Unbiased serum metabolomic analysis in cats with naturally occurring chronic enteropathies before and after medical intervention.

Chronic enteropathies (CE) are common disorders in cats and the differentiation between the two main underlying diseases, inflammatory bowel disease (IBD) and low-grade intestinal T-cell lymphoma (LGITL), can be challenging. Characterization of the serum metabolome could provide further information on alterations of disease-associated metabolic pathways and may identify diagnostic or therapeutic targets. Unbiased metabolomics analysis of serum from 28 cats with CE (14 cats with IBD, 14 cats with LGITL) and 14 healthy controls identified 1,007 named metabolites, of which 129 were significantly different in cats with CE compared to healthy controls at baseline. Random Forest analysis revealed a predictive accuracy of 90% for differentiating controls from cats with chronic enteropathy. Metabolic pathways found to be significantly altered included phospholipids, amino acids, thiamine, and tryptophan metabolism. Several metabolites were found to be significantly different between cats with IBD versus LGITL, including several sphingolipids, phosphatidylcholine 40:7, uridine, pinitol, 3,4-dihydroxybenzoic acid, and glucuronic acid. However, random forest analysis revealed a poor group predictive accuracy of 60% for the differentiation of IBD from LGITL. Of 129 compounds found to be significantly different between healthy cats and cats with CE at baseline, 58 remained different following treatment.

A multi-disciplinary commentary on preclinical research to investigate vascular contributions to dementia.

Although dementia research has been dominated by Alzheimer's disease (AD), most dementia in older people is now recognised to be due to mixed pathologies, usually combining vascular and AD brain pathology. Vascular cognitive impairment (VCI), which encompasses vascular dementia (VaD) is the second most common type of dementia. Models of VCI have been delayed by limited understanding of the underlying aetiology and pathogenesis. This review by a multidisciplinary, diverse (in terms of sex, geography and career stage), cross-institute team provides a perspective on limitations to current VCI models and recommendations for improving translation and reproducibility. We discuss reproducibility, clinical features of VCI and corresponding assessments in models, human pathology, bioinformatics approaches, and data sharing. We offer recommendations for future research, particularly focusing on small vessel disease as a main underpinning disorder.

Fecal Concentrations of Long-Chain Fatty Acids, Sterols, and Unconjugated Bile Acids in Cats with Chronic Enteropathy.

Chronic enteropathy (CE) in cats encompasses food-responsive enteropathy, chronic inflammatory enteropathy (or inflammatory bowel disease), and low-grade intestinal T-cell lymphoma. While alterations in the gut metabolome have been extensively studied in humans and dogs with gastrointestinal disorders, little is known about the specific metabolic profile of cats with CE. As lipids take part in energy storage, inflammation, and cellular structure, investigating the lipid profile in cats with CE is crucial. This study aimed to measure fecal concentrations of various fatty acids, sterols, and bile acids. Fecal samples from 56 cats with CE and 77 healthy control cats were analyzed using gas chromatography-mass spectrometry, targeting 12 fatty acids, 10 sterols, and 5 unconjugated bile acids. Fecal concentrations of nine targeted fatty acids and animal-derived sterols were significantly increased in cats with CE. However, fecal concentrations of plant-derived sterols were significantly decreased in cats with CE. Additionally, an increased percentage of primary bile acids was observed in a subset of cats with CE. These findings suggest the presence of lipid maldigestion, malabsorption, and inflammation in the gastrointestinal tract of cats with CE. Understanding the lipid alterations in cats with CE can provide insights into the disease mechanisms and potential future therapeutic strategies.

Dysbiosis index to evaluate the fecal microbiota in healthy cats and cats with chronic enteropathies.

OBJECTIVES: Previous studies have identified various bacterial taxa that are altered in cats with chronic enteropathies (CE) vs healthy cats. Therefore, the aim of this study was to develop a targeted quantitative molecular method to evaluate the fecal microbiota of cats. METHODS: Fecal samples from 80 client-owned healthy cats and 68 cats with CE were retrospectively evaluated. A panel of quantitative PCR (qPCR) assays was used to measure the fecal abundance of total bacteria and seven bacterial taxa: Bacteroides, Bifidobacterium, Clostridium hiranonis, Escherichia coli, Faecalibacterium, Streptococcus and Turicibacter. The nearest centroid classifier algorithm was used to calculate a dysbiosis index (DI) based on these qPCR abundances. RESULTS: The abundances of total bacteria, Bacteroides, Bifidobacterium, C hiranonis, Faecalibacterium and Turicibacter were significantly decreased, while those of E coli and Streptococcus were significantly increased in cats with CE (P <0.027 for all). The DI in cats with CE was significantly higher compared with healthy cats (P <0.001). When the cut-off value of the DI was set at 0, it provided 77% (95% confidence interval [CI] 66-85) sensitivity and 96% (95% CI 89-99) specificity to differentiate the microbiota of cats with CE from those of healthy cats. Fifty-two of 68 cats with CE had a DI >0. CONCLUSIONS AND RELEVANCE: A qPCR-based DI for assessing the fecal microbiota of cats was established. The results showed that a large proportion of cats with CE had an altered fecal microbiota as evidenced by an increased DI. Prospective studies are warranted to evaluate the utility of this assay for clinical assessment of feline CE.

Long-Term Recovery of the Fecal Microbiome and Metabolome of Dogs with Steroid-Responsive Enteropathy.

The long-term impact of treatment of dogs with steroid-responsive enteropathy (SRE) on the fecal microbiome and metabolome has not been investigated. Therefore, this study aimed to evaluate the fecal microbiome and metabolome of dogs with SRE before, during, and following treatment with standard immunosuppressive therapy and an elimination diet. We retrospectively selected samples from 9 dogs with SRE enrolled in a previous clinical trial, which received treatment for 8 weeks, and had achieved remission as indicated by the post-treatment clinical scores. Long-term (1 year) samples were obtained from a subset (5/9) of dogs. Samples from 13 healthy dogs were included as controls (HC). We evaluated the microbiome using 16S rRNA sequencing and qPCR. To evaluate the recovery of gut function, we measured fecal metabolites using an untargeted approach. While improvement was observed for some bacterial taxa after 8 weeks of treatment, several bacterial taxa remained significantly different from HC. Seventy-five metabolites were altered in dogs with SRE, including increased fecal amino acids and vitamins, suggesting malabsorption as a component of SRE. One year after treatment, however, all bacterial species were evaluated by qPCR and 16S rRNA gene sequencing, and all but thirteen metabolites were no longer different from healthy controls.

UK Vessel Health and Preservation (VHP) Framework: a commentary on the updated VHP 2020.

BACKGROUND: In 2016, a UK vessel health and preservation (VHP) framework was developed to support healthcare staff to select the most appropriate vascular access device for patients requiring intravenous therapy. The VHP framework was based on available evidence and expert consensus. The VHP was based on available evidence and expert consensus. DEVELOPMENT OF THE VHP 2020 FRAMEWORK: A multidisciplinary team reviewed the original UK VHP framework and considered new published evidence, national and international guidelines and expert opinion. A literature search was performed using Cinahl and Medline, incorporating a variety of terms linked to vascular access devices, assessment and selection. Articles published in and after 2014 in English were included. Twelve articles were found to be relevant including three evidence-based guidelines, two randomised control trials and one systematic review. FINDINGS: Three main studies provided the evidence for the update: the MAGIC study that assessed the appropriateness of peripherally inserted central catheters in patients; a study that utilised the 'A-DIVA scale' to predict the likelihood of difficult venous access; and a study that incorporated an 'I-DECIDED tool' for peripheral intravenous catheter assessment and decision-making for device removal. In addition, published guidelines provided evidence that the original advice on appropriate osmolarity of medicines for peripheral administration needed updating. CONCLUSION: The 2020 UK VHP framework reflects latest evidence-based research and guidelines, providing healthcare staff updated guidance to assist in maintaining good practice in vascular access assessment and device selection and patient safety.

Central venous access devices for the delivery of systemic anticancer therapy (CAVA): a randomised controlled trial.

BACKGROUND: Hickman-type tunnelled catheters (Hickman), peripherally inserted central catheters (PICCs), and totally implanted ports (PORTs) are used to deliver systemic anticancer treatment (SACT) via a central vein. We aimed to compare complication rates and costs of the three devices to establish acceptability, clinical effectiveness, and cost-effectiveness of the devices for patients receiving SACT. METHODS: We did an open-label, multicentre, randomised controlled trial (Cancer and Venous Access [CAVA]) of three central venous access devices: PICCs versus Hickman (non-inferiority; 10% margin); PORTs versus Hickman (superiority; 15% margin); and PORTs versus PICCs (superiority; 15% margin). Adults (aged ≥18 years) receiving SACT (≥12 weeks) for solid or haematological malignancy from 18 oncology units in the UK were included. Four randomisation options were available: Hickman versus PICCs versus PORTs (2:2:1), PICCs versus Hickman (1:1), PORTs versus Hickman (1:1), and PORTs versus PICCs (1:1). Randomisation was done using a minimisation algorithm stratifying by centre, body-mass index, type of cancer, device history, and treatment mode. The primary outcome was complication rate (composite of infection, venous thrombosis, pulmonary embolus, inability to aspirate blood, mechanical failure, and other) assessed until device removal, withdrawal from study, or 1-year follow-up. This study is registered with ISRCTN, ISRCTN44504648. FINDINGS: Between Nov 8, 2013, and Feb 28, 2018, of 2714 individuals screened for eligibility, 1061 were enrolled and randomly assigned, contributing to the relevant comparison or comparisons (PICC vs Hickman n=424, 212 [50%] on PICC and 212 [50%] on Hickman; PORT vs Hickman n=556, 253 [46%] on PORT and 303 [54%] on Hickman; and PORT vs PICC n=346, 147 [42%] on PORT and 199 [58%] on PICC). Similar complication rates were observed for PICCs (110 [52%] of 212) and Hickman (103 [49%] of 212). Although the observed difference was less than 10%, non-inferiority of PICCs was not confirmed (odds ratio [OR] 1·15 [95% CI 0·78-1·71]) potentially due to inadequate power. PORTs were superior to Hickman with a complication rate of 29% (73 of 253) versus 43% (131 of 303; OR 0·54 [95% CI 0·37-0·77]). PORTs were superior to PICCs with a complication rate of 32% (47 of 147) versus 47% (93 of 199; OR 0·52 [0·33-0·83]). INTERPRETATION: For most patients receiving SACT, PORTs are more effective and safer than both Hickman and PICCs. Our findings suggest that most patients receiving SACT for solid tumours should receive a PORT within the UK National Health Service. FUNDING: UK National Institute for Health Research Health Technology Assessment Programme.

Untargeted metabolomic analysis in cats with naturally occurring inflammatory bowel disease and alimentary small cell lymphoma.

Feline chronic enteropathy (CE) is a common gastrointestinal disorder in cats and mainly comprises inflammatory bowel disease (IBD) and small cell lymphoma (SCL). Differentiation between IBD and SCL can be diagnostically challenging. We characterized the fecal metabolome of 14 healthy cats and 22 cats with naturally occurring CE (11 cats with IBD and 11 cats with SCL). Principal component analysis and heat map analysis showed distinct clustering between cats with CE and healthy controls. Random forest classification revealed good group prediction for healthy cats and cats with CE, with an overall out-of-bag error rate of 16.7%. Univariate analysis indicated that levels of 84 compounds in cats with CE differed from those in healthy cats. Polyunsaturated fatty acids held discriminatory power in differentiating IBD from SCL. Metabolomic profiles of cats with CE resembled those in people with CE with significant alterations of metabolites related to tryptophan, arachidonic acid, and glutathione pathways.

ACVIM consensus statement on pancreatitis in cats.

BACKGROUND: Pancreatitis in cats, although commonly diagnosed, still presents many diagnostic and management challenges. OBJECTIVE: To summarize the current literature as it relates to etiology, pathogenesis, diagnosis, and management of pancreatitis in cats and to arrive at clinically relevant suggestions for veterinary clinicians that are based on evidence, and where such evidence is lacking, based on consensus of experts in the field. ANIMALS: None. METHODS: A panel of 8 experts in the field (5 internists, 1 radiologist, 1 clinical pathologist, and 1 anatomic pathologist), with support from a librarian, was formed to assess and summarize evidence in the peer reviewed literature and complement it with consensus clinical recommendations. RESULTS: There was little literature on the etiology and pathogenesis of spontaneous pancreatitis in cats, but there was much in the literature about the disease in humans, along with some experimental evidence in cats and nonfeline species. Most evidence was in the area of diagnosis of pancreatitis in cats, which was summarized carefully. In contrast, there was little evidence on the management of pancreatitis in cats. CONCLUSIONS AND CLINICAL IMPORTANCE: Pancreatitis is amenable to antemortem diagnosis by integrating all clinical and diagnostic information available, and recognizing that acute pancreatitis is far easier to diagnose than chronic pancreatitis. Although both forms of pancreatitis can be managed successfully in many cats, management measures are far less clearly defined for chronic pancreatitis.

Characterization of the intestinal mucosal proteome in cats with inflammatory bowel disease and alimentary small cell lymphoma.

BACKGROUND: Current tests for diagnosis and differentiation of lymphoplasmacytic enteritis (LPE) and small cell lymphoma (SCL) in cats are expensive, invasive, and lack specificity. The identification of less invasive, more reliable biomarkers would facilitate diagnosis. OBJECTIVES: To characterize the mucosal proteome in endoscopically obtained, small intestinal tissue biopsy specimens. We hypothesized that differentially expressed proteins could be identified and serve as biomarker candidates for the differentiation of LPE and SCL in cats. ANIMALS: Six healthy control cats, 6 cats with LPE, and 8 cats with SCL. METHODS: The mucosal proteome was analyzed using 2-dimensional fluorescence difference gel electrophoresis (2D DIGE) and nanoflow liquid chromatography tandem mass spectrometry. For 5 proteins, results were verified by Western blot analysis. RESULTS: A total of 2349 spots were identified, of which 9 were differentially expressed with a ≥2-fold change between healthy cats and cats with LPE and SCL (.01 < P < .001). Eight of these 9 spots were also differentially expressed between cats with LPE and cats with SCL (P .001 < P < .04). However, Western blot analysis for malate dehydrogenase-1, malate dehydrogenase-2, apolipoprotein, annexin IV, and annexin V did not confirm significant differential protein expression for any of the 5 proteins assessed. CONCLUSIONS AND CLINICAL IMPORTANCE: Two-D DIGE did not identify potential biomarker candidates in the intestinal mucosa of cats with LPE and SCL. Future studies should focus on different techniques to identify biomarker candidates for cats with chronic enteropathies (CE).

Prospective Audit to Study urokinaSe use to restore Patency in Occluded centRal venous caTheters in haematology and oncology patients (PASSPORT 2).

BACKGROUND: Central venous catheter dysfunction may be associated with intraluminal clots, drug precipitates and lipid residues or extra luminal causes such as fibroblastic sleeve, tip malposition, pinch-off syndrome and venous thrombosis at the tip of central venous catheter. Failure to restore patency after addressing these causes, empirical treatment with thrombolytic agents should be considered. Urokinase is used widely as a thrombolytic agent but very few outcome studies have been published. METHODS: A multicentre group conducted a prospective audit of management of central venous catheter dysfunction after exclusion of common causes using in centre standardised doses of urokinase from September 2017 to February 2018 in haematology and oncology units. Data of catheter blood flow were collected anonymously following administration of 5000- to 25,000-IU urokinase in dysfunctional central venous catheter. RESULTS: A total of 117 patients were recruited from eight centres, 54 females and 63 males, median age was 60 (46-68). In total, 53% presented as partial withdrawal occlusion and 47% total occlusion. In partial withdrawal occlusion, patency was restored in 80% of interventions, in 82% of interventions using push lock and in 76% using dwell lock. In total occlusion, patency was restored in 88% of the interventions. The central venous catheter clearance rate was dose dependent; patency was restored in 83% of central venous catheter with 5000 IU, 89% with 10,000 IU and 92% with high dose of 25,000 IU. No adverse events were recorded. CONCLUSION: In this study, treatment of dysfunctional central venous catheter using standardised urokinase doses was safe and effective in restoring patency when no other mechanical causes could account for central venous catheter dysfunction.

Comprehensive comparison of upper and lower endoscopic small intestinal biopsy in cats with chronic enteropathy.

BACKGROUND: Integrating immunohistochemistry (IHC) and clonality testing with histopathology may improve the ability to differentiate inflammatory bowel disease (IBD) and alimentary small cell lymphoma (LSA) in cats. HYPOTHESIS/OBJECTIVES: To evaluate the utility of histopathology, IHC, and clonality testing to differentiate between IBD and LSA and agreement of diagnostic results for endoscopic biopsy (EB) samples from the upper (USI) and lower small intestine (LSI). ANIMALS: Fifty-seven cats with IBD or LSA. METHODS: All cases were categorized as definitive IBD (DefIBD), possible LSA (PossLSA), probable LSA (ProbLSA), or definitive LSA (DefLSA) based on histopathology alone. Results from IHC and clonality testing were integrated. RESULTS: Based on histopathology alone, 24/57 (42.1%), 15/57 (26.3%), and 18/57 (31.6%) cats were diagnosed with DefIBD, PossLSA or ProbLSA, and DefLSA, respectively. After integrating IHC and clonality testing, 11/24 cases (45.8%) and 15/15 cases (100%) previously categorized as DefIBD and PossLSA or ProbLSA, respectively, were reclassified as LSA. A final diagnosis of IBD and LSA was reported in 13/57 (22.8%) and 44/57 (77.2%) cats, respectively. Agreement between USI and LSI samples was moderate based on histopathology alone (κ = 0.66) and after integrating IHC and clonality testing (κ = 0.70). However, only 1/44 (2.3%) of the LSA cases was diagnosed based on LSI biopsy alone. CONCLUSIONS AND CLINICAL IMPORTANCE: Integrating IHC and clonality testing increased the number of cases diagnosed with LSA, but the consequence for patient outcome is unclear. There was moderate agreement between USI and LSI samples. Samples from the LSI rarely changed the diagnosis.

Characterization of the fecal microbiome in cats with inflammatory bowel disease or alimentary small cell lymphoma.

Feline chronic enteropathy (CE) is a common gastrointestinal disorder in cats and mainly comprises inflammatory bowel disease (IBD) and small cell lymphoma (SCL). Both IBD and SCL in cats share features with chronic enteropathies such as IBD and monomorphic epitheliotropic intestinal T-cell lymphoma in humans. The aim of this study was to characterize the fecal microbiome of 38 healthy cats and 27 cats with CE (13 cats with IBD and 14 cats with SCL). Alpha diversity indices were significantly decreased in cats with CE (OTU p = 0.003, Shannon Index p = 0.008, Phylogenetic Diversity p = 0.019). ANOSIM showed a significant difference in bacterial communities, albeit with a small effect size (P = 0.023, R = 0.073). Univariate analysis and LEfSE showed a lower abundance of facultative anaerobic taxa of the phyla Firmicutes (families Ruminococcaceae and Turicibacteraceae), Actinobacteria (genus Bifidobacterium) and Bacteroidetes (i.a. Bacteroides plebeius) in cats with CE. The facultative anaerobic taxa Enterobacteriaceae and Streptococcaceae were increased in cats with CE. No significant difference between the microbiome of cats with IBD and those with SCL was found. Cats with CE showed patterns of dysbiosis similar to those in found people with IBD.

Central venous access device-related sheaths: a predictor of infective and thrombotic incidence?

Central vascular access device (CVAD)-related sheaths, sometimes described as 'fibrin sheaths', may result in minor or significant sequelae, from persistent withdrawal occlusion (PWO) to infective sheaths associated with increased morbidity and mortality. The authors studied 179 patients who underwent isotope scans, where isotope was infused via the CVAD. Isotope was found to bind to the sheaths around the catheters of some patients. The amount of uptake was taken to be an extent to which a sheath had developed around the CVAD. The degree of uptake of isotope was categorised into three groups: low uptake, moderate uptake and high uptake. Patients were then followed up from the date the CVAD was inserted to 12 months after the date of the isotope scan, until the device was removed or to the date the patient died, to identify incidence of infection, thrombosis and PWO. PWO incidence in all levels of uptake was around 5-7%. Bloodstream infection (BSI) incidence for low uptake was 7% (9/130), moderate uptake 10% (3/30) and for patients with significant uptake 16% (3/19). Thrombosis for no uptake was less than 1% (1/130), moderate uptake 7% (2/30), and significant uptake had no incidence of thrombosis. Total complications: no uptake 15%, moderate uptake 23% and significant uptake 21%. This single-centre study showed that patients with isotope-highlighted sheaths experienced higher incidence of infective, thrombotic and total complications.

Longitudinal assessment of microbial dysbiosis, fecal unconjugated bile acid concentrations, and disease activity in dogs with steroid-responsive chronic inflammatory enteropathy.

BACKGROUND: Mounting evidence from human studies suggests that bile acid dysmetabolism might play a role in various human chronic gastrointestinal diseases. It is unknown whether fecal bile acid dysmetabolism occurs in dogs with chronic inflammatory enteropathy (CE). OBJECTIVE: To assess microbial dysbiosis, fecal unconjugated bile acids (fUBA), and disease activity in dogs with steroid-responsive CE. ANIMALS: Twenty-four healthy control dogs and 23 dogs with steroid-responsive CE. METHODS: In this retrospective study, fUBA were measured and analyzed. Fecal microbiota were assessed using a dysbiosis index. The canine inflammatory bowel disease activity index was used to evaluate remission of clinical signs. This was a multi-institutional study where dogs with steroid-responsive CE were evaluated over time. RESULTS: The dysbiosis index was increased in dogs with CE (median, 2.5; range, -6.2 to 6.5) at baseline compared with healthy dogs (median, -4.5; range, -6.5 to -2.6; P = .002) but did not change in dogs with CE over time. Secondary fUBA were decreased in dogs with CE (median, 29%; range, 1%-99%) compared with healthy dogs (median, 88%; 4%-96%; P = .049). The percent of secondary fUBA in dogs with CE increased from baseline values (median, 28%; range, 1%-99%) after 2-3 months of treatment (median, 94%; range, 1%-99%; P = 0.0183). CONCLUSIONS AND CLINICAL IMPORTANCE: These findings suggest that corticosteroids regulate fecal bile acids in dogs with CE. Additionally, resolution of clinical activity index in dogs with therapeutically managed CE and bile acid dysmetabolism are likely correlated. However, subclinical disease (i.e., microbial dysbiosis) can persist in dogs with steroid-responsive CE.

Altered lipoprotein profiles in cats with hepatic lipidosis.

OBJECTIVES: The aim of this study was to assess serum lipoprotein profiles using rapid single-spin continuous lipoprotein density profiling (CLPDP) in healthy control cats and cats with hepatic lipidosis (HL). METHODS: Analysis of serum lipoprotein profiles using the CLPDP was performed in 23 cats with HL and 20 healthy control cats. The area under the curve for each lipoprotein fraction, triglyceride (TG)-rich lipoproteins (TRLs), low-density lipoproteins (LDLs) and high-density lipoproteins (HDLs), was calculated. Serum cholesterol and TG concentrations were measured using a clinical chemistry analyzer. RESULTS: Serum cholesterol and TG concentrations were not significantly different between healthy control cats and cats with HL ( P = 0.5075 and P = 0.2541, respectively). LDL content was significantly higher in cats with HL than in healthy control cats ( P = 0.0001), while HDL content was significantly lower in cats with HL than in healthy control cats ( P = 0.0032). TRL content was not significantly different between the two groups ( P = 0.0699). The specific fraction (1.037-1.043 g/ml) within nominal LDL in serum distinguished healthy control cats from cats with HL with a sensitivity of 87% and a specificity of 90%. CONCLUSIONS AND RELEVANCE: Serum lipoprotein profiles were altered in cats with HL, even though serum cholesterol and TG concentrations were not significantly different compared with healthy control cats. The CLPDP might be a useful tool for assessing lipid metabolism in cats with HL.

Arterial blood gas sampling: using a safety and pre-heparinised syringe.

Taking arterial blood gases (ABG) is an essential part of the diagnosis and management of critically ill patients. An arterial blood sample is collected from an artery, primarily to determine the ABGs. Health professionals should only undertake this if the procedure is in the legal scope of practice for their profession in their country, and they have demonstrated skilled, proficient, safe practice after formal training. Blood samples can be obtained via an arterial catheter inserted into an artery or percutaneously by using a needle to directly puncture into the artery. This article provides an overview of this subject area. It includes case studies where the Pulsator Plus Arterial Blood Gas Syringe (Smiths Medical) was used to safely and effectively collect blood samples for analysis.