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.

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.

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.

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.

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.

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.

Investigating Associations Between Proliferation Indices, C-kit, and Lymph Node Stage in Canine Mast Cell Tumors.

Previous studies have evaluated cellular proliferation indices, KIT expression, and c-kit mutations to predict the clinical behavior of canine mast cell tumors (MCTs). The study purpose was to retrospectively compare mitotic index, argyrophilic nucleolar organizer regions (AgNORs)/nucleus, Ki-67 index, KIT labeling pattern, and internal tandem duplication mutations in c-KIT between stage I and stage II grade II MCTs. Medical records and tumor biopsy samples from dogs with Grade II MCTs with cytological or histopathological regional lymph node evaluation were included. Signalment, tumor location and stage, and presence of a recurrent versus de novo tumor were recorded. Mitotic index, AgNORs/nucleus, Ki-67, KIT staining pattern, and internal tandem duplication mutations in exon 11 of c-KIT were evaluated. Sixty-six tumors (51 stage I; 15 stage II) were included. Only AgNORs/nucleus and recurrent tumors were significantly associated with stage (odds ratio 2.8, 95% confidence interval [CI] 1.0-8.0, P = .049; odds ratio 8.8, 95% CI 1.1-69.5; P = .039). Receiver-operator characteristic analysis showed that the sensitivity and specificity of AgNORs/cell ≥ 1.87 were 93.3% and 27.4%, respectively, (area under the curve: 0.65) for predicting stage. Recurrent tumors and higher AgNORs/nucleus are associated with stage II grade II MCTs; however, an AgNOR cutoff value that reliably predicts lymph node metastasis was not determined.

Identification of prognostic collagen signatures and potential therapeutic stromal targets in canine mammary gland carcinoma.

Increasing evidence indicates that the tumor microenvironment plays a critical role in regulating the biologic behavior of breast cancer. In veterinary oncology, there is a need for improved prognostic markers to accurately identify dogs at risk for local and distant (metastatic) recurrence of mammary gland carcinoma and therefore would benefit from adjuvant therapy. Collagen density and fiber organization have been shown to regulate tumor progression in both mouse and human mammary tumors, with certain collagen signatures predicting poor outcomes in women with breast cancer. We hypothesized that collagen signatures in canine mammary tumor biopsies can serve as prognostic biomarkers and potential targets for treatment. We used second harmonic generation imaging to evaluate fibrillar collagen density, the presence of a tumor-stromal boundary, tumor associated collagen signatures (TACS) and individual collagen fiber characteristics (width, length and straightness) in grade I/II and grade III canine mammary tumors. Collagen density, as well as fiber width, length and straightness, were inversely correlated with patient overall survival time. Notably, grade III cases were less likely to have a tumor-stromal boundary and the lack of a boundary predicted poor outcome. Importantly, a lack of a defined tumor-stromal boundary and an increased collagen fiber width were associated with decreased survival even when tumor grade, patient stage, ovariohysterectomy status at the time of mammary tumor excision, and histologic evidence of lymphovascular invasion were considered in a multivariable model, indicating that these parameters could augment current methods to identify patients at high risk for local or metastatic progression/recurrence. Furthermore, these data, which identify for the first time, prognostic collagen biomarkers in naturally occurring mammary gland neoplasia in the dog, support the use of the dog as a translational model for tumor-stromal interactions in breast cancer.

Effects of various diets on the calcium and phosphorus composition of mealworms (Tenebrio molitor larvae) and superworms (Zophobas morio larvae).

OBJECTIVE To evaluate whether the nutritive quality of Tenebrio molitor larvae and Zophobas morio larvae, which are commonly cultured as live food sources, is influenced by 4 commercially available diets used as nutritional substrates; identify which diet best improved calcium content of larvae; and identify the feeding time interval that assured the highest calcium intake by larvae. ANIMALS 2,000 Zophobas morio larvae (ie, superworms) and 7,500 Tenebrio molitor larvae (ie, mealworms). PROCEDURES Larvae were placed in control and diet treatment groups for 2-, 7-, and 10-day intervals. Treatment diets were as follows: wheat millings, avian hand feeding formula, organic avian mash diet, and a high-calcium cricket feed. Control groups received water only. After treatment, larvae were flash-frozen live with liquid nitrogen in preparation for complete proximate and mineral analyses. Analyses for the 2-day treatment group were performed in triplicate. RESULTS The nutrient composition of the high-calcium cricket feed groups had significant changes in calcium content, phosphorus content, and metabolizable energy at the 2-day interval, compared with other treatment groups, for both mealworms and superworms. Calcium content and calcium-to-phosphorus ratios for larvae in the high-calcium cricket feed group were the highest among the diet treatments for all treatment intervals and for both larval species. CONCLUSIONS AND CLINICAL RELEVANCE A 2-day interval with the high-calcium cricket feed achieved a larval nutrient composition sufficient to meet National Research Council dietary calcium recommendations for nonlactating rats. Mealworm calcium composition reached 2,420 g/1,000 kcal at 48 hours, and superworm calcium composition reached 2,070g/1,000 kcal at 48 hours. These findings may enable pet owners, veterinarians, insect breeders, and zoo curators to optimize nutritive content of larvae fed to insectivorous animals.

T Regulatory Cells Support Plasma Cell Populations in the Bone Marrow.

Long-lived plasma cells (PCs) in the bone marrow (BM) are a critical source of antibodies after infection or vaccination, but questions remain about the factors that control PCs. We found that systemic infection alters the BM, greatly reducing PCs and regulatory T (Treg) cells, a population that contributes to immune privilege in the BM. The use of intravital imaging revealed that BM Treg cells display a distinct behavior characterized by sustained co-localization with PCs and CD11c-YFP+ cells. Gene expression profiling indicated that BM Treg cells express high levels of Treg effector molecules, and CTLA-4 deletion in these cells resulted in elevated PCs. Furthermore, preservation of Treg cells during systemic infection prevents PC loss, while Treg cell depletion in uninfected mice reduced PC populations. These studies suggest a role for Treg cells in PC biology and provide a potential target for the modulation of PCs during vaccine-induced humoral responses or autoimmunity.

Evaluation of the dynactin 1 gene in Leonbergers and Labrador Retrievers with laryngeal paralysis.

OBJECTIVE To sequence exons and splice consensus sites of the dynactin subunit 1 (DCTN1) gene in Leonbergers and Labrador Retrievers with clinical laryngeal paralysis. ANIMALS 5 unrelated Leonbergers with laryngeal paralysis, 2 clinically normal Leonbergers, 7 unrelated Labrador Retrievers with laryngeal paralysis, and 2 clinically normal Labrador Retrievers. PROCEDURES Primers were designed for the entire coding regions of the DCTN1 gene, a noncoding exon at the 5´ end of the gene, and a 900-bp single-nucleotide polymorphism (SNP)-rich region located 17 kb upstream of the DCTN1 gene by use of the CanFam3 assembly of the canine genome sequence. Sequences were generated and compared between clinically normal and affected dogs. The SNPs flanking the DCTN1 gene as well as a previously identified nonsynonymous SNP in exon 32 were genotyped in affected and clinically normal Leonbergers and Labrador Retrievers. RESULTS None of the affected dogs were homozygous for any mutation affecting coding regions or splicing consensus sequences. Of the 16 dogs tested for the missense SNP in exon 32, all were homozygous for the reference allele, except for 2 affected and 1 clinically normal Labrador Retriever and 1 clinically normal Leonberger. The DCTN1 gene sequences (5 dogs) and haplotypes of polymorphic markers surrounding the DCTN1 gene (all dogs) were not consistent with the hypothesis that laryngeal paralysis was associated with inheritance of the same DCTN1 disease-causing allele within all Labrador Retrievers or Leonbergers evaluated. CONCLUSIONS AND CLINICAL RELEVANCE Mutations in the DCTN1 gene did not appear to cause laryngeal paralysis in Leonbergers or Labrador Retrievers.

Palliative radiation therapy for solid tumors in dogs: 103 cases (2007-2011).

OBJECTIVE: To evaluate the clinical response, adverse effects, and outcomes associated with palliative radiation therapy (PRT) in dogs with various solid tumor types at various body locations. DESIGN: Retrospective case series. ANIMALS: 103 dogs with solid tumors. PROCEDURES: Medical records for dogs with solid tumors treated with PRT between July 2007 and January 2011 at a veterinary teaching hospital were reviewed. Data collected included signalment, tumor type and location, initial staging results, PRT protocol, other tumor-specific treatments, patient and tumor response, outcome, and acute and chronic adverse effects. Median progression-free survival time, median survival time (MST), and other descriptive statistics were calculated. RESULTS: Types of tumors treated included carcinoma, sarcoma, melanoma, primary bone tumor, mast cell tumor, and ameloblastoma. For all dogs, the overall tumor and clinical response rates to PRT were 75% and 77%, respectively, and the MST was 134 days, but those responses varied substantially among tumor types. Dogs that developed a positive clinical response or maintained stable disease after PRT had a significantly longer MST than did dogs with progressive disease. Tumor location was not significantly associated with median progression-free survival time or MST. Most dogs tolerated the PRT well. Acute and chronic adverse effects were observed in 57 and 8 dogs, respectively, but were generally self-limiting. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that dogs with various types of solid tumors that received PRT had objective beneficial responses and an improvement in quality of life that was positively associated with survival time.

Intrathecal resiniferatoxin in a dog model: efficacy in bone cancer pain.

Resiniferatoxin (RTX) is the most potent among all known endogenous and synthetic agonists for the transient receptor potential vanilloid 1 (TRPV1) receptor, which is a calcium-permeable nonselective cation channel, expressed on the peripheral and central terminals of small-diameter sensory neurons. Prolonged calcium influx induced by RTX causes cytotoxicity and death of only those sensory neurons that express the TRPV1 ion channel leading to selective targeting and permanent deletion of the TRPV1-expressing C-fiber neuronal cell bodies in the dorsal root ganglia. The goal of this project was to provide preclinical efficacy data, that intrathecal RTX could provide effective pain relief and improve function in dogs with bone cancer without significant long-term side effects. In a single-blind, controlled study, 72 companion dogs with bone cancer pain were randomized to standard of care analgesic therapy alone (control, n = 36) or 1.2 µg/kg intrathecal RTX in addition to standard of care analgesic therapy (treated, n = 36). Significantly more dogs in the control group (78%) required unblinding and adjustment in analgesic protocol or euthanasia within 6 weeks of randomization, than dogs that were treated with RTX (50%; P < 0.03); and overall, dogs in the control group required unblinding significantly sooner than dogs that had been treated with RTX (P < 0.02). The analgesic effect was documented in these dogs without any evidence of development of deafferentation pain syndrome that can be seen with neurolytic therapies.