Gynostemma pentaphyllum Hydrodistillate and Its Major Component Damulin B Promote Hair Growth-Inducing Properties In Vivo and In Vitro via the Wnt/ß-Catenin Pathway in Dermal Papilla Cells.

Alopecia, a prevalent yet challenging condition with limited FDA-approved treatments which is accompanied by notable side effects, necessitates the exploration of natural alternatives. This study elucidated the hair growth properties of Gynostemma pentaphyllum leaf hydrodistillate (GPHD) both in vitro and in vivo. Furthermore, damulin B, a major component of GPHD, demonstrated hair growth-promoting properties in vitro. Beyond its established anti-diabetic, anti-obesity, and anti-inflammatory attributes, GPHD exhibited hair growth induction in mice parallel to minoxidil. Moreover, it upregulated the expression of autocrine factors associated with hair growth, including VEGF, IGF-1, KGF, and HGF. Biochemical assays revealed that minoxidil, GPHD, and damulin B induced hair growth via the Wnt/ß-catenin pathway through AKT signaling, aligning with in vivo experiments demonstrating improved expression of growth factors. These findings suggest that GPHD and damulin B contribute to the hair growth-inducing properties of dermal papilla cells through the AKT/ß-catenin signaling pathway.

Suppression of Glioblastoma Stem Cell Potency and Tumor Growth via LRRK2 Inhibition.

Leucine-rich repeat kinase 2 (LRRK2), a large GTP-regulated serine/threonine kinase, is well-known for its mutations causing late-onset Parkinson's disease. However, the role of LRRK2 in glioblastoma (GBM) carcinogenesis has not yet been fully elucidated. Here, we discovered that LRRK2 was overexpressed in 40% of GBM patients, according to tissue microarray analysis, and high LRRK2 expression correlated with poor prognosis in GBM patients. LRRK2 and stemness factors were highly expressed in various patient-derived GBM stem cells, which are responsible for GBM initiation. Canonical serum-induced differentiation decreased the expression of both LRRK2 and stemness factors. Given that LRRK2 is a key regulator of glioma stem cell (GSC) stemness, we developed DNK72, a novel LRRK2 kinase inhibitor that penetrates the blood-brain barrier. DNK72 binds to the phosphorylation sites of active LRRK2 and dramatically reduced cell proliferation and stemness factors expression in in vitro studies. Orthotopic patient-derived xenograft mouse models demonstrated that LRRK2 inhibition with DNK72 effectively reduced tumor growth and increased survival time. We propose that LRRK2 plays a significant role in regulating the stemness of GSCs and that suppression of LRRK2 kinase activity leads to reduced GBM malignancy and proliferation. In the near future, targeting LRRK2 in patients with high LRRK2-expressing GBM could offer a superior therapeutic strategy and potentially replace current clinical treatment methods.

Incident non-infectious uveitis risk after immune checkpoint inhibitor treatment.

Our findings suggest that, while incident uveitis is rare in patients with cancer treated with anti-PD-1/PD-L1 inhibitors, there is an increased risk in those with skin melanoma, warranting vigilant monitoring for uveitis in this subgroup.

Seven-year follow-up of endovascular treatment of iatrogenic brachioradial artery injury complicating percutaneous coronary intervention: a case report.

The radial artery has been used increasingly for percutaneous coronary intervention because of its safety and feasible access route. Nevertheless, transradial complications are possible because of the variation in radial artery anatomy. We experienced a case of the brachioradial artery injury secondary to catheterization, presenting as hypovolemic shock. A 76-year-old woman presented at our emergency department complaining of effort-induced angina. Coronary angiography via the right radial artery showed critical stenosis in the middle of the left anterior descending coronary artery. After wiring into this vessel, balloon angioplasty using a 6-Fr Judkin left guiding catheter was performed with the deployment of the zotarolimus-eluting stent. There was difficulty in negotiating the guidewire and balloons in that resistance was experienced while passing the catheter in the upper arm. Therefore, retrograde radial arteriography was performed to determine any injury to radial artery. This showed contrast extravasation in the brachioradial artery. Initially, manual compression was tried. However, 2 hours later, the patient developed cold sweating and went into a stupor. Laboratory findings showed a decline in hemoglobin, leading to suspicion of hemorrhagic shock. We applied over 30 minutes of balloon inflation, but this was ineffective. While surgical repair was not available, a 6.0 × 50 mm Viabahn stent was placed over the axillary artery. Subsequent angiography showed no further leakage or occlusion of the brachioradial artery. The postprocedural period was uneventful, and the patient was discharged with dual antiplatelet agents. At a 7-year clinical follow-up, the patient was free from limb ischemia symptoms.

Multitask Deep Learning for Joint Detection of Necrotizing Viral and Noninfectious Retinitis From Common Blood and Serology Test Data.

Purpose: Necrotizing viral retinitis is a serious eye infection that requires immediate treatment to prevent permanent vision loss. Uncertain clinical suspicion can result in delayed diagnosis, inappropriate administration of corticosteroids, or repeated intraocular sampling. To quickly and accurately distinguish between viral and noninfectious retinitis, we aimed to develop deep learning (DL) models solely using noninvasive blood test data. Methods: This cross-sectional study trained DL models using common blood and serology test data from 3080 patients (noninfectious uveitis of the posterior segment [NIU-PS] = 2858, acute retinal necrosis [ARN] = 66, cytomegalovirus [CMV], retinitis = 156). Following the development of separate base DL models for ARN and CMV retinitis, multitask learning (MTL) was employed to enable simultaneous discrimination. Advanced MTL models incorporating adversarial training were used to enhance DL feature extraction from the small, imbalanced data. We evaluated model performance, disease-specific important features, and the causal relationship between DL features and detection results. Results: The presented models all achieved excellent detection performances, with the adversarial MTL model achieving the highest receiver operating characteristic curves (0.932 for ARN and 0.982 for CMV retinitis). Significant features for ARN detection included varicella-zoster virus (VZV) immunoglobulin M (IgM), herpes simplex virus immunoglobulin G, and neutrophil count, while for CMV retinitis, they encompassed VZV IgM, CMV IgM, and lymphocyte count. The adversarial MTL model exhibited substantial changes in detection outcomes when the key features were contaminated, indicating stronger causality between DL features and detection results. Conclusions: The adversarial MTL model, using blood test data, may serve as a reliable adjunct for the expedited diagnosis of ARN, CMV retinitis, and NIU-PS simultaneously in real clinical settings.

Uveitis Risk After the First Dose of COVID-19 Vaccination Based on Uveitis History: Matched Cohort and Crossover Case Series Study.

PURPOSE: To investigate the risk of noninfectious uveitis following the first dose of coronavirus disease 2019 (COVID-19) vaccination based on the uveitis history. DESIGN: Retrospective matched cohort and crossover case series study. METHODS: A random sample of 7 917 457 individuals who received COVID-19 vaccine between January 2021 and March 2022 in Korea, and had no recorded history of COVID-19 were categorized into the control and uveitis groups based on their uveitis history. After performing 3:1 propensity score matching, we assessed the cumulative incidence and risk of noninfectious uveitis in the 180 days after COVID-19 vaccination. Additionally, we performed a crossover case series analysis to compare the pre- and postvaccination incidence rate ratios (IRRs) of uveitis in individuals with and without a history of uveitis. RESULTS: In the matched cohort analysis, uveitis group had a significantly higher cumulative incidence of uveitis (15.4%) than control group (0.10%). The uveitis group exhibited increased risks of all uveitis types, anterior, and nonanterior uveitis in the first 60 days (hazard ratio [HR]: 169, 158, and 253, respectively) and in days 61 to 180 (HR: 166, 164, and 143, respectively) after vaccination. In the crossover case series analysis, uveitis occurred with relatively equal frequency in 20-day intervals during the 180 days before and after vaccination, regardless of uveitis history. For uveitis group, the adjusted IRRs for early and late postvaccination events were 0.92 (95% CI, 0.88-0.96) and 0.83 (95% CI, 0.80-0.85), respectively. CONCLUSIONS: COVID-19 vaccination did not increase the risk of uveitis, regardless of uveitis history.

Autophagy Genes and Otitis Media Outcomes.

Otitis media (OM) is a common cause of hearing loss in children that requires corrective surgery. Various studies have investigated the pathomechanisms and treatment of OM. Autophagy, an essential cellular recycling and elimination mechanism implicated in various diseases, is known to play an important role in the pathogenesis of OM. Here, we conducted a literature review on autophagy in OM, highlighting the relationship between expression patterns of autophagy-related factors and pathophysiological and clinical aspects of OM. We summarized the existing research results on the expression of autophagy-related factors in acute OM (AOM), OM with effusion (OME), chronic OM (COM) with cholesteatoma, and COM without cholesteatoma (CholeOM) in animals and humans. Autophagy-related factors are expressed in the middle ear mucosa or fluid of AOM, effusion of OME, granulation tissue of COM, and cholesteatoma of CholeOM. Among ATGs and other autophagy-related factors, the most extensively studied in relation to the pathogenesis of OM are mTOR, LC3II/I, PI3K, Beclin-1, FLIP, Akt, and Rubicon. Expression of autophagy-related factors is associated with AOM, OME, COM, and CholeOM. Inadequate expression of these factors or a decrease/increase in autophagy responses can result in OM, underscoring the critical role of ATGs and related factors in the pathogenesis of OM.

Quantification of the Carbon-Coating Effect on the Interfacial Behavior of Graphite Single Particles.

The effect of carbon coating on the interfacial charge transfer resistance of natural graphite (NG) was investigated by a single-particle measurement. The microscale carbon-coated natural graphite (NG@C) particles were synthesized by the simple wet-chemical mixing method using a phenolic resin as the carbon source. The electrochemical test results of NG@C using the conventional composite electrodes demonstrated desirable rate capability, cycle stability, and enhanced kinetic property. Moreover, the improvements in the composite electrodes were confirmed with the electrochemical parameters (i.e., charge transfer resistance, exchange current density, and solid phase diffusion coefficient) analyzed by a single-particle measurement. The surface carbon coating on the NG particles reduced the interfacial charge transfer resistance (Rct) and increased the exchange current density (i0). The Rct decreased from 81-101 (NG) to 49-67 Ω cm2 (NG@C), while i0 increased from 0.25-0.32 (NG) to 0.38-0.52 mA cm-2 (NG@C) after the coating process. The results suggested both electrochemically and quantitatively that the outer uniformly coated surface carbon layer on the graphite particles can improve the solid-liquid interface and other kinetic parameters, therefore enhancing the rate capabilities to obtain the high-power anode materials.

Pacing-induced cardiomyopathy in patients with preserved ejection fraction undergoing permanent cardiac pacemaker placement.

BACKGROUND: Chronic right-ventricular (RV) pacing can worsen heart failure in patients with a low ejection fraction (EF), but little is known about pacing-induced cardiomyopathy (PICM) in patients with preserved EF. We aimed to investigate risk factors of PICM in these patients during long-term follow-up. METHODS: The prospective registry at Chosun University Hospital, South Korea, included de novo patients with preserved EF undergoing transvenous permanent pacemaker (PPM) implantation for atrioventricular blockage from 2017 to 2021. Patients with EF ≥ 50% and expected ventricular pacing ≥ 40% were included. Composite outcomes were cardiac death (pump failure), hospitalization because of heart failure, PICM, and biventricular pacing (BVP) upgrade. RESULTS: A total of 168 patients (69 men, 76.3 ± 10.4 years) were included. During three years of follow-up, one patient died, 14 were hospitalized, 16 suffered PICM, and two underwent BVP upgrade. PICM were associated with reduced global longitudinal strain (GLS), prolonged paced QRS duration (pQRSd) and diastolic variables (E/e', LAVI). Cox regression analysis identified pQRSd (hazard ratio [HR], 1.111; 95% confidence interval [CI], 1.011-1.222; P = 0.03) and reduced GLS (HR, 1.569; 95% CI, 1.163-2.118; P = 0.003) as independent predictors of PICM. GLS showed high predictive accuracy for PICM, with an area under the curve of 0.84 (95% CI 0.779-0.894; P < 0.001) [GLS -12.0, 62.5% sensitivity, and 86.1% specificity]. CONCLUSION: RV pacing increased the risk of PICM in patients with preserved EF. Reduced GLS and prolonged pQRSd could help identify individuals at high risk of PICM even with preserved EF.

Noninfectious Uveitis Risk After COVID-19 Vaccination: A Nationwide Retrospective Cohort Study.

PURPOSE: To investigate the incidence and risk of noninfectious uveitis (NIU) following COVID-19 vaccination compared with an unvaccinated, uninfected control group. DESIGN: Retrospective population-based cohort study. METHODS: We included 5,185,153 individuals who received the first vaccine dose in the exposed group and 2,680,164 individuals in the unexposed, uninfected control group. The study observed for 180 days from their index date. Cumulative incidence and risk of NIU following COVID-19 vaccination, and attributable risk factors were assessed. RESULTS: Multivariable analysis showed elevated risk of nonanterior NIU within 60 days (hazard ratio [HR] 1.27 [95% confidence interval {CI} 1.03-1.55] and 61-180 days (HR 1.39 [95% CI 1.20-1.62]). Subgroup analysis highlighted an increased risk in females for early and delayed nonanterior uveitis (HR 1.44 [95% CI 1.08-1.92]; HR 1.78 [95% CI 1.43-2.20], respectively). Regardless of the location and onset timing of uveitis, a history of NIU was identified as the most significant risk factor, with a high hazard ratio ranging from 100 to 200. CONCLUSIONS: COVID-19 vaccination may modestly increase the risk of nonanterior uveitis especially in females. Despite adjustments, bias may persist in the exposed group, owing to significant differences between unexposed and exposed groups and low incidence of nonanterior uveitis in the unexposed group. Future research should aim to refine these findings by assessing uveitis risk in prior NIU patients and by enlarging the sample size or cohort matching.

Retinal Artery and Vein Occlusion Risks after Coronavirus Disease 2019 or Coronavirus Disease 2019 Vaccination.

PURPOSE: To evaluate the incidence of new retinal artery occlusion (RAO) and retinal vein occlusion (RVO) after the diagnosis of coronavirus disease 2019 (COVID-19) or vaccination against COVID-19 and compare the incidences with the population with neither. DESIGN: Nationwide population-based cohort study. PARTICIPANTS: From a nationwide population-based cohort, 8 418 590 patients were categorized into control (group 1), COVID-19 infection (group 2), and COVID-19 vaccination (group 3) groups. METHODS: The cumulative incidence of RAO and RVO was calculated in groups 1, 2, and 3 using the Kaplan-Meier method. We calculated hazard ratios (HRs) and 95% confidence intervals (CIs) based on the Poisson distribution for RAO and RVO according to each group and subgroup using Cox proportional hazards models, with group 1 as the reference. We conducted univariable and multivariable analyses for the risk factors of RAO and RVO according to each subgroup. MAIN OUTCOME MEASURES: Cumulative incidence and risks of incidence of RAO and RVO from the index date to day 60. RESULTS: In multivariable analysis, no significant increase in RAO and RVO risks after COVID-19 or COVID-19 vaccination were observed in either men or women. These results were observed consistently across various conditions in sensitivity analyses. In subgroup analysis, individuals who were vaccinated before infection showed no significant increase in RAO or RVO risks in both sexes compared with the control group. In the subgroup analysis of vaccinated patients, the HRs of RAO and RVO for different vaccine types did not show an increase compared with the control group; however, an exception was observed in women who received mRNA-1273 vaccines, who showed a higher RAO HR (4.65; 95% CI, 1.27-17.03; P = 0.021). CONCLUSIONS: Within 60 days of COVID-19 diagnosis or vaccination, RAO and RVO occurred rarely. We observed no increase in the HR of RVO and RAO relative to COVID-19 or COVID-19 vaccination except for a possible increase in the RAO HR in women who received mRNA-1273, for which the raw incidence was extremely low. Further investigation is required to validate this result. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Connectomic reconstruction predicts the functional organization of visual inputs to the navigation center of the Drosophila brain.

Many animals, including humans, navigate their surroundings by visual input, yet we understand little about how visual information is transformed and integrated by the navigation system. In Drosophila melanogaster, compass neurons in the donut-shaped ellipsoid body of the central complex generate a sense of direction by integrating visual input from ring neurons, a part of the anterior visual pathway (AVP). Here, we densely reconstruct all neurons in the AVP using FlyWire, an AI-assisted tool for analyzing electron-microscopy data. The AVP comprises four neuropils, sequentially linked by three major classes of neurons: MeTu neurons, which connect the medulla in the optic lobe to the small unit of anterior optic tubercle (AOTUsu) in the central brain; TuBu neurons, which connect the anterior optic tubercle to the bulb neuropil; and ring neurons, which connect the bulb to the ellipsoid body. Based on neuronal morphologies, connectivity between different neural classes, and the locations of synapses, we identified non-overlapping channels originating from four types of MeTu neurons, which we further divided into ten subtypes based on the presynaptic connections in medulla and postsynaptic connections in AOTUsu. To gain an objective measure of the natural variation within the pathway, we quantified the differences between anterior visual pathways from both hemispheres and between two electron-microscopy datasets. Furthermore, we infer potential visual features and the visual area from which any given ring neuron receives input by combining the connectivity of the entire AVP, the MeTu neurons' dendritic fields, and presynaptic connectivity in the optic lobes. These results provide a strong foundation for understanding how distinct visual features are extracted and transformed across multiple processing stages to provide critical information for computing the fly's sense of direction.

Retrospective evaluation of prognosis and survival with various immunosuppressants in 82 dogs diagnosed with meningoencephalitis of unknown etiology (2010-2021).

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.

Next-Generation Sequencing of Vitreoretinal Lymphoma by Vitreous Liquid Biopsy: Diagnostic Potential and Genotype/Phenotype Correlation.

Purpose: To determine the diagnostic potential of next-generation sequencing (NGS) in vitreous samples, analyze genotype-phenotype characteristics, and compare NGS of matched vitreous and brain samples in patients with associated central nervous system lymphoma (CNSL). Methods: A total of 32 patients suspected of vitreoretinal lymphoma (VRL) who underwent diagnostic vitrectomy and NGS were included in this retrospective observational case-series. Fresh vitreous specimens from diagnostic vitrectomy of VRL-suspected patients underwent NGS using a custom panel targeting 747 candidate genes for lymphoma. They also underwent malignancy cytology, interleukin (IL)-10/IL-6, immunoglobulin heavy chain (IGH)/immunoglobulin kappa light chain (IGK) monoclonality testing. MYD88 L265P mutation was examined from anterior chamber tap samples. The diagnosis of VRL was made based on typical clinical characteristics for VRL, as well as malignant cytology, IGH/IGK clonality, or IL-10/IL-6 > 1. Sensitivity and specificity of NGS were compared with conventional diagnostic tests. Brain tissues suspected of lymphoma were collected by stereotactic biopsy and underwent NGS. Genetic variations detected in NGS of vitreous and brain tissue specimens were compared. Results: The sensitivity values for cytology, IL-10/IL-6 > 1, clonality assays for IGH and IGK, MYD88 L265P detection in anterior chamber tap samples, and vitreous NGS were 0.23, 0.83, 0.68, 0.79, 0.67, and 0.85, with specificity values of 1.00, 0.83, 0.50, 0.25, 0.83, and 0.83, respectively. The sensitivity (0.85) of vitreous NGS was the highest compared to other conventional diagnostic tests for VRL. The most common mutations were MYD88 (91%), CDKN2A (36%), PIM1 (32%), IGLL5 (27%), and ETV6 (23%). Although several gene alterations demonstrated heterogeneity between the brain and eyes, some common mutational profiles were observed in matched vitreous and brain samples. Conclusions: Overall, NGS of the vitreous demonstrated high sensitivity among conventional diagnostic tests. VRL and CNSL appeared to have both shared and distinct genetic variations, which may suggest site-specific variations from a common origin.

Induction of Autophagy and Its Role in Peripheral Nerve Regeneration after Peripheral Nerve Injury.

No matter what treatment is used after nerve transection, a complete cure is impossible, so basic and clinical research is underway to find a cure. As part of this research, autophagy is being investigated for its role in nerve regeneration. Here, we review the existing literature regarding the involvement and significance of autophagy in peripheral nerve injury and regeneration. A comprehensive literature review was conducted to assess the induction and role of autophagy in peripheral nerve injury and subsequent regeneration. Studies were included if they were prospective or retrospective investigations of autophagy and facial or peripheral nerves. Articles not mentioning autophagy or the facial or peripheral nerves, review articles, off-topic articles, and those not written in English were excluded. A total of 14 peripheral nerve studies that met these criteria, including 11 involving sciatic nerves, 2 involving facial nerves, and 1 involving the inferior alveolar nerve, were included in this review. Studies conducted on rats and mice have demonstrated activation of autophagy and expression of related factors in peripheral nerves with or without stimulation of autophagy-inducing factors such as rapamycin, curcumin, three-dimensional melatonin nerve scaffolds, CXCL12, resveratrol, nerve growth factor, lentinan, adipose-derived stem cells and melatonin, basic fibroblast growth factor, and epothilone B. Among the most studied of these factors in relation to degeneration and regeneration of facial and sciatic nerves are LC3II/I, PI3K, mTOR, Beclin-1, ATG3, ATG5, ATG7, ATG9, and ATG12. This analysis indicates that autophagy is involved in the process of nerve regeneration following facial and sciatic nerve damage. Inadequate autophagy induction or failure of autophagy responses can result in regeneration issues after peripheral nerve damage. Animal studies suggest that autophagy plays an important role in peripheral nerve degeneration and regeneration.

Neuro-Ophthalmic Adverse Events of COVID-19 Infection and Vaccines: A Nationwide Cohort Study.

Purpose: To evaluate the association of COVID-19 infection and vaccination with neuro-ophthalmic adverse events. Methods: In this nationwide population-based retrospective cohort study, 8,498,353 patients were classified into three groups: control, COVID-19 infection, and COVID-19 vaccination. We conducted separate analyses for the early phase (within 60 days) and late phases (61-180 days) to estimate the incidence rates and hazard ratio (HR) for each neuro-ophthalmic adverse event. The adverse events included in this analysis were optic neuritis, papilledema, ischemic optic neuropathy, third nerve palsy, fourth nerve palsy, sixth nerve palsy, facial palsy, nystagmus, ptosis, blepharospasm, anomalies of pupillary function, and Guillain-Barré syndrome/Miller Fisher syndrome (GBS/MFS). Results: Neuro-ophthalmic adverse events other than ptosis and GBS/MFS exhibited no significant increase after COVID-19, and their incidence was extremely low. The incidence rate of ptosis in both phases was significantly higher in patients administered COVID-19 vaccination (HR = 1.65 in the early phase and HR = 2.02 in the late phase) than in the control group. Additionally, BNT162b2 conferred a lower ptosis risk than ChAdOx1. GBS/MFS had a significantly higher incidence rate in the early phase (HR = 5.97) in patients with COVID-19 infection than in the control group. Conclusions: Ptosis was associated with COVID-19 vaccination, particularly with the ChAdOx1 vaccine, while GBS/MFS was associated with COVID-19 infection. In contrast, no association was found between other neuro-ophthalmic adverse events and COVID-19 infection or vaccination. These results may provide helpful insights for diagnosing and treating the neuro-ophthalmological adverse events after COVID-19.

Palmar-plantar erythrodysesthesia syndrome resulting from toceranib phosphate in a dog with apocrine gland anal sac adenocarcinoma: a case report.

An 11-year-old neutered male Miniature Poodle with a stage 3 apocrine gland adenocarcinoma was started on chemotherapy with toceranib phosphate after surgery. Beginning on day 10 of toceranib, the dog's foot pads became erythematous and hyperkeratinized. The dog complained of pain, inability to walk, depression, and loss of appetite. The symptoms resolved when toceranib was discontinued and reappeared when toceranib was resumed. Grade 3 palmar-plantar erythrodysesthesia was identified as an adverse event of toceranib based on the VCOG-CTCAE and Naranjo scale. Although very rare in veterinary medicine, clinicians should consider that palmar-plantar erythrodysesthesia can occur after toceranib administration.