Prevalence of portal vein and splanchnic venous thrombosis in dogs with chronic hepatitis.

OBJECTIVES: Alterations in haemostasis have been described in dogs and humans with chronic hepatitis. Portal vein thrombosis is a recognised complication of chronic hepatitis in humans; however, its prevalence in dogs with chronic hepatitis has not been reported. We aimed to estimate the prevalence of, and describe clinical and laboratory data of dogs with chronic hepatitis and portal vein thrombosis and splanchnic venous thrombosis. MATERIALS AND METHODS: Retrospective cross-sectional study. Medical records of dogs admitted to a veterinary teaching hospital between 2009 and 2019 were reviewed. Dogs were included if chronic hepatitis was histopathologically confirmed, and if diagnostic imaging or necropsy indicated the presence of thrombosis. Clinical and laboratory data (i.e. haematology, biochemistry, coagulation panels) were recorded. Descriptive statistics were used to characterise dogs with and without thrombosis. RESULTS: Records from 136 dogs with chronic hepatitis were identified. Three of these dogs, 2.2% (95% confidence interval: 0.8 to 6.3%) all females, were diagnosed with portal vein thrombosis. Five dogs in total, (3.7%; 95% confidence interval: 1.6 to 8.3%), including three with portal vein thrombosis, all females, were diagnosed with splanchnic venous thrombosis. Dogs with portal vein and splanchnic venous thrombosis often had hyperbilirubinaemia, increased serum gamma-glutamyl transferase activity, and decreased plasma antithrombin 3 activity. They also had relatively high alternative Child-Pugh scores for dogs (median 6 out of 13). CLINICAL SIGNIFICANCE: Portal vein and splanchnic venous thrombosis are potentially serious complications that were identified in a relatively low proportion of dogs with chronic hepatitis.

Risk factors for urinary bacterial growth in dogs with congenital portosystemic shunts: 66 cases (1997-2019).

OBJECTIVE: To identify risk factors for urinary bacterial growth in dogs with confirmed congenital portosystemic shunts on which a quantitative urine culture was performed. MATERIALS AND METHODS: Sixty-six dogs were included in this retrospective cross-sectional study. Medical records were reviewed from 1997 through 2019. Variables of interest included age, sex and sexual status, clinical signs for a urinary tract infection, blood urea concentration, urinalysis abnormalities, ultrasound abnormalities of the urinary tract, and previous treatment. Univariable and multivariable analyses were performed. RESULTS: The median age of the dogs was one year (range: 0.2-11.0 years). Urinary tract ultrasound abnormalities (cystic calculi and cystic debris) were reported in 50 dogs (75.7%). Abnormalities on urinalysis included pyuria in nine dogs (13.6%), bacteriuria in 13 dogs (19.7%), and haematuria in 26 dogs (39.4%). The median urine specific gravity was 1.021 (range: 1.004-1.052). Sixteen dogs (24.2%) had a positive quantitative urine culture. Based on multivariable analysis, bacteriuria (Odds ratio, 116; 95% CI, 9.6-1393; P = < 0.001) was the only variable significantly associated with a significantly increased odds for a positive quantitative urine culture. CLINICAL SIGNIFICANCE: Clinical and subclinical bacteriuria can occur in dogs with congenital portosystemic shunts. In this group of dogs, bacteriuria was a risk factor for urinary bacterial growth.

Effect of clinical signs, endocrinopathies, timing of surgery, hyperlipidemia, and hyperbilirubinemia on outcome in dogs with gallbladder mucocele.

Gallbladder mucocele (GBM) is a common extra-hepatic biliary syndrome in dogs with death rates ranging from 7 to 45%. Therefore, the aim of this study was to identify the association of survival with variables that could be utilized to improve clinical decisions. A total of 1194 dogs with a gross and histopathological diagnosis of GBM were included from 41 veterinary referral hospitals in this retrospective study. Dogs with GBM that demonstrated abnormal clinical signs had significantly greater odds of death than subclinical dogs in a univariable analysis (OR, 4.2; 95% CI, 2.14-8.23; P<0.001). The multivariable model indicated that categorical variables including owner recognition of jaundice (OR, 2.12; 95% CI, 1.19-3.77; P=0.011), concurrent hyperadrenocorticism (OR 1.94; 95% CI, 1.08-3.47; P=0.026), and Pomeranian breed (OR, 2.46; 95% CI 1.10-5.50; P=0.029) were associated with increased odds of death, and vomiting was associated with decreased odds of death (OR, 0.48; 95% CI, 0.30-0.72; P=0.001). Continuous variables in the multivariable model, total serum/plasma bilirubin concentration (OR, 1.03; 95% CI, 1.01-1.04; P<0.001) and age (OR, 1.17; 95% CI, 1.08-1.26; P<0.001), were associated with increased odds of death. The clinical utility of total serum/plasma bilirubin concentration as a biomarker to predict death was poor with a sensitivity of 0.61 (95% CI, 0.54-0.69) and a specificity of 0.63 (95% CI, 0.59-0.66). This study identified several prognostic variables in dogs with GBM including total serum/plasma bilirubin concentration, age, clinical signs, concurrent hyperadrenocorticism, and the Pomeranian breed. The presence of hypothyroidism or diabetes mellitus did not impact outcome in this study.

Development, analytical validation, and initial clinical evaluation of a radioimmunoassay for the measurement of soluble CD25 concentrations in canine serum.

During immune activation, CD25 is expressed by T cells, and its soluble form (sCD25) is released into the extracellular matrix and the bloodstream. In humans, serum sCD25 concentrations are used as a surrogate marker for autoimmune diseases, malignancies, and transplant rejection. However, a canine-specific assay for the measurement of sCD25 in dog serum has not previously been described. Therefore, the aims of this study were to develop and analytically validate a radioimmunoassay to measure sCD25 in canine serum, to establish a reference interval for canine sCD25, and to test the clinical utility of this assay with serum samples for dogs with various diseases. A competitive radioimmunoassay (RIA) was developed and analytically validated. Analytical validation consisted of lower limit of detection (LLOD), dilutional parallelism, spiking recovery, and intra- and inter-assay variability using pooled surplus canine serum samples. A reference interval was established in healthy dogs and serum samples from dogs with various types of neoplasia, IBD, liver disease, suspected pancreatitis, or suspected small intestinal disease and serum samples with an increased C-reactive protein concentration (CRP) were analyzed to test the clinical utility of the assay. LLOD was calculated to be 0.5 ng/mL. The mean (±SD) observed-to-expected ratio (O/E) for serial dilutions was 101.7 ±â€¯14.0%, and the mean (± SD) O/E for spiking recovery was 93.2 ±â€¯4.2%. Coefficients of variation (CVs) for intra-assay variability were ≤12.5% (mean ±â€¯SD: 7.5 ±â€¯4.2%), and inter-assay CVs were ≤15.7% (mean ±â€¯SD: 11 ±â€¯4.4%). A reference interval (RI) for canine sCD25 of 1.2-4.2 ng/mL was established from a population of 112 clinically healthy dogs. Dogs with neoplasia and dogs with suspected small intestinal disease had decreased concentrations of serum sCD25 when compared to healthy dogs (p < 0.0001, respectively). However, the majority of clinical samples used in this study were within the reference interval. Median concentrations of serum sCD25 were 1.9 ng/mL for healthy dogs. Dogs with cancer, IBD, liver disease, suspected pancreatitis, or suspected small intestinal disease, as well as sera with an increased serum CRP concentration, had median serum sCD25 concentrations of 1.6 ng/mL, 2.1 ng/mL, 2.2 ng/mL, 1.7 ng/mL, 1.5 ng/mL, and 1.8 ng/mL, respectively. Thus, the RIA described here is linear, accurate, precise, and reproducible for measuring sCD25 in canine serum. However, this assay shows little clinical utility of sCD25 as a biomarker for dogs with inflammatory, autoimmune, and/or neoplastic conditions.

Effects of oral versus parenteral cobalamin supplementation on methylmalonic acid and homocysteine concentrations in dogs with chronic enteropathies and low cobalamin concentrations.

The objective of this study was to compare the effects of parenteral (PE) versus oral (PO) cobalamin supplementation on serum methylmalonic acid (MMA) and homocysteine (HCY) concentrations in dogs with hypocobalaminaemia. Thirty-six dogs with serum cobalamin concentrations below 285ng/L (reference interval (RI): 244-959ng/L) were treated with PO (0.25-1.0mg daily) or PE cobalamin (0.25-1.2mg/injection) using a block-randomized schedule. Serum MMA and HCY concentrations were analysed at day 0, 28 and 90 after start of supplementation. There was no significant difference between the PO and PE group regarding serum MMA or HCY concentrations at any time point. Median (range, P comparing baseline and 28 days, P comparing 28days and 90 days) serum MMA concentrations (nmol/L; RI 415-1193) were 932 (566-2468) in the PO and 943 (508-1900) in the PE group at baseline, respectively, 705 (386-1465, P<0.0001) and 696 (377-932, P<0.0001) after 28 days, and 739 (450-1221, P=0.58) and 690 (349-1145, P=0.76) after 90 days. Serum HCY concentrations (median (range), P comparing baseline and 28 days, P comparing 28days and 90 days, µmol/L; RI 5.9-31.9) in the PO and PE groups were 12.2 (3.3-62.2) and 8.4 (3.7-34.8) at baseline, 12.5 (5.0-45.0, P=0.61) and 8.0 (3.8-18.3, P=0.28) after 28 days, and 17.7 (7.3-60.0 P=0.07) and 12.4 (6.3-33.1, P=0.0007) after 90 days, respectively. Oral and parenteral cobalamin supplementation had the same effect on serum MMA concentrations in this group of dogs.

Serum α1-proteinase inhibitor concentrations in dogs with exocrine pancreatic disease, chronic hepatitis or proteinuric chronic kidney disease.

Serum canine α1-proteinase inhibitor (cα1-PI) concentrations were evaluated in dogs with pancreatitis (n=24), exocrine pancreatic insufficiency (EPI; n=29), chronic hepatitis (CH; n=11) or proteinuric chronic kidney disease (CKD-P; n=61) to determine whether systemic proteinase/proteinase-inhibitor balance is altered in these conditions. Dogs with CKD-P had significantly lower cα1-PI concentrations than dogs with pancreatitis, EPI or CH; 16% of dogs with CKD-P had serum cα1-PI concentrations below the reference interval. Serum and urine cα1-PI concentrations were inversely correlated in dogs with CKD-P, but not in dogs with CH. This suggests that renal loss of cα1-PI contributes to decreased serum concentrations in dogs with CKD-P, while hepatic cα1-PI synthesis with CH either is not compromised or is counterbalanced by extrahepatic production.

Hepatic Fibrosis in Dogs.

Hepatic fibrosis is commonly diagnosed in dogs, often as a sequela to chronic hepatitis (CH). The development of fibrosis is a crucial event in the progression of hepatic disease that is of prognostic value. The pathophysiology of hepatic fibrosis in human patients and rodent models has been studied extensively. Although less is known about this process in dogs, evidence suggests that fibrogenic mechanisms are similar between species and that activation of hepatic stellate cells is a key step. Diagnosis and staging of hepatic fibrosis in dogs requires histopathological examination of a liver biopsy specimen. However, performing a liver biopsy is invasive and assessment of fibrotic stage is complicated by the absence of a universally accepted staging scheme in veterinary medicine. Serum biomarkers that can discriminate among different fibrosis stages are used in human patients, but such markers must be more completely evaluated in dogs before clinical use. When successful treatment of its underlying cause is feasible, reversal of hepatic fibrosis has been shown to be possible in rodent models and human patients. Reversal of fibrosis has not been well documented in dogs, but successful treatment of CH is possible. In human medicine, better understanding of the pathomechanisms of hepatic fibrosis is leading to the development of novel treatment strategies. In time, these may be applied to dogs. This article comparatively reviews the pathogenesis of hepatic fibrosis, its diagnosis, and its treatment in dogs.

A dysbiosis index to assess microbial changes in fecal samples of dogs with chronic inflammatory enteropathy.

Recent studies have identified various bacterial groups that are altered in dogs with chronic inflammatory enteropathies (CE) compared to healthy dogs. The study aim was to use quantitative PCR (qPCR) assays to confirm these findings in a larger number of dogs, and to build a mathematical algorithm to report these microbiota changes as a dysbiosis index (DI). Fecal DNA from 95 healthy dogs and 106 dogs with histologically confirmed CE was analyzed. Samples were grouped into a training set and a validation set. Various mathematical models and combination of qPCR assays were evaluated to find a model with highest discriminatory power. The final qPCR panel consisted of eight bacterial groups: total bacteria, Faecalibacterium, Turicibacter, Escherichia coli, Streptococcus, Blautia, Fusobacterium and Clostridium hiranonis. The qPCR-based DI was built based on the nearest centroid classifier, and reports the degree of dysbiosis in a single numerical value that measures the closeness in the l2 - norm of the test sample to the mean prototype of each class. A negative DI indicates normobiosis, whereas a positive DI indicates dysbiosis. For a threshold of 0, the DI based on the combined dataset achieved 74% sensitivity and 95% specificity to separate healthy and CE dogs.

Opportunistic Invasive Cutaneous Fungal Infections Associated with Administration of Cyclosporine to Dogs with Immune-mediated Disease.

BACKGROUND: Opportunistic invasive fungal infections (OIFIs) occur in dogs administered immunosuppressive medications. However, the epidemiology of OIFIs among dogs undergoing immunosuppressive treatment is poorly understood. The aims of this study were to (1) estimate the incidence of OIFIs among dogs diagnosed with certain immune-mediated diseases and treated with immunosuppressive drugs, and (2) determine if administration of particular drug(s) was a risk factor for OIFIs. HYPOTHESIS: Dogs receiving cyclosporine treatment (alone or as part of a multidrug protocol) are at higher risk of developing OIFIs. ANIMALS: One hundred and thirteen client-owned dogs diagnosed with select immune-mediated diseases: 42 with IMHA, 29 with ITP, 34 with IMPA, and 8 with Evans syndrome. METHODS: Retrospective cohort study. Medical records of dogs presenting to the Texas A&M University, Veterinary Medical Teaching Hospital between January 2008 and December 2015, and treated for 1 or more of IMHA, IMPA, ITP, or Evans syndrome were retrospectively reviewed. Dogs that did not develop an OIFI were excluded if they died, were euthanized, or were lost to follow-up within 120 days of initiation of immunosuppressive treatment. RESULTS: Fifteen dogs of 113 (13%) were diagnosed with an OIFI based on 1 or more of cytology, culture, or histopathology. The odds of developing an OIFI were greater among dogs that were treated with cyclosporine (OR = 7.1, P = 0.017; 95% CI, 1.5-34.4) and among male dogs (OR = 5.1, P = 0.018; 95% CI, 1.4-17.9). CONCLUSIONS AND CLINICAL IMPORTANCE: OIFIs were significantly more likely in male dogs and those receiving cyclosporine. It is important to consider OIFIs as a potential complication of immunosuppressive treatment, particularly cyclosporine.

Interobserver Agreement Using Histological Scoring of the Canine Liver.

BACKGROUND: Grading schemes for the assessment of hepatic fibrosis and necroinflammatory activity in humans previously have been applied to dogs with chronic hepatitis. Interobserver agreement is a desirable characteristic for any histological scoring scheme. HYPOTHESIS/OBJECTIVES: To assess interobserver agreement associated with pathologists using a previously published histological scoring scheme to assess hepatic fibrosis and necroinflammatory activity in dogs and to compare fibrosis scores assigned to serial sections stained with hematoxylin & eosin (H&E) and picrosirius red. ANIMALS: Histological sections of liver from 50 dogs with variable degrees of hepatic fibrosis and necroinflammatory activity were selected from institutional tissue archives. METHODS: Six board-certified veterinary anatomic pathologists assigned fibrosis and necroinflammatory activity scores to the histological sections. The multiuser kappa statistic was calculated to assess interobserver agreement. Fibrosis stage assigned to serial sections stained with picrosirius red and H&E was compared using the Wilcoxon signed-rank test. RESULTS: Multiuser kappa statistics for assessment of fibrosis and necroinflammatory activity from H&E-stained sections were 0.35 and 0.16, respectively. There was no difference in median fibrosis scores assigned to serial section stained with H&E and picrosirius red (P = .248). CONCLUSIONS AND CLINICAL IMPORTANCE: There was fair interobserver agreement when pathologists assessed fibrosis and poor agreement when they assessed necroinflammatory activity. This suboptimal agreement must be taken into account by clinicians making decisions based on histology reports of the liver and in the design of studies evaluating these findings. To decrease this variability, ideally >1 pathologist should evaluate each section.

Prevalence and Clinicopathological Features of Triaditis in a Prospective Case Series of Symptomatic and Asymptomatic Cats.

BACKGROUND: The term triaditis designates the concurrent presence of idiopathic inflammatory bowel disease (IBD), cholangitis, and pancreatitis in cats. HYPOTHESIS/OBJECTIVES: The histopathology of concurrent, but often subclinical, inflammatory processes in the small intestine, liver, and pancreas of cats is poorly described. We aimed to investigate the frequency of enteritis, cholangitis, pancreatitis, or some combination of these in symptomatic and asymptomatic cats, compare clinicopathological features, and correlate histopathological with laboratory findings. ANIMALS: Domestic cats (27 symptomatic, 20 asymptomatic, and 8 normal). METHODS: Prospective study. Physical examination, laboratory variables (CBC, serum biochemistry profile, serum thyroxine concentration, serum feline trypsin-like immunoreactivity [fTLI], feline lipase immunoreactivity [fPLI, as measured by Spec fPL(®) ], urinalysis, and fecal analysis), imaging, and histopathological examinations were conducted. Feline liver, pancreas, and small intestine were biopsied during laparotomy. RESULTS: Inflammatory lesions were detected in 47 cats (27 symptomatic, 20 asymptomatic). In total, 20 cats had histopathologic lesions of IBD (13/47, 27.7%), cholangitis (6/47, 12.8%), or pancreatitis (1/47, 2.1%) alone, or inflammation involving >1 organ (27/47, 57.4%). More specifically, 16/47 cats (34.0%) had concurrent lesions of IBD and cholangitis, 3/47 (6.4%) of IBD and pancreatitis, and 8/47 cats (17%) of triaditis. Triaditis was identified only in symptomatic cats (8/27, 29.6%). A mild, positive correlation was detected between the severity (score) of IBD lesions and the number of comorbidities (rho = +0.367, P = .022). CONCLUSIONS AND CLINICAL IMPORTANCE: Histopathological evidence of IBD or IBD with comorbidities was detected in both symptomatic and asymptomatic cats. The possibility of triaditis should be considered in symptomatic cats with severe IBD.

Serum C-reactive protein and S100A12 concentrations in dogs with hepatic disease.

OBJECTIVES: To describe serum C-reactive protein and S100A12 concentrations in dogs with hepatic disease and to determine whether there is a relationship between the concentration of either and the severity of hepatic necroinflammation. METHODS: Serum C-reactive protein and S100A12 concentrations were measured in 46 dogs undergoing hepatic biopsy. Dogs were divided into three groups: congenital portosystemic shunts, chronic hepatitis and hepatic neoplasia. The histological severity of hepatic necroinflammation was scored. RESULTS: C-reactive protein and S100A12 concentrations were greater than the upper limit of the reference intervals in 39 and 26% of dogs, respectively. There was no association of disease group with C-reactive protein (P=0·1733) or S100A12 (P=0·1513) concentrations. There was a positive correlation between serum C-reactive protein concentration and hepatic necroinflammatory activity (rs =0·428, P=0·006). CLINICAL SIGNIFICANCE: Increased serum C-reactive protein and S100A12 concentrations were observed in a subpopulation of dogs with various types of hepatic diseases, suggesting acute-phase inflammation and activation of phagocytic cells, respectively. Dogs with higher hepatic necroinflammatory activity scores tended to have higher serum C-reactive protein concentrations. Further studies are needed to confirm this finding in a larger group of dogs.

A Prospective, Placebo-Controlled Pilot Evaluation of the Effect of Omeprazole on Serum Calcium, Magnesium, Cobalamin, Gastrin Concentrations, and Bone in Cats.

BACKGROUND: Chronic proton pump inhibitor administration has been associated with electrolyte and cobalamin deficiency, disrupted bone homeostasis, hypergastrinemia, and rebound acid hypersecretion in humans. It is unknown if this occurs in cats. OBJECTIVES: Prolonged oral omeprazole results in altered bone mineral density or content, serum calcium, magnesium, cobalamin, and gastrin concentrations in healthy cats. ANIMALS: Six healthy adult DSH cats. METHODS: In a within subjects, before and after design, cats received placebo followed by omeprazole (0.83-1.6 mg/kg PO q12h) for 60 days each. Analysis of serum calcium, magnesium, cobalamin, and gastrin concentrations was performed on days 0, 30, and 60. Bone density and content were evaluated on days 0 and 60 of each intervention. Continuous data were analyzed using a two-way ANOVA (α = 0.006). On day 60 of omeprazole administration, continuous intragastric pH monitoring was performed in 2 cats to evaluate the effects of abrupt withdrawal of omeprazole. RESULTS: No significant changes were detected between treatments for any variables, except serum gastrin, which was significantly higher during omeprazole treatment in comparison to placebo (P = 0.002). Evidence of gastric hyperacidity was seen in both cats in which intragastric pH monitoring was performed following cessation of omeprazole. CONCLUSIONS AND CLINICAL IMPORTANCE: Although further studies with larger populations of cats will be needed to draw any definitive conclusions, these preliminary results suggest that prolonged PPI treatment results in hypergastrinemia and abrupt PPI withdrawal might result in RAH in cats.

Giant cell glioblastoma in the cerebrum of a Pembroke Welsh corgi.

A 6-year-old, neutered female Pembroke Welsh corgi was presented with a 1-month history of ataxia and panting. The clinical signs progressed until the dog became anorexic, obtunded and exhibited circling to the left. At necropsy examination, a mass was detected in the left forebrain, impinging on the cribriform plate. Microscopically, the mass was composed of sheets of round to pleomorphic neoplastic cells with vacuolated cytoplasm. Nuclear atypia, anisocytosis and anisokaryosis were common. Numerous bizarre, multinucleated giant cells containing 60 or more nuclei and giant mononuclear cells were present. The matrix contained abundant reticulin. Immunohistochemistry revealed the neoplastic cells uniformly to express vimentin, and a small number of neoplastic cells expressed glial fibrillary acid protein. A diagnosis of giant cell glioblastoma was made. Although well recognized in man, this tumour has been documented rarely in the veterinary literature.