Diagnostic contribution of individual components of adrenal function tests to diagnose canine hyperadrenocorticism.

There is limited information regarding the value of constitutive components of the ACTH stimulation test (ACTHST) and low-dose dexamethasone suppression test (LDDST) including serum baseline cortisol (BC), difference between post-ACTH stimulation cortisol (PC) and BC (ΔACTHC), cortisol concentration 4h after dexamethasone administration (4HC), difference between 4HC and BC (Δ4C), and the difference between cortisol concentration 8h after dexamethasone administration and 4HC (Δ8C). Therefore, the objective of this study was to determine if these components can predict hyperadrenocorticism, pituitary-dependent hyperadrenocorticism (PDH), or functional adrenocortical tumor (FAT) in dogs. Cortisol concentrations were normalized, as fold change (FC), to the PC reference interval upper limit. A total of 1267 dogs were included, with hyperadrenocorticism diagnosed in 537 (PDH, n=356; FAT, n=28; undetermined, n=153) and excluded in 730. The area under the receiver operating curves for BC, ΔACTHC, 4HC, Δ4C, and Δ8C to predict hyperadrenocorticism were 0.76 (95% confidence interval (CI), 0.73-0.79), 0.91 (95% CI, 0.89-0.93), 0.83 (95% CI, 0.80-0.87), 0.55 (95% CI, 0.50-0.60), and 0.67 (95% CI, 0.62-0.72), respectively. A diagnostic limit of ≥0.78 FC for ΔACTHC had excellent sensitivity (1.00; 95% CI, 0.74-1.00), but poor specificity (0.67; 95% CI, 0.64-0.71), to predict FAT in dogs with a positive ACTHST. A diagnostic limit of ≥-0.26 FC for Δ4C had excellent sensitivity (1.00; 95% CI, 0.79-1.00), but poor specificity (0.21; 95% CI, 0.18-0.26), to predict FAT in dogs with a positive LDDST. In hyperadrenocorticoid dogs that have positive ACTHST or LDDST results, ΔACTHC or Δ4C, respectively, could be used to exclude FAT.

Immune function and serum vitamin D in shelter dogs: A case-control study.

This study sought to establish a baseline understanding of immune function and its association with serum vitamin D in shelter dogs. Ten apparently healthy shelter dogs housed in the Arizona Humane Society for ≥7 days and 10 apparently healthy, age, breed, and sex-matched control dogs were included. Serum 25-hydroxyvitamin D (25[OH]D), the major circulating vitamin D metabolite, was measured using high performance liquid chromatography. Whole blood samples were stimulated with lipopolysaccharide (LPS), lipoteichoic acid, or phosphate buffer solution, and tumor necrosis factor (TNF)-ɑ, interleukin (IL)-6, and IL-10 were measured using a canine-specific multiplex bead-based assay. Phagocytosis of opsonized-Escherichia coli and E. coli-induced oxidative burst were evaluated with flow cytometry. Shelter dogs had decreased percentages of granulocytes and monocytes (GM) that had phagocytized opsonized-E coli (P = 0.019) and performed E. coli-induced oxidative burst (P = 0.011). There were no significant differences in TNF-α, IL-6, IL-10, or 25(OH)D concentrations between shelter and control dogs. Serum 25(OH)D concentrations had a weak positive association with the intensity of GM E. coli-induced oxidative burst (r2 = 0.23, P = 0.03). There was a moderate inverse association between serum 25(OH)D concentration and LPS-stimulated TNF-ɑ production in shelter dogs (r2 = 0.40, P = 0.04). These results demonstrate immune dysregulation in vitro in shelter dogs housed for ≥7 days when compared to age, breed, and sex-matched control dogs. While serum 25(OH)D concentrations did not differ between shelter and control dogs, significant associations between 25(OH)D concentration and immune function parameters in vitro were identified.

Pulmonary hypertension secondary to respiratory disease and/or hypoxia in dogs: Clinical features, diagnostic testing and survival.

Pulmonary hypertension (PH) is associated with substantial morbidity and if untreated, mortality. The human classification of PH is based on pathological, hemodynamic characteristics, and therapeutic approaches. Despite being a leading cause of PH, little is known about dogs with respiratory disease and/or hypoxia (RD/H)-associated PH. Therefore, our objectives were to retrospectively describe clinical features, diagnostic evaluations, final diagnoses and identify prognostic variables in dogs with RD/H and PH. In 47 dogs identified with RD/H and PH, chronic airway obstructive disorders, bronchiectasis, bronchiolar disease, emphysema, pulmonary fibrosis, neoplasia and other parenchymal disorders were identified using thoracic radiography, computed tomography, fluoroscopy, tracheobronchoscopy, bronchoalveolar lavage, and histopathology. PH was diagnosed using transthoracic echocardiography. Overall median survival was 276.0 days (SE, 95% CI; 216, 0-699 days). Dogs with an estimated systolic pulmonary arterial pressure (sPAP) ≥47mmHg (n=21; 9 days; 95% CI, 0-85 days) had significantly shorter survival times than those <47mmHg (n=16; P=0.001). Estimated sPAP at a cutoff of ≥47mmHg was a fair predictor of non-survival with sensitivity of 0.78 (95% CI, 0.52-0.94) and specificity of 0.63 (95% CI, 0.38-0.84). Phosphodiesterase-5 (PDE5) inhibitor administration was the sole independent predictor of survival in a multivariable analysis (hazard ratio: 4.0, P=0.02). Canine PH is present in a diverse spectrum of respiratory diseases, most commonly obstructive disorders. Similar to people, severity of PH is prognostic in dogs with RD/H and PDE5 inhibition could be a viable therapy to improve outcome.

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.

Effect of calcitriol on in vitro whole blood cytokine production in critically ill dogs.

Hypovitaminosis D has been identified as a predictor of mortality in human beings, dogs, cats and foals. However, the immunomodulatory effects of vitamin D in critically ill dogs has not been evaluated. The aim of this study was to evaluate the effect of calcitriol on cytokine production from whole blood collected from critically ill dogs in vitro. Twelve critically ill dogs admitted to a veterinary intensive care unit (ICU) were enrolled in a prospective cohort study. Whole blood from these dogs was incubated with calcitriol (2×10-7M) or ethanol (control) for 24h. Subsequent to this incubation, lipopolysaccharide (LPS)-stimulated whole blood production of tumor necrosis factor (TNF)-α, interleukin (IL)-6 and IL-10 were measured using a canine-specific multiplex assay. Calcitriol significantly increased LPS-stimulated whole blood production of IL-10 and decreased TNF-α production without significantly altering IL-6 production. There was no significant difference in whole blood cytokine production capacity between survivors and non-survivors at the time of discharge from the ICU or 30days after discharge. These data suggests that calcitriol induces an anti-inflammatory phenotype in vitro in whole blood from critically ill dogs.

Gallbladder Mucocele: Variables Associated with Outcome and the Utility of Ultrasonography to Identify Gallbladder Rupture in 219 Dogs (2007-2016).

BACKGROUND: Gallbladder mucocele (GBM) is an increasingly recognized extrahepatic biliary disease in dogs. OBJECTIVES: To investigate cases of GBM and identify variables associated with survival and the sensitivity and specificity of ultrasonography to identify gallbladder rupture. ANIMALS: Two hundred and nineteen client-owned dogs with GBM. METHODS: Multicenter, retrospective study of dogs with GBM, presented from January 2007 to November 2016 to 6 academic veterinary hospitals in the United States. Interrogation of hospital databases identified all cases with the inclusion criteria of a gross and histopathologic diagnosis of GBM after cholecystectomy and intraoperative bacteriologic cultures of at least 1 of the following: gallbladder wall, gallbladder contents, or abdominal effusion. RESULTS: Two hundred and nineteen dogs fulfilled the inclusion criteria. Dogs with GBM and gallbladder rupture with bile peritonitis at the time of surgery were 2.7 times more likely to die than dogs without gallbladder rupture and bile peritonitis (P = 0.001; 95% confidence interval [CI], 1.50-4.68; n = 41). No significant associations were identified between survival and positive bacteriologic cultures, antibiotic administration, or time (days) from ultrasonographic identification of GBM to the time of surgery. The sensitivity, specificity, positive, and negative likelihood ratios for ultrasonographic identification of gallbladder rupture were 56.1% (95% CI, 39.9-71.2), 91.7% (95% CI, 85.3-95.6), 6.74, and 0.44, respectively. CONCLUSION AND CLINICAL IMPORTANCE: Dogs in our study with GBM and intraoperative evidence of gallbladder rupture and bile peritonitis had a significantly higher risk of death. Additionally, abdominal ultrasonography had low sensitivity for identification of gallbladder rupture.

Vasoproliferative process resembling pulmonary capillary hemangiomatosis in a cat.

BACKGROUND: Pulmonary capillary hemangiomatosis is a rare, vascular obstructive disorder that uniformly causes pulmonary arterial hypertension. Clinically, pulmonary capillary hemangiomatosis is indistinguishable from primary pulmonary arterial hypertension and histology is required for definitive diagnosis. The distinctive histologic feature of pulmonary capillary hemangiomatosis is non-malignant extensive proliferation of capillaries in the alveolar septae. Vasodilator treatment of humans with primary arterial hypertension due to pulmonary capillary hemangiomatosis can result in fatal acute pulmonary edema. Computed tomography is thus critical to discern pulmonary capillary hemangiomatosis from other causes of pulmonary arterial hypertension prior to vasodilator therapy. This is the first report of a vasoproliferative process resembling pulmonary capillary hemangiomatosis in the feline species. CASE PRESENTATION: A 15-year-old, male castrated, domestic shorthair cat presented for persistent labored breathing presumptively due to congestive heart failure despite treatment with diuretics for 7 days. Echocardiography showed evidence of hypertrophic cardiomyopathy with severe pulmonary hypertension; however, a normal sized left atrium was not consistent with congestive heart failure. Thoracic computed tomography was performed and showed evidence of diffuse ill-defined nodular ground glass opacities, enlarged pulmonary arteries, and filling defects consistent with pulmonary thromboembolism. The cat acutely decompensated after a single dose of sildenafil and was euthanized. Histopathology of the lungs showed severe multifocal alveolar capillary proliferation with respiratory bronchiolar infiltration, marked type II pneumocyte hyperplasia and multifocal pulmonary arterial thrombosis. CONCLUSION: This is the first description in a cat of a vasoproliferative disorder resembling pulmonary capillary hemangiomatosis complicated by multifocal pulmonary arterial thrombosis. Inspiratory and expiratory ventilator-driven breath holds with angiography revealed lesions predominantly characterized by ground glass opacification and vascular filling defects with absence of air trapping. The results from this report suggest that, as in humans, the cat can develop a pulmonary capillary hemangiomatosis-like disease in which vasodilator therapy to address pulmonary hypertension may lead to fatal pulmonary edema.