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).

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).

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.

Investigation of efficacy of two different chemotherapy protocols used in neoadjuvant chemotherapy in clinical stages II-IV canine malignant mammary tumours.

The first aim of this study is to demonstrate the clinical efficacy and reliability of two different neoadjuvant chemotherapy (NAC) protocols consisting of doxorubicin/cyclophosphamide (AC) and paclitaxel in dogs with clinical stages II-IV canine malignant mammary tumours (CMTs). Secondly, to determine the Luminal A, Luminal B, HER2-positive and triple-negative molecular subtypes and their value in predicting clinical response to NAC in biopsy samples, and thirdly, to reveal the changes in Ki-67, human epidermal growth factor receptor type 2 (HER2), oestrogen receptor (ER), and progesterone receptor (PgR) expression levels induced by NAC. Thirty dogs with clinical stages II-IV CMTs (T1-3N0-1M0) according to the modified TNM system were included in the study. Dogs in group-1 (n = 15) AC combination and dogs in group-2 (n = 15) were administered paclitaxel. Partial response (PR) was the most common clinical response in both treatment groups (66.66% and 86.66%, respectively). There was no difference between the groups regarding clinical response parameters (p = .001). The rate of treatment responders was higher than the rate of non-responders in both groups (p < .001). The adverse effects observed in both groups were mostly limited to grades 1 and 2 and all were easy to manage. The most frequently detected molecular subtype was Luminal A (59.25%). Complete response (CR) was achieved in 33.33% of dogs with triple-negative CMT in the AC group and 14.29% of the Luminal A subtype in the paclitaxel group. Alterations in Ki-67, HER2, ER, and PgR expressions after chemotherapy were not statistically significant (p > .05). As a result, we have shown that these neoadjuvant chemotherapy protocols are effective and safe alternative treatment options for CMTs.

Alternating rabacfosadine and doxorubicin for treatment of naïve canine lymphoma.

The current standard of care treatment for canine lymphoma is a multi-agent, CHOP-based chemotherapy protocol. Single agent doxorubicin (DOX) is less burdensome; however, multi-agent chemotherapy protocols are often superior. The recently approved drug rabacfosadine (RAB, Tanovea) provides an attractive option for combination therapy with DOX, as both drugs demonstrate efficacy against lymphoma and possess different mechanisms of action. A previous study evaluating alternating RAB/DOX reported an overall response rate (ORR) of 84%, with a median progression-free survival time (PFS) of 194 days. The aim of this prospective trial was to evaluate the same protocol in an additional population of dogs. Fifty-nine dogs with treatment naïve lymphoma were enrolled. RAB (1.0 mg/kg IV) was alternated with DOX (30 mg/m2 IV) every 21 days for up to six total treatments (3 cycles). Response assessment and adverse event (AE) evaluation were performed every 21 days using VCOG criteria. The ORR was 93% (79% CR, 14% PR). The median time to maximal response was 21.5 days; median PFS was 199 days. T cell immunophenotype and lack of treatment response were predictive of inferior outcomes. AEs were mostly gastrointestinal. Six dogs developed presumed or confirmed pulmonary fibrosis; four were grade 5. One dog experienced grade 3 extravasation injury with RAB that resolved with supportive treatment. These data mirror those of the previously reported RAB/DOX study, and support the finding that alternating RAB/DOX is a reasonable treatment option for canine lymphoma.

Retrospective evaluation of toceranib phosphate (Palladia) in the treatment of canine carcinomatosis and mesothelioma.

Canine carcinomatosis (CC) and mesothelioma (CM) are rare but aggressive neoplasms that historically have been associated with poor prognoses. There is limited information regarding treatment for CC and CM. The purpose of this retrospective study was to evaluate the efficacy and tolerability of toceranib phosphate (Palladia) in dogs with CC and CM. Cases were solicited from the American College of Veterinary Internal Medicine (ACVIM) Oncology listserv and retrospectively reviewed. For eligibility, a cytologic and/or histopathologic diagnosis of CC or CM was required. A total of 23 cases were included (CC = 14, CM = 8, both = 1). Eighty-two percent (19/23) of dogs presented with effusion. The best overall response rate (BORR) was 30.4% (13% complete response [CR], 17.3% partial response [PR]). Stable disease (SD) was appreciated in 14 dogs (60.8%) including the four dogs without effusion. The most common toceranib-related adverse events were either Grade 1 and 2 diarrhea or hyporexia. The median progression-free survival (PFS) was 171 days (range, 7-519 days) and overall median survival time (MST) was 301 days (range, 49-875 days) for all dogs. When evaluating dogs solely with effusion, the median PFS and overall MST were 171 days (range, 7-519 days) and 285 days (range, 49-875 days), respectively. This report demonstrates that toceranib is both well tolerated and a potential treatment for CC and CM. A randomised, controlled, prospective study would be needed to objectively assess the survival benefit of toceranib in the management of CC and CM, with and without effusion.

Placement of a subcutaneous ureteral bypass in a Miniature Pinscher with presumed xanthine urolithiasis as a result of allopurinol treatment.

INTRODUCTION: This case report describes the long-term success of a subcutaneous ureteral bypass device in a dog for treatment of a ureteral obstruction. The suspected xanthine urolithiasis was secondary to treatment with allopurinol for leishmaniasis. The dog presented initially with lethargy, anuria and abdominal pain. Mild azotemia was found on biochemical analysis and abdominal ultrasound revealed bilateral ureteral obstruction. A subcutaneous ureteral bypass was subsequently placed using a standard surgical technique. The dog recovered uneventfully and the azotemia resolved within days. Follow-up examinations were performed every trimester for over three years and no complications like obstruction of the bypass tubes, urinary tract infection or azotemia were recognized during this follow-up period. Allopurinol was replaced with domperidone as long-term treatment against Leishmaniasis which resulted in a mild increase of the leishmania serum antibody titer. The subcutaneous ureteral bypass placement was successful and safe in this dog and is a valuable alternative in cases of ureteral obstruction also in dogs.

INTRODUCTION: Ce rapport de cas décrit le succès à long terme d'une dérivation urétérale sous-cutanée chez un chien pour le traitement d'une obstruction urétérale. L'urolithiase xanthique suspectée était secondaire à un traitement à l'allopurinol contre la leishmaniose. Le chien a d'abord présenté une léthargie, une anurie et des douleurs abdominales. L'analyse biochimique a révélé une légère azotémie et l'échographie abdominale a révélé une obstruction urétérale bilatérale. Une dérivation urétérale sous-cutanée a été mise en place selon une technique chirurgicale standard. Le chien s'est rétabli sans incident et l'azotémie a disparu en quelques jours. Des examens de suivi ont été effectués tous les trimestres pendant plus de trois ans et aucune complication telle qu'une obstruction du tube de dérivation, une infection urinaire ou une azotémie n'a été constatée au cours de cette période de suivi. L'allopurinol a été remplacé par de la dompéridone dans le cadre d'un traitement à long terme contre la leishmaniose, ce qui a entraîné une légère augmentation du titre des anticorps sériques contre la leishmaniose. La mise en place d'une dérivation urétérale sous-cutanée s'est avérée efficace et sûre chez ce chien et constitue une alternative intéressante en cas d'obstruction urétérale, y compris chez les chiens.

Antibacterial effects of chitosan-based hydrogels containing Trachyspermum ammi essential oil on pathogens isolated from dogs with otitis externa.

BACKGROUND: Growing antibiotic resistance has made treating otitis externa (OE) increasingly challenging. On the other hand, local antimicrobial treatments, especially those that combine essential oils (EOs) with nanoparticles, tend to be preferred over systemic ones. It was investigated whether Ajwain (Trachyspermum ammi) EO, combined with chitosan nanoparticles modified by cholesterol, could inhibit the growth of bacterial pathogens isolated from OE cases in dogs. In total, 57 dogs with clinical signs of OE were examined and bacteriologically tested. Hydrogels of Chitosan were synthesized by self-assembly and investigated. EO was extracted (Clevenger machine), and its ingredients were checked (GC-MS analysis) and encapsulated in chitosan-cholesterol nanoparticles. Disc-diffusion and broth Micro-dilution (MIC and MBC) examined its antimicrobial and therapeutic properties. RESULTS: Staphylococcus pseudintermedius (49.3%) was the most common bacteria isolated from OE cases, followed by Pseudomonas aeruginosa (14.7%), Escherichia coli (13.3%), Streptococcus canis (9.3%), Corynebacterium auriscanis (6.7%), Klebsiella pneumoniae (2.7%), Proteus mirabilis (2.7%), and Bacillus cereus (1.3%). The investigation into the antimicrobial properties of Ajwain EO encapsulated in chitosan nanoparticles revealed that it exhibited a more pronounced antimicrobial effect against the pathogens responsible for OE. CONCLUSIONS: Using chitosan nanoparticles encapsulated with EO presents an effective treatment approach for dogs with OE that conventional antimicrobial treatments have not cured. This approach not only enhances antibacterial effects but also reduces the required dosage of antimicrobials, potentially preventing the emergence of antimicrobial resistance.

Basic triage in dogs and cats: Part III.

Background: Emergency cases can be presented at any time of the day or night. All small animal practitioners need to have the skills to triage and stabilize common emergency cases, even if the ultimate goal is to refer the animal to another facility. Objective and procedure: The third and final part of this 3-part review article series discusses arrhythmias typical in emergency cases and the approach to animals that are presented with an inability to stand up and walk normally. A stepwise method to categorize and stabilize these cases is outlined, along with helpful tips to optimize the referral experience, if indicated. Results: Recognizing and knowing how to treat tachy- and bradyarrhythmias is important in stabilizing a dog's or cat's condition. Understanding how to differentiate the various reasons that a dog or cat is unable to stand on its own allows a veterinarian to both treat and communicate outcome expectations for those animals. Conclusion and clinical relevance: Do not refer emergent cases before basic stabilization is completed. Many emergency cases can either be worked up by the primary veterinarian or sent to a referral clinic on an appointment basis after appropriate stabilization steps have occurred.

Triage de base chez les chiens et les chats : Partie III. Mise en contexte: Les cas d'urgence peuvent être présentés à toute heure du jour ou de la nuit. Tous les praticiens des petits animaux doivent avoir les compétences nécessaires pour trier et stabiliser les cas d'urgence courants, même si le but ultime est de référer l'animal vers un autre établissement. Objectif et procédure: La troisième et dernière partie de cette série d'articles de synthèse en trois parties traite des arythmies typiques des cas d'urgence et de l'approche des animaux présentant une incapacité à se lever et à marcher normalement. Une méthode par étapes pour catégoriser et stabiliser ces cas est décrite, ainsi que des conseils utiles pour optimiser l'expérience de référence, si cela est indiqué. Résultats: Reconnaître et savoir comment traiter les tachy- et bradyarythmies est important pour stabiliser l'état d'un chien ou d'un chat. Comprendre comment différencier les différentes raisons pour lesquelles un chien ou un chat est incapable de se tenir seul permet au vétérinaire de traiter et de communiquer les attentes en matière de résultats pour ces animaux. Conclusion et pertinence clinique: Ne référez pas les cas urgents avant que la stabilisation de base ne soit terminée. De nombreux cas d'urgence peuvent être traités par le vétérinaire initial ou envoyés à une clinique de référence sur rendez-vous après que les mesures de stabilisation appropriées ont été prises.(Traduit par Dr Serge Messier).

A retrospective study of chemotherapeutic effect without wide-margin surgery or radiation therapy in dogs with oral malignant melanoma.

Background: Effective treatment for canine oral malignant melanoma (e.g., curative-intent surgery) may not be feasible or radiation therapy may be unavailable. However, chemotherapy is usually an option, and more information is needed regarding its use without adequate local treatments. Objective: Our objective was to investigate the efficacy of chemotherapy in canine oral malignant melanoma without adequate local control, using carboplatin with dose reduction in small-breed dogs and metronomic chemotherapy. Animals and procedure: Client-owned dogs with histopathologically diagnosed oral malignant melanoma were retrospectively enrolled from 2016 to 2022. The chemotherapy protocol in each case was determined by the attending clinician. Results: Thirteen dogs were included. The median progression-free interval of all 13 dogs was 42 d (14 to 953 d). The median overall survival time of dogs with chemotherapy as their only systemic treatment was 181 d (50 to 960 d; n = 11). The median dosage of carboplatin was 250 mg/m2. Response to treatment and clinical stage were significant prognostic factors. Conclusion and clinical relevance: As chemotherapy provided a median survival of 6 mo, it could be considered when adequate local control is infeasible. Earlier clinical stages or achievement of at least stable disease during chemotherapy may indicate better survival in dogs.

Une étude rétrospective de l'effet chimiothérapeutique sur le mélanome malin buccal canin dépourvu de chirurgie et de radiothérapie á large marge : le stade clinique et la réponse au traitement prédisent les résultats du patient. Mise en contexte: Des traitements efficaces pour le mélanome malin oral canin, tels que la chirurgie á visée curative, ne sont parfois pas réalisables ou la radiothérapie n'est pas disponible dans certaines régions. La chimiothérapie reste une option de traitement et davantage d'informations devraient être fournies pour les cas qui n'ont pas eu accés á un traitement local adéquat. Objectif: Cette étude visait á étudier l'efficacité de la chimiothérapie dans le mélanome malin oral canin sans contrôle local adéquat, en utilisant le carboplatine avec réduction de dose chez les chiens de petite race et la chimiothérapie métronomique. Animaux et procédure: Treize chiens appartenant á des clients atteints d'un mélanome malin oral diagnostiqué par histopathologie ont été rétrospectivement inscrits de 2016 á 2022. Le protocole de chimiothérapie a été déterminé par le clinicien traitant. Résultats: L'intervalle médian sans progression des treize chiens était de 42 jours (14­953 jours). La durée médiane de survie globale des chiens ayant reçu une chimiothérapie comme seul traitement systémique était de 181 jours (50­960 jours; n = 11). La dose médiane de carboplatine était de 250 mg/m2. La réponse au traitement et le stade clinique étaient des facteurs pronostiques importants. Conclusion et pertinence clinique: La chimiothérapie pouvait encore être envisagée lorsqu'un contrôle local adéquat était impossible. Des stades cliniques plus précoces ou des patients atteignant au moins une maladie stable pendant la chimiothérapie peuvent indiquer une meilleure survie.(Traduit par les auteurs).

Efficacy of moxidectin, using various dose regimens, against JYD-34, a macrocyclic lactone resistant isolate of Dirofilaria immitis.

BACKGROUND: Macrocyclic lactones (MLs) are the only class of drugs currently commercially available that are effective for preventing heartworm disease. The data presented in this article provide information on the efficacy of oral moxidectin against JYD-34, a known ML-resistant Dirofilaria immitis isolate, when dogs are treated under various dosing regimens. METHODS: Fifty-two purpose-bred Beagle dogs were used in five laboratory studies. All dogs were inoculated with 50 D. immitis third-stage larvae (L3) (JYD-34 isolate) 30 days prior to the first treatment. Dogs were randomized to treatment (four to five animals in each group) with one, three, or five monthly doses of oral moxidectin ranging from 6 to 100 µg/kg body weight. In each study, control dogs were not treated. Five to 6 months after L3 inoculation, dogs were euthanized, and adult worms were counted to evaluate efficacy of the dosing regimens. RESULTS: Adult heartworms were recovered from all control dogs, with an overall geometric mean of 29.7 worms (range 15.2 to 38.0, individual counts ranged from 8 to 51). Five monthly doses of 6 µg/kg provided 83.3% and 90.2%, efficacy, and the same number of monthly doses of 9 µg/kg demonstrated 98.8% and 94.1% efficacy. Three monthly doses of 30 and 50 µg/kg demonstrated 97.9% and 99.0% efficacy, respectively, while a single dose of 100 µg/kg demonstrated 91.1% efficacy. CONCLUSIONS: Five monthly doses of 9 µg/kg provided similar or only marginally lower efficacy against JYD-34, a known ML-resistant isolate, compared to substantially higher doses administered for 3 months. This underscores the importance of duration of exposure to moxidectin when facing ML-resistant isolates. Repeated administration of lower doses of moxidectin are an alternative to higher doses in the prevention of heartworm disease associated with less susceptible or resistant isolates.

Evaluation of clinical response and prognostic factors in canine multicentric lymphoma treated with first rescue therapy.

Despite an initial strong response in most dogs with multicentric lymphoma treated with chemotherapy, relapse remains common. There is no clearly superior first rescue protocol described either for resistant or relapsed canine multicentric lymphoma. The objectives of this study were to assess clinical response and outcomes for canine multicentric lymphoma treated with first rescue protocols. The secondary objective was to assess prognostic variables for dogs undergoing these protocols. This was a bi-institutional retrospective cohort study. Two hundred and sixty-five dogs were treated with first rescue chemotherapy, including anthracycline-based combination chemotherapy (CHOP-like, n = 50), nitrosourea alkylating agent-rich chemotherapy (n = 45), anthracycline-based or related compound chemotherapy (n = 34), or nitrosourea single-agent chemotherapy (n = 136). The overall median progression free survival time of first rescue protocol was 56.0 days (0-455 days). Important prognostic factors identified for first rescue protocol included the attainment of a complete response to the first rescue chemotherapy (p < .001), the use of a CHOP-like first rescue protocol (p = .009), duration of first remission (HR 0.997, p = .028), and if prednisolone was included in the first rescue protocol (HR 0.41, p = .003). Adverse events (AE) were common, with 81.1% of dogs experiencing at least one AE during first rescue chemotherapy. This study highlights the need for improved first rescue therapies to provide durable remission in canine resistant or relapsed lymphoma.

Efficacy of monthly treatment with oral fluralaner (Bravecto® 1-Month) against Tunga penetrans in dogs in Brazil: a randomized, double-blind, controlled field study.

BACKGROUND: Tungiasis is a neglected tropical disease caused by the adult female sand flea (Tunga penetrans). Dogs are considered important reservoirs of T. penetrans in Brazil. The aim of this study was to determine the monthly insecticidal efficacy of a single oral administration of fluralaner at a dose of 10-18 mg/kg (Bravecto® 1-Month, also registered as Defenza® in some countries; MSD Animal Health) in dogs naturally infested with T. penetrans. METHODS: This clinical trial was conducted in a rural community located in Ilhéus, Bahia, Brazil. A total of 64 dogs were selected and distributed in a completely randomized design between a treated group (TG) that received one single dose of Bravecto® 1-Month (Defenza®) and a negative control group (CG) that received no treatment. Each group was composed of 32 dogs. The evaluations took place on days 0, 7 ± 2, 14 ± 2, 21 ± 2, 28 ± 2, 35 ± 2, and 42 ± 2 post treatment, in which the dogs were inspected to evaluate the infestation stage and classify lesions associated with tungiasis. The primary efficacy was determined from the percentage of treated dogs free of fleas (stage II and III lesions) after administration of the formulation at each evaluation time. Secondary efficacy was based on the number of active lesions (stages II and III) in each group at each evaluation time. The clinical condition of the animals was defined based on the Severity Score for Acute Dog Tungiasis (SCADT), which is related to the number and severity of lesions. RESULTS: The primary efficacy of the product was greater than 95.0% from days 7 to 21 and reached 100.0% between days 28 and 42, with a significant association between treatment and infestation decline (P < 0.025) between days 7 and 42. Secondary drug efficacy was greater than 99.9% from days 7 to 21, reaching 100.0% between days 28 and 42 (P < 0.05). The treated dogs also scored lower on the SCADT than the control animals did during the entire clinical evaluation period (P < 0.05). CONCLUSIONS: A single administration of Bravecto® 1-Month (Defenza®) was effective in eliminating Tunga penetrans infestations, as well as in preventing parasitism for at least 42 days after treatment.

Effect of the sodium-glucose cotransporter-2 inhibitor, DWP16001, as an add-on therapy to insulin for diabetic dogs: A pilot study.

BACKGROUND: Sodium-glucose cotransporter-2 (SGLT2) inhibitors are a novel class of anti-hyperglycaemic agents. OBJECTIVE: This study aimed to evaluate the safety and the adjuvant glycaemic control effect of an SGLT2 inhibitor, DWP16001, in diabetic dogs receiving insulin treatment. METHODS: Nineteen diabetic dogs receiving insulin treatment (NPH, porcine lente and glargine insulin) were divided into two groups according to dosing frequency: DWP TOD group (n = 10) and DWP SID group (n = 9). In the DWP TOD group, 0.025 mg/kg of DWP16001 was administered once every 3 days, whereas, in the DWP SID group, 0.025 mg/kg of DWP16001 was administered once a day. Food intake was maintained during the trial period. Hypoglycaemia, ketoacidosis or unexpected life-threatening reactions were assessed as adverse effects before and after DWP16001 administration. We compared insulin requirement reduction and blood glucose level control between two groups. RESULTS: No specific adverse effects were observed during the clinical trial, and haematological parameter remained unchanged. Moreover, the fasting glucose levels and daily insulin dose in the DWP TOD group were lower than the pre-administration values, but not significantly different for 8 weeks. Systolic blood pressure, fructosamine and insulin dose decreased significantly in the DWP SID group compared to the DWP TOD group at 8 weeks (p < 0.05) without affecting food consumption. Among these patients, 10 patients were monitored while receiving DWP16001 for 12 months (DWP TOD group n = 5, DWP SID group n = 5). The fasting glucose and fructosamine levels and daily insulin dose were reduced in both groups at 12 months compared with those before receiving DWP16001. CONCLUSION: When DWP16001, an SGLT2 inhibitor, was supplied to dogs with type 1 diabetes, no adverse effects were observed, and it was confirmed that the administered insulin dose can be reduced in controlling blood glucose.

Effects of trastuzumab emtansine on canine urothelial carcinoma cells in vitro and in vivo.

Urothelial carcinoma (UC) is the most common malignancy of the urinary tract in dogs and has aggressive behaviour. Although human epidermal growth factor receptor 2 (HER2) is a known therapeutic target with evidence in canine UC, the efficacy of anti-HER2 antibody drugs remains unknown. This study aimed to investigate the effects of anti-HER2 antibody drugs including trastuzumab and trastuzumab emtansine (T-DM1) on canine UC cell lines in vitro and in vivo. Four canine UC cell lines (Nene, TCCUB, Love, and Sora) were used. In western blotting, HER2 protein expression was observed in all the cell lines. Although both trastuzumab and T-DM1 showed dose-dependent growth inhibitory activity in the cell lines, T-DM1 showed much stronger activity than that of trastuzumab. In flow cytometry analyses with the canine UC cell line (Sora), T-DM1 but not trastuzumab significantly increased the percentages of early and late apoptotic cells in annexin V apoptotic assays and the sub-G1 phase fraction in cell cycle analyses. For the in vivo experiment, the canine UC cells (Sora) were subcutaneously injected into nude mice. Four days after inoculation, trastuzumab, T-DM1, or vehicle was administered intraperitoneally once a week for three times. Tumour volumes were significantly smaller in the T-DM1 group compared to the trastuzumab and vehicle control groups. These findings indicate that T-DM1 exerts a stronger antitumour effect than that of trastuzumab on canine UC cells in vitro and in vivo, possibly by inducing apoptosis due to DM1.

Reinfection of farm dogs following praziquantel treatment in an endemic region of cystic echinococcosis in southeastern Iran.

Cystic Echinococcosis (CE) as a prevalent tapeworm infection of human and herbivorous animals worldwide, is caused by accidental ingestion of Echinococcus granulosus eggs excreted from infected dogs. CE is endemic in the Middle East and North Africa, and is considered as an important parasitic zoonosis in Iran. It is transmitted between dogs as the primary definitive host and different livestock species as the intermediate hosts. One of the most important measures for CE control is dog deworming with praziquantel. Due to the frequent reinfection of dogs, intensive deworming campaigns are critical for breaking CE transmission. Dog reinfection rate could be used as an indicator of the intensity of local CE transmission in endemic areas. However, our knowledge on the extent of reinfection in the endemic regions is poor. The purpose of the present study was to determine E. granulosus reinfection rate after praziquantel administration in a population of owned dogs in Kerman, Iran. A cohort of 150 owned dogs was recruited, with stool samples collected before praziquantel administration as a single oral dose of 5 mg/kg. The re-samplings of the owned dogs were performed at 2, 5 and 12 months following initial praziquantel administration. Stool samples were examined microscopically using Willis flotation method. Genomic DNA was extracted, and E. granulosus sensu lato-specific primers were used to PCR-amplify a 133-bp fragment of a repeat unit of the parasite genome. Survival analysis was performed using Kaplan-Meier method to calculate cumulative survival rates, which is used here to capture reinfection dynamics, and monthly incidence of infection, capturing also the spatial distribution of disease risk. Results of survival analysis showed 8, 12 and 17% total reinfection rates in 2, 5 and 12 months following initial praziquantel administration, respectively, indicating that 92, 88 and 83% of the dogs had no detectable infection in that same time periods. The monthly incidence of reinfection in total owned dog population was estimated at 1.5% (95% CI 1.0-2.1). The results showed that the prevalence of echinococcosis in owned dogs, using copro-PCR assay was 42.6%. However, using conventional microscopy, 8% of fecal samples were positive for taeniid eggs. Our results suggest that regular treatment of the dog population with praziquantel every 60 days is ideal, however the frequency of dog dosing faces major logistics and cost challenges, threatening the sustainability of control programs. Understanding the nature and extent of dog reinfection in the endemic areas is essential for successful implementation of control programs and understanding patterns of CE transmission.

Longitudinal antimicrobial susceptibility trends of canine Staphylococcus pseudintermedius.

Antimicrobial resistance within Staphylococcus pseudintermedius poses a significant risk for the treatment of canine pyoderma and as a reservoir for resistance and potential zoonoses, but few studies examine long-term temporal trends of resistance. This study assesses the antimicrobial resistance prevalence and minimum inhibitory concentration (MIC) trends in S. pseudintermedius (n=1804) isolated from canine skin samples at the Cornell University Animal Health Diagnostic Center (AHDC) between 2007 and 2020. Not susceptible (NS) prevalence, Cochran-Armitage tests, logrank tests, MIC50 and MIC90 quantiles, and survival analysis models were used to evaluate resistance prevalence and temporal trends to 23 antimicrobials. We use splines as predictors in accelerated failure time (AFT) models to model non-linear temporal trends in MICs. Multidrug resistance was common among isolates (47%), and isolates had moderate to high NS prevalence to the beta-lactams, chloramphenicol, the fluoroquinolones, gentamicin, the macrolides/lincosamides, the tetracyclines, and trimethoprim-sulfamethoxazole. However, low levels of NS to amikacin, rifampin, and vancomycin were observed. Around one third of isolates (38%) were found to be methicillin resistant S. pseudintermedius (MRSP), and these isolates had a higher prevalence of NS to all tested antimicrobials than methicillin susceptible isolates. Amongst the MRSP isolates, one phenotypically vancomycin resistant isolate (MIC >16 µg/mL) was identified, but genomic sequence data was unavailable. AFT models showed increasing MICs across time to the beta-lactams, chloramphenicol, the fluoroquinolones, gentamicin, and the macrolides/lincosamides, and decreasing temporal resistance (decreasing MICs) to doxycycline was observed amongst isolates. Notably, ATF modeling showed changes in MIC distributions that were not identified using Cochran-Armitage tests on prevalence, MIC quantiles, and logrank tests. Increasing resistance amongst these S. pseudintermedius isolates highlights the need for rational, empirical prescribing practices and increased antimicrobial resistance (AMR) surveillance to maintain the efficacy of current therapeutic agents. AFT models with non-linear predictors may be a useful, breakpoint-independent, surveillance tool alongside other modeling methods and antibiograms.

A randomized double-blind clinical trial: Comparison of oclacitinib with a traditional Chinese herbal medicine product (Dihuang Guiqin capsule) in the treatment of canine atopic dermatitis.

Canine atopic dermatitis (cAD) is a common chronic inflammatory skin disease, which seriously affects the quality of life for both dogs and their owners. Currently, the common therapeutic drugs in the clinic have disadvantages such as obvious adverse effects and high prices. Traditional Chinese herbal medicine (TCHM) has great potential for the treatment of cAD. The aim of this study is to compare the effects of different doses of the TCHM product (Dihuang Guiqin capsule) and oclacitinib in the treatment of cAD through a randomized, double-blind trial. Sixty dogs diagnosed with AD were randomly and evenly divided into four groups (n = 15). The TCHM treatment group consisted of three subgroups that received three different oral doses (20, 40, and 60 mg/kg BW), while the control group received 0.5 mg/kg BW of oclacitinib. Each group was administered twice daily for 14 consecutive days. The results showed that both TCHM and oclacitinib significantly improved cAD-induced itching (evaluated by pVAS) and skin lesions (evaluated by CADESI-04), while interleukin 31 (IL-31) concentrations decreased significantly (P < 0.05) and serum biochemical indicators returned to normal. In particular, The therapeutic effects of TCHM medium- and high-dose groups were similar to those of oclacitinib (P > 0.05). The preliminary recommended dose of Dihuang Guiqin capsule for the treatment of cAD has been determined to be 40-60 mg/kg BW twice daily for 14 consecutive days, which can be reduced to once daily as appropriate. Dihuang Guiqin capsule was safe and well tolerated, which may be a new option for the treatment of cAD.

Dose regimen optimization of cephalothin for surgical prophylaxis against Staphylococcus aureus and coagulase negative staphylococci in dogs by pharmacokinetic/pharmacodynamic modeling.

First generation cephalosporins such cephalothin of cefazolin are indicated for antimicrobial prophylaxis for clean and clean contaminated surgical procedures because its antimicrobial spectrum, relative low toxicity and cost. Anesthesia and surgery could alter the pharmacokinetic behavior of different drugs administered perioperative by many mechanisms that affect distribution, metabolism or excretion processes. Intravenous administration of the antimicrobial within 30 and 60 min before incision is recommended in order to reach therapeutic serum and tissue concentrations and redosing is recommended if the duration of the procedure exceeds two half-life of the antimicrobial. To the author's knowledge there are no pharmacokinetic studies of cephalothin in dogs under anesthesia/surgery conditions. The aim of this study was (1) to evaluate the pharmacokinetics of cephalothin in anesthetized dogs undergoing ovariohysterectomy by a nonlinear mixed-effects model and to determine the effect of anesthesia/surgery and other individual covariates on its pharmacokinetic behavior; (2) to determine the MIC and conduct a pharmacodynamic modeling of time kill curves assay of cephalothin against isolates of Staphylococcus spp. isolated from the skin of dogs; (3) to conduct a PK/PD analysis by integration of the obtained nonlinear mixed-effects models in order to evaluate the antimicrobial effect of changing concentrations on simulated bacterial count; and (4) to determine the PK/PD endpoints and PK/PDco values in order to predict the optimal dose regimen of cephalothin for antimicrobial prophylaxis in dogs. Anesthesia/surgery significantly reduced cephalothin clearance by 18.78%. Based on the results of this study, a cephalothin dose regimen of 25 mg/kg q6h by intravenous administration showed to be effective against Staphylococcus spp. isolates with MIC values ≤2 µg/mL and could be recommended for antimicrobial prophylaxis for clean surgery in healthy dogs.