Case report: Naturally occurring neurogenic stunned myocardium in a dog secondary to status epilepticus.

A 4-year-old male neutered Boston Terrier was presented with status epilepticus. He was diagnosed with idiopathic epilepsy and hospitalized with supportive care. During hospitalization, the patient developed both supraventricular and ventricular arrhythmias as well as focal left ventricular dyskinesis. Cardiac troponin I was significantly increased, which was supportive of myocardial damage. Neurogenic stunned myocardium was suspected, and the patient was treated and responded to esmolol. Follow-up echocardiography demonstrated the resolution of the ventricular dyskinesia. This report describes the clinical presentation, diagnostic findings, treatment, management, and outcome of the first reported case of naturally occurring neurogenic stunned myocardium in a dog. Electrocardiogram monitoring, cardiac troponin I, and echocardiography should be considered in patients presenting with seizure activity, especially when exhibiting cluster seizures or in status epilepticus

Association between dyslipidemia and asthma in children: a systematic review and multicenter cohort study using a common data model

Background The association between dyslipidemia and asthma in children remains unclear. Purpose This study investigated the association between dyslipidemia and cholesterol levels in children. Methods A systematic literature review was performed to identify studies investigating the association between dyslipidemia and asthma in children. The PubMed database was searched for articles published from January 2000–March 2022. Data from a cohort study using electronic health records from 5 hospitals, converted to the Observational Medical Outcomes Partnership Common Data Model (OMOP-CDM), were used to identify the association between total cholesterol (TC) levels and asthma in children. This cohort study used the Cox proportional hazards model to examine hazard ratio (HR) of asthma after propensity score matching, and included an aggregate meta-analysis of HR. Results We examined 11 studies reporting an association between dyslipidemia and asthma in children. Most were cross-sectional; however, their results were inconsistent. In OMOP-CDM multicenter analysis, the high TC (>170 mg/dL) group included 29,038 children, while the normal TC (≤170 mg/dL) group included 88,823 children including all hospital datasets. In a meta-analysis of this multicenter cohort, a significant association was found between high TC levels and later development of asthma in children <15 years of age (pooled HR, 1.30; 95% confidence interval, 1.12–1.52). Conclusion Elevated TC levels in children may be associated with asthma

Guided bone regeneration with beta-tricalcium phosphate and poly L-lactide-co-glycolide-co-epsilon-caprolactone membrane in partial defects of canine humerus

This study was performed to evaluate the effect of beta-tricalcium phosphate and poly L-lactide-co-glycolide-co-epsilon-caprolactone (TCP/PLGC) membrane in the repair of partial bone defects in canine proximal humerus. Three adult mixed-breed dogs were used during the experimental period. The length of the defect was quarter of the full length of humerus, and width of the defect was quarter of middle diameter of the lateral aspect of humerus. The humeri of each dog were divided into treatment (TCP/PLGC) and control groups. The defect was covered with TCP/PLGC membrane in treatment group. To evaluate regeneration of the bone, computerized tomography (CT) and histopathologic examination were performed. The radiopaque lines were appeared at the original defect sites in TCP/PLGC group but below the original site in control at 4th week. Radiopacity and thickness of the defect sites, and radiopaque lines were more increased at 8th week than those of 4th week. Histopathologic findings revealed fibrous connective tissue migration into the defect and the migration inhibited the structure of new cortex to be placed in the original level in control whereas new cortex growth was found in the level of original line in TCP/PLGC group. However, the new cortical bone in the TCP/PLGC group was thinner and less organized than the adjacent intact cortex, and the amount of new cancellous bones were also scanty. The result suggested that TCP/PLGC membrane is a good guided bone regeneration material to restore the original morphology of humerus in partial defect

Cerebellar vermian hypoplasia in a Cocker Spaniel

An eight-week-old female Cocker Spaniel was presented with ataxia, dysmetria and intention tremor. At 16 weeks, the clinical signs did not progress. Investigation including imaging studies of the skull and cerebrospinal fluid analysis were performed. The computed tomography revealed a cyst-like dilation at the level of the fourth ventricle associated with vermal defect in the cerebellum. After euthanasia, a cerebellar hypoplasia with vermal defect was identified on necropsy. A polymerase chain reaction amplification of cerebellar tissue revealed the absence of an in utero parvoviral infection. Therefore, the cerebellar hypoplasia in this puppy was consistent with diagnosis of primary cerebellar malformation comparable to Dandy-Walker syndrome in humans

Medial canthoplasty for epiphora in dogs: A retrospective study of 23 cases

The medical records of 23 dogs that underwent medial canthoplasty for treatment of epiphora were reviewed. The most prevalent breed encountered was the shih tzu. Other affected breeds included the Pekingese, Maltese, toy poodle, and pug. All dogs had epiphora associated with medial canthal trichiasis and/or entropion. Other ocular abnormalities included conjunctivitis, keratitis, pigmentary keratitis, corneal ulceration, globe prolapse, and nasal fold trichiasis. After medial canthoplasty, the epiphora resolved in all dogs.The authors thank the veterinarians who referred the dogs, and illustrator Un Gyu Lim for his drawing in the preparation of the illustration

Erratum: Establishment of a canine spinal cord injury model induced by epidural balloon compression

A model that provides reproducible, submaximal yet sufficient spinal cord injury is needed to allow experiments leading to development of therapeutic techniques and prediction of clinical outcome to be conducted. This study describes an experimental model for spinal cord injury that uses three different volumes of balloon inflation and durations of compression to create a controlled gradation outcome in adult dogs. Twenty-seven mongrel dogs were used for this study. A 3-french embolectomy catheter was inserted into the epidural space through a left hemilaminectomy hole at the L4 vertebral arch. Balloons were then inflated with 50, 100, or 150 µl of a contrast agent at the L1 level for 6, 12, or 24 h and spinal canal occlusion (SCO) measured using computed tomography. Olby score was used to evaluate the extent of spinal cord injury and a histopathologic examination was conducted 1 week after surgery. The SCO of the 50, 100, and 150 µl inflations was 22-46%, 51-70%, and 75-89%, respectively (p < 0.05). Olby scores were diminished significantly by a combination of the level of SCO and duration of inflation in all groups. Olby scores in the groups of 150 µl-12 h, 150 µl-24 h, and 100 µl-24 h were 0.5, 0, and 1.7, respectively. Based on these results, a SCO > 50% for 24 h, and > 75% for 12 h induces paraplegia up to a week after spinal cord injury

Implantation of canine umbilical cord blood-derived mesenchymal stem cells mixed with beta-tricalcium phosphate enhances osteogenesis in bone defect model dogs

This study was performed to evaluate the osteogenic effect of allogenic canine umbilical cord blood-derived mesenchymal stem cells (UCB-MSCs) mixed with beta-tricalcium phosphate (β-TCP) in orthotopic implantation. Seven hundred milligrams of β-TCP mixed with 1 × 106 UCB-MSCs diluted with 0.5 ml of saline (group CM) and mixed with the same volume of saline as control (group C) were implanted into a 1.5 cm diaphyseal defect and wrapped with PLGC membrane in the radius of Beagle dogs. Radiographs of the antebrachium were made after surgery. The implants were harvested 12 weeks after implantation and specimens were stained with H&E, toluidine blue and Villanueva-Goldner stains for histological examination and histomorphometric analysis of new bone formation. Additionally, UCB-MSCs were applied to a dog with non-union fracture. Radiographically, continuity between implant and host bone was evident at only one of six interfaces in group C by 12 weeks, but in three of six interfaces in group CM. Radiolucency was found only near the bone end in group C at 12 weeks after implantation, but in the entire graft in group CM. Histologically, bone formation was observed around β-TCP in longitudinal sections of implant in both groups. Histomorphometric analysis revealed significantly increased new bone formation in group CM at 12 weeks after implantation (p < 0.05). When applied to the non-union fracture, fracture healing was identified by 6 weeks after injection of UCB-MSCs. The present study indicates that a mixture of UCB-MSCs and β-TCP is a promising osteogenic material for repairing bone defects

Functional recovery and neural differentiation after transplantation of allogenic adipose-derived stem cells in a canine model of acute spinal cord injury

In this study, we evaluated if the implantation of allogenic adipose-derived stem cells (ASCs) improved neurological function in a canine spinal cord injury model. Eleven adult dogs were assigned to three groups according to treatment after spinal cord injury by epidural balloon compression: C group (no ASCs treatment as control), V group (vehicle treatment with PBS), and ASC group (ASCs treatment). ASCs or vehicle were injected directly into the injured site 1 week after spinal cord injury. Pelvic limb function after transplantation was evaluated by Olby score. Magnetic resonance imaging, somatosensory evoked potential (SEP), histopathologic and immunohistichemical examinations were also performed. Olby scores in the ASC group increased from 2 weeks after transplantation and were significantly higher than C and V groups until 8 weeks (p < 0.05). However, there were no significant differences between the C and V groups. Nerve conduction velocity based on SEP was significantly improved in the ASC group compared to C and V groups (p < 0.05). Positive areas for Luxol fast blue staining were located at the injured site in the ASC group. Also, GFAP, Tuj-1 and NF160 were observed immunohistochemically in cells derived from implanted ASCs. These results suggested that improvement in neurological function by the transplantation of ASCs in dogs with spinal cord injury may be partially due to the neural differentiation of implanted stem cells

Transplantation of canine umbilical cord blood-derived mesenchymal stem cells in experimentally induced spinal cord injured dogs

This study was to determine the effects of allogenic umbilical cord blood (UCB)-derived mesenchymal stem cells (MSCs) and recombinant methionyl human granulocyte colony-stimulating factor (rmhGCSF) on a canine spinal cord injury model after balloon compression at the first lumbar vertebra. Twenty-five adult mongrel dogs were assigned to five groups according to treatment after a spinal cord injury: no treatment (CN); saline treatment (CP); rmhGCSF treatment (G); UCB-MSCs treatment (UCB-MSC); co-treatment (UCBG). The UCB-MSCs isolated from cord blood of canine fetuses were prepared as 106 cells/150 µl saline. The UCB-MSCs were directly injected into the injured site of the spinal cord and rmhGCSF was administered subcutaneously 1 week after the induction of spinal cord injury. The Olby score, magnetic resonance imaging, somatosensory evoked potentials and histopathological examinations were used to evaluate the functional recovery after transplantation. The Olby scores of all groups were zero at the 0-week evaluation. At 2 week after the transplantation, the Olby scores in the groups with the UCB-MSC and UCBG were significantly higher than in the CN and CP groups. However, there were no significant differences between the UCB-MSC and UCBG groups, and between the CN and CP groups. These comparisons remained stable at 4 and 8 week after transplantation. There was significant improvement in the nerve conduction velocity based on the somatosensory evoked potentials. In addition, a distinct structural consistency of the nerve cell bodies was noted in the lesion of the spinal cord of the UCB-MSC and UCBG groups. These results suggest that transplantation of the UCB-MSCs resulted in recovery of nerve function in dogs with a spinal cord injury and may be considered as a therapeutic modality for spinal cord injury

YH29407 with anti-PD-1 ameliorates anti-tumor effects via increased T cell functionality and antigen presenting machinery in the tumor microenvironment

Among cancer cells, indoleamine 2, 3-dioxygenase1 (IDO1) activity has been implicated in improving the proliferation and growth of cancer cells and suppressing immune cell activity. IDO1 is also responsible for the catabolism of tryptophan to kynurenine. Depletion of tryptophan and an increase in kynurenine exert important immunosuppressive functions by activating regulatory T cells and suppressing CD8+ T and natural killer (NK) cells. In this study, we compared the anti-tumor effects of YH29407, the best-in-class IDO1 inhibitor with improved pharmacodynamics and pharmacokinetics, with first and second-generation IDO1 inhibitors (epacadostat and BMS-986205, respectively). YH29407 treatment alone and anti-PD-1 (aPD-1) combination treatment induced significant tumor suppression compared with competing drugs. In particular, combination treatment showed the best anti-tumor effects, with most tumors reduced and complete responses. Our observations suggest that improved anti-tumor effects were caused by an increase in T cell infiltration and activity after YH29407 treatment. Notably, an immune depletion assay confirmed that YH29407 is closely related to CD8+ T cells. RNA-seq results showed that treatment with YH29407 increased the expression of genes involved in T cell function and antigen presentation in tumors expressing ZAP70, LCK, NFATC2, B2M, and MYD88 genes. Our results suggest that an IDO1 inhibitor, YH29407, has enhanced PK/PD compared to previous IDO1 inhibitors by causing a change in the population of CD8+ T cells including infiltrating T cells into the tumor. Ultimately, YH29407 overcame the limitations of the competing drugs and displayed potential as an immunotherapy strategy in combination with aPD-1