Documentation of results and medication prescribing after combinatorial psychiatric pharmacogenetic testing: A case for discrete results.

PURPOSE: Combinatorial pharmacogenetic (PGx) panels intended to aid psychiatric prescribing are available to clinicians. Here, we evaluated the documentation of PGx panel results and subsequent prescribing patterns within a tertiary health care system. METHODS: We performed a query of psychiatry service note text in our electronic health record using 71 predefined PGx terms. Patients who underwent combinatorial PGx testing were identified, and documentation of test results was analyzed. Prescription data following testing were examined for the frequency of prescriptions influenced by genes on the panel along with the medical specialties involved. RESULTS: A total of 341 patients received combinatorial PGx testing, and documentation of results was found to be absent or incomplete for 198 patients (58%). The predominant method of documentation was through portable document formats uploaded to the electronic health record's "Media" section. Among patients with at least 1 year of follow-up, a large majority (194/228, 85%) received orders for medications affected by the tested genes, including 132 of 228 (58%) patients receiving at least 1 non-psychiatric medication influenced by the test results. CONCLUSION: Results from combinatorial PGx testing were poorly documented. Medications affected by these results were often prescribed after testing, highlighting the need for discrete results and clinical decision support.

Patient and Physician Perspectives on Discussing Addiction Recovery and Spirituality in the Primary Care Setting.

BACKGROUND: Spirituality is an important component of recovery for many individuals with substance use disorder (SUD). However, few studies have compared patient and physician attitudes on spirituality in SUD recovery. OBJECTIVE: This study investigates patient and physician beliefs about the role of spirituality in SUD recovery and about discussing spirituality in relationship to recovery in primary care settings. DESIGN: Semi-structured interviews were conducted with primary care physicians recruited at two academic hospitals, and patients recruited from a faith-based residential therapeutic community. Interview transcripts were independently coded by two researchers and a grounded theory approach was used to generate themes that reflected participants' experiences. KEY RESULTS: Interviews were conducted with 15 patients and 10 physicians. Patients had diverse views about the impact of spirituality on their SUD recovery, including positive, negative, and neutral. Patient and physician opinions on discussing spirituality in a primary care setting differed: most physicians felt positively towards this, believing that understanding their patients' spirituality helped them care for their patients as whole people. Many patients felt neutral, stating that they did not feel like these conversations were necessary for their care, and that they believed physicians preferred not to discuss spirituality in medical settings. Tolerance from both the patient and physician, open-ended questioning, and an individualized approach were identified as facilitators to effective discussions about spirituality and recovery. CONCLUSIONS: Spirituality can have diverse effects on an individual's SUD recovery. Physicians endorsed the benefits of discussing spirituality in the context of their patients' recovery, while patients expressed reservations about engaging in these conversations with their physicians. This variation in perspectives highlights the need for additional research to understand the individual and structural factors that contribute to it, as well as best practices for engaging in effective, non-judgmental conversations about spirituality in recovery.

Low alanine aminotransferase activity gene variant in a Siberian Husky with copper-associated hepatopathy.

BACKGROUND: Alanine aminotransferase (ALT) is commonly used as a marker of hepatocellular injury. Increased serum ALT activity due to hepatocyte injury occurs in copper-associated hepatopathy (CuCH) and other necroinflammatory liver conditions. Blood ALT concentrations are frequently used to monitor therapy in cases of CuCH. Low serum ALT activities have been associated with an allele at a CFA13 locus. CASE PRESENTATION: A 9-year-old female spayed Siberian Husky was diagnosed with CuCH (hepatic copper dry weight 2680 µg/g [normal, 120-400 µg/g; toxic, > 1500 µg/g]) and a normal ALT (78 U/L; reference range, 10-125 U/L). Mild hepatocellular necrosis was evident histologically. Genetic testing (Embark) revealed that the dog was heterozygous for the low ALT activity gene allele. CONCLUSIONS: This case report illustrates the clinical implications for diagnosing and managing necroinflammatory liver disease such as CuCH in dogs with a low ALT activity genotype.

Laparoscopic vertical sleeve gastrectomy in felines: A cadaveric feasibility study and experimental case series in two cats.

OBJECTIVE: To evaluate the feasibility of laparoscopic vertical sleeve gastrectomy (LVSG) in feline cadavers using endoscopic stapling equipment and report clinical outcomes in two live feline subjects. STUDY DESIGN: Cadaveric study and experimental case series. ANIMALS: Ten feline cadavers; two feline subjects. METHODS: LVSG technique was refined on feline cadavers and included retraction of the liver, dissection of the stomach, assessment of proper location for gastrectomy via stapling, and leak testing. Appropriateness of gastrectomy, gastrectomy %, surgical times and complications were recorded. The procedure was performed on two live feline subjects, and they were followed for 4 months to report surgical complications. RESULTS: LVSG was completed in 9/10 cadavers and both live patients. Stenosis at the incisura was recorded in 2/9 cadavers. No obvious leaks were seen in the 8 cadavers that were tested or either live patient. The mean surgical time for all cadaver procedures and live patients was 110.4 and 115 minutes, respectively. Mean weight of resected cadaver stomach was 10 g and the mean % of the total stomach weight resected was 27.6%. No intra- or postoperative surgical complications occurred in the live subjects. CONCLUSION: LVSG technique appears feasible and safe for use in live patients. CLINICAL RELEVANCE: This LVSG technique may be safely used for partial gastric resection in cats. Further studies are necessary to determine if it is effective at reversing the effects of obesity and diabetes in this population.

Interfacial studies on the effects of patterned anodes for guided lithium deposition in lithium metal batteries.

The lifetime and health of lithium metal batteries are greatly hindered by nonuniform deposition and growth of lithium at the anode-electrolyte interface, which leads to dendrite formation, efficiency loss, and short circuiting. Lithium deposition is influenced by several factors including local current densities, overpotentials, surface heterogeneity, and lithium-ion concentrations. However, due to the embedded, dynamic nature of this interface, it is difficult to observe the complex physics operando. Here, we present a detailed model of the interface that implements Butler-Volmer kinetics to investigate the effects of overpotential and surface heterogeneities on dendrite growth. A high overpotential has been proposed as a contributing factor in increased nucleation and growth of dendrites. Using computational methods, we can isolate the aspects of the complex physics at the interface to gain better insight into how each component affects the overall system. In addition, studies have shown that mechanical modifications to the anode surface, such as micropatterning, are a potential way of controlling deposition and increasing Coulombic efficiency. Micropatterns on the anode surface are explored along with deformations in the solid-electrolyte interface layer to understand their effects on the dendritic growth rates and morphology. The study results show that at higher overpotentials, more dendritic growth and a more branched morphology are present in comparison to low overpotentials, where more uniform and denser growth is observed. In addition, the results suggest that there is a relationship between surface chemistries and anode geometries.

Rural Trauma Team Development Course Instills Confidence in Critical Access Hospitals.

PURPOSE: The American College of Surgeons' Rural Trauma Team Development Course (RTTDC) was designed to help rural hospitals optimize a team approach to trauma management recognizing the need for early transfer. Little literature exists on the success of RTTDC achieving its objectives. The purpose of this study was to determine the impact of RTTDC on rural trauma team members. METHODS: RTTDC was hosted at seven rural hospitals. A pre-course 30-question Likert survey gauging confidence managing trauma patients was administered to participants. Four weeks following, participants received a post-course survey with corresponding Likert questions and 11 trauma knowledge-based questions. Chi-square, Fisher's exact tests and general linear models were utilized. Statistical significance is set as p < 0.05. RESULTS: 111 participants completed the pre-course survey; 53 (48%) completed the post-course survey. Results presented on a 5-point Likert scale with 1 = "not at all comfortable" to 5 = "extremely comfortable." Participants knowing their role in the trauma team improved by 16% (p = 0.02). Familiarity with the roles of other trauma team members was significantly improved (3.4 vs. 4.15; p < 0.01). Participants comfort with resuscitating trauma patients and managing traumatic brain injury significantly improved (3.29 vs. 3.69; p = 0.01 and 2.62 vs. 3.14; p = 0.004, respectively). Comfortability communicating with the regional trauma center improved significantly (3.64 vs. 4.19; p = 0.004). Participant decision to transfer trauma patients within 15 min of arrival improved by 3.2%. Participants answered 82% of the knowledge-based questions correctly. CONCLUSION: RTTDC instills confidence in providers at rural hospitals. The information taught is well retained, allowing for quality care and timely patient transfer to the nearest trauma center.

Common bile duct obstruction palliated with common bile duct re-implantation (choledochoduodenostomy) in a cat.

A cat was presented with complete biliary obstruction at the level of the distal common bile duct (CBD), with loss of normal architecture. The area was excised and submitted for histopathology. Concurrent cholecystitis and gall bladder necrosis necessitated cholecystectomy. The proximal CBD was preserved and re-implanted adjacent to the original duodenal papilla. The cat recovered and remained asymptomatic for 6 months. At clinical relapse a carcinoma of suspected biliary origin was confirmed, and the cat was euthanized. In situations in which the CBD lumen cannot be re-established, the pathology is limited to the distal CBD, and the gall bladder is not available for cholecystoenterostomy, CBD re-implantation may be an option to salvage and retain a functional biliary tree.

Remédiation d'une obstruction du canal cholédoque par réimplantation du canal cholédoque (cholédochoduodenostomie) chez un chat. Un chat fut présenté avec une obstruction biliaire complète au niveau du canal cholédoque distal (CBD), avec perte de l'architecture normale. La région a été excisée et soumise pour examen histopathologique. Une cholécystite concomitante et une nécrose de la vésicule biliaire ont nécessité une cholécystectomie. Le CBD proximal fut préservé et réimplanté de manière adjacente à la papille duodénale originale. Le chat a récupéré et est demeuré asymptomatique pendant 6 mois. Lors d'une rechute clinique une suspicion de carcinome d'origine biliaire fut confirmée, et le chat euthanasié. Dans des situations où la lumière du CBD ne peut être ré-établie, que la pathologie est limitée au CBD distal, et que la vésicule biliaire n'est pas disponible pour une cholécystoenterostomie, la réimplantation du CBD peut être une option pour sauvegarder et maintenir un système biliaire fonctionnel.(Traduit par Dr Serge Messier).

Assessment of short reports using a human rights-based approach to tobacco control to the Commitee on Economics, Cultural and Social Rights.

BACKGROUND: The health impact of tobacco use remains a major global public health concern and a human rights issue. The Human Rights and Tobacco Control Network (HRTCN) was established to increase the visibility of tobacco as a human rights issue. HRTCN submitted short reports to the UN Committee on Economic Social and Cultural Rights evaluating individual nations' tobacco control policies and offering recommendations. METHODS: HRTCN reviewed Concluding Observations documents for nations for which the HRTCN submitted reports. If tobacco was mentioned in the Concluding Observations through acknowledging the Framework Convention on Tobacco Control ratification, policy changes or discussing tobacco in the recommendations, this was scored as a positive finding. HRTCN also reviewed Concluding Observations for nations for which HRTCN did not submit reports as a comparison. RESULTS: Thirty-eight HRTCN reports were submitted and tobacco was mentioned in Concluding Observations for 11 nations for a rate of 28.9%. In a comparison set of Concluding Observations (n=59), 7% had comments or recommendations relative to tobacco. CONCLUSIONS: This was not a controlled study and the 28.9% 'success rate' for impacting the Concluding Observations, although encouraging, is less than optimal-and leaves room for improvement. The higher rate of tobacco mentions for the cases where the HRTCN short reports were submitted provides preliminary indications that the short reports may have potential to increase the state focus on tobacco control. Future work will seek to improve the design and scope of the reports, and the specificity of the background information and recommendations offered.

Evaluation of plasma inflammatory cytokine concentrations in racing sled dogs.

In human athletes significant changes in cytokine concentrations secondary to exercise have been observed. This prospective study evaluated the effect of a multi-day stage sled dog race on plasma concentrations of monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor-alpha (TNF-α), interleukin-2 (IL-2), interleukin-6 (IL-6), interleukin-8 (IL-8), and interleukin-10 (IL-10). Samples from 20 dogs were harvested prior to and on days 2 and 8 of an 8-day race. Exercise resulted in significantly decreased TNF-α and IL-8 as well as increases of MCP-1, IL-6, and IL-10 concentrations (P-value between 0.01 and < 0.0001 for all parameters). The proportion of values for IL-2 that were below the detection limit increased from 40% on day 0 to 75% on day 2 and decreased on day 8 to 40% (P = 0.04). Racing sled dogs show cytokine-concentration changes that are different from those in humans.

Évaluation des concentrations plasmatiques de cytokines inflammatoires chez des chiens de traîneau de course. Chez les athlètes humains, des changements importants des concentrations de cytokines secondaires à l'exercice ont été observés. Cette étude prospective a évalué l'effet d'une course de chiens de traîneau par étapes de plusieurs jours sur les concentrations plasmatiques des protéines-1 chimio-attractives des monocytes (MCP-1), du facteur-alpha nécrosant des tumeurs (TNF-α), d'interleukine-2 (IL-2), d'interleukine-6 (IL-6), d'interleukine-8 (IL-8) et d'interleukine-10 (IL-10). Des échantillons ont été prélevés sur 20 chiens avant la course et aux jours 2 et 8 d'une course de 8 jours. L'exercice a produit des valeurs significativement réduites de TNF-α et d'IL-8 ainsi qu'une hausse des concentrations de MCP-1, d'IL-6 et d'IL-10 (la valeur-P entre 0,01 et < 0,0001 pour tous les paramètres). La proportion des valeurs pour IL-2 qui étaient inférieures au seuil de détection a augmenté de 40 % le jour 0 à 75 % le jour 2 et a baissé le jour 8 à 40 % (P = 0,04). Les chiens de traîneau de course montrent des changements de la concentration des cytokines qui sont différents de ceux observés chez les humains.(Traduit par Isabelle Vallières).

Imaging diagnosis--meningoencephalitis secondary to suppurative rhinitis and meningoencephalocele infection in a dog.

Nasal encephaloceles (meningoceles or meningoencephaloceles) are rare and not reported to be infected or coupled with a facial deformity in dogs. This report describes an older dog with acute worsening of seizures due to suppurative meningoencephalitis with coexisting suppurative rhinitis and infection of a meningoencephalocele. Additionally, the dog had a facial deformity for at least 5 years. The results of necropsy, computed tomography, and postmortem magnetic resonance imaging are compared. The development of nasal encephaloceles is discussed, including the potential role of early trauma, and whether separation of neural ectoderm from the surface ectoderm is part of the pathogenesis.

Short-term parenteral infusions with high-osmolality amino acid solutions can be safely administered through peripheral catheters in dogs treated for hypoaminoacidemia-related conditions.

OBJECTIVE: To compare complications between central and peripheral administration of high-osmolarity (approx 700 to 1,000 mOsm/L) amino acid (± lipid) infusions. ANIMALS: 18 client-owned dogs diagnosed with aminoaciduric canine hypoaminoacidemic hepatopathy syndrome or superficial necrolytic dermatitis receiving parenteral amino acid ± lipid infusions. METHODS: In this retrospective case series, medical records were reviewed for administration route (central vs peripheral), catheter details and infusion characteristics (product osmolarity, concurrent lipid administration, infusion volume, duration, and rate), and complications for each infusion. RESULTS: 18 dogs received 277 infusions (median, 8.5; range, 1 to 84). Effective infusion osmolarities were 683 mOsm/L in 22% of infusions, 791 mOsm/L in 8%, 802 mOsm/L in 2%, 837 mOsm/L in 45%, and 998 mOsm/L in 23% (65% peripheral, 35% central). Most (n = 230 [83%]) infusions were given peripherally. The osmolarities of solutions administered by each route (P = .53), the infusion rate indexed to body weight (P = .17), or the lipid infusion rates indexed to body weight (P = .89) did not differ. One dog suffered 2 complications in 63 infusions-1 mild, 1 severe-both occurring with peripheral infusions. Thus, the overall complication rate was 2 of 277 (0.9%) infusions. CLINICAL RELEVANCE: Short-term peripherally administered amino acid ± lipid infusions < 1,000 mOsm/L confer little risk compared to centrally administered infusions. Additional studies are needed to determine the safety of infusions with longer durations. Due to the relative ease of peripheral catheterization, clinicians should consider this route for medically managing aminoaciduric canine hypoaminoacidemic hepatopathy syndrome and superficial necrolytic dermatitis in dogs.

Glucagon infusion alters the circulating metabolome and urine amino acid excretion in dogs.

Glucagon plays a central role in amino acid (AA) homeostasis. The dog is an established model of glucagon biology, and recently, metabolomic changes in people associated with glucagon infusions have been reported. Glucagon also has effects on the kidney; however, changes in urinary AA concentrations associated with glucagon remain under investigation. Therefore, we aimed to fill these gaps in the canine model by determining the effects of glucagon on the canine plasma metabolome and measuring urine AA concentrations. Employing two constant rate glucagon infusions (CRI) - low-dose (CRI-LO: 3 ng/kg/min) and high-dose (CRI-HI: 50 ng/kg/min) on five research beagles, we monitored interstitial glucose and conducted untargeted liquid chromatography-tandem mass spectrometry (LC-MS/MS) on plasma samples and urine AA concentrations collected pre- and post-infusion. The CRI-HI induced a transient glucose peak (90-120 min), returning near baseline by infusion end, while only the CRI-LO resulted in 372 significantly altered plasma metabolites, primarily reductions (333). Similarly, CRI-HI affected 414 metabolites, with 369 reductions, evidenced by distinct clustering post-infusion via data reduction (PCA and sPLS-DA). CRI-HI notably decreased circulating AA levels, impacting various AA-related and energy-generating metabolic pathways. Urine analysis revealed increased 3-methyl-l-histidine and glutamine, and decreased alanine concentrations post-infusion. These findings demonstrate glucagon's glucose-independent modulation of the canine plasma metabolome and highlight the dog's relevance as a translational model for glucagon biology. Understanding these effects contributes to managing dysregulated glucagon conditions and informs treatments impacting glucagon homeostasis.

Serum vitamin D metabolite and acute-phase protein concentrations are frequently abnormal in a cohort of hospitalized dogs and cats.

OBJECTIVE: To determine whether serum 25-hydroxyvitamin D (25[OH]D) and 1,25-dihydroxyvitamin D (1,25[OH]2D) concentrations are associated with survival and negatively correlate with acute-phase protein (APP) concentrations in ill dogs and cats admitted to nursing care units. ANIMALS: Client-owned dogs (n = 79) and cats (16) admitted to 2 academic veterinary hospital nursing care units. METHODS: A prospective cohort study was conducted between August 12, 2019, and October 26, 2021. A diagnostic laboratory measured 25(OH)D, 1,25(OH)2D, and haptoglobin (HPT) in dogs and cats; C-reactive protein (CRP) in dogs; and serum amyloid A (SAA) in cats. Serum was collected within 12 hours of admission. Illness severity (acute patient physiologic and laboratory evaluation [APPLEfast]) scores and survival data were recorded. RESULTS: Serum 25(OH)D concentrations were in the deficient range for 22 of 79 dogs and 2 of 16 cats. There were no associations between serum analyte concentrations (25[OH]D, 1,25[OH]2D, and APP) or APPLEfast score and survival in dogs or cats. In dogs, HPT was negatively correlated with 25(OH)D (P = .002; r = -0.34) and 1,25(OH)2D (P = .012; r = -0.28), while CRP was positively correlated with HPT (P = .001; r = 0.32) and APPLEfast score (P = .014; r = 0.16). In cats, 1,25(OH)2D was negatively correlated with APPLEfast scores (P = .055; r = -0.49) and SAA was positively correlated with HPT (P = .002; r = 0.73). CLINICAL RELEVANCE: Serum 25(OH)D or 1,25(OH)2D was not associated with survival in our hospitalized patient population. Relationships between APP and serum vitamin D metabolites with APPLEfast scores in cats warrant further investigation as illness severity biomarkers.

A prospective cohort study to identify clinical diagnostic and prognostic markers of primary immune thrombocytopenia in dogs.

BACKGROUND: Primary immune thrombocytopenia (pITP) in dogs presents a diagnostic challenge, and clinical markers of severity are lacking. OBJECTIVES: Identify clinicopathologic features that differentiate pITP from secondary ITP (sITP) and markers related to bleeding severity, transfusion, and survival of dogs with pITP. ANIMALS: Ninety-eight thrombocytopenic dogs (58 pITP and 40 sITP). METHODS: Client-owned dogs with platelet counts <50 000/µL were enrolled in a prospective, multi-institution cohort study. History and treatment information, through a maximum of 7 days, was recorded on standard data forms. Bleeding severity was scored daily using a bleeding assessment tool (DOGiBAT). At-admission blood samples were collected for CBC, biochemistry, C-reactive protein concentration, and coagulation panels, and to measure platelet surface-associated immunoglobulin G (PSAIg) and expression of platelet membrane proteins and phospholipids. Dogs with evidence of coincident disease were classified as sITP. RESULTS: No definitive pITP diagnostic test was found. However, pITP cases were characterized by lower platelet counts, D dimer concentrations, and platelet membrane protein expression than sITP cases. Differentiation between pITP and sITP was further enhanced using logistic regression modeling combining patient sex, coagulation profile, platelet count, D dimer, and PSAIg. A second model of pITP severity indicated that low hematocrit and high BUN concentration were associated with non-survival. Low hematocrit at admission, but not platelet count or DOGiBAT score, was associated with transfusion. CONCLUSIONS AND CLINICAL IMPORTANCE: Pending validation studies, models constructed from at-admission clinicopathologic findings may improve differentiation of pITP from sITP and identify the most severe pITP cases at the time of presentation.

A veterinary-calibrated point-of-care glucometer accurately measures blood glucose concentration in dogs and cats.

OBJECTIVE: To determine the clinical and analytical accuracy of a new veterinary-calibrated portable blood glucose monitor (PBGM) compared to a reference laboratory analyzer. ANIMALS: Client-owned dogs (n = 77) and cats (n = 64). METHODS: Peripheral and paired capillary whole-blood glucose concentrations measured via PBGM were compared to plasma glucose concentrations measured via a Cobas c501 reference analyzer (Roche). Analytical accuracy was evaluated with the Spearman rank correlation coefficient, Bland-Altman difference plot analysis, and Deming regression. Clinical accuracy was evaluated with Parkes error grid analysis. Paired peripheral and capillary blood samples were compared with the Wilcoxon matched-pairs signed-rank test. RESULTS: There was a high correlation between PBGM and reference analyzer readings in dogs and cats. Human quality assurance standards (International Organization for Standardization 15197:2013 guidelines) for analytical accuracy were met for 95% of feline peripheral blood samples and 89% of canine samples. Similar veterinary standards (American Society of Veterinary Clinical Pathology guidelines) were met for 89% of canine and 92% of feline peripheral blood glucose measurements. Error grid analysis showed that all peripheral canine and 97% of feline measurements were clinically accurate (zone A). Any altered clinical decision for the remaining feline measurements was expected to minimally impact outcome (zone B). No significant difference was found between peripheral and capillary blood glucose measurements in either species. CLINICAL RELEVANCE: The PBGM produced clinically accurate results and is suitable for use in veterinary and home settings to measure blood glucose.

Serum metabolome analysis in hyperthyroid cats before and after radioactive iodine therapy.

Hyperthyroidism is the most common feline endocrinopathy. In hyperthyroid humans, untargeted metabolomic analysis identified persistent metabolic derangements despite achieving a euthyroid state. Therefore, we sought to define the metabolome of hyperthyroid cats and identify ongoing metabolic changes after treatment. We prospectively compared privately-owned hyperthyroid cats (n = 7) admitted for radioactive iodine (I-131) treatment and euthyroid privately-owned control (CON) cats (n = 12). Serum samples were collected before (T0), 1-month (T1), and three months after (T3) I-131 therapy for untargeted metabolomic analysis by MS/MS. Hyperthyroid cats (T0) had a distinct metabolic signature with 277 significantly different metabolites than controls (70 increased, 207 decreased). After treatment, 66 (T1 vs. CON) and 64 (T3 vs. CON) metabolite differences persisted. Clustering and data reduction analysis revealed separate clustering of hyperthyroid (T0) and CON cats with intermediate phenotypes after treatment (T1 & T3). Mevalonate/mevalonolactone and creatine phosphate were candidate biomarkers with excellent discrimination between hyperthyroid and healthy cats. We found several metabolic derangements (e.g., decreased carnitine and α-tocopherol) do not entirely resolve after achieving a euthyroid state after treating hyperthyroid cats with I-131. Further investigation is warranted to determine diagnostic and therapeutic implications for candidate biomarkers and persistent metabolic abnormalities.

Plasma concentrations of glucagon and glucagon-like peptide-1 are reduced in dogs with aminoaciduric canine hypoaminoacidemic hepatopathy syndrome versus healthy dogs: a preliminary study.

OBJECTIVE: To compare plasma concentrations of glucagon and glucagon-like peptide-1 (GLP-1) between healthy dogs and dogs with aminoaciduric canine hypoaminoacidemic hepatopathy syndrome (ACHES) dogs. ANIMALS: Privately owned healthy (n = 5) control (CON) and ACHES (8; including 3 with diabetes mellitus) dogs enrolled between October 2, 2019, and March 4, 2020. PROCEDURES: This was a prospective case-control study. Fasting and 15-minute postprandial plasma glucagon total GLP-1 concentrations were measured with commercial immunoassays. RESULTS: Dogs with ACHES had lower fasting (median, 0.5; mean difference, 3.8; 95% CI, 0.52 to 7.0 pmol/L; P = .021) and postprandial (median, 0.35; mean difference, 5.0; 95% CI, 1.8 to 8.3 pmol/L; P = .002) plasma glucagon concentrations than CON (fasting and postprandial medians, 3.5 and 4.6 pmol/L, respectively). ACHES dogs had significantly (median, 4.15; mean difference, 12.65; 95% CI, 2.0 to 16.3 pg/ml; P = .011) lower postprandial plasma GLP-1 concentrations than CON (median, 16.8 pg/ml). There was no significant difference between fasting GLP-1 levels between the 2 groups. CLINICAL RELEVANCE: Lower postprandial plasma GLP-1 concentrations may contribute to the propensity of diabetes mellitus in ACHES. Lower glucagon concentrations may reflect an appropriate physiologic response to hypoaminoacidemia.

Randomized controlled trial of hydrolyzed fish diets in dogs with chronic enteropathy.

BACKGROUND: The role of diet in the pathogenesis and treatment of chronic enteropathies (CE) in dogs is unresolved. OBJECTIVES: To compare the ability of diets composed of hydrolyzed fish, rice starch, and fish oil without (HF) or with prebiotics, turmeric, and high cobalamin (HF+) against a limited ingredient diet containing mixed nonhydrolyzed antigens and oils (control) to resolve clinical signs and maintain serum cobalamin and folate concentrations in dogs with nonprotein losing CE (non-PLE). To determine the ability of hydrolyzed fish diets to support recovery and remission in dogs with PLE. ANIMALS: Thirty-one client-owned dogs with CE: 23 non-PLE, 8 PLE. METHODS: Randomized, blinded, controlled trial. Diets were fed for 2 weeks; responders continued for 12 weeks. Nonresponders were crossed over to another diet for 12 weeks. Response was determined by standardized clinical evaluation with long-term follow-up at 26 weeks. Concurrent medications were allowed in PLE. RESULTS: Nineteen of 23 (83%; 95% confidence interval [CI], 60%-94%) non-PLE CE responded clinically to their initial diet, with no difference between diets (P > .05). Four nonresponders responded to another diet, with sustained remission of 18/18 (100%; 95%CI, 78%-100%) at 26 weeks. Serum cobalamin concentration was increased (P < .05) and maintained by diet. Serum folate concentration decreased posttreatment (P < .05) but was restored by dietary supplementation. Hydrolyzed fish diets supported weight gain, serum albumin concentration, and recovery (P < .05) in dogs with PLE. CONCLUSIONS AND CLINICAL IMPORTANCE: Changing diet, independent of antigen restriction or supplemental ingredients, induced long-term remission in dogs with non-PLE CE. Serum cobalamin and folate concentrations were maintained by diet. Hydrolyzed fish diets supported clinical recovery and remission in PLE.

Untargeted metabolomic profiles reveal widespread metabolic perturbations and identify candidate biomarkers in aminoaciduric canine hypoaminoacidemic hepatopathy syndrome.

OBJECTIVE: To identify metabolites and metabolic pathways affected in dogs with aminoaciduric canine hypoaminoacidemic hepatopathy syndrome (ACHES) compared to healthy control (CON) dogs of similar ages and breeds. To improve our understanding of ACHES pathophysiology and identify novel candidate biomarkers associated with ACHES. ANIMALS: A prospective case-control study. Privately owned dogs with ACHES (n = 19) and healthy (CON) dogs (n = 9) were recruited between February 18, 2015, and April 18, 2018. METHODS: A prospective case-control study. Plasma and urine were collected from ACHES and CON dogs. The Cornell University Proteomics and Metabolomics Core Facility conducted an untargeted metabolomic analysis. RESULTS: After controlling for age, sex, and weight, 111 plasma and 207 urine metabolites significantly differed between ACHES and CON dogs. Data reduction and cluster analysis revealed robust segregation between ACHES and CON dogs. Enrichment analysis of significant compounds in plasma or urine identified altered metabolic pathways, including those related to AA metabolism, cellular energetics, and lipid metabolism. Biomarker analysis identified metabolites that best-distinguished ACHES from CON dogs, including pyruvic acid isomer and glycerol-3-phosphate in the plasma and an alanine isomer and choline in the urine. CLINICAL RELEVANCE: Our findings provide an in-depth analysis of metabolic perturbations associated with ACHES. Several affected metabolic pathways (eg, lipid metabolism) offer a new understanding of ACHES pathophysiology. Novel candidate biomarkers warrant further evaluation to determine their potential to aid in ACHES diagnosis, prognosis, and treatment monitoring.

Laparoscopic twist technique has the best overall artifact profile when comparing three laparoscopic hepatic cup biopsy techniques for dogs.

OBJECTIVE: To determine the difference in histologic artifacts and morphologic diagnosis among 3 laparoscopic cup biopsy forceps techniques and wedge hepatic samples. ANIMALS: Cadavers of 20 client-owned dogs following euthanasia for unrelated reasons between January 3 and July 29, 2021. PROCEDURES: Four biopsy techniques were performed from the margin of 3 liver lobes/dog. Laparoscopic techniques used 5-mm cup biopsy forceps to obtain biopsy samples by pulling the forceps forcefully caudally to free a sample (the PULL technique), rotating the forceps 360° in 1 direction until freed (the TWST technique), or pulling the forceps through a 5-mm cannula to remove the sample (the CAN technique); wedge biopsy samples served as the control (CON). Data collected included sample weight, histologic features, diagnosis, and artifact characterization. Gwet AC1 or intraclass correlation coefficients (ICCs) were calculated to detect agreement among techniques. RESULTS: Sample weights for CON and TWST were significantly larger (P < .001 and P = .035, respectively) than for PULL and CAN. There was excellent agreement among all techniques for most diagnostic features (Gwet AC1, 0.93 to 1). The TWST technique resulted in the best overall artifact profile for laparoscopic techniques, with 90% of samples (54/60) having crisp edges and 65% of samples (39/60) having no or mild tearing. The agreement was moderate to good (ICC, 0.73 for edges and 0.76 for tearing) among all cup biopsy forceps techniques. CLINICAL RELEVANCE: The TWST technique resulted in the largest sample and had the fewest artifacts, supporting its continued use during laparoscopic procedures.