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Background: Limited current information exists regarding discospondylitis within breeds commonly affected by congenital vertebral body malformations. Hypothesis/Objectives: Report the prevalence of discospondylitis in English and French bulldogs and investigate for possible associations of discospondylitis with congenital vertebral body malformations. Animals: 108 client‐owned dogs. Methods: Retrospective multi‐institutional study between June 2010 and 2020. Cases with a diagnosis of discospondylitis on computed tomography (CT) or magnetic resonance imaging (MRI) and complete medical records included. Signalment, discospondylitis location, presence of congenital vertebral body malformations, and the site of maximal kyphosis were recorded. Results: The prevalence of discospondylitis was 3.4 (1.6‐6.7, 95% confidence interval [CI]) times higher in French bulldogs (P <.001) and 4.3 (1.7‐9.8, 95% CI) times higher in English bulldogs (<.001), compared with the overall hospital cohort. One or more vertebral malformations were present in 12 French bulldogs (92.3%), 6 English bulldogs (75.0%), and 1 "other" breed dog (1.1%). Discospondylitis was diagnosed adjacent to congenital vertebral body malformations in 12 (80%) intervertebral discs in French bulldogs and 5 (50%) intervertebral discs in English bulldogs. The median age at presentation was significantly younger in French bulldogs (1.1 years; range, 0.5‐9.2 years) and English bulldogs (1.0 years; range, 0.4‐7.0 years), compared with "other" breed dogs (7.3 years; range, 0.3‐14.0 years; both P <.001). Conclusions and Clinical Importance: Congenital vertebral body malformations were frequently associated with discospondylitis in French and English bulldogs, with clinical signs commonly encountered at a significantly younger age. [ABSTRACT FROM AUTHOR]

Purpose: To accelerate whole‐brain quantitative T2$$ {\mathrm{T}}_2 $$ mapping in preclinical imaging setting. Methods: A three‐dimensional (3D) multi‐echo spin echo sequence was highly undersampled with a variable density Poisson distribution to reduce the acquisition time. Advanced iterative reconstruction based on linear subspace constraints was employed to recover high‐quality raw images. Different subspaces, generated using exponential or extended‐phase graph (EPG) simulations or from low‐resolution calibration images, were compared. The subspace dimension was investigated in terms of T2$$ {\mathrm{T}}_2 $$ precision. The method was validated on a phantom containing a wide range of T2$$ {\mathrm{T}}_2 $$ and was then applied to monitor metastasis growth in the mouse brain at 4.7T. Image quality and T2$$ {\mathrm{T}}_2 $$ estimation were assessed for 3 acceleration factors (6/8/10). Results: The EPG‐based dictionary gave robust estimations of a large range of T2$$ {\mathrm{T}}_2 $$. A subspace dimension of 6 was the best compromise between T2$$ {\mathrm{T}}_2 $$ precision and image quality. Combining the subspace constrained reconstruction with a highly undersampled dataset enabled the acquisition of whole‐brain T2$$ {\mathrm{T}}_2 $$ maps, the detection and the monitoring of metastasis growth of less than 500 μm3$$ \mu {\mathrm{m}}^3 $$. Conclusion: Subspace‐based reconstruction is suitable for 3D T2$$ {\mathrm{T}}_2 $$ mapping. This method can be used to reach an acceleration factor up to 8, corresponding to an acquisition time of 25 min for an isotropic 3D acquisition of 156 μ$$ \mu $$m on the mouse brain, used here for monitoring metastases growth. [ABSTRACT FROM AUTHOR]

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Abstract Background Limited current information exists regarding discospondylitis within breeds commonly affected by congenital vertebral body malformations. Hypothesis/Objectives Report the prevalence of discospondylitis in English and French bulldogs and investigate for possible associations of discospondylitis with congenital vertebral body malformations. Animals 108 client‐owned dogs. Methods Retrospective multi‐institutional study between June 2010 and 2020. Cases with a diagnosis of discospondylitis on computed tomography (CT) or magnetic resonance imaging (MRI) and complete medical records included. Signalment, discospondylitis location, presence of congenital vertebral body malformations, and the site of maximal kyphosis were recorded. Results The prevalence of discospondylitis was 3.4 (1.6‐6.7, 95% confidence interval [CI]) times higher in French bulldogs (P

Objective To investigate the impact of metabolic labeling on Porphyromonas gingivalis (Pg) and compare the imaging effects of two fluorescent probes. Methods This study was reviewed by the unit Ethics Committee and was approved by the Experimental Animal Welfare Ethics Branch of the Unit Experimental Biomedical Ethics Committee. Pg integrated N-azidoacetylgalactosamine (Ac4GalNAz) via a bioorthogonal reaction and was labeled with Cy5-DBCO or Cy7-DBCO via a click chemistry reaction. The bacteria were divided into Pg group (control, not fluorescently labeled), Cy5-Pg group (tagged by Cy5-DBCO), and Cy7-Pg group (tagged by Cy7-DBCO). A live/dead staining kit was applied to test the viability of Pg, Cy5-Pg, and Cy7-Pg. The mRNA levels of interleukin-6 (IL-6) and IL-8 and cell proliferation were examined in human gingival fibroblasts (HGFs) after the challenge of Cy5-Pg, Cy7-Pg, or Pg. To investigate the stability of metabolic labeling, Cy5-Pg or Cy7-Pg was cocultured with Escherichia coli (E. coli). Cy5-Pg and Cy7-Pg signal intensity with serial dilutions were examined using an in vivo imaging system (IVIS). Finally, C57BL/6J mice were orally administered Cy5-Pg or Cy7-Pg for IVIS detection, and the signal-to-background ratios were calculated. Results Metabolic labeling could be applied to label live Pg in vitro. The optimal labeling concentrations for Cy5 and Cy7 were 20 μmol/L and 30 μmol/L, respectively. The area ratios of live to dead bacteria were approximately 2.0 in the three groups (F = 0.318, P>0.05). After a 6-h challenge with Cy5-Pg, Cy7-Pg, or Pg, the mRNA levels of HGFs increased by 7.86-, 7.46-, and 6.56-fold for IL-6, respectively (F = 40.886, PF = 18.781, PP>0.05). HGFs were further challenged by Cy5-Pg, Cy7-Pg, or Pg at different MOIs, and cell proliferation was significantly inhibited (MOI = 104∶1, F = 153.52, P5∶1, F = 331.21, P6∶1, F = 533.65, PP>0.05). Within 24 h of co-culturing Cy5-Pg or Cy7-Pg with E. coli, minimal E. coli was detected. The intensities of Cy5 and Cy7 remained stable for 3 h. Additionally, the fluorescence signal intensities of Cy5 and Cy7 were linearly correlated with the concentration (R2 = 0.97). After oral gavage of Cy5-Pg or Cy7-Pg in mice for the abdominal region at 1 h and 3 h, the signal-to-background ratios of Cy7-Pg were approximately 4.24-fold (t = 6.893, Pt = 4.407, PPg. For the isolated gastrointestinal tracts at 3 h, the signal-to-background ratio of Cy7-Pg was 5.19-fold higher than that of Cy5-Pg (t = 4.418, P

Background: The recent emergence of targeted radionuclide therapy has increased the demand for imagers capable of visualizing pharmacokinetics in developing radiopharmaceuticals in the preclinical phase. Some radionuclides emit hard x‐rays and gamma‐rays below 100 keV, in which energy range the performance of conventional NaI scintillators is poor. Multipinhole collimators are also used for small animal imaging with a good spatial resolution but have a limited field of view (FOV). Purpose: In this study, a new imager with high sensitivity over a wide FOV in the low‐energy band (<$<$100 keV) was developed for the pharmacokinetic study. Methods: We developed an x‐ray and gamma‐ray camera for high‐resolution spectroscopy, named "CdTe XG‐Cam," equipped with a cadmium telluride semiconductor detector and a parallel‐hole collimator using a metal 3D printer. To evaluate the camera‐system performance, phantom measurements with single and dual nuclides (99mTc$^{\rm 99m}{\rm Tc}$, 111In$^{111}{\rm In}$, and 125I)$^{125}{\rm I)}$ were performed. The performance for in vivo imaging was evaluated using tumor‐bearing mice to which a nuclide (99mTc$^{\rm 99m}{\rm Tc}$ or 125I)$^{125}{\rm I)}$ administered. Results: We simultaneously obtained information on 111In$^{111}{\rm In}$ and 125I$^{125}{\rm I}$, which emit emission lines in the low‐energy band with peak energies close to each other (23–26 keV for 111In$^{111}{\rm In}$ and 27–31 keV for 125I)$^{125}{\rm I)}$, and applied an analytical method based on spectral model fitting to determine the individual radioactivities accurately. In the small animal imaging, the distributions of the nuclide in tumors were accurately quantified and time‐activity curves in tumors are obtained. Conclusions: The demonstrated capability of our system to perform in vivo imaging suggests that the camera can be used for applications of pharmacokinetics research. [ABSTRACT FROM AUTHOR]

BackgroundManaging risk effectively within small animal veterinary practice is integral for staff, patient and client safety. Veterinary personnel are exposed to many risks, including bites, scratches, sharps injuries and exposure to zoonotic diseases and multi-resistant organisms. Patients may also be exposed to healthcare-associated infections, including multi-resistant organisms. While veterinary owners/managers have a duty of care under legislated Workplace Health and Safety requirements, all staff have a responsibility to contribute to assessing and minimizing risk. The application of standard and transmission precautions will help with risk minimization. This study aimed to determine how small animal veterinary staff understand and perceive infection prevention and control risk and to provide recommendations to assist with risk mitigation.MethodsA mixed methods design was used. A digital questionnaire was administered to small animal veterinary staff in Australia to identify knowledge, attitudes and practices of risk related behaviors. Follow up focus groups were conducted with small animal practitioners to explore factors supporting and preventing veterinary staff from implementing recommended practices identified in the questionnaire.ResultsSmall animal veterinary staff acknowledged they participated in many high-risk activities, including recapping needles and eating and drinking in patient care areas. Injuries were common, with 77% of staff receiving a bite or scratch, and 22% receiving a sharps injury in the preceding six months. Less than one in five of these incidents was reported. Staff agreed effective infection prevention and control was the responsibility of all staff, but a designated staff member should take responsibility for managing it. The practice owner/manager was integral to supporting and promoting recommended strategies, contributing to a positive workplace culture and improving safety for staff and patients.ConclusionSmall animal veterinary staff have some understanding of how to identify, report, manage and mitigate risk but were limited by their knowledge of infection prevention and control principles.

Positron emission tomography (PET) is the most sensitive in vivo molecular imaging technique available. Small animal PET has been widely used in studying pharmaceutical biodistribution and disease progression over time by imaging a wide range of biological processes. However, it remains true that almost all small animal PET studies using mouse or rat as preclinical models are either limited by the spatial resolution or the sensitivity (especially for dynamic studies), or both, reducing the quantitative accuracy and quantitative precision of the results. Total-body small animal PET scanners, which have axial lengths longer than the nose-to-anus length of the mouse/rat and can provide high sensitivity across the entire body of mouse/rat, can realize new opportunities for small animal PET. This article aims to discuss the technical opportunities and challenges in developing total-body small animal PET scanners for mice and rats.

Background: The recognition and diagnosis of canine temporomandibular joint (TMJ) disease can be a challenge, often leaving them undiagnosed. Although computed tomography (CT) has proved to be highly efficacious in detecting joint disease in the TMJ, morphometric and morphological studies of the normal TMJ have been scarce. Especially, skull type specific anatomical differences of the TMJ in dogs of different weights and skull morphologies have received limited attention. Objective: This study aimed to compare the TMJ morphologies of dogs across different weight classes and skull types. Study design: Retrospective study. Methods: CT scans were used to measure the depth and width of the Fossa mandibularis and two angles between the Fossa mandibularis and the Caput mandibulae in a total of 92 dogs and 182 mandibular joints, respectively. Results: The TMJ varied in terms of weight groups and skull indices. Shallow mandibular pits, underdeveloped retroarticular processes, and reduced joint congruency were observed particularly in light-weight and brachycephalic dogs. Conversely, dolichocephalic animals displayed deep joint pits, pronounced joint congruency, and a well-developed Processus retroarticularis. Main limitations: Observer learning curve; not every skull shape was represented in each weight group. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To describe coagulation profiles in dogs with echocardiographic evidence of pulmonary hypertension (PH), to compare them to coagulation profiles in dogs without echocardiographic evidence of PH, and to determine the relationship between coagulation profiles and echocardiographic probability of PH. ANIMALS: 66 dogs with PH (cases) and 86 dogs without PH (controls). METHODS: Retrospective evaluation of records between 2013 and 2021 of dogs that had both an echocardiogram and a coagulation panel performed within 7 days. Dogs that received antithrombotics within 7 days of evaluation and dogs diagnosed with congenital or acquired coagulopathy or other severe systemic disease that could lead to coagulopathy were excluded. Dogs with a low echocardiographic probability of PH were also excluded. The dogs were divided into a PH group and non-PH group based on echocardiographic results. Demographic, clinicopathologic, and traditional coagulation parameters and VCM Vet (Entegrion) parameters were compared between the 2 groups. RESULTS: Dogs with PH were significantly older (median, 11 years vs 9.5 years, P = .02) and had a significantly lower body weight (median, 7.3 kg vs 19.3 kg, P < .001) than controls. Dogs with PH also had a significantly greater percent increase in prothrombin time (PT; P = .02), partial thromboplastin time (PTT; P < .0001), and fibrinogen (P = .045); however, their antithrombin concentration was lower (P = .005) compared to controls. Eight of 65 dogs (12.3%) in the PH group and 1/86 (1.2%) dogs in the non-PH group had an elevation of PT and/or PTT greater than 50% above the reference interval (P = .005). Dogs with PH had 11.9 times (95% CI, 1.5 to 97.9; P = .02) greater odds of being hypocoagulable than dogs without PH based on PT and PTT. CLINICAL RELEVANCE: This study demonstrated an association between a moderate to high echocardiographic probability of PH and a hypocoagulable state in dogs as determined by traditional coagulation assays. It underscores the importance of monitoring the coagulation status in canine patients with PH, particularly before initiating antithrombotic medications. [ABSTRACT FROM AUTHOR]

Canine primary pulmonary carcinomas (PCCs) are commonly treated with surgery with overall median survival times (MST) around a year; however, due to extent of disease, prognosis, or client preference, alternative treatments have been considered. Stereotactic body radiation therapy (SBRT) has been utilized in human cancer patients for local control of lung tumours as a surgical alternative. Twenty‐one PCCs in 19 dogs that received SBRT for local control were retrospectively evaluated. Dogs were staged according to the canine lung carcinoma stage classification (CLCSC) system with three as Stage 1, five as Stage 2, three as Stage 3, and eight as Stage 4. Overall MST was 343 days with 38% of patients alive at 1 year. Stage did not significantly impact survival time (p =.72). Five (26%) dogs had lymphadenopathy and MST was not significantly different from dogs without lymphadenopathy (343 vs. 353 days; p =.54). Five out of 18 evaluable dogs (28%) experienced acute lung VRTOG effects and 2 of 12 dogs (17%) experienced late lung VRTOG effects. Median lung dose, V5, V20, and D30 to the lung did not correlate significantly with the development of adverse radiation events. Twelve dogs had follow‐up imaging and the best response included a complete response (17%), partial response (42%), and stable disease (42%). Progressive disease was noted in seven dogs a median of 229 days after SBRT. SBRT was documented to be a safe and effective alternative to surgery and may have survival advantages for Stage 3 or 4 dogs according to the CLCSC. [ABSTRACT FROM AUTHOR]

BackgroundThe recognition and diagnosis of canine temporomandibular joint (TMJ) disease can be a challenge, often leaving them undiagnosed. Although computed tomography (CT) has proved to be highly efficacious in detecting joint disease in the TMJ, morphometric and morphological studies of the normal TMJ have been scarce. Especially, skull type specific anatomical differences of the TMJ in dogs of different weights and skull morphologies have received limited attention.ObjectiveThis study aimed to compare the TMJ morphologies of dogs across different weight classes and skull types.Study designRetrospective study.MethodsCT scans were used to measure the depth and width of the Fossa mandibularis and two angles between the Fossa mandibularis and the Caput mandibulae in a total of 92 dogs and 182 mandibular joints, respectively.ResultsThe TMJ varied in terms of weight groups and skull indices. Shallow mandibular pits, underdeveloped retroarticular processes, and reduced joint congruency were observed particularly in light-weight and brachycephalic dogs. Conversely, dolichocephalic animals displayed deep joint pits, pronounced joint congruency, and a well-developed Processus retroarticularis.Main limitationsObserver learning curve; not every skull shape was represented in each weight group.

High-resolution imaging in small animal models of neurologic disease is a technical challenge. In a pilot project, we have explored a non-destructive synchrotron imaging technique for the 3D visualization of intracerebral tissue transplants in a well-established small animal model of Huntington’s disease. Four adult female Sprague Dawley rats each received injections of 0.12 M quinolinic acid (QA) into two target positions in the left striatum, thus creating unilateral left-sided striatal lesions similar to those frequently seen in patients suffering from Huntington’s disease. One week after lesioning, the animals received transplants prepared from whole ganglionic eminences (wGEs) obtained from 13- to 14-day-old rat embryos. Of the four lesioned animals, three received transplants of GNP-loaded cells and one animal received a transplant of naïve cells, serving as control. Post-mortem synchrotron-based microCT was used to obtain images of the neurotransplants. The images obtained of GNP-loaded tissue transplants at the synchrotron corresponded in size and shape to the histological images of transplants developed from naïve cells. Thus, we conclude that non-destructive synchrotron imaging techniques such as phase-contrast imaging are suitable to obtain high-resolution images of GNP-loaded tissue transplants.

High-resolution imaging in small animal models of neurologic disease is a technical challenge. In a pilot project, we have explored a non-destructive synchrotron imaging technique for the 3D visualization of intracerebral tissue transplants in a well-established small animal model of Huntington's disease. Four adult female Sprague Dawley rats each received injections of 0.12 M quinolinic acid (QA) into two target positions in the left striatum, thus creating unilateral left-sided striatal lesions similar to those frequently seen in patients suffering from Huntington's disease. One week after lesioning, the animals received transplants prepared from whole ganglionic eminences (wGEs) obtained from 13- to 14-day-old rat embryos. Of the four lesioned animals, three received transplants of GNP-loaded cells and one animal received a transplant of naïve cells, serving as control. Post-mortem synchrotron-based microCT was used to obtain images of the neurotransplants. The images obtained of GNP-loaded tissue transplants at the synchrotron corresponded in size and shape to the histological images of transplants developed from naïve cells. Thus, we conclude that non-destructive synchrotron imaging techniques such as phase-contrast imaging are suitable to obtain high-resolution images of GNP-loaded tissue transplants. [ABSTRACT FROM AUTHOR]

The updated VCOG-CTCAE v2 guidelines contain several important updates and additions since the last update (v1.1) was released in 2011 and published within Veterinary and Comparative Oncology in 2016. As the Veterinary Cooperative Oncology Group (VCOG) is no longer an active entity, the original authors and contributors to the VCOG-CTCAE v1.0 and v1.1 were consulted for input, and additional co-authors sought for expansion and refinement of the adverse event (AE) categories. VCOG-CTCAE v2 includes expanded neurology, cardiac and immunologic AE sections, and the addition of procedural-specific AEs. It is our intent that, through inclusion of additional authors from ACVIM subspecialties and the American College of Veterinary Surgery, that we can more comprehensively capture AEs that are observed during clinical studies conducted across a variety of disease states, clinical scenarios, and body systems. It is also our intent that these updated veterinary CTCAE guidelines will offer improved application and ease of use within veterinary practice in general, as well as within clinical trials that assess new therapeutic strategies for animals with a variety of diseases. Throughout the revision process, we strived to ensure the grading structure for each AE category was reflective of the decision-making process applied to determination of dose-limiting events. As phase I trial decisions are based on these criteria and ultimately determine the maximally tolerated dose, there is impact on standard dosing recommendations for any new drug registration or application. This document should be updated regularly to reflect ongoing application to clinical studies carried out in veterinary patients.

Lower urinary tract problems were increasingly encountered in small animal practice. Urinary stones and crystals are common problems in these cases and are still a problem in cats and dogs. Dilution of urine or restriction of mineral intake is a way to reduce urolithiasis/crystalluria. Viburnum Opulus was prescribed as anti-urolitiatic in human medicine. The objective of this study was to evaluate the efficacy of Viburnum Opulus in urolithiasis or crystalluria in companion animals. For this purpose, 42 animals were presented with urinary system problems and diagnosed with urolithiasis or crystalluria, which were included in the study and divided into two main groups (21 calcium oxalate, 21 struvite) and two subgroups (Control and Study). The urinary score was noted as the presence of pollakiuria, crystals in the microscopic examination, hematuria, stranguria, proteinuria, leucocytes, and blood in the urine. The mean ages were 3.81 and 3.95 for the calcium oxalate and struvite groups, respectively. It was determined that the clinical urinary score of the calcium oxalate control group was 11.39 before the treatment and increased to 14.06 at the end of 2 weeks. However, it was observed that this score decreased from 10.71 to 8.71 in the calcium oxalate study group. In calcium oxalate-diagnosed animals, a decrease in clinical scores was significant in the Viburnum opulus group than in controls. The urinary scores decreased in both struvite subgroups, but no statistical differences were determined. All animals except the calcium oxalate control group were clinically healthy at the second visit. Using Viburnum opulus as an integrative medical approach will provide safe and effective treatment for urolithiasis/crystalluria. [ABSTRACT FROM AUTHOR]

Objective: To determine if an association between ionized magnesium (iMg) and total magnesium (tMg) exists in healthy and hospitalized dogs admitted through an emergency service and to assess the associations between iMg and tMg with total protein, albumin, ionized calcium, and total calcium. Design: Prospective cohort study. Setting: Veterinary teaching hospital. Animals: Sixty‐nine dogs were enrolled. The healthy control group (group 1) included 24 dogs, and the hospitalized group (group 2) included 45 dogs. Interventions: None. Measurements and Main Results: For both groups, signalment, a venous blood gas, and serum biochemistry were obtained. In addition, the presumptive diagnosis was recorded for group 2. Blood was obtained prior to any therapeutic interventions. Group 1 tMg was within the reference interval (RI), and the values for iMg were used to provide a healthy group range (HGR) of 0.44–0.50 mmol/L. Group 2 tMg was within the RI, but iMg was below the calculated HGR range (group 2 median iMg = 0.4 mmol/L; range = 0.27–0.70). There was a significant positive correlation between iMg and tMg in each group (group 1: r = 0.6713, P = 0.0003; group 2: r = 0.5312, P = 0.0002). Ionized Mg and tMg were not significantly associated with any of the other evaluated variables in either group. Conclusions: Ionized Mg and tMg were significantly associated in both healthy and hospitalized dogs, but the relationship was weaker in the hospitalized dogs compared with the healthy population. For hospitalized dogs, the relationship was weak enough to question the validity of using iMg and tMg interchangeably to track magnesium status. [ABSTRACT FROM AUTHOR]

Expression of programmed death ligand 1 (PD‐L1) on tumour cells provides an immune evasion mechanism by inducing suppression of cytotoxic T cells. Various regulatory mechanisms of PD‐L1 expression have been described in human tumours, however, little is known in canine tumours. To investigate whether inflammatory signalling is involved in PD‐L1 regulation in canine tumours, the effects of interferon (IFN)‐γ and tumour necrosis factor (TNF)‐α treatment were examined in canine malignant melanoma cell lines (CMeC and LMeC) and an osteosarcoma cell line (HMPOS). The protein level of PD‐L1 expression was upregulated by IFN‐γ and TNF‐α stimulation. Upon IFN‐γ stimulation, all cell lines showed an increase in expression of PD‐L1, signal transducer and activator of transcription (STAT)1, STAT3 and genes regulated by STAT activation. Upregulated expression of these genes was suppressed by the addition of a JAK inhibitor, oclacitinib. Contrastingly, upon TNF‐α stimulation, all cell lines exhibited higher gene expression of the nuclear factor kappa B (NF‐κB) gene RELA and genes regulated by NF‐κB activation, whereas expression of PD‐L1 was upregulated in LMeC only. Upregulated expression of these genes was suppressed by the addition of an NF‐κB inhibitor, BAY 11‐7082. The expression level of cell surface PD‐L1 induced by IFN‐γ and TNF‐α treatment was reduced by oclacitinib and BAY 11‐7082, respectively, indicating that upregulation of PD‐L1 expression by IFN‐γ and TNF‐α stimulation is regulated via the JAK‐STAT and NF‐κB signalling pathways, respectively. These results provide insights into the role of inflammatory signalling in PD‐L1 regulation in canine tumours. [ABSTRACT FROM AUTHOR]

Due to the complex nature of tumour biology and the integration between host tissues and molecular processes of the tumour cells, a continued reliance on the status of the microscopic cellular margin should not remain our only determinant of the success of a curative‐intent surgery for patients with cancer. Based on current evidence, relying on a purely cellular focus to provide a binary indication of treatment success can provide an incomplete interpretation of potential outcome. A more holistic analysis of the cancer margin may be required. If we are to move ahead from our current situation – and allow treatment plans to be more intelligently tailored to meet the requirements of each individual tumour – we need to improve our utilisation of techniques that either improve recognition of residual tumour cells within the surgical field or enable a more comprehensive interrogation of tumour biology that identifies a risk of recurrence. In the second article in this series on defining the relevance of surgical margins, the authors discuss possible alternative strategies for margin assessment and evaluation in the canine and feline cancer patient. These strategies include considering adoption of the residual tumour classification scheme; intra‐operative imaging systems including fluorescence‐guided surgery, optical coherence tomography and Raman spectroscopy; molecular analysis and whole transcriptome analysis of tissues; and the development of a biologic index (nomogram). These techniques may allow evaluation of individual tumour biology and the status of the resection margin in ways that are different to our current techniques. Ultimately, these techniques seek to better define the risk of tumour recurrence following surgery and provide the surgeon and patient with more confidence in margin assessment. [ABSTRACT FROM AUTHOR]

Abstract Positron emission tomography (PET) is the most sensitive in vivo molecular imaging technique available. Small animal PET has been widely used in studying pharmaceutical biodistribution and disease progression over time by imaging a wide range of biological processes. However, it remains true that almost all small animal PET studies using mouse or rat as preclinical models are either limited by the spatial resolution or the sensitivity (especially for dynamic studies), or both, reducing the quantitative accuracy and quantitative precision of the results. Total-body small animal PET scanners, which have axial lengths longer than the nose-to-anus length of the mouse/rat and can provide high sensitivity across the entire body of mouse/rat, can realize new opportunities for small animal PET. This article aims to discuss the technical opportunities and challenges in developing total-body small animal PET scanners for mice and rats.

Objective: To report summative data from the American College of Veterinary Emergency and Critical Care Veterinary Committee on Trauma (VetCOT) registry. Design: Multi‐institutional registry data report, April 1, 2017 to December 31, 2019. Setting: VetCOT identified and verified Veterinary Trauma Centers (VTCs). Animals: Dogs and cats with evidence of trauma. Interventions: Data were input to a web‐based data capture system (Research Electronic Data Capture) by data entry personnel trained in data software use and operational definitions of data variables. Data on demographics, trauma type, preadmission care, trauma severity assessment at presentation (modified Glasgow Coma Scale and Animal Trauma Triage score), key laboratory parameters, interventions, and case outcome were collected. Summary descriptive data for each species are reported. Measurements and Main Results: Thirty‐one VTCs contributed data from 20,842 canine and 4003 feline trauma cases during the 33‐month reporting period. Most cases presented directly to a VTC (82.1% dogs, 82.1% cats). Admission to hospital rates were slightly lower in dogs (27.8%) than cats (32.7%). Highest mortality rates by mechanism of injury in dogs were struck by vehicle (18.3%), ballistic injury (17.6%), injured inside vehicle (13.2%), nonpenetrating bite wound (10.2%), and choking/pulling injury (8.5%). Highest mortality rates by mechanism of injury in cats were struck by vehicle (43.3%), ejected from vehicle (33.3%), nonpenetrating bite wound (30.7%), ballistic injury (27.8%), and choking/pulling injury (25.0%). The proportion of animals surviving to discharge was 93.1% (dogs) and 82.5% (cats). Conclusions: The VetCOT registry is a powerful resource for collection of a large dataset on trauma in dogs and cats seen at VTCs. Overall survival to discharge was high indicating low injury severity for most recorded cases. Further evaluation of data on subsets of injury types, patient assessment parameters, interventions, and associated outcome are warranted. Data from the registry can be leveraged to inform clinical trial design and justification for naturally occurring trauma as a translational model to improve veterinary and human trauma patient outcome. [ABSTRACT FROM AUTHOR]

The goal of cancer surgery is to achieve a "clean" microscopic resection, with no residual tumour remaining in the wound. To achieve that goal, the surgeon typically incorporates a measured buffer of grossly normal tissue about the entire circumference of the tumour. Microscopic analysis of the resection boundaries is then performed to determine if all traces of the tumour have been completely removed. This analysis is thought to provide a surrogate indication as to the likelihood for that tumour to recur after surgery. However, it is recognised that tumour recurrence may not occur even when microscopic evidence of tumour has been identified at the resection margins, and recurrence can also occur when conventional histology has considered the tumour to have been completely removed. The explanations for this dichotomy are numerous and include technical and practical limitations of the processing methodology, and also several surgeon‐related and tumour‐related reasons. Ultimately, the inability to confidently determine when a tumour has been removed sufficiently to prevent recurrence can impact on the ability to provide owners with confident treatment advice. In this article, the authors describe the challenges with defining the true extent of the tumour margin from the perspective of the surgeon, the pathologist and the tumour. The authors also provide an analysis of why our current efforts to ensure that all traces of the local tumour have been successfully removed may provide an imperfect assessment of the risk of recurrence. [ABSTRACT FROM AUTHOR]

Animal movement is one of the important phenotypes in animal research. A large number of small animals can be tested in high-throughput studies using multiwell plates to study the effects of different genes, chemicals, and the external environment on animal locomotion. In this paper, we propose AniWellTracker, which is a free image analysis software optimized for analyzing individual animal locomotion using multiwell plates. In the tracking mode, the center coordinates of individual animals are calculated by analyzing images. In the review mode, not only the animal's movement path, but also its speed, distance traveled, location frequency, rotation angle, etc. are analyzed and visualized using the built-in chart function. To test the usefulness of AniWellTracker, a case study was conducted to investigate the effect of two household cleaning agents on the swimming speed of zebrafish. AniWellTracker, written in Visual Basic.NET, is a standalone graphical user-interface software that does not use commercial software or external image analysis libraries and is expected to be of significant help to researchers. [ABSTRACT FROM AUTHOR]

The importance and implications of small animal neonatology were underestimated until recent times. Despite the recent increasing interest for this branch of veterinary medicine, however, perinatal mortality rates in canine and feline species remain high, representing an important challenge for the clinician. In this perspective, the prompt identification of newborns requiring additional and tailored assistance becomes a key to reduce the perinatal losses in small animals. To achieve this goal, clinical and laboratory findings must be carefully evaluated. This paper focuses on biochemical parameters and their reported influence on neonatal survival, guiding through the evaluation of canine and feline newborn laboratory analyses, with a thorough discussion about the use of different biological material in these subjects. Beside blood, other biological material, such as urines and fetal fluids proved to be interesting for the identification of possible prognostic markers, thanks also to their easy and safe collection. However, the correct reading-through the results must consider many variables such as type of delivery, anesthesia protocol in case of Caesarean section, age of the newborn at samples collection, and for blood analysis, also the type of blood, site of collection, modality of collection and storage must be considered. Notwithstanding the recent progress in literature, for most of the parameters more research is needed to define cut-off values with certainty. • High neonatal mortality rates must be reduced in dogs and cats. • Prompt evaluation at birth for a targeted small animal newborn assistance. • Biochemical prognostic factors for dog and cat newborns. • Blood samples, urines, fetal fluids as matrices for prognostic factors detection. [ABSTRACT FROM AUTHOR]

Objective: To describe the successful case management of an extradural hematoma secondary to anticoagulant rodenticide toxicity causing spinal compression and paraplegia. Case Summary: A 3‐month‐old, female intact, mixed breed dog was presented for a 12‐hour history of paraplegia. CBC and biochemistry results were unremarkable, and a coagulation panel revealed prolonged prothrombin time with normal activated partial thromboplastin time. Magnetic resonance imaging revealed an extradural compressive lesion within the vertebral canal extending from T6 to T11, most consistent with an extradural hematoma. Further coagulation testing revealed a coagulopathy caused by vitamin K1 deficiency and confirmed exposure to the anticoagulant rodenticide, diphacinone. The dog was medically managed with fresh frozen plasma, aminocaproic acid, and oral vitamin K1 therapy. A right‐sided T6 to T11 hemilaminectomy was later performed for removal of the extradural hematoma and spinal decompression. The dog's neurological status gradually improved postoperatively and, at the time of discharge, was nonambulatory paraparetic with voluntary micturition. Four weeks postoperatively, the dog had normal prothrombin and activated partial thromboplastin times and was nonambulatory paraparetic with strong motor function. New or Unique Information Provided: This is the first reported case of a dog with an extradural hematoma secondary to anticoagulant rodenticide causing spinal cord compression and neurological deficits. Surgical management of this case was successful and resulted in improvement of neurological signs. Extradural hematoma should be considered as a potential location of bleeding in rodenticide toxicity as well as a differential diagnosis in patients with neurological deficits. [ABSTRACT FROM AUTHOR]

Currently, intraoperative tumour margin imaging is not routinely utilized in veterinary medicine. Optical coherence tomography (OCT) allows for real‐time assessment of tissue morphology of 1–2 mm depth. The aims of this study were (1) to compare the histologic and OCT features of excised canine skin and subcutaneous specimens, and (2) to determine the diagnostic accuracy of OCT for surgical margin evaluation. The authors hypothesized that OCT imaging would correlate well with histopathology and that OCT would be sensitive for detection of incomplete margins. Eighty dogs were prospectively enrolled. Tumours were excised, and the surgical margins were imaged using a spectral domain OCT system. The tumour type and completeness of excision were determined by histopathology. Nine blinded observers received training in OCT image interpretation and were then given a set of OCT images and videos. The observers assigned each image/video a grade from 1 (no tumour) to 4 (tumour) and the results were compared to histopathology. The overall median sensitivity and specificity of OCT imaging for detection of incomplete margins were 86.7% and 84.6%, respectively. A potential limitation is that observers had varied experience with OCT image interpretation, ranging from no prior experience to participating in a previous OCT project. OCT is sensitive for detection of incomplete margins and could be a promising real‐time surgical margin imaging modality. Further study is needed to evaluate intraoperative applications of OCT and its impact on tumour recurrence and long‐term outcome. [ABSTRACT FROM AUTHOR]

Autologous peripheral blood haematopoietic stem cell transplantation (HCT) cures 33%–40% of dogs with high‐grade B‐cell lymphoma. We hypothesized, based on human allogeneic bone marrow transplantation literature, that transplanting dogs using canine donor leukocyte‐matched CD34+ cells would lead to fewer relapses and increased cure rates. We retrospectively reviewed medical records of dogs diagnosed with high‐grade B‐cell lymphoma who received an identical allogeneic HCT. A total of 15 dogs transplanted at four facilities were identified. Five of fifteen dogs relapsed before transplant. The mean number of donor CD34+ cells/kg harvested and infused into recipient dogs was 8.0 × 106/kg (range: 2.08 × 106/kg–2.9 × 107/kg). The median disease‐free interval and overall survival of all dogs was 1095 days (range: 9–2920 days) and 1115 days (range: 9–2920 days), respectively. Two of five dogs, not in remission at transplant, died in the hospital. The median disease‐free interval and overall survival of the remaining three dogs was 25 days (range: 15–250 days) and 1100 days (range: 66–1902 days), respectively. The median disease‐free interval and overall survival of the 10 dogs who had not relapsed was 1235 days (range: 19–2920 days) and 1235 days (range: 19–2920 days), respectively. One dog died soon after discharge of presumed gastric‐dilatation‐volvulus. Eight of nine remaining dogs lived >4 yrs post‐alloHCT, leading to a cure rate of 89%. Acute graft versus host disease was seen in three dogs. These results suggest that allogeneic HCT can cure ~50% more dogs than those treated with autologous HCT. [ABSTRACT FROM AUTHOR]

• Developed focal irradiation tool enables precise irradiation in small animal models. • Accurate radiation dose delivery to extremely small regions and shallow depths. • Preserved neural stem cells and minimized microglial activation in non-target regions. • Promising for enhancing radiotherapy research and minimizing surrounding damage. This study aims to emphasize the necessity of a focal irradiation tool for small animals and compare the beam characteristics of a tool developed using a brachytherapy system with a linear accelerator (LINAC)-based tool. A 1-mm tungsten collimator was designed for a Ir-192 brachytherapy system. The percent depth dose (PDD) and horizontal profile of the collimator were measured and compared with a 4-mm commercial cone in the LINAC. Monte Carlo simulations validated all the measurements. Mouse brains were irradiated using a focal irradiation tool, and immunohistochemistry was performed on the brain samples to assess the dose accuracy. PDD showed that the maximum dose (d max) for Ir-192 was at the surface in both measurements and simulations. At a depth of 1 mm, the collimator measured doses of 25.6 % and 21.0 %, respectively. At 6 MV in the LINAC, the d max was observed at depths of 0.7 and 0.8 cm in measurements and simulations, respectively. The full width at half maximum (FWHM) at a depth of 1 mm was 1.0 and 1.1 mm for Ir-192 in the measurements and simulations, respectively. For small cone sizes at d max , FWHM was 4.0 and 4.1 mm for the measurements and simulations, respectively. Immunohistochemistry results indicated that focal irradiation with Ir-192 affected small superficial brain areas while sparing the contralateral side and subventricular zone. The focal irradiation tool accurately delivered doses to small regions and shallow depths in the mouse brain, making it valuable for precise radiotherapy during small animal experiments. [ABSTRACT FROM AUTHOR]

A novel irradiation platform for preclinical proton therapy studies foresees proton imaging for accurate setup and treatment planning. Imaging at modern synchrocyclotron-based proton therapy centers with high instantaneous particle flux is possible with an integration mode setup. The aim of this work is to determine an object’s water-equivalent thickness (WET) with a commercially available large-area CMOS sensor. Image contrast is achieved by recording the proton energy deposition in detector pixels for several incoming beam energies (here, called probing energies) and applying a signal decomposition method that retrieves the water-equivalent thickness. A single planar 114 mm × 65 mm CMOS sensor (49.5 µm pixel pitch) was used for this study, aimed at small-animal imaging. In experimental campaigns, at two isochronous cyclotron-based facilities, probing energies suitable for small-animal-sized objects were produced once with built-in energy layer switching and the other time, using a custom degrader wheel. To assess water-equivalent thickness accuracy, a micro-CT calibration phantom with 10 inserts of tissue-mimicking materials was imaged at three phantom-to-detector distances: 3 mm, 13 mm, and 33 mm. For 3 mm and 13 mm phantom-to-detector distance, the average water-equivalent thickness error compared to the ground truth was about 1% and the spatial resolution was 0.16(3) mm and 0.47(2) mm, respectively. For the largest separation distance of 33 mm air gap, proton scattering had considerable impact and the water-equivalent thickness relative error increased to 30%, and the spatial resolution was larger than 1.75 mm. We conclude that a pixelated CMOS detector with dedicated post-processing methods can enable fast proton radiographic imaging in a simple and compact setup for small-animal-sized objects with high water-equivalent thickness accuracy and spatial resolution for reasonable phantom-to-detector distances.

Background: Descriptive probability modifiers are used often to convey the uncertainty of a pathology diagnosis, but they also contribute to ambiguity in communication between pathologists and clinicians. Objectives: Our goal was to determine the frequency and use of probability modifiers in canine and feline lymph node cytology diagnoses, and to determine the actual likelihood of neoplasia for diagnoses with and without modifiers, based on the histologic outcome. Methods: Canine and feline lymph node cytology and histology reports over an 11-year period (2001-2011; n = 367) were evaluated retrospectively. Diagnoses were categorized as neoplastic/malignant (lymphoma, metastatic) or non-neoplastic/benign. The frequency and type of modifier, and the sensitivity, specificity, and predictive values for neoplasia were determined for modified and unmodified diagnoses using histology as the gold standard. Results: Ninety-one of 367 (24.8%) cytology diagnoses were modified by probability terms, including 25/204 (12.2%) diagnoses of non-neoplastic lesions and 66/163 (40.5%) diagnoses of neoplasia. In addition, 26 unmodified diagnoses of neoplasia were followed by a probability phrase indicating specific tumor type. Based on the histologic outcome, modified diagnoses had higher sensitivity (87.3%, confidence interval [CI] 75.5, 94.7%) but lower specificity (50.0%, CI 32.9, 67.1%) for neoplasia than did unmodified diagnoses (60.6 and 100%, respectively; P < 0.0001, Chi square). Modified phrases indicating the probability of a specific tumor type were accurate in 22/26 (84.6%) cases. Positive predictive values for neoplasia were 100% (CI 96.2, 100%) for unmodified and 72.7% (CI 60.4, 83.0%) for modified diagnoses. Negative predictive values were 65.9% (CI 58.5, 72.8%) for unmodified and 72.0% (CI 60.4, 83.0%) for modified diagnoses. No significant difference was found in the likelihood of neoplasia for individual terms used to modify a cytologic diagnosis except for "cannot rule out" (P = 0.0368). Conclusions: Most modified diagnoses of cancer in canine and feline lymph node cytology have a 60-83% likelihood of neoplasia based on histologic outcome, compared with 96-100% for unmodified diagnoses. Non-neoplastic lesions, regardless of modifiers, have a 12-49% likelihood of neoplasia. A limited number of risk categories based on these likelihoods may be a more effective and accurate way to communicate the risk of malignancy in lymph node cytology.

Objective. Image guidance and precise irradiation are fundamental to ensure the reliability of small animal oncology studies. Accurate positioning of the animal and the in-beam monitoring of the delivered radio-therapeutic treatment necessitate several imaging modalities. In the particular context of proton therapy with a pulsed beam, information on the delivered dose can be retrieved by monitoring the thermoacoustic waves resulting from the brief and local energy deposition induced by a proton beam (ionoacoustics). The objective of this work was to fabricate a multimodal phantom (x-ray, proton, ultrasound, and ionoacoustics) allowing for sufficient imaging contrast for all the modalities. Approach. The phantom anatomical parts were extracted from mouse computed tomography scans and printed using polylactic acid (organs) and a granite/polylactic acid composite (skeleton). The anatomical pieces were encapsulated in silicone rubber to ensure long term stability. The phantom was imaged using x-ray cone-beam computed tomography, proton radiography, ultrasound imaging, and monitoring of a 20 MeV pulsed proton beam using ionoacoustics. Main results. The anatomical parts could be visualized in all the imaging modalities validating the phantom capability to be used for multimodal imaging. Ultrasound images were simulated from the x-ray cone-beam computed tomography and co-registered with ultrasound images obtained before the phantom irradiation and low-resolution ultrasound images of the mouse phantom in the irradiation position, co-registered with ionoacoustic measurements. The latter confirmed the irradiation of a tumor surrogate for which the reconstructed range was found to be in reasonable agreement with the expectation. Significance. This study reports on a realistic small animal phantom which can be used to investigate ionoacoustic range (or dose) verification together with ultrasound, x-ray, and proton imaging. The co-registration between ionoacoustic reconstructions of the impinging proton beam and x-ray imaging is assessed for the first time in a pre-clinical scenario. [ABSTRACT FROM AUTHOR]

Orally administered daily chemotherapy offers a novel treatment approach for canine lymphoma in a population of dogs that have failed or not tolerated maximum tolerable dose chemotherapy. A multidrug oral chemotherapy protocol was designed and implemented for the treatment of 50 dogs with multicentric lymphoma with minimal side effects. The protocol consisted of oral procarbazine, prednisolone and cyclophosphamide (PPC) administered daily. Efficacy and toxicity were evaluated by clinical and laboratory evaluation. An overall response rate of 70% was achieved, with 24% and 46% of dogs having a partial and complete response, respectively, to treatment with the PPC protocol. Response to the PPC protocol (complete or partial) and age were the only factors identified as prognostic for time from initiation of the PPC chemotherapy until death. Overall, the protocol was very well tolerated with only one dog requiring protocol discontinuation due to grade 4 thrombocytopenia. Eight dogs recorded gastrointestinal toxicities, seven grade I and one grade II toxicity. These findings demonstrate that the administration of a continuous oral combination chemotherapy can provide comparable survival times in the rescue setting in dogs with multicentric lymphoma with minimal side effects. [ABSTRACT FROM AUTHOR]

Background: Minimally-invasive ablation with radio frequency (RF) and cryoablation have been widely adopted to treat conditions with aberrant neural activity such as excessive mucus production in rhinitis, but neurological and inflammatory effects on treated tissues are poorly understood. Objective: To gain an understanding of the physiological changes caused by nerve ablation using RF and cryoablation devices. Methods: Using clinical devices for rhinitis treatment that ablate nerves with access from the nasal cavity, we applied temperature-controlled RF and cryoablation to rat sciatic nerves. To model the ablation through mucosal tissue similarly to the rhinitis procedure, RF ablation and cryoablation were applied through a layer of muscle. Results: Both ablation techniques induced acute and sustained neurodegeneration visualized with histological sections at two days and one month after treatment. After both treatments, rats showed a change in muscle tone, but small increases in sensitivity measured by a von Frey test were only observed 2 days after cryoablation and one month after the RF ablation. Both treatments caused reductions in nerve conduction velocity at one month after treatment. Inflammation in treated nerves and surrounding tissues that persisted to one month. Conclusions: The two neurolytic devices used in the clinic work similarly by axonal disintegration and which leads to disruption of electrical signals. The data suggest that these methods are effective methods of nerve ablation that could be used to treat diseases related to elevated neuron activity such as rhinitis. [ABSTRACT FROM AUTHOR]

In traditional Chinese veterinary medicine, the gastrointestinal (GI) system from mouth to anus belongs to the Earth Element. There are numerous TCVM Patterns that affect the harmonious balance of the Earth Zang-fu organs, Spleen and Stomach. As an adjunct to the use of TCVM Pattern differentiation based on the Eight Principles, Five Elements and Zang-fu organ relationships to treat Earth Element disorders, the author discusses how to use Balance Method acupuncture. The core of the Balance Method approach is the identification (Step 1) of the affected (sick) Channel, followed by selection of a Channel that balances the affected Channel (Step 2), and finally selection of the least number of distal acupoints in the balancing Channel(s) (Step 3) to generate equilibrium again. In addition to the 3-Step method of balancing Channel pathology, the concept of “Four Exceptional Meridians” and “Eight Plus One Extraordinary Points” to balance digestive disturbances with Balance Method acupuncture is introduced. Using Balance Method acupuncture to treat GI disease is a unique approach that increases the number of acupoint choices a veterinary practitioner can select from to solve simple or complicated GI diseases in animals. [ABSTRACT FROM AUTHOR]

Objective: To report the use of caffeine as a respiratory stimulant in a cat with hypoventilation. Case summary: A cat was mechanically ventilated due to persistent hypercapnia (Petco2 > 75 mm Hg) following median sternotomy and thymectomy. After 3 days of mechanical ventilatory support, the cat would initiate breaths but failed weaning due to persistent hypercapnia. Following administration of intravenous caffeine (total 12 mg/kg over 24 h), respiratory and mental status rapidly improved. The cat was subsequently extubated and able to maintain Pvco2 < 50 mm Hg. The cat was later diagnosed with myasthenia gravis. Quality of life 13 months after discharge was reported as excellent by her owner. New or unique information provided: Caffeine may be considered as a respiratory stimulant in cats with hypoventilation. [ABSTRACT FROM AUTHOR]

Primary pulmonary histiocytic sarcoma (PHS) is a rare form of dendritic cell or macrophage neoplasia originating within the pulmonary parenchyma. There is limited literature describing prognosis in dogs with PHS receiving curative‐intent treatment consisting of surgical excision and adjuvant chemotherapy. The primary objective of this study was to report outcomes in dogs with localized PHS treated with standardized local and systemic therapy. A secondary objective was to identify prognostic factors in this population. A multi‐institutional retrospective study was performed and medical records including all surgical and histopathologic reports were retrospectively reviewed. For inclusion, dogs were required to have confirmed localized PHS and they must have undergone curative‐intent surgery with resection of all gross primary tumour and enlarged tracheobronchial lymph nodes; additionally, they must have received curative‐intent treatment with adjuvant single‐agent CCNU chemotherapy. Twenty‐seven dogs from six veterinary teaching hospitals and five private practices treated from 2008–2019 were included. The overall median survival time was 432 days. Higher CCNU dose was demonstrated to have a negative impact on survival on univariate, but not multivariable, analysis. Factors that were not found to be associated with survival on univariate analysis included body weight, breed, clinical signs at the time of diagnosis, hypoalbuminaemia, tumour size, lung lobe affected, lymph node metastasis, surgical margins and CCNU dose reductions. This study supports a favourable prognosis for dogs diagnosed with localized PHS treated with curative‐intent surgery in addition to adjuvant CCNU chemotherapy and suggests that multimodal treatment may be advisable to attempt to prolong survival. [ABSTRACT FROM AUTHOR]

Adjuvant chemotherapy improves survival time in dogs receiving adequate local control for appendicular osteosarcoma, but most dogs ultimately succumb to metastatic disease. The fluoroquinolone antibiotic enrofloxacin has been shown to inhibit survival and proliferation of canine osteosarcoma cells in vitro. Others have reported that fluoroquinolones may modulate cellular responses to DNA damaging agents and that these effects may be differentially mediated by p53 activity. We therefore determined p53 status and activity in three canine osteosarcoma cell lines and examined the effects of enrofloxacin when used alone or in combination with doxorubicin or carboplatin chemotherapy. Moresco and Abrams canine osteosarcoma cell lines contained mutations in p53, while no mutations were identified in the D17 cells or in a normal canine osteoblast cell line. The addition of enrofloxacin to either doxorubicin or carboplatin resulted in further reductions in osteosarcoma cell viability; this effect was apparent regardless of p53 mutational status or downstream activity.

Experimental toxicological studies in laboratory animals and epidemiological human studies have reported a possible association between water fluoridation and osteosarcoma (OSA). To further explore this possibility, a case-control study of individual dogs evaluated by the UC Davis Veterinary Medical Teaching Hospital was conducted using ecologic data on water fluoridation based on the owner's residence. The case group included 161 dogs with OSA diagnosed between 2008-2012. Two cancer control groups included dogs diagnosed with lymphoma (LSA) or hemangiosarcoma (HSA) during the same period (n = 134 and n = 145, respectively). Dogs with OSA were not significantly more likely to live in an area with optimized fluoride in the water than dogs with LSA or HSA. Additional analyses within OSA patients also revealed no significant differences in age, or skeletal distribution of OSA cases relative to fluoride status. Taken together, these analyses do not support the hypothesis that optimal fluoridation of drinking water contributes to naturally occurring OSA in dogs.

Occupational burnout is a critical issue affecting the welfare of veterinary care providers, their patients, and the sustainability of veterinary healthcare organizations. The current research aimed to evaluate the prevalence of and factors contributing to stress, wellbeing, burnout symptoms and job satisfaction among clinical and non-clinical staff at a large specialist small animal hospital in Australia. Participants completed an anonymous online survey including self-report measures of job satisfaction and symptoms of burnout, and open-text response questions probing sources of stress and wellbeing. Subsequently, participants rated how frequently they experienced commonly reported sources of veterinary stress, and a series of focus groups were conducted with clinical and non-clinical teams. The survey was completed by 249 participants (overall response rate = 70%; 67.1% “clinical;” 17.3% “non-clinical;” 5.6% “other”). Five focus groups (including 38 of the survey participants) were subsequently conducted with groups of clinical and non-clinical staff. The majority of respondents (80.7%) reported being satisfied, very satisfied, or extremely satisfied with their job. At the same time, 57.7% of respondents exceeded the threshold for burnout on at least one burnout dimension, with 48.1% reporting high levels of emotional exhaustion, 30.2% reported high levels of cynicism, and 16.3% reporting low levels of professional efficacy. Open text responses and focus group transcripts revealed three common sources of stress and wellbeing. Stressors included communication (conflict within teams), clients (dealing with client emotions and expectations), and heavy caseload. Wellbeing was enhanced by people (team cohesion, respect for colleagues), practice (variety, autonomy, challenge), and purpose (meaningful work and impact). Overall, for both clinical and non-clinical survey respondents, “heavy workload” was rated as the most frequent source of stress. Despite high levels of job satisfaction, approximately two thirds of respondents reported at least one symptom of burnout. Convergent results from the survey and focus groups indicated that strong relationships with colleagues and the intrinsic meaningfulness of the work were key sources of wellbeing and job satisfaction. On the other hand, challenging workplace interactions with colleagues and clients, as well as heavy workload, were identified as key stressors contributing to burnout symptoms.

Objective: To describe the development and implementation of a small animal hemovigilance program at a university veterinary teaching hospital. Design: Retrospective observational descriptive study performed between October 2014 and March 2019. Setting: University teaching hospital. Animals: Dogs and cats receiving blood product transfusions. Interventions: None. Measurements and Main Results: A hemovigilance working group composed of veterinary specialists in clinical pathology, internal medicine, and emergency and critical care was established. This group developed evidence‐based definitions of transfusion reactions, reaction classification systems, and a transfusion reaction reporting form. The reporting form contained sections for patient information, transfusion information, administration details, and reaction details. Reaction events were classified by reaction type, severity grade, and imputability to the transfusion. Following implementation of the hemovigilance program, transfusion reaction data were collected and examined for the period spanning October 2014 and March 2019. During the study period, 718 canine transfusions (4 whole blood, 400 packed RBC [pRBC], 300 fresh frozen plasma [FFP], 7 platelet rich plasma, and 7 cryoprecipitate) and 124 feline transfusions (5 whole blood, 95 pRBC, and 24 FFP) were administered. There were 32 total reactions (27 canine and 5 feline), with the most common reaction being febrile nonhemolytic transfusion reactions (19/32; 59%). The incidence rate of transfusion reactions was found to be 3.8% in dogs and 4.0% in cats. For the confirmed reactions, classification criteria for case definition, reaction severity grade, and imputability were able to be determined and recorded. This allowed targeted interventions to be implemented in order to potentially reduce future reactions. Conclusions: A hemovigilance program can be instituted successfully in a veterinary hospital setting and once developed, standardized reporting tools could be utilized by multiple hospitals and provide the basis for more widespread reaction reporting in veterinary medicine. [ABSTRACT FROM AUTHOR]

Objective: To compare the diagnostic utility of traditional diagnostic tests (ie, radiographs and focused assessment using sonography for trauma [FAST] scans) to whole‐body computed tomography (WBCT) for characterizing injuries in polytrauma patients. A secondary objective was to compare costs of traditional diagnostic tests to WBCT. Design: Prospective, observational study. Setting: Private, level 1 veterinary trauma center. Animals: Convenience sample of 21 client‐owned cats and dogs presenting with polytrauma. Interventions: Abdominal and thoracic FAST were performed by the primary clinician, if indicated. Radiographs were performed on areas concerning for trauma at the primary clinician's discretion. A WBCT was performed on each patient within 24 h of presentation and was blindly interpreted by a board‐certified radiologist. Patients were only placed under anesthesia if further procedures were planned. IV contrast administration was employed at the discretion of the primary clinician and radiologist. Measurements and Main Results: Twenty‐one patients (14 dogs and 7 cats) were enrolled. Sources of trauma included blunt force (80%), penetrating wounds (10%), and unknown sources (10%). Twelve injuries were missed on traditional diagnostics tests. Injuries missed on traditional diagnostic workup included pneumothorax, pneumomediastinum, pulmonary contusions, pleural effusion, traumatic bulla, peritoneal effusion, and an appendicular skeleton fracture. A distal metacarpal fracture was missed on WBCT. Traditional diagnostic tests misdiagnosed a diaphragmatic hernia and a ruptured urinary bladder, whereas WBCT was able to rule out these injuries. There were no adverse outcomes associated with missed injuries. The median cost of traditional diagnostic tests was significantly less than the cost of WBCT (P < 0.001). Conclusions: Although cost is higher, WBCT is a single test that can provide more comprehensive information and may help decrease the risk of missed injuries compared to traditional diagnostic tests. WBCT may be considered as a first‐line diagnostic in severely traumatized patients. [ABSTRACT FROM AUTHOR]

Purpose: T1ρ dispersion quantification can potentially be used as a cardiac magnetic resonance index for sensitive detection of myocardial fibrosis without the need of contrast agents. However, dispersion quantification is still a major challenge, because T1ρ mapping for different spin lock amplitudes is a very time consuming process. This study aims to develop a fast and accurate T1ρ mapping sequence, which paves the way to cardiac T1ρ dispersion quantification within the limited measurement time of an in vivo study in small animals. Methods: A radial spin lock sequence was developed using a Bloch simulation-optimized sampling pattern and a view-sharing method for image reconstruction. For validation, phantom measurements with a conventional sampling pattern and a gold standard sequence were compared to examine T1ρ quantification accuracy. The in vivo validation of T1ρ mapping was performed in N = 10 mice and in a reproduction study in a single animal, in which ten maps were acquired in direct succession. Finally, the feasibility of myocardial dispersion quantification was tested in one animal. Results: The Bloch simulation-based sampling shows considerably higher image quality as well as improved T1ρ quantification accuracy (+ 56%) and precision (+ 49%) compared to conventional sampling. Compared to the gold standard sequence, a mean deviation of − 0.46 ± 1.84% was observed. The in vivo measurements proved high reproducibility of myocardial T1ρ mapping. The mean T1ρ in the left ventricle was 39.5 ± 1.2 ms for different animals and the maximum deviation was 2.1% in the successive measurements. The myocardial T1ρ dispersion slope, which was measured for the first time in one animal, could be determined to be 4.76 ± 0.23 ms/kHz. Conclusion: This new and fast T1ρ quantification technique enables high-resolution myocardial T1ρ mapping and even dispersion quantification within the limited time of an in vivo study and could, therefore, be a reliable tool for improved tissue characterization. [ABSTRACT FROM AUTHOR]

The development of novel PET imaging agents for synaptic vesicle glycoprotein 2A (SV2A) allowed for the in vivo detection of synaptic density changes, which are correlated with the progression and severity of a variety of neuropsychiatric diseases. While multiple ongoing clinical investigations using SV2A PET are expanding its applications rapidly, preclinical SV2A PET imaging in animal models is an integral component of the translation research and provides supporting and complementary information. Herein, we overview preclinical SV2A PET studies in animal models of neurodegenerative disorders and discuss the opportunities and practical challenges in small animal SV2A PET imaging. At the Yale PET Center, we have conducted SV2A PET imaging studies in animal models of multiple diseases and longitudinal SV2A PET allowed us to evaluate synaptic density dynamics in the brains of disease animal models and to assess pharmacological effects of novel interventions. In this article, we discuss key considerations when designing preclinical SV2A PET imaging studies and strategies for data analysis. Specifically, we compare the brain imaging characteristics of available SV2A tracers, i.e., [11C]UCB-J, [18F]SynVesT-1, [18F]SynVesT-2, and [18F]SDM-16, in rodent brains. We also discuss the limited spatial resolution of PET scanners for small brains and challenges of kinetic modeling. We then compare different injection routes and estimate the maximum throughput (i.e., number of animals) per radiotracer synthesis by taking into account the injectable volume for each injection method, injected mass, and radioactivity half-lives. In summary, this article provides a perspective for designing and analyzing SV2A PET imaging studies in small animals. [ABSTRACT FROM AUTHOR]

Cancer stem‐like cells (CSCs) cause treatment failure in various tumours; however, establishing CSC‐targeted therapies has been hampered by difficulties in the identification and isolation of this small sub‐population of cells. Recent studies have revealed that tumour cells with low proteasome activity display a CSC phenotype that can be utilized to image CSCs in canines. This study visualizes and reveals the CSC‐like properties of tumour cells with low proteasome activity in HMPOS (osteosarcoma) and MegTCC (transitional cell carcinoma), which are canine cell lines. The parent cells were genetically engineered to express ZsGreen1, a fluorescent protein connected to the carboxyl‐terminal degron of canine ornithine decarboxylase that accumulates with low proteasome activity (ZsG+ cells). ZsG+ cells were imaged and the mode of action of this system was confirmed using a proteasome inhibitor (MG‐132), which increased the ZsGreen1 fluorescence intensity. The CSC‐like properties of ZsG+ cells were evaluated on the basis of cell divisions, cell cycle, the expression of CSC markers and tumourigenicity. ZsG+ cells underwent asymmetric divisions and had a low percentage of G0/G1 phase cells; moreover, ZsG+ cells expressed CSC markers such as CD133 and showed a large tumourigenic capability. In histopathological analysis, ZsG+ cells were widely distributed in the tumour samples derived from ZsG+ cells and in the proliferative regions of the tumours. The results of this study indicate that visualized canine tumour cells with low proteasome activity have a CSC‐like phenotype and that this visualization system can be utilized to identify and isolate canine CSCs. [ABSTRACT FROM AUTHOR]

While the majority of canine osteosarcomas (OSA) arise from the medullary cavity, a subset arises from the surface of bone. In humans, surface OSA often has a more indolent disease course with better outcomes than medullary OSA. The aim of this retrospective case series was to evaluate the clinical outcome and potential prognostic factors of dogs with surface OSA. Medical records from 11 dogs previously diagnosed with surface OSA were included. Histopathology of cases was evaluated during case review by two veterinary anatomic pathologists. Median progression free interval (PFI) and overall median survival time (OST) were estimated using Kaplan–Meier methods. Intergroup comparisons were performed using log‐rank tests. Six dogs were diagnosed with periosteal OSA, 4 dogs with parosteal OSA, and one dog with an unclassified surface OSA. Two dogs were found to have metastatic disease at the time of diagnosis and four developed metastatic lesions after treatment. The median PFI and median OST for all dogs with surface OSA was 425 and 555 days, respectively. The 6 dogs diagnosed with periosteal OSA had a median PFI of 461 days and median OST of 555 days, while the 4 dogs with parosteal OSA had a PFI of 350 days and the OST could not be calculated. Multiple prognostic factors (surgery, systemic adjunctive therapy, elevated alkaline phosphatase at diagnosis, appendicular vs axial location, mitotic count, and tumour grade) were evaluated and none were prognostic for PFI or OST. Dogs with surface OSA appear to have prolonged PFI and OST, consistent with humans with surface OSA. [ABSTRACT FROM AUTHOR]

The purpose of this retrospective cohort study was to determine prevalence of sternal lymphadenopathy in a population of dogs undergoing splenectomy, and to evaluate if the prevalence was associated with splenic malignancy. In addition, the study investigated if survival in dogs diagnosed with hemangiosarcoma (HSA) differed between those with or without sternal lymphadenopathy at the time of surgery. Digital radiographs and medical records for dogs who underwent splenectomy from 2013 to 2016 where retrospectively reviewed. One hundred ninety‐five dogs underwent splenectomy during the study period. The overall prevalence of sternal lymphadenopathy was 12.8%. The prevalence of sternal lymphadenopathy in dogs with hemangiosarcoma was 16.2% (12/74), other malignancy was 15.8% (3/19), and with a benign process 9.8% (10/102). There was no significant association between sternal lymphadenopathy with hemoperitoneum (p =.20) or between sternal lymphadenopathy and presence of neoplasia (p =.37). There was no significant difference in survival probability in all dogs with or without sternal lymphadenopathy (p =.073). However, sternal lymphadenopathy was associated with lower survival in 74 dogs with HSA (p =.036) and 19 with other splenic malignancies (p =.039). The presence of sternal lymphadenopathy should not be considered a negative prognostic indicator if present in dogs presenting with a hemoperitoneum. Although the presence of sternal lymphadenopathy at the time of initial presentation was not significantly associated with survival time in all dogs with splenic disease, it may have predictive value related to survival of dogs with splenic malignancy. [ABSTRACT FROM AUTHOR]

The development of novel PET imaging agents for synaptic vesicle glycoprotein 2A (SV2A) allowed for the in vivo detection of synaptic density changes, which are correlated with the progression and severity of a variety of neuropsychiatric diseases. While multiple ongoing clinical investigations using SV2A PET are expanding its applications rapidly, preclinical SV2A PET imaging in animal models is an integral component of the translation research and provides supporting and complementary information. Herein, we overview preclinical SV2A PET studies in animal models of neurodegenerative disorders and discuss the opportunities and practical challenges in small animal SV2A PET imaging. At the Yale PET Center, we have conducted SV2A PET imaging studies in animal models of multiple diseases and longitudinal SV2A PET allowed us to evaluate synaptic density dynamics in the brains of disease animal models and to assess pharmacological effects of novel interventions. In this article, we discuss key considerations when designing preclinical SV2A PET imaging studies and strategies for data analysis. Specifically, we compare the brain imaging characteristics of available SV2A tracers, i.e., [11C]UCB-J, [18F]SynVesT-1, [18F]SynVesT-2, and [18F]SDM-16, in rodent brains. We also discuss the limited spatial resolution of PET scanners for small brains and challenges of kinetic modeling. We then compare different injection routes and estimate the maximum throughput (i.e., number of animals) per radiotracer synthesis by taking into account the injectable volume for each injection method, injected mass, and radioactivity half-lives. In summary, this article provides a perspective for designing and analyzing SV2A PET imaging studies in small animals.