Plasma glucagon-like peptide-2 concentrations are lower in dogs with chronic enteropathies than in healthy dogs.

OBJECTIVE: To compare plasma glucagon-like peptide-2 (GLP-2) concentrations in dogs with treatment-naïve chronic enteropathies to healthy dogs and describe changes over time in dogs with chronic enteropathies (CE). ANIMALS: 18 client-owned dogs with treatment-naïve CE and 17 client-owned healthy control dogs. METHODS: This was a prospective study. Fasting, 1-hour, and 3-hour postprandial plasma GLP-2 concentrations were measured using a commercial immunoassay in healthy dogs and dogs with uncontrolled, untreated CE. Repeated fasting and postprandial plasma concentrations were measured in dogs with CE after initiating directed treatment for gastrointestinal disease. RESULTS: There was no significant difference between fasting and postprandial GLP-2 concentrations in either group. Dogs with treatment-naïve CE had lower fasting (mean, 424 ± SD 176 pg/mL) plasma GLP-2 concentrations than healthy dogs (1184 ± 435 pg/mL; P < .0001). Fasted plasma GLP-2 concentrations (624 ± 314 pg/mL) remained lower in dogs with CE than in healthy dogs at recheck. CLINICAL RELEVANCE: Dogs with CE have disrupted GLP-2 secretion. Future studies are required to evaluate subsets of CE and changes in response to therapy.

Clinical response in dogs with acute hemorrhagic diarrhea syndrome following randomized probiotic treatment or fecal microbiota transplant.

Probiotics and fecal microbiota transplants (FMTs) are two microbiome-targeted therapies that have been investigated for use in gastrointestinal diseases associated with dysbiosis. The aim of this study was to compare the effects of an oral multi-strain probiotic and enema-administered FMTs on clinical signs and serum lipopolysaccharide in dogs with acute hemorrhagic diarrhea syndrome (AHDS). A total of 18 client-owned dogs with a diagnosis of AHDS were enrolled in a randomized, blinded study at the time of hospital admission. The dogs were randomized into two groups: the probiotic group received a daily oral probiotic (200 × 109 CFU/10kg q 24 h) for 14 days and a single sham enema; the FMT group received a single FMT via retention enema (10 mL/kg) and placebo oral capsule for 14 days. All dogs received concurrent standard-of-care therapy, including intravenous fluids and anti-emetics; no dogs received antimicrobials. The fecal score, disease severity scores, and serum lipopolysaccharide were measured on days 0, 3, and 14. Fourteen of eighteen enrolled dogs completed the study (n = 9 probiotics; n = 5 FMT). Lipopolysaccharide decreased on days 3 and 14 from baseline and correlated with fecal and disease severity scores. There was no difference in the duration or severity of clinical signs in dogs with AHDS following an enema-administered FMT compared to probiotic treatment. Further evaluation of serum lipopolysaccharide as a marker of disease severity and recovery is warranted.

Long-acting injectable methadone (methadone-fluconazole) provides safe and effective postoperative analgesia in a randomized clinical trial for dogs undergoing soft tissue surgery.

OBJECTIVE: To assess the pharmacokinetics, clinical efficacy, and adverse effects of injectable methadone with the pharmacokinetic enhancer fluconazole (methadone-fluconazole), compared with the standard formulation of injectable methadone, in dogs after ovariohysterectomy. We hypothesized that 2 doses of methadone-fluconazole would provide 24 hours of postoperative analgesia. ANIMALS: 3 purpose-bred dogs (pharmacokinetic preliminary study) and 42 female dogs from local shelters (clinical trial) were included. PROCEDURES: Pharmacokinetics were preliminarily determined. Clinical trial client-owned dogs were blocked by body weight into treatment groups: standard methadone group (methadone standard formulation, 0.5 mg/kg, SC, q 4 h; n = 20) or methadone-fluconazole group (0.5 mg/kg methadone with 2.5 mg/kg fluconazole, SC, repeated once at 6 h; n = 22). All dogs also received acepromazine, propofol, and isoflurane. Surgeries were performed by experienced surgeons, and dogs were monitored perioperatively using the Glasgow Composite Measure Pain Scale-Short Form (CMPS-SF) and sedation scales. Evaluators were masked to treatment. RESULTS: Findings from pharmacokinetic preliminary studies supported that 2 doses of methadone-fluconazole provide 24 hours of drug exposure. The clinical trial had no significant differences in treatment failures or postoperative CMPS-SF scores between treatments. One dog (methadone-fluconazole group) had CMPS-SF > 6 and received rescue analgesia. All dogs had moderate sedation or less by 1 hour (methadone-fluconazole group) or 4 hours (standard methadone group) postoperatively. Sedation was completely resolved in all dogs the day after surgery. CLINICAL RELEVANCE: Methadone-fluconazole with twice-daily administration was well tolerated and provided effective postoperative analgesia for dogs undergoing ovariohysterectomy. Clinical compliance and postoperative pain control may improve with an effective twice-daily formulation.

Intravenous iron sucrose is safe but does not prevent development of anemia or iron deficiency in healthy cats undergoing serial venipuncture.

OBJECTIVE: To evaluate IV iron sucrose safety and impact on hematologic and iron indices in healthy cats. ANIMALS: 5 healthy research cats. PROCEDURES: Cats were administered iron sucrose (0.5 mg/kg, IV) over 30 minutes. Monitoring for acute reactions (temperature, heart rate, respiratory rate, and blood pressure) was performed every 5 minutes during injection and every 15 minutes for an additional hour. Baseline, 24-hour, and 1-, 2-, and 3-week postinjection measurements of CBC with reticulocyte indices, iron panel (ferritin, total iron-binding capacity, and iron), calculated transferrin saturation (TSAT), and serum amyloid A (SAA) concentration were performed. RESULTS: No cat experienced an acute drug reaction. SAA concentration was increased at 24 hours versus baseline. TSAT and ferritin decreased over time, with 3 cats developing concurrent functional iron deficiency (FID) and anemia. Hct (Spearman correlation [rs] = 0.805), hemoglobin (rs = 0.770), and reticulocyte hemoglobin content (rs = 0.581) correlated with TSAT. CLINICAL RELEVANCE: IV iron sucrose was well tolerated in healthy cats but was associated with transient increase in the systemic inflammatory marker SAA. Efficacy evaluation of dose based on iron deficit is needed in sick cats. Despite cumulative blood draw volume below recommended limits, anemia and FID were observed, which has important implications for experimental designs and serial hematologic monitoring. Further evaluation of inflammatory response to IV iron sucrose administration is warranted.

Pathology in Practice.

In collaboration with the American College of Veterinary Pathologists.

What Is Your Diagnosis?

In collaboration with the American College of Veterinary Radiology.

Preliminary evaluation of probiotic effects on gastrointestinal signs in dogs with multicentric lymphoma undergoing multi-agent chemotherapy: A randomised, placebo-controlled study.

BACKGROUND: Gastrointestinal (GI) toxicity is a major dose-limiting factor in dogs undergoing chemotherapy. A proposed mechanism of GI toxicity includes chemotherapy-driven GI dysbiosis. This study was designed to determine the effects of probiotic administration on GI side-effects in dogs receiving multi-agent chemotherapy. METHODS: Ten client-owned dogs with multicentric lymphoma were enrolled in a prospective, randomised, placebo-controlled single-blinded study. On the first day of the cyclophosphamide doxorubicin vincristine prednisone (CHOP)-based chemotherapy protocol, dogs were randomised to receive either daily oral probiotic at a dose of 200 × 109 cfu/10 kg (n = 5) or daily oral placebo (n = 5). Complete blood count, faecal score (FS), faecal microbiome analysis (qPCR) and adverse events scores were performed at baseline and on the day of each subsequent chemotherapy dose, as well as 3 days after doxorubicin (days 0, 7, 14, 21, 24 and 28). RESULTS: Overall, 40% of dogs had an abnormal GI microbiome at baseline, specifically decreased faecal C. hiranonis and Fusobacterium abundances. Dogs receiving probiotics had increased faecal Streptococcus (p = 0.02) and E. coli. (p = 0.01). No dogs receiving probiotics experienced diarrhoea (FS ≥ 3.5) compared to four of five receiving placebo. (F 2.895; p = 0.13). CONCLUSION: GI microbiome dysbiosis was common in this group of dogs with multicentric lymphoma. Probiotics were well-tolerated, with no negative side effects. Further studies are needed to explore broader microbiome and metabolome changes, as well as clinical benefit.

Anemia, iron deficiency, and cobalamin deficiency in cats with chronic gastrointestinal disease.

BACKGROUND: Iron deficiency and cobalamin deficiency, as sequelae to chronic gastrointestinal (GI) disease, could result in anemia and increased morbidity in cats with chronic enteropathies. OBJECTIVE: To evaluate iron deficiency in cats with chronic GI disease and its relationship with hypocobalaminemia, anemia, and disease severity. ANIMALS: Twenty client-owned cats with primary GI disease. METHODS: Prospective, cross-sectional study. Cats were enrolled at the time of evaluation for chronic GI disease, after exclusion of comorbidities. CBC with reticulocyte indices, iron metabolism (serum iron and ferritin concentrations, total iron binding capacity [TIBC]), serum methylmalonic acid (MMA), cobalamin, and folate concentrations, pancreatic lipase and trypsin-like immunoreactivity, and disease severity were evaluated. RESULTS: Anemia (hematocrit <30%), iron deficiency, and cobalamin deficiency were diagnosed in 4/20, 7/20, and 8/20 cats, respectively. Hematocrit (rs = -.45; P < .05) and body condition score (rs = -.60; P < .01) negatively correlated with MMA. Median TIBC was lower in cats with increased vs normal MMA (218 µg/mL; range, 120-466 µg/mL vs 288 µg/mL; range, 195-369 µg/mL; P = .02). Hematocrit (rs = .51; P = .02), reticulocyte MCV (rs = .52; P = .02), reticulocyte hemoglobin content (rs = .71; P < .001), and percent transferrin saturation (rs = .79; P < .0001) positively correlated with serum iron concentration. CONCLUSIONS AND CLINICAL IMPORTANCE: Functional iron deficiency was common in cats with chronic GI disease. Associations between hypocobalaminemia, iron parameters, and hematologic parameters warrant further investigation on the impact of iron deficiency on chronic GI disease morbidity in cats.

Effects of oral Akkermansia muciniphila supplementation in healthy dogs following antimicrobial administration.

OBJECTIVE To measure effects of oral Akkermansia muciniphila administration on systemic markers of gastrointestinal permeability and epithelial damage following antimicrobial administration in dogs. ANIMALS 8 healthy adult dogs. PROCEDURES Dogs were randomly assigned to receive either A muciniphila (109 cells/kg; n = 4) or vehicle (PBS solution; 4) for 6 days following metronidazole administration (12.5 mg/kg, PO, q 12 h for 7 d). After a 20-day washout period, the same dogs received the alternate treatment. After another washout period, experiments were repeated with amoxicillin-clavulanate (13.5 mg/kg, PO, q 12 h) instead of metronidazole. Fecal consistency was scored, a quantitative real-time PCR assay for A muciniphila in feces was performed, and plasma concentrations of cytokeratin-18, lipopolysaccharide, and glucagon-like peptides were measured by ELISA before (T0) and after (T1) antimicrobial administration and after administration of A muciniphila or vehicle (T2). RESULTS A muciniphila was detected in feces in 7 of 8 dogs after A muciniphila treatment at T2 (3/4 experiments) but not at T0 or T1. After metronidazole administration, mean change in plasma cytokeratin-18 concentration from T1 to T2 was significantly lower with vehicle than with A muciniphila treatment (-0.27 vs 2.4 ng/mL). Mean cytokeratin-18 concentration was lower at T1 than at T0 with amoxicillin-clavulanate. No other significant biomarker concentration changes were detected. Probiotic administration was not associated with changes in fecal scores. No adverse effects were attributed to A muciniphila treatment. CONCLUSIONS AND CLINICAL RELEVANCE Detection of A muciniphila in feces suggested successful gastrointestinal transit following oral supplementation in dogs. Plasma cytokeratin-18 alterations suggested an effect on gastrointestinal epithelium. Further study is needed to investigate effects in dogs with naturally occurring gastrointestinal disease.

Serum cobalamin concentrations and small intestinal ultrasound changes in 75 cats with clinical signs of gastrointestinal disease: a retrospective study.

Objectives The aim of the study was to evaluate ultrasonographic changes in the small intestine of cats with clinical signs of gastrointestinal disease and low or low-normal serum cobalamin concentrations. Methods Records for client-owned cats presenting to the small animal hospital with signs of gastrointestinal disease and in which serum cobalamin concentrations were measured from 2000-2013 were reviewed. Inclusion criteria were cobalamin concentrations <500 ng/l, abdominal ultrasound within 1 month of cobalamin testing and definitive diagnosis. Results Of 751 serum cobalamin measurements, hypocobalaminemia or low-normal cobalamin was identified in 270 cats, abdominal ultrasound was performed in 207 of those cats and a diagnosis was available for 75 of them. Small intestinal ultrasound changes were detected in 49/75 (65%) cats. Abnormalities included thickening, loss of wall layer definition, echogenicity alterations and discrete masses. Serum cobalamin concentrations <500 ng/l were observed with diagnoses of inflammatory disease, neoplasia, infectious disease and normal histopathology. Cobalamin concentration was significantly lower in cats with lymphoma or inflammatory bowel disease compared with other gastrointestinal neoplasia ( P = 0.031). No difference was found between cobalamin concentration and the presence of ultrasound abnormalities, specific ultrasound changes or albumin concentration. Conclusions and relevance One-third of symptomatic cats with hypocobalaminemia or low-normal cobalamin concentrations may have an ultrasonographically normal small intestine. For the majority of cats in this study, histopathologic abnormalities were observed in the small intestine, regardless of ultrasound changes. These findings suggest gastrointestinal disease should not be excluded based on low-normal cobalamin concentrations, even with a concurrent normal ultrasound examination. Additional studies are needed in cats with low-normal serum cobalamin concentrations, as a definitive diagnosis was not pursued consistently in those cats. However, data from this study suggest that careful monitoring, histopathologic evaluation and future cobalamin supplementation may be warranted.