Arthroscopic Caudal Cruciate Ligament Damage in Canine Stifles with Cranial Cruciate Ligament Disease.

OBJECTIVE: The aim of this study was to describe the arthroscopic changes to the caudal cruciate ligament (CdCL) in dogs with cranial cruciate ligament disease. STUDY DESIGN: Arthroscopic video recordings (n = 117) of the stifle with cranial cruciate ligament disease were reviewed. The extent of CdCL tearing was described. Signalment, palpable stifle stability and the presence of a meniscal tear were recorded. Pathology of the synovial joint and the synovium overlying the CdCL were scored at two time points.Two-way interactions were investigated (p < 0.05). Univariate analysis and a Wald test (p < 0.20) were performed. Factors were retained with a Wald test p < 0.05 or if a confounder, then a changing model coefficient >15%. A weighted kappa statistic was used to evaluate intraobserver agreement. RESULTS: Caudal cruciate ligament tearing was identified in 94% of stifles. Longitudinal tearing (76%) was the most common type of damage (45% partial, 31% full thickness). Synovitis was present in all joints and changes to the synovium overlying the CdCL were less frequently identified (67%).Synovitis was associated with the degree to CdCL tearing. Synovitis overlying the CdCL was associated with lower body weight and lower CdCL damage. CONCLUSION: Caudal cruciate ligament damage is common in dogs with cranial cruciate ligament disease and longitudinal tearing was the most common injury identified. Severity of joint pouch synovitis was positively correlated with the degree of CdCL damage and the portion of the CdCL not exposed to the synovium was unaffected. These findings suggest synovitis is likely a contributor to CdCL injury.

Pain Treatment in the Companion Canine Model to Validate Rodent Results and Incentivize the Transition to Human Clinical Trials.

One of the biggest challenges for analgesic drug development is how to decide if a potential analgesic candidate will work in humans. What preclinical data are the most convincing, incentivizing and most predictive of success? Such a predicament is not unique to analgesics, and the pain field has certain advantages over drug development efforts in areas like neuropsychiatry where the etiological origins are either unknown or difficult to ascertain. For pain, the origin of the problem frequently is known, and the causative peripheral tissue insult might be observable. The main conundrum centers around evaluation of translational cell- and rodent-based results. While cell and rodent models are undeniably important first steps for screening, probing mechanism of action, and understanding factors of adsorption, distribution metabolism and excretion, two questions arise from such studies. First, are they reliable indicators of analgesic performance of a candidate drug in human acute and chronic pain? Second, what additional model systems might be capable of increasing translational confidence? We address this second question by assessing, primarily, the companion canine model, which can provide particularly strong predictive information for candidate analgesic agents in humans. This statement is mainly derived from our studies with resiniferatoxin (RTX) a potent TRPV1 agonist but also from protein therapeutics using a conjugate of Substance P and saporin. Our experience, to date, is that rodent models might be very well suited for acute pain translation, but companion canine models, and other large animal studies, can augment initial discovery research using rodent models for neuropathic or chronic pain. The larger animal models also provide strong translational predictive capacity for analgesic performance in humans, better predict dosing parameters for human trials and provide insight into behavior changes (bladder, bowel, mood, etc.) that are not readily assessed in laboratory animals. They are, however, not without problems that can be encountered with any experimental drug treatment or clinical trial. It also is important to recognize that pain treatment is a major veterinary concern and is an intrinsically worthwhile endeavor for animals as well as humans.

Evaluation of short-term risk factors associated with dehiscence and death following full-thickness incisions of the large intestine in cats: 84 cases (1993-2015).

OBJECTIVE: To evaluate short-term risk factors associated with dehiscence and death in cats undergoing full-thickness large intestinal incisions. ANIMALS: 84 client-owned cats that had undergone full-thickness large intestinal incisions and for which information regarding outcome through postoperative day 7 was available. PROCEDURES: Medical records from 4 veterinary teaching hospitals were reviewed. For cats that met the inclusion criteria, signalment, history, laboratory test results, surgical and medical procedures, perioperative complications, and outcome were analyzed. A Fisher exact or Wilcoxon rank sum test was used to identify individual variables associated with dehiscence of intestinal incisions or patient nonsurvival to hospital discharge or both. RESULTS: 84 cats met the inclusion criteria. The overall dehiscence and survival to hospital discharge rates were 8.3% (7/84 cats) and 94% (79/84 cats), respectively. Factors associated with dehiscence and nonsurvival to hospital discharge included presence of band neutrophils, performance of partial colectomy with colonic resection and anastomosis, administration of blood products, postoperative cardiopulmonary arrest, and incisional inflammation or infection. Factors associated with nonsurvival to hospital discharge only included low serum globulin concentration, repair of colonic trauma or dehiscence, and postoperative colonic dehiscence. Factors associated with dehiscence only included hypoalbuminemia, renal dysfunction, administration of blood products or > 2 classes of antimicrobials, and intra-abdominal fecal contamination. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that intestinal dehiscence and mortality rates associated with large intestinal incisions in cats may be higher than previously proposed, although the risk of either outcome was still low. Factors suggestive of systemic illness were associated with colonic dehiscence or death, and focused prospective studies of risk factors are warranted.

Evaluation of scar revision after inadequate primary excision of cutaneous mast cell tumors in 85 dogs (2000-2013).

OBJECTIVE: To determine the frequency of residual tumor, and factors associated with local recurrence and disease progression in dogs with incompletely excised mast cell tumors (MCT) following scar revision surgery. STUDY DESIGN: Retrospective study. ANIMALS: Eighty-five dogs. METHODS: Medical records from January 2000 to April 2013 were reviewed. Dogs with scar revision surgery after incomplete primary MCT excision were included. Recorded were signalment; initial tumor size, location and grade; time interval between primary excision and scar revision surgery; presence of MCT in the resected scar; local recurrence, lymph node metastasis, systemic metastasis, and cause of death. RESULTS: Eighty six tumors in 85 dogs were studied. Residual MCT was found in 23 (27%) resected scars. Seven (8%) scars with residual MCT had incomplete or narrow margins. Follow-up was available for 68 dogs (69 tumors; median 403 days; range 4-2939). Local recurrence was reported in three (4%) dogs at 212, 555, and 993 days. Disease progressed in 10 dogs (14.5%) with regional or systemic metastasis at a median of 207 days (64-1583). Margin status and presence of MCT in the resected scar were not associated with local recurrence or disease progression. Lymph node metastasis (p = .004), locoregional recurrence (p = .013), and disease progression (p = .001) were significantly more likely in Grade III tumors. CONCLUSION: Twenty-seven percent of resected scars contained residual MCT, but recurrence was uncommon after surgical revision. CLINICAL SIGNIFICANCE: Clinicians should primarily consider tumor grade when estimating the likelihood of local recurrence and disease progression and determining the need for ancillary treatment of MCT after scar resection.

Arthroscopic Articular Cartilage Scores of the Canine Stifle Joint with Naturally Occurring Cranial Cruciate Ligament Disease.

OBJECTIVE: This study aimed to evaluate frequency, location and severity of cartilage pathology in dogs with naturally occurring cranial cruciate ligament (CCL) disease. STUDY DESIGN: Stifle arthroscopic video recordings (n = 120) were reviewed. A modified Outerbridge classification system (MOCS) (0-4) was used to score cartilage at 10 locations in the femorotibial (medial and lateral femoral condyles and tibial plateaus) and patellofemoral compartments (proximal, middle and distal locations of the patella and femoral trochlear groove) of the stifle joint. Synovial pathology was scored and the presence of a medial meniscal tear was recorded. A Kruskal-Wallis test was used to evaluate association of location and synovitis with cartilage score; and presence of meniscal tear with cartilage and synovitis scores. Bonferroni correction was utilized and p < 0.05 was considered significant. RESULTS: Cartilage pathology and synovitis were identified in all joints. Overall cartilage severity scores were low (median MOCS 1). The median MOCS of the proximal trochlear groove (2) was significantly higher than all other locations evaluated. Higher synovitis scores were significantly associated with higher cartilage severity scores and a medial meniscal tear had no association with cartilage severity scores or synovitis. CONCLUSION: Arthroscopic articular cartilage lesions are common in dogs with CCL disease at the time of surgical intervention, although the severity of cartilage damage is mild. The proximal trochlear groove of the femur had the most severe cartilage score in the stifle joint.

Efficacy and toxicity of mustargen, vincristine, procarbazine and prednisone (MOPP) for the treatment of relapsed or resistant lymphoma in cats.

OBJECTIVES: The aims of this study were to evaluate the safety of mustargen, vincristine, procarbazine and prednisone (MOPP) chemotherapy in the treatment of relapsed or refractory feline lymphoma, and to determine the overall response rate and median remission time with this protocol. METHODS: The medical records of 38 cats with relapsed or refractory lymphoma treated with MOPP chemotherapy at three institutions (University of Pennsylvania, the Animal Medical Center, and VCA Western Veterinary Specialist and Emergency Centre) were examined. Information evaluated included patient signalment, feline immunodeficiency virus/feline leukemia virus status, anatomic location(s) of lymphoma, prior protocols (type and number), MOPP doses, MOPP response, remission duration, hematologic and biochemical parameters, and owner-reported adverse effects. RESULTS: Overall, 70.3% of cats responded to MOPP chemotherapy. Among the responders, the median remission duration was 166 days. The most common adverse effects were neutropenia and gastrointestinal upset, which were reported in 18.4% of cats. In 55.3% of cats, no adverse effects were reported. In total, 30.8% of responders continued to respond 6 months following the initiation of MOPP, and 15.4% maintained a response 1 year after starting MOPP. CONCLUSIONS AND RELEVANCE: MOPP is a safe protocol for the treatment of relapsed or refractory feline lymphoma, with a promising overall response rate and median remission time.

A randomized clinical efficacy study targeting mPGES1 or EP4 in dogs with spontaneous osteoarthritis.

Canine studies of spontaneous osteoarthritis (OA) pain add valuable data supporting drug treatment mechanisms that may translate to humans. A multicenter, randomized, double-blind, placebo- and active-controlled study was conducted in client-owned dogs with moderate OA pain to evaluate efficacy of LYA, an inhibitor of microsomal prostaglandin E synthase-1 (mPGES1), an EP4 antagonist (LYB), and carprofen, versus placebo. Of 255 dogs screened, 163 were randomized (placebo/LYA/LYB/carprofen: n = 43/39/42/39) and 158 completed treatment. Efficacy versus placebo was assessed using Bayesian mixed-effect model for repeated measure analyses of the Canine Brief Pain Inventory (CBPI) pain interference score (PIS; primary endpoint), pain severity score, and overall impression, as well as the Liverpool Osteoarthritis in Dogs (LOAD) mobility score. The posterior probability that the difference to placebo was <0 at week 2 was 80% for LYA and 54% for LYB for CBPI PIS (both <95% predefined threshold). For secondary endpoints, the posterior probability that the difference to placebo was <0 at week 2 ranged from 89 to 96% for LYA and from 56 to 89% for LYB. The posterior probabilities comparing carprofen to placebo groups were ≥90% for all efficacy endpoints. The proportion of dogs with one or more adverse event was not significantly different from placebo (32.6%) for LYA (35.9%) or carprofen (25.6%), but the rate for LYB (59.5%) was higher versus placebo (P = 0.017). LYA treatment demonstrated consistent improvement in all efficacy measures, suggesting that inhibition of mPGES1 may be an effective treatment for chronic pain associated with OA.

Evaluation of short-term outcomes and potential risk factors for death and intestinal dehiscence following full-thickness large intestinal incisions in dogs.

OBJECTIVE: To determine complication rates for dogs in which full-thickness large intestinal incisions were performed, assess potential risk factors for death during hospitalization and for intestinal dehiscence following these surgeries, and report short-term mortality rates for these patients. ANIMALS: 90 dogs. PROCEDURES: Medical records of 4 veterinary referral hospitals were reviewed to identify dogs that underwent large intestinal surgery requiring full-thickness incisions. Signalment, history, clinicopathologic data, medical treatments, surgical procedures, complications, and outcomes were recorded. Descriptive statistics were calculated; data were analyzed for association with survival to discharge (with logistic regression analysis) and postoperative intestinal dehiscence (with Fisher exact or Wilcoxon rank sum tests). RESULTS: Overall 7-day postoperative intestinal dehiscence and mortality rates were 9 of 90 (10%) and 15 of 90 (17%). Dogs with preoperative anorexia, hypoglycemia, or neutrophils with toxic changes and those that received preoperative antimicrobial treatment had greater odds of death than did dogs without these findings. Preexisting colon trauma or dehiscence, preexisting peritonitis, administration of blood products, administration of > 2 classes of antimicrobials, positive microbial culture results for a surgical sample, and open abdominal management of peritonitis after surgery were associated with development of intestinal dehiscence. Five of 9 dogs with intestinal dehiscence died or were euthanized. CONCLUSIONS AND CLINICAL RELEVANCE: Factors associated with failure to survive to discharge were considered suggestive of sepsis. Results suggested the dehiscence rate for full-thickness large intestinal incisions may not be as high as previously reported, but several factors may influence this outcome and larger, longer-term studies are needed to confirm these findings.

Outcomes in 40 cats with discrete intermediate- or large-cell gastrointestinal lymphoma masses treated with surgical mass resection (2005-2015).

OBJECTIVE: To report outcomes in cats with discrete intermediate- and large-cell gastrointestinal (GI) lymphoma masses after surgical resection. STUDY DESIGN: Retrospective clinical case series. ANIMALS: Forty client-owned cats in which intermediate- or large-cell GI lymphoma was diagnosed. METHODS: Records of 40 cats in which discrete intermediate- or large-cell GI lymphoma masses were diagnosed between 2005 and 2015 were reviewed. Cats were included if they survived curative intent surgery and had a known outcome for at least two weeks. Postoperative death was permitted. Data collected included anatomic site, surgical margins, lymphoma subtype, chemotherapy use, and postoperative and long-term outcome (beyond two weeks). RESULTS: Affected sites consisted of small intestines (n = 23), large intestines (n = 9), and stomach (n = 8). Thirty-six of 40 cats survived to discharge, and 31 cats were alive at suture removal. Median long-term follow-up of 22 cats was 111 days (range, 16-1407). Cats that survived to suture removal had a median survival time (MST) of 185 days (95% confidence interval: 72-465). Cats with large intestinal masses lived longer than those with small intestinal or gastric masses whether all cats (MST, 675, 64, 96 days, respectively; P = .03) or only those surviving to suture removal were considered. Complete surgical resection (n = 20) was positively associated with survival (370 vs 83 days, P = .016). CONCLUSION: Most cats in this population survived the perioperative period, with MST similar to those reported historically with medical management. CLINICAL SIGNIFICANCE: Surgical resection may be a reasonable consideration in cats with solitary lymphoma, particularly those with large intestinal masses.

Clinicopathological Features, Risk Factors and Predispositions, and Response to Treatment of Eosinophilic Oral Disease in 24 Dogs (2000-2016).

The objectives of this study were to retrospectively describe clinicopathological features of eosinophilic oral disease in dogs, to identify possible risk factors or predispositions to the condition, and to report overall treatment response. Canine medical records from a veterinary teaching hospital and private referral practice over a 17-year period were reviewed for a diagnosis of eosinophilic oral disease. Twenty-four dogs with 26 lesions met the inclusion criteria. Patient mean age and body weight were 6.8 (3.8) years and 13.4 kg, respectively. Fifteen breeds were represented including Cavalier King Charles spaniel (16.7%), Labrador retriever (12.5%), and West Highland white terrier (12.5%). Eosinophilic lesions were found in the palate (65.4%), tongue (26.9%), and other oral locations (7.7%). Median follow-up time was 5 months. Analysis revealed statistically significant associations between lesion location and body weight (palatal and tongue lesions were more likely in smaller dogs, whereas lesions in the other category [lip or mucosa] were more likely in larger dogs). There was a correlation in lesion location and resolution (all dogs with palatal lesions became asymptomatic at their last recheck), and resolution and the use of antibiotics plus prednisone (greater likelihood of resolution without the use of this combination). Seventy percent of asymptomatic dogs resolved without medication or with allergen therapy alone, suggesting that asymptomatic dogs may respond well to conservative management. No associations were found between lesion location and breed, signalment and response to therapy, lesion resolution and the use of glucocorticoids, or significance of peripheral eosinophilia.

Radiation exposure of dogs and cats undergoing fluoroscopic procedures and for operators performing those procedures.

OBJECTIVE: To evaluate radiation exposure of dogs and cats undergoing procedures requiring intraoperative fluoroscopy and for operators performing those procedures. SAMPLE: 360 fluoroscopic procedures performed at 2 academic institutions between 2012 and 2015. PROCEDURES: Fluoroscopic procedures were classified as vascular, urinary, respiratory, cardiac, gastrointestinal, and orthopedic. Fluoroscopy operators were classified as interventional radiology-trained clinicians, orthopedic surgeons, soft tissue surgeons, internists, and cardiologists. Total radiation exposure in milligrays and total fluoroscopy time in minutes were obtained from dose reports for 4 C-arm units. Kruskal-Wallis equality of populations rank tests and Dunn pairwise comparisons were used to compare differences in time and exposure among procedures and operators. RESULTS: Fluoroscopy time (median, 35.80 minutes; range, 0.60 to 84.70 minutes) was significantly greater and radiation exposure (median, 137.00 mGy; range, 3.00 to 617.51 mGy) was significantly higher for vascular procedures than for other procedures. Median total radiation exposure was significantly higher for procedures performed by interventional radiology-trained clinicians (16.10 mGy; range, 0.44 to 617.50 mGy), cardiologists (25.82 mGy; range, 0.33 to 287.45 mGy), and internists (25.24 mGy; range, 3.58 to 185.79 mGy). CONCLUSIONS AND CLINICAL RELEVANCE: Vascular fluoroscopic procedures were associated with significantly longer fluoroscopy time and higher radiation exposure than were other evaluated fluoroscopic procedures. Future studies should focus on quantitative radiation monitoring for patients and operators, importance of operator training, intraoperative safety measures, and protocols for postoperative monitoring of patients.

Observer Variability of Arthroscopic Cartilage Grading Using the Modified Outerbridge Classification System in the Dog.

OBJECTIVE: The aim of this study was to determine the inter- and intra-observer variability of the modified Outerbridge cartilage classification system in canine joints evaluated via arthroscopy. MATERIALS AND METHODS: Fifty arthroscopic videos of canine cartilage were scored by six observers, where three of the observers had significant arthroscopic experience and three had minimal to no experience. The kappa (κ) statistic was used to evaluate overall and individual score inter-observer variability, as well as experience variability. The weighted κ statistic was used to evaluate the overall intra-observer variability for each observer, and for individual score intra-observer variability across experience groups. Landis and Koch cut-offs were used to determine strength of agreement associated with each κ-value. RESULTS: The overall inter-and intra-observer variability of the modified Outerbridge cartilage classification system showed fair and substantial strengths of agreement, respectively. The most extreme scores of 0 and 4 had the best inter- and intra-agreement and the middle scores of 1, 2 and 3 had decreased strengths of agreement. Experience of the observer increased the strength of agreement between the scores. CLINICAL SIGNIFICANCE: The modified Outerbridge classification system is an acceptable method for the evaluation of canine cartilage. Observer agreement is improved if the observer has experience with arthroscopy and viewing cartilage changes, and if the same observer is used for subsequent cartilage evaluations.

Ability of ultrasonography to predict the presence and location of histologic lesions in the small intestine of cats.

BACKGROUND: Diagnosis of infiltrative small intestinal (SI) disease in cats is challenging, and debate continues regarding optimal biopsy techniques. Ultrasonography may facilitate selection of biopsy type and location. HYPOTHESIS/OBJECTIVES: Assess ability of ultrasonography to predict histologic lesions by SI segment and tissue layer. ANIMALS: One-hundred sixty-nine cats that had abdominal ultrasonography and full-thickness SI biopsies performed. METHODS: Ultrasonographic images and full-thickness biopsy samples were retrospectively reviewed, and each SI wall layer evaluated for lesions according to published standards. RESULTS: Ultrasonographic SI lesions were present in 132 cats (63 duodenum; 115 jejunum; 71 ileum). Samples were obtained at laparotomy (60) or necropsy (109). Ultrasonographic abnormalities had high positive predictive value (PPV) for histologic lesions (duodenum, 82.0%; 95% confidence interval [CI], 68.6-91.4; jejunum, 91.0%; 95% CI, 81.5-96.6; ileum, 88.1%; 95% CI, 74.4-96.0), but poor negative predictive value (duodenum, 27.1%; 95% CI, 17.2-39.1; jejunum, 27.3%; 95% CI, 10.7-50.2; ileum, 40.4%; 95% CI, 26.4-55.7). The ability of ultrasonography to predict histologic lesions in this population, which had high disease prevalence (SI histologic lesions in 78.1% of cats) was high for mucosal lesions (PPV, 72.7%-100%) but low for submucosal or muscularis lesions (PPV, 18.9%-57.1%). CONCLUSIONS AND CLINICAL IMPORTANCE: In a population with high disease prevalence, most cats with SI mucosal ultrasonographic lesions will have mucosal histologic lesions. Small intestinal submucosal and muscularis ultrasonographic lesions are not predictive of histologic disease in those layers, suggesting that full-thickness biopsy may not be essential in these cats. Ultrasonography may help guide decisions about biopsy type in individual cats.

Prevalence of naturally occurring non-AB blood type incompatibilities in cats and influence of crossmatch on transfusion outcomes.

BACKGROUND: Recognition of the feline red blood cell (RBC) antigen Mik and the presence of naturally occurring anti-Mik antibodies resulting in acute hemolytic transfusion reactions prompted the recommendation to perform a crossmatch before a cat's first RBC transfusion, but this guideline has not yet become a standard practice. OBJECTIVE: To determine the prevalence of naturally occurring non-AB alloantibodies detectable by tube crossmatch, and to compare transfusion outcomes in cats with and without a crossmatch performed. ANIMALS: Three hundred cats that received an RBC transfusion, with or without a major crossmatch performed. METHODS: Retrospective study. RESULTS: Major crossmatch incompatibilities were documented in 23 of 154 transfusion-naive cats (14.9%) and in 15 of 55 previously transfused cats (27%; P = 0.042). Type-specific packed RBCs (pRBCs) were administered to 167 and 82 cats with and without a crossmatch, respectively. Median volume of pRBCs administered during the first transfusion was 5.3 mL/kg (range, 2.4-18 mL/kg). Median change in PCV scaled to dose of pRBCs was +0.8%/mL/kg; administration of crossmatch-compatible pRBCs was not associated with a greater increase in PCV. Febrile transfusion reactions occurred more often in cats that received non-crossmatched (10.1%) compared to crossmatched (2.5%) pRBCs (P = 0.022). Seventy-six percent of cats that received pRBC transfusions survived to hospital discharge. A crossmatch was not associated with improved survival to discharge or at 30 or 60 days posttransfusion. CONCLUSIONS AND CLINICAL IMPORTANCE: The prevalence of naturally occurring non-AB incompatibilities is sufficiently high to justify the recommendation to perform a crossmatch before all (including the first) RBC transfusions in cats.

Factors associated with survival to hospital discharge for cats treated surgically for thoracic trauma.

OBJECTIVE To determine the most common types of injuries in cats surgically treated for thoracic trauma, complications associated with surgical treatment, and factors associated with mortality rate and evaluate the effectiveness of the animal trauma triage (ATT) scoring system for predicting outcome. DESIGN Retrospective case series with nested observational study. ANIMALS 23 client-owned cats surgically treated for thoracic trauma at 7 veterinary teaching hospitals between 1990 and 2014. PROCEDURES Medical records were reviewed to collect data on signalment, medical history, clinical signs and physical examination findings at initial evaluation, clinicopathologic findings, initial emergency treatments and diagnostic tests performed, type of trauma sustained, imaging findings, surgery details, postoperative complications, duration of hospitalization, and cause of death, if applicable. All variables were evaluated for associations with survival to hospital discharge. RESULTS Types of trauma that cats had sustained included dog bite or attack (n = 8 [35%]), motor vehicle accident (6 [26%]), other animal attack (2 [9%]), impalement injury or fall (2 [9%]), projectile penetrating trauma (1 [4%]), or unknown origin (4 [17%]). Intrathoracic surgery was required for 65% (15/23) of cats. The overall perioperative mortality rate was 13% (3/23). Mean ± SD ATT scores for surviving and nonsurviving cats were 6.4 ± 2.2 and 10.0 ± 1.7, respectively. Nineteen of 20 cats with no cardiopulmonary arrest survived to discharge, compared with 1 of 3 cats with cardiopulmonary arrest. Only these 2 variables were significantly associated with outcome. CONCLUSIONS AND CLINICAL RELEVANCE The perioperative mortality rate was low in this series of cats with thoracic trauma; however, those with cardiopulmonary arrest were less likely to survive to hospital discharge than other cats. Cats with a low ATT score were more likely to survive than cats with a high ATT score.

Long-term pain relief in canine osteoarthritis by a single intra-articular injection of resiniferatoxin, a potent TRPV1 agonist.

The translational potential of analgesic approaches emerging from basic research can be augmented by client-owned dog trials. We report on a peripheral interventional approach that uses intra-articular injection of the ultrapotent TRPV1 agonist resiniferatoxin (RTX) to produce a selective long-term chemoinactivation of nociceptive primary afferent nerve endings for pain control in naturally occurring canine osteoarthritis. A single injection of 10 µg of RTX, produced suppression of pain, improvement in gait, weight bearing, and improvement in the dog's activities of daily living lasting 4 months or longer. Two to 3 years after the injection, there are no alterations to suggest that removal of inflammatory pain caused accelerated joint degeneration (Charcot joint) in any of the dogs. To amplify the effective use of canine subjects in translational analgesia research, we report a high-quality canine dorsal root ganglion transcriptome. Some targets for analgesia are highly conserved both in protein sequence and level of expression within a target tissue while others diverge substantially from the human. This knowledge is especially important for development of analgesics aimed at peripheral molecular targets and provides a template for informed translational research. The peripheral site of action, long duration of analgesia, apparent safety, and retention of coordination, all resulting from a single dose suggest that intra-articular RTX may be an effective intervention for osteoarthritis pain with few or no side effects and lead to an improved quality of life.

Perioperative mortality rate and risk factors for death in dogs undergoing surgery for treatment of thoracic trauma: 157 cases (1990-2014).

OBJECTIVE To determine perioperative mortality rate and identify risk factors associated with outcome in dogs with thoracic trauma that underwent surgical procedures and to evaluate the utility of the animal trauma triage (ATT) score in predicting outcome. DESIGN Retrospective case series. ANIMALS 157 client-owned dogs. PROCEDURES Medical records databases of 7 veterinary teaching hospitals were reviewed. Dogs were included if trauma to the thorax was documented and the patient underwent a surgical procedure. History, signalment, results of physical examination and preoperative laboratory tests, surgical procedure, perioperative complications, duration of hospital stay, and details of follow-up were recorded. Descriptive statistics and ATT scores were calculated, and logistic regression analysis was performed. RESULTS 123 of 157 (78%) patients underwent thoracic surgery, and 134 of 157 (85.4%) survived to discharge. Mean ± SD ATT score for nonsurvivors was 8 ± 2.4. In the multivariable model, female dogs and dogs that did not experience cardiac arrest as a postoperative complication had odds of survival 6 times and 102 times, respectively, those of male dogs and dogs that did experience cardiac arrest as a postoperative complication. Additionally, patients with a mean ATT score < 7 had odds of survival 5 times those of patients with an ATT score ≥ 7. CONCLUSIONS AND CLINICAL RELEVANCE The overall perioperative mortality rate was low for patients with thoracic trauma undergoing surgery in this study. However, male dogs and dogs that experienced cardiac arrest had a lower likelihood of survival to discharge. The ATT score may be a useful adjunct to assist clinical decision-making in veterinary patients with thoracic trauma.

Development and psychometric testing of the Canine Owner-Reported Quality of Life questionnaire, an instrument designed to measure quality of life in dogs with cancer.

OBJECTIVE To describe development and initial psychometric testing of an owner-reported questionnaire designed to standardize measurement of general quality of life (QOL) in dogs with cancer. DESIGN Key-informant interviews, questionnaire development, and field trial. SAMPLE Owners of 25 dogs with cancer for item development and pretesting and owners of 90 dogs with cancer for reliability and validity testing. PROCEDURES Standard methods for development and testing of questionnaire instruments intended to measure subjective states were used. Items were generated, selected, scaled, and pretested for content, meaning, and readability. Response items were evaluated with exploratory factor analysis and by assessing internal consistency (Cronbach α) and convergence with global QOL as determined with a visual analog scale. Preliminary tests of stability and responsiveness were performed. RESULTS The final questionnaire-which was named the Canine Owner-Reported Quality of Life (CORQ) questionnaire-contained 17 items related to observable behaviors commonly used by owners to evaluate QOL in their dogs. Several items pertaining to physical symptoms performed poorly and were omitted. The 17 items were assigned to 4 factors-vitality, companionship, pain, and mobility-on the basis of the items they contained. The CORQ questionnaire and its factors had high internal consistency (Cronbach α = 0.68 to 0.90) and moderate to strong correlations (r = 0.49 to 0.71) with global QOL as measured on a visual analog scale. Preliminary testing indicated good test-retest reliability and responsiveness to improvements in overall QOL. CONCLUSIONS AND CLINICAL RELEVANCE The CORQ questionnaire was a valid, reliable owner-reported questionnaire that measured general QOL in dogs with cancer and showed promise as a clinical trial outcome measure for quantifying changes in individual dog QOL occurring in response to cancer treatment and progression.

Pain control through selective chemo-axotomy of centrally projecting TRPV1+ sensory neurons.

Agonists of the vanilloid receptor transient vanilloid potential 1 (TRPV1) are emerging as highly efficacious nonopioid analgesics in preclinical studies. These drugs selectively lesion TRPV1+ primary sensory afferents, which are responsible for the transmission of many noxious stimulus modalities. Resiniferatoxin (RTX) is a very potent and selective TRPV1 agonist and is a promising candidate for treating many types of pain. Recent work establishing intrathecal application of RTX for the treatment of pain resulting from advanced cancer has demonstrated profound analgesia in client-owned dogs with osteosarcoma. The present study uses transcriptomics and histochemistry to examine the molecular mechanism of RTX action in rats, in clinical canine subjects, and in 1 human subject with advanced cancer treated for pain using intrathecal RTX. In all 3 species, we observe a strong analgesic action, yet this was accompanied by limited transcriptional alterations at the level of the dorsal root ganglion. Functional and neuroanatomical studies demonstrated that intrathecal RTX largely spares susceptible neuronal perikarya, which remain active peripherally but unable to transmit signals to the spinal cord. The results demonstrate that central chemo-axotomy of the TRPV1+ afferents underlies RTX analgesia and refine the neurobiology underlying effective clinical use of TRPV1 agonists for pain control.

Associations between owner personality and psychological status and the prevalence of canine behavior problems.

Behavioral problems are a major source of poor welfare and premature mortality in companion dogs. Previous studies have demonstrated associations between owners' personality and psychological status and the prevalence and/or severity of their dogs' behavior problems. However, the mechanisms responsible for these associations are currently unknown. Other studies have detected links between the tendency of dogs to display behavior problems and their owners' use of aversive or confrontational training methods. This raises the possibility that the effects of owner personality and psychological status on dog behavior are mediated via their influence on the owner's choice of training methods. We investigated this hypothesis in a self-selected, convenience sample of 1564 current dog owners using an online battery of questionnaires designed to measure, respectively, owner personality, depression, emotion regulation, use of aversive/confrontational training methods, and owner-reported dog behavior. Multivariate linear and logistic regression analyses identified modest, positive associations between owners' use of aversive/confrontational training methods and the prevalence/severity of the following dog behavior problems: owner-directed aggression, stranger-directed aggression, separation problems, chasing, persistent barking, and house-soiling (urination and defecation when left alone). The regression models also detected modest associations between owners' low scores on four of the 'Big Five' personality dimensions (Agreeableness, Emotional Stability, Extraversion & Conscientiousness) and their dogs' tendency to display higher rates of owner-directed aggression, stranger-directed fear, and/or urination when left alone. The study found only weak evidence to support the hypothesis that these relationships between owner personality and dog behavior were mediated via the owners' use of punitive training methods, but it did detect a more than five-fold increase in the use of aversive/confrontational training techniques among men with moderate depression. Further research is needed to clarify the causal relationship between owner personality and psychological status and the behavioral problems of companion dogs.