Intra- and interobserver assessments of intestinal wall thickness and segmentations from transverse sections of feline abdominal ultrasound images.

Measurements of intestinal wall thicknesses from ultrasound imaging (US) are routinely used to support diagnoses of intestinal disorders in cats, however published studies describing observer agreement are currently lacking. The aim of this retrospective, observer agreement study was to quantify inter- and intraobserver repeatability and agreement in the measurement of intestinal wall layer thicknesses and the segmentation of transverse sections of small intestines in US images of 20 cats. Intestinal wall layer thickness measurements of the mucosa, submucosa, muscularis, serosa layer, and total thickness of these layers were performed on five cats with small cell epitheliotropic lymphoma, five with inflammatory bowel disease, and 10 with other conditions. Thickness measurements and the segmentation encompassing the serosa layer were obtained from five observers four times non-sequentially. The average standard deviation in thickness measurements (95% confidence interval) in the mucosa, submucosa, muscularis, serosa, and total thickness were 0.35 (0.07-0.95), 0.24 (0.07-0.52), 0.22 (0.06-0.49), 0.20 (0.05-0.49), and 0.57 (0.11-1.60) mm, respectively. The average intraclass correlation coefficients, which estimates the degree of consistency in thickness measurements and segmentation areas for each observer, ranged from 0.355 to 0.870 and 0.850 to 0.993, respectively. The interclass correlation coefficient, which estimates the degree of consistency when measuring a thickness or segmentation area over all observers ranged from 0.115 to 0.753, and 0.811 to 0.902, respectively. The overall average Dice Coefficient, which estimates the extent of overlap of the segmentations for all observers was 0.957 (0.933 to 0.972). Our results suggest segmentations of small intestines have a higher interobserver agreement than measurements of intestinal wall thicknesses.

Measurement of feline-specific pancreatic lipase aids in the diagnosis of pancreatitis in cats.

OBJECTIVE: To establish a reference interval for a feline-specific pancreatic lipase assay (Spec fPL test; Idexx Laboratories Inc) in healthy cats and determine the sensitivity and specificity of the Spec fPL test in a large group of ill cats with and without pancreatitis. ANIMALS: 41 healthy cats, 141 cats with clinical signs consistent with pancreatitis, and 786 stored sera with known feline pancreatic lipase immunoreactivity (fPLI) concentrations. METHODS: This was a prospective, cross-sectional, nonrandomized study. Based on a detailed review of the medical history and results of physical examination, CBC, serum biochemical profile, urinalysis, abdominal ultrasonography, and clinical outcome, each cat was categorized by 2 board-certified internists masked to the fPLI test results into 1 of 6 categories from definitely pancreatitis to definitely not pancreatitis. RESULTS: The reference interval for the Spec fPL test, determined from the central 95th percentile of results from healthy cats, was fPLI of 0.7 to 3.5 µg/L. An fPLI concentration of ≥ 5.4 µg/L was determined to be consistent with pancreatitis. With an fPLI of 5.4 µg/L as the diagnostic cutoff, the sensitivity of the Spec fPL test for feline pancreatitis (definitely pancreatitis and probably pancreatitis) was 79.4%, the specificity for cats characterized as probably not pancreatitis and definitely not pancreatitis was 79.7%, and positive and negative predictive values were 69% and 87%, respectively. CLINICAL RELEVANCE: These findings support the use of the Spec fPL test as a valuable diagnostic test for feline pancreatitis.

ACVIM consensus statement on the diagnosis of immune thrombocytopenia in dogs and cats.

Immune thrombocytopenia (ITP) is the most common acquired primary hemostatic disorder in dogs. Immune thrombocytopenia less commonly affects cats but is an important cause of mortality and treatment-associated morbidity in both species. Immune thrombocytopenia remains a diagnosis of exclusion for which diagnostic guidelines are lacking. Primary, or non-associative, ITP refers to autoimmune platelet destruction. Secondary, or associative, ITP arises in response to an underlying disease trigger. However, evidence for which comorbidities serve as ITP triggers has not been systematically evaluated. To identify key diagnostic steps for ITP and important comorbidities associated with secondary ITP, we developed 12 Population Evaluation/Exposure Comparison Outcome (PECO) format questions. These questions were addressed by evidence evaluators utilizing a literature pool of 287 articles identified by the panelists using a structured search strategy. Evidence evaluators, using panel-designed templates and data extraction tools, summarized evidence and created guideline recommendations that then were integrated by diagnosis and comorbidity domain chairs. The revised PECO responses underwent a Delphi survey process to reach consensus on final guidelines. A combination of panel expertise and PECO responses were employed to develop algorithms for diagnosis of ITP in dogs and cats, which also underwent 4 iterations of Delphi review. Comorbidity evidence evaluators employed an integrated measure of evidence (IME) tool to determine evidence quality for each comorbidity; IME values combined with evidence summaries for each comorbidity were integrated to develop ITP screening recommendations, which also were subjected to Delphi review. Commentary was solicited from multiple relevant professional organizations before finalizing the consensus. The final consensus statement provides clinical guidelines for the diagnosis of, and underlying disease screening for, ITP in dogs and cats. The systematic consensus process identified numerous knowledge gaps that should guide future studies. This statement is a companion manuscript to the ACVIM Consensus Statement on the Treatment of Immune Thrombocytopenia.

Preliminary evaluation of a flow cytometric assay with microsphere controls for the detection of platelet-bound antibodies in canine immune thrombocytopenia.

BACKGROUND: Canine immune thrombocytopenia (ITP) ranges from a mild to severe bleeding disorder, and platelet counts do not reliably predict clinical disease course. The detection of platelet autoantibodies may further define the disease phenotype, but variability in assay configurations and a lack of well-characterized controls limit the diagnostic utility of anti-platelet antibody assays. OBJECTIVES: We aimed to develop control reagents to facilitate the characterization of canine platelet surface-associated immunoglobulin (PSAIg) in flow cytometric assays. METHODS: Silica microspheres were coated with canine IgG and IgM to assess the reactivity of goat and rabbit origin anti-canine immunoglobulin reagents. They were also used as positive controls in the PSAIg assay. Preliminary assay evaluation and determination of sample stability used PRP isolated from seven healthy dogs and 26 dogs newly diagnosed with thrombocytopenia. RESULTS: Blood sample stability was established for up to a 48-hour storage time. The conjugated positive control microspheres demonstrated stable fluorescent labeling over a 2-year observation period. Rabbit and goat origin anti-dog IgM fluorescent antibody labels reacted nonspecifically with canine IgG. Rabbit origin anti-dog IgG antibody demonstrated greater class specificity for canine IgG than a goat origin antibody. Thrombocytopenic dogs had a broad range of membrane-bound immunoglobulin. Median PSAIgG for dogs with primary or secondary ITP (18.4%, 34.1%, respectively) were significantly higher than controls (3.8%, P < .05). CONCLUSIONS: The described assay reagents and procedures provide positive controls and allow consistent thresholding to define a positive test result, suitable for any flow cytometer. A rabbit anti-dog IgG fluorescent label demonstrated specificity for canine IgG and was useful for the detection of PSAIgG in thrombocytopenic dogs.

ACVIM consensus statement on pancreatitis in cats.

BACKGROUND: Pancreatitis in cats, although commonly diagnosed, still presents many diagnostic and management challenges. OBJECTIVE: To summarize the current literature as it relates to etiology, pathogenesis, diagnosis, and management of pancreatitis in cats and to arrive at clinically relevant suggestions for veterinary clinicians that are based on evidence, and where such evidence is lacking, based on consensus of experts in the field. ANIMALS: None. METHODS: A panel of 8 experts in the field (5 internists, 1 radiologist, 1 clinical pathologist, and 1 anatomic pathologist), with support from a librarian, was formed to assess and summarize evidence in the peer reviewed literature and complement it with consensus clinical recommendations. RESULTS: There was little literature on the etiology and pathogenesis of spontaneous pancreatitis in cats, but there was much in the literature about the disease in humans, along with some experimental evidence in cats and nonfeline species. Most evidence was in the area of diagnosis of pancreatitis in cats, which was summarized carefully. In contrast, there was little evidence on the management of pancreatitis in cats. CONCLUSIONS AND CLINICAL IMPORTANCE: Pancreatitis is amenable to antemortem diagnosis by integrating all clinical and diagnostic information available, and recognizing that acute pancreatitis is far easier to diagnose than chronic pancreatitis. Although both forms of pancreatitis can be managed successfully in many cats, management measures are far less clearly defined for chronic pancreatitis.

Lower respiratory tract infection due to Capnocytophaga cynodegmi in a cat with pulmonary carcinoma.

A 10-year-old male castrated domestic shorthair cat was evaluated for coughing and lethargy. Thoracic radiographs revealed a soft tissue lung mass and diffuse peribronchial infiltrates. Bronchoscopy was performed and Capnocytophaga cynodegmi was cultured from bilateral bronchoalveolar lavage samples. Clinical signs and bacterial colonization resolved following treatment with enrofloxacin. A lung lobectomy was performed to remove the lung mass, which was diagnosed as pulmonary carcinoma. C cynodegmi is most frequently isolated from localized wound and corneal infections in humans. Specialized growth characteristics of C cynodegmi may result in low sensitivity for bacterial culture. To the authors' knowledge, this case represents the first report of C cynodegmi infection in a veterinary patient and only the second case in human or veterinary medicine where the organism has been isolated from a bronchoalveolar lavage sample. Based on this report, Capnocytophaga species should be considered as potential opportunistic pathogens.

Prospective diagnostic accuracy evaluation and clinical utilization of a modified assay for platelet-associated immunoglobulin in thrombocytopenic and nonthrombocytopenic dogs.

BACKGROUND: No diagnostic tests reliably distinguish primary immune-mediated thrombocytopenia (pIMT) from other causes of thrombocytopenia. OBJECTIVES: The purpose of the study was to evaluate diagnostic sensitivity and specificity using modified direct and indirect platelet-associated immunoglobulin (PAIg) assays and reticulated platelets (RP) by flow cytometry for the classification of thrombocytopenic dogs and differentiating pIMT. METHODS: Platelets were isolated from plasma samples of thrombocytopenic dogs and nonthrombocytopenic healthy and ill dogs. For direct PAIg, they were analyzed by flow cytometry after incubation with anti-human amylase fluorescein isothiocyanate (FITC, negative control), anti-canine IgG-FITC, anti-canine IgM-FITC, and anti-human CD61-conjugated fluorochrome (AF647). For indirect PAIg, platelets from normothrombocytic dogs were incubated with thrombocytopenic dog plasma and analyzed similar to direct PAIg. RP percentages were determined based on forward light scatter vs thiazole orange fluorescence. RESULTS: Seventy-five thrombocytopenic dogs, 16 nonthrombocytopenic ill dogs, and 24 healthy dogs were evaluated. Diagnostic sensitivity and specificity utilizing direct IgG was 29.4% and 75.9%, respectively; when combining direct/indirect assays (IgG/IgM), it was 76.5% and 65.5%, respectively, for distinguishing pIMT. For RP, no significant difference between pIMT and sIMT was noted. RP > 8% with positive PAIg had a sensitivity of 94% and specificity of 27.6% for distinguishing pIMT. There was a significant difference in platelet concentration and CD61% staining between control and pIMT. CONCLUSIONS: The combined modified assays resulted in fair diagnostic sensitivity and specificity for the diagnosis of pIMT. The modification of the immunoglobulin assays improved diagnostic accuracy; however, a single panel to accurately classify thrombocytopenia remains elusive.

5-fluorouracil toxicity with severe bone marrow suppression in a dog.

This report describes 5-fluorouracil (5-FU) toxicity in a dog that resulted in severe bone marrow suppression. The dog initially was presented with neurologic and gastrointestinal signs and developed pancytopenia characterized by severe neutropenia and thrombocytopenia. Examination of bone marrow aspirate showed aplasia. The dog also had marked echinocytosis, which has been previously associated with in vitro 5-FU exposure. The patient was given aggressive supportive care and recovered within 25 d of exposure. To the authors' knowledge, this is the first report of a case of 5-FU toxicity in a dog to include results of bone marrow examination, as well as the first to describe echinocytosis related to 5-FU toxicity.