Canine Patients Research Articles

Abstract 7554: The histone deacetylase inhibitor romidepsin is a potential therapeutic for metastatic osteosarcoma

Abstract Osteosarcoma predominately affects adolescents, young adults, and canines. For human patients, the five-year survival rate of those with detectable lung metastases is only 30% while most canine patients with metastatic disease die within 1-2 years. Standard therapy is not effective for this patient group, so it is therefore necessary to identify novel therapies that target the progression of lung metastases. Our lab previously screened 114 FDA-approved anti-cancer drugs to identify agents that decrease the growth of 3D spheroids (sarcospheres) generated from highly metastatic osteosarcoma cell lines. The top hits included both histone deacetylase inhibitors (HDIs) that were tested. In follow-up experiments measuring potency on sarcospheres and toxicity on non-transformed cells, romidepsin was the top hit of the 114-drug panel as well of the two additional FDA-approved HDIs and seven HDIs that are in clinical oncology trials. Our goal was therefore to further evaluate romidepsin as a potential therapy for metastatic osteosarcoma. Romidepsin potently decreased viability in sarcospheres from established highly metastatic osteosarcoma cell lines (relative ED50s = 3-36nM). About 50% of the patients (both canine and human) had similar responses to romidepsin (relative ED50s = 1- 18nM) suggesting that those patients might be good candidates for romidepsin therapy. This includes patients who had been heavily pretreated with standard-of-care osteosarcoma chemotherapeutics. Mechanistically, romidepsin blocks proliferation and causes a G2/M cell cycle arrest in fast growing sarcospheres (143B and MG63.3) while in slow growing sarcospheres (LM7 and K7M2) where primarily induces cytotoxicity and there is no cell cycle arrest. Patient-derived sarcospheres are slow growing, so we predict that the primary mechanism will be cytotoxicity. Using a tail vein injection model of osteosarcoma lung metastases, romidepsin dose dependently prolonged survival and reduced the area and number of lung metastases in immunodeficient mice injected with 143B cells and a syngeneic model using K7M2 cells. Romidepsin will be evaluated in mice with metastases from patient-derived cells and if effective, will be repurposed for canine and human clinical trials to improve outcomes in metastatic osteosarcoma without the associated costs and extensive timeframe of traditional drug discovery. Citation Format: Emily E. Seiden, Spencer M. Richardson, Shrey Ramnath, Tia Whiteside, Kathryn L. Coy, Anthony L. Sinn, Maegan L. Capitano, Karen E. Pollok, Chris D. Collier, Ed M. Greenfield. The histone deacetylase inhibitor romidepsin is a potential therapeutic for metastatic osteosarcoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 7554.

Abstract 3480: Alterations in the tumor microenvironment and key signaling pathways in naturally-occurring canine gliomas mirror those seen in human patients

Abstract Background: Malignant gliomas are the most common type of primary brain tumors, with patient outcomes that are generally dismal. Recently, pet dogs have been assessed as a valuable model in which to study gliomas. Gliomas in pet dogs occur at similar rates to those seen in humans, and a recent study comparing canine and human gliomas identified high similarity in terms of mutational rates, aneuploidy, the timing of mutations, and methylation patterns. Here, we further compare naturally-occurring canine and human gliomas, focusing on the tumor microenvironment (TME) and key pathways dysregulated in human gliomas. Methods: Spontaneously occurring gliomas from adult and pediatric human, and canine patients were utilized for this study. RNA, whole genome/whole exome, and bisulfite sequencing data from adult and canine samples were downloaded from the Genomic Data Commons and the National Cancer Institute’s Integrated Canine Data Commons, respectively. Pediatric tumor RNA-seq and genomic data were obtained from the Gabriella Miller Kids First database. Normal adult human and canine brain tissue served as control tissue. Only tumors with a clear diagnosis of astrocytoma, oligodendroglioma, or oligoastrocytoma were included in this study. Results: Overall, we found that key canonical pathways that are altered in human gliomas are also altered in canine gliomas. A comparison of high-grade gliomas in pet dogs to normal canine brain tissues showed significant abnormal gene expression in 3 canonical oncogenic pathways of human GBM: the TP53, RB1, and RTK/RAS/PI3K pathways. Similarities between species included increased expression of PDGF, and receptors PDGFRA and PDGFRB. Frequent copy number alterations and mutations were also observed in PDGFRA and EGFR. Differences between species include the mutation rate of TP53, which we found to be mutated frequently in adults but not in pediatric or canine gliomas, however, expression of TP53 as assessed by RNA-seq was significantly increased in both adult and canine gliomas. IDH1, which drives methylation, was significantly overexpressed in adults but underexpressed in canine. Correspondingly, each of the promotor regions of TERT, PD1 and MGMT was hypermethylated in adults, but hypomethylated in canine. Although an analysis of the TME from RNA-seq data revealed an influx of immune cells in adult, pediatric and canine gliomas, there was a concurrent influx of immunosuppressive cells. Gene expression profiles of astrocytomas and oligodendrogliomas show differences in alterations of immune-related and TME-specific pathways. Conclusion: We found that similar TME and pathway alterations were observed between human and canine gliomas, and that TME alterations were different between canine astrocytomas and oligodendrogliomas. The canine TME, like that in humans, appears to be immunosuppressive. Citation Format: Nadia A. Lanman, Sagar Utturkar, Harish Kothandaraman, Deepika Dhawan, Danni Liu, Min Zhang, Matthew Beyers, Deborah W. Knapp, R. Timothy Bentley. Alterations in the tumor microenvironment and key signaling pathways in naturally-occurring canine gliomas mirror those seen in human patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3480.

Niclosamide: A career builder

My contribution to honoring Professor Kinam Park celebrates and resonates with his scholarly career in drug delivery, his commitment to encouraging the next generation(s), and his efforts to keep us focused on clinically effective formulations. To do this I take as my example, niclosamide, a small molecule protonophore that, uniquely, can “target” all cell membranes, both plasma and organelle. As such, it acts upstream of many cell pathways and so has the potential to affect many of the essential events that a cell, and particularly a diseased cell or other entities like a virus, use to stay alive and prosper. Literature shows that it has so far been discovered to positively influence (at least): cancer, bacterial and viral infection, metabolic diseases such as Type II diabetes, NASH and NAFLD, artery constriction, endometriosis, neuropathic pain, rheumatoid arthritis, sclerodermatous graft-versus-host disease, systemic sclerosis, Parkinson's, and COPD. With such a fundamental action and broad-spectrum activity, I believe that studying niclosamide in all its manifestations, discovering if and to what extent it can contribute positively to disease control (and also where it can't), formulating it as effective therapeutics, and testing them in preclinical and clinical trials is a career builder for our next generation(s).The article is divided into two parts: Part I introduces niclosamide and other proton shunts mainly in cancer and viral infections and reviews an exponentially growing literature with some concepts and physicochemical properties that lead to its proton shunt mechanism. Part II focuses on repurposing by reformulation of niclosamide. I give two examples of “carrier-free formulations”, — one for cancer (as a prodrug therapeutic of niclosamide stearate for i.v. and other administration routes, exemplified by our recent work on Osteosarcoma in mice and canine patients), and the other as a niclosamide solution formulation (that could provide the basis for a preventative nasal spray and early treatment option for COVID19 and other respiratory virus infections).My goal is to excite and enthuse, encourage, and motivate all involved in the drug development and testing process in academia, institutes, and industry, to learn more about this interesting molecule and others like it. To enable such endeavors, I give many proposed ideas throughout the document, that have been stimulated and inspired by gaps in the literature, urgent needs in disease, and new studies arising from our own work. The hope is that, by reading through this document and studying the suggested topics and references, the drug delivery and development community will continue our lineage and benefit from our legacy to achieve niclosamide's potential as an effective contributor to the treatment and control of many diseases and conditions.

Ophthalmic findings associated with Australian tick paralysis (holocyclotoxicity) in hospitalized domestic dogs and cats.

To describe ophthalmic findings in hospitalized canine and feline patients with tick paralysis (TP) and investigate possible predisposing factors. Forty-seven dogs and 28 cats hospitalized with TP assessed with an ophthalmic examination performed by an ABVO resident. Dogs and cats were hospitalized with TP from October 2021 to January 2022 and had an ophthalmic examination performed by an ABVO resident. Patient signalment data, information regarding tick number and location, hospitalization duration, medications used, and patient paralysis grades were recorded. Statistical analysis was performed to correlate findings. Corneal ulcers developed in up to 34.8% of dogs and up to 42.9% of cats hospitalized with TP. An absent palpebral reflex ipsilaterally increased the odds of a concurrent corneal ulcer being present by 14.7× in dogs and 20.1× in cats (p < .0001). Palpebral reflexes were absent in 38.3% of dogs and 35.7% of cats hospitalized with TP and were correlated with more severe gait paralysis (p = .01) and respiratory paralysis (p = .005) in dogs, and respiratory paralysis in cats (p = .041). STT-1 findings <10 mm/min were present in 27.7% of dogs and 57.1% of cats examined and were associated with increasing gait paralysis (p = .017) and respiratory paralysis (p = .007) in dogs, and increasing gait paralysis in cats (p = .017). Simple corneal ulcers, loss of a complete palpebral reflex, and reduced STT-1 scores frequently occurred in dogs and cats hospitalized for TP. The frequency of these findings increased as the degree of patient paralysis increased.

Micropulse transscleral cyclophotocoagulation in canine glaucoma: A retrospective study evaluating sweep velocity.

To report preliminary results of MP-TSCP in canine patients with glaucoma while evaluating sweep velocity, treatment efficacy, and safety utilizing standardized surgical parameters. Client-owned dogs that underwent MP-TSCP at a veterinary referral hospital. Medical records of 19 eyes (14 dogs) treated with MP-TSCP were reviewed. Eleven eyes were treated with a 10 s/sweep (s) velocity and 8 eyes with a 20 s/s. Laser duty cycle was set at 31.3%, mean laser energy was 2766 mW, and mean duration was 120 s per hemisphere. Minimum post-operative follow-up was 6 months. Outcomes of intraocular pressure (IOP), vision status, degree of antiglaucoma medications, and complications were evaluated. There was a significantly lower median (IQR) IOP (<25 mmHg) at each timepoint postoperatively compared to IOP pre-operatively (p < 0.05). The overall success rate for IOP control at 6 months was 84%, 100% for the 10 s/s and 62.5% for the 20 s/s. Vision was preserved in 10/11 (90%) eyes from the 10 s/s group and 4/8 (50%) eyes from the 20 s/s group at 6 months. Average number of glaucoma medications in the 10 s/s group decreased from 4.4 to 1.5 and from 3.3 to 2.5 in the 20 s/s group. Post-operative complications were mild and resolved within 1 week. MP-TSCP is a non-invasive treatment alternative for canine glaucoma. Employing higher energy levels rendered long-term IOP control while retaining a high safety profile with minimal postoperative complications. There was no statistical difference between a 10 s/s and 20 s/s surgical velocity, both leading to successful surgical outcomes up to 6 months post-operatively.

Assessing the efficacy of acupuncture as the sole analgesic for canine chronic pain

PICO Question In dogs with chronic pain, is acupuncture alone, compared to a placebo, more efficacious in alleviating pain and pain-related dysfunction? Clinical bottom line Category of research Treatment. Number and type of study designs reviewed Four randomised, placebo-controlled clinical trials were critically appraised. Strength of evidence Weak. Outcomes reported A single study evaluating the efficacy of gold bead implantation, a form of permanent acupuncture, on pain associated with canine hip dysplasia (CHD) endorsed acupuncture’s superior pain alleviation and locomotion improvement through owner and veterinarian subjective outcome evaluation. Three studies concluded that, overall, acupuncture was not efficacious regarding pain reduction or dysfunction improvement compared with placebo treatment. Conclusion Based on the limited current evidence, acupuncture could have analgesic effects as perceived by owners, but acupuncture, as a sole analgesic, is unlikely to be effective in alleviating pain and pain-related dysfunction in canine chronic pain associated with musculoskeletal causes. Evidence is lacking on chronic pain due to neurological and oncological causes. Further studies need to focus on researching various acupuncture modalities’ effects on chronic pain with musculoskeletal, neuropathic and oncological causes when utilised as a component of multimodal therapy. Currently, for canine patients with chronic pain, there is insufficient evidence for a veterinarian to recommend that a client utilise acupuncture as the sole method for pain management. How to apply this evidence in practice The application of evidence into practice should take into account multiple factors, not limited to: individual clinical expertise, patient’s circumstances and owners’ values, country, location or clinic where you work, the individual case in front of you, the availability of therapies and resources. Knowledge Summaries are a resource to help reinforce or inform decision making. They do not override the responsibility or judgement of the practitioner to do what is best for the animal in their care.

Surgical tooth extraction in cats and dogs. Part 2: dental extraction techniques

Background: Considering over 80 per cent of canine and feline patients over the age of three years have dental disease (Kortegaard and others 2008), dental extractions are undoubtedly some of the most commonly performed surgeries in first‐opinion practice. Yet, general knowledge and confidence with regards to these procedures is often lacking, resulting in veterinary dentistry having an undeserved reputation for being difficult and unrewarding. However, with the correct knowledge, a basic set of instruments and proper techniques it can quickly become a much more straightforward and immensely rewarding task.Aim of the article: This two‐part series provides readers with the tools needed to perform extractions successfully. Part one, published in the previous issue of In Practice, reviewed clinical anatomy, dental instrumentation and the basic principles of exodontics, while this article will focus on extraction techniques.

How Successful Are Veterinary Weight Management Plans for Canine Patients Experiencing Poor Welfare Due to Being Overweight and Obese?

Overweight and obesity is one of the most significant health and welfare issues affecting companion animals and are linked to several serious medical conditions, reduced welfare, and shortened lifespan. The number of overweight and obese pets increases every year. Overweight and obesity are associated with multiple chronic diseases. Underlying causes include human-related and animal-related factors. Veterinarians encounter overweight and obese canine patients in daily practice and they play an important role in weight management. This research examines the level of veterinary engagement and the success of veterinary management plans for overweight and obese canines over a five-year period. Electronic medical records (EMRs) were collected for 500 canine patients assessed as either overweight or obese and statistically analyzed for level of veterinary engagement (VE), weight loss success, prescription weight loss diet (RX) use, and comorbidities. The average age at the beginning of the study was 61.5 months. A starting Body Condition Score (BCS) of 6 or 7 was most common (87.2%). Twelve different small and large dog breeds were most highly represented (61.1%). Average weight loss rates were low and more dogs gained rather than lost weight (56.5% vs. 43.5%). While VE is important, this study suggests current VE levels are not adequate to successfully combat overweight and obesity or result in improved animal welfare.

Surgical interventions and outcome in a population of canine trauma patients.

To determine signalment, injury type, trauma severity score, and outcome of canine trauma patients undergoing surgical (emergency room [ER] or operating room [OR]) and nonsurgical treatment in addition to time to surgery, specialty services involved, and cost in the OR surgery population. Retrospective evaluation of medical record and hospital trauma registry data on canine trauma cases. University teaching hospital. One thousand six hundred and thirty dogs presenting for traumatic injury between May 2017 and July 2020. None. Demographics and outcome were compared for canine trauma patients undergoing OR surgery (12.8%, 208/1630), ER surgery (39.1%, 637/1630), or no surgical intervention (48.2%, 785/1630). Among the 2 surgical groups, 98.9% (836/845) survived to discharge compared with 92.2% (724/785) of the nonsurgical group (P<0.0001). The OR surgical group had significantly higher median Animal Trauma Triage scores (2vs 1, P<0.0001) and median days in hospital (2vs<1, P<0.0001) compared with the other groups. For the OR surgical cohort, electronic medical records were reviewed to determine the specialty surgery service involved, time to and duration of anesthesia and surgery, and visit cost. The most common surgery services involved were orthopedics (45.2%, 94/208) and general surgery (26.9%, 56/208). Neurology and general surgery cases required the longest median length of stay in hospital, and ophthalmology and dentistry cases required the shortest. The median cost of visit was highest in neurology ($10,032) and lowest in ophthalmology ($2305) and dentistry ($2404). Surgical intervention in canine trauma patients appears to be associated with higher survival rates, and among the surgery groups, mortality was highest in the ER and general surgery groups. OR surgical intervention, in particular general surgery and neurology, was associated with increased length of hospitalization, increased cost, and higher Animal Trauma Triage scores.

Patient weight has diverse effects on the prescribing of different antibiotics to dogs.

Various factors including body weight-associated treatment cost may influence the probability of dispensing antibiotics to dogs in first-opinion practice, but their effect on specific drug choice remains unclear. Multiple membership regression modeling was used to investigate the probability of dispensing 12 different antibiotics to dogs of different weights in the context of various disease presentations, using anonymized data obtained from electronic health records of 18 clinics between 2020 and 2022. Data from 14,259 dogs were analyzed. Treatment choice varied significantly with animal weight. Higher body weight was associated with an increased likelihood of dispensing lower cost antimicrobials such as amoxicillin and trimethoprim sulfonamide, while use of higher cost antimicrobials such as cefovecin was strongly biased to smaller animals. However, these effects were limited when restricted treatment options were available for the target condition. This work demonstrates that anticipated financial costs may result in different treatment choices for canine patients depending on their body weight. Further work is needed to understand the impact of financial pressures on veterinarians' treatment choices, and the implications for the optimization of antimicrobial stewardship in first opinion practice.

An exploratory study of the effect of forced warm air on dermal bacterial populations in anesthetized canine patients prior to surgery

An exploratory study of the effect of forced warm air on dermal bacterial populations in anesthetized canine patients prior to surgery

Retrospective assessment of ophthalmic disease development in domestic dogs and cats when hospitalised with tick paralysis caused by Ixodes holocyclus.

To investigate the incidence and predisposing factors leading to the development of corneal ulcers and the loss of a palpebral reflex in hospitalised canine and feline patients with tick paralysis (TP). A total of 102 dogs and 100 cats retrospectively were assessed from previously hospitalised patients. A retrospective cohort study was performed on 102 different canine and 100 different feline patients who were hospitalised for TP from October 2020-January 2022. Patient data were collected, and logistic regression was conducted to determine factors affecting the palpebral reflex and the development of corneal ulcers. Corneal ulcers occurred in 23/102 (22.5%) dogs during hospitalisation and were strongly associated with an incomplete palpebral reflex ipsilaterally during hospitalisation (P < 0.001), hospitalisation ≥3 days (P = 0.004), mechanical ventilation ≥3 days (P = 0.015) or a tick location cranial to C1 (P = 0.003). An incomplete palpebral reflex during hospitalisation was observed in 29/102 (28.4%) dogs and was significantly associated with decreasing patient weight (P = 0.018), increasing days hospitalised (P = 0.001), having a tick found cranial to C1 (P = 0.004), highest recorded GP grade (P = 0.01), highest recorded RP grade (P = 0.005), use of amoxycillin-clavulanic acid during hospitalisation (P = 0.002) and use of piperacillin/tazobactam during hospitalisation (P = 0.003). There was a significant association between the loss of a complete palpebral reflex and mortality during hospitalisation in dogs (OR = 4.5, P = 0.029). Corneal ulcers occurred in 10/100 (10.0%) cats during hospitalisation, and was significantly more likely to occur to an eye if an incomplete palpebral reflex was observed ipsilaterally during hospitalisation (OR = 20.1, P < 0.0001) and with increasing patient age (P = 0.019). The absence of a complete palpebral reflex during hospitalisation was observed in 18/10 (18.0%) cats and was significantly associated with increasing days hospitalised (P = 0.034). There was no significant association between the loss of a complete palpebral reflex and mortality during hospitalisation in cats. The frequency of corneal ulcers and loss of palpebral reflexes were significant in dogs and cats hospitalised by TP, with many factors contributing to the risk of these developing.

Quantitative studies on B-mode ultrasound and point shear wave elastography of kidneys in nonazotemic dogs.

Renal diseases in dogs can be diagnosed effectively using B-mode ultrasound. Point shear wave elastography (pSWE) has demonstrated usefulness in diagnosing renal diseases in human medicine. However, its application in veterinary medicine is in its nascent stage. It was hypothesized that establishing pSWE reference values in nonazotemic dogs would prove valuable in differentiating renal diseases. In light of this, a single-center, quantitative study with an objective to normalize B-mode ultrasound parameters and pSWE values of the kidney in nonazotemic dogs was conducted. A total of 198 animals presented with clinical signs of anorexia, vomiting, weight loss, and dehydration were enrolled in the study spanning 2 years. Among them, 52 nonazotemic dogs were included as subjects for the study. B-mode ultrasound quantitative parameters, including length (L), breadth (B), height (H), cortical thickness (RCT), and medulla thickness (RMT) of the kidneys, as well as the diameter of the aorta (Ao), were normalized. Additionally, calculated parameters such as L:Ao, B:Ao, H:Ao, RCT:Ao, and corticomedullary ratios were worked out. Point shear wave elastography values were obtained from the cranial and caudal poles of renal cortices using ElastPQ stiffness software. The pSWE values of kidneys in nonazotemic dogs were normalized. The mean±standard error values were 1.04±0.08m/s (95% confidence interval: 0.88-1.19m/s) and 4.18±0.62kPa (95% confidence interval: 2.93-5.42kPa). In conclusion, B-mode ultrasound quantitative parameters, ratios, and pSWE values were normalized in nonazotemic dogs, which may prove valuable in differentiating renal pathologies in canine patients.

Nursing care of the recumbent canine patient after ventral slot surgery

Ventral slot surgery may be required in canine patients with intervertebral disc (IVD) herniation in the cervical spine. Causes of IVD herniation include trauma, neoplasia and discospondylitis. Herniation results in displacement of disc material into the vertebral canal, causing damage to or inflammation of the spinal cord. Patients can initially appear with varied presentations, from pain to recumbency. Management of the postoperative patient requires intensive monitoring and nursing care. Assessing the progression or deterioration of these patients is vital to allow further and potentially life-saving interventions to be implemented. Nursing care can include pain assessment and management; bladder management, such as expression and assisted posturing; exercise rehabilitation to allow return to normal movement; stress reduction, such as interaction; and enrichment and nutritional management, such as assisted feeding. This article discusses how these patients present, surgical interventions, assessment, post-anaesthetic recovery and ongoing monitoring. Postoperative complications are also discussed, along with how to identify these complications and what nursing care to implement for the benefit of the patient and its recovery.

Microarray Gene Expression Analysis of Lesional Skin in Canine Pemphigus Foliaceus.

Canine pemphigus foliaceus (PF) is considered the most common autoimmune skin disease in dogs; the mechanism of PF disease development is currently poorly understood. Therefore, this study aimed to characterize the molecular mechanisms and altered biological pathways in the skin lesions of canine PF patients. Using an RNA microarray on formalin-fixed, paraffin-embedded samples, we analyzed the transcriptome of canine PF lesional skin (n = 7) compared to healthy skin (n = 5). Of the 800 genes analyzed, 420 differentially expressed genes (DEGs) (p < 0.05) were found. Of those, 338 genes were significantly upregulated, including pro-inflammatory and Th17-related genes. Cell type profiling found enhancement of several cell types, such as neutrophils, T-cells, and macrophages, in PF skin compared to healthy skin. Enrichment analyses of the upregulated DEGs resulted in 78 statistically significant process networks (FDR < 0.05), including the Janus kinase signal transducer and activator of transcription (JAK-STAT) and mitogen-activated protein kinase (MAPK) signaling. In conclusion, canine PF lesional immune signature resembles previously published changes in human pemphigus skin lesions. Further studies with canine PF lesional skin using next-generation sequencing (e.g., RNA sequencing, spatial transcriptomics, etc.) and the development of canine keratinocyte/skin explant PF models are needed to elucidate the pathogenesis of this debilitating disease.

Prepubic urethral transposition, with prostatic urethral anastomosis to penile urethra, after severe membrane urethral injury in dog - case report

Rupture of the membranous urethra caused by automobile trauma in dogs, accounting for only 5% of genitourinary tract injuries. The higher prevalence in male dogs is noteworthy due to pelvic anatomy and locomotion habits. Clinical signs include edema, anuria, hematuria, pain, and uroperitoneum, requiring an emergency approach. Diagnosis is usually based on history and imaging tests such as ultrasonography and urethrocystography. Treatment varies based on the location of the injury, with surgical intervention being crucial in complete tears. Prepubic urethral transposition with terminal anastomosis from the prostatic urethra to the penile urethra, although little used in veterinary medicine, presents benefits in male dogs, providing a new urinary path without significant aesthetic changes. The case report presents the successful application of this technique in a canine patient with rupture of the membranous urethra due to automobile trauma, aiming to establish an efficient urinary flow without complications and without compromising genital aesthetics.

Improved characterization and translation of NK cells for canine immunotherapy.

The field of cancer immunology has seen a meteoric rise in interest and application due to the discovery of immunotherapies that target immune cells, often leading to dramatic anti-tumor effects. However, successful cellular immunotherapy for solid tumors remains a challenge, and the application of immunotherapy to dogs with naturally occurring cancers has emerged as a high yield large animal model to bridge the bench-to-bedside challenges of immunotherapies, including those based on natural killer (NK) cells. Here, we review recent developments in the characterization and understanding of canine NK cells, a critical springboard for future translational NK immunotherapy research. The characterization of canine NK cells is exceptionally pertinent given the ongoing challenges in defining them and contextualizing their similarities and differences compared to human and murine NK cells compounded by the limited availability of validated canine specific reagents. Additionally, we summarize the current landscape of the clinical and translational literature employing strategies to capitalize on endogenous and exogenous NK cell immunotherapy in canine cancer patients. The insights regarding efficacy and immune correlates from these trials provide a solid foundation to design and test novel combinational therapies to enhance NK cell activity with the added benefit of motivating comparative work to translate these findings to human cancers with extensive similarities to their canine counterparts. The compilation of knowledge from basic canine NK phenotype and function to applications in first-in-dog clinical trials will support the canine cancer model and enhance translational work to improve cancer outcomes for both dogs and humans.

Spontaneous resorption of a C7–T1 intervertebral disc extrusion in a Cavalier King Charles spaniel confirmed via low‐field MRI

AbstractA 4‐year‐old, male, neutered Cavalier King Charles spaniel was referred to the neurology service with a 10‐day history of cervical hyperaesthesia. A low‐field magnetic resonance imaging scan of the cervical spine identified a large C7–T1 intervertebral disc extrusion, resulting in severe spinal cord compression. The patient was treated with conservative therapy (exercise restriction and analgesia for 4 weeks). Repeat magnetic resonance imaging of the cervical spine was performed 4 months after initial presentation, and identified spontaneous resorption of the extruded C7–T1 disc material. There are very few documented cases of spontaneously resorbed cervical intervertebral disc extrusions in canine patients following successful conservative therapy. To the authors’ knowledge, this is the first report of spontaneous resorption of an intervertebral disc extrusion at an unusual C7–T1 location confirmed via follow‐up low‐field magnetic resonance imaging following conservative therapy.

Investigation of Gastrointestinal Toxicities Associated with Concurrent Abdominal Radiation Therapy and the Tyrosine Kinase Inhibitor Sunitinib in a Mouse Model.

Tyrosine kinase inhibitors (TKIs) may be combined with radiation therapy (RT) to enhance tumor control; however, increased incidences of gastrointestinal (GI) toxicity have been reported with this combination. We hypothesize that toxicity is due to compromised intestinal healing caused by inhibition of vascular repair and proliferation pathways. This study explores underlying tissue toxicity associated with abdominal RT and concurrent sunitinib in a mouse model. Four groups of CD-1 mice were treated with 12 Gy abdominal RT, oral sunitinib, abdominal RT + sunitinib, or sham treatment. Mice received oral sunitinib or the vehicle via gavage for 14 days. On day 7, mice were irradiated with 12 Gy abdominal RT or sham treated. Mice were euthanized on day 14 and intestinal tract was harvested for semiquantitative histopathologic evaluation and immunohistochemical quantification of proliferation (Ki67) and vascular density (CD31). Non-irradiated groups had stable weights while abdominal irradiation resulted in weight loss, with mice receiving RT + SUN having greater weight loss than mice receiving RT alone. Semiquantitative analysis showed significant increases in inflammation in irradiated groups. The difference in the density of CD31+ cells was significantly increased in RT alone compared to SUN alone. Ki67+ density was not significant. In summary, we identify a lack of angiogenic response in irradiated GI tissues when abdominal RT is combined with a TKI, which may correlate with clinical toxicities seen in canine and human patients receiving combined treatment.

An Evaluation of Hemostatic Dysregulation in Canine Multicentric Lymphoma

Multiple hemostatic abnormalities are associated with paraneoplastic syndrome and some malignant tumors. Lymphoma is the most common hematopoietic neoplasm in dogs, sometimes associated with hemostatic changes. The objectives of this study were to evaluate the behavior of coagulation parameters in dogs with multicentric lymphoma compared with diseased dogs without lymphoma, to separately evaluate the effect of immunophenotype (B lymphoma versus T lymphoma) on the variables of interest as well as the effect of disease stage (stage II to IV versus stage V). Specifically, a cross-sectional study was performed with a matched comparison group considering 170 dogs with B or T lymphoma (group 1) and 170 dogs with no lymphoma or other neoplastic processes but other diseases (group 0). Eight coagulation parameters were evaluated: platelet count (Plt), activated partial thromboplastin time (aPTT), prothrombin time (PT), thrombin time (TT), fibrinogen, fibrin/products of fibrinogen degradation (FDPs), fibrin D-dimers, and antithrombin (AT). Dogs with lymphoma showed prolonged PT and TT, decreased fibrinogen, increased FDP, and decreased Plt compared with group 0. The effect of disease stage was evaluated separately for dogs with stage II to IV lymphoma and dogs with stage V lymphoma; patients with stage II–IV lymphoma showed no significant differences, while in dogs with stage V lymphoma, a prolongation of PT and TT, a decrease in fibrinogen, an increase in FDPs and a decrease in Plt were found compared with the group 0. Finally, the comparison between B lymphoma and T lymphoma showed no significant differences in coagulation parameters between the two groups. Logistic regression analysis demonstrated that low fibrinogen and platelet levels were the most significant predictors of lymphoma in a cohort of canine patients. These hemostatic abnormalities in lymphoma appeared to be associated with the stage of the disease rather than the lymphoma immunophenotype. These findings pave the way for the possible scenario of lymphoma-associated fibrinolysis and the so far undescribed pattern of hyperfibrinolysis associated with the most severe stage of lymphoma.