Markov models to estimate and describe survival time and experience in cohorts with high euthanasia frequency

Unique to survival analysis of veterinary clinical data is classification of observations from euthanized animals. The first study highlighted limitations of Kaplan-Meier product limit analysis (KM) of veterinary clinical data. Three data sets with different outcome proportions (alive, lost-to-follow-up, dead due to disease, dead due to other, euthanized due to disease, euthanized due to other) were used. Different classifications of observations from euthanized animals caused inconsistent conclusions of significant differences between strata within data sets. At times, ranking of median survival time estimates for strata was reversed. The KM was found inappropriate to evaluate observations from euthanized animals. This finding, coupled with restriction of KM to two-state description of disease (alive to outcome), prompted exploration of an alternate analysis method. Markov models allow modeling of multiple health states and outcomes. A 5-state, time-homogeneous, Markov chain was used for a cohort of 64 dogs with generalized lymphoma. The model contained two transient (WELL, TOXIC) and three absorbing (DEAD, EUTHANASIA, LOST-TO-FOLLOWUP) states. The transition probability matrix (P) was used to iterate future transitions and survival probabilities. Matrix solution and Monte Carlo simulation were used to estimate survival time. Estimates appeared reliable. Markov modeling was extended for comparison of vaccine-associated sarcoma progression after treatment in a cohort of 294 cats. For a 5-state model, transition probabilities derived from exponential transformation of incidence rates were used to construct P for each treatment - NONE (no surgery), SX (surgery) and SX+RAD (surgery and radiation). Monte Carlo estimates of durations in transient states and expected survival showed SX+RAD prolonged expected survival significantly longer than SX than NONE. Commitment to repeated treatment with surgery and radiation did prolong expected survival of cats with vaccine-associated sarcoma. Assumptions of Markov modeling did not appear prohibitive for analysis of veterinary clinical data and further exploration is warranted

Computed tomographic, ultrasonographic, MRI and radiographic findings of a venous malformation with phleboliths in the thoracic limb of a dog

An 11-month-old entire male Rottweiler was referred for further investigation of raised, soft, compressible, non-pulsatile, subcutaneous tubular structures along the right antebrachium that had been diagnosed to be a vascular malformation on histopathology of a subcutaneous biopsy. Computed tomographic (CT) with angiography did not reveal an arteriovenous malformation or fistula. Ultrasonography of the limb demonstrated a venous malformation with thrombi and phleboliths. An MRI study of the limb was consistent with a venous malformation with small rounded luminal signal voids that were confirmed to be phleboliths. Radiography at follow-up demonstrated phleboliths. This is the first report describing the combined CT, ultrasonographic, MRI and radiographic characteristics of venous malformation with phleboliths in a limb of a dog.https://wileyonlinelibrary.com/journal/vrc2Companion Animal Clinical Studie

Comparison of electrical impedance tomography and spirometry-based measures of airflow in healthy adult horses

Electrical impedance tomography (EIT) is a non-invasive diagnostic tool for evaluating lung function. The objective of this study was to compare respiratory flow variables calculated from thoracic EIT measurements with corresponding spirometry variables. Ten healthy research horses were sedated and instrumented with spirometry via facemask and a single-plane EIT electrode belt around the thorax. Horses were exposed to sequentially increasing volumes of apparatus dead space between 1,000 and 8,500 mL, in 5–7 steps, to induce carbon dioxide rebreathing, until clinical hyperpnea or a tidal volume of 150% baseline was reached. A 2-min stabilization period followed by 2 minutes of data collection occurred at each timepoint. Peak inspiratory and expiratory flow, inspiratory and expiratory time, and expiratory nadir flow, defined as the lowest expiratory flow between the deceleration of flow of the first passive phase of expiration and the acceleration of flow of the second active phase of expiration were evaluated with EIT and spirometry. Breathing pattern was assessed based on the total impedance curve. Bland-Altman analysis was used to evaluate the agreement where perfect agreement was indicated by a ratio of EIT:spirometry of 1.0. The mean ratio (bias; expressed as a percentage difference from perfect agreement) and the 95% confidence interval of the bias are reported. There was good agreement between EIT-derived and spirometry-derived peak inspiratory [−15% (−46–32)] and expiratory [10% (−32–20)] flows and inspiratory [−6% (−25–18)] and expiratory [5% (−9–20)] times. Agreement for nadir flows was poor [−22% (−87–369)]. Sedated horses intermittently exhibited Cheyne-Stokes variant respiration, and a breath pattern with incomplete expiration in between breaths (crown-like breaths). Electrical impedance tomography can quantify airflow changes over increasing tidal volumes and changing breathing pattern when compared with spirometry in standing sedated horses

Hypocoagulability and Platelet Dysfunction Are Exacerbated by Synthetic Colloids in a Canine Hemorrhagic Shock Model

Background: Hemorrhagic shock and volume replacement can alter coagulation. Synthetic colloids, hydroxyethyl starch (HES), and gelatin, may enhance hypocoagulability. Our primary objective was to describe the effect of four fluid products on coagulation in canine hemorrhagic shock. Our secondary objective was to compare measurements of coagulation during shock to baseline in all dogs.Methods: Anesthetized greyhounds subjected to atraumatic hemorrhage for 60 min were administered 20 mL kg−1 of either fresh whole blood (FWB), 6% HES 130/0.4, 4% succinylated gelatin (GELO), or 80 mL kg−1 of isotonic crystalloid over 20 min (n = 6 per group). Platelet closure time (PCT), rotational thromboelastometry (ROTEM) and plasma coagulation assays were measured at baseline, end of hemorrhage (shock), and 40 (T60), and 160 (T180) min after study fluid. ROTEM parameters included clotting time (CT), clot formation time (CFT), alpha angle, maximum clot firmness (MCF), lysis index at 60 min (LI60), and thrombodynamic potential index (TPI) for INTEM, EXTEM, FIBTEM (MCF only), and APTEM (LI60 only) profiles. Plasma coagulation assays included prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen concentration and activities of factor VII (FVII), factor VIII (FVIII), and von Willebrand Factor antigen (vWF). Between-group differences were tested using linear mixed models with post-hoc between-group comparisons (Bonferroni-Holm corrected). Differences between baseline and shock were tested using paired t-tests. Significance was set at P < 0.05.Results: GELO showed longer PCT at T60, compared with FWB and CRYST, and at T180, compared with all other groups. HES showed longer EXTEM CT at T60, compared with all other groups. HES showed lower INTEM and EXTEM MCF at T60 and lower INTEM MCF at T180, compared with FWB. Some plasma coagulation assays showed greater hypocoagulability with HES. Comparing shock to baseline, EXTEM CT, INTEM CFT, EXTEM CFT, PT, and FVIII significantly increased and PCT, INTEM CT, INTEM MCF, EXTEM MCF, EXTEM LI60, EXTEM TPI, FIBTEM MCF, APTT, fibrinogen, FVII, and vWF significantly decreased.Conclusions: In dogs with hemorrhagic shock, volume replacement with GELO caused mild platelet dysfunction and HES was associated with coagulation changes consistent with hypocoagulability, beyond effects of hemodilution. Shock alone produced some evidence of hypocoagulability

Thoracic Electrical Impedance Tomography—The 2022 Veterinary Consensus Statement

Electrical impedance tomography (EIT) is a non-invasive real-time non-ionising imaging modality that has many applications. Since the first recorded use in 1978, the technology has become more widely used especially in human adult and neonatal critical care monitoring. Recently, there has been an increase in research on thoracic EIT in veterinary medicine. Real-time imaging of the thorax allows evaluation of ventilation distribution in anesthetised and conscious animals. As the technology becomes recognised in the veterinary community there is a need to standardize approaches to data collection, analysis, interpretation and nomenclature, ensuring comparison and repeatability between researchers and studies. A group of nineteen veterinarians and two biomedical engineers experienced in veterinary EIT were consulted and contributed to the preparation of this statement. The aim of this consensus is to provide an introduction to this imaging modality, to highlight clinical relevance and to include recommendations on how to effectively use thoracic EIT in veterinary species. Based on this, the consensus statement aims to address the need for a streamlined approach to veterinary thoracic EIT and includes: an introduction to the use of EIT in veterinary species, the technical background to creation of the functional images, a consensus from all contributing authors on the practical application and use of the technology, descriptions and interpretation of current available variables including appropriate statistical analysis, nomenclature recommended for consistency and future developments in thoracic EIT. The information provided in this consensus statement may benefit researchers and clinicians working within the field of veterinary thoracic EIT. We endeavor to inform future users of the benefits of this imaging modality and provide opportunities to further explore applications of this technology with regards to perfusion imaging and pathology diagnosis

Angioleiomyosarcoma in the Nasal Vestibule of a Dog: Surgical Excision via a Modified Lateral Approach

This case report describes an 11 yr old spayed female German shepherd dog weighing 42 kg that presented with intermittent epistaxis from the left nostril. A nonulcerated pale irregular polypoid mass was visualized within the left nares. Computed tomography revealed a pedunculated mass arising from the ventrolateral nasal mucosal of the left nasal cavity with no evidence of involvement or invasion of adjacent soft tissues or bony structures. Histological and immunohistochemical examination of rhinoscopic biopsies returned a diagnosis of an angioleiomyosarcoma. The mass was excised using a modified lateral approach to the nasal cavity. Fulguration of the wound bed was performed. Clean surgical margins were identified on histopathology. The dog remained clinically free of recurrence 28 mo postsurgically. Angioleiomyosarcomas are rare tumors originating from the smooth muscle cells of blood vessel walls and are included in the spectrum of perivascular wall tumor, a subgroup of soft-tissue sarcomas

Acetylcholinesterase concentrations in heparinized blood of Hispaniolan Amazon parrots (Amazona ventralis)

Organophosphate and carbamate pesticides inhibit acetylcholinesterase (AChE) at nerve synapses. Blood samples from 22 Hispaniolan Amazon parrots (Amazona ventralis) were assayed for cholinesterase levels by two different techniques. Using the modified Michel method, the whole-blood cholinesterase activity levels ranged from 0.082 to 0.616 deltapH/hr with a mean value of 0.35 deltapH/hr. A reference range (0.08-0.62 deltapH/hr) for cholinesterase was established in birds. The modified Ellman spectrophotometric method was used to measure AChE activity by adding acetylthiocholine or pseudocholinesterase (plasma cholinesterase) activity by adding butyrylthiocholine. The reference range of the AChE activity using the modified Ellman spectrophotometric method was 0-1.12 micromol/ml/min with a mean of 0.48 micromol/ml/min, and for pseudocholinesterase the range was 0.09-0.98 micromol/ml/min with a mean of 0.53 micromol/ml/min

Immunohistochemical staining of urokinase plasminogen activator-like and urokinase plasminogen activator receptor-like proteins in the urinary tract of healthy dogs

OBJECTIVE: To determine distribution of urokinase plasminogen activator-like protein and urokinase plasminogen activator receptor-like protein in urinary tract tissues of healthy dogs. ANIMALS: 11 healthy dogs. PROCEDURES: Necropsy specimens from kidney, ureter, bladder, urethra, prostate, and testis were obtained from 4 sexually intact female dogs, 5 sexually intact males, and 2 castrated males; dogs ranged in age from juvenile to adult. Urokinase plasminogen activator-like protein and urokinase plasminogen activator receptor-like protein in tissue lysates from kidney, prostate, and testis were identified by use of SDS-PAGE, western blot analysis, and immunoprecipitation. Urokinase plasminogen activator-like protein and urokinase plasminogen activator receptor-like protein in kidney, ureter, urinary bladder, urethra, prostate, and testis were identified by use of immunohistochemical staining of tissue sections. RESULTS: Urokinase plasminogen activator-like protein and urokinase plasminogen activator receptor-like protein in the molecular-weight range published for urokinase and urokinase receptor (53 and 33 kd for urokinase and 60 to 65 kd for urokinase receptor) were identified. Distribution of the proteins identified by use of immunohistochemical staining was comparable with published information for humans and mice for the urinary tract. Staining of these proteins was detected in more tissue types than reported in healthy humans. CONCLUSIONS AND CLINICAL RELEVANCE: Urokinase plasminogen activator-like protein and urokinase plasminogen activator receptor-like protein were detected in the urinary tract of healthy dogs. This information is important for further evaluation of the functions of urokinase and urokinase receptor in the canine urinary tract and the pathophysiologic features of urinary tract disease

Quantitative ultrasonography for assessment of bone mineral density in the canine radius and tibia

Quantitative ultrasound allows noninvasive assessment of cortical bone density. Potential applications include monitoring of fracture healing, rehabilitation, and skeletal diseases. The objectives of this study were to determine the three most accessible portals to obtain speed of sound measurements of the radius and tibia with an Omnisense multisite quantitative ultrasound device and to determine probe-dependent intra- and interoperator variability for speed of sound measurements of the radius and tibia in six healthy hounds. The radius was most accessible at the cranial proximal metaphysis, the cranial middiaphysis, and medial distal metaphysis. Speed of sound measurements were possible at these sites on the radius with acceptable intra- and interoperator variation (1.6-4.6%). Measurements differed significantly when performed with different probes at the cranial proximal radial metaphysis. The tibia was most accessible at the cranial proximal metaphysis, the medial middiaphysis, and medial distal metaphysis. The medial middiaphyseal and mediodistal tibial sites allowed measurements with lowest intra- and interoperator variation (\u3c 3.5%). A smaller probe allowed tibial measurements with lowest interoperator variation. Measurements did not differ significantly at each tibial site when different probes were used. Measurements did not differ significantly between observers when measuring with the same probe at each specific site on radius and tibia. A medium-size probe allowed for most time-efficient measurements and the least number of failed measurements on the radius and tibia. Speed of sound can be consistently measured by different observers on the radius and tibia in healthy hounds