@article{vernier_fick_johnson_ueda_vigani_2024, title={Case report: use of pleural dialysis as an alternate means of renal replacement therapy in three cats}, volume={11}, ISSN={["2297-1769"]}, DOI={10.3389/fvets.2024.1447629}, abstractNote={Objective The objective of this case series is to describe the indications, methodology, and short-term outcomes of three cats with severe azotemia managed with pleural dialysis. Case summary Three cats were presented separately to the emergency room (ER) on referral for severe azotemia of varying etiologies. Despite aggressive medical and/or surgical management, none of the cats showed improvement in their blood urea nitrogen (BUN) or creatinine values. Renal replacement therapy was recommended, but for varying reasons, the patients were unable to undergo a traditional extracorporeal method, such as intermittent hemodialysis (IDH). Instead, pleural dialysis was performed, and all three cats showed improvement in their renal values during and after their treatment. No significant complications were documented as a result of pleural dialysis. Two of the three cats were discharged from the hospital and the third cat was humanely euthanized due to poor prognosis. New or unique information provided Pleural dialysis is a novel therapeutic procedure that is not documented in veterinary or human literature. This method of renal replacement therapy was well-tolerated and had no reported complications. Careful case selection and risk-benefit analysis should be considered before attempting this procedure. Further studies are necessary to further define the utility of this therapeutic intervention, evaluate the incidence of complications, and determine long term outcomes following the procedure.}, journal={FRONTIERS IN VETERINARY SCIENCE}, author={Vernier, Mara E. and Fick, Meghan E. and Johnson, Tyler E. and Ueda, Yu and Vigani, Alessio}, year={2024}, month={Oct} } @article{hobbs_davis_cooper_ueda_burke_sheats_2024, title={Hemadsorption extracorporeal therapy removes cytokines ex vivo in horses}, volume={85}, ISSN={["1943-5681"]}, DOI={10.2460/ajvr.24.01.0022}, abstractNote={Plasma cytokine adsorption has shown benefit as an adjunctive therapy in human sepsis but has yet to be investigated in horses. We hypothesized that ex vivo filtration of equine plasma with a novel cytokine adsorption device would significantly reduce concentrations of lipopolysaccharide-stimulated cytokines. We also hypothesized that the device would adsorb medications commonly used to treat sepsis.}, number={6}, journal={AMERICAN JOURNAL OF VETERINARY RESEARCH}, author={Hobbs, Kallie J. and Davis, Jennifer L. and Cooper, Bethanie L. and Ueda, Yu and Burke, Megan J. and Sheats, Katie}, year={2024}, month={Jun} } @article{wimbish_lynch_knych_ueda_messenger_2024, title={Pharmacokinetics of a continuous intravenous infusion of hydromorphone in healthy dogs}, volume={11}, ISSN={["2297-1769"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-85191704117&partnerID=MN8TOARS}, DOI={10.3389/fvets.2024.1362730}, abstractNote={Introduction Dosing recommendations for hydromorphone intravenous constant rate infusion (IV CRI) are derived from simulations following IV bolus administration. While this extrapolated dose regimen has been described clinically, pharmacokinetics (PK) of hydromorphone infusions in dogs are not yet described. The study objective was to describe the PK of hydromorphone in healthy dogs receiving an IV bolus followed by an IV CRI for 48 h. Methods A prospective, experimental study was performed involving the administration of hydromorphone (0.1 mg/kg IV bolus then IV CRI 0.01 mg/kg/h over a 48 h period) to 6 healthy Beagle dogs. Blood samples were collected at 16 time points between 0 and 58 h relative to the initial bolus. Plasma hydromorphone concentrations were analyzed by high pressure liquid chromatography with tandem mass spectrometry detection. Pharmacokinetic parameter estimates were obtained with compartmental methods using commercially available software. Results A two-compartment model with first order elimination was used. At the end of the infusion, median (range) plasma hydromorphone concentrations were 6.8 (5.5–19.6) ng/mL. The median total body clearance was 30.4 (19.8–36.7) mL/min/kg; volume of distribution at steady state was 4.5 (3.2–7.8) L/kg; and terminal elimination half-life was 11.2 (7.6–24.3) h. Conclusion Hydromorphone (0.1 mg/kg IV bolus then IV CRI of 0.01 mg/kg/h) maintained steady-state plasma concentrations above the minimum human analgesic target in healthy Beagle dogs with minimal side effects. Further studies are needed to determine the effective plasma concentrations of hydromorphone in painful dogs.}, journal={FRONTIERS IN VETERINARY SCIENCE}, author={Wimbish, Candace and Lynch, Alex M. and Knych, Heather K. and Ueda, Yu and Messenger, Kristen M.}, year={2024}, month={Apr} } @article{rivas_vandewege_ueda_kaplan_reader_roberts_stern_2024, title={Transcriptomic and genetic profiling in a spontaneous non-human primate model of hypertrophic cardiomyopathy and sudden cardiac death}, volume={14}, ISSN={["2045-2322"]}, DOI={10.1038/s41598-024-82770-4}, abstractNote={Hypertrophic cardiomyopathy (HCM) afflicts humans, cats, pigs, and rhesus macaques. Disease sequelae include congestive heart failure, thromboembolism, and sudden cardiac death (SCD). Sarcomeric mutations explain some human and cat cases, however, the molecular basis in rhesus macaques remains unknown. RNA-Seq of the LV tissues of five HCM-affected and seven healthy control rhesus macaques was employed for differential transcriptomic analyses. DNA from 15 severely HCM-affected and 21 healthy geriatric rhesus macaques were selected for whole-genome sequencing. A genome-wide association study (GWAS) of disease status and SCD outcome was performed. 614 down- and 1,065 upregulated differentially expressed genes (DEGs) were identified between groups. The top DEG (MAFF) was overexpressed in affected animals (log2FoldChange = 4.71; PAdjusted-value = 1.14E-133). Channelopathy-associated enriched terms were identified in ~ 57% of downregulated DEGs providing transcriptomic evidence of hypertrophic and arrhythmic disease processes. For GWAS, no putative variant withstood segregation. Polygenic modeling analysis resulted in poor prediction power and burden testing could not explain HCM by an association of multiple variants in any gene. Neither single nor compound genetic variant(s), or identified polygenic profile, suggest complex genotype–phenotype interactions in rhesus macaques. Brought forth is an established dataset of robustly phenotyped rhesus macaques as an open-access resource for future cardiovascular disease genetic studies.}, number={1}, journal={SCIENTIFIC REPORTS}, author={Rivas, Victor N. and Vandewege, Michael W. and Ueda, Yu and Kaplan, Joanna L. and Reader, Jrachel and Roberts, Jeffrey A. and Stern, Joshua A.}, year={2024}, month={Dec} } @article{hobbs_le sueur_hallowell_martin_sheats_ueda_2024, title={Use of extracorporeal hemoperfusion therapy in an adult horse with Clostridioides difficile colitis and severe systemic inflammatory response syndrome}, volume={8}, ISSN={["1939-1676"]}, url={https://doi.org/10.1111/jvim.17154}, DOI={10.1111/jvim.17154}, abstractNote={An 8-year-old American Quarter Horse gelding was treated with extracorporeal hemoperfusion (HP) therapy for treatment of Clostridioides difficile (C. difficile) colitis-induced systemic inflammatory response syndrome (SIRS). The gelding developed C. difficile associated peracute colitis and severe SIRS as evidenced by a positive fecal C. difficile PCR and tachypnea, tachycardia, fever, neutropenia, altered mucous membrane color, and hyperlactatemia. Concurrent acute kidney injury in the horse limited the use of routine anti-inflammatory and anti-lipopolysaccharide treatments, including flunixin meglumine and polymyxin B, because of potential for nephrosis. Extracorporeal HP therapy was performed twice within 48 hours of the onset of severe SIRS during which the horse's physical examination variables stabilized. The horse was euthanized after 4 days because of laminitis. These findings support further investigation of extracorporeal HP therapy as an adjunctive treatment for severe SIRS/sepsis in horses.}, journal={JOURNAL OF VETERINARY INTERNAL MEDICINE}, author={Hobbs, Kallie J. and Le Sueur, Andre N. V. and Hallowell, Kimberly and Martin, Emily and Sheats, Mary Katherine and Ueda, Yu}, year={2024}, month={Aug} } @article{rank_lynch_green_reed-jones_harrell_ueda_2023, title={Case report: Laryngospasm following ethanol ablation of a parathyroid nodule in a dog with primary hyperparathyroidism}, volume={10}, ISSN={["2297-1769"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-85164445744&partnerID=MN8TOARS}, DOI={10.3389/fvets.2023.1201663}, abstractNote={A 12-year-old female spayed dachshund was presented for emergency assessment of respiratory distress, characterized by inspiratory dyspnea with stridor. Percutaneous ultrasound-guided ethanol ablation of a functional parathyroid tumor was performed 72-h earlier for management of primary hyperparathyroidism. The dog was hypocalcemic (ionized calcium 0.7 mmol/L, reference interval: 0.9–1.3 mmol/L) at the time of presentation and had evidence of laryngospasm on a sedated oral exam. The dog was managed conservatively with supplemental oxygen, anxiolysis, and parenteral calcium administration. These interventions were associated with rapid and sustained improvement in clinical signs. The dog did not demonstrate any recurrence of signs afterwards. To the authors' knowledge, this is the first description of laryngospasm following ethanol ablation of a parathyroid nodule in a dog that developed hypocalcemia.}, journal={FRONTIERS IN VETERINARY SCIENCE}, author={Rank, Kaitlyn and Lynch, Alex M. and Green, Randolph and Reed-Jones, Leslie and Harrell, Karyn and Ueda, Yu}, year={2023}, month={Jun} } @article{rank_lynch_ruterbories_li_ueda_2023, title={Evaluation of thrombin generation in dogs administered clopidogrel}, volume={10}, ISSN={2297-1769}, url={http://dx.doi.org/10.3389/fvets.2023.1194242}, DOI={10.3389/fvets.2023.1194242}, abstractNote={IntroductionThe antiplatelet effect of clopidogrel can vary between patients. A modified thromboelastography (TEG) protocol (TEG-Platelet Mapping assay® [TEG-PM]) can be used for clopidogrel monitoring but is not widely available. Thrombin generation (TG) assays could offer a novel alternative. The main objective of this pilot study was to assess TG assay variables (lag time, peak, endogenous thrombin potential [ETP]) in dogs before and after 7 days of clopidogrel administration and compare with TEG-PM variables (maximum amplitude [MA]-ADP and percentage (%) inhibition).MethodsSix healthy mix-breed dogs were enrolled in this pilot study. Blood samples for platelet count, TG assays, and TEG-PM were obtained at two time points, corresponding to baseline, and after 7 days of clopidogrel administration (mean 2.3 +/− 0.3 mg/kg PO q24 hours). Data were then compared with a Student’s t-test.ResultsThere was no significant change in TG assay variables performed on platelet poor plasma after 7 days of clopidogrel administration: lag time (Day 1: 1.8 +/− 0.2 min, Day 7: 1.8 +/− 0.2 min, p = 0.42); peak (Day 1: 76 +/− 7 nM, Day 7: 72 +/− 10 nM, p = 0.49); and ETP (Day 1: 399 +/− 27 nM*min, Day 7: 392 +/− 32 nM*min; p = 0.49). There were significant changes in TEG MA-ADP (Day 1: 19 +/− 8 mm, Day 7: 9 +/− 6 mm, p = 0.04) and % inhibition (Day 1: 58 +/− 27, Day 7: 99 +/− 0.3, p = 0.02).DiscussionClopidogrel administration did not lead to changes in TG assay variables performed on platelet poor plasma samples, despite concomitant changes in TEG-PM variables consistent with platelet inhibition. Based on this pilot study, thrombin generation performed on platelet poor plasma may not be a useful antiplatelet monitoring tool in dogs.}, journal={Frontiers in Veterinary Science}, publisher={Frontiers Media SA}, author={Rank, Kaitlyn and Lynch, Alex M. and Ruterbories, Laura K. and Li, Ronald H. L. and Ueda, Yu}, year={2023}, month={Aug} } @article{stern_rivas_kaplan_ueda_oldach_ontiveros_kooiker_dijk_harris_2023, title={Hypertrophic cardiomyopathy in purpose-bred cats with the A31P mutation in cardiac myosin binding protein-C}, volume={13}, ISSN={["2045-2322"]}, url={https://publons.com/wos-op/publon/63367066/}, DOI={10.1038/s41598-023-36932-5}, abstractNote={AbstractWe sought to establish a large animal model of inherited hypertrophic cardiomyopathy (HCM) with sufficient disease severity and early penetrance for identification of novel therapeutic strategies. HCM is the most common inherited cardiac disorder affecting 1 in 250–500 people, yet few therapies for its treatment or prevention are available. A research colony of purpose-bred cats carrying the A31P mutation in MYBPC3 was founded using sperm from a single heterozygous male cat. Cardiac function in four generations was assessed by periodic echocardiography and measurement of blood biomarkers. Results showed that HCM penetrance was age-dependent, and that penetrance occurred earlier and was more severe in successive generations, especially in homozygotes. Homozygosity was also associated with progression from preclinical to clinical disease. A31P homozygous cats represent a heritable model of HCM with early disease penetrance and a severe phenotype necessary for interventional studies aimed at altering disease progression. The occurrence of a more severe phenotype in later generations of cats, and the occasional occurrence of HCM in wildtype cats suggests the presence of at least one gene modifier or a second causal variant in this research colony that exacerbates the HCM phenotype when inherited in combination with the A31P mutation.}, number={1}, journal={SCIENTIFIC REPORTS}, author={Stern, Joshua A. and Rivas, Victor N. and Kaplan, Joanna L. and Ueda, Yu and Oldach, Maureen S. and Ontiveros, Eric S. and Kooiker, Kristina B. and Dijk, Sabine J. and Harris, Samantha P.}, year={2023}, month={Jun} } @article{rivas_ueda_stern_2023, title={Sex-specific differences and predictors of echocardiographic measures of diastolic dysfunction in rhesus macaques (Macaca mulatta)}, volume={7}, ISSN={["1600-0684"]}, url={https://doi.org/10.1111/jmp.12662}, DOI={10.1111/jmp.12662}, abstractNote={AbstractBackgroundDiastolic dysfunction in humans is an age‐related process with an overrepresentation in women. In rhesus macaques (Macaca mulatta), the incidence and predictors of diastolic dysfunction have yet to be reported.MethodsData from routine echocardiographic evaluations on clinically healthy rhesus macaques was obtained and used for univariate, bivariate, hypothesis testing, and linear regression statistical analyses interrogating differences and predictors of diastolic function.ResultsRhesus macaques fully recapitulate previously reported human hemodynamic studies. Female monkeys display impaired diastology and are at an increased risk for developing diastolic dysfunction. Age, sex, and proxies of exercise activity are confirmed predictors for measures of diastolic dysfunction, regardless of specific pathogen‐free status.ConclusionsRhesus macaques share common sex‐ and age‐related echocardiographic findings as humans, therefore, serve as a valuable translational nonhuman primate model for future studies of diastolic dysfunction. These findings confirm the importance of sex‐ and age‐matching within future rhesus macaque cardiovascular research.}, journal={JOURNAL OF MEDICAL PRIMATOLOGY}, author={Rivas, Victor N. and Ueda, Yu and Stern, Joshua A.}, year={2023}, month={Jul} } @article{rivas_stern_ueda_2023, title={The Role of Personalized Medicine in Companion Animal Cardiology}, volume={53}, ISSN={["1878-1306"]}, url={https://publons.com/wos-op/publon/65523949/}, DOI={10.1016/j.cvsm.2023.05.016}, abstractNote={Cardiomyopathies remain one of the most common inherited cardiac diseases in both human and veterinary patients. To date, well over 100 mutated genes are known to cause cardiomyopathies in humans with only a handful known in cats and dogs. This review highlights the need and use of personalized one-health approaches to cardiovascular case management and advancement in pharmacogenetic-based therapy in veterinary medicine. Personalized medicine holds promise in understanding the molecular basis of disease and ultimately will unlock the next generation of targeted novel pharmaceuticals and aid in the reversal of detrimental effects at a molecular level.}, number={6}, journal={VETERINARY CLINICS OF NORTH AMERICA-SMALL ANIMAL PRACTICE}, author={Rivas, Victor N. and Stern, Joshua A. and Ueda, Yu}, year={2023}, month={Nov}, pages={1255–1276} } @article{walker_ueda_crofton_harris_stern_2022, title={Ambulatory electrocardiography, heart rate variability, and pharmacologic stress testing in cats with subclinical hypertrophic cardiomyopathy}, volume={12}, ISSN={["2045-2322"]}, url={https://europepmc.org/articles/PMC8817045}, DOI={10.1038/s41598-022-05999-x}, abstractNote={AbstractThe utility of ambulatory electrocardiography (AECG) to evaluate cats with subclinical hypertrophic cardiomyopathy (HCM) for arrhythmias and heart rate variability (HRV) is not well defined but may provide information regarding risk stratification. This prospective study used AECG to evaluate ectopy and HRV in subclinical HCM cats compared to healthy controls and is the first to implement a pharmacologic cardiac stress test. Twenty-three purpose-bred, Maine coon cross cats (16 HCM, 7 control) underwent 48-h of continuous AECG. Terbutaline (0.2–0.3 mg/kg) was administered orally at 24 and 36 h. Heart rate, ectopy frequency and complexity and HRV parameters, including standard deviation of normal R-R intervals (SDNN), were compared pre-terbutaline and post-terbutaline and across phenotype, genotype and sex. Genotype for an HCM-causative mutation was significantly associated with the frequency of supraventricular (P = 0.033) and ventricular (P = 0.026) ectopy across all cats. Seven HCM cats and zero healthy cats had a sinus arrhythmia. Mean heart rate was significantly higher post-terbutaline (p < 0.0001). HCM cats had significantly greater HRV compared to controls (SDNN: p = 0.0006). Male cats had significantly higher HRV (SDNN: p = 0.0001) and lower mean heart rates (p = 0.0001). HRV decreased post-terbutaline (SDNN: p = 0.0008) and changes in HRV observed between sexes were attenuated by terbutaline.}, number={1}, journal={SCIENTIFIC REPORTS}, author={Walker, Ashley L. and Ueda, Yu and Crofton, Amanda E. and Harris, Samantha P. and Stern, Joshua A.}, year={2022}, month={Feb} } @article{salmelin_ueda_gilbert_martinez_2022, title={Comparison of Trauma in Dogs due to Direct Motor Vehicle Collision or Fall from Open Pick-up Truck Bed during Transportation (2002-2020)}, volume={12}, ISSN={["2567-6911"]}, DOI={10.1055/s-0042-1756516}, abstractNote={Abstract Objective The aim of this study was to report injuries sustained by dogs following motor vehicle trauma: direct motor vehicle collision (MVC), and fall from an open pickup truck bed during transportation (PTB). Study Design Medical records of dogs involved in motor vehicle trauma between 2002 and 2020 were reviewed. Signalment, mode of injury, injuries sustained, and treatments performed were recorded. An owner questionnaire investigated effects of the trauma on the dog and owner. Results Six hundred and ninety-eight dogs met the inclusion criteria (569 MVC, 102 PTB). Orthopaedic trauma was significantly more common after PTB (90.2%) (MVC, 75.6%; p = 0.011). There were not any differences in the prevalence of soft tissue injuries between groups (76.4% MVC, 67.6% PTB; p = 0.058), however, MVC dogs had significantly more thoracic (26.9% MVC, 4.4% PTB) and abdominal (12.9% MVC, 0% PTB) trauma (p <0.001). Surgical treatments were performed significantly more often after PTB (71.6%) (MVC, 47.6%) (p <0.001). Discharge rate after PTB (95.0%) was significantly higher (MVC, 84.0%) (p <0.001). Aftercare was reported to be significantly more difficult after PTB (76.2%) (MVC, 34.0%; p = 0.002). Conclusion MVC and PTB result in significantly different trauma. PTB causes predominantly orthopaedic and integument injuries, whereas MVC results in thoracic and abdominal trauma. Survival to discharge is greater following PTB than MVC.}, journal={VETERINARY AND COMPARATIVE ORTHOPAEDICS AND TRAUMATOLOGY}, author={Salmelin, Bettina R. M. and Ueda, Yu and Gilbert, Peter J. and Martinez, Steven A.}, year={2022}, month={Dec} } @article{chalifoux_butty_mauro_moyle_ehrhardt_robertson_labato_culler_londono_vigani_et al._2022, title={Outcomes of 434 dogs with non-steroidal anti-inflammatory drug toxicosis treated with fluid therapy, lipid emulsion, or therapeutic plasma exchange}, volume={12}, ISSN={["1939-1676"]}, url={http://dx.doi.org/10.1111/jvim.16603}, DOI={10.1111/jvim.16603}, abstractNote={AbstractBackgroundTraditional management of non‐steroidal anti‐inflammatory drug (NSAID) intoxication includes gastrointestinal decontamination, intravenous administration of fluids (IVF), and gastroprotection. Intravenous administration of lipid emulsion (ILE) and therapeutic plasma exchange (TPE) are popular novel therapeutic strategies.HypothesisCompare outcomes of dogs treated with IVF, ILE, and TPE for NSAID intoxications and evaluate outcome predictors for drug subgroups.AnimalsFour hundred thirty‐four dogs with NSAID intoxications (2015‐2020).MethodsMulticenter retrospective study of ibuprofen, carprofen, and naproxen intoxication. An ordinal outcome was defined as mild gastrointestinal, moderate kidney, or signs of severe central nervous system disease.ResultsSigns of neurological disease were overrepresented and acute kidney injury underrepresented in the TPE group among dogs exposed to kidney‐ or CNS‐toxic doses (P = .05), though all TPE dogs with signs of neurological disease had evidence of neurotoxicity at presentation. Dogs treated with IVF had a higher maximal creatinine concentration (median, 1.1 mg/dL; range, 0.4‐8.44 mg/dL) compared with IVF + ILE (median, 0.9 mg/dL; range, 0.4‐6.2 mg/dL; P = .01). Increased maximum time to presentation (P < .001), higher baseline creatinine (P < .001) and PCV (P = .007), and absence of induced emesis (P < .001) were associated with greater clinical severity. Ibuprofen toxicosis was associated with more severe clinical signs compared with carprofen (P = .03). Overall survival rate was 99%.Conclusions and Clinical ImportanceNSAID toxicosis generally carries an excellent prognosis in dogs. Despite similar outcomes of lower incidence of AKI in the TPE group, and slightly lower maximal creatinine concentration in dogs treated with ILE vs IVF alone, ILE and TPE should be considered in the management of severe NSAID toxicosis.}, number={1}, journal={JOURNAL OF VETERINARY INTERNAL MEDICINE}, publisher={Wiley}, author={Chalifoux, Nolan V. and Butty, Emmanuelle M. and Mauro, Katie D. and Moyle, Rachel B. and Ehrhardt, Caryn M. and Robertson, James B. and Labato, Mary A. and Culler, Christine A. and Londono, Leonel A. and Vigani, Alessio and et al.}, year={2022}, month={Dec} } @article{butty_suter_chalifoux_lynch_mauro_moyle_ehrhardt_robertson_culler_londono_et al._2022, title={Outcomes of nonsteroidal anti-inflammatory drug toxicosis treated with therapeutic plasma exchange in 62 dogs}, volume={8}, ISSN={["1939-1676"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-85136301395&partnerID=MN8TOARS}, DOI={10.1111/jvim.16507}, abstractNote={AbstractBackgroundTherapeutic plasma exchange (TPE) is gaining popularity for the management of nonsteroidal anti‐inflammatory drug (NSAID) overdose in dogs.Hypothesis/ObjectivesDescribe a population of dogs treated with TPE for NSAID overdose.AnimalsSixty‐two dogs with NSAID overdose treated with TPE.MethodsMulticenter retrospective study of dogs treated with TPE for ibuprofen, carprofen, or naproxen overdose.ResultsThe median dose of ibuprofen, carprofen or naproxen ingested was 533 mg/kg (range, 36‐4857 mg/kg), 217 mg/kg (range, 88‐625 mg/kg) and 138 mg/kg (range, 26‐3000 mg/kg), respectively. Based on previously established toxic ranges for each NSAID, 2 (3.2%), 14 (22.6%), and 46 (74.2%) dogs ingested a gastrointestinal, renal, and neurological toxic dose, respectively. The median time between ingestion and presentation was 4 hours (range, 1‐20 hours). The median number of plasma volumes processed was 1.6 (range, 0.4‐2.2). The median TPE session duration was 2 hours (range, 1‐4.5 hours). Circuit clotting developed during 8 (12.9%) sessions. Patient adverse events reported during 21 (33.8%) sessions consisted of urticaria (12.9%), asymptomatic hypocalcemia (9.6%), and hypotension (9.6%). The median duration of hospitalization was 2.25 days (range, 1‐11 days). Sixty‐one (98.4%) dogs survived to discharge, and none were rehospitalized. Thirty‐one (91.1%) of the 34 dogs with at least 1 follow‐up visit were not azotemic at the time of reevaluation.Conclusions and Clinical ImportanceThis population of dogs managed with TPE had excellent outcomes, even in cases of high NSAID dose ingestion. When TPE is available and the time frame is appropriate, this extracorporeal modality should be considered for the management of NSAID overdose.}, number={5}, journal={JOURNAL OF VETERINARY INTERNAL MEDICINE}, author={Butty, Emmanuelle M. and Suter, Steven E. and Chalifoux, Nolan V and Lynch, Alex M. and Mauro, Katie D. and Moyle, Rachel B. and Ehrhardt, Caryn M. and Robertson, James B. and Culler, Christine A. and Londono, Leonel A. and et al.}, year={2022}, month={Aug} } @article{tan_li_ueda_stern_hussain_haginoya_sharpe_gunther-harrington_epstein_nguyen_2022, title={Platelet Priming and Activation in Naturally Occurring Thermal Burn Injuries and Wildfire Smoke Exposure Is Associated With Intracardiac Thrombosis and Spontaneous Echocardiographic Contrast in Feline Survivors}, volume={9}, ISSN={2297-1769}, url={http://dx.doi.org/10.3389/fvets.2022.892377}, DOI={10.3389/fvets.2022.892377}, abstractNote={Wildfires pose a major health risk for humans, wildlife, and domestic animals. We previously discovered pathophysiologic parallels between domestic cats with naturally occurring smoke inhalation and thermal burn injuries and human beings with similar injuries; these were characterized by transient myocardial thickening, cardiac troponin I elevation and formation of intracardiac thrombosis. While the underlying mechanisms remain unclear, results from murine models suggest that platelet priming and activation may contribute to a global hypercoagulable state and thrombosis. Herein, we evaluated and compared the degree of platelet activation, platelet response to physiologic agonists and levels of platelet-derived microvesicles (PDMV) in 29 cats with naturally occurring wildfire thermal injuries (WF), 21 clinically healthy cats with subclinical hypertrophic cardiomyopathy (HCM) and 11 healthy cats without HCM (CC). We also quantified and compared circulating PDMVs in WF cats to CC cats. In addition, we examined the association between thrombotic events, severity of burn injuries, myocardial changes, and the degree of platelet activation in cats exposed to wildfires. Flow cytometric detection of platelet surface P-selectin expression showed that WF cats had increased platelet response to adenosine diphosphate (ADP) and thrombin compared to the two control groups indicating the presence of primed platelets in circulation. In addition, cats in the WF group had increased circulating levels of PDMV, characterized by increased phosphatidylserine on the external leaflet. Cats in the WF group with documented intracardiac thrombosis had elevated platelet activation and platelet priming in the presence of ADP. While high dose arachidonic acid (AA) mostly resulted in platelet inhibition, persistent response to AA was noted among cats in the WF group with intracardiac thrombosis. Univariate and multiple logistic regression analyses demonstrated that increased platelet response to AA was independently associated with thrombotic events. This is the first study reporting the significant association between platelet priming and intracardiac thrombosis in domestic cats with naturally occurring wildfire-related injuries and smoke inhalation. Further studies are required to delineate additional mechanisms between inflammation and thrombosis, especially regarding platelet primers and the cyclooxygenase pathway.One Sentence SummaryPlatelet activation and shedding of platelet-derived microvesicles due to platelet priming is present following naturally occurring wildfire smoke exposure and thermal burn injuries in a population of domestic cats.}, journal={Frontiers in Veterinary Science}, publisher={Frontiers Media SA}, author={Tan, Avalene W. K. and Li, Ronald H. L. and Ueda, Yu and Stern, Joshua A. and Hussain, Mehrab and Haginoya, Satoshi and Sharpe, Ashely N. and Gunther-Harrington, Catherine T. and Epstein, Steven E. and Nguyen, Nghi}, year={2022}, month={Jul} } @article{ueda_li_nguyen_ontiveros_kovacs_oldach_vernau_court_stern_2021, title={A genetic polymorphism in P2RY(1) impacts response to clopidogrel in cats with hypertrophic cardiomyopathy}, volume={11}, ISSN={["2045-2322"]}, url={https://europepmc.org/articles/PMC8206363}, DOI={10.1038/s41598-021-91372-3}, abstractNote={AbstractClopidogrel is converted to its active metabolite by cytochrome P450 isoenzymes and irreversibly inhibits platelet activation by antagonizing the adenosine-diphosphate (ADP) receptor. It is frequently used in cats with hypertrophic cardiomyopathy (HCM) to prevent thromboembolic complications. However, significant interpatient variability of the response to clopidogrel therapy has been suspected. In this study, we assessed the impact of single nucleotide polymorphisms (SNPs) within ADP receptor (P2RY1, P2RY12) and cytochrome P450 isoenzyme (CYP2C41) genes on platelet inhibition by clopidogrel administration in cats with HCM. Forty-nine cats completed the study, and blood samples were obtained before and after clopidogrel therapy to assess the degree of platelet inhibition based on flow cytometry and whole blood platelet aggregometry. Plasma concentrations of clopidogrel metabolites were measured after the last dose of clopidogrel. Whole blood platelet aggregometry revealed a significant reduction of platelet inhibition by clopidogrel in cats with the P2RY1:A236G and the P2RY12:V34I variants. The association with the P2RY1:A236G variant and clopidogrel resistance remained significant after adjustment for multiple comparisons. This study demonstrated that a genetic polymorphism in the P2RY1 gene altered response to clopidogrel therapy and suggests that clinicians may consider alternative or additional thromboprophylactic therapy in cats with the P2RY1:A236G variant.}, number={1}, journal={SCIENTIFIC REPORTS}, author={Ueda, Yu and Li, Ronald H. L. and Nguyen, Nghi and Ontiveros, Eric S. and Kovacs, Samantha L. and Oldach, Maureen S. and Vernau, Karen M. and Court, Michael H. and Stern, Joshua A.}, year={2021}, month={Jun} } @article{oldach_ueda_ontiveros_fousse_visser_stern_2021, title={Acute pharmacodynamic effects of pimobendan in client-owned cats with subclinical hypertrophic cardiomyopathy}, volume={17}, ISSN={["1746-6148"]}, url={https://europepmc.org/articles/PMC7903657}, DOI={10.1186/s12917-021-02799-9}, abstractNote={Abstract Background Prior studies have suggested that pimobendan is associated with several positive effects in cats, including improved survival in cats with congestive heart failure and improved left atrial function in research colony cats with hypertrophic cardiomyopathy (HCM) and normal cats. However, there is still a paucity of pharmacodynamic data refuting or supporting the use of pimobendan in a clinical cat population. This clinical trial aimed to evaluate the pharmacodynamic effects and tolerability of a single dose of pimobendan in cats with HCM. Echocardiograms and Doppler-derived systolic blood pressures were performed in 21 client-owned cats with subclinical HCM at baseline and 90-min after oral administration of 1.25 mg of pimobendan (Vetmedin). Seven additional cats were evaluated post-placebo administration to account for intra-day variability. Results Heart rate, systolic blood pressure, and murmur grade were not significantly different between baseline and post-pimobendan evaluations. Left auricular blood flow velocity, left atrial size, and left ventricular fractional shortening were not significantly different between baseline and post-pimobendan evaluations. Mean (± standard deviation) tissue Doppler peak systolic velocity of the mitral annulus was significantly higher following pimobendan (7.4 cm/s ± 1.5 vs 8.5 ± 1.6; p = 0.02). Median (min, max) left-ventricular outflow tract maximum velocity was significantly higher following pimobendan [1.9 m/sec (1.5, 3.4) vs 2.6 m/sec (2.0, 4.0); p = 0.01]. Mean right-ventricular outflow tract maximum velocity was also significantly higher following pimobendan (1.5 m/s ± 0.51 vs 2.0 ± 0.53; p = 0.004). Mean left atrial fractional shortening was significantly higher following pimobendan (28% ± 6 vs 32% ± 7; p = 0.02). No adverse events were observed following pimobendan administration. Right ventricular outflow tract velocity was significantly higher following placebo in control cats (1.02 ± 0.21 versus 1.31 ± 0.31; p = 0.01). No other significant differences were detected. Conclusions In client-owned cats with HCM, pimobendan acutely increased left atrial function and mildly increased left ventricular systolic function. Left ventricular outflow tract velocity was increased after pimobendan. Pimobendan was well tolerated in the acute setting in cats with HCM. The findings of this prospective, acute-dosing study confirm previous findings in research animals and retrospective analyses and suggest that chronic dosing studies are safe and warranted. }, number={1}, journal={BMC VETERINARY RESEARCH}, author={Oldach, Maureen S. and Ueda, Yu and Ontiveros, Eric S. and Fousse, Samantha L. and Visser, Lance C. and Stern, Joshua A.}, year={2021}, month={Feb} } @article{grigg_ueda_walker_hart_simas_stern_2021, title={Comparative Assessment of Heart Rate Variability Obtained via Ambulatory ECG and Polar Heart Rate Monitors in Healthy Cats: A Pilot Study}, volume={8}, ISSN={["2297-1769"]}, url={https://europepmc.org/articles/PMC8606523}, DOI={10.3389/fvets.2021.741583}, abstractNote={Chronic exposure to stressful environments can negatively impact cats' health and welfare, affecting behavioral, autonomic, endocrine, and immune function, as with cats in shelters. Low-stress handling practices likely improve shelter cat welfare, but data supporting improved outcomes remain limited. Cardiac activity, particularly heart rate variability (HRV), is an indicator of stress and emotional state in humans and non-human animals, tracking important body functions associated with stress responsiveness, environmental adaptability, mental, and physical health. HRV studies in cats are limited, involving mainly anesthetized or restrained cats. This pilot study tested the feasibility of obtaining HRV data from unrestrained cats, using a commercially available cardiac monitoring system (Polar H10 with chest strap), compared with data from a traditional ambulatory electrocardiogram. Simultaneous data for the two systems were obtained for five adult cats. Overall, the Polar H10 monitor assessments of HRV were lower than the true HRV assessment by ambulatory ECG, except for SDNN. Correlation between the two systems was weak. Possible reasons for the lack of agreement between the two methods are discussed. At this time, our results do not support the use of Polar H10 heart rate monitors for studies of HRV in cats.}, journal={FRONTIERS IN VETERINARY SCIENCE}, author={Grigg, Emma K. and Ueda, Yu and Walker, Ashley L. and Hart, Lynette A. and Simas, Samany and Stern, Joshua A.}, year={2021}, month={Nov} } @article{ueda_kovacs_reader_roberts_stern_2021, title={Heritability and Pedigree Analyses of Hypertrophic Cardiomyopathy in Rhesus Macaques (Macaca Mulatta)}, volume={8}, ISSN={["2297-1769"]}, url={https://europepmc.org/articles/PMC8206789}, DOI={10.3389/fvets.2021.540493}, abstractNote={In a colony of rhesus macaques at California National Primate Research Center (CNPRC), naturally occurring hypertrophic cardiomyopathy (HCM) classified by left ventricular hypertrophy without obvious underlying diseases has been identified during necropsy over the last two decades. A preliminary pedigree analysis suggested a strong genetic predisposition of this disease with a founder effect. However, the mode of inheritance was undetermined due to insufficient pedigree data. Since 2015, antemortem examination using echocardiographic examination as well as other cardiovascular analyses have been performed on large numbers of rhesus macaques at the colony. Based on antemortem examination, HCM was diagnosed in additional 65 rhesus macaques. Using HCM cases diagnosed based on antemortem and postmortem examinations, the heritability (h2) was estimated to determine the degree of genetic and environmental contributions to the development of HCM in rhesus macaques at the CNPRC. The calculated mean and median heritability (h2) of HCM in this colony of rhesus macaques were 0.5 and 0.51 (95% confidence interval; 0.14–0.82), respectively. This suggests genetics influence development of HCM in the colony of rhesus macaques. However, post-translational modifications and environmental factors are also likely to contribute the variability of phenotypic expression. Based on the pedigree analysis, an autosomal recessive trait was suspected, but an autosomal dominant mode of inheritance with incomplete penetrance was also possible. Further investigation with more data from siblings, offspring, and parents of HCM-affected rhesus macaques are warranted. Importantly, the findings of the present study support conducting genetic investigations such as whole genome sequencing to identify the causative variants of inherited HCM in rhesus macaques.}, journal={FRONTIERS IN VETERINARY SCIENCE}, author={Ueda, Yu and Kovacs, Samantha and Reader, Rachel and Roberts, Jeffrey A. and Stern, Joshua A.}, year={2021}, month={Jun} } @article{kielb basile_lynch_ruterbories_castaneda_griffith_ueda_2021, title={Influence of long-stay jugular catheters on hemostatic variables in healthy dogs}, volume={7}, ISSN={["1476-4431"]}, url={https://doi.org/10.1111/vec.13085}, DOI={10.1111/vec.13085}, abstractNote={AbstractObjectiveTo compare hemostatic variables performed on blood samples obtained from indwelling jugular catheters or direct venipuncture over a 72‐hour period.DesignProspective experimental study.SettingUniversity research laboratory.AnimalsFive healthy neutered male purpose‐bred Beagle dogs.InterventionsEach dog was sedated to facilitate placement of a long‐stay 20‐Ga polyurethane IV catheter into the jugular vein. Blood samples were obtained from the preplaced catheters at 4 time points corresponding to 0, 24, 48, and 72 hours relative to placement. Blood samples were also obtained by direct venipuncture of a peripheral vein using a 21‐Ga butterfly catheter and evacuated blood tubes at the same time points. Platelet count, platelet closure time, prothrombin time, activated partial thromboplastin time, fibrinogen, and kaolin‐activated thromboelastography were performed on these paired samples at each time point. The patency of the indwelling catheters was maintained by flushing every 6 hours with heparinized saline.Measurements and Main ResultsNo significant differences were identified in any of the hemostatic variables obtained by either blood collection technique at any time point during the study (P > 0.05). There was also no significant day‐to‐day variation in any catheter‐derived hemostatic variable obtained from individual dogs identified over the course of the study.ConclusionsThese data suggest that accurate hemostatic variables may be obtained using blood collected from indwelling jugular catheters, maintained with heparinized saline for at least 72 hours, in healthy dogs.}, number={5}, journal={JOURNAL OF VETERINARY EMERGENCY AND CRITICAL CARE}, author={Kielb Basile, Jessica L. and Lynch, Alex M. and Ruterbories, Laura and Castaneda, Kady and Griffith, Emily and Ueda, Yu}, year={2021}, month={Jul} } @article{ueda_duler_elliot_sosa_roberts_stern_2020, title={Echocardiographic reference intervals with allometric scaling of 823 clinically healthy rhesus macaques (Macaca mulatta)}, volume={16}, ISSN={["1746-6148"]}, url={https://europepmc.org/articles/PMC7510309}, DOI={10.1186/s12917-020-02578-y}, abstractNote={Abstract Background Echocardiography is commonly used for assessing cardiac structure and function in various species including non-human primates. A few previous studies reported normal echocardiographic reference intervals of clinically healthy rhesus macaques under sedation. However, these studies were under-powered, and the techniques were not standardized. In addition, body weight, age, and sex matched reference intervals should be established as echocardiographic measurements are commonly influenced by these variables. The purpose of this study was to establish reference intervals for complete echocardiographic parameters based on a large cohort of clinically healthy rhesus macaques with wide ranges of weight and age distributions using allometric scaling. Results A total of 823 rhesus macaques (ages 6 months to 31 years old; body weights 1.4 to 22.6 kg) were enrolled. Of these rhesus macaques, 421 were males and 402 were females. They were assessed with a complete echocardiographic examination including structural and functional evaluation under sedation with ketamine hydrochloride. The reference intervals of the key echocardiographic parameters were indexed to weight, age, and sex by calculating the coefficients of the allometric eq. Y = aMb. On correlation matrix, body weight, age, sex, and heart rate were significantly correlated with various echocardiographic parameters and some of the parameters were strongly correlated with body weight and age. Multiple regression analysis revealed that heart rate and body weight statistically significantly predicted several echocardiographic parameters. Valve regurgitation including tricuspid, aortic, pulmonic, and mitral regurgitations without other cardiac structural and functional abnormalities are common in clinically healthy rhesus macaques under ketamine sedation. Conclusions In this study, the reference intervals of echocardiographic parameters were established by performing complete echocardiographic examinations on a large number of clinical healthy rhesus macaques. In addition, allometric scaling was performed based on their weight, and further indexed to age and sex. These allometrically scaled reference intervals can be used to accurately evaluate echocardiographic data in rhesus macaques and diagnose structural and functional evidence of cardiac disease. }, number={1}, journal={BMC VETERINARY RESEARCH}, author={Ueda, Yu and Duler, Laetitia M. M. and Elliot, Kami J. and Sosa, Paul-Michael D. and Roberts, Jeffrey A. and Stern, Joshua A.}, year={2020}, month={Sep} } @article{willcox_belanger_burton_yu_ueda_visser_skorupski_stern_2020, title={Intramuscular Diphenhydramine Does Not Affect Acute Doxorubicin Infusion-Related Arrhythmia Number or Severity in a Prospective Crossover Study in Canine Lymphoma: A Pilot Study}, volume={7}, ISSN={["2297-1769"]}, url={https://europepmc.org/articles/PMC7379900}, DOI={10.3389/fvets.2020.00368}, abstractNote={Background: Doxorubicin (DOX) is one of the most effective chemotherapeutics for canine high-grade lymphoma. In addition to dose-dependent chronic cardiotoxicity, DOX can trigger acute cardiac arrhythmias during drug infusion. Diphenhydramine premedication is commonly used, as histamine release is a proposed mechanism for DOX-associated arrhythmogenesis. Hypothesis/Objectives: The study objectives were to evaluate the incidence and severity of DOX infusion-related cardiac arrhythmias in dogs with high-grade lymphoma and evaluate the effect of diphenhydramine premedication on arrhythmia frequency and severity during and after DOX infusion. Animals: Twenty-two client-owned dogs with cytologically/histopathologically confirmed high-grade lymphoma were recruited, of which 19 were enrolled and 9 completed the study. Methods: Dogs were screened by echocardiogram and concurrent electrocardiogram for this randomized prospective crossover study. Group A received no premedication for DOX #1 and was premedicated with diphenhydramine for DOX #2; Group B received diphenhydramine with DOX #1 and no premedication for DOX #2. For both visits, Holter monitor data were collected for 1 h pre-DOX and 3 h post-DOX administration. Results: Nineteen dogs were enrolled and 9 dogs [Group A (5), Group B (4)] completed the protocol. There was no statistical difference between the DOX alone and DOX + diphenhydramine when evaluating the total number of ventricular premature complexes (VPCs, P = 0.34), change in VPCs/hour (P = 0.25), total number of atrial premature complexes (APCs, P = 0.5), change in APCs/hour (P = 0.06), or ventricular arrhythmia severity score (P > 0.99). Conclusions and clinical importance: This study demonstrates that in these dogs with rigorous pretreatment cardiovascular screening, DOX infusion did not induce significant arrhythmias. Furthermore, these data suggest that, with this screening approach, diphenhydramine may not alter the arrhythmia number or severity in canine DOX recipients.}, journal={FRONTIERS IN VETERINARY SCIENCE}, author={Willcox, Jennifer Lindley and Belanger, Catherine and Burton, Jenna Hart and Yu, Lydia and Ueda, Yu and Visser, Lance C. and Skorupski, Katherine and Stern, Joshua A.}, year={2020}, month={Jul} } @article{morimoto_hyodo_kamata_kadoba_itoh_fukushima_chiba_takenaka_mochizuki_ueda_et al._2020, title={Navigator-triggered and breath-hold 3D MRCP using compressed sensing: image quality and method selection factor assessment}, url={https://doi.org/10.1007/s00261-020-02403-y}, DOI={10.1007/s00261-020-02403-y}, journal={Abdominal Radiology}, author={Morimoto, Daisuke and Hyodo, Tomoko and Kamata, Ken and Kadoba, Tomoya and Itoh, Makoto and Fukushima, Hiroyuki and Chiba, Yasutaka and Takenaka, Mamoru and Mochizuki, Tomohiro and Ueda, Yu and et al.}, year={2020}, month={Oct} } @article{gunther-harrington_sharpe_vernau_ueda_montgomery_surmick_fernandez_ontiveros_walker_stern_2021, title={Reference intervals for radiographic, echocardiographic and N-terminal pro B-type natriuretic peptide values in healthy kittens}, volume={23}, ISSN={["1532-2750"]}, url={https://doi.org/10.1177/1098612X20946461}, DOI={10.1177/1098612X20946461}, abstractNote={Objectives Assessment of heart size in kittens is important, and there is a need for reference intervals (RIs) to prevent misinterpretation of cardiomegaly in this patient population. The purpose of this study was to generate RIs for echocardiographic and radiographic quantification of cardiac size in healthy kittens. Methods In total, 88 kittens aged 6–16 weeks were enrolled in this study. Physical examination, and radiographic and echocardiographic evaluations were performed without sedation. Thoracic radiographs and echocardiographic images were measured to establish RIs for vertebral heart score (VHS), cardiac thoracic ratio (CTR) and multiple echocardiographic variables. N-terminal pro B-type natriuretic peptide (NT-proBNP) was measured. Statistical correlations between echocardiographic parameters and age, body weight and sex were all evaluated and RIs were generated. Results Low-grade heart murmurs were appreciated in 26/88 kittens (29.5%). Kittens had a median VHS of 9.5 vertebrae (95% RI 8.0–10.9) and a median CTR of 67.2% (95% RI 54.4–79.8%). Measured NT-proBNP levels were comparable to healthy adult cats with a median of 31 pmol/l (upper reference limit 75 pmol/l). Multiple moderate-to-strong correlations between body weight and age with various echocardiographic parameters were observed and allometric scaling was performed for body weight. RIs for echocardiographic parameters were generated based on patient weight using allometric scaling formulas. Tricuspid valve regurgitation was a common finding and was present in 37.5% (n = 33) of the kittens. Conclusions and relevance This study establishes RIs for thoracic radiograph assessment, echocardiography and cardiac biomarkers in kittens, which fills a critical gap in the veterinary literature. The VHS reported in this study is higher than previously reported for adult cats. }, number={4}, journal={JOURNAL OF FELINE MEDICINE AND SURGERY}, author={Gunther-Harrington, Catherine T. and Sharpe, Ashley N. and Vernau, Karen M. and Ueda, Yu and Montgomery, Elizabeth A. and Surmick, Jennifer D. and Fernandez, Nicole and Ontiveros, Eric and Walker, Ashley L. and Stern, Joshua A.}, year={2021}, month={Apr}, pages={293–301} }