General anesthesia does not induce ultrasonographic changes in the pleura of healthy adult horses anesthetized for elective magnetic resonance imaging.

OBJECTIVE: To compare thoracic ultrasonographic findings in healthy horses before and after general anesthesia for elective MRI utilizing a recently developed ultrasonographic scoring system to aid clinicians in the early identification of pneumonia following anesthesia. ANIMALS: 13 adult horses > 3 years of age. PROCEDURES: Prior to anesthesia, horses underwent a thorough physical examination, CBC, thoracic radiography, and thoracic ultrasonography. Horses were then anesthetized for elective MRI, and thoracic ultrasonography was repeated within 3 hours after recovery. Thoracic ultrasonographic findings were scored utilizing a recently developed scoring system, and scores were compared before and after anesthesia. RESULTS: There was no significant difference identified in total thoracic ultrasonography score before and after anesthesia, and there was no correlation between thoracic ultrasonography score following anesthesia and the body weight of the horse, the time recumbent, and the dependent side. CLINICAL RELEVANCE: In healthy horses undergoing anesthesia for elective imaging, there was no significant change in thoracic ultrasonographic findings 3 hours after recovery from anesthesia. These data can aid clinicians in determining the clinical significance of ultrasonographic changes in the lung in the immediate postanesthetic period.

Comparison of thoracic ultrasonography and thoracic radiography between healthy adult horses and horses with bacterial pneumonia using a novel, objective ultrasonographic scoring system.

Background: Thoracic ultrasonography (TUS) is widely used in equine practice but comparison to radiography is limited in horses. Objectives: To validate a novel, objective scoring system for TUS in adult horses and to compare ultrasonographic and radiographic findings. Animals: 13 healthy horses and 9 with confirmed bacterial pneumonia. Methods: Prospective study in which TUS and radiography were performed on healthy horses and those with bacterial pneumonia confirmed by clinical signs and results of transtracheal wash analysis. Ultrasonography was scored utilizing a novel scoring system evaluating number of comet tail lesions, the presence or absence of pleural effusion and/or pulmonary consolidation in each intercostal space. Eighteen horses had thoracic radiographs taken that were scored by a board-certified radiologist utilizing a previously described system. Total scores were recorded and compared between control and diseased patients. Results/Findings: Ultrasonographic scores were significantly higher in the diseased group (median= 126) than in the control group (median = 20, p = 0.01). Receiver operating characteristics (ROC) analysis identified a sensitivity of 66.7% (95% CI 0.417-1) and specificity of 92.3% (95% CI 0.462-1) for the ability of ultrasonography to identify bacterial pneumonia utilizing a TUS score cutoff of 37. Conclusions and clinical importance: TUS had moderate sensitivity and high specificity for identification of bacterial pneumonia in adult horses. TUS appears to be an acceptable stand-alone imaging modality for diagnosis of bacterial pneumonia in horses when radiography is not practical.

Comparison of Fluid Analysis and Cytologic Findings of Cerebrospinal Fluid Between Three Collection Sites in Adult Equids With Neurological Disease.

Cerebrospinal fluid (CSF) is routinely collected from three sites in the horse, the atlanto-occipital (AO), atlantoaxial (AA), and lumbosacral (LS) space. A comparison between fluid analysis parameters [total protein, total nucleated cell count (TNCC), red blood cell (RBC) count, and morphologic analysis] from samples obtained at each of the three sites has not previously been performed. A retrospective analysis was performed to evaluate the differences in fluid analysis of CSF between the AO, AA, and LS sites in equids presented to a referral service for evaluation of suspected neurological disease. A total of 113 equids aged ≥1 year that underwent CSF collection between 2008 and 2020 were included. Total nucleated cell count, RBC concentration, total protein (TP), and morphologic evaluation between CSF samples obtained from the three sites were compared. When comparing all samples, LS centesis was associated with higher RBC compared to other sites (p < 0.05); TP was lower in the AA group than in the LS group (p < 0.05). Within a subset of cytologically unremarkable samples, RBC concentration was highest in LS samples (p < 0.01); TP was higher in LS samples compared to AA samples (p < 0.05) and TNCC was higher (p < 0.01) in AA and LS groups compared to the AO. In cytologically abnormal samples, there were no significant differences between sites in any parameter. Abnormal cytology was correlated with non-survival (p = 0.0002). Non-survival was associated with higher TNCC (p < 0.01). The receiver operating characteristic (ROC) curve for TNCC had an area under the curve of 0.67 (95% CI, 0.55-0.79) and indicated that a cutoff value of 24 cells/µL maximized specificity (72%) and sensitivity (54%) to predict non-survival in all horses. Positive predictive value was 45%; negative predictive value was 78%. The concentration of RBC was higher in samples from the LS site. This has clinical implications due to the importance of comparative diagnostics and its potential impact on cytologic evaluation. There were minimal differences in multiple other parameters between sites, which are likely clinically insignificant.

Comparison of two glucose-monitoring systems for use in horses.

OBJECTIVE: To determine the accuracy of 2 interstitial glucose-monitoring systems (GMSs) for use in horses compared with a point-of-care (POC) glucometer and standard laboratory enzymatic chemistry method (CHEM). ANIMALS: 8 clinically normal adult horses. PROCEDURES: One of each GMS device (Dexcom G6 and Freestyle Libre 14-day) was placed on each horse, and blood glucose concentration was measured via POC and CHEM at 33 time points and compared with simultaneous GMS readings. An oral glucose absorption test (OGAT) was performed on day 2, and glucose concentrations were measured and compared. RESULTS: Glucose concentrations were significantly correlated with one another between all devices on days 1 to 5. Acceptable agreement was observed between Dexcom G6 and Freestyle Libre 14-day when compared with CHEM on days 1, 3, 4, and 5 with a combined mean bias of 10.45 mg/dL and 1.53 mg/dL, respectively. During dextrose-induced hyperglycemia on day 2, mean bias values for Dexcom G6 (10.49 mg/dL) and FreeStyle Libre 14-day (0.34 mg/dL) showed good agreement with CHEM. CLINICAL RELEVANCE: Serial blood glucose measurements are used to diagnose or monitor a variety of conditions in equine medicine; advances in near-continuous interstitial glucose monitoring allow for minimally invasive glucose assessment, thereby reducing stress and discomfort to patients. Data from this study support the use of the Dexcom G6 and Freestyle Libre 14-day interstitial glucose-monitoring systems to estimate blood glucose concentrations in horses.

Development of a Colic Scoring System to Predict Outcome in Horses.

Acute abdominal pain in the horse is a common emergency presenting to equine practices. The wide variety of etiologies makes prognosticating survival a challenge. A retrospective, multi-institutional clinical study was performed to determine clinical parameters associated with survival of horses with colic, and to use them to develop a colic survival scoring system. The scoring system was then validated using clinical data in the prospective portion of the study. Medical records from 67 horses presenting for acute abdominal pain were evaluated to develop the colic assessment score. Twenty eight variables were compared between survivors and non-survivors and entered into logistic regression models for survival. Of these, six variables were included in the colic assessment score. A total colic assessment score range was from 0 to 12, with the highest score representing the lowest probability of survival. The optimal cutoff value to predict survival was seven resulting in an 86% sensitivity and 64% specificity with a positive predictive value of 88% and a negative predictive value of 57%. Data from 95 horses presenting for abdominal pain to two equine hospitals was then collected prospectively to validate the colic assessment score. Horses from the prospective portion of the study that received a score >7 were classified as predicted to die and those with a score ≤7 were predicted to survive. The classification was compared to the actual outcome, of which the sensitivity, specificity, positive and negative predictive values of the colic assessment score were 84, 62, 88, and 52%, respectively.

Blood thiamine (vitamin B1 ), ascorbic acid (vitamin C), and cortisol concentrations in healthy and ill neonatal foals.

BACKGROUND: Sepsis is common in foals and several treatments are used to facilitate recovery. Evidence in people suggests an association between low blood concentrations of thiamine, ascorbic acid, and cortisol and sepsis, with further evidence suggesting that administration of hydrocortisone, thiamine, and ascorbic acid may improve outcome. No information is available with regard to these treatments in foals. HYPOTHESIS/OBJECTIVES: To compare blood concentrations of thiamine, ascorbic acid, and cortisol in healthy and ill foals. ANIMALS: Fifteen healthy and 27 ill (septic and sick-nonseptic [SNS]) foals were evaluated at admission. Fewer healthy and ill foals were available for sampling at 72 and 120 hours. METHODS: Prospective study. Blood was collected from healthy foals at 12 (n = 15), 72 (n = 11), and 120 (n = 9) hours of age and from ill foals <48 hours old at admission (n = 27), 72 (n = 8), and 120 (n = 8) hours after presentation. Thiamine, ascorbic acid, and cortisol concentrations were measured in blood samples and compared between groups of foals. RESULTS: Blood concentrations of thiamine were significantly lower in septic compared to healthy foals at 72 (median, 1.72 ng/mL; P = .02) and 120 (median, 2.0 ng/mL; P = .04) hours after admission; blood concentrations of ascorbic acid also were significantly lower in septic compared to healthy foals at 72 (median, 4.4 µg/mL; P = .02) and 120 hours (median, 4.8 µg/mL; P = .03). Blood concentrations of ascorbic acid were lower in SNS compared to healthy foals at 72 (median, 6.9 µg/mL; P = .03) and 120 (median, 6.4 µg/mL; P = .04) hours after admission. Serum cortisol concentrations were significantly higher at admission in septic (median, 4.23 µg/dL) compared to SNS (median, 1.8 µg/dL; P = .01) and healthy (median, 2.2 µg/dL; P = .002) foals. CONCLUSIONS AND CLINICAL IMPORTANCE: A potential association exists between illness in foals and lower blood concentrations of thiamine and ascorbic acid during hospitalization. Additional studies are needed to examine a larger population of foals and determine the clinical impact of low vitamin concentrations, if any, on morbidity and mortality.

Dynamics of androgens in healthy and hospitalized newborn foals.

BACKGROUND: Information on steroids derived from the adrenal glands, gonads, or fetoplacental unit is minimal in newborn foals. OBJECTIVE: To measure androgen concentrations in serum and determine their association with disease severity and outcome in hospitalized foals. ANIMALS: Hospitalized (n = 145) and healthy (n = 80) foals. METHODS: Prospective, multicenter, cross-sectional study. Foals of ≤3 days of age from 3 hospitals and horse farms were classified as healthy and hospitalized (septic, sick nonseptic, neonatal maladjustment syndrome [NMS]) based on physical exam, medical history, and laboratory findings. Serum androgen and plasma ACTH concentrations were measured with immunoassays. Data were analyzed by nonparametric methods and univariate analysis. RESULTS: Serum dehydroepiandrosterone (DHEA), androstenedione, testosterone, and dihydrotestosterone (DHT) concentrations were higher upon admission in hospitalized foals (P < .05), were associated with nonsurvival, decreased to 4.9-10.8%, 5.7-31%, and 30.8-62.8% admission values in healthy, SNS, and septic foals, respectively (P < .05), but remained unchanged or increased in nonsurviving foals. ACTH:androgen ratios were higher in septic and NMS foals (P < .05). Foals with decreased androgen clearance were more likely to die (odds ratio > 3; P < .05). CONCLUSIONS AND CLINICAL IMPORTANCE: Similar to glucocorticoids, mineralocorticoids, and progestagens, increased serum concentrations of androgens are associated with disease severity and adverse outcome in hospitalized newborn foals. In healthy foals, androgens decrease over time, however, remain elevated longer in septic and nonsurviving foals. Androgens could play a role in or reflect a response to disorders such as sepsis or NMS in newborn foals.

Pharmacokinetics and Tissue Levels of Pantoprazole in Neonatal Calves After Intravenous Administration.

Background: Neonatal calves are at risk of developing abomasal ulceration, but there is a lack of pharmacokinetic data for potential anti-ulcerative therapies, such as pantoprazole, in ruminant species. Objective: The study objectives were to estimate plasma pharmacokinetic parameters for pantoprazole in neonatal dairy calves after intravenous (IV) administration. A secondary objective was to quantify the concentrations of pantoprazole in edible tissues after IV dosing. Methods: Pantoprazole was administered to 9 neonatal Holstein calves at a dose of 1 mg/kg IV. Plasma samples were collected over 24 h and analyzed via HPLC-MS for determining pantoprazole concentrations. Pharmacokinetic parameters were derived via non-compartmental analysis. Tissue samples were collected at 1, 3, and 5 days after administration and analyzed via HPLC-MS. Results: Following IV administration, plasma clearance, elimination half-life, and volume of distribution of pantoprazole were estimated at 4.46 mL/kg/min, 2.81 h, and 0.301 L/kg, respectively. The global extraction ratio was estimated at 0.053 ± 0.015. No pantoprazole was detected in the edible tissues 1, 3, or 5 days after administration. A metabolite, pantoprazole sulfone was detected in all the edible tissues 1 and 3 days after administration. Conclusion: The reported plasma clearance for pantoprazole is less than that reported for alpacas but higher than reported in foals. The elimination half-life in calves appears to be longer than observed in foals and alpacas. While pantoprazole sulfone was detected in the tissues after IV administration, further research is needed as to the metabolism and potential tissue accumulation of other pantoprazole metabolites in calves. Future pharmacodynamic studies are necessary to determine the efficacy of pantoprazole on abomasal acid suppression in calves.

Evaluation of Locally Injected Mycobacterium Cell Wall Fraction in Horses with Sarcoids.

A reformulation of Mycobacterium cell wall fraction immunotherapeutic can be used to successfully treat sarcoids in horses. Sarcoids are reported to be the most common equine skin tumors with tumor type and location influencing the choice of treatment. Wide surgical excision is curative for many tumors, but may not always be feasible. Previous studies have reported sarcoid regression after injection with mycobacterial cell wall immunotherapeutics. A new formulation of the Mycobacterium phlei cell wall fraction immunostimulant (Immunocidin Equine) was used to treat cutaneous tumors in horses. Equids with skin tumors diagnosed as sarcoids were enrolled in the study. Sarcoids were injected at the initial visit with Immunocidin Equine and subsequently at approximately 2-week intervals. Of 17 cases, nine cases were completely resolved at the end of the study period evaluation or at the time of final follow-up (52.9%). Three cases were reported as improved (smaller), but not resolved (17.6%). Three cases were discontinued from the study as the respective masses were growing larger or not resolving (17.6%). One case (5.8%) with two masses had resolution of one mass, whereas the other tumor had a small regrowth 5 months after the last treatment. One case (5.8%) was lost to follow-up. All cases had mild to moderate swelling of the injection site, and some cases had discharge after the second, third, or fourth injections. No serious systemic side effects or complications were encountered during the study.

Multiple adrenocortical steroid response to administration of exogenous adrenocorticotropic hormone to hospitalized foals.

BACKGROUND: The hypothalamic-pituitary-adrenal axis regulates the response to sepsis-associated stress. Relative adrenal insufficiency or adrenocorticotropic hormone (ACTH):cortisol imbalance, defined as a poor cortisol response to administration of ACTH, is common and associated with death in hospitalized foals. However, information on other adrenal steroid response to ACTH stimulation in sick foals is minimal. OBJECTIVE: To investigate the response of multiple adrenocortical steroids to administration of ACTH in foals. ANIMALS: Hospitalized (n = 34) and healthy (n = 13) foals. METHODS: In this prospective study, hospitalized foals were categorized into 2 groups using cluster analysis based on adrenal steroids response to ACTH stimulation: Cluster 1 (n = 11) and Cluster 2 (n = 23). After baseline blood sample collection, foals received 10 µg of ACTH with additional samples collected at 30 and 90 minutes after ACTH. Steroid and ACTH concentrations were determined by immunoassays. The area under the curve (AUC) and Delta0-30 were calculated for each hormone. RESULTS: The AUC for cortisol, aldosterone, androstenedione, pregnenolone, 17α-OH-progesterone, and progesterone were higher in critically ill (Cluster 1) compared to healthy foals (P < .01). Delta0-30 for cortisol and 17α-OH-progesterone was lower in Cluster 1 (24%, 26.7%) and Cluster 2 (16%, 11.2%) compared to healthy foals (125%, 71%), respectively (P < .05). Foals that died had increased AUC for endogenous ACTH (269 versus 76.4 pg/mL/h, P < .05) accompanied by a low AUC for cortisol (5.5 versus 15.5 µg/dL/h, P < .05), suggesting adrenocortical dysfunction. CONCLUSION AND CLINICAL IMPORTANCE: The 17α-OH-progesterone response to administration of ACTH was a good predictor of disease severity and death in hospitalized foals.

Engraftment and bone mass are enhanced by PTHrP 1-34 in ectopically transplanted vertebrae (vossicle model) and can be non-invasively monitored with bioluminescence and fluorescence imaging.

Evidence exists that parathyroid hormone-related protein (PTHrP) 1-34 may be more anabolic in bone than parathyroid hormone 1-34. While optical imaging is growing in popularity, scant information exists on the relationships between traditional bone imaging and histology and bioluminescence (BLI) and fluorescence (FLI) imaging. We aimed to evaluate the effects of PTHrP 1-34 on bone mass and determine if relationships existed between radiographic and histologic findings in bone and BLI and FLI indices. Vertebrae (vossicles) from mice coexpressing luciferase and green fluorescent protein were implanted subcutaneously into allogenic nude mice. Transplant recipients were treated daily with saline or PTHrP 1-34 for 4 weeks. BLI, FLI, radiography, histology, and µCT of the vossicles were performed over time. PTHrP 1-34 increased bioluminescence the most after 2 weeks, fluorescence at all time points, and decreased the time to peak bioluminescence at 4 weeks (P ≤ 0.027), the latter of which suggesting enhanced engraftment. PTHrP 1-34 maximized vertebral body volume at 4 weeks (P < 0.0001). The total amount of bone observed histologically increased in both groups at 2 and 4 weeks (P ≤ 0.002); however, PTHrP 1-34 exceeded time-matched controls (P ≤ 0.044). A positive linear relationship existed between the percentage of trabecular bone and (1) total bioluminescence (r = 0.595; P = 0.019); (2) total fluorescence (r = 0.474; P = 0.074); and (3) max fluorescence (r = 0.587; P = 0.021). In conclusion, PTHrP 1-34 enhances engraftment and bone mass, which can be monitored non-invasively by BLI and FLI.

Vitamin D Metabolites and Their Association with Calcium, Phosphorus, and PTH Concentrations, Severity of Illness, and Mortality in Hospitalized Equine Neonates.

BACKGROUND: Hypocalcemia is a frequent abnormality that has been associated with disease severity and outcome in hospitalized foals. However, the pathogenesis of equine neonatal hypocalcemia is poorly understood. Hypovitaminosis D in critically ill people has been linked to hypocalcemia and mortality; however, information on vitamin D metabolites and their association with clinical findings and outcome in critically ill foals is lacking. The goal of this study was to determine the prevalence of vitamin D deficiency (hypovitaminosis D) and its association with serum calcium, phosphorus, and parathyroid hormone (PTH) concentrations, disease severity, and mortality in hospitalized newborn foals. METHODS AND RESULTS: One hundred newborn foals ≤72 hours old divided into hospitalized (n = 83; 59 septic, 24 sick non-septic [SNS]) and healthy (n = 17) groups were included. Blood samples were collected on admission to measure serum 25-hydroxyvitamin D3 [25(OH)D3], 1,25-dihydroxyvitamin D3 [1,25(OH) 2D3], and PTH concentrations. Data were analyzed by nonparametric methods and univariate logistic regression. The prevalence of hypovitaminosis D [defined as 25(OH)D3 <9.51 ng/mL] was 63% for hospitalized, 64% for septic, and 63% for SNS foals. Serum 25(OH)D3 and 1,25(OH) 2D3 concentrations were significantly lower in septic and SNS compared to healthy foals (P<0.0001; P = 0.037). Septic foals had significantly lower calcium and higher phosphorus and PTH concentrations than healthy and SNS foals (P<0.05). In hospitalized and septic foals, low 1,25(OH)2D3 concentrations were associated with increased PTH but not with calcium or phosphorus concentrations. Septic foals with 25(OH)D3 <9.51 ng/mL and 1,25(OH) 2D3 <7.09 pmol/L were more likely to die (OR=3.62; 95% CI = 1.1-12.40; OR = 5.41; 95% CI = 1.19-24.52, respectively). CONCLUSIONS: Low 25(OH)D3 and 1,25(OH)2D3 concentrations are associated with disease severity and mortality in hospitalized foals. Vitamin D deficiency may contribute to a pro-inflammatory state in equine perinatal diseases. Hypocalcemia and hyperphosphatemia together with decreased 1,25(OH)2D3 but increased PTH concentrations in septic foals indicates that PTH resistance may be associated with the development of these abnormalities.

Sudden death of a horse with supraventricular tachycardia following oral administration of flecainide acetate.

OBJECTIVE: To describe a case of supraventricular tachycardia and sudden death in a horse following administration of flecainide acetate. CASE SUMMARY: An 8-year-old Hanoverian warmblood gelding was treated for chronic, naturally occurring, supraventricular tachycardia with digoxin, procainamide hydrochloride, quinidine sulfate, and flecainide acetate. After oral administration of flecainide, polymorphic ventricular tachycardia (torsades de pointes) and ventricular fibrillation developed, leading to cardiovascular collapse and death. NEW OR UNIQUE INFORMATION PROVIDED: Atrial fibrillation is the most commonly diagnosed dysrhythmia associated with poor performance in horses, while atrial tachycardia is rarely documented. Here, we describe a case of sudden death in a horse with atrial tachycardia following the oral administration of flecainide acetate, after the lack of response to other antiarrhythmic drugs. Information provided in this case report is new and will make clinicians aware of the potential complications of flecainide alone or in combination with other drugs, in horses with cardiac dysrhythmias.

Development of a likelihood of survival scoring system for hospitalized equine neonates using generalized boosted regression modeling.

BACKGROUND: Medical management of critically ill equine neonates (foals) can be expensive and labor intensive. Predicting the odds of foal survival using clinical information could facilitate the decision-making process for owners and clinicians. Numerous prognostic indicators and mathematical models to predict outcome in foals have been published; however, a validated scoring method to predict survival in sick foals has not been reported. The goal of this study was to develop and validate a scoring system that can be used by clinicians to predict likelihood of survival of equine neonates based on clinical data obtained on admission. METHODS AND RESULTS: Data from 339 hospitalized foals of less than four days of age admitted to three equine hospitals were included to develop the model. Thirty seven variables including historical information, physical examination and laboratory findings were analyzed by generalized boosted regression modeling (GBM) to determine which ones would be included in the survival score. Of these, six variables were retained in the final model. The weight for each variable was calculated using a generalized linear model and the probability of survival for each total score was determined. The highest (7) and the lowest (0) scores represented 97% and 3% probability of survival, respectively. Accuracy of this survival score was validated in a prospective study on data from 283 hospitalized foals from the same three hospitals. Sensitivity, specificity, positive and negative predictive values for the survival score in the prospective population were 96%, 71%, 91%, and 85%, respectively. CONCLUSIONS: The survival score developed in our study was validated in a large number of foals with a wide range of diseases and can be easily implemented using data available in most equine hospitals. GBM was a useful tool to develop the survival score. Further evaluations of this scoring system in field conditions are needed.