Open label clinical trial of orally administered molnupiravir as a first-line treatment for naturally occurring effusive feline infectious peritonitis.

BACKGROUND: Before the discovery of effective antiviral drugs, feline infectious peritonitis (FIP) was a uniformly fatal disease of cats. Multiple antiviral treatments have been recognized, but optimization of treatment protocols is needed. OBJECTIVE: To evaluate the efficacy of PO molnupiravir (MPV; EIDD-2801) to treat effusive FIP. ANIMALS: Ten cats with naturally occurring effusive FIP and 10 historical control cats with effusive FIP treated with PO GS-441524. METHODS: A single-center, prospective, open-label longitudinal, non-inferiority trial with historical controls. Ten cats with FIP were enrolled and treated with PO MPV (10-15 mg/kg PO q12h) for 84 days. Cats were evaluated at 0, 6, and 16 weeks, and the proportion of cats in clinical remission at 16 weeks was determined. Survival and clinicopathologic features were compared with historical control cats with effusive FIP treated with PO GS-441524. RESULTS: Eight of the 10 cats treated with MPV survived and were in remission at 16 weeks. The 2 non-survivors died in the first 24 hours of treatment. No adverse events that necessitated discontinuation of treatment were observed. Survival of cats treated with PO MPV was non-inferior to historic control cats treated with PO GS-441524 (5/9 [55%] survived), with a difference in survival of 25% (90% confidence interval, -9.3% to 59.3%). Clinicopathologic features associated with FIP normalized during the study period, and no differences in clinicopathologic data at each study time point were observed when comparing cats treated with MPV and GS-441524. CONCLUSIONS AND CLINICAL IMPORTANCE: Molnupiravir is an effective antiviral treatment for effusive FIP.

A lentivirus-vectored feline erythropoietin gene therapy strategy in tissue culture and rodent models for the potential treatment of chronic renal disease-associated anemia.

OBJECTIVE: The aim of this study was to assess the efficacy and safety of a third-generation lentivirus-based vector encoding the feline erythropoietin (EPO) (feEPO) gene in vitro and in rodent models in vivo. This vector incorporates a genetic mechanism to facilitate the termination of the therapeutic effect in the event of supraphysiologic polycythemia, the herpes simplex virus thymidine kinase (HSV-TK) "suicide gene." ANIMALS: CFRK cells and replication-defective lentiviral vectors encoding feEPO were used for in vitro experiments. Eight Fischer rats were enrolled in the pilot in vivo study, 24 EPO-deficient mice were used in the initial mouse study, and 15 EPO-deficient mice were enrolled in the final mouse study. METHODS: Efficacy of a third-generation lentivirus encoding feEPO was determined in vitro using western blot assays. Subsequently, in a series of rodent experiments, animals were administered the viral vector in progressively increasing inoculation doses with serial measurements of blood packed cell volume (PCV) over time. RESULTS: We documented production of feEPO protein in transduced CRFK cells with subsequent cessation of production when treated with the HSV-TK substrate ganciclovir. In vivo, we demonstrated variably persistent elevated PCV values in treated rats and mice with eventual return to baseline values over time. CLINICAL RELEVANCE: These results provide justification for a lentiviral gene therapy approach to the treatment of nonregenerative anemia associated with chronic renal disease in cats.

Correction: Cook et al. An Optimized Bioassay for Screening Combined Anticoronaviral Compounds for Efficacy against Feline Infectious Peritonitis Virus with Pharmacokinetic Analyses of GS-441524, Remdesivir, and Molnupiravir in Cats. Viruses 2022, 14, 2429.

In the original publication [...].

Gingival squamous cell carcinoma in 2 lions under managed care.

Neoplasia is one of the main causes of euthanasia in geriatric captive nondomestic felids. However, few studies have examined oral tumors in these animals. We describe here the clinicopathologic features of gingival squamous cell carcinoma (SCC) in 2 lions (Panthera leo) from separate zoologic collections. In both cases, the lions had a history of sialorrhea, bloody oral discharge, and anorexia. Autopsy findings in both lions were similar and were characterized by poorly circumscribed, friable, and bloody gingival masses with grossly apparent invasion of the mandibular bone; a pathologic fracture was observed in 1 case. Histologically, the masses consisted of poorly circumscribed, unencapsulated, densely cellular proliferations of neoplastic epithelial cells arranged in irregular islands, cords, and anastomosing trabeculae with formation of keratin pearls, which, coupled with positive immunohistochemistry for pancytokeratin, were diagnostic for SCC. Although no metastases were found in either animal, both lions were ultimately euthanized because of poor prognosis.

Serologic, Virologic and Pathologic Features of Cats with Naturally Occurring Feline Infectious Peritonitis Enrolled in Antiviral Clinical Trials.

Feline infectious peritonitis (FIP) is a multisystemic, generally lethal immuno-inflammatory disease of domestic cats caused by an infection with a genetic variant of feline coronavirus, referred to as the FIP virus (FIPV). We leveraged data from four different antiviral clinical trials performed at the University of California, Davis. Collectively, a total of 60 client-owned domestic cats, each with a confirmed diagnosis of naturally occurring FIP, were treated with a variety of antiviral compounds. The tested therapies included the antiviral compounds GS-441524, remdesivir, molnupiravir and allogeneic feline mesenchymal stem/stroma cell transfusions. Four client-owned cats with FIP did not meet the inclusion criteria for the trials and were not treated with antiviral therapies; these cats were included in the data set as untreated FIP control cats. ELISA and Western blot assays were performed using feline serum/plasma or ascites effusions obtained from a subset of the FIP cats. Normalized tissue/effusion viral loads were determined in 34 cats by a quantitative RT-PCR of nucleic acids isolated from either effusions or abdominal lymph node tissue. Twenty-one cats were PCR "serotyped" (genotyped) and had the S1/S2 region of the coronaviral spike gene amplified, cloned and sequenced from effusions or abdominal lymph node tissue. In total, 3 untreated control cats and 14 (23.3%) of the 60 antiviral-treated cats died or were euthanized during (13) or after the completion of (1) antiviral treatment. Of these 17 cats, 13 had complete necropsies performed (10 cats treated with antivirals and 3 untreated control cats). We found that anticoronaviral serologic responses were persistent and robust throughout the treatment period, primarily the IgG isotype, and focused on the viral structural Nucleocapsid and Membrane proteins. Coronavirus serologic patterns were similar for the effusions and serum/plasma of cats with FIP and in cats entering remission or that died. Viral RNA was readily detectable in the majority of the cats in either abdominal lymph node tissue or ascites effusions, and all of the viral isolates were determined to be serotype I FIPV. Viral nucleic acids in cats treated with antiviral compounds became undetectable in ascites or abdominal lymph node tissue by 11 days post-treatment using a sensitive quantitative RT-PCR assay. The most common pathologic lesions identified in the necropsied cats were hepatitis, abdominal effusion (ascites), serositis, pancreatitis, lymphadenitis, icterus and perivasculitis. In cats treated with antiviral compounds, gross and histological lesions characteristic of FIP persisted for several weeks, while the viral antigen became progressively less detectable.

Pathological Spectrum of Ovine Pulmonary Adenocarcinoma in Small Ruminants: A Focus on the Mixed Form.

Ovine pulmonary adenocarcinoma (OPA) is a contagious respiratory tumor of small ruminants, manifesting in chronic weight loss and respiratory failure. Infection with the betaretrovirus jaagsiekte sheep retrovirus (JSRV) is the cause of OPA. Here, we describe the gross and microscopic features of twenty-six sheep and one goat with naturally occurring JSRV-associated OPA. All the animals included in this study had pulmonary lesions morphologically consistent with OPA, but the majority of the observed lesions demonstrated features of both the classical and the atypical form of OPA, and were, therefore, classified grossly as mixed. The gross lesions were located mainly in the cranial pulmonary lobes, were multifocal to coalescing, variable in number and size, flat to slightly raised, firm, and white to grey. Histologically, the cases were classified according to the predominant architectural patterns as lepidic, papillary, acinar, or mixed; the mixed histological pattern was the most prevalent. The aim of this study was to describe the gross and microscopic spectrum of OPA in naturally infected small ruminants from Spain. The mixed form of OPA is less commonly reported, and can be confused with other concurrent pulmonary pathologies (such as BALT hyperplasia in SRLV-associated pneumonia or lungworm granulomas).

Efficacy of Oral Remdesivir Compared to GS-441524 for Treatment of Cats with Naturally Occurring Effusive Feline Infectious Peritonitis: A Blinded, Non-Inferiority Study.

Nucleoside analogs GS-441524 and remdesivir (GS-5734) are effective in treating cats with feline infectious peritonitis (FIP). However, no studies have compared the efficacy between antiviral medications. The objective of this study was to evaluate the efficacy of orally administered GS-442514 (12.5-15 mg/kg) compared to orally administered remdesivir (25-30 mg/kg) in a double-blinded non-inferiority trial. Eighteen cats with effusive FIP were prospectively enrolled and randomly assigned to receive either GS-442514 or remdesivir. Cats were treated daily for 12 weeks and evaluated at week 0, 12, and 16. Survival and disease remission at week 16 were compared between groups. Five of 9 (55%) cats treated GS-441524 and 7/9 (77%) cats treated with remdesivir survived, with no difference in survival rate (p = 0.2). Remdesivir fulfilled the criteria for non-inferiority with a difference in survival of 22% (90% CI; -13.5-57.5%). Three of the 18 cats died within 48 h of enrollment. Excluding these cats, 5/6 (83%) of the cats treated with GS-441524 and 7/9 (77%) of the cats treated with remdesivir survived. These findings suggest that both orally administered GS-441524 and remdesivir are safe and effective anti-viral medications for the treatment of effusive FIP. Further optimization of the first 48 h of treatment is needed.

The Late Asymptomatic and Terminal Immunodeficiency Phases in Experimentally FIV-Infected Cats-A Long-Term Study.

Feline immunodeficiency virus (FIV) is a lentivirus in the family Retroviridae that infects domestic cats resulting in an immunodeficiency disease featuring a progressive and profound decline in multiple sets of peripheral lymphocytes. Despite compelling evidence of FIV-associated immunopathology, there are conflicting data concerning the clinical effects of FIV infection on host morbidity and mortality. To explore FIV-associated immunopathogenesis and clinical disease, we experimentally inoculated a cohort of four specific pathogen-free kittens with a biological isolate of FIV clade C and continuously monitored these animals along with two uninfected control animals for more than thirteen years from the time of inoculation to the humane euthanasia endpoint. Here, we report the results obtained during the late asymptomatic and terminal phases of FIV infection in this group of experimentally FIV-infected cats.

Odontogenic-like neoplasms of the rabbit cheek: pathological features and comparison to cutaneous trichoblastoma and jaw-associated ameloblastoma.

Odontogenic neoplasms demonstrate unique histopathological features and are thought to arise from the germinal tissues of the developing tooth germ, effectively restricting their anatomic origin to the tooth-bearing regions of the jaw and directly associated soft tissues of the oral cavity. Ectopic odontogenic-like neoplasms located in the skin of cats, rabbits, and human beings challenge these assumptions. Here we describe the clinical, pathological, and immunohistochemical features of 6 spontaneously occurring odontogenic-like neoplasms arising in the cutaneous tissue of the cheek in client-owned pet rabbits, including ameloblastoma-like (n = 3), ameloblastic fibroma-like (n = 2), and ameloblastic carcinoma-like neoplasms (n = 1). Microscopically, all the cheek tumors featured neoplastic epithelium exhibiting odontogenic architectural structures (plexiform ribbons, anastomosing trabeculae, follicles, cysts, and irregular structures with rounded botryoid protuberances) and 1 or more cardinal odontogenic epithelial features (basal palisading, antibasilar nuclei, and central stellate reticulum-like cells). The pancytokeratin, cytokeratin 5/6, cytokeratin 14, and vimentin immunohistochemical patterns of these odontogenic-like lesions were most similar to those of jaw-associated ameloblastoma and differed from those of cutaneous trichoblastoma. All neoplasms were narrowly excised, and for lesions with clinical follow-up information, none had evidence of recurrence 1-7 months after surgical removal. Although evidence suggests that these odontogenic-like tumors of the rabbit cheek may be derived from ectopic rests of transformed tooth germ, the histogenesis of these lesions remains unresolved.

Medical Management of Canine Chronic Ulcerative Stomatitis Using Cyclosporine and Metronidazole.

Canine chronic ulcerative stomatitis (CCUS) is a spontaneously occurring, painful, and often debilitating condition of the oral cavity, with a suspected immune-mediated component. The response to pharmacological treatment is generally poor, thus the need to identify more effective medical therapies for this condition. This article describes a prospective clinical trial that was designed to evaluate the efficiency of a combination of cyclosporine and metronidazole in managing CCUS. The hypothesis was that a combination of cyclosporine and metronidazole would effectively minimize clinical signs associated with CCUS. Ten client-owned dogs with a biopsy-confirmed diagnosis consistent with CCUS were prescribed cyclosporine (5 mg/kg) for 1 week, followed by the addition of metronidazole (15-20 mg/kg), both administered orally once daily. The cyclosporine dosage interval was lengthened over time. Dogs were observed for a 6-month period and evaluated using a 32-point Canine Ulcerative Stomatitis Disease Activity Index (CUSDAI). Regular cyclosporine therapeutic drug monitoring was also conducted by the measurement of whole blood cyclosporine levels and the pharmacodynamic assessment of the T-cell expression of IL-2. The results demonstrated that a combination of cyclosporine and metronidazole was effective in minimizing the clinical signs of CCUS and in reducing CUSDAI scores. Neither blood cyclosporine levels nor the T-cell expression of IL-2 predicted improvement in clinical signs and CUSDAI scores, although there was a correlation between blood drug concentrations and the suppression of T-cell IL-2 expression. The evaluation of clinical signs and CUSDAI scores appears to be the most effective means of assessing response to therapy, and therapeutic drug level monitoring does not appear to be routinely indicated.

Use of Enrofloxacin and Hydrotherapy in the Management of Fibrodysplasia Ossificans Progressiva (FOP) in a Savannah Cat.

FOP is a rare genetic condition, described mainly in man and cats, characterized by progressive, painful debilitation and shortened lifespan. A 10-month-old neutered male Savannah cat was referred for progressive gait abnormalities and multifocal firm masses within the soft-tissues that were unresponsive to previous treatment. Diagnosis of FOP was based on histopathological evaluation of intralesional biopsies, which revealed osteo-cartilaginous metaplasia and fibrocellular proliferation with intralesional chondrogenesis and endochondral ossification. The cat was managed with 5 mg/kg BID enrofloxacin and hydrotherapy for 3 years until acute death. During that three-year period, the cat displayed consistent improvement in endurance, quality of life, and range of motion. Postmortem histopathology further confirmed the diagnosis of FOP via identification of intramuscular and intra-fascial ossification with lymphoplasmacytic infiltration, degeneration, and regeneration of adjacent myocytes. To the authors' knowledge, this is the first report of long-term enrofloxacin treatment and hydrotherapy for the management of FOP in a cat, leading to improved mobility and survival time, and the first report of FOP in an exotic breed cat.

An Optimized Bioassay for Screening Combined Anticoronaviral Compounds for Efficacy against Feline Infectious Peritonitis Virus with Pharmacokinetic Analyses of GS-441524, Remdesivir, and Molnupiravir in Cats.

Feline infectious peritonitis (FIP) is a fatal disease of cats that currently lacks licensed and affordable vaccines or antiviral therapeutics. The disease has a spectrum of clinical presentations including an effusive ("wet") form and non-effusive ("dry") form, both of which may be complicated by neurologic or ocular involvement. The feline coronavirus (FCoV) biotype, termed feline infectious peritonitis virus (FIPV), is the etiologic agent of FIP. The objective of this study was to determine and compare the in vitro antiviral efficacies of the viral protease inhibitors GC376 and nirmatrelvir and the nucleoside analogs remdesivir (RDV), GS-441524, molnupiravir (MPV; EIDD-2801), and ß-D-N4-hydroxycytidine (NHC; EIDD-1931). These antiviral agents were functionally evaluated using an optimized in vitro bioassay system. Antivirals were assessed as monotherapies against FIPV serotypes I and II and as combined anticoronaviral therapies (CACT) against FIPV serotype II, which provided evidence for synergy for selected combinations. We also determined the pharmacokinetic properties of MPV, GS-441524, and RDV after oral administration to cats in vivo as well as after intravenous administration of RDV. We established that orally administered MPV at 10 mg/kg, GS-441524 and RDV at 25 mg/kg, and intravenously administered RDV at 7 mg/kg achieves plasma levels greater than the established corresponding EC50 values, which are sustained over 24 h for GS-441514 and RDV.

Clinical, Diagnostic and Histological Findings Involving Cheek Teeth Hypercementosis in Nine Horses.

Hypercementosis is infrequently reported to affect the cheek teeth of horses and presents as mineral deposits either attached (peripheral) or solitary ovoid (nodular) structures in the tooth bearing region. There is overlap between radiological and histological appearance of hypercementosis, cementoma, and equine odontoclastic tooth resorption and hypercementosis (EOTRH). The clinical presentation, imaging features, surgical management, and histological findings of nine horses that presented for dental lesions and associated hypercementosis of cheek teeth are reported. Horses were 4-15 years old and presented for either nasal discharge or facial swelling. Peripheral and nodular mineral structures were identified using radiographs or computed tomography in six and three horses, respectively. Eight of nine cases involved maxillary cheek teeth. Of six cases with peripheral hypercementosis, three had enlargement of the apical cross-sectional area that was greater than the coronal cross-sectional area thus preventing extraction along the normal eruption pathway and necessitating sectioning (two cases) and repulsion. Nodular hypercementosis lesions were extracted in three of the four cases. Post-extraction complications occurred in five cases; four cases required additional procedures. All horses returned to their intended use, ie riding or pasture. Histology of extracted dental and proliferative mineral material revealed hypercementosis characterized by large sheets of eosinophilic matrix with lacunae (usually empty; presumed artifact) and frequent, irregular, basophilic cement lines. All cases had evidence of chronic inflammation, such as caries, chronic fractures and/or pulpitis. The findings of this case series share many features with previous published descriptions of cementoma and with histological findings of hypercementosis lesions of EOTRH. Further investigation into differentiation of these entities is warranted.

Ameloblastic carcinoma in horses: case report and literature review.

Ameloblastic carcinoma is a malignant odontogenic neoplasm that has been reported only rarely in veterinary species. A 16-y-old Arabian crossbred mare was presented for evaluation of a hard mass on the body of the mandible, with evidence of osteolysis on radiographs. Incisional biopsies revealed an invasive neoplasm comprised of spindloid epithelial cells with a high mitotic count and partial dual cytokeratin-vimentin immunoreactivity. The horse was euthanized because of rapid tumor progression 3 mo after presentation. Postmortem evaluation revealed partial obliteration of the mandible by a large, firm-to-hard, tan, locally destructive and invasive mass with no gross or histologic evidence of metastasis. Postmortem histology revealed a poorly differentiated epithelial neoplasm with variably prominent features suggestive of odontogenic histogenesis: a plexiform ribbon architecture, infrequent basilar palisading with antibasilar nuclei, rare basilar cytoplasmic clearing, subepithelial matrix hyalinization, and partial dual cytokeratin-vimentin immunoreactivity. Features of malignancy included regions of necrosis, pronounced cellular atypia, a high mitotic count, extensive tissue invasion and local tissue destruction, and extension of neoplastic cells beyond the margins of the mandibular bone. Collectively, these features are most consistent with mandibular ameloblastic carcinoma. Including our case described here, ameloblastic carcinoma has been reported in only 5 horses. The microscopic features reported most consistently are dual cytokeratin-vimentin immunoreactivity, a high mitotic count, and basilar palisading. Ameloblastic carcinoma should be considered as a differential diagnosis for rapidly growing, locally invasive masses arising from the dentate jaw of horses.

Investigation of monotherapy and combined anticoronaviral therapies against feline coronavirus serotype II in vitro.

OBJECTIVES: Feline infectious peritonitis (FIP), caused by genetic mutants of feline enteric coronavirus known as FIPV, is a highly fatal disease of cats with no currently available vaccine or US Food and Drug Administration-approved cure. Dissemination of FIPV in affected cats results in a range of clinical signs, including cavitary effusions, anorexia, fever and lesions of pyogranulomatous vasculitis and perivasculitis, with or without central nervous system or ocular involvement. The objectives of this study were to screen an array of antiviral compounds for anti-FIPV (serotype II) activity, determine cytotoxicity safety profiles of identified compounds with anti-FIPV activity and strategically combine identified monotherapies to assess compound synergy against FIPV in vitro. Based upon clinically successful combination treatment strategies for human patients with HIV and hepatitis C virus infections, we hypothesized that a combined anticoronaviral therapy approach featuring concurrent multiple mechanisms of drug action would result in an additive or synergistic antiviral effect. METHODS: This study screened 90 putative antiviral compounds for efficacy and cytotoxicity using a multimodal in vitro strategy, including plaque bioassays, real-time RT-PCR viral inhibition and cytotoxicity assays. RESULTS: Through this process, we identified 26 compounds with effective antiviral activity against FIPV, representing a variety of drug classes and mechanisms of antiviral action. The most effective compounds include GC376, GS-441524, EIDD2081 and EIDD2931. We documented antiviral efficacy for combinations of antiviral agents, with a few examined drug combinations demonstrating evidence of limited synergistic antiviral activity. CONCLUSIONS AND RELEVANCE: Although evidence of compound synergy was identified for several combinations of antiviral agents, monotherapies were ultimately determined to be the most effective in the inhibition of viral transcription.

Osteochondral necrosis of the femoral condyles in Thoroughbred foals: eight cases (2008-2018).

OBJECTIVE: To describe clinical, imaging, gross, and histopathological abnormalities associated with osteochondral necrosis of the femoral condyles in foals and identify features suggestive of a common pathogenesis. ANIMALS: 8 Thoroughbred foals euthanized with a presumptive diagnosis of necrosis of the femoral condyles. PROCEDURES: Postmortem CT was performed on all distal femoral epiphyseal samples. The articular epiphyseal cartilage complex (AECC) of affected distal femurs was examined grossly and histologically, focusing on lesions of interest identified on CT images. RESULTS: 7 foals were between 9 and 23 days old at the time of euthanasia; 1 foal was 85 days old. Concurrent illness (neonatal maladjustment syndrome, neonatal isoerythrolysis, or infection such as enteritis and omphalitis) was diagnosed in 7 foals. The characteristic antemortem radiographic and postmortem CT finding was a crescent-shaped osteochondral flap displaced from the affected medial femoral condyle. Synovial fluid cytology from affected joints was either within normal limits or consistent with mild inflammation. Histologically, all lesions were characterized by osteochondral necrosis and detachment of the AECC. In 6 foals, polymorphonuclear cells were found within growth cartilage canals, representing septic cartilage canals. CLINICAL RELEVANCE: Osteochondral necrosis was interpreted to be secondary to bacterial colonization of the distal femoral AECC, evidenced by septic cartilage canals identified in 6 of 8 foals. This uncommon condition was previously thought to arise from an ischemic event, but the disease process was not well understood. An improved understanding of the pathogenesis of osteochondral necrosis is the first step in formulating more successful preventative and treatment strategies.

Caprine Arthritis Encephalitis Virus Is Associated with Renal Lesions.

Caprine arthritis encephalitis virus (CAEV) is a monocyte/macrophage-tropic lentivirus that primarily infects goats resulting in a well-recognized set of chronic inflammatory syndromes focused on the joint synovium, tissues of the central nervous system, pulmonary interstitium and mammary gland. Clinically affected animals generally manifest with one or more of these classic CAEV-associated tissue lesions; however, CAEV-associated renal inflammation in goats has not been reported in the peer-reviewed literature. Here we describe six goats with chronic, multisystemic CAEV infections in conjunction with CAEV-associated renal lesions. One of the animals had CAEV antigen-associated thrombotic arteritis resulting in infarction of both the kidney and heart. These goats had microscopic evidence of inflammatory renal injury (interstitial nephritis) with detectable renal immunolabeling for CAEV antigen in three of six animals and amplifiable proviral sequences consistent with CAEV in all six animals. Cardiac lesions (vascular, myocardial or endocardial) were also identified in four of six animals. Within the viral promoter (U3) region, known transcription factor binding sites (TFBSs) were generally conserved, although one viral isolate had a duplication of the U3 A region encoding a second gamma-activated site (GAS). Despite the TFBS conservation, the isolates demonstrated a degree of phylogenetic diversity. At present, the clinical consequence of CAEV-associated renal injury is not clear.

Rickets in a Thoroughbred-cross foal: case report and review of the literature.

Rickets is a metabolic bone disease associated with failure of endochondral ossification and impaired osteoid mineralization in growing animals. As a consequence, affected individuals can develop gross and microscopic bone malformations. The most common causes of rickets in domestic species include vitamin D and phosphorus deficiency. Rickets has been described in multiple species; however, comprehensive postmortem characterizations with confirmatory histopathology in equids have not been published. A 6-mo-old, Thoroughbred-cross foal was diagnosed with rickets based on gross autopsy findings and microscopic examination of the ribs and long bones. Grossly, all costochondral junctions of the ribs were enlarged with a "rachitic rosary" appearance, and there were multiple fracture calluses in the rib bodies. Epiphyses and metaphyses of the long bones appeared widened on sagittal section, and their physes were irregularly thickened. Histologically, there were poorly organized columns of hypertrophic chondrocytes within the physes of affected bones, islands of chondrocytes embedded within the primary and secondary spongiosa, and faintly eosinophilic seams of poorly mineralized osteoid within the bone trabeculae. Areas of focally increased osteoclastic activity were observed in some of the sections, perhaps pointing to a more complex metabolic bone disease in a growing animal. Low serum concentrations of calcium and 25-hydroxyvitamin D were detected in an antemortem sample. The pathogenesis of these imbalances was not definitively established, but lack of sunlight exposure, low concentration of vitamin D precursors in the diet (perhaps secondary to malnutrition), or both, were suspected; a genetic basis cannot be ruled out.

Chondrosesamoidean ligament enthesopathy: Prevalence and findings in a population of lame horses imaged with positron emission tomography.

BACKGROUND: Increased 18 F-Sodium Fluoride (18 F-NaF) uptake at the chondrosesamoidean ligament (ChSL) attachment on the distal phalanx was identified in an exploratory positron emission tomography (PET) study. The prevalence and significance of this lesion has not been previously investigated. OBJECTIVES: The goal of this study was to assess the prevalence of this lesion, its association with other imaging findings and with clinical signs. STUDY DESIGN: Retrospective cross-sectional analytical study. METHODS: All horses with 18 F-NaF PET and computed tomography (CT) imaging of the feet performed between October 2016 and December 2017 were included in the study. All PET scans were independently assessed by two radiologists for increased uptake at the ChSL attachment site and concurrent imaging was reviewed. Clinical findings, treatment and outcome were retrieved from the medical records. RESULTS: Fourteen of 30 horses (20/56 feet) had increased 18 F-NaF uptake in the region of interest. ChSL enthesopathy was the primary lesion in three horses. Other PET abnormalities included navicular bone uptake (13 feet) and ipsilateral palmar process uptake (9 feet). There was no significant association between ChSL enthesopathy and other lesions. ChSL enthesopathy was significantly associated with foot lameness. CT abnormalities at the ChSL attachment were initially identified in one foot, and retrospectively noted in another five following the results of PET imaging. MAIN LIMITATIONS: The study is retrospective and there was a limited sample size. CONCLUSIONS: PET led to identification of ChSL enthesopathy in a large proportion of horses with foot pain. This finding is most commonly associated with other lesions but may also represent the main abnormality. The axial border of the palmar processes of the distal phalanx should be carefully assessed on cross sectional imaging to identify this lesion. ChSL enthesopathy may be an important but previously not recognised component of foot pathology in horses.