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Background There is a paucity of veterinary literature on the safety or outcome of zoledronic acid (ZA) use in dogs for either bone pain or hypercalcemia. Hypothesis/Objectives The primary aim was to report the adverse events in dogs receiving intravenous administration of ZA. Animals Ninety‐five dogs with ZA use. Methods A retrospective cohort study was performed; all dogs that received at least 1 dose of ZA and had a serum biochemistry profile performed before and after treatment were reviewed. Diagnosis, indication for treatment, adverse events and survival times were recorded. Results Ninety‐five dogs met the inclusion criteria. Thirty‐one (33%) received multiple intravenous infusions of ZA (range, 2‐7), making a total of 166 administrations in all dogs. The dose range was 0.13 to 0.32 mg/kg, given at intervals of 4 to 6 weeks. Thirteen adverse events were recorded in 10 dogs: azotemia (n = 8), vomiting (n = 2), pancreatitis (n = 1), cutaneous ulceration (n = 1), and diarrhea (n = 1). Zoledronic acid could not be confirmed as the cause of azotemia in any case. The change in serum creatinine concentration from dose to dose was not related to the total dose received (P = .46). Five dogs (5%) changed Veterinary Comparative Oncology Group Common Terminology Criteria (VCOG‐CTAE) renal/genitourinary grade after administration of ZA; their total dose 0.4 mg/kg (range, 0.26‐0.66) was not significantly different to the group which did not change VCOG‐CTAE renal/genitourinary grade 0.35 mg/kg (range, 0.2‐1.50; P = .93). Conclusions and Clinical Importance Multiple doses of ZA were well tolerated in dogs within this study. A small number of dogs developed progressive azotemia which was not associated with cumulative dose.

Background There is currently a lack of reference intervals (RIs) for the novel measures like 3‐dimensional (3D) echocardiography or speckle‐tracking strain for assessment of right ventricular (RV) structure and function. Objectives To generate RIs and to determine the influence of age, heart rate, and body weight (BW) on various RV function indices using a dedicated RV software for 3D RV end‐diastolic volume (EDV), end‐systolic volume (ESV), ejection fraction (EF), global and free wall RV longitudinal strain (RVLS), end‐diastolic area (RVEDA), end‐systolic area (RVESA), fractional area change (FAC), tricuspid annular plane systolic excursion (TAPSE), and tissue Doppler imaging (TVI)‐derived systolic myocardial velocity of the lateral tricuspid annulus (S′). Animals Healthy adult client‐owned dogs (n = 211) of various breeds and ages. Methods Prospective study. Reference intervals were estimated as statistical prediction intervals using allometric scaling for BW‐dependent variables. Right‐sided (upper limit) or left‐sided (lower limit) 95% RIs were calculated for every variable. Inter‐ and intraobserver variability was determined. Results Most variables showed clinically acceptable repeatability with coefficient of variation less than 10. Upper or respectively lower RI after allometric scaling to normalize for different BWs were: EDVn ≤ 2.5 mL/kg0.942, ESVn ≤ 1.2 mL/kg0.962, TAPSEn ≥ 4.5 mm0.285, RVEDAn ≤ 1.4 cm2/kg0.665, RVESAn ≤ 0.8 cm2/kg0.695, and TVI S′n ≥ 5.6 cm/s/kg0.186. The calculated limits for indices without allometric normalization were: EF > 42.1%, FAC > 30.0%, free wall RVLS

BACKGROUND: Metabolic profiling identifies seasonal variance of serum metabolites in humans. Despite the presence of seasonal disease patterns, no studies have assessed whether serum metabolites vary seasonally in dogs.HYPOTHESIS: There is seasonal variation in the serum metabolite profiles of healthy dogs.ANIMALS: Eighteen healthy, client-owned dogs.METHODS: A prospective cohort study. Serum metabolomic profiles were assessed monthly in 18 healthy dogs over a 12-month period. Metabolic profiling was conducted using a canine-specific proton nuclear magnetic resonance spectroscopy platform, and the effects of seasonality were studied for 98 metabolites using a cosinor model. Seasonal component was calculated, which describes the seasonal variation of each metabolite.RESULTS: We found no evidence of seasonal variation in 93 of 98 metabolites. Six metabolites had statistically significant seasonal variance, including cholesterol (mean 249 mg/dL [6.47 mmol/L] with a seasonal component amplitude of 9 mg/dL [0.23 mmol/L]; 95% confidence interval [CI] 6-13 mg/dL [0.14-0.33 mmol/L], P CONCLUSIONS AND CLINICAL IMPORTANCE: We found no clear evidence that seasonal reference ranges need to be established for serum metabolites of dogs.

Background Superficial necrolytic dermatitis (SND) in dogs is a rare disorder most commonly associated with hepatocutaneous syndrome. Although often reported as fatal, sporadically reported long‐term remissions might be more common than previously believed and linked to treatment regimens. Hypothesis/Objectives Evaluate treatments and associated outcomes in dogs with hepatocutaneous‐associated hepatopathy (HCH) with or without SND, designated collectively aminoaciduric canine hypoaminoacidemic hepatopathy syndrome (ACHES). Animals Forty‐one dogs of various breeds and ages diagnosed with ACHES. Methods Retrospective study. Electronic surveys, medical records (2014‐2019), and communication with veterinarians provided data. Three treatment categories were each dichotomized: IV amino acid (IV‐AA) infusions (≥2 vs 1783 days, P = .02) than variably treated dogs (MST, 214 days). Conclusions and Clinical Importance Optimized ACHES management can resolve SND and HCH and confer long‐term survival.

Background Carcinoma‐associated thrombocytosis involves tumor production of mediators such as interleukin‐6 (IL‐6) and thrombopoietin (TPO) that increase thrombopoiesis and may play a role in tumor evasion and metastasis. Carcinoma‐associated thrombocytosis is described in people, but has not been described in dogs. Hypothesis/Objectives Evaluate the concentrations of IL‐6 and TPO in dogs diagnosed with carcinoma with or without thrombocytosis. We hypothesized that IL‐6 and TPO concentrations would be higher in dogs with carcinoma compared to healthy dogs, and that IL‐6 and TPO concentrations would be higher in dogs with carcinoma and thrombocytosis when compared to dogs with carcinoma and normal platelet counts. Animals One‐hundred sixteen dogs: 63 with carcinoma and 53 healthy control dogs. Methods Complete blood count was performed in all dogs, and they were stratified for sub‐group analysis based on the presence or absence of thrombocytosis (platelet count > 500 103/µL). Serum TPO and IL‐6 concentrations were measured by ELISA. Results of selected numeric variables were compared using Wilcoxon rank sum tests for pairwise comparisons. A value of P < .05 was considered significant. Results Twelve of the dogs with carcinoma (12/63, 19.0%) and none of the healthy control dogs (0%) had thrombocytosis. Thrombopoietin concentrations (median [range]) were significantly higher in dogs with carcinoma when compared to controls (87.42 pg/mL [0 to >600] vs 15.99 pg/mL [0 to >600], P

Background Improved understanding of Bartonella spp. serology in dogs may aid clinical decision making. Objective Describe demographic and geographic patterns of Bartonella spp. seroreactivity in dogs, and describe hematologic and serum biochemical abnormalities in Bartonella spp. seroreactive and nonseroreactive dogs. Animals Serum samples from 5957 dogs in the United States, previously submitted to IDEXX Reference Laboratories. Methods Serum was tested using 3 indirect ELISAs for B. henselae, B. vinsonii subsp. berkhoffii, and B. koehlerae. Complete blood count and serum biochemistry panel results were reviewed retrospectively. Results Overall, 6.1% of dogs were Bartonella spp. seroreactive. Toy breeds were less likely to be seroreactive (3.9%) than mixed breeds (7.5%; adjusted odds ratio [aOR], 0.48; 95% confidence interval [CI], 0.32‐0.72), and dogs

Background Metabolic syndrome is associated with formation of calcium oxalate (CaOx) uroliths in humans. Objectives To investigate the association between obesity and hyperlipidemia with CaOx lower urinary tract uroliths in client‐owned dogs. Animals Dogs with (n = 55, U [uroliths]‐dogs) and without (n = 39, UF [uroliths‐free]‐dogs) CaOx lower urinary tract uroliths. Methods Case‐control study. U‐dogs were retrospectively enrolled and compared to UF‐dogs. Body condition score (BCS; 1‐9 scoring scale), serum triglyceride (TG) and total cholesterol (CH) concentrations and glycemia (after >12‐hour food withholding) were recorded in both groups. Results On univariate logistic regression, when excluding Miniature Schnauzers, odds of having uroliths increased by a factor of 3.32 (95% CI 1.38‐11.12) for each mmol/L of TG (P = .027), of 39 (95% CI 9.27‐293.22) for each mmol/L of glycemia (P

Background Creatine kinase (CK) and aspartate aminotransferase (AST) activity can be increased with myositis associated with Toxoplasma and Neospora infection in dogs. Hypothesis/Objectives Serum activity of CK and AST can be used as a rapid screen for predicting positive serology in meningoencephalitis caused by Toxoplasma gondii or Neospora caninum in dogs compared to dogs with noninfectious meningoencephalitis. Animals Eighty dogs with meningoencephalitis based on magnetic resonance imaging and cerebrospinal fluid analysis. Methods Retrospective case‐control study. Serological cutoffs (≥1:800 immunofluorescence for Neospora and ≥1:400 IgG or ≥1:64 IgM or both for Toxoplasma) categorized dogs as infected (n = 21, all neosporosis) or noninfected (n = 59). Activities of CK and AST between infected and noninfected groups were compared using a Mann‐Whitney U test and receiver operating characteristic curve analysis. Results No dogs were diagnosed with toxoplasmosis. Serum CK and AST activities were significantly increased (P 99%. An AST cutoff of 57 U/L had 94.44% sensitivity and 85.71% specificity with an estimated negative predicative value of 99%. Conclusions and Clinical Importance High serum CK and AST activity can increase suspicion for neosporosis while awaiting serological tests for dogs with meningoencephalitis.

Background Cytoscopic‐guided laser ablation (CLA) is a technique that can be used to correct intramural ectopic ureters (EUs) in dogs. Hypothesis/Objectives To describe clinicopathologic, imaging, and cystoscopic findings in dogs undergoing CLA for intramural EU correction, and whether any of these findings are associated with continence outcomes. Animals Thirty‐one client‐owned dogs undergoing CLA between 2009 and 2019. Methods Retrospective cohort study. Data collected from medical records included signalment, clinical findings (including continence score at presentation), clinicopathologic findings (serum biochemistry profile, urinalysis, and urine culture results before CLA), ultrasonography, and cystoscopy findings. Follow‐up information was collected at 1 day to 1 week, 1 week to 1 month, and at >1 month time points after CLA. Final continence score was determined based on this follow‐up information. Multiple logistic regression was used to determine factors that were associated with final continence score. Results Median continence score of dogs at initial evaluation was 2 (range, 2‐4). Median continence score after CLA alone was 3 (range, 1‐5). Seventeen of 31 (54.8%) dogs received adjunctive medical management after CLA. Median continence score after CLA with or without adjunctive medical management was 5 (range, 1‐5). Overall, 67.7% of dogs were considered continent after CLA with or without adjunctive medical management. No preoperative or perioperative factors were found to be associated with final continence score. Conclusions Cystoscopic‐guided laser ablation for intramural EU in female dogs provides improvement in incontinence. Dogs remaining incontinent after CLA may improve with adjunctive medical management. Surgical management is required to manage incontinence in dogs with extramural EU.

Background Kidney infarction is a renovascular disease diagnosed by contrast‐enhanced computed tomography (CECT) in humans. Objectives To describe the frequency of kidney infarction and to determine the detection of kidney infarction with CECT in dogs. Animals Eight hundred and twenty‐six abdominal CECT studies of 826 dogs. Methods A cross‐sectional retrospective study. Dogs with abdominal CT scans including CECT were retrospectively retrieved. Kidney infarction was classified into 3 grades based on the extent of infarction relative to total kidney area. The location and number of kidney infarctions in each kidney were expressed as number and percentage. The ability of visualization of kidney infarction in each multiplanar reconstruction (MPR) image plane was evaluated by agreement of 2 observers. Results The frequency of kidney infarction in dogs was 3.15% (26/826 dogs; 95% CI = 2.05‐4.61). Most kidney infarctions were classified as grade 1, or the lesions were less than 25% of the kidney (47/56, 83.93%) and most were detected at the caudal pole of the kidney (31/56, 55.35%) on the sagittal plane. On MPR image planes, the sagittal plane had the highest proportion (34/56, 60.71%) of excellent visual category to detect kidney infarction. Conclusions and Clinical Importance The CECT, especially the sagittal plane, is a useful diagnostic tool for the detection of kidney infarction in dogs.

BACKGROUND: Radioiodine (131 I) is the treatment of choice for cats with hyperthyroidism. After 131 I, however, euthyroidism is not always achieved, with 5% to 10% of cats remaining persistently hyperthyroid and 20% to 50% developing iatrogenic hypothyroidism. OBJECTIVES: To identify pretreatment factors that may help predict persistent hyperthyroidism and iatrogenic hypothyroidism after treatment of cats using a novel 131 I dosing algorithm. ANIMALS: One thousand and four hundred hyperthyroid cats treated with 131 I. METHODS: Prospective, before-and-after study. Pretreatment predictors (clinical, laboratory, scintigraphic, 131 I dose, 131 I uptake measurements) of treatment failure or iatrogenic hypothyroidism were identified by multivariable logistic regression analysis. RESULTS: Cats that developed iatrogenic hypothyroidism were more likely to be older (odds ratio [OR] = 1.10; 95% confidence interval [CI], 1.04-1.17; P = .001), female (OR = 2.04; 95% CI, 1.54-2.70; P < .001), have detectable serum thyroid-stimulating hormone (TSH) concentrations (OR = 4.19; 95% CI, 2.0-8.81; P < .001), have bilateral thyroid nodules (OR = 1.57; 95% CI, 1.19-2.08; P < .001), have homogeneous, bilateral distribution of 99m Tc-pertechnetate uptake (OR = 2.93; 95% CI, 2.05-4.19; P < .001), have milder severity score (OR = 0.62; 95% CI, 0.49-0.79; P < .001), and have higher 131 I uptake (OR = 2.40; 95% CI, 1.75-3.28; P < .001). In contrast, cats remaining persistently hyperthyroid were more likely to be younger (OR = 0.81; 95% CI, 0.72-0.92; P < .001), have higher severity score (OR = 1.87; 95% CI, 1.51-2.31; P < .001), and have lower 131 I uptake (OR = 3.50; 95% CI, 1.8-6.80; P < .001). CONCLUSIONS AND CLINICAL IMPORTANCE: Age, sex, serum TSH concentration, bilateral and homogeneous 99m Tc-pertechnetate uptake on scintigraphy, severity score, and percent 131 I uptake are all factors that might help predict outcome of 131 I treatment in hyperthyroid cats. Cats with persistent hyperthyroidism had many predictive factors that directly contrasted those of cats that developed 131 I-induced hypothyroidism.

Background Cytauxzoon felis is a life‐threatening protozoan disease of cats. Identification of schizont‐laden macrophages is a point‐of‐care diagnostic test for acute cytauxzoonosis. Hypothesis/Objectives The primary objective determined cytologic agreement between sample types to diagnose acute cytauxzoonosis. The secondary objective evaluated novices' ability to identify cytauxzoon organisms in blood films and tissue aspirates. Animals Thirty‐eight cats with suspected acute cytauxzoonosis and 5 controls examined postmortem. Methods Cases were prospectively submitted and collected. Blood film, lymph node, and splenic aspirates were blindly reviewed for sample quality, presence of schizont‐laden macrophages, and agreement between sample types. A subset of cases and controls were evaluated by 12 blinded novice observers to determine sensitivity and specificity for identifying organisms in various sample types. Results Acute cytauxzoonosis diagnosis was made on at least 1 sample type in 28/38 cats. Schizont‐laden macrophages were seen on 33% (10/30) of blood films, 56% (19/34) lymph node aspirates, 77% (26/34) splenic aspirates. Schizont‐laden macrophages were more likely seen on splenic than lymph node aspirates (McNemar's, P = .03) or blood film (McNemar's, P =

Background There is no standardized methodology to measure antibiotic drug use (AU) in small animal veterinary hospitals. Objectives To estimate AU prevalence in a small animal veterinary teaching hospital and characterize usage by indication and evidence of infection. To establish an AU measurement methodology for veterinary settings. Animals Electronic medical records of cats and dogs seen by primary care, urgent care, emergency and critical care, internal medicine, and surgery services during November 2018 to October 2019. Methods On 1 day each month, data (signalment, visit reason, diagnostics, and antibiotic details, including indication) were collected for all animals seen on study services. Results Of 168 inpatient dogs and 452 outpatient dogs, 98 (58.3%) and 107 (23.7%,) were receiving at least 1 antibiotic on the day of data collection, respectively. For cats 15/49 (30.6%) inpatients and 29/187 (15.5%) outpatients were receiving at least 1 antibiotic. Common drug classes prescribed for dogs were potentiated penicillins (28.7%), first‐generation cephalosporins (22.1%), and nitroimidazoles (14.7%), and for cats, common drug classes administered were potentiated penicillins (26.9%), fluoroquinolones (13.5%), and penicillins (11.5%). Common indications for antibiotics included skin, respiratory, gastrointestinal, perioperative, aural, and urinary conditions. Conclusions and Clinical Importance Serial point‐prevalence surveys (PPS) can estimate AU in a large specialty hospital setting and identify targets for antimicrobial stewardship. The methodology developed during this study can be adapted for use in private practice, including large animal practice. Mirroring methods used in human healthcare, the data collection tool can also be used to describe AU nationally through completion of national PPS.

Background In humans, washing stored blood products before transfusion reduces storage lesions and incidence of transfusion reactions, but the effectiveness of washing canine blood is unknown. Objectives The objective was to determine if manually washing units of stored blood would reduce storage lesions without adversely affecting erythrocytes. We hypothesized that washing stored units would reduce concentrations of storage lesions and cause minimal erythrocyte damage. Animals Eight healthy research dogs. Methods Repeated measure cohort study. Units of whole blood were stored for 28 days and washed 3 times with 0.9% NaCl. Blood samples were collected before and after storage, after each wash, and after being held at a simulated transfusion temperature. Variables measured included CBC variables, blood gas analysis, erythrocyte morphology, mean corpuscular fragility (MCF), and eicosanoid concentrations. A Friedman's test was used to evaluate changes in variables (P < .05 was considered significant). Results After the first wash, compared to values after storage, there was a significant decrease in potassium (4.3 mmol/L [4.0‐4.7] to 1.2 mmol/L [1‐1.6]; P < .0001, median [range]), lactate (1.45 mmol/L [1.07‐1.79] to 0.69 mmol/L [0.39‐0.93]; P = .002), and partial pressure carbon dioxide (102 mm Hg [80.2‐119.2] to 33.7 mm Hg [24.5‐44.5]; P < .0001), and increase in MCV (69.3 fL [65.7‐72.3] to 74 fL [69.6‐79.5]; P = .0003), and MCF (0.444 fL [0.279‐0.527] to 0.491 fL [0.43‐0.616]; P = .0006). Conclusions and Clinical Importance A single wash of stored whole blood significantly reduces most extracellular storage lesions, and additional washing might cause hemolysis.

Background Catheter‐based occlusion of patent ductus arteriosus (PDA) can be performed using different devices. Transvenous embolization using the Amplatzer vascular plug II (AVP‐II) has been studied in humans, but it has not been described in dogs. Objective Evaluate the feasibility and success of transvenous embolization of PDA using the AVP‐II in dogs. Animals Nineteen client‐owned dogs with left‐to‐right shunting PDA, with minimal ductal diameter >2.5 mm. Methods Prospective observational study using AVP‐II with transvenous access for PDA closure in dogs. Results Angiography showed a conical ductus with a long (n = 17) or short (n = 2) ampulla. The minimal diameter of the duct was 4.34 ± 1.11 mm, and the maximal diameter of the ampulla was 13.18 ± 3.47 mm. Technical success was achieved in 18 of the 19 (94.7%) patients after the first intervention and in all 19 (100%) patients after the second intervention. Postrelease angiography documented complete occlusion of the PDA in 10 of 19 (52.6%) dogs. Mild flow acceleration or stenosis of the left pulmonary artery was found in 6 and 1 of the 17 analyzed cases, respectively, by Doppler examination. The closure rate 24 hours after intervention was 94.7% (18/19). The remaining dog had a moderate residual shunt, and delayed complete closure after 3 months led to a 100% closure rate. Conclusion and Clinical Importance The AVP‐II is a safe and effective device for transvenous embolization in dogs with moderate to large PDA.

Background Acute enteropathy is a trigger of chronic gastrointestinal (GI) disease in humans. Objective To report the prevalence of and explore possible risk factors for signs of chronic GI disease in dogs after an episode of acute hemorrhagic diarrhea (AHD). Animals One hundred and fifty‐one dogs, 80 dogs with a historical diagnosis of AHD, 71 control dogs with no history of AHD. Methods In this retrospective longitudinal study, data were collected from dogs with a historical diagnosis of AHD and healthy controls matched by breed, age and sex, aged between 1 year and 15 years of age, for which a follow‐up of at least 12 months after enrolment was available. Dog owners responded to a questionnaire to determine the history of signs of chronic GI disease. Results There was a higher prevalence of signs of chronic GI disease in the dogs with a previous episode of AHD compared to control dogs (AHD 28%; controls 13%; P = .03; odds ratio = 2.57; confidence interval [CI] 95% 1.12‐6.31) over a similar observation time (median 4 years; range, 1‐12 years). Conclusions and Clinical Importance Severe intestinal mucosal damage and associated barrier dysfunction might trigger chronic GI disease later in life.

Background Hyperadrenocorticism (HAC) is a common endocrine disorder in dogs; however, there are no reports on the use of the corticotropin‐releasing hormone test (CRHT) to differentiate between pituitary‐dependent hyperadrenocorticism (PDH) and cortisol‐producing adrenal tumors (CPATs), both causative of HAC. Objectives To evaluate the usefulness of CRHT as a tool to differentiate between PDH and CPAT in dogs and to determine the reference intervals for CRHT in healthy, PDH, and CPAT dogs. Animals Dogs diagnosed with PDH (n = 21), CPAT (n = 6), and healthy beagle dogs (n = 33). Methods This prospective study included dogs with a definitive diagnosis of PDH and CPAT and healthy beagle dogs, in which CRHT was performed, were prospectively evaluated. We investigated the correlations of CRHT (endogenous adrenocorticotropic hormone [ACTH] concentration, endogenous ACTH concentration [EAC], and poststimulation ACTH concentration [PAC]) with pituitary‐to‐brain ratio (PBR) (in PDH) and with indices of adrenal ultrasonography (smaller and larger adrenal gland dorsoventral thickness in PDH and CPAT). Results For EAC, the area under the curve (AUC) was 0.95, with a cutoff value of 26.3 pg/mL (sensitivity: 90.62%, specificity: 87.50%). The AUC for PAC was 0.96 with a cutoff value of 54.5 pg/mL (sensitivity: 100.00%, specificity: 66.67%). The 95% reference interval for CRHT in healthy (control) dogs ranged 5.00 to 79.8 pg/mL (1.10‐17.57 pmol/L) for EAC, and 1.92 to 153.42 pg/mL (0.42‐33.78 pmol/L) for PAC. There was no significant correlation between PBR and CRHT, nor adrenal size and CRHT. Conclusions and Clinical Importance CRHT appears to be a rapid and reliable test for differentiating PDH from CPAT in dogs.

Background:\ud Orthostatic tremor (OT) is a rare movement disorder characterized by high-frequency (>12 Hz) involuntary, rhythmic, sinusoidal movements affecting predominantly the limbs while standing.\ud \ud Objective:\ud To describe the signalment, presenting complaints, phenotype, diagnostic findings, treatment, and outcome of a large sample of dogs with OT.\ud \ud Animals:\ud Sixty dogs diagnosed with OT based on conscious electromyography.\ud \ud Methods:\ud Multicenter retrospective case series study. Dogs were included if they had a conscious electromyography consistent with muscle discharge frequency >12 Hz while standing.\ud \ud Results:\ud Fifty-three cases were diagnosed with primary OT (POT). Giant breed dogs represented most cases (83%; 44/53). Most dogs (79%; 42/53) were younger than 2 years of age at onset of signs, except for Retrievers which were all older than 3.5 years of age. The most common presenting complaints were pelvic limb tremors while standing (85%; 45/53) and difficulty when rising or sitting down (45%; 24/53). Improvement of clinical signs occurred in most dogs (85%; 45/53) treated medically with phenobarbital, primidone, gabapentin, pregabalin or clonazepam, but it was mostly partial rather than complete. Orthostatic tremor-plus was seen in 7 dogs that had concurrent neurological diseases.\ud \ud Conclusions and Clinical Importance:\ud Primary OT is a progressive disease of young, purebred, giant/large-breed dogs, which appears to begin later in life in Retrievers. Primary OT apparently responds partially to medications. Orthostatic tremor-plus exists in dogs and can be concomitant or associated with other neurological diseases.

Background Despite multiple reports of chemotherapy overdoses (ODs) in human and veterinary medicine, anthracycline ODs have been described infrequently. Hypothesis/Objectives Describe toxicities, treatments, and overall outcome after anthracycline OD in dogs. Animals Twelve mitoxantrone (MTX) and 4 doxorubicin (DOX) ODs were evaluated. Methods Multicenter retrospective analysis. The American College of Veterinary Internal Medicine oncology and internal medicine listservs were solicited for cases in which a chemotherapy OD occurred. Results Sixteen anthracycline cases were collected. Anthracycline ODs occurred because of an error in chemotherapy preparation (n = 9), or dose miscalculation (n = 7). The overall median OD was 1.9× (range, 1.4‐10×) the prescribed amount. Most ODs were identified immediately after drug administration (n = 11), and the majority of patients were hospitalized on supportive care (n = 11) for an average of 8 days (range, 3‐34 days). Adverse events after the OD included neutropenia (94%), thrombocytopenia (88%), anemia (63%), diarrhea (63%), anorexia (56%), vomiting (38%), lethargy (31%), and nausea (25%). Two patients did not survive the OD. High grade neutropenia was common and did not appear to be mitigated by the administration of filgrastim. Conclusions and Clinical Importance All patients received supportive care after identifying the OD and death was uncommon. Further evaluation is needed to determine ideal therapeutic guidelines anthracycline OD.

Background Necrotizing meningoencephalitis (NME, aka Pug dog encephalitis) is an inflammatory brain condition associated with advanced disease at initial presentation, rapid progression, and poor response to conventional immunomodulatory therapy. Hypothesis/objectives That genetic risk for NME, defined by a common germline DNA haplotype located on chromosome 12, is associated with altered blood cytokine concentrations and leukocyte subsets in asymptomatic Pugs. Animals Forty Pug dogs asymptomatic for NME from a hospital sample. Methods Prospective observational cohort study, including germline genome-wide genotyping, plasma cytokine determination by multiplexed profiling, and leukocyte subset characterization by flow cytometric analysis. Results Seven (18%) dogs were high risk, 10 (25%) medium risk, and 23 (58%) low risk for NME, giving a risk haplotype frequency of 30%. High and medium risk Pugs had significantly lower proportion of CD4+ T cells (median 22% [range, 7.3%-38%] vs 29% [range, 16%-41%], P = .03) and higher plasma IL-10 concentrations than low-risk Pugs (median 14.11 pg/mL [range, 9.66-344.19 pg/mL] vs 12.21 pg/mL [range, 2.59-18.53 pg/mL], P = .001). No other variables were significantly associated with the NME haplotype-based risk. Conclusions and clinical importance These data suggest an immunological underpinning to NME and a biologic rationale for future clinical trials that investigate novel diagnostic, preventative, and therapeutic strategies for this disease.

Background Persistent leptospiruria in naturally infected dogs occurs despite appropriate antibiotic treatment. Hypothesis/Objectives To determine the frequency of persistent leptospiruria in naturally infected dogs and the association of persistent leptospiruria with different antibiotic treatments. Animals Thirty‐two dogs of varying age and breed diagnosed with leptospirosis via urine polymerase chain reaction assay (PCR). Methods A prospective observational study of dogs diagnosed with leptospirosis was undertaken to determine the frequency of persistent leptospiruria as determined by PCR. Clinical presentation of leptospirosis, antibiotic treatment, serum creatinine concentration, and outcome were recorded. Results Fifteen of 32 dogs had a negative urine PCR on the first submission in the study, 5 of 15 received only an aminopenicillin. The remaining 17 dogs had a negative urine PCR on the second (n = 6 dogs), third (n = 5), fourth (n = 5), and eighth (n = 1) submissions. Acute kidney injury was reported in 32/32 dogs. Two of 32 dogs developed chronic kidney disease. Conclusions and Clinical Importance Persistent leptospiruria is common despite treatment with antibiotics frequently recommended for treatment. Follow‐up urine PCR to confirm clearance of the organism is recommended in all dogs. In dogs with persistent leptospiruria, chronic kidney disease can develop after acute kidney injury.

Background Early recognition of acute kidney injury (AKI) is hindered by current definitions and use of traditional, insensitive markers. Hypothesis/objectives Urinary (u) activity of γ-glutamyl transpeptidase (GGT) and alkaline phosphatase (ALP), and concentrations of heat-shock protein 70 (HSP70) and interleukins (ILs) -6 and -18, are predictive biomarkers for AKI and survival. Animals Nonazotemic, hospitalized dogs (n = 118) and healthy controls (n = 20). Methods A prospective observational study. Nonazotemic dogs at risk of AKI were recruited and their urinary biomarker concentrations were measured at presentation. Serum creatinine (sCr) and symmetric dimethylarginine (sSDMA) were measured daily until discharge/death. Results The overall case fatality rate was 18.6%. Fifteen dogs (12.7%) developed AKI, which was associated with death (relative risk, 3.2; 95% confidence interval [CI], 1.57-6.55). All 5 urinary biomarkers were significantly higher in hospitalized dogs compared to controls, with minimal overlap. uHSP70/uCr, uGGT/uCr, and uIL-6/uCr at presentation were higher in dogs which later developed AKI. Areas under the receiver operator characteristic curve (AUROC) (95% CI) for the 3 biomarkers as predictors of AKI were 0.67 (0.51-0.83), 0.68 (0.55-0.81), and 0.78 (0.65-0.91), respectively. When they were categorically classified as elevated/normal, each additional elevated biomarker increased the odds for AKI (OR, 2.83; 95% CI, 1.23-6.52, P = .01). Agreement between sCr and sSDMA was poor (Cohen's kappa = .071). The AUROC of SDMA at presentation for AKI prediction was 0.73 (0.51-0.95). Conclusions and clinical importance Kidney injury was common, irrespective of subsequent worsening of azotemia or death. The predictive value of individual urinary biomarkers was reduced by moderate sensitivities and specificities. SDMA showed moderate discriminatory utility for AKI prediction, and often displayed discordant results with sCr.

Background In dogs, antimicrobial drugs are widely prescribed for aspiration pneumonia (AP) despite poor documentation of bacterial infection in AP (b‐AP) using bronchoalveolar lavage fluid (BALF) analysis. Interpretating discordant cytology and culture results is challenging, contributing to lack of a criterion standard, and highlighting differences between veterinary and human medical criteria for b‐AP. Objectives Determine how many dogs with AP had BALF collection and differences in diagnosis of b‐AP using veterinary vs human medical criteria. Report findings of noninvasive markers (e.g. fever, band neutrophilia, radiographic severity score) in dogs with and without b‐AP. Animals Retrospective cohort study of client‐owned dogs (n = 429) with AP at 2 university veterinary hospitals. Twenty‐four dogs met enrollment criteria. Methods Inclusion criteria were radiographic diagnosis of AP, ≥1 risk factor, CBC findings, and BALF cytology and culture results. Veterinary medical b‐AP criteria were cytology findings compatible with sepsis with or without positive culture, or cytology findings not consistent with sepsis and positive culture (≥1.7 × 103 cfu/mL). Human medical b‐AP criteria required culture with ≥104 cfu/mL or > 7% cells with intracellular bacteria on cytology. Results Only 24/429 dogs met all enrollment criteria; 379/429 dogs lacked BALF collection. Diagnosis of b‐AP differed using veterinary (79%) vs human (29%) medical criteria. Fever, band neutrophils and high radiographic scores were noted in dogs with and without b‐AP. Conclusions and Clinical Importance Lack of routine BALF collection hampers definitive recognition of bacterial infection in AP. Differences in dogs meeting veterinary vs human medical definitions for b‐AP and usefulness of noninvasive markers warrant further study to improve understanding of the role of bacteria in AP.

Background The nasopharyngeal bacterial and fungal microbiota of normal horses and those with nasopharyngeal cicatrix syndrome (NCS) are unknown. Hypotheses/objectives To describe the microbiota from nasopharyngeal washes of healthy horses and of horses acutely affected with NCS. Animals Twenty-six horses acutely affected with NCS horses and 14 unaffected horses. Methods Prospective, observational cohort study. Horses were recruited by investigators through personal communications in central Texas. Bacterial (16s RNA) and fungal (internal transcribed spacer) microbiota from nasopharyngeal washes were evaluated. Polymerase chain reaction for detection of Pythium insidiosum was performed. Results Results indicated that 6 fungal genera (Alternaria, Bipolaris, Microascus, Spegazzinia, Paraconiothyrium, Claviceps) and 1 bacterial genera (Staphylococcus) were significantly different between affected and unaffected horses. The fungal genus Bipolaris had increased abundance in NCS affected horses and on NCS affected farms. Pythium insidiosum was absent in the nasopharyngeal wash of all horses, irrespective of health status. Conclusion and clinical importance Significant differences were identified in the fungal microbiota in horses affected with NCS and farms affected with NCS compared to those unaffected. Therefore, Bipolaris warrants further investigation.

Background Although precursor-targeted immune-mediated anemia (PIMA) is thought to be caused by immune targeting of erythroid precursors (nucleated RBCs, nRBCs), its pathogenesis is unknown. Immunoglobulin G (IgG) or phosphatidylserine (PS) may promote nRBC destruction in PIMA. Hypothesis Dogs with PIMA have increased nRBC IgG and PS, and dogs with immune-mediated hemolytic anemia (IMHA) have increased RBC PS compared to healthy dogs. Animals Blood from 20 healthy dogs and from dogs with IMHA (11) or other (non-IMHA) conditions (9), and marrow aspirates with or without blood from 10 healthy dogs and from dogs with PIMA (17) or other (non-IMHA, non-PIMA) conditions (7). Methods Marrow nRBC stages were separated by density gradient. Flow cytometry was used to assess the percentage of RBCs or nRBCs with increased IgG or PS. Results Red blood cell (RBC) IgG positivity was increased in 9/11 IMHA dogs and 0/9 non-IMHA dogs. Red blood cell PS positivity was increased in 10/11 IMHA dogs and 2/9 non-IMHA dogs. Five of 17 PIMA dogs had increased nRBC IgG positivity in mid- or late-stage fractions, whereas all 7 non-PIMA dogs were negative. Mid- and late-stage erythroid precursor PS was significantly higher in PIMA dogs compared to healthy dogs. Five of 14 PIMA dogs had increased RBC IgG positivity. Conclusions Immunoglobulin G and PS may promote destruction of nRBCs in PIMA dogs; PS may promote destruction of RBCs in IMHA dogs.

Background Cats with moderate to advanced chronic kidney disease (CKD) often display clinical signs such as vomiting and decreased appetite, and frequently receive omeprazole or other acid suppressants despite a lack of evidence to support their use. Hypothesis/objectives To evaluate the effect of once-daily PO omeprazole on appetite in cats with CKD. We hypothesized that omeprazole would improve subjective appetite assessments in cats with CKD. Animals Fourteen client-owned cats with International Renal Interest Society (IRIS) stage 2 or 3 CKD and hyporexia. Methods Cats were prospectively enrolled in a multi-institutional, double-blinded, randomized, crossover study to evaluate the effect of a 14-day trial of once-daily PO omeprazole (1 mg/kg) or placebo (lactose gel capsule) on vomiting frequency and appetite. A daily log was completed by the owner during all treatment and rest periods to assess appetite using a subjective, qualitative, and 5-point scoring system. Mixed model analyses of variance were performed to determine if average daily percentage food consumed or appetite score, as measured by subjective owner assessment, differed between treatments. Results Compared to placebo, a negligible but statistically significant difference in percentage of food consumed was observed between treatments (P = .04) with once-daily omeprazole treatment resulting in a 2.7% increase in food consumption compared to placebo. No significant difference, however, was found in appetite score, body weight, or serum creatinine concentration between treatments. Conclusions and clinical importance Once-daily omeprazole does not markedly increase appetite in cats with CKD and should not be used as a first-line treatment in the absence of evidence of gastrointestinal ulceration.

Background Atrial fibrillation (AF) is associated with increased risk of sudden cardiac death (SCD) in humans, independent of secondary risk factors such as thrombogenic disorders. In dogs, SCD is described in a number of heart diseases, but an association between AF and SCD is unreported. Hypothesis (a) A higher proportion of dogs with AF will experience SCD, and (b) SCD will be associated with complex ventricular arrhythmias. Animals One‐hundred forty‐two dogs with AF, and 127 dogs without AF. Methods Retrospective, multicenter, case‐control study. Dogs included in the AF group were compared to a control group of dogs in sinus rhythm, matched for echocardiographic diagnosis. Descriptive statistics were used to identify proportions of each group suffering SCD, compared using chi‐squared testing. Risk factors for SCD in dogs with AF were evaluated at the univariable and multivariable level using binary logistic regression. Significance was P

Background A flash glucose monitoring system (FGMS; FreeStyle Libre) is useful for monitoring hypoglycemic dogs with diabetes. Objective To assess the utility of this FGMS in dogs with induced hypoglycemia and rapid fluctuations in blood glucose (BG) concentrations. Animals Twenty‐four apparently healthy research (n = 10) and teaching (n = 14) dogs. Methods Prospective, observational study performed in tandem with a teaching laboratory. Regular insulin was administered to dogs and resulting hypoglycemia was corrected. Before insulin administration and every 10 minutes over a 90‐minute period, serial measurements of interstitial glucose (IG) with FGMS and BG with a portable blood glucose meter (PBGM) and clinical chemistry analyzer concentrations were made. Portable blood glucose meter and FGMS readings were compared to that of the clinical chemistry analyzer. Analytical and clinical accuracy were assessed using ISO 15197:2013 criteria, including Parkes error grid analysis. Results The proportions of readings in the low BG range (BG

Background Frunevetmab, a felinized antinerve growth factor monoclonal antibody, effectively decreases osteoarthritis (OA) pain in cats. Objective To evaluate the efficacy of frunevetmab given at monthly intervals in a randomized, placebo-controlled, parallel-group, double-blind superiority study. Animals Two hundred seventy-five client-owned cats with naturally-occurring OA pain and associated mobility impairment and disability. Methods Randomized, placebo-controlled, parallel-group, double-blind, superiority study. Following screening, cats received frunevetmab (nominal dose of 1.0 mg/kg, SC [effective dose range of 1.0-2.8 mg/kg]) or placebo on days 0, 28, and 56. Outcome measures were owner questionnaires and veterinary physical and orthopedic evaluations at days 28, 56, and 84. Success/failure rates (and numbers needed treat, NNT) and change in scores (and standardized effect size, ES) were analyzed. Results Frunevetmab (182) and placebo (93) treated cats were enrolled and received at least 1 treatment. Significant improvement with frunevetmab over placebo occurred at days 28 and 56 for the client specific outcome measures (CSOM) questionnaire (success rates and total scores [NNT of 9 and ES of 0.3 at day 56]); at days 28 and 56 for owner-assessed global treatment response; and at days 56 and 84 for veterinarian-assessed joint pain (ES of 0.18 at day 56). Adverse events did not differ between groups, except skin disorders which collectively occurred significantly more frequently in frunevetmab treated (32/182 cats) vs placebo (8/93 cats). Conclusions and clinical importance Frunevetmab has the potential to address a critical gap in the treatment of pain because of osteoarthritis in cats.

Background: Cytopathology is a minimally invasive and convenient diagnostic procedure, often used as a substitute for histopathology to diagnose and characterize lymphoma in dogs. Objectives: Assess the diagnostic performance of cytopathology in diagnosing lymphoma and its histopathological subtypes in dogs. Animals: One-hundred and sixty-one lymph node samples from 139 dogs with enlarged peripheral lymph nodes. Methods: Based only on cytopathology, 6 examiners independently provided the following interpretations on each sample: (a) lymphoma vs nonlymphoma; (b) grade and phenotype; and (c) World Health Organization (WHO) histopathological subtype. Histopathology and immunohistochemistry (IHC) findings were used as reference standards to evaluate diagnostic performance of cytopathology. Clinical, clinicopathologic, and imaging data also were considered in the definitive diagnosis. Results: Classification accuracy for lymphoma consistently was >80% for all examiners, whereas it was >60% for low grade T-cell lymphomas, >30% for high grade B-cell lymphomas, >20% for high grade T-cell lymphomas, and

Background Pituitary pars intermedia dysfunction (PPID) is a common endocrinopathy of horses diagnosed with a thyrotropin-releasing hormone (TRH) stimulation test. Hypothesis/objectives Describe the repeatability of TRH stimulation in horses with and without PPID in winter and autumn. Animals Twenty adult horses; 6 controls and 6 with PPID tested in autumn, 8 controls and 6 with PPID tested in winter with 3 controls and 3 with PPID tested in both seasons. Methods Thyrotropin-releasing hormone stimulation was performed on 2 consecutive occasions, 1 week before and 1 week after the winter solstice and the autumn equinox. Blood was collected before and 30 minutes after IV injection of 1 mg of TRH. ACTH concentration was determined by a chemiluminescent assay. Repeatability and test-retest reliability were assessed by repeated measures analysis of variance, intraclass correlation coefficient and within-horse coefficients of variation (CV). Bland-Altman plots were generated to visualize agreement between repetitions. Results In winter, no week effect was detected on the results of the TRH simulation and the test had an excellent test-retest reliability. In autumn, after-TRH ACTH concentrations were significantly lower on week 2 (P = .02) and the test only had a good test-retest reliability. There were significantly larger within-horse CV during autumn (P = .04) and after TRH stimulation (P = .04). There were 2 misclassifications in winter and 4 in autumn. Conclusions and clinical importance The TRH stimulation test was repeatable when performed 2 weeks apart in winter; however, in autumn, more variability in after-TRH ACTH concentrations resulted in decreased repeatability.

Background: The use of adrenocorticotropic hormone stimulation test as method to monitor efficacy of trilostane treatment of hypercortisolism (HC) in dogs has been questioned. Objectives: To evaluate and compare 12 methods with which to monitor efficacy of trilostane treatment in dogs with HC. Animals: Forty-five client-owned dogs with HC treated with trilostane q12h. Methods: Prospective cross-sectional observational study. The dogs were categorized as well-controlled, undercontrolled, and unwell through a clinical score obtained from an owner questionnaire. The ability to correctly identify trilostane-treatment control of dogs with HC with the following variables was evaluated: before trilostane serum cortisol (prepill), before-ACTH serum cortisol, post-ACTH serum cortisol, plasma endogenous ACTH concentrations, prepill/eACTH ratio, serum haptoglobin (Hp) concentration, serum alanine aminotransferase (ALT), gamma-glutamyl transferase (γGT) and alkaline phosphatase activity, urine specific gravity, and urinary cortisol:creatinine ratio. Results: Ninety-four re-evaluations of 44 dogs were included; 5 re-evaluations of 5 unwell dogs were excluded. Haptoglobin was significantly associated with the clinical score (P

Background The majority of dogs with coccidioidomycosis recover with administration of fluconazole or itraconazole, although some cases are refractory or the dogs do not tolerate administration of these medications. Objectives The objective was to describe the treatment outcomes and therapeutic monitoring of 8 dogs with refractory coccidioidomycosis treated with posaconazole. Animals Eight dogs with refractory coccidioidomycosis. Methods Retrospective case series. Medical records from Veterinary Specialty Center of Tucson were searched to identify dogs with refractory coccidioidomycosis that were treated with posaconazole. Clinical information and the results of monitoring trough serum posaconazole concentrations were retrieved. Results Eight dogs with refractory coccidioidomycosis were treated with 2.5 to 10 mg/kg per day of posaconazole. Six of 8 dogs recovered or developed clinical remission while administered posaconazole. Thirteen serum concentrations from 8 dogs tested were >1 μg/mL (range, 1.52 to >6 μg/mL) and the drug was well‐tolerated by 7 dogs. One dog required dosage reductions and treatment was ultimately discontinued because of hepatotoxicosis. Conclusions and Clinical Importance Posaconazole should be considered as a treatment option for dogs with refractory coccidioidomycosis. Monitoring of indicators of liver function or injury along with therapeutic drug monitoring is recommended to tailor dosage in the event of hepatic toxicosis.

Background Symmetric dimethylarginine (SDMA) is a renal biomarker correlated with glomerular filtration rate (GFR). Objectives Describe changes in SDMA in clinically healthy foals and their mares during the first month postfoaling. Animals Convenience sampling of healthy periparturient Thoroughbred mares and their full‐term foals from a population of client‐owned horses. Methods Serum and EDTA whole blood samples were collected from mares in their last month of pregnancy and then from mares and foals at approximately

Background: Ursodeoxycholic acid is used in human medicine for litholytic management of choleliths, but the efficacy of medical management in dogs with cholelithiasis is unknown. Objectives: To describe the clinical features and outcomes of dogs with cholelithiasis, focusing on cases that received medical treatment, and to identify patient factors that influenced decision���making for surgical or medical management. Animals: Thirty���eight dogs with cholelithiasis identified on abdominal ultrasonography (AUS). Methods: Medical records of dogs with cholelithiasis on AUS between 2010 and 2019 were retrospectively reviewed. Cases were classified as symptomatic (n = 18) or incidental (n = 20) and divided into medically treated (n = 13), surgically treated (n = 10), and no treatment (n = 15) groups. Biochemical variables and cholelith location were compared between symptomatic and incidental groups using Mann���Whitney U and chi���squared tests, respectively. Survival times were compared using Kaplan���Meier survival analysis. Results: Symptomatic cases had higher alkaline phosphatase (P = .03), gamma���glutamyl transferase (P = .03), and alanine transferase (P = .02) activities than did incidental cases. A higher proportion of symptomatic cases (44.4%) had choledocholithiasis than did incidental cases (0%; P = .003). Seventy percent of surgically managed dogs, 7.7% of medically managed dogs, and 0% of nontreated dogs had choledocholiths at presentation. Seventeen dogs had follow���up AUS: cholelithiasis completely resolved in 4/8 medically treated, 5/7 of surgically treated, and 1/2 nontreated dogs. Median survival time was 457.4 days, with no significant difference between incidental and symptomatic dogs. Conclusions and Clinical Importance: Medical treatment can be effective for management of cholelithiasis in dogs, with clinical presentation and cholelith location playing important roles in treatment decision���making.

Background Radiation therapy is commonly used as an adjunct to incomplete surgical excision in dogs with mast cell tumors (MCT), but the optimal dose and fractionation regimen have yet to be determined. Hypothesis We assessed outcomes (time to local recurrence, patient survival and toxicity) of a large population of dogs with MCT that received adjunctive radiation therapy. Animals Three hundred dogs with 302 MCT treated using adjunctive radiation therapy. Methods Retrospective observational study. Clinical records of 4 veterinary radiation centers were reviewed. Results Local recurrence rates were similar regardless of radiation protocol with 6.6% of patients developing recurrent cutaneous MCT at a median of 526 days. Local recurrence rate was similar between high and low‐risk MCT. Mast cell tumor related death was reported in 19% of all dogs, with 13% of dogs with low‐risk MCT dying of their disease compared to 29% of dogs with high‐risk MCT. No SC MCT (SCMCT) recurred after radiation therapy and only 7% of dogs with SCMCT were reported to have died of their disease. Mild late toxicity was common in both protocols and severe late toxicity occurred in 1.9% of dogs many years after treatment. Conclusions and Clinical Importance Our study supports the use of adjunctive radiation for the long‐term control of incompletely or narrowly excised cutaneous and SCMCT in dogs. More moderate dose and fractionation protocols may be appropriate in the adjunctive treatment of low‐risk MCT in dogs. Large multicenter prospective studies are required to establish the optimal dose and fractionation for MCT of different risk categories.

BACKGROUND: The neurotransmitter serotonin (5-HT) affects valvular degeneration and dogs with myxomatous mitral valve disease (MMVD) exhibit alterations in 5-HT signaling. In Maltese dogs, 3 single nucleotide polymorphisms (SNPs) in the 5-HT transporter (SERT) gene are suggested to associate with MMVD.HYPOTHESIS/OBJECTIVES: Determine the association of SERT polymorphisms on MMVD severity and serum 5-HT concentration in Cavalier King Charles Spaniels (CKCS). Additionally, investigate the association between selected clinical and hematologic variables and serum 5-HT and assess the correlation between HPLC and ELISA measurements of serum 5-HT.ANIMALS: Seventy-one CKCS (42 females and 29 males; 7.8 [4.7;9.9] years (median [Q1;Q3])) in different MMVD stages.METHODS: This prospective study used TaqMan genotyping assays to assess SERT gene polymorphisms. Neurotransmitter concentrations were assessed by HPLC and ELISA.RESULTS: TaqMan analyses identified none of the selected SERT polymorphisms in any of the CKCS examined. Serum 5-HT was associated with platelet count (P CONCLUSIONS AND CLINICAL IMPORTANCE: Selected SERT SNPs associated with MMVD in Maltese dogs were not found in CKCS and only platelet count influenced serum 5-HT concentration. These SNPs are unlikely to be associated with MMVD pathophysiology or serum 5-HT concentration in CKCS. HPLC and ELISA serum 5-HT demonstrated good correlation but ELISA systematically underestimated 5-HT.

Background Many medical conditions are thought to cause gastroduodenal ulceration or erosion (GUE) in dogs. However, evidence for the association between many of these conditions and GUE in dogs is lacking. Objective To identify medical conditions associated with GUE in dogs. Animals One hundred and sixty-eight dogs with GUE and 168 randomly selected control dogs without evidence of GUE identified on necropsy between January 2008 and September 2018. Methods Patient signalment, blood urea nitrogen (BUN) and serum creatinine concentrations, recently administered ulcerogenic drugs, as well as necropsy findings were recorded. The association between these findings and presence of GUE was assessed by univariable and multivariable analysis. Results In the final multivariable model, the following factors were associated with GUE: Nonsteroidal anti-inflammatory drug (NSAID) administration (odds ratio [OR], 6.3; 95% confidence interval [CI], 2.3-17.4; P = .0004), glucocorticoid administration (OR, 3.0; 95% CI, 1.5-5.9; P = .001), gastrointestinal neoplasia (OR, 13.5; 95% CI, 1.7-108.0; P = .01) and gastrointestinal mechanical disease (foreign bodies, gastric dilatation, and volvulus; OR, 4.8; 95% CI, 1.2-19.7; P = .03). Additionally, working dog breeds were predisposed to GUE compared to mixed breed dogs (OR, 2.8; 95% CI, 1.1-7.4; P = .04). Insufficient clinical data was available to either support or refute a role of other putative risk factors evaluated. Conclusion and clinical importance Administration of NSAID or glucocorticoid and gastrointestinal neoplasia or mechanical disease were associated with GUE in dogs. The potential predisposition of working breed dogs for GUE requires further investigation.

Background Awareness of exocrine pancreatic insufficiency (EPI) in cats has increased since the development of an assay for feline trypsin-like immunoreactivity (fTLI). Ultrasound findings in cats with EPI have only been reported rarely and described as nonspecific. Hypothesis/objectives To describe the ultrasonographic findings, clinical signs, and concurrent diseases in cats with EPI. Animals Twenty-two client-owned cats with EPI. Methods Multicenter retrospective descriptive study including cats with serum fTLI concentration ≤8 μg/L and an abdominal ultrasound examination performed within 6 weeks of fTLI measurement. Sonographic measurements of maximal pancreatic thickness and maximal pancreatic duct diameter as well as ratios of pancreatic duct diameter to pancreatic thickness were obtained. Additional sonographic findings, concurrent conditions, and clinical signs were recorded. Results The most common clinical sign was weight loss (15/22 cats). Chronic enteropathy was the most common concurrent disease (13/22 cats). In 39% of cats, the pancreas had minimal or no sonographic alterations. Pancreatic duct dilatation (>2.5 mm), pancreatic duct tortuosity with variable diameter, or both were seen in 6/13 cats. The pancreatic parenchyma was subjectively thin in 6 cats. A significant relationship was found between subjectively thin pancreatic parenchyma and increased pancreatic duct size : pancreatic thickness ratio (P = .004). Diffuse gastrointestinal dilatation with echogenic content was observed in 8/22 cats. Conclusion Exocrine pancreatic insufficiency often causes minimal to no sonographic pancreatic changes. Nonetheless, the findings of thin pancreatic parenchyma, pancreatic duct dilatation, or diffuse small intestinal dilatation with echogenic contents in cats with unexplained weight loss or unformed feces should raise clinical suspicion for EPI.

Rising engine efficiency, increasingly stringent exhaust limits, and the use of synthetic and renewable fuels are all factors that demand a deeper knowledge of the combustion process. State-of-the-art investigations employ optical and laser-optical measurement techniques that rely on having optical access to the engine. In this paper, a new endoscopic system that provides full optical access to a high-speed large-bore engine is compared by thermodynamic experimentation to the equivalent all-metal engine. This comparison provides an insight into the altered combustion behavior resulting from modifying the engine to accommodate the optical elements. The successfully realized concept consists of two individually usable access points integrated in an engine with a bore of 170 mm and a stroke of 210 mm. The lateral endoscopic access is designed for full-load operating conditions and provides the best comparability to an all-metal engine. It is compared directly to the all-metal engine in the present investigations. Despite the changes in engine-out emissions from the optical engine, the experimental results display relatively equal combustion behavior in both setups. The lateral endoscopic access is then extended by adding a fisheye endoscope in place of one exhaust valve. This setup is compared to findings obtained with the endoscopic lateral access. The investigations reveal further deviations of the combustion process due to the more extensive modifications needed to fit the fisheye endoscope to the cylinder head. Nevertheless, the results display an overall good level of comparability of the combustion behaviors in these setups and, in turn, of the validity of further fundamental experiments based on the optical engine.

Background Historical and recent literature disagree on whether a higher PO 131I dosage, compared to IV or SC routes, is required for successful resolution of spontaneous hyperthyroidism in cats, necessitating investigation into the effect of PO and injectable radioactive iodine administration on % thyroidal radioactive iodine uptake (RAIU). Hypothesis/Objectives To investigate the effect of PO and SC routes of 123I administration on paired % thyroidal RAIU in euthyroid cats. Specifically, a 1.5‐fold difference (50% relative change) was hypothesized, which in absolute terms can be expressed as a 3.25% increase in the mean %RAIU of 7.04% after PO 123I administration to 10.56% after SC dosing. Animals Seven healthy euthyroid teaching‐research colony cats. Methods A randomized, radiologist‐blinded crossover study comparing %RAIU after PO and SC 123I administration. Results Percentage thyroidal RAIU values (mean ± SD; 95% confidence interval) after PO (4.81% ± 1.63%; 3.30%‐6.23%) and SC (5.26% ± 2.43%; 3.01%‐7.51%) 123I administration were associated with a median within‐pair absolute difference of 0.2% (range: min, 0.1%‐max, 4.9%). Statistical significance was not achieved (P = .45). Six of 7 cats had a within‐pair absolute difference of 0.1% to 0.9% (relative change of 4%‐20%), but a single outlier cat had a within‐pair absolute difference of 4.9% (relative change of 108%). Conclusions and Clinical Importance This study did not detect an effect of 123I administration route on paired % thyroidal RAIU in euthyroid cats. However, a type 2 statistical error due to small sample size is possible.

Background Clinical signs and their progression in Beagles with Lafora disease are poorly described. Objectives To describe clinical signs in Beagles with Lafora disease. Animals Twenty‐eight Beagles with Lafora disease confirmed by genetic testing or histopathology. Methods Retrospective multicenter case series. Data regarding signalment, clinical signs, diagnostic tests and treatment were retrieved from hospital data files. A questionnaire was sent to owners asking about neurological deficits, changes in cognitive functions, behavioral changes, response to treatment and survival time. Results Onset of clinical signs was 8.3 years (mean; range, 6.3‐13.3). All dogs had myoclonic episodes as an initial clinical sign with tonic‐clonic seizures in n = 11/28 (39%) and n = 12/28 (43%) later developing tonic‐clonic seizures. Deficits of coordination (n = 21/25; 84%), impaired vision (n = 15/26; 58%), and impaired hearing (n = 13/26; 50%) developed later. Mental decline was observed as loss of house training (urination; n = 8/25; 32%), difficulties performing learned tasks (n = 9/25; 36%), and difficulties learning new tasks (n = 7/23; 30%). Common behavioral changes were: increased photosensitivity (n = 20/26; 77%), staring into space (n = 16/25; 64%), reduced stress resistance (n = 15/26; 58%), increased noise sensitivity (n = 14/26; 54%), and separation anxiety (n = 11/25; 44%). Twenty‐one dogs were alive (median age 11.9 years; range, 9.8‐18.6), and 7 dogs were dead (mean age 12.1 years; SD: 1.3; range, 10.5‐12.6) at time of writing. Conclusions and Clinical Importance Lafora disease in Beagles causes significant behavioral changes, and mental decline as well as neurological deficits in addition to myoclonic episodes and generalized tonic‐clonic seizures. Nevertheless, a relatively normal life span can be expected.

BackgroundSerum phosphorylated neurofilament-heavy chain (pNF-H) has not been longitudinally evaluated in dogs that develop progressive myelomalacia (PMM) after Type I intervertebral disc herniation (IVDH).ObjectivesTo determine if serum pNF-H concentrations would predict outcome of neuroligical disease in dogs with acute, severe thoracolumbar myelopathy secondary to Type I IVDH.AnimalsThirty-nine client-owned dogs with thoracolumbar myelopathy secondary to IVDH.MethodsProspective controlled cohort study. Serum was collected from dogs undergoing hemilaminectomy at multiple timepoints. Final neurological status was established at 12 months and groups were stratified accordingly. Comparisons between outcome and pNF-H concentration at each timepoint was examined using Kruskal-Wallis analysis of variance on ranks and receiver operator characteristics curve analysis.ResultsMedian serum pNF-H concentrations were not significantly different between deep pain negative dogs that did or did not recover at any timepoint (baseline: 0.37 ng/mL [0-0.9 ng/mL] vs 0 ng/mL [0-0.9 ng/mL], P > 1; 24 hours: 1.25 ng/mL [0.35-7.23 ng/mL] vs 1.53 ng/mL [0-11.94 ng/mL], P > 1; 48 hours: 1.22 ng/mL [0.63-6.62 ng/mL] vs 2.12 ng/mL [0-20.72 ng/mL], P > 1; 72 hours: 2.77 ng/mL [1.33-6.62 ng/mL] vs 16.69 ng/mL [4.02-40.12 ng/mL], P > 1). Dogs that developed PMM had significantly higher serum pNF-H concentrations after surgery compared to all other cohorts at 24 hours: 39.88 ng/mL (25.74-50.68 ng/mL); P

Background Medical dissolution of struvite uroliths in dogs is commonly recommended, but data on success rates and complications are limited. Objectives To evaluate the efficacy of medical dissolution for suspected struvite cystoliths in dogs. Animals Fifty client-owned dogs fed a therapeutic dissolution diet, with or without administration of antimicrobials, for treatment of suspected struvite cystoliths. Methods Single institution, retrospective case series. Medical records were reviewed for dogs with at least 1 follow-up visit. Dissolution success, complications, and possible predictors of success were evaluated. Results Full dissolution of cystoliths was achieved in 58% (29/50) of dogs within a median of 35 days (range, 13-167). Of 21 dogs without success, 7 each had partial dissolution, no dissolution, or undetermined outcome. Uroliths containing >10% nonstruvite mineral were common in the nonsuccess group (11/16 analyzed). Maximum urolith diameter, number of uroliths, and baseline urine pH did not differ significantly between dogs with and without success. Dissolution was more likely in dogs receiving antimicrobial therapy (OR = 16.3, 95% confidence interval 1.9-787.4, P = .002). Adverse events occurred in 9 dogs (18%); urethral obstructions were the most common, but 3 of 4 dogs with this complication were obstructed on presentation, before trial initiation. Conclusions and clinical importance Results support a medical dissolution trial for dogs with suspected struvite cystoliths. If no reduction in urolith size or number occurs by 1 month, a nonstruvite composition is likely, and alternative interventions should be considered. Dogs presenting with urethral obstructions should not be considered candidates for medical dissolution.

Background Irreversible sensorineural auditory loss has been reported in humans treated with aminoglycosides but not in horses. Objective Investigate if auditory loss occurs in horses treated using the recommended IV daily dosage of gentamicin for 7 consecutive days. Animals Ten healthy adult horses (7-15 years; females and males, 5 each). Methods Prospective study. Physical and neurological examinations and renal function tests were performed. Gentamicin sulfate was administered at a dosage of 6.6 mg/kg via the jugular vein on alternating sides for 7 days. Gentamicin peak and trough concentrations were measured. Horses were sedated using detomidine hydrochloride IV to perform brainstem auditory evoked responses (BAER) before the first dose, immediately after the last dose, and 30 days after the last dose. Peaks latencies, amplitudes, and amplitude ratios were recorded. Data from the second and last BAER were compared to results at baseline. Bone conduction was performed to rule out conduction disorders. Results Seven horses had auditory loss: complete bilateral (N = 1), complete unilateral (N = 2), and partial unilateral (N = 4). Based on physical examination and BAER results, sensorineural auditory loss was suspected. Absent bone conduction ruled out a conduction disorder and further supported sensorineural auditory loss in horses with completely absent BAER. Auditory dysfunction was reversible in 4 of 7 horses. Conclusions and clinical importance Gentamicin at recommended doses may cause sensorineural auditory loss in horses that might be irreversible. Follow-up studies are needed to investigate if other dosing protocols present a similar risk.

Background Fibroblast growth factor (FGF)‐23 is increased first in the sequence of changes associated with chronic kidney disease (CKD)‐mineral and bone disorder. Thus, its measurement may serve as a predictive indicator of incident hyperphosphatemia. Objectives To investigate whether serum FGF‐23 concentration in normophosphatemic dogs with CKD is associated with the risk of the subsequent development of hyperphosphatemia and CKD progression. Animals Forty‐two normophosphatemic dogs with CKD. Methods Blood samples and medical records were retrospectively investigated. Hyperphosphatemia was defined as a serum phosphorous concentration >5.0 mg/dL. Progression was defined as a >1.5‐fold increase in serum creatinine concentration. The time periods and hazard ratios for these outcomes were assessed using Kaplan‐Meier analysis, log‐rank test, and univariate Cox regression analysis. The variables associated with the outcomes in the univariate analysis were included in the multivariate Cox regression model with backward selection. Results Serum FGF‐23 concentration >528 pg/mL was associated with a shorter time to development of hyperphosphatemia (P

Background: \ud Hereditary sensory and autonomic neuropathies (HSANs) are a group of genetic disorders affecting the peripheral nervous system. Two different associated variants have been identified in dogs: 1 in Border Collies and 1 in Spaniels and Pointers.\ud \ud Objectives: \ud Clinically and genetically characterize HSAN in a family of mixed breed dogs.\ud \ud Animals: \ud Five 7-month-old mixed breed dogs from 2 related litters were presented for evaluation of a 2-month history of acral mutilation and progressive pelvic limb gait abnormalities.\ud \ud Methods: \ud Complete physical, neurological, electrodiagnostic, and histopathological evaluations were performed. Whole genome sequencing of 2 affected dogs (1 from each litter) was used to identify variants that were homozygous or heterozygous in both cases, but wild type in 217 control genomes of 100 breeds. Immunohistochemistry was used to assess protein expression.\ud \ud Results: \ud Complete physical, neurological, electrodiagnostic, and histopathological evaluations confirmed a disorder affecting sensory and autonomic nerves. Whole genome sequencing identified a missense variant in the RETREG1 (reticulophagy regulator 1) gene (c.656C > T, p.P219L). All affected dogs were homozygous for the variant, which was not detected in 1193 dogs from different breeds. Immunohistochemistry showed no expression of RETREG1 in the cerebellum of affected dogs. One of the affected dogs lived for 5 years and showed gradual progression of the clinical signs.\ud \ud Conclusions and Clinical Importance: \ud We confirmed the diagnosis of HSAN in a family of mixed breed dogs and identified a novel and possibly pathogenic RETREG1 variant. Affected dogs experienced gradual deterioration over several years.

Background Glucocorticoids are used for a variety of purposes in veterinary medicine but often are associated with clinically important adverse effects. Polyuria and polydipsia are the most frustrating adverse effects noted by owners. Objective To determine whether administration of desmopressin ameliorates polyuria and polydipsia associated with prednisolone administration. Animals Seven healthy adult Walker Hounds. Methods Prospective hypothesis testing study. Daily water intake and urine specific gravity (USG) were measured in dogs under 4 separate sequential conditions: no medications (C), prednisolone only (P), prednisolone and desmopressin (PD), and prednisolone after discontinuation of desmopressin (PAD). Results When compared to baseline, 6 of 7 dogs became polydipsic after administration of prednisolone (0.5 mg/kg PO q12h). When desmopressin (5 μg/dog SC q12h) was administered to dogs receiving prednisolone, significant decreases in water intake and serum sodium concentration occurred, and USG increased significantly. Conclusions and Clinical Importance Administration of desmopressin to dogs receiving prednisolone significantly decreased water intake and serum sodium concentration, and increased USG. Our results suggest that, in some dogs, desmopressin ameliorates the most important adverse effect of prednisolone noted by owners, but that hyponatremia is an important complication associated with desmopressin use.

Background Implantable vagus nerve stimulation (VNS) devices can be used to treat epilepsy in dogs. Adverse effects and short-term complications associated with delivering suggested therapeutic electrical stimulation (>1.5 mA) are not well-described. Objectives To compare complications and adverse effects observed with standard and rapid protocols of current increase. Animals Sixteen client-owned dogs with idiopathic epilepsy. Methods Nonrandomized, nonblinded prospective cohort study. Surgical complications, stimulation-related adverse effects, modifications to stimulator settings, number of hospital visits, and time to reach 1.5 mA stimulation current without intolerable adverse effects were described in dogs receiving current increases every 1 to 3 weeks (slow ramping) and dogs receiving current increases every 8 to 12 hours (fast ramping). Results Self-resolving surgery site seromas formed in 6 dogs. No other surgical complications were observed. Fourteen dogs reached 1.5 mA. Coughing (11/14 dogs; 5 slow, 6 fast ramping) was the most common adverse effect. Intolerable coughing that limited current increases despite changing other stimulus parameters occurred in 6/7 of the fast-ramping group and in none of the slow-ramping group. Median time to 1.5 mA was 72 days (range, 28-98) in the slow-ramping group and 77 days (range, 3-152) in the fast-ramping group. Median number of clinic visits was 6 for the slow-ramping group (range, 5-6) and 3 for the fast-ramping group (range, 1-7). Conclusions and clinical importance Coughing is a common adverse effect of VNS in dogs and generally is well tolerated, particularly if current is increased slowly and other stimulation parameters are adapted for effect.

Background Polymorphisms of the vitamin D receptor (VDR) are associated with calcium oxalate (CaOx) nephrolithiasis in humans. Objectives To investigate the association between VDR polymorphisms and susceptibility to CaOx urolithiasis in dogs. Animals Thirty‐five dogs with CaOx urolithiasis were compared with 40 stone‐free dogs. Methods This was a case‐control study. Two VDR gene polymorphisms (rs851998024 and rs852900542) were detected by specific TaqMan real‐time polymerase chain reaction assay, and their relationship with serum 1,25‐dihydroxyvitamin D, serum and urinary electrolyte concentrations was evaluated. Results The distribution of the rs852900542 polymorphism was significantly different between the case and the control dogs (x 2 = 6.369, P = .04). Dogs with a CC or CT genotype had an increased risk of CaOx stones than those with the TT genotype (odds ratio = 3.82, 95% confidence interval 1.04‐13.98). The CaOx dogs with the TT genotype had a significantly lower urinary calcium‐to‐creatinine ratio than the CT+CC genotypes. 1,25‐(OH)2D concentrations did not differ between the cases and the controls (308.7 ± 217.4 vs 286.7 ± 185.1 pg/mL, P = .45). Conclusions and Clinical Importance This finding suggests that vitamin D metabolism might play a role in CaOx stone formation in dogs.