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Title => Evaluation of 3 Serological Tests for Early Detection Of Leptospira-specific Antibodies in Experimentally Infected Dogs Abstract => Background: Leptospirosis in dogs is a disease of global importance. Early detection and appropriate therapeutic intervention are necessary to resolve infection and prevent zoonotic transmission. However, its diagnosis is hindered by nonspecific clinical signs and lack of rapid diagnostic tests of early infection. Recently, 2 rapid point-of-care tests (WITNESS Lepto [WITNESS Lepto, Zoetis LLC, Kalamazoo, MI, USA] and SNAP Lepto [SNAP Lepto, IDEXX Laboratories, Westbrook, ME, USA]) for detection of Leptospira-specific antibodies in canine sera were developed. Hypothesis: Immunoglobulin M-based WITNESS Lepto containing multiple detection antigens can detect Leptospira-specific antibodies to common leptospiral serovars earlier in the course of infection as compared to microscopic agglutination test (MAT) and SNAP Lepto. Animals: Four groups of 8 6- to 8-month-old male Beagle dogs were used. Methods: Thirty-two healthy seronegative dogs were inoculated experimentally with serovars Canicola, Grippotyphosa, Icterohaemorrhagiae, and Pomona (8 dogs/serovar). Acute-phase sera were collected at regular intervals and monitored for Leptospira-specific antibodies by WITNESS Lepto, MAT, and SNAP Lepto. Results: Seroconversion was detected in all dogs by day 10 by WITNESS Lepto and in 30 of 32 dogs by day 14 by MAT. The SNAP Lepto test detected seroconversion in 3 dogs during the 2 weeks postchallenge. Conclusions: Immunoglobulin M-based WITNESS Lepto detected immune responses specific to multiple leptospiral serovars early in the course of infection and identified seroconversion in all animals earlier than did the gold standard MAT. The SNAP Lepto test displayed considerably lower and inconsistent performance during the study period. At the point-of-care, WITNESS Lepto should be the test of choice for rapid and reliable screening of acutely ill dogs suspected to have leptospirosis. Authors => J. Lizer | S. Velineni | A. Weber | M. Krecic | P. Meeus published => First published: 13 November 2017 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.14865

Title => Cholangitis and Cholangiohepatitis in Dogs: A Descriptive Study of 54 Cases Based on Histopathologic Diagnosis (2004–2014) Abstract => Background: Cholangitis in dogs appears to be more common than previously thought, but understanding of the disease remains incomplete. Objective: To describe a population of dogs with cholangitis or cholangiohepatitis. Animals: Fifty-four client-owned dogs with cholangitis or cholangiohepatitis. Methods: Medical records of dogs with cholangitis or cholangiohepatitis confirmed by histopathology between January 2004 and December 2014 were identified using a computer-based search and retrospectively reviewed. Results: Clinical signs included vomiting (72.2%), lethargy (70.4%), and inappetence (64.8%). Most dogs (49/50) had increased liver enzyme activities, hyperbilirubinemia (32/50), and hypercholesterolemia (24/43). Ultrasonographic abnormalities of the hepatobiliary system were seen in 84% of cases. On histopathology, 53 of 54 affected dogs had neutrophilic cholangitis (NC) or cholangiohepatitis, whereas 1 dog had lymphocytic cholangitis. Most cases (42/54) were chronic. Evidence of concurrent biliary disease (46.2%) and biliary tract obstruction (42.6%) was common. Seventeen of 36 biliary and 11 of 25 liver cultures were positive for bacterial growth; Escherichia coli and Enterococcus spp. were most common. Median patient survival was 671 days (95% confidence interval [CI]: 114–1,426). On Cox regression, dogs that did not have a cholecystectomy performed had a 2.1 greater hazard for death (P = 0.037; 95% CI: 1.0–4.3) compared to cholecystectomized dogs. Dogs >13 years old had a 5.0 greater hazard for death (P = 0.001; 95% CI: 1.9–13.2) compared to younger dogs. Conclusions and Clinical Significance: Chronic NC or cholangiohepatitis was most common. Cholecystitis and biliary tract obstruction often occurred in conjunction with cholangitis. Cholecystectomized dogs had decreased risk of death; thus, cholecystectomy may improve patient outcome. Authors => J.L. Harrison | B.J. Turek | D.C. Brown | C. Bradley | J. Callahan Clark published => First published: 13 November 2017 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.14866

Title => Efficacy of Radiation Therapy for the Treatment of Sialocele in Dogs Abstract => Background: Sialocele is a collection of saliva that has leaked from a damaged salivary gland or duct and is surrounded by granulation tissue. Surgery is the recognized first-line treatment. Recurrence rate after surgery is 5–14%. Salivary gland tissue is very sensitive to radiation therapy (RT). Hypothesis/Objectives: Radiation therapy will be useful for the treatment of sialocele. The aims were to characterize response rate and clinical course of dogs with sialocele treated with RT and to determine a starting dose for clinical use. Animals: Eleven dogs with sialocele. Methods: Retrospective study of response and outcome after RT. Results: All dogs had cervical sialocele. Seven dogs (63.6%) were treated with 3 weekly fractions of 4 Gray (Gy); (total dose, 12 Gy). Three dogs (27.3%) received 4 fractions of 4 Gy (16 Gy) and 1 dog received 5 fractions of 4 Gy (20 Gy) on a Monday-Wednesday-Friday schedule. Six dogs (54%) achieved a complete response (CR), and 5 dogs (45%) achieved a partial response (PR). Three dogs had progression of their sialocele 2, 3, and 9 months after RT; all three had received 12 Gy initially and 2 received 2 additional fractions of 4 Gy (cumulative total dose, 20 Gy) and subsequently achieved remission for >2 years. Conclusions and Clinical Importance: Radiation therapy is useful for the treatment of recurrent sialocele refractory to surgical management and a minimum total dose of 16 or 20 Gy in 4 Gy fractions appears effective. Authors => V.J. Poirier | S. Mayer-Stankeová | J. Buchholz | D.M. Vail | B. Kaser Hotz published => First published: 13 November 2017 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.14868

Title => Ischemic Optic Neuropathy in a Dog with Acute Bilateral Blindness and Primary Systemic Hypertension Abstract => Authors => L. Mari | R. Stavinohova | E. Dominguez | J. Premont | J. Oliver | L. De Risio published => First published: 12 November 2017 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.14878

Title => STAT3 Expression and Activity are Up-Regulated in Diffuse Large B Cell Lymphoma of Dogs Abstract => Background: The Janus Kinase (JAK) and Signal Transducer and Activator of Transcription (STAT) pathways play important roles in the pathogenesis of diffuse large B cell lymphoma (DLBCL) in humans, and up-regulated STAT3 expression and activity are associated with worse clinical outcome in humans. No studies have evaluated the JAK-STAT signaling pathway in DLBCL of dogs. Hypothesis: STAT3 pathway is deregulated in DLBCL in dogs. We aim to assess the expression, activation, and cellular localization of STAT3 and mitogen-activated protein kinase ERK1/2 in DLBCL of dogs. Animals: Forty-three client-owned dogs diagnosed with DLBCL by histopathology Methods: Retrospective analysis of DLBCL in dogs, including patient characteristics and treatment, immunohistochemistry, and protein expressions by Western blot. Results: A higher percentage of STAT3 and p-STAT3 immunolabelled cells were observed in DLBCL of dogs when compared to normal canine lymph nodes. In STAT3 immunolabelled cells, STAT3 has higher nuclear expression in lymphoma samples than in normal or reactive lymph nodes. In addition to up-regulated STAT3 expression and activation, mitogen-activated kinase ERK1/2 activation is up-regulated in DLBCL of dogs. Conclusion and Clinical Importance: Compared with the normal canine lymph node, DLBCL of dogs has up-regulated STAT3 pathway. Our results support future investigation of JAK inhibitors in the treatment of DLBCL in dogs. Authors => A.L.F.V. Assumpção | P.C. Jark | C.C. Hong | Z. Lu | H.M. Ruetten | C.M. Heaton | M.E. Pinkerton | X. Pan published => First published: 09 November 2017 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.14860

Title => Pharmacokinetics of Single Oral Dose Extended-Release Levetiracetam in Healthy Cats Abstract => Background: Repeated PO dosing of anti-epileptic drugs may contribute to poor compliance in treated cats. Intermediate-release levetiracetam has been used safely in cats, but must be given q8h to maintain serum concentrations in the therapeutic interval for humans (5–45 μg/mL). Approved extended-release levetiracetam (XRL) for human use may require less frequent dosing, but the large dosing unit has limited its use in cats. Hypotheses: In healthy cats, serum levetiracetam concentration will remain above 5 μg/mL for at least 24 hours after administration of a single dose of XRL PO and will be well tolerated. Animals: 7 healthy cats. Methods: Extended-release levetiracetam (500 mg) was administered PO. Blood was collected and neurologic examination findings recorded at scheduled times over 30 hours. Serum levetiracetam concentration was quantitated by an immunoassay validated in cats. Data were subjected to noncompartmental analysis. Descriptive statistics were reported. Results: The median dosage of 86.2 mg/kg, (range, 80–94.3) achieved a mean maximum concentration (Cmax) of 89.8 ± 25.8 μg/mL at 4.9 ±1.57 hours. Serum levetiracetam was >5 μg/mL in all cats by 90 minutes. Mean concentrations were 43.7 ± 18.4 and 4.9 ± 3.4 μg/mL at 12 and 24 hours, respectively. The half-life was 4.1 ± 1.0 hours. The drug was well tolerated. Conclusions and Clinical Importance: A single 500 mg PO dose of XRL safely maintained serum levetiracetam concentration ≥5 μg/mL in healthy cats for at least 21 hours. Clinical efficacy studies in epileptic cats receiving XRL are indicated; however, monitoring should be implemented for individual cats. Authors => L. Barnard | H. Barnes Heller | D.M. Boothe published => First published: 08 November 2017 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.14863

Title => Quality Control of Compounded Crystalloid Fluids for Intravenous Delivery to Horses Abstract => Background: Periodic lack of availability and high cost of commercially produced isotonic fluids for intravenous (IV) use in horses have increasingly led to use of home-made or commercially compound fluids by veterinarians. Data regarding the quality control and safety of compounded fluids would be of benefit to equine veterinarians. Objectives: To compare electrolyte concentrations, sterility, and endotoxin contamination of commercially available fluids to 2 forms of compounded isotonic crystalloid fluids intended for IV use in horses. Methods: Prospective study. Two methods of preparing compounded crystalloids formulated to replicate commercial Plasma-Lyte A (Abbott, Chicago, IL) were compared. One formulation was prepared by a hand-mixed method involving chlorinated drinking water commonly employed by equine practitioners, and the other was prepared by means of ingredients obtained from a commercial compounding pharmacy. The variables for comparison were electrolyte concentrations, sterility, and presence of endotoxin contamination. Results: Electrolyte concentrations were consistent within each product but different between types of fluids (P < 0.0001). Hand-mixed fluids had significantly more bacterial contamination compared to commercial Plasma-Lyte A (P = 0.0014). One of the hand-mixed fluid samples had detectable endotoxin contamination. Conclusions and Clinical Importance: Chlorinated drinking water is not an acceptable source of water to compound isotonic fluids for IV administration. Equine practitioners should be aware of this risk and obtain the informed consent of their clients. Authors => C.B. Magnusson | K.P. Poulsen | J.A. Budde | F.A. Hartmann | N.A. Aulik | S.M. Raabis | A.S.D. Moreira | B.J. Darien | S.F. Peek published => First published: 08 November 2017 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.14864

Title => Research Communications of the 27th ECVIM-CA Congress: Intercontinental, Saint Julian's, Malta, 14th to 16th September 2017 Abstract => None Abstract Authors => published => First published: 07 November 2017 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.14858

Title => Canine GM2-Gangliosidosis Sandhoff Disease Associated with a 3-Base Pair Deletion in the HEXB Gene Abstract => Background: GM2-gangliosidosis is a fatal neurodegenerative lysosomal storage disease (LSD) caused by deficiency of either β-hexosaminidase A (Hex-A) and β-hexosaminidase B (Hex-B) together, or the GM2 activator protein. Clinical signs can be variable and are not pathognomonic for the specific, causal deficiency. Objectives: To characterize the phenotype and genotype of GM2-gangliosidosis disease in an affected dog. Animals: One affected Shiba Inu and a clinically healthy dog. Methods: Clinical and neurologic evaluation, brain magnetic resonance imaging (MRI), assays of lysosomal enzyme activities, and sequencing of all coding regions of HEXA, HEXB, and GM2A genes. Results: A 14-month-old, female Shiba Inu presented with clinical signs resembling GM2-gangliosidosis in humans and GM1-gangliosidosis in the Shiba Inu. Magnetic resonance imaging (MRI) of the dog's brain indicated neurodegenerative disease, and evaluation of cerebrospinal fluid (CSF) identified storage granules in leukocytes. Lysosomal enzyme assays of plasma and leukocytes showed deficiencies of Hex-A and Hex-B activities in both tissues. Genetic analysis identified a homozygous, 3-base pair deletion in the HEXB gene (c.618-620delCCT). Conclusions and Clinical Importance: Clinical, biochemical, and molecular features are characterized in a Shiba Inu with GM2-gangliosidosis. The deletion of 3 adjacent base pairs in HEXB predicts the loss of a leucine residue at amino acid position 207 (p.Leu207del) supporting the hypothesis that GM2-gangliosidosis seen in this dog is the Sandhoff type. Because GM1-gangliosidosis also exists in this breed with almost identical clinical signs, genetic testing for both GM1- and GM2-gangliosidosis should be considered to make a definitive diagnosis. Authors => P. Wang | P.S. Henthorn | E. Galban | G. Lin | T. Takedai | M. Casal published => First published: 06 November 2017 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.14862

Title => Successful Treatment of Disseminated Nocardiosis Caused by Nocardia veterana in a Dog Abstract => Authors => S. Yaemsiri | J.E. Sykes published => First published: 04 November 2017 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.14855

Title => Questionnaire-based Analysis of Owner-reported Scratching and Pain Signs in Cavalier King Charles Spaniels Screened for Chiari-like Malformation and Syringomyelia Abstract => Background: Chiari-like malformation (CM) and syringomyelia (SM) cause a pain syndrome in Cavalier King Charles spaniels (CKCS). Clinical signs are not consistently apparent on neurologic examination, and owner reporting of signs provides vital clinical history. However, owner questionnaires for this disease are not well developed. Objectives: To develop a tool to capture owner-reported clinical signs for use in clinical trials and to compare owner-reported signs with the presence of pain on neurologic examination and SM on magnetic resonance imaging (MRI). Animals: Fifty client-owned CKCS. Methods: Owners completed a questionnaire and pain/scratch map. Each dog underwent a neurologic examination and craniocervical magnetic resonance imaging (MRI). Questionnaire responses were developed into scores, area of shading for pain/scratch maps was measured, and consistency of responses between these tools was assessed. Owner-reported findings were compared with neurologic examination findings and presence and severity of SM on MRI. Results: Thirty-three dogs were symptomatic and 17 asymptomatic; 30 had SM. The most common sign of pain was crying out when lifted (n = 11). Extent of shaded areas on maps positively correlated with questionnaire scores for pain (r2 = 0.213, P = 0.006) and scratch (r2 = 0.104, P = 0.089). Owner-reported findings were not significantly associated with presence or severity of SM or neurologic examination findings. Owner-reported lateralization of signs was significantly associated with SM lateralization (P < 0.0001). Conclusions: The questionnaire and maps may be useful for clinical trials. Lack of association of owner-reported signs with SM highlights our lack of understanding of the pathophysiology of pain in this disease. Authors => C.R. Sparks | S. Cerda-Gonzalez | E.H. Griffith | B.D.X. Lascelles | N.J. Olby published => First published: 04 November 2017 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.14856

Title => A 6-bp Deletion Variant in a Novel Canine Glutathione-S-Transferase Gene (GSTT5) Leads to Loss of Enzyme Function Abstract => Objectives: Glutathione-S-transferases (GSTs) detoxify reactive xenobiotics, and defective GST gene polymorphisms increase cancer risk in humans. A low activity GST-theta variant was previously found in research beagles. The purpose of our study was to determine the molecular basis for this phenotype and its allele frequency in pet dogs. Methods: Banked livers from 45 dogs of various breeds were screened for low GST-theta activity by the substrate 1,2-dichloro-4-nitrobenzene (DCNB), and were genotyped for variants in a novel canine GST gene, GSTT5. Whole-genome sequences from 266 dogs were genotyped at one discovered variant GSTT5 locus. Results: Canine livers ranged 190-fold in GST-theta activities, and a GSTT5 exon coding variant 385_390delGACCAG (Asp129_Gln130del) was significantly associated with low activity (P < 0.0001) and a marked decrease in hepatic protein expression (P = 0.0026). Recombinant expression of variant GSTT5 led to a 92% decrease in Vmax for DCNB (P = 0.0095). The minor allele frequency (MAF) for 385_390delGACCAG was 0.144 in 45 dog livers, but was significantly higher in beagles (0.444) versus nonbeagles (0.007; P = 0.0004). The homozygous genotype was significantly over-represented in Pembroke Welsh corgis (P < 0.0001) based on available whole-genome sequence data. Conclusions: An Asp129_Gln130del variant in canine GSTT5 is responsible for marked loss of GST-theta enzyme activity. This variant is significantly over-represented in purpose-bred laboratory beagles and in Pembroke Welsh corgis. Additional work will determine the prevalence of this variant among other purebred dogs, and will establish the substrate range of this polymorphic canine enzyme with respect to common environmental carcinogens. Authors => S. Craft | J. Ekena | J. Sacco | K. Luethcke | L. Trepanier published => First published: 03 November 2017 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.14861

Title => Clinical Evaluation of Tavocept to Decrease Diuresis Time and Volume in Dogs with Bladder Cancer Receiving Cisplatin Abstract => Background: Transitional cell carcinoma is the most common bladder cancer of dogs. Cisplatin combined with piroxicam provides superior response rates, but unacceptable rates of nephrotoxicity. Tavocept is a chemoprotectant that has mitigated cisplatin toxicity and decreased the required infusion/diuresis volume in clinical trials in humans. Hypothesis/Objectives: We hypothesized that Tavocept would decrease diuresis volume and time and facilitate safe administration of a cisplatin/piroxicam protocol to dogs with bladder cancer. Secondary objectives were to compare response rate and survival times to an historical comparator group treated without Tavocept. Animals: Fourteen client-owned dogs were prospectively enrolled. Methods: Tumor volume was measured by computed tomography at days 0, 42, and 84. Dogs received combination Tavocept/cisplatin with a shortened diuresis protocol. A total of 4 doses was planned, with concurrent administration of piroxicam. Serial biochemical analyses were evaluated for azotemia. Results: A 90-minute infusion/diuresis time was used for all dogs. Three dogs (21%) had concurrent increases in serum creatinine (>2.0 mg/dL) and BUN (>42 mg/dL) concentrations; 2 of these dogs were isosthenuric. This frequency of nephrotoxicity is significantly less (P = 0.0406) than that of an historical control group treated without Tavocept. Overall response rate was 27%. Median survival time was comparable to historical controls (253 vs. 246 days). Conclusions and Clinical Importance: Tavocept decreased the required diuresis time with cisplatin from > 6 hours to 90 minutes, while also decreasing occurrence of azotemia. Survival time was comparable, but the response rate was inferior to an historical comparator group. Further evaluation in other tumors susceptible to platinum agents is warranted. Authors => C.J. Henry | B.K. Flesner | S.A. Bechtel | J.N. Bryan | D.J. Tate | K.A. Selting | J.C. Lattimer | M.E. Bryan | L. Grubb | F. Hausheer published => First published: 27 October 2017 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.14848

Title => Measurement Variation and Repeatability of Echocardiographic Variables Used to Estimate Pulmonary Artery Pressure in Dogs Abstract => Background: Pulmonary hypertension (PH) is an important clinical entity in dogs. Pulmonary hypertension is generally identified based on echocardiographic findings, but measurement variation of the variables most often used in this context has not been reported. Objective: To define measurement variation of echocardiographic variables that are used to estimate pulmonary artery pressure. Animals: Four dogs with subclinical tricuspid valve regurgitation were selected from a hospital population. Methods: Prospective descriptive study - dogs were subject to repeated echocardiographic examination by 2 operators. Each dog was echocardiographically examined 12 times, once by each operator during mornings and afternoons of 3 nonconsecutive days. Measurement variation was defined by coefficients of variation and by mean square errors (MSE) from ANOVA models. Repeatability coefficients (RC) were calculated from MSE. Results: Of 50 within-day, between-day, and interoperator coefficients of variation (CVs), 37 were less than 10% and 46 were less than 15%. The range of peak velocity of tricuspid valve regurgitation (VTR) VTR was 1.87–3.34 m/s. Analysis of variance revealed a significant effect (P < 0.05) of operator for 7 of 10 measurements. Within-operator/between-day/within-subject and between-operator/between-day/within-subject RCs of VTR were, respectively, 0.3 and 0.6 m/s. Conclusions and Clinical Importance: With regard to repeatability, VTR is superior to other methods used for echocardiographic estimation of systolic pulmonary artery pressure. When TR is absent, the acceleration time of pulmonary ejection and the acceleration-to-ejection time ratio are alternative measures. A change in VTR exceeding 0.3 m/s might be outside the range of expected within-operator variation. Authors => J.A. Abbott | J.M. Gentile-Solomon published => First published: 14 October 2017 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.14846

Title => Glutathione Peroxidase Activity, Plasma Total Antioxidant Capacity, and Urinary F2- Isoprostanes as Markers of Oxidative Stress in Anemic Dogs Abstract => Background: Oxidative stress plays a role in the pathophysiology of several diseases and has been documented as a contributor to disease in both the human and veterinary literature. One at-risk cell is the erythrocyte, however, the role of oxidative stress in anemia in dogs has not been widely investigated. Hypothesis/Objective: Anemic dogs will have an alteration in the activity of glutathione peroxidase (GPx), a decrease in of total antioxidant capacity (TAC), and an increased concentration of urinary 15-F2-isoprostanes (F2-IsoP) when compared to healthy dogs. Animals: 40 client-owned dogs with anemia (PCV <30%) age-matched to 40 client-owned healthy control dogs. Methods: Prospective, cross-sectional study. Whole blood GPx activity, plasma TAC, and urinary F2-isoprostane concentrations were evaluated in each dog and compared between groups. Results: Anemic dogs had significantly lower GPx activity (43.1 × 103 +/- 1.6 × 103 U/L) than did dogs in the control group (75.8 × 103 +/- 2.0 × 103 U/L; P < 0.0001). The GPx activity in dogs with hemolysis (103 +/- 0.8 × 103 U/L) was not significantly different (P = 0.57) than in dogs with nonhemolytic anemia (43.5 × 103 +/- 1.1 × 103 U/L). The TAC concentrations (P = 0.15) and urinary F2-isoprostanes (P = 0.73) did not significantly differ between groups. Conclusions and Clinical Importance: Glutathione peroxidase activity was significantly decreased in anemic dogs indicating oxidative stress. Additional studies are warranted to determine if antioxidant supplementation would improve survival and overall outcome as part of a therapeutic regimen for anemic dogs. Authors => A. Kendall | A. Woolcock | A. Brooks | G.E Moore published => First published: 14 October 2017 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.14847

Title => Risk Factors for Death in Dogs Treated for Esophageal Foreign Body Obstruction: A Retrospective Cohort Study of 222 Cases (1998–2017) Abstract => Background: Limited data exist describing risk factors for death, and long-term outcomes in dogs with esophageal foreign body (EFB) obstruction. Hypothesis/Objectives: To evaluate short- and long-term outcomes, and analyze risk factors for death in dogs with EFB obstruction. We hypothesized duration of entrapment and treatment type would affect outcome. Animals: A total of 222 dogs were treated for EFB obstruction at an emergency and referral hospital between March 1998 and March 2017. Methods: Medical records for dogs with EFB were retrospectively evaluated. Results: Foreign material most frequently was osseous (180/222 [81%]), with distal esophagus the most common location (110/222 [49.5%]). Duration of clinical signs was not associated with risk of death (OR = 1.08, 95% CI 0.99–1.17; P = 0.2). Entrapment was treated by endoscopy (204/222 [91.8%]), surgery after endoscopic attempt (13/222 [5.9%]), and repeat endoscopy after surgery was recommended but declined (5/222 [2.3%]). In-hospital case fatality rate was 11/222 (5%). Risk of death was significantly higher with surgery (OR = 20.1, 95% CI 3.59–112.44; P = 0.001), and 5/5 (100%) of dogs died if undergoing endoscopy after surgery was recommended but declined. Increasing numbers of postprocedural complications (OR = 3.44, CI 2.01–5.91; P < 0.001), esophageal perforation (OR = 65.47, CI 4.27–1004.15; P = 0.003), and postprocedure esophageal hemorrhage (OR = 11.81, CI 1.19–116.77; P = 0.04) increased in-hospital risk of death. Esophageal strictures were reported in 4/189 (2.1%) of survivors available for follow-up. Conclusions and Clinical Importance: Death is uncommon in canine EFB; however, treatment type affects outcome, and these data should be used to guide decision-making in dogs with EFB. Authors => A.G. Burton | C.T. Talbot | M.S. Kent published => First published: 14 October 2017 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.14849

Title => Evaluation of Renal Perfusion in Hyperthyroid Cats before and after Radioiodine Treatment Abstract => Background: Hyperthyroidism and chronic kidney disease (CKD) are common in elderly cats. Consequently, both diseases often occur concurrently. Furthermore, renal function is affected by thyroid status. Because changes in renal perfusion play an important role in functional renal changes in hyperthyroid cats, investigation of renal perfusion may provide novel insights. Objectives: To evaluate renal perfusion in hyperthyroid cats with contrast-enhanced ultrasound (CEUS). Animals: A total of 42 hyperthyroid cats was included and evaluated before and 1 month after radioiodine treatment. Methods: Prospective intrasubject clinical trial of contrast-enhanced ultrasound using a commercial contrast agent (SonoVue) to evaluate renal perfusion. Time-intensity curves were created, and perfusion parameters were calculated by off-line software. A linear mixed model was used to examine differences between pre- and post-treatment perfusion parameters. Results: An increase in several time-related perfusion parameters was observed after radioiodine treatment, indicating a decreased blood velocity upon resolution of the hyperthyroid state. Furthermore, a small post-treatment decrease in peak enhancement was present in the renal medulla, suggesting a lower medullary blood volume. Conclusions and Clinical Importance: Contrast-enhanced ultrasound indicated a higher cortical and medullary blood velocity and higher medullary blood volume in hyperthyroid cats before radioactive treatment in comparison with 1-month post-treatment control. Authors => E. Stock | S. Daminet | D. Paepe | E. Buresova | E. Vandermeulen | P. Smets | L. Duchateau | J.H. Saunders | K. Vanderperren published => First published: 14 October 2017 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.14852

Title => The Frequency and Clinical Implications of Bacteriuria in Chronically Paralyzed Dogs Abstract => Background: Paralysis is a known risk factor for urinary tract infections (UTI), sepsis, and death in paralyzed people, but there are no data available on diagnostic criteria for UTI versus bacteriuria, their frequency, or clinical implications in chronically paralyzed dogs. Hypothesis/Objectives: That chronically paralyzed dogs suffer frequent bacteriuria causing reduced duration of survival. We documented the frequency of bacteriuria, associated clinical signs, and survival rate in chronically paralyzed dogs. Animals: Forty-seven client-owned dogs paralyzed with no pelvic limb pain perception for >3 months and at least one urine culture (UC) performed. Methods: Retrospective, observational study. Medical records of dogs meeting inclusion criteria were reviewed for results of UC, urinalysis, and clinical signs. Outcome was compared between dogs with and without bacteriuria. Results: Thirty-five of 47 dogs had at least 1 positive UC, and 13 had recurrent bacteriuria. Rectal temperature and urinalysis results were extracted from records. Fever was present at time of UC in 5 of 68 observations, 2 with and 3 without bacteriuria. Pyuria was significantly associated with positive cultures (P < 0.001), cloudiness was not (P = 0.076). Survival data in 35 dogs (8 dead) showed no association between bacteriuria and survival (P = 0.69). Conclusions and Clinical Importance: Bacteriuria is common in paralyzed dogs but does not cause fever; diagnostic criteria of UTI are unclear. We did not detect an association of bacteriuria with survival, but this needs further confirmation. Authors => S. Rafatpanah Baigi | S. Vaden | N.J. Olby published => First published: 14 October 2017 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.14854

Title => Ectopic Bone as a Nidus for Calcium Oxalate Urocystolithiasis in a Cat Abstract => Authors => J.P. Lulich | H.S. Prasad | M. Manno | B. Bagley published => First published: 14 October 2017 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.14859

Title => Altered Serum Thyrotropin Concentrations in Dogs with Primary Hypoadrenocorticism before and during Treatment Abstract => Background: Thyrotropin (TSH) can be increased in humans with primary hypoadrenocorticism (HA) before glucocorticoid treatment. Increase in TSH is a typical finding of primary hypothyroidism and both diseases can occur concurrently (Schmidt's syndrome); therefore, care must be taken in assessing thyroid function in untreated human patients with HA. Objective: Evaluate whether alterations in cTSH can be observed in dogs with HA in absence of primary hypothyroidism. Animals: Thirty dogs with newly diagnosed HA, and 30 dogs in which HA was suspected but excluded based on a normal ACTH stimulation test (controls) were prospectively enrolled. Methods: cTSH and T4 concentrations were determined in all dogs and at selected time points during treatment (prednisolone, fludrocortisone, or DOCP) in dogs with HA. Results: cTSH concentrations ranged from 0.01 to 2.6 ng/mL (median 0.29) and were increased in 11/30 dogs with HA; values in controls were all within the reference interval (range: 0.01–0.2 ng/dL; median 0.06). There was no difference in T4 between dogs with increased cTSH (T4 range 1.0-2.1; median 1.3 μg/dL) compared to those with normal cTSH (T4 range 0.5-3.4, median 1.4 μg/dL; P=0.69) and controls (T4 range 0.3-3.8, median 1.8 μg/dL; P=0.35). After starting treatment, cTSH normalized after 2–4 weeks in 9 dogs and after 3 and 4 months in 2 without thyroxine supplementation. Conclusions and Clinical Relevance: Evaluation of thyroid function in untreated dogs with HA can lead to misdiagnosis of hypothyroidism; treatment with glucocorticoids for up to 4 months can be necessary to normalize cTSH. Authors => C.E. Reusch | F. Fracassi | N.S. Sieber-Ruckstuhl | W.A. Burkhardt | N. Hofer-Inteeworn | C. Schuppisser | M. Stirn | R. Hofmann-Lehmann | F.S. Boretti published => First published: 11 October 2017 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.14840

Title => Short-Term Efficacy and Safety of Torasemide and Furosemide in 366 Dogs with Degenerative Mitral Valve Disease: The TEST Study Abstract => Background: Furosemide is the only loop diuretic recommended by the ACVIM consensus guidelines for treatment of congestive heart failure (CHF) in dogs related to degenerative mitral valve disease (DMVD). Torasemide is another potent loop diuretic with a longer half-life and a higher bioavailability. Objectives: (1) To demonstrate that torasemide given once a day (q24h) is noninferior to furosemide given twice a day (q12h) for treating dogs with CHF; (2) and to compare the effect of the 2 drugs on the time to reach a composite cardiac endpoint “spontaneous cardiac death, euthanasia due to heart failure or CHF class worsening.” Animals: A total of 366 dogs with CHF attributable to DMVD. Methods: Analysis of 2 prospective randomized single-blinded reference-controlled trials was performed. Dogs orally received either torasemide q24h (n = 180) or furosemide q12h (n = 186) in addition to standard CHF therapy over 3 months. The primary efficacy criterion was the percentage of dogs with treatment success assessed in each study. The time to reach the composite cardiac endpoint was used as secondary criterion in the overall population. Results: Torasemide was noninferior to furosemide (Ptorasemide − Pfurosemide = +7%; 95% CI [−8%; +22%] and Ptorasemide − Pfurosemide = +1%; 95% CI [−12%; +14%], respectively, in Study 1 and Study 2). Torasemide (median dose = 0.24 mg/kg/d q24h; range = 0.10–0.69 mg/kg/d) was associated with a 2-fold reduction in the risk of reaching the composite cardiac endpoint (adjusted HR = 0.47; 95% CI = 0.27–0.82; P = 0.0077) as compared with furosemide (median dose = 1.39 mg/kg q12h; range = 0.70–6.30 mg/kg q12h). Conclusions and Clinical Importance: Torasemide q24h is an effective oral diuretic in dogs with CHF. Authors => V. Chetboul | J.-L. Pouchelon | J. Menard | J. Blanc | L. Desquilbet | A. Petit | S. Rougier | L. Lucats | F. Woehrle | the TEST study investigators published => First published: 04 October 2017 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.14841

Title => Antihistone Autoantibodies in Dobermans With Hepatitis Abstract => Background: Immune system involvement is suggested as an underlying cause for Doberman hepatitis (DH) based on female predisposition, lymphocyte infiltration, abnormal hepatocyte expression of major histocompatibility complex class II antigens, and homozygosity for dog leukocyte antigen DRB1*00601. Objective: To measure serum antinuclear antibodies (ANA) and serum antihistone antibodies (AHA) in Dobermans with hepatitis. To determine whether increased serum ANA or serum AHA could be used to support the diagnosis of Doberman hepatitis (DH). Animals: Privately owned 25 subclinically and 13 clinically affected DH Dobermans and 17 healthy control Dobermans. Methods: Case–control study. Indirect immunofluorescence (IIF) microscopy and line blot tests were employed for the ANA pilot studies and an enzyme-linked immunosorbent assay (ELISA) assay for detection of IgG AHA. Results: Indirect immunofluorescence revealed ANA-positive cases, and line blot showed AHA reactivity. In ELISA, importantly increased concentrations of AHA were found in 92% (23/25) of dogs in the subclinical stage and 84.6% (11 of 13) of dogs in the clinical stage of DH compared with no control dogs (0/17) (P < 0.0005). The mean AHA absorbance values of the blood samples obtained from the 25 subclinical DH dogs (1.36 ± 0.60, mean ± SD) and the 13 clinically affected dogs (1.46 ± 0.49) were significantly higher than in 17 control dogs (0.51 ± 0.18; P < 0.0001). Conclusions and Clinical Importance: As the presence of AHA indicates autoimmune activity, our results favor an autoimmune background as one cause for DH. Antihistone antibody could represent a novel means for screening Dobermans with increased serum alanine transaminase concentrations and suspicion of DH. Authors => H. Dyggve | S. Meri | T. Spillmann | H. Jarva | M. Speeti published => First published: 30 September 2017 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.14838

Title => Fluoroscopic Estimation of Thoracic Dimensional Changes in Healthy Dogs Abstract => Background: Current methods available for assessing alterations in lung mechanics require sophisticated equipment and are of limited availability. A method that could assess lung area change with respiration might be a clinically useful surrogate for assessing lung compliance. Objective: To use fluoroscopy to determine percent change in thoracic and lung areas in healthy dogs. Animals: Forty-four client-owned dogs with no evidence of respiratory disease. Methods: Prospective study. Resting respiration was recorded fluoroscopically, and peak inspiratory and expiratory frames were captured for 3 typical respiratory cycles. The number of intrathoracic pixels in the entire thoracic cavity was measured for both inspiration and expiration, and the average percent change in intrathoracic area was determined for each dog. This process was repeated by a hemithorax measurement of lung area that excluded the mediastinum and cardiac silhouette. Proposed reference ranges (and 95% confidence intervals [CI]) were computed by a nonparametric percentile distribution. Results: Median percent change in thoracic dimension for the total thorax measurement was 12.5% (CI, 8.9–24.0%). Median percent change for the hemithorax measurement was significantly (P < 0.001) larger (20.8%, CI, 14.3–37.6%). Both measurement techniques were correlated with body weight but not with age, sex, thoracic conformation, body condition score (BCS), or breed. Conclusions and Clinical Importance: Fluoroscopy allows a noninvasive and repeatable measure of lung area changes during respiration that must be corrected for body weight. Additional studies in dogs with respiratory diseases are needed to determine its utility in detecting clinically useful alterations in lung area changes. Authors => J.C. Chan | L.R. Johnson | C.S. Brown | R.E. Pollard published => First published: 29 September 2017 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.14825

Title => Clinical Characteristics of Dogs with Progressive Myelomalacia Following Acute Intervertebral Disc Extrusion Abstract => Background: Progressive myelomalacia (PMM) is a catastrophic disease associated with acute intervertebral disc extrusion (IVDE). Published data on the clinical characteristics of this disease are limited. Objective: To describe the onset and progression of clinical signs of PMM in a large case cohort. Animals: Fifty-one dogs, 18 with histopathologically confirmed PMM, 33 presumptively diagnosed based on clinical signs and diagnostic imaging. Methods: Retrospective study. Dogs with confirmed IVDE and either a histopathologic diagnosis of PMM or a high clinical suspicion were identified by medical record search. Data on nature and progression of signs were extracted. Results: Twenty-four of 51 dogs were Dachshunds. T12–T13 was the most common site of disc extrusion (12 of 56), and 18 of 55 of mid-to-caudal lumbar discs (between L3 and L6) were affected. Onset of PMM signs ranged from present at first evaluation (17/51) to 5 days after presentation, with 25 of 51 cases developing signs within 48 hours. Progression of signs from onset of PMM to euthanasia or death, excluding 7 cases euthanized at presentation, ranged from 1 to 13 days with 23 being euthanized within 3 days. Nonspecific systemic signs were documented in 30 of 51 dogs. Conclusion and Clinical Importance: The majority of dogs developed PMM within 2 days of presentation and was euthanized within another 3 days. However, onset can be delayed up to 5 days after presentation with progression to euthanasia taking as long as 2 weeks. Mid-to-caudal lumbar discs might be associated with an increased risk of PMM. Authors => A. Castel | N.J. Olby | C.L. Mariani | K.R. Muñana | P.J. Early published => First published: 29 September 2017 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.14829

Title => Scintigraphic Assessment of Deposition of Radiolabeled Fluticasone Delivered from a Nebulizer and Metered Dose Inhaler in 10 Healthy Dogs Abstract => Background: Aerosolized medications are increasingly being used to treat respiratory diseases in dogs. No previous studies assessing respiratory tract deposition of radiolabeled aerosols have been performed in conscious dogs. Hypothesis/Objectives: Assess respiratory tract deposition of radiolabeled, inhalant corticosteroid (fluticasone propionate labeled with 99mTc) delivered from a nebulizer and metered dose inhaler (MDI) to healthy dogs. Animals: Ten healthy Foxhounds. Methods: Prospective, randomized, cross-over pilot study. Initial inhalation method (nebulizer or MDI) was randomly assigned. Treatments were crossed over after a 7-day washout period. Treatments initially were performed using sedation. Dogs were imaged using 2-dimensional planar scintigraphy, with respiratory tract deposition quantified by manual region-of-interest analysis. Deposition calculated as percentage of delivered dose. Six of 10 dogs were randomly selected and reassessed without sedation. Results: Inhalation method had significant effect on respiratory tract deposition (P = 0.027). Higher deposition was achieved by nebulization with mean deposition of 4.2% (standard deviation [SD], 1.4%; range, 1.9–6.1%); whereas MDI treatment achieved a mean of 2.3% (SD, 1.4%; range, 0.2–4.2%). Nebulization achieved higher respiratory tract deposition than MDI in 7 of 10 dogs. No statistical difference (P = 0.68) was found between mean respiratory tract deposition achieved in dogs when unsedated (3.8%; SD, 1.5%) or sedated (3.6%; SD, 1.7%). Conclusions and Clinical Importance: Study confirms respiratory tract deposition of inhalant medications delivered from a nebulizer and MDI in healthy dogs, breathing tidally with and without sedation. Respiratory tract deposition in these dogs was low compared to reported deposition in adult humans, but similar to reported deposition in children. Authors => K.E. Chow | D. Tyrrell | M. Yang | L.A. Abraham | G.A. Anderson | C.S. Mansfield published => First published: 29 September 2017 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.14832

Title => Long-term Treatment with Methylene Blue in a Dog with Hereditary Methemoglobinemia Caused by Cytochrome b5 Reductase Deficiency Abstract => Authors => J.A. Jaffey | M.R. Harmon | N.A. Villani | E.K. Creighton | G.S. Johnson | U. Giger | J.R. Dodam published => First published: 29 September 2017 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.14843

Title => Prediction of Packed Cell Volume after Whole Blood Transfusion in Small Ruminants and South American Camelids: 80 Cases (2006–2016) Abstract => Background: Calculation of desired whole blood transfusion volume relies on an estimate of an animal's circulating blood volume, generally accepted to be 0.08 L/kg or 8% of the animal's body weight in kilograms. Objective: To use packed cell volume before and after whole blood transfusion to evaluate the accuracy of a commonly used equation to predict packed cell volume after transfusion in small ruminants and South American camelids; to determine the nature and frequency of adverse transfusion reactions in small ruminants and camelids after whole blood transfusion. Animals: Fifty-eight small ruminants and 22 alpacas that received whole blood transfusions for anemia. Methods: Retrospective case series; medical record review for small ruminants and camelids that received whole blood transfusions during hospitalization. Results: Mean volume of distribution of blood as a fraction of body weight in sheep (0.075 L/kg, 7.5% BW) and goats (0.076 L/kg, 7.6% BW) differed significantly (P < 0.01) from alpacas (0.103 L/kg, 10.3% BW). Mild transfusion reactions were noted in 16% of transfusions. Conclusions and Clinical Relevance: The generally accepted value of 8% for circulating blood volume (volume of distribution of blood) is adequate for calculation of transfusion volumes; however, use of the species-specific circulating blood volume can improve calculation of transfusion volume to predict and achieve desired packed cell volume. The incidence of transfusion reactions in small ruminants and camelids is low. Authors => D. Luethy | D. Stefanovski | R. Salber | R.W. Sweeney published => First published: 29 September 2017 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.14844

Title => JAK1/2 Inhibitors AZD1480 and CYT387 Inhibit Canine B-Cell Lymphoma Growth by Increasing Apoptosis and Disrupting Cell Proliferation Abstract => Background: Canine diffuse large B-cell lymphoma (DLBCL) is a common and aggressive hematologic malignancy. The lack of conventional therapies with sustainable efficacy warrants further investigation of novel therapeutics. The Janus kinase (JAK) and signal transducer and activator of transcription (STAT) pathways play important roles in the pathogenesis of hematologic malignancies in humans including DLBCLs. AZD1480 and CYT387 are novel JAK1/2 inhibitors that have been used in clinical trials for treating various hematologic cancers in humans. No studies have characterized the antitumor effects of JAK inhibitors on DLBCL in dogs. Hypothesis/Objectives: We hypothesize that JAK1/2 inhibitors AZD1480 and CYT387 can effectively inhibit growth of canine DLBCL in vitro. We aim to assess the antitumor activity of AZD1480 and CYT387 in canine DLBCL and to determine the underlying mechanisms of action. Methods: In vitro study of canine lymphoma cell growth, proliferation, and apoptosis by viability, proliferation and apoptosis assays. Results: A significant decrease in viable canine lymphoma cells was observed after AZD1480 and CYT387 treatments. In addition, AZD1480 and CYT387 treatment resulted in decreased lymphoma cell proliferation and increased early apoptosis. Conclusion and Clinical Importance: AZD1480 and CYT387 inhibit canine lymphoma cell growth in a dose-dependent manner. Our findings justify further phase I/II clinical investigations of the safety and efficacy of JAK1/2 inhibitors in canine DLBCL and suggest new opportunities for novel anticancer therapies. Authors => Z. Lu | C.C. Hong | P.C. Jark | A.L.F.V. Assumpção | N. Bollig | G. Kong | X. Pan published => First published: 27 September 2017 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.14837

Title => Chronic Gingivostomatitis with Esophagitis in Cats Abstract => Background: Chronic gingivostomatitis in cats (FCG) is a debilitating disease with potentially deleterious effects on overall health. Hypothesis/Objectives: Little is known about the pathophysiology and overall impact of FCG. The aims of our study were to investigate whether gingivostomatitis occurs concurrently with esophagitis, if FCG treatment contributes to esophagitis and if esophagitis exacerbates signs of FCG. Animals: Fifty-eight cats with clinical signs of FCG and 12 healthy control cats exhibiting no signs of oral disease, all client-owned. Methods: Prospective study. Physical, oral and endoscopic examinations were performed on all cats. Measurements of salivary and esophageal lumen pH were obtained from both groups. Biopsies were acquired from sites of esophageal inflammation in cats with FCG and from normal-appearing esophageal mucosa in control cats. Results: The majority of cats with clinical signs of FCG exhibited some degree of esophagitis especially in the proximal (44/58) and distal (53/58) parts (P < 0.001) with or without columnar metaplasia, compared to controls. All cats lacked signs related to gastrointestinal disease. Salivary and esophageal lumen pH were not statistically different compared to controls. Conclusions and Clinical Importance: Feline chronic gingivostomatitis seems to occur concurrently with esophagitis. Esophagitis also should be managed in cats with chronic gingivostomatitis because it may aggravate the existing condition. Authors => M.I. Kouki | S.A. Papadimitriou | D. Psalla | A. Kolokotronis | T.S. Rallis published => First published: 27 September 2017 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.14850

Title => Clinical Consequences of Hypertriglyceridemia-Associated Proteinuria in Miniature Schnauzers Abstract => Background: Primary hypertriglyceridemia is a common condition in older Miniature Schnauzers that recently has been associated with proteinuria and underlying glomerular pathology, particularly glomerular lipid thromboemboli. Consequences of glomerular disease can include hypertension, thromboembolic disease, and cardiac disease. The incidence of these sequelae in Miniature Schnauzers with hypertriglyceridemia-associated proteinuria (HTGP) is unknown. Objective: To investigate prevalence of hypertension, decreased antithrombin III activity, and cardiac disease in Miniature Schnauzers with and without HTGP. Animals: Thirty-two Miniature Schnauzers ≥7 years old. Methods: Prospective case-control study. Data collected from dogs included a CBC, biochemistry panel, urinalysis, urine protein-to-creatinine ratio, urine cortisol-to-creatinine ratio, serum total thyroxine concentration, fasting serum triglyceride concentration, indirect blood pressure, antithrombin III activity, and serum cardiac troponin I concentration. Results from dogs with HTGP (serum triglyceride concentration ≥ 100 mg/dL and urine protein-to-creatinine ratio >0.5) were statistically compared to normotriglyceridemic, nonproteinuric dogs. Results: Eighteen of the 32 dogs (56%) had primary hypertriglyceridemia. Of those dogs, 8 of 18 had proteinuria. None of the HTGP dogs were azotemic or hypoalbuminemic. Serum albumin concentration, alkaline phosphatase activity, and cholesterol concentration were significantly increased in dogs with HGTP compared to those without HGTP. No increased risk of hypertension, decreased antithrombin III activity, or cardiac disease was noted. Limited data from 8 dogs with HTGP showed no development of hypoalbuminemia or azotemia over a median follow-up period of 18 months. Conclusions and Clinical Importance: Geriatric Miniature Schnauzers with HGTP may have a good prognosis overall, and are not typically azotemic or hypoalbuminemic. Authors => R.E. Smith | J.L. Granick | C.D. Stauthammer | D.J. Polzin | D.A. Heinrich | E. Furrow published => First published: 23 September 2017 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.14833

Title => Influence of Various Factors on Circulating 25(OH) Vitamin D Concentrations in Dogs with Cancer and Healthy Dogs Abstract => Background: Low blood 25-hydroxyvitamin D (25(OH)D) concentrations have been associated with cancer in dogs. Little research has examined what other factors may affect 25(OH)D concentrations. Objectives: (1) To determine whether the presence of cancer (lymphoma, osteosarcoma, or mast cell tumor [MCT]) in dogs is associated with plasma 25(OH)D concentrations and (2) identify other factors related to plasma 25(OH)D concentrations in dogs. Animals: Dogs newly diagnosed with osteosarcoma (n = 21), lymphoma (n = 27), and MCT (n = 21) presented to a tertiary referral oncology center, and healthy, client-owned dogs (n = 23). Methods: An observational study design was used. Dietary vitamin D intake, sex, age, body condition score (BCS), muscle condition score (MCS), and plasma concentrations of 25(OH)D, 24,25-dihydroxyvitamin D (24,25(OH)2D) (a marker of CYP24A1 activity), as well as ionized calcium (ICa), parathyroid hormone, and parathyroid hormone-related protein concentrations were measured. An analysis of covariance was used to model plasma 25(OH)D concentrations. Results: Cancer type (P = 0.004), plasma 24,25(OH)2D concentrations (P < 0.001), and plasma ICa concentrations (P = 0.047) had significant effects on plasma 25(OH)D concentrations. Effects of age, sex, body weight, BCS, MCS, and plasma PTH concentrations were not identified. A significant interaction between ICa and cancer was found (P = 0.005). Plasma 25(OH)D concentrations increased as ICa concentrations increased in dogs with cancer, whereas plasma 25(OH)D concentrations decreased as ICa concentrations increased in healthy dogs. Conclusions and Clinical Importance: Results support a relationship between cancer and altered vitamin D metabolism in dogs, mediated by plasma ICa concentrations. The CYP24A1 activity and plasma ICa should be measured in studies examining plasma 25(OH)D concentrations in dogs. Authors => N. Weidner | J.P. Woods | P. Conlon | K.A. Meckling | J.L. Atkinson | J. Bayle | A.J. Makowski | R.L. Horst | A. Verbrugghe published => First published: 23 September 2017 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.14834

Title => Effect of Laparoscopic-assisted Gastropexy on Gastrointestinal Transit Time in Dogs Abstract => Background: Prophylactic gastropexy has been promoted as a means of preventing gastric volvulus during gastric dilatation and volvulus (GDV) syndrome. Little is known about the impact of gastropexy on gastrointestinal transit time. Hypothesis: Laparoscopic-assisted gastropexy (LAG) will not alter gastrointestinal transit times when comparing gastric (GET), small and large bowel (SLBTT), and whole gut transit times (TTT) before and after surgery. Animals: 10 healthy client-owned large-breed dogs. Methods: Prospective clinical trial. Before surgery, all dogs underwent physical examination and diagnostic evaluation to ensure normal health status. Dogs were fed a prescription diet for 6 weeks before determination of gastrointestinal transit with a wireless motility capsule. LAG was then performed, and dogs were fed the diet for 6 additional weeks. Measurement of transit times was repeated 6 weeks after surgery. Results: Ten dogs of various breeds at-risk for GDV were enrolled. No complications were encountered associated with surgery or capsule administration. There were no significant differences in GET 429 [306–1,370] versus 541 [326–1,298] (P = 0.80), SLBTT 1,243 [841–3,070] versus 1,540 [756–2,623] (P = 0.72), or TTT 1,971 [1,205–3,469] versus 1,792 [1,234–3,343] minutes (median, range) (P = 0.65) before and after LAG. Conclusions and Clinical Importance: An effect of LAG on gastrointestinal transit time was not identified, and wireless motility capsule can be safely administered in dogs after LAG. Authors => I.M. Balsa | W.T.N. Culp | K.J. Drobatz | E.G. Johnson | P.D. Mayhew | S.L. Marks published => First published: 20 September 2017 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.14816

Title => Insect Bite Hypersensitivity in Horses is Associated with Airway Hyperreactivity Abstract => Background: Genetic and epidemiologic evidence suggests that in horses, as in other species, different manifestations of hypersensitivity may occur together. Hypothesis: Horses affected with insect bite hypersensitivity (IBH) show airway hyperreactivity (AH) to inhaled histamine, even in the absence of overt clinical signs of equine asthma (EA). Animals: Twenty-two healthy controls (group C), 24 horses suffering from IBH alone (group IBH), and 23 horses suffering from IBH and EA (group IBH/EA). Methods: The clinical histories were assessed using 2 standardized questionnaires, the Horse Owner Assessed Respiratory Signs Index (HOARSI), and IBH scoring. Horses were classified as EA-affected if their HOARSI was >1 and as IBH-affected if IBH score was >0. Confounding disorders were excluded by clinical examination. The arterial partial pressure of oxygen (PaO2) was measured and flowmetric plethysmography used to assess airway reactivity to increasing doses of inhaled histamine. Results: The median histamine provocation concentration (PC) when ∆flow values increased by 35% (PC35) was significantly higher in group C (5.94 [1.11–26.33] mg/mL) compared to group IBH (2.95 [0.23–10.13] mg/mL) and group IBH/EA (2.03 [0.43–10.94] mg/mL; P < 0.01). The PC50 and PC75 showed very similar differences between groups. Furthermore, PaO2 was significantly lower in group IBH (84 ± 8 mmHg) and group IBH/EA (78 ± 11 mmHg) compared to group C (89 ± 6 mmHg; P < 0.01). Conclusions and Clinical Importance: IBH is associated with AH and decreased PaO2, even in the absence of overt respiratory clinical signs. Authors => S. Lanz | A. Brunner | C. Graubner | E. Marti | V. Gerber published => First published: 18 September 2017 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.14817

Title => Effects of Oral Prednisone Administration on Serum Cystatin C in Dogs Abstract => Background: Oral administration of glucocorticoid alters serum cystatin C (sCysC) concentration in humans. Objective: To determine if oral administration of prednisone alters sCysC in dogs without pre-existing renal disease. Animals: Forty six dogs were included: 10 dogs diagnosed with steroid responsive meningitis arteritis (SRMA; group A), 20 dogs diagnosed of pituitary-dependent hyperadrenocorticism (PDH; group B), and 16 healthy control dogs (group C). Methods: Retrospective observational study. SRMA diagnosed dogs were administered prednisone 4 mg/kg/24 h PO 7 days, reducing the dose to 2 mg/kg/24 h 7 days before medication withdrawal. In group A, sampling was performed at days 0, 7, 14 and a final control at day 21. Blood and urine samples were collected in the 3 groups, and in group A, sampling was performed at all time points (days 1, 7, 14, and 21). Results: In group A, sCysC was significantly higher at day 7 compared to the control group (0.4 ± 0.04 mg/L vs. 0.18 ± 0.03 mg/L mean ± SEM respectively P < 0.01); sCysC values decreased to basal at day 14 when the dose was decreased and after 1 week of withdrawal of prednisone (0.27 ± 0.03 mg/L for group A at day 14 and 0.15 ± 0.02 mg/L at day 21; P > 0.05). Dogs with PDH included in group B did not have significant differences in sCysC (0.22 ± 0.03 mg/L) compared to control (P > 0.05). Conclusions and Clinical Importance: Oral administration of prednisone unlike altered endogenous glucocorticoid production, increases sCysC in dogs in a dose-dependent fashion. Authors => J. Muñoz | P. Soblechero | F.J. Duque | B. Macías-García | P. Ruiz | C. Zaragoza | R. Barrera published => First published: 18 September 2017 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.14820

Title => Detection of Bovine Coronavirus in Healthy and Diarrheic Dairy Calves Abstract => Background: BCoV is identified in both healthy and diarrheic calves, complicating its assessment as a primary pathogen. Objectives: To investigate the detection rates of bovine coronavirus (BCoV) in feces of healthy and diarrheic calves and to describe the usefulness of a pancoronavirus reverse transcriptase (RT) PCR (PanCoV-RT-PCR) assay to identify BCoV in samples of diarrheic calves. Animals: Two hundred and eighty-six calves <21 days. Calves with liquid or semiliquid feces, temperature >39.5°C, and inappetence were considered as cases, and those that had pasty or firm feces and normal physical examination were designated as controls. Methods: Prospective case–control study. A specific BCoV-RT-PCR assay was used to detect BCoV in fecal samples. Association between BCoV and health status was evaluated by exact and random effect logistic regression. Fecal (n = 28) and nasal (n = 8) samples from diarrheic calves were tested for the presence of BCoV by both the PanCoV-RT-PCR and a specific BCoV-RT-PCR assays. A Kappa coefficient test was used to assess the level of agreement of both assays. Results: BCoV was detected in 55% (157/286) of calves; 46% (66/143), and 64% (91/143) of healthy and diarrheic calves, respectively. Diarrheic calves had higher odds of BCoV presence than healthy calves (OR: 2.16, 95% CI: 1.26 to 3.83, P = 0.004). A good agreement between PanCoV-RT-PCR and BCoV-RT-PCR to detect BCoV was identified (κ = 0.68, 95% CI: 0.392 to 0.967; P < 0.001). Conclusions and Clinical Importance: BCoV was more likely to be detected in diarrheic than healthy calves. The PanCoV-RT-PCR assay can be a useful tool to detect CoV samples from diarrheic calves. Authors => D.E. Gomez | L.G. Arroyo | Z. Poljak | L. Viel | J.S. Weese published => First published: 15 September 2017 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.14811

Title => Long-term Stability of a Compounded Suspension of Torsemide (5 mg/mL) for Oral Administration Abstract => Background: Torsemide use for congestive heart failure (CHF) has been reported, but prescription frequency is unknown. Commercially available tablet sizes in North America limit dosing precision, indicating a need to evaluate its strength and stability in suspension. Objectives: To determine the frequency of torsemide prescriptions and to determine a beyond use date (BUD) of a compounded suspension of torsemide for oral administration stored under 2 temperature conditions for 90 days. Animals: No animals used. Methods: Pharmacy records were retrospectively reviewed for torsemide and furosemide prescriptions from 2008 to 2015 at 2 veterinary referral centers. After preliminary strength testing, compounded torsemide suspension (5 mg/mL) for oral administration was prepared using torsemide tablets suspended in OraPlus:OraSweet 1:1, buffered to a pH of 8.3 and stored at refrigeration (2–8°C) and room temperature (20–25°C) in 2 oz amber plastic bottles. Samples were analyzed by reverse phase high-performance liquid chromatography (RP-HPLC) on days 0, 14, 30, 60, and 90. Results: Prescriptions for torsemide increased from 2008 to 2015. Analysis of the torsemide 5 mg/mL suspension for oral administration at each time point met United States Pharmacopeia (USP) requirements for torsemide content of 90–110% of label claim. The average strength at 90 days decreased to 92 ± 3% at 2–8°C and 95 ± 2% at 20–25°C. Stability testing did not detect unknown impurities. Conclusions: Increasing torsemide use warrants availability of a validated and stable compounded formulation. Our results support the assignment of a 90-day BUD for torsemide 5 mg/mL suspension for oral administration compounded in OraPlus:Sweet 1:1 buffered to a pH of 8.3. Authors => D. Adin | P.R. Johnson | C.H. Kim | T. Nguyenba | S. Rosen published => First published: 15 September 2017 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.14819

Title => Effects of 6 Weeks of Parenteral Cobalamin Supplementation on Clinical and Biochemical Variables in Cats with Gastrointestinal Disease Abstract => Background: Effects and duration of commonly used protocols for cobalamin (Cbl) supplementation on cellular Cbl deficiency have not been determined in hypocobalaminemic cats. Hypothesis/Objectives: To evaluate effect of Cbl supplementation on clinical signs, serum and urine methylmalonic acid (MMA) concentrations over 16 weeks. Animals: Twenty client-owned hypocobalaminemic cats with enteropathy. Methods: Prospective study. Serum Cbl and serum and urine MMA concentrations were determined prospectively in cats at enrollment (t0), immediately before (t6), and 4 (t10) and 10 weeks (t16) after 6th Cbl injection (250 μg, IM q 7 days). Clinical signs severity (activity, appetite, vomiting, diarrhea, body weight) graded at each time point and expressed as clinical disease activity score. Results: Clinical disease activity score decreased during supplementation and increased after treatment discontinuation. Median serum Cbl concentration increased significantly from t0 (111 pmol/L, range 111–212) to t6 (2,332.5 pmol/L, range 123–22,730) (P < 0.01). Values at t10 were 610.5 pmol/L (range, 111–2,527) and 180.5 pmol/L (range, 111–2,262) at t16 (P < 0.01). Median baseline serum MMA concentration (372 μmol/L, range 0.39–147,000) decreased significantly to 1.62 μmol/L (range, 0.18–806) at t6 (P < 0.01) and gradually increased to 5.34 μmol/L (range, 0.13–1,730) at t10 and 189 μmol/L (range, 0.4–983) at t16. Similar, nonsignificant, pattern observed for urine MMA concentration. Serum and urine MMA concentrations had not normalized in 12 and 6 cats, respectively, at t6. Conclusion and Clinical Importance: The Cbl supplementation protocol used here did not lead to complete normalization of cellular Cbl deficiency in all examined cats, and biochemical improvements were transient. Authors => J. Kempf | M. Hersberger | R.H. Melliger | C.E. Reusch | P.H. Kook published => First published: 12 September 2017 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.14830

Title => Thrombocytosis in 715 Dogs (2011–2015) Abstract => Background: Thrombocytosis is a hematologic abnormality in dogs that has been associated with various neoplastic, metabolic, and inflammatory conditions. Objective: To classify thrombocytosis in dogs based on severity and evaluate whether there are associations between severity and underlying disease processes. Animals: Seven hundred and fifteen dogs with thrombocytosis and 1,430 dogs with normal numbers of platelets. Methods: Retrospective study. Medical records of dogs with increased (>500 × 103/μL; thrombocytosis group) and normal (300–500 × 103/μL; control group) platelet counts between 2011 and 2015 were reviewed. Dogs were characterized by severity of platelet increase and diagnosis. Diagnostic categories included neoplasia, endocrine disease, inflammatory disease, or miscellaneous. Results: A total of 1,254 complete blood counts with thrombocytosis from 715 dogs were included in the study. Median platelet count in this population was 582 × 103/μL (500–1,810 × 103/μL). No correlation between severity of thrombocytosis and diagnosis was identified. Causes of secondary thrombocytosis included neoplasia (55.7%), endocrine disease (12.0%), and inflammatory disease (46.6%). Immune-mediated disease was common (22.2%), associated with frequent glucocorticoid administration, and had a significantly higher median platelet count (636 × 103/μL [500–1,262 × 103/μL] versus 565 × 103/μL [500–1,810 × 103/μL]) when compared to the other inflammatory processes (P < 0.001). The diagnoses in the thrombocytosis dogs differed significantly from the control population (P < 0.001). Conclusions and Clinical Importance: Thrombocytosis is commonly associated with carcinoma and immune-mediated disease in dogs. Authors => A.D Woolcock | A. Keenan | C. Cheung | J.A. Christian | G.E. Moore published => First published: 12 September 2017 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.14831

Title => Prevalence of Elevated Serum Creatinine Concentration in Dogs Presenting to a Veterinary Academic Medical Center (2010–2014) Abstract => Background: The epidemiology of kidney disease is not extensively described in dogs. Hypothesis/Objectives: To better understand the prevalence of elevated serum creatinine concentration in dogs. Animals: Client-owned dogs. Methods: A retrospective, observational cross-sectional study design was used. We made a dataset of 115,631 hospital visits of all dogs presenting from October 2010 to October 2014. We estimated the prevalence and risk of elevated serum creatinine, defined as >1.6 mg/dL, in evaluated dogs. Results: Of 115,631 visits, 98,693 were outpatient visits and 16,938 were hospital admissions. Among outpatient visits, 9,983 (10.1%) had serum creatinine assessment (4,423 [44.3%] visits were first visits), whereas, among hospital admissions, 12,228 (60.0%) had at least 1 serum creatinine (7,731 [75.6%] admissions were first admissions). The prevalence of elevated serum creatinine concentration in all evaluated dogs was 11.5% (95% CI: 11.0%, 11.9%); 10.2% (95% CI: 9.6%, 10.8%) of inpatients and 12.9% (95% CI: 12.1%, 13.8%) of outpatients had elevated serum creatinine concentration. The relative risk (RR) of elevated serum creatinine concentration was significantly higher in geriatric dogs (outpatient RR 1.45 [95% CI: 1.23, 1.70], inpatient RR 1.43 [95% CI: 1.16, 1.76]) and lower in young dogs (outpatient RR 0.39 [95% CI: 0.26, 0.59], inpatient RR 0.44 [95% CI: 0.32, 0.62]) when compared to the measured population risk. Conclusions and Clinical Importance: When selected for laboratory evaluation, the proportion of dogs presenting to an academic medical center with evidence of kidney injury is high compared to previous reports and might reflect a population of sicker dogs. Authors => J.M. Babyak | D.E. Weiner | F. Noubary | C.R. Sharp published => First published: 11 September 2017 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.14823

Title => Syringomyelia and Craniocervical Junction Abnormalities in Chihuahuas Abstract => Background: Chiari-like malformation (CM) and syringomyelia (SM) are widely reported in Cavalier King Charles Spaniels and Griffon Bruxellois dogs. Increasing evidence indicates that CM and SM also occur in other small and toy breed dogs, such as Chihuahuas. Objectives: To describe the presence of SM and craniocervical junction (CCJ) abnormalities in Chihuahuas and to evaluate the possible association of CCJ abnormalities with SM. To describe CM/SM-related clinical signs and neurologic deficits and to investigate the association of CM/SM-related clinical signs with signalment, SM, or CCJ abnormalities. Animals: Fifty-three client-owned Chihuahuas. Methods: Prospective study. Questionnaire analyses and physical and neurologic examinations were obtained before magnetic resonance and computed tomography imaging. Images were evaluated for the presence of SM, CM, and atlantooccipital overlapping. Additionally, medullary kinking, dorsal spinal cord compression, and their sum indices were calculated. Results: Scratching was the most common CM/SM-related clinical sign and decreased postural reaction the most common neurologic deficit in 73 and 87% of dogs, respectively. Chiari-like malformation and SM were present in 100 and 38% of dogs, respectively. Syringomyelia was associated with the presence of CM/SM-related clinical signs (P = 0.034), and medullary kinking and sum indices were higher in dogs with clinical signs (P = 0.016 and P = 0.007, respectively). Conclusions and Clinical Importance: Syringomyelia and CCJ abnormalities are prevalent in Chihuahuas. Syringomyelia was an important factor for the presence of CM/SM-related clinical signs, but many dogs suffered from similar clinical signs without being affected by SM, highlighting the clinical importance of CCJ abnormalities in Chihuahuas. Authors => A.-M. Kiviranta | C. Rusbridge | O. Laitinen-Vapaavuori | A. Hielm-Björkman | A.K. Lappalainen | S.P. Knowler | T.S. Jokinen published => First published: 11 September 2017 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.14826

Title => Pharmacokinetics of Mycophenolic Acid after Intravenous Administration of Mycophenolate Mofetil to Healthy Cats Abstract => Background: Mycophenolate mofetil (MMF), the prodrug of mycophenolic acid (MPA), is becoming increasingly popular as an alternative immunosuppressant in feline medicine. Pharmacokinetic information is not available for cats. Objective: The purpose of this study was to determine whether MMF is biotransformed into the active metabolite MPA and to evaluate the disposition of MPA after a 2-hour constant rate intravenous (IV) infusion of MMF in healthy cats. Animals: Healthy cats (n = 6). Methods: This was a prospective pilot study. All cats were administered MMF at 20 mg/kg every 12 hours over a 2-hour constant rate infusion for 1 day. The concentrations of MPA and its derivatives in blood were determined using a validated UHPLC–UV method. Results: All cats biotransformed MMF into MPA. The mean AUC0-14 h ranged from 6 to 50 h*mg/L after IV dosing of MMF. Transient large bowel diarrhea was recorded in 2 of 6 cats after medication administration. Conclusion and Clinical Importance: The disposition of MPA in plasma was highly variable, which could result in high interindividual variability in the safety and efficacy of treatment with MMF in cats. Authors => J.E. Slovak | S.M. Rivera | J.K. Hwang | M.H. Court | N.F. Villarino published => First published: 11 September 2017 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.14827

Title => Desoxycorticosterone Pivalate Duration of Action and Individualized Dosing Intervals in Dogs with Primary Hypoadrenocorticism Abstract => Background: Clinicians alter dosing for desoxycorticosterone pivalate (DOCP) to mitigate costs, but this practice has not been critically evaluated in a prospective clinical trial. Hypothesis/Objectives: The duration of action of DOCP is longer than 30 days in dogs with primary hypoadrenocorticism (PH). Animals: A total of 53 client-owned dogs with PH. Twenty-four dogs with newly diagnosed PH (Group 1) and 29 dogs with treated PH (Group 2). Methods: Prospective, multicenter, clinical trial. For phase I, DOCP was administered and plasma sodium and potassium concentrations were measured until the dog developed hyponatremia or hyperkalemia at a planned evaluation, or displayed clinical signs with plasma electrolyte concentrations outside of the reference interval independent of a planned evaluation, thus defining DOCP duration of action. Plasma electrolyte concentrations then were assessed at the end of the individualized dosing interval (IDI; i.e., DOCP duration of action minus 7 days, phase II and at least 3 months after concluding phase II, phase III). Results: The duration of action of DOCP in dogs in phase I with naïve PH (n = 24) ranged from 32 to 94 days (median, 62 days; 95% confidence interval [CI], 57, 65) and previously treated PH (n = 29) from 41 to 124 days (median, 67 days; CI, 56, 72). Overall, the final DOCP dosing interval for all dogs that completed phase II (n = 36) ranged from 38 days to 90 days (median, 58 days; CI, 53, 61). No dog that completed phase III (n = 15) required reduction in the IDI. The DOCP duration of action, independent of group, was not significantly associated with several baseline variables. The median drug cost reduction using IDI was approximately 57.5% per year. Conclusion and Clinical Importance: The duration of action of DOCP in dogs with PH is >30 days, and plasma sodium and potassium concentrations can be maintained with an IDI >30 days long term. Authors => J.A. Jaffey | P. Nurre | A.B. Cannon | A.E. DeClue published => First published: 11 September 2017 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.14828

Title => Interobserver Variation in the Diagnosis of Neurologic Abnormalities in the Horse Abstract => Background: The diagnosis of equine protozoal myeloencephalitis (EPM) relies heavily on the clinical examination. The accurate identification of neurologic signs during a clinical examination is critical to the interpretation of laboratory results. Objective: To investigate the level of agreement between board-certified veterinary internists when performing neurologic examinations in horses. Animals: Ninety-seven horses admitted to the Veterinary Teaching Hospital at The Ohio State University from December 1997 to June 1998. Methods: A prospective epidemiologic research design was used. Horses enrolled in the study were examined by the internist responsible for care of the horse, and later by an internist who was not aware of the presenting complaint or other patient history. Data were analyzed by descriptive statistics, and kappa (K) statistics were calculated to assess interobserver agreement. Results: Ninety-seven horses were enrolled in the study. Overall, examiners, also referred to as observers, agreed that 60/97 (61.9%) were clinically abnormal, 21/97 (21.6%) were clinically normal, and the status of 16/97 (16.5%) of horses was contested. There was complete agreement among the examiners with regard to cranial nerve signs and involuntary movements. Disagreement involving severity of clinical signs occurred in 31 horses, and 25 of those horses (80.6%) were considered either normal or mildly affected by the primary observer. When examining the results of all paired clinical examinations for 11 different categories, there was wide variability in the results. When examiners rated the presence or absence of any neurologic abnormalities, lameness, or ataxia, the agreement among observers was either good or excellent for 80% of horses. When assessing truncal sway, the agreement among observers was good or excellent for 60% of the horses. When examining the horses for asymmetry of deficits, agreement was either good or excellent for 40% of the horses. Agreement among observers was excellent or good for only 20% of the horses when assessing muscle atrophy, spasticity (hypermetria), and overall assessment of the severity of neurologic abnormalities. Conclusions and Clinical Importance: This study underscores the subjectivity of the neurologic examination and demonstrates a reasonable level of agreement that may be achieved when different clinicians examine the same horse. Authors => W.J.A. Saville | S.M. Reed | J.P. Dubey | D.E. Granstrom | P.S. Morley | K.W. Hinchcliff | C.W. Kohn | T.E. Wittum | J.D. Workman published => First published: 09 September 2017 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.14822

Title => Opportunistic Invasive Cutaneous Fungal Infections Associated with Administration of Cyclosporine to Dogs with Immune-mediated Disease Abstract => Background: Opportunistic invasive fungal infections (OIFIs) occur in dogs administered immunosuppressive medications. However, the epidemiology of OIFIs among dogs undergoing immunosuppressive treatment is poorly understood. The aims of this study were to (1) estimate the incidence of OIFIs among dogs diagnosed with certain immune-mediated diseases and treated with immunosuppressive drugs, and (2) determine if administration of particular drug(s) was a risk factor for OIFIs. Hypothesis: Dogs receiving cyclosporine treatment (alone or as part of a multidrug protocol) are at higher risk of developing OIFIs. Animals: One hundred and thirteen client-owned dogs diagnosed with select immune-mediated diseases: 42 with IMHA, 29 with ITP, 34 with IMPA, and 8 with Evans syndrome. Methods: Retrospective cohort study. Medical records of dogs presenting to the Texas A&M University, Veterinary Medical Teaching Hospital between January 2008 and December 2015, and treated for 1 or more of IMHA, IMPA, ITP, or Evans syndrome were retrospectively reviewed. Dogs that did not develop an OIFI were excluded if they died, were euthanized, or were lost to follow-up within 120 days of initiation of immunosuppressive treatment. Results: Fifteen dogs of 113 (13%) were diagnosed with an OIFI based on 1 or more of cytology, culture, or histopathology. The odds of developing an OIFI were greater among dogs that were treated with cyclosporine (OR = 7.1, P = 0.017; 95% CI, 1.5–34.4) and among male dogs (OR = 5.1, P = 0.018; 95% CI, 1.4–17.9). Conclusions and Clinical Importance: OIFIs were significantly more likely in male dogs and those receiving cyclosporine. It is important to consider OIFIs as a potential complication of immunosuppressive treatment, particularly cyclosporine. Authors => B.B. McAtee | K.J. Cummings | A.K. Cook | J.A. Lidbury | J.C. Heseltine | M.D. Willard published => First published: 09 September 2017 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.14824

Title => Gene Expression of Matrix Metalloproteinases and their Inhibitors (TIMPs) in Meningiomas of Dogs Abstract => Background: Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) are considered to be key mediators of tumor invasion and metastasis. MMP-2 and MMP-9 are expressed in meningiomas of dogs, but TIMP expression, and variations of specific MMP/TIMP ratios still are unknown in this tumor. Hypothesis/Objectives: Expression of MMP/TIMP might increase progressively from grade I to grade III meningioma. Therefore, genetic expression of MMP-2 and MMP-9, and specific TIMP-2 and TIMP-1, respectively, has been investigated in meningiomas of different grades. Animals: Selected formalin-fixed paraffin-embedded tissue from 43 meningiomas of dogs was evaluated. Methods: Genetic material was obtained from pathologic samples and used for quantitative reverse transcriptase real-time polymerase chain reaction (RT-qPCR). Results: MMP-9 was not expressed in all of the tumors, but MMP-2 was significantly more expressed in papillary meningioma. Likewise, the MMP-2/TIMP-2 ratio was numerically higher in papillary meningiomas compared to all grades (>3.5 times) showing a strong bias in favor of metalloproteinase. In the papillary meningioma, TIMP-1 gene expression was significantly higher than in grades I and III. Conclusions and Clinical Importance: MMP-2/TIMP-2 imbalance might contribute to the aggressive biologic behavior of papillary meningiomas in dogs. TIMP-1 expression may play a role independent of MMP-9 expression in neoplastic progression. These results further support that therapeutic and prognostic evaluations of dogs with meningioma need to be addressed according to different histologic patterns as is performed in humans. Authors => M.T. Mandara | A. Reginato | G. Foiani | S. De Luca | G. Guelfi published => First published: 05 September 2017 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.14809

Title => Effect of Body Position, Exercise, and Sedation on Estimation of Pulmonary Artery Pressure in Dogs with Degenerative Atrioventricular Valve Disease Abstract => Background: Severity of pulmonary hypertension (PH) in dogs is related to clinical signs and prognosis. Hypothesis/Objectives: We hypothesized that Doppler echocardiographic (DE) indices of pulmonary artery pressure (PAP) and pulmonary vascular resistance (PVR) are influenced by independent factors that create clinically important variability of DE-based estimates of PH in dogs. Animals: Thirty-eight client owned dogs with naturally acquired degenerative atrioventricular valve disease and tricuspid regurgitation (TR). Methods: Dogs were prospectively enrolled, and target variables were acquired during 4 echocardiographic study periods (lateral recumbency, standing, lateral recumbency after a 6-minute walk test [6MWT], and lateral recumbency after sedation with butorphanol 0.25 mg/kg IM). Statistical methods included repeated measures ANOVA, mixed model analysis, and Chi-squared test of association. Results: There was a significant increase in peak TR flow velocity (TRFV; P < 0.01) after sedation in 78% of dogs, with TRFV increasing by >0.4 m/s in 42% of dogs, independent of stroke volume. A significant effect of study period on DE-estimated PVR was not found (P = 0.15). There were negligible effects of sonographer, body position, and 6MWT on echocardiographic variables of PH. Clinically relevant cyclic variation of TRFV was found. There was an association between estimation of right atrial pressure based on subjective assessment and estimation based on cranial vena cava collapsibility (P = 0.03). Conclusions and Clinical Importance: The increase in TRFV observed with sedation could change assessment of PH severity and impact prognostication and interpretation of treatment response. Further studies with invasive validation are needed. Authors => J.D. Rhinehart | K.E. Schober | B.A. Scansen | V. Yildiz | J.D. Bonagura published => First published: 02 September 2017 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.14814

Title => Suspected Phenobarbital-Induced Pseudolymphoma in a Dog Abstract => Authors => R. Lampe | J. Manens | N. Sharp published => First published: 02 September 2017 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.14818

Title => Neonatal Encephalopathy in Calves Presented to a University Hospital Abstract => Background: While studies have examined bovine dystocia in relation to calf survival, little has been published regarding perinatal morbidity and treatment of newborn calves beyond failure of transfer of passive immunity (FTPI). Neonatal encephalopathy (NE) is a clinical syndrome commonly diagnosed in infants and foals but is poorly described in calves. Hypothesis/Objectives: To identify risk factors for development of NE in calves and factors predictive of survival. Animals: Neonatal calves presented to a University hospital over a 10-year period. Methods: Retrospective cohort study (2005–2015). Medical records of all neonatal calves presented to the hospital were examined, and cases of NE were identified. Data pertaining to demographics, dam parity, labor, treatment, and outcome were collected and analyzed with univariate and multivariate statistics. Results: Of 200 calves in the final analysis, 58 (29%; 95% CI: 22.8–35.8%) were classified as NE and 142 calves as non-NE. In univariate analysis, factors significantly associated with diagnosis of NE included male sex, presence of dystocia, abnormal position in the birth canal, and prolonged labor. In the multivariate model, only orientation of the calf in the birth canal remained significant (OR 2.14; 95% CI: 1.02–4.49; P = 0.044). Overall survival of calves with NE was good (45/58; 77.6%; 95% CI: 64.7–87.5); dam parity and being a twin was significantly associated with nonsurvival. Conclusions: Calves born after dystocia, especially if malpresented, should be closely monitored for nursing behavior within the first 24 hours of life. Prognosis for survival is good, but supportive care might be required for several days. Authors => A.W. Bianco | G.E. Moore | S.D. Taylor published => First published: 02 September 2017 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.14821

Title => Immunophenotype of Peripheral Blood Lymphocytes in Dogs with Inflammatory Bowel Disease Abstract => Background: Inflammatory bowel disease (IBD) is common in dogs. Despite the known importance of intestinal lymphocytes in its pathogenesis, little is known about the role of peripheral blood lymphocytes (PBLs) in IBD. Objectives: The aims of this study were (1) comparison of PBLs analyzed by flow cytometry (FCM) in IBD dogs and healthy controls and (2) comparison of PBLs in IBD dogs at the time of diagnosis and in dogs in clinical remission. Animals: Whole blood samples of 19 IBD dogs at the time of diagnosis and blood samples of 6 dogs in clinical remission were collected. Ten healthy dogs served as controls. Methods: In this prospective observational study, PBLs were analyzed with multicolor FCM by staining with a panel of anticanine and cross-reactive monoclonal antibodies against T- and B-cell differentiation antigens, including CD45, CD3, CD4, CD8α, CD8β, TCRαβ, TCRγδ, CD79αcy, and CD21. Results: The IBD patients’ PBLs had significantly decreased percentages of TCRγδ+ T lymphocytes (median: healthy dogs, 3.32; IBD dogs, 0.97; P = 0.03) and CD21+ B cells (median: healthy dogs, 27.61; IBD dogs, 17.26; P = 0.04). There were no significant differences in PBLs between pretreatment and follow-up samples. Conclusions and Clinical Importance: The differences between PBLs in healthy and IBD dogs analyzed by FCM indicate an imbalance of lymphocytes with different immunologic functions and emphasize the potential value of this technique in a larger cohort of dogs. The PBLs did not differ between IBD dogs before treatment and clinically well-controlled dogs after treatment. Authors => A. Galler | B.C. Rütgen | E. Haas | A. Saalmüller | R.A. Hirt | W. Gerner | I. Schwendenwein | B. Richter | J.G. Thalhammer | N. Luckschander-Zeller published => First published: 01 September 2017 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.14812

Title => Effects of Hydroxyethyl Starch 130/0.4 on Serum Creatinine Concentration and Development of Acute Kidney Injury in Nonazotemic Cats Abstract => Background: Hydroxyethyl-starch (HES) solutions might have renal adverse effects in humans and dogs. Objective: To determine if administration of 6% HES-130/0.4 is associated with an increase in serum creatinine concentration and development of acute kidney injury (AKI) in nonazotemic cats. Animals: A total of 62 critically ill cats; 26 HES exposed and 36 unexposed. Methods: Retrospective cohort study (2012–2015). Serum creatinine concentrations were recorded and changes in serum creatinine concentrations before exposure (baseline) and 2–10 and 11–90 days, respectively, were determined. Development of AKI was defined as a > 150% increase or >26 μmol/L increase in serum creatinine concentration from baseline. Risk factors, such as HES administration, cumulative volume of HES (mL/kg) and number of days of HES administration leading to development of AKI, and change in serum creatinine were analyzed. Results: Cats in the HES cohort received a mean volume of 98.5 ± 76.2 mL/kg (range, 8–278 mL/kg) HES over a median of 4 (range, 1–11) days, resulting in a median dose of 20.1 (range, 8–40.5) mL/kg per day. Short-term %change in serum creatinine concentration (P = 0.40) and development of AKI (P = 0.32) were not significantly different between cohorts. Multivariable logistic regression did not identify HES dose in mL/kg (P = 0.33) and number of days of HES application (P = 0.49) as a risk factor for development of AKI. Conclusion and Clinical Importance: Hydroxyethyl-starch administration to critically ill nonazotemic cats seems to be safe. A larger prospective study is required to determine the effect of HES administration at higher dosages and for prolonged time periods. Authors => N.E. Sigrist | N. Kälin | A. Dreyfus published => First published: 01 September 2017 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.14813

Title => Feline Differential Leukocyte Count with ProCyte Dx: Frequency and Severity of a Neutrophil-Lymphocyte Error and How to Avoid It Abstract => Background: Erroneous neutrophil and lymphocyte counts from analysis of feline blood samples were transferred directly into the hospital information system from the ProCyte Dx hematology instrument in our after-hours laboratory. Errors usually were not detected by the users. Hypothesis/Objectives: To quantify the frequency and severity of errors associated with the ProCyte Dx analyzer and to identify methods to avoid the errors. Animals: One-hundred six EDTA blood samples routinely submitted from feline hospital patients were analyzed. Methods: ProCyte differential leukocyte counts were compared to 2 reference methods: Advia 2120 hematology instrument and manual enumeration. Limits for unacceptable deviation from the reference methods were defined as 18 for % lymphocytes and 23 for % neutrophils. Results: Fourteen of 106 samples had unacceptable errors for both lymphocytes and neutrophils compared to both reference methods. Median % lymphocytes in those 14 samples were 11.2, 15.0, and 53.0% for Advia, manual, and ProCyte, respectively. Median % neutrophils were 85.4, 81.5, and 34.2% for Advia, manual, and ProCyte, respectively. All errors were avoided by rejecting automated ProCyte differential leukocyte results whenever the dot plot appeared clearly incorrect, but only 9 of these 14 samples had a ProCyte WBC distribution error flag. Conclusions and Clinical Importance: Results reported by ProCyte had markedly falsely increased lymphocyte and decreased neutrophil counts in 13% of feline patient samples. Users must reject automated differential leukocyte count results when the WBC dot plot appears overtly incorrect. Rejection based only on ProCyte WBC error flag was insufficient. Authors => H.W. Tvedten | V. Andersson | I.E. Lilliehöök published => First published: 01 September 2017 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.14815

Title => Factors Associated with Colostrum Quality and Effects on Serum Gamma Globulin Concentrations of Calves in Swiss Dairy Herds Abstract => Background: Previous studies have shown a high prevalence of failure of passive transfer of immunity (FPT) in Swiss dairy calves. Objectives: To investigate risk factors associated with poor colostrum quality and FPT on Swiss dairy farms. Animals: Colostrum and serum samples from 373 dam-calf pairs at 141 farms. Methods: The gamma globulin (Gg) concentrations of the dams’ colostrum and the calves’ serum samples were determined by electrophoresis. Potential risk factors were assessed by logistic regression of questionnaire data. Results: Prevalence values of 15.5% (95% confidence interval [CI], 12.0–19.6%) for low-quality colostrum (<50 g Gg/L) in cows and 43.5% (95% CI, 38.4–48.8%) for FPT (serum Gg < 10 g/L) in calves were estimated. The main factors associated with low colostrum quality included colostrum leakage before or during parturition and a time lag > 6 hours between parturition and first milking. The results confirm that the occurrence of FPT in calves primarily was influenced by the quality of colostrum, the amount of ingested colostrum, and the time between birth and first feeding. Conclusions and Clinical Importance: These results confirm a large potential for improvement in colostrum harvesting and colostrum feeding procedures in the study herds. Control for colostrum leaking intra-partum, early colostrum milking, and ensuring that the calves ingest a sufficient volume of colostrum within the first hours of life are measures that can be readily implemented by farmers to decrease the incidence of FPT without additional workload. Authors => C. Reschke | E. Schelling | A. Michel | F. Remy-Wohlfender | M. Meylan published => First published: 23 August 2017 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.14806

Title => A Retrospective Study on the Safety and Efficacy of Leflunomide in Dogs Abstract => Background: Little clinical information is available concerning the use of leflunomide in dogs with immune-mediated diseases. Objectives: To report the safety and efficacy of leflunomide for the treatment of naturally occurring immune-mediated diseases in dogs. Animals: Ninety-two dogs treated with leflunomide for management of suspected immune-mediated diseases. Methods: Retrospective medical record review from Jan 1995 to Dec 2014. Data that were extracted from the medical records included signalment, body weight, underlying indication for leflunomide, dosage of leflunomide, treatment duration, concurrent medications, treatment response, and adverse events. Results: Adverse events that could be related to leflunomide administration included diarrhea (3 of 92, 3.3%), lethargy (2 of 92, 2.2%), unexplained hemorrhage (3 of 92, 3.3%), thrombocytopenia (2 of 31, 6.5%), and increased liver enzyme activities (1 of 16, 6.3%). Significant dose differences between dogs with adverse events (n = 11; median, 2.9 mg/kg/d; range, 1.8–3.6 mg/kg/d) and dogs without adverse events (n = 81; median, 1.6 mg/kg/d; range, 0.8–4.3 mg/kg/d) were found (P < 0.001). Treatment response could be evaluated in 17 dogs. Of these 17 dogs, 12 dogs (70.5%) had an apparent positive response to the use of leflunomide. There was no significant difference (P = 0.22) in dosages between dogs that responded to leflunomide (n = 12; median, 1.9 mg/kg/d; range, 1.0–3.5 mg/kg/d) and those that did not respond (n = 5; median, 1.7 mg/kg/d; range, 1.0–2.0 mg/kg/d). Conclusions and Clinical Importance: Results suggest that the starting dosage of leflunomide should be 2 mg/kg/d rather than the currently suggested dosage of 3–4 mg/kg/d. Authors => M. Sato | J.K. Veir | M. Legare | M.R. Lappin published => First published: 21 August 2017 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.14810

Title => GM2 Gangliosidosis in Shiba Inu Dogs with an In-Frame Deletion in HEXB Abstract => Authors => A. Kolicheski | G.S. Johnson | N.A. Villani | D.P. O'Brien | T. Mhlanga-Mutangadura | D.A. Wenger | K. Mikoloski | J.S. Eagleson | J.F. Taylor | R.D. Schnabel | M.L. Katz published => First published: 20 August 2017 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.14794

Title => Development of a Multivariate Predictive Model to Estimate Ionized Calcium Concentration from Serum Biochemical Profile Results in Dogs Abstract => Background: Ionized calcium concentration is the gold standard to assess calcium status in dogs, but measurement is not always available. Objectives: (1) To predict ionized calcium concentration from biochemical results and compare the diagnostic performance of predicted ionized calcium concentration (piCa) to those of total calcium concentration (tCa) and 2 corrected tCa formulas; and (2) to study the relationship between biochemical results and variation of measured ionized calcium concentration (miCa). Animals: A total of 1,719 dogs with both miCa and biochemical profile results available. Methods: Cross-sectional study. Using 1,200 dogs, piCa was determined using a multivariate adaptive regression splines model. Its accuracy and performance were tested on the remaining 519 dogs. Results: The final model included creatinine, albumin, tCa, phosphorus, sodium, potassium, chloride, alkaline phosphatase, triglycerides, and age, with tCa, albumin, and chloride having the highest impact on miCa variation. Measured ionized calcium concentration was better correlated with piCa than with tCa and corrected tCa and had higher overall diagnostic accuracy to diagnose hypocalcemia and hypercalcemia, but not significantly for hypercalcemia. For hypercalcemia, piCa was as sensitive (64%) but more specific (99.6%) than tCa and corrected tCa. For hypocalcemia, piCa was more sensitive (21.8%) and as specific (98.4%) as tCa. Positive and negative predictive values of piCa were high for both hypercalcemia (90% and 98%, respectively) and hypocalcemia (70.8% and 87.7%, respectively). Conclusions and clinical importance: Predicted ionized calcium concentration can be obtained from readily available biochemical and patient results and seems more useful than tCa and corrected tCa to assess calcium disorders in dogs when miCa is unavailable. Validation on external data, however, is warranted. Authors => J. Danner | M.D. Ridgway | S.I. Rubin | K. Le Boedec published => First published: 20 August 2017 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.14800

Title => Effect of Intravenously Administered Crystalloid Solutions on Acid-Base Balance in Domestic Animals Abstract => Authors => W. Muir published => First published: 20 August 2017 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.14803

Title => The Relationship between Brachycephalic Head Features in Modern Persian Cats and Dysmorphologies of the Skull and Internal Hydrocephalus Abstract => Background: Cat breeders observed a frequent occurrence of internal hydrocephalus in Persian cats with extreme brachycephalic head morphology. Objective: To investigate a possible relationship among the grade of brachycephaly, ventricular dilatation, and skull dysmorphologies in Persian cats. Animals: 92 Persian-, 10 Domestic shorthair cats. Methods: The grade of brachycephaly was determined on skull models based on CT datasets. Cranial measurements were examined with regard to a possible correlation with relative ventricular volume, and cranial capacity. Persians with high (peke-face Persians) and lower grades of brachycephaly (doll-face Persians) were investigated for the presence of skull dysmorphologies. Results: The mean cranial index of the peke-face Persians (0.97 ± 0.14) was significantly higher than the mean cranial index of doll-face Persians (0.66 ± 0.04; P < 0.001). Peke-face Persians had a lower relative nasal bone length (0.15 ± 0.04) compared to doll-face (0.29 ± 0.08; P < 0.001). The endocranial volume was significantly lower in doll-face than peke-face Persians (89.6 ± 1.27% versus 91.76 ± 2.07%; P < 0.001). The cranial index was significantly correlated with this variable (Spearman's r: 0.7; P < 0.0001). Mean ventricle: Brain ratio of the peke-face group (0.159 ± 0.14) was significantly higher compared to doll-face Persians (0.015 ± 0.01; P < 0.001). Conclusion and Clinical Relevance: High grades of brachycephaly are also associated with malformations of the calvarial and facial bones as well as dental malformations. As these dysmorphologies can affect animal welfare, the selection for extreme forms of brachycephaly in Persian cats should be reconsidered. Authors => M.J. Schmidt | M. Kampschulte | S. Enderlein | D. Gorgas | J. Lang | E. Ludewig | A. Fischer | A. Meyer-Lindenberg | A.R. Schaubmar | K. Failing | N. Ondreka published => First published: 20 August 2017 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.14805

Title => Evaluation of Gastric pH and Serum Gastrin Concentrations in Cats with Chronic Kidney Disease Abstract => Background: Chronic kidney disease (CKD) is a highly prevalent condition in cats. Advanced CKD is associated with hyporexia and vomiting, which typically are attributed to uremic toxins and gastric hyperacidity. However, gastric pH studies have not been performed in cats with CKD. Hypothesis/Objectives: To determine if cats with CKD have decreased gastric pH compared to age-matched, healthy cats. Based on previous work demonstrating an association of hypergastrinemia and CKD, we hypothesized that cats with CKD would have decreased gastric pH compared to healthy, age-matched control cats. Animals: 10 CKD cats; 9 healthy control cats. Methods: All cats with concurrent disease were excluded on the basis of history, physical examination, CBC, plasma biochemistry profile, urinalysis, urine culture, serum total thyroxine concentration, and serum symmetric dimethylarginine concentration (controls only) obtained within 24 hours of pH monitoring and assessment of serum gastrin concentrations. Serum for gastrin determination was collected, and 12-hour continuous gastric pH monitoring was performed in all cats. Serum gastrin concentration, mean pH, and percentage time that gastric pH was strongly acidic (pH <1 and <2) were compared between groups. Results: No significant differences in serum gastrin concentrations were observed between groups (medians [range]: CKD, 18.7 ng/dL [<10–659.0]; healthy, 54.6 ng/dL [<10–98.0]; P-value = 0.713) or of any pH parameters including mean ± SD gastric pH (CKD, 1.8 ± 0.5; healthy, 1.6 ± 0.3; P-value = 0.23). Conclusions and Clinical Importance: These findings suggest that cats with CKD may not have gastric hyperacidity compared to healthy cats and, therefore, may not need acid suppression. Thus, further studies to determine if there is a benefit to acid suppression in cats with CKD are warranted. Authors => M.K. Tolbert | S. Olin | S. MacLane | E. Gould | J.M. Steiner | S. Vaden | J. Price published => First published: 20 August 2017 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.14807

Title => Cell-Free DNA and DNase Activity in Dogs with Immune-Mediated Hemolytic Anemia Abstract => Background: Immune-mediated hemolytic anemia (IMHA) in dogs has a high risk of thrombosis and is associated with marked neutrophilia and necrosis. Cell death and release of neutrophil extracellular traps contribute to increased serum concentrations of cell-free DNA, and in human autoimmune disease reduced DNase activity further increases cell-free DNA. Free DNA in blood has prothrombotic properties and could contribute to hypercoagulability in IMHA. Hypothesis: Cell-free DNA is elevated and DNase activity reduced in dogs with IMHA compared to healthy dogs. Animals: Dogs presenting to two referral hospitals with IMHA (n = 28) and healthy controls (n = 20). Methods: Prospective observational study. Blood was collected and death and thrombotic events occurring in the first 14 days after hospitalization recorded. DNA was extracted from plasma with a commercial kit and quantified by PicoGreen fluorescence. DNase activity of serum was measured by radial diffusion assay. Results: Cell-free DNA was significantly higher in cases (median: 45 ng/mL, range: 10–2334 ng/mL) than controls (26 ng/mL, range 1–151 ng/mL, P = 0.0084). DNase activity was not different between cases and controls (P = 0.36). Four cases died and there were five suspected or confirmed thrombotic events. Cell-free DNA concentration was associated with death (odds ratio for upper quartile versus lower 3 quartiles: 15; 95% confidence interval 1.62–201; P = 0.03) but not thrombosis (P = 0.57). Conclusions and Clinical Importance: Cell-free DNA is elevated in dogs with IMHA and likely reflects increased release rather than impaired degradation of DNA. Cell-free DNA concentration is potentially associated with death and might be a prognostic indicator, but this requires confirmation in a larger population. Authors => U. Jeffery | L. Ruterbories | R. Hanel | D.N. LeVine published => First published: 20 August 2017 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.14808

Title => Clinicopathologic Features and Magnetic Resonance Imaging Findings in 24 Cats With Histopathologically Confirmed Neurologic Feline Infectious Peritonitis Abstract => Background: Feline infectious peritonitis (FIP) is the most common infectious central nervous system (CNS) disease in the cat and is invariably fatal. Improved means of antemortem diagnosis is required to facilitate clinical decision making. Information regarding the magnetic resonance imaging (MRI) findings of neurologic FIP currently is limited, resulting in the need for better descriptions to optimize its use as a diagnostic tool. Objective: To describe the clinicopathologic features and MRI findings in cases of confirmed neurologic FIP. Animals: Twenty-four client-owned cats with histopathologic confirmation of neurologic FIP. Methods: Archived records from 5 institutions were retrospectively reviewed to identify cases with confirmed neurologic FIP that had undergone antemortem MRI of the CNS. Signalment, clinicopathologic, MRI, and histopathologic findings were evaluated. Results: Three distinct clinical syndromes were identified: T3-L3 myelopathy (3), central vestibular syndrome (7), and multifocal CNS disease (14). Magnetic resonance imaging abnormalities were detected in all cases, including meningeal contrast enhancement (22), ependymal contrast enhancement (20), ventriculomegaly (20), syringomyelia (17), and foramen magnum herniation (14). Cerebrospinal fluid was analysed in 11 cases; all demonstrated a marked increase in total protein concentration and total nucleated cell count. All 24 cats were euthanized with a median survival time of 14 days (range, 2–115) from onset of clinical signs. Histopathologic analysis identified perivascular pyogranulomatous infiltrates, lymphoplasmacytic infiltrates, or both affecting the leptomeninges (16), choroid plexuses (16), and periventricular parenchyma (13). Conclusions and Clinical Importance: Magnetic resonance imaging is a sensitive means of detecting neurologic FIP, particularly in combination with a compatible signalment, clinical presentation, and CSF analysis. Authors => A.H. Crawford | A.L. Stoll | D. Sanchez-Masian | A. Shea | J. Michaels | A.R. Fraser | E. Beltran published => First published: 19 August 2017 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.14791

Title => Serum Thymidine Kinase 1, Canine-C-Reactive Protein, Haptoglobin, and Vitamin D Concentrations in Dogs with Immune-Mediated Hemolytic Anemia, Thrombocytopenia, and Polyarthropathy Abstract => Background: Relapses of immune-mediated hemolytic anemia (IMHA), thrombocytopenia (ITP), or polyarthropathy (IMPA) occur despite normal hematologic and cytologic parameters. Thymidine kinase 1 (TK1), canine C-reactive protein (c-CRP), haptoglobin (HPT), and 25-Hydroxyvitamin-D (25(OH)D) might be adjunct to current monitoring strategies. Hypothesis/Objectives: Compare serum concentrations of TK1, c-CRP, HPT, and 25(OH)D in dogs with well- and poorly controlled primary IMHA, ITP, or IMPA. Animals: Thirty-eight client-owned dogs. Methods: Prospective descriptive study. Dogs diagnosed with IMHA, ITP, or IMPA had serum biomarker concentrations measured commercially. Disease control was assessed by hematocrit/PCV and reticulocyte count, platelet count, and synovial fluid cytology for IMHA, ITP, and IMPA, respectively. Statistical analysis performed by Mann-Whitney rank-sum tests and receiver operating characteristic curves. Results: TK1 and c-CRP, but not HPT significantly decreased with well- versus poorly controlled IMHA (P = 0.047, P = 0.028, P = 0.37). C-CRP, but not TK or HPT was significantly lower with well- versus poorly controlled IMPA (P = 0.05, P = 0.28, P = 0.84). Sensitivity and specificity of TK and c-CRP (simultaneously) for detecting dogs with poorly controlled IMHA were 88 and 100%, respectively. Sensitivity and specificity of c-CRP for detecting poorly controlled dogs with IMPA were 13 and 100%, respectively. 92% of dogs were vitamin D insufficient (<100 ng/mL) regardless of disease control. Conclusions and Clinical Importance: Combining TK1 and c-CRP might act markers of disease control in dogs with IMHA. Canine-CRP cannot be recommended as an independent marker of disease control in IMPA. 25(OH)D insufficiency in immune-mediated disorders might benefit from further study to determine if supplementation could improve therapeutic response or reduce disease risk. Authors => M. Grobman | H. Outi | H. Rindt | C. Reinero published => First published: 14 August 2017 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.14787

Title => Pre- and Post-Transfusion Alloimmunization in Dogs Characterized by 2 Antiglobulin-Enhanced Cross-match Tests Abstract => Background: When dogs are transfused, blood compatibility testing varies widely but may include dog erythrocyte antigen (DEA) 1 typing and rarely cross-matching. Objectives: Prospective study to examine naturally occurring alloantibodies against red blood cells (RBCs) and alloimmunization by transfusion using 2 antiglobulin-enhanced cross-match tests. Animals: Eighty client-owned anemic, 72 donor, and 7 control dogs. Methods: All dogs were typed for DEA 1 and some also for DEA 4 and DEA 7. Major cross-match tests with canine antiglobulin-enhanced immunochromatographic strip and gel columns were performed 26–129 days post-transfusion (median, 39 days); some dogs had an additional early evaluation 11–22 days post-transfusion (median, 16 days). Plasma from alloimmunized recipients was cross-matched against RBCs from 34 donor and control dogs. Results: The 2 cross-match methods gave entirely concordant results. All 126 pretransfusion cross-match results for the 80 anemic recipients were compatible, but 54 dogs died or were lost to follow up. Among the 26 recipients with follow-up, 1 dog accidently received DEA 1-mismatched blood and became cross-match-incompatible post-transfusion. Eleven of the 25 DEA 1-matched recipients (44%) became incompatible against other RBC antigens. No naturally occurring anti-DEA 7 alloantibodies were detected in DEA 7− dogs. Conclusions and clinical importance: The antiglobulin-enhanced immunochromatographic strip cross-match and laboratory gel column techniques identified no naturally occurring alloantibodies against RBC antigens, but a high degree of post-transfusion alloimmunization in dogs. Cross-matching is warranted in any dog that has been previously transfused independent of initial DEA 1 typing and cross-matching results before the first transfusion event. Authors => I. Goy-Thollot | U. Giger | C. Boisvineau | R. Perrin | M. Guidetti | B. Chaprier | A. Barthélemy | C. Pouzot-Nevoret | B. Canard published => First published: 14 August 2017 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.14801

Title => Portal Vein/Aorta Ratio in Dogs with Acquired Portosystemic Collaterals Abstract => Background: The portal vein (PV) diameter increases in humans with portal hypertension (PH). However, there is no evidence of PV enlargement in dogs with PH. Objectives: To measure the PV-to-aorta (PV/Ao) ratio in dogs with PH (chronic hepatitis [CH], primary hypoplasia of the PV [PHPV]), in dogs with extrahepatic congenital portosystemic shunt (EH-CPSS), and in healthy dogs, and to evaluate the relationship between PV/Ao ratio and splenic pulp pressure (SPP). Animals: Twenty-five dogs with acquired portosystemic collaterals (APSCs; 15 with CH, 10 with PHPV), 32 dogs with EH-CPSS, and 20 healthy dogs. Methods: Retrospective study. The PV/Ao ratio was calculated with images obtained by computed tomography. SPP was measured at the time of liver biopsy in 45 dogs. Results: Median PV/Ao ratio was similar between dogs with CH (1.35, range 1.05–2.01) and healthy dogs (0.95, 0.80–1.15), but differed significantly between the CH group and both the PHPV (0.40, 0.24–0.67) and EH-CPSS groups (0.30, 0.11–0.64) (P < .001). The PV/Ao ratio was significantly lower in the PHPV group than in healthy dogs (P < .05). It also correlated positively with SPP (rs = 0.71; P < .001). However, there was no intragroup correlation between SPP and the PV/Ao ratio in any group. Conclusions and Clinical Importance: The PV/Ao ratio can be evaluated in dogs with APSCs on computed tomography. Further studies are needed to examine the relationship between SPP and the PV/Ao ratio in larger groups of dogs with PH and to determine its clinical relevance. Authors => Y. Sakamoto | M. Sakai | T. Watari published => First published: 14 August 2017 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.14802

Title => Relationship between Total Homocysteine, Folic Acid, and Thyroid Hormones in Hypothyroid Dogs Abstract => Background: Both elevated homocysteine and decreased folic acid concentrations are observed in human patients with hypothyroidism and can influence the development of numerous secondary disorders. Objectives: The aim of the study was to assess total homocysteine concentration in serum and to examine its relationship with the concentration of folic acid and thyroid hormones (tT4 and fT4). Animals: Ten healthy and 19 hypothyroid client-owned dogs. Methods: Dogs with clinical signs of hypothyroidism had the diagnosis confirmed by additional tests. Total homocysteine, folic acid, total thyroxine, and free thyroxine concentrations in serum were evaluated. Results: Hypothyroid dogs were diagnosed with increased homocysteine (median 22.20 μmol/L; range, 16.50–37.75) and decreased folic acid (median 20.62 nmol/L; range, 10.54–26.35) concentrations, as compared to healthy dogs (11.52 μmol/L; range, 10.00–16.65 and 30.68 nmol/L; range, 22.84–38.52, respectively). In sick dogs, total homocysteine was inversely correlated with folic acid (ρ = −0.47, P < 0.001), total thyroxine (ρ = −0.69, P = 0.0092), and free thyroxine (ρ = −0.56, P = 0.0302). Conclusions: Hypothyroidism in dogs causes hyperhomocysteinemia. Concomitant mild folic acid decrease in hypothyroid dogs might be as a result of hyperhomocysteinemia. Authors => M. Gołyński | K. Lutnicki | W. Krumrych | M. Szczepanik | M. Gołyńska | P. Wilkołek | Ł. Adamek | Ł. Sitkowski | Ł. Kurek published => First published: 14 August 2017 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.14804

Title => Relationship Between β-cell Response and Insulin Sensitivity in Horses based on the Oral Sugar Test and the Euglycemic Hyperinsulinemic Clamp Abstract => Background: A hyperbolic relationship between β-cell response and insulin sensitivity (IS) has been described in several species including rodents, dogs, and humans. This relationship has not been elucidated in the horse. Hypothesis/Objectives: To determine whether the hyperbolic relationship between β-cell response and IS exists in horses by using indices of β-cell response from the oral sugar test (OST) and IS measurements from the euglycemic hyperinsulinemic clamp (EHC). A second aim was to compare how well IS estimates from the OST and EHC correlate. Animals: Forty-nine horses with different degrees of insulin regulation (normal-to-severe insulin dysregulation). Methods: Cross-sectional study. Horses were examined with an OST and an EHC. Results: Decreased IS was associated with increased β-cell response in the horses. Nine of 12 comparisons between indices of β-cell response and IS measures fulfilled the criteria for a hyperbolic relationship. Indices of IS calculated from the OST correlated highly with the insulin-dependent glucose disposal rate (M) and the insulin-dependent glucose disposal rate per unit of insulin (M/I) determined from the EHC (r = 0.81–0.87). Conclusions and Clinical Importance: A hyperbolic relationship between β-cell response and IS exists in horses, which suggest that horses with insulin dysregulation respond not only with postprandial hyperinsulinemia but are also insulin resistant. The OST is primarily a test for β-cell response rather than a test for IS, but calculated indices of IS from the OST may be useful to estimate IS in horses, especially when the horse is insulin resistant. Authors => S. Lindåse | K. Nostell | J. Söder | J. Bröjer published => First published: 10 August 2017 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.14799

Title => Relationship between Device Size and Body Weight in Dogs with Patent Ductus Arteriosus Undergoing Amplatz Canine Duct Occluder Deployment Abstract => Background: Deployment of the Amplatz Canine Duct Occluder (ACDO) is the preferred method for minimally invasive occlusion of patent ductus arteriosus (PDA) in dogs, with appropriate device sizing crucial to successful closure. Dogs of any body weight can be affected by PDA. Objectives: To describe the range of ACDO sizes deployed in dogs of various body weights for improved procedural planning and inventory selection and to investigate for correlation between minimal ductal diameter (MDD) and body weight. Animals: A total of 152 dogs undergoing ACDO deployment between 2008 and 2016. Methods: Body weight, age, breed, sex, and MDD obtained by angiography (MDD-A), MDD obtained by transesophageal echocardiography (MDD-TEE), and ACDO size deployed were retrospectively evaluated. Results: Correlation between body weight and ACDO size, MDD-A and MDD-TEE was poor, with R-squared values of 0.4, 0.36, and 0.3, respectively. Femoral artery diameter in the smallest population of dogs placed inherent limitations on the use of larger device sizes, with no limitations on the wide range of device sizes required as patient size increased. The most commonly used ACDO devices were size 3 through 6, representing 57% of the devices deployed within the entire study population. Conclusions and Clinical Importance: Patent ductus arteriosus anatomy varies on an individual basis, with poor correlation between MDD and body weight. Weight-based assumptions about expected ACDO device size for a given patient are not recommended. Authors => S. Wesselowski | A.B. Saunders | S.G. Gordon published => First published: 07 August 2017 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.14797

Title => Long-Term Management with Adipose Tissue-Derived Mesenchymal Stem Cells and Conventional Treatment in a Dog with Hepatocutaneous Syndrome Abstract => Authors => A. Nam | S.-M. Han | D.-M. Go | D.-Y. Kim | K.-W. Seo | H.-Y. Youn published => First published: 07 August 2017 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.14798

Title => Ciprofloxacin Pharmacokinetics in Clinical Canine Patients Abstract => Background: Ciprofloxacin generic tablets approved for human use frequently are administered to dogs for treatment of bacterial infections because they are inexpensive and readily available. However, previous work indicated low and variable oral absorption in healthy research dogs. Objective: To examine orally administered ciprofloxacin in a group of clinical canine patients using population pharmacokinetics in order to identify minimum inhibitory concentrations (MIC) that potentially could be achieved with orally administered ciprofloxacin in dogs. Animals: Thirty-four clinical canine patients; mean weight, 22.95 kg (range, 4.6–57 kg). Methods: Ciprofloxacin generic tablets intended for human use were administered to dogs in a prospective study (mean dose, 23.5 mg/kg). Sparse blood sampling was used to obtain population pharmacokinetic results with nonlinear mixed-effects modeling. These data were used to estimate a breakpoint for susceptible bacteria. Monte Carlo simulations were used to determine the probability of target attainment (PTA) for an area under the curve (AUC)/MIC ratio of ≥100, the pharmacokinetic-pharmacodynamic target for fluoroquinolones. Results: The values for volume of distribution, peak concentration, and half-life were 10.7 L/kg (11.7%), 1.9 μg/mL (11.66%), and 4.35 hours (7.62%), respectively (mean, % coefficient of variation [CV]). The size of the dog was an important covariate with larger dogs achieving lower plasma drug concentrations than smaller dogs, despite a similar mg/kg dose. Ninety percent PTA was obtained for a MIC ≤ 0.06 μg/mL. Conclusions and Clinical Importance: A breakpoint (susceptible) of ≤0.06 μg/mL should be considered when ciprofloxacin tablets are administered to dogs at a dose of 25 mg/kg once daily, which is much lower than the breakpoint of ≤1 μg/mL in humans. Authors => M.G. Papich published => First published: 03 August 2017 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.14788

Title => Influence of the Respiratory Cycle on Caudal Vena Cava Diameter Measured by Sonography in Healthy Foals: A Pilot Study Abstract => Background: Intravascular volume assessment in foals is challenging. In humans, intravascular volume status is estimated by the caudal vena cava (CVC) collapsibility index (CVC-CI) defined as (CVC diameter at maximum expiration [CVCmax] – CVC diameter at minimal inspiration [CVCmin])/CVCmax × 100%. Hypothesis/Objectives: To determine whether the CVC could be sonographically measured in healthy foals, determine differences in CVCmax and CVCmin, and calculate inter- and intrarater variability between 2 examiners. We hypothesized that the CVC could be measured sonographically at the subxiphoid view and that there would be a difference between CVCmax and CVCmin values. Animals: Sixty privately owned foals <1-month-old. Methods: Prospective study. A longitudinal subxiphoid sonographic window in standing foals was used. The CVCmax and CVCmin were analyzed by a linear mixed effect model. Inter-rater agreement and intrarater variability were expressed by Bland-Altman and intraclass correlation coefficients, respectively. Results: Measurements were attained from 58 of 60 foals with mean age of 15 ± 7.9 days and mean weight of 75.7 ± 17.7 kg. The CVCmax was significantly different from CVCmin (D = 0.515, SE = 0.031, P < 0.001). Inter-rater agreement of the CVC-CI differed by an average of −0.9% (95% limits of agreement, −12.5 to +10.7%). Intrarater variability of CVCmax was 0.540 and 0.545, of CVCmin was 0.550 and 0.594, and of CVC-CI was 0.894 and 0.853 for observers 1 and 2, respectively. Conclusions and Clinical Importance: These results indicate it is possible to reliably measure the CVC sonographically in healthy foals, and the CVC-CI may prove useful in assessing the intravascular volume status in hypovolemic foals. Authors => M.C. Tuplin | A.E. Romero | S.R. Boysen published => First published: 01 August 2017 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.14793

Title => European Veterinary Renal Pathology Service: A Survey Over a 7-Year Period (2008–2015) Abstract => Background: The European Veterinary Renal Pathology Service (EVRPS) is the first Web-based registry for canine renal biopsy specimens in Europe. Hypothesis/Objectives: The aim was to verify whether differences exist between the clinical and laboratory presentation of dogs with nephropathy according to renal pathological findings, as defined by light and electron microscopy of renal biopsy specimens submitted to EVRPS. Animals: Renal biopsy specimens of dogs were collected from the archive of the service (n = 254). Cases were included if both light and electron microscopy were available (n = 162). Methods: Renal biopsy specimens were classified based on the morphological diagnoses. Thereafter, they were grouped into 3 disease categories, including immune-complex-mediated glomerulonephritis (ICGN), non-immune-complex-mediated GN (non-ICGN), and renal lesions not otherwise specified (RL-NOS). Differences among morphological diagnoses and among disease categories were investigated for clinical and laboratory variables. Results: Serum albumin concentration was lower in dogs with ICGN than in those with non-ICGN (P = 0.006) or RL-NOS (P = 0.000), and the urine protein-to-creatinine ratio (UPC) was significantly higher in ICGN than in the other 2 disease categories. Regarding morphological diagnoses, albumin was significantly lower in amyloidosis (AMY) and membranous (MGN), membranoproliferative (MPGN) or mixed glomerulonephritis (MixGN) than in minimal change disease, primary (FSGS I) or secondary (FSGS II) focal and segmental glomerulosclerosis and juvenile nephropathies (JN). The UPC was higher in MPGN than in FSGS I and FSGS II. Conclusions and clinical importance: Dogs with ICGN, in particular MPGN, had higher protein loss than those with non-ICGN or RL-NOS, leading to more severe hypoalbuminemia. Clinical and laboratory differentiation among dogs with the different morphological diagnoses and among dogs with different disease categories was difficult due to overlapping results. Authors => L. Aresu | V. Martini | S.L. Benali | C. Brovida | R.E. Cianciolo | R. Dalla Riva | D. Trez | J.J. Van Der Lugt | A. Van Dongen | E. Zini published => First published: 01 August 2017 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.14796

Title => Diagnostic Utility of Wireless Video-Electroencephalography in Unsedated Dogs Abstract => Background: Poor agreement between observers on whether an unusual event is a seizure drives the need for a specific diagnostic tool provided by video-electroencephalography (video-EEG) in human pediatric epileptology. Objective: That successful classification of events would be positively associated with increasing EEG recording length and higher event frequency reported before video-EEG evaluation; that a novel wireless video-EEG technique would clarify whether unusual behavioral events were seizures in unsedated dogs. Animals: Eighty-one client-owned dogs of various breeds undergoing investigation of unusual behavioral events at 4 institutions. Methods: Retrospective case series: evaluation of wireless video-EEG recordings in unsedated dogs performed at 4 institutions. Results: Electroencephalography achieved/excluded diagnosis of epilepsy in 58 dogs (72%); 25 dogs confirmed with epileptic seizures based on ictal/interictal epileptiform discharges, and 33 dogs with no EEG abnormalities associated with their target events. As reported frequency of the target events decreased (annually, monthly, weekly, daily, hourly, minutes, seconds), EEG was less likely to achieve diagnosis (P < 0.001). Every increase in event frequency increased the odds of achieving diagnosis by 2.315 (95% confidence interval: 1.36–4.34). EEG recording length (mean = 3.69 hours, range: 0.17–22.5) was not associated (P = 0.2) with the likelihood of achieving a diagnosis. Conclusions and Clinical Importance: Wireless video-EEG in unsedated dogs had a high success for diagnosis of unusual behavioral events. This technique offered a reliable clinical tool to investigate the epileptic origin of behavioral events in dogs. Authors => F.M.K. James | M.A. Cortez | G. Monteith | T.S. Jokinen | S. Sanders | F. Wielaender | A. Fischer | H. Lohi published => First published: 31 July 2017 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.14789

Title => Association between Gallbladder Ultrasound Findings and Bacterial Culture of Bile in 70 Cats and 202 Dogs Abstract => Background: Bacterial cholecystitis often is diagnosed by combination of gallbladder ultrasound (US) findings and positive results of bile culture. The value of gallbladder US in determining the likelihood of bile bacterial infection in cats and dogs with suspected biliary disease is unknown. Hypothesis/Objectives: To determine the value of gallbladder US in predicting bile bacterial culture results, identify most common bacterial isolates from bile, and describe complications after cholecystocentesis in cats and dogs with suspected hepatobiliary disease. Animals: Cats (70) and dogs (202) that underwent an abdominal US and submission of bile for culture were included in the study. Methods: A cross-sectional study design was used to determine the association of gallbladder US abnormalities and the results of bile cultures, and complications of cholecystocentesis. Results: Abnormal gallbladder US had high sensitivity (96%) but low specificity (49%) in cats with positive and negative results of bile bacterial culture, respectively. Cats with normal gallbladder US findings were unlikely to have positive bile bacterial culture (negative predictive value of 96%). Gallbladder US had lower sensitivity (81%), specificity (31%), positive predictive value (20%), and negative predictive value (88%) in dogs. The most common bacterial isolates were of enteric origin, the prevalence being higher in cats. Incidence of complications after cholecystocentesis was 3.4%. Conclusions and clinical importance: Gallbladder US has a high negative predictive value for bile culture results in cats. This modality is less predictive of infection in dogs. Percutaneous US-guided cholecystocentesis has a low complication rate. Authors => R. Policelli Smith | J.L. Gookin | W. Smolski | M.F. Di Cicco | M. Correa | G.S. Seiler published => First published: 29 July 2017 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.14792

Title => Randomized, Controlled, Crossover trial of Prevention of Clindamycin-Induced Gastrointestinal Signs Using a Synbiotic in Healthy Research Cats Abstract => Background: Synbiotics often are prescribed to limit antibiotic-associated gastrointestinal signs (AAGS) in cats, but data to support this recommendation are lacking. Objective: To determine whether synbiotic co-administration mitigates AAGS in healthy research cats treated with clindamycin. Animals: 16 healthy research cats. Methods: A randomized, double-blinded, placebo-controlled, 2-way, 2-period, crossover study with a 6-week washout was performed. Each study period consisted of a 1-week baseline and a 3-week treatment period. Cats received 75 mg clindamycin with food once daily for 3 weeks, followed 1 hour later by either 2 capsules of a synbiotic or placebo. Food consumption, vomiting, fecal score, and completion of treatment were compared using repeated measures split plot or crossover designs with covariates, with P < 0.05 considered significant. Results: Cats that received the synbiotic were more likely to complete treatment in period 1 (100% vs. 50%, P = 0.04). Cats vomited less when receiving the synbiotic but this was not significant, but there were significant period effects (F-value = 11.4, P < 0.01). Cats had higher food intake while receiving the synbiotic (F-value = 31.1, P < 0.01) despite period effects (F-value = 8.6, P < 0.01). There was no significant effect of treatment on fecal scores, which significantly increased over time (F-value = 17.9, P < 0.01). Conclusions and Clinical Importance: Administration of a synbiotic 1 hour after clindamycin administration decreased hyporexia and vomiting in healthy cats. Additionally, significant period effects suggest that clinical benefits of synbiotic administration persist for at least 6 weeks after discontinuation, decreasing the severity of AAGS in cats that subsequently received clindamycin with placebo. Unlike in people, synbiotic administration did not decrease antibiotic-associated diarrhea. Authors => J.E. Stokes | J.M. Price | J.C. Whittemore published => First published: 29 July 2017 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.14795

Title => Hypophysitis, Panhypopituitarism, and Hypothalamitis in a Scottish Terrier Dog Abstract => Authors => L. Polledo | M. Oliveira | J. Adamany | P. Graham | K. Baiker published => First published: 26 July 2017 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.14790

Title => 2017 ACVIM Forum Research Report Program Abstract => None Abstract Authors => published => First published: 20 July 2017 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.14784

Title => Paroxysmal Dyskinesia in Border Terriers: Clinical, Epidemiological, and Genetic Investigations Abstract => Background: In the last decade, a disorder characterized by episodes of involuntary movements and dystonia has been recognized in Border Terriers. Objectives: To define clinical features of paroxysmal dyskinesia (PD) in a large number of Border Terriers and to study the genetics of the disease. Animals: 110 affected and 128 unaffected client-owned Border Terriers. Methods: A questionnaire regarding clinical characteristics of PD was designed at Utrecht University and the University of Helsinki. Thirty-five affected Border Terriers underwent physical examination and blood testing (hematology and clinical biochemistry). Diagnostic imaging of the brain was performed in 17 affected dogs and electroencephalograms (EEG) between episodes were obtained in 10 affected dogs. A genomewide association study (GWAS) was performed with DNA of 110 affected and 128 unaffected dogs. Results: One hundred forty-seven questionnaires were included in the study. The most characteristic signs during episodes were dystonia, muscle fasciculations, and falling over. The majority of owners believed that their dogs remained conscious during the episodes. A beneficial effect of anti-epileptic therapy was observed in 29 of 43 dogs. Fifteen owners changed their dogs’ diet to a hypoallergenic, gluten-free diet, and all reported reasonable to good improvement of signs. Clinical examinations and diagnostic test results were unremarkable. The GWAS did not identify significantly associated chromosome regions. Conclusions and Clinical Importance: The survey results and EEG studies provided further evidence that the observed syndrome is a PD rather than epilepsy. Failure to achieve conclusive results by GWAS indicates that inheritance of PD in Border Terriers probably is complex. Authors => Q.E.M. Stassen | L.L.E. Koskinen | F.G. van Steenbeek | E.H. Seppälä | T.S. Jokinen | P.G.M. Prins | H.G.J. Bok | M.M.J.M. Zandvliet | M. Vos-Loohuis | P.A.J. Leegwater | H. Lohi published => First published: 13 July 2017 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.14731

Title => Chronic Diarrhea in Dogs – Retrospective Study in 136 Cases Abstract => Background: Chronic diarrhea (CD) is common in dogs, and information on frequency and distribution of primary and secondary causes is lacking. Objectives: To evaluate underlying causes and predictors of outcome in dogs with CD. Animals: One hundred and thirty-six client-owned dogs with CD (≥3 weeks duration). Methods: Retrospective review of medical records (Small Animal Clinic, Freie Universität Berlin, Germany, 09/2009-07/2011). Quantification of final diagnoses and comparison of clinical aspects including disease severity and clinicopathological abnormalities among dogs with clinical remission (either complete [gastrointestinal signs absent] or partial [clinical improvement of gastrointestinal signs and reduced episodes with shortened duration]), and those without recovery. Results: Ninety percent of dogs were diagnosed with a primary enteropathy: inflammatory (71%; of those 66% dietary responsive, 23% idiopathic, 11% antibiotic responsive), infectious (13%), neoplastic (4%), and in one dog each mechanical disease or systemic vasculitis. Secondary causes were diagnosed in 10% of dogs: exocrine pancreatic (6%), endocrine (2%), and in one dog each hepatic, renal, and cardiac disease. In total, 87% of dogs had clinical remission, whereas 13% died or did not respond to treatment: Lack of recovery was frequently recorded for dogs with primary inflammatory (idiopathic) or neoplastic disease and was significantly associated with increased disease severity scores (P = .005), anemia (hematocrit < 40%, P < .001), severe hypoalbuminemia (serum albumin <2.0 g/dL, P = .008), and severe hypocobalaminemia (serum cobalamin concentration <200 pg/mL, P = .006). Conclusions and clinical importance: Inflammatory enteropathies and particularly those of dietary origin were the most common causes of CD in dogs. Findings support the usefulness of hematocrit, and serum albumin and cobalamin concentration as prognostic markers in dogs with CD. Authors => M. Volkmann | J.M. Steiner | G.T. Fosgate | J. Zentek | S. Hartmann | B. Kohn published => First published: 13 July 2017 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.14739

Title => Letter to the Editor Abstract => None Abstract Authors => A. Willems DVM, DECVIM-CA | D. Paepe DVM, DECVIM-CA | S. Daminet DVM, DECVIM-CA, DACVIM published => First published: 04 July 2017 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.14785

Title => Letter to the Editor Abstract => None Abstract Authors => B. McKenzie MA, MSc, VMD published => First published: 04 July 2017 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.14786

Title => Effects of Benazepril on Survival of Dogs with Chronic Kidney Disease: A Multicenter, Randomized, Blinded, Placebo-Controlled Clinical Trial Abstract => Background: Chronic kidney disease (CKD) is an important cause of morbidity and mortality in dogs. Objective: To evaluate the efficacy in prolonging survival and safety of benazepril administration to dogs with CKD. Animals: Forty-nine client-owned dogs with CKD. Methods: Dogs were randomized to benazepril (0.25 to <0.5 mg/kg) or placebo once daily for up to 2 years in a prospective, multicenter, blinded clinical trial. The primary endpoint variable was the renal survival time, defined as the time from inclusion in the study to the treatment failure endpoint of death or euthanasia or need for administration of parenteral fluids related to renal failure. Results: No benefit of benazepril versus placebo was detected for renal survival time in all dogs; median (95% confidence interval (CI)) survival times were 305 (53–575) days in the benazepril group and 287 (152-not available) in the placebo group (P = .53). Renal survival times were not significantly longer with benazepril compared to placebo for subgroups: hazard ratios (95% CI) were 0.50 (0.21–1.22) with P = .12 for initial urine protein-to-creatinine ratio (UPC) >0.5, and 0.38 (0.12–1.19) with P = .080 for initial UPC >0.5 plus plasma creatinine ≤440 μmol/L. Proteinuria, assessed from the UPC, was significantly (P = .0032) lower after treatment with benazepril compared to placebo. There were no significant differences between groups for clinical signs or frequencies of adverse events. Conclusions and Clinical Relevance: Benazepril significantly reduced proteinuria in dogs with CKD. Insufficient numbers of dogs were recruited to allow conclusions on survival time. Authors => J.N. King | A. Font | J.-F. Rousselot | R.A. Ash | U. Bonfanti | C. Brovida | I.D. Crowe | D. Lanore | D. Pechereau | W. Seewald | G. Strehlau published => First published: 01 July 2017 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.14726

Title => The Effect of Geographic Location on Circannual Adrenocorticotropic Hormone Plasma Concentrations in Horses in Australia Abstract => Background: Longitudinal evaluation of plasma endogenous ACTH concentration in clinically normal horses has not been investigated in the Southern Hemisphere. Objectives: To longitudinally determine monthly upper reference limits for plasma ACTH in 2 disparate Australian geographic locations and to examine whether location affected the circannual rhythm of endogenous ACTH in the 2 groups of horses over a 12-month period. Animals: Clinically normal horses <20 years of age from 4 properties (institutional herd and client owned animals) in Perth (n = 40) and Townsville (n = 41) were included in the study. Methods: A prospective longitudinal descriptive study to determine the upper reference limit and confidence intervals for plasma ACTH in each geographic location using the ASVCP reference interval (RI) guidelines, for individual months and monthly groupings for 12 consecutive months. Results: Plasma endogenous ACTH concentrations demonstrated a circannual rhythm. The increase in endogenous ACTH was not confined to the autumnal months but was associated with changes in photoperiod. During the quiescent period, plasma ACTH concentrations were lower, ≤43 pg/mL (upper limit of the 90% confidence interval (CI)) in horses from Perth and ≤67 pg/mL (upper limit of the 90% CI) in horses from Townsville, than at the acrophase, ≤94 pg/mL (upper limit of the 90% CI) in horses from Perth, ≤101 pg/mL (upper limit of the 90% CI) in horses from Townsville. Conclusions and Clinical Importance: Circannual rhythms of endogenous ACTH concentrations vary between geographic locations, this could be due to changes in photoperiod or other unknown factors, and upper reference limits should be determined for specific locations. Authors => C.J. Secombe | R.H.H. Tan | D.I. Perara | D.P. Byrne | S.P. Watts | J.G. Wearn published => First published: 29 June 2017 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.14782

Title => Prevalence of Methicillin-Resistant Staphylococcus aureus from Equine Nasopharyngeal and Guttural Pouch Wash Samples Abstract => Background: Methicillin-resistant Staphylococcus aureus (MRSA) is recognized as a cause of nosocomial infections in both human and veterinary medicine. Studies that examine the nasopharynx and guttural pouches of the horse as carriage sites for MRSA have not been reported. Hypothesis/Objective: MRSA colonizes the nasopharynx and guttural pouch of horses. To determine the prevalence of MRSA in equine nasopharyngeal wash (NPW) and guttural pouch lavage (GPL) samples in a field population of horses. Samples: One hundred seventy-eight samples (123 NPW and 55 GPL) from 108 horses. Methods: Prospective study. Samples were collected from a convenience population of clinically ill horses with suspected Streptococcus equi subsp. equi (S. equi) infection, horses convalescing from a known S. equi infection, and asymptomatic horses undergoing S. equi screening. Samples were submitted for S. aureus aerobic bacterial culture with mannitol salt broth and two selective agars (cefoxitin CHROMagar as the PBP2a inducer and mannitol salt agar with oxacillin). Biochemical identification of Staphylococcus species and pulsed-field gel electrophoresis (PFGE), to determine clonal relationships between isolates, were performed. Results: Methicillin-resistant Staphylococcus (MRS) was isolated from the nasopharynx of 7/108 (4%) horses. Three horses had MRSA (2.7%), and 4 had MR-Staphylococcus pseudintermedius (MRSP). MRSA was isolated from horses on the same farm. PFGE revealed the 3 MRSA as USA 500 strains. Conclusions and Clinical Importance: Sampling the nasopharynx and guttural pouch of community-based horses revealed a similarly low prevalence rate of MRSA as other studies sampling the nares of community-based horses. More study is required to determine the need for sampling multiple anatomic sites when screening horses for MRSA. Authors => A.G. Boyle | S.C. Rankin | L.A. Duffee | D. Morris published => First published: 29 June 2017 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.14783

Title => Erratum Abstract => None Abstract Authors => published => First published: 20 June 2017 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.14772

Title => Evaluation of Serum 3-Bromotyrosine Concentrations in Dogs with Steroid-Responsive Diarrhea and Food-Responsive Diarrhea Abstract => Background: The clinical usefulness of serum 3-BrY concentrations for subclassifying dogs with food-responsive diarrhea (FRD) and steroid-responsive diarrhea (SRD) has not been studied. Hypothesis/Objectives: To compare serum 3-BrY concentrations in dogs with FRD, dogs with SRD, and healthy control dogs. Animals: 38 dogs with FRD, 14 dogs with SRD, and 46 healthy dogs. Methods: Prospective study. Measurement of 3-BrY concentration in serum samples was performed by gas chromatography/mass spectrometry. Results: There was no association of peripheral eosinophilia in dogs with FRD, SRD, and healthy control dogs (P = 0.069). There was no significant correlation between peripheral eosinophil counts and serum 3-BrY concentrations (ρ = −0.15, P = 0.13). Serum 3-BrY concentrations in dogs with SRD (median [range] = 3.27, 0.9–26.23 μmol/L) were significantly higher than in dogs with FRD (median [range] = 0.99, 0.62–8.82 μmol/L; P = 0.007) or in healthy dogs (median [range] = 0.62, 0.62–1.79 μmol/L; P < 0.001). Also, serum 3-BrY concentrations in dogs with FRD were significantly higher than in healthy dogs (P = 0.025). There was no significant correlation between the canine chronic enteropathy clinical activity index and serum 3-BrY concentrations (ρ = 0.17, P = 0.23). Conclusions and Clinical Importance: Measurement of serum 3-BrY concentrations, but not the peripheral eosinophil count, is helpful for detecting dogs with SRD and FRD. Authors => P. Sattasathuchana | K. Allenspach | R. Lopes | J.S. Suchodolski | J.M. Steiner published => First published: 19 June 2017 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.14742

Title => Whole-Blood Taurine Concentrations in Cats With Intestinal Disease Abstract => Background: Increased delivery of taurine-conjugated bile acids to the distal bowel can lead to dysbiosis resulting in colitis in mouse models of inflammatory bowel disease. A similar situation also could occur in cats with intestinal disease and might therefore result in decreased whole-body taurine concentration. Hypothesis/Objectives: To determine whether whole-blood taurine concentrations are decreased at the time of diagnosis in cats with intestinal disease and to correlate concentrations with clinical and laboratory variables. Animals: Twenty-one cats with chronic inflammatory enteropathy and 7 cats with intestinal neoplasia from the University of Bristol. Methods: Cats that had undergone a thorough investigation consisting of a CBC, serum biochemistry, serum cobalamin and folate concentrations, transabdominal ultrasound examination and histopathology of intestinal biopsy specimens, as well as additional testing if indicated, were included. Whole-blood from these cats collected at the time of histologic diagnosis and stored in ethylenediaminetetraacetic acid was retrospectively analyzed for taurine with an automated high-performance liquid chromatography amino acid analyzer. Results: Although whole-blood taurine concentrations remained within the reference range, those cats with predominantly large intestinal clinical signs had significantly lower concentrations than did cats with small intestinal and mixed bowel clinical signs (P = 0.033) and this difference also was significant when assessed only in cats with chronic inflammatory enteropathy (P = 0.019). Conclusions and Clinical Importance: Additional studies are needed to determine whether large intestinal signs in cats with chronic inflammatory enteropathy are caused by alterations in the microbiota arising as a consequence of increased delivery of taurine-conjugated bile acids. Authors => A. Kathrani | A.J. Fascetti | J.A. Larsen | C. Maunder | E.J. Hall published => First published: 19 June 2017 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.14773

Title => Pharmacokinetics and Relative Bioavailability of Orally Administered Innovator-Formulated Itraconazole Capsules and Solution in Healthy Dogs Abstract => Background: Itraconazole is commonly used for treatment of systemic and cutaneous mycoses in veterinary medicine. Two formulations, capsule and solution, are used interchangeably in dogs. However, marked differences in bioavailability have been reported in other species. Similar investigations have not been performed in dogs. Objective: To determine and compare pharmacokinetics of itraconazole in dogs after oral administration of commercially available capsule and solution formulations intended for use in humans. Animals: Eight healthy, adult, purpose-bred dogs. Methods: Dogs received approximately 10 mg/kg of innovator-formulated itraconazole solution and capsule PO in randomized, crossover design with a 10-day washout period. To ensure maximal absorption, solution was administered to fasted dogs, whereas capsules were co-administered with food. Blood samples were collected at predetermined time points, and plasma drug concentrations were measured using high-pressure liquid chromatography. Pharmacokinetic parameters were determined with compartmental analysis. Results: The mean relative bioavailability of the capsule was 85% that of the solution, but drug absorption was variable, and overall drug concentrations were similar between formulations. Mean elimination half-lives of both formulations were nearly identical at approximately 33 hours. Regardless of formulation, simulations suggest that a loading dose of 20 mg/kg, followed by 10 mg/kg once every 24 hours, will result in plasma concentrations considered to be adequate in most dogs. Conclusions and Clinical Importance: Contrary to findings reported in other species, overall drug exposures after capsule and solution administration are not substantially different in dogs. Despite some pharmacokinetic differences between itraconazole capsule and solution, formulation-specific dosages do not appear to be necessary. Authors => A.E. Hasbach | D.K. Langlois | E.J. Rosser | M.G. Papich published => First published: 19 June 2017 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.14779

Title => Letter to the Editor Abstract => None Abstract Authors => P.R. Fox DVM, DACVIM (Cardiology) | M.D. Kittleson DVM, PhD, DACVIM (Cardiology) | C. Basso MD, PhD, FESC | G. Thiene MD, FCRP, FESC published => First published: 19 June 2017 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.14780

Title => Letter to the Editor Abstract => None Abstract Authors => T. Ishikawa DVM, PhD | N. Makita MD, PhD | H. Aoki DVM | Y. Saida DVM, PhD published => First published: 19 June 2017 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.14781

Title => Efficacy of Azithromycin and Compounded Atovaquone for Treatment of Babesia gibsoni in Dogs Abstract => Background: Approximately one-third of dogs confiscated during dogfighting investigations are infected with Babesia gibsoni. Traditional management of B. gibsoni with polymerase chain reaction (PCR)-screening, treatment with commercially available azithromycin and atovaquone, and PCR testing after 60 and 90 days is costly and impractical for large numbers of dogs at a time. Hypothesis/Objectives: To assess the efficacy of an alternative protocol in which commercial atovaquone was replaced by compounded medication and PCR monitoring was initiated at 30 days after the end of treatment to decrease the total management time. Methods: Prospective observational study. Forty-two pit bull-type dogs confiscated as part of an investigation of dogfighting, diagnosed with B. gibsoni infection, and judged to be suitable for adoption were treated with azithromycin (10 mg/kg PO q24h) and compounded atovaquone (13.4 mg/kg PO q8h with a fatty meal) for 10 days. PCR testing was repeated at 30 and 60 days after end of treatment if dogs with positive PCR tests at either time were tested at 90 days. Treatment was considered successful; 2 PCR tests 30 days apart were negative. Results: Treatment was successful in 39 dogs (93%) as defined by 2 consecutive PCR-negative test results 30 days apart. In 38 dogs (90%), PCR results were the same at 30 and 60 days. Conclusions and Clinical Importance: Use of compounded atovaquone and a reduced monitoring period can reduce costs and holding times without compromising treatment efficacy. This more economical protocol can remove barriers to mass screening and management of B. gibsoni infections in dogfighting cases. Authors => S.K. Kirk | J.K. Levy | P.C. Crawford published => First published: 17 June 2017 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.14777

Title => Investigation of an N-Terminal Prohormone of Brain Natriuretic Peptide Point-of-Care ELISA in Clinically Normal Cats and Cats With Cardiac Disease Abstract => Background: N-terminal prohormone of brain natriuretic peptide (NT-proBNP) concentrations may be increased in cats with various cardiac disorders. The point-of-care (POC) ELISA assay uses the same biologic reagents as the quantitative NT-proBNP ELISA. Previous studies have evaluated the sensitivity and specificity of the POC ELISA in cats with cardiac disease. Objectives: To prospectively evaluate the diagnostic utility of the POC ELISA in a select population of cats. Animals: Thirty-eight client-owned cats presented to the University of Florida Cardiology Service for cardiac evaluation. Fifteen apparently healthy cats recruited as part of another study. Methods: Physical examination and echocardiography were performed in all cats. The POC ELISA was assessed visually as either positive or negative by a reader blinded to the echocardiographic findings, and results were analyzed relative to quantitative assay results. Results: Twenty-six cats were diagnosed with underlying cardiac disease, and 27 cats were considered free of cardiac disease. Cats with cardiac disease included: 21 with hypertrophic cardiomyopathy, 2 with unclassified cardiomyopathy, 2 with restrictive cardiomyopathy, and 1 with 3rd degree atrioventricular (AV) block. The POC ELISA differentiated cats with cardiac disease with a sensitivity of 65.4% and specificity of 100%. Conclusions and Clinical Importance: The POC NT-proBNP ELISA performed moderately well in a selected population of cats. A negative test result cannot exclude the presence of underlying cardiac disease, and a positive test result indicates that cardiac disease likely is present, but further diagnostic investigation would be indicated for a definitive diagnosis. Authors => A.N. Harris | S.S. Beatty | A.H. Estrada | B. Winter | M. Bohannon | I. Sosa | J. Hanscom | C.A. Mainville | A.E. Gallagher published => First published: 15 June 2017 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.14776

Title => 2017 ACVIM Forum Research Abstract Program Abstract => None Abstract Authors => published => First published: 15 June 2017 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.14778

Title => Breed, Coat Color, and Hair Length as Risk Factors for Hyperthyroidism in Cats Abstract => Background: Hyperthyroidism is very common in older cats, but the etiopathogenesis is poorly understood. Decreased risk of hyperthyroidism has been reported in certain colorpoint breeds, and this observation previously has been hypothesized to result from relatively greater tyrosine availability for thyroid hormone production because of limited ability to convert tyrosine to melanin pigment. However, studies investigating a potential link between coat pigmentation and risk of hyperthyroidism are limited. Objective: To identify associations between coat phenotype and hyperthyroidism by investigation of breed, coat color, and hair length as risk factors for the disease. Animals: Data were used from 4,705 cats aged ≥10 years, referred to a single veterinary teaching hospital (2006–2014) in the United Kingdom. Methods: Retrospective, epidemiological, cross-sectional study using Bayesian multivariable logistic regression to assess risk factors for hyperthyroidism. Results: Burmese (odds ratio [OR], 0.01; 0.00–0.23; P = .004), Tonkinese (OR, 0.05; 0.00–0.95; P = .046), Persian (OR, 0.21; 0.10–0.44; P < .001), Siamese (OR, 0.27; 0.12–0.61; P = .002), Abyssinian (OR, 0.04; 0.00–0.74; P = .031), and British shorthair (OR, 0.47; 0.28–0.79; P = .004) breeds had decreased risk of hyperthyroidism compared to domestic shorthairs. Longhaired, nonpurebred cats (OR, 1.30; 1.03–1.64; P = .028) were at increased risk of hyperthyroidism. Coat color/pattern was not associated with hyperthyroidism in nonpurebred cats. Conclusions and Clinical Importance: We identified decreased risk of hyperthyroidism in the Tonkinese, Abyssinian, and British shorthair breeds, identified an association between risk of hyperthyroidism and hair length, and confirmed decreased risk in Burmese, Siamese, and Persian breeds. Additional studies are warranted to further investigate these findings. Authors => V.J. Crossley | A. Debnath | Y.M. Chang | R.C. Fowkes | J. Elliott | H.M. Syme published => First published: 13 June 2017 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.14737

Title => Use of a Granulocyte Immunofluorescence Assay Designed for Humans for Detection of Antineutrophil Cytoplasmic Antibodies in Dogs with Chronic Enteropathies Abstract => Background: Perinuclear antineutrophil cytoplasmic antibodies (pANCA) previously have been shown to be serum markers in dogs with chronic enteropathies, with dogs that have food-responsive disease (FRD) having higher frequencies of seropositivity than dogs with steroid-responsive disease (SRD). The indirect immunofluorescence (IIF) assay used in previous publications is time-consuming to perform, with low interobserver agreement. Hypothesis/Objectives: We hypothesized that a commercially available granulocyte IIF assay designed for humans could be used to detect perinuclear antineutrophil cytoplasmic antibodies in dogs. Animals: Forty-four dogs with FRD, 20 dogs with SRD, 20 control dogs, and 38 soft-coated wheaten terrier (SCWT) or SCWT-cross dogs. Methods: A granulocyte assay designed for humans was used to detect pANCA, cANCA, and antinuclear antibodies (ANA), as well as antibodies against proteinase-3 protein (PR-3) and myeloperoxidase protein (MPO) in archived serum samples. Results: Sensitivity of the granulocyte assay to predict FRD in dogs was 0.61 (95% confidence interval (CI), 0.45, 0.75), and specificity was 1.00 (95% CI, 0.91, 1.00). A significant association was identified between positive pANCA or cANCA result and diagnosis of FRD (P < 0.0001). Agreement between the two assays to detect ANCA in the same serum samples from SCWT with protein-losing enteropathy/protein-losing nephropathy (PLE/PLN) was substantial (kappa, 0.77; 95% CI, 0.53, 1.00). Eight ANCA-positive cases were positive for MPO or PR-3 antibodies. Conclusions and Clinical Importance: The granulocyte immunofluorescence assay used in our pilot study was easy and quick to perform. Agreement with the previously published method was good. Authors => J. Florey | A. Viall | S. Streu | V. DiMuro | A. Riddle | J. Kirk | L. Perazzotti | K. Affeldt | R. Wagner | S. Vaden | T. Harris | K. Allenspach published => First published: 13 June 2017 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.14774

Title => Cardiac and Metabolic Variables in Obese Dogs Abstract => Background: The etiology of obesity-related cardiac dysfunction (ORCD) is linked to metabolic syndrome in people. Studies have indicated that obese dogs have components of metabolic syndrome, warranting evaluation for ORCD in obese dogs. Objectives: To evaluate cardiac structure and function and metabolic variables in obese dogs compared to ideal weight dogs. Animals: Forty-six healthy, small-breed (<25 pounds), obese dogs (n = 29) compared to ideal weight dogs (n = 17). Methods: A cross-sectional study of cardiac structure and function by standard and strain echocardiographic measurements and quantification of serum metabolic variables (insulin:glucose ratios, lipid analysis, adiponectin, inflammatory markers). Results: Compared to the ideal weight controls, obese dogs had cardiac changes characterized by an increased interventricular septal width in diastole to left ventricular internal dimension in diastole ratio, decreased ratios of peak early to peak late left ventricular inflow velocities, and ratios of peak early to peak late mitral annular tissue velocities, and increased fractional shortening and ejection fraction percentages. The left ventricular posterior wall width in diastole to left ventricular internal dimension in diastole ratios were not significantly different between groups. Systolic blood pressure was not significantly different between groups. Obese dogs had metabolic derangements characterized by increased insulin:glucose ratios, dyslipidemias with increased cholesterol, triglyceride, and high-density lipoprotein concentrations, decreased adiponectin concentrations, and increased concentrations of interleukin 8 and keratinocyte-derived chemokine-like inflammatory cytokines. Conclusions and Clinical Importance: Compared to ideal weight controls, obese dogs have alterations in cardiac structure and function as well as insulin resistance, dyslipidemia, hypoadiponectinemia, and increased concentrations of inflammatory markers. These findings warrant additional studies to investigate inflammation, dyslipidemia, and possibly systemic hypertension as potential contributing factors for altered cardiac function. Authors => M. Tropf | O.L. Nelson | P.M. Lee | H.Y. Weng published => First published: 13 June 2017 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.14775

Title => Evaluation of Mollicutes Microorganisms in Respiratory Disease of Cattle and Their Relationship to Clinical Signs Abstract => Background: Bovine respiratory disease (BRD) is an important problem in cattle production that is responsible for economic losses in dairy herds. Mycoplasma spp. are described as an important etiological agent of BRD. Hypothesis: To evaluate the occurrence of the most important mycoplasmas in the lower respiratory tract of healthy and BRD cattle in relationship to clinical signs of BRD. Animals: Sixty young dairy cattle were classified as healthy (n = 32) or cattle showing clinical signs of BRD (n = 28). Methods: Tracheal lavage samples were collected and added to tubes containing Hayflick media. Mycoplasma spp. were identified by the presence of “fried egg” like colonies, biochemical tests and polymerase chain reaction (PCR). Occurrence of Mollicutes, M. bovis, M. mycoides subsp. mycoides SC and M. dispar was evaluated. The association between clinical signs of BRD and the presence of Mycoplasma spp. also was evaluated. Results: Colonies were obtained from a 1-year-old BRD calf only. However, species identification was not possible. Mollicutes (P = .035) and M. dispar (P = .036) were more common in BRD cattle. The relationship between Mollicutes and crackle (P = .057) was not significant. M. dispar was associated to tachypnea (P = .045) and mixed dyspnea (P = .003). Relationships to heart rate (P = .062) and crackle (P = .062) were not significant. Conclusions and clinical importance: The results confirmed the importance of mycoplasma as an etiologic agent of BRD and suggested M. dispar as part of the respiratory microbiota and its possible role in the development of BRD. Authors => G. Tortorelli | N. Carrillo Gaeta | B.L. Mendonça Ribeiro | L. Miranda Marques | J. Timenetsky | L. Gregory published => First published: 10 June 2017 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.14721

Title => Mitral Regurgitation Severity and Left Ventricular Systolic Dimension Predict Survival in Young Cavalier King Charles Spaniels Abstract => Background: Development and progression of myxomatous mitral valve disease (MMVD) in dogs are difficult to predict. Identification at a young age of dogs at high risk of adverse outcome in the future is desirable. Hypothesis/Objectives: To study the predictive value of selected clinical and echocardiographic characteristics associated with MMVD obtained at a young age for prediction of long-term cardiac and all-cause mortality in Cavalier King Charles Spaniels (CKCS). Animals: 1125 privately owned CKCS. Methods: A retrospective study including CKCS examined at the age of 1–3 years. Long-term outcome was assessed by telephone interview with owners. The value of variables for predicting mortality was investigated by Cox proportional hazard and Kaplan-Meier analyses. Results: Presence of moderate to severe mitral regurgitation (MR) (hazard ratio (HR) = 3.03, 95% confidence interval (95% CI) = 1.48–6.23, P = 0.0025) even intermittent moderate to severe MR (HR = 2.23, 95% CI = 1.48–6.23, P = 0.039) on color flow Doppler echocardiography was significantly associated with increased hazard of cardiac death. An interaction between MR and sex was significant for all-cause mortality (P = 0.035), showing that males with moderate to severe MR had a higher all-cause mortality compared to males with no MR (HR = 2.38, 95% CI = 1.27–4.49, P = 0.0071), whereas no difference was found between female MR groups. The risk of cardiac (HR = 1.37, 95% CI = 1.14–1.63, P < 0.001) and all-cause (HR = 1.13, 95% CI = 1.02–1.24, P = 0.016) mortality increased with increasing left ventricular end-systolic internal dimension normalized for body weight (LVIDSN). Conclusions and clinical importance: Moderate to severe MR, even if intermittent, and increased LVIDSN in dogs <3 years of age were associated with cardiac death later in life in CKCS. Authors => M.J. Reimann | J.E. Møller | J. Häggström | T. Martinussen | S.S.C. Zatrazemi | L. Svanholm | L.B.M. Nielsen | H.D. Pedersen | L.H. Olsen published => First published: 01 June 2017 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.14759

Title => Effect of Dexamethasone and Fluticasone on Airway Hyperresponsiveness in Horses With Inflammatory Airway Disease Abstract => Background: Airway hyperresponsiveness (AWHR), expressed as hypersensitivity (PC75RL) or hyperreactivity (slope of the histamine dose-response curve), is a feature of inflammatory airway disease (IAD) or mild equine asthma in horses. Glucocorticoids are used empirically to treat IAD. Objectives: To determine whether dexamethasone (DEX) (0.05 mg/kg IM q24h) and inhaled fluticasone (FLUT) (3,000 μg q12h) administered by inhalation are effective in decreasing AWHR, lung inflammation, and clinical signs in horses with IAD. Methods: A randomized crossover study design was used. Eight horses with IAD were assigned to a treatment group with either DEX or FLUT. Measured outcomes included lung mechanics during bronchoprovocative challenges, bronchoalveolar lavage fluid (BALF) cytology, and scoring of clinical signs during exercise. Results: Dexamethasone and FLUT abolished the increase in RL by 75% at any histamine bronchoprovocative dose in all horses after the first week of treatment. However, after 2 weeks of FLUT treatment, 1 horse redeveloped hypersensitivity. There was a significant decrease in the number of lymphocytes after treatment with both DEX and FLUT (P = .039 for both) but no significant differences in other BALF cell types or total cell counts (P > .05). There was no difference in the scoring of the clinical signs during each treatment and washout period (P > .05). Conclusions and Clinical Importance: Both DEX and FLUT treatments significantly inhibit airway hypersensitivity and hyperreactivity in horses with IAD. There are no significant effects on the clinical signs or the number of inflammatory cells (except lymphocytes) in BALF. The treatments have no residual effect 3 weeks after discontinuation. Authors => R. Léguillette | T. Tohver | S.L. Bond | J.A. Nicol | K.J. McDonald published => First published: 31 May 2017 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.14740

Title => Validation of a Point-of-Care Quantitative Equine IgG Turbidimetric Immunoassay and Comparison of IgG Concentrations Measured with Radial Immunodiffusion and a Point-of-Care IgG ELISA Abstract => Background: Point-of-care (POC) diagnostic tests with good sensitivity and specificity are needed for diagnosing failure of transfer of passive immunity (FTPI) in foals. Turbidimetric immunoassays (TIA) have these characteristics and provide quantitative results. A commercially available TIA-based POC test (POC-TIA) has not been validated in horses. Objective: To validate a POC-TIA and compare results of POC-TIA, a POC-ELISA, and radial immunodiffusion (RID). Animals: Heparinized blood samples (n = 127) from 48 hospitalized foals (<12 hour to 48 days). Methods: Prospective validation study. IgG concentrations were measured using RID (gold standard), POC-TIA, and POC-ELISA. Agreement between assays was assessed using Bland–Altman analysis. Sensitivity and specificity were calculated using ROC curves. Inter- and intra-assay coefficients of variation (CVs) and linearity were evaluated for POC-TIA. Results: The mean bias (95% limits of agreement) between RID and POC-TIA was −4 (−185 to 176), 27 (−201 to 255), and 308 (−377 to 993) mg/dL for samples with IgG concentrations of <400, 400–800, and >800 mg/dL, respectively. Sensitivity and specificity at optimal cutoff were 94 and 100% for the POC-TIA and 94 and 100% for the POC-ELISA to detect IgG <400 mg/dL, and 85 and 87% (POC-TIA) and 69 and 79% (POC-ELISA) to detect IgG ≤800 mg/dL. Intra- and interassay CVs for POC-TIA ranged between 1.6–3.8 and 11.9–18.8%, respectively. Linearity of the dilution series was preserved (R2 > 0.96). Conclusions and Clinical Importance: The POC-TIA provided unambiguous results and had sufficient sensitivity, specificity, accuracy, and precision to be used as an alternative to other POC tests to assess FTPI in foals. Authors => S. Ujvari | C.C. Schwarzwald | N. Fouché | J. Howard | A. Schoster published => First published: 31 May 2017 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.14770

Title => Prevalence of Vector-Borne Pathogens in Southern California Dogs With Clinical and Laboratory Abnormalities Consistent With Immune-Mediated Disease Abstract => Background: Studies investigating the prevalence of vector-borne pathogens in southern California dogs are limited. Occult infections might be misdiagnosed as idiopathic immune-mediated disease. Hypothesis/Objectives: (1) To determine the prevalence of vector-borne pathogens in southern California dogs with compatible clinical findings using PCR and serologic panels and (2) to determine whether testing convalescent samples and repeating PCR on acute samples using the same and different gene targets enhance detection. Animals: Forty-two client-owned dogs with clinical signs of vector-borne disease presenting to specialty practices in San Diego County. Methods: Combined prospective and retrospective observational study. Forty-two acute and 27 convalescent samples were collected. Acute samples were prospectively tested for antibodies to Rickettsia, Ehrlichia, Bartonella, Babesia, Borrelia, and Anaplasma species. PCR targeting Ehrlichia, Babesia, Anaplasma, hemotropic Mycoplasma, and Bartonella species was also performed. Retrospectively, convalescent samples were tested for the same organisms using serology, and for Ehrlichia, Babesia, Anaplasma, and Bartonella species using PCR. Acute samples were retested using PCR targeting Ehrlichia and Babesia species. Results: Evidence of exposure to or infection with a vector-borne pathogen was detected in 33% (14/42) of dogs. Ehrlichia and Babesia species were most common; each was identified in 5 dogs. Convalescent serologic testing, repeating PCR, and using novel PCR gene targets increased detection by 30%. Conclusions and Clinical Importance: Repeated testing using serology and PCR enhances detection of infection by vector-borne pathogens in dogs with clinical signs of immune-mediated disease. Larger prevalence studies of emerging vector-borne pathogens in southern California dogs are warranted. Authors => L. Kidd | B. Qurollo | M. Lappin | K. Richter | J.R. Hart | S. Hill | C. Osmond | E.B. Breitschwerdt published => First published: 30 May 2017 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.14735

Title => Clinical Trials in Veterinary Medicine: A New Era Brings New Challenges Abstract => Authors => M.A. Oyama | S.S. Ellenberg | P.A. Shaw published => First published: 30 May 2017 URL => https://onlinelibrary.wiley.com//doi/10.1111/jvim.14744