Pharmacokinetics of subcutaneous ketamine administration via the Omnipod® system in dogs.

Ketamine is an injectable anesthetic agent with analgesic and antidepressant effects that can prevent maladaptive pain. Ketamine is metabolized by the liver into norketamine, an active metabolite. Prior rodent studies have suggested that norketamine is thought to contribute up to 30% of ketamine's analgesic effect. Ketamine is usually administered as an intravenous (IV) bolus injection or continuous rate infusion (CRI) but can be administered subcutaneously (SC) and intramuscularly (IM). The Omnipod® is a wireless, subcutaneous insulin delivery device that adheres to the skin and delivers insulin as an SC CRI. The Omnipod® was used in dogs for postoperative administration of ketamine as a 1 mg/kg infusion bolus (IB) over 1 hour (h). Pharmacokinetics (PK) showed plasma ketamine concentrations between 42 and 326.1 ng/mL. The median peak plasma concentration was 79.5 (41.9-326.1) ng/mL with a Tmax of 60 (30-75) min. After the same infusion bolus, the corresponding norketamine PK showed plasma drug concentrations between 22.0 and 64.8 ng/mL. The median peak plasma concentration was 43.0 (26.1-71.8) ng/mL with a median Tmax of 75 min. The median peak ketamine plasma concentration exceeded 100 ng/mL in dogs for less than 1 h post infusion. The Omnipod® system successfully delivered subcutaneous ketamine to dogs in the postoperatively.

Clinical and imaging findings in dogs with nerve root signature associated with cervical intervertebral disc herniation.

BACKGROUND: Intervertebral disc herniation (IVDH) is the most common spinal cord disease in dogs. Little information is available regarding the clinical presentation of nerve root signature (NRS) associated with cervical IVDH. HYPOTHESIS/OBJECTIVE: To detail the clinical and magnetic resonance imaging (MRI) findings in dogs with NRS associated with cervical IVDH. ANIMALS: Forty-seven client-owned dogs presenting with thoracic limb NRS and MRI confirmed IVDH. METHODS: Medical records from 2010 to 2020 were retrospectively reviewed for dogs that met inclusion criteria. Imaging studies were evaluated by 2 individuals to characterize location and severity of neural tissue compression. RESULTS: Chondrodystrophoid dogs comprised the majority of the study cohort, with dachshund the most common breed (n = 10). Three-quarters of dogs were ≥7 years of age. Interobserver agreement was moderate or good for all of the imaging variables evaluated. The C6-C7 intervertebral disc space was significantly overrepresented (P = .01), comprising 32% (15/47) of the affected discs. However, 42% (20/47) of cases involved C2-C3 though C4-C5 disc sites. Disc material was more frequently located laterally compared to medially within the vertebral canal (P = .0005), and to be associated with compression of the nerve root at the level of the intervertebral foramen (P = .012). CONCLUSION/CLINICAL IMPORTANCE: NRS is most commonly associated with lateralized or foraminal cervical disc herniations. It is most prevalent with C6-C7 intervertebral disc involvement, suggesting that there might be unique anatomic factors that contribute to development of NRS at this site, but can be a clinical manifestation of IVDH occurring anywhere along the cervical spine.

Implantation Corridors in Canine Thoracic Vertebrae: A Morphometric Study in Dogs of Varying Sizes.

OBJECTIVE: Surgical stabilization to treat fractures, luxations, and congenital malformations in the thoracic spine can be difficult due to its unique anatomy and surrounding structures. Our objective was to document the morphometrics of the thoracic vertebrae relating to an ideal trajectory for dorsolateral implant placement in a variety of dog sizes and to assess proximity to important adjacent critical anatomical structures using computed tomography (CT) studies. STUDY DESIGN: Medical records for 30 dogs with thoracic CT were evaluated. Implantation corridor parameters for thoracic vertebrae (T1-T13) were measured, including the length, width, angle from midline, and allowable deviation angle for corridors simulated using an ideal implant trajectory. The distances from each vertebra to the trachea, lungs, aorta, subclavian artery, and azygos vein were also measured. RESULTS: Implantation corridor widths were often very narrow, particularly in the mid-thoracic region, and allowable deviation angles were frequently small. Distances to critical anatomical structures were often less than 1 mm, even in larger dogs. CONCLUSION: Thoracic implantation requires substantial precision to avoid breaching the canal, ineffective implant placement, and potential life-threatening complications resulting from invasion of surrounding anatomical structures.

Magnetic resonance imaging characteristics of atlanto-axial subluxation in 42 dogs: Analysis of joint cavity size, subluxation distance, and craniocervical junction anomalies.

Background: Atlanto-axial (AA) subluxation can be a complex syndrome in dogs. Accurate identification and assessment of this condition are key to providing treatment and resolution. Aim: The purpose of this retrospective study was to describe the magnetic resonance imaging (MRI) characteristics of AA subluxation and associated neurologic deficits. Methods: A multicenter review of dogs with a diagnosis of AA subluxation was conducted, evaluating signalment, neurologic grade, duration of signs, and MRI characteristics. MRI characteristics included degree of spinal cord compression and joint subluxation, integrity of odontoid ligaments, presence of a dens, spinal cord signal intensity, and presence of syringohydromyelia, hydrocephalus, and Chiari-like malformation. A control population with normal AA joints was also evaluated. MR images of 42 dogs with AA subluxation were compared to 26 age and breed-matched control dogs. Results: Affected dogs had a median age of 27 months and a median weight of 2.7 kg, and the most commonly affected breed was the Yorkshire terrier (47.5%). Spinal cord signal hyperintensity, increased AA joint size, and cross-sectional cord compression at the level of the dens and mid-body C2 were associated with AA subluxation. No associations were found between cord compression, the appearance of the dens, or cord signal intensity and neurologic grade. Affected dogs did not have a higher incidence of Chiari-like malformation, syringohydromyelia, or hydrocephalus than control dogs, and their neurologic grade was not associated with MRI findings. Lack of dens and/or odontoid ligaments was associated with larger subluxations. Conclusion: Dogs with clinical signs of AA subluxation were significantly more likely to have intramedullary hyperintensity at the level of compression ( p = 0.0004), an increased AA joint cavity size ( p = 0.0005), and increased spinal cord compression at the level of dens and mid-body C2 (p ≤ 0.05). The authors suggest an AA joint cavity size >1.4 mm and a subluxation distance >2.5 mm as cutoffs for MRI diagnosis of AA subluxation in dogs. No differences were noted between dogs with AA subluxation and control dogs regarding syringohydromyelia, hydrocephalus, and Chiari-like malformation.

Gold Nanostars Obviate Limitations to Laser Interstitial Thermal Therapy (LITT) for the Treatment of Intracranial Tumors.

PURPOSE: Laser interstitial thermal therapy (LITT) is an effective minimally invasive treatment option for intracranial tumors. Our group produced plasmonics-active gold nanostars (GNS) designed to preferentially accumulate within intracranial tumors and amplify the ablative capacity of LITT. EXPERIMENTAL DESIGN: The impact of GNS on LITT coverage capacity was tested in ex vivo models using clinical LITT equipment and agarose gel-based phantoms of control and GNS-infused central "tumors." In vivo accumulation of GNS and amplification of ablation were tested in murine intracranial and extracranial tumor models followed by intravenous GNS injection, PET/CT, two-photon photoluminescence, inductively coupled plasma mass spectrometry (ICP-MS), histopathology, and laser ablation. RESULTS: Monte Carlo simulations demonstrated the potential of GNS to accelerate and specify thermal distributions. In ex vivo cuboid tumor phantoms, the GNS-infused phantom heated 5.5× faster than the control. In a split-cylinder tumor phantom, the GNS-infused border heated 2× faster and the surrounding area was exposed to 30% lower temperatures, with margin conformation observed in a model of irregular GNS distribution. In vivo, GNS preferentially accumulated within intracranial tumors on PET/CT, two-photon photoluminescence, and ICP-MS at 24 and 72 hours and significantly expedited and increased the maximal temperature achieved in laser ablation compared with control. CONCLUSIONS: Our results provide evidence for use of GNS to improve the efficiency and potentially safety of LITT. The in vivo data support selective accumulation within intracranial tumors and amplification of laser ablation, and the GNS-infused phantom experiments demonstrate increased rates of heating, heat contouring to tumor borders, and decreased heating of surrounding regions representing normal structures.

Presumed pituitary apoplexy in 26 dogs: Clinical findings, treatments, and outcomes.

BACKGROUND: Pituitary apoplexy refers to hemorrhage or infarction within the pituitary gland resulting in acute neurological abnormalities. This condition is poorly described in dogs. OBJECTIVES: To document presenting complaints, examination findings, endocrinopathies, magnetic resonance imaging (MRI), treatments, and outcomes of dogs with pituitary apoplexy. ANIMALS: Twenty-six client-owned dogs with acute onset of neurological dysfunction. METHODS: Retrospective case series. Dogs were diagnosed with pituitary apoplexy if MRI or histopathology documented an intrasellar or suprasellar mass with evidence of hemorrhage or infarction in conjunction with acute neurological dysfunction. Clinical information was obtained from medical records and imaging reports. RESULTS: Common presenting complaints included altered mentation (16/26, 62%) and gastrointestinal dysfunction (14/26, 54%). Gait or posture changes (22/26, 85%), mentation changes (18/26, 69%), cranial neuropathies (17/26, 65%), cervical or head hyperpathia (12/26, 46%), and hyperthermia (8/26, 31%) were the most frequent exam findings. Ten dogs (38%) lacked evidence of an endocrinopathy before presentation. Common MRI findings included T1-weighted hypo- to isointensity of the hemorrhagic lesion (21/25, 84%), peripheral enhancement of the pituitary mass lesion (15/25, 60%), brain herniation (14/25, 56%), and obstructive hydrocephalus (13/25, 52%). Fifteen dogs (58%) survived to hospital discharge. Seven of these dogs received medical management alone (median survival 143 days; range, 7-641 days) and 8 received medications and radiation therapy (median survival 973 days; range, 41-1719 days). CONCLUSIONS AND CLINICAL IMPORTANCE: Dogs with pituitary apoplexy present with a variety of acute signs of neurological disease and inconsistent endocrine dysfunction. Dogs that survive to discharge can have a favorable outcome.

A lightweight magnetically shielded room with active shielding.

Magnetically shielded rooms (MSRs) use multiple layers of materials such as MuMetal to screen external magnetic fields that would otherwise interfere with high precision magnetic field measurements such as magnetoencephalography (MEG). Optically pumped magnetometers (OPMs) have enabled the development of wearable MEG systems which have the potential to provide a motion tolerant functional brain imaging system with high spatiotemporal resolution. Despite significant promise, OPMs impose stringent magnetic shielding requirements, operating around a zero magnetic field resonance within a dynamic range of ± 5 nT. MSRs developed for OPM-MEG must therefore effectively shield external sources and provide a low remnant magnetic field inside the enclosure. Existing MSRs optimised for OPM-MEG are expensive, heavy, and difficult to site. Electromagnetic coils are used to further cancel the remnant field inside the MSR enabling participant movements during OPM-MEG, but present coil systems are challenging to engineer and occupy space in the MSR limiting participant movements and negatively impacting patient experience. Here we present a lightweight MSR design (30% reduction in weight and 40-60% reduction in external dimensions compared to a standard OPM-optimised MSR) which takes significant steps towards addressing these barriers. We also designed a 'window coil' active shielding system, featuring a series of simple rectangular coils placed directly onto the walls of the MSR. By mapping the remnant magnetic field inside the MSR, and the magnetic field produced by the coils, we can identify optimal coil currents and cancel the remnant magnetic field over the central cubic metre to just |B|= 670 ± 160 pT. These advances reduce the cost, installation time and siting restrictions of MSRs which will be essential for the widespread deployment of OPM-MEG.

Novel subcutaneous cytarabine infusion with the Omnipod system in dogs with meningoencephalomyelitis of unknown etiology.

OBJECTIVE: To investigate the feasibility and pharmacokinetics of cytarabine delivery as a subcutaneous continuous-rate infusion with the Omnipod system. ANIMALS: 6 client-owned dogs diagnosed with meningoencephalomyelitis of unknown etiology were enrolled through the North Carolina State University Veterinary Hospital. PROCEDURES: Cytarabine was delivered at a rate of 50 mg/m2/hour as an SC continuous-rate infusion over 8 hours using the Omnipod system. Plasma samples were collected at 0, 4, 6, 8, 10, 12, and 14 hours after initiation of the infusion. Plasma cytarabine concentrations were measured by high-pressure liquid chromatography. A nonlinear mixed-effects approach generated population pharmacokinetic parameter estimates. RESULTS: The mean peak plasma concentration (Cmax) was 7,510 ng/mL (range, 5,040 to 9,690 ng/mL; SD, 1,912.41 ng/mL), average time to Cmax was 7 hours (range, 4 to 8 hours; SD, 1.67 hours), terminal half-life was 1.13 hours (SD, 0.29 hour), and the mean area under the curve was 52,996.82 hours X µg/mL (range, 35,963.67 to 71,848.37 hours X µg/mL; SD, 12,960.90 hours X µg/mL). Cmax concentrations for all dogs were more than 1,000 ng/mL (1.0 µg/mL) at the 4-, 6-, 8-, and 10-hour time points. CLINICAL RELEVANCE: An SC continuous-rate infusion of cytarabine via the Omnipod system is feasible in dogs and was able to achieve a steady-state concentration of more than 1 µg/mL 4 to 10 hours postinitiation of cytarabine and a Cmax of 7,510 ng/mL (range, 5,040 to 9,690 ng/mL; SD, 1,912.41 ng/mL). These are comparable to values reported previously with IV continuous-rate infusion administration in healthy research Beagles and dogs with meningoencephalomyelitis of unknown etiology.

Inter-pathologist agreement on diagnosis, classification and grading of canine glioma.

Histopathological evaluation of tumours is a subjective process, but studies of inter-pathologist agreement are uncommon in veterinary medicine. The Comparative Brain Tumour Consortium (CBTC) recently published diagnostic criteria for canine gliomas. Our objective was to assess the degree of inter-pathologist agreement on intracranial canine gliomas, utilising the CBTC diagnostic criteria in a cohort of eighty-five samples from dogs with an archival diagnosis of intracranial glioma. Five pathologists independently reviewed H&E and immunohistochemistry sections and provided a diagnosis and grade. Percentage agreement and kappa statistics were calculated to measure inter-pathologist agreement between pairs and amongst the entire group. A consensus diagnosis of glioma subtype and grade was achieved for 71/85 (84%) cases. For these cases, percentage agreement on combined diagnosis (subtype and grade), subtype only and grade only were 66%, 80% and 82%, respectively. Kappa statistics for the same were 0.466, 0.542 and 0.516, respectively. Kappa statistics for oligodendroglioma, astrocytoma and undefined glioma were 0.585, 0.566 and 0.280 and were 0.516 for both low-grade and high-grade tumours. Kappa statistics amongst pairs of pathologists for combined diagnosis varied from 0.352 to 0.839. 8 % of archival oligodendrogliomas and 61% of archival astrocytomas were reclassified as another entity after review. Inter-pathologist agreement utilising CBTC guidelines for canine glioma was moderate overall but varied from fair to almost perfect between pairs of pathologists. Agreement was similar for oligodendrogliomas and astrocytomas but lower for undefined gliomas. These results are similar to pathologist agreement in human glioma studies and with other tumour entities in veterinary medicine.

Using OPM-MEG in contrasting magnetic environments.

Magnetoencephalography (MEG) has been revolutionised by optically pumped magnetometers (OPMs). "OPM-MEG" offers higher sensitivity, better spatial resolution, and lower cost than conventional instrumentation based on superconducting quantum interference devices (SQUIDs). Moreover, because OPMs are small, lightweight, and portable they offer the possibility of lifespan compliance and (with control of background field) motion robustness, dramatically expanding the range of MEG applications. However, OPM-MEG remains nascent technology; it places stringent requirements on magnetic shielding, and whilst a number of viable systems exist, most are custom made and there have been no cross-site investigations showing the reliability of data. In this paper, we undertake the first cross-site OPM-MEG comparison, using near identical commercial systems scanning the same participant. The two sites are deliberately contrasting, with different magnetic environments: a "green field" campus university site with an OPM-optimised shielded room (low interference) and a city centre hospital site with a "standard" (non-optimised) MSR (higher interference). We show that despite a 20-fold difference in background field, and a 30-fold difference in low frequency interference, using dynamic field control and software-based suppression of interference we can generate comparable noise floors at both sites. In human data recorded during a visuo-motor task and a face processing paradigm, we were able to generate similar data, with source localisation showing that brain regions could be pinpointed with just ∼10 mm spatial discrepancy and temporal correlations of > 80%. Overall, our study demonstrates that, with appropriate field control, OPM-MEG systems can be sited even in city centre hospital locations. The methods presented pave the way for wider deployment of OPM-MEG.

Subaxial cervical articular process subluxation and dislocation: Cervical locked facet injuries in dogs.

OBJECTIVE: To describe neurologic signs, diagnostic imaging findings, potential treatments, and outcomes in dogs with subaxial cervical articular process subluxation and dislocation, or a "locked facet." STUDY DESIGN: Retrospective case series. ANIMALS: Ten client-owned dogs. METHODS: Dogs with a diagnosis of cervical locked facets were identified through medical records and imaging reports searches. Data on presenting signs, diagnostic findings, treatment, and outcome were recorded. RESULTS: All cases were small or toy-breed dogs with preceding trauma. Four dogs were tetraplegic with intact pain perception, five were nonambulatory tetraparetic, and one was ambulatory tetraparetic, with half of the tetraparetic dogs having worse motor function in the thoracic limbs. The only sites affected were C5/6 (n = 6) and C6/7 (n = 4). All dogs had unilateral dorsal displacement of the cranial articular process of the caudal vertebra relative to the caudal articular process of the cranial vertebra at the luxation site. Five dogs were treated surgically, three by external coaptation, one by restriction, and one was euthanized the day after diagnosis. All dogs with outcome data (n = 8) became ambulatory. Nonambulatory dogs returned to ambulation in a median of 4 weeks (IQR 1-12; range 1-28). CONCLUSION: In these dogs, locked facet injuries affected the caudal cervical vertebrae in small breeds and could be identified on imaging through the presence of dorsal displacement of a cranial articular process. Our small cohort had a functional recovery regardless of treatment. CLINICAL SIGNIICANCE: Locked facet injuries should be a differential for small or toy-breed dogs with a cervical myelopathy secondary to trauma.

High-field MRI using standard pulse sequences has moderate to substantial interobserver agreement and good accuracy for differentiation between intracranial extra-axial histiocytic sarcoma and meningioma in dogs.

Intracranial extra-axial histiocytic sarcoma shares common MRI features with meningioma. As histiocytic sarcoma carries a generally worse prognosis than meningioma, the ability to differentiate between these two neoplasms is of clinical value. The aim of this retrospective diagnostic accuracy and observer agreement study was to evaluate the accuracy and reliability of high-field MRI to differentiate between these two tumors, using standard pulse sequences and published MRI features. A total of 51 dogs were included (26 meningiomas and 25 histiocytic sarcomas). Magnetic resonance imaging examinations were independently assessed by three experienced board-certified radiologists, evaluating 18 imaging features. They were asked to assign each case to one of three categories (meningioma, histiocytic sarcoma, and undetermined). Agreement for the MRI diagnosis across all three reviewers was moderate (κ 0.54) while paired interobserver agreement ranged from moderate to substantial (κ 0.58-0.74) with percent agreement ranging between 86.1% and 87.7%. Overall, the probability of correctly diagnosing meningioma in a dog with this tumor ranged between 79.2% and 94.4%, and the probability of correctly diagnosing histiocytic sarcoma in a dog with this tumor ranged between 76.0% and 92.3%. The overall probability to diagnose the correct tumor, irrespective of type, ranged between 79.2% and 89.7%. Histiocytic sarcomas tended to have more extensive edema and more often had combined perilesional and distant meningeal enhancement affecting both pachy- and leptomeninges, while for meningiomas, meningeal enhancement tended to more commonly be perilesional and pachymeningeal. Imaging features that seemed more useful to make a correct diagnosis included "location/type of meningeal enhancement," "osseous changes in the adjacent neurocranium," "cystic changes," and "herniation severity."

Immunohistochemical evaluation of immune cell infiltration in canine gliomas.

Evasion of the immune response is an integral part of the pathogenesis of glioma. In humans, important mechanisms of immune evasion include recruitment of regulatory T cells (Tregs) and polarization of macrophages toward an M2 phenotype. Canine glioma has a robust immune cell infiltrate that has not been extensively characterized. The purpose of this study was to determine the distribution of immune cells infiltrating spontaneous intracranial canine gliomas. Seventy-three formalin-fixed, paraffin-embedded tumor samples were evaluated using immunohistochemistry for CD3, forkhead box 3 (FOXP3), CD20, Iba1, calprotectin (Mac387), CD163, and indoleamine 2,3-dioxygenase (IDO). Immune cell infiltration was present in all tumors. Low-grade and high-grade gliomas significantly differed in the numbers of FoxP3+ cells, Mac387+ cells, and CD163+ cells (P = .006, .01, and .01, respectively). Considering all tumors, there was a significant increase in tumor area fraction of CD163 compared to Mac387 (P < .0001), and this ratio was greater in high-grade tumors than in low-grade tumors (P = .005). These data warrant further exploration into the roles of macrophage repolarization or Treg interference therapy in canine glioma.

Vascular endothelial growth factor concentrations in the cerebrospinal fluid of dogs with neoplastic or inflammatory central nervous system disorders.

BACKGROUND: Vascular endothelial growth factor (VEGF) is a key molecular driver of angiogenesis and vascular permeability and is expressed by a wide variety of neoplasms. Although blood VEGF concentrations have been quantified in intracranial tumors of dogs, cerebrospinal fluid (CSF) VEGF concentration might be a more sensitive biomarker of disease. OBJECTIVE: Concentrations of VEGF in CSF are higher in dogs with central nervous system (CNS) neoplasia compared to those with meningoencephalomyelitis and other neurologic disorders. ANIMALS: One hundred and twenty-six client-owned dogs presented to a veterinary teaching hospital. METHODS: Case-control study. Cerebrospinal fluid was archived from dogs diagnosed with CNS neoplasia and meningoencephalomyelitis. Control dogs had other neurological disorders or diseases outside of the CNS. A commercially available kit was used to determine VEGF concentrations. RESULTS: Detectable CSF VEGF concentrations were present in 49/63 (77.8%) neoplastic samples, 22/24 (91.7%) inflammatory samples, and 8/39 (20.5%) control samples. The VEGF concentrations were significantly different between groups (P < .0001), and multiple comparison testing showed that both neoplastic and inflammatory groups had significantly higher concentrations than did controls (P < .05), but did not differ from each other. Gliomas and choroid plexus tumors had significantly higher VEGF concentrations than did the control group (P < .05). CONCLUSIONS AND CLINICAL IMPORTANCE: Cerebrospinal fluid VEGF concentrations may serve as a marker of neoplastic and inflammatory CNS disorders relative to other conditions.

The bioavailability of cytarabine in dogs with meningoencephalitis of unknown etiology through iontophoresis and rectal delivery.

Background: Cytarabine (CA) is used to treat dogs with meningoencephalitis of unknown etiology (MUE) by subcutaneous or intravenous administration. Aim: The objective was to investigate transdermal iontophoresis and rectal administration as alternative routes of CA delivery. Methods: Two client-owned dogs with MUE were studied. The ActivaPatch® IONTOGO™ 12.0 iontophoresis drug delivery system delivered 200 mg/m2 CA transdermally. Blood samples were collected by sparse sampling technique after initiation of the device. At another visit, 100 mg/m2 CA was administered rectally. Blood samples were collected by sparse sampling technique after administration. Plasma CA concentrations were measured by high-pressure liquid chromatography. Results: The concentration of plasma CA after transdermal and rectal administration was below the limits of quantification (0.1 µg/ml) in all samples suggesting inadequate bioavailability with transdermal and rectal administration. Conclusion: Transdermal and rectal CA administration are not reasonable alternative routes of delivery.

Personalized-induced neural stem cell therapy: Generation, transplant, and safety in a large animal model.

In this study, we take an important step toward clinical translation by generating the first canine-induced neural stem cells (iNSCs). We explore key aspects of scale-up, persistence, and safety of personalized iNSC therapy in autologous canine surgery models. iNSCs are a promising new approach to treat aggressive cancers of the brain, including the deadly glioblastoma. Created by direct transdifferentiation of fibroblasts, iNSCs are known to migrate through the brain, track down invasive cancer foci, and deliver anticancer payloads that significantly reduce tumor burden and extend survival of tumor-bearing mice. Here, skin biopsies were collected from canines and converted into the first personalized canine iNSCs engineered to carry TNFα-related apoptosis-inducing ligand (TRAIL) and thymidine kinase (TK), as well as magnetic resonance imaging (MRI) contrast agents for in vivo tracking. Time-lapse analysis showed canine iNSCs efficiently migrate to human tumor cells, and cell viability assays showed both TRAIL and TK monotherapy markedly reduced tumor growth. Using intraoperative navigation and two delivery methods to closely mimic human therapy, canines received autologous iNSCs either within postsurgical cavities in a biocompatible matrix or via a catheter placed in the lateral ventricle. Both strategies were well tolerated, and serial MRI showed hypointense regions at the implant sites that remained stable through 86 days postimplant. Serial fluid sample testing following iNSC delivery showed the bimodal personalized therapy was well tolerated, with no iNSC-induced abnormal tissue pathology. Overall, this study lays an important foundation as this promising personalized cell therapy advances toward human patient testing.

Use of Top Hat Audience Response Software in a Third-Year Veterinary Medicine and Surgery Course.

Audience response devices are useful tools that can improve student engagement and learning during instructional sessions. The purpose of this article is to describe our experience with a new cloud-based application known as Top Hat, which includes audience response tools in its application suite. The software was used in a multi-specialty, multi-instructor medicine and surgery course in the third year of a veterinary curriculum. In addition to standard multiple-choice and short-answer questions, Top Hat has several unique question types and methods of displaying the responses given. These include displaying free-text responses in a word cloud format and a "click-on-target" question type that allows students to indicate their response by clicking on a location within an image. Responses for this latter question type are displayed in a heat map format. A discussion tool is also available, which allows students to respond, read other students' responses in real time, and then reply again if warranted. This feature also supports drawing-based responses. The variety of question types was very useful in keeping students engaged during teaching sessions, giving this application several advantages over systems that are limited to multiple-choice questions only. In addition, the application allowed rapid identification of areas of student knowledge and misunderstandings, which facilitated the direction of further discussion and clarification of important learning issues.

Accuracy and safety of three-dimensionally printed animal-specific drill guides for thoracolumbar vertebral column instrumentation in dogs: Bilateral and unilateral designs.

OBJECTIVE: To evaluate the safety and accuracy of a unilateral three-dimensionally printed animal-specific drill guide (3DASDG) design for unilateral stabilization in the thoracolumbar vertebral column of dogs compared to a bilateral design. STUDY DESIGN: Cadaveric study. SAMPLE POPULATION: Fifty-two corridors in one canine cadaver. METHODS: Two 3DASDG designs with 2 drilling tubes each were created from T8 to L7 vertebrae. Fifty-two corridors were drilled on the right and the left sides by using unilateral and bilateral designs, respectively. Planned and postoperative trajectories (entry point, exit point, angle) were compared to establish the accuracy. Statistical analysis was used for accuracy comparison between designs. Safety was evaluated by using Zdichavsky classification. RESULTS: Unilateral and bilateral drill guide designs were not different for entry point and angle deviations; however, they were different for the exit point deviations. Two corridors breached outside the vertebra. For all guides, mean entry and exit point deviations were less than 1 and 2 mm, respectively. The maximum entry or exit point deviation in both groups was 4.7 mm. The mean angle deviation was <3.5°, and the maximum angle deviation was 9.3°. CONCLUSION: No difference was detected in accuracy of entry points and angle deviations between drill guide designs tested in normal vertebrae. The technique was classified as highly safe. CLINICAL SIGNIFICANCE: A unilateral drill guide design may be a safe alternative to bilateral guides for unilateral stabilization of the thoracolumbar vertebral column in dogs.

Continuous rate infusion of midazolam as emergent treatment for seizures in dogs.

BACKGROUND: Midazolam delivered by continuous rate infusion (CRI) might be effective in dogs with cluster seizures (CS) or status epilepticus (SE). OBJECTIVE: To describe the use and safety of midazolam CRI in dogs with CS or SE. ANIMALS: One-hundred six client-owned dogs presenting to a veterinary teaching hospital with CS or SE. METHODS: Retrospective review of medical records for dogs with CS or SE treated with a midazolam CRI. RESULTS: Seventy-nine dogs presented with CS and 27 dogs had SE. Seizure control was achieved in 82/106 dogs (77.4%) receiving a midazolam CRI. The median dose associated with seizure control was 0.3 mg/kg/h (range, 0.1-2.5 mg/kg/h). The median duration of CRI was 25 hours (range, 2-96 hours). Seizures were controlled in 34/40 dogs (85%) with idiopathic epilepsy, 32/43 dogs (74%) with structural epilepsy, 12/16 dogs (75%) with unknown epilepsy, and 4/7 dogs (57%) with reactive seizures (P = .20). Seizure control was achieved in 81% of dogs with CS and 67% in dogs with SE (P = .18). Dogs with idiopathic/unknown epilepsy were more likely to survive than those with structural epilepsy (87% vs 63%, P = .009). Adverse effects were reported in 24 dogs (22.6%) and were mild in all cases. CONCLUSIONS AND CLINICAL IMPORTANCE: Midazolam CRI is apparently safe and might be an effective treatment in dogs with CS or SE.

Accuracy of three-dimensionally printed animal-specific drill guides for implant placement in canine thoracic vertebrae: A cadaveric study.

OBJECTIVE: To assess the accuracy of three-dimensionally (3-D) printed drill guides in constraining the trajectory of drill tracts for implants in canine thoracic vertebrae. STUDY DESIGN: Experimental ex vivo study. SAMPLE POPULATION: Five canine thoracic vertebral column specimens. METHODS: Guides to constrain drill trajectories were designed on the basis of computed tomographic (CT) imaging of six thoracic vertebrae (T8-T13) and were 3-D printed. The guides were used to create drill tracts in these vertebrae by both an experienced and a novice surgeon, and CT imaging was repeated. The entry point and angulation of actual and planned drill tracts were compared for both surgeons. Unintended cortical violations were also assessed by using a modified Zdichavsky classification. RESULTS: Fifty-eight drill tracts were created in 30 vertebrae. Mean entry point deviation was 1.4 mm (range, 0.4-3.4), and mean angular deviation was 5.1° (range, 1.5°-10.8°). There were no differences between surgeons in entry point deviation (P = .07) or angular deviation (P = .22). There were no unintended cortical bone violations, and all drill tracts were classified as modified Zdichavsky grade I. CONCLUSION: The 3-D printed guides used in the current study yielded drill tracts with small linear and angular errors from intended paths and 100% accuracy for placement within vertebral pedicles and bodies. This technique was conveniently used by both an experienced and a novice surgeon. CLINICAL SIGNIFICANCE: This technique might be immediately applicable to clinical cases requiring thoracic vertebral stabilization and may allow safe and accurate implant placement for surgeons with varying experience levels.