Infant rhesus macaques immunized against SARS-CoV-2 are protected against heterologous virus challenge 1 year later.

The U.S. Food and Drug Administration only gave emergency use authorization of the BNT162b2 and mRNA-1273 SARS-CoV-2 vaccines for infants 6 months and older in June 2022. Yet questions regarding the durability of vaccine efficacy, especially against emerging variants, in this age group remain. We demonstrated previously that a two-dose regimen of stabilized prefusion Washington SARS-CoV-2 S-2P spike (S) protein encoded by mRNA encapsulated in lipid nanoparticles (mRNA-LNP) or purified S-2P mixed with 3M-052, a synthetic Toll-like receptor (TLR) 7/8 agonist, in a squalene emulsion (Protein+3M-052-SE) was safe and immunogenic in infant rhesus macaques. Here, we demonstrate that broadly neutralizing and spike-binding antibodies against variants of concern (VOCs), as well as T cell responses, persisted for 12 months. At 1 year, corresponding to human toddler age, we challenged vaccinated rhesus macaques and age-matched nonvaccinated controls intranasally and intratracheally with a high dose of heterologous SARS-CoV-2 B.1.617.2 (Delta). Seven of eight control rhesus macaques exhibited severe interstitial pneumonia and high virus replication in the upper and lower respiratory tract. In contrast, vaccinated rhesus macaques had faster viral clearance with mild to no pneumonia. Neutralizing and binding antibody responses to the B.1.617.2 variant at the day of challenge correlated with lung pathology and reduced virus replication. Overall, the Protein+3M-052-SE vaccine provided superior protection to the mRNA-LNP vaccine, emphasizing opportunities for optimization of current vaccine platforms. The observed efficacy of both vaccines 1 year after vaccination supports the implementation of an early-life SARS-CoV-2 vaccine.

Early post-infection treatment of SARS-CoV-2 infected macaques with human convalescent plasma with high neutralizing activity had no antiviral effects but moderately reduced lung inflammation.

Early in the SARS-CoV-2 pandemic, there was a high level of optimism based on observational studies and small controlled trials that treating hospitalized patients with convalescent plasma from COVID-19 survivors (CCP) would be an important immunotherapy. However, as more data from controlled trials became available, the results became disappointing, with at best moderate evidence of efficacy when CCP with high titers of neutralizing antibodies was used early in infection. To better understand the potential therapeutic efficacy of CCP, and to further validate SARS-CoV-2 infection of macaques as a reliable animal model for testing such strategies, we inoculated 12 adult rhesus macaques with SARS-CoV-2 by intratracheal and intranasal routes. One day later, 8 animals were infused with pooled human CCP with a high titer of neutralizing antibodies (RVPN NT50 value of 3,003), while 4 control animals received normal human plasma. Animals were monitored for 7 days. Animals treated with CCP had detectable but low levels of antiviral antibodies after infusion. In comparison to the control animals, CCP-treated animals had similar levels of viral RNA in upper and lower respiratory tract secretions, similar detection of viral RNA in lung tissues by in situ hybridization, but lower amounts of infectious virus in the lungs. CCP-treated animals had a moderate, but statistically significant reduction in interstitial pneumonia, as measured by comprehensive lung histology. Thus overall, therapeutic benefits of CCP were marginal and inferior to results obtained earlier with monoclonal antibodies in this animal model. By highlighting strengths and weaknesses, data of this study can help to further optimize nonhuman primate models to provide proof-of-concept of intervention strategies, and guide the future use of convalescent plasma against SARS-CoV-2 and potentially other newly emerging respiratory viruses.

Corrigendum: Craniomaxillofacial Trauma in Dogs-Part I: Fracture Location, Morphology and Etiology.

[This corrects the article DOI: 10.3389/fvets.2020.00241.].

SARS-CoV-2 Infection of Rhesus Macaques Treated Early with Human COVID-19 Convalescent Plasma.

Human clinical studies investigating use of convalescent plasma (CP) for treatment of coronavirus disease 2019 (COVID-19) have produced conflicting results. Outcomes in these studies may vary at least partly due to different timing of CP administration relative to symptom onset. The mechanisms of action of CP include neutralizing antibodies but may extend beyond virus neutralization to include normalization of blood clotting and dampening of inflammation. Unresolved questions include the minimum therapeutic titer in the CP units or CP recipient as well as the optimal timing of administration. Here, we show that treatment of macaques with CP within 24 h of infection does not reduce viral shedding in nasal or lung secretions compared to controls and does not detectably improve any clinical endpoint. We also demonstrate that CP administration does not impact viral sequence diversity in vivo, although the selection of a viral sequence variant in both macaques receiving normal human plasma was suggestive of immune pressure. Our results suggest that CP, administered to medium titers, has limited efficacy, even when given very early after infection. Our findings also contribute information important for the continued development of the nonhuman primate model of COVID-19. These results should inform interpretation of clinical studies of CP in addition to providing insights useful for developing other passive immunotherapies and vaccine strategies. IMPORTANCE Antiviral treatment options for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remain very limited. One treatment that was explored beginning early in the pandemic (and that is likely to be tested early in future pandemics) is plasma collected from people who have recovered from coronavirus disease 2019 (COVID-19), known as convalescent plasma (CP). We tested if CP reduces viral shedding or disease in a nonhuman primate model. Our results demonstrate that administration of CP 1 day after SARS-CoV-2 infection had no significant impact on viral loads, clinical disease, or sequence diversity, although treatment with normal human plasma resulted in selection of a specific viral variant. Our results demonstrate that passive immunization with CP, even during early infection, provided no significant benefit in a nonhuman primate model of SARS-CoV-2 infection.

Early post-infection treatment of SARS-CoV-2 infected macaques with human convalescent plasma with high neutralizing activity reduces lung inflammation.

Early in the SARS-CoV-2 pandemic, there was a high level of optimism based on observational studies and small controlled trials that treating hospitalized patients with convalescent plasma from COVID-19 survivors (CCP) would be an important immunotherapy. However, as more data from controlled trials became available, the results became disappointing, with at best moderate evidence of efficacy when CCP with high titers of neutralizing antibodies was used early in infection. To better understand the potential therapeutic efficacy of CCP, and to further validate SARS-CoV-2 infection of macaques as a reliable animal model for testing such strategies, we inoculated 12 adult rhesus macaques with SARS-CoV-2 by intratracheal and intranasal routes. One day later, 8 animals were infused with pooled human CCP with a high titer of neutralizing antibodies (RVPN NT 50 value of 3,003), while 4 control animals received normal human plasma. Animals were monitored for 7 days. Animals treated with CCP had detectable levels of antiviral antibodies after infusion. In comparison to the control animals, they had similar levels of virus replication in the upper and lower respiratory tract, but had significantly reduced interstitial pneumonia, as measured by comprehensive lung histology. By highlighting strengths and weaknesses, data of this study can help to further optimize nonhuman primate models to provide proof-of-concept of intervention strategies, and guide the future use of convalescent plasma against SARS-CoV-2 and potentially other newly emerging respiratory viruses. AUTHOR SUMMARY: The results of treating SARS-CoV-2 infected hospitalized patients with COVID-19 convalescent plasma (CCP), collected from survivors of natural infection, have been disappointing. The available data from various studies indicate at best moderate clinical benefits only when CCP with high titer of neutralizing antibodies was infused early in infection. The macaque model of SARS-CoV-2 infection can be useful to gain further insights in the value of CCP therapy. In this study, animals were infected with SARS-CoV-2 and the next day, were infused with pooled human convalescent plasma, selected to have a very high titer of neutralizing antibodies. While administration of CCP did not result in a detectable reduction in virus replication in the respiratory tract, it significantly reduced lung inflammation. These data, combined with the results of monoclonal antibody studies, emphasize the need to use products with high titers of neutralizing antibodies, and guide the future development of CCP-based therapies.

Early treatment with a combination of two potent neutralizing antibodies improves clinical outcomes and reduces virus replication and lung inflammation in SARS-CoV-2 infected macaques.

There is an urgent need for effective therapeutic interventions against SARS-CoV-2, including new variants that continue to arise. Neutralizing monoclonal antibodies have shown promise in clinical studies. We investigated the therapeutic efficacy of a combination of two potent monoclonal antibodies, C135-LS and C144-LS that carry half-life extension mutations, in the rhesus macaque model of COVID-19. Twelve young adult macaques (three groups of four animals) were inoculated intranasally and intra-tracheally with a high dose of SARS-CoV-2 and 24 hours later, treated intravenously with a high (40 mg/kg) or low (12 mg/kg) dose of the C135-LS and C144-LS antibody combination, or a control monoclonal antibody. Animals were monitored for 7 days. Compared to the control animals, animals treated with either dose of the anti-SARS-CoV-2 antibodies showed similarly improved clinical scores, lower levels of virus replication in upper and lower respiratory tract, and significantly reduced interstitial pneumonia, as measured by comprehensive lung histology. In conclusion, this study provides proof-of-concept in support of further clinical development of these monoclonal antibodies against COVID-19 during early infection.

Clinical and videofluoroscopic outcomes of laparoscopic treatment for sliding hiatal hernia and associated gastroesophageal reflux in brachycephalic dogs.

OBJECTIVE: To describe a laparoscopic technique for treatment of sliding hiatal hernia (SHH) and associated gastroesophageal reflux (GER) in brachycephalic dogs and document clinical and videofluoroscopic outcomes postoperatively. STUDY DESIGN: Prospective clinical trial. ANIMALS: Eighteen client-owned dogs. METHODS: A three-port laparoscopic approach was used. Intracorporeal suturing was used for hiatal plication and esophagopexy, and left-sided laparoscopic or laparoscopic-assisted gastropexy was performed. A standardized canine dysphagia assessment tool (CDAT) questionnaire was completed by owners pre- and postoperatively. Videofluoroscopic swallow studies (VFSS) were used to evaluate esophageal function, and impedance planimetry was used to assess lower esophageal sphincter geometry preoperatively and in a subset of dogs postoperatively. RESULTS: Median age was 27.5 (range 5-84) months. Conversion to open surgery was necessary in 1 (5.5%) of 18 dogs. Regurgitation after eating, and associated with activity/exercise, improved significantly when comparing pre- and postoperative CDAT assessments. Hiatal hernia and GER severity scores improved significantly between pre- and postoperative VFSS assessments, whereas SHH and GER frequency scores did not. One dog developed pneumothorax intraoperatively, underwent cardiopulmonary arrest, and died. Minor complications included splenic (n = 6) and hepatic lacerations (n = 3) that did not require specific therapy. CONCLUSION: A laparoscopic approach to treatment of SHH and GER led to improvements in clinical and VFSS indices in the majority of brachycephalic dogs. However, a subset of dogs still demonstrated some clinical signs postoperatively. CLINICAL RELEVANCE: In experienced hands, laparoscopic treatment of SHH and GER offers a minimally invasive alternative to open surgery.

Evaluation of radiographic predictors of left heart enlargement in dogs with known or suspected cardiovascular disease.

Radiographic assessment of heart size is important for clinical management of dogs with cardiovascular disease (CVDz). We sought to compare the ability of vertebral heart size (VHS), vertebral left atrial size (VLAS), and radiologists' assessment of left atrial size (RadLAE) to predict echocardiographic left atrial size (EchoLAE), an important marker of left heart disease severity. We also compared the ability of VHS and VLAS to predict echocardiographic criteria for ACVIM stage B2 (EchoB2) in dogs with myxomatous mitral valve disease (MMVD). This prospective observational study enrolled 183 dogs with known or suspected CVDz that had an echocardiographic examination and thoracic radiographs obtained within 24 h. Compared to increased VHS, VLAS >2.3 was a more accurate predictor of EchoLAE (P = .002). VLAS >2.3 and RadLAE (both P <.0001) were independently associated with EchoLAE but VHS was not (P = .45). Optimal cutoffs for VLAS and VHS to predict EchoLAE were >2.3 vertebrae (sensitivity [Sn] = 90.3%, specificity [Sp] = 73.6%) and >11.1 vertebrae (Sn = 75.8%, Sp = 76.0%), respectively. Diagnostic accuracy of VLAS (AUC 0.84, 95% CI 0.73-0.92) and VHS (AUC 0.78, 95% CI 0.66-0.88) to predict EchoB2 in dogs with subclinical MMVD (n = 64) were not significantly different (P = .17). Results demonstrate that VLAS and RadLAE were superior indicators of EchoLAE compared to VHS in dogs with known or suspected CVDz. Both VLAS and VHS are useful predictors of EchoB2 in dogs with subclinical MMVD. When echocardiography is unavailable, VLAS represents a useful radiographic measurement to aid clinical management of dogs with known or suspected CVDz.

Induction of Irritation and Inflammation in a 3D Innervated Tissue Model of the Human Cornea.

Detection of slight changes in the chemical, thermal, and physical environments of the ocular surface is necessary to protect eyesight. The cornea, as the most densely innervated peripheral tissue in the body, can be damaged as a result of caustic chemical exposure. Such damage can be painful and debilitating, thus underscoring the need to understand mechanisms of ocular irritation. Both ethical and translational limitations regarding the use of animal subjects in part drive the need to develop relevant in vitro cell and tissue models that emulate the physiology of the human cornea. In this study, we utilized our 3D in vitro cornea-like tissue model to study the effects of irritation mediated by transient receptor potential (TRP) channels vanilloid 1 and ankyrin 1 (TRPV1; TRPA1) in response to allyl isothiocyanate (AITC) stimulation. Changes in gene expression were analyzed to characterize wound healing responses of the epithelial, stromal, and neuronal cell populations in the corneal tissue models. Key findings of the study include indications of wound healing, such as stromal myofibroblast differentiation and epithelial barrier re-establishment, amplification of pro-inflammatory cytokines, and downstream ECM protein remodeling due to irritation with the addition of sensory innervation. This study further establishes this in vitro tissue model as a useful tool for studying corneal irritation in vitro in a holistic manner with promise as a novel and sensitive tool for studying chemical exposures and subsequent responses.

Craniomaxillofacial Trauma in Dogs-Part II: Association Between Fracture Location, Morphology and Etiology.

Treatment of craniomaxillofacial (CMF) trauma in dogs requires a thorough understanding of the CMF skeletal structures involved. The human medical literature has several examples of CMF trauma and fracture classification, including the classically described Le Fort fractures. The recent classification schemes require large studies using computed tomography (CT). In the veterinary medical literature, such studies are lacking. The aims of part II of this retrospective study were to use a large number of CT studies of dogs evaluated for CMF trauma to determine whether specific fracture locations in the CMF region occur concurrently, and whether trauma etiology influences fracture morphology. This information may then be used to form a fracture classification scheme in the future. The medical records and CT studies of 165 dogs over a 10-year period were evaluated. The skeletal location of CMF fractures as well as the severity of displacement and fragmentation of each fracture was recorded. Dogs' demographic data and trauma etiology were also recorded. Fractured portions of the mandible tended to occur with fractures of adjacent bones, with the major exception of symphyseal separation, which occurred simultaneously with fractures of the cribriform plate. Fractures of the maxillary bone were accompanied by many concurrent fractures affecting the majority of the midface, skull base, and cranial vault. When the zygomatic bone was fractured, the other bones comprising the orbit also tended to fracture. Fractures of the relatively superficially located frontal and nasal bones were often accompanied by fractures of the skull base. Fracture etiology influenced fracture morphology such that vehicular trauma resulted in a relatively higher number of severely displaced and comminuted fractures than did other trauma etiologies. This study provides examples of fractures that, when found, should prompt veterinarians to look for additional injuries in specific locations. In addition, it further highlights the need for thorough CT evaluation of the entire CMF region, even when clinically apparent fractures appear relatively superficial.

Craniomaxillofacial Trauma in Dogs-Part I: Fracture Location, Morphology and Etiology.

Treatment of craniomaxillofacial (CMF) trauma in dogs often requires a multidisciplinary approach and a thorough understanding of the CMF skeletal structures involved. The aim of this retrospective study was to use a large number of CT studies of dogs evaluated for CMF trauma and to describe fracture location and morphology in relation to demographic data and trauma etiology. The medical records and CT studies of 165 dogs over a 10-year period were evaluated. The skeletal location of CMF fractures as well as the severity of displacement and fragmentation of each fracture was recorded. Patient demographic data and trauma etiology were also recorded. Animal bites accounted for the majority of trauma (50%), followed by unknown trauma (15%), vehicular accidents (13%), and blunt force trauma (13%). Small dogs, <10 kg, and juveniles accounted for the majority of patients (41.8 and 25.5%, respectively). The most likely bone or region to be fractured was the maxillary bone, followed by the premolar and molar regions of the mandible. Up to 37 bones or regions were fractured in any given patient, with an average of 8.2 fractured bones or regions per dog. The most commonly fractured location varied according to trauma etiology. Specifically, vehicular accidents tended to result in more locations with a higher probability of fracture than other trauma types. A major conclusion from this study is that every bone of the CMF region was fractured in at least one case and many cases had a large number of fractured regions. Thus, the need for comprehensive assessment of the entire CMF region, preferably using CT, is underscored.

Ultrasonographic characterization of cervical lymph nodes in healthy dogs.

Ultrasonography provides a minimally invasive method to evaluate the cervical lymph nodes in dogs as part of staging head and neck cancer; however, standardized cohesive reports of the normal lymph node size and appearance are lacking. The purpose of this prospective, descriptive, reference interval study was to characterize the ultrasonographic appearance of cervical lymph nodes in 27 clinically healthy dogs. The size, shape, echogenicity, and margination of the mandibular, medial retropharyngeal, and superficial cervical lymph nodes were evaluated and correlated with age, breed, sex, body weight, and stage of dental disease. The appearance of the lymph nodes was variable among the population. The majority were cigar or ovoid in shape with smooth margins. The echogenicity of the mandibular lymph nodes was predominantly hypoechoic whereas the medial retropharyngeal lymph nodes were predominantly isoechoic compared to the salivary glands. The superficial cervical lymph nodes were predominantly hyperechoic to the surrounding muscle bellies. Higher body weight and younger age were associated with increased size in the medial retropharyngeal and superficial cervical lymph nodes (P-values < .05). Sex and breed were not found to correlate with lymph node characteristics, and there was no trend noted in lymph node appearance associated with dental disease. These data establish normal parameters for the ultrasonographic size and appearance of cervical lymph nodes in dogs and can provide a reference of comparison for future canine cervical ultrasounds, which can be considered for routine staging procedures for head and neck cancer.

Videofluoroscopic Evaluation of the Pharynx and Upper Esophageal Sphincter in the Dog: A Systematic Review of the Literature.

Background: Diseases of the pharynx and upper esophageal sphincter can result in debilitating respiratory difficulty, dysphagia or a combination of both. An exact diagnosis is essential to properly prognosticate and guide therapy. Videofluoroscopic assessment of the pharynx and upper esophageal sphincter with or without orally administered contrast material is the diagnostic of choice for many diseases as both anatomic and functional information is gleaned. The purpose of this review is to assess for continuity in imaging protocols across institutions and to record quantitative and qualitative parameters used for analysis of videofluoroscopy of the pharynx and upper esophageal sphincter in dogs. Methods: A systematic literature search was performed including articles published in peer-reviewed veterinary journals involving the topic of videofluoroscopy of the pharynx and upper esophageal sphincter through August 1, 2018. Specifics of study acquisition technique were recorded. Quantitative and qualitative videofluoroscopic parameters were recorded and compared across institutions where appropriate using one-way ANOVA with p ≤ 0.05 being considered significant. Results: Videofluoroscopy of the pharynx and upper esophageal sphincter is performed either in right lateral or standing postures depending on the institution. Bolus size and consistency used during contrast videofluoroscopy of swallowing differs between institutions. Some institutions evaluate videofluoroscopic studies using qualitative criteria while others apply quantitative measures. Reported quantitative measures include inter-swallow interval, swallow rate, jaw cycles per swallow ratio, time to upper esophageal opening, maximal pharyngeal contraction, maximum laryngeal excursion, upper esophageal closure, epiglottic re-opening, and pharyngeal constriction ratio. Measurement outcomes are significantly different between institutions and when bolus size/consistency is variable when assessing healthy dogs. Conclusions: The current peer-reviewed literature on fluoroscopic evaluation of the pharynx and UES in dogs shows a lack of standardization regarding imaging protocol. There is not a standard set of quantitative criteria applied amongst the institutions and there are significant differences in the outcomes obtained from videofluoroscopic assessment of swallowing suggesting significant inter-observer or inter-institutional variability. A consensus statement regarding imaging protocol and what parameters should be used to interpret airway and swallowing videofluoroscopic studies of the pharynx and UES in dogs is needed along with targeted analysis of observer variability.

Corneal pain and experimental model development.

The cornea is a valuable tissue for studying peripheral sensory nerve structure and regeneration due to its avascularity, transparency, and dense innervation. Somatosensory innervation of the cornea serves to identify changes in environmental stimuli at the ocular surface, thereby promoting barrier function to protect the eye against injury or infection. Due to regulatory demands to screen ocular safety of potential chemical exposure, a need remains to develop functional human tissue models to predict ocular damage and pain using in vitro-based systems to increase throughput and minimize animal use. In this review, we summarize the anatomical and functional roles of corneal innervation in propagation of sensory input, corneal neuropathies associated with pain, and the status of current in vivo and in vitro models. Emphasis is placed on tissue engineering approaches to study the human corneal pain response in vitro with integration of proper cell types, controlled microenvironment, and high-throughput readouts to predict pain induction. Further developments in this field will aid in defining molecular signatures to distinguish acute and chronic pain triggers based on the immune response and epithelial, stromal, and neuronal interactions that occur at the ocular surface that lead to functional outcomes in the brain depending on severity and persistence of the stimulus.

Human Corneal Tissue Model for Nociceptive Assessments.

New in vitro tissue models to mimic in vivo conditions are needed to provide insight into mechanisms involved in peripheral pain responses, potential therapeutic strategies to address these responses, and to replace animal models for such indications. For example, the rabbit cornea Draize test has become the standard method used for decades to screen ophthalmic drug and consumer product toxicity. In vitro tissue models with functional innervation have the potential to replace in vivo animal testing and provide sophisticated bench tools to study ocular nociception and its amelioration. Herein, full thickness, innervated, 3D human corneal tissues are grown under physiologically relevant culture conditions to study nociceptive-related responses, by mimicking ocular environmental cues, including intraocular pressure (IOP) and tear flow (TF). Capsaicin, a chili pepper-derived irritant known to cause a burning sensation in mammalian tissues is utilized as a nociceptive stimulant to induce pain, while subsequent serum treatment is used to mimic healing. Pain mediators released upon capsaicin stimulation and cell regrowth after serum treatment are characterized to assess ocular responses in this new, innervated, human corneal tissue system for comparison of outcomes to established animal and related responses.

Ultrasonography does not consistently detect parathyroid glands in healthy cats.

Ultrasound is used to evaluate the parathyroid glands of several species but there are limited reports of its use in cats. With this prospective anatomic study, we hypothesized that ultrasound could identify two parathyroid glands as hypoechoic nodules associated with each thyroid lobe and that a normal size range could be established. Six cat cadavers were imaged with ultrasound and histopathology of the thyroid and parathyroid tissue was performed for comparison. In addition, clinically healthy adult cats were prospectively recruited and placed in Group 1 (2-6 years; n = 11) or Group 2 (7-13 years; n = 9). Ultrasound of the cervical region was performed using a 7-15 MHz linear transducer. Number, size, and location of all hypoechoic nodules within or immediately adjacent to the thyroid lobes were documented. Ultrasound identified between 0-6 hypoechoic nodules per thyroid lobe in cat cadavers and between 0-3 hypoechoic nodules per thyroid lobe in clinically healthy cats, which does not correlate with the normal anatomy. In conclusion, parathyroid glands were frequently not ultrasonographically observed or were not distinguishable from thyroid tissue and this problem was worse in older cats because of the prevalence of nodular thyroid lesions, which primarily included foci of adenomatous hyperplasia.

The prevalence of dynamic pharyngeal collapse is high in brachycephalic dogs undergoing videofluoroscopy.

The aim of this retrospective study was to determine the frequency of pharyngeal collapse in a large group of brachycephalic dogs undergoing videofluoroscopic assessment of swallowing or airway diameter. We hypothesized that brachycephalic dogs would have pharyngeal collapse more frequently than dolichocephalic or mesocephalic dogs with or without airway collapse. The medical records database was searched for brachycephalic dogs undergoing videofluoroscopy of swallowing or airway diameter between January 1, 2006 and December 31, 2015. A cohort of dolichocephalic/mesocephalic dogs with videofluoroscopically confirmed airway collapse was age and time matched for comparison. A control group of dolichocephalic/mesocephalic dogs that did not have documented airway collapse was also evaluated. All fluoroscopic studies were assessed by a board certified veterinary radiologist for the presence and degree of pharyngeal collapse. Results demonstrate that pharyngeal collapse was significantly more common in brachycephalic dogs (58/82; 72%) than in nonbrachycephalic dogs with (7/25; 28%) and without (2/30; 7%) airway collapse. Pharyngeal collapse is more prevalent in brachycephalic dogs undergoing videofluoroscopy than in dolichocephalic/mesocephalic dogs with or without airway collapse.

Diagnostic outcome of contrast videofluoroscopic swallowing studies in 216 dysphagic dogs.

Determining the anatomic and functional origin for dysphagia is critical for development of an appropriate therapeutic plan and determination of the prognosis. The purpose of this retrospective study was to report the quantitative and qualitative outcome of contrast videofluoroscopic swallowing studies in a large cohort of dysphagic dogs presenting to a tertiary veterinary care hospital. The videofluoroscopic swallowing studies were reviewed to generate values for pharyngeal constriction ratio, timing of swallowing events (maximum pharyngeal contraction, opening of upper esophageal sphincter, closing of upper esophageal sphincter, and reopening of epiglottis), type of esophageal peristalsis generated, and esophageal transit time. One or more anatomic locations for origin of dysphagia were assigned (pharyngeal, cricopharyngeal, esophageal (primary motility disorder), other esophageal (stricture, vascular ring anomaly, mass), lower esophageal sphincter/hiatus. Sixty-one of 216 studies (28%) were deemed unremarkable. Twenty-seven of 216 dogs (13%) had pharyngeal dysphagia, 17/216 dogs (8%) had cricopharyngeal dysphagia, 98/216 dogs (45%) had dysphagia secondary to esophageal dysmotility, 19/216 dogs (9%) had dysphagia secondary to focal esophageal disorders, and 97/216 dogs (45%) had dysphagia of lower esophageal sphincter/hiatus origin. Multiple abnormalities were present in 82/216 (38%) dogs. Elevated pharyngeal constriction ratio was associated with pharyngeal, cricopharyngeal, and esophageal motility disorders, delayed upper esophageal sphincter opening was associated with cricopharyngeal disorders, a lower percentage of primary esophageal peristaltic waves was associated with cricopharyngeal, pharyngeal, or primary esophageal motility disorders. In conclusion, videofluoroscopic swallowing studies was pivotal in the diagnosis of dysphagia with 155/216 (72%) dogs receiving a final diagnosis.

INDIRECT COMPUTED TOMOGRAPHIC LYMPHOGRAPHY FOR ILIOSACRAL LYMPHATIC MAPPING IN A COHORT OF DOGS WITH ANAL SAC GLAND ADENOCARCINOMA: TECHNIQUE DESCRIPTION.

Sentinel lymph node mapping can help to direct surgical oncologic staging and metastatic disease detection in patients with complex lymphatic pathways. We hypothesized that indirect computed tomographic lymphography (ICTL) with a water-soluble iodinated contrast agent would successfully map lymphatic pathways of the iliosacral lymphatic center in dogs with anal sac gland carcinoma, providing a potential preoperative method for iliosacral sentinel lymph node identification in dogs. Thirteen adult dogs diagnosed with anal sac gland carcinoma were enrolled in this prospective, pilot study, and ICTL was performed via peritumoral contrast injection with serial caudal abdominal computed tomography scans for iliosacral sentinel lymph node identification. Technical and descriptive details for ICTL were recorded, including patient positioning, total contrast injection volume, timing of contrast visualization, and sentinel lymph nodes and lymphatic pathways identified. Indirect CT lymphography identified lymphatic pathways and sentinel lymph nodes in 12/13 cases (92%). Identified sentinel lymph nodes were ipsilateral to the anal sac gland carcinoma in 8/12 and contralateral to the anal sac gland carcinoma in 4/12 cases. Sacral, internal iliac, and medial iliac lymph nodes were identified as sentinel lymph nodes, and patterns were widely variable. Patient positioning and timing of imaging may impact successful sentinel lymph node identification. Positioning in supported sternal recumbency is recommended. Results indicate that ICTL may be a feasible technique for sentinel lymph node identification in dogs with anal sac gland carcinoma and offer preliminary data to drive further investigation of iliosacral lymphatic metastatic patterns using ICTL and sentinel lymph node biopsy.