Scholarly Works, Small Animal Clinical Sciences

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Case report: Placental chorioadenoma in a primiparous pug dog
Balogh, 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 dogs
Paranjape, 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 Ablation
Hay, 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 disease
Campelo, 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 Tumors
May, 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 Tumors
Rossmeisl, 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 gliomas
Garcia 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 report
LaVine, 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 Model
Hay, 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 Learning
Nappier, 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, China
Shu, 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, bla_CTX-M was the most prevalent ESBL genotype (73.42%, 58/79), and bla_CTX-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 Dogs
Henao-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 concentration
Olsen, 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 Dogs
Paranjape, 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 (ρ_c), 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, ρ_c 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 hyperlipidemia
Villm, 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.
The Pathophysiological Changes and Clinical Effects of Tetramethylpyrazine in ICR Mice with Fluoride-Induced Hepatopathy
Zhang, Shuai; Zheng, Yilei; Du, Hong; Zhang, Wei; Li, Haohuan; Ou, Yangping; Xu, Funeng; Lin, Juchun; Fu, Hualin; Ni, Xueqing; Chang, Li-Jen; Shu, Gang (MDPI, 2023-06-19)
The excessive intake of fluoride, one of the trace elements required to maintain health, leads to liver injury. Tetramethylpyrazine (TMP) is a kind of traditional Chinese medicine monomer with a good antioxidant and hepatoprotective function. The aim of this study was to investigate the effect of TMP on liver injury induced by acute fluorosis. A total of 60 1-month-old male ICR mice were selected. All mice were randomly divided into five groups: a control (K) group, a model (F) group, a low-dose (LT) group, a medium-dose (MT) group, and a high-dose (HT) group. The control and model groups were given distilled water, while 40 mg/kg (LT), 80 mg/kg (MT), or 160 mg/kg (HT) of TMP was fed by gavage for two weeks, with a maximum gavage volume for the mice of 0.2 mL/10 g/d. Except for the control group, all groups were given fluoride (35 mg/kg) by an intraperitoneal injection on the last day of the experiment. The results of this study showed that, compared with the model group, TMP alleviated the pathological changes in the liver induced by the fluoride and improved the ultrastructure of liver cells; TMP significantly decreased the levels of ALT, AST, and MDA (p < 0.05) and increased the levels of T-AOC, T-SOD, and GSH (p < 0.05). The results of mRNA detection showed that TMP significantly increased the mRNA expression levels of Nrf2, HO-1, CAT, GSH-Px, and SOD in the liver compared with the model group (p < 0.05). In conclusion, TMP can inhibit oxidative stress by activating the Nrf2 pathway and alleviate the liver injury induced by fluoride.
Improved Therapeutic Delivery Targeting Clinically Relevant Orthotopic Human Pancreatic Tumors Engrafted in Immunocompromised Pigs Using Ultrasound-Induced Cavitation: A Pilot Study
Imran, Khan Mohammad; Tintera, Benjamin; Morrison, Holly A.; Tupik, Juselyn D.; Nagai-Singer, Margaret A.; Ivester, Hannah; Council-Troche, McAlister; Edwards, Michael; Coutermarsh-Ott, Sheryl; Byron, Christopher; Clark-Deener, Sherrie; Uh, Kyungjun; Lee, Kiho; Boulos, Paul; Rowe, Cliff; Coviello, Christian; Allen, Irving C. (MDPI, 2023-05-24)
Pancreatic tumors can be resistant to drug penetration due to high interstitial fluid pressure, dense stroma, and disarrayed vasculature. Ultrasound-induced cavitation is an emerging technology that may overcome many of these limitations. Low-intensity ultrasound, coupled with co-administered cavitation nuclei consisting of gas-stabilizing sub-micron scale SonoTran Particles, is effective at increasing therapeutic antibody delivery to xenograft flank tumors in mouse models. Here, we sought to evaluate the effectiveness of this approach in situ using a large animal model that mimics human pancreatic cancer patients. Immunocompromised pigs were surgically engrafted with human Panc-1 pancreatic ductal adenocarcinoma (PDAC) tumors in targeted regions of the pancreas. These tumors were found to recapitulate many features of human PDAC tumors. Animals were intravenously injected with the common cancer therapeutics Cetuximab, gemcitabine, and paclitaxel, followed by infusion with SonoTran Particles. Select tumors in each animal were targeted with focused ultrasound to induce cavitation. Cavitation increased the intra-tumor concentrations of Cetuximab, gemcitabine, and paclitaxel by 477%, 148%, and 193%, respectively, compared to tumors that were not targeted with ultrasound in the same animals. Together, these data show that ultrasound-mediated cavitation, when delivered in combination with gas-entrapping particles, improves therapeutic delivery in pancreatic tumors under clinically relevant conditions.
The T2-FLAIR mismatch sign as an imaging biomarker for oligodendrogliomas in dogs
Garcia-Mora, Josefa; Parker, Rell L.; Cecere, Thomas; Robertson, John L.; Rossmeisl, John H. Jr. (Wiley, 2023-05)
BackgroundIn humans, the T2-weighted (T2W)-fluid-attenuated inversion recovery (FLAIR) mismatch sign (T2FMM) is a specific imaging biomarker for the isocitrate dehydrogenase 1 (IDH1)-mutated, 1p/19q non-codeleted low-grade astrocytomas (LGA). The T2FMM is characterized by a homogeneous hyperintense T2W signal and a hypointense signal with a hyperintense peripheral rim on FLAIR sequences. In gliomas in dogs, the T2FMM has not been described. Hypotheses/ObjectivesIn dogs with focal intra-axial brain lesions, T2FMM will discriminate gliomas from other lesions. The T2FMM will be associated with the LGA phenotype and presence of microcysts on histopathology. Interobserver agreement for T2FMM magnetic resonance imaging (MRI) features will be high. AnimalsOne hundred eighty-six dogs with histopathologically diagnosed focal intra-axial lesions on brain MRI including oligodendrogliomas (n = 90), astrocytomas (n = 47), undefined gliomas (n = 9), cerebrovascular accidents (n = 33), and inflammatory lesions (n = 7). MethodsTwo blinded raters evaluated the 186 MRI studies and identified cases with the T2FMM. Histopathologic and immunohistochemical slides of T2FMM cases were evaluated for morphologic features and IDH1-mutations and compared to cases without the T2FMM. Gene expression analyses were performed on a subset of oligodendrogliomas (n = 10) with and without T2FMM. ResultsThe T2FMM was identified in 14/186 (8%) of MRI studies, and all dogs with T2FMM had oligodendrogliomas (n = 12 low-grade [LGO], n = 2 high-grade [HGO]; P < .001). Microcystic change was significantly associated with the T2FMM (P < .00001). In oligodendrogliomas with T2FMM, IDH1-mutations or specific differentially expressed genes were not identified. Conclusion and Clinical ImportanceThe T2FMM can be readily identified on routinely obtained MRI sequences. It is a specific biomarker for oligodendroglioma in dogs, and was significantly associated with non-enhancing LGO.
Histotripsy ablation for the treatment of feline injection site sarcomas: a first-in-cat in vivo feasibility study
Ruger, Lauren N.; Yang, Ester; Coutermarsh-Ott, Sheryl; Vickers, Elliana; Gannon, Jessica; Nightengale, Marlie; Hsueh, Andy; Ciepluch, Brittany; Dervisis, Nikolaos; Vlaisavljevich, Eli; Klahn, Shawna (Taylor & Francis, 2023)
Purpose Feline soft tissue sarcoma (STS) and injection site sarcoma (fISS) are rapidly growing tumors with low metastatic potential, but locally aggressive behavior. Histotripsy is a non-invasive focused ultrasound therapy using controlled acoustic cavitation to mechanically disintegrate tissue. In this study, we investigated the in vivo safety and feasibility of histotripsy to treat fISS using a custom 1 MHz transducer. Materials and Methods Three cats with naturally-occurring STS were treated with histotripsy before surgical removal of the tumor 3 to 6 days later. Gross and histological analyses were used to characterize the ablation efficacy of the treatment, and routine immunohistochemistry and batched cytokine analysis were used to investigate the acute immunological effects of histotripsy. Results Results showed that histotripsy ablation was achievable and well-tolerated in all three cats. Precise cavitation bubble clouds were generated in all patients, and hematoxylin & eosin stained tissues revealed ablative damage in targeted regions. Immunohistochemical results identified an increase in IBA-1 positive cells in treated tissues, and no significant changes in cytokine concentrations were identified post-treatment. Conclusions Overall, the results of this study demonstrate the safety and feasibility of histotripsy to target and ablate superficial feline STS and fISS tumors and guide the clinical development of histotripsy devices for this application.

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