Impact of unscheduled nurse-led virtual care for people with diabetes on nursing practices and patient satisfaction.

BACKGROUND: The COVID-19 pandemic and its social restrictions accelerated the expansion of virtual clinical care, and this has been reported to be safe, low cost and flexible. AIM: This study aimed to examine nursing practices and patient satisfaction with unscheduled nurse-led virtual care for people with diabetes. METHODS: A cross-sectional descriptive survey of clinical nurse specialists and patients was carried out, using an activities log for nursing practices and a satisfaction and enablement survey for callers. FINDINGS: Patients reported high satisfaction levels and greater self-confidence in keeping themselves healthy after receiving virtual care. Most calls (74.8%) from patients were for advice and education. Each call led to an average of 2.5 actions for the clinical nurse specialist. CONCLUSION: The service is highly valued and is effective, but adds to the nurse workload burden.

Ketones provide an extra source of fuel for the failing heart without impairing glucose oxidation.

BACKGROUND: Cardiac glucose oxidation is decreased in heart failure with reduced ejection fraction (HFrEF), contributing to a decrease in myocardial ATP production. In contrast, circulating ketones and cardiac ketone oxidation are increased in HFrEF. Since ketones compete with glucose as a fuel source, we aimed to determine whether increasing ketone concentration both chronically with the SGLT2 inhibitor, dapagliflozin, or acutely in the perfusate has detrimental effects on cardiac glucose oxidation in HFrEF, and what effect this has on cardiac ATP production. METHODS: 8-week-old male C57BL6/N mice underwent sham or transverse aortic constriction (TAC) surgery to induce HFrEF over 3 weeks, after which TAC mice were randomized to treatment with either vehicle or the SGLT2 inhibitor, dapagliflozin (DAPA), for 4 weeks (raises blood ketones). Cardiac function was assessed by echocardiography. Cardiac energy metabolism was measured in isolated working hearts perfused with 5 mM glucose, 0.8 mM palmitate, and either 0.2 mM or 0.6 mM ß-hydroxybutyrate (ßOHB). RESULTS: TAC hearts had significantly decreased %EF compared to sham hearts, with no effect of DAPA. Glucose oxidation was significantly decreased in TAC hearts compared to sham hearts and did not decrease further in TAC hearts treated with high ßOHB or in TAC DAPA hearts, despite ßOHB oxidation rates increasing in both TAC vehicle and TAC DAPA hearts at high ßOHB concentrations. Rather, increasing ßOHB supply to the heart selectively decreased fatty acid oxidation rates. DAPA significantly increased ATP production at both ßOHB concentrations by increasing the contribution of glucose oxidation to ATP production. CONCLUSION: Therefore, increasing ketone concentration increases energy supply and ATP production in HFrEF without further impairing glucose oxidation.

Automated echocardiographic left ventricular dimension assessment in dogs using artificial intelligence: Development and validation.

BACKGROUND: Artificial intelligence (AI) could improve accuracy and reproducibility of echocardiographic measurements in dogs. HYPOTHESIS: A neural network can be trained to measure echocardiographic left ventricular (LV) linear dimensions in dogs. ANIMALS: Training dataset: 1398 frames from 461 canine echocardiograms from a single specialist center. VALIDATION: 50 additional echocardiograms from the same center. METHODS: Training dataset: a right parasternal 4-chamber long axis frame from each study, labeled by 1 of 18 echocardiographers, marking anterior and posterior points of the septum and free wall. VALIDATION DATASET: End-diastolic and end-systolic frames from 50 studies, annotated twice (blindly) by 13 experts, producing 26 measurements of each site from each frame. The neural network also made these measurements. We quantified its accuracy as the deviation from the expert consensus, using the individual-expert deviation from consensus as context for acceptable variation. The deviation of the AI measurement away from the expert consensus was assessed on each individual frame and compared with the root-mean-square-variation of the individual expert opinions away from that consensus. RESULTS: For the septum in end-diastole, individual expert opinions deviated by 0.12 cm from the consensus, while the AI deviated by 0.11 cm (P = .61). For LVD, the corresponding values were 0.20 cm for experts and 0.13 cm for AI (P = .65); for the free wall, experts 0.20 cm, AI 0.13 cm (P < .01). In end-systole, there were no differences between individual expert and AI performances. CONCLUSIONS AND CLINICAL IMPORTANCE: An artificial intelligence network can be trained to adequately measure linear LV dimensions, with performance indistinguishable from that of experts.

Advancing Treatments for Feline Hypertrophic Cardiomyopathy: The Role of Animal Models and Targeted Therapeutics.

Feline HCM is the most common cardiovascular disease in cats, leading to devastating outcomes, including congestive heart failure (CHF), arterial thromboembolism (ATE), and sudden death. Evidence demonstrating long-term survival benefit with currently available therapies is lacking. Therefore, it is imperative to explore intricate genetic and molecular pathways that drive HCM pathophysiology to inspire the development of novel therapeutics. Several clinical trials exploring new drug therapies are currently underway, including those investigating small molecule inhibitors and rapamycin. This article outlines the key work performed using cellular and animal models that has led to and continues to guide the development of new innovative therapeutic strategies.

Exploration of Mediators Associated with Myocardial Remodelling in Feline Hypertrophic Cardiomyopathy.

Hypertrophic cardiomyopathy (HCM) affects both humans and cats and exhibits considerable interspecies similarities that are exemplified by underlying pathological processes and clinical presentation to the extent that developments in the human field may have direct relevance to the feline disease. Characteristic changes on histological examination include cardiomyocyte hypertrophy and interstitial and replacement fibrosis. Clinically, HCM is characterised by significant diastolic dysfunction due to a reduction in ventricular compliance and relaxation associated with extracellular matrix (ECM) remodelling and the development of ventricular hypertrophy. Studies in rodent models and human HCM patients have identified key protein mediators implicated in these pathological changes, including lumican, lysyl oxidase and TGF-ß isoforms. We therefore sought to quantify and describe the cellular location of these mediators in the left ventricular myocardium of cats with HCM and investigate their relationship with the quantity and structural composition of the ECM. We identified increased myocardial content of lumican, LOX and TGF-ß2 mainly attributed to their increased expression within cardiomyocytes in HCM cats compared to control cats. Furthermore, we found strong correlations between the expressions of these mediators that is compatible with their role as important components of cellular pathways promoting remodelling of the left ventricular myocardium. Fibrosis and hypertrophy are important pathological changes in feline HCM, and a greater understanding of the mechanisms driving this pathology may facilitate the identification of potential therapies.

Experiences of shared decision making in acute hospitals: A mixed methods secondary analysis of the Irish National Inpatient Experience Survey.

INTRODUCTION: This study explored patient experiences of shared decision making (SDM) in public acute hospitals in Ireland. METHODS: Quantitative and qualitative data from three years of the Irish National Inpatient Experience Survey were analysed. Survey questions were mapped to definitions of SDM and subjected to principal components analysis. Three SDM subscales (care on the ward; treatments; discharge) and one overall SDM scale were created. Differences in experiences of SDM by aspects of care and patient group were assessed. Thematic analysis of qualitative responses was undertaken. RESULTS: 39,453 patients participated in the survey. The mean SDM experience score was 7.60 ± 2.43. Experience scores were highest on the treatments sub-scale, and lowest during discharge. Patients who had a non-emergency admission, those aged 51-80 years and men had more positive experiences than other groups. Patient comments highlighted that opportunities to clarify information and facilitation of families/caregivers in SDM were found to be lacking. CONCLUSION: There were differences in experiences of SDM by aspects of care and patient group. PRACTICE IMPLICATIONS: Efforts to improve SDM in acute hospitals are required, particularly at the time of discharge. SDM may be improved by facilitation of more time for discussion between clinicians and patients and/or their families/caregivers.

Design of a chimeric ACE-2/Fc-silent fusion protein with ultrahigh affinity and neutralizing capacity for SARS-CoV-2 variants.

Background: As SARS-CoV-2 continues to mutate into Variants of Concern (VOC), there is growing and urgent need to develop effective antivirals to combat COVID-19. Monoclonal antibodies developed earlier are no longer capable of effectively neutralizing currently active VOCs. This report describes the design of variant-agnostic chimeric molecules consisting of an Angiotensin-Converting Enzyme 2 (ACE-2) domain mutated to retain ultrahigh affinity binding to a wide variety of SARS-CoV-2 variants, coupled to an Fc-silent immunoglobulin domain that eliminates antibody-dependent enhancement and extends biological half-life. Methods: Molecular modeling, Surrogate Viral Neutralization tests (sVNTs) and infection studies of human airway organoid cultures were performed with synthetic chimeras, SARS-CoV-2 spike protein mimics and SARS-CoV-2 Omicron variants B.1.1.214, BA.1, BA.2 and BA.5. Results: ACE-2 mutations L27, V34 and E90 resulted in ultrahigh affinity binding of the LVE-ACE-2 domain to the widest variety of VOCs, with KDs of 93 pM and 73 pM for binding to the Alpha B1.1.7 and Omicron B.1.1.529 variants, and notably, 78fM, 133fM and 1.81pM affinities to the Omicron BA.2, BA2.75 and BQ.1.1 subvariants, respectively. sVNT assays revealed titers of ≥4.9 ng/ml, for neutralization of recombinant viral proteins corresponding to the Alpha, Delta and Omicron variants. The values above were obtained with LVE-ACE-2/mAB chimeras containing the FcRn-binding Y-T-E sequence which extends biological half-life 3-4-fold. Conclusions: The ACE-2-mutant/Fc silent fusion proteins described have ultrahigh affinity to a wide variety of SARS-CoV-2 variants including Omicron. It is proposed that these chimeric ACE-2/mABs will constitute variant-agnostic and cost-effective prophylactics against SARS-CoV-2, particularly when administered nasally.

Regenerative and Anti-Inflammatory Potential of Regularly Fed, Starved Cells and Extracellular Vesicles In Vivo.

BACKGROUND: Mesenchymal stem/stromal cells (MSC) have been employed successfully in immunotherapy and regenerative medicine, but their therapeutic potential is reduced considerably by the ischemic environment that exists after transplantation. The assumption that preconditioning MSC to promote quiescence may result in increased survival and regenerative potential upon transplantation is gaining popularity. METHODS: The purpose of this work was to evaluate the anti-inflammatory and regenerative effects of human bone marrow MSC (hBM-MSC) and their extracellular vesicles (EVs) grown and isolated in a serum-free medium, as compared to starved hBM-MSC (preconditioned) in streptozotocin-induced diabetic fractured male C57BL/6J mice. RESULTS: Blood samples taken four hours and five days after injection revealed that cells, whether starved or not, generated similar plasma levels of inflammatory-related cytokines but lower levels than animals treated with EVs. Nonetheless, starved cells prompted the highest production of IL-17, IL-6, IL-13, eotaxin and keratinocyte-derived chemokines and induced an earlier soft callus formation and mineralization of the fracture site compared to EVs and regularly fed cells five days after administration. CONCLUSIONS: Preconditioning may be crucial for refining and defining new criteria for future MSC therapies. Additionally, the elucidation of mechanisms underpinning an MSC's survival/adaptive processes may result in increased cell survival and enhanced therapeutic efficacy following transplantation.

Metabolic, structural and biochemical changes in diabetes and the development of heart failure.

Diabetes contributes to the development of heart failure through various metabolic, structural and biochemical changes. The presence of diabetes increases the risk for the development of cardiovascular disease (CVD), and since the introduction of cardiovascular outcome trials to test diabetic drugs, the importance of improving our understanding of the mechanisms by which diabetes increases the risk for heart failure has come under the spotlight. In addition to the coronary vasculature changes that predispose individuals with diabetes to coronary artery disease, diabetes can also lead to cardiac dysfunction independent of ischaemic heart disease. The hyperlipidaemic, hyperglycaemic and insulin resistant state of diabetes contributes to a perturbed energy metabolic milieu, whereby the heart increases its reliance on fatty acids and decreases glucose oxidative rates. In addition to changes in cardiac energy metabolism, extracellular matrix remodelling contributes to the development of cardiac fibrosis, and impairments in calcium handling result in cardiac contractile dysfunction. Lipotoxicity and glucotoxicity also contribute to impairments in vascular function, cardiac contractility, calcium signalling, oxidative stress, cardiac efficiency and lipoapoptosis. Lastly, changes in protein acetylation, protein methylation and DNA methylation contribute to a myriad of gene expression and protein activity changes. Altogether, these changes lead to decreased cardiac efficiency, increased vulnerability to an ischaemic insult and increased risk for the development of heart failure. This review explores the above mechanisms and the way in which they contribute to cardiac dysfunction in diabetes.

Rhythm disturbances associated with lidocaine administration in four dogs with supraventricular tachyarrhythmias.

OBJECTIVE: To describe arrhythmias associated with administration of lidocaine in dogs treated for supraventricular tachyarrhythmias. CASE SUMMARIES: Four dogs with recent-onset supraventricular tachyarrhythmias: 3 dogs had atrial fibrillation (AF), and 1 had focal atrial tachycardia (FAT), which was thought to be AF at the time of assessment. The substrate of the supraventricular tachyarrhythmia was considered to be due to primary cardiomyopathy in 1 dog, high vagal tone in 2 dogs, and the change in hemodynamics from heavy sedation in 1 dog. Pharmacological cardioversion using lidocaine was only successful in the 2 dogs with vagally mediated AF. In these 2 cases, lidocaine administration resulted in a paroxysmal atrial flutter that was self-limiting and quickly led to sinus rhythm within 10 seconds in 1 dog but did not change over a 5-minute interval and required additional boluses in another dog. In the latter case, the dog showed severe bradycardia for 17.5 seconds prior to achieving sinus rhythm. The 2 unsuccessful cases both developed ventricular arrhythmias shortly after the lidocaine administration, with 1 case degenerating into ventricular fibrillation and cardiac arrest. NEW OR UNIQUE INFORMATION PROVIDED: Arrhythmias associated with lidocaine should be considered when treating dogs with supraventricular tachyarrhythmia.

A versatile technique for high-resolution three-dimensional imaging of human arterial segments using microcomputed tomography.

BACKGROUND: Quantitative methods for evaluating microstructure of arterial specimens typically rely on histologic techniques that involve random sampling, which cannot account for the unique spatial distribution of features in three dimensions. METHODS: To overcome this limitation, we demonstrate a nondestructive method for three-dimensional imaging of intact human blood vessels using microcomputed tomography (microCT). Human artery segments were dehydrated and stained in an iodine solution then imaged with a standard laboratory microCT scanner. Image visualization and segmentation was performed using commercially available and open source software. RESULTS: Staining of cadaveric vessels with iodine enabled clear visualization of the arterial wall with microCT, preserved tissue morphology, and generated high-resolution images with a voxel size of 5.4 µm. Various components of the arterial wall were segmented using a combination of manual and automatic thresholding algorithms. CONCLUSIONS: Our approach allows for spatial mapping of human artery tissue samples that can guide targeted histologic analysis of smaller tissue segments, provide geometric data to inform finite element models, quantify degree of atherosclerosis, and help to evaluate the foreign body response to intravascular medical implants. (JVS-Vascular Science 2020;2:13-19.). CLINICAL RELEVANCE: In this article, we describe a powerful technique for whole artery analysis of pathologic human tissue specimens that provides high-resolution spatial detail regarding composition of the blood vessel wall. The protocol described here is a valuable adjunct that can be used as a research tool to inform finite element modeling of arteries, quantify pathologic response (ie, neointimal hyperplasia and vascular calcification), and evaluate the tissue/device interface of implanted medical devices.

Emergency endovascular stent-graft repair of a traumatic ruptured renal artery aneurysm: A case report.

To describe the endovascular treatment of a traumatic rupture of a renal artery aneurysm (RAA) in an unstable patient using a stent-graft. A 49-year-old patient presented following trauma to her right chest and flank. The patient was unstable on arrival and following resuscitation, contrast CT angiogram identified a rupture of a left RAA. To occlude the aneurysm, a graft-stent was placed successfully to arrest the haemorrhage. In this case of ruptured RAA, an endovascular approach allowed rapid control of bleeding and preservation of the kidney function, whilst avoiding open surgery and possible nephrectomy.

Immunohistological Evaluation of Von Willebrand Factor in the Left Atrial Endocardium and Atrial Thrombi from Cats with Cardiomyopathy.

Aortic thromboembolism (ATE) occurs in cats with cardiomyopathy and often results in euthanasia due to poor prognosis. However, the underlying predisposing mechanisms leading to left atrial (LA) thrombus formation are not fully characterised. von Willebrand Factor (vWF) is a marker of endothelium and shows increased expression following endothelial injury. In people with poor LA function and LA remodelling, vWF has been implicated in the development of LA thrombosis. In this study we have shown (1) the expression of endocardial vWF protein detected using immunohistofluorescence was elevated in cats with cardiomyopathy, LA enlargement (LAE) and clinical signs compared to cats with subclinical cardiomyopathy and control cats; (2) vWF was present at the periphery of microthrombi and macrothrombi within the LA where they come into contact with the LA endocardium and (3) vWF was integral to the structure of the macrothrombi retrieved from the atria. These results provide evidence for damage of the endocardial endothelium in the remodelled LA and support a role for endocardial vWF as a pro-thrombotic substrate potentially contributing to the development of ATE in cats with underlying cardiomyopathy and LAE. Results from this naturally occurring feline model may inform research into human thrombogenesis.

Clinical features and outcome of dogs and cats with bidirectional and continuous right-to-left shunting patent ductus arteriosus.

BACKGROUND: Studies describing the clinical progression of animals with reverse patent ductus arteriosus (PDA) are lacking. OBJECTIVES: To describe the signalment, presenting signs, echocardiographic features, and survival in a group of dogs and cats with bidirectional and continuous right-to-left PDA. ANIMALS: Forty-six client-owned animals included, comprising 43 dogs and 3 cats with bidirectional or continuous right-to-left PDA. METHODS: Retrospective multicenter study. Medical records and echocardiographic findings reviewed from animals diagnosed with bidirectional or continuous right-to-left PDA. Impact of ductal morphology, spectral Doppler flow profile, PCV, sildenafil treatment at presentation, sildenafil dose, severity of pulmonary hypertension, general anesthesia with or without surgery and the presence of right-sided congestive heart failure (R-CHF) on crude mortality rate were evaluated via Mantel-Cox log rank comparison of Kaplan-Meier survival curves. Univariable and multivariable Cox proportional hazards analysis was performed, and hazard ratio (HR) (95% confidence intervals [CI]) was presented. RESULTS: Hindlimb collapse was the most common presenting sign in dogs (n = 16). Clinical signs in cats were variable. Median survival time was 626 days in dogs (range 1-3628 days). Dogs with R-CHF had a shorter median survival time (58 days vs 1839 days, P = .03). Dogs treated with sildenafil at initial presentation survived longer (1839 days vs 302 days, P = .03), which was the only independent predictor of survival (HR 0.35, CI 0.15-0.86, P = 0.021). CONCLUSIONS AND CLINICAL IMPORTANCE: Dogs and cats with reverse PDA have a variable clinical presentation and prognosis. Survival time was longer in animals prescribed sildenafil at diagnosis. Dogs with R-CHF at presentation have a worse overall outcome.

Increased insulin-like growth factor 1 concentrations in a retrospective population of non-diabetic cats diagnosed with hypertrophic cardiomyopathy.

OBJECTIVES: The aim of the study was to document whether a proportion of non-diabetic cats with left ventricular hypertrophy (LVH) previously diagnosed with hypertrophic cardiomyopathy (HCM) have elevated circulating insulin-like growth factor 1 (IGF-1) concentrations. METHODS: A retrospective analysis of residual blood samples obtained at the time of echocardiographic diagnosis of HCM from a population of 60 non-diabetic cats were analysed for circulating IGF-1 concentrations using a validated radioimmunoassay and compared with a control group of 16 apparently healthy cats without LVH. Clinical and echocardiographic data for cats with an IGF-1 level >1000 ng/ml were compared with those with an IGF-1 level <800 ng/ml. RESULTS: In total, 6.7% (95% confidence interval 1.8-16.2%) of cats with HCM had an IGF-1 level >1000 ng/ml. The prevalence of an IGF-1 level >1000 ng/ml in the control group was zero. CONCLUSIONS AND RELEVANCE: A small proportion of non-diabetic cats previously diagnosed with HCM had an IGF-1 concentration at a level that has been associated with feline hypersomatotropism (fHS) in the diabetic cat population. Further prospective research is required to confirm or refute the presence of fHS in non-diabetic cats with LVH and increased IGF-1.

Echocardiographic, morphometric and biomarker changes in female cats followed from 6 to 24 months of life.

OBJECTIVES: The aim of the study was to evaluate cardiac size and early growth through echocardiographic, body weight (BW), body condition score (BCS), morphometric and biomarker changes in cats followed from 6 to 24 months of age. METHODS: Twenty-four female European shorthair colony cats were evaluated at birth for BW and at 6, 12, 18 and 24 months of age for BW, BCS, head length (HL) and head width (HW), N-terminal pro B-type natriuretic peptide (NT-proBNP), insulin-like growth factor-1 (IGF-1) and echocardiographic measurements. RESULTS: BCS, HW, left ventricular free wall in diastole, left atrium diameter and aortic diameter increased significantly between 6 and 12 months, while BW, HL and interventricular septum in diastole increased significantly between 6, 12 and 18 months, and BW decreased significantly between 18 and 24 months. NT-proBNP decreased significantly between 6 and 12 months. IGF-1 increased significantly between 6 and 12 months but decreased significantly between 12 and 18 months. CONCLUSIONS AND RELEVANCE: This study prospectively evaluated changes in echocardiographic measurements, BW, BCS, HL, HW, IGF-1 and NT-proBNP in cats during the first 2 years of life. Results show a comparable change over time for different variables. These findings contribute to the understanding of a possible relationship between cardiac measures and body size from young age through to adulthood.

A comparison of treatment planning techniques for low-dose-rate (LDR) prostate brachytherapy.

PURPOSE: The purpose of this study was to compare low-dose-rate prostate brachytherapy treatment plans created using three retrospectively applied planning techniques with plans delivered to patients. METHODS AND MATERIALS: Treatment plans were created retrospectively on transrectal ultrasound (TRUS) scans for 26 patients. The technique dubbed 4D Brachytherapy was applied, using TRUS and MRI to obtain prostatic measurements required for the associated webBXT online nomogram. Using a patient's MRI scan to create a treatment plan involving loose seeds was also explored. Plans delivered to patients were made using an intraoperative loose seed TRUS-based planning technique. Prostate V100 (%), prostate V150 (%), prostate D90 (Gy), rectum D0.1cc (Gy), rectum D2cc (Gy), urethra D10 (%), urethra D30 (%), and prostate volumes were measured for each patient. Statistical analysis was used to assess and compare plans. RESULTS: Prostate volumes measured by TRUS and MRI were significantly different. Prostate volumes calculated by the webBXT online nomogram using TRUS- and MRI-based measurements were not significantly different. Compared with delivered plans, TRUS-based 4D Brachytherapy plans showed significantly lower rectum D0.1cc (Gy) values, MRI-based 4D Brachytherapy plans showed significantly higher prostate V100 (%) values and significantly lower rectum D0.1cc (Gy), urethra D10 (%), and urethra D30 (%) values, and loose seed MRI-based plans showed significantly lower prostate V100 (%), prostate D90 (Gy), rectum D0.1cc (Gy), rectum D2cc (Gy), urethra D10 (%), and urethra D30 (%) values. CONCLUSIONS: TRUS-based 4D Brachytherapy plans showed similar dosimetry to delivered plans; rectal dosimetry was superior. MRI can be integrated into the 4D Brachytherapy workflow. The webBXT online nomogram overestimates the required number of seeds.

Blood taurine concentrations in dogs with exocrine pancreatic insufficiency.

OBJECTIVE: To determine whether blood taurine concentrations in dogs with exocrine pancreatic insufficiency (EPI) were lower than the reference interval (200 to 350 nmol/mL) or the cutoff used to indicate taurine deficiency (< 150 nmol/mL). ANIMALS: 18 dogs with clinical or presumptive subclinical EPI with residual blood samples available for taurine concentration analysis. PROCEDURES: Dogs were classified as having clinical EPI if they had a serum trypsin-like immunoreactivity concentration of < 2.0 µg/L and presumptive subclinical EPI if they had a concentration of 2.0 to 5.0 µg/L. Archived, frozen blood samples stored in EDTA were submitted for measurement of taurine concentration with an automated high-performance liquid chromatography amino acid analyzer. Medical record data were examined for associations with blood taurine concentration. RESULTS: None of the 18 dogs had a blood taurine concentration < 150 nmol/mL. Two dogs had a concentration < 200 nmol/mL. No clinical signs, physical examination findings, or serum biochemical abnormalities were associated with blood taurine concentration. Eleven of the 17 dogs for which diet histories were available were not receiving a diet that met recommendations of the World Small Animal Veterinary Association Global Nutrition Committee. CONCLUSIONS AND CLINICAL RELEVANCE: A low blood taurine concentration was noted in a small subset of dogs with EPI. Additional research is needed to determine whether EPI was the primary cause of this low concentration. Findings suggested the importance of obtaining complete diet histories and ensuring dietary requirements are sufficiently met in dogs with EPI. (Am J Vet Res 2020;81:958-963).

Large Animal Models in Regenerative Medicine and Tissue Engineering: To Do or Not to Do.

Rapid developments in Regenerative Medicine and Tissue Engineering has witnessed an increasing drive toward clinical translation of breakthrough technologies. However, the progression of promising preclinical data to achieve successful clinical market authorisation remains a bottleneck. One hurdle for progress to the clinic is the transition from small animal research to advanced preclinical studies in large animals to test safety and efficacy of products. Notwithstanding this, to draw meaningful and reliable conclusions from animal experiments it is critical that the species and disease model of choice is relevant to answer the research question as well as the clinical problem. Selecting the most appropriate animal model requires in-depth knowledge of specific species and breeds to ascertain the adequacy of the model and outcome measures that closely mirror the clinical situation. Traditional reductionist approaches in animal experiments, which often do not sufficiently reflect the studied disease, are still the norm and can result in a disconnect in outcomes observed between animal studies and clinical trials. To address these concerns a reconsideration in approach will be required. This should include a stepwise approach using in vitro and ex vivo experiments as well as in silico modeling to minimize the need for in vivo studies for screening and early development studies, followed by large animal models which more closely resemble human disease. Naturally occurring, or spontaneous diseases in large animals remain a largely untapped resource, and given the similarities in pathophysiology to humans they not only allow for studying new treatment strategies but also disease etiology and prevention. Naturally occurring disease models, particularly for longer lived large animal species, allow for studying disorders at an age when the disease is most prevalent. As these diseases are usually also a concern in the chosen veterinary species they would be beneficiaries of newly developed therapies. Improved awareness of the progress in animal models is mutually beneficial for animals, researchers, human and veterinary patients. In this overview we describe advantages and disadvantages of various animal models including domesticated and companion animals used in regenerative medicine and tissue engineering to provide an informed choice of disease-relevant animal models.

The gut microbiome in dogs with congestive heart failure: a pilot study.

Compromised gut health and dysbiosis in people with heart failure has received a great deal of attention over the last decade. Whether dogs with heart failure have a similar dysbiosis pattern to what is described in people is currently unknown. We hypothesised that dogs with congestive heart failure have quantifiable dysbiosis compared to healthy dogs that are similar in sex and age. A total of 50 dogs (15 healthy dogs and 35 dogs with congestive heart failure) were prospectively recruited, and their faecal gut microbiome was assessed using 16S rRNA sequencing (Illumina MiSeq platform). There was no significant change in the microbial diversity and richness in dogs with congestive heart failure. However, there was an increase in abundance of Proteobacteria in the congestive heart failure group (p = 0.014), particularly due to an increase in the family Enterobacteriaceae (p = 0.002) and Escherichia coli (p = 0.033). We conclude that dogs with congestive heart failure have dysbiosis, and we show additional trends in our data suggesting that dogs may have a similar pattern to that described in people. The results of this study provide useful preliminary information and raise the possibility that dogs represent a clinically relevant animal model of dysbiosis in people with heart failure.