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Cancer immunotherapy remains limited by poor antigenicity and a regulatory tumor microenvironment (TME). Here, we create "onion-like" multi-lamellar RNA lipid particle aggregates (LPAs) to substantially enhance the payload packaging and immunogenicity of tumor mRNA antigens. Unlike current mRNA vaccine designs that rely on payload packaging into nanoparticle cores for Toll-like receptor engagement in immune cells, systemically administered RNA-LPAs activate RIG-I in stromal cells, eliciting massive cytokine/chemokine response and dendritic cell/lymphocyte trafficking that provokes cancer immunogenicity and mediates rejection of both early- and late-stage murine tumor models. In client-owned canines with terminal gliomas, RNA-LPAs improved survivorship and reprogrammed the TME, which became "hot" within days of a single infusion. In a first-in-human trial, RNA-LPAs elicited rapid cytokine/chemokine release, immune activation/trafficking, tissue-confirmed pseudoprogression, and glioma-specific immune responses in glioblastoma patients. These data support RNA-LPAs as a new technology that simultaneously reprograms the TME while eliciting rapid and enduring cancer immunotherapy.
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Inmunoterapia , Lípidos , ARN , Microambiente Tumoral , Animales , Perros , Femenino , Humanos , Ratones , Antígenos de Neoplasias/inmunología , Neoplasias Encefálicas/terapia , Neoplasias Encefálicas/inmunología , Vacunas contra el Cáncer/inmunología , Vacunas contra el Cáncer/uso terapéutico , Línea Celular Tumoral , Citocinas/metabolismo , Células Dendríticas/inmunología , Células Dendríticas/metabolismo , Glioblastoma/terapia , Glioblastoma/inmunología , Glioma/terapia , Glioma/inmunología , Inmunoterapia/métodos , Ratones Endogámicos C57BL , Neoplasias/terapia , Neoplasias/inmunología , ARN/química , ARN/uso terapéutico , ARN Mensajero/metabolismo , ARN Mensajero/genética , Lípidos/químicaRESUMEN
OBJECTIVE: To characterize the clinical features, neurological examination findings, diagnostic imaging results, histopathological findings, and outcome following transsphenoidal hypophysectomy (TSH) in dogs with nonfunctional sellar masses (NFSM). STUDY DESIGN: Multi-institutional retrospective study. METHODS: Medical records of dogs that underwent TSH for a NFSM were reviewed for clinical signs, physical and neurological examination findings, diagnostic imaging results, endocrine testing, surgery reports, and outcome. Magnetic resonance (MR) imaging was rereviewed, and tumors were classified using the previously described system according to pituitary tumor extension and vascular involvement. Owners of dogs that survived to discharge were contacted. RESULTS: The majority of dogs presented for mentation change (12/15). The mean pituitary to brain ratio (P/B ratio) was 1.05 (0.6-1.4). Eight dogs had a tumor imaging classification of 5B. Eleven dogs were diagnosed with a nonfunctional pituitary adenoma (NFPA). Perioperative mortality was 33% (5/15). The median survival for all dogs was 232 days (0-1658). When dogs that did not survive to discharge were excluded, the median survival time was 708 days. Seven of 10 dogs that survived the perioperative period received adjunctive therapy. Owner assessment of outcome was excellent (6/7) to good (1/7). CONCLUSION: The common presenting complaint for dogs with large NFSM causing mass effect was mentation changes. Dogs with NFPA that survived to discharge and received adjunctive therapy had good to excellent outcomes. CLINICAL SIGNIFICANCE: Transsphenoidal debulking with adjunctive therapy can be considered for the treatment of NFSM causing clinical signs of mass effect in dogs. Successful long-term outcomes are possible.
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Enfermedades de los Perros , Neoplasias Hipofisarias , Perros , Animales , Hipofisectomía/veterinaria , Hipofisectomía/efectos adversos , Hipofisectomía/métodos , Estudios Retrospectivos , Enfermedades de los Perros/diagnóstico por imagen , Enfermedades de los Perros/cirugía , Hipófisis/patología , Hipófisis/cirugía , Neoplasias Hipofisarias/cirugía , Neoplasias Hipofisarias/veterinaria , Neoplasias Hipofisarias/patología , Tirotropina , Resultado del TratamientoRESUMEN
Veterinary professionals are taught to recognize that "old age is not a disease." However, clients may have the perception that older dogs and cats undergo an unavoidable physical, mental, and behavioral decline attributable simply to old age. The veterinary team's role includes providing medical care and support to senior pets to maintain their quality of life, as well as supporting and educating clients on proper senior animal care and addressing any misconceptions about the aging process. These Guidelines describe a systematic approach to the healthcare of the senior pet that is based on an evidence-guided assessment of both healthy and unhealthy canine and feline patients. By using evidence-guided medicine, which may include conventional and integrative approaches as well as environmental management for the senior pet, the patient's quality of life can be enhanced and potentially extended during this vulnerable life stage. Developing a senior program for the veterinary practice requires appropriate training of the entire healthcare team and includes a robust client education program that focuses on the wellbeing of the senior pet. Palliative and hospice care should be included in the education and information provided for both the veterinary team and the families of senior pets.
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Enfermedades de los Gatos , Enfermedades de los Perros , Gatos , Animales , Perros , Enfermedades de los Gatos/terapia , Calidad de Vida , Enfermedades de los Perros/terapiaRESUMEN
A case of presumptive fibrocartilaginous embolic myelopathy in a pet pot-bellied pig is described in this report. This case, which was associated with a previous trauma, highlighted the importance of advanced diagnostic imaging in pigs with clinical signs consistent with a myelopathy.
Myélopathie à la suite d'une embolie fibrino-cartilagineuse présumée chez un cochon vietnamien. Ce rapport décrit un cas de myélopathie à la suite d'une embolie fibrino-cartilagineuse présumée chez un cochon vietnamien. Ce cas, qui était associé avec un traumatisme antérieur, met en évidence l'importance de l'imagerie diagnostique avancée chez les porcs avec des signes cliniques compatibles avec une myélopathie.(Traduit par Dr Serge Messier).
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Enfermedades de los Cartílagos , Embolia , Enfermedades de la Médula Espinal , Enfermedades de los Porcinos , Animales , Enfermedades de los Cartílagos/diagnóstico , Enfermedades de los Cartílagos/veterinaria , Embolia/veterinaria , Enfermedades de la Médula Espinal/diagnóstico , Enfermedades de la Médula Espinal/veterinaria , Porcinos , Enfermedades de los Porcinos/diagnósticoRESUMEN
Translation of nanoparticles (NPs) into human clinical trials for patients with refractory cancers has lagged due to unknown biologic reactivities of novel NP designs. To overcome these limitations, simple well-characterized mRNA lipid-NPs have been developed as cancer immunotherapeutic vaccines. While the preponderance of RNA lipid-NPs encoding for tumor-associated antigens or neoepitopes have been designed to target lymphoid organs, they remain encumbered by the profound intratumoral and systemic immunosuppression that may stymie an activated T cell response. Herein, we show that systemic localization of untargeted tumor RNA (derived from whole transcriptome) encapsulated in lipid-NPs, with excess positive charge, primes the peripheral and intratumoral milieu for response to immunotherapy. In immunologically resistant tumor models, these RNA-NPs activate the preponderance of systemic and intratumoral myeloid cells (characterized by coexpression of PD-L1 and CD86). Addition of immune checkpoint inhibitors (ICIs) (to animals primed with RNA-NPs) augments peripheral/intratumoral PD-1+CD8+ cells and mediates synergistic antitumor efficacy in settings where ICIs alone do not confer therapeutic benefit. These synergistic effects are mediated by type I interferon released from plasmacytoid dendritic cells (pDCs). In translational studies, personalized mRNA-NPs were safe and active in a client-owned canine with a spontaneous malignant glioma. In summary, we demonstrate widespread immune activation from tumor loaded RNA-NPs concomitant with inducible PD-L1 expression that can be therapeutically exploited. While immunotherapy remains effective for only a subset of cancer patients, combination therapy with systemic immunomodulating RNA-NPs may broaden its therapeutic potency.
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Glioma/tratamiento farmacológico , Inmunoterapia , Lípidos/administración & dosificación , Nanopartículas/administración & dosificación , Medicina de Precisión , Animales , Antígeno B7-2/antagonistas & inhibidores , Antígeno B7-2/genética , Antígeno B7-2/inmunología , Antígeno B7-H1/antagonistas & inhibidores , Antígeno B7-H1/genética , Antígeno B7-H1/inmunología , Linfocitos T CD8-positivos/efectos de los fármacos , Linfocitos T CD8-positivos/inmunología , Vacunas contra el Cáncer/inmunología , Vacunas contra el Cáncer/uso terapéutico , Células Dendríticas/inmunología , Modelos Animales de Enfermedad , Perros , Glioma/inmunología , Glioma/patología , Glioma/veterinaria , Humanos , Lípidos/química , Lípidos/inmunología , Activación de Linfocitos/inmunología , Nanopartículas/química , ARN Neoplásico/química , ARN Neoplásico/genética , ARN Neoplásico/inmunología , Transcriptoma/genéticaRESUMEN
This study used a cross-sectional survey designed to inquire about antiepileptic drug (AED) use in newly diagnosed idiopathic epileptic dogs among board-certified emergency and neurology specialists. Results were obtained from 300 completed surveys by 128 board-certified neurologists and 172 board-certified emergency and critical care (ECC) specialists. Case volume was slightly different between groups, with 36% of neurologists and 18% of ECC specialists managing >50 cases of first-time canine seizure patients yearly. The initial AED of choice was similar between the groups, with 66% of neurologists and 64% of ECC specialists using phenobarbital and 16% of neurologists and 26% of ECC specialists using levetiracetam. Although most respondents gave a loading dose of phenobarbital, roughly one-fourth of neurologists did not load the drug versus 6% of ECC specialists. The total loading dose was similar between respondents (16 mg/kg) but varied in administration protocol. Approximately half of neurologists and nearly two-thirds of ECC specialists gave a higher initial dose of levetiracetam than recommended. Almost all the respondents who gave a higher initial dose of levetiracetam used 60 mg/kg IV once. Understanding the common practices in AED use may promote future discussions regarding best practices in the management of canine idiopathic epilepsy.
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Anticonvulsivantes/uso terapéutico , Enfermedades de los Perros/tratamiento farmacológico , Epilepsia/veterinaria , Veterinarios , Animales , Anticonvulsivantes/administración & dosificación , Estudios Transversales , Recolección de Datos , Perros , Esquema de Medicación , Medicina de Emergencia , Epilepsia/tratamiento farmacológico , NeurologíaRESUMEN
A 5-year-old neutered male Labrador retriever dog was presented on referral for anuric acute kidney injury (AKI) presumed secondary to parenteral gentamicin administration. Initial management of AKI included a high dose of furosemide for 16 hours which may have contributed to the renal and cochlear damage. The dog received a total of 8 intermittent hemodialysis sessions during hospitalization. While in hospital, the dog became deaf, and brainstem auditory evoked response testing revealed absence of waveforms in both ears, consistent with bilateral deafness due to severe cochleotoxicity. After 33 days of hospitalization, the dog was discharged with persistent deafness, confirmed by a second brainstem auditory evoked response.
Cochléotoxicité et dommage rénal aigu secondaires à l'administration parentérale de gentamicine à un chien. Un chien mâle castré de race Labrador âgé de 5 ans a été présenté en référence pour dommage rénal aigu anurique (AKI) présumé secondaire à l'administration parentérale de gentamicine. La gestion initiale de l'AKI incluait une dose élevée de furosémide pour 16 heures, ce qui pourrait avoir contribué aux dommages rénaux et cochléaire. Le chien a reçu un total de huit sessions intermittentes d'hémodialyse pendant son hospitalisation. Durant son séjour à l'hôpital, le chien est devenu sourd, et un test pour les potentiels évoqués auditifs du tronc cérébral a révélé l'absence d'ondes dans les deux oreilles, ce qui est cohérent avec une surdité bilatérale due à une cochléotoxicité sévère. Après 33 jours d'hospitalisation, le chien a obtenu son congé malgré une surdité persistante, confirmée par un deuxième test de potentiels évoqués auditifs du tronc cérébral.(Traduit par Dr Serge Messier).
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Lesión Renal Aguda/veterinaria , Gentamicinas , Animales , Enfermedades de los Perros , Perros , Potenciales Evocados Auditivos del Tronco Encefálico , Riñón , MasculinoRESUMEN
Electrodiagnostic testing is an integral part of the evaluation of the motor unit in many neurologic conditions. Literature about the peripheral nervous system of flying foxes ( Pteropus spp) is sparse, and reference range values for motor nerve conduction velocities in vivo have not been established in Chiropterans. The goals of this study were to determine reference range conduction velocities in flying fox for the thoracic and pelvic limb nerve. Eight Pteropus vampyrus, large flying foxes, of varying ages and gender underwent nerve conduction studies of the median nerve and sciatic-tibial nerve. Mean (SD) conduction velocity values were 49.8 (12.7) m/sec for the median nerve and 42.1 (10.2) m/sec for the sciatic-tibial nerve. Median nerve conduction velocities were not significantly faster than sciatic-tibial nerve conduction velocities, although a trend was seen. Differences by sex or age class were not statistically significant. It was also noted that flying foxes rapidly lose body heat under general anesthesia.
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Quirópteros/fisiología , Nervio Mediano/fisiología , Conducción Nerviosa/fisiología , Nervio Tibial/fisiología , Animales , Femenino , Miembro Posterior/inervación , Masculino , Alas de Animales/inervaciónRESUMEN
Objective: The objective of this study was to determine if surface electromyography (sEMG) demonstrates differences in muscle activation between normal and dogs recovering from spinal cord injury due to intervertebral disk extrusion. Animals: Two groups of client-owned small-breed chondrodysplastic-type dogs were tested. Group 1 consisted of seven ambulatory paraparetic dogs that had undergone a hemilaminectomy procedure in the T3-L3 region for intervertebral disk extrusion 1 month prior. Group 2 was made up of seven normal dogs that had no history of intervertebral disk disease or spinal surgery. Procedures: Each subject walked 10 feet on a nonslip surface for at least five gait cycles for the sEMG to capture muscle activation of the vastus lateralis and gluteus medius, bilaterally. Muscle activation was quantified as the total myoelectric output area under the curve, averaged across all gait cycles. Results: Muscle activation was significantly greater in the post-operative hemilaminectomy group (p = 0.012). There was a significant difference in muscle activation between each hindlimb in the post-operative hemilaminectomy group, but not in the normal group. The muscle activation was significantly lower on the side that underwent surgery compared to the opposite limb (p = 0.0034). Conclusion and clinical importance: Post-operative hemilaminectomy dogs have greater hindlimb muscle activation compared to normal dogs, which likely represents a lack of descending inhibition secondary to upper motor neuron syndrome. The side of surgery is correlated with decreased muscle activation. Surface EMG can be used to evaluate muscle activity in dogs recovering from spinal decompression surgery.
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BACKGROUND: No available literature supports the claim that the patellar and withdrawal (flexor) reflexes are the only reliable segmental reflexes in dogs. OBJECTIVE: Measure intra- and interobserver agreement of 8 segmental reflexes in dogs without clinical evidence of orthopedic or neurologic disease. ANIMALS: One-hundred and one client- or staff-owned dogs between 1 and 10 years of age with no clinical evidence of orthopedic disease, myelopathy, or neuromuscular disease. METHODS: Descriptive study. The intraobserver proportion of agreement (%) of responses to selected segmental reflexes in right versus left limbs by 3 observers was calculated and reported. The interobserver agreement of 2 observers of responses to selected reflexes was estimated by calculating proportions of agreement, kappa values, and 95% confidence intervals. A segmental reflex with an acceptable agreement was defined as that with a proportion of agreement ≥90% and a Kappa value ≥0.61 in both limbs. RESULTS: The intraobserver proportion of agreement for all 3 observers was high (≥95%) for the extensor carpi radialis, withdrawal, patellar, and cranial tibial reflexes. Between observers 1 and 3 and observers 2 and 3, the interobserver proportion of agreement was high (≥ 92%) for the extensor carpi radialis (κ 0.66, not determined [ND]), withdrawal (both limbs, κ ND), patellar (κ ND), and cranial tibial reflexes (κ ND). CONCLUSIONS AND CLINICAL IMPORTANCE: The extensor carpi radialis, withdrawal, patellar, and cranial tibial reflexes had a higher proportion of agreement and kappa values between 2 observers.
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Enfermedades de los Perros , Enfermedades de la Médula Espinal , Humanos , Perros , Animales , Variaciones Dependientes del Observador , Reflejo , Extremidades , Enfermedades de la Médula Espinal/veterinaria , Reproducibilidad de los ResultadosRESUMEN
Telangiectatic osteosarcoma is a rare variant of osteosarcoma histologically and clinically similar to hemangiosarcoma (HSA). This case series describes the imaging and cytologic features of four histologically confirmed telangiectatic osteosarcomas, including the use of cytochemical stains. Alkaline phosphatase (ALP) was applied to Wright-Giemsa-stained cytology slides, and Factor VIII immunohistochemistry was evaluated. Cytologic characteristics included atypical mesenchymal cells with evidence of acute and chronic hemorrhage. Telangiectatic osteosarcoma cases had positive ALP cytochemical staining, while control HSA cases were negative. Factor VIII immunohistochemistry was negative in telangiectatic osteosarcoma and positive in HSA. Cytologic diagnosis of telangiectatic osteosarcoma with positive ALP cytochemical staining can help differentiate this neoplasm from HSA.
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Neoplasias Óseas , Enfermedades de los Perros , Hemangiosarcoma , Osteosarcoma , Perros , Animales , Factor VIII , Enfermedades de los Perros/diagnóstico , Osteosarcoma/diagnóstico , Osteosarcoma/veterinaria , Hemangiosarcoma/patología , Hemangiosarcoma/veterinaria , Colorantes , Neoplasias Óseas/diagnóstico , Neoplasias Óseas/veterinariaRESUMEN
An 11-year-old male neutered Yorkshire Terrier was presented with a cervical mass that developed a draining tract. Aside from the dysphagia reported by the owner, his neurologic exam was normal. Three years prior, the patient was diagnosed with an atlantoaxial subluxation that was ventrally stabilized with polymethylmethacrylate (PMMA) and self-tapping titanium screws. There were no postoperative complications until presenting with the cervical mass and dysphagia. Computerized tomography (CT) of the cervical spine confirmed caudal migration of the PMMA and screws with an abscess surrounding the implant. A surgical explant of the PMMA and screws was performed without complication. The atlantoaxial joint remained normally aligned on postoperative radiographs. Cultures of the implant grew Streptococcus bovis. He was treated with cephalexin (22 mg/kg PO BID) for 30 days. At the time of his one-month recheck, he was swallowing normally with no neurologic deficits. He remains normal at the time of this report (17 months later). This case reports a successful explant of a chronic atlantoaxial implant infection.
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OBJECTIVE: To describe the clinical presentation and outcome of small animals that sustained ballistic trauma to the axial skeleton. DESIGN: Retrospective, multicenter observational study. SETTING: Two university teaching hospitals. ANIMALS: Twelve client-owned dogs and 1 client-owned cat sustaining ballistic trauma to the axial skeleton. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Thirteen animals sustaining ballistic trauma to the axial skeleton with complete medical records were included in this study. Twelve of 13 animals survived to discharge; 1 animal was euthanized shortly after presentation. Two animals had ophthalmic abnormalities, 9 animals had neurologic lesions, and 2 animals had no significant ophthalmic or neurologic deficits. Neurolocalization of injury included peripheral vestibular (n = 1), multifocal brain (n = 1), brainstem (n = 1), C1-C5 (n = 1), C6-T2 (n = 1), T3-L3 (n = 3), and L4-S3 (n = 1). Seven dogs underwent surgical intervention: 5 neurosurgical, 1 enucleation, and 1 laparotomy. Median hospitalization time was 6 days with a range from 1 to 31 days. CONCLUSIONS: Overall prognosis and outcome are variable and dependent on specific injury location and degree of injury.
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Enfermedades de los Gatos , Enfermedades de los Perros , Animales , Perros , Gatos , Estudios Retrospectivos , Enfermedades de los Perros/patología , Pronóstico , Registros MédicosRESUMEN
BACKGROUND: Limited recent data exists regarding discospondylitis in dogs. HYPOTHESIS/OBJECTIVES: (i) Describe the signalment, clinical and imaging findings, etiologic agents, treatment, and outcome of dogs with discospondylitis, (ii) determine diagnostic agreement between radiographs, CT, and MRI with regard to the presence of discospondylitis and its location, and (iii) determine risk factors for relapse and progressive neurological deterioration. ANIMALS: Three hundred eighty-six dogs. METHODS: Multi-institutional retrospective study. Data extracted from medical records were: signalment, clinical and examination findings, diagnostic results, treatments, complications, and outcome. Potential risk factors were recorded. Breed distribution was compared to a control group. Agreement between imaging modalities was assessed via Cohen's kappa statistic. Other analyses were performed on categorical data, using cross tabulations with chi-squared and Fisher's exact tests. RESULTS: Male dogs were overrepresented (236/386 dogs). L7-S1 (97/386 dogs) was the most common site. Staphylococcus species (23/38 positive blood cultures) were prevalent. There was a fair agreement (κ = 0.22) between radiographs and CT, but a poor agreement (κ = 0.05) between radiographs and MRI with regard to evidence of discospondylitis. There was good agreement between imaging modalities regarding location of disease. Trauma was associated with an increased risk of relapse (P = .01, OR: 9.0, 95% CI: 2.2-37.0). Prior steroid therapy was associated with an increased risk of progressive neurological dysfunction (P = .04, OR: 4.7, 95% CI: 1.2-18.6). CONCLUSIONS AND CLINICAL IMPORTANCE: Radiograph and MRI results could be discrepant in dogs with discospondylitis. Prior trauma and corticosteroids could be associated with relapse and progressive neurological dysfunction, respectively.
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Discitis , Enfermedades de los Perros , Masculino , Perros , Animales , Estudios Retrospectivos , Discitis/veterinaria , Radiografía , Imagen por Resonancia Magnética/veterinaria , Recurrencia , Enfermedades de los Perros/diagnóstico por imagen , Enfermedades de los Perros/tratamiento farmacológicoRESUMEN
To prospectively determine whether brain tumors will respond to immune checkpoint inhibitors (ICIs), we developed a novel mRNA vaccine as a viral mimic to elucidate cytokine release from brain cancer cells in vitro. Our results indicate that cytokine signatures following mRNA challenge differ substantially from ICI responsive versus non-responsive murine tumors. These findings allow for creation of a diagnostic assay to quickly assess brain tumor immunogenicity, allowing for informed treatment with ICI or lack thereof in poorly immunogenic settings.
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Messenger RNA (mRNA) has emerged as a remarkable tool for COVID-19 prevention but its use for induction of therapeutic cancer immunotherapy remains limited by poor antigenicity and a regulatory tumor microenvironment (TME). Herein, we develop a facile approach for substantially enhancing immunogenicity of tumor-derived mRNA in lipid-particle (LP) delivery systems. By using mRNA as a molecular bridge with ultrapure liposomes and foregoing helper lipids, we promote the formation of 'onion-like' multi-lamellar RNA-LP aggregates (LPA). Intravenous administration of RNA-LPAs mimics infectious emboli and elicits massive DC/T cell mobilization into lymphoid tissues provoking cancer immunogenicity and mediating rejection of both early and late-stage murine tumor models. Unlike current mRNA vaccine designs that rely on payload packaging into nanoparticle cores for toll-like receptor engagement, RNA-LPAs stimulate intracellular pathogen recognition receptors (RIG-I) and reprogram the TME thus enabling therapeutic T cell activity. RNA-LPAs were safe in acute/chronic murine GLP toxicology studies and immunologically active in client-owned canines with terminal gliomas. In an early phase first-in-human trial for patients with glioblastoma, we show that RNA-LPAs encoding for tumor-associated antigens elicit rapid induction of pro-inflammatory cytokines, mobilization/activation of monocytes and lymphocytes, and expansion of antigen-specific T cell immunity. These data support the use of RNA-LPAs as novel tools to elicit and sustain immune responses against poorly immunogenic tumors.
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The use of cannabidiol (CBD) in childhood refractory seizures has become a common therapeutic approach for specific seizure disorders in human medicine. Similarly, there is an interest in using CBD, cannabidiolic acid (CBDA) or cannabinoid-rich hemp products in the treatment of idiopathic epilepsy in dogs. We aimed to examine a small cohort in a pilot investigation using a CBD and CBDA-rich hemp product for the treatment of refractory epileptic seizures in dogs. Fourteen dogs were examined in a 24-week randomized cross-over study being provided placebo or CBD/CBDA-rich hemp extract treatment at 2 mg/kg orally every 12 h for each 12-week arm of the study. Serum chemistry, complete blood counts, serum anti-seizure medication (ASM) concentrations and epileptic seizure frequency were followed over both arms of the cross-over trial. Results demonstrated that besides a mild increase in alkaline phosphatase, there were no alterations observed on routine bloodwork at 2, 6, and 12 weeks during either arm of the study. Epileptic seizure frequency decreased across the population from a mean of 8.0 ± 4.8 during placebo treatment to 5.0 ± 3.6 with CBD/CBDA-rich hemp extract (P = 0.02). In addition, epileptic seizure event days over the 12 weeks of CBD/CBDA-rich hemp treatment were 4.1 ± 3.4, which was significantly different than during the 12 weeks of placebo treatment (5.8 ± 3.1; P =0.02). The number of dogs with a 50% reduction in epileptic activity while on treatment were 6/14, whereas 0/14 had reductions of 50% or greater while on the placebo (P = 0.02). No differences were observed in serum zonisamide, phenobarbital or bromide concentrations while on the treatment across groups. Adverse events were minimal, but included somnolence (3/14) and transient increases in ataxia (4/14) during CBD/CBDA-rich hemp extract treatment; this was not significantly different from placebo. This further indicates that providing CBD/CBDA-rich hemp extract during refractory epilepsy (only partially responsive to ASM), in conjunction with other ASM appears safe. Based on this information, the use of 2 mg/kg every 12 h of a CBD/CBDA-rich hemp extract can have benefits in reducing the incidence of epileptic seizures, when used concurrently with other ASMs.
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BACKGROUND: Magnetic resonance imaging is the method of choice for diagnosing spinal cord neoplasia, but the accuracy of designating the relationship of a neoplasm to the meninges and agreement among observers is unknown. OBJECTIVES: To determine agreement among observers and accuracy of diagnosis compared with histology when diagnosing lesion location based on relationship to the meninges. ANIMALS: Magnetic resonance images from 53 dogs with intradural extramedullary and intramedullary spinal neoplasms and 17 dogs with degenerative myelopathy. METHODS: Six observers were supplied with 2 sets of 35 images at different time points and asked to designate lesion location. Agreement in each set was analyzed using kappa (κ) statistics. We tabulated total correct allocations and calculated sensitivity, specificity, and likelihood ratios for location designation from images compared with known histologic location for lesions confined to 1 location only. RESULTS: Agreement in the first set of images was moderate (κ = 0.51; 95% confidence interval [CI], 0.43-0.58) and in the second, substantial (κ = 0.69; 95% CI, 0.66-0.79). In the accuracy study, 180 (75%) of the 240 diagnostic calls were correct. Sensitivity and specificity were moderate to high for all compartments, except poor sensitivity was found for intradural extramedullary lesions. Positive likelihood ratios were high for intradural extramedullary lesions and degenerative myelopathy. CONCLUSIONS AND CLINICAL IMPORTANCE: Overall accuracy in diagnosis was reasonable, and positive diagnostic calls for intradural extramedullary lesions and negative calls for intramedullary lesions are likely to be helpful. Observers exhibited considerable disagreement in designation of lesions relationship to the meninges.
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Enfermedades de los Perros , Enfermedades de la Médula Espinal , Neoplasias de la Médula Espinal , Animales , Enfermedades de los Perros/diagnóstico por imagen , Perros , Imagen por Resonancia Magnética/veterinaria , Médula Espinal , Enfermedades de la Médula Espinal/diagnóstico por imagen , Enfermedades de la Médula Espinal/veterinaria , Neoplasias de la Médula Espinal/diagnóstico por imagen , Neoplasias de la Médula Espinal/veterinariaRESUMEN
BACKGROUND: Non-suppurative encephalitides in a variety of species, including humans and dogs, have been linked to infection by astroviruses and bornaviruses. HYPOTHESIS/OBJECTIVES: To determine whether or not ribonucleic acid of astroviruses or bornaviruses was present in the cerebrospinal fluid (CSF) of dogs with clinically diagnosed meningoencephalomyelitis of unknown etiology (MUE). ANIMALS: Twenty-five client-owned dogs evaluated by CSF analysis at a single university referral hospital. METHODS: Prospective case-control study. Cerebrospinal fluid was collected from clinically diagnosed MUE and control cases and evaluated by reverse-transcriptase polymerase chain reaction for the presence of astrovirus and bornavirus. RESULTS: Neither astrovirus nor bornavirus nucleic acids were identified in CSF collected from 20 clinically diagnosed MUE and 5 control cases. CONCLUSIONS AND CLINICAL IMPORTANCE: The negative results of this investigation suggest that astrovirus and bornavirus are not commonly detectable in CSF of dogs with MUE.
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Infecciones por Astroviridae/veterinaria , Astroviridae , Bornaviridae , Enfermedades de los Perros/virología , Meningoencefalitis/veterinaria , Infecciones por Mononegavirales/veterinaria , Animales , Infecciones por Astroviridae/líquido cefalorraquídeo , Infecciones por Astroviridae/virología , Estudios de Casos y Controles , Enfermedades de los Perros/líquido cefalorraquídeo , Perros , Femenino , Masculino , Meningoencefalitis/líquido cefalorraquídeo , Meningoencefalitis/virología , Infecciones por Mononegavirales/líquido cefalorraquídeo , Infecciones por Mononegavirales/virología , Estudios ProspectivosRESUMEN
OBJECTIVES: The aim of this study was to compile an overview of the clinical features of intracranial complication of otitis media/interna (OMI) in cats managed across five veterinary referral hospitals. Of additional interest were culture results that could inform empirical antibiotic selection, as well as outcome with both medical and surgical management. METHODS: A retrospective medical record review was conducted at five veterinary referral practices to identify cats with a diagnosis of intracranial complication secondary to OMI between 2009 and 2017. Clinical features, diagnostic findings, treatment and outcome were recorded. RESULTS: At total of 19 cats were identified. Sixty-three percent had no previous history of ear infection. Otoscopic examination was normal in 47% of cases. The most common bacterial isolate was Pasteurella multocida, which was identified in 24% of cases. Outcome was successful for 83% of cats managed with ventral bulla osteotomy (VBO) and in 66% of cats managed without surgical intervention. CONCLUSIONS AND RELEVANCE: Clinical suspicion of intracranial complications of OMI should remain high in cats with central vestibular disease even if otoscopic examination is normal. Antibiotic selection should be based on a culture and sensitivity; however, initial antibiotic therapy should include broad-spectrum coverage with special consideration for P multocida. Cats with intracranial complications of OMI can have a good outcome with either surgical or medical management and prospective studies are needed to assess the role of VBO in enhancing recovery.