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- Comparison of the Anesthetic Effects of Alfaxalone Combined with Xylazine or Dexmedetomidine in Captive Formosa Serows (Capricornis swinhoei)Chang, Li-Jen; Ishihara, Toshitsugu; Lien, Chen-Yeh; Chen, Kuan-Sheng (MDPI, 2025-01-22)Formosan serows are an endemic species in Taiwan. Alfaxalone, a γ-aminobutyric acidA agonist, induces or maintains anesthesia in various veterinary species with reported potential adverse effects of respiratory depression and tachycardia. α2-Adrenoceptor agonists exert sedative and muscle relaxation effects, along with substantial cardiovascular adverse effects. Here, we aimed to evaluate the anesthetic effects of alfaxalone combined with xylazine or dexmedetomidine (AX vs. AD, respectively) in Formosan serows. In this randomized, masked study, AX was administered to four serows, and AD was administered to five serows intramuscularly via blow dart. The time and score of induction and recovery were recorded. Post-intubation, isoflurane was administered for maintenance anesthesia. Heart rate (HR), respiratory rate (RR), peripheral saturation of oxygenation (SpO2), rectal temperature (RT), and end-tidal CO2 (EtCO2) were recorded every five to eight minutes. Atipamezole and tolazoline were administered to antagonize dexmedetomidine and xylazine post-procedure, respectively. Both combinations allowed smooth induction and recovery. The AD group exhibited significantly lower HR and SpO2 and significantly higher RT and EtCO2 than the AX group (both p < 0.01). The AD-treated serows exhibited notable muscle rigidity after induction and significant hypoventilation and hypoxemia during the procedure. Although alfaxalone combined with dexmedetomidine or xylazine can produce satisfactory induction and recovery in Formosa serows, notable hypoxemia and hypoventilation are induced by the alfaxalone–dexmedetomidine combination compared to the alfaxalone–xylazine combination.
- Comparison of anesthetic effects of xylazine combined with alfaxalone or ketamine and maintained with isoflurane in captive Formosan Reeve’s Muntjac (Muntiacus reevesi micrurus)Chang, Li-Jen; Wang, Zixuan; Lien, Chen-Yeh; Wen, Amanda H. (2025-02-08)Formosan Reeve’s muntjac is a Cervidae species endemic to Southeast China and Taiwan. However, research on different anesthetic protocols, their effects, and their safety in Formosan Reeve’s muntjac is limited. This study evaluated the effects of ketamine-xylazine (KX) and alfaxalone-xylazine (AX) administered via blow darts to nine muntjacs. Induction and recovery times as well as the quality were assessed by a blinded observer. Peripheral oxygen saturation (SpO2), heart rate, respiratory rate, and rectal temperature were recorded for at least 30 min. Tolazoline (4 mg/kg) was used post-procedure to reverse xylazine’s effects. The mean doses were 4.68 ± 2.18 mg/kg for ketamine and 3.22 ± 1.33 mg/kg for xylazine in the KX group. In the AX group, the mean doses were 4.38 ± 0.31 mg/kg for alfaxalone and 1.19 ± 0.26 mg/kg for xylazine. The median induction times were 339.5 s (range 180.0-375.0) for KX and 125.0 s (range 71.0–334.0) for AX, with both groups scoring 3.0 for induction quality. The recovery times were 507.5 s (range 266.0–1081.0) for KX and 243.0 s (range 92.0–480.0) for AX, with recovery scores of 2.3 and 3.0, respectively, showing no significant difference. Hypoxemia (SpO2 < 90%) was more severe in the KX group when compared to the AX group (SpO2 > 92%), and rectal temperatures were higher in the former during the first 15 min. Heart and respiratory rates showed no significant differences between groups. Our findings demonstrate that both anesthetic combinations achieve reliable induction and satisfactory recovery in Formosan Reeve’s muntjac, with the ketamine-xylazine combination causing a more profound hypoxemia post-induction compared to the alfaxalone-xylazine combination.
- First-In-DOg HISTotripsy for Intracranial Tumors Trial: The FIDOHIST StudyVezza, Christina; Ruger, Lauren; Langman, Maya; Vickers, Elliana; Prada, Francesco; Sukovich, Jonathan; Hall, Timothy; Xu, Zhen; Parker, Rell L.; Vlaisavljevich, Eli; Rossmeisl, John H. (SAGE Publications, 2024-10-17)Objective: Brain tumors represent some of the most treatment refractory cancers, and there is a clinical need for additional treatments for these tumors. Domesticated dogs are the only other mammalian species which commonly develop spontaneous brain tumors, making them an ideal model for investigating novel therapies. Histotripsy is a non-thermal ultrasonic ablation method that emulsifies tissue through acoustic cavitation. The primary objectives of this prospective study were to assess the feasibility and safety of histotripsy to ablate naturally occurring canine brain tumors. Secondary endpoints included characterization of magnetic resonance imaging (MRI) responses to histotripsy treatment, and exploratory immunogenomic tumor response analyses. Methods: The study design utilized a treat and resect paradigm, where tumors were approached using craniotomy, partially ablated with histotripsy delivered through the cranial defect, imaged with MRI, and then resected. Dogs were evaluated with clinical, brain MRI, immunopathologic, and genomic examinations before treatment, intraoperatively, and 1, 14, and 42 days post-treatment. Here we report the results of the three dogs with meningiomas, all of which were treated with a custom eight element 1 MHz histotripsy transducer at a pulse repetition frequency of 100 Hz and a treatment dosage of 400 pulses/point. Results: Histotripsy was successfully delivered to all dogs, resulting in histopathologic evidence of ablations that were sharply demarcated from untreated tumor, with measured treatments approximating planned volumes in 2/3 dogs. One dog experienced an adverse event consisting of transient cerebral edema that was possibly attributable to histotripsy. Histotripsy ablations could be grossly visualized and identified on MRI, with features consistent with hemorrhage and necrosis. Significant expression or upregulation of the damage associated molecular pattern HMGB1, cytokine-cytokine receptor interaction, and NF-κb signaling pathways were observed in histotripsy treated tumors. Conclusion: Ablation of canine meningiomas with histotripsy through an open cranial window was feasible and clinically well tolerated.
- Cancer detection in dogs using rapid Raman molecular urinalysisRobertson, John L.; Dervisis, Nikolaos G.; Rossmeisl, John H. Jr.; Nightengale, Marlie; Fields, Daniel; Dedrick, Cameron; Ngo, Lacey; Issa, Amr Sayed; Guruli, Georgi; Orlando, Giuseppe; Senger, Ryan S. (Frontiers, 2024-02-07)Introduction: The presence of cancer in dogs was detected by Raman spectroscopy of urine samples and chemometric analysis of spectroscopic data. The procedure created a multimolecular spectral fingerprint with hundreds of features related directly to the chemical composition of the urine specimen. These were then used to detect the broad presence of cancer in dog urine as well as the specific presence of lymphoma, urothelial carcinoma, osteosarcoma, and mast cell tumor. Methods: Urine samples were collected via voiding, cystocentesis, or catheterization from 89 dogs with no history or evidence of neoplastic disease, 100 dogs diagnosed with cancer, and 16 dogs diagnosed with non-neoplastic urinary tract or renal disease. Raman spectra were obtained of the unprocessed bulk liquid urine samples and were analyzed by ISREA, principal component analysis (PCA), and discriminant analysis of principal components (DAPC) were applied using the Rametrix®Toolbox software. Results and discussion: The procedure identified a spectral fingerprint for cancer in canine urine, resulting in a urine screening test with 92.7% overall accuracy for a cancer vs. cancer-free designation. The urine screen performed with 94.0% sensitivity, 90.5% specificity, 94.5% positive predictive value (PPV), 89.6% negative predictive value (NPV), 9.9 positive likelihood ratio (LR+), and 0.067 negative likelihood ratio (LR-). Raman bands responsible for discerning cancer were extracted from the analysis and biomolecular associations were obtained. The urine screen was more effective in distinguishing urothelial carcinoma from the other cancers mentioned above. Detection and classification of cancer in dogs using a simple, non-invasive, rapid urine screen (as compared to liquid biopsies using peripheral blood samples) is a critical advancement in case management and treatment, especially in breeds predisposed to specific types of cancer.
- Case report: Placental chorioadenoma in a primiparous pug dogBalogh, Orsolya; Diab, Santiago; Parker, Acadia; de Sousa, Gabriela C.; Cecere, Julie T.; McCarter, Samantha J.; Sponenberg, Dan Phillip (Frontiers, 2024-11-27)A single 1.7 cm × 1.2 cm × 1 cm focal, raised, smooth, round, pink to flesh-colored mass protruding from the chorioallantois of the zonary placenta was found during Cesarean section in a primiparous pug bitch. Microscopically, the non-encapsulated, non-infiltrative, exophytic mass originated from the chorioallantoic stroma overlying the labyrinth and was composed of many arborizing fronds generally lined by 1 to 2 layers of cuboidal, columnar and occasionally polygonal, large trophoblastic cells, but frequently by a larger number of cells that occasionally piled up to form small nests or nodules. The gross and microscopic characteristics of this mass were compatible with a benign neoplastic process arising in the chorioallantois and involving placental trophoblasts, hence the diagnosis of a placental chorioadenoma. Five of the six newborn puppies were viable and of normal birthweight, while one puppy, which had lower birthweight than the others, could not be resuscitated and was humanely euthanized. Although placental tumors in dogs are very rare, this case is compelling evidence in the argument for routine inspection of canine placentas to identify potentially deleterious macro- or microscopic conditions that may be linked to negative fetal outcomes.
- Performance of four cardiac output monitoring techniques vs. intermittent pulmonary artery thermodilution during a modified passive leg raise maneuver in isoflurane-anesthetized dogsParanjape, Vaidehi V.; Henao-Guerrero, Natalia; Menciotti, Giulio; Saksena, Siddharth (Frontiers, 2023-09-14)Objective: This study investigated the performance among four cardiac output (CO) monitoring techniques in comparison with the reference method intermittent pulmonary artery thermodilution (iPATD) and their ability to diagnose fluid responsiveness (FR) during a modified passive leg raise (PLRM) maneuver in isoflurane-anesthetized dogs undergoing acute blood volume manipulations. The study also examined the simultaneous effect of performing the PLRM on dynamic variables such as stroke distance variation (SDV), peak velocity variation (PVV), and stroke volume variation (SVV). Study design: Prospective, nonrandomized, crossover design. Study animals: Six healthy male Beagle dogs. Methods: The dogs were anesthetized with propofol and isoflurane and mechanically ventilated under neuromuscular blockade. After instrumentation, they underwent a series of sequential, nonrandomized steps: Step 1: baseline data collection; Step 2: removal of 33 mL kg−1 of circulating blood volume; Step 3: blood re-transfusion; and Step 4: infusion of 20 mL kg−1 colloid solution. Following a 10-min stabilization period after each step, CO measurements were recorded using esophageal Doppler (EDCO), transesophageal echocardiography (TEECO), arterial pressure waveform analysis (APWACO), and electrical cardiometry (ECCO). Additionally, SDV, PVV, and SVV were recorded. Intermittent pulmonary artery thermodilution (iPATDCO) measurements were also recorded before, during, and after the PLRM maneuver. A successful FR diagnosis made using a specific test indicated that CO increased by more than 15% during the PLRM maneuver. Statistical analysis was performed using one-way analysis of variance for repeated measures with post hoc Tukey test, linear regression, Lin’s concordance correlation coefficient (ρc), and Bland–Altman analysis. Statistical significance was set at p < 0.05. Results: All techniques detected a reduction in CO (p < 0.001) during hemorrhage and an increase in CO after blood re-transfusion and colloid infusion (p < 0.001) compared with baseline. During hemorrhage, CO increases with the PLRM maneuver were as follows: 33% for iPATD (p < 0.001), 19% for EC (p = 0.03), 7% for APWA (p = 0.97), 39% for TEE (p < 0.001), and 17% for ED (p = 0.02). Concurrently, decreases in SVV, SDV, and PVV values (p < 0.001) were also observed. The percentage error for TEE, ED, and EC was less than 30% but exceeded 55% for APWA. While TEECO and ECCO slightly underestimated iPATDCO values, EDCO and APWACO significantly overestimated iPATDCO values. TEE and EC exhibited good and acceptable agreement with iPATD. However, CO measurements using all four techniques and iPATD did not differ before, during, and after PLRM at baseline, blood re-transfusion, and colloid infusion. Conclusion and clinical relevance: iPATD, EC, TEE, and ED effectively assessed FR in hypovolemic dogs during the PLRM maneuver, while the performance of APWA was unacceptable and not recommended. SVV, SDV, and PVV could be used to monitor CO changes during PLRM and acute blood volume manipulations, suggesting their potential clinical utility.
- Investigation of High Frequency Irreversible Electroporation for Canine Spontaneous Primary Lung Tumor AblationHay, Alayna N.; Aycock, Kenneth N.; Lorenzo, Melvin F.; David, Kailee; Coutermarsh-Ott, Sheryl; Salameh, Zaid; Campelo, Sabrina N.; Arroyo, Julio P.; Ciepluch, Brittany; Daniel, Gregory; Davalos, Rafael V.; Tuohy, Joanne (MDPI, 2024-09-07)In this study, the feasibility of treating canine primary lung tumors with high-frequency irreversible electroporation (H-FIRE) was investigated as a novel lung cancer treatment option. H-FIRE is a minimally invasive tissue ablation modality that delivers bipolar pulsed electric fields to targeted cells, generating nanopores in cell membranes and rendering targeted cells nonviable. In the current study, canine patients (n = 5) with primary lung tumors underwent H-FIRE treatment with an applied voltage of 2250 V using a 2-5-2 µs H-FIRE waveform to achieve partial tumor ablation prior to the surgical resection of the primary tumor. Surgically resected tumor samples were evaluated histologically for tumor ablation, and with immunohistochemical (IHC) staining to identify cell death (activated caspase-3) and macrophages (IBA-1, CD206, and iNOS). Changes in immunity and inflammatory gene signatures were also evaluated in tumor samples. H-FIRE ablation was evident by the microscopic observation of discrete foci of acute hemorrhage and necrosis, and in a subset of tumors (n = 2), we observed a greater intensity of cleaved caspase-3 staining in tumor cells within treated tumor regions compared to adjacent untreated tumor tissue. At the study evaluation timepoint of 2 h post H-FIRE, we observed differential gene expression changes in the genes IDO1, IL6, TNF, CD209, and FOXP3 in treated tumor regions relative to paired untreated tumor regions. Additionally, we preliminarily evaluated the technical feasibility of delivering H-FIRE percutaneously under CT guidance to canine lung tumor patients (n = 2). Overall, H-FIRE treatment was well tolerated with no adverse clinical events, and our results suggest H-FIRE potentially altered the tumor immune microenvironment.
- Burst sine wave electroporation (B-SWE) for expansive blood–brain barrier disruption and controlled non-thermal tissue ablation for neurological diseaseCampelo, Sabrina N.; Salameh, Zaid S.; Arroyo, Julio P.; May, James L.; Altreuter, Sara O.; Hinckley, Jonathan; Davalos, Rafael V.; Rossmeisl, John H. Jr. (AIP Publishing, 2024-05-30)The blood–brain barrier (BBB) limits the efficacy of treatments for malignant brain tumors, necessitating innovative approaches to breach the barrier. This study introduces burst sine wave electroporation (B-SWE) as a strategic modality for controlled BBB disruption without extensive tissue ablation and compares it against conventional pulsed square wave electroporation-based technologies such as high-frequency irreversible electroporation (H-FIRE). Using an in vivo rodent model, B-SWE and H-FIRE effects on BBB disruption, tissue ablation, and neuromuscular contractions are compared. Equivalent waveforms were designed for direct comparison between the two pulsing schemes, revealing that B-SWE induces larger BBB disruption volumes while minimizing tissue ablation. While B-SWE exhibited heightened neuromuscular contractions when compared to equivalent H-FIRE waveforms, an additional low-dose B-SWE group demonstrated that a reduced potential can achieve similar levels of BBB disruption while minimizing neuromuscular contractions. Repair kinetics indicated faster closure post B-SWE-induced BBB disruption when compared to equivalent H-FIRE protocols, emphasizing B-SWE’s transient and controllable nature. Additionally, finite element modeling illustrated the potential for extensive BBB disruption while reducing ablation using B-SWE. B-SWE presents a promising avenue for tailored BBB disruption with minimal tissue ablation, offering a nuanced approach for glioblastoma treatment and beyond.
- Retrospective Comparison of the Anesthetic Effects of Tiletamine-Zolazepam with Dexmedetomidine and Ketamine with Dexmedetomidine in Captive Formosan Serow (Capricornis swinhoei)Chang, Li-Jen; Weng, Hsin-Yi; Lien, Chen-Yeh; Chen, Kuan-Sheng (MDPI, 2024-05-08)Formosan serows are endemic to the mountainous regions of Taiwan. This crossover study aimed to assess and compare the anesthetic induction and recovery using either dexmedetomidine–tiletamine–zolazepam (DZ) or dexmedetomidine–ketamine (DK) by intramuscular injection from a blow-dart in a zoo environment. Ten anesthetic procedures were performed with five adult Formosan serows. Each participant was anesthetized with both combinations at least once with a minimal 12-month washout. The average dosages were 22.6 ± 8.3 µg/kg and 35.8 ± 2.5 µg/kg for dexmedetomidine and 185.6 ± 123.6 and 357.8 ± 25.2 µg/kg for atipamezole for the DZ and DK groups, respectively. The doses of tiletamine–zolazepam and ketamine were 2.1 ± 0.25 mg/kg and 3.6 ± 0.3 mg/kg, respectively, in the DZ and DK groups. All participants were induced within 10 min (median: 8 min for both groups), except one serow in the DK group with an induction time of 22 min. Serows in the DZ group had a lower respiratory rate (p = 0.016) and lower rectal temperature (p = 0.008) than those in the DK group. The quality of recovery was poor for DZ because of paddling, prolonged recovery, and ataxia after antagonism of dexmedetomidine with atipamezole. The induction of anesthesia with dexmedetomidine–tiletamine–zolazepam was uneventful and rapid. However, recovery from this combination was not smooth.
- An Illustrated Scoping Review of the Magnetic Resonance Imaging Characteristics of Canine and Feline Brain TumorsMay, James L.; Garcia-Mora, Josefa; Edwards, Michael; Rossmeisl, John H. Jr. (MDPI, 2024-03-29)Magnetic resonance imaging (MRI) is used pervasively in veterinary practice for the antemortem diagnosis of intracranial tumors. Here, we provide an illustrated summary of the published MRI features of primary and secondary intracranial tumors of dogs and cats, following PRISMA scoping review guidelines. The PubMed and Web of Science databases were searched for relevant records, and input from stakeholders was solicited to select data for extraction. Sixty-seven studies of moderate to low-level evidence quality describing the MRI features of pathologically confirmed canine and feline brain tumors met inclusion criteria. Considerable variability in data inclusion and reporting, as well as low case numbers, prohibited comparative data analyses. Available data support a holistic MRI approach incorporating lesion number, location within the brain, shape, intrinsic signal appearances on multiparametric sequences, patterns of contrast enhancement, and associated secondary changes in the brain to prioritize differential imaging diagnoses, and often allows for accurate presumptive diagnosis of common intracranial tumors. Quantitative MRI techniques show promise for improving discrimination of neoplastic from non-neoplastic brain lesions, as well as differentiating brain tumor types and grades, but sample size limitations will likely remain a significant practical obstacle to the design of robustly powered radiomic studies. For many brain tumor variants, particularly in cats, there remains a need for standardized studies that correlate clinicopathologic and neuroimaging data.
- Phase I/II Trial of Urokinase Plasminogen Activator-Targeted Oncolytic Newcastle Disease Virus for Canine Intracranial TumorsRossmeisl, John H. Jr.; King, Jamie N.; Robertson, John L.; Weger-Lucarelli, James; Elankumaran, Subbiah (MDPI, 2024-01-29)Neurotropic oncolytic viruses are appealing agents to treat brain tumors as they penetrate the blood–brain barrier and induce preferential cytolysis of neoplastic cells. The pathobiological similarities between human and canine brain tumors make immunocompetent dogs with naturally occurring tumors attractive models for the study of oncolytic virotherapies. In this dose-escalation/expansion study, an engineered Lasota NDV strain targeting the urokinase plasminogen activator system (rLAS-uPA) was administered by repetitive intravenous infusions to 20 dogs with intracranial tumors with the objectives of characterizing toxicities, immunologic responses, and neuroradiological anti-tumor effects of the virus for up to 6 months following treatment. Dose-limiting toxicities manifested as fever, hematologic, and neurological adverse events, and the maximum tolerated dose (MTD) of rLAS-uPA was 2 × 107 pfu/mL. Mild adverse events, including transient infusion reactions, diarrhea, and fever were observed in 16/18 of dogs treated at or below MTD. No infectious virus was recoverable from body fluids. Neutralizing antibodies to rLAS-uPA were present in all dogs by 2 weeks post-treatment, and viral genetic material was detected in post-treatment tumors from six dogs. Tumor volumetric reductions occurred in 2/11 dogs receiving the MTD. Systemically administered rLAS-uPA NDV was safe and induced anti-tumor effects in canine brain tumors, although modifications to evade host anti-viral immunity are needed to optimize this novel therapy.
- Comparison of linear and volumetric criteria for the determination of therapeutic response in dogs with intracranial gliomasGarcia Mora, Josefa Karina; Robertson, John L.; Hsu, Fang-Chi; Shinn, Richard Levon; Larson, Martha M.; Rylander, Christopher G.; Whitlow, Christopher T.; Debinski, Waldemar; Davalos, Rafael V.; Daniel, Gregory B.; Rossmeisl, John H. Jr. (Wiley, 2022-05)Background: Brain tumor therapeutic responses can be quantified from magnetic resonance images (MRI) using 1- (1D) and 2-dimensional (2D) linear and volumetric methods, but few studies in dogs compare these techniques. Hypotheses: Linear methods will be obtained faster, but have less agreement than volumetric measurements. Therapeutic response agreement will be highest with the total T2W tumor volumetric (TTV) method. Therapeutic response at 6-weeks will correlate with overall survival (OS). Animals: Forty-six dogs with intracranial gliomas. Methods: Prospective study. Three raters measured tumors using 1D and 2D linear, TTV, and contrast-enhancing volumetric (CEV) techniques on 143 brain MRI to determine agreement between methods, define therapeutic responses, and assess relations with OS. Results: Raters performed 1D the fastest (2.9 ± 0.57 minutes) and CEV slowest (17.8 ± 6.2 minutes). Inter- and intraobserver agreements were excellent (intraclass correlations ≥.91) across methods. Correlations between linear (1D vs 2D; ρ >.91) and volumetric (TTV vs CEV; ρ >.73) methods were stronger than linear to volumetric comparisons (ρ range,.26-.59). Incorporating clinical and imaging data resulted in fewer discordant therapeutic responses across methods. Dogs having partial tumor responses at 6 weeks had a lower death hazard than dogs with stable or progressive disease when assessed using 2D, CEV, and TTV (hazard ration 2.1; 95% confidence interval, 1.22-3.63; P =.008). Conclusions and Clinical Importance: One-dimensional, 2D, CEV, and TTV are comparable for determining therapeutic response. Given the simplicity, universal applicability, and superior performance of the TTV, we recommend its use to standardize glioma therapeutic response criteria.
- Non-coagulopathic hemothorax in a dog: A case reportLaVine, Danielle; Conner, Bobbi; Daniel, Gregory B.; Freeman, Mark D. (Wiley, 2022-09)An 8-year-old, female-spayed, Blue Heeler presented with suspected non-coagulopathic spontaneous, hemothorax with neoplasia as the most likely differential as coagulation parameters were normal and no obvious history of trauma was reported. Computed tomography scan was crucial for diagnosis of a traumatic partial vascular avulsion injury that was successfully managed supportively.
- Ablative and Immunostimulatory Effects of Histotripsy Ablation in a Murine Osteosarcoma ModelHay, Alayna N.; Imran, Khan Mohammad; Hendricks-Wenger, Alissa; Gannon, Jessica M.; Sereno, Jacqueline; Simon, Alex; Lopez, Victor A.; Coutermarsh-Ott, Sheryl; Vlaisavljevich, Eli; Allen, Irving C.; Tuohy, Joanne L. (MDPI, 2023-10-09)Background: Osteosarcoma (OS) is the most frequently occurring malignant bone tumor in humans, primarily affecting children and adolescents. Significant advancements in treatment options for OS have not occurred in the last several decades, and the prognosis remains grim with only a 70% rate of 5-year survival. The objective of this study was to investigate the focused ultrasound technique of histotripsy as a novel, noninvasive treatment option for OS. Methods: We utilized a heterotopic OS murine model to establish the feasibility of ablating OS tumors with histotripsy in a preclinical setting. We investigated the local immune response within the tumor microenvironment (TME) via immune cell phenotyping and gene expression analysis. Findings: We established the feasibility of ablating heterotopic OS tumors with ablation characterized microscopically by loss of cellular architecture in targeted regions of tumors. We observed greater populations of macrophages and dendritic cells within treated tumors and the upregulation of immune activating genes 72 h after histotripsy ablation. Interpretation: This study was the first to investigate histotripsy ablation for OS in a preclinical murine model, with results suggesting local immunomodulation within the TME. Our results support the continued investigation of histotripsy as a novel noninvasive treatment option for OS patients to improve clinical outcomes and patient prognosis.
- Differences in Sleep Quality and Sleepiness among Veterinary Medical Students at Multiple Institutions before and after the Pandemic Induced Transition to Online LearningNappier, Michael T.; Alvarez, Elizabeth E.; Bartl-Wilson, Lara; Boynton, Elizabeth P.; Hanlon, Alexandra L.; Lozano, Alicia J.; Ng, Zenithson; Ogunmayowa, Oluwatosin; Shoop, Tiffany; Welborn, Nancy D.; Wuerz, Julia (University of Toronto Press)Poor sleep health has been previously documented in veterinary medical students. However, it is not known how universal or widespread this problem is. This study evaluated Pittsburgh Sleep Quality Index (PSQI) and Epworth Sleepiness Scale (ESS) scores to measure sleep health among students at seven colleges of veterinary medicine in the United States (US). Inadvertently, the transition to online only learning due to the global COVID-19 pandemic was also captured. Veterinary students were found to have universally poor sleep quality and high daytime sleepiness. The transition to online only learning appeared to have little impact on sleep quality, but improved daytime sleepiness scores were observed. The findings suggest poor sleep health is common among veterinary medical students at multiple institutions in the US and that further investigation is necessary.
- Association between Phenotypes of Antimicrobial Resistance, ESBL Resistance Genes, and Virulence Genes of Salmonella Isolated from Chickens in Sichuan, ChinaShu, Gang; Qiu, Jianyu; Zheng, Yilei; Chang, Lijen; Li, Haohuan; Xu, Funeng; Zhang, Wei; Yin, Lizi; Fu, Hualin; Yan, Qigui; Gan, Ting; Lin, Juchun (MDPI, 2023-08-31)The aim of this study was to explore the association between antimicrobial resistance, ESBL genes, and virulence genes of Salmonella isolates. From 2019 to 2021, a total of 117 Salmonella isolates were obtained from symptomatic chickens in Sichuan Province, China. The strains were tested for antimicrobial resistance and the presence of ESBL according to the Clinical and Laboratory Standards Institute (CLSI) instructions. The presence of ESBL genes and genes for virulence was determined using Polymerase Chain Reaction (PCR). In addition, Multilocus Sequence Typing (MLST) was applied to confirm the molecular genotyping. Moreover, the mechanism of ESBL and virulence gene transfer and the relationships between the resistance phenotype, ESBL genes, and virulence genes were explored. The isolates exhibited different frequencies of resistance to antibiotics (resistance rates ranged from 21.37% to 97.44%), whereas 68.38% and 41.03% of isolates were multi-drug resistance (MDR) and ESBL-producers, respectively. In the PCR analysis, blaCTX-M was the most prevalent ESBL genotype (73.42%, 58/79), and blaCTX-M-55 showed the most significant effect on the resistance to cephalosporins as tested by logistic regression analysis. Isolates showed a high carriage rate of invA, avrA, sopB, sopE, ssaQ, spvR, spvB, spvC, stn, and bcfC (ranged from 51.28% to 100%). MLST analysis revealed that the 117 isolates were divided into 11 types, mainly ST92, ST11, and ST3717. Of 48 ESBL-producers, 21 transconjugants were successfully obtained by conjugation. Furthermore, ESBL and spv virulence genes were obtained simultaneously in 15 transconjugants. These results highlighted that Salmonella isolates were common carriers of ESBLs and multiple virulence genes. Horizontal transfer played a key role in disseminating antimicrobial resistance and pathogenesis. Therefore, it is necessary to continuously monitor the use of antimicrobials and the prevalence of AMR and virulence in Salmonella from food animals and to improve the antibiotic stewardship for salmonellosis.
- A Comparison of Dobutamine, Norepinephrine, Vasopressin, and Hetastarch for the Treatment of Isoflurane-Induced Hypotension in Healthy, Normovolemic DogsHenao-Guerrero, Natalia; Ricco-Pereira, Carolina H.; Paranjape, Vaidehi V. (MDPI, 2023-08-19)Isoflurane is a commonly used inhalation anesthetic in species undergoing veterinary care that induces hypotension, impacting organ perfusion, making it imperative to minimize its occurrence or identify effective strategies for treating it. This study evaluated and compared the hemodynamic effects of DOB, NEP, VAS, and HES in twelve isoflurane-anesthetized Beagle dogs. The order of the first three treatments was randomized. HES was administered last. Data were collected before treatments (baseline) and after 10 min of a sustained MAP of <45 mmHg induced by a high end-tidal isoflurane concentration (T0). Once treatment was initiated and the target MAP was achieved (65 to 80 mmHg) or the maximum dose reached, data were collected after 15 min of stabilization (T1) and 15 min after (T2). A 15 min washout period with a MAP of ≥65 mmHg was allowed between treatments. The intravenous dosage regimens started and were increased by 50% every five minutes until the target MAP or maximum dose was reached. The dosages were as follows: DOB, 5–15 μg/kg/min; NEP, 0.1–2 μg/kg/min; VAS, 0.5–5 mU/kg/min; and HET, 6% 1–20 mL/kg/min. DOB improved CO, DO2, and VO2, but reduced SVR. VAS elevated SVR, but decreased CO, DO2, and VO2. HES minimally changed BP and mildly augmented CO, DO2, and VO2. These treatments failed to reach the target MAP. NEP increased the arterial BP, CO, MPAP, and PAWP, but reduced HR. Norepinephrine infusion at 0.44 ± 0.19 μg/kg/min was the most efficient therapy for correcting isoflurane-induced hypotension.
- Bead size has a greater effect on in vitro elution from antimicrobial-impregnated calcium sulfate beads than drug concentrationOlsen, Ronald S.; Sawyere, Dominique M.; Davis, Jennifer L.; Lanz, Otto I.; Werre, Stephen R. (American Veterinary Medical Association, 2023-05)OBJECTIVE To compare the elution characteristics of amikacin-impregnated calcium sulfate (CaSO4) beads based on different drug concentrations and bead size configurations. SAMPLE Six groups of amikacin-impregnated CaSO4 beads and one negative control group. PROCEDURES Amikacin-impregnated CaSO4 beads were formed with either 500 mg (low-concentration) or 1 g (high-concentration) of amikacin per 15 g CaSO4 hemihydrate powder. The number of beads necessary to approximate 150 mg of amikacin for each of the 3 bead sizes (3 mm, 5 mm, and 7 mm) at both low and high concentrations were placed in 6 mL of phosphate-buffered saline. The saline was sampled at 14 time points over 28 days. Amikacin concentrations were determined using liquid chromatography-mass spectrometry. RESULTS Smaller beads reached higher mean peak concentrations than larger beads (P < .0006). Peak concentrations for the low-and high-concentration groups were 20.5 mg/mL and 27.4 mg/mL, 13.1 mg/mL and 14.0 mg/mL, and 8.85 mg/mL and 6.75 mg/mL for the 3 mm, 5 mm, and 7 mm beads, respectively. Bead size also affected the length of therapeutic duration, lasting 6 days for the 3 mm and 5 mm beads and 9 days for the 7 mm beads. However, this was only statistically evident among the high-concentration beads (P < .044). Antimicrobial concentration within the same bead sizes did not affect elution. CLINICAL RELEVANCE Amikacin-impregnated CaSO4 beads achieved extreme supratherapeutic eluent concentrations. While additional studies are needed, bead size significantly affected elution with smaller beads reaching higher peak concentrations and 7 mm, high-concentration beads demonstrating a longer therapeutic duration than smaller beads.
- Evaluation of Electrical Cardiometry for Measuring Cardiac Output and Derived Hemodynamic Variables in Comparison with Lithium Dilution in Anesthetized DogsParanjape, Vaidehi V.; Garcia-Pereira, Fernando L.; Menciotti, Giulio; Saksena, Siddharth; Henao-Guerrero, Natalia; Ricco-Pereira, Carolina H. (MDPI, 2023-07-20)Numerous cardiac output (CO) technologies were developed to replace the ‘gold standard’ pulmonary artery thermodilution due to its invasiveness and the risks associated with it. Minimally invasive lithium dilution (LiD) shows excellent agreement with thermodilution and can be used as a reference standard in animals. This study evaluated CO via noninvasive electrical cardiometry (EC) and acquired hemodynamic variables against CO measured using LiD in six healthy, anesthetized dogs administered different treatments (dobutamine, esmolol, phenylephrine, and high-dose isoflurane) impacting CO values. These treatments were chosen to cause drastic variations in CO, so that fair comparisons between EC and LiD across a wide range of CO values (low, intermediate, and high) could be made. Statistical analysis included linear regression, Bland–Altman plots, Lin’s concordance correlation coefficient (ρc), and polar plots. Values of p < 0.05 represented significance. Good agreement was observed between EC and LiD, but consistent underestimation was noted when the CO values were high. The good trending ability, ρc of 0.88, and low percentage error of ±31% signified EC’s favorable performance. Other EC-acquired variables successfully tracked changes in CO measured using LiD. EC may be a pivotal hemodynamic tool for continuously monitoring circulatory changes, as well as guiding and treating cardiovascular anesthetic complications in clinical settings.
- Evaluation of gallbladder motility assessed by ultrasonography in dogs with hyperlipidemiaVillm, Jessica A.; DeMonaco, Stefanie M.; Panciera, David L.; Larson, Martha M.; Bolton, Timothy A. (Wiley, 2023-05)Background: The pathogenesis of gallbladder (GB) mucoceles in dogs is unknown. It has been proposed that hyperlipidemia could impair GB motility and contribute to GB mucocele formation. Hypothesis/Objectives: The objective of this study was to compare GB motility in dogs with hyperlipidemia to control dogs using ultrasonography. We hypothesized that hyperlipidemic dogs will have decreased GB motility compared with controls. Animals: Twenty-six hyperlipidemic and 28 healthy, age-matched control dogs were prospectively enrolled. Methods: Cholesterol and triglyceride concentrations were measured in all dogs. Hyperlipidemia was defined as hypercholesterolemia (>332 mg/dL) and/or hypertriglyceridemia (>143 mg/dL) using a biochemical analyzer. Ultrasound was performed before feeding, and 60 and 120 minutes after ingestion of a high fat diet. Gallbladder volumes (GBV) and ejection fractions (EF) were calculated. Results: Hyperlipidemic dogs had significantly larger GBVs (ml/kg) before feeding and 60 minutes after feeding of 1.2 (0.4-7.5; P = .008) and 0.6 (0.1-7.2; P = .04) compared with controls 0.6 (0.2-2.6) and 0.4 (0.1-1.9), respectively. Severely hyperlipidemic dogs had significantly larger GBV at baseline, 60 minutes, and 120 minutes of 1.7 (0.6-7.5; P = .03), 1.3 (0.4-7.2; P = .02), and 1.3 (0.2-8.2; P = .04), respectively compared with mildly hyperlipidemic dogs. EFs at 60 and 120 minutes between controls, hyperlipidemic, and severely hyperlipidemic were all 0.3 at 60 minutes and 0.5, 0.3, and 0.3 at 120 minutes, respectively which were not statistically different. Conclusions and Clinical Importance: Hyperlipidemia leads to GB distention in dogs which could lead to retention of bile and gallbladder disease.