Search

Background: Acute illness can result in changes in serum total thyroxine (tT4), total triiodothyronine (tT3), and thyrotropin (TSH) concentrations in euthyroid dogs defined as nonthyroidal illness syndrome, but longitudinal evaluation of these hormones during the recovery phase is lacking. Objective s : To longitudinally evaluate serum tT4, tT3, and TSH concentrations during the acute phase and recovery from acute illness in dogs. Animals: Nineteen euthyroid client‐owned dogs hospitalized for acute illness at a veterinary teaching hospital. Methods: Prospective longitudinal study. Serum tT4, tT3, and TSH concentrations were measured at the admission (T0), at last day of hospitalization (T1), and during the recovery phase at 3, 7, 14, and 21 days after the discharge (T2, T3, T4, and T5), respectively. Results: tT4 and tT3 were below the reference interval (RI) at T0 in 3 (16%) and 18 (95%) dogs, respectively; tT4 normalized in all dogs early in the recovery phase, while low tT3 persisted at the end of the study in 16 (83%) dogs. Median TSH concentrations were increased at T5 compared with T1 (0.19 ng/mL [range 0.03‐0.65] vs 0.11 ng/mL [range (0.05‐0.26)], mean difference = 0.09 ng/mL; P =.03). Five (26%) dogs had TSH above the RI at least at 1 time point during the recovery phase. None of the dogs had concurrent low tT4 and high TSH during the study. Conclusions and Clinical Relevance: In euthyroid dogs acute illness can interfere with evaluation of thyroid function up to 21 days during the recovery phase. Thyroid testing should be avoided or postponed in these dogs. [ABSTRACT FROM AUTHOR]

Objective: To discuss the definitions of sepsis in human and veterinary medicine. Design: International, multicenter position statement on the need for consensus definitions of sepsis in veterinary medicine. Setting: Veterinary private practice and university teaching hospitals. Animals: Dogs and cats. Interventions: None. Measurements and Main Results: Sepsis is a life‐threatening condition associated with the body's response to an infection. In human medicine, sepsis has been defined by consensus on 3 occasions, most recently in 2016. In veterinary medicine, there is little uniformity in how sepsis is defined and no consensus on how to identify it clinically. Most publications rely on modified criteria derived from the 1991 and 2001 human consensus definitions. There is a divergence between the human and veterinary descriptions of sepsis and no consensus on how to diagnose the syndrome. This impedes research, hampers the translation of pathophysiology insights to the clinic, and limits our abilities to optimize patient care. It may be time to formally define sepsis in veterinary medicine to help the field move forward. In this narrative review, we present a synopsis of prior attempts to define sepsis in human and veterinary medicine, discuss developments in our understanding, and highlight some criticisms and shortcomings of existing schemes. Conclusions: This review is intended to serve as the foundation of current efforts to establish a consensus definition for sepsis in small animals and ultimately generate evidence‐based criteria for its recognition in veterinary clinical practice. [ABSTRACT FROM AUTHOR]

Background: Dogs with myxomatous mitral valve disease (MMVD) can experience progressive renal tubular damage and dysfunction. The prevalence of renal tubular damage is not known in dogs with stable MMVD. Objective: To evaluate renal tubular damage in dogs with stable MMVD by evaluation of urinary neutrophil gelatinase‐associated lipocalin (NGAL). Animals: Ninety‐eight MMVD dogs grouped according to the American College of Veterinary Internal Medicine (ACVIM) staging (group B1, n = 23; group B2, n = 27; group C + D, n = 48) and 46 healthy dogs. Methods: Multicenter prospective observational study. Serum and urine chemistry including NGAL reported as uNGAL concentration (uNGAL) and normalized with urinary creatinine (uNGALC) were compared between MMVD dogs and healthy controls, and among different MMVD ACVIM stages. Results: The MMVD dogs had significantly higher uNGAL and uNGALC (1204 pg/mL; range, 30‐39 732 and 1816 pg/mg; range, 22‐127 693, respectively) compared to healthy dogs (584 pg/mL; range, 56‐4072 and 231 pg/mg; range, 15‐2407, respectively; P =.002 and P <.0001, respectively). Both uNGAL and uNGALC increased with the increasing ACVIM stage (P =.001 and P <.001, respectively). Conclusions and Clinical Importance: Renal tubular damage is present in dogs with stable MMVD, as measured by increased uNGAL. This tubular damage is subclinical, occurs in all stages of MMVD even in the absence of azotemia, and increases with the severity of MMVD. Reno‐protective approaches to manage MMVD dogs should be explored to slow the progression of renal tubular damage in these patients. [ABSTRACT FROM AUTHOR]

Objective: To compare the impact of an IV bolus of hydroxyethyl starch 130/0.4 (HES) or hypertonic saline 7.5% (HS) on hemostasis in dogs resuscitated for gastric‐dilation‐volvulus (GDV). Design: Open‐label, parallel‐group randomized clinical trial. Animals: Twenty‐three client‐owned dogs. Interventions: Dogs affected by GDV and shock were randomly assigned to receive HES at 10 mL/kg or HS at 4 mL/kg every 15 minutes. Blood samples were collected for blood gas analysis, PCV, total plasma protein, albumin, standard coagulation profile, and thromboelastometry (ROTEM) at baseline (T0) and at the end of bolus (T1). To assess the differences between the 2 groups at T1, Student's t‐test or Wilcoxon rank‐sum test was used. To evaluate the differences between T0 and T1, ANOVA for paired data or Wilcoxon matched‐pairs signed‐ranks test was used. P < 0.05 was considered significant. Measurement and main results: Hemostasis was evaluated by means of prothrombin time, activated partial thromboplastin time, fibrinogen, and ROTEM. The study included 13 dogs in the HES group and 10 dogs in the HS group. Differences were found between groups at T1: increase in clotting time (P = 0.018) and decrease in fibrinogen level (P = 0.021) in the HS‐treated group. Between T0 and T1, there were differences for the HES group: increase in clot formation time (P = 0.046), decrease in maximum clot firmness (P = 0.002) in ex‐TEM profile, and decrease in maximum clot firmness (P = 0.0117) in fib‐TEM profile. Between T0 and T1, the following differences were noted for the HS group: increase in clotting time (P = 0.048) and clot formation time (P = 0.0019), decrease in maximum clot firmness (P = 0.031) and α angle (P = 0.036) in ex‐TEM profile, decrease in α angle (P = 0.036) in in‐TEM profile, and decrease in maximum clot firmness (P = 0.017) in fib‐TEM profile. Conclusion: In dogs affected by GDV, HES or HS infusion caused a similar tendency toward hypocoagulability, with few differences between the 2 groups. [ABSTRACT FROM AUTHOR]

Background: Urine neutrophil gelatinase‐associated lipocalin (NGAL) is a promising biomarker of acute kidney injury (AKI) in dogs. Objectives: To evaluate the utility of urinary NGAL for characterizing AKI according to volume responsiveness, presence of inflammation and sepsis, and prognosis. Animals: Dogs with AKI (n = 76) and healthy controls (n = 10). Methods: Prospective study. Clinical and clinicopathologic data including absolute urine NGAL concentration (uNGAL) and NGAL normalized to urine creatinine concentration (uNGALC) were measured upon admission. Dogs were graded according to International Renal Interest Society (IRIS) AKI guidelines and compared based on AKI features: volume‐responsive (VR‐) AKI vs. intrinsic (I‐) AKI based on IRIS criteria; VR‐AKI and I‐AKI based on urine chemistry; inflammatory versus noninflammatory; septic versus nonseptic; and survivors versus nonsurvivors. Nonparametric statistics were calculated, and significance set at P <.05. Results: Urinary NGAL was significantly higher in dogs with AKI compared to controls, regardless of AKI grade. Urinary NGAL did not differ between dogs with VR‐AKI and I‐AKI based on IRIS criteria, whereas higher uNGALC was recorded in dogs with I‐AKI based on urine chemistry. Urinary NGAL was significantly higher in dogs with inflammatory AKI, whereas no difference with respect to sepsis or outcome was identified. Conclusions and Clinical Importance: Urinary NGAL is a sensitive marker for AKI in dogs, but its specificity is affected by systemic inflammation. Increased urinary NGAL in both I‐AKI and VR‐AKI also suggests the presence of tubular damage in transient AKI. Combining urine chemistry data with IRIS criteria could facilitate AKI characterization in dogs. [ABSTRACT FROM AUTHOR]

Background: The value of fractional excretion (FE) of electrolytes to characterize and prognosticate acute kidney injury (AKI) is poorly documented in dogs. Objectives: To evaluate the diagnostic and prognostic roles of FE of electrolytes in dogs with AKI. Animals: Dogs (n = 135) with AKI treated with standard care (February 2014‐December 2016). Methods: Prospective study. Clinical and laboratory variables including FE of electrolytes, were measured upon admission. Dogs were graded according to the AKI‐IRIS guidelines and grouped according to AKI features (volume‐responsive, VR‐AKI; intrinsic, I‐AKI) and outcome (survivors/non‐survivors). Group comparison and regression analyses with hazard ratios (HR) evaluation for I‐AKI and mortality were performed. P < .05 was considered significant. Results: Fifty‐two of 135 (39%) dogs had VR‐AKI, 69/135 (51%) I‐AKI and 14/135 (10%) were unclassified. I‐AKI dogs had significantly higher FE of electrolytes, for example, FE of sodium (FENa, %) 2.39 (range 0.04‐75.81) than VR‐AKI ones 0.24 (range 0.01‐2.21; P < .001). Overall, case fatality was 41% (55/135). Increased FE of electrolytes were detected in nonsurvivors, for example, FENa 1.60 (range 0.03‐75.81) compared with survivors 0.60 (range 0.01‐50.45; P = .004). Several risk factors for death were identified, including AKI‐IRIS grade (HR = 1.39, P = .002), FE of electrolytes, for example, FENa (HR = 1.03, P < .001), and urinary output (HR = 5.06, P < .001). Conclusions and Clinical Importance: Fractional excretion of electrolytes performed well in the early differentiation between VR‐AKI and I‐AKI, were related to outcome, and could be useful tools to manage AKI dogs in clinical practice. [ABSTRACT FROM AUTHOR]

Objective To investigate the prognostic value of the acute patient physiologic and laborartory evaluation (APPLE) score and relevant clinicopathological markers in dogs with systemic inflammatory response syndrome (SIRS). Design Prospective observational cohort study. Setting Veterinary teaching hospital. Animals Thirty-three dogs with SIRS admitted to the intensive care unit (ICU) were compared to 35 healthy control dogs. Dogs with SIRS were divided into septic ( n = 20) and nonseptic ( n = 13) etiologies and as survivors (alive to discharge, n = 22) and nonsurvivors ( n = 11: died, n = 6, or humanely euthanized, n = 5). Measurements and Main Results For all dogs, physiological and laboratory parameters were prospectively collected for the calculation of the APPLEfast score. No difference between septic and nonseptic SIRS dogs was detected for any parameter evaluated. Survivors had significantly higher total protein, albumin concentrations, antithrombin activity (ATA), and base excess (BE), as well as significantly lower lactate, urea, creatinine concentrations, urinary protein to creatinine ratio and APPLEfast score compared to nonsurvivors. Higher values of creatinine, lactate, anion gap, alanine transaminase (ALT), and APPLEfast score were significantly associated with an increased risk of death in SIRS dogs, while higher values of total protein, albumin, ATA, and BE were associated with a significantly reduced risk of mortality. When a multivariate binary logistic regression analysis was performed, the APPLEfast score was the only significant parameter retained. Conclusions The determination of the APPLEfast score in clinical setting, as well as the measurement of APP, ATA, lactate, BE, anion gap, ALT, urinary proteins, and electrolytes may be beneficial for a better assessment of dogs with SIRS. Identified parameters were significantly related with the presence of SIRS and their evaluation should be considered for the assessment of disease severity, and guidance of the decision-making process in critically ill dogs. [ABSTRACT FROM AUTHOR]

Retinal gene therapy with adeno‐associated viral (AAV) vectors is safe and effective in humans. However, AAV's limited cargo capacity prevents its application to therapies of inherited retinal diseases due to mutations of genes over 5 kb, like Stargardt's disease (STGD) and Usher syndrome type IB (USH1B). Previous methods based on ‘forced’ packaging of large genes into AAV capsids may not be easily translated to the clinic due to the generation of genomes of heterogeneous size which raise safety concerns. Taking advantage of AAV's ability to concatemerize, we generated dual AAV vectors which reconstitute a large gene by either splicing (trans‐splicing), homologous recombination (overlapping), or a combination of the two (hybrid). We found that dual trans‐splicing and hybrid vectors transduce efficiently mouse and pig photoreceptors to levels that, albeit lower than those achieved with a single AAV, resulted in significant improvement of the retinal phenotype of mouse models of STGD and USH1B. Thus, dual AAV trans‐splicing or hybrid vectors are an attractive strategy for gene therapy of retinal diseases that require delivery of large genes. Synopsis: The Authors provide proof‐of‐concept of gene therapy for two inherited retinal degeneration conditions by using dual AAV vectors. This allows the expansion of AAV cargo capacity for gene therapy of syndromes that require the transfer of large genes. Dual AAV vectors significantly expand AAV cargo capacity in the retina.Unlike dual AAV overlapping vectors, trans‐splicing and hybrid vectors efficiently transduce photoreceptors.Subretinal delivery of dual AAV vectors improves the retinal phenotype of murine models of inherited blinding conditions due to mutations in large genes. The Authors provide proof‐of‐concept of gene therapy for two inherited retinal degeneration conditions by using dual AAV vectors. This allows the expansion of AAV cargo capacity for gene therapy of syndromes that require the transfer of large genes. [ABSTRACT FROM AUTHOR]

To perform a qualitative evaluation of procalcitonin gene (CALCA) expression in a tissue-specific manner in dogs with signs of the systemic inflammatory response syndrome (SIRS). Observational study. University Veterinary Teaching Hospital. Nine clinical cases and 5 research dogs. None. Fresh tissue samples (thyroid, lung, liver, spleen) from 9 dogs that died with a diagnosis of parvoviral infection or SIRS were collected and immediately stored at -80°C. Diagnosis of parvoviral infection was based on clinical signs, positive fecal antigen test, and confirmed by polymerase chain reaction (PCR). Clinical diagnosis of SIRS was based on the clinical criteria reported in veterinary literature. Necropsy was performed on all subjects in the study. Furthermore, thyroid, lung, liver, spleen were collected from 5 normal research dogs immediately postmortem for testing. The 9 dogs with a clinical diagnosis of SIRS died from either parvovirus ( n=5), bacterial sepsis ( n=3), or neoplasia ( n=1). CALCA was amplified by PCR in the following samples: thyroid (9/9), spleen (6/9), lung (4/9), liver (3/9). Only thyroid expressed CALCA in the 5 normal dogs. In SIRS, extrathyroidal transcription of CALCA was documented. Quantitative analysis (real-time polymerase chain reaction) in a wider population of SIRS and normal dogs will provide essential information about the extent and source of extrathyroidal expression of canine CALCA induced by septic and nonseptic systemic inflammation. [ABSTRACT FROM AUTHOR]