Efficacy and safety of once daily oral administration of sodium-glucose cotransporter-2 inhibitor velagliflozin compared with twice daily insulin injection in diabetic cats.

BACKGROUND: Options for treatment of diabetes mellitus in cats are limited to insulin injections and monitoring for hypoglycemia. HYPOTHESIS: Once daily sodium-glucose cotransporter-2 inhibitor velagliflozin PO is noninferior to insulin injections. ANIMALS: Client-owned diabetic cats (127 safety; 116 efficacy assessment). METHODS: Prospective, randomized (1 mg/kg velagliflozin), positive controlled (titrated Caninsulin), open label, noninferiority field trial, comparing number of cats with treatment success in ≥1 clinical variable and ≥1 glycemic variable (margin Δ: 15%) on Day 45; secondary endpoints included glycemic and clinical assessments during 91 days. RESULTS: On Day 45, 29/54 (54%) velagliflozin-treated cats and 26/62 (42%) Caninsulin-treated cats showed treatment success, demonstrating noninferiority (difference -11.8%; upper 1-sided 97.5% confidence interval, -∞ to 6.3%). By Day 91, quality of life (QoL), polyuria, and polydipsia had improved in 81%, 54% and 61% (velagliflozin); on blood glucose (BG) curves, mean BG was <252 mg/dL in 42/54 (78%; velagliflozin) and 37/62 (60%; Caninsulin); minimum BG was <162 mg/dL in 41/54 (76%; velagliflozin) and 41/62 (66%; Caninsulin); serum fructosamine was <450 µmol/L in 41/54 (76%; velagliflozin) and 38/62 (61%; Caninsulin). Velagliflozin's most frequent adverse events were loose feces/diarrhea (n = 23/61, 38%), positive urine culture (n = 19/61, 31%), and nonclinical hypoglycemia (BG <63 mg/dL; n = 8/61, 13%); Caninsulin's: clinical and nonclinical hypoglycemia (n = 35/66, 53%), positive urine culture (n = 18/66, 27%), and loose feces/diarrhea (n = 10/66, 15%). Diabetic ketoacidosis occurred in 4/61 (7%; velagliflozin) and 0/66 (Caninsulin). CONCLUSIONS AND CLINICAL IMPORTANCE: Once daily oral administration of velagliflozin was noninferior to insulin injections, showed good QoL and glycemia without clinical hypoglycemia.

Comparison of Doppler ultrasonic sphygmomanometry, oscillometry and high-definition oscillometry for non-invasive blood pressure measurement in conscious cats.

OBJECTIVES: Systemic arterial hypertension is a common occurrence and can have serious adverse consequences in cats. Therefore, measuring blood pressure is very important. There are many indirect blood pressure measurement devices available. This study compared Doppler, oscillometric (petMAP Graphic II, SunTech Vet20, the Cardell Insight-X0000) and high-definition oscillometry devices for the non-invasive measurement of blood pressure in conscious cats. METHODS: In this prospective study, blood pressure was measured in 32 cats using the different devices according to the recommendations of the American College of Veterinary Internal Medicine Consensus Statement. Blood pressures (systolic blood pressure [SBP], diastolic blood pressure [DBP], mean arterial pressure [MAP]), time to complete measurements, number of attempts needed, coefficient of variation (CV) between the blood pressure measurements of the different devices, ease of completing measurements and apparent stress level of the cat were assessed. RESULTS: There was a significant difference between devices in the time taken to obtain blood pressure readings and the number of attempts necessary to obtain six reliable measurements. The CV of the Doppler device was significantly smaller than that of the rest of the devices, but there were no other differences between the devices. The mean SBP, DBP and MAP measured by the petMAP device were significantly higher than the measurements from the other devices. The perceived ease of measurement was not significantly different between the various machines. The perceived level of stress of measurement with the Doppler device was significantly higher compared with the other devices but did not lead to an increased SBP. CONCLUSIONS AND RELEVANCE: Using a Doppler device to measure blood pressure in conscious cats is fast, relatively easy and gives reliable results. A disadvantage is that the Doppler device can only measure SBP, while oscillometric devices also provide DBP and MAP. However, in veterinary medicine, systolic hypertension is considered the most relevant.

Whole transcriptome analysis of canine pheochromocytoma and paraganglioma.

Pheochromocytomas and paragangliomas (PPGLs) are neuroendocrine tumors arising from the chromaffin cells in the adrenal medulla and extra-adrenal paraganglia, respectively. Local invasion, concurrent disorders, and metastases prevent surgical removal, which is the most effective treatment to date. Given the current lack of effective medical treatment, there is a need for novel therapeutic strategies. To identify druggable pathways driving PPGL development, we performed RNA sequencing on PPGLs (n = 19) and normal adrenal medullas (NAMs; n = 10) of dogs. Principal component analysis (PCA) revealed that PPGLs clearly clustered apart from NAMs. In total, 4,218 genes were differentially expressed between PPGLs and NAMs. Of these, 232 had a log2 fold change of >3 or < -3, of which 149 were upregulated in PPGLs, and 83 were downregulated. Compared with NAMs, PPGLs had increased expression of genes related to the cell cycle, tumor development, progression and metastasis, hypoxia and angiogenesis, and the Wnt signaling pathway, and decreased expression of genes related to adrenal steroidogenesis. Our data revealed several overexpressed genes that could provide targets for novel therapeutics, such as Ret Proto-Oncogene (RET), Dopamine Receptor D2 (DRD2), and Secreted Frizzled Related Protein 2 (SFRP2). Based on the PCA, PPGLs were classified into 2 groups, of which group 1 had significantly higher Ki67 scores (p = 0.035) and shorter survival times (p = 0.04) than group 2. Increased expression of 1 of the differentially expressed genes between group 1 and 2, pleiotrophin (PTN), appeared to correlate with a more aggressive tumor phenotype. This study has shed light on the transcriptomic profile of canine PPGL, yielding new insights into the pathogenesis of these tumors in dogs, and revealed potential novel targets for therapy. In addition, we identified 2 transcriptionally distinct groups of PPGLs that had significantly different survival times.

Laparoscopic vs. open adrenalectomy: perioperative data and survival analysis in 70 dogs with an adrenal tumor.

Adrenalectomy is the treatment of choice in case of functional adrenal tumors and malignant adrenal incidentalomas. Laparoscopic adrenalectomy (LA) in dogs has gained popularity in recent years, however, clinical studies on large patient populations are scarce. This retrospective study describes perioperative and recurrence data, survival, and prognostic factors in 70 dogs that underwent LA or open adrenalectomy (OA) in our hospital between 2008 and 2022. Diagnosis was based on history, clinical signs, endocrine function tests and advanced diagnostic imaging. Laparoscopic adrenalectomy was performed in 42 dogs (n = 27 naturally occurring hypercortisolism, n = 4 pheochromocytoma, n = 1 pheochromocytoma with concurrent hypercortisolism, n = 10 incidentaloma) and OA in 28 dogs (n = 22 hypercortisolism, n = 3 pheochromocytoma, n = 3 incidentaloma). Bilateral adrenalectomy was performed in 8/70 dogs. Surgical duration of LA and OA did not differ significantly in unilateral and bilateral procedures (P = 0.108 and P = 0.101, respectively). Systemic hypertension occurred in 7/41 and 1/28 dogs during LA and OA, respectively (P = 0.130). Hypotension occurred in 2/41 and 4/28 dogs during LA and OA, respectively (P = 0.214). A total of 40/42 dogs in the LA group and 27/28 in the OA group survived to discharge (P = 0.810). Mean hospital stay was significantly shorter (P = 0.006) after LA (1.5 days, range 1-3) than after OA (2.2 days, range 1-4). No significant differences were demonstrated between LA and OA groups in recurrence of adrenal-dependent endocrine disease (P = 0.332), disease-free period (P = 0.733) and survival time (P = 0.353). The disease-specific 1-, 2- and 3-year survival rates were 95, 89, and 89% after LA and 92, 88, and 81% after OA. Tumor size was significantly associated with the occurrence of a recurrence. In addition, tumor size had a negative effect on the disease-free period and survival time. This study shows a favorable outcome of both LA and OA in dogs. Based on low perioperative complication rate, short hospitalization time and long-term outcomes comparable to OA in selected cases, the less invasive laparoscopic approach is considered the preferred technique.

Contribution of cats and dogs to SARS-CoV-2 transmission in households.

Introduction: SARS-CoV-2 is known to jump across species. The occurrence of transmission in households between humans and companion animals has been shown, but the contribution of companion animals to the overall transmission within a household is unknown. The basic reproduction number (R0) is an important indicator to quantify transmission. For a pathogen with multiple host species, such as SARS-CoV-2, the basic reproduction number needs to be calculated from the partial reproduction numbers for each combination of host species. Method: In this study, the basic and partial reproduction numbers for SARS-CoV-2 were estimated by reanalyzing a survey of Dutch households with dogs and cats and minimally one SARS-CoV-2-infected human. Results: For households with cats, a clear correlation between the number of cats and the basic reproduction number (Spearman's correlation: p 0.40, p-value: 1.4 × 10-5) was identified, while for dogs, the correlation was smaller and not significant (Spearman's correlation: p 0.12, p-value: 0.21). Partial reproduction numbers from cats or dogs to humans were 0.3 (0.0-2.0) and 0.3 (0.0-3.5) and from humans to cats or dogs were 0.6 (0.4-0.8) and 0.6 (0.4-0.9). Discussion: Thus, the estimations of within-household transmission indicated the likelihood of transmission from these companion animals to humans and vice versa, but the observational nature of this study limited the ability to establish conclusive evidence. This study's findings support the advice provided during the pandemic to COVID-19 patients to maintain distance from companion animals as a precautionary measure and given the possibility of transmission, although there is an overall relatively limited impact on the pandemic when compared to human-to-human transmission.

Prevalence of persistent hypertension and situational hypertension in a population of elderly cats in The Netherlands.

OBJECTIVES: Systemic arterial hypertension is increasingly recognised and can have serious adverse consequences in cats. Unfortunately, the act of measuring blood pressure itself may cause an increase in blood pressure, known as situational hypertension. It is currently unknown how often this phenomenon occurs. The aim of this study was to evaluate the prevalence of persistent hypertension and situational hypertension in an elderly population of cats in a first-opinion clinic and to assess which factors were associated with systolic hypertension. METHODS: In this prospective study, systolic blood pressure was measured in 185 cats aged ⩾10 years using the Doppler sphygmomanometry method according to the recommendations of the American College of Veterinary Internal Medicine consensus statement. Age, sex, body weight, body condition score, position during blood pressure measurement and apparent stress level were assessed. If a systolic blood pressure >160 mmHg was found, measurements were repeated to evaluate if persistent hypertension or situational hypertension was present. The first set of blood pressure measurements were used for all the statistical analyses. RESULTS: The median systolic blood pressure for this population was 140 mmHg. The prevalence of persistent hypertension was at least 14.6% and situational hypertension at least 5.4%. Factors significantly associated with hypertension were age, higher apparent stress levels and a sitting position during measurement. Sex, body weight or body condition score did not significantly influence systolic blood pressure. CONCLUSIONS AND RELEVANCE: Both persistent hypertension and situational hypertension are common in elderly cats. There are no reliable parameters to distinguish between the two, underlining the importance of a standard protocol and repeating measurements during a follow-up visit when hypertension is found. Age, demeanour and body position during blood pressure measurement influenced blood pressure in this population of elderly cats.

Reference intervals for plasma, urinary, and salivary concentrations of free metanephrines in dogs: Relevance to the diagnosis of pheochromocytoma.

BACKGROUND: Measurement of free metanephrines is recommended for screening of pheochromocytoma (PCC) but requires appropriate reference intervals (RIs). HYPOTHESIS/OBJECTIVES: To report RIs for plasma, urinary and salivary concentrations of free metanephrines and to determine the diagnostic performance of plasma free normetanephrine (pNMN) and metanephrine (pMN) concentrations in dogs with PCC, hypercortisolism (HC), and nonadrenal illness (NAI). ANIMALS: Eighty healthy dogs, 11 PCC dogs, 25 HC dogs, 6 NAI dogs. METHODS: Plasma, urine, and saliva were collected prospectively from healthy dogs, and free metanephrine concentrations were determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS). In addition, medical records of dogs that had plasma free metanephrine concentrations measured by LC-MS/MS between 2018-2021 were studied retrospectively. RESULTS: The RIs for free metanephrines in plasma, urine and saliva are reported. Dogs with PCC had significantly higher pNMN than dogs with HC (P < .001) and NAI (P = .002). The PCC dogs had significantly higher pMN than HC dogs (P < .001), but not higher than NAI dogs (P = .29). Using the upper reference limit, pNMN (>3.56 nmol/L) showed high sensitivity (100%, 95% confidence interval [CI]: 72-100) and specificity (94%, 95% CI: 79-99) for diagnosis of PCC, whereas pMN (>2.49 nmol/L) showed moderate sensitivity (73%, 95% CI: 39-94) and high specificity (94%, 95% CI: 79-99). CONCLUSIONS AND CLINICAL IMPORTANCE: With establishment of these RIs, biochemical testing for PCC in dogs can be substantially improved. Measurement of pNMN is superior to pMN in dogs with PCC.

Transcriptome sequencing reveals two subtypes of cortisol-secreting adrenocortical tumours in dogs and identifies CYP26B1 as a potential new therapeutic target.

Cushing's syndrome (CS) is a serious endocrine disorder that is relatively common in dogs, but rare in humans. In ~15%-20% of cases, CS is caused by a cortisol-secreting adrenocortical tumour (csACT). To identify differentially expressed genes that can improve prognostic predictions after surgery and represent novel treatment targets, we performed RNA sequencing on csACTs (n = 48) and normal adrenal cortices (NACs; n = 10) of dogs. A gene was declared differentially expressed when the adjusted p-value was <.05 and the log2 fold change was >2 or < -2. Between NACs and csACTs, 98 genes were differentially expressed. Based on the principal component analysis (PCA) the csACTs were separated in two groups, of which Group 1 had significantly better survival after adrenalectomy (p = .002) than Group 2. Between csACT Group G1 and Group 2, 77 genes were differentially expressed. One of these, cytochrome P450 26B1 (CYP26B1), was significantly associated with survival in both our canine csACTs and in a publicly available data set of 33 human cortisol-secreting adrenocortical carcinomas. In the validation cohort, CYP26B1 was also expressed significantly higher (p = .012) in canine csACTs compared with NACs. In future studies it would be interesting to determine whether CYP26B1 inhibitors could inhibit csACT growth in both dogs and humans.

The function of the pituitary-testicular axis in dogs prior to and following surgical or chemical castration with the GnRH-agonist deslorelin.

Chemical castration, that is the reduction of circulating testosterone concentrations to castrate levels by administration of a GnRH-agonist implant, is a popular alternative to surgical castration in male dogs. Detailed information concerning the pituitary-testicular axis following administration of a GnRH-agonist implant is still scarce. Therefore, GnRH-stimulation tests were performed in male dogs, prior to and after surgical and chemical castration. This approach also allowed us to determine plasma concentrations of testosterone and oestradiol in intact male dogs for future reference and to directly compare the effects of surgical and chemical castration on the pituitary-testicular axis. In intact male dogs (n = 42) of different breeds GnRH administration induced increased plasma LH, FSH, oestradiol and testosterone concentrations. After surgical castration basal and GnRH-induced plasma FSH and LH concentrations increased pronouncedly. Additionally, basal and GnRH-induced plasma oestradiol and testosterone concentrations decreased after surgical castration. After chemical castration, with a slow-release implant containing the GnRH-agonist deslorelin, plasma LH and FSH concentrations were lower than prior to castration and lower compared with the same interval after surgical castration. Consequently, plasma oestradiol and testosterone concentrations were lowered to values similar to those after surgical castration. GnRH administration to the chemically castrated male dogs induced a significant increase in the plasma concentrations of LH, but not of FSH. In conclusion, after administration of the deslorelin implant, the plasma concentrations of oestradiol and testosterone did not differ significantly from the surgically castrated animals. After GnRH-stimulation, none of the dogs went to pre-treatment testosterone levels. However, at the moment of assessment at 4,4 months (mean 133 days ± SEM 4 days), the pituitary gonadotrophs were responsive to GnRH in implanted dogs. The increase of LH, but not of FSH, following GnRH administration indicates a differential regulation of the release of these gonadotrophins, which needs to be considered when GnRH-stimulation tests are performed in implanted dogs.

SARS-CoV-2 infection in dogs and cats is associated with contact to COVID-19-positive household members.

Several domestic and wild animal species are susceptible to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Reported (sero)prevalence in dogs and cats vary largely depending on the target population, test characteristics, geographical location and time period. This research assessed the prevalence of SARS-CoV-2-positive cats and dogs (PCR- and/or antibody positive) in two different populations. Dogs and cats living in a household with at least one confirmed COVID-19-positive person (household (HH) study; 156 dogs and 152 cats) and dogs and cats visiting a veterinary clinic (VC) (VC study; 183 dogs and 140 cats) were sampled and tested for presence of virus (PCR) and antibodies. Potential risk factors were evaluated and follow-up of PCR-positive animals was performed to determine the duration of virus shedding and to detect potential transmission between pets in the same HH. In the HH study, 18.8% (27 dogs, 31 cats) tested SARS-CoV-2 positive (PCR- and/or antibody positive), whereas in the VC study, SARS-CoV-2 prevalence was much lower (4.6%; six dogs, nine cats). SARS-CoV-2 prevalence amongst dogs and cats was significantly higher in the multi-person HHs with two or more COVID-19-positive persons compared with multi-person HHs with only one COVID-19-positive person. In both study populations, no associations could be identified between SARS-CoV-2 status of the animal and health status, age or sex. During follow-up of PCR-positive animals, no transmission to other pets in the HH was observed despite long-lasting virus shedding in cats (up to 35 days). SARS-CoV-2 infection in dogs and cats appeared to be clearly associated with reported COVID-19-positive status of the HH. Our study supports previous findings and suggests a very low risk of pet-to-human transmission within HHs, no severe clinical signs in pets and a negligible pet-to-pet transmission between HHs.

Normothermic Ex Vivo Liver Platform Using Porcine Slaughterhouse Livers for Disease Modeling.

Metabolic and toxic liver disorders, such as fatty liver disease (steatosis) and drug-induced liver injury, are highly prevalent and potentially life-threatening. To allow for the study of these disorders from the early stages onward, without using experimental animals, we collected porcine livers in a slaughterhouse and perfused these livers normothermically. With our simplified protocol, the perfused slaughterhouse livers remained viable and functional over five hours of perfusion, as shown by hemodynamics, bile production, indocyanine green clearance, ammonia metabolism, gene expression and histology. As a proof-of-concept to study liver disorders, we show that an infusion of free fatty acids and acetaminophen results in early biochemical signs of liver damage, including reduced functionality. In conclusion, the present platform offers an accessible system to perform research in a functional, relevant large animal model while avoiding using experimental animals. With further improvements to the model, prolonged exposure could make this model a versatile tool for studying liver diseases and potential treatments.

High level of polarized engraftment of porcine intrahepatic cholangiocyte organoids in decellularized liver scaffolds.

In Europe alone, each year 5500 people require a life-saving liver transplantation, but 18% die before receiving one due to the shortage of donor organs. Whole organ engineering, utilizing decellularized liver scaffolds repopulated with autologous cells, is an attractive alternative to increase the pool of available organs for transplantation. The development of this technology is hampered by a lack of a suitable large-animal model representative of the human physiology and a reliable and continuous cell source. We have generated porcine intrahepatic cholangiocyte organoids from adult stem cells and demonstrate that these cultures remained stable over multiple passages whilst retaining the ability to differentiate into hepatocyte- and cholangiocyte-like cells. Recellularization onto porcine scaffolds was efficient and the organoids homogeneously differentiated, even showing polarization. Our porcine intrahepatic cholangiocyte system, combined with porcine liver scaffold paves the way for developing whole liver engineering in a relevant large-animal model.

Evaluation of the FreeStyle Libre, a flash glucose monitoring system, in client-owned cats with diabetes mellitus.

OBJECTIVES: Home blood glucose monitoring using a portable blood glucose meter is important in the management of feline diabetes mellitus, but taking blood samples may be stressful for owners and cats. A flash glucose monitoring system measuring interstitial glucose, such as the FreeStyle Libre, overcomes some of these drawbacks. The aim of this study was to evaluate the practical use and analytical and clinical accuracy of the FreeStyle Libre in 41 client-owned diabetic cats. METHODS: In this prospective study, interstitial glucose concentrations were measured with the FreeStyle Libre and compared with blood glucose concentrations measured with a portable blood glucose meter (AlphaTRAK) on days 1, 7 or 8 and 14 after application of the device. Cat behaviour during application, location, skin reaction at the attachment site and owner satisfaction were assessed. Accuracy was determined by fulfilment of ISO 15197:2013 criteria, including Bland-Altman plotting and error grid analysis. RESULTS: Placing the device was easy, with 70% of cats showing no reaction. Most sensors were placed on the thoracic wall. Skin reactions at the attachment site were not present or mild in almost all cats. Owners were very satisfied with the use of the FreeStyle Libre. Median functional life of the sensor was 10 days (range 1-14). Good correlation was found between interstitial and blood glucose measurements (rho[r] = 0.88, P <0.0001). Fifty-three percent of interstitial glucose concentrations were within a maximum deviation of 15% from blood glucose concentrations and 92.7% were within the safe risk zones 0 and 1 of the surveillance error grid. CONCLUSIONS AND RELEVANCE: The flash glucose monitoring system was easy to use and owners of diabetic cats were satisfied with its use. Although the device did not completely fulfil ISO requirements, it is sufficiently accurate for glucose monitoring in diabetic cats.

Dilated cardiomyopathy in a cat with congenital hyposomatotropism.

Case summary: A 7-month-old domestic shorthair cat was presented for evaluation of stunted growth, recurrent hypoglycaemia during the first months of its life and altered mentation. Complete blood count and biochemistry were unremarkable, except for mildly elevated serum creatinine concentration (despite low muscle mass) and concurrent isosthenuria. Hyposomatotropism was diagnosed based on persistent low circulating insulin-like growth factor 1 concentrations and a lack of response of circulating growth hormone (GH) concentration after the administration of GH-releasing hormone. Other endocrinopathies such as hypothyroidism and hypoadrenocorticism were excluded. MRI of the brain revealed a fluid-filled empty sella tursica, consistent with a pituitary cyst and atrophy/hypoplasia of the pituitary. Echocardiography was unremarkable at the time of diagnosis of hyposomatotropism. Three months later, ovariohysterectomy revealed immature ovaries, raising the suspicion of luteinising and follicle-stimulating hormone deficiency. At 1 year of age, the cat developed congestive heart failure secondarily to dilated cardiomyopathy (DCM) with severely reduced left ventricular systolic function and died a few days later. Pathology showed atrophy of the adenohypophysis, epithelial delineation of the pituitary cysts, mild cardiomegaly, multifocal fibrosis of the left ventricle and a mild, multifocal, chronic epicarditis. Relevance and novel information: GH deficiency is a very rare endocrinopathy in cats. This is the first case to describe the development of DCM with concurrent hyposomatotropism, which has previously been reported in human medicine. Other notable abnormalities that could be related to GH deficiency are juvenile self-limiting hypoglycaemia, behavioural changes and possible nephropathy.

Fibroblast growth factor-21 (FGF21) analogs as possible treatment options for diabetes mellitus in veterinary patients.

Fibroblast growth factors (FGFs) are involved in numerous metabolic processes. The endocrine subfamily of FGFs, consisting of FGF19, FGF21, and FGF23, might have beneficial effects in the treatment of diabetes mellitus (DM) and/or obesity. The analog with the greatest potential, FGF21, lowers blood glucose levels, improves insulin sensitivity, and induces weight loss in several animal models. In this review we summarize recent (pre)clinical findings with FGF21 analogs in animal models and men. Furthermore, possible applications of FGF21 analogs for pets with DM will be discussed. As currently, information about the use of FGF21 analogs in pet animals is scarce.

Circulating MicroRNAs as Non-invasive Biomarkers for Canine Cushing's Syndrome.

Canine Cushing's syndrome (hypercortisolism) can be caused by a pituitary tumor (pituitary-dependent hypercortisolism; PDH) or a cortisol-secreting adrenocortical tumor (csACT). For both cases, non-invasive biomarkers that could pre-operatively predict the risk of recurrence after surgery would greatly impact clinical decision making. The aim of this study was to determine whether circulating microRNAs (miRNAs) can be used as diagnostic (presence of PDH or csACT) and/or prognostic (disease recurrence, histological grade) non-invasive biomarkers for canine Cushing's syndrome. After a pilot study with 40 miRNAs in blood samples of healthy dogs (n = 3), dogs with PDH (n = 3) and dogs with a csACT (n = 4), we selected a total of 20 miRNAs for the definitive study. In the definitive study, these 20 miRNAs were analyzed in blood samples of healthy dogs (n = 6), dogs with PDH (n = 19, pre- and post-operative samples) and dogs with a csACT (n = 26, pre-operative samples). In dogs with PDH, six miRNAs (miR-122-5p, miR-126-5p, miR-141-3p, miR-222-3p, miR-375-3p and miR-483-3p) were differentially expressed compared to healthy dogs. Of one miRNA, miR-122-5p, the expression levels did not overlap between healthy dogs and dogs with PDH (p = 2.9x10-4), significantly decreased after hypophysectomy (p = 0.013), and were significantly higher (p = 0.017) in dogs with recurrence (n = 3) than in dogs without recurrence for at least one year after hypophysectomy (n = 7). In dogs with csACTs, two miRNAs (miR-483-3p and miR-223-3p) were differentially expressed compared to healthy dogs. Additionally, miR-141-3p was expressed significantly lower (p = 0.009) in dogs with csACTs that had a histopathological Utrecht score of ≥ 11 compared to those with a score of <11. These results indicate that circulating miRNAs have the potential to be non-invasive biomarkers in dogs with Cushing's syndrome that may contribute to clinical decision making.

Evaluation of hypophysectomy for treatment of hypersomatotropism in 25 cats.

BACKGROUND: Successful treatment of cats with hypersomatotropism by transsphenoidal hypophysectomy is described in small numbers of cats. OBJECTIVES: To describe the endocrine profile, survival, and remission rates of hypersomatotropism and diabetes mellitus in a cohort of cats with hypersomatotropism that underwent hypophysectomy between 2008 and 2020. ANIMALS: Twenty-five client-owned cats with spontaneous hypersomatotropism. METHODS: Retrospective study. Diagnosis of hypersomatotropism was based on clinical signs, plasma insulin-like growth factor-1 (IGF-1) concentration, and imaging of the pituitary gland. Growth hormone (GH) and IGF-1 concentrations were measured repeatedly after surgery. Survival times were calculated based on follow-up information from owners and referring veterinarians. RESULTS: Median postoperative hospital stay was 7 days (range, 3-18 days). One cat died within 4 weeks of surgery. Median plasma GH concentration decreased significantly from 51.0 ng/mL (range, 5.0-101.0 ng/mL) before surgery to 3.8 ng/mL (range, 0.6-13.0 ng/mL) at 5 hours after surgery. Remission of hypersomatotropism, defined as normalization of plasma IGF-1 concentration, occurred in 23/24 cats (median, 34 ng/mL; range, 14-240 ng/mL) and 22/24 cats entered diabetic remission. Median survival time was 1347 days (95% confidence interval, 900-1794 days; range, 11-3180 days) and the overall 1-, 2-, and 3-year all-cause survival rates were 76%, 76%, and 52%, respectively. CONCLUSIONS AND CLINICAL IMPORTANCE: This study shows the beneficial outcome of hypophysectomy in cats with hypersomatotropism, marked by low death rate and a high percentage of diabetic remission and definitive cure.

Planar and single-photon emission computed tomography imaging in dogs with thyroid tumors: 68 cases.

BACKGROUND: Information on scintigraphy findings in dogs with thyroid neoplasia is scarce. The use of single-photon emission computed tomography (SPECT) could improve detection of metastatic disease. HYPOTHESIS/OBJECTIVES: To describe planar and SPECT imaging findings in dogs with thyroid tumors, and to compare SPECT and thoracic radiography for metastasis detection. ANIMALS: Sixty-eight dogs with thyroid neoplasia. METHODS: Retrospective study, search of medical records for dogs with thyroid neoplasia (2008-2018). RESULTS: Thyroid scintigraphy was available from 68 dogs, of which 6 presented after surgical resection. Radionuclide uptake was increased in 56% of dogs, decreased in 24%, and comparable to that of the salivary glands in 13%. The remainder had multiple masses with variable uptake. A homogeneous uptake pattern was present in 16% and a heterogeneous uptake pattern in 73%. In 11% (all dogs with multiple masses), various uptake patterns were present. Thyroid tumors were well delineated in 55%. There was a significant association between hormone status and uptake pattern (P = .009), with a heterogeneous uptake pattern in the majority of euthyroid dogs, and hormone status and tumor circumscription (P = .003), with well-circumscribed margins in the majority of hypothyroid and hyperthyroid dogs. Thoracic SPECT imaging was available in 39 dogs and identified metastatic lesions in 15 dogs. Thoracic radiographs were performed in 14 of these dogs, and detected metastases in 3 dogs. CONCLUSIONS AND CLINICAL IMPORTANCE: SPECT imaging is a viable imaging technique to screen for thoracic metastasis and wider use of SPECT imaging is recommended in dogs with thyroid neoplasia.

Primary Hyperaldosteronism in Cats: An Underdiagnosed Disorder.

Primary hyperaldosteronism, also known as Conn's syndrome, is the most common adrenocortical disease in cats. As in humans, this disease is underdiagnosed in cats. Cats presenting with systemic arterial hypertension, hypokalemia, or both quite often are only treated symptomatically without further investigations. This practice may potentially exclude a significant number of cats from receiving appropriate treatment. It is therefore important for general practitioners to be aware of the disease. This article describes the (patho)physiology, clinical presentation, diagnostic approach, and treatment options of for feline primary hyperaldosteronism.

Influence of macronutrient composition of commercial diets on circulating leptin and adiponectin concentrations in overweight dogs.

Leptin and adiponectin play important roles in obesity-related inflammation and comorbidities. Previous research suggests that alterations in dietary macronutrient composition can modify circulating leptin and adiponectin concentrations in people, but limited research on this subject has been performed in dogs. This study investigated the effects of commercial high protein (HP), high fat (HF) and high carbohydrate medium protein (HCMP) diets on baseline (T-1 ) concentrations, post-prandial peak concentrations and total release in a ten-hour time span of leptin and adiponectin in dogs, when compared to a maintenance high carbohydrate low protein (HCLP) diet. Thirty-six overweight dogs were fed the HCLP diet in a one-week control period, after which the animals were assigned to one of three groups. In three four-week periods, each group was fed all test diets in a different sequence. At the last day of each period, blood was sampled at one hour before feeding (T-1 ) and at three (T3 ), six (T6 ) and nine (T9 ) hours after feeding. Feeding caused peak leptin concentrations at T6 and T9 (p < .001). No significant post-prandial change in adiponectin concentrations was found (p = .056). The HP diet resulted in lower leptin peak concentrations (p = .004) and AUCT-1-T9 (p = .01), but none of the diets influenced baseline leptin concentrations (p = .273). Baseline adiponectin concentrations were lower for the HF diet (p = .018) and HCMP (p < .001), and the HP, HF and HCMP AUCT-1-T9 (p < .001) were lower compared with the HCLP diet. Female dogs had lower adiponectin baseline concentrations (p = .041) and AUCT-1-T9 (p = .023) than male dogs. In conclusion, the HP diet was associated with the lowest post-prandial peak leptin concentration and the least decrease in adiponectin release, suggesting that a HP diet may improve immune-metabolic health and post-prandial satiety in overweight dogs.