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The gastrointestinal (GI) mucosal barrier is continuously exposed to noxious toxins, reactive oxygen species, microbes, and drugs, leading to the development of inflammatory, erosive, and ultimately ulcerative lesions. This report offers a consensus opinion on the rational administration of GI protectants to dogs and cats, with an emphasis on proton pump inhibitors (PPIs), histamine type-2 receptor antagonists (H2 RAs), misoprostol, and sucralfate. These medications decrease gastric acidity or promote mucosal protective mechanisms, transforming the management of dyspepsia, peptic ulceration, and gastroesophageal reflux disease. In contrast to guidelines that have been established in people for the optimal treatment of gastroduodenal ulcers and gastroesophageal reflux disease, effective clinical dosages of antisecretory drugs have not been well established in the dog and cat to date. Similar to the situation in human medicine, practice of inappropriate prescription of acid suppressants is also commonplace in veterinary medicine. This report challenges the dogma and clinical practice of administering GI protectants for the routine management of gastritis, pancreatitis, hepatic disease, and renal disease in dogs and cats lacking additional risk factors for ulceration or concerns for GI bleeding. Judicious use of acid suppressants is warranted considering recent studies that have documented adverse effects of long-term supplementation of PPIs in people and animals.

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., (© 2024 The Author(s). Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.)

Introduction: Canine protein-losing enteropathy (PLE) is a syndrome characterized by gastrointestinal loss of proteins. While fecal microbiome and metabolome perturbations have been reported in dogs with chronic enteropathy, they have not been widely studied in dogs with PLE. Therefore, the study aims were to investigate gut microbiome and targeted fecal metabolites in dogs with inflammatory PLE (iPLE) and evaluate whether treatment affects these changes at short-term follow-up., Methods: Thirty-eight dogs with PLE and histopathological evidence of gastrointestinal inflammation and 47 healthy dogs were enrolled. Fecal samples were collected before endoscopy (T0) and after one month of therapy (T1). Microbiome and metabolome alterations were investigated using qPCR assays (dysbiosis index, DI) and gas chromatography/mass spectrometry (long-chain fatty acids, sterols, unconjugated bile acids), respectively., Results: Median (min-max) DI of iPLE dogs was 0.4 (-5.9 to 7.7) and was significantly higher ( p < 0.0001) than median DI in healthy dogs [-2.0 (-6.0 to 5.3)]. No significant associations were found between DI and selected clinicopathological variables. DI did not significantly differ between T0 and T1. In iPLE dogs, at T0, myristic, palmitic, linoleic, oleic, cis-vaccenic, stearic, arachidonic, gondoic, docosanoic, erucic, and nervonic acids were significantly higher ( p < 0.0001) than healthy dogs. In iPLE dogs, oleic acid ( p = 0.044), stearic acid ( p = 0.013), erucic acid ( p = 0.018) and nervonic acid ( p = 0.002) were significantly decreased at T1. At T0, cholesterol and lathosterol ( p < 0.0001) were significantly higher in iPLE dogs compared to healthy dogs, while total measured phytosterols were significantly lower ( p = 0.001). No significant differences in total sterols, total phytosterols and total zoosterols content were found at T1, compared to T0. At T0, total primary bile acids and total secondary bile acids did not significantly differ between healthy control dogs and iPLE dogs. No significant differences in fecal bile acid content were found at T1., Discussion: Dysbiosis and lipid metabolism perturbations were observed in dogs with iPLE. Different therapeutic protocols lead to an improvement of some but not all metabolome perturbations at short-term follow-up., Competing Interests: JS, MT, C-CC, and PRG are employed by the Gastrointestinal Laboratory at Texas A&M University, which provides assays for intestinal function and microbiota analysis on a fee-for-service basis. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Cagnasso, Suchodolski, Borrelli, Borella, Bottero, Benvenuti, Ferriani, Tolbert, Chen, Giaretta and Gianella.)

Acid-suppressant drugs (ASDs) have revolutionized the treatment of acid-related disorders such as gastroesophageal reflux and gastrointestinal ulceration in both human and veterinary species. However, continued advancement in this field is dependent on a shared understanding of both human and veterinary research as well as an appreciation for species similarities and differences. In this Currents in One Health article, we will compare the efficacy of and indications for ASDs in humans and small animals, noting species differences and knowledge gaps when applicable. We will also highlight areas where further research is needed, specifically emphasizing the need for more feline research and a better understanding of which diseases may benefit from gastroprotection. Finally, given the rising overuse of ASDs in both human and veterinary medicine, we will explore the known adverse effects of these drugs in dogs and cats. This article is focused on our current understanding of these drugs in veterinary medicine and their clinical implications. The companion Currents in One Health article by Gould et al, AJVR, October 2024, will explore the future of ASD research and use by evaluating these drugs' pH-independent effects in humans and rodent models.

Objective: To describe the demographic factors of owners and their dogs associated with owner feeding choices and the regularity with which those diets were fed to a US-based population of dogs., Methods: This cross-sectional analysis examined 40,367 initial survey responses from US dog owners participating in the Dog Aging Project. The surveys were collected from January 2, 2020, to December 31, 2022, and included primary and secondary diet component types and dog and owner demographic variables. Each demographic variable was compared across diet type choices with a χ2 test of independence., Results: Most owners (82%) fed a commercially prepared extruded dry diet (kibble) as the primary diet component. Most owners (89%) reported that they fed their dogs a consistent diet over time. Owner demographic factors (income, education level) were less correlated with difference in diet choices than dog demographic factors (size, neuter status, purebred status, activity level), but owner age did correlate with choice: younger owners tended to feed kibble more compared to older owners. Home-cooked diets were most often consumed by small (< 30-lb) dogs, purebred dogs in poorer health status, and dogs with owners aged 45 years or older. Raw diets were more commonly fed to purebred, intact, and highly active dogs. Ten percent of service dogs were reportedly fed a raw diet of some sort., Conclusions: Demographic variables are associated with statistically significant differences in diet types selected. Nutrition studies examining health outcomes associated with the feeding of different diet types should account for these factors during design or analysis in order to avoid bias. An epidemiological tool, the directed acyclic graph, is presented., Clinical Relevance: This information will help clinicians in their discussions with clients about pet nutrition.

Our understanding of the use of acid-suppressant drugs (ASDs) in companion animals is largely centered around the treatment of acid-related disorders including gastroesophageal reflux and gastrointestinal ulceration. The companion article by Grady et al, JAVMA, October 2024, summarizes our current knowledge of the efficacy of and indications for ASDs for the treatment of acid-related disorders. Far less is understood about both the benefits of and potential for adverse effects of ASDs outside of the parietal cell including those directed toward inflammation and immunomodulation, tumorigenesis, fibrosis, and oxidative stress. In this Currents in One Health article, we summarize the pH-independent properties of ASDs as demonstrated in studies conducted largely in humans and rodents. The objective of this review is to highlight and increase awareness of the pH-independent effects of ASDs to elucidate the need for further veterinary research in this area.

Background: More than 50% of dogs with protein-losing enteropathy (PLE) fail to respond to standard therapies. Octreotide, a somatostatin analogue, is used in cases of intestinal lymphangiectasia (IL) in humans with some success., Objectives: Describe the use of octreotide in dogs with PLE including reason for and details of prescription, adverse effects, and apparent response., Animals: Eighteen dogs with PLE, 13 with histopathology available. Ninety-two percent (12/13) had IL diagnosed on biopsy. All 13 dogs had intestinal inflammatory infiltrates noted., Methods: Multicenter, retrospective, descriptive study. Cases were volunteered for inclusion by individual attending veterinarians who reported the use of octreotide in cases of PLE., Results: In 16/18 (89%) cases octreotide was prescribed to PLE dogs with a clinical suspicion or confirmed diagnosis of IL that were refractory to standard therapies. Median serum albumin at the time of octreotide prescription was 1.7 g/dL (range, 1.0-3.1 g/dL). The median dose of octreotide prescribed was 20 μg/kg, SQ, daily with a range of 4-39 μg/kg, SQ, daily. Adverse effects were noted in 3/18 (17%, 95% CI [4%, 41%]) of dogs; discontinuation of the drug was necessary in 1 dog. Improvement in clinical signs was noted in 6/12 (50%, 95% CI [21%, 79%])., Conclusions and Clinical Importance: Octreotide was most commonly prescribed to dogs with PLE and suspected or confirmed IL that had failed to respond to standard therapies. Though a benefit to PLE dogs cannot be confirmed, octreotide was well tolerated by the majority of dogs at the doses prescribed in this study., (© 2023 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.)

Background: Proton pump inhibitors can cause diarrhea and a transient increase in fecal dysbiosis index in dogs. It is unknown if concurrent probiotic administration mitigates these effects., Objective/hypothesis: To assess the fecal Canine Microbial Dysbiosis Index (CMDI), fecal short chain fatty acid (SCFA), and fecal calprotectin concentrations in dogs administered esomeprazole with and without a probiotic., Animals: Eleven healthy dogs., Methods: Prospective, within-subjects before and after study. All dogs received 7-day courses of esomeprazole (1 mg/kg PO q 24h) alone followed by esomeprazole with a probiotic (15 billion CFU/kg), separated by a 4-week washout period. Data were compared between phases using mixed effects ANOVA or generalized estimating equations with post-hoc Holm adjustment for 2-way comparisons., Results: Compared to baseline (mean CMDI -2.66, SD 3.04), fecal CMDI was not different with esomeprazole administration alone (mean CMDI -1.48, SD 3.32, P = .08), but there was a significant increase (Diff 3.05, 95% CI [1.37, 4.74], P < .001, Effect size 2.02) when esomeprazole and a probiotic were administered concurrently (mean CMDI 0.39, SD 2.83). CMDI was significantly higher when esomeprazole was administered with a probiotic than alone (Diff 1.87, 95% CI [0.19, 1.87], P = .02, Effect size 1.24). Fecal calprotectin and SCFA concentrations did not differ between phases. The occurrence of vomiting and diarrhea was not different from baseline when esomeprazole was administered alone (36%/27%) or with a probiotic (46%/9%)., Conclusions and Clinical Importance: In healthy dogs, concurrent administration of a probiotic is unlikely to lessen adverse effects associated with esomeprazole administration., (© 2023 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.)

Background: Gastric hyperacidity and hypergastrinemia are purported to cause gastric ulceration in dogs with chronic kidney disease (CKD); however, no published studies have evaluated gastric pH with serum gastrin concentrations in dogs with CKD., Hypothesis: To compare mean intragastric pH, mean percent pH distribution, and serum gastrin concentrations in dogs with CKD to age-matched, healthy dogs. We hypothesized there would be no difference in mean gastric pH or serum gastrin between groups., Animals: Thirteen dogs with CKD; 10 aged-matched healthy dogs., Methods: Prospective, case-control study. Serum chemistry, complete blood count, urinalysis, and serum gastrin concentrations were evaluated in all dogs before radiographic-assisted gastric placement of a pH capsule. Forty-eight-hour continuous gastric pH monitoring was performed in all dogs. Serum gastrin concentration, mean pH, and mean percentage time that gastric pH was strongly acidic (pH <1 and pH <2) were compared between groups using a repeated measures mixed-model ANOVA., Results: No significant differences were observed between groups for any pH measurements, including mean ± SD gastric pH (CKD, 2.37 ± 0.87; healthy, 2.39 ± 0.99; P > .05). Serum gastrin concentrations were not significantly different between groups (median [range]: CKD, 10.5 ng/dL [<10-17.1]; healthy, 10.9 ng/dL [<10-15]; P > .05)., Conclusions and Clinical Importance: Our client-owned dogs with CKD did not have lower gastric pH or higher serum gastrin concentrations compared to healthy dogs. Our results suggest that prophylactic gastric acid suppression in dogs with CKD is not warranted unless other clinical indications for use are present., (© 2023 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.)

Acute diarrhea is a common reason for non-wellness veterinary visits in dogs. Treatment for acute diarrhea usually consists of supportive care with nutritional intervention, fluid therapy, anthelmintics, and often an antibiotic - commonly metronidazole in North America. The empirical use of metronidazole for acute diarrhea in dogs has been a common practice in veterinary medicine for many decades; however, recent studies evaluating its use suggest it may be inappropriately utilized in many cases. Herein, we review the evidence evaluating the use of metronidazole and other antibiotics in acute diarrhea in the human and veterinary literature. Recommendations on the use of metronidazole and other antibiotics as well as other therapeutic considerations in the treatment of acute diarrhea are also provided., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objectives: Exercise-induced gastrointestinal syndrome occurs in dogs and people and might compromise athlete performance by increasing intestinal permeability and causing gastrointestinal erosions. Racing sled dogs often receive acid suppressant prophylaxis which decreases the incidence of gastric erosions induced by exercise. The objectives were to quantify intestinal injury by measuring serum pro-inflammatory cytokine concentrations before and after exercise and to evaluate gastrointestinal mucosa using video capsule endoscopy after exercise., Materials and Methods: Prospective study of 12 racing Alaskan sled dogs receiving approximately 1 mg/kg omeprazole once daily from the day before the race until race completion. Blood was drawn before and 8 to 10 hours after an endurance race for the quantification of cytokines. Gastrointestinal tract mucosa was assessed with video capsule endoscopy immediately post-race., Results: Eight of nine dogs (89%; 95% confidence interval 52 to 100%) had gastric erosions; all dogs (100%, 95% confidence interval 63 to 100%) had small intestinal erosions. Most of the dogs (seven of nine) had straw or foreign material present. Cytokine levels were not different from before to after the race., Clinical Significance: Video capsule endoscopy identified gastrointestinal tract mucosal erosions after exercise in all dogs receiving once-daily omeprazole treatment, though other causes for the lesions besides exercise are possible., (© 2023 The Authors. Journal of Small Animal Practice published by John Wiley & Sons Ltd on behalf of British Small Animal Veterinary Association.)

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., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Zhang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

DNA shotgun sequencing is an untargeted approach for identifying changes in relative abundances, while qPCR allows reproducible quantification of specific bacteria. The canine dysbiosis index (DI) assesses the canine fecal microbiota by using a mathematical algorithm based on qPCR results. We evaluated the correlation between qPCR and shotgun sequencing using fecal samples from 296 dogs with different clinical phenotypes. While significant correlations were found between qPCR and sequencing, certain taxa were only detectable by qPCR and not by sequencing. Based on sequencing, less than 2% of bacterial species (17/1190) were consistently present in all healthy dogs ( n = 76). Dogs with an abnormal DI had lower alpha-diversity compared to dogs with normal DI. Increases in the DI correctly predicted the gradual shifts in microbiota observed by sequencing: minor changes (R = 0.19, DI < 0 with any targeted taxa outside the reference interval, RI), mild-moderate changes (R = 0.24, 0 < DI < 2), and significant dysbiosis (R = 0.54, 0.73, and 0.91 for DI > 2, DI > 5, and DI > 8, respectively), compared to dogs with a normal DI (DI < 0, all targets within the RI), as higher R-values indicated larger dissimilarities. In conclusion, the qPCR-based DI is an effective indicator of overall microbiota shifts observed by shotgun sequencing 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., (© 2023 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.)

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., (© 2023 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.)

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 β-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., Competing Interests: Conflict of Interest None to disclose., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Objective: To characterize gastrointestinal transit times (GITTs) and pH in dogs, and to compare to data recently described for cats., Animals: 7 healthy, colony-housed Beagles., Procedures: The GITTs and pH were measured using a continuous pH monitoring system. For the first period (prefeeding), food was withheld for 20 hours followed by pH capsule administration. Five hours after capsule administration, dogs were offered 75% of their historical daily caloric intake for 1 hour. For the second period (postfeeding), food was withheld for 24 hours. Dogs were allowed 1 hour to eat, followed by capsule administration. Both periods were repeated 3 times. The GITTs and pH were compared to published feline data., Results: The mean ± SD transit times in dogs for the pre- and postfeeding periods, respectively, were esophageal, 3 ± 5 minutes and 13 ± 37 minutes; gastric, 31 ± 60 minutes and 829 ± 249 minutes; and intestinal, 795 ± 444 minutes and 830 ± 368 minutes. The mean ± SD gastrointestinal pH in dogs for the pre- and postfeeding periods, respectively, were esophageal, 6.6 ± 0.6 and 5.7 ± 1.0; gastric, 3.0 ± 1.4 and 1.8 ± 0.3; intestinal, 7.9 ± 0.3 and 7.7 ± 0.6; first-hour small intestinal, 7.6 ± 0.5 and 7.1 ± 0.4; and last-hour large intestinal, 7.9 ± 0.6 and 7.7 ± 1.0. The first-hour small intestinal pH and total transit times varied between dogs and cats depending on feed period (P = .002 and P = .04, respectively). Post hoc analysis revealed significantly shorter total transit times in dogs prefeeding (P = .005; mean ± SD for cats, 2,441 ± 1,359 minutes; for dogs, 828 ± 439 minutes) and postfeeding (P = .03; mean ± SD for cats, 3,009 ± 1,220 minutes; for dogs, 1,671 ± 513 minutes). Total transit time for dogs was also shorter pre- versus postfeeding (P = .003)., Clinical Relevance: GITT is faster in Beagles compared to cats, but gastrointestinal pH are similar when fed the same diet.

Background: Although proton pump inhibitors (PPIs) are commonly administered to hospitalized dogs, prescribing patterns and appropriateness of use require continued investigation., Hypothesis/objective: Describe prescription patterns and appropriateness of use associated with PPIs in hospitalized dogs at a single tertiary care facility. We hypothesized that the majority of prescriptions would not comply with current guidelines for the rational use of acid suppressants., Animals: Two hundred randomly selected hospitalized dogs., Methods: Retrospective evaluation of the medical records associated with a randomly selected sample of hospitalized dogs that received PPIs between January 2013 and December 2018., Results: A total of 12 610 dogs were admitted for first-time hospitalization between January 2013 and December 2018. Forty percent of these dogs (5062/12610) were prescribed a PPI PO or IV. Of the 200 randomly selected records, an adequate indication for use was identified in 27% of dogs (54/200). Of the dogs surviving to discharge, 54% (95/175) were discharged with a PPI and 51.6% (49/95) of those were prescribed an inadequate dose., Conclusions and Importance: Our findings support other studies in which the majority of PPI prescriptions for hospitalized dogs at a tertiary care hospital lacked an appropriate indication. Furthermore, analysis of the prescribing patterns of dispensed PPIs identified a frequent occurrence of dosages considered inadequate, raising concern for ineffective treatment even with appropriate indications of use. With growing concern of adverse effects associated with PPI and other acid suppressant administration in human and veterinary medicine, rational use of these medications following consensus guidelines should be emphasized and treatment should be reserved for dogs with historical, physical examination, clinicopathologic, and imaging findings supportive of an appropriate indication for use., (© 2022 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.)

Here we describe the development and evaluation of a survey instrument to assess the research suitability of veterinary electronic medical records (EMRs) through the conduct of two studies as part of the Dog Aging Project (DAP). In study 1, four reviewers used the instrument to score a total of 218 records in an overlapping matrix of pairs to assess inter-rater agreement with respect to appropriate format (qualification), identification match (verification), and record quality. Based upon the moderate inter-rater agreement with respect to verification and the relatively large number of records that were incorrectly rejected the instrument was modified and more specific instructions were provided. In study 2, a modified instrument was again completed by four reviewers to score 100 different EMRs. The survey scores were compared to a gold standard of board-certified specialist review to determine receiver operating curve statistics. The refined survey had substantial inter-rater agreement across most qualification and verification questions. The cut-off value identified had a sensitivity of 95 and 96% (by reviewer 1 and reviewer 2, respectively) and a specificity of 82% and 91% (by reviewer 1 and reviewer 2, respectively) to predict gold standard acceptance or rejection of the record. Using just qualification and verification questions within the instrument (as opposed to full scoring) minimally impacted sensitivity and specificity and resulted in substantial time savings in the review process., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Praczko, Tinkle, Arkenberg, McClelland, Creevy, Tolbert, Barnett, Chou, Evans, McNulty, Dog Aging Project Consortium and Levine.)

Osteoarthritis (OA) is one of the most prevalent age-related chronic conditions that afflict companion dogs, and multiple joint supplements are available to prevent or treat OA, though the efficacy of these treatments is controversial. While the demographic factors that are associated with OA diagnosis are well established, the factors that are associated with joint supplement use are not as well studied. Using data collected from the Dog Aging Project, we analyzed owner survey responses regarding joint supplement administration and OA diagnosis for 26,951 adult dogs. In this cross-sectional analysis, logistic regression models and odds-ratios (OR) were employed to determine demographic factors of dogs and their owners that were associated with joint supplement administration. Forty percent of adult dogs in our population were given some type of joint supplement. Perhaps not surprisingly, dogs of older age, larger size, and those that were ever overweight were more likely to receive a joint supplement. Younger owner age, urban living, owner education, and feeding commercial dry food were associated with a reduced likelihood of administration of joint supplements to dogs. Interestingly, mixed breed dogs were also less likely to be administered a joint supplement (OR: 0.73). Dogs with a clinical diagnosis of OA were more likely to receive a joint supplement than those without a reported OA diagnosis (OR: 3.82). Neutered dogs were more likely to have a diagnosis of OA, even after controlling for other demographic factors, yet their prevalence of joint supplement administration was the same as intact dogs. Overall, joint supplement use appears to be high in our large population of dogs in the United States. Prospective studies are needed to determine if joint supplements are more commonly administered as a preventative for OA or after an OA clinical diagnosis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Hoffman, Tolbert, Promislow and The Dog Aging Project Consortium.)

Background: To evaluate the efficacy of a single intramuscular adminsitration of long-acting omeprazole (LA-OMEP) in increasing gastric pH in dogs., Hypothesis: We hypothesized that LA-OMEP would meet in healthy dogs the clinical goals defined for human patients for treatment of gastroduodenal ulceration., Animals: Nine healthy research dogs., Methods: Prospective experimental study. Dogs were given a 4 mg/kg intramuscular injection of LA-OMEP. Intragastric pH was continuously recorded on treatment days 0 to 7. Daily mean pH and mean percentage time (MPT) intragastric pH was ≥3 or ≥4 were determined., Results: The mean onset of action for the LA-OMEP was 98.11 min (SD 46.39). The mean number of days the dogs' pH met established goals for MPT pH ≥3 was 5.5 days (range, 3-7) and 5.25 days for MPT pH ≥4 (range, 3-7). Long-acting omeprazole met the human clinical goals pH ≥3 for 72 hours in 8/8 of the dogs and MPT pH ≥4 for 96 hours in 7/8 of dogs., Conclusions and Clinical Importance: The LA-OMEP formulation produced gastric acid suppression in healthy dogs for an average of 5 days and up to 7 days, after a single intramuscular injection. No major adverse effects were observed., (© 2022 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.)

A variety of diets have been studied for possible anti-aging effects. In particular, studies of intermittent fasting and time-restricted feeding in laboratory rodents have found evidence of beneficial health outcomes. Companion dogs represent a unique opportunity to study diet in a large mammal that shares human environments. The Dog Aging Project has been collecting data on thousands of companion dogs of all different ages, sizes, and breeds since 2019. We leveraged this diverse cross-sectional dataset to investigate associations between feeding frequency and cognitive function (n = 10,474) as well as nine broad categories of health conditions (n = 24,238). Controlling for sex, age, breed, and other potential confounders, we found that dogs fed once daily rather than more frequently had lower mean scores on a cognitive dysfunction scale, and lower odds of having gastrointestinal, dental, orthopedic, kidney/urinary, and liver/pancreas disorders. Therefore, we find that once-daily feeding is associated with better health in multiple domains. Future research with longitudinal data can provide stronger evidence for a possible causal effect of feeding frequency on health in companion dogs., (© 2022. The Author(s), under exclusive licence to American Aging Association.)

Chronic idiopathic enteropathy is a clinical condition defined by the exclusion of infectious, metabolic or neoplastic causes of gastrointestinal signs and is categorised by a response to treatment including management with diet change, immunosuppressant medication or interventions that directly target the microbiome (e.g. antibiotics, faecal transplantation or probiotics). Animals that fail these therapies are categorised as non-responsive or refractory chronic idiopathic enteropathy. This specific categorisation implies that nutritional intervention is only needed for a subset of patients with enteropathy. However, often dogs with chronic idiopathic enteropathy are malnourished, have nutrient malabsorption or have gastrointestinal inflammation that occurs as a result of a breakdown in tolerance to luminal antigens including microorganism or dietary components. Thus, all dogs with chronic idiopathic enteropathy benefit from a nutritional assessment and targeted nutritional intervention. Among dogs presenting for chronic idiopathic enteropathy, the response rate to diet alone is roughly 50% in the referral population giving the impression that the overall response could be even higher especially when more than one nutritional intervention is attempted and strict adherence is maintained. The objectives of this review article are to outline the nutritional approach to a dog with chronic idiopathic enteropathy, including the nutritional assessment, and to highlight areas for nutritional intervention., (© 2022 British Small Animal Veterinary Association.)

Background: Bone foreign bodies are commonly encountered in small animal practice. Esophageal bone foreign bodies (E-bFBs) warrant removal, whereas gastric bone foreign bodies might not., Objectives: Describe management and outcomes for dogs with esophageal or gastric bone foreign bodies., Animals: One hundred twenty-nine dogs with esophageal (n = 45) or gastric (n = 84) bone foreign bodies., Methods: Retrospective review of medical records., Results: Dogs with E-bFBs were younger than dogs with gastric bone foreign bodies (median age esophageal, 4 years [IQR 2-8]; median age gastric, 6 years [IQR 3-10]; P = .03), and had a higher bone cross-sectional area relative to body weight (median esophageal, 98.21 mm 2 /kg [IQR 48.25-142.6]; median gastric, 28.6 mm 2 /kg [IQR 17.25-64.28]; P < .001). Forty-two of 45 esophageal foreign bodies were resolved non-surgically and 3 by esophagotomy. Esophageal erosions were more likely with distal entrapment (OR 12.88, [95% CI 31.95-129.29], P = .01) and longer duration (OR 18.82 [95% CI 2.22-273.97], P = .01). Sixty-two of 84 bone gastric foreign bodies were left in situ. Endoscopic removal was successful in 20 of 22 (91%; 95% CI 70-99) attempts., Conclusions and Clinical Importance: While all E-bFBs were dislodged either by advancement into the stomach, endoscopic removal, or esophagotomy, the majority of gastric bone foreign bodies were left in situ for dissolution, with no reported complications. Gastric advancement of E-bFBs should be considered when oral removal is not feasible, and dissolution can be considered even with large bones., (© 2022 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.)

Background: Esophageal varices (EV) are abnormally dilated veins in the esophagus caused by alterations of blood flow or pressure. Esophageal variceal hemorrhage is a major complication of hepatic disease in humans, but a lack of information exists regarding associated adverse events in dogs., Objective: To describe the clinical manifestations and associated etiologies and outcomes of dogs with EV., Animals: Twenty-five client-owned dogs with EV diagnosed via computed tomography (CT), endoscopy, or fluoroscopy., Methods: Retrospective case series. Cases were identified by review of the hospital imaging records database between 2010 and 2020. Signalment, clinical signs, and outcomes were documented. When present, additional collateral vasculature was also recorded. Cases were subcategorized into suspected etiology based upon the anatomic location or absence of an attributable underlying disease process, as well as the direction of blood flow., Results: Twenty-four of 25 cases were identified via CT, with a prevalence of 0.012% (24/1950 total studies). Presenting clinical signs were nonspecific, and more likely because of the underlying cause as opposed to complications secondary to EV themselves. Etiologic anatomic locations were similar in occurrence between the abdomen (N = 14) and thorax (N = 11). All cases with an abdominal etiologic location had presumed or confirmed portal hypertension and 9/11 cases with a thoracic etiologic location had pulmonary, caval, or systemic hypertension. No cases died or were euthanized as a direct result of EV or associated hemorrhage., Conclusions and Clinical Importance: Esophageal varices are rarely reported in dogs and commonly identified concurrently with portal, pulmonary, and caval hypertension. Hemorrhage is not a common clinical manifestation of EV., (© 2022 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.)

Gastrointestinal (GI) complications and their clinical implications are poorly characterized in dogs treated surgically for acute thoracolumbar intervertebral disc extrusion (TL-IVDE). The objective of this retrospective study was to characterize GI signs (including vomiting, diarrhea, melena, and hematochezia) in dogs undergoing hemilaminectomy for acute TL-IVDE. One-hundred and sixteen dogs were included. Frequency, type and severity of GI signs during hospitalization, duration of hospitalization and outcome were obtained from the medical record. Potential risk factors for the development of GI signs were explored using univariable and multivariable analyses. Gastrointestinal signs occurred in 55/116 dogs (47%); 22/55 dogs (40%) had one episode and 21/55 (38%) had ≥5 episodes. Diarrhea was the most common (40/55, 73%) while melena was rare (1/55, 2%). GI signs developed in 8/11 dogs (73%) treated perioperatively with both non-steroidal anti-inflammatories and corticosteroids with or without a washout period and in 25/52 dogs (48%) treated prophylactically with proton pump inhibitors. Median hospitalization was 7 days (4-15 days) vs. 5 days (4-11 days) in dogs with or without GI signs, respectively. Duration of hospitalization was associated with development of any GI signs, diarrhea and more severe GI signs ( p = 0.001, 0.005, 0.021, respectively). Pre-operative paraplegia with absent pain perception was identified on univariable analysis ( p = 0.005) and longer anesthetic duration on multivariable analysis to be associated with development of more severe GI signs ( p = 0.047). In dogs undergoing surgery for acute TL-IVDE, GI signs were common and associated with duration of hospitalization and anesthesia. The influence of specific medications and neurologic severity on development of GI signs requires further investigation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Mehra, Tolbert, Moore and Lewis.)

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., (© 2021 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.)

Gastrointestinal disease is a common clinical problem in captive cheetahs ( Acinonyx jubatus ). It is reported that gastritis affects the vast majority of the captive population of cheetahs. Pancreatitis and acute and chronic enteritis have also been reported. These issues pose significant long-term health and welfare implications for cheetahs. Cobalamin, folate, methylmalonic acid (MMA), gastrin, feline pancreatic-specific lipase immunoreactivity (fPLI), and feline trypsin-like immunoreactivity (fTLI) immunoassays are important biomarkers of gastrointestinal disease in domestic cats. The goal of this study was to determine if these immunoassays validated in domestic cats could be used clinically in cheetahs, by establishing reference intervals (RI) for these biomarkers in cheetahs. A cohort of 40 clinically healthy cheetahs was selected from three zoological institutions on the basis of being free of clinical gastrointestinal disease and extra-gastrointestinal disease that could affect biomarkers, as well as having banked frozen serum. Cheetah biomarker RI, with domestic cat RI for comparison in parentheses, are as follows: cobalamin 470-618 pg/ml (290-1500 pg/ml), folate 2.2-15.7 ng/ml (9.7-21.6 ng/ml), MMA 365-450 nM/L (139-897 nM/L), fPLI 0.5-1.2 µg/L (0-4 µg/L), and gastrin 30-50 pg/ml (<10 -3 9.5 pg/ml). This study shows that RI for gastrointestinal biomarkers can be notably different, even between species that are as closely related as the domestic cat and the cheetah. Additionally, it was found that the fTLI assay does not cross-immunoreact with cheetahs. In conclusion, this study emphasizes the importance of developing species-specific RI for biomarker assays and using caution when extrapolating RI from other species.

Background: Nonsteroidal anti-inflammatory drugs (NSAIDs) are the most common pharmaceutical associated with gastroduodenal ulceration and perforation. The prevalence of gastrointestinal (GI) injury associated with chronic use of NSAIDs in dogs is unknown., Objective/hypothesis: To determine the prevalence of GI mucosal erosions in dogs receiving chronic treatment with NSAIDs. We hypothesized that dogs receiving NSAIDs would have more GI mucosal erosions and longer GI transit time than a control population., Animals: Fourteen client-owned medium- and large-breed dogs receiving an NSAID for at least 30 days and 11 client-owned control dogs undergoing video capsule endoscopy (VCE) for evaluation of chronic GI disease., Methods: Dogs were prospectively recruited after determining no clinically relevant comorbidities were present and VCE was performed. The GI transit time and the presence of mucosal lesions were recorded., Results: Twelve dogs receiving NSAIDs and 11 retrospectively evaluated control dogs were included. The NSAIDs administered included carprofen (9 dogs), meloxicam (2 dogs), and firocoxib (1 dog) for a median of 6 months. Ten (83.3%; 95% confidence interval; 51.6%-97.9%) NSAID-treated dogs had GI erosions. Erosions were seen with all 3 NSAIDs in at least 1 dog. Three of 11 control dogs had gastric erosions. Dogs receiving NSAIDs had more erosions detected (P = .004)., Conclusions and Clinical Relevance: Subclinical GI erosions are more common in dogs receiving chronic treatment with NSAIDs than in control dogs with chronic GI disease, suggesting that NSAIDs be used with caution, particularly in dogs with comorbidities predisposing them to GI ulceration., (© 2021 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC. on behalf of the American College of Veterinary Internal Medicine.)

Background: Enteric-coated omeprazole capsules are commonly used as a gastric acid suppressant in dogs. However, the efficacy of this formulation has not been evaluated for clinical use in dogs., Hypothesis/objectives: To evaluate the efficacy of a 10 mg PO omeprazole capsule (TriviumVet) undergoing FDA approval to increase gastric pH in dogs. We hypothesized that encapsulated omeprazole would significantly increase the gastric pH compared to placebo and reach pH goals extrapolated from people for the treatment of esophagitis and duodenal ulceration., Animals: Six healthy research dogs., Methods: Randomized, blinded, 2-way crossover study. Dogs were PO administered omeprazole at 0.5 to 1.0 mg/kg or placebo (empty gelatin capsules) twice-daily for 5 days. The intragastric pH was recorded on days 2 to 5 of treatment. Mean pH and the mean percentage time (MPT) intragastric pH was ≥3 or ≥4 were compared between and within treatment groups., Results: Dogs treated with omeprazole had a significantly higher MPT ± SD intragastric pH ≥3 (91.2% ± 11.0%), ≥4 (86.9% ± 13.7%) and mean ± SD pH (5.4 ± 0.8) than dogs treated with placebo (19.7% ± 15.5%, 28.3 ± 20.7, and 2.4 ± 1.0, respectively) (P < .001 for all)., Conclusions and Clinical Importance: The 10 mg enteric-coated omeprazole capsule PO administered evaluated in this study is an effective gastric acid suppressant in healthy dogs., (© 2021 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC. on behalf of the American College of Veterinary Internal Medicine.)

A range of gastroprotective drugs are available for the treatment of esophagitis and gastroduodenal mucosal injury including acid suppressants (ie, histamine-2 receptor antagonists, proton pump inhibitors), coating agents, prostaglandin analogs, and antacids. Of these, the proton pump inhibitors are the most effective drugs for the medical treatment of upper gastrointestinal injury. However, proton pump inhibitors are not effective for all causes of upper gastrointestinal injury. The choice of gastroprotective drug should be guided by the cause and location of gastrointestinal injury and the potential for adverse effects., Competing Interests: Disclosure The author is a consultant for TriviumVet, Inc. Studies performed by the author in the text above were supported by the Comparative Gastroenterology Society, American Veterinary Medical Foundation, Winn Feline Foundation (W17-017), Miller Trust (MT18-004), UTK Companion Animal Fund, and the ACVIM Foundation., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objectives: The aim of this study was to describe the pharmacokinetics of oral transmucosal (OTM) detomidine gel in healthy cats and assess its effects on sedation and hemodynamic variables., Methods: Eight adult cats weighing 4.12 kg ± 0.72 received 4 mg/m 2 detomidine gel onto the buccal mucosa. Level of sedation, heart rate (HR), blood pressure (BP) and respiratory rate ( f  R) were assessed at predetermined intervals following administration. Blood samples for plasma detomidine concentrations and venous blood gas variables were collected from a medial saphenous catheter. Plasma detomidine concentrations were analyzed using ultra-high-pressure liquid chromatography with mass spectrometry detection, and pharmacokinetic estimates were obtained with compartmental methods. Data were analyzed using ANOVA and paired t -test or appropriate non-parametric tests., Results: Sedation occurred in all cats, and was increased from baseline at 30 mins ( P <0.001). Decreases in HR occurred from 15-60 mins, ranging from 140 to 165 beats per min ( P <0.001). Blood glucose increased from 101 ± 12 mg/dl to 168 ± 27.3 mg/dl at 60 mins ( P  = 0.004). Systolic blood pressure decreased from baseline (139 ± 14.8 mmHg) to 103 ± 23.0 mmHg at 60 mins ( P  = 0.023). All changes abated by 120 mins. Emesis occurred in 7/7 cats within 2 mins of gel administration. Geometric mean (coefficient of variation) for clearance was 220.7 ml/min/kg (35.3 ml/min/kg), volume of distribution was 14.9 l/kg (39.9 l/kg) (both a function of bioavailability) and elimination half-life was 46.9 mins (16.0 mins). Maximum plasma concentrations of 10.5 ng/ml (35.5 ng/ml) detomidine occurred at 36.9 mins (21.5 mins)., Conclusions and Relevance: OTM detomidine gel produced moderate sedation with minimal undesirable side effects in healthy cats, although emesis occurred in all cats. The pharmacokinetic profile supports short-term, minimally invasive sedation in this species. Further studies are warranted to assess its safety and feasibility for use in debilitated cats, or prior to general anesthesia.

Background: Proton pump inhibitors (eg, omeprazole) commonly are administered concurrently with nonsteroidal anti-inflammatory drugs (NSAIDs; eg, carprofen) as prophylaxis to decrease the risk of gastrointestinal (GI) injury. However, evidence to support this practice is weak, and it might exacerbate dysbiosis and inflammation., Hypothesis/objectives: To evaluate the effect of carprofen alone or combined with omeprazole in dogs. We hypothesized that coadministration of omeprazole and carprofen would significantly increase GI permeability and dysbiosis index (DI) compared to no treatment or carprofen alone., Animals: Six healthy adult colony beagle dogs., Methods: Gastrointestinal permeability and inflammation were assessed by serum lipopolysaccharide (LPS) concentration, plasma iohexol concentration, fecal DI, and fecal calprotectin concentration in a prospective, 3-period design. In the first 7-day period, dogs received no intervention (baseline). During the 2nd period, dogs received 4 mg/kg of carprofen q24h PO for 7 days. In the 3rd period, dogs received 4 mg/kg of carprofen q24h and 1 mg/kg of omeprazole q12h PO for 7 days. Gastrointestinal permeability testing was performed at the end of each period. Data were analyzed using repeated measures mixed model analysis of variance with Tukey-Kramer post hoc tests (P < .05)., Results: Serum LPS and plasma iohexol concentrations did not differ between treatments. Fecal calprotectin concentrations differed between treatments (P = .03). The DI varied over time based on the treatment received (P = .03). Coadministration of omeprazole and carprofen significantly increased fecal calprotectin concentration and DI compared to baseline and carprofen alone., Conclusions and Clinical Importance: Omeprazole prophylaxis induces fecal dysbiosis and increases intestinal inflammatory markers when coadministered with carprofen to otherwise healthy dogs with no other risk factors for GI bleeding., (© 2020 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.)

Background: Proton pump inhibitors (PPIs) are among the most commonly prescribed medications for esophagitis and upper gastrointestinal erosion and ulceration in cats. Newer PPIs such as lansoprazole and esomeprazole are believed to be effective in cats, but the effect of many of these PPIs on gastric pH in cats has not been explored., Hypothesis/objectives: To evaluate the efficacy of PO esomeprazole, dexlansoprazole, and lansoprazole on intragastric pH in healthy cats. We hypothesized that esomeprazole and lansoprazole would provide superior acid suppression compared to dexlansoprazole and reach pH goals extrapolated from people for the treatment of esophagitis and duodenal ulceration., Animals: Twelve healthy research cats., Methods: Randomized, 3-way crossover study. Cats were given esomeprazole and lansoprazole at a dosage of 1 mg/kg PO q12h or dexlansoprazole at 6 mg/kg PO q12h. Intragastric pH was recorded at baseline and for 4 days of treatment. Mean pH and the mean percentage time (MPT) intragastric pH was ≥3 or ≥4 were compared among and within treatment groups., Results: Cats treated with lansoprazole had a lower MPT ± SD of intragastric pH ≥3 (8.8 ± 6.8%) and mean ± SD pH (1.6 ± 0.5) than did cats treated with dexlansoprazole (41.2 ± 34.6% and 3.11 ± 1.6, respectively) or esomeprazole (54 ± 33.8% and 4.1 ± 3.9, respectively;P ≤ .04). Esomeprazole was the only treatment that achieved the goals defined for people for the treatment of duodenal ulceration by Day 4 of treatment (MPT ± SD of intragastric pH ≥4 of 77.1 ± 29.2%)., Conclusions and Clinical Importance: Orally administered esomeprazole might be a superior acid suppressant in cats compared to PO lansoprazole or dexlansoprazole., (© 2020 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.)

Background: Upper gastrointestinal (GI) ulceration and bleeding in critically ill dogs can cause severe anemia and increase morbidity. Acid suppressants using proton pump inhibitors or histamine-2 receptor blockers administered IV is commonly recommended., Hypothesis/objectives: To evaluate the efficacy of IV administered esomeprazole, pantoprazole, and famotidine constant rate infusion (CRI) on increasing the intragastric pH of dogs. We hypothesized that esomeprazole and famotidine CRI would provide superior acid suppression compared to pantoprazole and reach pH goals for the treatment of GI bleeding., Animals: Nine healthy research Beagles., Methods: Randomized, 3-way crossover. Dogs received pantoprazole or esomeprazole at 1 mg/kg IV q12h and famotidine with a loading dose of 1 mg/kg followed by 8 mg/kg IV CRI daily for 3 consecutive days. The intragastric pH was recorded at baseline and for 72 hours of treatment. The mean pH and the mean percentage time (MPT) the intragastric pH was ≥3 or ≥4 were compared among and within treatment groups., Results: Significant increases in mean pH (P < 0.0001), MPT ≥3 (P < 0.001), and MPT ≥4 (P = 0.0006) were noted over time with all 3 treatments. The time effect did not differ by treatment for mean pH, MPT ≥3, and MPT ≥4 (P = .29, .56, and .37, respectively); however, only esomeprazole and famotidine CRI achieved the goals established for the treatment of gastroduodenal ulceration in people., Conclusions and Clinical Importance: Famotidine CRI and esomeprazole might be superior acid suppressants compared to standard doses of pantoprazole for the first 72 hours of treatment., (© 2020 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.)

Background: Famotidine is sometimes administered as a continuous rate infusion (CRI) to treat gastrointestinal ulceration in critically ill dogs. However, clinical studies have not evaluated the efficacy of a famotidine CRI in dogs., Hypothesis/objectives: To evaluate the efficacy of famotidine at raising intragastric pH when it is administered as a CRI in dogs. We hypothesized that CRI treatment with famotidine would meet clinical goals for raising intragastric pH ≥3 and 4., Animals: Nine healthy Beagle dogs., Methods: Randomized 2-way crossover. All dogs received 1.0 mg/kg IV q12h famotidine or CRI famotidine at 1.0 mg/kg IV loading dose and 8.0 mg/kg/d for 3 consecutive days. Beginning on day 0 of treatment, intragastric pH monitoring was used to continuously record intragastric pH. Mean percentage times (MPTs) for which intragastric pH was ≥3 and ≥4 were compared between groups using analysis of variance., Results: There was a statistically significant difference (P < .05) in MPT ≥3 and ≥4 between the CRI and IV q12h groups on all treatment days. On days 1, 2, and 3, the MPTs ± SD for which pH was ≥3 were 92.1 ± 8.5, 96.3 ± 6.2, and 90.0 ± 15.7 for the CRI treatment group and 49.3 ± 27.3, 42.2 ± 19.6, and 45.8 ± 10.1, respectively, for the twice-daily group., Conclusions and Clinical Importance: These results suggest that a famotidine CRI, but not standard doses of famotidine, achieves the clinical goals established in people to promote healing of gastric tissue injury and offers an alternative to intravenous treatment with proton pump inhibitors in dogs., (© 2019 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.)

Tritrichomonas foetus is a common cause of large bowel diarrhea in cats. Probiotics have been suggested to be effective for many intestinal pathogens; however, there are a lack of studies evaluating the effect of probiotics in T. foetus infection. In vitro studies were performed to evaluate the effect of a probiotic containing Enterococcus faecium (Efm) SF68 and a novel probiotic, Enterococcus hirae, on the inhibition of T. foetus growth, adhesion to, and cytotoxicity towards the intestinal epithelium. The effect of enterococci on T. foetus proliferation during co-culture was evaluated throughout log phase T. foetus growth. The previously validated in vitro co-culture model system using porcine intestinal epithelial cells (IPEC-J2) was used to evaluate the effect of enterococci on T. foetus adhesion and cytotoxicity towards intestinal epithelial cells. Cytotoxicity was assessed using fluorescent microscopy and spectrophotometry. Interactions of T. foetus, enterococci, and intestinal epithelial cells were assessed using scanning electron microscopy and immunofluorescence assays (IFA). Enterococcus-induced inhibition of T. foetus growth was demonstrated at concentrations as low as 10 4 enterococci colony forming units (CFU)/mL and was dependent, in part, on environmental pH and the presence of viable enterococci organisms. T. foetus adhesion, including with a ronidazole-resistant strain, was reduced with pretreatment of intestinal epithelial cells with enterococci but was not significantly affected when enterococci were introduced simultaneously or following T. foetus infection. Compared to Efm, E. hirae more effectively decreased T. foetus adhesion, suggesting its superior potential as a novel probiotic for T. foetus infection. There was no effect of enterococci treatment on T. foetus-induced intestinal epithelial cell cytotoxicity. Our results support further study into the investigation of a possible benefit of enterococci-containing probiotic treatment for prevention of T. foetus infection in at-risk uninfected cats., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: The purpose of this study was to determine whether heparinized saline (HS) would be more effective in maintaining the patency of central venous catheters (CVCs) in dogs compared to 0.9% sodium chloride. This was a prospective randomized blinded study conducted at a University Veterinary Teaching Hospital., Methods: A total of 24 healthy purpose-bred dogs were randomized into two groups: a treatment and a control group. A CVC was placed in the jugular vein of each dog. Each dog in the treatment group had their CVC flushed with 10 IU/mL HS, while dogs in the control group had their CVC flushed with 0.9% sodium chloride every 6 h for 72 h. Immediately prior to flushing, each catheter was evaluated for patency by aspiration of blood. The catheter site was also evaluated for phlebitis, and a rectal temperature was obtained in each dog every 6 h. Prothrombin (PT) and activated partial thromboplastin (aPTT) times were evaluated prior to the administration of any flush solution. Results were then compared to values obtained 72 h later., Results: All CVCs in both groups were patent after 72 h, which was demonstrated by aspiration of blood and ease of flushing the catheter. Two CVCs in the 0.9% sodium chloride group had a negative aspiration at hour 12 and 36, respectively. One CVC in the HS group had a negative aspiration at hour 18. Signs of phlebitis occurred in three dog: two in the 0.9% sodium chloride group and one in the HS group. No dog was hyperthermic (>103 °F). Two catheters were inadvertently removed by dogs in the HS group during the study. There were no significant differences in catheter patency, incidence of phlebitis, or incidence of negative aspirations between both groups. aPTT and PT values remained within the normal reference range for all dogs in both groups. Ultimately, 0.9% sodium chloride was as effective as 10 IU/mL HS in maintaining the patency of CVCs for up to 72 h in healthy dogs. Further evaluation in clinical patients is warranted., Competing Interests: The authors declare that they have no competing interests.

Background: Famotidine is commonly administered to cats. Prolonged famotidine administration results in decreased efficacy in humans, dogs, and cows, but the long-term effects in cats are unknown., Objectives: To compare the effect of 2 oral administration frequencies of famotidine, twice daily (Group 1) and twice daily every second day (Group 2), on intragastric pH and serum gastrin concentrations in cats. We hypothesized a diminished effect on intragastric pH would be observed over time in Group 1 but not Group 2., Animals: Sixteen healthy cats., Methods: Randomized, 2-factor repeated measures crossover design. Cats received 0.5-1.24 mg/kg (median, 0.87 mg/kg) famotidine twice daily or twice daily every second day for 14 consecutive days. Intragastric pH monitoring was used to record intragastric pH on treatment days 1-3 and 11-13. Mean pH and mean percentage time (MPT) intragastric pH was ≥3 and 4 were compared between and within treatment groups by analysis of variance., Results: Significant treatment group by time interactions were observed for mean intragastric pH, MPT intragastric pH ≥3 and 4 (P = .009, P = .02, P = .005, respectively). Interaction post hoc tests identified significant decreases in mean intragastric pH (P = .001), MPT ≥3 (P = .001), and MPT ≥4 (P = .001) on day 13 compared to day 1 in Group 1 but not in Group 2., Conclusions and Clinical Importance: Oral famotidine administration results in a diminished effect on intragastric pH in healthy cats when given twice daily every day., (© 2019 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.)

Objectives The aim was to retrospectively evaluate the effects of acid-suppressant therapy in a population of cats with chronic kidney disease (CKD). The study objectives were to evaluate the effects of acid-suppressant therapy on clinicopathologic variables and progression of CKD over time. Methods The databases of two institutions were searched over an 11 year time span for cats fitting inclusion criteria for CKD. A total of 89 cats met the criteria for inclusion and were grouped according to either early (ie, stages 1-2) or advanced (ie, stages 3-4) CKD. Variables were statistically analyzed before and after treatment with either: (1) proton pump inhibitors (PPIs; n = 17), (2) histamine-2 receptor antagonists (H2RAs; n = 30), (3) combined acid-suppressant therapy (PPI + H2RA; n = 6) or (4) no acid-suppressant therapy (n = 36). Shapiro-Wilk testing and Q-Q plots were used to assess normality and variance, respectively. A complete randomized design with a mixed-effects repeated measures ANOVA was used to evaluate for differences in stage, treatment and time, as well as the interaction between these effects. Results A significant increase in blood creatinine concentration was found over time independent of severity of CKD and treatment group ( P = 0.0087). A significant increase in blood sodium concentration (change of 3.12 mmol/l) was found independent of stage in cats receiving PPI therapy ( P = 0.0109). A significant decrease in total blood magnesium (change of 0.15 mmol/l) was detected in two cats with early CKD receiving combined acid suppressants ( P = 0.0025). Conclusions and relevance Results of this retrospective study suggest that cats with CKD receiving PPI therapy may develop alterations in blood sodium concentrations but do not experience more rapid progression of CKD.

Although they have historically been thought of as safe medications, proton pump inhibitors such as omeprazole have been associated with an increased risk of enteric, particularly Clostridium difficile , infections in people. In cats, omeprazole is often the first choice acid suppressant prescribed for the treatment of upper gastrointestinal (GI) ulceration and bleeding. Despite this, no studies to date have explored the effect of omeprazole on the feline fecal microbiome and metabolome. Therefore, the purpose of this pilot study was to evaluate the effect of prolonged omeprazole administration on the fecal microbiome and metabolome in healthy cats to identify targets for analysis in a larger subset of cats with GI disease. A within-subjects, before and after, pilot study was performed whereby six healthy adult cats received 60 days of placebo (250 mg lactose PO q 12 h) followed by 5 mg (0.83-1.6 mg/kg PO q 12 h) omeprazole. On days 0, 30, and 60 of placebo and omeprazole therapy, the fecal microbiome and metabolome were characterized utilizing 16S ribosomal RNA sequencing by Illumina and untargeted mass spectrometry-based methods, respectively. Omeprazole administration resulted in no significant changes in the global microbiome structure or richness. However, transient changes were noted in select bacterial groups with omeprazole administration resulting in an increased sequence percentage of Streptococcus, Lactobacillus, Clostridium , and Faecalibacterium spp. and a decreased sequence percentage of Bifidobacterium spp. Significance was lost for all of these bacterial groups after adjustment for multiple comparisons. The fecal concentration of O -acetylserine and aminomalonate decreased with omeprazole therapy, but significance was lost after adjustment for multiple comparisons. The results of this pilot study conclude that omeprazole has a mild and transient impact on the fecal microbiome and metabolome when orally administered to healthy cats for 60 days. Based on the findings of this pilot study, evaluation of the effect of omeprazole specifically on Streptococcus, Lactobacillus, Clostridium, Faecalibacterium , and Bifidobacterium spp. is warranted in cats with primary GI disease.

Tritrichomonas foetus (T. foetus) is a flagellated protozoa that infects the distal ileum and proximal colon of domestic cats, as well as the urogenital tract of cattle. Feline trichomonosis is recognized as a prevalent cause of chronic diarrhea in cats worldwide. The suspected route of transmission is fecal-oral, with cats in densely crowded environments at highest risk for infection. Thus, the recommended strategy for minimizing spread of infection is to identify and isolate T. foetus-positive cats from the general population. Rapid identification of infected cats can be challenging due to the inability to accurately and quickly detect the organism in samples at point of care facilities. Thus, identification of targets for use in development of a novel diagnostic test, as well as a vaccine or therapy for T. foetus infection is a significant area of research. Despite a difference in organ tropism between T. foetus genotypes, evidence exists for conserved virulence factors between feline and bovine T. foetus. The bovine T. foetus surface antigen, TF1.17, is an adhesin that is conserved across isolates. Vaccination with the purified antigen results in amelioration of cytopathogenicity and more rapid clearance of infection in cattle. We previously showed that three feline isolates of T. foetus were positive for TF1.17 antigen so we further hypothesized that TF1.17 is conserved across feline T. foetus isolates and that this antigen would represent an attractive target for development of a novel diagnostic test or therapy for feline trichomonosis. In these studies, we used monoclonal antibodies previously generated against 1.15 and 1.17 epitopes of the bovine T. foetus TF1.17 antigen, to evaluate for the presence and role of TF1.17 in the cytopathogenicity of feline T. foetus. A previously validated in vitro co-culture approach was used to model feline T. foetus infection. Immunoblotting, immunofluorescence assays, and flow cytometric analysis confirmed the presence and surface localization of antigen TF1.17 across all feline T. foetus isolates tested. Antigen TF1.17 was notably absent in the presumably nonpathogenic intestinal trichomonad, Pentatrichomonas hominis, a parasite that can be confused microscopically with T. foetus. Similar to bovine trichomoniasis, TF1.17 was found to promote T. foetus adhesion to the intestinal epithelium. These results support further characterization and development of the TF1.17 antigen as a possible target for the diagnosis and prevention of feline T. foetus infection., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Tritrichomonas foetus (T. foetus) is a flagellated protozoan parasite that is recognized as a significant cause of diarrhea in domestic cats with a prevalence rate as high as 30%. No drugs have been shown to consistently eliminate T. foetus infection in all cats. Cysteine proteases (CPs) have been identified as mediators of T. foetus-induced adhesion-dependent cytotoxicity to the intestinal epithelium. These CPs represent novel targets for the treatment of feline trichomonosis. However, cats also produce CPs that are part of life-critical systems. Thus, parasitic CPs need to be selectively targeted to reduce the potential for host toxicity. Previous studies have demonstrated the importance of a specific CP, CP30, in mediating bovine and human trichomonad cytopathogenicity. This CP has also recently been identified in feline T. foetus, although the function of this protease in the feline genotype remains unknown. Therefore, the study objectives were to characterize the presence of CP30 in feline T. foetus isolates and to evaluate the effect of targeted inhibition of CP30 on feline T. foetus-induced adhesion dependent cytotoxicity. The presence of CP30 in feline T. foetus isolates was identified by In gel zymography and proteomic analysis, indirect immunofluorescence (IF), and flow cytometry using a rabbit polyclonal antibody that targets bovine T. foetus CP30 (α-CP30). The effect of inhibition of CP30 activity on T. foetus adhesion and cytotoxicity was determined using CFSE-labeled feline T. foetus and crystal violet spectrophotometric assays in a previously validated co-culture model. CP30 expression was confirmed in all feline T. foetus isolates tested by all assays. Targeted inhibition of feline T. foetus CP30 resulted in decreased T. foetus adhesion to and cytotoxicity towards IPEC-J2 monolayers compared to rabbit IgG-treated T. foetus isolates. These studies establish that CP30 is expressed by feline T. foetus isolates and may be an important virulence factor in the cytopathogenicity of feline T. foetus. The results of these studies provide strong evidence-based justification for investigation of CP30 as a novel target for the treatment of feline trichomonosis., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: Chronic kidney disease (CKD) is a highly prevalent condition in cats. Advanced CKD is associated with hyporexia and vomiting, which typically are attributed to uremic toxins and gastric hyperacidity. However, gastric pH studies have not been performed in cats with CKD., Hypothesis/objectives: To determine if cats with CKD have decreased gastric pH compared to age-matched, healthy cats. Based on previous work demonstrating an association of hypergastrinemia and CKD, we hypothesized that cats with CKD would have decreased gastric pH compared to healthy, age-matched control cats., Animals: 10 CKD cats; 9 healthy control cats., Methods: All cats with concurrent disease were excluded on the basis of history, physical examination, CBC, plasma biochemistry profile, urinalysis, urine culture, serum total thyroxine concentration, and serum symmetric dimethylarginine concentration (controls only) obtained within 24 hours of pH monitoring and assessment of serum gastrin concentrations. Serum for gastrin determination was collected, and 12-hour continuous gastric pH monitoring was performed in all cats. Serum gastrin concentration, mean pH, and percentage time that gastric pH was strongly acidic (pH <1 and <2) were compared between groups., Results: No significant differences in serum gastrin concentrations were observed between groups (medians [range]: CKD, 18.7 ng/dL [<10-659.0]; healthy, 54.6 ng/dL [<10-98.0]; P-value = 0.713) or of any pH parameters including mean ± SD gastric pH (CKD, 1.8 ± 0.5; healthy, 1.6 ± 0.3; P-value = 0.23)., Conclusions and Clinical Importance: These findings suggest that cats with CKD may not have gastric hyperacidity compared to healthy cats and, therefore, may not need acid suppression. Thus, further studies to determine if there is a benefit to acid suppression in cats with CKD are warranted., (Copyright © 2017 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.)

CASE DESCRIPTION A 6-year-old castrated male Boxer was evaluated for a 5-week history of frequent vomiting, melena, and signs of abdominal pain following accidental ingestion of 5 to ten 15-mg meloxicam tablets (approx ingested dose, 3.1 to 6.2 mg/kg [1.4 to 2.8 mg/lb]). CLINICAL FINDINGS Clinical signs persisted despite 3 weeks of treatment with sucralfate (41.8 mg/kg [19 mg/lb], PO, q 8 h) and omeprazole (0.8 mg/kg [0.36 mg/lb], PO, q 24 h). Results of a CBC and serum biochemical analysis were unremarkable. Abdominal ultrasonography revealed peptic ulceration, and esophagogastroduodenoscopy confirmed the presence of severe proximal duodenal ulceration. TREATMENT AND OUTCOME A radiotelemetric pH-monitoring capsule was placed in the gastric fundus under endoscopic guidance for continuous at-home monitoring of intragastric pH and response to treatment. Treatment was continued with sucralfate (as previously prescribed) and omeprazole at an increased administration frequency (0.8 mg/kg, PO, q 12 h). Intragastric pH was consistently ≥ 3.0 for > 75% of the day during treatment, with the exception of 1 day when a single dose of omeprazole was inadvertently missed. Ulceration and clinical signs completely resolved. CLINICAL RELEVANCE Continuous radiotelemetric monitoring of intragastric pH in the dog of this report was useful for confirming that treatment achieved a predetermined target pH and for demonstrating the impact of missed doses. Duodenal ulceration resolved with twice-daily but not once-daily omeprazole administration. Findings suggested that twice-daily administration of omeprazole may be necessary to achieve this target pH and that a pH ≥ 3.0 for 75% of the day may promote healing of peptic ulcers in dogs.