Gadoxetate disodium (Gd-EOB-DTPA) contrast-enhanced magnetic resonance imaging for differentiation between benign and malignant splenic lesions in dogs.

Malignant splenic lesions in dogs are common, with hemangiosarcoma diagnosed most frequently, and there have been no consistent clinicopathologic, gross, or imaging characteristics identified that differentiate malignant from benign splenic lesions. Histopathology is required for definitive diagnosis, and given the poor long-term prognosis of malignant splenic lesions, a noninvasive tool to aid in diagnosis would be valuable. This prospective cohort study utilized gadoxetate disodium, a liver-specific contrast agent (Gd-EOB-DPTA; Eovist), to identify the general lesion and pre- and postcontrast signal characteristics of benign and malignant splenic and hepatic lesions in dogs with naturally occurring disease. Twenty-five dogs were enrolled, Eovist-enhanced MRI was performed, and dogs were taken to surgery for splenectomy and other organ biopsy. All histopathology and MRI studies were evaluated by a single pathologist and a single radiologist, respectively. The associations between the tumor type and numerous variables defined on MRI were evaluated using Fisher's exact tests, and the significance was identified at a P-value of .05. Malignant splenic masses were identified in 11/25 (44%) dogs, and 5/11 malignancies represented hemangiosarcoma. The presence of abdominal effusion (P = .017) and the presence of hepatic nodules on MRI (P = .009) were associated with splenic malignancy. There were no benign T2 hyperintense and no malignant T2 hypointense lesions (P = .021). Utilization of the T2 W MRI sequence may aid in the identification of malignant splenic lesions, particularly when accompanied by abdominal effusion and hepatic lesions.

Lunasin reduces the susceptibility of IL-10 deficient mice to inflammatory bowel disease and modulates the activation of the NLRP3 inflammasome.

Inflammatory bowel disease (IBD) is a chronic inflammatory condition that can cause severe damage to the gastrointestinal tract leading to lower quality of life and productivity. Our goal was to investigate the protective effect of the soy peptide lunasin in an in vivo model of susceptibility to IBD and to identify the potential mechanism of action in vitro. In IL-10 deficient mice, oral administration of lunasin reduced the number and frequency of mice exhibiting macroscopic signs of susceptibility to inflammation and significantly decreased levels of the proinflammatory cytokines TNF-α, IL-1ß, IL-6, and IL-18 by up to 95%, 90%, 90%, and 47%, respectively, in different sections of the small and large intestines. Dose-dependent decrease of caspase-1, IL-1ß, and IL-18 in LPS-primed and ATP-activated THP-1 human macrophages demonstrated the ability of lunasin to modulate the NLRP3 inflammasome. We demonstrated that lunasin can decrease susceptibility to IBD in genetically susceptible mice by exerting anti-inflammatory properties.

UTILITY OF URINE ANTIGEN TESTING FOR DIAGNOSIS OF BLASTOMYCOSIS IN NONDOMESTIC FELIDS.

Blastomycosis caused by the fungus Blastomyces dermatitidis has been reported to cause disease in numerous species of nondomestic felids. Diagnosis of blastomycosis in domestic species often relies on the combination of clinical signs, radiographic findings, and commercial urinary antigen testing. In this report, the sensitivity, specificity, and positive and negative predictive values for urine blastomyces antigen testing for use in nondomestic felids were examined and compared with findings on postmortem examination. The study showed a sensitivity of 100%, specificity of 91.86%, positive predictive value of 50%, and negative predictive value of 100% for urine antigen testing. Furthermore, radiographic and hematologic findings were compared with those of animals diagnosed with blastomycosis. Radiographic evidence consistent with blastomycosis was found in those animals diagnosed via urine antigen testing, but no significant differences in plasma biochemistry parameters between diseased and nondiseased animals were found. This study provides evidence that a positive blastomycosis antigenuria test result should be combined with other diagnostic methods to confirm the presence of infection with B. dermatitidis, whereas a negative antigenuria test result is 100% effective in predicting the absence of disease.

Evaluation of a Probability-Based Predictive Tool on Pathologist Agreement Using Urinary Bladder as a Pilot Tissue.

Inter-pathologist variation is widely recognized across human and veterinary pathology and is often compounded by missing animal or clinical information on pathology submission forms. Variation in pathologist threshold levels of resident inflammatory cells in the tissue of interest can further decrease inter-pathologist agreement. This study applied a predictive modeling tool to bladder histology slides that were assessed by four pathologists: first without animal and clinical information, then with this information, and finally using the predictive tool. All three assessments were performed twice, using digital whole-slide images (WSI) and then glass slides. Results showed marked variation in pathologists' interpretation of bladder slides, with kappa agreement values of 7-37% without any animal or clinical information, 23-37% with animal signalment and history, and 31-42% when our predictive tool was applied, for digital WSI and glass slides. The concurrence of test pathologists to the reference diagnosis was 60% overall. This study provides a starting point for the use of predictive modeling in standardizing pathologist agreement in veterinary pathology. It also highlights the importance of high-quality whole-slide imaging to limit the effect of digitization on inter-pathologist agreement and the benefit of continued standardization of tissue assessment in veterinary pathology.

Endometrial hyperplasia and pyometra in captive lions (Panthera leo) and tigers (Panthera tigris).

Endometrial hyperplasia (EH) is a pathologic condition of the uterus with increased endometrial gland to stroma ratio compared to normal cyclic uterine proliferation. In domestic animals, EH often involves cystic distension of proliferating endometrial glands and may be concurrent with pyometra. In large captive nondomestic felids, an association between EH and pyometra is common; however, detailed species differences between the histological uterine findings in lions (Panthera leo) and tigers (Panthera tigris) and clinical manifestations have yet to be described. Uterine sections from 14 lions and 24 tigers with EH and/or pyometra were scored for several histological parameters and clinical histories were recorded. The percentage of endometrium affected by hyperplasia, endometrial gland to stroma ratio, and adenomyosis were significantly (P = .0385, P = .0008, and P = .0463, respectively) more severe in lions compared to tigers as univariate analytes. Although tubular complexity was not statistically significant (P = .3254), when combined as a proposed EH grading scheme, these 4 features confirmed lions had significantly (P = .0068) more severe EH compared to tigers. Endometrial hyperplasia severity significantly correlated with inflammation/pyometra severity when controlling for species (P = .0203). A significant correlation exists between pyometra-associated clinical sign severity and the presence of pyometra in tigers, (P = .0026) but not in lions (P = .1144). There was no statistical difference in the severity of clinical signs associated with pyometra between these species (P = .1986). This proposed grading scheme may have clinical utility in providing a more consistent and objective evaluation of EH in large captive felids.

RETROSPECTIVE REVIEW OF MORBIDITY AND MORTALITY IN A POPULATION OF CAPTIVE BUDGERIGARS (MELOPSITTACUS UNDULATES).

This retrospective study reviews the diseases associated with morbidity and mortality in 221 budgerigars (Melopsittacus undulates) from a captive population from 2013 to 2019. The study aimed to evaluate the health status of a flock of budgerigars typical of today's zoologic collections. Based on previous literature, it was hypothesized that age-related conditions such as neoplasia would be common, whereas metabolic and nutritional disorders would be less common. Neoplasia was widespread among the population, affecting 34% of birds (75/221). Carcinomas made up most neoplastic processes and most commonly affected the renal system (n = 22), followed by the proventriculus (n = 7). Pituitary, adrenal, and hepatocellular carcinomas were less commonly diagnosed. Sarcomas affected the population less often than carcinomas and were found within the coelom (undifferentiated four cases), within the spleen (three cases), within the kidney (two cases), and one subcutaneous soft tissue sarcoma. There were five cases of multicentric lymphoma found most commonly affecting the spleen and liver. Benign neoplasms affected the pituitary most commonly (nine cases), followed by the reproductive system, with seminomas (seven cases) being most common. Macrorhabdus ornithogaster (MO) was found in 56 cases. The majority (38 cases) were found in conjunction with a range of comorbidities, but several birds experienced MO infections alone, and it was thought to have been the cause of death in these birds (22 cases). In contrast to our hypothesis, disease associated with nutritional or metabolic disorders impacted a substantial portion of the population; hepatic lipidosis (26 cases) was the most common along with obesity (26 cases), followed by atherosclerosis, xanthomas, and gout (8, 7, and 4 cases, respectively). Traumatic lesions were noted in 41 cases and were most commonly characterized by head trauma and cerebral hemorrhage. Toxicity was rare; five total cases caused by a single carbon monoxide event were identified.

Pathology in Practice.

In collaboration with the American College of Veterinary Pathologists.

Blood concentration of symmetric dimethylarginine correlates with kidney damage as assessed with a proposed histologic grading system for chronic kidney disease in tigers (Panthera tigris).

OBJECTIVE: To determine the utility of blood symmetric dimethylarginine (SDMA) concentration measurement as a diagnostic tool for chronic kidney disease (CKD) in tigers (Panthera tigris) by comparing results for SDMA with those for traditional renal biomarkers and investigating correlations between these biomarkers and histopathologic kidney changes in tigers with CKD. SAMPLE: Blood, urine, and kidney samples from 35 tigers with CKD from 2 sanctuaries. PROCEDURES: Blood (serum or plasma) and urine samples were collected antemortem. Necropsy, including gross and histologic assessment, was performed for tigers that died or were euthanized for quality-of-life reasons. Results for CKD biomarkers in blood (BUN, creatinine, phosphorus, and SDMA concentrations) and urine (protein concentration, urine protein-to-creatinine ratio, and urine specific gravity) were evaluated for correlation with histologic kidney damage scored with an objective grading scale defined by percentage of inflammation, fibrosis, and tubular atrophy. RESULTS: Symmetric dimethylarginine had the strongest significant correlation (ρ = 0.667) with histologic kidney damage score, followed by urine specific gravity (ρ = -0.639), blood creatinine concentration (ρ = 0.624), and BUN (ρ = 0.588). No significant correlation with kidney score was identified for blood phosphorus concentration, urine protein concentration, or the urine protein-to-creatinine ratio. CLINICAL RELEVANCE: We recommend SDMA be prioritized as a renal biomarker in tigers, with SDMA results considered in addition to those of other traditional renal biomarkers when assessing kidney function in tigers. Additionally, the grading scale we developed could be replicated across patients and pathologists for more consistent postmortem assessment of CKD in tigers.

Facing the "Fear of Failure": Veterinary Students in Clinical Rotations.

Failing a student is difficult for both educator and student, but administering a failing grade is critical for protecting and ensuring adequate learning for an unsafe student. The failure to fail clinical students has been commonly reported and explored among educators in the human health professions but has not been formally addressed in veterinary education. Forty-three participants attending the Veterinary Educators Collaborative symposium were surveyed concerning their attitudes and experiences failing clinical veterinary students. Results indicated that the failure to fail phenomenon exists among veterinary educators, as the majority of veterinary educators often felt reluctant and unprepared to fail a student on clinical rotations. The most common barriers to failing students were institutional culture and unsatisfactory assessor development or evaluation tools. Veterinary educators must face this fear of failure and explore strategies to overcome existing barriers that can ultimately transform student failure into success.

Intrahistiocytic Storage of Clofazimine Crystals in a Cat.

A 13-year-old castrated male Maine coon cat with a 5-year history of atypical mycobacteriosis was euthanized and submitted for necropsy. The cat had been kept in clinical remission since diagnosis using a combination of the antimycobacterial drug clofazimine and additional multimodal antimicrobial therapy. Grossly, tissues were diffusely discolored red-brown to yellow. Histologically, the myocardial interstitum was expanded by numerous, often multinucleated cells, which were distended by uniformly shaped acicular cytoplasmic spaces. These cells were immunopositive for CD18 and immunonegative for desmin, suggesting a histiocytic rather than muscular origin. Macrophages in other tissues contained similar acicular spaces. Ultrastructurally, the spaces were surrounded by 2 lipid membranes, resembling an autophagosome. Based on the clinical history and histologic, immunohistochemical, and ultrastructural data, we diagnosed clofazimine crystal storage. To our knowledge, this is the first report of clofazimine storage in a cat or within myocardial interstitial macrophages.

Alterations in pregnancy-associated glycoprotein concentrations of pregnant sheep experimentally infected with bovine viral diarrhea virus.

OBJECTIVE: To compare pregnancy-associated glycoprotein 1 (PAG1) concentrations in maternal (jugular vein) and fetal (uterine vein) circulations and amniotic fluid samples between pregnant ewes that were and were not experimentally infected with bovine viral diarrhea virus (BVDV). ANIMALS: 11 healthy pregnant yearling ewes. PROCEDURES: Before study initiation, all ewes were naïve to BVDV and confirmed pregnant by transabdominal ultrasonography at approximately 60 days of gestation. At 65 days of gestation, ewes were intranasally inoculated with a noncytopathic BVDV type 1b strain (concentration, 107 TCID50/mL; 2 mL/nostril; n = 6) or an equal volume of BVDV-free viral culture medium (control; 5). A blood sample was collected for measurement of PAG1 concentration before inoculation. At 80 days of gestation, each ewe was anesthetized and underwent an ovariohysterectomy. While sheep were anesthetized, blood samples from the jugular and uterine veins and an amniotic fluid sample were collected for measurement of PAG1 concentration. Fetal tissues underwent real-time PCR analysis for BVDV RNA, and placental specimens underwent histologic evaluation and immunohistochemical staining for BVDV antigen. RESULTS: At 80 days of gestation, BVDV RNA in fetal tissues and mild placentitis were detected in 5 of 6 BVDV-inoculated ewes. Mean PAG1 concentrations in the maternal and fetal circulations of BVDV-inoculated ewes were significantly less than those in control ewes. Mean amniotic fluid PAG1 concentration did not differ significantly between the 2 groups. CONCLUSIONS AND CLINICAL RELEVANCE: Concentration of PAG1 in the maternal circulation may be a useful biomarker for determining placental health in sheep after viral infection of the reproductive tract.

Uterine Torsion Dystocia Complicated by Perosomus Elumbis in an Angus Calf Associated with a Consanguineous Mating.

A six-year-old multiparous Angus cow was presented for dystocia. Vaginal and rectal examinations revealed an approximately 360° counterclockwise uterine torsion. The torsion was corrected by rolling the cow counterclockwise (three episodes) with the aid of a plank coupled with manual detorsion via the vagina. The placement of obstetric chains followed by manual traction ultimately delivered a stillborn male calf with evidence of vertebral aplasia, arthrogryposis, and abdominal organ herniation. Patient history and subsequent parentage verification revealed that the calf was the result of a consanguineous (mother to son) mating. Tissue samples from the affected calf and blood samples from the dam, sire, and ten half siblings were collected for genetic testing and parentage verification. Necropsy, radiographic, and computed tomography examinations all supported a diagnosis of perosomus elumbis. Perosomus elumbis is a congenital abnormality of unknown origin(s), and this is the first report of a case associated with a consanguineous mating.

HISTOLOGIC EVIDENCE OF SPONTANEOUS OVULATION IN TIGERS (PANTHERA TIGRIS).

Spontaneous ovulation has been identified in several wild felid species and domestic cats previously thought to undergo only induced ovulation. Two studies have assessed ovulation patterns in tigers (Panthera tigris) and have not found evidence of spontaneous ovulation in this species. However, uterine pathology typically associated with prolonged progesterone exposure has been identified in unbred tigers, suggesting spontaneous ovulation occurs. Ovaries from 47 tigers were reviewed with histologic examination. The presence or lack of active corpora lutea was documented and compared with social housing conditions for each animal. Social housing categories were as follows: female housed alone, female housed with other females, and female housed with at least one male. Active corpora lutea were identified in 66% (10/15) of females housed alone, 85% (6/7) of females housed with other females, and 58% of females housed with a male. A chi-squared test found the presence of active corpora lutea was independent of social housing condition. These results offer strong evidence of spontaneous ovulation in tigers. This finding suggests that a luteal control protocol with an early follicular inhibition agent may improve assisted reproduction efforts and supports spaying nonreproductive or postreproductive female tigers to reduce the rate of uterine infections.

HYPERGAMMAGLOBULINEMIA AND MYELOMA IN FIVE TIGERS (PANTHERA TIGRIS): CLINICOPATHOLOGICAL FINDINGS.

Five adult tigers (Panthera tigris) presented with a range of clinical signs, including paresis (2/5), lameness (2/5), ataxia (3/5), anorexia (5/5), and lethargy (5/5). Each tiger demonstrated elevated plasma globulin levels (7.8-14.8 g/dl; [reference interval 2-5.1 g/dl]) on routine biochemistry, confirmed as a monoclonal gammopathy using protein electrophoresis. Serum gammaglobulin concentration ranged from 5 to 7.5 g/dl, or 45.1-63.4% of total protein concentration. Azotemia was present in three tigers. Diagnostics and management varied with the presenting signs but included magnetic resonance imaging, radiography, chemotherapy, supportive care, and euthanasia. In each case, necropsy revealed a neoplastic plasma cell proliferation in the bone marrow and one or more extramedullary sites. Lytic lesions in the thoraco-lumbar spine were found in three animals, and one lesion was associated with spinal cord compression. Splenomegaly was present in 4/5 cases. Histopathology confirmed a plasma cell neoplasm in each case, and immunohistochemistry staining with multiple myeloma oncogene 1 (MUM1) was positive in each case. CD20 staining was performed in two cases and was positive in one. CD3 staining was performed in the same two cases, and was negative in each. Based on the clinical, gross, microscopic, and immunohistochemical findings, myeloma was diagnosed in all five tigers.

Description and characterization of a hair coat disorder in schipperkes.

BACKGROUND: Schipperkes develop bilaterally symmetrical alopecia preceded by lightening of the hair coat not associated with systemic clinical signs. The alopecia is presumptively diagnosed as Alopecia X but has never been investigated. HYPOTHESIS/OBJECTIVES: The purpose of this study was to describe clinical features, histopathological and laboratory abnormalities associated with symmetrical, noninflammatory alopecia in schipperkes. ANIMALS: Three healthy and eight affected schipperkes. METHODS AND MATERIALS: Complete blood count (CBC), serum chemistry panel, urinalysis (UA), urine cortisol: creatinine ratio (UCCR), total thyroxine (T4 ), free thyroxine by equilibrium dialysis (fT4 ed), thyroid stimulating hormone (TSH) and pre- and post-stimulation cortisol with sex hormone analyses were performed for all dogs. A minimum of two skin biopsy sites were sampled for histopathological evaluation. RESULTS: The CBC, serum chemistry panel, UA, T4 , fT4 ed, TSH and post-ACTH cortisol concentrations were normal for all dogs. Androstenedione concentrations were increased for all dogs; two of three healthy and five of eight affected dogs had increased post-ACTH androstenedione concentrations. Estradiol concentrations were increased for all healthy and four of eight affected dogs, with post-ACTH estradiol concentrations increased for all healthy and five of eight affected dogs. Progesterone concentrations were increased for two of three healthy and four of eight affected dogs. Post-ACTH progesterone concentrations were increased for one of three healthy and four of eight affected dogs. For one of three healthy and two of eight affected dogs, 17-hydroxyprogesterone concentrations were increased; post-ACTH 17-hydroxyprogesterone concentrations were increased in three of eight affected dogs only. Histopathology results from affected dogs were consistent with hair cycle arrest. CONCLUSIONS AND CLINICAL IMPORTANCE: This disorder resembles Alopecia X clinically and histologically.

Effects of hyperbaric oxygen therapy on uncomplicated incisional and open wound healing in dogs.

OBJECTIVE: To determine the safety of a hyperbaric oxygen therapy (HBOT) protocol and its influence on the healing of uncomplicated open and incisional wounds in dogs. STUDY DESIGN: Prospective, controlled experimental study. ANIMALS: Adult dogs (n = 10). METHODS: Two 2 × 2-cm open wounds and two 3-cm-long full-thickness dermal incisions were created on the dorsum of each dog. Dogs in the hyperbaric oxygen treatment group (HBO) received HBOT once daily (1.7 atmospheres absolute [ATA], 30 minutes on day 1; 2.0 ATA, 40 minutes on days 2-7) for 7 consecutive days, and dogs in the control group (CON) received standardized wound care. Dogs were monitored during HBOT for adverse side effects. Total wound area, percentage epithelialization, and percentage contraction were compared for the open wounds. Subjective wound scores were compared for the open and incisional wounds. Biopsies of both wound types were taken and used to determine histopathology scores. Bacterial cultures were completed on open wounds. RESULTS: No difference was detected between HBO and CON uncomplicated open and incisional wounds at any time for contraction, epithelialization, subjective wound scores, histopathology scores, or bacterial loads. All HBO dogs tolerated hyperbaric oxygen treatments with no adverse effects. CONCLUSION: The HBOT protocol tested here was safe but did not enhance the healing of uncomplicated acute wounds and incisions of dogs. CLINICAL SIGNIFICANCE: These results do not provide evidence to support the use of HBOT to manage uncomplicated wounds in dogs.

Lymphocytic Mural Folliculitis Resembling Epitheliotropic Lymphoma in Tigers ( Panthera tigris).

A striking form of lymphocytic mural folliculitis is described in 6 tigers ( Panthera tigris). Clinically, all tigers exhibited regionally extensive chronic, variably waxing and waning alopecia with minimal scaling and crusting most pronounced over the head, neck, and shoulders. More severely affected tigers exhibited marked hyperpigmentation and lichenification. Pruritus was not a feature. Tigers generally lacked signs of systemic illness and clinical pathology findings were unremarkable. Histologic examination of skin biopsies revealed infiltrative lymphocytic mural folliculitis extending the length of the hair follicle. Mild epidermal lymphocytic infiltrates were frequent. The surrounding dermis was histologically unremarkable in 4 of 6 tigers or associated with mild perifollicular and periadnexal mixed inflammation in 2 of 6 tigers. The cause of the mural folliculitis was not identified, and tigers responded poorly to immunomodulatory therapy. Lymphocytic mural folliculitis might be a nonspecific hypersensitivity reaction pattern in tigers, and care should be taken to differentiate this reaction pattern from epitheliotropic T-cell lymphoma.

ATTEMPTED SURGICAL CORRECTION OF A PERSISTENT RIGHT FOURTH AORTIC ARCH IN A JUVENILE ROTHSCHILD'S GIRAFFE (GIRAFFA CAMELOPARDALIS ROTHSCHILDI).

A 5-mo-old female Rothschild's giraffe ( Giraffa camelopardalis rothschildi) presented for regurgitation. Esophagoscopy at 24 wk of age revealed a markedly dilated cranial esophagus with a tight stricture at the level of the heart base consistent with a vascular ring anomaly. Surgical exploration confirmed persistent right fourth aortic arch with ductus originating from left subclavian artery at its junction with the aorta and left subclavian artery. The patent ductus arteriosus was surgically ligated. The procedure was complicated by limited surgical access and vascular friability resulting in uncontrollable hemorrhage, and the animal was euthanatized. The animal's large size and unique shape precluded preoperative examination by computed tomography. Surgical accessibility was poor because cranial retraction of the thoracic limb was limited. Histology revealed focal degeneration of the aorta and subclavian artery and muscular degeneration of the esophagus. Degeneration was attributed to local hypoxia from compression by the vascular structure as the animal grew.

Calcific band keratopathy in an alpaca.

A 4-year-old female Suri alpaca was presented for evaluation of acute onset weakness, lethargy, and recent development of opacities in both eyes. On ophthalmic examination, bilaterally symmetrical corneal opacities were noted along the interpalpebral fissures with a few corneal blood vessels intermingled. A presumed diagnosis of calcific band keratopathy was made based on location and appearance. The patient was euthanized a short while after diagnosis due to reasons unrelated to the eyes and histologic examination of the corneas revealed subepithelial calcium and vascularization, consistent with calcific band keratopathy. This case report is the first to document this ocular condition in an alpaca.