High concordance of blood glucose measurement in cats between a beta prototype glucometer device and a reference laboratory standard in a clinical setting.

OBJECTIVE: The objective of this study was to evaluate the accuracy of a beta prototype version of a new portable blood glucose meter in feline patients. ANIMALS: 60 client-owned cats. METHODS: In this prospective study, 3-mL blood samples were collected from each cat and analyzed in triplicate using a beta prototype device (AlphaTRAK 3 [AT3]) and by a reference lab standard immediately after collection. Accuracy of the AT3 device was determined in accordance with the International Organization of Standardization (ISO) 15197:2013 criteria, including Bland-Altman plotting and consensus error grid analysis. A Passing-Bablok regression analysis was also performed. RESULTS: 96% of feline measurements fell within the ISO accuracy threshold, and 100% of measurements fell within zones A and B of the consensus error grid, meeting the ISO accuracy requirements. There was no significant bias in the data according to the Bland-Altman analysis. Within the full range of glucose concentrations (20 to 750 mg/dL) the correlation coefficient between the AT3 and the reference lab standard was 0.99. There was no significant constant or proportional bias present in the data. CLINICAL RELEVANCE: The AT3 device met the ISO requirements and is accurate for measurement of blood glucose concentrations in cats.

Associations of abdominal discomfort and length of clinical signs with surgical procedure in 181 cases of canine small intestinal foreign body obstruction.

BACKGROUND: Gastrointestinal foreign bodies are a common indication for abdominal exploratory surgery. OBJECTIVES: The objective of this study was to evaluate the relationship of pre-operative abdominal discomfort and duration of clinical signs with surgical resolution of canine small intestinal foreign body obstructions (SIFBO). METHODS: We performed a retrospective study of 181 canine abdominal exploratory surgeries for confirmed SIFBO at two referral hospitals. Animals were categorized into five surgical groups (gastrotomy after manipulation into the stomach, enterotomy, resection-and-anastomosis [R&A], manipulated into colon, already in colon) and further grouped by whether entry into the gastrointestinal tract (GIT) was required. RESULTS: Abdominal discomfort was noted in 107/181 cases (59.1%), but no significant differences in abdominal discomfort rates were present among the surgical groups or between GIT entry and no entry groups. Clinical sign duration was associated with surgical procedure; median durations were R&A = 3 days (range, 1-9), enterotomy = 2 days (range, 1-14), gastrotomy = 2 days (range, 1-6), already in colon = 1.5 days (range, 1-2), and manipulated into colon = 1 day (range, 1-7). In a pairwise comparison, differences in the duration of clinical signs were found for obstructions manipulated into the colon versus R&A, gastrotomy versus R&A, and in colon versus R&A. When patients were grouped according to GIT entry, cases with entry had a longer duration of clinical signs (median = 2 days [range, 1-14] versus 1 day [range, 1-7], respectively). CONCLUSIONS: Abdominal discomfort was not associated with surgical complexity; however, the duration of clinical signs was associated with surgical complexity, with longer duration being associated with entry into the GIT and R&A. Despite statistical significance, the maximum difference of 2 days between surgical groups is unlikely to be clinically relevant.

Comparison of the pharmacokinetics of continuous and intermittent infusions of ampicillin-sulbactam in dogs with septic peritonitis.

OBJECTIVE: To evaluate the time-course of ampicillin-sulbactam and percentage of time that its concentration is above a given MIC (T% > MIC) in dogs with septic peritonitis when delivered as either a continuous infusion (CI) or intermittent infusion (II). ANIMALS: 11 dogs with septic peritonitis. PROCEDURES: Dogs were randomized to receive ampicillin-sulbactam as either CI or II. Continuous infusions were delivered as a 50 mg/kg bolus IV followed by a rate of 0.1 mg/kg/min. Intermittent infusions were administered as 50 mg/kg IV q8h. Serum ampicillin-sulbactam concentrations were measured at hours 0, 1, 6, and every 12 hours after until patients were transitioned to an oral antimicrobial equivalent. All other care was at the discretion of the attending clinician. Statistical analysis was used to determine each patient's percentage of time T% > MIC for 4 MIC breakpoints (0.25, 1.25, 8, and 16 µg/mL). RESULTS: No dogs experienced adverse events related to ampicillin-sulbactam administration. Both CI and II maintained a T% > MIC of 100% of MIC 0.25 µg/mL and MIC 1.25 µg/mL. The CI group maintained a higher T% > MIC for MIC 8 µg/mL and MIC 16 µg/mL; however, these differences did not reach statistical significance (P = .15 and P = .12, respectively). CLINICAL RELEVANCE: This study could not demonstrate that ampicillin-sulbactam CI maintains a greater T% > MIC in dogs with septic peritonitis than II; however, marginal differences were noted at higher antimicrobial breakpoints. While these data support the use of antimicrobial CI in septic and critically ill patients, additional prospective trials are needed to fully define the optimal doses and the associated clinical responses.

Pharmacokinetic Exposures Associated With Oral Administration of Sorafenib in Dogs With Spontaneous Tumors.

Sorafenib is a multi-kinase small molecule inhibitor that targets serine/threonine and tyrosine kinases including the RAF kinase family, VEGFR-2, and PDGFR. The aim of this study was to evaluate the systemic pharmacokinetics of a previously defined tolerable oral dose of sorafenib in tumor-bearing dogs. Six client-owned dogs with a cytologic or histologic diagnosis of cancer were enrolled in this open-label, tolerability study. Dogs were administered sorafenib at an intended dose of 3 mg/kg and serum samples were obtained for analysis of sorafenib serum concentrations at 0, 1, 2, 6, 12, 24, 48, 72, 96, and 168 h post-drug administration. Median time to peak serum sorafenib concentration occurred at 4 h (range 2-12 h) resulting in an average serum concentration of 54.9 ± 33.5 ng/mL (118.2 ± 72.1 nM). Mean sorafenib levels declined by over 70% relative to peak serum concentrations by 24 h in all dogs, suggesting the value of at least twice daily administration. Doses of 3 mg/kg were well-tolerated and no patients in the study experienced adverse events that were attributable to sorafenib. Future trials in dogs with cancer are recommended at this dosing schedule to assess the effect of sorafenib administration on anti-tumor efficacy signals and relevant pharmacodynamic target modulation in vivo.

Prevalence and clinical features of thoracolumbar intervertebral disc-associated epidural hemorrhage in dogs.

BACKGROUND: Intervertebral disc-associated epidural hemorrhage (EH) in dogs is a poorly understood neurological condition. OBJECTIVE: To compare the clinical presentation, magnetic resonance imaging (MRI) changes, and clinical outcome of dogs with acute thoracolumbar intervertebral disc herniation (TL-IVDH) with and without EH. ANIMALS: One hundred sixty client-owned dogs that underwent MRI and hemilaminectomy for acute TL-IVDH at a private practice in Colorado, including 63 dogs with EH and 97 dogs without EH. METHODS: Retrospective review of medical record data from 160 dogs presenting sequentially to a single practice with acute TL-IVDH that underwent MRI and hemilaminectomy surgery. RESULTS: Sixty-three of 160 (39%) dogs had confirmed EH. French Bulldogs were significantly overrepresented (23/63; odds ratio [OR]: 4.1; 95% confidence interval [CI]: 1.8-9.0; P < .001) of the EH cases. Dogs with EH were more likely to present with clinical signs less than 48 hours than were dogs without EH (24-48 vs 48-72 hours; OR: 2.4; 95% CI: 1.2-4.6; P = .02) and were more likely to be nonambulatory on presentation (OR: 2.1; 95% CI: 1.0-4.1; P = .04). Dogs with EH were more likely to have <50% cross-sectional spinal cord compression than dogs without EH (OR: 2.3 vs. 0.4; 95% CI: 1.2-4.4 and 0.2-0.9, respectively), longer longitudinal spinal cord compression (3 spaces vs 1 space, P < .001), and greater intrinsic spinal cord change (grade 3/severe vs grade 1/mild; P < .001) based on MRI. The location of the intervertebral disc herniation in French Bulldogs with EH was more likely to be thoracolumbar (OR: 10.8; 95% CI: 2.1-55.7; P = .03). CONCLUSIONS AND CLINICAL IMPORTANCE: French Bulldogs have a high prevalence of intervertebral disc-associated EH. Dogs with EH have a shorter clinical course and are more likely to be nonambulatory on initial presentation.

Feasibility of circulating tumor DNA analysis in dogs with naturally occurring malignant and benign splenic lesions.

Comparative studies of naturally occurring canine cancers have provided new insight into many areas of cancer research. Development and validation of circulating tumor DNA (ctDNA) analysis in pet dogs can help address diagnostic needs in veterinary as well as human oncology. Dogs have high incidence of naturally occurring spontaneous cancers, demonstrate molecular heterogeneity and clonal evolution during therapy, allow serial sampling of blood from the same individuals during the course of disease progression, and have relatively compressed intervals for disease progression amenable to longitudinal studies. Here, we present a feasibility study of ctDNA analysis performed in 48 dogs including healthy dogs and dogs with either benign splenic lesions or malignant splenic tumors (hemangiosarcoma) using shallow whole genome sequencing (sWGS) of cell-free DNA. To enable detection and quantification of ctDNA using sWGS, we adapted two informatic approaches and compared their performance for the canine genome. At the time of initial clinical presentation, mean ctDNA fraction in dogs with malignant splenic tumors was 11.2%, significantly higher than dogs with benign lesions (3.2%; p = 0.001). ctDNA fraction was 14.3% and 9.0% in dogs with metastatic and localized disease, respectively (p = 0.227). In dogs treated with surgical resection of malignant tumors, mean ctDNA fraction decreased from 11.0% prior to resection to 7.9% post-resection (p = 0.047 for comparison of paired samples). Our results demonstrate that ctDNA analysis is feasible in dogs with hemangiosarcoma using a cost-effective approach such as sWGS. Additional studies are needed to validate these findings, and determine the role of ctDNA to assess burden of disease and treatment response in dogs with cancer.

Leukocyte and cytokine variables in asymptomatic Pugs at genetic risk of necrotizing meningoencephalitis.

BACKGROUND: Necrotizing meningoencephalitis (NME, aka Pug dog encephalitis) is an inflammatory brain condition associated with advanced disease at initial presentation, rapid progression, and poor response to conventional immunomodulatory therapy. HYPOTHESIS/OBJECTIVES: That genetic risk for NME, defined by a common germline DNA haplotype located on chromosome 12, is associated with altered blood cytokine concentrations and leukocyte subsets in asymptomatic Pugs. ANIMALS: Forty Pug dogs asymptomatic for NME from a hospital sample. METHODS: Prospective observational cohort study, including germline genome-wide genotyping, plasma cytokine determination by multiplexed profiling, and leukocyte subset characterization by flow cytometric analysis. RESULTS: Seven (18%) dogs were high risk, 10 (25%) medium risk, and 23 (58%) low risk for NME, giving a risk haplotype frequency of 30%. High and medium risk Pugs had significantly lower proportion of CD4+ T cells (median 22% [range, 7.3%-38%] vs 29% [range, 16%-41%], P = .03) and higher plasma IL-10 concentrations than low-risk Pugs (median 14.11 pg/mL [range, 9.66-344.19 pg/mL] vs 12.21 pg/mL [range, 2.59-18.53 pg/mL], P = .001). No other variables were significantly associated with the NME haplotype-based risk. CONCLUSIONS AND CLINICAL IMPORTANCE: These data suggest an immunological underpinning to NME and a biologic rationale for future clinical trials that investigate novel diagnostic, preventative, and therapeutic strategies for this disease.

Development of a veterinary emergency open standard competency framework using a competency-based model of medical education.

OBJECTIVE: To address the shortage of emergency veterinarians, the profession is exploring accelerated training pathways. We sought to contribute to the solution by developing the foundation for an open standard, competency-based veterinary emergency training curriculum for use by any program. We also developed a curricular delivery, tracking, and assessment system to demonstrate how the framework can be integrated into training programs.  DESIGN: Hybrid Delphi method.  SETTING: Academia and referral practice.  ANIMALS: None. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: An emergency veterinary competency framework was developed by adapting the human Model of the Clinical Practice of Emergency Medicine, which aligns with the Competency-Based Veterinary Education framework, to produce 4 areas of core competency: Patient Care, Interpersonal/Communication, Professionalism, and Practice-based Learning/Improvement. A comprehensive list of veterinary emergency skills was generated and organized within the framework utilizing the hybrid Delphi method. An initial survey completed by 133 emergency and critical care specialists and emergency room clinicians produced data regarding the value of specific skills. An 11-member focus group consisting of survey participants iterated upon the survey results to produce a master library of skills and cases, including 56 Patient Care, 43 Interpersonal/Communication, 11 Practice-based Learning/Improvement, and 20 Professionalism skills, as well as 155 case types. The curricular delivery system tracks and assesses case management proficiency and development of knowledge and professional skills using a patient care eLearning program and simulation training environment.  CONCLUSIONS: The increasing need for emergency veterinarians is a shared industry-wide challenge. To contribute toward a collective solution, we have undergone an evidence-based process to create the foundation for an open standard competency framework composed of a library of skills and cases. We offer this open standard framework to the veterinary profession and hope it continues to grow and evolve as we drive toward developing competency-based training programs that address the shortage of emergency veterinarians.

Prospective observational study of dogs with splenic mass rupture suggests potentially lower risk of malignancy and more favourable perioperative outcomes.

Haemoperitoneum secondary to ruptured splenic tumours can be either benign or malignant in origin. The majority of previous studies of canine haemoperitoneum have been retrospective, which are associated with well-recognized biases, such as the potential to underappreciate the diversity of outcomes in a complex presentation such as haemoperitoneum. This study seeks to prospectively define perioperative morbidity and mortality of haemoperitoneum in dogs secondary to ruptured splenic masses. Forty dogs with haemoperitoneum secondary to a ruptured splenic mass met the inclusion criteria. As expected, the cohort predominately consisted of older large breed dogs. All dogs underwent preoperative staging and had a splenectomy performed. Histopathologic analysis was performed on the splenic mass, as well as any possible metastatic lesions that were noted intra-operatively. Perioperative care outside of splenectomy was delivered in specialty practices using current conventional approaches to care (eg, transfusions and anti-arrhythmic medications). Fifteen dogs (37.5%) had benign splenic tumours and were cured with surgery alone, whereas 62.5% had malignant disease (most often haemangiosarcoma [HSA]). Surgical outcomes were highly favourable in the vast majority of dogs. Indeed, 38 dogs (95%) survived and were discharged after a median hospitalization of 39.5 hours. Independent predictors of longer hospitalization times included receiving a transfusion and the development of an arrhythmia. Although small, this cohort defines distinctive and optimistic perspectives for dogs with haemoperitoneum from splenic tumour rupture. These favourable outcomes from this prospective study are sufficient to ask if larger prospective studies should be conducted to better inform owners during this challenging cancer emergency presentation.

Antibiotic use in critical illness.

OBJECTIVE: To provide a review on the current use of antimicrobials with a discussion on the pharmacokinetic and pharmacodynamic profiles of antimicrobials in critically ill patients, the challenges of drug resistance, the use of diagnostic testing to direct therapy, and the selection of the most likely efficacious antimicrobial protocol. ETIOLOGY: Patients in the intensive care unit often possess profound pathophysiologic changes that can complicate antimicrobial therapy. Although many antimicrobials have known pharmacodynamic profiles, critical illness can cause wide variations in their pharmacokinetics. The two principal factors affecting pharmacokinetics are volume of distribution and drug clearance. Understanding the interplay between critical illness, drug pharmacokinetics, and antimicrobial characteristics (ie, time-dependent vs concentration-dependent) may improve antimicrobial efficacy and patient outcome. DIAGNOSIS: Utilizing bacterial culture and susceptibility can aid in identifying drug resistant infections, selecting the most appropriate antimicrobials, and hindering the future development of drug resistance. THERAPY: Having a basic knowledge of antimicrobial function and how to use diagnostics to direct therapeutic treatment is paramount in managing this patient population. Diagnostic testing is not always available at the time of initiation of antimicrobial therapy, so empiric selections are often necessary. These empiric choices should be made based on the location of the infection and the most likely infecting bacteria. PROGNOSIS: Studies have demonstrated the importance of moving away from a "one dose fits all" approach to antimicrobial therapy. Instead there has been a move toward an individualized approach that takes into consideration the pharmacokinetic and pharmacodynamic variabilities that can occur in critically ill patients.