Management of acute-onset pancreatitis in dogs: a Narrative Review.

Acute-onset pancreatitis (AP) is common in dogs and presents diagnostic as well as management challenges. Until recently, the management of AP in dogs was based mainly on supportive and symptomatic care. Identification and management of a possible cause of the disease is important, but the majority of cases are considered to be idiopathic. Fluid therapy that is tailored to the patient's needs is crucial to provide adequate hydration while preventing overhydration. Antiemetics are required to control vomiting and fluid loss and aid in early nutritional support. Recognition and management of complications is also crucial. Furthermore, analgesics for abdominal pain are very important. More recently, pharmaceutical modification of the inflammatory cascade has gained interest and the first specific therapeutic agent for the treatment of AP, fuzapladib sodium, has been shown to have a reasonable expectation of effectiveness in a pilot study. This drug has been licensed for the treatment of clinical signs of AP in dogs in Japan and also has achieved FDA conditional approval in the US. Antibiotics should not be used indiscriminately but are indicated for patients with aspiration pneumonia, gastrointestinal bacterial translocation, or evidence of another bacterial infection. Proton pump inhibitors and plasma are not routinely prescribed in pancreatitis unless specifically indicated. Nonsteroidal anti-inflammatory drugs should be avoided. Corticosteroid therapy, once thought to be contraindicated, may have some beneficial effects, as shown in a single retrospective study. However, further studies are required before their routine use can be recommended. Finally, a surgical approach is rarely indicated.

The effect of feeding on serum concentrations of cobalamin, folate, trypsin-like immunoreactivity, and pancreatic lipase immunoreactivity in dogs with signs of chronic gastrointestinal disease.

BACKGROUND: It is unknown if serum concentrations of cobalamin, folate, canine pancreatic lipase immunoreactivity (cPLI), and canine trypsin-like immunoreactivity (cTLI) obtained postprandially are equivalent to measurements obtained after withholding food in dogs with suspected gastrointestinal disease. HYPOTHESIS/OBJECTIVES: Measurements of serum concentrations of cobalamin, folate, cPLI, and cTLI postprandially will be equivalent to measurements after 12 hours of withholding food in dogs with signs of chronic gastrointestinal disease. Changes observed will not alter clinical interpretation. ANIMALS: 51 client-owned dogs with signs of gastrointestinal disease. METHODS: Prospective single arm clinical trial. Serum concentrations of cobalamin, folate, cPLI and cTLI 2, 4, and 8 hours postprandially were compared by equivalence testing to values after withholding food for 12 hours (baseline). RESULTS: Mean serum cobalamin concentrations 2 hours (498.1 ± 213.1 ng/L; P = 0.024) and 4 hours (501.9 ± 207.4 ng/L; P = 0.008) postprandial were equivalent to baseline (517.3 ± 211.5 ng/L). Mean serum cTLI 2 hours (31.3 ± 14 µg/L; P < 0.001) and 4 hours (29.6 ± 13.1 µg/L; P = 0.027) postprandial were equivalent to baseline (31.1 ± 15 µg/L). Mean serum folate concentration 2 hours postprandial (15 ± 7.7 µg/L) was equivalent to baseline (13.7 ± 8.3 µg/L; P < 0.001). Equivalence could not be assessed for cPLI due to results below the lower limit of quantification. Feeding altered the clinical interpretation in 27% (cobalamin), 35% (folate), 20% (cTLI), and 12% (cPLI) of dogs. CONCLUSIONS AND CLINICAL IMPORTANCE: The clinical interpretation for a substantial number of samples changed after feeding, therefore withholding food before sample collection is prudent.

Clustering analysis of lipoprotein profiles to identify subtypes of hypertriglyceridemia in Miniature Schnauzers.

BACKGROUND: Hypertriglyceridemia (HTG) is prevalent in Miniature Schnauzers, predisposing them to life-threatening diseases. Varied responses to management strategies suggest the possibility of multiple subtypes. HYPOTHESIS/OBJECTIVE: To identify and characterize HTG subtypes in Miniature Schnauzers through cluster analysis of lipoprotein profiles. We hypothesize that multiple phenotypes of primary HTG exist in this breed. ANIMALS: Twenty Miniature Schnauzers with normal serum triglyceride concentration (NTG), 25 with primary HTG, and 5 with secondary HTG. METHODS: Cross-sectional study using archived samples. Lipoprotein profiles, generated using continuous lipoprotein density profiling, were clustered with hierarchical cluster analysis. Clinical data (age, sex, body condition score, and dietary fat content) was compared between clusters. RESULTS: Six clusters were identified. Dogs with primary HTG were dispersed among 4 clusters. One cluster showed the highest intensities for triglyceride-rich lipoprotein (TRL) and low-density lipoprotein (LDL) fractions and also included 4 dogs with secondary HTG. Two clusters had moderately high TRL fraction intensities and low-to-intermediate LDL intensities. The fourth cluster had high LDL but variable TRL fraction intensities with equal numbers of NTG and mild HTG dogs. The final 2 clusters comprised only NTG dogs with low TRL intensities and low-to-intermediate LDL intensities. The clusters did not appear to be driven by differences in the clinical data. CONCLUSIONS AND CLINICAL IMPORTANCE: The results of this study support a spectrum of lipoprotein phenotypes within Miniature Schnauzers that cannot be predicted by triglyceride concentration alone. Lipoprotein profiling might be useful to determine if subtypes have different origins, clinical consequences, and response to treatment.

Prognostic value of C-reactive protein in dogs with elevated serum pancreatic lipase immunoreactivity concentrations.

OBJECTIVE: To determine the prognostic value of serum C-reactive protein (CRP) in dogs with pancreatitis. ANIMALS: 503 client-owned animals with pancreatic lipase immunoreactivity (PLI) > 600 µg/L. METHODS: Routine submissions to the Texas A&M Gastrointestinal Laboratory were monitored for canine samples with PLI > 600 µg/L. Clinics were emailed 2 weeks after PLI measurement and asked the following questions: (1) was the dog hospitalized, and (2) is the patient alive? If a response was received, serum CRP concentration was measured using leftover serum. RESULTS: Paired PLI and CRP results were available for 503 dogs. Median PLI was 984 µg/L (range, 603 to 2,001 µg/L); median CRP was 9.9 mg/L (range, 9.9 to 395.3 mg/L; ref: < 10 mg/L). Inpatient care was provided to 136 dogs (27.0%); 49 dogs (9.7%) died or were euthanized. Median PLI values for dogs that died versus survived were similar. Median CRP was higher in hospitalized dogs (36.1 vs 9.9 mg/L; P < .0001) and those that died (37.2 vs 9.9 mg/L; P < .0001). Compared to dogs with CRP < 10 mg/L, those with CRP > 10 mg/L were 5.3 times more likely to die (CI, 2.7 to 10.2) and 5.7 times (CI, 3.7 to 8.7) more likely to be hospitalized. CLINICAL RELEVANCE: In dogs with PLI > 600 µg/L, CRP > 10 mg/L was associated with increased risk of hospitalization or death. This biomarker may provide prognostic information in dogs with evidence of pancreatitis and guide decisions regarding hospitalization or referral.

A retrospective study of structural brain lesions identified by magnetic resonance imaging in 114 cats with neurological signs.

Background and Aim: Magnetic resonance imaging (MRI) has been widely used as a non-invasive modality to evaluate neurological organ structures. However, brain MRI studies in cats with neurological signs are limited. This study evaluated the association between patient characteristics, neurological signs, and brain lesion locations identified by MRI. Blood profiles of cats with presumptive inflammatory and structural brain lesions were also determined. Materials and Methods: Medical records of 114 cats that underwent brain MRI were retrospectively reviewed. Cats were categorized into five groups based on the location of their lesion: Cerebrum, brainstem, cerebellum, multifocal, and non-structural. Patient characteristics, neurological signs, and hematological profiles were obtained from their medical records. Disease classification was categorized based on their etiologies. Associations were determined using Fisher's exact test. Blood parameters were compared using the Kruskal-Wallis test. Results: A total of 114 cats met the inclusion criteria. Lesions were identified in the cerebrum (21.1%), brainstem (8.8%), cerebellum (6.1%), multifocal (39.5%), and non-structural (24.6%) of the cats. Common neurological signs included seizure activity (56.1%), cerebellar signs (41.2%), and anisocoria (25.4%). The most common brain abnormality was inflammation (40.4%). There was no significant difference in hematological profiles between cats with presumptive inflammatory and non-inflammatory brain lesions. Neutrophils, platelets, total protein, and globulin concentrations were higher in cats with structural brain lesions. Conclusion: The most common neurological signs and brain disease category were seizure activity and inflammation, respectively. However, the hematological profile did not predict inflammatory and structural brain lesions.

Serum Bile Acids Concentrations and Liver Enzyme Activities after Low-Dose Trilostane in Dogs with Hyperadrenocorticism.

Hyperadrenocorticism (HAC) often leads to vacuolar hepatopathy. The impact of trilostane treatment on serum total bile acids (SBAs) concentrations in dogs with HAC remains unknown. This study investigated SBAs concentrations in healthy dogs and those with HAC following trilostane therapy. Ten healthy dogs and fifteen dogs with HAC were prospectively enrolled. A biochemistry profile and pre- and post-prandial SBAs concentrations were determined in each dog. Dogs with HAC were reassessed at 1 and 3 months after the initiation of trilostane treatment. Dogs with HAC had significantly higher serum ALT, ALP, and GGT activities, and cholesterol, triglyceride, and pre-prandial SBAs concentrations compared to healthy dogs. After 3 months of trilostane treatment, polyuria/polydipsia and polyphagia were completely resolved in 42.8% and 35.7%, respectively. Significant improvements in serum ALT and ALP activities and cholesterol concentrations were observed within 1-3 months of trilostane treatment. However, pre- and post-prandial SBAs concentrations did not significantly decrease. These findings suggest that treatment with low-dose trilostane for 3 months appears to reduce serum liver enzyme activities, but not SBAs concentrations. Further investigation is warranted to explore the effects of low-dose trilostane treatment on SBAs concentrations for a longer duration or after achieving appropriate post-ACTH cortisol levels.

Serum and Fecal 3-Bromotyrosine Concentrations in Dogs with Chronic Inflammatory Enteropathy: Clinical Parameters and Histopathological Changes.

Chronic inflammatory enteropathies (CIEs) in dogs involve the infiltration of gastrointestinal tissue with inflammatory cells. This study aimed to assess the sensitivity of serum and fecal 3-bromotyrosine (3-BrY) concentrations in dogs with CIE. The difference in 3-BrY concentrations in dogs with different gastrointestinal (GI) pathological changes was also assessed. In total, 68 dogs with CIE were enrolled in the study. The median serum 3-BrY concentration was 3.3 µmol/L, while the median 3-day mean and maximum fecal 3-BrY concentrations were 38.9 and 63.2 mmol/g of feces, respectively. The median serum C-reactive protein concentration was 45.0 mg/L. The median 3-day mean and maximum fecal α1-proteinase inhibitor concentrations were 6.1 and 9 µg/g of feces, respectively. Increased 3-BrY concentrations were observed in 90.9% of CIE dogs based on serum concentrations, 75.8% based on mean fecal concentrations, and 69.4% based on maximum fecal concentrations. A weak correlation (ρ = 0.31, p < 0.0118) was found between serum CRP and serum 3-BrY concentrations. There was no correlation between the canine chronic enteropathy clinical activity index and serum or fecal 3-BrY concentrations (p > 0.05). Additionally, no significant difference in serum or fecal 3-BrY concentrations was found among CIE dogs with different GI pathological changes (p > 0.05). In conclusion, dogs with CIE have increased 3-BrY concentrations in serum and fecal samples. However, 3-BrY concentrations may not accurately indicate the severity of gastrointestinal inflammation.

Impact of fatty acid composition on markers of exocrine pancreatic stimulation in dogs.

Chronic pancreatitis in dogs is typically managed with a low-fat diet. Human research suggests that consumption of medium-chain triglycerides (MCT) may lessen pancreatic enzyme release compared to consumption of long-chain fatty acids (LCFA). Twelve healthy adult colony dogs were fed a meal of cod and rice with either 3% metabolizable energy (ME) fat (control), high MCT (25% ME MCT oil, 25% ME butter), high saturated LCFA (50% ME butter), or high unsaturated LCFA (50% ME canola oil) in a 4-period by 4-treatment crossover design. Serum concentrations of canine pancreatic lipase immunoreactivity, gastrin, cholesterol, triglycerides, and serum activities of amylase and DGGR lipase (1,2-o-dilauryl-rac-glycero-3-glutaric acid-(69-methylresorufin) ester lipase) were measured at times 0 (fasted), 30, 120 and 180 minutes post-prandially. Following a 3-or 4-day wash-out period, each dog was assigned a new diet and the process was repeated for all treatments. Data were analyzed as a repeated-measures mixed model ANOVA. Post-hoc pairwise comparisons were run using Tukey-Kramer adjusted p-values. Shapiro-Wilk tests were used to evaluate residual normality. All statistical assumptions were sufficiently met. Statistical significance was defined as P<0.05. Of the markers tested, only serum triglyceride concentrations were affected by treatment, with consumption of high MCT resulting in lower triglycerides than both LCFA groups at times 120 and 180 minutes (P<0.0001). As expected, the high MCT group had higher triglycerides compared to the control group (P<0.0001). The type of dietary fat consumed had little acute impact on most markers of exocrine pancreatic stimulation in healthy dogs.

Investigation of the cardiac effects of exercise testing on apparently healthy Boxer dogs.

BACKGROUND: Holter electrocardiographic monitoring is a cornerstone of diagnostic testing for arrhythmogenic cardiomyopathy (ACM) in Boxer dogs, but physical activity during monitoring is not controlled. In humans, exercise testing (ExT) can identify latent tachyarrhythmias associated with cardiomyopathy, and exercise increases serum cardiac troponin-I concentrations ([hs-cTnI]). These effects have not yet been investigated in Boxer dogs. HYPOTHESIS/OBJECTIVES: Subjecting Boxer dogs to brief, moderate-intensity ExT can identify changes in Holter recordings and [hs-cTnI] compared to baseline results. ANIMALS: Thirty overtly healthy, client-owned Boxer dogs. METHODS: Prospective interventional study. Dogs underwent baseline diagnostic testing including 24-hour Holter monitoring and [hs-cTnI], followed by brief ExT (accompanied, brisk stair-climbing and -descending for <5 minutes). RESULTS: Eleven dogs (37%) had >100 premature ventricular complexes (PVCs)/24 hours at baseline (3), ExT (3), or both (5). After ExT, these dogs had more PVCs/24 hours and greater increases in [hs-cTnI] compared to those with ≤100 PVCs/24 hours. Dogs with the striatin mutation had more PVCs/24 hours and a greater increase in [hs-cTnI] after ExT than did dogs without the striatin mutation. CONCLUSIONS AND CLINICAL IMPORTANCE: Exercise testing may improve the binary classification of Boxer dogs with or without ACM by increasing the number of PVCs and [hs-cTnI] in affected dogs to a greater degree than in unaffected dogs. This effect also is associated with presence or absence of the striatin mutation. Exercise should be a controlled variable when screening Boxer dogs for ACM.

Analytical validation of an ELISA for the measurement of feline pancreas-specific lipase and re-evaluation of the reference interval and decision threshold for diagnosing pancreatitis.

BACKGROUND: The diagnosis of feline pancreatitis can be challenging. The clinical presentation often includes mild, nonspecific clinical signs, such as vomiting, anorexia, and weight loss. Measurement of feline pancreatic lipase immunoreactivity (fPLI) concentration in serum has been reported to be sensitive and specific for a diagnosis of pancreatitis in cats. However, analytical validation for a widely available commercial assay for the measurement of fPLI concentration has not been published. OBJECTIVE: We aimed to analytically validate the Spec fPL assay (IDEXX Laboratories, Westbrook, ME), a commercial ELISA for the measurement of fPLI concentration, and re-evaluate its reference interval and decision threshold for diagnosing pancreatitis in cats. METHODS: Dilutional linearity, accuracy, precision, and the effect of interfering substances were assessed. The upper limit of the reference interval was calculated based on the 95th percentile of results from clinically healthy cats (n = 107), and a decision threshold for diagnosing pancreatitis was calculated with an expected specificity of 99%. RESULTS: Analytical validation demonstrated good linearity, accuracy, and precision, as well as the absence of interference from lipemia, hemolysis, or icterus. The upper limit of the reference interval for Spec fPL was determined to be 4.4 µg/L, and the decision threshold (a theoretical cut-off) for diagnosing pancreatitis was determined to be 8.8 µg/L based on a desired specificity of 99%. CONCLUSIONS: The Spec fPL assay is analytically valid, and results suggest that a decision threshold of 8.8 µg/L would have high diagnostic specificity for excluding clinically healthy cats.

Specificity of a pancreatic lipase point-of-care test and agreement with pancreatic lipase immunoreactivity in cats without clinical evidence of pancreatitis.

OBJECTIVES: The aim of this study was to determine the specificity of a rapid point-of-care test for the estimation of feline pancreatic lipase (SNAP fPL) in healthy and sick cats without clinical evidence of pancreatitis. A second objective was to evaluate the agreement between SNAP fPL and serum pancreatic lipase immunoreactivity (fPLI), as measured by Spec fPL. METHODS: A total of 150 cats were prospectively enrolled into this study. Of them, 82 cats were healthy while 68 cats had various diseases but no clinical signs (eg, anorexia, depression, vomiting) raising a suspicion of pancreatitis. RESULTS: SNAP fPL was normal in 133/150 cats (specificity 89%) without obvious clinical pancreatitis. SNAP fPL was normal in 74/82 healthy cats (specificity 90%) and in 59/68 cats that were sick but without typical signs of pancreatitis (specificity 87%). The agreement between SNAP fPL and Spec fPL was substantial (k = 0.64) in healthy cats and almost perfect (k = 0.93) in sick cats. The overall agreement between SNAP fPL and Spec fPL was almost perfect (k = 0.81). CONCLUSIONS AND RELEVANCE: The specificity of SNAP fPL in this group of cats was high. There was a substantial and almost perfect agreement between the SNAP fPL and Spec fPL in healthy cats and sick cats without suspected pancreatitis, respectively. In the small percentage of cats with abnormal SNAP fPL and/or Spec fPL results, the possibility of subclinical pancreatitis cannot be excluded.

Serum α1-Proteinase Inhibitor, Calprotectin, and S100A12 Concentrations in the Characterization of Pancreatitis in Dogs.

Miniature Schnauzers are predisposed to develop pancreatitis, with familial hypertriglyceridemia (HTG) described as a potential risk factor. Diagnosing pancreatitis in dogs is based on the integration of serum canine-specific pancreatic lipase (cPLI) concentration, clinical presentation, and diagnostic imaging findings. However, markers of systemic inflammation and antiprotease activity have not been extensively investigated in the characterization and prognostication of pancreatitis in dogs. Serum concentrations of alpha1-proteinase inhibitor (α1PI; as a marker of systemic antiprotease response) and calprotectin and S100A12 (as markers of systemic inflammation) were measured in serum samples from 35 Miniature Schnauzers diagnosed with pancreatitis (serum cPLI concentration >400 µg/L, clinical signs, abdominal imaging findings). These markers were evaluated for possible associations with patient characteristics, clinical presentation, risk factors for pancreatitis, and outcome. The study showed that biomarkers of systemic inflammation and antiprotease activity are commonly increased in Miniature Schnauzers with pancreatitis. Whereas serum calprotectin and S100A12 concentrations were found to have limited utility in differentiating pancreatitis presentations, serum α1PI concentrations and potentially also the serum calprotectin-to-S100A12 ratio might be non-invasive surrogate markers of disease severity in dogs with pancreatitis.

Serum cobalamin and methylmalonic acid concentrations in juvenile dogs with parvoviral enteritis or other acute enteropathies.

BACKGROUND: Low serum cobalamin concentrations have been associated with ileal malabsorption in dogs with chronic enteropathy. Increased serum methylmalonic acid (MMA) concentrations indicate cobalamin deficiency on a cellular level. Few studies have evaluated serum cobalamin concentrations or methylmalonic acid concentrations in juvenile dogs with parvoviral enteritis or nonparvoviral acute enteropathies. OBJECTIVES: Evaluate serum cobalamin and methylmalonic acid concentrations in juvenile dogs (6 weeks to 10 months old) with parvoviral enteritis or nonparvoviral acute enteropathy. ANIMALS: Thirty-one juvenile dogs with parvoviral enteritis, 29 dogs with nonparvoviral acute diarrhea (NPVAD), and 40 healthy juvenile control dogs. METHODS: Single-center, prospective, observational, cross-sectional study. Serum cobalamin and, when sufficient serum was available, MMA concentrations were measured. RESULTS: Most serum cobalamin concentrations were within the adult reference interval. Serum cobalamin concentrations in healthy dogs (median, 848 ng/L; range, 293-1912 ng/L) were significantly higher than in dogs with parvoviral enteritis (P = .0002; median, 463 ng/L; range, <150-10 000 ng/L) or dogs with NPVAD (P = .02; median, 528 ng/L; range, 160-8998 ng/L). Serum MMA concentrations were not significantly different between groups (healthy dogs: median, 796 nmol/L; range, 427-1933 nmol/L; parvoviral enteritis: median, 858 nmol/L; range, 554-3424 nmol/L; NPVAD: median, 764 nmol/L; range, 392-1222 nmol/L; P = .1). CONCLUSIONS AND CLINICAL IMPORTANCE: Juvenile dogs with parvoviral enteritis or NPVAD had lower serum cobalamin concentrations than healthy juvenile dogs. However, based on serum MMA concentrations cellular cobalamin deficiency was not apparent.

The Intestinal Microbiome in Dogs with Chronic Enteropathies and Cobalamin Deficiency or Normocobalaminemia-A Comparative Study.

Cobalamin deficiency is a common sequela of chronic enteropathies (CE) in dogs. Studies comparing the intestinal microbiome of CE dogs with cobalamin deficiency to those that are normocobalaminemic are lacking. Therefore, our aim was to describe the fecal microbiome in a prospective, comparative study evaluating 29 dogs with CE and cobalamin deficiency, 18 dogs with CE and normocobalaminemia, and 10 healthy control dogs. Dogs with cobalamin deficiency were also analyzed after oral or parenteral cobalamin supplementation. Overall microbiome composition (beta diversity) at baseline was significantly different in CE dogs with cobalamin deficiency when compared to those with normocobalaminemia (p = 0.001, R = 0.257) and to healthy controls (p = 0.001, R = 0.363). Abundances of Firmicutes and Actinobacteria were significantly increased (q = 0.010 and 0.049), while those of Bacteroidetes and Fusobacteria were significantly decreased (q = 0.002 and 0.014) in CE dogs with cobalamin deficiency when compared to healthy controls. Overall microbiome composition in follow-up samples remained significantly different after 3 months in both dogs receiving parenteral (R = 0.420, p = 0.013) or oral cobalamin supplementation (R = 0.251, p = 0.007). Because cobalamin supplementation, in combination with appropriate therapy, failed to restore the microbiome composition in the dogs in our study, cobalamin is unlikely to be the cause of those microbiome changes but rather an indicator of differences in underlying pathophysiology that do not influence clinical severity but result in a significant aggravation of dysbiosis.

Urinary 15-F2t-Isoprostane Concentrations in Dogs with Liver Disease.

Isoprostanes are stable end products of lipid peroxidation that can be used as markers of oxidative stress. It was previously reported that a cohort of dogs with various liver diseases had increased urinary isoprostane concentrations compared to healthy control (HC) dogs. The aim of this study was to measure and report urinary isoprostane concentrations in dogs with different types of liver diseases. Urine was collected from 21 HC dogs and from 40 dogs with liver disease, including 25 with chronic hepatitis (CH), 7 with steroid hepatopathy (SH), and 8 with a congenital portosystemic shunt (CPSS). In this prospective, observational study, urinary 15-F2t-isoprostane (F2-IsoP) concentrations were measured by liquid chromatography/mass spectrometry and normalized to urinary creatinine concentrations. Concentrations were compared between groups using a Kruskal-Wallis test followed by Dunn's multiple comparisons tests. Significance was set at p < 0.05. The median (range) urinary F2-IsoP to creatinine ratios (ng/mg UCr) were 3.6 (2.2-12.4) for HC dogs, 5.7 (2.4-11.3) for dogs with CH, 4.8 (2.4-8.6) for dogs with SH, and 12.5 (2.9-22.9) for dogs with CPSS. CPSS dogs had significantly higher urinary F2-IsoP concentrations than HC dogs (p = 0.004), suggesting increased oxidative stress among this cohort.

Double-blinded placebo-controlled clinical trial of prophylactic omeprazole in dogs treated surgically for acute thoracolumbar intervertebral disc extrusion.

BACKGROUND: Proton pump inhibitors are administered prophylactically in dogs treated surgically for acute thoracolumbar intervertebral disc extrusion (TL-IVDE). However, their efficacy in decreasing gastrointestinal (GI) complications is unknown. HYPOTHESIS: Omeprazole does not decrease the frequency of GI complications compared to placebo in dogs treated surgically for acute TL-IVDE. ANIMALS: Thirty-seven client-owned dogs undergoing hemilaminectomy for acute TL-IVDE. METHODS: Randomized double-blinded placebo-controlled prospective clinical trial. Dogs received PO placebo or omeprazole at 1 mg/kg q12h for 5 days during hospitalization. Development of GI signs (e.g., diarrhea, vomiting, regurgitation, hematochezia, melena) was recorded daily. Clinicopathologic testing performed during hospitalization and at 2 and 4-week re-evaluations included: fecal occult blood, PCV, blood urea nitrogen/creatinine ratio, fecal calprotectin, canine pancreatic lipase immunoreactivity and fecal alpha-1 proteinase inhibitor concentrations. Omeprazole and placebo groups were compared using chi-squared or Fisher's exact tests. RESULTS: Gastrointestinal signs developed in 10/20 (50%) dogs in the omeprazole group and in 7/17 (41%) dogs in the placebo group (P = .59). Diarrhea was common (8/20 omeprazole, 5/17 placebo), hematochezia was rare (1/20 omeprazole, 1/17 placebo); melena was not observed. Clinicopathologic evidence suggestive of bleeding was present in 9/20 dogs treated with omeprazole and in 11/17 dogs that received placebo (P = .23). Fecal occult blood positivity was more common in dogs with GI signs (P = .03). Canine pancreatic lipase immunoreactivity was higher during hospitalization compared to re-evaluations (P = .01). CONCLUSIONS AND CLINICAL IMPORTANCE: Short-term, prophylactic omeprazole treatment did not decrease clinically detectable GI complications in dogs with acute TL-IVDE.

Esomeprazole induces structural changes and apoptosis and alters function of in vitro canine neoplastic mast cells.

Histamine-2 receptor antagonists such as famotidine and proton pump inhibitors such as esomeprazole are commonly used in canine MCT disease, but direct effects on dog MCs have not been evaluated. Omeprazole is a proton pump inhibitor which has been demonstrated to cause structural and functional changes to in vitro murine mast cells (MCs). It has not yet been determined if esomeprazole, the commercially available and commonly prescribed S-isomer of omeprazole, has similar effects. Our primary study objective was to evaluate and compare the effects of acid suppressants (esomeprazole and famotidine) on MC ultrastructure, viability, and function in vitro using both healthy and neoplastic MCs. Murine bone marrow derived mast cells (BMMC), human LAD2, and canine C2 and BR cells, were used for these studies, representing a single healthy (i.e., BMMCs) MC model and multiple neoplastic MC models (i.e., LAD2, C2, BR), respectively. The rat basophilic leukemic (RBL-2H3) and canine B cell lymphoma 17-71 cell lines served as granulocytic and agranulocytic control lines for experiments, respectively. The treatment effect of acid suppressants on MC ultrastructure was assessed via both light and transmission electron microscopy. Differences in MC viability was assessed between groups via MTS-based, colorimetric assays and flow cytometry. Degranulation was assessed by quantification of ß-hexosaminidase (i.e., LAD2 and RBL-2H3). Esomeprazole-treated MCs of all lines exhibited dramatic time and concentration-dependent alterations in ultrastructure (i.e., increased vacuolization, compromise of cell membrane), increased apoptosis, and altered degranulation responses in comparison to famotidine and vehicle-treated cells. The canine B cell lymphoma cells consistently exhibited either no significant (i.e., cytotoxicity assays) or greatly diminished treatment responses (i.e., apoptosis) compared to MCs. Esomeprazole, but not famotidine, induces significant cytotoxicity, as well as alterations to cell structure and function to multiple lines of in vitro neoplastic MCs. Continued in vitro work investigating the specific mechanisms by which proton pump inhibitors induce these effects, as well as prospective, in vivo work comparing the treatment effects of acid suppressants on canine MCTs, are warranted.

Clinical utility of an immunoglobulin A-based serological panel for the diagnosis of chronic enteropathy in dogs.

BACKGROUND: A panel of IgA-based serologic assays might aid in the diagnosis of chronic enteropathy (CE) in dogs, a syndrome encompassing conditions such as food-responsive enteropathy, immunosuppressant-responsive enteropathy, and inflammatory bowel disease (also referred to as chronic inflammatory enteropathy). However, it is unclear whether these biomarkers discriminate between CE and other types of primary intestinal disorders. OBJECTIVES: To evaluate a diagnostic panel that measures serum concentrations of IgA directed against OmpC (ACA), canine calprotectin (ACNA), and gliadin-derived peptides (AGA) in dogs with well-characterized intestinal diseases. ANIMALS: Fifty-five dogs with primary intestinal disease. METHODS: Serum ACA, ACNA, and AGA concentrations were measured in 30 dogs with CE and 25 dogs with other intestinal diseases (non-CE population), including histoplasmosis, parasitism, E. coli-associated granulomatous colitis, and lymphoma. Serum IgA concentrations were compared among populations, and sensitivities and specificities were calculated using laboratory-provided cut-points. RESULTS: Twenty-six of 30 (87%) CE dogs and 21 of 25 (84%) non-CE dogs had abnormal concentrations (intermediate or high) of at least 2 markers; these proportions were not significantly different (P = .99). A serum ACA concentration ≥15 EU/mL was 86.7% (95% confidence interval [CI], 69.3%-96.2%) sensitive and 24.0% (95% CI, 9.4%-45.1%) specific for CE diagnosis. High AGA concentrations were observed in 16 of 25 (64%) non-CE dogs. CONCLUSIONS AND CLINICAL IMPORTANCE: The evaluated serologic markers were poorly specific for CE diagnosis, which raises concerns that their use in clinical practice might lead to misdiagnoses and delayed or even detrimental treatments in dogs with non-CE intestinal diseases.

Cardiovascular abnormalities in dogs with acute pancreatitis.

BACKGROUND: The prevalence and clinical importance of cardiac abnormalities in dogs with acute pancreatitis (AP) is unknown. ANIMALS: Twelve dogs with AP and 60 archived serum samples from dogs with suspected AP. METHODS: Two-phase study. PHASE I: Analysis of archived serum samples from dogs with clinical signs of AP and high Spec cPL concentrations. High sensitivity troponin I (TnIH) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) concentrations were measured in achieved serum samples. PHASE II: Prospective observational study. Dogs with AP underwent echocardiography and Holter monitoring. Serum cardiac troponin I (cTnI) and plasma NT-proBNP concentrations were measured. Previously described disease severity indices were calculated for each dog. RESULTS: Phase I: 41 of 60 dogs suspected of having AP had abnormally high TnIH concentrations and 13 of 60 had abnormally high serum NT-proBNP concentrations. Higher TnIH concentrations were observed in dogs with Spec cPL concentration >2000 µg/L as compared to those with concentrations of 1000-2000 µg/L. PHASE II: 11 of 12 dogs diagnosed with pancreatitis had abnormal cTnI concentrations (median: 0.384 ng/mL, range: 0.041-2.966 ng/mL, RI: ≤0.06 ng/mL) and 7 of 12 dogs had plasma NT-proBNP concentrations above the reference interval (median: 971 pmol/L, range: 250-2215 pmol/L, RI: ≤900 pmol/L). Supraventricular and ventricular ectopic beats occurred in 3 dogs. Echocardiographic abnormalities were detected in 5 dogs. Cardiovascular variables were not associated with indices of disease severity. CONCLUSIONS AND CLINICAL IMPORTANCE: Myocardial injury is common in dogs with AP, but clinical consequences appeared to be uncommon in our small cohort. Cardiac biomarkers should be interpreted with caution in dogs with AP.