of 1st and 2nd follow-up showed significantly increased amplitudes (median from 0.19 to 0.45 mV) and decreased latencies (from 69.38 to 40.26 ms; P = .01 and .001, respectively). At 2nd follow-up latencies were significantly associated with ambulatory status (P = .024). T2WLR obtained before surgery correlated with latencies at 2nd follow-up (P = .04). Conclusions: TMMEP reflect motor function recovery after severe spinal cord injury. Authors => Johannes S. Siedenburg | Adriano Wang-Leandro | Hanna-Luise Amendt | Karl Rohn | Andrea Tipold | Veronika M. Stein published => First published: 22 March 2018 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.15058

Title => Comparison of two melphalan protocols and evaluation of outcome and prognostic factors in multiple myeloma in dogs Abstract => Background: Multiple myeloma (MM) in dogs typically is treated with melphalan. A daily melphalan dosing schedule reportedly is well tolerated and associated with favorable outcome. Although anecdotally a pulse dose regimen has resulted in successful responses, little long-term outcome and safety data is available regarding this dosing regimen for dogs with MM. Hypothesis/objectives: (1) To compare outcome and adverse event profiles between pulse dose and daily dose melphalan schedules and (2) to report prognostic factors in dogs with MM treated with melphalan. We hypothesized that both protocols would have similar outcomes and tolerability. Animals: Thirty-eight client-owned dogs diagnosed with MM receiving pulse dose (n = 17) or daily dose (n = 21) melphalan. Methods: Retrospective cohort study assessing outcome and adverse events in dogs receiving either protocol. Risk factors were evaluated for their prognostic relevance. Results: Both regimens were well tolerated and similarly effective, with an overall median survival time of 930 days. Renal disease and neutrophil-to-lymphocyte ratio (NLR) were negative prognostic factors, whereas hypercalcemia and osteolytic lesions were not prognostic factors in this study population. Conclusions and Clinical Importance: Positive results support the use of either dosing regimen for the treatment of dogs with MM, and renal disease and NLR were negative prognostic factors. Prospective, controlled, and randomized studies are warranted to confirm these findings. Authors => Ricardo Fernández | Esther Chon published => First published: 22 March 2018 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.15084

Title => ACVIM consensus update on Lyme borreliosis in dogs and cats Abstract => Authors => Meryl P. Littman | Bernhard Gerber | Richard E. Goldstein | Mary Anna Labato | Michael R. Lappin | George E. Moore published => First published: 22 March 2018 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.15085

Title => Erratum Abstract => None Abstract Authors => published => First published: 22 March 2018 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.15115

Title => Effect of calibration methods on the accuracy of angiographic measurements during transcatheter procedures in dogs Abstract => Background: Different methods to perform reference calibration of an angiographic image exist; however, a prospective comparison of calibration methods has yet to be investigated in veterinary medicine. Objective: To compare angiographic measurements using two commonly employed reference calibration methods, an esophageal pigtail marker catheter (EC) versus a radiopaque table ruler (TR). Animals: Thirty-five client-owned dogs undergoing transcatheter intervention. Methods: Prospective comparison study. Two reference calibration methods, EC and TR, were recorded in dogs undergoing transcatheter procedures from May 2016 to July 2017. Relevant measurements were performed in triplicate and averaged after image calibration to either EC or TR. Comparisons between methods were made by correlation, paired t-test, the method of Bland and Altman, and Passing-Bablok regression. Results: A total of 39 angiographic structures were measured. Interventions included balloon pulmonary valvuloplasty (n = 21), patent ductus arteriosus occlusion (n = 11), subaortic or sub-pulmonary balloon dilatation (n = 4), and cor triatriatum membranostomy (n = 3). Angiographic measurements were larger when calibrated to EC versus TR (P < .0001). The mean bias was 0.86 mm, with greater bias for larger measurements. The EC measurements were ∼10% greater than TR based on regression analysis. Weight was correlated to the difference between methods (ρ = 0.55, P = .0003). Conclusions and Clinical Importance: Angiographic image calibration using a ruler placed on the fluoroscopy table underestimates the size of a structure by ∼10% as compared with a marker catheter placed within the esophagus. This effect is greatest when measuring larger structures such as the pulmonary valve annulus and in larger dogs. Authors => Lauren E. Markovic | Brian A. Scansen published => First published: 12 March 2018 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.15082

Title => An experimental model for calcium carbonate urolithiasis in goats Abstract => Background: Calcium carbonate is a common urolith type in small ruminants with no high-yield experimental model to evaluate animal susceptibility or preventative measure response. Hypothesis: That novel plastic winged implants would allow accumulation and quantification of calcium carbonate calculus formation in goats on a high-calcium diet and identify individual variation between goats in the mass of calculi produced. Animals: Eight nonpregnant 3- and 4-year-old Boer-cross does, weighing 22.3–39.5 kg, determined to be healthy based on physical examination, were used in these experiments. Methods: Prospective cohort study for in vivo experimental model development. Implants were placed into the urinary bladder lumen in 8 goats over 2 evaluation periods. The alfalfa-based ration had a total ration Ca : P of 3.29 and 3.84 : 1, respectively. Urine was collected at 0, 28, 56, and 84 days in the 1st experiment; blood and urine at those timepoints in the 2nd experiment. For each evaluation period, the implants were removed 84 days after implantation and weighed. Accumulated calculi mass was calculated and compared between goats and was analyzed for composition. Results: Implant retention was 100% and 86% in the 2 studies. All goats with retained implants accumulated calcium carbonate at a mean implant gain per day across studies ranging from 0.44 to 57.45 mg. Two goats accumulated (0.44–7.65 mg/day and 33.64 & 57.45 mg/day) significantly more urolith material than the cohort across both studies (P = .047). No routine analytes on blood or urine were found to be explanatory for the difference observed. Conclusions and Clinical Importance: These findings form a basis for implant and diet selection for use in future studies of urolithiasis development and for studies regarding individual susceptibility to urolithiasis. Authors => Meredyth L. Jones | Brandon J. Dominguez | Michael A. Deveau published => First published: 10 March 2018 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.15061

Title => Incomplete endothelialization of an intravascular implant and fatal late-onset bacterial ductal arteritis in a dog with occluded patent ductus arteriosus Abstract => Authors => Niek Jozef Beijerink | Wilhelmina Bergmann | Viktor Szatmári published => First published: 10 March 2018 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.15074

Title => Computed Tomographic Angiography of the Pancreas in Cats with Chronic Diabetes Mellitus Compared to Normal Cats Abstract => Background: Diabetes mellitus (DM) is a common endocrinopathy in cats. No known diagnostic test or patient characteristic at the time of diagnosis can predict likely disease course, unlike in people in whom computed tomographic angiography (CTA) is used. No published data exist regarding the CTA appearance of the pancreas in cats with DM, and thus, it is unknown what if any CTA variables should be further assessed for associations with pancreatic endocrine function. Hypothesis/Objectives: A significant difference in pancreatic attenuation, volume, and size will be identified between normal cats and those with chronic DM on CTA. Animals: Ten healthy control cats and 15 cats with naturally occurring DM present for >12 months. Methods: Prospective cross-sectional study comparing pancreatic attenuation, enhancement pattern, size, volume, pancreatic volume-to-body weight ratio (V:BW), pancreatic arterial: portal phase ratio (A:P), time-to-arterial enhancement, and time-to-peak portal enhancement on CTA between sedated healthy control cats and those with chronic DM. Results: The pancreas in cats with chronic DM was significantly larger, had higher volume, higher V:BW, and shorter time-to-peak portal enhancement on CTA when compared to normal cats. Conclusions and Clinical Importance: Peak portal enhancement time, pancreatic size, pancreatic volume, and V:BW can be used to differentiate normal sedated cats from those with chronic DM by CTA. These variables warrant further investigation to identify possible associations with endocrine function. Authors => S. Secrest | A. Sharma | A. Bugbee published => First published: 02 March 2018 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.14899

Title => Evaluation of individual low-dose dexamethasone suppression test patterns in naturally occurring hyperadrenocorticism in dogs Abstract => Background: Dogs with hyperadrenocorticism (HAC) may be more mildly affected at the time of diagnosis today, which could influence the prevalence of associated clinical and clinicopathological abnormalities and diagnostic test performance. Different low-dose dexamethasone suppression test (LDDST) result patterns have not been evaluated individually. Objectives: To assess the current features of HAC and evaluate if the diagnostic test performance of individual LDDST result patterns differ. Animals: One hundred and twenty-three dogs undergoing investigation for HAC. Methods: Retrospective evaluation of dogs in which a LDDST was performed and HAC confirmed or excluded by alternative means. Cases with basal cortisol concentrations (t0) < 1 μg/dL were excluded. Each LDDST result was classified as (a) complete suppression (t3 and t8 < 1 μg/dL), (b) lack of suppression (t3 and t8 > 1 μg/dL and both > 50% t0), (c) partial suppression (t3 and t8 > 1 μg/dL but either < 50% t0), (d) escape (t8 > 1 μg/dL and t3 < 1 μg/dL) or (e) inverse (t3 > 1 μg/dL and t8 < 1 μg/dL) pattern. Results: Fifty-nine (48%) dogs were diagnosed with HAC and 64 (52%) with non-adrenal illness. Hyperadrenocorticism cases had similar clinicopathological abnormalities compared to previous reports. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) (95% confidence interval [CI]) of the LDDST for diagnosing HAC were 96.6 (91.9-100)%, 67.2 (55.7-78.7)%, 73.1 (63.2-82.9)%, and 95.6 (89.5-100)%, respectively. Lack of suppression pattern had the highest PPV (93.9 [85.8-100]%) followed by the partial suppression pattern (67.9 [50.6–85.2]%) and escape or inverse pattern (36.8 [15.1–58.5]%). Conclusions and Clinical Importance: A lack of suppression LDDST pattern has the highest PPV for diagnosing HAC followed by a partial suppression pattern. By contrast, the escape or inverse pattern provided limited support of HAC. Authors => Michael Bennaim | Robert E. Shiel | Christopher Forde | Carmel T. Mooney published => First published: 02 March 2018 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.15079

Title => Concurrent renal amyloidosis and thymoma resulting in a fatal ventricular thrombus in a dog Abstract => Authors => Jennifer M. Loewen | Rachel E. Cianciolo | Liwen Zhang | Michael Yaeger | Jessica L. Ward | Jodi D. Smith | Dana N. LeVine published => First published: 27 February 2018 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.15062

Title => Evaluation of potential serum biomarkers of hepatic fibrosis and necroinflammatory activity in dogs with liver disease Abstract => Background: Serum interleukin 6 (IL-6), chemokine ligand 2 (CCL2), C-reactive protein (CRP), and the ratio of aspartate transaminase to alanine transaminase (AST:ALT) have been correlated with fibrosis and necroinflammatory activity in humans with various hepatopathies. Hypothesis/Objectives: To determine whether increases in serum IL-6, CCL2, CRP, or AST:ALT were associated with moderate to severe fibrosis or necroinflammatory activity in dogs with various hepatopathies. Animals: Forty-four client-owned dogs with clinical evidence of liver disease and 10 healthy purpose-bred dogs, all undergoing liver biopsies by laparoscopy or laparotomy. Methods: Measurement of serum IL-6, CCL2, CRP, AST, and ALT before scheduled liver biopsy and evaluation of liver histopathology using the METAVIR scoring system used in human medicine, blinded to clinical presentation. Results: Median serum IL-6 was approximately twice as high in dogs with high fibrosis scores (15.5 pg/mL; range, 1.4 to 235 pg/mL) compared to dogs with low fibrosis scores (7.6 pg/mL; range, 1.4 to 148.1 pg/mL), with marginal significance (P = .05). Median serum CCL2 was significantly higher in dogs with active necroinflammation (444 pg/mL; range, 144 to 896 pg/mL) compared to dogs without detectable necroinflammation (326 pg/mL; range, 59 to 1692 pg/mL; P = .008), but with considerable overlap between groups. Neither serum CRP nor AST:ALT ratios were significantly different based on fibrosis or necroinflammatory scores. Conclusions and Clinical Importance: Because of substantial variability among dogs, single measurements of IL-6 and CCL2 have limited diagnostic utility for identifying fibrosis or necroinflammation, respectively, in dogs with various chronic liver diseases. The value of these biomarkers should be explored further in monitoring response to treatment in individual dogs with chronic hepatopathies. Authors => Chantel Raghu | Joanne Ekena | John M. Cullen | Craig B. Webb | Lauren A. Trepanier published => First published: 27 February 2018 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.15064

Title => Effect of ionization, bedding, and feeding on air quality in a horse stable Abstract => Background: Organic dust is associated with Equine asthma. Ionization should reduce airborne dust levels. Objectives: To determine the effect of ionization of air, type of bedding, and feed on the levels of airborne dust, endotoxin, and fungal colonies in horse stables. Animals: 24 healthy University-owned horses occupied the stables. Methods: A randomized controlled cross-over study. Four units with 6 stables were equipped with an ionization installation (25 VA, 5000 Volt Direct Current). Horses were kept either on wood shavings and fed haylage (2 units), or on straw and fed dry hay (2 units). Measurements were performed with and without activated ionization, during daytime and nighttime, repeatedly over the course of a week and repeatedly during 4-6 weeks. Statistical analysis was performed using a mixed effect model with Akaike's Information Criterion for model reduction and 95% profile (log) likelihood confidence intervals (CI). Results: Ionization did not alter concentrations of dust, endotoxin, or fungi, fewer. In the units with straw and hay, the concentration of dust, endotoxin, and fungi (difference in logarithmic mean 1.92 (95%CI 1.71-2.12); 2.86 (95%CI 2.59-3.14); 1.75 (95%CI 1.13-2.36)) were significantly higher compared to wood shavings and haylage. Conclusions and Clinical Importance: The installation of a negative air-ionizer in the horse stable did not reduce concentrations of dust, endotoxin, and viable fungal spores. The substantial effect of low dust bedding and feed is confirmed. Authors => Esther Willemijn Siegers | Milou Anthonisse | Frank J. C. M. van Eerdenburg | Jan van den Broek | Inge M. Wouters | Cornélie Martine Westermann published => First published: 27 February 2018 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.15069

Title => A de novo mutation in the EXT2 gene associated with osteochondromatosis in a litter of American Staffordshire Terriers Abstract => Background: We aimed to identify mutations associated with osteochondromatosis in a litter of American Staffordshire Terrier puppies. Hypothesis: We hypothesized that the associated mutation would be located in a gene that causes osteochondromatosis in humans. Animals: A litter of 9 American Staffordshire puppies, their sire and dam, 3 of 4 grandparents, 26 healthy unrelated American Staffordshire Terriers, and 154 dogs of 27 different breeds. Methods: Whole genome sequencing was performed on the proband, and variants were compared against polymorphisms derived from 154 additional dogs across 27 breeds, as well as single nucleotide polymorphism database 146. One variant was selected for follow-up sequencing. Parentage and genetic mosaicism were evaluated across the litter. Results: We found 56,301 genetic variants unique to the proband. Eleven variants were located in or near the gene exostosin 2 (EXT2), which is strongly associated with osteochondromatosis in humans. One heterozygous variant (c.969C > A) is predicted to result in a stop codon in exon 5 of the gene. Sanger sequencing identified the identical mutation in all affected offspring. The mutation was absent in the unaffected offspring, both parents, all available grandparents, and 26 healthy unrelated American Staffordshire Terriers. Conclusions and Clinical Importance: These findings represent the first reported mutation associated with osteochondromatosis in dogs. Because this mutation arose de novo, the identical mutation is unlikely to be the cause of osteochondromatosis in other dogs. However, de novo mutations in EXT2 are common in humans with osteochondromatosis, and by extension, it is possible that dogs with osteochondromatosis could be identified by sequencing the entire EXT2 gene. Authors => Steven G. Friedenberg | Daniella Vansteenkiste | Oriana Yost | Amy E. Treeful | Kathryn M. Meurs | Debra A. Tokarz | Natasha J. Olby published => First published: 27 February 2018 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.15073

Title => Two-Year Follow-Up Magnetic Resonance Imaging and Spectroscopy Findings and Cerebrospinal Fluid Analysis of a Dog with Sandhoff's Disease Abstract => Authors => D. Ito | C. Ishikawa | N.D. Jeffery | K. Ono | M. Tsuboi | K. Uchida | O. Yamato | M. Kitagawa published => First published: 25 February 2018 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.15041

Title => Borrelia burgdorferi Infection and Lyme Disease in North American Horses: A Consensus Statement Abstract => Authors => T.J. Divers | R.B. Gardner | J.E. Madigan | S.G. Witonsky | J.J. Bertone | E.L. Swinebroad | S.E. Schutzer | A.L. Johnson published => First published: 22 February 2018 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.15042

Title => 10th Annual European College of Equine Internal Medicine Congress: 2—4 November, 2017 Abstract => None Abstract Authors => published => First published: 22 February 2018 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.15044

Title => The Effect of Urine Concentration and pH on the Growth of Escherichia Coli in Canine Urine In Vitro Abstract => Background: Lower urinary tract infections are common in dogs, and Escherichia coli is the most common bacterial pathogen isolated. The literature has conflicting evidence regarding the inhibitory effects of urine concentration and pH on E. coli growth. Hypothesis/Objectives: To determine the effect of different pH and urine concentrations on E. coli growth in vitro. Animals: Voided urine samples from 10 apparently healthy spayed female dogs were used. Methods: A matrix of 9 urine specific gravity (USG; 1.010, 1.020, and 1.030) and pH (5.5, 7.0, and 8.5) combinations was prepared by diluting and titrating filtered voided urine samples. Three E. coli isolates were obtained from urine of female dogs with signs of lower urinary tract infection and cultured at different urine pH and USG combinations in wells of a microtiter plate. The number of E. coli colony-forming units (CFU) per mL of urine was calculated after aerobic incubation of the urine at 37°C for 18 hours, and statistically compared. Results: Significant differences were identified in the mean log CFU/mL among different combinations of pH and USG. The lowest log CFU/mL were observed in alkaline concentrated urine (pH 8.5 and USG 1.030). Conclusions and Clinical Importance: Escherichia coli in vitro growth was higher in neutral to acidic and diluted urine compared to alkaline and concentrated urine. The impact of non-alkalizing diluting diets on the incidence of E. coli lower urinary tract infections should be further explored. Authors => L.A. Thornton | R.K. Burchell | S.E. Burton | N. Lopez-Villalobos | D. Pereira | I. MacEwan | C. Fang | A.C. Hatmodjo | M.A. Nelson | A. Grinberg | N. Velathanthiri | A. Gal published => First published: 22 February 2018 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.15045

Title => Assessment of Canine Pancreas-Specific Lipase and Outcomes in Dogs with Hemodialysis-Dependent Acute Kidney Injury Abstract => Background: Renal replacement therapies can be life-saving for dogs with severe acute kidney injury (AKI), however, comorbidities including pancreatitis might affect outcome. Hypothesis/Objectives: To investigate the prevalence of pancreas-specific lipase (Spec cPL) measurements consistent with pancreatitis (≥400 μg/L) in dogs undergoing intermittent hemodialysis (IHD) for treatment of AKI and to determine whether there were associations between 30-days outcomes and Spec cPL measurements. Animals: Fifty-three client-owned dogs presented to teaching hospitals between November 2008 and September 2016 that underwent IHD. Methods: Retrospective medical record review from dogs that received IHD for management of AKI and also had a Spec cPL measurement. Association between survival, dialysis-dependency, and Spec cPL measurements was assessed. Results: Forty of 53 (76%) dogs were alive at 30-days and 33/53(62%) had a Spec cPL result ≥400 μg/L. Spec cPL was not significantly different either between surviving (635.5 μg/L, range 29–1,001) and nonsurviving dogs (860 μg/L, range 56–1,001; P = 0.75) or between dialysis-dependent (1,001 μg/L, range 177–1,001) and nondialysis-dependent dogs (520 μg/L, range 29–1,001; P = 0.08). Spec cPL ≥400 μg/L was not significantly associated either with survival (P = 0.74) or dialysis-dependency (P = 0.33). Conclusions and Clinical Importance: Results revealed a high prevalence of Spec cPL ≥400 μg/L in dogs with AKI treated with IHD. No significant associations between Spec cPL and survival or dialysis-dependency in dogs with AKI at 30 days were identified in the current study, however, the latter could be due to lack of power in this study. Authors => K. Takada | C.A. Palm | S.E. Epstein | L.D. Cowgill published => First published: 22 February 2018 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.15047

Title => Effects of Diagnostic Work-Up on Medical Decision-Making for Canine Urinary Tract Infection: An Observational Study in Danish Small Animal Practices Abstract => Background: Clinical signs of urinary tract disease in dogs often lead to prescription of antibiotics. Appropriate diagnostic work-up could optimize treatment and reduce the risk of inappropriate use of antibiotics. Hypothesis/Objectives: To describe and evaluate the impact of diagnostic work-up on decision to treat (DTT) and choice of antibiotic treatment (COT) for dogs presenting with clinical signs of urinary tract disease. Animals: One hundred and fifty-one dogs presenting to 52 Danish veterinary practices. Methods: Prospective, observational study. Clinical signs, diagnostic work-up, and prescriptions were recorded. Urine samples were submitted to a reference laboratory for quantitative bacterial culture (QBC) and susceptibility testing. The laboratory results were used as reference for assessing the appropriateness of DTT and COT. Results: In the majority of dogs, veterinarians performed dipstick (99%), microscopic examination of urine (80%) and bacterial culture (56%). Fifty-one percent of dogs had urinary tract infection (UTI) based on reference QBC. Appropriate DTT was made for 62% of the dogs, while 36% were over-prescribed and 2% under-prescribed. Inappropriate use of second-line agents was found in 57% of the UTI cases. Performing microscopy—but not culture—significantly impacted DTT (P = 0.039) while no difference was seen in COT (P = 0.67). The accuracy of in-house microscopy and culture were 64.5 and 77%, respectively. Authors => T.M. Sørensen | C.R. Bjørnvad | G. Cordoba | P. Damborg | L. Guardabassi | V. Siersma | L. Bjerrum | L.R. Jessen published => First published: 22 February 2018 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.15048

Title => Variability of Symmetric Dimethylarginine in Apparently Healthy Dogs Abstract => Background: Symmetric dimethylarginine (SDMA) is a screening tool for early kidney dysfunction and monitoring treatment in cases of chronic kidney disease (CKD). There are no current studies describing the suitability of this test for use with published population-based reference intervals. Hypothesis/Objectives: To determine the components of biological variability, the index of individuality (IOI), the critical difference between sequential measurements (CD) and the number of measurements required to assess the homeostatic set point (HSP), for both SDMA and serum creatinine (sCr), in apparently healthy dogs. Animals: Twenty apparently healthy adult dogs owned by clients or staff at a veterinary teaching hospital. Methods: Prospective, observational study. Blood was collected from each dog on 9 occasions, and SDMA and sCr were measured in duplicate using commercially available assays. Results: SDMA and sCr had intermediate and low IOI values of 0.87 and 0.28, respectively. The CD of SDMA and sCr, was 1.34 µg/dL and 0.89 µmol/L, respectively. The sample numbers required for estimation of an individual's HSP (with 90 and 95% CI) for SDMA and sCr were 8 and 45, and 2 and 12 sequential measurements, respectively. Conclusions and Clinical Importance: Based on our findings, in comparison to sCr, SDMA is better suited for use with population-based reference intervals. False-negative test results could occur when comparing a single test result from an individual to such intervals. Ideally CD should be used with sequential measurements. Authors => M.A. Kopke | R.K. Burchell | C.G. Ruaux | S.E. Burton | N. Lopez-Villalobos | A. Gal published => First published: 22 February 2018 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.15050

Title => Calcitonin Response to Naturally Occurring Ionized Hypercalcemia in Cats with Chronic Kidney Disease Abstract => Background: Hypercalcemia is commonly associated with chronic kidney disease (CKD) in cats. Objectives: To explore the calcitonin response to naturally occurring ionized hypercalcemia in cats with azotemic CKD, and to assess the relationship of plasma calcitonin with ionized calcium, alkaline phosphatase (ALP), and urinary calcium excretion. Animals: Thirty-three client-owned cats with azotemic CKD and ionized hypercalcemia from first opinion practice. Methods: Cohort study. Calcitonin was measured with an immunoradiometric assay in heparinized plasma. Simple correlations were assessed with Kendall's rank correlation, and the within-subject correlations of calcitonin with ionized calcium and other clinicopathological variables were calculated with a bivariate linear mixed effects model. Results: Calcitonin concentrations above the lower limit of detection (>1.2 pg/mL; range, 1.7–87.2 pg/mL) were observed in 11 of 33 hypercalcemic cats (responders). Blood ionized calcium concentration did not differ significantly between responders (median, 1.59 [1.46, 1.66] mmol/L) and nonresponders (median, 1.48 [1.43, 1.65] mmol/L; P = 0.22). No evidence was found for calcitonin and ionized calcium to correlate between cats (τb = 0.14; P = 0.31; n = 33), but significant positive correlation was evident within individual responders over time (within-subject correlation coefficient [rwithin], 0.83; 95% confidence interval [CI], 0.63–0.92). Calcitonin correlated negatively over time with plasma ALP (rwithin, −0.55; 95% CI, −0.79 to −0.16). Conclusions and Clinical Importance: Calcitonin does not appear to have an important role in calcium metabolism in cats with CKD. Authors => D.H.N. van den Broek | R.F. Geddes | T.L. Williams | Y.-M. Chang | J. Elliott | R.E. Jepson published => First published: 22 February 2018 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.15051

Title => Vitamin D Receptor Expression in Dogs Abstract => Background: There is growing evidence linking low blood vitamin D concentration to numerous diseases in people and in dogs. Vitamin D influences cellular function by signaling through the vitamin D receptor (VDR). Little is known about which non-skeletal tissues express the VDR or how inflammation influences its expression in the dog. Objectives: To define which non-skeletal canine tissues express the VDR and to investigate expression in inflamed small intestine. Animals: Thirteen non-skeletal tissues were collected prospectively from 6 control dogs. Thirty-five dogs diagnosed with a chronic enteropathy (CE) and 24 control dogs were prospectively enrolled and duodenal biopsies were evaluated for VDR expression. Methods: Prospective; blinded assessment of canine intestinal VDR. Dogs with CE were included once other identifiable causes of intestinal disease were excluded. Age matched controls were included with no intestinal clinical signs. VDR expression was assessed immunohistochemically in all samples, using a Rat IgG VDR monoclonal antibody. Quantitative real-time polymerase chain reaction (qPCR) was also used for duodenal biopsies. Results: VDR expression as assessed by immunohistochemistry (IHC) was highest in the kidney, duodenum, skin, ileum and spleen, and weak in the colon, heart, lymph node, liver, lung, and ovary. Gastric and testicular tissue did not express the VDR. There was no statistical difference in duodenal VDR expression between the 24 healthy dogs and 34 dogs with CE when quantified by either qPCR (P = 0.87) or IHC (P = 0.099). Conclusions and Clinical Importance: The lack of down regulation of VDR expression in inflamed intestine contrasts with previous studies in humans. Our findings support future studies to investigate whether vitamin D and its analogues can be used to modulate intestinal inflammation in the dog. Authors => J.A. Cartwright | A.G. Gow | E. Milne | D. Drummond | S. Smith | I. Handel | R.J. Mellanby published => First published: 22 February 2018 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.15052

Title => Survey of Equine Referring Veterinarians' Satisfaction with Their Most Recent Equine Referral Experience Abstract => Background: Little is known about the veterinary referral process and factors that contribute to positive outcomes. Objective: To investigate equine referring veterinarians' (rDVMs') satisfaction with their most recent referral experience and compare rDVM and specialist perspectives. Sample: 187 rDVMs and 92 specialists (referral care providers). Methods: Cross-sectional observational study. An online survey was administered to both rDVMs and specialists. Referring veterinarian satisfaction with their most recent referral experience was evaluated. Both rDVMs and specialists were asked to identify factors influencing a rDVM's decision where to refer, and the top 3 factors they perceive are barriers to referral care. Results: Median rDVM satisfaction with their most recent referral care experience was 80 of 100 (mean, 75; range, 8–100). Referring veterinarians provided the lowest satisfaction score for the item asking about “The competition the referral hospital poses to your practice” (mean, 56.96; median, 62; range, 0–100). The top factor rDVMs identified as influencing their decision where to refer was “quality of care,” whereas specialists identified “quality of communication and updates from the clinician.” Referring veterinarians' top barrier to referral care was “high cost of referral care,” and for specialists was “poor service provided to the client by the referral hospital.” Conclusions and Clinical Importance: Referring veterinarians generally were satisfied with referral care, but areas exist where rDVMs and specialists differ in what they view as important to the referral process. Exploring opportunities to overcome these differences is likely to support high quality care. Authors => C. Best | J.B. Coe | J. Hewson | M. Meehan | D. Kelton published => First published: 22 February 2018 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.15053

Title => Comparison of diagnostic accuracy of laparoscopic 3 mm and 5 mm cup biopsies to wedge biopsies of canine livers Abstract => Background: Diagnostic accuracy of the 3 mm laparoscopic cup biopsy forceps for collection of tissue samples from canine livers is unproven. Hypotheses/Objectives: Compare sample surface area and portal triad count between 3 mm and 5 mm laparoscopic cup biopsies and compare the histologic diagnosis obtained by each instrument to a standard necropsy wedge. The hypothesis was that more portal triads and greater sample surface area would be found with the 5 mm samples and the laparoscopic instruments would not have significantly different levels of agreement with necropsy wedge diagnosis. Animals: Twenty-one client-owned dogs undergoing necropsy. Methods: Prospective ex vivo study. Three samples (3 mm, 5 mm, and wedge) were taken of 2 different hepatic divisions within 24 hours of death. Morphologic diagnosis, World Small Animal Veterinary Association histologic features, surface area, and portal triad numbers were compared among the 3 samples. Results: There were significantly more portal triads (mean 21.4 versus 13.8; P < .0001) and a higher surface area (20.3 mm2 versus 11.5 mm2; P < .0001) in the 5 mm samples compared to 3 mm samples. Kappa coefficients and percent agreement for histologic diagnosis as compared to the wedge biopsy were not significantly different between the 2 instrument sizes (κ = 0.383 and 0.436, respectively; 67% and 69%, respectively). Conclusions and Clinical Importance: Despite yielding smaller sample sizes, the 3 mm laparoscopic cup biopsy has a similar level of histologic diagnostic accuracy to the 5 mm instrument. Authors => Tiffany L. Kimbrell | Milan Milovancev | Ronald Olsen | Christiane V. Löhr published => First published: 20 February 2018 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.15054

Title => Effect of sotalol on heart rate, QT interval, and atrial fibrillation cycle length in horses with atrial fibrillation Abstract => Background: Based on its pharmacokinetic profile and electrophysiological effects in healthy horses, sotalol potentially could be used as a long-term PO antiarrhythmic drug in horses. Objectives: To evaluate the effect of sotalol on heart rate (HR), QT interval, atrial fibrillatory rate, and success of cardioversion in horses with naturally occurring chronic atrial fibrillation (AF). Animals: Twenty-eight horses referred for transvenous electrical cardioversion of AF were treated with 2 mg/kg sotalol PO q12h for 3 days before cardioversion, and 13 horses underwent the same protocol without sotalol administration. Methods: Retrospective study. Before and after sotalol or no treatment, the HR was measured at rest and during an exercise test. The QT interval and atrial fibrillation cycle length (AFCL) were measured at rest using tissue Doppler velocity imaging. Results: In the control group, no significant differences were found between the 2 examinations. In the sotalol group, the HR at rest and during exercise was significantly lower after sotalol treatment, whereas the QT interval and AFCL measured by tissue Doppler increased significantly. Cardioversion to sinus rhythm was achieved in 25/28 horses in the sotalol group and all horses in the control group, but the median number of shocks and energy at cardioversion were significantly lower in the sotalol group. Conclusions and Clinical Importance: In horses with AF, sotalol administration results in class III antiarrhythmic effects and β-blocking activity, with moderate HR reduction during exercise. Authors => Annelies Decloedt | Barbara Broux | Dominique De Clercq | Piet Deprez | Glenn Van Steenkiste | Lisse Vera | Sofie Ven | Gunther van Loon published => First published: 20 February 2018 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.15055

Title => Catheter-associated venous air embolism in hospitalized horses: 32 cases Abstract => Background: Venous air embolism is a potentially life-threatening complication of IV catheter use in horses. Despite widespread anecdotal reports of their occurrence, few cases have been reported in the literature and the prognosis is currently unknown. Hypothesis/Objectives: Our objective was to describe the surrounding circumstances, clinical signs, treatment, progression, and outcome of venous air embolism in hospitalized horses. Animals: Thirty-two horses with acute onset of compatible clinical signs associated with IV catheter disconnection or damage. Methods: Multicenter retrospective study. Data extracted from clinical records included signalment, presenting complaint, catheter details, clinical signs, treatments, and outcome. Results: Most cases resulted from extension set disconnection occurring within approximately 24 hours after catheter placement. In fewer horses, extension set damage was cited as a cause. Common clinical signs included tachycardia, tachypnea, recumbency, muscle fasciculations and agitation, with abnormal behavior including kicking and flank biting. Less commonly, pathological arrhythmias or more severe neurologic signs, including blindness and seizures, were noted. Progression was unpredictable, with some affected horses developing delayed-onset neurologic signs. Mortality was 6/32 (19%), including 2 cases of sudden death and other horses euthanized because of persistent neurologic deficits. Negative outcomes were more common in horses with recorded blindness, sweating or recumbency, but blindness resolved in 5/8 affected horses. Conclusions and Clinical Importance: The prognosis for resolution of clinical signs after air embolism is fair, but permanent neurologic deficits or pathologic cardiac arrhythmias can arise. Unpredictable progression warrants close monitoring. Systematic clinic-based surveillance could provide additional useful information to aid prevention. Authors => Nicholas J. Parkinson | Harold C. McKenzie | Michelle H. Barton | Jennifer L. Davis | Bettina Dunkel | Amy L. Johnson | Elizabeth S. MacDonald published => First published: 20 February 2018 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.15057

Title => JVIM manuscript reviewers who critiqued in the 2017 calendar year Abstract => None Abstract Authors => published => First published: 20 February 2018 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.15059

Title => Deafness and vestibular dysfunction in a Doberman Pinscher puppy associated with a mutation in the PTPRQ gene Abstract => Background: A congenital syndrome of hearing loss and vestibular dysfunction affects Doberman Pinschers. Its inheritance pattern is suspected to be autosomal recessive and it potentially represents a spontaneous animal model of an autosomal recessive syndromic hearing loss. Hypothesis/Objectives: The objectives of this study were to use whole genome sequencing (WGS) to identify deleterious genetic variants in candidate genes associated with the syndrome and to study the prevalence of candidate variants among a population of unaffected Doberman Pinschers. Animals: One affected Doberman Pinscher and 202 unaffected Doberman Pinschers. Methods: WGS of the affected dog with filtering of variants against a database of 154 unaffected dogs of diverse breeds was performed. Confirmation of candidate variants was achieved by Sanger sequencing followed by genotyping of the control population of unaffected Doberman Pinschers. Results: WGS and variant filtering identified an alteration in a gene associated with both deafness and vestibular disease in humans: protein tyrosine phosphatase, receptor type Q (PTPRQ). There was a homozygous A insertion at CFA15: 22 989 894, causing a frameshift mutation in exon 39 of the gene. This insertion is predicted to cause a protein truncation with a premature stop codon occurring after position 2054 of the protein sequence that causes 279 C-terminal amino acids to be eliminated. Prevalence of the variant was 1.5% in a cohort of 202 unaffected Doberman Pinschers; all unaffected Doberman Pinschers were heterozygous or heterozygous for the reference allele. Conclusion and Clinical Importance: We report the identification of a genetic alteration on the PTPRQ gene that is associated with congenital hearing and vestibular disorder in a young Doberman Pinscher dog. Authors => Julien Guevar | Natasha J. Olby | Kathryn M. Meurs | Oriana Yost | Steven G. Friedenberg published => First published: 20 February 2018 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.15060

Title => Immediate, short-, and long-term changes in tracheal stent diameter, length, and positioning after placement in dogs with tracheal collapse syndrome Abstract => Background: Intraluminal tracheal stenting is a minimally invasive procedure shown to have variable degrees of success in managing clinical signs associated with tracheal collapse syndrome (CTCS) in dogs. Objectives: Identify immediate post-stent changes in tracheal diameter, determine the extent of stent migration, and stent shortening after stent placement in the immediate-, short-, and long-term periods, and evaluate inter-observer reliability of radiographic measurements. Animals: Fifty client-owned dogs. Methods: Retrospective study in which medical records were reviewed in dogs with CTCS treated with an intraluminal tracheal stent. Data collected included signalment, location, and type of collapse, stent diameter and length, and post-stent placement radiographic follow-up times. Radiographs were used to obtain pre-stent tracheal measurements and post-stent placement measurements. Results: Immediate mean percentage change was 5.14%, 5.49%, and 21.64% for cervical, thoracic inlet, and intra-thoracic tracheal diameters, respectively. Ultimate mean follow-up time was 446 days, with mean percentage change of 2.55%, 15.09%, and 8.65% for cervical, thoracic inlet, and intra-thoracic tracheal diameters, respectively. Initial mean stent length was 26.72% higher than nominal length and ultimate long-term tracheal mean stent shortening was only 9.90%. No significant stent migration was identified in the immediate, short-, or long-term periods. Good inter-observer agreement of radiographic measurements was found among observers of variable experience level. Conclusions and Clinical Importance: Use of an intraluminal tracheal stent for CTCS is associated with minimal stent shortening with no clinically relevant stent migration after fluoroscopic placement. Precise stent sizing and placement techniques likely play important roles in avoiding these reported complications. Authors => Matthew Raske | Chick Weisse | Allyson C. Berent | Renee McDougall | Kenneth Lamb published => First published: 20 February 2018 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.15063

Title => Association of fecal calprotectin concentrations with disease severity, response to treatment, and other biomarkers in dogs with chronic inflammatory enteropathies Abstract => Background: Calprotectin is a marker of inflammation, but its clinical utility in dogs with chronic inflammatory enteropathies (CIE) is unknown. Objective: Evaluation of fecal calprotectin in dogs with biopsy-confirmed CIE. Animals: 127 dogs. Methods: Prospective case-control study. Dogs were assigned a canine chronic enteropathy clinical activity index (CCECAI) score, and histologic lesions severity was assessed. Fecal calprotectin, fecal S100A12, and serum C-reactive protein (CRP) were measured. Food- or antibiotic-responsive cases (FRE/ARE, n = 13) were distinguished from steroid-/immunosuppressant-responsive or -refractory cases (SRE/IRE, n = 20). Clinical response to treatment in SRE/IRE dogs was classified as complete remission (CR), partial response (PR), or no response (NR). Results: Fecal calprotectin correlated with CCECAI (ρ = 0.27, P = .0065) and fecal S100A12 (ρ = 0.90, P < .0001), some inflammatory criteria, and cumulative inflammation scores, but not serum CRP (ρ = 0.16, P = .12). Dogs with SRE/IRE had higher fecal calprotectin concentrations (median: 2.0 μg/g) than FRE/ARE dogs (median: 1.4 μg/g), and within the SRE/IRE group, dogs with PR/NR had higher fecal calprotectin (median: 37.0 μg/g) than dogs with CR (median: 1.6 μg/g). However, both differences did not reach statistical significance (both P = .10). A fecal calprotectin ≥15.2 μg/g separated both groups with 80% sensitivity (95% confidence interval [95%CI]: 28%-100%) and 75% specificity (95%CI: 43%-95%). Conclusions and Clinical Importance: Fecal calprotectin could be a useful surrogate marker of disease severity in dogs with CIE, but larger longitudinal studies are needed to evaluate its utility in predicting the response to treatment. Authors => Romy M. Heilmann | Nora Berghoff | Joanne Mansell | Niels Grützner | Nolie K. Parnell | Corinne Gurtner | Jan S. Suchodolski | Jörg M. Steiner published => First published: 20 February 2018 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.15065

Title => Exercise-induced pulmonary hemorrhage in barrel racing horses in the Pacific Northwest region of the United States Abstract => Background: Exercise-induced pulmonary hemorrhage (EIPH) refers to bleeding from the lungs in association with strenuous exercise. It has been documented in race horses but little information exists on EIPH in barrel racing horses. Hypothesis/Objectives: Our goals were to evaluate the presence of EIPH in barrel racing horses and estimate its prevalence in the Pacific Northwest. Animals: 149 barrel racing horses enrolled at events in WA (11), ID (3), and MT (33). Methods: Observational cross-sectional study. Data collected included signalment, history of illness, respiratory disease, race division, and pre-race medications. Endoscopy was performed and tracheobronchoscopic (TBE) EIPH score was assigned based on quantity of blood in the trachea (0 = no blood to 4 = abundance of blood within the trachea). After TBE, bronchoalveolar lavage (BAL) was performed. Erythrocyte (red blood cell, RBC) counts were obtained from bronchoalveolar lavage fluid (BALF). Statistical analysis included linear and logistic regression, Fisher's exact t test, and calculation of correlation coefficient. Significance was set at P < .05. Results: The prevalence of EIPH based on TBE EIPH score was 54%. When based on BALF RBC count >1,000 cells, EIPH prevalence was 66%. Race time did not significantly affect the presence of EIPH. A significant (P < .0001) positive linear relationship between the TBE and BAL erythrocyte count was identified, but its strength was poor (r2 = .15). Conclusions and Clinical Importance: EIPH occurs in over 50% of barrel racing horses in the Pacific Northwest. Precise determination of the impact of EIPH on health of barrel racers requires further study. Authors => Jenifer R. Gold | Donald P. Knowles | Todd Coffey | Warwick M. Bayly published => First published: 20 February 2018 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.15066

Title => Cerebrospinal fluid Lyme multiplex assay results are not diagnostic in horses with neuroborreliosis Abstract => Background: The accuracy of the Lyme multiplex assay for the diagnosis of neuroborreliosis in horses is unknown. Hypothesis/Objectives: To describe Lyme multiplex results in horses with a postmortem diagnosis of neuroborreliosis. The hypothesis was that paired serum and cerebrospinal fluid (CSF) results and a CSF : serum ratio would allow differentiation of horses with neuroborreliosis from those with other neurologic diseases. Animals: Ninety horses that had neurologic examinations, serum and CSF Lyme multiplex analyses, and postmortem examination of the nervous system performed. Methods: Retrospective study. Data collected included signalment, ante- and postmortem diagnoses, and serum and CSF Lyme multiplex results. The CSF : serum ratio was calculated by dividing CSF median fluorescent intensity (MFI) by serum MFI for each result. Results: Ten horses had a final diagnosis of neuroborreliosis, 70 were diagnosed with other neurologic diseases, and 10 had no neurologic disease. Not all horses with neuroborreliosis had positive results: 4/10 had at least 1 positive serum result, 5/10 had at least 1 positive CSF result, and 3/10 had at least 1 CSF result 4-fold higher than the corresponding serum result. Results were similar for the 70 horses with other neurologic diseases: 53% had at least 1 positive serum result, 50% had at least 1 positive CSF result, and 16% had at least 1 CSF result 4-fold higher than the corresponding serum result. Conclusions and Clinical Importance: Positive Lyme multiplex results were common in horses with neurologic diseases and did not adequately differentiate horses with neuroborreliosis from horses with other disorders. Authors => Amy L. Johnson | Laura K. Johnstone | Darko Stefanovski published => First published: 20 February 2018 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.15067

Title => Comparative, multidimensional imaging of patent ductus arteriosus and a proposed update to the morphology classification system for dogs Abstract => Background: Accurately assessing the morphology and shape of the patent ductus arteriosus (PDA) and obtaining measurements are important to avoid procedural complications. Objectives: To characterize and compare PDA morphology, shape, and dimensions with angiography and echocardiography. Animals: 25 client-owned dogs with echocardiographically confirmed PDA. Methods: Prospective case series. Imaging consisted of single plane angiography, transthoracic echocardiography from the right (TTE-R) and left (TTE-L), and two-dimensional, biplane, and three-dimensional transesophageal echocardiography (TEE-2D and TEE-3D). Measurements included angiographic minimal ductal diameter (MDD), echocardiographic pulmonary ostium in a single dimension (TTE-R, TTE-L, and TEE-2D) and in perpendicular dimensions (TEE-3D) with similar measurements of the ampulla 3 mm above the MDD or pulmonary ostium. The morphology and shape of the PDA were characterized. Results: Catheter-based occlusion (N = 20) and surgical ligation (N = 5) were performed without complication. Angiographic morphology was classified as type II (N = 19), type III (N = 1), and other (N = 1). Angiographic MDD and TEE-2D pulmonary ostium measurements were significantly (P = .008) but weakly correlated (r = .56); similar relationships were found for ampulla diameter measurements (P < .0001; r = .75). In general, TEE-2D did not correlate with other imaging modalities measurements. Based on TEE-3D measurements, the majority of pulmonary ostium (17/24; 71%) and ampulla (19/24; 79%) were oval. Conclusions and Clinical Importance: Measurements using different imaging modalities are not interchangeable. TEE-3D provided an en face view of the PDA that cannot be replicated with other echocardiographic techniques and demonstrated an oval shape in the majority of dogs. We propose an update to the current classification system to include additional PDA morphologies. Authors => Kelley R. Doocy | Ashley B. Saunders | Sonya G. Gordon | Nicholas Jeffery published => First published: 20 February 2018 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.15068

Title => Aberrant migration and surgical removal of a heartworm (Dirofilaria immitis) from the femoral artery of a cat Abstract => Authors => Maureen S. Oldach | Catherine T. Gunther-Harrington | Ingrid M. Balsa | Ehren M. McLarty | Kyle A. Wakeman | Kathryn L. Phillips | Juhana Honkavaara | Lance C. Visser | Joshua A. Stern published => First published: 20 February 2018 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.15070

Title => Prospective evaluation of an indwelling esophageal balloon dilatation feeding tube for treatment of benign esophageal strictures in dogs and cats Abstract => Background: Despite multiple dilatation procedures, benign esophageal strictures (BES) remain a recurring cause of morbidity and mortality in dogs and cats. Objective: Investigate the use of an indwelling Balloon Dilatation esophagostomy tube (B-Tube) for treatment of BES in dogs and cats. Animals: Nine dogs and 3 cats. Methods: Animals with BES were recruited for our prospective study. Endoscopic and fluoroscopic evaluation of the esophagus and balloon dilatation were performed under general anesthesia, followed by placement of an indwelling B-Tube. The animals' owners performed twice daily at-home inflations for approximately 6 weeks. Repeat endoscopy was performed before B-Tube removal. Animals were reevaluated for changes in modified dysphagia score (MDS) after B-Tube removal. Results: The B-Tube management was relatively well tolerated and effective in maintaining dilatation of a BES while in place. These animals underwent a median of 2 anesthetic episodes and were monitored for a median of 472 days (range, 358-1736 days). The mean MDS before treatment was 3.1 ± 0.5/4.0 and final follow-up MDS were significantly (P < .0001) improved at 0.36 ± 0.65/4.0. Eleven of 12 animals (91.7%) had improved MDS at the end of the follow-up period, with 8/12 (66.7%) having an MDS of 0/4, 2/12 (16.7%) an MDS of 1/4, and 1/12 (8.3%) an MDS of 2/4. One dog died. Conclusions and Clinical Importance: The B-Tube offers an effective, and more economical method, and often decreased anesthetic time to repeated balloon dilatation procedures for the treatment of BES in dogs and cats. Authors => Desmond K. Tan | Chick Weisse | Allyson Berent | Kenneth E. Lamb published => First published: 20 February 2018 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.15071

Title => Fecal microbiota transplantation in puppies with canine parvovirus infection Abstract => Background: Diarrhea associated with parvovirus infection is common in dogs. Supportive care is the mainstay of treatment, but recovery may be prolonged and mortality rate can be high. Modification of the intestinal bacterial microbiota has been promising in human and veterinary medicine as an adjunctive treatment of various enteric diseases. Objectives: To investigate the safety and efficacy of fecal microbiota transplantation (FMT) on the clinical recovery of puppies with acute hemorrhagic diarrhea syndrome. Animals: Sixty-six puppies with parvovirus infection were evaluated at 2 veterinary hospitals. Methods: Randomized clinical trial. Puppies were randomly distributed into 2 groups: standard treatment (STD) and standard treatment + FMT (STD + FMT). The STD puppies (n = 33) received only treatment with IV fluids and antimicrobials and the STD + FMT puppies (n = 33) received FMT in addition to standard treatment. For FMT, 10 g of feces from a healthy dog diluted in 10 mL of saline were administered rectally 6-12 hours post-admission. Results: Among survivors, treatment with FMT was associated with faster resolution of diarrhea (P < .001) and shorter hospitalization time (P = .001; median, 3 days in STD + FMT; median, 6 days in STD) compared to standard treatment. Mortality in STD was 36.4% (12/33) as compared to 21.2% (7/33) in puppies treated with FMT, but there was no statistical difference between groups (P = .174). Polymerase chain reaction indicated that all animals carried canine parvovirus, strain CPV-2b. Conclusions: Fecal microbiota transplantation in parvovirus-infected puppies was associated with faster resolution of diarrhea. Authors => Giorgio Q. Pereira | Lucas A. Gomes | Iago S. Santos | Alice F. Alfieri | J. S. Weese | Marcio C. Costa published => First published: 20 February 2018 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.15072

Title => Effect of sucralfate on gastric permeability in an ex vivo model of stress-related mucosal disease in dogs Abstract => Background: Sucralfate is a gastroprotectant with no known systemic effects. The efficacy of sucralfate for prevention and treatment of stress-related mucosal diseases (SRMD) in dogs is unknown. Hypothesis/Objectives: To develop a canine ex vivo model of SRMD and to determine the effect of sucralfate on mucosal barrier function in this model. Animals: Gastric antral mucosa was collected immediately postmortem from 29 random-source apparently healthy dogs euthanized at a local animal control facility. Methods: Randomized experimental trial. Sucralfate (100 mg/mL) was applied to ex vivo canine gastric mucosa concurrent with and after acid injury. Barrier function was assessed by measurement of transepithelial electrical resistance (TER) and radiolabeled mannitol flux. Results: Application of acidified Ringers solution to the mucosal side of gastric antrum caused a reduction in gastric barrier function, and washout of acidified Ringers solution allowed recovery of barrier function (TER: 34.0 ± 2.8% of control at maximum injury, 71.3 ± 5.5% at recovery, P < .001). Sucralfate application at the time of injury or after injury significantly hastened recovery of barrier function (TER: 118.0 ± 15.2% of control at maximum injury, P < .001 and 111.0 ± 15.5% at recovery, P = .35). Conclusions and Clinical Importance: Sucralfate appeared effective at restoring defects in gastric barrier function induced by acid and accelerating repair of tissues subjected to acid in this model, suggesting that sucralfate could have utility for the treatment and prevention of SRMD in dogs. Authors => Tracy L. Hill | B. Duncan X. Lascelles | Anthony T. Blikslager published => First published: 20 February 2018 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.15076

Title => Clinical Risk Factors for Early Seizure Recurrence in Dogs Hospitalized for Seizure Evaluation Abstract => Background: Epileptic seizures are a common cause for neurological evaluations in dogs. Hypothesis/Objectives: To determine the timing, frequency, and risk factors for early seizure recurrence (ESR) among dogs admitted to the hospital for seizure evaluation and to facilitate rapid decision making about whether dogs should be placed in the intensive care unit (ICU) or day ward. Animals: Nine-hundred twenty-two dogs referred for seizure investigation; 214 patients were included. Methods: Retrospective study. Medical records between 2000 and 2017 were reviewed to determine risk factors for ESR. Findings were compared among dogs diagnosed with idiopathic epilepsy (IE), structural epilepsy (StE) and reactive seizures (RS), as well as in all selected cases together. Results: Fifty percent of dogs had a seizure while hospitalized. In the group 53.1 and 52.2% in the StE group, whereas in the RS 40.44% had ESR. The average time to ESR was 7 hours. In IE group, abnormal postictal neurological examination with prosencephalon signs predicted ESR. In StE group, a single generalized or focal seizure 72 hours before hospital admission and abnormal neurologic examination predicted ESR. In the RS group, ERS was predicted by long-term antiepileptic monotheraphy. When all dogs were analyzed together, abnormal neurological examination, the occurrence of cluster seizures, status epilepticus, or combination of them 72 hours before presentation predicted ESR. Conclusions and Clinical Importance: Epileptic seizures recurred in 50% of patients within a mean time of 7 hours. In general, when cluster seizures, status epilepticus or both occurred 72 hours before presentation and neurological examination was abnormal upon presentation, the dog should be placed in ICU for observation. Authors => M. Kwiatkowska | A. Tipold | E. Huenerfauth | A. Pomianowski published => First published: 18 February 2018 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.15046

Title => Characterization of Paroxysmal Gluten-Sensitive Dyskinesia in Border Terriers Using Serological Markers Abstract => Background: Paroxysmal gluten-sensitive dyskinesia (PGSD) in border terriers (BTs) results from an immunologic response directed against transglutaminase (TG)2 and gliadin. Recent evidence suggests that PGSD is only one aspect of a range of possible manifestations of gluten sensitivity in the breed. Hypothesis/Objectives: Gluten sensitivity in BTs is a heterogeneous disease process with a diverse clinical spectrum; to characterize the phenotype of PGSD using TG2 and gliadin autoantibodies as diagnostic markers. Animals: One hundred twenty-eight client-owned BTs with various disorders. Methods: Prospective study. BTs with paroxysmal episodes and a normal interictal examination were phenotyped using footage of a representative episode and assigned to 3 groups: idiopathic epilepsy (IE), paroxysmal dyskinesia (PD), or other. Owners of each dog completed a questionnaire to obtain information regarding clinical signs. Healthy BTs formed a control group. Serum antibodies against TG2 and AGA were measured in all dogs. Results: One hundred twenty-eight BTs were enrolled; 45 with PD, 28 with IE, 35 with other conditions, and 20 controls. Three overlapping phenotypes were identified; PD, signs suggestive of gastrointestinal disease, and dermatopathy. AGA-IgG concentrations were increased in PD, compared with IE (P = 0.012), controls (P < 0.0001) and other (P = 0.018) conditions. Anti-canine TG2-IgA concentrations were increased in PD, compared with IE (P < 0.0001), controls (P < 0.0001) and other (P = 0.012) conditions. Serological markers are highly specific for PGSD but lack sensitivity. Conclusions: PGSD appears part of a syndrome of gluten intolerance consisting of episodes of transient dyskinesia, signs suggestive of gastrointestinal disease, and dermatological hypersensitivity. Authors => M. Lowrie | O.A. Garden | M. Hadjivassiliou | D.S. Sanders | R. Powell | L. Garosi published => First published: 09 February 2018 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.15038

Title => Evaluation of SNAP cPL, Spec cPL, VetScan cPL Rapid Test, and Precision PSL Assays for the Diagnosis of Clinical Pancreatitis in Dogs Abstract => Background: The sensitivity, specificity, and agreement of 4 diagnostic assays (SNAP canine pancreatic lipase (cPL), specific cPL (Spec cPL), VetScan cPL Rapid Test, and Precision PSL) for pancreatitis in dogs have not been directly compared. Hypothesis/Objectives: To determine the level of agreement among each of the 4 assays and a clinical suspicion score, level of agreement among the assays, and sensitivity and specificity of each assay in a clinically relevant patient group. Animals: Fifty client-owned dogs with clinical signs of gastrointestinal disease. Methods: Prospective study. History, physical examination, complete blood count, serum biochemistry, abdominal ultrasound examination, and the 4 diagnostic assays for pancreatitis were performed. Intraclass correlation coefficients (ICC) were used to determine the level of agreement between each assay and a clinical suspicion score determined by a panel of 5 board-certified veterinary internists. Results: The ICC between the clinical suspicion score and the 4 assays were SNAP cPL, 0.61; Spec cPL, 0.68; VetScan cPL Rapid Test, 0.68; and Precision PSL, 0.60. The sensitivities of the assays ranged from 73.9 to 100.0%, whereas the specificities were SNAP cPL, 71.1–77.8%; Spec cPL, 74.1–81.1%; VetScan cPL Rapid Test, 76.9–83.8%; and Precision PSL, 64.0–74.3%. Conclusions and Clinical Importance: A good to excellent level of agreement was demonstrated among the 4 assays. The previously unreported sensitivity and specificity of the VetScan cPL Rapid Test were 73.9–83.3% and 76.9–83.8%, respectively. Results of any of the 4 diagnostic assays alone, in the absence of supporting clinical findings, are insufficient to establish a diagnosis of clinical pancreatitis in dogs. Authors => H. Cridge | A.G. MacLeod | G.E. Pachtinger | A.J. Mackin | A.M. Sullivant | J.M. Thomason | T.M. Archer | K.V. Lunsford | K. Rosenthal | R.W. Wills published => First published: 09 February 2018 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.15039

Title => Zinc Deficiency-Like Syndrome in Fleckvieh Calves: Clinical and Pathological Findings and Differentiation from Bovine Hereditary Zinc Deficiency Abstract => Background: Zinc deficiency-like (ZDL) syndrome is an inherited defect of Fleckvieh calves, with striking similarity to bovine hereditary zinc deficiency (BHZD). However, the causative mutation in a phospholipase D4 encoding gene (PLD4) shows no connection to zinc metabolism. Objectives: To describe clinical signs, laboratory variables, and pathological findings of ZDL syndrome and their utility to differentiate ZDL from BHZD and infectious diseases with similar phenotype. Animals: Nine hospitalized calves with crusting dermatitis and confirmed mutation in PLD4 and medical records from 25 calves with crusting dermatitis or suspected zinc deficiency. Methods: Prospective and retrospective case series. Results: The 9 calves (age: 5–53 weeks) displayed a moderate to severe crusting dermatitis mainly on the head, ventrum, and joints. Respiratory and digestive tract inflammations were frequently observed. Zinc supplementation did not lead to remission of clinical signs in 4 calves. Laboratory variables revealed slight anemia in 8 calves, hypoalbuminemia in 6 calves, but reduced serum zinc concentrations in only 3 calves. Mucosal erosions/ulcerations were present in 7 calves and thymus atrophy or reduced thymic weights in 8 calves. Histologically, skin lesions were indistinguishable from BHZD. Retrospective analysis of medical records revealed the presence of this phenotype since 1988 and pedigree analysis revealed a common ancestor of several affected calves. Conclusions and Clinical Importance: ZDL syndrome should be suspected in Fleckvieh calves with crusting dermatitis together with diarrhea or respiratory tract inflammations without response to oral zinc supplementation. Definite diagnosis requires molecular genetic confirmation of the PLD4 mutation. Authors => M.C. Langenmayer | S. Jung | M. Majzoub-Altweck | F.M. Trefz | C. Seifert | G. Knubben-Schweizer | R. Fries | W. Hermanns | N.S. Gollnick published => First published: 09 February 2018 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.15040

Title => Streptococcus equi Infections in Horses: Guidelines for Treatment, Control, and Prevention of Strangles—Revised Consensus Statement Abstract => Authors => A.G. Boyle | J.F. Timoney | J.R. Newton | M.T. Hines | A.S. Waller | B.R. Buchanan published => First published: 09 February 2018 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.15043

Title => Clinical Utility of Plasma Fructosamine Concentration as a Hypoglycemic Biomarker during Early Lactation in Dairy Cattle Abstract => Background: Plasma fructosamine concentration ([FRA]) is a widely used long term hyperglycemic biomarker in humans and dogs, but its clinical usefulness as a hypoglycemic biomarker in dairy cattle is uncertain. Objectives: To evaluate the relationship between plasma [FRA] and glucose concentration ([gluc]) as well as indices of energy balance during early lactation in dairy cattle, and to characterize the influence of plasma total protein concentration ([TP]) and albumin concentration ([albumin]) on [FRA]. Animals: Convenience sample comprising 103 periparturient Holstein–Friesian cattle. Methods: Plasma [gluc], [TP], [albumin], and other clinicopathologic indices of energy status were determined periodically from Day 4 postpartum. Body condition score (BCS) was assessed, and backfat thickness (BFT) and longissimus dorsi muscle thickness (LDT) were measured ultrasonographically. Plasma [FRA] was measured at approximately 28 days postpartum. Associations between plasma [FRA] and study variables were evaluated using Spearman's rho and stepwise forward linear regression. Statistical significance was declared at P < 0.05. Results: A positive association was detected between plasma [FRA] and mean plasma [gluc] from Days 4–28 postpartum (rs = +0.36, P < 0.001), and between plasma [FRA] and LDT (rs = +0.28, P = 0.007), BCS (rs = +0.23, P = 0.029), and BFT (rs = +0.21, P = 0.043). Multivariable regression identified a positive association between plasma [FRA] and mean plasma [gluc] and [albumin] from Days 4–28 postpartum. Correcting plasma [FRA] for [albumin] improved the association (rs = +0.46, P < 0.001) between plasma [FRA] and mean plasma [gluc]. Conclusions and Clinical Importance: Plasma [FRA] does not provide a clinically useful method for quantifying the magnitude of hypoglycemia or negative energy balance in dairy cows during early lactation. Authors => A.A. Megahed | M.W.H. Hiew | P.D. Constable published => First published: 09 February 2018 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.15049

Title => Effects of 6% Tetrastarch and Lactated Ringer's Solution on Extravascular Lung Water and Markers of Acute Renal Injury in Hemorrhaged, Isoflurane-Anesthetized Healthy Dogs Abstract => Background: Tetrastarch can cause acute kidney injury (AKI) in humans with sepsis, but less likely to result in tissue edema than lactated Ringer's solution (LRS). Objectives: Compare effects of volume replacement (VR) with LRS and 6% tetrastarch solution (TS) on extravascular lung water (EVLW) and markers of AKI in hemorrhaged dogs. Animals: Six healthy English Pointer dogs (19.7–35.3 kg). Methods: Prospective crossover study. Animals underwent anesthesia without hemorrhage (Control). Two weeks later, dogs hemorrhaged under anesthesia on 2 occasions (8-week washout intervals) and randomly received VR with LRS or TS at 3 : 1 or 1 : 1 of shed blood, respectively. Anesthesia was maintained until 4 hour after VR for EVLW measurements derived from transpulmonary thermodilution cardiac output. Neutrophil gelatinase-associated lipocalin (NGAL) and creatinine concentrations in plasma and urine were measured until 72 hour after VR. Results: The EVLW index (mL/kg) was lower at 1 hour after TS (10.0 ± 1.9) in comparison with controls (11.9 ± 3.4, P = 0.04), and at 4 hour after TS (9.7 ± 1.9) in comparison with LRS (11.8 ± 2.7, P = 0.03). Arterial oxygen partial pressure-to-inspired oxygen fraction ratio did not differ among treatments from 0.5 to 4 hour after VR. Urine NGAL/creatinine ratio did not differ among treatments and remained below threshold for AKI (120,000 pg/mg). Conclusions and Clinical Importance: Although TS causes less EVLW accumulation than LRS, neither fluid produced evidence of lung edema (impaired oxygenation). Both fluids appear not to cause AKI when used for VR after hemorrhage in healthy nonseptic dogs. Authors => M.S. Diniz | F.J. Teixeira-Neto | N. Celeita-Rodríguez | C.H. Girotto | M.W. Fonseca | A.C. Oliveira-Garcia | B. López-Castañeda published => First published: 28 January 2018 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.14853

Title => Efficacy of Oral Administration of Sodium Iodide to Prevent Bovine Respiratory Disease Complex Abstract => Background: The prevention of bovine respiratory disease complex (BRD) in beef cattle is important to maintaining health and productivity of calves in feeding operations. Objective: Determine whether BRD bacterial and viral pathogens are susceptible to the lactoperoxidase/hydrogen peroxide/iodide (LPO/H2O2/I−) system in vitro and to determine whether the oral administration of sodium iodide (NaI) could achieve sufficient concentrations of iodine (I) in the respiratory secretions of weaned beef calves to inactivate these pathogens in vivo. Animals: Sixteen weaned, apparently healthy, commercial beef calves from the University of Missouri, College of Veterinary Medicine teaching herd. Methods: In vitro viral and bacterial assays were performed to determine susceptibility to the LPO/H2O2/I− system at varying concentrations of NaI. Sixteen randomly selected, healthy crossbred beef weanlings were administered 70 mg/kg NaI, or water, orally in a blinded, placebo-controlled trial. Blood and nasal secretions were collected for 72 hours and analyzed for I− concentration. Results: Bovine herpesvirus-1, parainfluenza-3, Mannheimia haemolytica and Bibersteinia trehalosi were all inactivated or inhibited in vitro by the LPO/H2O2/I− reaction. Oral administration of NaI caused a marked increase in nasal fluid I concentration with a Cmax = 181 (1,420 μM I), T12, a sufficient concentration to inactivate these pathogens in vitro. Conclusions and Clinical Importance: In vitro, the LPO/H2O2/I− system inactivates and inhibits common pathogens associated with BRD. The administration of oral NaI significantly increases the I concentration of nasal fluid indicating that this system might be useful in preventing bovine respiratory infections. Authors => B.M. Shoemake | B.L. Vander Ley | B.W. Newcomer | M.C. Heller published => First published: 28 January 2018 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.14903

Title => Rapid Diagnosis of Babesia gibsoni by Point-of-Need Testing by Insulated Isothermal PCR in Dogs at High Risk of Infection Abstract => Background: Dogs seized by law enforcement agencies during dogfighting investigations are at increased risk of Babesia gibsoni infection. A rapid and cost-effective diagnostic test would increase the feasibility of mass screening of dogs for infection and monitoring treatment efficacy in B. gibsoni-infected dogs. Objective: To determine the performance of a point-of-need insulated isothermal PCR (iiPCR) test for diagnosis of B. gibsoni in dogs rescued in dogfighting investigations. Animals: Two hundred and thirty-three dogs seized in dogfighting investigations. Methods: Cross-sectional study. Whole blood samples were tested for B. gibsoni and Babesia spp. by iiPCR. Results were compared to a reference standard comprised of concordant results from real-time PCR in a commercial diagnostic laboratory and antibody titers. Results: The iiPCR system was quick to learn, portable, and had a short processing time of <2 hours. Sensitivity and specificity of the iiPCR assay for B. gibsoni were 90% (95% confidence interval [CI] 81–95%) and 99% (CI, 95–100%), respectively. Sensitivity and specificity of the iiPCR assay for Babesia spp. were 87% (CI, 78–93%) and 98% (CI, 0.94–99%), respectively. Conclusions and Clinical Importance: The iiPCR system produced few false-positive results, indicating that positive results are likely to represent true infections when used in high-risk animals. The iiPCR system can fail to identify 10–15% of truly infected dogs. However, the portability, speed, and economy of the iiPCR system compared to testing through a reference laboratory can allow rescue groups to screen and identify infection in more dogs. Authors => K.L. Cooke | P. Frenzer | S.J. Tucker | P.C. Crawford | S.K. Kirk | J.K. Levy published => First published: 28 January 2018 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.15033

Title => Gallbladder Agenesis in 17 Dogs: 2006–2016 Abstract => Background: Gallbladder agenesis (GBA) is extremely rare in dogs. Hypothesis/Objectives: To describe the history, clinical signs, diagnosis, treatment, and outcomes of dogs with GBA. Animals: Seventeen client-owned dogs with GBA. Methods: Medical records from 2006 through 2016 were retrospectively reviewed. Dogs were included when GBA was suspected on abdominal ultrasonography and confirmed by gross evaluation. Signalment, clinical signs, clinicopathological data, diagnostic imaging, histopathology, treatment, and outcome were recorded. Results: Dogs were of 6 different breeds, and Chihuahuas (10 of 17) were most common. Median age at presentation was 1.9 (range, 0.7–7.4) years. Clinical signs included vomiting (5 of 17), anorexia (2 of 17), ascites (2 of 17), diarrhea (1 of 17), lethargy (1 of 17), and seizures (1 of 17). All dogs had increased serum activity of at least 1 liver enzyme, most commonly alanine aminotransferase (15 of 17). Fifteen dogs underwent computed tomography (CT) cholangiography; common bile duct (CBD) dilatation was confirmed in 12, without evidence of bile duct obstruction. Gross evaluation confirmed malformation of the liver lobes in 14 of 17 dogs and acquired portosystemic collaterals in 5 of 17. Ductal plate malformation was confirmed histologically in 16 of 17 dogs. During follow-up (range, 4–3,379 days), 16 of 17 dogs remained alive. Conclusions and Clinical Importance: Dogs with GBA exhibit clinicopathological signs of hepatobiliary injury and hepatic histopathological changes consistent with a ductal plate abnormality. Computed tomography cholangiography was superior to ultrasound examination in identifying accompanying nonobstructive CBD distention. Computed tomography cholangiography combined with laparoscopic liver biopsy is the preferable approach to characterize the full disease spectrum accompanying GBA in dogs. Authors => K. Sato | M. Sakai | S. Hayakawa | Y. Sakamoto | Y. Kagawa | K. Kutara | K. Teshima | K. Asano | T. Watari published => First published: 28 January 2018 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.15034

Title => Echocardiographic Evaluation of the Right Atrial Area Index in Dogs with Pulmonary Hypertension Abstract => Background: Right atrial area (RAA) is a prognostic factor in human patients with pulmonary arterial hypertension (PAH). Reference intervals for RAA have been described in healthy dogs. Objectives: To evaluate RAA indexed to the body surface area in dogs with PAH as an indicator of right atrial size, PAH severity and right-sided congestive heart failure (R-CHF). Animals: A total of 119 client-owned dogs, 48 dogs with PAH and 71 control dogs. Methods: Prospective observational study. Pulmonary arterial hypertension was classified according to the tricuspid regurgitation pressure gradient (TRPG) as mild (36–50 mmHg), moderate (51–75 mmHg), or severe (>75 mmHg). The RAA index was calculated as the RAA divided by body surface area. Results: The RAA index was higher in dogs with moderate PAH (13.3 cm2/m2; range, 3.4–24.7 cm2/m2) and severe PAH (12.1 cm2/m2; range, 5.4–21.8 cm2/m2) than in those with mild PAH (6.7 cm2/m2; range, 4.8–10.7 cm2/m2) or in controls (7.3 cm2/m2; range, 4.2–10.2 cm2/m2; P < 0.001). The RAA index was higher (P < 0.0001) in dogs with R-CHF (17.5 cm2/m2; range, 12.7–24.7 cm2/m2) compared to those without R-CHF (7.6 cm2/m2; range, 4.4–19.4 cm2/m2). The most accurate cutoff value of the RAA index to identify R-CHF was >12.3 cm2/m2 (sensitivity, 100%; specificity, 89.5%). In dogs with PAH, severity of tricuspid regurgitation (TR) was the only independent predictor of RAA index based on multivariate analysis (P < 0.02). Conclusions and Clinical Importance: The RAA index can be used to evaluate right atrial size in dogs and may be more effective than TRPG in predicting R-CHF in dogs with PAH. The severity of TR is the main determinant of the RAA index in dogs with PAH. Authors => T. Vezzosi | O. Domenech | M. Iacona | F. Marchesotti | E. Zini | L. Venco | R. Tognetti published => First published: 28 January 2018 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.15035

Title => Evaluation of Serum Symmetric Dimethylarginine Concentration as a Marker for Masked Chronic Kidney Disease in Cats With Hyperthyroidism Abstract => Background: Hyperthyroidism can complicate (mask) the diagnosis of chronic kidney disease (CKD) because it increases glomerular filtration rate and decreases body muscle mass, both of which can lower serum creatinine concentrations. Currently, there is no clinical test that can reliably predict which hyperthyroid cats have concurrent azotemic CKD that will become apparent after treatment of the hyperthyroidism. Objectives: To investigate serum symmetric dimethylarginine (SDMA) concentration as a potential marker of masked azotemia in untreated hyperthyroid cats. Animals: Two hundred and sixty-two hyperthyroid cats and 206 aged-matched, clinically normal cats. Methods: Prospective study. We measured creatinine, urea nitrogen, SDMA, T4, and TSH concentrations before and 1, 3, and 6 months after treatment with radioiodine (131I) and classified 131I-treated cats as azotemic or nonazotemic based on persistent, post-treatment creatinine concentrations >2.1 mg/dL. Groups were compared via nonparametric tests, and diagnostic accuracy was determined by receiver operating characteristic analysis and logistic regression. Results: No hyperthyroid cats were azotemic before treatment, but 42 (16%) became azotemic when rechecked at 4–8 months (median, 6 months) after 131I treatment; of these, 14 had high SDMA concentrations before treatment. As a diagnostic test for pre-azotemic (masked) CKD in untreated hyperthyroid cats, SDMA showed a sensitivity of 33.3% and specificity of 97.7%. Conclusions and Clinical Importance: Finding a high serum SDMA concentration in a hyperthyroid cat can help predict development of azotemia after treatment. The test has high diagnostic test specificity (few false-positive results) but relatively low sensitivity (fails to predict azotemia in most hyperthyroid cats). Authors => M.E. Peterson | F.V. Varela | M. Rishniw | D.J. Polzin published => First published: 28 January 2018 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.15036

Title => Decreased Clinical Severity of Strangles in Weanlings Associated with Restricted Seroconversion to Optimized Streptococcus equi ssp equi Assays Abstract => Background: Streptococcus equi ssp. equi causes characteristic clinical signs that are most severe in young horses, including fever, purulent nasal discharge, and lymph node abscessation in the head region. Hypothesis/Objectives: Clinical, serologic, and microbiologic factors related to unexpectedly mild disease severity in a natural outbreak of strangles in immunologically naïve weanlings were investigated. Animals: One-hundred and twelve warmblood weanlings. Methods: Prospective longitudinal observational study of a natural outbreak of strangles. The entire cohort was examined at the peak of the outbreak by deep nasal swabs for culture and quantitative PCR (qPCR) for the presence of S. equi and clinically and serologically in a sequential manner by an optimized ELISA from the index case throughout the outbreak until resolution. Descriptive statistics were calculated and comparisons made using a nondirectional Wilcoxon signed-rank test. Results: Outbreak morbidity was 53%, with 9 of 14 horses culture positive and 26 of 53 horses qPCR positive for S. equi lacking clinical signs characteristic of strangles. By resolution, 91 of 112 had seroconverted to Antigen A by ELISA but seroconversion to antigen C (part of the SeM protein) was minimal. Sequencing of the isolates detected no alterations in the SeM protein, but identified a 61 bp deletion in the gene SEQ_0402. Conclusions and Clinical Importance: Absence of clinical signs alone in naïve horses may be an insufficient criterion to release horses from strangles quarantine measures. Restricted seroconversion to antigen C may have been associated with decreased clinical severity. The role of a minor gene deletion in SEQ_0402 in the virulence of S. equi warrants further investigation. Authors => L. Tscheschlok | M. Venner | K. Steward | R. Böse | M. Riihimäki | J. Pringle published => First published: 28 January 2018 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.15037

Title => Investigation of the Role of Campylobacter Infection in Suspected Acute Polyradiculoneuritis in Dogs Abstract => Background: Acute polyradiculoneuritis (APN) is an immune-mediated peripheral nerve disorder in dogs that shares many similarities with Guillain-Barré syndrome (GBS) in humans, in which the bacterial pathogen Campylobacter spp. now is considered to be a major triggering agent. Little information is available concerning the relationship between APN and Campylobacter spp. in dogs. Hypothesis/Objectives: To estimate the association between Campylobacter spp. infection and APN. Associations with additional potential risk factors also were investigated, particularly consumption of raw chicken. Animals: Twenty-seven client-owned dogs suffering from suspected APN and 47 healthy dogs, client-owned or owned by staff members. Methods: Case-control study with incidence density-based sampling. Fecal samples were collected from each enrolled animal to perform direct culture, DNA extraction, and polymerase chain reaction (PCR) for detection of Campylobacter spp. In some cases, species identification was performed by sequence analysis of the amplicon. Data were obtained from the medical records and owner questionnaires in both groups. Results: In cases in which the fecal sample was collected within 7 days from onset of clinical signs, APN cases were 9.4 times more likely to be positive for Campylobacter spp compared to control dogs (P < 0.001). In addition, a significant association was detected between dogs affected by APN and the consumption of raw chicken (96% of APN cases; 26% of control dogs). The most common Campylobacter spp. identified was Campylobacter upsaliensis. Conclusions and Clinical Importance: Raw chicken consumption is a risk factor in dogs for the development of APN, which potentially is mediated by infection with Campylobacter spp. Authors => L. Martinez-Anton | M. Marenda | S.M. Firestone | R.N. Bushell | G. Child | A.I. Hamilton | S.N. Long | M.A.R. Le Chevoir published => First published: 22 January 2018 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.15030

Title => Familial Congenital Methemoglobinemia in Pomeranian Dogs Caused by a Missense Variant in the NADH-Cytochrome B5 Reductase Gene Abstract => Background: In veterinary medicine, congenital methemoglobinemia associated with nicotinamide adenine dinucleotide (NADH)-cytochrome b5 reductase (b5R) deficiency is rare. It has been reported in several breeds of dogs, but little information is available about its etiology. Objectives: To analyze the NADH-cytochrome b5 reductase gene, CYB5R3, in a Pomeranian dog family with methemoglobinemia suspected to be caused by congenital b5R deficiency. Animals: Three Pomeranian dogs from a family with methemoglobinemia were analyzed. Five healthy beagles and 5 nonrelated Pomeranian dogs without methemoglobinemia were used as controls. Methods: Methemoglobin concentration, b5R activity, and reduced glutathione (GSH) concentration were measured, and a turbidity index was used to evaluate Heinz body formation. The CYB5R3 genes of the affected dog and healthy dogs were analyzed by direct sequencing. Results: Methemoglobin concentrations in erythrocytes of the affected dogs were remarkably higher than those of the control dogs. The b5R activity of the affected dogs was notably lower than that of the control dogs. DNA sequencing indicated that this Pomeranian family carried a CYB5R3 gene missense variant (ATC→CTC at codon 194) that resulted in the replacement of isoleucine (Ile) by leucine (Leu). Conclusions and Clinical Importance: This dog family had familial congenital methemoglobinemia caused by b5R deficiency, which resulted from a nonsynonymous variant in the CYB5R3 gene. This variation (c.580A>C) led to an amino acid substitution (p.Ile194Leu), and Ile194 was located in the proximal region of the NADH-binding motif. Our data suggested that this variant in the canine CYB5R3 gene would affect function of the b5R in erythrocytes. Authors => H. Shino | Y. Otsuka-Yamasaki | T. Sato | K. Ooi | O. Inanami | R. Sato | M. Yamasaki published => First published: 22 January 2018 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.15031

Title => Serum Cytokine Profiling in Cats with Acute Idiopathic Cystitis Abstract => Background: Feline idiopathic cystitis (FIC) is a common lower urinary tract disorder of domestic cats that resembles interstitial cystitis/painful bladder syndrome (IC/PBS) in humans. Diagnosis of FIC is based on clinical signs and exclusion of other disorders because of a lack of specific pathologic findings or other objective biomarkers. Cytokines are potential noninvasive biomarkers to define the presence, severity, and progression of disease, and response to treatment. Objectives: The objective of this pilot study was to determine concentrations of selected cytokines in serum from healthy cats and cats with acute FIC. Animals: Serum samples from 13 healthy cats and from 12 cats with nonobstructive acute FIC were utilized. Methods: Multiplex analysis of 19 cytokines (CCL2, CCL5, CXCL1, CXCL12, CXCL8, Flt3L, GM-CSF, IFN-γ, IL-12 (p40), IL-13, IL-18, IL-1β, IL-2, IL-4, IL-6, PDGF-BB, SCF, sFas, and TNF-α) was performed with a commercially available feline-specific multiplex bead-based assay. Results: Mean serum concentrations of IL-12 (p40; P < 0.0001), CXCL12 (P = 0.002), IL-18 (P = 0.032), and Flt3L (P = 0.0024) were significantly increased in FIC cats compared to healthy cats. GM-CSF, IL-1b, IL-2, and PDGF-BB were undetectable or detected in an insufficient number of cats to allow meaningful comparisons. Conclusions and Clinical Importance: We have identified increased serum concentrations of pro-inflammatory cytokines and chemokines CXCL12, IL-12, IL-18, and Flt3L in FIC-affected cats. These findings suggest potential candidates for noninvasive biomarkers for diagnosis, staging, and therapeutic outcome monitoring of affected cats and provide additional insight into the etiopathogenesis of FIC. Authors => M. Parys | V. Yuzbasiyan-Gurkan | J.M. Kruger published => First published: 22 January 2018 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.15032

Title => Effect of Intravenous Administration of Cobalt Chloride to Horses on Clinical and Hemodynamic Variables Abstract => Background: Cobalt chloride (CoCl2) is administered to racehorses to enhance performance. The purpose of this study was to evaluate the clinical, cardiovascular, and endocrine effects of parenterally administered CoCl2. Objectives: To describe the effects of weekly intravenous doses of CoCl2 on Standardbred horses. Animals: Five, healthy Standardbred mares. Methods: Prospective, randomized, experimental dose-escalation pilot. Five Standardbred mares were assigned to receive 1 of 5 doses of CoCl2 (4, 2, 1, 0.5, or 0.25 mg/kg) weekly IV for 5 weeks. Physical examination, blood pressure, cardiac output, and electrocardiography (ECG) were evaluated for 4 hours after administration of the first and fifth doses. Blood and urine samples were collected for evaluation of cobalt concentration, CBC and clinical chemistry, and hormone concentrations. Results: All mares displayed pawing, nostril flaring, muscle tremors, and straining after CoCl2 infusion. Mares receiving 4, 2, or 1 mg/kg doses developed tachycardia after dosing (HR 60–126 bpm). Ventricular tachycardia was noted for 10 minutes after administration of the 4 mg/kg dose. Increases in systolic arterial pressure (SAP), diastolic arterial pressure (DAP), and mean arterial pressure (MAP) occurred after administration of all doses (4, 2, 1, 0.5, and 0.25 mg/kg). Profound hypertension was observed after the 4 mg/kg dose (SAP/DAP, MAP [mmHg] = 291–300/163–213, 218–279). Hemodynamics normalized by 1–2 hours after administration. ACTH and cortisol concentrations increased within 30 minutes of administration of all CoCl2 doses, and cardiac troponin I concentration increased after administration of the 4 and 2 mg/kg doses. Conclusions and Clinical Importance: The degree of hypertension and arrhythmia observed after IV CoCl2 administration raises animal welfare and human safety concerns. Authors => T.A. Burns | K.A. Dembek | A. Kamr | S.B. Dooley | L.K. Dunbar | T.K. Aarnes | L.S. Bednarski | C. O'Brien | J. Lakritz | B. Byrum | A. Wade | R. Farmer | S. Tan | R.E. Toribio published => First published: 29 December 2017 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.15029

Title => Sonographic Evaluation of Liver Hemodynamic Indices in Overweight and Obese Dogs Abstract => Background: Hepatic circulatory disturbances have been associated with obesity and fatty liver in humans. In the veterinary literature, however, there is limited information regarding the effects of different body condition scores (BCS) on liver hemodynamic indices in dogs. Objectives: To investigate the influence of BCS on liver hemodynamic indices. Animals: Fifty-three client-owned dogs of various breeds were included. Methods: Prospective observational study. Dogs were divided into 3 BCS groups using a 5-point scale: G1 – 12 ideal dogs, G2 – 21 overweight dogs, G3 – 20 obese dogs. Mean portal velocity (MPV), portal blood flow volume (PBFV), portal congestion index (PCI), hepatic artery resistivity index (HARI), and hepatic vein (HV) spectral wave were obtained by pulsed Doppler sonography. Alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT), and alanine aminotransferase (ALT) activities were determined. Liver enzymes activities and liver hemodynamic indices were compared among groups. Results: Obese dogs had lower MPV, higher percentage of abnormal hepatic vein spectral wave and higher median ALP activity than did ideal dogs (P < 0.05). Overweight and obese dogs had lower PBFV than ideal dogs (P < 0.01). Overweight dogs had higher median GGT activity than ideal dogs (P < 0.05). No difference was observed for PCI, HARI and median ALT activity among the groups. Conclusions and Clinical Importance: Obesity was associated with changes in portal vein indices and in HV spectral wave. These changes were accompanied by significant differences in some liver enzymes activities and could be a sign of early liver disease. Authors => A.F. Belotta | C.R. Teixeira | C.R. Padovani | S.C. Rahal | M.N. Mayer | M.J. Mamprim published => First published: 27 December 2017 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.14883

Title => Effect of Heat-treatment on Accuracy of Infrared Spectroscopy and Digital and Optical Brix Refractometers for Measuring Immunoglobulin G Concentration in Bovine Colostrum Abstract => Background: Heat-treatment of colostrum is a method developed to reduce calf exposure to pathogens. Infrared (IR) spectroscopy and Brix refractometers can be used for measuring colostral IgG concentration and assessing colostrum quality. Objectives: To determine the impact of heat-treatment on accuracy of IR spectroscopy and Brix refractometers for measuring colostral IgG concentration and assessing colostrum quality before and after heat-treatment. Animals: A total of 60 Holstein dairy cows on 8 commercial dairy farms. Methods: A cross-sectional study was designed to determine the effect of heat-treatment at 60°C and 63°C each for 30 and 60 minutes duration on colostral IgG concentration measured by the reference radial immunodiffusion (RID) assay, IR spectroscopy, and digital and optical refractometers. Results: Colostrum IgG concentration significantly decreased after heat-treatment at 63°C for 30 or 60 minutes as measured by RID, but the IgG values remained unchanged when measured by IR spectroscopy and refractometers. The lowest correlation coefficient found between IR spectroscopy (r = 0.70) and RID results was in colostrum heat-treated at 63°C for 60 minutes. For digital (r = 0.48) and optical (r = 0.50) refractometers, the lowest correlation coefficient was at 63°C for 30 minutes when compared to RID. The accuracy of the IR spectroscopy, digital and optical Brix refractometers was decreased from 91.7 to 80%, 81.7 to 45%, and 80 to 45%, respectively, when colostrum heat-treated at 63°C for 60 minutes. Conclusions and Clinical Importance: Radial immunodiffusion, IR spectroscopy, and Brix refractometers exhibit utility for measuring IgG concentration when colostrum heat-treated at 60°C but does not detect decrease IgG concentrations when heat-treated at 63°C. Authors => I. Elsohaby | J.T. McClure | N. Dow | G.P. Keefe published => First published: 27 December 2017 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.15025

Title => Effect of Continuous Digital Hypothermia on Lamellar Inflammatory Signaling When Applied at a Clinically-Relevant Timepoint in the Oligofructose Laminitis Model Abstract => Background: Although continuous digital hypothermia (CDH) protects lamellae from injury in the oligofructose (OF) model of sepsis-related laminitis (SRL), conflicting results exist from these studies regarding effects of CDH on lamellar inflammatory events. Hypothesis/Objectives: To determine the effect of CDH on lamellar inflammatory events in normal and OF-treated horses when instituted at a clinically relevant time point (onset of clinical signs of sepsis in this model). Animals: Standardbred geldings (n = 15) aged 3–11 years were used. Methods: In a randomized, controlled discovery study, animals were administered either OF (OF group, n = 8) or water (CON group, n = 8) by nasogastric tube and CDH was initiated in one forelimb (ICE) 12 hours later. Lamellar tissue samples were collected 24 hours after initiation of CDH (ICE and ambient [AMB] forelimbs). Lamellar mRNA concentrations of inflammatory mediators and lamellar leukocyte numbers were assessed using qPCR and immunohistochemistry, respectively; values from four sample groups (CON AMB, OF AMB, CON ICE, and OF ICE) were analyzed using mixed model linear regression. Results: Although lamellar mRNA concentrations of multiple inflammatory mediators (IL-1β, IL-6, CXCL1, MCP2, COX-2) were increased after OF administration (OF AMB group versus CON AMB; P < 0.05), only 2 inflammatory mediators (IL-6 and COX-2) and lamellar leukocyte numbers were decreased with CDH (OF ICE versus OF AMB; P < 0.05). Conclusions and Clinical Importance: Continuous digital hypothermia initiated at a time point similar to that commonly used clinically (clinical onset of sepsis) resulted in a more focused inhibition of inflammatory signaling. Authors => K. Dern | A. van Eps | T. Wittum | M. Watts | C. Pollitt | J. Belknap published => First published: 27 December 2017 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.15027

Title => Effect of Prophylactic Calcitriol Administration on Serum Ionized Calcium Concentrations after Parathyroidectomy: 78 Cases (2005–2015) Abstract => Background: Prophylactic administration of calcitriol has been suggested to mitigate the risk of hypocalcemia after parathyroidectomy. The effect of calcitriol on postoperative serum ionized calcium concentrations has not been evaluated in dogs after parathyroidectomy. Hypothesis/Objectives: To determine the effect of prophylactic calcitriol administration on postoperative serum ionized calcium (iCa) concentrations in dogs with primary hyperthyroidism (PHPTH) treated by parathyroidectomy. Animals: Seventy-eight dogs with primary hyperparathyroidism treated surgically. Methods: Multi-institutional retrospective case study. Medical records from 2005 to 2015 were evaluated. Dogs were included if they had a diagnosis of PHPTH and had surgery to remove parathyroid tissue. Serum iCa concentrations were monitored for a minimum of 2 days postoperatively. Two study groups were evaluated: calcitriol administration and no calcitriol administration. Results: Serial postoperative iCa concentrations measured at 12-hour time intervals for 2 days postoperatively were positively associated with preoperative iCa concentrations. This association was evident at each time interval, and the effect of preoperative iCa concentrations on postoperative iCa concentrations decreased as time elapsed (12 hours, P < 0.0001; 24 hours, P < 0.0001; 36 hours, P < 0.04; and 48 hours, P = 0.01). Prophylactic calcitriol administration was not found to be significantly associated with postoperative iCa concentrations or its rate of decrease after parathyroidectomy. Conclusion and Clinical Importance: We found no protective value in administering calcitriol prophylactically to prevent hypocalcemia in the immediate postoperative period (48 hours) after parathyroidectomy. Preoperative iCa concentrations had a significant positive association with postoperative iCa concentrations throughout the monitoring period. Authors => A.J. Armstrong | J.G. Hauptman | B.J. Stanley | E. Klocke | M. Burneko | D.E. Holt | J.J. Runge | J.A. Rubin published => First published: 27 December 2017 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.15028

Title => Transcranial Doppler Ultrasound Examination in Dogs with Suspected Intracranial Hypertension Caused by Neurologic Diseases Abstract => Background: Transcranial Doppler ultrasound examination (TCD) is a rapid, noninvasive technique used to evaluate cerebral blood flow and is useful for the detection of intracranial hypertension in humans. However, the clinical usefulness of TCD in diagnosing intracranial hypertension has not been demonstrated for intracranial diseases in dogs. Objectives: To determine the association between the TCD variables and intracranial hypertension in dogs with intracranial diseases. Animals: Fifty client-owned dogs with neurologic signs. Methods: Cross-sectional study. All dogs underwent TCD of the basilar artery under isoflurane anesthesia after magnetic resonance imaging (MRI). Dogs were classified into 3 groups based on MRI findings: no structural diseases (group I), structural disease without MRI evidence of intracranial hypertension (group II), and structural disease with MRI evidence of intracranial hypertension (group III). The TCD vascular resistance variables (resistive index [RI], pulsatility index [PI], and the ratio of systolic to diastolic mean velocity [Sm/Dm]) were measured. Results: Fifteen, 22, and 13 dogs were classified into groups I, II, and III, respectively. Dogs in group III had significantly higher Sm/Dm (median, 1.78; range, 1.44–2.58) than those in group I (median, 1.63; range, 1.43–1.75) and group II (median, 1.62; range, 1.27–2.10). No significant differences in RI and PI were identified among groups. Conclusions and Clinical Importance: Our findings suggest that increased Sm/Dm is associated with MRI findings of suspected intracranial hypertension in dogs with intracranial diseases and that TCD could be a useful tool to help to diagnose intracranial hypertension. Authors => K. Sasaoka | K. Nakamura | T. Osuga | T. Morita | N. Yokoyama | K. Morishita | N. Sasaki | H. Ohta | M. Takiguchi published => First published: 19 December 2017 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.14900

Title => Evaluation of the Live Biotherapeutic Product, Asymptomatic Bacteriuria Escherichia coli 2-12, in Healthy Dogs and Dogs with Clinical Recurrent UTI Abstract => Background: Antimicrobial resistance is an emerging problem. Hypothesis/Objective: To investigate the safety and efficacy of a live biotherapeutic product, ASB E. coli 2-12 for UTI treatment. Animals: Six healthy research dogs; nine client-owned dogs with recurrent UTI. Methods: Prospective noncontrolled clinical trial. For safety data, research dogs were sedated, a urinary catheter was inserted into the bladder; 1010 CFU/mL of ASB E. coli 2-12 was instilled. Urine was cultured on days 1, 3, and 8 post-instillation and dogs were observed for lower urinary tract signs (LUTS). For client-owned dogs, ASB E. coli 2-12 was instilled similarly and urine cultures analyzed on days 1, 7, and 14 days postinstillation. Results: No LUTS were noted in any of the 6 research dogs after ASB E. coli 2-12 infusion. Pulse field gel electrophoresis (PFGE) studies confirmed the bacterial strains isolated matched that ASB E. coli 2-12 strain. Four of the nine client-owned dogs had complete or nearly complete clinical cures by day 14. Of these four dogs, 3 also had microbiologic cures at day 14; one of these dogs had subclinical bacteriuria (in addition to ASB E. coli 2-12). Three of these four dogs had ASB E. coli 2-12 isolated from their urine at day 14. With the exception of mild, temporary, self-limiting, hyporexia in two dogs on the day of biotherapeutic administration, there were no major adverse effects. Conclusions and Clinical Importance: These results suggest ASB E. coli 2-12 is safe and should be investigated in a larger controlled study evaluating clinical UTI in dogs. Authors => G. Segev | J.E. Sykes | D.J. Klumpp | A.J. Schaeffer | E.M. Antaki | B.A. Byrne | R.E. Yaggie | J.L. Westropp published => First published: 15 December 2017 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.14851

Title => Transient Myocardial Thickening in Cats Associated with Heart Failure Abstract => Background: Cats with hypertrophic cardiomyopathy (HCM) and congestive heart failure (CHF) can have resolution of both left ventricular hypertrophy and CHF. Objectives: To describe the clinical characteristics of cats with transient myocardial thickening (TMT) and CHF compared with a control population of cats without resolution of HCM. Animals: A total of 21 cats with TMT, 21 cats with HCM. Methods: Retrospective study. Clinical records at 4 veterinary centers were searched for TMT cases and a control group of cats with HCM and CHF. TMT was defined as initial maximal left ventricular wall thickness (LVWT) ≥6 mm with left-sided CHF, with subsequent resolution of CHF, reduction in left atrium/aorta (LA/Ao), and LVWT<5.5 mm. HCM was defined as persistent LVWT ≥6 mm. Results: Cats with TMT were younger (2 [0.4–11.4] years) than cats with HCM (8 [1.6–14] years) (P < 0.0001), and antecedent events were more common (15/21 versus 6/21, respectively) (P = 0.01). In cats with TMT, LVWT normalized from 6.8 [6.0–9.7] mm to 4.8 [2.8–5.3] mm and LA/Ao decreased from 1.8 [1.6–2.3] to 1.45 [1.2–1.7] after a mean interval of 3.3 (95% CI: 1.8–4.7) months. CHF recurred in 1 of 21 TMT and 15 of 21 cats with HCM. Cardiac treatment was discontinued in 20 of 21 cats with TMT and 0 of 21 HCM cats. All cats with TMT survived, whereas 8 of 19 cats with HCM died during the study period. Conclusions and Clinical Importance: TMT occurs in younger cats, and antecedent events are common. The prognosis is better in cats with CHF associated with TMT than HCM. Authors => J. Novo Matos | N. Pereira | T. Glaus | L. Wilkie | K. Borgeat | J. Loureiro | J. Silva | V. Law | A. Kranjc | D.J. Connolly | V. Luis Fuentes published => First published: 15 December 2017 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.14897

Title => Erratum Abstract => None Abstract Authors => published => First published: 13 December 2017 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.15026

Title => Kinetics of Plasma Cell-Free DNA and Creatine Kinase in a Canine Model of Tissue Injury Abstract => Background: Cell-free DNA (cfDNA) comprises short, double-stranded circulating DNA sequences released from damaged cells. In people, cfDNA concentrations correlate well with disease severity and tissue damage. No reports are available regarding cfDNA kinetics in dogs. Objectives/Hypothesis: Cell-free DNA will have a short biological half-life and would be able to stratify mild, moderate, and severe tissue injury. Our study aims were to determine the kinetics and biological half-life of cfDNA and to contrast them with those of creatine kinase (CK). Animals: Three groups of 10 dogs undergoing open ovariohysterectomy, surgery for cranial cruciate ligament rupture (CCLR), or hemilaminectomy. Methods: Plasma for cfDNA and CK analysis was collected at admission, at induction of anesthesia, postsurgery (time 0) and at 6, 12, 24, 36, 48, 60, and 72 hours after surgery. Results: The biological half-life of plasma cfDNA and CK were 5.64 hours (95% confidence interval [CI 95], 4.36–7.98 hours) and 28.7 hours (CI95, 25.3–33.3 hours), respectively. In the hemilaminectomy group, cfDNA concentrations differed significantly from admission at 6–12 hours after surgery. Creatine kinase activity differed among the surgical groups and reached a peak 6 hours after surgery. In the ovariohysterectomy and CCLR groups, plasma CK activity 72 hours after surgery did not differ from admission activity of the ovariohysterectomy group. In contrast, in the hemilaminectomy group, plasma CK activity after 72 hours did not return to the ovariohysterectomy group admission activity. Conclusions and Clinical Importance: Plasma CK activity has a longer biological half-life than previously thought. In contrast to plasma CK activity, cfDNA has a short half-life and could be a useful marker for peracute severe tissue injury. Authors => I.J. Wilson | R.K. Burchell | A.J. Worth | S.E. Burton | K.R. Gedye | K.J. Clark | K.R. Crosse | M. Jack | T.F. Odom | S.J. De Grey | K.M.S. McGlade | S.C. Tomlin | N. Lopez-Villalobos | A. Gal published => First published: 12 December 2017 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.14901

Title => Symmetric Dimethylarginine in Cats with Hypertrophic Cardiomyopathy and Diabetes Mellitus Abstract => Background: Symmetric dimethylarginine (SDMA) has been increasingly used as a marker of early chronic kidney disease (CKD) in cats, but little is known about the influence of comorbidities on SDMA in this species. Hypothesis: Hypertrophic cardiomyopathy (HCM) and diabetes mellitus (DM), independently of CKD, are associated with changes in serum SDMA. Animals: Ninety-four cats (17 with CKD, 40 with HCM, 17 with DM, and 20 healthy controls). Methods: Case-control study. Clinical examination, echocardiography, ECG, blood pressure, CBC, biochemistry, thyroxine, and SDMA measurement were performed. Urinalysis was performed in controls and cats with CKD and DM. Analysis of variance was used to compare overall differences in the log-transformed SDMA data among groups. A random forest algorithm was applied to explore which clinical and other factors influenced serum SDMA. Results: Median (range) serum SDMA for the renal group (positive control) was 19 (10–93) μg/dL, whereas for the control group (negative control), it was 10 (5–15) μg/dL. For the cardiac and diabetic groups, serum SDMA was 9 (4–24) μg/dL and 7 (3–11) μg/dL, respectively. The renal group had significantly higher SDMA concentrations and the diabetic group significantly lower SDMA concentrations compared to all other groups. Conclusions and Clinical Importance: Serum SDMA concentrations in cats with HCM were not significantly different from those of healthy control cats. Cats with DM, however, had significantly lower SDMA concentrations than controls, a finding that needs further investigation and should be kept in mind when evaluating renal function of cats with this endocrinopathy. Authors => R. Langhorn | I.N. Kieler | J. Koch | L.B. Christiansen | L.R. Jessen published => First published: 12 December 2017 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.14902

Title => Echocardiographic Estimates of Right Ventricular Systolic Function in Dogs with Myxomatous Mitral Valve Disease Abstract => Background: Right ventricular (RV) dysfunction independently predicts outcomes in human myxomatous mitral valve disease (MMVD). There is limited information regarding RV systolic function in dogs with MMVD. Hypothesis: Right ventricular systolic function differs among stages of disease, decreasing in decompensated MMVD. Animals: Thirty-sixclient-owned dogs with MMVD not receiving oral cardiovascular medications. Methods: Prospective clinical study. Dogs were categorized according to disease severity as ACVIM Stage B1, B2, or C. Seven echocardiographic indices of RV systolic function were measured. Groups were compared by 1-way ANOVA and Tukey's HSD test. Frequencies of cases with cardiac remodeling falling outside previously established reference intervals were compared using Fisher's exact test. Intra- and interobserver measurement variability was calculated for each RV function index. Results: The indices TAPSE (P = 0.029), RV StL (P = 0.012), and RV StRL (P = 0.041) were significantly different between groups. A greater proportion of B2 dogs (7 of 12) had TAPSE values above reference intervals compared with B1 (2 of 12) or C (2 of 12) dogs (P = 0.027). Measurement variability of TAPSE, RV S', and RV StG was clinically acceptable. Conclusions and Clinical Importance: Right ventricular systolic function differs between stages of MMVD, increasing in stage B2, and declining in stage C. The prognostic importance of RV function indices, particularly TAPSE, might be worth evaluating in dogs with MMVD. Authors => E.H. Chapel | B.A. Scansen | K.E. Schober | J.D. Bonagura published => First published: 10 December 2017 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.14884

Title => Association of California Mastitis Test Scores with Intramammary Infection Status in Lactating Dairy Cows Admitted to a Veterinary Teaching Hospital Abstract => Background: Subclinical mastitis is of concern in veterinary hospitals because contagious mastitis pathogens might be unknowingly transmitted to susceptible cows and then back to their farm of origin. Objectives: To evaluate the California mastitis test (CMT) as an indicator of intramammary infection (IMI) in lactating dairy cows admitted to a veterinary hospital. Animals: A total of 139 admissions of 128 lactating dairy cows admitted to the University of Illinois Veterinary Teaching Hospital over a 2-year period. Methods: A retrospective study with a convenience sample was conducted. Medical records of cows with CMT results and milk culture results for the day of admission were reviewed. Breed, age, season, maximum CMT score for the 4 quarters, maximum CMT score difference, and clinical diagnosis were evaluated as predictors of IMI by the chi-square test and stepwise logistic regression. Results: An IMI was identified in 51% of quarters. For cows admitted without evidence of clinical mastitis, the sensitivity of a CMT score ≥trace in predicting an IMI on a quarter or cow basis was 0.45 and 0.68, respectively. The distributions of maximal quarter CMT score and the maximum difference in quarter CMT score for cows without evidence of clinical mastitis did not differ (P = 0.28, P = 0.84, respectively) for cows with and without IMI. Stepwise logistic regression did not identify significant predictors of IMI in cows without clinical mastitis. Conclusions: Lactating dairy cattle admitted to a veterinary hospital should be managed as if they have an IMI, even in the absence of clinical mastitis. Authors => S.A. Kandeel | D.E. Morin | C.D. Calloway | P.D. Constable published => First published: 09 December 2017 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.14876

Title => Evaluation and Comparison of 2 On-Farm Tests for Estimating Somatic Cell Count in Quarter Milk Samples from Lactating Dairy Cattle Abstract => Background: The somatic cell count (SCC) is commonly used to monitor udder health and diagnose subclinical intramammary infection (IMI) in dairy cattle. Hypothesis: The Somaticell test (ST)2 and California mastitis test (CMT) are clinically useful cow-side tests for diagnosing subclinical IMI. Animals: One hundred and eleven dairy cows at dry-off and 92 cows within 4–7 days postcalving. Methods: Quarter foremilk samples were obtained and analyzed with a DeLaval cell counter (DCC, reference method),1 ST, and CMT. The ST was run in a simulated cow-side manner using milk at 37°C instead of 0–8°C as recommended by the manufacturer. Test performance for diagnosing IMI (DCC SCC >200,000 cells/mL) was evaluated by calculating the area under the receiver operating characteristic curve (AUC) and the kappa coefficient (κ) at the optimal cut-point for each test. The effect of milk/reagent temperature also was evaluated. Results: Compared to the reference method, the ST run in a simulated cow-side manner had an AUC = 0.68 and κ = 0.24 at dry-off, and AUC = 0.74 and κ = 0.40 in fresh cows. The CMT performed much better than the ST in diagnosing subclinical IMI with AUC = 0.88 and κ = 0.77 at dry-off, and AUC = 0.87 and κ = 0.76 in fresh cows. The measured ST value decreased with increasing temperature of the milk/reagent mixture. Conclusions/Clinical Importance: The ST is optimized for use on milk at 0–8°C and is therefore designed for on-farm use on refrigerated milk samples. The ST is not suited for use as a cow-side screening test for IMI because the milk temperature exceeds the recommended range for the test. Authors => S.A. Kandeel | A.A. Megahed | F.K. Arnaout | P.D. Constable published => First published: 09 December 2017 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.14888

Title => Effect of a Pheromone on Stress-Associated Reactivation of Feline Herpesvirus-1 in Experimentally Inoculated Kittens Abstract => Background: Stress contributes to reactivation of feline herpesvirus-1 (FHV-1). The usage of pheromones to decrease stress in FHV-1 experimentally inoculated kittens has not previously been investigated. Hypothesis/Objectives: To determine whether a feline pheromone would lessen stress, resulting in decreased recurrence of FHV-1-associated illness in kittens. Animals: Twelve 5-month-old, purpose-bred kittens. Methods: Randomized, double-blind, placebo-controlled clinical trial. Kittens previously infected with the same dose of FHV-1 were randomized into 2 separate but identical group rooms. After a 2-week equilibration period, a diffuser containing either the pheromone or placebo was placed in each of the rooms, and the kittens acclimated for an additional 2 weeks. Every 2 weeks thereafter, for the 8-week study period, housing was alternated between kennel- and group housing. Blinded observers applied a standardized clinical and behavioral scoring rubric daily. After each 2-week period, serum cortisol concentrations and quantitative PCR for FHV-1 and glyceraldehyde 3-phosphate dehydrogenase (GAPDH) ratios were evaluated. Clinical, behavioral, and laboratory test results were compared between groups within individual and combined study periods. Results: Sneezing occurred more frequently in the placebo group during individual (P = 0.006) and combined study periods (P = 0.001). Sleep at the end of observation periods occurred more frequently in the pheromone group during individual (P = 0.006) and combined study periods (P < 0.001). Conclusions and Clinical Importance: The findings suggest that the pheromone decreased stress, and the decrease in stress response may have resulted in decreased sneezing associated with FHV-1. Authors => Elena T. Contreras | E. Hodgkins | V. Tynes | A. Beck | F. Olea-Popelka | M.R. Lappin published => First published: 08 December 2017 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.14894

Title => Neutrophil Extracellular Traps in Plasma from Dogs with Immune-mediated Hemolytic Anemia Abstract => Background: Neutrophil extracellular traps (NETs) are part of the innate immune response and are essential in local pathogen control, but are associated with pathological inflammation, organ damage, autoimmunity, and thrombosis. Immune-mediated hemolytic anemia (IMHA) is a pro-inflammatory, prothrombotic disease associated with high mortality. Hypothesis/Objectives: Neutrophil extracellular traps (NETs) are a feature of the inflammatory process in dogs with IMHA. The objective of the study was to evaluate plasma from dogs with IMHA for the presence of 2 indirect markers and 1 direct marker of NETs. Animals: Healthy client-owned dogs (56) and hospitalized dogs with IMHA (n = 35). Methods: Prospective study. Plasma samples for all dogs were evaluated for cell-free DNA using a fluorescence assay, histone-DNA (hisDNA) complex using an ELISA, and citrullinated histone H3 (specific for NETosis) using Western blot. Reference intervals were generated using plasma from healthy dogs. Results: In dogs with IMHA, cell-free DNA concentration was above the reference interval in 17% of samples with a median (range) of 1.0 μg/mL (0.1–17.3), and hisDNA concentration was above the reference interval in 94% of samples with a median (range) of 30.7 × pooled normal plasma (PNP; 0.6–372.1). Western blot for citrullinated histone H3 identified detectable bands in 84% samples from dogs with IMHA. Conclusions and Clinical Importance: The assay for cell-free DNA detected evidence of NETs in fewer dogs than did the other approaches. Excessive NETs appears to be a feature of IMHA in dogs and contributions to the prothrombotic state deserve further study. Authors => C. Lawson | S.A. Smith | M. O'Brien | M. McMichael published => First published: 07 December 2017 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.14881

Title => Longitudinal Analysis of Quality of Life, Clinical, Radiographic, Echocardiographic, and Laboratory Variables in Dogs with Preclinical Myxomatous Mitral Valve Disease Receiving Pimobendan or Placebo: The EPIC Study Abstract => Background: Changes in clinical variables associated with the administration of pimobendan to dogs with preclinical myxomatous mitral valve disease (MMVD) and cardiomegaly have not been described. Objectives: To investigate the effect of pimobendan on clinical variables and the relationship between a change in heart size and the time to congestive heart failure (CHF) or cardiac-related death (CRD) in dogs with MMVD and cardiomegaly. To determine whether pimobendan-treated dogs differ from dogs receiving placebo at onset of CHF. Animals: Three hundred and fifty-four dogs with MMVD and cardiomegaly. Materials and Methods: Prospective, blinded study with dogs randomized (ratio 1:1) to pimobendan (0.4–0.6 mg/kg/d) or placebo. Clinical, laboratory, and heart-size variables in both groups were measured and compared at different time points (day 35 and onset of CHF) and over the study duration. Relationships between short-term changes in echocardiographic variables and time to CHF or CRD were explored. Results: At day 35, heart size had reduced in the pimobendan group: median change in (Δ) LVIDDN −0.06 (IQR: −0.15 to +0.02), P < 0.0001, and LA:Ao −0.08 (IQR: −0.23 to +0.03), P < 0.0001. Reduction in heart size was associated with increased time to CHF or CRD. Hazard ratio for a 0.1 increase in ΔLVIDDN was 1.26, P = 0.0003. Hazard ratio for a 0.1 increase in ΔLA:Ao was 1.14, P = 0.0002. At onset of CHF, groups were similar. Conclusions and Clinical Importance: Pimobendan treatment reduces heart size. Reduced heart size is associated with improved outcome. At the onset of CHF, dogs treated with pimobendan were indistinguishable from those receiving placebo. Authors => A. Boswood | S.G. Gordon | J. Häggström | G. Wess | R.L. Stepien | M.A. Oyama | B.W. Keene | J. Bonagura | K.A. MacDonald | M. Patteson | S. Smith | P.R. Fox | K. Sanderson | R. Woolley | V. Szatmári | P. Menaut | W.M. Church | M.L. O'Sullivan | J.-P. Jaudon | J.-G. Kresken | J. Rush | K.A. Barrett | S.L. Rosenthal | A.B. Saunders | I. Ljungvall | M. Deinert | E. Bomassi | A.H. Estrada | M.J. Fernandez Del Palacio | N.S. Moise | J.A. Abbott | Y. Fujii | A. Spier | M.W. Luethy | R.A. Santilli | M. Uechi | A. Tidholm | C. Schummer | P. Watson published => First published: 06 December 2017 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.14885

Title => Systematic Review and Meta-Analysis of Diagnostic Accuracy of Serum Refractometry and Brix Refractometry for the Diagnosis of Inadequate Transfer of Passive Immunity in Calves Abstract => Background: Transfer of passive immunity in calves can be assessed by direct measurement of immunoglobulin G (IgG) by methods such as radial immunodiffusion (RID) or turbidimetric immunoassay (TIA). IgG can also be measured indirectly by methods such as serum refractometry (REF) or Brix refractometry (BRIX). Objectives: To determine the accuracy of REF and BRIX for assessment of inadequate transfer of passive immunity (ITPI) in calves. Design: Systematic review and meta-analysis of diagnostic accuracy studies. Methods: Databases (PubMed and CAB Abstract, Searchable Proceedings of Animal Science) and Google Scholar were searched for relevant studies. Studies were eligible if the accuracy (sensitivity and specificity) of REF or BRIX was determined using direct measurement of IgG by RID or turbidimetry as the reference standard. The study population included calves <14 days old that were fed with natural colostrum (colostrum replacement products were excluded). Quality assessment was performed by the QUADAS-2 tool. Hierarchical models were used for meta-analysis. Results: From 1,291 references identified, 13 studies of 3,788 calves were included. Of these, 11 studies evaluated REF and 5 studies evaluated BRIX. The median (range) prevalence of ITPI (defined as calves with IgG <10 g/L by RID or TIA) was 21% (1.3–56%). Risk of bias and applicability concerns were generally low or unclear. For REF, summary estimates were obtained for 2 different cutoffs: 5.2 g/dL (6 studies) and 5.5 g/dL (5 studies). For the 5.2 g/dL cutoff, the summary sensitivity (95% CI) and specificity (95% CI) were 76.1% (63.8–85.2%) and 89.3% (82.3–93.7%), and 88.2% (80.2–93.3%) and 77.9% (74.5–81.0%) for the 5.5 g/dL cutoff. Due to the low number of studies using the same cutoffs, summary estimates could not be obtained for BRIX. Conclusions and Clinical Importance: Despite their widespread use on dairy farms, evidence about the optimal strategy for using refractometry, including the optimal cutoff, are sparse (especially for BRIX). When using REF to rule out ITPI in herds, the 5.5 g/dL cutoff may be used whereas for ruling in ITPI, the 5.2 g/dL cutoff may be used. Authors => S. Buczinski | E. Gicquel | G. Fecteau | Y. Takwoingi | M. Chigerwe | J.M. Vandeweerd published => First published: 05 December 2017 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.14893

Title => Prognostic Value of Cardiac Troponin I and L-Lactate in Blood of Dairy Cows Affected by Downer Cow Syndrome Abstract => Background: The downer cow syndrome (DCS) is a challenging health issue in the dairy industry. No cow-side test is available to provide an accurate prognosis for DCS cases in farm settings. Hypothesis/Objectives: Local or systemic hypoperfusion and myocardial lesions lead to an increase in blood concentration of biomarkers cardiac troponin I (cTnI) and L-lactate. The objective was to determine the prognostic values of these biomarkers assessed cow-sides in addition to clinical examinations in prognostication of a negative outcome (NO: death or euthanasia within 7 days). Animals: 218 client-owned dairy cows affected by DCS. Methods: In a prospective study, animals were monitored for 60 days after inclusion of each cow. Blood cTnI and L-lactate concentrations were measured on the day of inclusion. The prognostic accuracy of both biomarkers and physical examination variables was estimated to predict NO. A mixed multivariable logistic regression model was used for data analysis. Results: Prevalence of NO in this study was 63% on day 7. Troponin concentrations greater than 0.7 ng/mL had sensitivity and specificity of 54.1% (95% CI: 45.3–62.7%) and 78.4% (95% CI: 67.3–87.1%), respectively, for predicting NO. Blood L-lactate was not associated with the outcome. The multivariable model revealed that heart rate >100 bpm (OR; 95% CI: 3.7; 1.3–10.2) and cTnI > 0.7 ng/mL (OR; 95% CI: 5.5; 2.1–14.6) were associated with the risk of NO. Conclusions and Clinical Importance: Hypertroponinemia and tachycardia were associated with reduced survival in DCS cases. The use of cow-side blood cTnI concentrations and heart rate could help to rapidly identify cows in farm setting that have poor chances of recovery and would benefit from a more aggressive treatment or euthanasia. Authors => J. Labonté | J. Dubuc | J.-P. Roy | S. Buczinski published => First published: 04 December 2017 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.14874

Title => Impact of Pretreatment Neutrophil Count on Chemotherapy Administration and Toxicity in Dogs with Lymphoma Treated with CHOP Chemotherapy Abstract => Background: Prechemotherapy absolute neutrophil count (ANC) cutoffs are arbitrary and vary across institutions and clinicians. Similarly, subjective guidelines are utilized for the administration of prophylactic antibiotics in neutropenic dogs. Objectives: To evaluate the impact of various ANC cutoffs on chemotherapy administration in dogs with lymphoma treated with CHOP chemotherapy and to determine whether an association between prechemotherapy ANC and subsequent toxicity exists. The secondary objective was to evaluate a currently used ANC cutoff to indicate prescription of prophylactic antibiotics. Animals: Dogs diagnosed with lymphoma treated with CHOP chemotherapy (n = 64). Methods: Six hundred and fifteen ANCs were stratified into 6 classes. The 3 ANC cutoffs 1.5 × 103/μL, 2.0 × 103/μL, and 2.5 × 103/μL were assessed. The presence of an association between prechemotherapy ANC class and toxicity was determined. Afebrile neutropenic dogs with ANC <1.5 × 103/μL but above the criteria for prophylactic antibiotics were evaluated. Results: Chemotherapy was not administered in 7% of visits with an ANC cutoff of 1.5 × 103/μL; chemotherapy would not have been administered in 10% and 16% of visits with an ANC cutoff of 2.0 × 103/μL or 2.5 × 103/μL, respectively. There was no association among the 3 lower prechemotherapy ANC classes and toxicity. All dogs with ANC 0.75–1.5 × 103/μL recovered spontaneously without medical intervention. Conclusion and Clinical Importance: The number of dose delays was minimized with a prechemotherapy ANC cutoff of 1.5 × 103/μL, and the prechemotherapy ANC class 1.5–1.99 × 103/μL was not associated with an increased toxicity. Further investigation of an ANC cutoff near 0.75 × 103/μL in which to prescribe prophylactic antibiotics is indicated. Authors => Q. Fournier | J.-C. Serra | I. Handel | J. Lawrence published => First published: 04 December 2017 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.14895

Title => Retrospective Evaluation of the Effect of Heart Rate on Survival in Dogs with Atrial Fibrillation Abstract => Background: Atrial fibrillation (AF) usually is associated with a rapid ventricular rate. The optimal heart rate (HR) during AF is unknown. Hypothesis/Objectives: Heart rate affects survival in dogs with chronic AF. Animals: Forty-six dogs with AF and 24-hour ambulatory recordings were evaluated. Methods: Retrospective study. Holter-derived HR variables were analyzed as follows: mean HR (meanHR, 24-hour average), minimum HR (minHR, 1-minute average), maximum HR (maxHR, 1-minute average). Survival times were recorded from the time of presumed adequate rate control. The primary endpoint was all-cause mortality. Cox proportional hazards analysis identified variables independently associated with survival; Kaplan-Meier survival analysis estimated the median survival time of dogs with meanHR <125 bpm versus ≥125 bpm. Results: All 46 dogs had structural heart disease; 31 of 46 had congestive heart failure (CHF), 44 of 46 received antiarrhythmic drugs. Of 15 dogs with cardiac death, 14 had CHF. Median time to all-cause death was 524 days (Interquartile range (IQR), 76–1,037 days). MeanHR was 125 bpm (range, 62–203 bpm), minHR was 82 bpm (range, 37–163 bpm), maxHR was 217 bpm (range, 126–307 bpm). These were significantly correlated with all-cause and cardiac-related mortality. For every 10 bpm increase in meanHR, the risk of all-cause mortality increased by 35% (hazard ratio, 1.35; 95% CI, 1.17–1.55; P < 0.001). Median survival time of dogs with meanHR<125 bpm (n = 23) was significantly longer (1,037 days; range, 524-open) than meanHR ≥125 bpm (n = 23; 105 days; range, 67–267 days; P = 0.0012). Mean HR was independently associated with all-cause and cardiovascular mortality (P < 0.003). Conclusions and Clinical Importance: Holter-derived meanHR affects survival in dogs with AF. Dogs with meanHR <125 bpm lived longer than those with meanHR ≥ 125 bpm. Authors => B. Pedro | J. Dukes-McEwan | M.A. Oyama | M.S. Kraus | A.R. Gelzer published => First published: 04 December 2017 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.14896

Title => Gallbladder Mucocele: Variables Associated with Outcome and the Utility of Ultrasonography to Identify Gallbladder Rupture in 219 Dogs (2007–2016) Abstract => Background: Gallbladder mucocele (GBM) is an increasingly recognized extrahepatic biliary disease in dogs. Objectives: To investigate cases of GBM and identify variables associated with survival and the sensitivity and specificity of ultrasonography to identify gallbladder rupture. Animals: Two hundred and nineteen client-owned dogs with GBM. Methods: Multicenter, retrospective study of dogs with GBM, presented from January 2007 to November 2016 to 6 academic veterinary hospitals in the United States. Interrogation of hospital databases identified all cases with the inclusion criteria of a gross and histopathologic diagnosis of GBM after cholecystectomy and intraoperative bacteriologic cultures of at least 1 of the following: gallbladder wall, gallbladder contents, or abdominal effusion. Results: Two hundred and nineteen dogs fulfilled the inclusion criteria. Dogs with GBM and gallbladder rupture with bile peritonitis at the time of surgery were 2.7 times more likely to die than dogs without gallbladder rupture and bile peritonitis (P = 0.001; 95% confidence interval [CI], 1.50–4.68; n = 41). No significant associations were identified between survival and positive bacteriologic cultures, antibiotic administration, or time (days) from ultrasonographic identification of GBM to the time of surgery. The sensitivity, specificity, positive, and negative likelihood ratios for ultrasonographic identification of gallbladder rupture were 56.1% (95% CI, 39.9–71.2), 91.7% (95% CI, 85.3–95.6), 6.74, and 0.44, respectively. Conclusion and Clinical Importance: Dogs in our study with GBM and intraoperative evidence of gallbladder rupture and bile peritonitis had a significantly higher risk of death. Additionally, abdominal ultrasonography had low sensitivity for identification of gallbladder rupture. Authors => J.A. Jaffey | A. Graham | E. VanEerde | E. Hostnik | W. Alvarez | J. Arango | C. Jacobs | A.E. DeClue published => First published: 04 December 2017 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.14898

Title => Plasma NT-proBNP and Cell-Free DNA Concentrations after Prolonged Strenuous Exercise in Working Farm Dogs Abstract => Background: Plasma N-terminal pro–B-type natriuretic peptide (NT-proBNP) concentration is increased in dogs with myocardial dysfunction, and cell-free DNA (cfDNA) increases in numerous disease states. In humans, both of these biomarkers can be altered after endurance exercise. Objective: To investigate the effect of prolonged strenuous exercise on circulating NT-proBNP and cfDNA concentrations in working farm dogs. Animals: Six healthy, privately owned working farm dogs (4 Huntaways and 2 heading dogs) from the same hill country farm in New Zealand. Methods: Prospective, nonrandomised cohort study. Venous blood samples were collected before and after the dogs worked over 4 days. Plasma NT-proBNP concentrations were measured by a commercially available ELISA assay and cfDNA concentrations were determined by fluorometry without prior DNA extraction. Results: The baseline (before work, Day 1) median plasma NT-proBNP concentration was 664 pmol/L. A linear mixed-effects model showed that work increased plasma NT-proBNP concentrations by 101 ± 9% (P < 0.001), but with each consecutive day of work, NT-proBNP concentrations declined by 16 ± 4% (P < 0.001). The baseline median plasma cfDNA concentration was 653 ng/mL, and plasma cfDNA concentrations increased by 138 ± 45 ng/mL after work (P = 0.004). Conclusions and Clinical Importance: The plasma concentration of NT-proBNP in healthy Huntaways and heading dogs after work can exceed the upper limit of the reference range. Results in dogs sampled on the day of prolonged strenuous exercise should be interpreted with caution. Plasma concentrations of cfDNA also increase with exercise, but further studies are needed to establish reference ranges in healthy dogs. Authors => H. Hunt | N. Cave | J. Bridges | K. Gedye | K. Hill published => First published: 02 December 2017 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.14835

Title => Pyelonephritis in Dogs: Retrospective Study of 47 Histologically Diagnosed Cases (2005–2015) Abstract => Background: The clinicopathologic aspects of pyelonephritis have not been reported in companion animals. Hypothesis/Objectives: To evaluate the prevalence of pyelonephritis diagnosed in dogs in a academic referral population, describe the clinical signs and the diagnostic test results in dogs with pyelonephritis, and identify concurrent disorders in order to determine potential risk factors for pyelonephritis. Animals: Forty-seven dogs with a histopathologic diagnosis of pyelonephritis from the teaching hospitals of three Canadian veterinary colleges. Methods: Retrospective case series. Review of medical records and renal histologic sections. Results: Pyelonephritis was diagnosed in 0.4–1.3% of the cases at necropsy. Clinical signs included anorexia or inappetence (n = 27, 57%), lethargy (n = 24, 51%), vomiting (n = 17, 36%), and dehydration (n = 12, 25%). Thirty-five dogs (75%) had concomitant disease(s). Escherichia coli was the most common pathogen isolated (37%). Pyelonephritis was classified as acute (n = 12, 26%), subacute (n = 9, 19%), and chronic (n = 26, 55%) disease; and mild (n = 7, 15%), moderate (n = 11, 24%), and severe (n = 28, 61%). Fever was significantly associated with histopathologically subacute pyelonephritis (P = 0.01). Conclusions: In referral hospitals, pyelonephritis has a very low prevalence at necropsy. Nonspecific clinical presentation, concomitant diseases, and high variability in the diagnostic tests results make the antemortem diagnosis of pyelonephritis challenging. Neither the histopathologic stage nor the severity of the pyelonephritis was associated with fever, lumbar pain, or signs of a urinary tract infection (ie, lower urinary tract infection, upper urinary tract infection, or both) except for subacute pyelonephritis which was associated with fever. Authors => J. Bouillon | E. Snead | J. Caswell | C. Feng | P. Hélie | J. Lemetayer published => First published: 02 December 2017 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.14836

Title => Efficacy of Minocycline in Naturally Occurring Nonacute Ehrlichia canis Infection in Dogs Abstract => Background: Minocycline has been used in the treatment of Ehrlichia canis infection in dogs as an alternative to doxycycline, the recommended treatment. However, efficacy of this alternative therapy is unknown. Objective: To assess the efficacy of minocycline in the treatment of natural occurring E. canis infection in dogs. Animals: Ten privately owned dogs of mixed breed positive for E. canis by blood PCR. Methods: Prospective, randomized clinical study. Dogs positive for E. canis by PCR were housed in a kennel environment and randomly allocated to receive doxycycline 10 mg/kg bodyweight PO once daily (“gold standard” control group) or minocycline (extralabel) 10 mg/kg bodyweight PO twice daily (treatment test group) for 28 days. Blood, analyzed by PCR to determine the presence or absence of E. canisDNA, was collected weekly during treatment starting on the first day of treatment and including through day 35, 7 days after the last treatment. Results: In both groups, one dog tested negative after 7 days of treatment. For the doxycycline group, the latest time to a negative PCR test was after 3 weeks of treatment. For the minocycline group, the latest time was on day 28 of treatment. All dogs tested negative 7 days after the end of treatment. Conclusion and Clinical Importance: Minocycline can be an effective alternative to doxycycline for clearing E. canis from the blood in nonacute infections. Authors => S. Jenkins | J.K. Ketzis | J. Dundas | D. Scorpio published => First published: 02 December 2017 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.14842

Title => A Remote Assay for Measuring Canine Platelet Activation and the Inhibitory Effects of Antiplatelet Agents Abstract => Background: Antiplatelet medications are increasingly used in dogs. Remote analysis of platelet activity is challenging, limiting assessment of antiplatelet drug efficacy. Hypothesis/Objectives: To evaluate a method used in humans for stimulation and remote analysis of canine platelet activity. Animals: Forty-five dogs of various ages without a coagulopathy or thrombocytopenia. Six were receiving antiplatelet medication. Methods: Prospective observational study. Platelets were stimulated with combinations of arachidonic acid (AA) and epinephrine (Epi) or adenosine diphosphate (ADP) and the thromboxane A2-mimetic U46619 (U4). PAMFix was added to the blood samples to facilitate delayed analysis of platelet activity. Activity was assessed by flow cytometric measurement of surface P-selectin (CD62P) expression. Results: Canine platelets could be stimulated with both AA/Epi and ADP/U4. The levels of P-selectin were significantly greater than paired, unstimulated samples (P < 0.001). Inhibition of P-selectin expression occurred after this stimulation by adding antiplatelet drugs in vitro. The efficacy of antiplatelet drugs in samples from treated dogs was also measurable ex vivo using this method. Delayed analysis of platelet activity at time points up to 22 days demonstrated excellent correlation between respective mf values at each time point (r2 = 0.92, P < 0.0001). Conclusions and Clinical Importance: This study evaluated a new method to remotely assess canine platelet activity. It shows that PAMFix can be used for this purpose. This provides opportunities to interrogate the inhibitory action of antiplatelet drugs in clinical settings. Authors => M. Dunning | J. May | J. Adamany | S. Heptinstall | S. Fox published => First published: 02 December 2017 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.14845

Title => Metagenomic Investigation of Idiopathic Meningoencephalomyelitis in Dogs Abstract => Background: Meningoencephalomyelitis of unknown origin (MUO) is a common and life-threatening neuroinflammatory disease in dogs. Features of the disease are suggestive of an underlying immune-mediated process, but the association of this disease with a pathogen is still unknown. Hypothesis/Objectives: To search for candidate etiologic agent associated with cases if MUO using next generation metagenomic sequencing. Animals: Twenty-two dogs diagnosed with either MUO (11/22; 10 CSF and 3 brain), or noninflammatory CNS diseases inconsistent with MUO (11/22; 11 CSF and 2 brain) that served as negative controls. Methods: A case control study was performed by identifying MUO and non-MUO cases. Samples were blindly processed and then unblinded for comparative analyses. Inclusion criteria for MUO cases included consistent MRI lesions and inflammatory CSF with a negative PCR panel for infectious agents or histopathologic diagnosis. Dogs with glucocorticoid therapy within 2 weeks of sample collection were excluded. Fresh-frozen cerebrospinal fluid (CSF; 21) and brain (5) samples were collected and RNA and DNA were extracted separately for shotgun metagenomic sequencing. Known positive samples were used as controls to validate our sequencing and analysis pipelines and to establish limits of detection. Sequencing results were analyzed at a nucleotide and protein level for broad comparison to known infectious organisms. Results: No candidate etiologic agents were identified in dogs with MUO. Conclusions and Clinical Importance: These results support but do not prove the hypothesis that MUO is not associated with infectious agents and might be an autoimmune disease. Authors => L.L. Hoon-Hanks | S. McGrath | K.L. Tyler | C. Owen | M.D. Stenglein published => First published: 02 December 2017 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.14877

Title => Bartonella Seroepidemiology in Dogs from North America, 2008–2014 Abstract => Background: Improved understanding of Bartonella species seroepidemiology in dogs may aid clinical decision making and enhance current understanding of naturally occurring arthropod vector transmission of this pathogen. Objectives: To identify demographic groups in which Bartonella exposure may be more likely, describe spatiotemporal variations in Bartonella seroreactivity, and examine co-exposures to other canine vector-borne diseases (CVBD). Animals: A total of 15,451 serology specimens from dogs in North America were submitted to the North Carolina State University, College of Veterinary Medicine Vector Borne Disease Diagnostic Laboratory between January 1, 2008, and December 31, 2014. Methods: Bartonella henselae, Bartonella koehlerae, and Bartonella vinsonii subspecies berkhoffii indirect fluorescent antibody (IFA) serology results, as well as results from a commercial assay kit screening for Dirofilaria immitis antigen and Ehrlichia species, Anaplasma phagocytophilum, and Borrelia burgdorferi antibodies, and Ehrlichia canis, Babesia canis, Babesia gibsoni, and Rickettsia species IFA results were reviewed retrospectively. Results: Overall, 3.26% of dogs were Bartonella spp. seroreactive; B. henselae (2.13%) and B. koehlerae (2.39%) were detected more frequently than B. vinsonii subsp. berkhoffii (1.42%, P < 0.0001). Intact males had higher seroreactivity (5.04%) than neutered males (2.87%, P < 0.0001) or intact or spayed females (3.22%, P = 0.0003). Mixed breed dogs had higher seroreactivity (4.45%) than purebred dogs (3.02%, P = 0.0002). There was no trend in seasonal seroreactivity; geographic patterns supported broad distribution of exposure, and co-exposure with other CVBD was common. Conclusions and Clinical Importance: Bartonella spp. exposure was documented throughout North America and at any time of year. Male intact dogs, mixed breed dogs, and dogs exposed to other CVBD have higher seroreactivity to multiple Bartonella species. Authors => E. Lashnits | M. Correa | B.C. Hegarty | A. Birkenheuer | E.B. Breitschwerdt published => First published: 02 December 2017 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.14890

Title => The Influence of Chronic Kidney Disease on the Structural and Mechanical Properties of Canine Bone Abstract => Background: Chronic kidney disease (CKD) is common in companion animals. Secondary hyperparathyroidism is an inevitable consequence of the disease and may have deleterious effect on the bone; however, the information regarding CKD-associated bone abnormalities in companion animals is scarce. Hypothesis/Objectives: Dogs with CKD have decreased bone quality compared to dogs without CKD. Animals: Nine dogs diagnosed with naturally occurring CKD for at least 6 months and 9 age-matched controls. Methods: Dogs with CKD were enrolled and compared to 9 age-, weight-, and sex-matched control dogs with no evidence of CKD. Samples were assessed using light microscopy, mechanical testing, and microcomputed tomography. Variables evaluated included microstructural features such as number, size, and density of Haversian canals, resorption cavities and osteocytic lacunae, bone mineral density, porosity and Young's modulus. Results: Median lacunae size was significantly smaller in the CKD group compared to the control group (P = 0.001). Resorption cavity density was higher in the CKD compared to the control group (10 [8–14] vs. 7 [4–9]/mm2, respectively, P = 0.001). Overall porosity was significantly (2.3-fold) higher in the CKD compared to the control group. There was no difference in Young's moduli between groups. Conclusions and Clinical Importance: Naturally occurring CKD affects bone quality in dogs, but these changes are relatively mild and likely not to be manifested clinically. The duration of the disease in dogs evaluated here is short compared to cats and human patients, likely accounting for the more subtle changes in dogs compared to other species. Authors => A. Shipov | R. Shahar | N. Sugar | G. Segev published => First published: 30 November 2017 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.14879

Title => Effects of Toceranib Phosphate on the Hypothalamic-Pituitary-Thyroid Axis in Tumor-Bearing Dogs Abstract => Background: Thyroid dysfunction is associated with the use of tyrosine kinase inhibitors (TKI) in people. Hypothesis/Objectives: To determine whether dysfunction in the hypothalamic-pituitary-thyroid axis occurs in dogs receiving the TKI, toceranib phosphate. Animals: Forty-three client-owned dogs with cancer. Methods: Prospective, observational study. Concentrations of total thyroxine (TT4), free thyroxine (FT4), total triiodothyronine (TT3), and thyroid-stimulating hormone (TSH) were evaluated on day 0, 30, and 90. Dogs also were evaluated for the presence of thyroglobulin autoantibodies. Results: The proportion of dogs with low TT4, low FT4, low TT3, high TSH, or primary hypothyroidism (increased TSH and decreased TT4, FT4 or both) did not change over 90 days. Hormone concentrations remained within laboratory reference intervals, but FT4 (P = 0.0032) and TSH (P < 0.0001) changed over time. Mean FT4 was 1.22 ng/dL (95% confidence interval [CI], 1.10–1.34) on day 0 and 1.00 ng/dL (95% CI, 0.86–1.16) on day 90. Mean TSH was 0.17 ng/mL (95% CI, 0.13–0.23) on day 0 and 0.34 ng/mL (95% CI, 0.24–0.48) on day 90. Furthermore, TT4/TT3 ratio also changed over time (P = 0.0086). Mean TT4/TT3 ratio was 2.57 (95% CI, 2.26–2.88) on day 0 and 2.02 on day 90 (95% CI, 1.61–2.44). Thyroglobulin autoantibodies were not detected in any dog. Conclusions and Clinical Importance: Toceranib phosphate can disrupt the hypothalamic-pituitary-thyroid axis in dogs. Periodic evaluation of TT4, FT4, TT3, and TSH should be carried out in dogs receiving long-term treatment with this medication. Authors => K.R. Hume | V.L. Rizzo | J.R. Cawley | C.E. Balkman published => First published: 30 November 2017 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.14882

Title => Comparison of Multiplate, Platelet Function Analyzer-200, and Plateletworks in Healthy Dogs Treated with Aspirin and Clopidogrel Abstract => Background: Platelet function testing may be warranted to assess response to aspirin and clopidogrel. Hypothesis/Objectives: To evaluate the effects of aspirin, clopidogrel, or combination therapy using 3 platelet function tests: Multiplate Analyzer (MP), Platelet Function Analyzer-200 (PFA), and Plateletworks (PW). Animals: Six healthy laboratory Beagles. Methods: Randomized double-blind placebo-controlled study (crossover design). Dogs were given aspirin 1 mg/kg, clopidogrel 2 mg/kg, or combination therapy for 1 week each, with a washout period of 2 weeks. Platelet function was assessed on days 0 and 7 of each phase using MP (adenosine diphosphate [ADP], arachidonic acid [AA], collagen [COL] agonists), PFA (P2Y, COL-ADP [CADP], COL-Epinephrine [CEPI] cartridges), and PW (ADP, AA, COL agonists). Platelet counts were obtained with impedance and optical counters. Results: For MP, mean aggregation was decreased for COL and AA with combination therapy and for ADP with all treatments. For PFA, mean CT was increased for the CEPI cartridge with aspirin; and for the P2Y and CADP cartridges with clopidogrel or combination therapy. More dogs receiving clopidogrel showed an increase in PFA CT using the P2Y than the CADP cartridge. For PW, mean aggregation was decreased for AA with all treatments; for ADP with clopidogrel or combination therapy; and for COL with clopidogrel. The PW results with the 2 hematology counters showed almost perfect agreement. Conclusion and Clinical Importance: All platelet function tests detected treatment effects in some dogs and may have utility for monitoring therapy. Authors => S. Saati | A.C.G. Abrams-Ogg | S.L. Blois | R.D. Wood published => First published: 30 November 2017 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.14886

Title => Differences in Epidural Pathology between Cervical and Thoracolumbar Intervertebral Disk Extrusions in Dogs Abstract => Background: Although the basic pathophysiology is the same in both cervical and thoracolumbar intervertebral disk (IVD) extrusions, there are considerable clinical differences that have only been partially explained. Hypothesis/Objectives: The epidural inflammatory response differs between cervical and thoracolumbar IVD extrusions. Animals: Fifty-five dogs with cervical and 80 dogs with thoracolumbar IVD extrusions. Methods: Clinical data and histopathologic variables were investigated. Associations between severity of epidural inflammation and clinical and pathologic variables, impact of chondrodystrophic phenotype, and localization (cervical versus thoracolumbar) were evaluated statistically. Results: Dogs with cervical IVD extrusion were significantly older (P < 0.001), had less severe and longer duration of neurologic signs (both P < 0.001), were more painful (P = 0.038), and had a better outcome (P = 0.005) than dogs with a thoracolumbar IVD extrusion. On histopathology, cervical epidural material had less severe calcification (P = 0.002) and inflammation (P < 0.001). No significant differences regarding chondrodystrophic phenotype were found. Conclusion and Clinical Importance: There was significantly less intensive inflammatory response in the cervical epidural space. This observation correlated positively with less nucleus pulposus calcification in cervical extrusions indicating biochemical, metabolic, and biomechanical differences between the 2 locations, which remain to be characterized in future studies. Authors => L. Züger | A. Fadda | A. Oevermann | F. Forterre | M. Vandevelde | D. Henke published => First published: 30 November 2017 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.14887

Title => c-Kit Mutation and Localization Status as Response Predictors in Mast Cell Tumors in Dogs Treated with Prednisone and Toceranib or Vinblastine Abstract => Background: KIT inhibitors, such as toceranib (TOC), and vinblastine (VBL) have not been prospectively compared in the treatment of macroscopic mast cell tumors (MCTs). Also, it is unknown whether VBL or TOC is superior for treating MCT without c-kit mutations. Hypothesis/Objectives: To determine the value of KIT genotyping and localization in treatment decisions for dogs with macroscopic MCT. We hypothesized that c-kit mutated MCT would have a better response to TOC than VBL. Animals: Eighty-eight client-owned dogs with macroscopic MCT. Methods: Prospective, randomized trial. Dogs were randomized to TOC (2.75 mg/kg EOD) or VBL (2.5 mg/m2 weekly × 4 then EOW) by KIT localization and c-kit mutation status using an adaptive randomization scheme. Results: Sixty dogs were allocated to TOC and 28 to VBL. Of the dogs receiving TOC, 20% had c-kit mutations, compared to 30% receiving VBL (P = 0.74). Overall response rates were 46% (TOC) and 30% (VBL) (odds ratio = 1.56 [0.62–3.92]; P = 0.28). Median progression-free survival (PFS) for dogs receiving VBL was 78 days (7–1,521) and for TOC 95.5 (14–990); hazard ratio (HR) = 1.34 [0.72–2.50]; P = 0.36. Median overall survival (OS) was 241.5 days (10–1,521) for the VBL group and 159 (20–990) for the TOC group; HR = 0.80 ([0.45–1.41]; P = 0.44). Conclusions and Clinical Importance: Neither PFS nor OS was significantly different between treatment groups. As the proportion of dogs with c-kit mutations was not different between treatment groups in this population of dogs, c-kit mutation status did not predict treatment response. Authors => K.M. Weishaar | E.J. Ehrhart | A.C. Avery | J.B. Charles | R.E. Elmslie | D.M. Vail | C.A. London | C.A. Clifford | J.C. Eickhoff | D.H. Thamm published => First published: 30 November 2017 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.14889

Title => Hepatic Fibrosis in Dogs Abstract => Authors => V.M. Eulenberg | J.A. Lidbury published => First published: 30 November 2017 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.14891

Title => Absence Seizures as a Feature of Juvenile Myoclonic Epilepsy in Rhodesian Ridgeback Dogs Abstract => Authors => F. Wielaender | F.M.K. James | M.A. Cortez | G. Kluger | J.N. Neßler | A. Tipold | H. Lohi | A. Fischer published => First published: 30 November 2017 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.14892

Title => Spectrophotometry and Ultracentrifugation for Measurement of Plasma Lipids in Dogs with Diabetes Mellitus Abstract => Background: There are conflicting reports of plasma lipoprotein lipid content in dogs with diabetes mellitus (DM). Objectives: To determine lipoprotein lipid content of plasma of dogs with DM by spectrophotometry and ultracentrifugation; to compare lipoprotein lipid content in diabetic and healthy dogs; and to quantify apolipoprotein B-100 (ApoB) in dogs with DM. Animals: 22 dogs with DM and 9 healthy dogs. Methods: Cross-sectional study. Triglyceride (TG), total cholesterol (TC), and high-density lipoprotein cholesterol (HDL-C) concentrations were measured by spectrophotometry. Very low-density lipoprotein cholesterol (VLDL-C) and low-density lipoprotein cholesterol (LDL-C) concentrations were calculated after ultracentrifugation. Non-HDL-C cholesterol was calculated by subtracting HDL-C from TC. ApoB was quantified by ELISA. The Mann-Whitney test was used for comparison of median lipoprotein concentrations, and Spearman's correlation was used to assess associations between ApoB and lipoprotein fractions. Results: All values are reported in mg/dL. Median TG (122), TC (343.5), HDL-C, (200), VLDL-C, (27) LDL-C (68), non-HDL-C (114), and ApoB (320) were significantly higher in dogs with DM, compared to healthy dogs (57, 197, 168, 12, 16, 31, and 258, respectively, P-values 0.0079, <0.001, 0.029, 0.011, <0.001, <0.001, 0.025, respectively). A significant association was found between ApoB and LDL-C (Spearman's rho = 0.41, P = 0.022) and between ApoB and non-HDL-C (Spearman's rho = 0.40, P = 0.027). Conclusions and Clinical Importance: Dyslipidemia of dogs with DM is characterized by pronounced increases in LDL-C and non-HDL-C concentrations, although all lipoprotein fractions are significantly increased. Knowledge of specific lipoprotein fraction alterations in dogs with DM can enhance treatment options for diabetic dyslipidemia in dogs. Authors => E.C. Seage | K.J. Drobatz | R.S. Hess published => First published: 29 November 2017 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.14880

Title => Regional Citrate Anticoagulation for Intermittent Hemodialysis in Dogs Abstract => Background: The traditional systemic heparinization used for anticoagulation in extracorporeal therapies may cause fatal complications in animals at risk of bleeding. Hypothesis/Objectives: To develop and validate a protocol of regional citrate anticoagulation (RCA) for intermittent hemodialysis in dogs. Animals: A total of 172 dogs treated with hemodialysis for acute kidney injury. Methods: In vitro titration was performed, adding trisodium citrate and calcium chloride to heparinized canine blood. A tentative protocol was used first in 66 treatments with additional heparinization and subsequently in 518 heparin-free treatments. Safety and adequacy of RCA were assessed based on clinical and laboratory monitoring, dialyzer pressure gradient, treatment completion, and visual scoring of the extracorporeal circuit. Results: Addition of 1 mmol/L citrate to heparinized blood decreased the ionized calcium concentration by 0.23 mmol/L (95% confidence interval [CI], 0.16–0.30) and 1 mmol/L calcium increased it by 0.62 mmol/L (95% CI, 0.45–0.79). Heparin-free treatments were initiated with infusion of trisodium citrate (102 mmol/L) at 2.55 mmol/L blood and calcium chloride (340 mmol/L) at 0.85 mmol/L. Citrate and calcium administrations were adjusted in 27 and 34% of the treatments, respectively. Overall, anticoagulation was satisfactory in 92% of the treatments, with expected azotemia reduction in 95% (urea) and 86% (creatinine), stable dialyzer pressure gradient in 82%, and clean extracorporeal circuits in 92% of the treatments. Eighteen treatments (3.5%) were discontinued prematurely, 9 because of clotting and 9 for reasons unrelated to the RCA procedure. Conclusions and Clinical Importance: Regional citrate anticoagulation allows safe and efficient heparin-free hemodialysis in dogs at risk of bleeding. Authors => T. Francey | A. Schweighauser published => First published: 24 November 2017 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.14867

Title => Contrast-Enhanced Ultrasound Examination for the Assessment of Renal Perfusion in Cats with Chronic Kidney Disease Abstract => Background: Contrast-enhanced ultrasound examination (CEUS) is a functional imaging technique allowing noninvasive assessment of tissue perfusion. Studies in humans show that the technique holds great potential to be used in the diagnosis of chronic kidney disease (CKD). However, data in veterinary medicine are currently lacking. Objectives: To evaluate renal perfusion using CEUS in cats with CKD. Animals: Fourteen client-owned cats with CKD and 43 healthy control cats. Methods: Prospective case-controlled clinical trial using CEUS to evaluate renal perfusion in cats with CKD compared to healthy control cats. Time-intensity curves were created, and perfusion parameters were calculated using off-line software. A linear mixed model was used to examine differences between perfusion parameters of cats with CKD and healthy cats. Results: In cats with CKD, longer time to peak and shorter mean transit times were observed for the renal cortex. In contrast, a shorter time to peak and rise time were seen for the renal medulla. The findings for the renal cortex indicate decreased blood velocity and shorter total duration of enhancement, likely caused by increased vascular resistance in CKD. Increased blood velocity in the renal medulla has not been described before and may be because of a different response to regulatory factors in cortex and medulla. Conclusions and Clinical Importance: Contrast-enhanced ultrasound examination was capable of detecting perfusion changes in cats with CKD. Further research is warranted to assess the diagnostic capabilities of CEUS in early stage of the disease process. Authors => E. Stock | D. Paepe | S. Daminet | E. Vandermeulen | L. Duchateau | J.H. Saunders | K. Vanderperren published => First published: 24 November 2017 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.14869

Title => 24-Hour Kinetics of Cardiac Troponin-T Using a “High-Sensitivity” Assay in Thoroughbred Chuckwagon Racing Geldings after Race and Associated Clinical Sampling Guidelines Abstract => Background: A “high-sensitivity” cardiac troponin-T (hscTnT) assay recently has been validated for use in horses and is a specific biomarker of myocardial damage. Postexercise release kinetics of cTnT utilizing the hscTnT assay have yet to be established in horses. Objectives: To determine: (1) cTnT release kinetics in racing Thoroughbreds after a high-intensity 5/8th mile Chuckwagon race; (2) the effects of age on pre- and postrace cTnT concentrations; and (3) sampling guidelines for clinicians evaluating horses presenting after exercise. Animals: Samples were obtained from 38 Thoroughbred geldings aged 5–16 years before racing and immediately, 2, 3, 4, 6, 12, and 24 hour postrace. Methods: Prospective, observational study with convenience sampling. A fifth-generation hscTnT assay was used for plasma sample analysis, and concentrations were compared at all time-points. Correlations were determined between cTnT concentrations and age. Biochemistry analysis was performed to assess rhabdomyolysis, renal failure, and exercise-induced dehydration. Results: All horses with measureable cTnT concentrations had significant postexercise increases in cTnT with a median peak (8.0 ng/L) at 3-hour postrace. All horses had peak postexercise cTnT concentrations 2- to 6-hour postrace ≤ the 99th percentile upper reference limit of 23.2 ng/L, after which all cTnT concentrations decreased until returning to baseline by 12–24 hours. There was no correlation over time between cTnT concentrations and age. Conclusions and Clinical Importance: In racing Thoroughbreds completing short-duration, high-intensity Chuckwagon races, cTnT concentrations are expected to be increased 2- to 6-hour postrace and to decrease by 12–24 hours while remaining ≤23.2 ng/L throughout. This study contributes to establishing guidelines for clinical use of the hscTnT assay in exercising horses. Authors => E. Shields | I. Seiden-Long | S. Massie | R. Leguillette published => First published: 24 November 2017 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.14870

Title => In vitro Inhibition of Canine Complement-Mediated Hemolysis Abstract => Background: Immune-mediated hemolytic anemia (IMHA) is the most common hematologic immune-mediated disease in dogs. Complement fixation on erythrocytes causes hemolysis. Complement inhibition decreases hemolysis in people with the hemolytic disease and also may prove effective in treating IMHA in dogs. Hypothesis/Objectives: Evaluate the in vitro efficacy of 2 complement inhibitors used in humans against canine complement. Methods: The inhibitory activity of the C3-inhibitor compstatin and recombinant human C1-esterase inhibitor (C1-INH) was evaluated using an in vitro hemolytic assay and spectrophotometric measurement of released hemoglobin. Dose-response curves for each inhibitor were generated. Results: Compstatin decreased approximately 50% of canine complement-mediated hemolysis in initial experiments. This inhibition largely was lost when a new lot of drug was purchased. C1-INH showed a dose-dependent inhibition. The highest concentration of C1-INH tested (500 μg/mL) decreased >80% of canine complement-mediated hemolysis, and the lowest concentration tested (31.25 μg/mL) decreased hemolysis >60%. Conclusions and Clinical Importance: Human C1-INH is a robust inhibitor of canine complement-mediated hemolysis, whereas compstatin was minimally and variably effective. Human C1-INH may substantially decrease complement-mediated hemolysis in dogs with IMHA and warrants further investigation. Authors => D.M. Hernandez | R. Goggs | E. Behling-Kelly published => First published: 24 November 2017 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.14871

Title => Comparison of Single, Averaged, and Pooled Urine Protein:Creatinine Ratios in Proteinuric Dogs Undergoing Medical Treatment Abstract => Background: Monitoring urine protein:creatinine ratios (UPC) in dogs with protein-losing nephropathy (PLN) is challenging because of day-to-day variation in UPC results. Hypothesis/Objectives: Determine whether single, averaged, or pooled samples from PLN dogs receiving medical treatment yield comparable UPCs, regardless of degree of proteinuria. Animals: Twenty-five client-owned PLN dogs receiving medical treatment. Methods: UPC ratios were prospectively measured in each dog utilizing 3 methods: single in-hospital sample (day 3), average sample (days 1–3), and pooled sample (equal pooling of urine from days 1–3). Bland-Altman analysis was performed to evaluate agreement between methods for all dogs, as well as in subgroups of dogs (UPC ≤4 or UPC >4). Results: For all dogs, Bland-Altman log-transformed 95% limits of agreement were −0.07–0.18 (single versus pooled UPC), −0.06–0.16 (single versus average UPC), and −0.06–0.04 (pooled versus average UPC). For dogs with UPC ≤4, Bland-Altman 95% limits of agreement were −0.42–0.82 (single versus pooled UPC), −0.38–0.76 (single versus average UPC), and −0.27–0.25 (pooled versus average UPC). For dogs with UPC >4, Bland-Altman 95% limits of agreement were −0.17–2.4 (single versus pooled UPC), −0.40–2.2 (single versus average UPC), and −0.85–0.43 (pooled versus average UPC). Conclusions and Clinical Importance: UPC ratios from all methods were comparable in PLN dogs receiving medical treatment. In PLN dogs with UPC >4, more variability between methods exists likely because of higher in-hospital results, but whether this finding is clinically relevant is unknown. Authors => S. Shropshire | J. Quimby | R. Cerda published => First published: 24 November 2017 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.14872

Title => Investigation of Known Genetic Mutations of Arabian Horses in Egyptian Arabian Foals with Juvenile Idiopathic Epilepsy Abstract => Background: The carrier status of lavender foal syndrome (LFS), cerebellar abiotrophy (CA), severe combined immunodeficiency (SCID), and occipitoatlantoaxial malformation (OAAM1) in foals with juvenile idiopathic epilepsy (JIE) is unknown. Hypothesis/Objectives: To determine the carrier status of LFS, CA, SCID, and OAAM1 in foals with JIE. Animals: Ten foals with JIE. Materials and Methods: Archived DNA samples were tested for known genetic mutations causing LFS, CA, SCID, and OAAM1. The inclusion criteria consisted of having been diagnosed with JIE by ruling out other causes of seizures in foals and supported by electroencephalographic examination. Results: Ten Egyptian Arabian horses (5 females and 5 males) were phenotyped as foals with JIE by electroencephalography (EEG). All foals were negative for the genetic mutations that cause LFS, CA, SCID, and OAAM1 except for 1 foal that was a carrier of CA. Conclusions and Clinical Importance: Juvenile idiopathic epilepsy of Egyptian Arabian foals and LFS appear to be phenotypically and genetically distinct disorders. There was no apparent association between JIE and LFS, CA, SCID, and OAAM1. Authors => M. Aleman | C.J. Finno | K. Weich | M.C.T. Penedo published => First published: 24 November 2017 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.14873

Title => The Gastrointestinal Microbiome: A Review Abstract => Authors => P.C. Barko | M.A. McMichael | K.S. Swanson | D.A. Williams published => First published: 24 November 2017 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.14875

Title => A Double-blind, Placebo-controlled, Multicenter, Prospective, Randomized Study of Beraprost Sodium Treatment for Cats with Chronic Kidney Disease Abstract => Background: Chronic kidney disease (CKD) is a common progressive and irreversible disease in cats. The efficacy and safety of beraprost sodium (BPS) in cats with CKD have not been evaluated. Hypothesis/Objectives: To evaluate the efficacy and safety of BPS in the treatment of cats with CKD, as compared to placebo. Animals: Seventy-four client-owned cats with naturally occurring CKD. Methods: Double-blind, placebo-controlled, multicenter, prospective, randomized trial. The cats received BPS (55 μg/cat) or a placebo PO q12 h for 180 days. The primary endpoint was prospectively defined as a change in the serum creatinine (sCr), serum phosphorus-to-calcium ratio or urine specific gravity (USG). Results: The sCr increased significantly (P = 0.0030) in the placebo group (mean ± SD: 2.8 ± 0.7 to 3.2 ± 1.3 mg/dL) but not in the BPS group (2.4 ± 0.7 to 2.5 ± 0.7 mg/dL). The difference between the groups at day 180 was significant (0.8 mg/dL, 95% CI: 0.2 to 1.3 mg/dL, P = 0.0071). The serum phosphorus-to-calcium ratio was significantly (P = 0.0037) increased in the placebo group (0.46 ± 0.10 to 0.52 ± 0.21 mg/dL) but not in the BPS group (0.50 ± 0.08 to 0.51 ± 0.11 mg/dL). There was no significant change in the USG in either group. An adverse event judged as being treatment-related included vomiting that occurred in 1 case in the placebo group. No clinically relevant change was observed in the CBC and other blood chemistry tests. Conclusions and Clinical Importance: Beraprost sodium treatment was well tolerated and safe in cats with CKD. BPS inhibited the reduction in renal filtration function as measured by sCr increase. Authors => M. Takenaka | A. Iio | R. Sato | T. Sakamoto | H. Kurumatani | the KT-140 Clinical Study Group published => First published: 13 November 2017 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.14839

Title => Immune Function in Critically Ill Dogs Abstract => Background: People with critical illness (CI) commonly develop various forms of immune dysfunction, however, there is limited information concerning immune dysfunction in dogs with CI. Hypothesis: The immune response in CI dogs differs from that of healthy dogs. Animals: Immunologic variables were compared between 14 dogs with CI, defined as APPLEfast score of >20 points, admitted to the University of Missouri Veterinary Health Center Small Animal Clinic Intensive Care Unit and healthy controls (n = 15). Methods: Cohort study evaluating constitutive and lipopolysaccharide (LPS)-stimulated TNF-α, IL-6, and IL-10 production, phagocytosis of opsonized E. coli and respiratory burst capacity after opsonized E. coli or phorbol 12-myristate 13-acetate (PMA) stimulation, peripheral blood lymphocyte phenotype, and monocyte expressions of HLA-DR and TLR-4. Results: Lipopolysaccharide-stimulated leukocyte TNF-α (median, Q1, Q3; CI, 49, 49, 120; control, 655, 446, 1174 pg/mL; P = < 0.001), IL-6 (median, Q1, Q3; CI, 49, 49, 64; control, 100, 49, 166 pg/mL; P = 0.029), and IL-10 (CI, 49, 49, 56; control, 96, 49, 203 pg/mL; P = 0.014) production and both E. coli (median, Q1, Q3; CI, 60.5, 43, 88.5; control, 86.6, 81, 89.2%; P = 0.047) and PMA (CI, 40, 11.7, 70; control, 93, 83, 97.6%; P = < 0.001)-stimulated respiratory burst capacity significantly decreased in CI dogs. Percentage of monocytes expressing TLR-4 greater in the CI dogs (median, Q1, Q3; CI, 46.9, 24.3, 64.2; control, 16.4, 9.4, 26.2%; P = 0.005). Conclusion: These findings suggest dogs with CI develop immune system alterations that result in reduced respiratory burst function and cytokine production despite upregulation of TLR-4. Authors => D. Hoffman | J. Amorim | A. DeClue published => First published: 13 November 2017 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.14857