A retrospective study of 157 hospitalized cats with pancreatitis in a tertiary care center: Clinical, imaging and laboratory findings, potential prognostic markers and outcome

Ran Nivy, Alina Kaplanov, Sharon Kuzi, Michal Mazaki‐Tovi, Einat Yas, Gilad Segev, Jennifer Ben‐O, Eran Lavy, Itamar Aroch 

J Vet Intern Med.2018;32:1874–1885.

Background

Pancreatitis in cats (FP) has been increasingly diagnosed in recent years, but clinical studies of large numbers of affected cats are scarce.

Objectives

To describe a large cohort of cats with FP requiring hospitalization.

Animals

One hundred and fifty‐seven client‐owned cats.

Methods

Retrospective study, including cats diagnosed with pancreatitis based on sonographic evidence, positive SNAP feline pancreatic lipase immunoreactivity test results, increased 1,2‐o‐dilauryl‐rac‐glycerol‐glutaric Acid‐(6′‐methylresorufin ester)‐lipase activity, histopathology, or some combination of these.

Results

One‐hundred and twenty‐two cats (77.7%) survived to discharge.

Median time from onset of clinical signs to presentation was longer (P = .003) in nonsurvivors. Causes of FP included recent general anesthesia, trauma, hemodynamic compromise, and organophosphate intoxication, but most cases (86.6%) were idiopathic. Ultrasonographic findings consistent with pancreatitis were documented in 134 cats, including pancreatomegaly (81.3%), decreased (31.3%), or increased (14.9%) pancreatic echogenicity, extra‐hepatic biliary tract dilatation (24%), and increased peri‐pancreatic echogenicity (13%). Lethargy (P = .003), pleural effusion (P = .003), hypoglycemia (P = .007), ionized hypocalcemia (P = .016), azotemia (P = .014), parenteral nutrition administration (P = .013), and persistent anorexia during hospitalization (P = .001) were more frequent in nonsurvivors, whereas antibiotics were more frequently administered to survivors (P = .023). Nevertheless, when Bonferroni's correction for multiple comparisons was applied, none of the variables was statistically significant.

Conclusions and Clinical Importance

Previously unreported, clinically relevant, potential prognostic factors, including hypoglycemia, azotemia, parenteral nutrition, and withholding antibacterial treatment were identified in this exploratory study. These preliminary results should be examined further in confirmatory studies.

 

Effect of an extruded animal proteinfree diet on fecal microbiota of dogs with foodresponsive enteropathy

Francesca Bresciani, Yasushi Minamoto, Jan S. Suchodolski, Giorgia Galiazzo, Carla G. Vecchiato, Carlo Pinna, Giacomo Biagi, Marco Pietra

J Vet Intern Med.2018;32:1903–1910.

Background

Dietary interventions are thought to modify gut microbial communities in healthy individuals. In dogs with chronic enteropathies, resolution of dysbiosis, along with remission of clinical signs, is expected with treatment.

Hypothesis/Objective

To evaluate changes in the fecal microbiota in dogs with food‐responsive chronic enteropathy (FRE) and in healthy control (HC) dogs before and after an elimination dietary trial with an animal protein‐free diet (APFD).

Animals

Dogs with FRE (n = 10) and HC (n = 14).

Methods

Dogs were fed the APFD for 60 days. Fecal microbiota was analyzed by Illumina 16S rRNA sequencing and quantitative polymerase chain reaction (PCR).

Results

A significantly lower bacterial alpha‐diversity was observed in dogs with FRE compared with HC dogs at baseline, and compared with FRE dogs after the trial. Distinct microbial communities were observed in dogs with FRE at baseline compared with HC dogs at baseline and compared with dogs with FRE after the trial. Microbial communities still were different in FRE dogs after the trial compared with HC dogs at baseline. In HC dogs, the fecal microbiota did not show a significant modification after administration of the APFD.

Conclusion and Clinical Importance

Our results suggest that, in FRE dogs, treatment with the APFD led to a partial recovery of the fecal microbiota by significantly increasing microbiota richness, which was significantly closer to a healthy microbiota after the treatment. In contrast, no changes were detected in the fecal microbiota of HC dogs fed the same APFD.

 

Assessment of eosinophils in gastrointestinal inflammatory disease of dogs

Idil Bastan, Aaron K. Rendahl, Davis Seelig, Michael J. Day, Edward J. Hall, Savita P. Rao, Robert J. Washabau, P. Sriramarao

J Vet Intern Med.2018;32:1911–1917.

Background

Accurate identification of eosinophils in the gastrointestinal (GI) tract of dogs with eosinophilic GI disease (EGID) by histological evaluation is challenging. The currently used hematoxylin and eosin (H&E) staining method detects intact eosinophils but does not detect degranulated eosinophils, thus potentially underrepresenting the number of infiltrating eosinophils.

Objective

To develop a more sensitive method for identifying and quantifying both intact and degranulated eosinophils to diagnose EGID more accurately.

Methods

Endoscopically obtained paraffin‐embedded intestinal biopsy specimens from dogs with GI signs were examined. The study groups were dogs with eosinophilic enteritis (EE), lymphoplasmacytic and mixed enteritis, and control dogs with GI signs but no histologic changes on tissue sections. Consecutive sections were immunolabeled with monoclonal antibodies (mAbs) against the eosinophil granule protein eosinophil peroxidase (Epx) and stained by H&E, respectively. The number of eosinophils was manually quantified and classified as intact or degranulated.

Results

The number of intact eosinophils detected in Epx mAb‐labeled duodenal sections was significantly higher compared with that in H&E‐stained sections, with a similar relationship noted in the colon and stomach. The Epx mAb allowed the unique assessment of eosinophil degranulation. The number of intact and degranulated eosinophils was significantly higher in duodenal lamina propria of the EE and mixed group compared to the control group.

Conclusion

Immunohistochemical detection of Epx provides a more precise method to detect GI tract eosinophils compared to H&E staining and could be used as an alternative and reliable diagnostic tool for assessment of biopsy tissues from dogs with EGID.

 

Comparison of intestinal expression of the apical sodium‐dependent bile acid transporter between dogs with and without chronic inflammatory enteropathy

Paula R. Giaretta, Raquel R. Rech, Blake C. Guard, Amanda B. Blake, Anna K. Blick, Jörg M. Steiner Jonathan A. Lidbury, Audrey K. Cook ,Mohsen Hanifeh, Thomas Spillmann, Susanne Kilpinen, Pernilla Syrjä, Jan S. Suchodolski

J Vet Intern Med.2018;32:1918–1926.

Background

Intestinal absorption of bile acids is mediated by the apical sodium‐dependent bile acid transporter (ASBT). Fecal bile acid dysmetabolism has been reported in dogs with chronic inflammatory enteropathy (CIE).

Objective

Characterization of ASBT distribution along the intestinal tract of control dogs and comparison to dogs with CIE.

Animals

Twenty‐four dogs with CIE and 11 control dogs.

Methods

The ASBT mRNA and protein expression were assessed using RNA in situ hybridization and immunohistochemistry, respectively. The concentrations of fecal bile acids were measured by gas chromatography‐mass spectrometry. The fecal microbiota dysbiosis index was assessed with a quantitative polymerase chain reaction panel.

Results

In control dogs, ASBT mRNA expression was observed in enterocytes in all analyzed intestinal segments, with highest expression in the ileum. The ASBT protein expression was restricted to enterocytes in the ileum, cecum, and colon. Dogs with CIE had significantly decreased expression of ASBT protein in the ileum (P = .001), which was negatively correlated with histopathological score (ρ = −0.40; Pcorr = .049). Additionally, dogs with CIE had a significantly increased percentage of primary bile acids in feces compared to controls (P = .04). The fecal dysbiosis index was significantly higher in dogs with CIE than in control dogs (P = .01).

Conclusions and Clinical Importance

These findings indicate that ileal protein expression of ASBT is downregulated in dogs with CIE. This change may be linked to the inflammatory process, intestinal dysbiosis, and fecal bile acid dysmetabolism observed in these patients.

 

Hepatic copper concentrations in 546 dogs (1982–2015)

Jaimie M. Strickland DVM, John P. Buchweitz PhD , Rebecca C. Smedley DVM, MS, DACVP, Katherine J. Olstad DVM, DACVP, Ryan S. Schultz DVM, N. Bari Oliver DVM, PhD, DACVIM, Daniel K. Langlois DVM, DACVIM

J Vet Intern Med.2018;32:1943–1950.

Background

Copper associated hepatitis (CAH) has been increasingly recognized in dogs, and speculation exists that hereditary defects in copper metabolism have been exacerbated by increased environmental copper exposure. However, no broad epidemiological investigations have been performed to investigate quantitative hepatic copper concentrations ([Cu]H) over time in both dogs that are (predisposed breed [PB]), and are not (non‐predisposed breed [NPB]), considered at‐risk for CAH.

Objectives

To investigate [Cu]H in dogs and explore temporal, demographic, and histologic associations spanning 34 years.

Animals

546 archived liver specimens.

Methods

Retrospective study. Searches of the Michigan State University Veterinary Diagnostic Laboratory database identified dogs that had undergone hepatic histopathologic assessment. Cases with archived tissue were reviewed and classified by breed, time period, and presence or absence of hepatitis. Inductively coupled plasma mass spectrometry was used to determine [Cu]H.

Results

In time period 2009–2015, median [Cu]H were 101 μg/g and 313 μg/g greater than median [Cu]H in time period 1982–1988 for NPB and PB dogs, respectively (P < .001 for both comparisons). The proportion of dogs with [CU]H > 300 μg/g increased in NPB (28% to 49%) and PB dogs (48% to 71%) during these periods (P = .002 for both comparisons). Median [Cu]H in dogs with hepatitis increased 3‐fold over time in both NPB (P = .004) and PB populations (P < .001).

Conclusions and Clinical Importance

The frequent recognition of CAH in recent years is likely due to the observed increases in [Cu]H over time. Importantly, effects are not limited to PB dogs.

 

In vivo and in vitro assessment of mirtazapine pharmacokinetics in cats with liver disease

Rikki L. Fitzpatrick, Jessica M. Quimby, Kellyi K. Benson, Dominique Ramirez, Liberty G. Sieberg, Luke A. Wittenburg, Daniel L. Gustafson

J Vet Intern Med.2018;32:1951–1957.

Background

Liver disease (LD) prolongs mirtazapine half‐life in humans, but it is unknown if this occurs in cats with LD and healthy cats.

Hypothesis/Objectives

To determine pharmacokinetics of administered orally mirtazapine in vivo and in vitro (liver microsomes) in cats with LD and healthy cats.

Animals

Eleven LD and 11 age‐matched control cats.

Methods

Case‐control study. Serum was obtained 1 and 4 hours (22 cats) and 24 hours (14 cats) after oral administration of 1.88 mg mirtazapine. Mirtazapine concentrations were measured by liquid chromatography with tandem mass spectrometry. Drug exposure and half‐life were predicted using limited sampling modeling and estimated using noncompartmental methods. in vitro mirtazapine pharmacokinetics were assessed using liver microsomes from 3 LD cats and 4 cats without LD.

Results

There was a significant difference in time to maximum serum concentration between LD cats and control cats (median [range]: 4 [1‐4] hours versus 1 [1‐4] hours; P = .03). The calculated half‐life of LD cats was significantly prolonged compared to controls (median [range]: 13.8 [7.9‐61.4] hours versus 7.4 [6.7‐9.1] hours; P < .002). Mirtazapine half‐life was correlated with ALT (P = .002; r = .76), ALP (P < .0001; r = .89), and total bilirubin (P = .0008; r = .81). The rate of loss of mirtazapine was significantly different between microsomes of LD cats (–0.0022 min−1, CI: −0.0050 to 0.00054 min−1) and cats without LD (0.01849 min−1, CI: −0.025 to −0.012 min−1; P = .002).

Conclusions and Clinical Importance

Cats with LD might require less frequent administration of mirtazapine than normal cats.

 

Narrative review of therapies for chronic enteropathies in dogs and cats

Kelly Makielski, Jonah Cullen, Annette O'Connor, Albert E. Jergens

J Vet Intern Med.2019;33:11–22.

Background

The optimal medical treatment for chronic enteropathy (CE) in dogs and cats is controversial. Sequential treatment using diet, antimicrobials, and immunosuppressive drugs is the most common strategy used by clinicians.

Objectives

To review the evidence for the effectiveness of dietary, drug, and alternative health interventions for inducing clinical remission in dogs and cats with CE.

Animals

Retrospective study of dogs and cats with a diagnosis of chronic enteropathy.

Methods

MEDLINE and Centre for Agriculture and Bioscience International (CABI) databases (1950 to March 2017) were searched for randomized controlled trials (RCTs), observational studies, and case series. The primary outcome was induction of clinical remission. All studies were evaluated using the quality of evidence grading guidelines (I‐IV), which assign a score defining the strength and quality of the evidence.

Results

Twenty‐two studies (11 RCTs in dogs and 2 in cats and 9 cohort studies or case series) met the inclusion criteria for inducing remission of gastrointestinal (GI) signs. Of the 13 RCTs achieving grade I scores, 10 studies (totaling 218 dogs and 65 cats) compared single treatment: diet (n = 3), immunosuppressives (n = 3), antimicrobials (n = 2), anti‐inflammatory drugs (n = 1), and probiotics (n = 1). Three case series (grade III) reported clinical remission using an elimination diet fed to 55 cats and use of enrofloxacin to induce remission in dogs with granulomatous colitis (2 studies totaling 16 dogs).

Conclusions and Clinical Importance

The current evidence for treatment of CE is much greater in dogs than in cats. There is sufficient strong evidence to recommend the use of therapeutic GI diets, glucocorticoids, enrofloxacin, or some combination of these in dogs with CE. Therapeutic GI diets and glucocorticoids are most useful in cats with CE.

 

Prevalence of Clostridium perfringens netE and netF toxin genes in the feces of dogs with acute hemorrhagic diarrhea syndrome

Natalie Sindern, Jan S. Suchodolski, Christian M. Leutenegger, Iman Mehdizadeh Gohari, John F. Prescott, Anna‐Lena Proksch, Ralf S. Mueller, Kathrin Busch, Stefan Unterer

J Vet Intern Med.2019;33:100–105.

Background

Recently, novel pore‐forming toxin genes designated netE and netF were identified in a Clostridium perfringens type A strain isolated from a dog with acute hemorrhagic diarrhea.

Objectives

Pore‐forming toxins could play an important role in the disease pattern of acute hemorrhagic diarrhea syndrome (AHDS) in dogs. Thus, we aimed to determine the prevalence of C. perfringens genes encoding for netE and netF in the feces of dogs with AHDS and to evaluate any association between selected clinical variables and the presence of these toxin genes.

Animals

In total, 174 dogs were included in the study.

Methods

Fecal samples of all dogs were tested by real‐time polymerase chain reaction for netE and netF genes. Time to recovery, hospitalization time, and selected laboratory variables were compared between dogs with AHDS that were positive or negative for the toxin genes.

Results

A significant difference was found among the 3 groups in the prevalence of the pore‐forming toxin genes netE and netF: dogs with AHDS: 26 of 54 (48.1%); dogs with canine parvovirus (CPV) infection: 0 of 54 (0%); and healthy dogs: 8 of 66 (12.1%; P < .001). In dogs with AHDS, no significant difference was detected in any variables evaluated between netE‐positive and netF‐positive and netE‐negative and netF‐negative dogs.

Conclusions and Clinical Importance

The prevalence of C. perfringens encoding for netE and netF is significantly higher in dogs with AHDS compared to control dogs. Further studies are warranted to evaluate whether these toxins are an inciting cause for AHDS in dogs.

 

Association of circulating microRNA122 and microRNA29a with stage of fibrosis and progression of chronic hepatitis in Labrador Retrievers

Manabu Sakai, Bart Spee, Guy C. M. Grinwis, Louis C. Penning, Monique E. van Wolferen, Luc J. W. van der Laan, Hille Fieten

J Vet Intern Med.2019;33:151–157.

Background

Chronic hepatitis (CH) in dogs is common and has the tendency to progress to liver cirrhosis (LC). Circulating microRNAs might have the potential as markers for disease progression.

Objectives

To investigate whether concentration of specific microRNAs in serum correlate with the stage and grade of CH in Labrador Retrievers.

Animals

Twenty‐two Labrador Retrievers with histological CH (n = 8), LC (n = 7), and normal liver (NL, n = 7).

Methods

In this retrospective study, serum concentrations of miR‐122, miR‐29a, miR‐133a, miR‐181b, and miR‐17‐5p were measured by quantitative real‐time PCR and evaluated using univariate linear regression in dogs. A multivariate model was fit including the grade of hepatitis and the stage of fibrosis.

Results

Of the 5 microRNAs, only circulating miR‐122 and miR‐29a were significantly associated with the grade of hepatitis and the stage of fibrosis. A positive correlation was identified between the grade of hepatitis with miR‐122 (rs = 0.79, P < .001) and miR‐29a (rs = 0.78, P < .001). Both miR‐122 (rs = 0.81, P < .001) and miR‐29a (rs = 0.67, P < .001) showed a significant positive correlation with the stage of fibrosis. MiR‐122 concentrations were significantly higher in the CH (P < .01) and LC groups (P < .001) compared to the NL group. MiR‐29a concentrations were significantly higher in the CH (P < .001) and LC (P < .001) groups compared to the NL group.

Conclusions and Clinical Importance

Circulating miR‐122 and miR‐29a concentrations might be useful for monitoring the response to treatment and progression of canine CH.

 

Comparative pathophysiology and management of proteinlosing enteropathy

Melanie D. Craven, Robert J. Washabau

J Vet Intern Med.2019;33:383–402.

Protein‐losing enteropathy, or PLE, is not a disease but a syndrome that develops in numerous disease states of differing etiologies and often involving the lymphatic system, such as lymphangiectasia and lymphangitis in dogs. The pathophysiology of lymphatic disease is incompletely understood, and the disease is challenging to manage. Understanding of PLE mechanisms requires knowledge of lymphatic system structure and function, which are reviewed here. The mechanisms of enteric protein loss in PLE are identical in dogs and people, irrespective of the underlying cause. In people, PLE is usually associated with primary intestinal lymphangiectasia, suspected to arise from genetic susceptibility, or “idiopathic” lymphatic vascular obstruction. In dogs, PLE is most often a feature of inflammatory bowel disease (IBD), and less frequently intestinal lymphangiectasia, although it is not proven which process is the true driving defect. In cats, PLE is relatively rare. Review of the veterinary literature (1977‐2018) reveals that PLE was life‐ending in 54.2% of dogs compared to published disease‐associated deaths in IBD of <20%, implying that PLE is not merely a continuum of IBD spectrum pathophysiology. In people, diet is the cornerstone of management, whereas dogs are often treated with immunosuppression for causes of PLE including lymphangiectasia, lymphangitis, and crypt disease. Currently, however, there is no scientific, extrapolated, or evidence‐based support for an autoimmune or immune‐mediated mechanism. Moreover, people with PLE have disease‐associated loss of immune function, including lymphopenia, severe CD4+ T‐cell depletion, and negative vaccinal titers. Comparison of PLE in people and dogs is undertaken here, and theories in treatment of PLE are presented.

 

Development and validation of a novel clinical scoring system for shortterm prediction of death in dogs with acute pancreatitis

Virginie Fabrès, Olivier Dossin, Clémence Reif, Miguel Campos, Valerie Freiche, Christelle Maurey Fanny Pilot‐Storck, Loïc Desquilbet, Ghita Benchekroun

J Vet Intern Med.2019;33:499–507.

Background

Acute pancreatitis (AP) is associated with a high death rate in dogs, but accurate predictors of early death are still lacking.

Objectives

To develop a scoring system for prediction of short‐term case fatality in dogs with AP.

Animals

One hundred sixty‐nine dogs with AP including 138 dogs in the training cohort and 31 dogs in the validation cohort.

Methods

Multicenter, retrospective cohort study. Survival analysis was used to assess the associations with short‐term death (within 30 days after admission). Independent predictors of death were identified by a stepwise selection method and used for the score calculation.

Results

Death rate within 30 days after admission was 33% in the training cohort. Four independent risk factors for short‐term death were identified in the training cohort: presence of systemic inflammatory response syndrome, coagulation disorders, increased creatinine and ionized hypocalcemia. Canine Acute Pancreatitis Severity (CAPS) score was developed to predict short‐term death, integrating these 4 factors in a weighted way. A simplified version of CAPS score (sCAPS) including respiratory rate instead of SIRS was also assessed. The area under the receiver‐operating characteristic curve (AUC) of CAPS and sCAPS scores was 0.92 in the training cohort with an optimal cutoff of 11 (sensitivity, 89%; specificity, 90%) and 6 (sensitivity, 96%; specificity, 77%), respectively. CAPS and sCAPS score were validated in the validation cohort with respective AUC of 0.91 and 0.96.

Conclusions and Clinical Importance

We propose 2 scoring systems that allow early and accurate prediction of short‐term death in dogs with AP.

 

Comparison of 2 differently sized endoscopic biopsy forceps in the evaluation of intestinal disease in cats

Enrico Bottero, Emanuele Mussi, Camillo Pieramati, Davide De Lorenzi, Serenella Silvestri, Elvio Lepri

J Vet Intern Med.2019;33:523–530.

Background

In clinical practice, histopathological diagnosis of chronic intestinal disease is challenging because of difficulty in obtaining adequate duodenal samples. At present, no studies have investigated the influence of biopsy forceps size on sample quality in cats.

Objectives

Duodenal biopsy using larger biopsy forceps (2.4 mm) will provide higher quality samples.

Animals

Fifty client‐owned cats underwent endoscopy of the upper gastrointestinal tract for evaluation of chronic gastrointestinal signs, with inflammatory bowel disease (IBD) or intestinal lymphoma as differential diagnoses.

Methods

For each cat, duodenal biopsy specimens were obtained using both small (1.8 mm) and large (2.4 mm) forceps and evaluated for adequacy, orientation, the presence of artifacts, villi morphology, the presence of inflammation, and neoplastic infiltration.

Results

The percentage of adequate and evaluable biopsy specimens obtained using the larger forceps was significantly higher than that collected using the smaller forceps. Agreement between the forceps was variable for histological features and substantial in the case of lymphoma. However, in case of disagreement, the proper diagnosis usually was achieved only with the larger biopsy forceps.

Conclusions and Clinical Importance

Use of a larger biopsy forceps allows collection of a higher percentage of adequate and evaluable biopsy specimens compared to the commonly used smaller forceps and indirectly decreases the percentage of artifacts and increases the percentage of samples with evaluable villi. The use of a larger forceps could be helpful to obtain high‐quality samples and improve diagnostic accuracy.

 

Pharmacokinetics and pharmacodynamics of intravenous esomeprazole at 2 different dosages in dogs

Do‐Hyun Seo, Jong‐Bok Lee, Ji‐Hye Hwang, Jong‐Woo Jeong, Gun‐Ho Song, Tae‐Sung Koo, Kyoung‐Won Seo

J Vet Intern Med.2019;33:531–535.

Background

Although the demand for esomeprazole is increasing in veterinary medicine, the pharmacokinetics (PK) and pharmacodynamics of esomeprazole have been described in only a few studies.

Objective

To determine the PK of 0.5 and 1 mg/kg esomeprazole administered IV q12h and to investigate its effects on intragastric pH in healthy dogs.

Animals

Six adult Beagles.

Methods

Open‐label, randomized, and crossover design. The dogs received 0.5 or 1 mg/kg esomeprazole IV q12h for 48 hours. Plasma concentrations of esomeprazole were measured by high‐performance liquid chromatography‐tandem mass spectrometry. Intragastric pH was determined using the Bravo pH monitoring system and recorded as mean percentage time (MPT) for which pH was ≥3 and ≥4 for 24 hours in each group.

Results

The peak plasma concentration and area under the curve from the time of dosing to the last measurable concentration in the 1 mg/kg group were higher than those in the 0.5 mg/kg group. However, when the dosage normalized, intergroup differences were not significant. The MPTs for which intragastric pH was ≥3 and ≥4 for 48 hours were 88% ± 7% and 81% ± 9% for the 0.5 mg/kg group and 90% ± 9% and 85% ± 11% for the 1 mg/kg group, respectively, with no significant intergroup differences.

Conclusions and Clinical Importance

The pharmacokinetic parameters and acid suppressant effect for 0.5 and 1 mg/kg esomeprazole were not significantly different. Furthermore, the efficacy of esomeprazole 0.5 mg/kg IV q12h was sufficient to increase intragastric pH in Beagles.

 

Association of chronic enteropathy activity index, blood urea concentration, and risk of death in dogs with proteinlosing enteropathy

J Vet Intern Med.2019;33:536–543.

Aarti Kathrani, Fernando Sánchez‐Vizcaíno, Edward J. Hall

Background

Malnutrition is associated with increased risk of premature death in humans with inflammatory bowel disease.

Hypothesis/Objective

To determine if historical, clinical, and laboratory markers of malnutrition in dogs at the time of histologic diagnosis of protein‐losing enteropathy (PLE) caused by chronic enteropathy (CE) or lymphangiectasia are associated with increased risk of death.

Animals

Seventy‐one client‐owned dogs diagnosed with PLE.

Methods

The medical records were retrospectively searched for cases of PLE, diagnosed with CE or lymphangiectasia on the basis of histopathology of intestinal biopsies at a referral hospital. For each case, various variables at the time of diagnostic investigation were recorded and follow‐up obtained by telephone contact with the referring veterinarian.

Results

A multivariable cox model indicated that canine chronic enteropathy activity index (CCEAI) and blood urea concentration were significantly associated with death (P values <.01). For each unit increase in CCEAI, the hazard of death increased by 22.9% (confidence interval [CI]: 6.9%‐41.2%). Dogs with a CCEAI of ≤8 and dogs with urea ≤7 mmol/L survived 256 days longer (P = .001, CI: 106.7‐405.4 days) and 279 days longer (P = .009, CI: 70.0‐488.7 days) than those with a CCEAI of >8 and urea >7 mmol/L on average, respectively, when followed up for 647 days.

Conclusions and Clinical Importance

Increased CCEAI and blood urea concentration at the time of diagnosis might be predictive of death in dogs with PLE caused by CE or lymphangiectasia.

 

The frequency of oral famotidine administration influences its effect on gastric pH in cats over time

Elizabeth Golly, Adesola Odunayo  Maggie Daves, Julie Vose, Josh Price, Silke Hecht, Joerg M. Steiner, Shanna Hillsman, M. Katherine Tolbert

J Vet Intern Med.2019;33:544–550.

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.

 

Results of histopathology, immunohistochemistry, and molecular clonality testing of small intestinal biopsy specimens from clinically healthy clientowned cats

J Vet Intern Med.2019;33:551–558.

Sina Marsilio, Mark R. Ackermann, Jonathan A. Lidbury, Jan S. Suchodolski, Jörg M. Steiner

Background

Histopathology, immunohistochemistry, and molecular clonality testing are metrics frequently used to diagnose chronic enteropathy (CE) in cats. However, normal values for these metrics have been based mainly on samples from cats that were relatively young, specific pathogen‐free, or both.

Objectives

To describe results of histopathology, immunohistochemistry, and clonality testing of endoscopically‐derived biopsy specimens of the upper small intestinal tract from a cohort of clinically healthy client‐owned cats.

Animals

Twenty clinically healthy client‐owned cats ≥3 years of age.

Methods

Tissue specimens were collected from the stomach and duodenum and evaluated single blinded by a board‐certified pathologist. In addition, samples were evaluated by routine immunohistochemistry and clonality testing. Cats were followed after the procedure for signs of CE.

Results

Integrated results from histopathology, immunohistochemistry, and clonality testing were interpreted as consistent with small cell lymphoma (SCL; n = 12), emerging SCL (n = 1), lymphocytic enteritis (n = 6), and pseudoclonality (n = 1). On follow‐up, 3 cats eventually developed clinical signs of CE, of which 2 were euthanized 295 and 654 days post‐endoscopy. The remaining 17 cats did not show clinical signs of CE after a median of 709 days (range, 219‐869 days).

Conclusions and Clinical Importance

Intestinal biopsy specimens from clinically healthy client‐owned cats commonly had abnormal findings on histopathology, immunohistochemistry, clonality testing, or some combination of these without apparent clinical relevance. Current diagnostic metrics for diagnosing CE in cats may need modification to be applicable to the general population of cats.

 

Evaluation of duodenal perfusion by contrastenhanced ultrasonography in dogs with chronic inflammatory enteropathy and intestinal lymphoma

Khoirun Nisa, Sue Yee Lim, Masayoshi Shinohara, Tatsuyuki Osuga, Nozomu Yokoyama, Masahiro Tamura, Noriyuki Nagata, Kazuyoshi Sasaoka, Angkhana Dermlim, Rommaneeya Leela‐Arporn, Tomoya Morita, Noboru Sasaki, Keitaro Morishita, Kensuke Nakamura, Hiroshi Ohta, Mitsuyoshi Takiguchi

J Vet Intern Med.2019;33:559–568.

Background

Contrast‐enhanced ultrasonography (CEUS) can be used to evaluate intestinal perfusion in healthy dogs. It is helpful for diagnosing and monitoring inflammatory bowel disease in humans and could be useful for dogs with chronic intestinal diseases.

Objectives

To examine duodenal perfusion in dogs with chronic inflammatory enteropathy (CIE) and intestinal lymphoma.

Animals

Client‐owned dogs with CIE (n = 26) or intestinal lymphoma (n = 7) and dogs with gastrointestinal signs but histopathologically normal duodenum (controls, n = 14).

Methods

In this cross‐sectional study, dogs with CIE were classified into remission (n = 16) and symptomatic (n = 10) groups based on clinical scores determined at the time of CEUS. The duodenum was scanned after IV injection of Sonazoid® (0.01 mL/kg). CEUS‐derived perfusion parameters, including time‐to‐peak, peak intensity (PI), area under the curve (AUC), and wash‐in and wash‐out rates were evaluated.

Results

The PI was significantly higher in the symptomatic CIE group (median (range); 105.4 (89.3‐128.8) MPV) than in the control group (89.9 (68.5‐112.2) MPV). The AUC was significantly higher in the symptomatic CIE group (4847.9 (3824.3‐8462.8) MPV.sec) than in the control (3448.9 (1559.5‐4736.9) MPV.sec) and remission CIE (3862.3 (2094.5‐6899.0) MPV.sec) groups. The PI and clinical score were positively correlated in the CIE group. No significant differences in perfusion parameters were detected between the lymphoma and CIE groups or the lymphoma and control groups.

Conclusions and Clinical Importance

The PI and AUC can detect duodenal inflammation and hence are potentially useful for excluding a diagnosis of CIE.

 

Biomarkers of oxidative stress as an assessment of the redox status of the liver in dogs

Caitlin Barry‐Heffernan, Joanne Ekena, Sarah Dowling, Marie E. Pinkerton, Katrina Viviano

J Vet Intern Med.2019;33:611–617.

Background

Oxidative stress is associated with a diverse group of liver disorders across species.

Objectives

Determine whether glutathione (GSH) concentration in plasma and red blood cells correlates with liver GSH concentration in dogs and evaluate whether other markers of systemic oxidative stress, plasma vitamin E and urine 8‐isoprostanes/creatinine (F2‐IsoPs/Cr) concentrations, correlate with liver GSH.

Animals

Thirty‐four client‐owned dogs undergoing clinically indicated liver biopsy and 15 healthy control dogs.

Methods

Prospective, observational cross‐sectional study. Urine and blood were collected before liver biopsy. Plasma, erythrocyte, and liver GSH were measured using high performance liquid chromatography (HPLC); vitamin E was measured by HPLC, and F2‐IsoPs/Cr was measured by gas chromatography/mass spectrometry.

Results

All dogs were treated at the discretion of the attending clinician (24/34 received antioxidants; 4/34 fed therapeutic liver diet), which included dogs with primary or secondary liver disease (inflammatory (n = 21), metabolic (n = 9), vascular (n = 2), and neoplastic (n = 2)). Median GSH concentrations in plasma, erythrocyte, and liver were 0.18 mg/dL (range 0.14 to 0.56 mg/dL), 56.7 mg/dL (18.3 to 79.2 mg/dL), and 181 mg/dL (39.9 to 527 mg/dL), respectively. No significant correlations were found between liver GSH and erythrocyte GSH, plasma GSH, vitamin E, or F2‐IsoPs/Cr. Dogs undergoing clinically indicated liver biopsy had significantly higher urine F2‐IsoPs/Cr than did healthy controls (5.89 vs 2.98 ng/mg; P < .0001).

Conclusions and Clinical Importance

Erythrocyte and plasma GSH are not indicative of liver GSH concentration in dogs. In addition, dogs undergoing clinically indicated liver biopsy have evidence of increased systemic oxidative stress compared to healthy controls.

 

Daily oral cyanocobalamin supplementation in Beagles with hereditary cobalamin malabsorption (ImerslundGräsbeck syndrome) maintains normal clinical and cellular cobalamin status

Peter H. Kook, Martin Hersberger

J Vet Intern Med.2019;33:751–757.

Background

Efficacy of PO cobalamin (Cbl) supplementation in dogs with hereditary Cbl malabsorption (Imerslund‐Gräsbeck syndrome, IGS) is unknown.

Objectives

To evaluate PO Cbl supplementation in Beagles with IGS previously treated parenterally. We hypothesized that 1 mg cyano‐Cbl daily PO would maintain clinical and metabolic remission.

Animals

Three client‐owned Beagles with IGS and 48 healthy control dogs.

Methods

Prospective study. Daily PO cyanocobalamin (cyano‐Cbl; 1 mg) supplementation was monitored for 13 (2 dogs) and 8 months (1 dog). Health status was assessed by owner observations. Methylmalonic acid (MMA)‐to‐creatinine concentrations were measured using an ultra‐performance liquid chromatography‐tandem mass spectrometry (UPLC‐TMS) method on urine samples collected monthly. Concurrent measurements of serum MMA concentration (n = 7; UPLC‐TMS) were available for 1 dog.

Results

All dogs remained in excellent health during PO supplementation. Urine MMA remained consistently low in 2 dogs (median, 2.5 mmol/mol creatinine; range, 1.2‐9; healthy dogs [n = 30], median, 2.9 mmol/mol creatinine; range, 1.3‐76.5). Urine MMA ranged from 38.9‐84.9 mmol/mol creatinine during the first 6 months in 1 dog already known to excrete comparable amounts when supplemented parenterally. Brief antibiotic treatment for an unrelated condition after 6 months resulted in low urine MMA (median, 2.8 mmol/mol creatinine; range, 1.9‐4.8) for the next 7 months. All concurrent serum MMA concentrations (median, 651 nmol/L; range, 399‐919) before and after month 6 were within the established reference interval (393‐1476 nmol/L; n = 48).

Conclusions and Clinical Importance

One milligram of cyano‐Cbl daily PO appears efficacious for maintaining normal clinical status and normal cellular markers of Cbl metabolism in Beagles with IGS.

 

Hepatic copper accumulation in a young cat with familial variations in the ATP7Bgene

Hajime Asada, Mari Kojima, Takuro Nagahara, Yuko Goto‐Koshino, James K. Chambers, Taisuke Nakagawa, Nozomu Yokoyama, Kazuyuki Uchida, Hajime Tsujimoto, Koichi Ohno

J Vet Intern Med.2019;33:874–878.

A 9‐month‐old intact crossbred female cat was presented with jaundice, intermittent anorexia and lethargy, increased hepatic enzyme activities, and hyperammonemia. Abdominal ultrasound and computed tomographic examinations determined that the liver had a rounded and irregular margin, and histopathological examination identified excessive accumulation of copper hepatocytes in the liver. Concentrations of both blood and urine copper were higher than in healthy cats. The patient responded well to treatment with penicillamine. Clinicopathological abnormalities and clinical signs improved within 2 months, and the patient was alive for >9 months after starting treatment. Genetic examination determined that the patient and its littermate had a single‐nucleotide variation (SNV, p. T1297R) that impaired the function of the ATP7B gene product; the gene that is mutated in patients with Wilson's disease (WD). Hepatic copper accumulation was believed to be associated with the SNV of the ATP7B gene, and the patient had a genetic disorder of copper metabolism equivalent to WD in humans.

 

Clinical and histologic outcome in a dog surviving massive hepatic necrosis

Peter H. Kook, Miriam Baumstark, Maja Ruetten

J Vet Intern Med.2019;33:879–884.

This report describes the clinical and histologic recovery of a 2‐year‐old mixed‐breed dog presented with hypovolemic shock, markedly increased serum alanine amino transferase activity, and hemoabdomen. Emergency exploratory surgery revealed a friable liver with multiple capsule hemorrhages necessitating removal of the left lateral lobe. Histologic evaluation showed acute massive hepatic necrosis with centrilobular and midzonal distribution. The dog survived, and all monitored laboratory values normalized within 7 weeks. A liver biopsy taken 8 weeks after presentation revealed normal hepatic architecture with a few, randomly distributed neutrophilic foci. Follow‐up included intermittent determination of liver variables including liver function tests for a period of 7 years. The dog's health status, and all test results remained normal during this time. Complete recovery and good long‐term quality of life after life‐threatening acute liver failure secondary to massive hepatic necrosis is possible in dogs.