Bodyweight and body condition scores of Australian British shorthaired cats, 2008-2017.

Obesity is the most common nutritional problem in companion animals today, and Australian British shorthair (BSH) cats have been shown to have a greater likelihood of being overweight relative to other cat breeds. The objectives of this research were to quantify bodyweight (BW) and body condition scores (BCSs) of BSH cats attending first opinion practice in Australia for the period 2008-2017 and to determine if: (1) being classified as overweight was associated with geographical location (urban versus rural and socio-economic index); and (2) BW recorded in the first 12 months of life was associated with length of life beyond 12 months. Electronic medical records from BSH cats were obtained from VetCompass Australia and used for BW and BCS analysis. Desexed males (n = 971) had the highest mean BW followed by entire males (n = 79), desexed females (n = 815), and entire females (n = 82). The desexed males, desexed females, and entire females had a mean BCS classified as overweight using a 1-to-9 point BCS scale. The entire male population was the only group with a mean BCS classified as ideal. No statistically significant association between BW and urban-rural status and no consistent trend between BW and socioeconomic deprivation was found. For cats with at least one BW measurement in the first 12 months of life that was ≤3.3 kg, the age when 20 percent of the group had died or were euthanised was 12.3 (95% CI 11.7 to 13.1) years. For cats with at least one BW measurement in the first 12 months of life that was ≥3.3 kg age, the age when 20 percent of the group had died or were euthanised was 6.6 (95% CI 5.2 to 6.6) years. This was a substantial clinical difference in survival. The study concluded that a large proportion of BSH cats attending first opinion veterinary clinics in Australia between 2008 and 2017 (48%) were classified as overweight. Cats less than 12 months of age that were greater than 3.3 kg had a shortened lifespan beyond 12 months of age compared with cats that were less than 3.3 kg.

The association and reliability of the frontal plane projection angle during the lateral step down test on knee function in patients with patellofemoral pain.

BACKGROUND: The lateral step-down test is used by physical therapists (PT) to identify movement faults in patients with patellofemoral pain (PFP). The FPPA is a measure of knee valgus and PTs have access to open source video analysis software and high quality smart phones and video cameras to implement 2D video analysis into practice. The purpose of our study was to determine the reliability of PTs measuring the frontal plane projection angle (FPPA) during the lateral step-down test, and to determine if the FPPA was associated with pain, self-reported knee function and fear of movement. METHODS: Twenty-two subjects (mean age[SD] = 27.8 [6.6] years, females n = 14, males n = 8) with PFP were analyzed by six PTs using 2D video analysis software. The FPPA was measured during the lateral step down test. Numeric Pain Rating Scale (NPRS), Anterior Knee Pain Scale (AKPS) and the Tampa Scale of Kinesiophobia (TSK) were collected. Intraclass correlation (ICC) was used to assess for PT measurement reliability. Correlations between outcomes were calculated using Spearman correlation coefficient and standard error of measurement (SEM) and minimal detectable change (MDC) were reported. RESULTS: Reliability amongst PTs measuring the FPPA was good (ICC [95 %CI] = 0.85 [0.72-0.93]; SEM = 3.33°, MDC = 9.20°). There were no significant correlations (p > 0.05) between FPPA and NPRS(ρ = -0.046), AKPS(ρ = 0.066), or TSK(ρ = -0.204). CONCLUSIONS: Although reliability measuring FPPA was good, the large SEM and MDC associated with this measurement may limit its clinical utility in those with PFP.

A case-control study to identify risk factors for adult-onset idiopathic megaoesophagus in Australian dogs, 2017-2018.

BACKGROUND: Epidemiological investigations were carried out following detection of an outbreak of megaoesophagus in Victorian Police working dogs in early 2018 and an increase in the number of canine megaoesophagus cases reported by companion animal veterinarians in Eastern Australia starting in late 2017. VetCompass Australia data were used to quantify the incidence of canine megaoesophagus for the period January 2012 to February 2018 and a matched case-control study carried out to identify individual animal risk factors for canine megaoesophagus in 2017-2018. RESULTS: There was a 7-fold increase in the incidence rate of canine megaoesophagus from 2014 (0.11 [95% CI 0.02 to 0.58] cases per 100,000 dogs per day) to 2018 (0.82 [95% CI 0.19 to 4.2] cases per 100,000 dogs per day). Since 2013, the incidence of megaoesophagus in Australia has shown a seasonal pattern, with greater numbers of cases diagnosed during the warmer months of the year. In the case-control study, use of Mars Petcare Advance Dermocare as a source of food was 325 (95% CI 64 to 1644) times greater for cases, compared with controls. CONCLUSIONS: Our analyses provide evidence that the feeding of Advance Dermocare was responsible for the majority of cases in the outbreak of megaoesophagus in Eastern Australia in 2017-2018. The increase in the incidence rate of megaoesophagus in Australia since 2014-2015 warrants further investigation.

Compartmental fat distribution in the abdomen of dogs relative to overall body fat composition.

BACKGROUND: Adipose tissue may have different metabolic and endocrine functions depending on the region of the body in which it is located. While visceral or intra-abdominal fat has been found to contribute to leptin concentrations, insulin resistance and obesity-related diseases, there are only a few imaging studies documenting the preferential distribution of body fat to either the intra-abdominal or subcutaneous compartments in dogs. This study aimed to determine if CT-measured abdominal fat distributed preferentially to the visceral space (V) relative to the subcutaneous space (SQ), with increasing DXA-determined total body fat percentage; and if ultrasound measurements of the ventral midline subcutaneous (SAT) and visceral adipose thickness (VAT) can be used to estimate the distribution of fat to the subcutaneous and visceral abdominal spaces, in a sample of 22 dogs with variable body condition. RESULTS: Multivariate analysis showed no statistically significant correlation between visceral to subcutaneous fat ratio (V/SQ) and increasing total body fat percentage (ß = - 0.07, p = 0.733), but strong correlation with age (ß = 0.71 p = 0.002). A substantial amount of variation for the ultrasound visceral adipose thickness to subcutaneous fat thickness (VAT/SAT) could be explained by both CT V/SQ and sex (R2Adjusted = 0.477, p = 0.001), with female dogs having significant lower VAT/SAT ratios compared to the male dogs (p = 0.047). The ultrasound fat measurements appeared moderately reliable, but a larger sample number is required to confirm this. CONCLUSIONS: The findings suggest that dogs with a relatively healthy to slightly overweight body condition score, distribute fat relatively similarly between their peritoneal (visceral) and subcutaneous abdominal compartments with increasing total body fat percentage. However, there was increased fat distribution to the peritoneal space relative to the subcutaneous space with increasing age. Further, abdominal ultrasound may be useful in estimating the ratio of fat distribution to both the abdominal visceral and subcutaneous spaces.

Safety of dry needling to the upper lumbar spine: a pilot cadaver study.

Objective: When inserting a dry needle laterally into the upper lumbar spine (L1-L3) there is an increased risk of piercing the kidney; therefore, the objective of this study was to determine a zone of safety for practitioners to needle in the upper lumbar spine.Methods: Ten cadavers were screened for inclusion. L1 spinous process was identified and confirmed with ultrasound imaging. A digital caliper was used to measure laterally at 1.5 cm, 2.0 cm, and 2.5 cm. Dry needles were inserted maximally at each point and a binary decision, yes or no, was made to determine if bony contact was made. Needle depth and abdominal width measurements were also recorded. Safety of the dry needling procedure was interpreted as such if bony contact was made by the needle. If bony contact was made, then it was assumed that the needle cannot advance further into pleura or kidney.Results: Forty-four percent of needles did not make bony contact at 2.5 cm lateral of the L1 spinous process, whereas 22% did not make bony contact at 1.5 cm and 2.0 cm. There was a weak to moderate negative correlation between abdominal width measurements and needle depth at 1.5 cm (-0.48) and 2.0 cm (-0.45), and at 2.5 cm (-0.39).Conclusion: A safety zone of needling less than 2.5 cm is likely safe, but needs to be confirmed with future study. Dry needling 2.5 cm lateral appears more risky due to the higher frequency of not contacting a bony backdrop.

Effect of clinical signs, endocrinopathies, timing of surgery, hyperlipidemia, and hyperbilirubinemia on outcome in dogs with gallbladder mucocele.

Gallbladder mucocele (GBM) is a common extra-hepatic biliary syndrome in dogs with death rates ranging from 7 to 45%. Therefore, the aim of this study was to identify the association of survival with variables that could be utilized to improve clinical decisions. A total of 1194 dogs with a gross and histopathological diagnosis of GBM were included from 41 veterinary referral hospitals in this retrospective study. Dogs with GBM that demonstrated abnormal clinical signs had significantly greater odds of death than subclinical dogs in a univariable analysis (OR, 4.2; 95% CI, 2.14-8.23; P<0.001). The multivariable model indicated that categorical variables including owner recognition of jaundice (OR, 2.12; 95% CI, 1.19-3.77; P=0.011), concurrent hyperadrenocorticism (OR 1.94; 95% CI, 1.08-3.47; P=0.026), and Pomeranian breed (OR, 2.46; 95% CI 1.10-5.50; P=0.029) were associated with increased odds of death, and vomiting was associated with decreased odds of death (OR, 0.48; 95% CI, 0.30-0.72; P=0.001). Continuous variables in the multivariable model, total serum/plasma bilirubin concentration (OR, 1.03; 95% CI, 1.01-1.04; P<0.001) and age (OR, 1.17; 95% CI, 1.08-1.26; P<0.001), were associated with increased odds of death. The clinical utility of total serum/plasma bilirubin concentration as a biomarker to predict death was poor with a sensitivity of 0.61 (95% CI, 0.54-0.69) and a specificity of 0.63 (95% CI, 0.59-0.66). This study identified several prognostic variables in dogs with GBM including total serum/plasma bilirubin concentration, age, clinical signs, concurrent hyperadrenocorticism, and the Pomeranian breed. The presence of hypothyroidism or diabetes mellitus did not impact outcome in this study.

Treatment response and long term follow up in nineteen dogs diagnosed with chronic enteropathy in Australia.

Chronic enteropathy (CE) in dogs is common worldwide, but little data is available from Australia. The aim of this study was to describe treatment response and long-term outcome in a cohort of dogs with CE. Dogs were prospectively enrolled at Murdoch University and the University of Melbourne. After diagnostic investigation to rule out diseases other than CE, dogs underwent sequential therapeutic trials until achieving a clinical response (diet then antibiotics, and finally immunosuppressants). Success was defined as 75% reduction of clinical severity for a minimum of five weeks. A total of 21 dogs were enrolled, and 19 completed the study. One dog was euthanised for lack of response to treatment and one excluded for lack of owner compliance. Most dogs responded to diet (n = 10), followed by antibiotics (n = 7) and immunosuppressants (n = 2). Long-term remission (median 21.1 months, [3.0-44.7]) was achieved in eight out of ten dietary responders without additional treatment. In contrast, only two dogs with antibiotic response remained in long-term remission, of which one needed on-going antibiotic treatment. Longer term remission was achieved in the two dogs treated with immunosuppressants with on-going low dose therapy. This study concludes that most dogs referred for CE in Australia respond to dietary treatment (even after previous dietary interventions), and remission is long-term compared to dogs treated with an antibiotic. Furthermore, the need for long-term antibiotics in some dogs to maintain response may lead to antibiotic resistance. This study supports adequate dietary trials for CE in dogs, and a need for alternative second-line treatments.

Concentrations of interleukin-6, -8, -10 and tumour necrosis factor-α in the faeces of dogs with acute diarrhoea.

AIM: To compare the concentration of faecal cytokines interleukin (IL)-6, -8, -10, and tumour necrosis factor (TNF)-α in dogs with acute diarrhoea with clinically normal (non-diarrhoeic) dogs. METHODS: A total of 14 dogs presenting with acute diarrhoea, and 25 dogs with no history of gastrointestinal signs in the 2 months prior to enrolment, were recruited from two veterinary hospitals in Melbourne, Australia. Concentrations of IL-6, -8, -10, and TNF-α were measured in faecal samples using canine-specific ELISA. RESULTS: The diarrhoeic dogs were diagnosed with or managed for acute gastroenteritis (n = 6), extra-intestinal neoplasia (n = 2), parvoviral enteritis (n = 1), hepatopathy (n = 1), acute pancreatitis (n = 1), hypoadrenocorticism (n = 1), gastric dilatation volvulus (n = 1) and myelopathy (n = 1). IL-6 was detectable in the faeces of 10/14 (71%) diarrhoeic and 7/25 (28%) non-diarrhoeic dogs, and median concentrations were 10.8 (min 0.0, max 54.0) and 2.0 (min 0.0, max15.0) pg/mL, respectively (p = 0.01). IL-8 was detectable in the faeces of all diarrhoeic and 11 non-diarrhoeic dogs, and median concentrations were 149.7 (min 3.72, max 730.1) and 3.4 (min 0.0, max 22.5) pg/mL, respectively (p < 0.001). TNF-α was detected in the faeces of two of the diarrhoeic dogs (3.4 and 15.6 pg/mL) and none of the non-diarrhoeic dogs. IL-10 was not detected in the faeces of any dog. CONCLUSIONS: Faecal concentrations of IL-6 and -8 were higher in diarrhoeic compared to non-diarrhoeic dogs, and are therefore potential candidates for non-invasive biomarkers to assess the severity and resolution of acute intestinal disease in dogs. However their correlation with disease progression and severity needs to be further investigated before their full clinical application can be determined.

Abdominal volume computed tomography assessment of body composition in dogs.

BACKGROUND: Computed tomography (CT) has been used to estimate body composition and determine tissue distribution in dogs, despite limited validation. This may introduce error into estimates of body composition studies and its effect on health in dogs. Further, the modality has not been validated against dual-energy X-ray absorptiometry (DXA) or over a wide range of dog breeds, ages and sexes. The objective of this study was to validate the use of semi-automated, abdominal volume CT for estimating total body composition of dogs relative to DXA. Twenty-two staff-owned dogs (weighing between 5.1-60 kg) were sedated and underwent full body DXA scan and abdominal CT. Abdominal tissue composition was estimated by CT using semi-automated volume segmentation, over predetermined tissue Hounsfield threshold values. Abdominal tissue composition determined by the various CT threshold ranges was compared to total body composition determined by DXA. RESULTS: Abdominal tissue composition estimated by CT strongly correlated with the estimates derived from DXA with a small Bland-Altman mean percentage differences in values: total body mass (- 250/2000HU: r2 = 0.985; - 1.10%); total fat mass (- 250/-25HU: r2 = 0.981; - 1.90%); total lean tissue mass (- 25/150HU: r2 = 0.972; 3.47%); and total bone mineral content (150/2000HU: r2 = 0.900; - 0.87%). Although averaged CT values compared well to DXA analysis, there was moderate variation in the individual predicted values. There was near perfect inter- and intra-observer agreement in segmentation volumes for abdominal fat. CONCLUSIONS: Abdominal volume computed tomography (CT) accurately and reliably estimates total body composition in dogs, but greater variations may be observed in dogs weighing less than 10 kg.

Prevalence and risk factors for medical events following exercise at Australian Greyhound race meetings.

AIM: A prospective, observational study to determine the prevalence of post-exercise conditions at Australian Greyhound race meetings and to assess association with race performance and other environmental, race- and dog-related factors was undertaken. METHODS: A total of 4020 starters were observed (2813 Greyhounds, 1009 trainers, 536 races, 52 race meets, 48 race dates and 11 race tracks) following a race. The presence of diaphragmatic flutter (DF), ataxia, seizure, collapse or sudden death was recorded. Risk factors were screened by univariable logistic regression prior to multivariable backward stepwise model building. RESULTS: In this study, 962 starters (n = 768 dogs) had DF (23.9%), 16 starters were ataxic (0.4%) and there were no observed cases of collapse, seizure or sudden death. Race track location, increasing race distance, race grade based on increasing 1st place prize value, lower (earlier) race number at the meeting, age, a previous observation of DF at the last start, females, colour (white) and better finishing position were all associated with an increased risk of a Greyhound being observed with DF. However, when logistic regression assessing the random effect of dog was performed, the presence of previous DF was not significant. In this cohort, DF was common following strenuous exercise in Greyhounds and on its own does not appear to result in reduced performance or distress to the animal. CONCLUSION: The incidence of ataxia was low and collapse, seizure and sudden death were not observed. However, even though uncommon, ataxia has welfare concerns for racing Greyhounds that warrants further investigation.

Scintigraphic Assessment of Deposition of Radiolabeled Fluticasone Delivered from a Nebulizer and Metered Dose Inhaler in 10 Healthy Dogs.

BACKGROUND: Aerosolized medications are increasingly being used to treat respiratory diseases in dogs. No previous studies assessing respiratory tract deposition of radiolabeled aerosols have been performed in conscious dogs. HYPOTHESIS/OBJECTIVES: Assess respiratory tract deposition of radiolabeled, inhalant corticosteroid (fluticasone propionate labeled with 99m Tc) delivered from a nebulizer and metered dose inhaler (MDI) to healthy dogs. ANIMALS: Ten healthy Foxhounds. METHODS: Prospective, randomized, cross-over pilot study. Initial inhalation method (nebulizer or MDI) was randomly assigned. Treatments were crossed over after a 7-day washout period. Treatments initially were performed using sedation. Dogs were imaged using 2-dimensional planar scintigraphy, with respiratory tract deposition quantified by manual region-of-interest analysis. Deposition calculated as percentage of delivered dose. Six of 10 dogs were randomly selected and reassessed without sedation. RESULTS: Inhalation method had significant effect on respiratory tract deposition (P = 0.027). Higher deposition was achieved by nebulization with mean deposition of 4.2% (standard deviation [SD], 1.4%; range, 1.9-6.1%); whereas MDI treatment achieved a mean of 2.3% (SD, 1.4%; range, 0.2-4.2%). Nebulization achieved higher respiratory tract deposition than MDI in 7 of 10 dogs. No statistical difference (P = 0.68) was found between mean respiratory tract deposition achieved in dogs when unsedated (3.8%; SD, 1.5%) or sedated (3.6%; SD, 1.7%). CONCLUSIONS AND CLINICAL IMPORTANCE: Study confirms respiratory tract deposition of inhalant medications delivered from a nebulizer and MDI in healthy dogs, breathing tidally with and without sedation. Respiratory tract deposition in these dogs was low compared to reported deposition in adult humans, but similar to reported deposition in children.

Cricopharyngeal dysphagia and phenobarbitone-responsive sialoadenosis in a Miniature Poodle.

CASE REPORT: An 11-year-old male neutered Miniature Poodle was investigated for ptyalism, weight loss and anorexia. Cricopharyngeal dysphagia was diagnosed using fluoroscopy, and non-inflammatory salivary disease was diagnosed using a combination of cytology and computed tomography. The dog was successfully managed with phenobarbitone. CONCLUSION: To the authors' knowledge this is the first time acquired cricopharyngeal dysphagia and phenobarbitone-responsive sialoadenosis have been described together.

Gastrokine mRNA expression in gastric tissue from dogs with helicobacter colonisation but without inflammatory change during treatment.

Gastrokines (GKNs) are bioactive substances secreted by gastric cells. Evidence supports functional roles for GKNs in gastric homeostasis, immune responses and tumour suppression. Down-regulation has been reported in Helicobacter pylori associated gastritis and other inflammatory gastrointestinal conditions in mice and people. The aim of this study was to evaluate GKN gene expression in dogs positive for other Helicobacter spp. both before and after treatment. Expression of Gkn-1 and Gkn-2 mRNA was studied in endoscopic biopsy samples collected from seven healthy dogs over three time-points pre- (T0) and at 1 and 18 weeks post-treatment for Helicobacter spp. colonisation (T1 & T2). The relative expression software tool (REST) was used to provide efficiency corrected expression ratios for comparisons between groups and these results were compared to a standard 2ΔΔCT methodology. Compared with T1 Gkn1 and Gkn2 mRNA expression was greater at T0 by a mean factor of 2.53 (SE=1.83-3.54) for Gkn1 (P=0.000) and 2.85 (SE=2.23-3.75) for Gkn2 (P=0.000). This difference was attenuated when comparisons were made between T0 and T2. Histopathological evidence of gastritis was not present in any Helicobacter spp. positive sample. When compared to post-eradication samples Gkn gene expression is increased in the presence of Helicobacter spp. in dogs without evidence for concurrent inflammation. Further evaluation is required to determine the relevance of this finding, however given a suspected role in gastric homeostasis, up-regulation of GKN1 and GKN2 could limit development of gastritis in Helicobacter spp. positive dogs.

Comparison of in vivo confocal endomicroscopy with other diagnostic modalities to detect intracellular helicobacters.

Intracellular colonisation may serve as a protected niche where Helicobacter spp. organisms evade effective treatment. In dogs, non-Helicobacter pylori-helicobacters are frequently intracellular. Confocal endomicroscopy allows in vivo gastrointestinal imaging and has aided real-time identification of Helicobacter pylori and other intracellular and mucosally associated bacteria. The objectives of this study were: (1) to determine the utility of confocal endomicroscopy to identify non-Helicobacter pylori-helicobacters compared with other diagnostic modalities, and (2) to assess its ability to identify intracellular organisms. Fourteen clinically healthy dogs underwent standard gastroduodenoscopy followed by confocal endomicroscopy using topical acriflavine. Confocal images were obtained from at least five gastric sites. Endoscopic biopsies were obtained for histopathology, PCR and fluorescence in situ hybridisation (FISH). Methodologies were compared for their ability to determine the presence and spatial distribution of gastric helicobacters in dogs. Confocal endomicroscopy provided high quality images allowing in vivo identification of non-Helicobacter pylori-helicobacters in 13 dogs. Histopathology identified helicobacters in 11 dogs. Organisms were identified within the superficial gastric mucus and within gastric pits, and distribution throughout the stomach was diffuse and multi-focal. Confocal endomicroscopy findings correlated with PCR and FISH post-procedure analysis. Only FISH identified intracellular organisms, which were present in 13/14 dogs. Confocal endomicroscopy provided in vivo histology images and was capable of identifying non-Helicobacter pylori-helicobacters during gastroscopy, but was unable to identify intracellular organisms using the current fluorophore protocol.

A randomized, placebo-controlled phase III trial of masitinib plus gemcitabine in the treatment of advanced pancreatic cancer.

BACKGROUND: Masitinib is a selective oral tyrosine-kinase inhibitor. The efficacy and safety of masitinib combined with gemcitabine was compared against single-agent gemcitabine in patients with advanced pancreatic ductal adenocarcinoma (PDAC). PATIENTS AND METHODS: Patients with inoperable, chemotherapy-naïve, PDAC were randomized (1 : 1) to receive gemcitabine (1000 mg/m(2)) in combination with either masitinib (9 mg/kg/day) or a placebo. The primary endpoint was overall survival (OS) in the modified intent-to-treat population. Secondary OS analyses aimed to characterize subgroups with poor survival while receiving single-agent gemcitabine with subsequent evaluation of masitinib therapeutic benefit. These prospectively declared subgroups were based on pharmacogenomic data or a baseline characteristic. RESULTS: Three hundred and fifty-three patients were randomly assigned to receive either masitinib plus gemcitabine (N = 175) or placebo plus gemcitabine (N = 178). Median OS was similar between treatment-arms for the overall population, at respectively, 7.7 and 7.1 months, with a hazard ratio (HR) of 0.89 (95% CI [0.70; 1.13]. Secondary analyses identified two subgroups having a significantly poor survival rate when receiving single-agent gemcitabine; one defined by an overexpression of acyl-CoA oxidase-1 (ACOX1) in blood, and another via a baseline pain intensity threshold (VAS > 20 mm). These subgroups represent a critical unmet medical need as evidenced from median OS of 5.5 months in patients receiving single-agent gemcitabine, and comprise an estimated 63% of patients. A significant treatment effect was observed in these subgroups for masitinib with median OS of 11.7 months in the 'ACOX1' subgroup [HR = 0.23 (0.10; 0.51), P = 0.001], and 8.0 months in the 'pain' subgroup [HR = 0.62 (0.43; 0.89), P = 0.012]. Despite an increased toxicity of the combination as compared with single-agent gemcitabine, side-effects remained manageable. CONCLUSIONS: The present data warrant initiation of a confirmatory study that may support the use of masitinib plus gemcitabine for treatment of PDAC patients with overexpression of ACOX1 or baseline pain (VAS > 20mm). Masitinib's effect in these subgroups is also supported by biological plausibility and evidence of internal clinical validation. TRIAL REGISTRATION: ClinicalTrials.gov:NCT00789633.

Management of acute pancreatitis in dogs: a critical appraisal with focus on feeding and analgesia.

Knowledge about acute pancreatitis has increased recently in both the medical and veterinary fields. Despite this expansion of knowledge, there are very few studies on treatment interventions in naturally occurring disease in dogs. As a result, treatment recommendations are largely extrapolated from experimental rodent models or general critical care principles. General treatment principles involve replacing fluid losses, maintaining hydrostatic pressure, controlling nausea and providing pain relief. Specific interventions recently advocated in human medicine include the use of neurokinin-1 antagonists for analgesia and early interventional feeding. The premise for early feeding is to improve the health of the intestinal tract, as unhealthy enterocytes are thought to perpetuate systemic inflammation. The evidence for early interventional feeding is not supported by robust clinical trials to date, but in humans there is evidence that it reduces hospitalisation time and in dogs it is well tolerated. This article summarises the major areas of management of acute pancreatitis in dogs and examines the level of evidence for each recommendation.

Photo-induced toxicity of titanium dioxide nanoparticles to Daphnia magna under natural sunlight.

Titanium dioxide nanoparticles (TiO2 NP) are one of the most abundantly utilized nanoparticles in the world. Studies have demonstrated the ability of the anatase crystal of TiO2 NP to produce reactive oxygen species (ROS) in the presence of ultraviolet radiation (UVR), a co-exposure likely to occur in aquatic ecosystems. The goal of this study was to examine the photo-induced toxicity of anatase TiO2 NP under natural sunlight to Daphnia magna. D. magna were exposed to a range of UVR intensities and anatase TiO2 concentrations in an outdoor exposure system using the sun as the source of UVR. Different UVR intensities were achieved using UVR opaque and transparent plastics. AnataseTiO2-NP demonstrated the reciprocal relationship seen in other phototoxic compounds such as polycyclic aromatic hydrocarbons (PAHs) at higher UVR treatments. The calculated 8h LC50 of anatase TiO2 NP was 139 ppb under full intensity ambient natural sunlight, 778 ppb under 50% natural sunlight, and >500 ppm under 10% natural sunlight. Mortality was also compared between animals allowed to accumulate a body burden of anatase TiO2 for 1h and organisms whose first exposure to anatase TiO2 aqueous suspensions occurred under UVR. A significantly greater toxic effect was observed in aqueous, low body burden suspensions than that of TiO2 1h body burdens, which is dissimilar from the model presented in PAHs. Anatase TiO2 presents a unique photo-induced toxic model that is different than that of established phototoxic compounds.

Masitinib in advanced gastrointestinal stromal tumor (GIST) after failure of imatinib: a randomized controlled open-label trial.

BACKGROUND: Masitinib is a highly selective tyrosine kinase inhibitor with activity against the main oncogenic drivers of gastrointestinal stromal tumor (GIST). Masitinib was evaluated in patients with advanced GIST after imatinib failure or intolerance. PATIENTS AND METHODS: Prospective, multicenter, randomized, open-label trial. Patients with inoperable, advanced imatinib-resistant GIST were randomized (1 : 1) to receive masitinib (12 mg/kg/day) or sunitinib (50 mg/day 4-weeks-on/2-weeks-off) until progression, intolerance, or refusal. Primary efficacy analysis was noncomparative, testing whether masitinib attained a median progression-free survival (PFS) (blind centrally reviewed RECIST) threshold of >3 months according to the lower bound of the 90% unilateral confidence interval (CI). Secondary analyses on overall survival (OS) and PFS were comparative with results presented according to a two-sided 95% CI. RESULTS: Forty-four patients were randomized to receive masitinib (n = 23) or sunitinib (n = 21). Median follow-up was 14 months. Patients receiving masitinib experienced less toxicity than those receiving sunitinib, with significantly lower occurrence of severe adverse events (52% versus 91%, respectively, P = 0.008). Median PFS (central RECIST) for the noncomparative primary analysis in the masitinib treatment arm was 3.71 months (90% CI 3.65). Secondary analyses showed that median OS was significantly longer for patients receiving masitinib followed by post-progression addition of sunitinib when compared against patients treated directly with sunitinib in second-line [hazard ratio (HR) = 0.27, 95% CI 0.09-0.85, P = 0.016]. This improvement was sustainable as evidenced by 26-month follow-up OS data (HR = 0.40, 95% CI 0.16-0.96, P = 0.033); an additional 12.4 months survival advantage being reported for the masitinib treatment arm. Risk of progression while under treatment with masitinib was in the same range as for sunitinib (HR = 1.1, 95% CI 0.6-2.2, P = 0.833). CONCLUSIONS: Primary efficacy analysis ensured the masitinib treatment arm could satisfy a prespecified PFS threshold. Secondary efficacy analysis showed that masitinib followed by the standard of care generated a statistically significant survival benefit over standard of care. Encouraging median OS and safety data from this well-controlled and appropriately designed randomized trial indicate a positive benefit-risk ratio. Further development of masitinib in imatinib-resistant/intolerant patients with advanced GIST is warranted.

In vivo histologically equivalent evaluation of gastric mucosal topologic morphology in dogs by using confocal endomicroscopy.

BACKGROUND: Confocal endomicroscopy (CEM) is an endoscopic technology permitting in vivo cellular and subcellular imaging. CEM aids real-time clinical assessment and diagnosis of various gastrointestinal diseases in people. CEM allows in vivo characterization of small intestinal mucosal morphology in dogs. OBJECTIVE: To determine the feasibility of CEM to evaluate gastric mucosal morphology in dogs and to characterize the appearance in healthy dogs. ANIMALS: Fourteen clinically healthy research colony dogs. METHODS: Experimental study. Under general anesthesia, dogs underwent standard endoscopic evaluation and CEM of the gastric mucosa. In the initial 6 dogs, fluorescent contrast was provided with the fluorophore acriflavine (0.05% solution), applied topically. Subsequently, 8 dogs were assessed using a combination of fluorescein (10% solution, 15 mg/kg IV), followed by acriflavine administered topically. For each fluorophore, a minimum of 5 sites were assessed. RESULTS: Confocal endomicroscopy provided high quality in vivo histologically equivalent images of the gastric mucosa, but reduced flexibility of the endoscope tip limited imaging of the cranial stomach in some dogs. Intravenous administration of fluorescein allowed assessment of cellular cytoplasmic and microvasculature features. Topical application of acriflavine preferentially stained cellular nucleic acids, allowing additional evaluation of nuclear morphology. Identification of Helicobacter-like organisms was possible in 13 dogs. CONCLUSION AND CLINICAL IMPORTANCE: Confocal endomicroscopy provides in vivo images allowing assessment of gastric mucosal morphology during endoscopy, potentially permitting real-time diagnosis of gastrointestinal disease.