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Spontaneous hypercortisolism (HC) is a common endocrine disease of senior dogs, often overlapping in selected clinical signs and hematologic and blood biochemical abnormalities with nonadrenal diseases (NADs). HC and NAD could differentially affect cortisol metabolism, which is a complex 10-enzymatic pathway process. HC might also affect blood and urine lactate levels through its effects on mitochondrial function. We aimed to differentiate between HC and NAD via a urinary cortisol metabolites and lactate panel. We prospectively recruited 7 healthy dogs and 18 dogs with HC, 15 with congestive heart failure (CHF), and 9 with NAD. We analyzed urine by gas chromatography–mass spectrometry and liquid chromatography–mass spectrometry. We normalized urinary lactate and cortisol metabolites to urine creatinine concentration, and then compared groups using a linear-mixed model and principal component (PC) analysis. A machine-learning classification algorithm generated a decision tree (DT) model for predicting HC. The least-squares means of normalized urinary 6β-hydroxycortisol and PC1 of the HC and CHF groups were higher than those of the healthy and NAD groups ( p = 0.05). Creatinine-normalized urinary 6β-hydroxycortisol had better sensitivity (Se, 0.78; 95% CI: 0.55–0.91), specificity (Sp, 0.89; 95% CI: 0.57–0.99), and a likelihood ratio (LR; 7), than the Se (0.72; 95% CI: 0.49–0.88), Sp (0.89; 95% CI: 0.57–0.99), and LR (6.5) of PC1 for distinguishing HC from NAD. Lactate and dihydrocortisone had the highest decreasing node-weighted impurity value and were considered the most important features in the DT model; dihydrocortisol had no role in determining whether a dog had HC.

Nonadrenal diseases (NAD), including congestive heart failure (CHF), can affect the conversion of cortisone to cortisol favoring the production of cortisol’s urinary downstream metabolites 5α/5β-tetrahydrocortisol (THF) relative to tetrahydrocortisone (THE). We hypothesized that healthy dogs would have lower urinary levels of cortisol, cortisone, THF, and THE than dogs with hypercortisolism (HC) or CHF, and the latter would have higher urinary levels of THF and lower THE than dogs with HC. Four, 9, and 8 dogs with HC, CHF, and normal health, respectively, were included in a pilot prospective cross-sectional study. A single morning voided urine sample was analyzed for urinary cortisol metabolites by liquid chromatography–mass spectrometry. The percentages of conjugated urinary metabolites were significantly higher in dogs with CHF than in healthy dogs ( p = 0.001), and not different in HC dogs ( p = 0.07). Log-transformed urine cortisol metabolites–to–creatinine ratios in healthy dogs were significantly lower than the 2 other groups ( p

Babesia spp. are globally distributed hemoparasites that cause disease in many mammalian species. The species Babesia gibsoni (Asian genotype) is prevalent and endemic in many Asian countries but has also been reported in growing numbers in countries outside of Asia. Standard therapies for the treatment of B. gibsoni often fail to result in consistent and successful clearance of the organism. This study evaluated the use of a combination of three antibiotics: metronidazole, clindamycin and doxycycline after atovaquone and azithromycin failed to eliminate the infection on a polymerase chain reaction (PCR) test. The aim of this study was to determine whether the triple antibiotic combination was an appropriate alternative or additional treatment for the elimination of B. gibsoni. The medical records of 24 patients treated from December 2012 to July 2015 were retrospectively analyzed. The diagnosis of B. gibsoni was confirmed with a PCR test that was also used to assess treatment response. All patients were initially treated with the standard therapy, atovaquone and azithromycin with a 25% success rate clearing B. gibsoni. Dogs that remained positive on PCR using the standard therapy were then treated with the triple antibiotic protocol achieving an 87% success rate. The inclusion of an alternative and potentially effective protocol for the treatment of B. gibsoni would increase the options for the current therapeutic options, could aid in clearance of the organism and offer a more affordable option for clients.

Animal health is directly linked to population viability, which may be impacted by anthropogenic disturbances and diseases. Reference intervals (RIs) for haematology and blood biochemistry are essential tools for the assessment of animal health. However, establishing and interpreting robust RIs for threatened species is often challenged by small sample sizes. Bayesian predictive modelling is well suited to sample size limitations, accounting for individual variation and interactions between influencing variables. We aimed to derive baseline RIs for green turtles (Chelonia mydas) across two foraging aggregations in North Queensland, Australia, using Bayesian generalized linear mixed-effects models (n = 97). The predicted RIs were contained within previously published values and had narrower credible intervals. Most analytes did not vary significantly with foraging ground (76%, 22/29), body mass (86%, 25/29) or curved carapace length (83%, 24/29). Length and body mass effects were found for eosinophils, heterophil:lymphocyte ratio, alkaline phosphatase, aspartate transaminase and urea. Significant differences between foraging grounds were found for albumin, cholesterol, potassium, total protein, triglycerides, uric acid and calcium:phosphorus ratio. We provide derived RIs for foraging green turtles, which will be helpful in future population health assessments and conservation efforts. Future RI studies on threatened species would benefit from adapting established veterinary and biomedical standards.

Background: Symmetric dimethylarginine (SDMA) is a screening tool for early kidney dysfunction and monitoring treatment in cases of chronic kidney disease (CKD). There are no current studies describing the suitability of this test for use with published populationbased reference intervals. Hypothesis/Objectives: To determine the components of biological variability, the index of individuality (IOI), the critical difference between sequential measurements (CD) and the number of measurements required to assess the homeostatic set point (HSP), for both SDMA and serum creatinine (sCr), in apparently healthy dogs. Animals: Twenty apparently healthy adult dogs owned by clients or staff at a veterinary teaching hospital. Methods: Prospective, observational study. Blood was collected from each dog on 9 occasions, and SDMA and sCr were measured in duplicate using commercially available assays. Results: SDMA and sCr had intermediate and low IOI values of 0.87 and 0.28, respectively. The CD of SDMA and sCr, was 1.34 mg/dL and 0.89 mmol/L, respectively. The sample numbers required for estimation of an individual’s HSP (with 90 and 95% CI) for SDMA and sCr were 8 and 45, and 2 and 12 sequential measurements, respectively. Conclusions and Clinical Importance: Based on our findings, in comparison to sCr, SDMA is better suited for use with population based reference intervals. False-negative test results could occur when comparing a single test result from an individual to such intervals. Ideally CD should be used with sequential measurements.

Background: Lower urinary tract infections are common in dogs, and Escherichia coli is the most common bacterial pathogen isolated. The literature has conflicting evidence regarding the inhibitory effects of urine concentration and pH on E. coli growth. Hypothesis/Objectives: To determine the effect of different pH and urine concentrations on E. coli growth in vitro. Animals: Voided urine samples from 10 apparently healthy spayed female dogs were used. Methods: A matrix of 9 urine specific gravity (USG; 1.010, 1.020, and 1.030) and pH (5.5, 7.0, and 8.5) combinations was prepared by diluting and titrating filtered voided urine samples. Three E. coli isolates were obtained from urine of female dogs with signs of lower urinary tract infection and cultured at different urine pH and USG combinations in wells of a microtiter plate. The number of E. coli colony‐forming units (CFU) per mL of urine was calculated after aerobic incubation of the urine at 37°C for 18 hours, and statistically compared. Results: Significant differences were identified in the mean log CFU/mL among different combinations of pH and USG. The lowest log CFU/mL were observed in alkaline concentrated urine (pH 8.5 and USG 1.030). Conclusions and Clinical Importance: Escherichia coli in vitro growth was higher in neutral to acidic and diluted urine compared to alkaline and concentrated urine. The impact of non‐alkalizing diluting diets on the incidence of E. coli lower urinary tract infections should be further explored.

A 10-year-old neutered female soft-coated wheaten terrier and a 10-year-old, entire female Pomeranian were presented for vomiting and anorexia. Using ultrasound, an oval structure with a stellate, kiwifruit-like appearance typical of a gall bladder mucocoele was observed in the caudal abdomen of the soft-coated wheaten terrier and adjacent to the liver in the Pomeranian. There was also a moderate volume of abdominal effusion in both dogs. Cytology of the peritoneal fluid indicated a sterile exudative process but varied between the two dogs, with an absence of bile pigment in the soft-coated wheaten terrier and marked bile peritonitis in the Pomeranian. An entire free-floating ectopic mucocoele was confirmed via exploratory laparotomy with concomitant gall bladder rupture and common bile duct obstruction. Both dogs recovered completely after surgery. This is the first report of cases of gall bladder rupture with entire free-floating gall bladder mucocoeles in dogs.

The factors enhancing mucocoele development in dogs remain poorly understood. A 7-year-old female spayed Miniature Schnauzer was presented to the Massey University Veterinary Teaching Hospital for progressive lethargy, inappetance and abdominal discomfort. Initial physical examination findings revealed a moderate degree of cranial abdominal pain, with subsequent diagnostic tests confirming the patient as having diabetes mellitus, with a concurrent marked hypertriglyceridaemia. In an attempt to localise the source of pain, an ultrasound examination of the abdomen was performed, revealing a marked degree of gallbladder sludge. With appropriate medical management including ursodeoxycholic acid and insulin therapy, the patient stabilised and was discharged. With persistence of clinical signs three months later, progression of the gallbladder sludge towards mucocoele development was suspected. Exploratory laparotomy was instigated, and an emergency cholecystectomy was performed. This case report therefore entails a suspected gallbladder mucocoele that developed in a diabetic patient with previously diagnosed biliary sludge. A unique feature of this case report is the presence of diabetes mellitus, which has been suggested to be a causative factor in the development of gallbladder mucocoeles. It is also hypothesised that gallbladder sludge and mucocoeles are associated, however it is yet to be ascertained whether this association is causal or contributory. The authors examined the possible relationship between this endocrinopathy and biliary sludge, and their possible effects on mucocoele development. Specific associated factors to sludge formation are also examined. The medical and surgical management of gallbladder mucocoeles is discussed.

Sodium-glucose cotransporter type-2 inhibitors (SGLT2is) reduce glomerular hyperfiltration in diabetic people with early diabetic nephropathy. The objective of this report was to assess changes in glomerular filtration rate in healthy cats after treatment with a SGLT2i. Eight healthy research adult castrated male cats were used in a randomized, controlled, cross-over study design. We induced isolated renal tubular glucosuria by dosing cats with the SGLT2i dapagliflozin. The cats received by mouth 10 mg dapagliflozin or control every 24 h in each of the 4, 5-d trial periods that were separated by a 7-d washout period. We assessed glomerular filtration rate (iohexol clearance method), serum urea, creatinine, symmetric dimethylarginine, and 24-h sodium and chloride urinary excretion on the fifth day of each trial period. We analyzed the data with a mixed linear model that included the fixed effects of treatment (treated and control) and trial period, and the random effect of the cat. Compared with controls, cats treated with dapagliflozin had a significant increase in mean (±SE) glomerular filtration rate (3.1 ± 0.2 vs 2.5 ± 0.2 mL/kg/min; P = 0.01), whereas there were no significant differences in serum urea, creatinine and symmetric dimethylarginine, and 24-h urine sodium and chloride excretion. We propose that dapagliflozin-mediated delivery of sodium and glucose distal from the proximal convoluted tubule induced compensatory increased sodium absorption at the thick ascending loop of Henle that resulted in decreased sodium delivery to the distal tubule leading to tubuloglomerular feedback–mediated glomerular hyperfiltration. Future studies should determine if SGLT2is' renoprotective effect in people can be enhanced with the addition of a Na+-K+-Cl− diuretic and whether dapagliflozin will be useful in mitigating proteinuria and hypertension that follow glomerular hyperfiltration in diabetic companion animals in a similar mechanism as in people.

Canine acute hemorrhagic diarrhea syndrome (AHDS) has been associated in some studies with Clostridioides perfringens overgrowth and toxin-mediated necrosis of the intestinal mucosa. We aimed to determine the effect of a single fecal microbiota transplantation (FMT) on clinical scores and fecal microbiomes of 1 and 7 dogs with AHDS from New Zealand and South Africa. We hypothesized that FMT would improve AHDS clinical scores and increase microbiota alpha-diversity and short-chain fatty acid (SCFA)-producing microbial communities’ abundances in dogs with AHDS after FMT. We sequenced the V3-V4 region of the 16S-rRNA gene in the feces of AHDS FMT-recipients and sham-treated control dogs, and their healthy donors at admission, discharge, and 30 days post-discharge. There were no significant differences in median AHDS clinical scores between FMT-recipients and sham-treated controls at admission or discharge (P = 0.22, P = 0.41). At admission, the Shannon diversity index (SDI) was lower in AHDS dogs than healthy donors (P = 0.002). The SDI did not change from admission to 30 days in sham-treated dogs yet increased in FMT-recipients from admission to discharge (P = 0.04) to levels not different than donors (P = 0.33) but significantly higher than sham-treated controls (P = 0.002). At 30 days, the SDI did not differ between FMT recipients, sham-treated controls, and donors (P = 0.88). Principal coordinate analysis of the Bray-Curtis index separated post-FMT and donor dogs from pre-FMT and sham-treated dogs (P = 0.009) because of increased SCFA-producing genera’s abundances after FMT. A single co-abundance subnetwork contained many of the same OTUs found to be differentially abundant in FMT-recipients, and the abundance of this module was increased in FMT-recipients at discharge and 30 days, compared to sham-treated controls. We conclude in this small pilot study FMT did not have any clinical benefit. A single FMT procedure has the potential to increase bacterial communities of SCFA-producing genera important for intestinal health up to 30 days post-FMT.

A 7-week-old Labrador retriever presented for further investigation into acute onset regurgitation, following weaning from liquid to solid food. A videofluoroscopic swallow study demonstrated a severe, focal esophageal dilation in the mid-cervical region, with marked luminal narrowing distally. Computed tomography with angiography revealed esophageal stenosis, extending from C4-T2, secondary to circumferential esophageal wall thickening. With the concern for development of secondary aspiration pneumonia, the owners elected to euthanize the dog and consented to postmortem examination. A diagnosis of segmental, cervical esophageal muscular hypertrophy was made on necropsy, consistent with the fibromuscular thickening type of congenital esophageal stenosis reported in humans.

Bone marrow (BM) cytology and histopathology are complementary tools used to investigate hematological diseases. The purpose of this study was to determine if there are site-dependent differences in the diagnostic quality, myeloid to erythroid ratio (MER), and discordant findings in samples from different sites in the same dog. Eighteen apparently healthy dogs were used in the study. The sequence of sample acquisition was randomized according to a Latin square, and samples for BM cytology and histology were collected from both humeri and both ilial crests immediately after death. Board-certified clinical and anatomical pathologists read the cytology and histology, respectively. The data were analyzed using a mixed-effect model. The site of BM acquisition did not affect BM sample quality. The rate of discordant clinical findings between sites was 0.05 (95% confidence interval, 0.01–0.13). In general, by cytology, the MERs were slightly but significantly greater in samples from the ilial crests than from the humeri ( P = .01). The measured MER for histology was nearly twice that for cytology for all sites ( P < .001). In conclusion, there was a low-rate, site-dependent discordance in diagnostic findings in BM samples and differences in MER between the ilial crest and the humerus. A similar study is justified in sick dogs with hematological disease to determine the effect of sampling site on discordant findings between sites.

BACKGROUND Cell-free DNA (cfDNA) comprises short, double-stranded circulating DNA sequences released from damaged cells. In people, cfDNA concentrations correlate well with disease severity and tissue damage. No reports are available regarding cfDNA kinetics in dogs. OBJECTIVES/HYPOTHESIS Cell-free DNA will have a short biological half-life and would be able to stratify mild, moderate, and severe tissue injury. Our study aims were to determine the kinetics and biological half-life of cfDNA and to contrast them with those of creatine kinase (CK). ANIMALS Three groups of 10 dogs undergoing open ovariohysterectomy, surgery for cranial cruciate ligament rupture (CCLR), or hemilaminectomy. METHODS Plasma for cfDNA and CK analysis was collected at admission, at induction of anesthesia, postsurgery (time 0) and at 6, 12, 24, 36, 48, 60, and 72 hours after surgery. RESULTS The biological half-life of plasma cfDNA and CK were 5.64 hours (95% confidence interval [CI 95], 4.36-7.98 hours) and 28.7 hours (CI95, 25.3-33.3 hours), respectively. In the hemilaminectomy group, cfDNA concentrations differed significantly from admission at 6-12 hours after surgery. Creatine kinase activity differed among the surgical groups and reached a peak 6 hours after surgery. In the ovariohysterectomy and CCLR groups, plasma CK activity 72 hours after surgery did not differ from admission activity of the ovariohysterectomy group. In contrast, in the hemilaminectomy group, plasma CK activity after 72 hours did not return to the ovariohysterectomy group admission activity. CONCLUSIONS AND CLINICAL IMPORTANCE Plasma CK activity has a longer biological half-life than previously thought. In contrast to plasma CK activity, cfDNA has a short half-life and could be a useful marker for peracute severe tissue injury.

Background Canine joint sarcomas, designated synovial sarcomas, are uncommon malignant mesenchymal neoplasms that occur in the large joints of the extremities of middle-aged, large-breed dogs. We report the diagnosis of an intrathoracic sarcoma with ultrastructural characteristics reminiscent of human synovial sarcoma in a dog. Case presentation A 7-year-old female spayed Tibetan terrier crossbred dog was presented for acute severe labored breathing and diagnosed with an intrathoracic neoplastic mass. The neoplasm resulted in the accumulation of substantial amounts of viscous pleural fluid that led to dyspnea. The neoplastic mass consisted of interweaving bundles of large pleomorphic mesenchymal cells, supported by an alcian blue positive myxomatous matrix. The neoplastic cells were immunohistochemically negative for cytokeratin and CD18. Transmission electron microscopy indicated that the neoplastic cells had desmosome junctions, short microvilli-like structures and ample amounts of rough endoplasmic reticulum resembling type B-like synoviocytes and synovial sarcoma as reported in people. Despite complete surgical excision of the neoplastic mass, clinical signs recurred after a month and led to the euthanasia of the dog. Conclusion Currently, there are no immunohistochemical markers specific for synovial sarcoma. Canine neoplasms with transmission electron microscopy characteristics resembling type B-like synoviocytes should be considered similar to the human sarcomas that carry the specific translocations between chromosomes X and 18.

Objective: To determine the association between thoracic injuries evaluated by computed tomography (CT) and arterial blood gas and acid–base status in dogs with blunt thoracic trauma caused by motor vehicle accidents. Design: Prospective observational clinical study. Setting: University teaching hospital. Animals: Thirty‐one client owned traumatized dogs and 15 healthy dogs. Procedures: All trauma group dogs underwent a CT scan and simultaneous arterial blood gas analysis within 24 hours, but not before 4 hours, after the traumatic incident within a 45‐month enrollment period. Measurements and Main Results: Thorax injuries were classified as pulmonary, pleural space, or rib cage and each of these components was scored for severity using a CT composite pulmonary, pleural, and rib score. The trauma group arterial blood gas and acid–base status were evaluated for statistical difference from the control group. The pulmonary–arterial oxygen pressure was significantly lower in the trauma group compared to the control group that was supported by significant differences in the calculated variables of arterial blood oxygenation as well. There was also a significant correlation between the composite lung score and pleural score and the variables of arterial oxygen status. The pulmonary–arterial carbon dioxide pressure was not significantly different to any of the thoracic injury variables indicating normal alveolar ventilation. Acid–base imbalances were generally mild, insignificant, and variable. Conclusions and Clinical Relevance: Blunt thoracic trauma causes significant pulmonary and pleural injury and the blood oxygen economy is significantly affected by this. The functional measures of arterial blood oxygenation were well correlated with thoracic CT pathology. Alveolar ventilation was mostly spared but a clinically significant ventilation perfusion mismatch was present.

The acid–base disturbances in canine parvoviral (CPV) enteritis are not well described. In addition, the mechanisms causing these perturbations have not been fully elucidated. The purpose of the present study was to assess acid–base changes in puppies suffering from CPV enteritis, using a modified strong ion model (SIM). The hypothesis of the study was that severe acid–base disturbances would be present and that the SIM would provide insights into pathological mechanisms, which have not been fully appreciated by the Henderson–Hasselbalch model. The study analysed retrospective data, obtained from 42 puppies with confirmed CPV enteritis and 10 healthy control dogs. The CPV-enteritis group had been allocated a clinical score, to allow classification of the data according to clinical severity. The effects of changes in free water, chloride, l-lactate, albumin and phosphate were calculated, using a modification of the base excess algorithm. When the data were summated for each patient, and correlated to each individual component, the most important contributor to the metabolic acid–base changes, according to the SIM, was chloride (P

Myxomatous mitral valve disease (MMVD) is the most common heart disease of dogs. The current management of MMVD in dogs is mostly pharmacological, and the recommendations for treatment are based on a number of veterinary studies. Notwithstanding the current consensus regarding the medical management of MMVD, there remains active debate as to which drugs are the most effective. In order to understand how recommendations are constructed in the pharmacological management of diseases, the veterinarian needs to understand the concept of evidence-based veterinary medicine, and how the findings of these studies can be applied in their own practices. This review summarises the current veterinary literature and explains how the consensus regarding the management of MMVD has been reached. This review highlights the limitations of veterinary studies in order to provide veterinary practitioners with a sense of the difficulty there is in establishing the benefit of one treatment over the other. Veterinarians should therefore apply treatment recommendations based on the best evidence, integrated with a pathomechanistic understanding of the disease process and clinical experience.

A castrated 9-year-old intact male boerboel cross-breed dog was presented with a month-longhistory of stranguria. On physical examination, a mass was noted at the caudal extremity of the os penis. Haematology, serum chemistry and urinalysis were all unremarkable. Abdominal and urethral ultrasound demonstrated an enlarged bladder and a dilated urethra, whichwas followed to the caudal extremity of the os penis. A hyperechoic, roughly spherical,vascularised mass was noted at the caudal os penis, which resulted in obstruction of the penileurethra. Radiographs demonstrated a soft tissue mass with osteolysis of the os penis. Cytologysuggested an osteosarcoma. Treatment included amputation of the penis and adjuvantdoxorubicin with carboplatin. Histopathology of the penis confirmed a haemangiosarcoma. The patient survived for 20 months. This is only the second published case report describinga penile haemangiosarcoma, and the first published report demonstrating the treatment and outcome of a case of haemangiosarcoma of the os penis. Based on published and unpublished reports, haemangiosarcoma appears to be the most common neoplasm of the canine penis.

A number of key questions remain unanswered in the pathogenesis of myxomatous mitral valve disease (MMVD). As MMVD typically afflicts small-breed dogs, a genetic basis has been implied. In addition, the fact that not all dogs within a risk group develop MMVDis still unexplained. Research into the pathogenesis of MMVD typically falls under three categorical divisions, namely genetic factors, mechanical factors of the valve and systemic factors. Genetic studies have implicated certain loci in the pathogenesis of MMVD. Of particular interest is the insulin-like growth factor (IGF)-1 locus, as IGF-1 is also associated with growth. The mechanical structure and function of the mitral valve have also received much attention in recent years. What has emerged is the notion of a highly complex dynamic structure, which has an uneven distribution of stress and strain according to the flow of blood. Research efforts have also identified a number of systemic factors such as cytokines and signalling pathways that may contribute to the failure of the valve. Serotonin remains an area of interest in this field. Taken together, the amalgamation of research efforts in these three areas will go a long way towards resolving the understanding of this disease.Another area of focus in MMVD has been the development of clinical tests to diagnose the onset of congestive heart failure. To this end, echocardiographic indices and biochemical markers have been investigated. Echocardiographic indices such as left atrial to aortic ratio and the N-terminal of the prohormone brain natriuretic peptide (NT-proBNP) have been identified as specific risk factors to predict progression. Advanced imaging studies such as cardiac magnetic resonance imaging have enabled investigators to determine the earliest remodelling changes that occur in MMVD.

A castrated 9-year-old intact male boerboel cross-breed dog was presented with a month-long history of stranguria. On physical examination, a mass was noted at the caudal extremity of the os penis. Haematology, serum chemistry and urinalysis were all unremarkable. Abdominal and urethral ultrasound demonstrated an enlarged bladder and a dilated urethra, which was followed to the caudal extremity of the os penis. A hyperechoic, roughly spherical,vascularised mass was noted at the caudal os penis, which resulted in obstruction of the penile urethra. Radiographs demonstrated a soft tissue mass with osteolysis of the os penis. Cytology suggested an osteosarcoma. Treatment included amputation of the penis and adjuvant doxorubicin with carboplatin. Histopathology of the penis confirmed a haemangiosarcoma. The patient survived for 20 months. This is only the second published case report describing a penile haemangiosarcoma, and the first published report demonstrating the treatment and outcome of a case of haemangiosarcoma of the os penis. Based on published and unpublished reports, haemangiosarcoma appears to be the most common neoplasm of the canine penis.