Journal of Veterinary Internal Medicine

Understanding and correctly interpreting statistical results presented in scientific articles is a required skill for practicing evidence‐based veterinary medicine. A prerequisite for doing so is the adequate reporting of the results in scientific journals. However, most authors of veterinary publications determine the importance of their findings based on statistical significance (ie, P < .05), indicating that neither the limitations of using P values for inference nor the existence of more appropriate alternatives are widely appreciated in veterinary medicine. This deficiency in knowledge indicates a need to increase awareness in veterinary medicine regarding reporting statistical measures that quantify the magnitude of an effect along with its level of uncertainty, and then interpreting these results for clinical decision making. We utilize a hypothetical randomized controlled trial of dietary management in cats with chronic kidney disease to discuss some common misconceptions about P values and provide practical suggestions for alternatives. Reporting appropriate effect estimates along with their confidence intervals will allow veterinarians to easily and correctly determine whether the magnitude of the effect of interest meets clinical needs while acknowledging uncertainty in the results. We also describe confidence interval functions and show their utility as visual tools in aiding interpretation of confidence intervals. By providing practical guidance, we show that a change in reporting and interpreting statistical results is feasible and necessary. We hope this crucial step will promote clinical decision making based on effect estimates and confidence intervals.

Background Myocardial sleeves of the caudal vena cava are the predilection site for atrial tachycardia (AT) in horses. Caudal vena cava isolation guided by the ablation index, a lesion quality marker incorporating power, duration and contact force, might improve outcome. Objectives Describe the feasibility and outcome of caudal vena cava isolation using ablation index‐guided radiofrequency catheter ablation (RFCA) to treat AT in horses. Animals Ten horses with sustained AT. Methods Records from 10 horses with sustained AT treated by three‐dimensional electro‐anatomical mapping and ablation index‐guided RFCA (CARTO™ 3) were reviewed. Results Three‐dimensional electro‐anatomical mapping of the right atrium identified a macro‐reentry circuit in the caudomedial right atrium (n = 10). Point‐by‐point RFCA was performed to isolate the myocardial sleeves of the caudal vena cava in power‐controlled mode with a mean of 17 ± 7 applications. The ablation index target was 400‐450. A median ablation index of 436 (range, 311‐763) was reached using a median maximum power of 35 (range, 24‐45) W for a median duration of 20 (range, 8‐45) seconds, with a median contact force of 10 (range, 3‐48) g. Sinus rhythm was restored in all 10 horses. To date, 9‐37 months post‐ablation, none of the horses have had recurrence. Conclusions and Clinical Importance Caudal vena cava isolation using ablation index‐guided RFCA was feasible and effective to permanently treat sustained AT in horses. Ablation index guidance ensured efficient lesion creation, and isolation of the caudal vena cava eliminated the arrhythmogenic substrate, thereby minimizing the risk of recurrence.

Background Benazepril exhibits a dose‐dependent effect on biomarkers of the circulating renin‐angiotensin‐aldosterone system (RAAS) in dogs. Hypothesis/Objectives To characterize the dose‐exposure‐response relationship of a fixed‐dose combination product including benazepril and spironolactone (CARDALIS®) on RAAS biomarkers in dogs. Animals Eighteen purpose‐bred healthy beagle dogs. Methods Three groups of 6 dogs received different doses of CARDALIS® for 14 days following induction of RAAS activation by feeding a low‐sodium diet: (a) benazepril 0.25 mg/kg + spironolactone 2 mg/kg PO q24h (label dose); (b) benazepril 0.25 mg/kg + spironolactone 2 mg/kg PO q12h; or (c) benazepril 0.5 mg/kg + spironolactone 4 mg/kg PO q12h. Blood samples were collected at baseline and serial time intervals after CARDALIS® dosing to measure serum RAAS biomarkers and plasma concentrations of active drug metabolites. Time‐weighted averages for serum RAAS biomarkers after CARDALIS® dosing at steady state were compared between dosage groups using Wilcoxon rank‐sum testing. Results Compared to the label dose, the highest dose of CARDALIS® was associated with a 30% decrease in angiotensin II (P = .03), 94% increase in angiotensin 1‐7 (P = .03), 71% decrease in surrogate activity of ACE (P = .002), and 116% increase in circulating aldosterone (P = .02). CARDALIS® was well‐tolerated at all doses with no clinically relevant changes in renal values or serum electrolytes. Conclusions and Clinical Importance The combined CARDALIS® product leads to dose‐dependent alterations of RAAS metabolites. These results could help inform clinical trials in dogs with heart disease.

Background Although most cats with feline infectious peritonitis (FIP) respond to treatment with remdesivir or GS‐441524 or both with uneventful clinical courses, some die despite treatment. Objective Identify predictive factors associated with short‐term mortality in cats with FIP treated with IV remdesivir or PO GS‐441524 or both. Animals A total of 108 client‐owned cats with FIP. Methods Retrospective multicenter study using data collected from medical records. Factors associated with short‐term mortality, defined as death within 84 days, were identified. Univariate analysis a t‐test, Mann‐Whitney U test, or Fisher's exact test and multivariate logistic regression were performed to assess patient characteristics and clinicopathological variables between survivors and nonsurvivors. Results The short‐term mortality rate was 12.0% (95% confidence interval [CI], 6.6%‐19.7%). Univariate analysis identified plasma lactate dehydrogenase activity (LDH; P < .001) and bilirubin concentration (P = .001) as being significantly increased in nonsurvivors, whereas concentrations of albumin (P = .003), total protein (P = .03), sodium (P = .005), and potassium (P = .005) were significantly lower. Additionally, nonsurvivors were significantly less likely to be febrile (≥39.4°C; P = .006). Of these variables, only plasma LDH activity ≥323 U/L, a cut‐point determined by receiver operating characteristic curve analysis, was significantly associated with short‐term mortality by multivariate analysis (odds ratio, 15.30; 95% CI, 1.18‐198.00; P = .04). Conclusion Increased plasma LDH activity might be useful for predicting short‐term mortality, guiding monitoring, and establishing prognosis in cats with FIP.

Background Several tests are available to diagnose naturally‐occurring Cushing's syndrome in dogs but there is a paucity of information on how primary care veterinarians (PCVs) use or interpret them. Objectives Determine how PCVs from selected European countries diagnose Cushing's syndrome in dogs. Methods Cross‐sectional survey study assessing testing protocols used by PCVs for screening and differentiation of Cushing's syndrome. Results Two thousand one hundred and seventy‐eight responses from 9 European countries were included. When Cushing's syndrome was suspected, 98.7% of respondents perform endocrine testing, whereas 1.2% rely on a treatment trial. Among the former, 59.9% reported performing screening tests in the absence of supportive clinical signs but with consistent clinicopathological abnormalities. Of 2150 respondents who performed endocrine testing, 66.6% report always using the same initial screening tests regardless of their pretest suspicion of disease. The tests most reported are the ACTH stimulation test (34.8%), low‐dose dexamethasone suppression test (LDDST; 30.4%) or a combination of different tests (25.2%). In the absence of financial constraint, 1419 (66.0%) respondents always attempted differentiation, using abdominal ultrasonography (81.0%) and LDDST (46.1%). Overall, 69.8% of respondents reported offering referral to a specialist in ≤20% of cases suspected or diagnosed with Cushing's syndrome over the previous 5 years. Conclusions and Clinical Importance Testing protocols vary among PCVs. Almost 60% of respondents potentially screen dogs without consistent clinical signs, raising concerns for overdiagnosis. A proportion never attempt differentiation, which likely affects prognosis. Cases are rarely referred to a specialist, reflecting that Cushing's syndrome is mainly managed in primary care practices. These results suggest that there is room for further education of PCVs.

Background Azotemia is common in cats with congestive heart failure (CHF) and might be exacerbated by diuretic therapy. Hypothesis/Objectives Determine frequency, risk factors, and survival impact of progressive azotemia in cats treated for CHF. Animals One hundred and sixteen client‐owned cats with kidney function testing performed at least twice during acute or chronic CHF treatment. Methods Serum creatinine (sCr) and electrolyte concentrations were determined at multiple clinical timepoints to detect azotemia and kidney injury (KI; sCr increase ≥0.3 mg/dL). Furosemide dosage between timepoints was calculated. Multivariable modeling was performed to identify predictors of KI, change in serum biochemistry results, and survival. Results Azotemia was common at all timepoints, including initial CHF diagnosis (44%). Kidney injury was documented in 66% of cats. Use of a furosemide continuous rate infusion was associated with increased risk of KI during hospitalization (odds ratio, 141.6; 95% confidence interval [CI], 12.1‐6233; P = .01). Higher furosemide dosage was associated with increase in sCr during hospitalization (P = .03) and at first reevaluation (P = .01). Treatment with an angiotensin converting enzyme inhibitor was associated with fewer lifetime KI events (P = .02). Age in years was the only variable associated with shorter survival (hazard ratio, 1.1; 95% CI, 1.0‐1.1; P = .03). Neither sCr nor KI were associated with long‐term outcome. Conclusions and Clinical Importance Azotemia and KI were common in cats during CHF treatment but did not impact survival.

Background Chronic gingivostomatitis in cats (FCGS) is a moderately to severely painful condition, potentially caused by inadequate immune response to oral antigenic stimulation. Salivary peptidome analysis can identify inflammatory protein mediators and pathways involved in oral mucosal immune activation and may indicate potential therapeutic options for FCGS. Objective Evaluate the diversity and abundance of salivary peptides in cats with FCGS using matrix‐assisted laser desorption/ionization‐time‐of‐flight mass spectrometry (MALDI‐TOF MS) and nanoscale liquid chromatography‐tandem mass spectrometry (nano LC‐MS/MS). Animals Thirty‐two cats with FCGS and 18 healthy controls. Methods Case‐control cross‐sectional study. We compared the salivary peptide profiles of diseased and healthy cats. The diagnosis of FCGS was confirmed by histopathology. Saliva samples were analyzed for viral infections using polymerase chain reaction (PCR), peptide mass fingerprint (PMF) using MALDI‐TOF MS, and peptide identification using nano LC‐MS/MS. Results Distinct clusters of peptide profiles were observed between groups. In FCGS, 26 salivary peptides were altered, including apolipoprotein A1, nuclear receptor subfamily 1 group I member 3, fibrinogen alpha chain, interleukin 2 receptor gamma, interleukin 23 receptor, hemoglobin subunit alpha, and serpin peptidase inhibitor clade A (alpha‐1 antiproteinase, antitrypsin) member 12, protein‐tyrosine‐phosphatase, and cholinergic receptor nicotinic alpha 10 subunit. Protein‐anti‐inflammatory drug interaction networks were observed. Conclusions and Clinical Importance Peptide mass fingerprint and peptide profiles identified distinct clusters between FCGS and healthy cats. The 9 novel salivary peptide markers were associated with the JAK/STAT and PI3K/Akt pathways and immune responses. These potentially noninvasive biomarkers may facilitate understanding of FCGS pathophysiology and guide future therapeutic research.

Background Phenylbutazone is prescribed for laminitis‐associated pain and decreases glucose and insulin responses to an oral glucose test (OGT) in horses with insulin dysregulation (ID). Hypothesis/Objectives Investigate the effect of phenylbutazone administration on the enteroinsular axis in horses. Animals Sixteen horses, including 7 with ID. Methods Randomized cross‐over study design, with horses assigned to treatment with phenylbutazone (4.4 mg/kg IV q24h) or placebo (5 mL 0.9% saline). On Day 9 of treatment, an OGT was conducted, followed by a 10‐day washout period, administration of the alternative treatment, and repetition of the OGT. Glucose‐dependent insulinotropic polypeptide (GIP), and active glucagon‐like peptide 1 and 2 (aGLP‐1 and GLP‐2) concentrations were determined by ELISA. The effects of ID status and treatment on peptide concentrations were assessed using t tests and analyses of variance. Results Horses with ID had significantly higher maximum GIP concentrations (Cmax) than controls (median, 279.1; interquartile range [IQR], 117.5‐319.4 pg/mL vs median, 90.12; IQR, 74.62‐116.5 pg/mL; P = .01), but no significant effect of ID was detected on aGLP‐1 and GLP‐2 concentrations. In horses with ID, phenylbutazone treatment significantly decreased GIP Cmax compared with placebo (168.1 ± 59.26 pg/mL vs 242.8 ± 121.8 pg/mL; P = .04), but no significant effect of phenylbutazone was detected on aGLP‐1 and GLP‐2 concentrations. Conclusion and Clinical Importance Glucose‐dependent insulinotropic polypeptide, aGLP‐1 and GLP‐2 do not mediate the decrease in glucose and insulin concentrations observed after phenylbutazone administration. Only GIP was repeatedly associated with ID status, calling into question the role of the enteroinsular axis in ID.

Background Protothecosis in dogs is a rare, yet emerging disease, distinguished by its often‐aggressive clinical course and high fatality rate. Our study was conducted to enhance treatment protocols for affected dogs by better understanding the genetic diversity and drug resistance patterns of Prototheca species. Objectives To identify species and drug susceptibility profiles of an international collection of 28 Prototheca strains isolated from cases of protothecosis in dogs. Animals None. Methods Retrospective study. Species‐level identification was made for isolates from 28 dogs in 6 countries by molecular typing with the partial cytb gene as a marker. For the determination of minimum inhibitory concentrations (MICs) and minimum algicidal concentrations (MACs), the Clinical Laboratory Standards Institute (CLSI) protocol (M27‐A3) was used. Results Prototheca bovis was the most prevalent species, accounting for 75% (21/28) of the cases, followed by P. wickerhamii (18%; 5/28) and P. ciferrii (7%; 2/28). Of the 6 drugs tested, efinaconazole (EFZ) was the most potent in vitro, with its median MIC and MAC values equal to 0.125 mg/L. The lowest activity was found for fluconazole (FLU), with MIC and MAC medians of 48 mg/L and 64 mg/L, respectively. Conclusions and Clinical Importance Our study identifies P. bovis as the species that most frequently causes protothecosis in dogs, which suggests the possibility of cross‐species infection from other animals, especially cows. Additionally, it indicates that EFZ could be used in the treatment of infection in the colon.

Background Angiotensin‐converting enzyme inhibitors (ACEi) have the potential to cause worsening renal function (WRF). Therefore, reevaluation of renal function is recommended 1‐2 weeks after starting ACEi therapy. Objectives To identify risk factors for WRF in dogs receiving ACEi for cardiac diseases, proteinuria, or systemic hypertension. Animals A total of 156 client‐owned dogs that received ACEi were included. Methods Serum creatinine concentration was determined at the initial presentation and first reevaluation to detect and grade WRF (increase in sCr ≥ 0.3 mg/dL). Grade 1 (nonazotemic), 2 (mild), and 3 (moderate to severe) WRF were characterized by sCr remaining ≤1.6 mg/dL, 1.7‐2.5 mg/dL increase, and 2.6‐5.0 mg/dL increase, respectively. Demographic and serum chemistry data, such as total protein, albumin, blood urea nitrogen, creatinine, symmetric dimethylarginine, glucose, triglyceride, total cholesterol concentrations, and serum electrolyte concentrations at first presentation, were evaluated. Multivariable modeling was performed to identify risk factors for WRF after treatment with ACEi. Results Worsening renal function was identified in 27/156 (17%, 95% confidence interval [CI], 0.11‐0.23) dogs after ACEi treatment. It was classified as Grades 1, 2, and 3 in 17, 2, and 8 dogs, respectively. The only significant factors associated with WRF in dogs receiving ACEi were concurrent administration of furosemide (odds ratio, 5.05; 95% CI, 2.05‐12.4; P < .001) and pre‐existing azotemia (odds ratio, 3.21; 95% CI, 1.28‐8.03; P = .01). Conclusions and Clinical Importance Although WRF is uncommon and mild, ACEi should be cautiously prescribed in dogs receiving furosemide or those with pre‐existing azotemia.

Background Obesity is a risk factor for diabetes mellitus, which commonly coexists with pancreatitis in cats. However, obesity has not previously been associated with pancreatitis in cats. Objectives To evaluate factors affecting serum concentrations of pancreatic lipase immunoreactivity (fPLI), trypsin‐like immunoreactivity (fTLI), cobalamin and folate in clinically healthy lean, overweight and obese, or diabetic cats. Animals Seventy‐nine client‐owned cats (27 healthy lean [LN, BCS 4‐5/9], 30 healthy overweight and obese [OW, BCS 7‐9/9], and 22 diabetic [DM]) were included. Methods Cross‐sectional study. The cats underwent physical examination, and blood tests. Linear regression models compared differences in fPLI, fTLI, cobalamin, and folate concentrations. Fisher's exact test assessed the proportions of cats with fPLI and fTLI indicative of pancreatitis, and hypocobalaminemia. A random forest algorithm identified explanatory variables for cats having fPLI levels indicative of pancreatitis. Results No LN cats, while 6/30 (20%) of OW and 10/22 (45%) of DM cats had fPLI concentrations indicative of pancreatitis. Body condition score (P = .02) and body weight (P = .002) were positively associated with fPLI levels in LN and OW cats. Higher fPLI, and lower cobalamin concentrations were associated with higher age across groups. Conclusions and Clinical Importance Body condition score and body weight were associated with higher fPLI levels in nondiabetic cats. A larger proportion of OW and DM cats had fPLI concentrations indicative of pancreatitis compared to LN cats. Whether this indicates subclinical pancreatitis remains to be determined. Hypocobalaminemia was less frequent in OW compared to DM cats.

Background Gallbladder mucocele (GBM) is a common disease in the canine gallbladder. Although the pathogenesis of GBM remains unclear, we recently reported that the excessive accumulation of mucin in the gallbladder is not a result of overproduction by gallbladder epithelial cells (GBECs). Hypothesis/Objectives Changes in the function of GBECs other than the production of mucin are associated with the pathogenesis of GBM. We performed an RNA sequencing (RNA‐seq) analysis to comprehensively search for abnormalities in gene expression profiles of GBECs in dogs with GBM. Animals Fifteen dogs with GBM and 8 dogs euthanized for reasons other than gallbladder disease were included. Methods The GBECs were isolated from gallbladder tissues to extract RNA. The RNA‐seq analysis was performed using the samples from 3 GBM cases and 3 dogs with normal gallbladders, and the gene expression profiles were compared between the 2 groups. Differences in mRNA expression levels of the extracted differentially expressed genes (DEGs) were validated by quantitative reverse transcription polymerase chain reaction (RT‐qPCR) using samples of 15 GBM cases and 8 dogs with normal gallbladders. Results Comparison of gene expression profiles by RNA‐seq extracted 367 DEGs, including ANO1, a chloride channel associated with changes in mucin morphology, and HTR4, which regulates the function of chloride channels. The ANO1 and HTR4 genes were confirmed to be downregulated in the GBM group by RT‐qPCR. Conclusions and Clinical Importance Our results suggest that GBM may be associated with decreased function of chloride channels expressed in GBECs.

Background Knowledge about primary hypoadrenocorticism coexisting with immune‐mediated thyroiditis (Schmidt's syndrome) in dogs is limited. Objective To evaluate thyroid function in dogs with naturally occurring hypoadrenocorticism before and during treatment. Animals Sixty‐six client‐owned dogs. Methods Measurement of canine thyroid stimulating hormone (cTSH), total thyroxine (T4), free thyroxine, and autoantibodies against thyroglobulin, T4, and total triiodothyronine. Results Thirty‐eight dogs were assessed before and 28 during treatment. Follow‐up data were available for 24/38 and 17/28 dogs, with median follow‐up duration of 3.8 years (range, <1.0‐8.8 years) and 4 years (range, 1.1 weeks to 10.5 years), respectively. Canine thyroid stimulating hormone was above the reference range at the time of diagnosis of hypoadrenocorticism in 10 of 38 dogs but decreased into the reference range in 7 for which follow‐up data was available. Hypothyroidism was confirmed in 5 dogs at a median age of 11 years (range, 7‐15 years). In 4 dogs, the condition was diagnosed after a median treatment duration of 5.75 years (range, 2.6‐10 years), while in 1 dog, the diagnosis was made concurrently. One dog had detectable thyroid autoantibodies. Conclusions and Clinical Relevance Hypothyroidism occurs as a rare concurrent condition in dogs with hypoadrenocorticism, potentially at any phase of treatment. Close monitoring of cTSH levels in these dogs could be beneficial, as early changes might indicate the onset of hypothyroidism. The low prevalence of detectable thyroid autoantibodies suggests that nonimmune mechanisms might contribute to thyroid dysfunction.

Understanding and incorporating evidence‐based veterinary medicine (EBVM) into clinical practice and research continues to pose a challenge for our profession despite over 2 decades of increasing awareness of this concept. Reasons for this include a lack of understanding of its importance to the practice of medicine, veterinary literature that often fails to adhere to evidence‐based standards, inadequate attention to teaching EBVM at the university level, and the inherent reluctance of clinicians to alter historical practice styles. For many practitioners, EBVM continues to be an abstract concept they believe requires advanced training in statistics and epidemiology resulting in them relying on less robust sources for clinical guidance. This unfortunately results in suboptimal care for our patients and delayed medical advancements for our profession. As part of the 20th anniversary of the founding of the Evidence‐Based Veterinary Medicine Association (EBVMA), we are refocusing our efforts to highlight the need for dedicated teaching of EBVM at the university level, for rigorous adherence to established research reporting guidelines, for expansion of EBVM infrastructure, and for the provision of easily accessible tools that permit clinicians to incorporate EBVM into their daily practice. As the quality of veterinary literature improves, so too will development of more effective clinical practice guidelines that ultimately can be widely adopted if they are flexible enough to support the triadic relationship between veterinarians, our clients and our patients. Ultimately, EBVM is not an end unto itself, but rather a means to improve the quality of care we provide our patients.

Background Myoclonus has been described in aging Cavalier King Charles Spaniels (CKCS), but the natural course of the disease and response to treatment have not been described. Objectives Report the clinical features and course of myoclonus in CKCS. Animals Twenty‐seven caregivers provided questionnaire responses at a median of 24 months after the onset of myoclonus in their CKCS. Fifteen caregivers completed a second follow‐up questionnaire at a median of 17 months after submission of the first questionnaire. Methods The caregivers of affected CKCS were invited to provide video footage for review. Owners of CKCS with videos demonstrating myoclonus then completed the online questionnaire for further evaluation. A second shortened questionnaire was sent to participants at least 6 months after completion of the first. Results Most CKCS displayed spontaneous myoclonus affecting predominantly the head (25/27). Overall, the majority had episodes that increased in frequency (20/27) and severity (17/27). Eighteen dogs had developed changes in behavior since the onset of myoclonus. These dogs were typically older and had experienced myoclonic episodes for longer than dogs without behavioral changes. Generalized epileptic seizures were reported in 4/27 dogs. Ten dogs received medical treatment. Eight were prescribed levetiracetam; all had an initial decrease in episode frequency, but a subsequent increase in both frequency and severity of episodes was common. Conclusions and Clinical Importance Myoclonus in CKCS tends to progress in frequency and severity regardless of treatment. Progressive behavioral changes suggestive of cognitive decline are common. These findings support the possibility of an underlying neurodegenerative process.

Background Limited information is available on electrolyte abnormalities in cats with chronic inflammatory enteropathy (CIE). Hypothesis/Objectives Report the prevalence of electrolyte abnormalities in cats with CIE compared to other gastrointestinal disorders, and determine their association with disease and outcome variables in cats with CIE. Animals Three hundred twenty‐eight client‐owned cats from 2 referral hospitals: CIE (132), alimentary small cell lymphoma (29), acute gastroenteritis (48), and healthy controls (119). Methods Retrospective study comparing serum electrolyte concentrations at time of diagnosis among the 4 groups of cats, and associations with clinical signs, intestinal mucosal fibrosis scores, treatment subclassification and outcome in CIE. Results Cats with CIE had lower sodium and higher potassium concentrations and lower sodium: potassium ratios compared with healthy cats (P < .001, P = .01, and P < .001, respectively). Cats with CIE and a duodenal mucosal fibrosis score of 2 had lower sodium and lower total calcium concentrations compared with cats that had a score of 0 (P = .02 and P = .01). Cats with CIE and a colonic mucosal fibrosis score of 1 had higher potassium concentrations and lower sodium: potassium ratios compared with cats that had a score of 0 (P = .03 and P = .01). Cats with CIE that died as a result of their disease had higher potassium concentrations and lower sodium: potassium ratios compared to cats that were alive (P = .02 and P = .01). Conclusions and Clinical Importance Electrolyte abnormalities occur with CIE and, in particular, in cats with higher fibrosis scores and worse outcomes. Further research should aim to determine the pathogenesis of these findings and identify novel therapeutic targets for cats with CIE.

Background Lesions causing refractory epilepsy, often associated with temporal lobe epilepsy (TLE), can be undetectable on standard magnetic resonance imaging (MRI) in dogs. Automated brain volumetry, widely used in human medicine, can now be applied in veterinary medicine because of the availability of brain atlases. Objectives This study aimed to develop an automatic volumetry method, translate the outcomes into the assessment of temporal lobe volumes in dogs with idiopathic epilepsy, and correlate the results with the electroencephalography (EEG) data of epileptiform discharges (EDs). Animals Thirty‐one dogs of various breeds with dominant temporal lobe discharge. Methods Retrospective, observational study. The MRI and EEG examination results of dogs referred for neurological diagnosis data between 2016 and 2021 were retrospectively analyzed. An automated volumetry method was developed, which allowed the evaluation of temporal lobe volumes of the dogs. The asymmetric ratio (AR) was then estimated, and the results were correlated with the EEG EDs. Results 12/31 (38%; 95% CI: 21.8%‐57.8%) dogs had an asymmetric ratio >6%. Among them, reduction in temporal lobe volumes correlated with the side of the EEG EDs in 7 cases. There was no statistical correlation between temporal lobe volume changes and ED location. Conclusions and Clinical Importance Preliminary volumetric analysis of the temporal lobes indicates the presence of volume differences between the lobes in some dogs with idiopathic epilepsy. Diagnosis of TLE in dogs based on MRI volumetry in correlation with EEG examination, especially for dogs with drug‐resistant epilepsy, can influence the development of new therapeutic options, such as surgery.

Background Primary glomerular disease resulting in protein‐losing nephropathy (PLN) is an uncommon cause of chronic kidney disease in cats, yet is important to recognize because it warrants specific treatment that impacts outcome. Hypothesis/Objective Characterize clinicopathologic findings, prognostic indicators, and short‐ (≤30 days) and long‐term survival of cats with PLN. Animals Thirty‐seven cats with naturally occurring PLN. Methods Medical records of cats with PLN admitted to a veterinary teaching hospital were retrospectively reviewed. Results Median age was 3 years (range, 1.5‐11.5 years) and 17/37 (46%) were males. Short‐term survival was 57%. The estimated median survival time of all cats was 424 days (95% confidence interval [CI], 0‐1098 days). Common clinical signs included lethargy (57%), edema (46%) and weight loss (35%). Edema was more common in short‐term survivors compared with nonsurvivors (odds ratio [OR], 0.21; 95% CI, 0.05‐0.86‐20.4; P = .04). Serum creatinine concentration at presentation was negatively associated with long‐term survival (OR, 1.3; 95% CI, 1.03‐1.52; P = .01). Administration of immunosuppressive and antiproteinuric medications was more common among short‐term survivors compared with nonsurvivors (18/20 [90%] vs 9/16 [56%]; OR, 7.0; 95% CI, 1.2‐40.8; P = .05 and 17/20 [85%] vs 7/16 [44%]; OR, 7.3; 95% CI, 1.5‐35.2; P = .01, respectively). Partial or complete remission was documented in 11/31 (36%) cats and was associated with both short (OR, 3.3; 95% CI, 1.7‐6.5; P < .001) and long‐term survival (P = .003). Conclusion and Clinical Importance Cats with PLN have a guarded prognosis, but achieving remission improves outcome. Cats presented with edema rather than azotemia are more likely to respond to treatment.

A 7‐year‐old male castrated Cavalier King Charles Spaniel was hospitalized for 12 days for treatment of severe congestive heart failure secondary to myxomatous mitral valve disease. During that time, 6 serum samples from different days were analyzed for serum biochemical and renin‐angiotensin‐aldosterone system components. Serum chloride concentrations (ranging from 71.6 to 103.1 mmol/L) were inversely related to angiotensin I concentrations, aldosterone concentrations, a surrogate marker of renin activity, and a surrogate marker of adrenal responsiveness to angiotensin II. In light of recent studies showing that hypochloremia is associated with advanced heart failure in dogs and is associated with poor outcomes in people, the information from the dog in this report supports exploration of RAAS dysregulation as an underlying mechanism.

Background Workload associated with the high frequency Colombian Paso Fino gait has not been evaluated. Objectives To determine the oxygen consumption (V̇O2), heart rate (HR), stride frequency: breathing ratio, and hematology associated with the Paso Fino gait, including whether exercise‐induced pulmonary hemorrhage (EIPH) occurs. Animals Eleven Paso Fino horses. Methods Prospective cohort study. Horses performed a standardized Paso Fino gait test across a wooden sounding board, simulating competition. V̇O2 and ventilatory parameters (tidal volume [VT]; peak inspiratory and expiratory airflows [PkV̇I, PkV̇E]; respiratory rate [RR], minute ventilation [V̇E]) were measured using a portable ergospirometry facemask. Heart rate was measured using electrocardiograms. Post‐exercise lactate, hematocrit, bicarbonate, pH, electrolytes, and biochemistry concentrations were measured. EIPH was assessed via tracheobronchoscopy. Four horses completed a secondary high‐intensity gallop to elicit peak V̇O2 for comparative purposes. Results Median [IQR] mean individual HR during the Paso Fino gait was 190 [178, 201] bpm. Relative V̇O2 measured 49.8 [48.4, 59.5] mL/(kg min; VT = 8.6 [8.0, 10.7] L; RR = 87.1 [75.4, 99.5] bpm; V̇E = 869 [740, 902] L/min; PkV̇I = 33.4 [32.7, 37.2] L/s; PkV̇E = 44.2 [40.3, 46.0] L/s). Horses took 2.8 [2.7, 2.9] strides/second and had a stride frequency: breathing ratio of 2.0 [1.8, 2.3]. Post‐exercise blood lactate concentration and hematocrit measured 2.7 mmol/L and 50% respectively. Three horses showed endoscopic evidence of Grade‐1 EIPH. The Paso Fino gait V̇O2 and HR equaled 79% V̇O2pk and 91% maximal HR, respectively, based on the high‐intensity gallop. Conclusions and Clinical Importance The Paso Fino gait represents submaximal exercise based on V̇O2 < V̇O2pk and blood lactate.

Background Dogs with internal hydrocephalus do not necessarily have high intraventricular pressure (IVP). Hypothesis/Objectives Not all reported MRI findings indicate high IVP and some clinical signs might be associated with elevated IVP and syringomyelia. Animals Fifty‐three dogs. Materials and Methods Cross‐sectional study. Clinical signs and MRI findings were evaluated for an association of IVP >12 mm Hg and syringomyelia. Results High IVP was associated with obtundation OR 4.64 (95% CI 1.27‐16.93) (P = .02), head tilt OR 6.42 (95% CI 1.08‐37.97) (P = .04) and nystagmus OR 8.24 (95% CI 1.44‐47.07) (P = .02). Pain was associated with syringomyelia OR 3.4 (95% CI 0.98‐11.78) (P = .05). The number of affected ventricles was associated with high IVP OR 2.85 (95% CI 0.97‐8.33) (P = .05) and syringomyelia OR 12.74 (95% CI 2.93‐55.4) (P = .0007). Periventricular edema OR 24.46 (95% CI 4.54‐131.77), OR 7.61 (95% CI 1.91‐30.32) (P < .0002, P = .004) and signal void sign OR 17.34 (95% CI 4.01‐74.95), OR 4.18 (95% CI 1.16‐15.02) (P < .0001, P = .03) were associated with high IVP and syringomyelia. The probability for syringomyelia is lower with disruption of the internal capsule OR 0.19 (95% CI 0.05‐0.72) (P = .01) and higher VBR OR 0.25 (95% CI 0.1‐0.63) (P = .004). Conclusions and Clinical Importance Previously reported MRI findings are not predictive of high IVP. Clinical signs and MRI findings should be used to make a diagnosis of internal hydrocephalus in dogs with or without high IVP.

Background Esomeprazole use is increasing in dogs, but the gastrointestinal adverse events associated with q12h dosing necessitate pharmacodynamic evaluation of a reduced dose and frequency of administration. Objectives To compare the efficacy of 2 doses of (q24h) esomeprazole in raising intragastric pH in dogs. Animals Nine healthy, client‐owned dogs, >20 kg. Methods Prospective, randomized, double blinded, crossover study. Esomeprazole (0.5 or 1 mg/kg q24h) was orally administered for up to 5 days per treatment arm, and the mean percentage time intragastric pH was ≥3 (MPT3) and ≥4 (MPT4) for 24 hours periods were compared to pretreatment pH using a continuous pH monitoring system. Dogs failing to reach pH goals (MPT3 ≥75%, MPT4 ≥66%) with once daily dosing received esomeprazole 1 mg/kg PO q12h to determine if a higher dose would improve acid suppression. Results No significant difference in the MPT3 or MPT4 was identified between treatments for any time point (P > .05). Both doses increased the MPT pH ≥3 and 4 median [range] (0.5 mg/kg, 1 mg/kg) on days 1 (MPT3: 76.8% [44‐100], 69.2% [28.2‐100]; MPT4: 65.6% [16.7‐99.3], 54.9% [14.9‐93.3]; P = .0009) and 2 (MPT3:77.2% [27.4‐100], 75.4% [49.4‐89.5]; MPT4: 66.3% [15.5‐100], 59.7% [33.8‐81.2]; P = .0005) of PPI treatment compared to pretreatment (MPT3: 58.3% [0.02‐93.9], 52.6% [6.1‐94.7]; MPT4: 25.2% [0‐86.8], 32.4% [1.8‐89.3]). Six dogs (66%, [0.36, 0.97]) reached pH goals established in humans with q24h dosing. Conclusions and Clinical Importance Both q24h PO esomeprazole doses were effective in raising intragastric pH, despite high intersubject variability, but 33% of dogs required q12h dosing to reach pH goals.

Background Periparturient reproductive complications appear to be common in hospitalized goats. More information is needed about periparturient reproductive complications and survival in goats with these conditions. Objective Identify exposure factors associated with nonsurvival in periparturient does hospitalized ≤1 day or ≥2 days. Animals A total of 198 periparturient does presented to 9 university veterinary hospitals from October 2021 to June 2022. Methods Multicenter, matched case‐control study. Conditional logistic regression was used to identify exposure factors associated with nonsurvival in periparturient does hospitalized ≤1 day or ≥2 days. Results Overall doe survival was 79% (156/198). Survival in the 1st day of hospitalization was 71% (52/73) and survival in does hospitalized ≥2 days was 83% (104/125). Among goats hospitalized ≤1 day, labor duration before admission (odds ratio [OR] = 4.8; P = .04), uterine tears (OR = 48.2; P < .001), and vaginal/perineal trauma diagnosed during hospitalization (OR = 6.2; P = .03) were associated with nonsurvival. Among goats hospitalized ≥2 days, factors associated with nonsurvival included labor duration before admission (OR = 6.2; P = .004), pregnancy toxemia (OR = 6.07; P = .04), and Cesarean section (OR = 11.35; P = .02). Conclusions and Clinical Importance Longer labor duration before admission is an important predictor of nonsurvival in hospitalized does. Clients should be educated that early detection and veterinary care are critical for improving outcome in periparturient does.

Background Oxidative stress is a potential contributor to chronic kidney disease (CKD) progression but has not been evaluated in dogs and cats with CKD. Hypothesis Oxidative stress is higher in animals with CKD compared with healthy controls and decreases with the advancing CKD stage. The aim of this study was to determine the presence and intensity of oxidative stress in dogs and cats at different CKD stages. Animals Sixty dogs and 30 cats with naturally acquired CKD; 10 dogs and 14 cats, healthy controls. Methods Analytical cross‐sectional study. Oxidative stress was evaluated by measuring the urinary concentration of F2‐isoprostane (uF2‐IsoPs) normalized to urinary creatinine. Results Urinary F2‐isoprostanes normalized to urinary creatinine of healthy dogs and of dogs with CKD Stages 1 to 4 was 3.3 ng/mg, 4.7 ng/mg (range, 1.0‐73.4), 2.4 ng/mg (range, 0.4‐7.8), 0.52 ng/mg (range, 0.01‐2.9), and 0.37 ng/mg (range, 0.01‐0.6), respectively. Urinary F2‐isoprostanes differed among CKD stages (P < .001), but not compared with controls. uF2‐IsoPs of healthy cats and cats with CKD Stages 1 to 4 was 0.68 ng/mg (range, 0.2‐1.4), 0.97 ng/mg (range, 0.4‐1.8), 0.6 ng/mg (range, 0.002‐2.0), 0.94 ng/mg (range, 0.3‐2.3), and 0.2 ng/mg (range, 0.01‐0.4). Urinary F2‐isoprostanes differed among stages (P = .05) but not compared with healthy controls. Conclusion and Clinical Importance Oxidative stress might be present in dogs and cats with CKD. Its magnitude declines as the disease progresses, therefore, it should be considered a potential therapeutic target mostly at the early stages of the disease.

Background Milk fever (MF), a metabolic disorder in dairy cows characterized by low blood calcium concentrations postpartum, is well‐recognized clinically. However, comprehensive data on the alteration of metabolites associated with this condition remains sparse. Hypothesis Delineate serum metabolite profiles and metabolic pathways preceding, coinciding with, and after the onset of MF. Animals Twenty‐six cows, including 20 healthy cows and 6 cows initially affected by MF. Because of culling, the number of MF‐affected cows decreased to 4 at MF week, +4 weeks, and +8 weeks postpartum. Methods A nested case‐control longitudinal study was conducted, with blood samples collected at −8 and −4 weeks prepartum, MF week, and +4 and +8 weeks postpartum. Serum analysis utilized direct injection/liquid chromatography/tandem mass spectrometry (DI/LC/MS/MS) techniques. Results Key findings included the identification of diverse metabolites such as hexose, amino acids, phosphatidylcholines, lysophosphatidylcholines, and sphingomyelin, which varied between studied groups (P < .05). The most marked metabolic alterations were observed 4 weeks prepartum. In total, 42, 56, 38, 29, and 24 metabolites distinguished the MF group at the respective time points (P < .05). Additionally, 33 metabolic pathways, including amino acid, antioxidant metabolism, fatty acid degradation, and carbohydrate processing, were impacted (P < .05). Conclusions and Clinical Importance Metabolic disruptions in dairy cows begin several weeks before the clinical manifestation of MF and persist up to 8 weeks postpartum. These findings emphasize the complexity of MF, extending beyond only hypocalcemia and indicate the necessity for preemptive monitoring in dairy herd management.