Successful post-incomplete resection management of gastrointestinal stromal tumor using imatinib based on adenosine triphosphate-based tumor sensitivity assay in a dog.

Gastrointestinal stromal tumors arising from gastric cardia are uncommon in dogs. A few studies have shown the effectiveness of tyrosine kinase inhibitors in the treatment of canine gastrointestinal stromal tumors, but no standardized protocols are currently available. An 11-year-old spayed female Maltese dog was diagnosed with a gastrointestinal stromal tumor using histopathological and immunohistochemical analyses. An adenosine triphosphate-based tumor chemosensitivity assay revealed that imatinib at lower concentrations had a stronger inhibitory effect than toceranib. Based on the results of the assay, the dog was treated with imatinib after surgery. After 28 mo of therapy, there was no recurrence of the tumor. Key clinical message: Adenosine triphosphate-based tumor chemosensitivity assays may help clinicians to select appropriate postoperative chemotherapeutic drugs for incompletely resected gastrointestinal stromal tumors in dogs.

Gestion réussie à la suite d'une résection incomplète d'une tumeur stromale gastro-intestinale à l'aide de l'imatinib basée sur un test de sensibilité tumorale à base d'adénosine triphosphate chez un chien. Les tumeurs stromales gastro-intestinales résultant du cardia gastrique sont rares chez le chien. Quelques études ont montré l'efficacité des inhibiteurs de la tyrosine kinase dans le traitement des tumeurs stromales gastrointestinales canines, mais aucun protocole standardisé n'est actuellement disponible. Une chienne maltaise stérilisée de 11 ans a reçu un diagnostic de tumeur stromale gastro-intestinale à l'aide d'analyses histopathologiques et immunohistochimiques. Un test de chimiosensibilité tumorale à base d'adénosine triphosphate a révélé que l'imatinib à des concentrations plus faibles avait un effet inhibiteur plus fort que le tocéranib. Sur la base des résultats du test, le chien a été traité avec de l'imatinib après l'opération. Après 28 mois de traitement, il n'y a eu aucune récidive de la tumeur.Message clinique clé :Les tests de chimiosensibilité tumorale à base d'adénosine triphosphate peuvent aider les cliniciens à sélectionner les médicaments chimiothérapeutiques postopératoires appropriés pour les tumeurs stromales gastro-intestinales incomplètement réséquées chez le chien.(Traduit par Dr Serge Messier).

Evaluation of clopidogrel, hypercoagulability, and platelet count in dogs undergoing splenectomy for splenic masses.

Dogs that had splenectomy are predisposed to fatal thrombotic conditions, and thrombocytosis is a risk factor for post-splenectomy hypercoagulability. However, in veterinary medicine, there are no specific therapeutic approaches for managing this hypercoagulability. This study aimed to determine the preventive effect of clopidogrel on post-operative hypercoagulability during the first 2 weeks post-splenectomy in dogs with splenic masses. This study included 12 dogs that had splenectomy. Seven dogs received no treatment (group A), and five were treated with clopidogrel (group B). Clopidogrel was loaded at 10 mg/kg on day 2 and continued at 2 mg/kg until day 14. Blood samples were collected on the day of surgery and 2, 7, and 14 days after splenectomy in both groups. In group B, thromboelastography (TEG) was performed on the same days. In group A, there was significant elevation of platelet counts on days 7 (p = 0.007) and 14 (p = 0.001) compared to day 0. In group B, the platelet counts were significantly elevated on day 7 (p = 0.032) but no significant difference was found on day 14 compared to day 0. Platelet counts on day 14 were significantly higher in group A than in group B (p = 0.03). The lower platelet counts were correlated with alterations in TEG parameters, and no significant differences were found in the K and α-angle values at all postoperative assessment points compared to day 0. Our study suggests that clopidogrel may reduce post-operative thrombocytosis and hypercoagulability in dogs that undergo splenectomy for splenic masses.

Surveillance of Ancylostoma caninum in naturally infected dogs in Quebec, Canada, and assessment of benzimidazole anthelmintics reveal a variable efficacy with the presence of a resistant isolate in imported dogs.

Ancylostoma caninum is a widely prevalent parasitic nematode in dogs across the world. There has been a notable increase in reports of anthelmintic resistance in A. caninum within the United States of America in recent years, which has led us to investigate the potential of this scenario in Canada. The study objectives were to assess the prevalence of A. caninum in two different groups, including a colony of rescued dogs in Canada and three imported Greyhound dogs from USA, and to evaluate the efficacy of two benzimidazole (BZ) anthelmintics against A. caninum, complemented with a molecular genetic analysis adapted to low prevalence. Fecal samples were collected at pre- and post-treatment with fenbendazole for the native shelters-origin group, and a combination of anthelmintic formulations, including the pro-BZ febantel for the USA-origin group. The coprology analyses found several genera of internal parasites. Canine ancylostomiasis was the most prevalent parasitosis with 30.77% in the native group and 100% in the USA group, but with overall low average of A. caninum eggs per gram. Through the fecal egg count reduction test (FECRT), applying a cut-off at 90% as baseline of egg reduction for successful efficacy, BZ showed variable efficacy. Furthermore, molecular analysis confirmed the presence of A. caninum in both groups of dogs and found differences in the genetics linked to BZ resistance on the A. caninum ß-tubulin isotype 1 gene. In the isolate from the native group, both codons 167 and 200 were homozygous without the presence of single nucleotide polymorphism (SNP). In contrast, the selected isolate from the USA group, showed a homozygous allele at position 200 and a heterozygous SNP at position 167. The latter was congruent with the low efficacy in FECRT and agrees with the recent findings of USA A. caninum isolate resistant phenotype to the BZ anthelmintics. The limitations of the study include an overall low eggs-per-gram in both canine groups, and the shortage of additional fecal samples from the USA group, restraining the molecular analysis only to one out of the three Greyhounds. This study provided some insights on the efficacy of BZs against A. caninum and revealed the presence of BZ resistant isolates in imported dogs in Quebec, Canada. All this information should be considered, for choosing the best strategy in the control of A. caninum using anthelmintic drugs.

Perioperative analgesic effects of the erector spinae plane block with bupivacaine or bupivacaine-dexmedetomidine in dogs undergoing hemilaminectomy: A randomized controlled trial.

Objective: To compare the perioperative opioid requirements among dogs receiving an erector spinae plane (ESP) block with bupivacaine, with or without dexmedetomidine, and a control group. Animals and procedure: Thirty client-owned, healthy adult dogs undergoing hemilaminectomy were included in this randomized, prospective, blinded clinical study. Dogs were randomly assigned to 1 of 3 treatment groups: Group B, ESP block with bupivacaine; Group BD, ESP block with bupivacaine and dexmedetomidine; and Group C, control. Rescue intra- and postoperative analgesia consisted of fentanyl and methadone, respectively. Postoperative pain was evaluated using the short form of the Glasgow Composite Measure Pain Scale (CMPS-SF). Results: In Group BD, 0/10 dogs required intraoperative fentanyl, compared to 9/10 in Group C (P < 0.001), whereas 1/10 required postoperative methadone, compared to 9/10 in Group B (P = 0.003) and 10/10 in Group C (P < 0.001). The total amount of intraoperative fentanyl (µg/kg) was 0 (0 to 4) in Group B and 0 (0 to 0) in BD, compared to 6 (0 to 8) in C (P = 0.004 and P < 0.001, respectively). Postoperative methadone (mg/kg) required during the first 12 h was 0.5 (0 to 1.4) in Group B (P = 0.003) and 0 (0 to 0) in BD (P < 0.001), compared to C (P = 0.003 and P < 0.001, respectively). Conclusion: An ESP block with bupivacaine, with or without dexmedetomidine, was associated with a reduction in perioperative opioid consumption and provided effective acute pain control.

Effets analgésiques périopératoires du bloc des érecteurs du rachis avec de la bupivacaïne ou de la bupivacaïne-dexmédétomidine chez les chiens subissant une hémilaminectomie: un essai contrôlé randomisé. Objectif: Comparer les besoins périopératoires en opioïdes chez les chiens recevant un bloc des érecteurs de la colonne vertébrale (ESP) avec de la bupivacaïne, avec ou sans dexmédétomidine, et un groupe témoin. Animaux et procédure: Trente chiens adultes en bonne santé appartenant à des clients subissant une hémilaminectomie ont été inclus dans cette étude clinique randomisée, prospective et en aveugle. Les chiens ont été répartis au hasard dans 1 des 3 groupes de traitement: groupe B, bloc ESP avec bupivacaïne; groupe BD, bloc ESP avec bupivacaïne et dexmédétomidine; et groupe C, témoin. L'analgésie de secours peropératoire et postopératoire consistait respectivement en fentanyl et en méthadone. La douleur postopératoire a été évaluée à l'aide du formulaire abrégé de l'échelle de mesure de la douleur de Glasgow (CMPS-SF). Résultats: Dans le groupe BD, 0/10 chiens ont eu besoin de fentanyl peropératoire, contre 9/10 dans le groupe C (P < 0,001), tandis que 1/10 ont eu besoin de méthadone postopératoire, contre 9/10 dans le groupe B (P = 0,003) et 10/10 dans le groupe C (P < 0,001). La quantité totale de fentanyl peropératoire (µg/kg) était de 0 (0 à 4) dans le groupe B et de 0 (0 à 0) dans le groupe BD, contre 6 (0 à 8) dans le groupe C (P = 0,004 et P < 0,001, respectivement). La méthadone postopératoire (mg/kg) nécessaire au cours des 12 premières heures était de 0,5 (0 à 1,4) dans le groupe B (P = 0,003) et de 0 (0 à 0) dans le groupe BD (P < 0,001), par rapport au groupe C (P = 0,003). et P < 0,001, respectivement). Conclusion: Un bloc ESP avec de la bupivacaïne, avec ou sans dexmédétomidine, a été associé à une réduction de la consommation peropératoire d'opioïdes et a permis un contrôle efficace de la douleur aiguë.(Traduit par Dr Serge Messier).

Successful treatment of bifenthrin toxicosis using therapeutic plasma exchange.

OBJECTIVE: To describe a case of bifenthrin toxicosis in a dog with a successful outcome following the use of therapeutic plasma exchange (TPE) and intralipid therapy. CASE SUMMARY: An 8-month-old female neutered poodle mix dog ingested an unknown amount of powered bifenthrin, which resulted in acutely altered mentation, cranial nerve deficits, and intractable tremors that persisted in severity despite aggressive medical management to include intravenous fluids, intravenous lipid emulsion, anticonvulsant medications, and methocarbamol. TPE was initiated after lack of significant clinical improvement 12 hours after initial presentation. The dog underwent cardiopulmonary arrest (CPA) following approximately 1 plasma volume equivalent exchange. The dog was successfully resuscitated and showed marked improvement 12 hours postarrest and post-TPE treatment. Serum bifenthrin concentrations were analyzed prior to TPE (445.38 ng/mL) and ∼10 hours after TPE (51.18 ng/mL), which resulted in an 89% reduction in serum bifenthrin concentration. NEW INFORMATION: TPE may be a promising adjunctive therapeutic modality for bifenthrin toxicosis in dogs.

Owners' experiences of administering meglumine antimoniate injections to dogs with leishmaniosis: An online questionnaire study.

BACKGROUND: This study examined the experiences of owners of dogs with leishmaniosis who treated their dogs with daily subcutaneous meglumine antimoniate injections. The owners' perceived ease of administering the injections, the occurrence of problems and the effects on the owners and on the dog‒owner bond were evaluated. METHODS: Dogs prescribed meglumine antimoniate as a treatment for leishmaniosis were identified using the database of the veterinary pharmacy of the Faculty of Veterinary Medicine, Utrecht University. An online questionnaire was sent to the owners of these dogs to evaluate the perceived ease of administering the injections, the occurrence of problems and the effects on the owner and the dog-owner bond. RESULTS: Responses were received from 64 dog owners. Most respondents (78%) reported that administering the injections was not difficult. Pain or the development of nodules at the injection site was reported in 50% and 40% of the dogs, respectively. Polyuria was reported in 44% of the dogs. Some owners reported that administering the injections had a negative impact on their psychological wellbeing (20%), and some would have liked more veterinary support (11%). LIMITATIONS: Some questions were answered by a limited number of people, and their responses may not be representative. CONCLUSION: Dog owners remain highly motivated to persevere with meglumine antimoniate treatment and are willing to administer the injections themselves. The availability of active support when needed during the therapy cycle may further improve their acceptance of and confidence in giving the injections.

Assessment of tumor hypoxia in spontaneous canine tumors after treatment with OMX, a novel H-NOX oxygen carrier, with [18F]FMISO PET/CT.

BACKGROUND: Hypoxia is a detrimental factor in solid tumors, leading to aggressiveness and therapy resistance. OMX, a tunable oxygen carrier from the heme nitric oxide/oxygen-binding (H-NOX) protein family, has the potential to reduce tumor hypoxia. [18F]Fluoromisonidazole ([18F]FMISO) positron emission tomography (PET) is the most widely used and investigated method for non-invasive imaging of tumor hypoxia. In this study, we used [18F]FMISO PET/CT (computed tomography) to assess the effect of OMX on tumor hypoxia in spontaneous canine tumors. RESULTS: Thirteen canine patients with various tumors (n = 14) were randomly divided into blocks of two, with the treatment groups alternating between receiving intratumoral (IT) OMX injection (OMX IT group) and intravenous (IV) OMX injection (OMX IV group). Tumors were regarded as hypoxic if maximum tumor-to-muscle ratio (TMRmax) was greater than 1.4. In addition, hypoxic volume (HV) was defined as the region with tumor-to-muscle ratio greater than 1.4 on [18F]FMISO PET images. Hypoxia was detected in 6/7 tumors in the OMX IT group and 5/7 tumors in the OMX IV injection group. Although there was no significant difference in baseline hypoxia between the OMX IT and IV groups, the two groups showed different responses to OMX. In the OMX IV group, hypoxic tumors (n = 5) exhibited significant reductions in tumor hypoxia, as indicated by decreased TMRmax and HV in [18F]FMISO PET imaging after treatment. In contrast, hypoxic tumors in the OMX IT group (n = 6) displayed a significant increase in [18F]FMISO uptake and variable changes in TMRmax and HV. CONCLUSIONS: [18F]FMISO PET/CT imaging presents a promising non-invasive procedure for monitoring tumor hypoxia and assessing the efficacy of hypoxia-modulating therapies in canine patients. OMX has shown promising outcomes in reducing tumor hypoxia, especially when administered intravenously, as evident from reductions in both TMRmax and HV in [18F]FMISO PET imaging.

Prognostic role of the updated Kiel classification in canine high-grade T-cell lymphomas.

BACKGROUND: The aim of this study was to determine and describe the prognostic role of the morphological subtype determined according to the updated Kiel classification in dogs with high-grade T-cell lymphomas (HGTCLs) depending on the treatment applied. OBJECTIVES: The HGTCLs were classified into three subtypes according to the updated Kiel classification: pleomorphic mixed (PM), lymphoblastic lymphoma/acute lymphoblastic leukaemia and plasmacytoid (P). The treatment was divided into a palliative therapy (PlT) group and a chemotherapy (ChT) group. METHODS: The study was conducted between 2009 and 2017, and it enrolled 58 dogs in which cytomorphological and immunocytochemistry diagnoses were HGTCL. RESULTS: Overall survival (OS) was significantly longer in the ChT group (median OS-4 months, interquartile range [IQR] from 2 to 8 months) than in the PlT group (median OS-6 weeks, IQR from 1 week to 3 months). In the PlT group, PM subtype and glucocorticosteroids (GCSs) treatment proved significantly and independently linked to longer OS and approximately three-fold lower risk of death during the study period (adjusted hazard ratio [HRadj] = 0.26, confidence interval [CI] 95%: 0.08-0.81; p = 0.020 and HRadj = 0.30, CI 95%: 0.11-0.77; p = 0.013, respectively), although due to small group size, precision of estimations was poor (wide CI 95%). In the ChT group, >7 days elapsing between diagnosis and the beginning of chemotherapy and GCS treatment prior to chemotherapy were significantly associated with lower chance of complete remission (CR; p = 0.034 for both); GCS treatment prior to chemotherapy was significantly associated with shorter OS (p = 0.016); chemotherapy based on the modified CHOP protocol was significantly associated with higher chance of CR (p = 0.034) and longer OS (p = 0.039); and CR was significantly linked to longer OS (p = 0.001). CLINICAL SIGNIFICANCE: The morphological subtype of HGTCL has some prognostic value in dogs treated palliatively (with PM subtype associated with longer OS than P subtype); however, this effect is no longer visible when a dog is treated with chemotherapy.

Bacterial microbiota and proinflammatory cytokines in the anal sacs of treated and untreated atopic dogs: Comparison with a healthy control group.

The pathogenesis of anal sacculitis has not been extensively investigated, although atopic dogs seem to be predisposed to the disease. The aim of this study was therefore to characterize and compare the bacterial microbiota and pro-inflammatory cytokines in the anal sacs of dogs from three groups (healthy dogs, untreated atopic dogs and atopic dogs receiving antipruritic treatment or allergen-specific immunotherapy) in order to determine whether changes could be at the origin of anal sacculitis in atopic dogs. Bacterial populations of anal sac secretions from fifteen healthy dogs, fourteen untreated and six treated atopic dogs were characterized by sequencing the V4 region of the 16S rRNA gene using Illumina technology. Proinflammatory cytokines were analyzed with the Luminex multiplex test. Community membership and structure were significantly different between the anal sacs of healthy and untreated atopic dogs (P = 0.002 and P = 0.003, respectively) and between those of untreated and treated atopic dogs (P = 0.012 and P = 0.017, respectively). However, the community structure was similar in healthy and treated atopic dogs (P = 0.332). Among the proinflammatory cytokines assessed, there was no significant difference between groups, except for interleukin 8 which was higher in the anal sacs of untreated atopic dogs compared to treated atopic dogs (P = 0.02), and tumor necrosis factor-alpha which was lower in the anal sacs of healthy dogs compared to treated atopic dogs (P = 0.04). These results reveal a dysbiosis in the anal sacs of atopic dogs, which may partially explain the predisposition of atopic dogs to develop bacterial anal sacculitis. Treatments received by atopic dogs (oclacitinib, desloratadine and allergen-specific immunotherapy) shift the microbiota of the anal sacs towards that of healthy dogs. Further studies are required to identify significant cytokines contributing to anal sacculitis in atopic dogs.

Establishment of canine mammary gland tumor cell lines harboring PI3K/Akt activation as a therapeutic target.

Canine mammary gland tumors (MGT) have a poor prognosis in intact female canines, posing a clinical challenge. This study aimed to establish novel canine mammary cancer cell lines from primary tumors and characterize their cellular and molecular features to find potential therapeutic drugs. The MGT cell lines demonstrated rapid cell proliferation and colony formation in an anchorage-independent manner. Vimentin and α-SMA levels were significantly elevated in MGT cell lines compared to normal canine kidney (MDCK) cells, while CDH1 expression was either significantly lower or not detected at all, based on quantitative real-time PCR (qRT-PCR) analysis. Functional annotation and enrichment analysis revealed that epithelial-mesenchymal transition (EMT) phenotypes and tumor-associated pathways, particularly the PI3K/Akt signaling pathway, were upregulated in MGT cells. BYL719 (Alpelisib), a PI3K inhibitor, was also examined for cytotoxicity on the MGT cell lines. The results show that BYL719 can significantly inhibit the proliferation of MGT cell lines in vitro. Overall, our findings suggest that the MGT cell lines may be valuable for future studies on the development, progression, metastasis, and management of tumors.

Clinical effects and adverse effects of intravenous lipid emulsion treatment in dogs and cats with suspected poisoning.

This retrospective study aimed to evaluate the effects on the clinical signs of poisoning and adverse effects of intravenous lipid emulsion treatment in 82 animals (dogs and cats) with suspected poisonings over 18 months. Physical examination parameters and state of consciousness were documented every hour after the intravenous administration of a bolus of 2 ml/kg and 0.25 ml/kg/min over 60 minutes of a 20% intravenous lipid emulsion. The modified Glasgow coma scale and laboratory findings (blood gas analysis, triglyceride, lactate) were evaluated initially and three hours after discontinuing intravenous lipid emulsion administration. A statistical evaluation of the occurrence of adverse effects and the development of laboratory values was performed. A decrease in respiratory rate in the second control (8-12 hours) after ILE was observed. Three hours after completing of the intravenous lipid emulsion, triglyceride concentration increased about 10 times (p <0.001). Venous carbon dioxide partial pressure, bicarbonate, base excess, as well as the electrolytes sodium, potassium and ionized calcium decreased significantly (p <0.001). Patients who experienced a worsening of the modified Glasgow coma scale had a higher increase in triglyceride concentrations (p = 0.041) and plasma lactate (p = 0.034) and a larger decrease in bicarbonate concentrations (p = 0.053) compared to others. About 54% (n = 44) of the patients showed adverse effects which could be attributed to the administration of intravenous lipid emulsion and may be associated with a higher triglyceride increase. All of them were completely reversible within 33 hours. Adverse effects associated with intravenous lipid emulsion therapy were observed in half of the patients and were associated with a higher increase in triglycerides.

Heartworm-, Flea-, and Tick-associated Diseases in Dogs: A Review of Common Parasites and Drug Classes Prophylactic Against Them.

Throughout recorded history, the canine-human connection has varied by custom, purpose, and intensity. In many cultures worldwide, dogs have long been considered essential workers, protectors and guardians, and, often, an integral part of the family unit. Ensuring the health and quality of life of those companion animals is essential to preserving the bond between dogs and their owners. Fortunately, advances in veterinary science continue to improve treatments and cures for and prophylaxis against a variety of deadly canine diseases, several of which can be sourced to ectoparasites or endoparasites. For many veterinary patients, a customized preparation often proves to be the best therapeutic option, but many compounding-pharmacy stores also include a retail component that offers ready access to manufactured prescription medications, including those prophylactic against canine flea, tick, or heartworm infestation. Because dog owners often need guidance in selecting such products and assistance with obtaining them, this article will be of special interest to ompounders in those pharmacies. To that end, the following content addresses common canine parasites and classes of drugs that prevent the illnesses they cause, with emphasis on heartworm disease.

Case Report on the Effect of AlpaWash® on the Healing of a Post-surgical Wound in a Female Canine Initially Diagnosed with Pyometra.

Pyometra is a common disease in intact female canines characterized by an infection of the uterus. If it is not treated immediately, it could result in various complications such as fistulous tract development, sepsis, hemorrhage, uveitis, conjunctivitis, pyelonephritis, urinary tract infection, and myocarditis. In this case report, we highlight the benefits of the application of a topical ointment on wound healing after ovariohysterectomy in canine Pyometra. Following surgical intervention, the dog developed necrosis in her nipples and lost a portion of her mammary tissues. A large cyst formed and later ruptured, leaving the animal with a large wound. The vet applied a topical ointment, AlpaWash, to the affected area and prescribed antibiotic, analgesic, and antiinflammatory drugs to help manage the condition. The vet reported complete healing of the wounds within one month from the commencement of the treatment regimen.

Re-evaluating the placebo response in recent canine dietary epilepsy trials.

The placebo response is a common phenomenon. Limited evidence is available about its magnitude in canine epilepsy trials, even though it can significantly influence the efficacy evaluation of new treatments. It was hypothesised that the placebo response is diminished when epilepsy trials are conducted in a prospective crossover design. Seizure data spanning six months from three previous multicenter epilepsy studies were analysed. The monthly seizure frequency of 60 dogs diagnosed with idiopathic epilepsy was calculated, comparing baseline data with placebo treatment. Furthermore, differentiation was made between dogs randomised to the placebo group early (Phase 1: first 3 months) or later during the study (Phase 2: second 3 months).The analysis did not reveal any placebo response in terms of monthly seizure frequency. Instead, an increase was noted during the placebo treatment period, with a mean of 2.95 seizures per month compared to 2.30 seizures per month before study entry (p = 0.0378). Additionally, a notable phase effect was observed. Dogs receiving the placebo in the second study phase exhibited a significant increase in monthly seizure frequency compared to baseline (p = 0.0036). Conversely, no significant difference from baseline was observed for dogs receiving the placebo in the first study phase. These findings underscore the considerable variability in placebo responses observed in trials for canine epilepsy, contrasting with previous limited data. The identified phase effect should be carefully considered in the design and evaluation of canine epilepsy trials to ensure a more accurate assessment of efficacy for new treatments.

Pamidronate-induced irreversible symptomatic hypocalcemia in a dog with hypercalcemia after glucocorticoid withdrawal: a case report.

BACKGROUND: Pamidronate is used for the treatment of hypercalcemia. However, a rare but potential adverse event of pamidronate treatment is hypocalcemia. This report describes an unusual case of severe, irreversible hypocalcemia after a single injection of pamidronate for the treatment of hypercalcemia due to glucocorticoid withdrawal in a dog. CASE PRESENTATION: An 11-year-old castrated male Maltese dog presented with anorexia, vomiting, and diarrhea (day 0). The patient had calcinosis cutis throughout the body, calcification of intraabdominal organs, mild azotemia, and severe hypercalcemia. The severe calcification was attributed to long-term glucocorticoid administration, which was discontinued 1 month before presentation. Fluid therapy, diuretics, calcitonin, and a single intravenous injection of pamidronate were used for the treatment of hypercalcemia. On day 14, normocalcemia was achieved, but renal failure occurred. On day 20, severe and irreversible hypocalcemia occurred, and on day 42, the patient was euthanized at the owner's request because of worsened hypocalcemia and renal failure. CONCLUSIONS: Although hypocalcemia is an extremely rare adverse event of bisphosphonate treatment, bisphosphonates like pamidronate can result in potentially life-threatening conditions according to the patient's underlying conditions. Therefore, the patient's condition should be closely monitored and any underlying conditions should be carefully evaluated before initiating the treatment for hypercalcemia using pamidronate.

VDX-111 targets proliferative pathways in canine cancer cell lines.

VDX-111 (also identified as AMPI-109) is a vitamin D derivative which has shown anticancer activity. To further assess the function of this compound against multiple cancer types, we examined the efficacy of VDX-111 against a panel of 30 well characterized canine cancer cell lines. Across a variety of cancer types, VDX-111 induced widely variable growth inhibition, cell death, and migration inhibition, at concentrations ranging from 10 nM to 1 µM. Growth inhibition sensitivity did not correlate strongly with tumor cell histotype; however, it was significantly correlated with the expression of genes in multiple cell signaling pathways, including the MAPK and PI3K-AKT pathways. We confirmed inhibition of these signaling pathways as likely participants in the effects of VDX-111. These results suggest that a subset of canine tumors may be sensitive to treatment with VDX-111, and suggests possible predictive markers of drug sensitivity and pharmacodynamic biomarkers of drug exposure that could be employed in future clinical trials.

Comparative characterization of two monoclonal antibodies targeting canine PD-1.

Monoclonal antibodies targeting immune checkpoints have revolutionized oncology. Yet, the effectiveness of these treatments varies significantly among patients, and they are associated with unexpected adverse events, including hyperprogression. The murine research model used in drug development fails to recapitulate both the functional human immune system and the population heterogeneity. Hence, a novel model is urgently needed to study the consequences of immune checkpoint blockade. Dogs appear to be uniquely suited for this role. Approximately 1 in 4 companion dogs dies from cancer, yet no antibodies are commercially available for use in veterinary oncology. Here we characterize two novel antibodies that bind canine PD-1 with sub-nanomolar affinity as measured by SPR. Both antibodies block the clinically crucial PD-1/PD-L1 interaction in a competitive ELISA assay. Additionally, the antibodies were tested with a broad range of assays including Western Blot, ELISA, flow cytometry, immunofluorescence and immunohistochemistry. The antibodies appear to bind two distinct epitopes as predicted by molecular modeling and peptide phage display. Our study provides new tools for canine oncology research and a potential veterinary therapeutic.

Corticosteroid monotherapy versus combined cytarabine continuous rate infusion and corticosteroid therapy in dogs with meningoencephalitis of unknown origin: A blinded, randomized, controlled trial.

BACKGROUND: Treatment options available for meningoencephalitis of unknown origin (MUO) in dogs are suboptimal, and currently, no single treatment protocol appears to be superior. OBJECTIVES: Compare neurological deterioration rates at 7 days between dogs with MUO treated with corticosteroids alone or combined with cytosine arabinoside (CA) continuous rate infusion (CRI) and compare clinical deterioration and survival at 30 and 100 days. ANIMALS: Sixty-nine dogs with magnetic resonance imaging (MRI) and cerebrospinal fluid (CSF) features or both compatible with MUO. METHODS: Parallel, blinded, randomized controlled trial. Simple randomization into 2 treatment groups: 4 mg/kg/day prednisolone (or dexamethasone equivalent) for 2 days or 200 mg/m2 CA CRI over 8 hours plus 2 mg/kg/day prednisolone. Blinding of the treatment protocol was carried out using reversible redaction of clinical records, and treatment failure was defined as deterioration of neurological assessment or death. Using intention-to-treat analysis, proportions failing treatment at 7, 30, and 100 days were compared using Fisher's exact test. All-cause mortality at 100 days was compared using Kaplan-Meier survival curves. RESULTS: Thirty-five dogs were allocated to corticosteroid only, and 34 dogs were allocated to combined CA CRI and corticosteroid. Proportions failing treatment at 7, 30, and 100 days were 7/35 (20%), 9/35 (26%), and 15/35 (43%) in the corticosteroid-only group and 8/34 (24%), 11/34 (32%), and 23/34 (68%) in the corticosteroid and CA CRI group. All-cause mortality at 100 days was not significantly different between groups (P = .62). Clinically relevant treatment-related adverse effects were not observed. CONCLUSIONS AND CLINICAL IMPORTANCE: We found no difference in outcome between corticosteroid monotherapy and combined cytarabine CRI and corticosteroid therapy at 7, 30, and 100 days after diagnosis in dogs with MUO.

Preliminary evaluation of an indwelling epidural catheter for repeat methylprednisolone administration in canine lumbosacral stenosis.

Objective: To determine the complications, outcomes, and patency of a permanent epidural catheter and subcutaneous access port system (ECAPS) as part of conservative management of degenerative lumbosacral stenosis in dogs. Animals and procedure: Medical records of 11 client-owned dogs that underwent an ECAPS insertion were evaluated retrospectively. Clinical signs, complications related to the procedure, and system patency are reported. Results: All dogs had lumbosacral pain at their initial neurological assessment, with comfort levels adequately controlled following epidural infiltrations. None suffered from complications related to the ECAPS procedure. In 10 dogs, there were no malfunctions for the duration of the study. However, in 1 dog, there was a suspected leak at Day 814. The longest duration of patency reported in this study was 870 d (at the time of writing). Conclusion: Placement of an ECAPS is a feasible technique and a viable option to permit repeated epidural injections of steroids in dogs with degenerative lumbosacral stenosis that is managed conservatively. Further studies are required to evaluate complication rates.

Évaluation préliminaire d'un cathéter épidural permanent (à demeure) pour l'administration répétée de méthylprednisolone lors de sténose lombosacrée dégénérative chez le chien. Objectif: Décrire la technique, les complications, les résultats et la perméabilité d'un système composé d'un cathéter épidural et d'un port d'injection sous-cutanée (ECAPS) pour le traitement médical de la sténose lombosacrée dégénérative chez le chien. Animaux et protocole: Les dossiers médicaux de 11 chiens appartenant à des clients ayant subi l'implantation d'un ECAPS ont été évalués de façon rétrospective. Cette étude décrit les signes cliniques, les complications reliées à la procédure et la perméabilité du système. Résultats: Tous les patients inclus présentaient de la douleur lombosacrée à l'examen initial. Le niveau de confort de tous les patients suite aux injections épidurales fut maitrisé de façon adéquate. Aucun des patients n'a subi de complications reliées à l'implantation du système. Le système n'a pas démontré de dysfonctionnement dans le cas de dix patients. Chez un des patients, une fuite fut suspectée au jour 814. La durée maximale de perméabilité enregistrée dans cette étude est de 870 jours (au moment de la rédaction). Conclusion: L'implantation d'un système ECAPS représente une option faisable et viable pour l'administration additionnelle de stéroïdes pour une gestion conservatrice de sténose lombosacrée dégénérative chez les chiens atteints. Des recherches supplémentaires sont requises pour l'évaluation des taux de complications.(Traduit par les auteurs).