DENTAL DISEASES AND OTHER ORAL PATHOLOGIES OF CAPTIVE JAGUARS (PANTHERA ONCA) FROM BELIZE, CENTRAL AMERICA.

Dental and oral diseases are prevalent in many mammalian species including wild felids. Determining the dental and oral health status of captive animal populations can help establish preventive and therapeutic strategies, leading to improved welfare and conservation efforts. The aim of this study was to assess the prevalence of periodontal disease, endodontic disease, tooth resorption, and other clinically relevant dental and maxillofacial abnormalities in a population of captive jaguars (Panthera onca) using clinical, radiographic, and histopathological findings. Fifteen jaguars, ranging from young adult to geriatric, kept at a private zoo in Belize, Central America, had a detailed oral examination under general anesthesia between January 2015 and March 2019. Periodontitis was present in 3.8% (16/423) of examined teeth and 53.8% (7/13) of jaguars that underwent periodontal probing. Endodontic disease secondary to dentoalveolar trauma was found in 21.0% (89/423) of teeth in 73.3% (11/15) of animals. Tooth resorption, which has not been previously documented in jaguars, affected 1.4% (6/423) of teeth in 13.3% (2/15) of jaguars. Other abnormalities included metallic foreign material (gunshot) identified radiographically in 33.3% (5/15) of jaguars and nontraumatizing malocclusion in 9.1% (1/11) of jaguars that had occlusion evaluated. Much of the oral pathology identified in captive jaguars is suspected to arise from capture and/or captivity-associated behaviors, as suggested by gunshot around the oral cavity, fractures of rostral teeth (canine and incisor teeth), and abrasions consistent with cage-biting on canine teeth. Anesthetized oral examination-including full-mouth intraoral radiographs, periodontal probing, and charting-is recommended for jaguars with clinical signs of oral pain, as well as for routine systemic evaluation.

HYPERKALEMIA IN TWO JAGUARS ( PANTHERA ONCA) ANESTHETIZED WITH DEXMEDETOMIDINE, KETAMINE, AND ISOFLURANE.

Two jaguars were anesthetized with dexmedetomidine, ketamine, and isoflurane. Arterial blood samples analyzed shortly after darting revealed no abnormalities. Samples analyzed 2 and 1.5 hr after darting revealed moderate hyperkalemia in both animals (6.8 and 6.2 mEq/L, respectively). Shortly after hyperkalemia was recognized, one jaguar developed electrocardiographic abnormalities (sinoventricular rhythm and widened QRS complexes), and a few minutes later, suffered cardiopulmonary arrest. Resuscitation with chest compressions, intermittent positive-pressure ventilation, and epinephrine was successful, and autonomous breathing and circulation resumed within a few minutes. Anesthesia-related hyperkalemia has been reported in a variety of large felids but has not been reported previously in jaguars. In all reports, α-2 adrenergic agonists were used as part of the immobilization protocol. Due to the presumptively high incidence and mortality caused by this complication, frequent monitoring of electrolyte concentrations and prompt treatment of hyperkalemia is recommended when anesthetizing large felids, including jaguars.

Suspected Rhinolithiasis Associated With Endodontic Disease in a Cat.

Rhinoliths are rare, intranasal, mineralized masses formed via the precipitation of mineral salts around an intranasal nidus. Clinical signs are typically consistent with inflammatory rhinitis and nasal obstruction, but asymptomatic cases are possible. Rhinoliths may be classified as exogenous or endogenous depending on the origin of the nidus, with endogenous rhinoliths reportedly being less common. This case report describes a suspected case of endogenous rhinolithiasis in a cat which was detected as an incidental finding during radiographic assessment of a maxillary canine tooth with endodontic disease. Treatment consisted of removal of the suspected rhinolith via a transalveolar approach after surgical extraction of the maxillary canine tooth.

Staged double-layer closure of palatal defects in 6 dogs.

OBJECTIVE: To report a staged approach that includes selective dental extractions before definitive double-layer hard palate defect closure in dogs. STUDY DESIGN: Retrospective case series. ANIMALS: Dogs (n = 6) with a palatal defect. METHODS: Dogs had selective maxillary teeth extractions 4-8 weeks before definitive hard palate defect repair by double-layer local full-thickness mucosal flaps. RESULTS: All palatal defects were considered complex. Complete hard palate closure was achieved after initial attempt in 3 dogs; 2 dogs had revision surgery before complete closure, and in 1 dog, closure failed and further treatment was declined. No complications or long-term consequences were associated with selective dental extractions. CONCLUSIONS: Selective dental extractions before definitive surgical repair using mucosal flaps in a double-layer approach is an effective alternative when treating complex hard palate defects in dogs.

Craniomaxillofacial abnormalities in dogs with congenital palatal defects: computed tomographic findings.

OBJECTIVE: To evaluate craniomaxillofacial abnormalities in dogs with congenital palatal defects. STUDY DESIGN: Retrospective computed tomography (CT) study. ANIMALS: Dogs with congenital palatal defects (n = 9). METHODS: Medical records and CT reports (1995-2012) were searched for dogs with a diagnosis of cleft palate that had a CT study. Data retrieved were: breed, age, sex, weight, physical examination, and laboratory findings, number of previous palate surgeries, and oral/dental examination findings with the diagnosis of the cleft for each dog. CT studies of the head were reviewed on a structure-by-structure basis. RESULTS: Tympanic bullae were most commonly found to be abnormal (8 dogs), followed by nasal turbinates (6), nasal septum, vomer, cribriform plate (4), frontal sinuses, and lateral ventricles (3). Other abnormalities were related to occlusion, teeth, incisive bones, maxillary bones, mandibles, hyoid apparatus, cranial bones, and nasopharynx. The soft tissue defect of the cleft was always smaller than the bony defect. CONCLUSIONS: Craniomaxillofacial abnormalities in dogs with congenital palatal defects are common and some of these may negatively affect the quality of life. Importantly for surgical planning, the soft tissue component of the cleft may underestimate the extent of the bony defect, especially in failed repairs.

Morphological study of pulp cavity anatomy of canine teeth in domestic cats using micro-computed tomography.

An understanding of the pulp cavity anatomy of individual teeth is essential for success during endodontic therapy. The objective of this study was to document pulp cavity anatomy and summarize numerical data of maxillary and mandibular canine teeth of domestic cats using micro-computed tomography (micro-CT). Thirty-nine canine teeth from eleven domestic cat cadaveric specimens were extracted and prepared for scanning. Segmentation of the pulp cavity was performed using the Avizo (v2022.2) software package. The morphological features of the pulp cavity including overall shape, configuration, presence of apical deltas and lateral canals was recorded. A quantitative analysis was performed on thirty-one teeth to explore associations between pulp cavity volume and length, apical delta length, maximum apical delta foramina number and cusp-to-tip length using a linear mixed model. Correlation between pertinent continuous variables was assessed using a Pearson's correlation test. Most pulp cavities exhibited varying curvature and ranged from a cylindrical configuration in the coronal third to an ovoid configuration in the middle to apical third. A ribbon-like flattened canal was observed in 6/31 teeth (19%). All canine teeth depicted an apical delta with various configurations except for two teeth that showed a single canal exiting at the apex. In 15/31 teeth (48%), the primary root canal within the apical delta could be clearly identified and in 16/31 (52%) the primary root canal was indiscernible. The results showed that the pulp cavities of maxillary canine teeth were significantly larger and longer and the cusp-to-tip length was longer, when compared to mandibular teeth. The apical delta length was negatively correlated to the volume of the pulp cavity. No specimens depicted lateral canals. This study revealed that the anatomy of the canine tooth pulp cavity in cats can vary considerably and should be a consideration when performing thorough debridement, shaping and obturation of the endodontic system.

Trends of regenerative tissue engineering for oral and maxillofacial reconstruction in veterinary medicine.

Oral and maxillofacial (OMF) defects are not limited to humans and are often encountered in other species. Reconstructing significant tissue defects requires an excellent strategy for efficient and cost-effective treatment. In this regard, tissue engineering comprising stem cells, scaffolds, and signaling molecules is emerging as an innovative approach to treating OMF defects in veterinary patients. This review presents a comprehensive overview of OMF defects and tissue engineering principles to establish proper treatment and achieve both hard and soft tissue regeneration in veterinary practice. Moreover, bench-to-bedside future opportunities and challenges of tissue engineering usage are also addressed in this literature review.

Literature review details and supports the application of platelet-rich plasma products in canine medicine, particularly as an orthobiologic agent for osteoarthritis.

Platelet-rich plasma (PRP) and other platelet-derived products represent a subset of regenerative medicine and have been researched in the veterinary community for the treatment of osteoarthritis, soft tissue wounds, tendinopathies, periodontitis, and fracture repairs. PRP is simple to produce, relatively affordable, safe, and can be delivered on site, making it an appealing therapeutic agent in veterinary medicine. As an orthobiologic for the treatment of osteoarthritis, it is one of few interventions with clinical study support that possess anabolic potential. Platelet product variability is wide ranging and often described in terms of cellular content or platelet enrichment. Growth factors associated with platelet activation and subsequent degranulation may mediate inflammation, modulate cellular immune response, and promote tissue repair. Product composition, dosage, and application likely influence treatment outcomes depending on the classification of the disease targeted. Sufficient canine data regarding the formulation and clinical application of canine PRP exist to warrant review. The aim of this narrative is to provide scientific background and clinical insight for veterinarians regarding platelet product content/formulation, mechanisms of action, considerations for use, and clinical application in dogs.

Opportunities for targeted therapies: trametinib as a therapeutic approach to canine oral squamous cell carcinomas.

Oral tumors are relatively common in dogs, and canine oral squamous cell carcinoma (COSCC) is the most prevalent oral malignancy of epithelial origin. COSCC is locally aggressive with up to 20% of patients showing regional or distant metastasis at the time of diagnosis. The treatment of choice most typically involves wide surgical excision. Although long-term remission is possible, treatments are associated with significant morbidity and can negatively impact functionality and quality of life. OSCCs have significant upregulation of the RAS-RAF-MEK-MAPK signaling axis, and we had previously hypothesized that small-molecule inhibitors that target RAS signaling might effectively inhibit tumor growth and progression. Here, we demonstrate that the MEK inhibitor trametinib, an FDA-approved drug for human cancers, significantly blocks the growth of several COSCC cell lines established from current patient tumor samples. We further show clinical evidence that the drug is able to cause significant tumor regression in some patients with spontaneously occurring COSCC. Given the limited treatment options available and the high rate of owner rejection of these offered options, these findings provide new hope that more acceptable treatment options may soon enter the veterinary clinic.

Case report: Spontaneous mandibular body regeneration following unilateral subtotal mandibulectomy in a 3-month-old French bulldog.

Objective: To document a case of spontaneous regeneration of the mandibular body following subtotal mandibulectomy in a juvenile dog. Case summary: A 3-month-old male intact French bulldog was presented with papillary oral squamous cell carcinoma located at the dorsal aspect of the molar region of the left mandible. Initial biopsy of the mass was performed by the primary care veterinarian. Complete clinical staging revealed no signs of metastasis. Computed tomographic images of the head showed minimal contrast enhancement of the mass with no signs of periosteal or bone involvement. Subtotal mandibulectomy was performed. Histopathology indicated complete excision of the tumor. The patient returned 8-weeks later for follow up and cleft palate surgical repair, at which time bone was noted in the mandibulectomy area on palpation. Repeat computed tomography of the head revealed complete regeneration of the left mandibular body from the level of the ramus to the mandibular symphysis. No treatment for malocclusion was necessary due to the reformation of a functional mandible. Clinical relevance: The present case demonstrates that spontaneous regeneration of the mandibular body is possible following subtotal mandibulectomy in immature dogs. Subtotal mandibulectomy is a radical procedure that can lead to long term complications including mandibular drift, malocclusion, and oral pain. This case report provides evidence that these sequelae may be mitigated or eliminated in young patients undergoing this procedure.

Confirmation of canine acanthomatous ameloblastoma using RAS Q61R immunohistochemical staining of formalin-fixed paraffin-embedded tissues.

Differentiating canine acanthomatous ameloblastoma (CAA) from oral squamous cell carcinoma (OSCC) based on routine histopathology can be challenging. We have previously shown that more than 95% of CAAs harbor an HRAS p.Q61R somatic mutation, while OSCCs carry either wild-type alleles or other MAPK pathway activating mutations (e.g., HRAS p.Q61L, BRAF p.V595E). Given that HRAS p.Q61R mutations are highly prevalent in CAA, we hypothesized that a RAS Q61R-specific rabbit monoclonal antibody may be a useful tool for confirmation of CAA by immunohistochemical (IHC) staining. In the present study, we assessed IHC staining of archived formalin-fixed and paraffin-embedded biopsy samples with a diagnosis of CAA (n = 23), using a RAS Q61R-specific rabbit monoclonal antibody (SP174) and an automated IHC stainer. Negative control samples consisted of HRAS p.Q61R mutation-negative OSCC tumors with either a known HRAS p.Q61L mutation (n = 1), BRAF p.V595E mutation (n = 4), or wild-type corresponding alleles (n = 3). We found that all 23 CAAs showed diffuse and strong membranous RAS Q61R immunoreactivity (100% sensitivity), while none of the 8 OSCCs showed immunoreactivity (100% specificity). The data supports the use of RAS Q61R-specific rabbit monoclonal antibody for diagnostic IHC confirmation of CAA and ruling out OSCC in dogs.

Repair and remodeling of the mandibular head of the condylar process in four immature dogs.

Spontaneous repair and remodeling of the mandibular head of the condylar process is a rarely reported outcome following condylectomy. This clinical report describes the spontaneous repair and subsequent remodeling of the mandibular head of the condylar process in four immature dogs that sustained traumatic injuries, necessitating surgical intervention through arthroplasty via partial or complete condylectomy, or caudal mandibulectomy. In subsequent evaluations, it was observed that all dogs exhibited clinically functional TMJs, as evidenced by an appropriate range of motion. These findings were corroborated by the owners' reports of the patient's normal eating and drinking abilities. Conventional and cone-beam computed tomography studies demonstrated the repair and remodeling of the osseous tissues of the mandibular head of the condylar process. Histopathology was unavailable to assess the novel tissues. No evidence of intraarticular or extraarticular ankylosis or osteoarthritic changes was observed.

Microspatial distribution of trace elements in feline dental hard tissues: early life exposure to essential and toxic elements.

Introduction: Trace elements play a key role in dental tissue development, as dental hard tissues accumulate both essential and toxic trace elements during mineralization. Characterization of the spatial accumulation pattern of trace elements may provide insight into exposure to toxic elements over time and to the nature of disease processes affecting the hard dental tissues. Here, we present the first report of the use of laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS) to map the microspatial distribution of multiple trace elements, essential and toxic, across feline dental hard tissues. Methods: Eleven teeth were extracted from 8 cats. Nine teeth were from 7 cats diagnosed with idiopathic tooth resorption on intraoral radiographs prior to extraction. Two teeth were included from a cadaver that had no signs of tooth resorption on intraoral radiographs. The normal dental tissue was analyzed from each sample using LA-ICP-MS to map the microspatial distribution of essential and toxic trace elements across feline enamel, dentin, and cementum. Results: Results showed a higher accumulation of barium and strontium in coronal dentin as compared to root dentin. The timing of the accumulation mirrors nursing timelines seen in teeth from human and non-human primates, consistent with barium and strontium being sourced from maternal milk. Results also showed a higher uptake of lead in the coronal dentin, suggesting this lead exposure was likely passed from mother to offspring. Discussion: This work characterizes a baseline for elemental distribution in feline teeth linked to early life exposure to toxic elements such as lead and provides a framework for future studies investigating long-term environmental exposures to trace elements, essential and toxic, and their involvement in feline systemic and dental diseases.

Piezosurgical bone-cutting technology reduces risk of maxillectomy and mandibulectomy complications in dogs.

OBJECTIVE: To report the complication rate of dogs undergoing oral oncological surgery when using a bone-cutting piezoelectric unit for osteotomies. CLINICAL PRESENTATION AND PROCEDURES: Retrospective cohort evaluation of medical records from 2012 through 2022 for canine patients that underwent mandibulectomy or maxillectomy for the treatment of oral neoplasia at the Companion Animal Hospital at Cornell University. Cases were included if osteotomy was performed using a piezoelectric unit. Medical records were then reviewed for documentation of intraoperative hemorrhage and administration of blood products. RESULTS: 41 maxillectomies and 57 mandibulectomies met the inclusion criteria (98 in total). Only 1 (1.02%) case was associated with excessive surgical bleeding requiring administration of blood products. CLINICAL RELEVANCE: Results of this study show that intraoperative hemorrhage requiring the use of blood products during or immediately after a mandibulectomy or maxillectomy is rare when using a piezoelectric unit to perform osteotomies, and is substantially lower than that previously reported when using oscillating saws or other bone-cutting devices for maxillectomies.

Highly recurrent BRAF p.V595E mutation in canine papillary oral squamous cell carcinoma.

Oral squamous cell carcinoma (OSCC) is the most common oral epithelial malignancy in dogs. It exhibits locally aggressive biological behaviour with the potential to metastasize, and a reported 1-year survival rate of 0% when left untreated. Expression studies suggest that aberrant MAPK signalling plays a key role in canine OSCC tumorigenesis, which is consistent with BRAF and HRAS MAPK-activating mutations reported in some tumours. Several morphological subtypes of canine OSCC have been described, with papillary, conventional, and basaloid as the most common patterns. We hypothesized that mutational differences may underlie these phenotypic variations. In this study, targeted Sanger sequencing and restriction fragment length polymorphism assays demonstrate that up to 85.7% of canine papillary OSCC (n = 14) harbour a BRAF p.V595E mutation. Assessment of neoplastic epithelial cell proliferation using Ki67 immunolabelling (n = 10) confirmed a relatively high proliferation activity, consistent with their known aggressive clinical behaviour. These findings underscore a consistent genetic feature of canine papillary OSCC and provide a basis for the development of novel diagnostic and targeted therapeutic approaches that can improve the quality of veterinary care.

Transcriptomic signatures of feline chronic gingivostomatitis are influenced by upregulated IL6.

Feline chronic gingivostomatitis (FCGS) is a relatively common and debilitating disease characterized by bilateral inflammation and ulceration of the caudal oral mucosa, alveolar and buccal mucosa, and varying degrees of periodontal disease. The etiopathogenesis of FCGS remains unresolved. In this study, we performed bulk RNA-seq molecular profiling of affected tissues derived from a cohort of client-owned cats with FCGS compared to tissues from unaffected animals, to identify candidate genes and pathways that can help guide future exploration of novel clinical solutions. We complemented transcriptomic findings with immunohistochemistry and in situ hybridization assays to better understand the biological significance of the results and performed RNA-seq validation of biologically relevant differentially expressed genes using qPCR assays to demonstrate technical reproducibility. Transcriptomic profiles of oral mucosal tissues in cats with FCGS are enriched with immune- and inflammation-related genes and pathways that appear to be largely influenced by IL6, and include NFKB, JAK/STAT, IL-17 and IFN type I and II signaling, offering new opportunities to develop novel clinical applications based on a more rational understanding of the disease.

Transcriptomic signatures of feline chronic gingivostomatitis are influenced by upregulated IL6.

Feline chronic gingivostomatitis (FCGS) is a relatively common and debilitating disease characterized by bilateral inflammation and ulceration of the caudal oral mucosa, alveolar and buccal mucosa, and varying degrees of periodontal disease. The etiopathogenesis of FCGS remains unresolved. In this study, we performed bulk RNA-seq molecular profiling of affected tissues derived from a cohort of client-owned cats with FCGS compared to tissues from unaffected animals, to identify candidate genes and pathways that can help guide future exploration of novel clinical solutions. We complemented transcriptomic findings with immunohistochemistry and in situ hybridization assays to better understand the biological significance of the results and performed RNA-seq validation of selected differentially expressed genes using qPCR assays to demonstrate technical reproducibility. Transcriptomic profiles of oral mucosal tissues in cats with FCGS are enriched with immune- and inflammation-related genes and pathways that appear to be largely influenced by IL6 , and include NFKB, JAK/STAT, IL-17 and IFN type I and II signaling, offering new opportunities to develop novel clinical applications based on a more rational understanding of the disease.

Genomic landscape and gene expression profiles of feline oral squamous cell carcinoma.

Feline oral squamous cell carcinoma (FOSCC) is a cancer of the squamous cell lining in the oral cavity and represents up to 80% of all oral cancers in cats, with a poor prognosis. We have used whole exome sequencing (WES) and RNA sequencing of the tumor to discover somatic mutations and gene expression changes that may be associated with FOSCC occurrence. FOSCC offers a potential comparative model to study human head and neck squamous cell carcinoma (HNSCC) due to its similar spontaneous formation, and morphological and histological features. In this first study using WES to identify somatic mutations in feline cancer, we have identified tumor-associated gene mutations in six cats with FOSCC and found some overlap with identified recurrently mutated genes observed in HNSCC. Four samples each had mutations in TP53, a common mutation in all cancers, but each was unique. Mutations in other cellular growth control genes were also found such as KAT2B and ARID1A. Enrichment analysis of FOSCC gene expression profiles suggests a molecular similarity to human OSCC as well, including alterations in epithelial to mesenchymal transition and IL6/JAK/STAT pathways. In this preliminary study, we present exome and transcriptome results that further our understanding of FOSCC.

Complex Feline Disease Mapping Using a Dense Genotyping Array.

The current feline genotyping array of 63 k single nucleotide polymorphisms has proven its utility for mapping within breeds, and its use has led to the identification of variants associated with Mendelian traits in purebred cats. However, compared to single gene disorders, association studies of complex diseases, especially with the inclusion of random bred cats with relatively low linkage disequilibrium, require a denser genotyping array and an increased sample size to provide statistically significant associations. Here, we undertook a multi-breed study of 1,122 cats, most of which were admitted and phenotyped for nine common complex feline diseases at the Cornell University Hospital for Animals. Using a proprietary 340 k single nucleotide polymorphism mapping array, we identified significant genome-wide associations with hyperthyroidism, diabetes mellitus, and eosinophilic keratoconjunctivitis. These results provide genomic locations for variant discovery and candidate gene screening for these important complex feline diseases, which are relevant not only to feline health, but also to the development of disease models for comparative studies.

An Atypical Presentation of a Zygomatic Sialocele in a dog.

A sialocele is an accumulation of salivary fluid due to leakage into the interstitial space surrounding the affected salivary gland and/or its corresponding duct. Reported causes of salivary leakage include trauma, foreign bodies, sialoliths, and neoplasia, but in many cases the etiology is not identified. Clinical signs of sialoceles associated with the zygomatic salivary gland or corresponding duct usually include exophthalmos due to periorbital salivary accumulation, whereas sialoceles associated with the mandibular or sublingual glands or ducts usually manifest as cervical, pharyngeal and/or sublingual salivary accumulation. This case report describes an atypical cervical presentation of a zygomatic sialocele in a dog that resolved after zygomatic sialoadenectomy.