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Background: The study employs finite element analysis (FEA) to investigate stress distribution in the radius of toy poodles after screw removal. The examination focuses on the biomechanical implications of varied screw hole configurations using 1.5-mm and 2.0-mm locking compression plates (LCP) with notched head T-Plates. Aim: To provide a non-invasive approach to analyzing the immediate consequences of screw removal from the radius bone in toy poodles. Specifically, it explores the impact of varied plate designs and screw arrangements on stress distribution within the forelimb bones. Methods: The study constructs a three-dimensional bone model of the toy poodle's forelimb based on computed tomography (CT) images. Simulations were designed to replicate jumping and landing from a 40 cm height, comparing stress distribution in the radius post-screw removal. Results: The analysis reveals significant variations in stress distribution patterns between the two LCPs. The radius implanted with the 2.0-mm LCP displays a uniform stress distribution, contrasting with the 1.5-mm plates. Localized stress concentration is observed around the screw holes, while trabecular bone regions near the screw holes exhibit lower stress levels. Conclusion: The study highlights the plate designs and screw configurations that affect bone stress in toy poodle forelimbs post-screw removal. The findings provide valuable insights for veterinarians, aiding informed decisions in veterinary orthopedic practices. [Open Vet J 2024; 14(3.000): 885-894]

Atlanto-axial instability is a common disease that affects toy-breed dogs. Most cases of atlanto-axial instability are congenital. Furthermore, patients with atlanto-axial instability are predisposed to other concurrent diseases. Therefore, this study aimed to retrospectively determine the presence of concurrent diseases in cases with atlanto-axial instability using imaging data and analyze the relationship between clinical parameters and the incidence of complex malformations. The clinical data and imaging findings of 41 toy-breed dogs diagnosed with atlanto-axial instability were analyzed using their medical records and imaging data. Occipital dysplasia (17/27), atlanto-occipital overlapping (22/34), dens dysplasia (27/41), Chiari-like malformation (8/34), syringomyelia (5/34), lateral ventricular enlargement (20/36), and intracranial arachnoid cyst (5/35) were observed in patients with atlanto-axial instability. The body weight of the patients in the groups with atlanto-occipital overlapping and lateral ventricular enlargement was lower than that of those in the groups without these diseases (1.78 ± 0.71 vs 2.71 ± 1.15 kg, P = 0.0269, 1.60 ± 0.40 vs 2.75 ± 1.08 kg, P = 0.001, respectively). Furthermore, when the correlation between the total number of concurrent diseases and the age at onset and body weight was examined, it became clear that lower body weight was associated with the incidence of a greater number of concurrent diseases. Thus, the findings of this study suggest that toy-breed dogs are more likely to present with complex malformations and should be evaluated carefully with additional examinations and treatment methods.

Background: Accurate dose assessment during animal radiotherapy is beneficial for veterinary medicine and medical education. Aim: To visualize the radiation treatment distribution of orthovoltage X-ray equipment in clinical practice using Monte Carlo simulations and created a dog skull water phantom for animal-specific radiotherapy. Methods: EGSnrc-based BEAMnrc and DOSXYZnrc codes were used to simulate orthovoltage dose distributions. At 10, 20, 30, 40, 50 and 80 mm in a water phantom, depth dose was measured with waterproof Farmer dosimetry chambers and the diagonal off-axis ratio was measured with Gafchromic EBT3 film to simulate orthovoltage dose distributions. Energy differences between orthovoltage and linear accelerated radiotherapy were assessed with a heterogeneous bone and tissue virtual phantom. The animal-specific phantom for radiotherapy quality assurance was created from CT scans of a dog and printed with a three-dimensional printer using polyamide 12 nylon, with insertion points for dosimetry chambers and Gafchromic EBT3 film. Results: Monte Carlo simulated and measured dose distributions differed by no more than 2.0% along the central axis up to a depth of 80 mm. The anode heel effect occurred in shallow areas. The orthovoltage radiotherapy percentage depth dose in bone was >40%. Build-up was >40%, with build-down after bone exit, whereas linear accelerator radiotherapy absorption changed little in the bone. A highly water-impermeable, animal-specific dog skull water phantom could be created to evaluate dose distribution. Conclusion: Animal-specific water phantoms and Monte Carlo simulated pre-treatment radiotherapy is useful quality assurance for orthovoltage radiotherapy and yields a visually familiar phantom that will be useful for veterinary medical education. [Open Vet J 2023; 13(4.000): 427-432]

Background: Histiocytic sarcoma (HS) is an aggressive malignant neoplasm, and widespread metastasis occurs with a fatal outcome. HS involving the central nervous system is relatively uncommon. Spinal cord necrosis, a very rare condition, could be induced by ischemia or infarction. Here, we report a dog progressing non-ambulatory tetraparesis with spinal cord necrosis caused by HS. Case Description: A 9-year-old male Labrador retriever was presented with a progressing non-ambulatory tetraparesis. CT imaging revealed lysis of the spinous process of T7 and a ring-shaped lesion surrounding the soft tissue of lung fields. T2-weighted MRI showed the spinous processes of T6 to T8 as hyperintense, and the lesion infiltrated into the T7 vertebra and the spinal cord. After euthanasia, the final diagnosis upon necropsy was HS, which was observed in the lung, spinous process, thoracic cord, and the pulmonary hilar lymph node. Moreover, necrotic spots were spread widely through the thoracic spinal cord. Conclusion: This report outlines a case of canine HS in the lung, spinous process, thoracic cord, and pulmonary hilar lymph node. Ischemic deficit and necrosis of the thoracic spinal cord resulted from the compression of perivascular tumor cells, which rapidly led to progressive tetraparesis. Although the diagnosis was difficult, MRI and CT images helped determine the prognosis. To our knowledge, this is the first case report of canine HS with direct spinal cord involvement associated with spinal necrosis. [Open Vet J 2023; 13(3.000): 394-399]

Case summary A 10-year-old male neutered Abyssinian cat was presented with the chief complaint of a right pharyngeal mass. On palpation, the mass was easily palpable; it appeared well demarcated and mobile, and oval in shape. Radiographic examination showed a radiopaque pharyngeal mass, which was revealed to be a well-demarcated mass lesion with a radiopaque marginal area on CT examination. The inside of the mass was uniformly well enhanced on contrast CT examination. A three-dimensional image reconstructed from the CT images strongly suggested that the mass originated from the right stylohyoid bone. No abnormal lesions were observed in the thoracic and abdominal CT examinations. Surgical excision of the mass was scheduled 3 weeks after the first admission. The mass was bluntly separated from the surrounding musculature and resected together with the ipsilateral epihyoid bone adjacent to the mass. Histopathological examination of the resected mass showed neoplastic cells with osteoid formation, and the mass was histopathologically diagnosed as an osteosarcoma. The postoperative recovery from anaesthesia was uneventful, and the cat began feeding on its own from the third postoperative day. The 3-month postoperative CT evaluation revealed no local recurrence or distant metastasis. The cat showed no abnormal findings at the time of writing (6 months postoperatively). Relevance and novel information Although osteosarcoma derived from the hyoid bone has rarely been reported in the veterinary field, this report suggests that such tumours may occur in cats. In addition, partial excision of the hyoid apparatus seems to be well tolerated in cats.

Background: Intensity-modulated radiotherapy (IMRT), which allows generating steep dose gradients, is a beneficial treatment for companion animals with adjacent target and risk organs. IMRT is essential for high setup accuracy for avoiding overdose to risk organs, and optimal radiotherapy is important for evaluating the setup accuracy of companion animals. Aim: To use an immobilization device to evaluate setup errors in radiotherapy for companion animals Materials and methods: We calculated setup errors in radiotherapy for 386 animals (dogs and cats; 3261 registration images) that underwent radiotherapy between 2016 and 2022. The companion animals were immobilized with a customized bite block and vacuum lock device. A quantile–quantile plot with 95% confidence interval (CI) was used to evaluate the histogram of the setup errors, and the systematic and random setup errors were calculated for each region (brain, head and neck, chest and abdomen, pelvis, and spine). Results: The setup error in each direction presented an extremely narrow-interval histogram, with the following lower and upper 95% CIs: cranial–caudal (−0.08, −0.06 cm); left–right (−0.04, −0.02 cm); and dorsal–ventral (−0.13, −0.11 cm). The mean systematic setup error was 0.16 cm (range: 0.12–0.36 cm), and the random error was 0.15 cm (range: 0.08–0.34 cm). The pelvis showed the highest systematic and random setup errors (mean: 0.36 and 0.23 cm, respectively). Conclusion: The use of an immobilization device enables highly accurate radiotherapy for companion animals (95% CI < 0.15 cm). [Open Vet J 2022; 12(6.000): 929-935]

Background: Radiation therapy is considered important for the treatment of intranasal tumors in dogs and is believed to be essential for prolonging their survival. Aim: We investigated the contribution of clinical staging to improving outcomes of megavoltage radiotherapy for canine intranasal tumors. Methods: A total of 123 dogs with intranasal tumors were included in the study. Forty-eight dogs received orthovoltage radiotherapy after cytoreductive surgery (Group I), 21 received orthovoltage radiotherapy without surgery (Group II), and 54 received megavoltage radiotherapy without surgery (Group III). All cases in each group were classified into clinical stages 1–4, and the median survival time (MST) was compared for each stage in all groups. Results: The overall MST was not significantly difference among Group I (325 days), Group II (317 days) and Group III (488 days), however, the Group III was prolonged than Groups I and II. The MSTs for stages 1, 2, 3 and 4 were 597, 361, 267 and 325 days in Group I, and 633, 260, 233 and 329 days in Group II, and 931, 860, 368 and 176 days in Group III, respectively. The MST for stage 2 cases in Group III was significantly prolonged when compared with that in Groups I and II; no significant difference was observed at other stages, however, the MST in Group III was longer in stage 1. These results showed that megavoltage radiotherapy prolonged the MST in dogs with intranasal tumors when compared to orthovoltage radiation with or without cytoreductive surgery, and that improvements in MST at stage 2 contributed significantly to this. Conclusion: The improvement in the MST in dogs with stages 1 and 2 intranasal tumors highlights the importance of starting megavoltage radiotherapy in the early stages.

Background: For optimal treatment, it is important to maintain optimal multi-leaf collimator (MLC) transmission in intensity-modulated radiation therapy (IMRT). However, adjustment of transmissions has not been reported in veterinary medicine. Aim: This study aimed to demonstrate that appropriate MLC parameter adjustment for IMRT using 4- and 6-MV energy can reduce the need for quality assurance revalidation in real companion animal clinical cases. Methods: The MLC parameters (leaf transmission and leaf offset) of the treatment planning system were adjusted by evaluating seven plans (10 × 10 cm, 3ABUT, DMLC, 7segA, FOURL, HDMLC, and HIMRT) and 20 pre-clinical cases (10 cases each in 4 and 6 MV groups). Subsequently, 101 IMRT plans of 88 cases (77 dogs and 11 cats) were evaluated for absolute dose of plan target volume (PTV) and organs at risk (OAR) and were analyzed for the relative dose distribution by gamma analysis (3%/3 mm, >10%) using EBT3 film. Results: After adjustment of the MLC parameters (leaf transmission and leaf offset, 4 MV: 0.008 and 0, 6 MV: 0.005 and 0), the data from 101 plans (4MV: 64 plans and 6MV: 37 plans) treated with IMRT showed PTV

Background: dogs' nephroblastoma of the spinal cord is a rare neoplastic disease, with few reports of long-term survival after surgery. We experienced that surgical treatment with postoperative radiation therapy for spinal nephroblastoma in a dog resulted in the long-term survival of 11 years. Case Description: The patient presented to our veterinary hospital because of progressive hindlimb paralysis. Based on diagnostic imaging, she was diagnosed with a thoracolumbar spinal cord tumour and was treated with surgery. The gross tumour tissue was removed after laminectomy, followed by postoperative radiation therapy using orthovoltage equipment. The histopathological features of the surgical specimen were consistent with those of previously reported spinal nephroblastoma, although infrequent mitotic figures were observed. The dog recovered well after treatment and resumed her normal walking condition.No tumour recurrence was observed on periodic follow-up magnetic resonance imaging performed 10 and 21 months after surgery. Imaging evaluation for the gradual development of hindlimb weakness was performed 9 years after surgery; however, no recurrence of tumour tissue was observed, and spondylosis deformans, probably induced after laminectomy, were identified as a possible cause. The dog died of aspiration pneumonia 11 years after surgery, independent of spinal nephroblastoma. Conclusion: To date, no clinical cases of canine spinal cord primary nephroblastoma that survived for 11 years after surgery have been reported. This case strongly suggests that providing intensive treatment for canine spinal nephroblastoma is very important.

Background: Third-degree atrioventricular block is usually permanent, with transient cases being rare. Cats with transient third-degree atrioventricular block. It had been not reported in detail. Case Description: A 9.3-year-old, male shorthair cat was evaluated for possible nervous disease resulting from otitis interna. Under propofol and isoflurane anaesthesia, this cat developed a third-degree atrioventricular block. Isoproterenol was administered by continuous infusion to increase its heart rate. During recovery, heart rate returned to sinus bradycardia together with first-degree atrioventricular block without medical treatment. The cause of transient atrioventricular block was not observed at the examination. Conclusion: The case of this cat suggests that anaesthesia can result in a transient third-degree atrioventricular block.

Abstract Inhibition of programmed death 1 (PD-1), expressed on activated T cells, can break through immune resistance and elicit durable responses in human melanoma as well as other types of cancers. Canine oral malignant melanoma is one of the most aggressive tumors bearing poor prognosis due to its high metastatic potency. However, there are few effective treatments for the advanced stages of melanoma in veterinary medicine. Only one previous study indicated the potential of the immune checkpoint inhibitor, anti-canine PD-L1 therapeutic antibody in dogs, and no anti-canine PD-1 therapeutic antibodies are currently available. Here, we developed two therapeutic antibodies, rat-dog chimeric and caninized anti-canine PD-1 monoclonal antibodies and evaluated in vitro functionality for these antibodies. Moreover, we conducted a pilot study to determine their safety profiles and clinical efficacy in spontaneously occurring canine cancers. In conclusion, the anti-canine PD-1 monoclonal antibody was relatively safe and effective in dogs with advanced oral malignant melanoma and other cancers. Thus, our study suggests that PD-1 blockade may be an attractive treatment option in canine cancers.

Craniocervical junction abnormalities with atlantoaxial subluxation caused by ventral subluxation of C2 were diagnosed in a 6-month-old female Pomeranian with tetraplegia as a clinical sign. Lateral survey radiography of the neck with flexion revealed atlantoaxial subluxation with ventral subluxation of C2. Computed tomography revealed absence of dens and atlanto-occipital overlapping. Magnetic resonance imaging showed compression of the spinal cord and indentation of caudal cerebellum. The diagnosis was Chiari-like malformation, atlantoaxial subluxation with ventral displacement of C2, atlanto-occipital overlapping, and syringomyelia. The dog underwent foramen magnum decompression, dorsal laminectomy of C1, and ventral fixation of the atlantoaxial joint. Soon after the operation, voluntary movements of the legs were recovered. Finally, the dog could stand and walk without assistance. The dog had complicated malformations at the craniocervical junction but foramen magnum decompression and dorsal laminectomy for Chiari-like malformation, and ventral fixation for atlantoaxial subluxation resulted in an excellent clinical outcome.

We tested the hypotheses that hypoxic stimulation enhances growth potentials of canine lymphoma cells by activating hypoxia-inducible factor 1α (HIF-1α), and that the hypoxia-activated prodrug (TH-302) inhibits growth potentials in the cells. We investigated how hypoxic culture affects the growth rate, chemoresistance, and invasiveness of canine lymphoma cells and doxorubicin (DOX)-resistant lymphoma cells, and influences of TH-302 on survival rate of the cells under hypoxic conditions. Our results demonstrated that hypoxic culture upregulated the expression of HIF-1α and its target genes, including ATP-binding cassette transporter B1 (ABCB1), ATP-binding cassette transporter G2 (ABCG2), platelet-derived growth factor (PDGF), vascular endothelial growth factor (VEGF), and survivin, and enhanced the growth rate, DOX resistance, and invasiveness of the cells. Additionally, TH-302 decreased the survival rate of the cells under hypoxic condition. Our studies suggest that hypoxic stimulation may advance the tumorigenicity of canine lymphoma cells, favoring malignant transformation. Therefore, the data presented may contribute to the development of TH-302-based hypoxia-targeting therapies for canine lymphoma.

Background: The study employs finite element analysis to investigate stress distribution in the radius of toy poodles after screw removal. The examination focuses on the biomechanical implications of varied screw hole configurations using 1.5 and 2.0-mm locking compression plates (LCPs) with notched head T-Plates. Aim: To provide a noninvasive approach to analyzing the immediate consequences of screw removal from the radius bone in toy poodles. Specifically, it explores the impact of varied plate designs and screw arrangements on stress distribution within the forelimb bones. Methods: The study constructs a three-dimensional bone model of the toy poodle's forelimb based on computed tomography (CT) images. Simulations were designed to replicate jumping and landing from a 40 cm height, comparing stress distribution in the radius post-screw removal. Results: The analysis reveals significant variations in stress distribution patterns between the two LCPs. The radius implanted with the 2.0-mm LCP displays a uniform stress distribution, contrasting with the 1.5-mm plates. Localized stress concentration is observed around the screw holes, while trabecular bone regions near the screw holes exhibit lower stress levels. Conclusion: The study highlights the plate designs and screw configurations that affect bone stress in toy poodle forelimbs post-screw removal. The findings provide valuable insights for veterinarians, aiding informed decisions in veterinary orthopedic practices. [ABSTRACT FROM AUTHOR]

Background: The anti-programmed death 1 (PD-1) antibody has led to durable clinical responses in a wide variety of human tumors. We have previously developed the caninized anti-canine PD-1 antibody (ca-4F12-E6) and evaluated its therapeutic properties in dogs with advance-staged oral malignant melanoma (OMM), however, their therapeutic effects on other types of canine tumors remain unclear. Objective: The present clinical study was carried out to evaluate the safety profile and clinical efficacy of ca-4F12-E6 in dogs with advanced solid tumors except for OMM. Methods: Thirty-eight dogs with non-OMM solid tumors were enrolled prospectively and treated with ca-4F12-E6 at 3 mg/kg every 2 weeks of each 10-week treatment cycle. Adverse events (AEs) and treatment efficacy were graded based on the criteria established by the Veterinary Cooperative Oncology Group. Results: One dog was withdrawn, and thirty-seven dogs were evaluated for the safety and efficacy of ca-4F12-E6. Treatment-related AEs of any grade occurred in 13 out of 37 cases (35.1%). Two dogs with sterile nodular panniculitis and one with myasthenia gravis and hypothyroidism were suspected of immune-related AEs. In 30 out of 37 dogs that had target tumor lesions, the overall response and clinical benefit rates were 6.9% and 27.6%, respectively. The median progression-free survival and overall survival time were 70 days and 215 days, respectively. Conclusions: The present study demonstrated that ca-4F12-E6 was well-tolerated in non-OMM dogs, with a small number of cases showing objective responses. This provides evidence supporting large-scale clinical trials of anti-PD-1 antibody therapy in dogs. [ABSTRACT FROM AUTHOR]

Cystine-glutamate transporter (xCT) is a plasma membrane transporter that imports cystine and indirectly contributes to the oxidative stress resistance associated with increased intracellular glutathione levels. Canine adipose-derived stem cells (CADSCs) include an xCTpositive subpopulation and show relatively low expression of osteogenic markers during in vitro osteogenic differentiation. Sulfasalazine (SSZ), a drug used to treat rheumatoid arthritis, suppresses xCT expression in cancer cells. In this study, we found that the SSZ treatment at 100 µM significantly suppressed xCT mRNA expression in CADSCs but did not significantly affect cell proliferation under the same conditions. Additionally, this treatment decreased the intracellular glutathione concentration. During in vitro osteogenic differentiation, the SSZ treatment at 50 µM and 100 µM significantly increased alizarin red staining and its quantification, as well as the concentration-dependent osteogenic differentiation markers (BMP1 and SPP) mRNA expression. Our results suggested that SSZ enhances the osteogenic differentiation potential of CADSCs and can potentially exhibit a superior therapeutic profile in canine bone regenerative medicine. [ABSTRACT FROM AUTHOR]

Background: Intensity-modulated radiotherapy (IMRT), which allows generating steep dose gradients, is a beneficial treatment for companion animals with adjacent target and risk organs. IMRT is essential for high setup accuracy for avoiding overdose to risk organs, and optimal radiotherapy is important for evaluating the setup accuracy of companion animals. Aim: To use an immobilization device to evaluate setup errors in radiotherapy for companion animals. Methods: We calculated setup errors in radiotherapy for 386 animals (dogs and cats; 3,261 registration images) that underwent radiotherapy between 2016 and 2022. The companion animals were immobilized with a customized bite block and vacuum lock device. A quantile-quantile plot with 95% confidence interval (CI) was used to evaluate the histogram of the setup errors, and the systematic and random setup errors were calculated for each region (brain, head and neck, chest and abdomen, pelvis, and spine). Results: The setup error in each direction presented an extremely narrow-interval histogram, with the following lower and upper 95% CIs: cranial-caudal (-0.08, -0.06 cm); left-right (-0.04, -0.02 cm); and dorsal-ventral (-0.13, -0.11 cm). The mean systematic setup error was 0.16 cm (range: 0.12-0.36 cm), and the random error was 0.15 cm (range: 0.08-0.34 cm). The pelvis showed the highest systematic and random setup errors (mean: 0.36 and 0.23 cm, respectively). Conclusion: The use of an immobilization device enables highly accurate radiotherapy for companion animals (95% CI < 0.15 cm). [ABSTRACT FROM AUTHOR]

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A male 25-month-old Dalmatian dog attended our veterinary hospital because of anorexia and high circulating liver enzyme activities. Abdominal computed tomography showed a slightly small liver with rounded edges, and laparoscopic examination showed that the liver was yellowish. Histopathological examination revealed multifocal necrosis of hepatocytes and severe chronic hepatitis. Rhodanine staining showed severe copper accumulation in hepatocytes and a quantitative analysis of the copper content of the liver showed substantial accumulation (10.3 mg/g dry mass), suggesting a diagnosis of copper-associated hepatitis. Previously reported canine mutation in the COMMD1, the gene responsible for the copper-associated hepatitis in the Bedlington terrier, was not identified. To our knowledge, this is the first report of copperassociated hepatitis in a Dalmatian in Japan. [ABSTRACT FROM AUTHOR]

Adipose-derived stem cells (ADSCs) are promising cell sources for regenerative medicine due to the simplicity of their harvest and culture; however, their biological properties are not completely understood. Moreover, recent murine and human studies identified several functional subpopulations of ADSCs varying in differentiation potential; however, there is a lack of research on canine ADSCs. Cystine transporter (xCT) is a stem cell marker in gastric and colon cancers that interacts with CD44 to enhance cystine uptake from the cell surface and subsequently accelerates intercellular glutathione levels. In this study, we identified a ≈5% functional subpopulation of canine ADSCs with xCT+ expression (xCTHi). Compared with those of the xCT- subpopulation (xCTLo), the xCTHi subpopulation showed a significantly higher proliferation rate, higher expression of conventional stem cell markers (SOX2, KLF4, and c-Myc), and higher expression of adipogenic markers (FABP4 and PPARγ). By contrast, the xCTLo subpopulation showed significantly higher expression of osteogenic markers (BMP1 and SPP) than xCTHi cells. These results suggest xCT as a candidate marker for detecting a functional subpopulation of canine ADSCs. Mechanistically, xCT could increase the adipogenic potential while decreasing the osteogenic differentiation potential, which could serve as a valuable target marker in regenerative veterinary medicine. [ABSTRACT FROM AUTHOR]