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Abstract Background Severe muscle stiffness (SMS) in dogs with hypercortisolism (HC) is uncommon. Objectives To evaluate signalment, presentation, treatments, and long‐term outcomes of dogs with concurrent HC and SMS. Animals Thirty‐seven dogs. Methods Medical records of dogs with HC and concurrent SMS were recruited from 10 institutions. Clinical information, test results, therapeutic responses, and survival times were reviewed. Results All 37 dogs with HC and SMS had pituitary‐dependent hypercortisolism (PDH); 36/37 weighed

Abstract Erythroleukaemia is a malignant neoplasm of the erythroid lineage that rarely occurs in cats. It is associated with the feline leukaemia virus (FeLV), and owing to the poor prognosis, treatment is rarely reported. A 4‐year‐old female Korean domestic shorthair cat was presented with hyporexia, fever, lethargy, severe anaemia and rubricytosis. An FeLV antigen test was positive, but a subsequent polymerase chain reaction test was negative. Serum biochemistry analysis results were normal, except for slightly elevated alanine aminotransferase. The patient was tentatively diagnosed with acute erythroleukaemia, and single high‐dose (600 mg/m2) cytarabine chemotherapy was administered via constant rate infusion for 12 h a day for 5 days. After the first cytarabine administration, the clinical signs and anaemia improved, though no change was noted to other haematological parameters. The patient died of shock 16 days after the second cytarabine administration; the total survival time after diagnosis was 67 days. Post‐mortem cytological evaluation of bone marrow aspiration revealed that the myeloid/erythroid ratio was 0.49, the erythroid progenitor cells were 64% of all nucleated cells and the blast cells were 84% of the non‐erythroid cells. Histopathology images indicated that the spleen was diffusely expanded by atypical round cells, possibly erythroid precursors. This is the first case report on the prognosis and effects of high‐dose cytarabine chemotherapy for acute feline erythroleukaemia with FeLV infection. Although the clinical signs improved, the treatment was not effective. Further studies on erythroleukaemia chemotherapy protocols are required.

Abstract Background Endothelial cell-specific molecule-1 (ESM-1) has emerged as a potential biomarker for cardiovascular disease in humans. Myxomatous mitral valve disease (MMVD) is the most common heart disease in dogs, and we hypothesized that MMVD causes chronic inflammation that increases susceptibility to endothelial glycocalyx (eGCX) damage. In this study, we measured the concentration of ESM-1 in a group of dogs with MMVD and evaluated factors affecting eGCX damage. Results Sixty-four dogs (control, n = 6; MMVD, n = 58) were enrolled in this study. There was no significant difference in serum ESM-1 concentrations among the MMVD stages. The serum ESM-1 concentration was significantly higher in the death group than in the alive group in MMVD dogs. (p = 0.006). In five dogs with MMVD, serum ESM-1 concentrations tended to decrease when the cardiac drug (pimobendan, furosemide, and digoxin) dose was increased. Conclusions In cases where MMVD progressed to decompensated heart failure with clinical symptoms and resulted in death, the concentration of serum ESM-1 increased significantly. Therefore, ESM-1 could be utilized as a new potential negative prognostic factor in patients with MMVD.

Abstract Background The use of fenbendazole (FBZ) in terminal cancer patients has recently increased, as anthelminthic drugs, such as FBZ and benzimidazole, exhibit anti‐tubulin effects in tumour cells. Objectives The present study evaluated the in vitro anti‐cancer effects of FBZ in five canine melanoma cell lines originating from the oral cavity (UCDK9M3, UCDK9M4, UCDK9M5, KMeC and LMeC). Methods Five canine melanoma cell lines were treated with FBZ and analysed with cell viability assay, cell cycle analysis, western blot assay and immunofluorescence staining to identify apoptotic effect, cell cycle arrest, microtubule disruption and mitotic slippage. Results Cell viability was reduced in all melanoma cell lines in a dose‐dependent manner after FBZ treatment. Through cell cycle analysis, G2/M arrest and mitotic slippage were identified, which showed a time‐dependent change. All treatment concentrations induced increased cleaved PARP signals in western blot analysis compared to the control groups. Immunofluorescence of cells treated for 24 h revealed defects in microtubule structure, multinucleation or macronucleation. With the exception of UCDK9M3, the melanoma cells showed mitotic slippage and post‐slippage death, indicative of mitotic catastrophe. Conclusions These results indicate that FBZ exhibits anti‐cancer effects in vitro against canine melanoma cells; however, further in vivo studies regarding the clinical applications of FBZ are required.

Abstract Background Gallbladder mucocele (GBM) is a common biliary disorder in dogs that can be categorized into 6 types, but the value of this classification scheme remains unknown. Cholecystectomy is associated with high death rates and warrants additional interrogation. Objectives Investigate the clinical value of ultrasonographic diagnosis of type of GBM and identify prognostic factors in dogs with GBM undergoing cholecystectomy. Animals Two hundred sixteen dogs. Methods Retrospective cohort study. Dogs with GBM diagnosed from 2014 to 2019 at 6 veterinary referral hospitals in Asia. Ultrasonogram images were reviewed and a GBM type (ie, types I‐VI) assigned. Results Dogs with GBM type V as compared to I (OR, 8.6; 95% CI, 2.6‐27.8; P

Importance: This is the first reported case of fragrance products-induced recurrent oxidative hemolytic anemia in a dog, detailing the successful therapeutic approach employed. Case Presentation: A 4-year-old intact female Pomeranian dog presented with brown tongue, pigmenturia, peripheral edema, and vomiting. Blood smears revealed a high count of eccentrocytes and Heinz bodies, along with a precipitous decline in packed cell volume and an increase in blood methemoglobin levels, suggesting an oxidative hemolytic crisis. This clinicopathological pattern recurred several times after the patient returned home. Antioxidants, methylene blue, hyperbaric oxygen (HBO) therapy, and blood transfusion were successfully employed to address recurrent hemolytic anemia; however, oxidative hemolytic crises recurred. After the owner removed exposure to various home remedies and fragrances, the clinical signs and hemolytic crises did not recur. Conclusions and Relevance: Recurring oxidative hemolytic crises should raise suspicions of environmental toxicity, which, although harmless in small quantities to humans, can be devastating to small-breed dogs. In addition to removing the causative agents, methylene blue and other antioxidants, along with HBO, may be beneficial in the acute management of oxidative hemolytic anemia. [ABSTRACT FROM AUTHOR]

Background: The grade of tracheal collapse (TC) is assessed by the diameter of the narrowed lumen. However, studies on the relationship between TC grade and clinical symptom severity are lacking. Objectives: To investigate the clinical characteristics of small-breed dogs diagnosed with TC and determine if fluoroscopic grading correlates with cough severity. Methods: We retrospectively reviewed medical records from 2022 to 2024. TC diagnosis was confirmed using fluoroscopic examination. Multiple linear regression was employed to investigate factors influencing cough severity, with a significance level set at p < 0.05. Results: A total of 132 dogs with TC were identified, of which 22 were excluded. The final cohort consisted of 110 dogs, aged between 2-19 years, with no significant sex differences. The majority (97.2%) of dogs had a BCS of =4. Among the top four breeds (Maltese, Pomeranian, Poodle, and Chihuahua), the most severe collapse was observed in the carinal region. The grade of collapse on fluoroscopy was mostly related to high BCS (p < 0.007) and low body weight (p < 0.001). However, interestingly, fluoroscopic findings of collapse location and grade did not correlate with cough severity (p = 0.350). Notably, clinical symptoms improved in 86.6% of cases following interventions such as weight reduction, environmental changes, and pharmacotherapy. Conclusions and clinical relevance: In small-breed dogs, the severity of cough was not associated with the region or grade of TC diagnosed by fluoroscopy. [ABSTRACT FROM AUTHOR]

Background: Axitinib, a potent and selective inhibitor of vascular endothelial growth factor (VEGF) receptor (VEGFR) tyrosine kinase 1,2 and 3, is used in chemotherapy because it inhibits tumor angiogenesis by blocking the VEGF/VEGFR pathway. In veterinary medicine, attempts have been made to apply tyrosine kinase inhibitors with anti-angiogenic effects to tumor patients, but there are no studies on axitinib in canine mammary gland tumors (MGTs). Objectives: This study aimed to confirm the antitumor activity of axitinib in canine mammary gland cell lines. Methods: We treated canine MGT cell lines (CIPp and CIPm) with axitinib and conducted CCK, wound healing, apoptosis, and cell cycle assays. Additionally, we evaluated the expression levels of angiogenesis-associated factors, including VEGFs, PDGF-A, FGF-2, and TGF-β1, using quantitative real-time polymerase chain reaction. Furthermore, we collected canine peripheral blood mononuclear cells (PBMCs), activated them with concanavalin A (ConA) and lipopolysaccharide (LPS), and then treated them with axitinib to investigate changes in viability. Results: When axitinib was administered to CIPp and CIPm, cell viability significantly decreased at 24, 48, and 72 h ( p < 0.001), and migration was markedly reduced (6 h, p < 0.05; 12 h, p < 0.005). The apoptosis rate significantly increased ( p < 0.01), and the G2/M phase ratio showed a significant increase ( p < 0.001). Additionally, there was no significant change in the viability of canine PBMCs treated with LPS and ConA. Conclusion: In this study, we confirmed the antitumor activity of axitinib against canine MGT cell lines. Accordingly, we suggest that axitinib can be applied as a new treatment for patients with canine MGTs. [ABSTRACT FROM AUTHOR]

Background/Aim: Nuclear matrix protein-22 (NMP- 22) is widely used in human medicine as a prognostic and diagnostic tool for urothelial carcinoma (UC). In addition, the use of urinary exosomes as a liquid biopsy tool is emerging for the diagnosis of certain types of cancer in human medicine. This study aimed to investigate the change in urinary exosomal NMP-22 for the diagnosis of UC in dogs. Patients and Methods: Among canine patients who visited the veterinary hospital, urine was collected from those whose owners provided consent. A total of 23 dogs (UC group, n=6; control group, n=17) were included in the analysis. After exosomes were isolated from the urine, NMP-22 was measured using enzyme-linked immunosorbent assay. Results: In the UC group, the expression of NMP-22 in urinary exosomes was significantly higher than that in non-UC groups (p<0.0001). Conclusion: NMP-22 is significantly increased in exosomes in the urine of dogs diagnosed with UC, suggesting that urinary exosome NMP-22 can be considered as one of the liquid biopsy tools for diagnosing UC in dogs. [ABSTRACT FROM AUTHOR]

A 2-year-old, spayed female, Bichon Frise dog was presented with reluctance to exercise, back pain, and frequent sitting down. Multiple osteolysis, periosteal proliferation, and sclerosis of the vertebral endplates of T11–13 were observed in the radiography, computed tomography, and magnetic resonance imaging. The bacterial culture of the urine specimen, the polymerase chain reaction (PCR) of the blood, and the antibody tests were positive for Brucella canis. Accordingly, discospondylitis caused by B. canis was diagnosed and doxycycline was administered. The clinical signs resolved and the culture and PCR results were negative afterwards. Doxycycline was discontinued after 6 months. The clinical signs recurred 2 weeks later, and the combination treatment of doxycycline and enrofloxacin was initiated. Though no clinical signs were observed after 9 months and the bacterial cultures and PCR were negative, the antibody titre remained at 1: 200 or more. The dog will continue taking antibiotics until the antibody titre drops. To the best of our knowledge, this is the first case report of a clinical infection of B. canis associated with canine discospondylitis in the Republic of Korea. Although the clinical signs of brucellosis might improve with antibiotic treatment, the disease cannot be cured due to Brucella’s various strategies to evade host immune systems. Specifically, it can proliferate and replicate within the host cells, resulting in an environment that makes treatment less effective. Furthermore, owing to its zoonotic potential, owners and veterinarians should consider lifelong management or euthanasia. [ABSTRACT FROM AUTHOR]

Abstract Background Romiplostim, a thrombopoietin analog, is commonly used to treat immune‐mediated thrombocytopenia (ITP) in humans, but its use in dogs remains limited. Objectives Evaluate the effects and adverse events of romiplostim administration in dogs with thrombocytopenia caused by various underlying diseases. Animals Forty‐two client‐owned dogs with naturally occurring thrombocytopenia at 2 referral animal hospitals. Methods Retrospective, multi‐institutional analysis to evaluate the outcomes of romiplostim treatment in dogs. Results Among the dogs treated with romiplostim, 27 experienced an increase in platelet count and 26 maintained a platelet count within the reference range. Platelet count improvement was observed in various conditions: primary ITP (90%, n = 18/20), pancytopenia of unknown etiology (42.9%, n = 3/7), chemotherapy‐induced thrombocytopenia (50%, n = 3/6), babesiosis (100%, n = 1/1), radiotherapy‐induced thrombocytopenia (0%, n = 0/1), and disseminated intravascular coagulopathy (33.3%, n = 2/6). The median time for platelet recovery (>50 000/μL) after romiplostim administration was 4 days, and the median time for platelet count normalization was 7 days. Median hospitalization time for the improvement group (I) was 5 days. The survival‐to‐discharge rates were 85%, 40%, and 28.6% for dogs with primary ITP, secondary thrombocytopenia, and thrombocytopenia of unknown etiology, respectively. Conclusions and Clinical Importance Romiplostim is a well‐tolerated and promising treatment for primary ITP in dogs, suggesting its potential as a valuable therapeutic option for dogs with thrombocytopenia caused by various underlying conditions. These findings emphasize the need for further research to optimize romiplostim dosing and understand its role in treating secondary thrombocytopenia and pancytopenia of unknown etiology.

Abstract 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.

Abstract Background/Aim The soluble interleukin‐2 receptor (sIL‐2R) serve as a valuable biomarker for tumors in human patients, as its levels increase during the activation of T lymphocytes in clinical states such as inflammation, infection, and tumor. This study aimed to demonstrate that sIL‐2R levels can be also elevated in dogs with tumors and evaluate its applicability as a diagnostic and prognostic factor in canine cancer patients. Patients and Methods Serum was collected from 6 healthy dogs and 34 dogs with solid tumors. The concentration of sIL‐2R was measured using a commercial enzyme‐linked immunosorbent assay kit. Results The median sIL‐2R concentration was significantly higher in dogs with solid masses than in healthy dogs (117.3 vs 68.33 pg/ml, p = 0.016). The highest median sIL‐2R concentration was found in dogs with malignant tumors, followed by those with benign tumors, and healthy dogs (119.6 vs 93.74 vs 68.33 pg/ml, respectively). In dogs with malignant tumors, the mortality rate was significantly higher in the group with high sIL‐2R levels than in the group with low sIL‐2R levels. Dogs with solid tumors, particularly those with malignant tumors, had higher concentrations of sIL‐2R than healthy dogs. Among dogs with malignant tumors, a correlation between sIL‐2R concentration and mortality rate was confirmed. Conclusion Serum sIL‐2R levels may be used to detect malignant tumors and serve as a prognostic factor in dogs with malignant tumors.

Abstract Background Tracheal collapse (TC), a common disease in dogs, is characterized by cough; however, little is known about the serum biomarkers that can objectively evaluate the severity of cough in canine TC. Furthermore, studies elucidating the relationship of fluoroscopic characteristics with the severity of cough are lacking. Therefore, this study aimed to evaluate the relationship between cough severity and clinical characteristics, fluoroscopic images, and new serum biomarkers in canine TC. Results Fifty-one client-owned dogs diagnosed with TC based on fluoroscopic and clinical signs were enrolled in this study and divided into three groups according to the severity of cough (grade of cough: 0, 1, and 2). Signalments, comorbidities, and fluoroscopic characteristics were compared among the groups retrospectively. The serum matrix metalloproteinase-9 (MMP-9), interleukin-6 (IL-6), surfactant protein-A (SP-A), and syndecan-1 (SDC-1) levels were measured in all groups. No significant differences in age, breed, sex, or clinical history were observed among the groups. Concomitant pharyngeal collapse increased significantly with the severity of cough (p = .031). Based on the fluoroscopic characteristics, the TC grade of the carinal region increased significantly and consistently with the grade of cough (p = .03). The serum MMP-9 level was significantly higher in the grade 2 group than that in the grade 0 group (p = .014). The serum IL-6 level was significantly lower in the grade 1 group than that in the grade 0 group (p = .020). The serum SP-A and SDC-1 levels did not differ significantly among the groups. Conclusions The severity of cough with the progression of TC can be predicted with the fluoroscopic TC grade at the carinal region. MMP-9 may be used as an objective serum biomarker that represents cough severity to understand the pathogenesis.

Abstract Background Canine mammary gland cancer (CMGC) is a common neoplasm in intact bitches. However, the benefit of adjuvant chemotherapy is unclear. The aim of this study was to investigate the anti-proliferative effects of paclitaxel on CMGC in in-vitro and in-vivo settings. Results Paclitaxel dose-dependently inhibited viability and induced G2/M phase cell cycle arrest and apoptosis in both primary and metastatic CMGC cell lines (CIPp and CIPm). In animal experiments, the average tumour volume decreased significantly in proportion to the administered oral paclitaxel dose. By examining tumour tissue using a TUNEL assay and immunohistochemical staining with anti-CD31 as a marker of endothelial differentiation, respectively, it was confirmed that oral paclitaxel induced apoptosis and exerted an anti-angiogenetic effect in tumour tissues. Further, downregulation of cyclin D1 in tumour tissues suggested that oral paclitaxel induced cell cycle arrest in tumour tissues in-vivo. Conclusions Our results suggest that paclitaxel may have anti-cancer effects on CMGC through cell cycle arrest, induction of apoptosis, and anti-angiogenesis. This study could provide a novel approach to treat CMGC.

Abstract Background Meningoencephalomyelitis of unknown etiology (MUE) is a comprehensive term for non-infectious inflammatory brain diseases of the central nervous system (CNS) caused by abnormal autoimmune responses. This study aims to compare the differences in survival and clinical response of MUE according to the adjuvant immunosuppressant use. Medical records of 82 dogs diagnosed with MUE were reviewed retrospectively. Results The overall survival time was 769 days (range 14–2687 days). The median survival time for each adjunctive was: leflunomide 1035 days (range 126–2163 days), mycophenolate mofetil 865 days (range 39–2191 days), cyclosporin 441 days (range 11–2176 days), cytosine arabinoside 754 days (range 6–1898 days) and a combination of mycophenolate mofetil and cytosine arabinoside 132 days (range 23–1227 days). There was no significant difference in the incidence rate of adverse events according to the immunosuppressants, but moderate to severe anemia was confirmed in 3 patients (18.7%) in the leflunomide group. Conclusions The survival time and response rate of MUE dogs differed depending on which adjunctive immunosuppressants were used. Leflunomide showed a long survival time and a relatively good response rate in dogs with MUE. However, a large-scale further study with standardized doses of immunosuppressants and supportive treatment and constant monitoring interval is needed.

Abstract Background Subcutaneous emphysema and pneumomediastinum are rare complications associated with orbital blowout pathological fracture. Case presentation A 7-year old, castrated male Abbysinian cat presented with anorexia, lethargy, nausea, eyelid swelling, nasal discharge, and sneezing. Based on the clinical and diagnostic work-up, the cat was diagnosed with T cell high-grade nasal lymphoma associated with orbital pathological fracture due to the tumour invasion. After chemotherapy, the cat showed massive subcutaneous emphysema from frontal region to abdomen and pneumomediastinum due to orbital blowout pathological fracture. As the nasal mass decreased in volume; the air had moved from the maxillary sinus to the subcutaneous region and the mediastinum through fascial planes in the head and neck region. Conclusions This is a first case report of a massive subcutaneous emphysema and pneumomediastinum due to an orbital blowout pathological fracture following chemotherapy in feline nasal lymphoma in veterinary medicine.

Abstract Tumor-associated macrophages (TAMs) play an important role in the tumor microenvironment by producing cytokines and growth factors. Furthermore, TAMs play multifunctional roles in tumor progression, immune regulation, metastasis, angiogenesis, and chemoresistance. Hypoxia in the tumor microenvironment induces tumor-supporting transformation of TAMs, which enhances tumor malignancy through developing anti-cancer resistance, for example. In this study, a hybrid spheroid model of canine mammary gland tumor (MGT) cell lines (CIPp and CIPm) and canine macrophages (DH82) was established. The effects of hypoxia induced by the spheroid culture system on the anti-cancer drug resistance of canine MGT cells were investigated. A hybrid spheroid was created using an ultralow-adhesion plate. The interactions between canine MGT cells and DH82 were investigated using a co-culture method. When co-cultured with DH82, cell viability and expression levels of tumor growth factors and multi-drug resistance genes were increased in canine MGT cells under doxorubicin. Additionally, doxorubicin-induced apoptosis and G2/M cell cycle arrest were attenuated in canine MGT cells co-cultured with DH82. In conclusion, the hybrid spheroid model established in this study reflects the hypoxic TME, allowing DH82 to induce anti-cancer drug resistance in canine MGT cells.

Chronic kidney disease (CKD) commonly occurs in old dogs and cats. Oligo-fucoidan, fucoxanthin, and L-carnitine (OFL) compounds have a variety of reno-protective properties, including anti-inflammatory, anti-oxidative, and anti-fibrotic effects. Because their effects have not been investigated in naturally occurring canine CKD, we examined their reno-protective activities in dog patients with CKD. A total of 50 patients (OFL, n = 28; control, n = 22) were included in the analysis. A significant difference was identified in serum blood urea nitrogen and creatinine concentrations between the control and OFL groups at 6 months. No significant difference in electrolytes was found between the groups. A significant difference was identified in serum creatinine concentration between the control and OFL groups in azotemic (CKD IRIS stage 2–4) at 6 months. The OFL compounds showed a reno-protective effect, consistent with previous animal studies. The OFL combination can potentially delay the progression of canine CKD and be used as an adjuvant therapy.

Administering more than 10 times the therapeutic dose of insulin is extremely rare in diabetic dogs and is life threatening with hypoglycemia and seizures if not accompanied by appropriate treatment. A 15-year-old, castrated male miniature poodle dog managed for diabetes presented with depression, disorientation, ataxia, and cluster seizures. The dog had been administered 11.1 U/kg of neutral protamine hegadorn (NPH) insulin (10 times the prescribed dose) 3 h before the onset of symptoms. Blood analysis revealed hypoglycemia, with a circulating glucose level of