Ex vivo comparison of pin placement with patient-specific drill guides or freehand technique in canine cadaveric spines.

OBJECTIVE: To compare vertebral implant placement in the canine thoracolumbar spine between 3D-printed patient-specific drill guides (3DPG) and the conventional freehand technique (FH). STUDY DESIGN: Ex vivo study. ANIMALS: Cadaveric canine spines (n = 24). METHODS: Implant trajectories were established for the left and right sides of the T10 through L6 vertebrae based on computed tomography (CT) imaging. Customized drill guides were created for each vertebra of interest. Each cadaver was randomly assigned to one of six veterinarians with varying levels of experience placing vertebral implants. Vertebrae were randomly assigned a surgical order and technique (3DPG or FH) for both sides. Postoperative CT images were acquired. A single, blinded observer assessed pin placement using a modified Zdichavsky classification. RESULTS: A total of 480 implants were placed in 240 vertebrae. Three sites were excluded from the analysis; therefore, a total of 238 implants were evaluated using the FH technique and 239 implants using 3DPG. When evaluating implant placement, 152/239 (63.6%) of 3DPG implants were considered to have an acceptable placement in comparison with 115/248 (48.32%) with FH. Overall, pin placement using 3DPG was more likely to provide acceptable pin placement (p < .001) in comparison with the FH technique for surgeons at all levels of experience. CONCLUSION: The use of 3DPG was shown to be better than the conventional freehand technique regarding acceptable placement of implants in the thoracolumbar spine of canine cadavers. CLINICAL SIGNIFICANCE: Utilizing 3DPG can be considered better than the traditional FH technique when placing implants in the canine thoracolumbar spine.

Elastic Modulus and Its Relation to Apparent Mineral Density in Juvenile Equine Bones of the Lower Limb.

Density-modulus relationships are necessary to develop finite element models of bones that may be used to evaluate local tissue response to different physical activities. It is unknown if juvenile equine trabecular bone may be described by the same density-modulus as adult equine bone, and how the density-modulus relationship varies with anatomical location and loading direction. To answer these questions, trabecular bone cores from the third metacarpal (MC3) and proximal phalanx (P1) bones of juvenile horses (age <1 yr) were machined in the longitudinal (n = 134) and transverse (n = 90) directions and mechanically tested in compression. Elastic modulus was related to apparent computed tomography density of each sample using power law regressions. We found that density-modulus relationships for juvenile equine trabecular bone were significantly different for each anatomical location (MC3 versus P1) and orientation (longitudinal versus transverse). Use of the incorrect density-modulus relationship resulted in increased root mean squared percent error of the modulus prediction by 8-17%. When our juvenile density-modulus relationship was compared to one of an equivalent location in adult horses, the adult relationship resulted in an approximately 80% increase in error of the modulus prediction. Moving forward, more accurate models of young bone can be developed and used to evaluate potential exercise regimens designed to encourage bone adaptation.

Impact of periarticular osteophytes of the distal tarsus diagnosed in nonlame yearling Standardbred horses on racing performance.

OBJECTIVE: The aim of this study was to identify the radiographic prevalence of periarticular osteophytes of the distal tarsus in nonlame yearling Standardbred horses, and to evaluate its potential impact on race performance. STUDY DESIGN: Cross-sectional cohort study. ANIMALS: Client-owned yearling Standardbred horses (n = 416). METHODS: Bilateral tarsal radiographs were available from all horses for review. Osteophytes were measured on radiographs using clinical visualization software and categorized by size. Racing records were obtained from the United States Trotting Association. Regression analysis was used to determine associations between presence or size of periarticular osteophytes and performance parameters with sex and gait covariates. RESULTS: Of 416 Standardbred yearlings without clinical lameness, 113 (27.1%) had distal tarsal periarticular osteophytes. Regression analyses revealed few associations between the presence of periarticular osteophytes and performance parameters. Affected horses had fewer starts at 4 years of age (incident rate ratio [IRR] 0.92, p = .01) and fewer lifetime starts (IRR 0.95, p = .003), but the effect size was small. Within the affected group, osteophyte size was only associated with number of starts at 3 (IRR 0.67, p < .0001). Sex and gait affected many performance parameters. CONCLUSION: The prevalence of distal tarsal periarticular osteophytes was similar to that in other breeds. Periarticular osteophytes of the distal tarsus appeared to be a largely incidental finding in nonlame yearling Standardbreds intended for harness racing. CLINICAL SIGNIFICANCE: Distal tarsal periarticular osteophytes in young, nonlame Standardbred horses should affect racing potential only minimally. This is in contrast to reports from other disciplines.

Influence of feline brachycephaly on respiratory, gastrointestinal, sleep, and activity abnormalities.

OBJECTIVE: To determine the influence of brachycephaly on respiratory, gastrointestinal, sleep, and activity-related parameters in cats. STUDY DESIGN: Prospective questionnaire-based study. ANIMALS: A total of 194 BC and 1003 non-BC cats. METHODS: Owners completed an online questionnaire regarding respiratory, gastrointestinal, sleep, and activity-related parameters. Response options were scored, and individual scores summed to give a total clinical severity score for each cat. RESULTS: Brachycephalic cats had more frequent snoring (odds ratio [OR] 6.89; 95% confidence interval [CI]: 5.06-9.41), sneezing (OR 6.52; CI: 4.75-8.98), nasal discharge (OR 8.26; 95% CI 5.77-11.85), coughing (OR 1.75; CI: 1.17-2.59), and dyspnea (OR 5.32; CI: 3.42-8.28); shorter activity before becoming dyspneic (OR 2.71; CI: 1.93-3.79), slower recovery from activity (OR 3.17; CI: 2.19-4.57), lower activity levels (OR 2.16; CI: 1.59-2.95), and increased respiratory noise (OR 6.68; CI: 4.71-9.52); and more hypersalivation (OR 2.50; CI: 1.47-4.16), halitosis (OR 1.40; CI: 1.00-1.95), and difficulty chewing (OR 5.19; CI: 3.65-7.38). Median clinical severity scores were higher for BC cats than non-BC cats (p < .0001). CONCLUSIONS: Brachycephalic cats (BC) were at risk for respiratory, gastrointestinal, and activity-related symptoms compared to non-BC cats. CLINICAL RELEVANCE: Some BC cats exhibit clinically relevant symptoms and behaviors as reported by owners. Medical or surgical interventions may improve these symptoms and warrant investigation.

Heart rate, arterial pressure and propofol-sparing effects of guaifenesin in dogs.

OBJECTIVE: To evaluate the heart rate (HR) and systemic arterial pressure (sAP) effects, and propofol induction dose requirements in healthy dogs administered propofol with or without guaifenesin for the induction of anesthesia. STUDY DESIGN: Prospective blinded crossover experimental study. ANIMALS: A total of 10 healthy adult female Beagle dogs. METHODS: Dogs were premedicated with intravenous (IV) butorphanol (0.4 mg kg-1) and administered guaifenesin 5% at 50 mg kg-1 (treatment G50), 100 mg kg-1 (treatment G100) or saline (treatment saline) IV prior to anesthetic induction with propofol. HR, invasive sAP and respiratory rate (fR) were recorded after butorphanol administration, after guaifenesin administration and after propofol and endotracheal intubation. Propofol doses for intubation were recorded. Repeated measures analysis of variance (anova) was used to determine differences in propofol dose requirements among treatments, and differences in cardiopulmonary values over time and among treatments with p < 0.05 considered statistically significant. RESULTS: Propofol doses (mean ± standard deviation) for treatments saline, G50 and G100 were 3.3 ± 1.0, 2.7 ± 0.7 and 2.1 ± 0.8 mg kg-1, respectively. Propofol administered was significantly lower in treatment G100 than in treatment saline (p = 0.04). In treatments G50 and G100, HR increased following induction of anesthesia and intubation compared with baseline measurements. HR was higher in treatment G100 than in treatments G50 and saline following induction of anesthesia. In all treatments, sAP decreased following intubation compared with baseline values. There were no significant differences in sAP among treatments. fR was lower following intubation than baseline and post co-induction values and did not differ significantly among treatments. CONCLUSIONS AND CLINICAL RELEVANCE: When administered as a co-induction agent in dogs, guaifenesin reduced propofol requirements for tracheal intubation. HR increased and sAP and fR decreased, but mean values remained clinically acceptable.

CT volumetric analysis permits comparison of tongue size and tongue fat in different canine brachycephalic and mesaticephalic breeds.

While macroglossia is a newly accepted component of brachycephalic obstructive airway syndrome (BOAS) in dogs, macroglossia with increased tongue fat is a well-known cause for obstructive sleep apnea (OSA) in people, and targeted reduction procedures such as midline glossectomy are used to treat people with OSA. While midline glossectomy has been described in dogs, tissue contributions to macroglossia have not been characterized. The purpose of this retrospective, descriptive, case-control study was to describe and compare volumetric dimensions of the tongue and tongue fat in brachycephalic (BC) and mesaticephalic (MC) dogs using CT images. Data collected included head and neck CT images from 17 BC and 18 control MC dogs. Multiplanar reformatted and 3D reconstructed images were created using image segmentation and specialized visualization software to calculate volumetric dimensions of the total tongue, tongue fat, and tongue muscle. Rostral and caudal topographical distributions of fat were compared. Total tongue and tongue muscle volume (P < 0.0001) and tongue fat volume (P = 0.01) normalized to body weight (BW) were greater in BC dogs. More fat was localized in the caudal tongue in both groups (P < 0.04). In regression analysis, BC conformation and increased weight were significant predictors of increased tongue fat volume. As in people, increased tongue fat may contribute to macroglossia and sleep-disordered breathing in BC dogs. Use of CT volumetry to identify tongue fat deposits may permit targeted surgical reduction of tongue volume in BC dogs and contribute substantially to treatment of BOAS.

Identification and validation of genetic variants predictive of gait in standardbred horses.

Several horse breeds have been specifically selected for the ability to exhibit alternative patterns of locomotion, or gaits. A premature stop codon in the gene DMRT3 is permissive for "gaitedness" across breeds. However, this mutation is nearly fixed in both American Standardbred trotters and pacers, which perform a diagonal and lateral gait, respectively, during harness racing. This suggests that modifying alleles must influence the preferred gait at racing speeds in these populations. A genome-wide association analysis for the ability to pace was performed in 542 Standardbred horses (n = 176 pacers, n = 366 trotters) with genotype data imputed to ~74,000 single nucleotide polymorphisms (SNPs). Nineteen SNPs on nine chromosomes (ECA1, 2, 6, 9, 17, 19, 23, 25, 31) reached genome-wide significance (p < 1.44 x 10-6). Variant discovery in regions of interest was carried out via whole-genome sequencing. A set of 303 variants from 22 chromosomes with putative modifying effects on gait was genotyped in 659 Standardbreds (n = 231 pacers, n = 428 trotters) using a high-throughput assay. Random forest classification analysis resulted in an out-of-box error rate of 0.61%. A conditional inference tree algorithm containing seven SNPs predicted status as a pacer or trotter with 99.1% accuracy and subsequently performed with 99.4% accuracy in an independently sampled population of 166 Standardbreds (n = 83 pacers, n = 83 trotters). This highly accurate algorithm could be used by owners/trainers to identify Standardbred horses with the potential to race as pacers or as trotters, according to the genotype identified, prior to initiating training and would enable fine-tuning of breeding programs with designed matings. Additional work is needed to determine both the algorithm's utility in other gaited breeds and whether any of the predictive SNPs play a physiologically functional role in the tendency to pace or tag true functional alleles.

Performance of predictive models of survival in horses undergoing emergency exploratory laparotomy for colic.

OBJECTIVE: To evaluate previously published predictive survival models in a population of horses undergoing colic surgery in the midwestern United States. STUDY DESIGN: Retrospective cohort study; single referral hospital. ANIMALS: A total of 260 horses met the inclusion criteria. METHODS: Medical records of horses undergoing surgical treatment for colic were reviewed. Previously published models were applied to cohort data to predict outcome. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy for prediction of short-term survival were calculated. RESULTS: Single-variable and multivariable models performed similarly for prediction of survival, with a mean 79% sensitivity (range: 44%-94%), 48% specificity (range: 22%-83%), 63% PPV (range: 56%-72%), 73% NPV (range: 60%-83%), and 64% accuracy (range: 59%-72%). Blood lactate ≤6 mmol/l and the colic severity score (CSS) were highly sensitive for prediction of survival; however, both had poor specificity. CONCLUSION: Single-variable and multivariable predictive models did not perform as well for prediction of survival in the study cohort compared to original reports, suggesting that population-specific factors contribute to patient survival. CLINICAL SIGNIFICANCE: Predictive models of survival developed in one population may be less reliable when used to predict outcome in horses undergoing colic surgery from an independent population. Additional model testing and refinement using data from multiple surgical centers could be considered to improve prediction of outcome for horses undergoing laparotomy for treatment of colic.

The effect of repeated freezing and thawing on the suture pull-out strength in equine arytenoid and cricoid cartilages.

OBJECTIVE: To assess the effect of repeated freezing and thawing on the suture pull-out strength in arytenoid and cricoid cartilages subjected to the laryngoplasty (LP) procedure. STUDY DESIGN: Ex vivo experimental study. SAMPLE POPULATION: Ten grossly normal equine cadaveric larynges. METHODS: Bilateral LP constructs were created using a standard LP technique. One hemilarynx was randomly allocated to the single freeze and thaw group and the other allocated to the repeated freeze and thaw (3 complete cycles) group. The suture ends of each LP construct were attached to a load frame and subjected to monotonic loading until construct failure. Mean load (N) and displacement (mm) at LP construct failure were compared between groups. RESULTS: All LP constructs failed by suture pull through the arytenoid cartilage. The mean load at failure was similar between groups (118.9 ± 25.5 N in the single freeze and thaw group and 113.4 ± 20.5 N in the repeated freeze and thaw group, P = .62). The mean displacement at failure was similar between groups (54.4 ± 15.1 mm in the single freeze and thaw group and 54.4 ± 15.4 mm in the repeated freeze and thaw group, P = .99). CONCLUSION: Repeated freezing and thawing did not affect the suture pullout strength of the arytenoid and cricoid cartilages. CLINICAL SIGNIFICANCE: Laryngeal specimens that have been subjected to repeated freezing and thawing can be utilized in the experimental evaluation of LP procedures because there is no alteration of the suture pull-out strength of the relevant cartilages.

Evaluation of the airway mechanics of modified toggle laryngoplasty constructs using a vacuum chamber airflow model.

OBJECTIVE: To evaluate the airway mechanics of modified toggle LP constructs in an airflow chamber model and compare these to the airway mechanics of standard LP constructs. STUDY DESIGN: Ex-vivo experimental study. SAMPLE POPULATION: Fifty-one equine cadaveric larynges. METHODS: Bilateral LP constructs were performed using a modified toggle (n = 23) or a standard (n = 21) LP technique. Constructs were tested in an airflow model before and after cyclic loading which was designed to mimic postoperative swallowing. The cross-sectional area (CSA), peak translaryngeal airflow (L/s), and impedance (cmH2 0/L/s) were determined and compared between LP constructs before and after cycling. RESULTS: The mean CSA of the rima glottidis of the modified toggle LP constructs was 15.2 ± 2.6 cm2 before and 14.7 ± 2.6 cm2 after cyclic loading, and the mean CSA of the rima glottidis of the standard LP constructs was 16.4 ± 2.9 cm2 before and 15.7 ± 2.8 cm2 after cyclic loading. The modified toggle LP constructs had similar peak translaryngeal impedance before and after cyclic loading (p = .13); however, the standard LP constructs had higher peak translaryngeal impedance after cyclic loading (p = .02). CONCLUSION: The modified toggle and standard LP constructs had comparable airway mechanics in an ex-vivo model. CLINICAL SIGNIFICANCE: Further investigation is warranted to determine the extent to which the modified toggle LP technique restores normal airway function in horses with RLN.

Biomechanical properties of canine staphylectomies closed with barbed or smooth suture.

OBJECTIVE: To compare the duration of closure and biomechanical properties of staphylectomies closed with absorbable bidirectional barbed suture or smooth monofilament suture in a simple continuous or interrupted pattern STUDY DESIGN: Ex vivo study SAMPLE POPULATION: Soft palates (n = 60) harvested from mesaticephalic canine cadavers METHODS: One centimeter of tissue was excised from the caudal border of each soft palate, and the oral and nasopharyngeal mucosal surfaces were apposed with 2-0 bidirectional Quill Monoderm knotless closure device barbed suture (Q), 3-0 Monocryl in a simple continuous (MC) pattern, or 3-0 Monocryl in a simple interrupted (MI) pattern (n = 20 per group). Duration of closure was compared between groups. Tissues were tested under tension to failure, and mode of failure data were collected by video capture. RESULTS: Closure time was longer for MI closures than for Q and MC closures, with means of 259.9, 215.4, and 196.7 seconds, respectively (P < .0001). No difference was detected in yield force, force to first tissue rupture, maximum force, and energy required for yield and maximum force between groups. Energy to yield was 190.0, 167.8, and 188.95 N-mm for MI, Q, and MC closures, respectively. CONCLUSION: Biomechanical properties of staphylectomies closed with barbed or smooth sutures did not differ in this cadaveric model. CLINICAL SIGNIFICANCE: Barbed suture can be considered as an alternative for closure of canine staphylectomies. These results provide evidence to justify additional research to evaluate clinical outcomes in dogs undergoing staphylectomy.

Differential gene expression analysis reveals pathways important in early post-traumatic osteoarthritis in an equine model.

BACKGROUND: Post-traumatic osteoarthritis (PTOA) is a common and significant problem in equine athletes. It is a disease of the entire joint, with the synovium thought to be a key player in disease onset and progression due to its role in inflammation. The development of effective tools for early diagnosis and treatment of PTOA remains an elusive goal. Altered gene expression represents the earliest discernable disease-related change, and can provide valuable information about disease pathogenesis and identify potential therapeutic targets. However, there is limited work examining global gene expression changes in early disease. In this study, we quantified gene expression changes in the synovium of osteoarthritis-affected joints using an equine metacarpophalangeal joint (MCPJ) chip model of early PTOA. Synovial samples were collected arthroscopically from the MCPJ of 11 adult horses before (preOA) and after (OA) surgical induction of osteoarthritis and from sham-operated joints. After sequencing synovial RNA, Salmon was used to quasi-map reads and quantify transcript abundances. Differential expression analysis with the limma-trend method used a fold-change cutoff of log2(1.1). Functional annotation was performed with PANTHER at FDR < 0.05. Pathway and network analyses were performed in Reactome and STRING, respectively. RESULTS: RNA was sequenced from 28 samples (6 preOA, 11 OA, 11 sham). "Sham" and "preOA" were not different and were grouped. Three hundred ninety-seven genes were upregulated and 365 downregulated in OA synovium compared to unaffected. Gene ontology (GO) terms related to extracellular matrix (ECM) organization, angiogenesis, and cell signaling were overrepresented. There were 17 enriched pathways, involved in ECM turnover, protein metabolism, and growth factor signaling. Network analysis revealed clusters of differentially expressed genes involved in ECM organization, endothelial regulation, and cellular metabolism. CONCLUSIONS: Enriched pathways and overrepresented GO terms reflected a state of high metabolic activity and tissue turnover in OA-affected tissue, suggesting that the synovium may retain the capacity to support healing and homeostasis in early disease. Limitations of this study include small sample size and capture of one point post-injury. Differentially expressed genes within key pathways may represent potential diagnostic markers or therapeutic targets for PTOA. Mechanistic validation of these findings is an important next step.

Effect of Preparation Method on the Protein Profile of Equine Amnion Dressings.

The protein content of amnion is thought to be the primary contributor to its efficacy as a biological dressing for wounds. Protein elution into antibiotic processing media has been reported, but the effect of antiseptic-based processing methods is unknown. Amniotic membranes were collected from eight healthy mares. Samples were collected after removal of gross debris. Tissues were subsequently divided and processed with either 0.05% chlorhexidine or 2% iodine/0.25% acetic acid. After protein extraction and trypsin digestion, the proteins were labeled with 8-plex iTRAQ tags, combined, and analyzed by high-resolution liquid chromatography-mass spectrometry. The MaxQuant-Perseus software suite was used to identify and quantify sample proteins, with functional annotation performed in PANTHER. There were 220 unique proteins identified, of which 144 were found in all individuals and across all conditions, several with a known role in wound healing. Contrary to expectations, processing did not significantly alter the protein content of the amnion tissue. Limitations include the small sample size and single time point. These results suggest that either processing method is acceptable for use in the preparation of equine amnion dressings. The role of expressed proteins in the biological activity of amnion dressings remains to be elucidated.

Effects of 2 preparation methods and long-term storage on structural integrity and bacterial loads of equine amnion.

OBJECTIVE: To determine the influence of tissue preparation and long-term storage methods on structural integrity and risk of bacterial contamination of equine amnion. STUDY DESIGN: Prospective experimental investigation SAMPLE POPULATION: Amniotic membranes from 8 healthy mares (n = 440 tested samples). METHODS: Samples for baseline bacteriology and histology were taken after removal of debris. The remaining tissue was divided and processed with 0.05% chlorhexidine or 2% iodine/0.25% acetic acid. Processed amnion samples were assigned to 1 of 9 combinations of storage media (saline, chlorhexidine, acetic acid) and temperature (4 °C, -20 °C, -80 °C). Samples were submitted for quantitative bacteriology and histopathology at 1 week, 4 weeks, and 3, 6, 9, and 12 months. RESULTS: Baseline bacterial levels ranged from <200 to > 150 000 colony-forming units (cfu)/mL. None of the potentially pathogenic bacteria in baseline samples were subsequently cultured throughout the study. Nonpathogenic bacteria (median 20 cfu/mL), most commonly Bacillus sp, were cultured sporadically across storage conditions. Tissue architecture was minimally affected histologically by processing protocol, storage temperature, or storage duration. CONCLUSION: The 2 processing protocols tested here resulted in minimal bacterial contamination or loss of structural integrity of equine amnion stored for up to 12 months at 4 °C, -20 °C, or -80 °C. CLINICAL SIGNIFICANCE: Amnion collected during the foaling season may be stored for up to 12 months without significant bacterial contamination or structural alterations.

Long-term outcome after stifle arthroscopy in 82 Western performance horses (2003-2010).

OBJECTIVE: To report the outcome of horses engaged in Western performance disciplines after stifle arthroscopy and identify prognostic factors for return to performance. STUDY DESIGN: Retrospective case series. SAMPLE POPULATION: Eighty-two Western performance horses undergoing stifle arthroscopy. METHODS: Medical records were reviewed for horses involved in athletic performance/training for various Western performance disciplines and undergoing arthroscopy for lameness localized to the stifle. Follow-up was obtained ≥2 years postoperatively by telephone interviews with the owners. Preoperative and intraoperative findings as well as postoperative treatment were analyzed for their association with return to athletic performance as the primary outcome of interest. RESULTS: The most common disciplines represented were cutting (n = 38), Western pleasure (n = 13), and reining (n = 13). Approximately 40% (32/82) of horses returned to intended use after surgery. Increased age, higher degree of lameness, longer duration of lameness, and the presence of partial-thickness cartilage lesions decreased the odds of returning to athletic performance. Postoperative therapies (intra-articular: stem cells, corticosteroids, interleukin-1 receptor antagonist protein, hyaluronic acid/polysulfated glycosaminoglycans; systemic: nonsteroid anti-inflammatory drugs, hyaluronic acid/polysulfated glycosaminoglycans, oral joint supplements) did not affect the odds of returning to intended use. CONCLUSION: Less than half of the Western performance horses that underwent stifle arthroscopy returned to intended use. Older age, longer duration of lameness, and presence of partial-thickness cartilage lesions affected the odds of a horse returning to intended use. Postoperative therapies did not affect the outcome in this population. CLINICAL SIGNIFICANCE: The prognosis of Western performance horses undergoing stifle arthroscopy is as guarded as that previously reported in horses of other disciplines.

Outcomes in Pediatric Autoimmune Hepatitis and Significance of Azathioprine Metabolites.

OBJECTIVES: Autoimmune hepatitis (AIH) is a common pediatric liver disease and long-term remission is usually maintained with azathioprine (AZA). There is no consensus on the target range for AZA active metabolite 6-thioguanine (6-TGN) levels in pediatric AIH. The aim of the present study was to characterize the outcomes of pediatric patients with AIH and determine correlations between AZA dosing or 6-TGN metabolite levels and biochemical remission. METHODS: A retrospective chart review was performed and data on presentation, laboratories including AZA metabolite levels, medication use, and outcomes were collected. RESULTS: Between 2002 and 2013, 66 children with AIH were identified (mean age at diagnosis 9.6 ±â€Š5.1 years) with a mean follow-up period of 2.9 ±â€Š3.2 years. Common presenting symptoms included jaundice, fatigue, and abdominal pain. The majority of subjects received steroids for induction and AZA for maintenance of remission. Seventy-nine percent achieved biochemical remission (mean time to remission 6.2 ±â€Š9.2 months), 14% were in the induction phase of therapy, 6% required liver transplantation, and 18% were weaned off immunosuppression and remained in remission. 6-TGN levels ranging from 50 to 250 pmol/8 × 10 red blood cell count were associated with biochemical remission (alanine aminotransferase levels of ≤50 U/L). CONCLUSIONS: The vast majority of children with AIH maintain a sustained remission with AZA monotherapy. Biochemical remission was maintained with 6-TGN levels much lower than that recommended for inflammatory bowel disease. These findings suggest that patients should be maintained at the lowest AZA dose possible that is associated with biochemical remission.

Identification and validation of risk loci for osteochondrosis in standardbreds.

BACKGROUND: Osteochondrosis (OC), simply defined as a failure of endochondral ossification, is a complex disease with both genetic and environmental risk factors that is commonly diagnosed in young horses, as well as other domestic species. Although up to 50 % of the risk for developing OC is reportedly inherited, specific genes and alleles underlying risk are thus far completely unknown. Regions of the genome identified as associated with OC vary across studies in different populations of horses. In this study, we used a cohort of Standardbred horses from the U.S. (n = 182) specifically selected for a shared early environment (to reduce confounding factors) to identify regions of the genome associated with tarsal OC. Subsequently, putative risk variants within these regions were evaluated in both the discovery population and an independently sampled validation population of Norwegian Standardbreds (n = 139) with tarsal OC. RESULTS: After genome-wide association analysis of imputed data with information from >200,000 single nucleotide polymorphisms, two regions on equine chromosome 14 were associated with OC in the discovery cohort. Variant discovery in these and 30 additional regions of interest (including 11 from other published studies) was performed via whole-genome sequencing. 240 putative risk variants from 10 chromosomes were subsequently genotyped in both the discovery and validation cohorts. After correction for population structure, gait (trot or pace) and sex, the variants most highly associated with OC status in both populations were located within the chromosome 14 regions of association. CONCLUSIONS: The association of putative risk alleles from within the same regions with disease status in two independent populations of Standardbreds suggest that these are true risk loci in this breed, although population-specific risk factors may still exist. Evaluation of these loci in other populations will help determine if they are specific to the Standardbred breed, or to tarsal OC or are universal risk loci for OC. Further work is needed to identify the specific variants underlying OC risk within these loci. This is the first step towards the long-term goal of constructing a genetic risk model for OC that allows for genetic testing and quantification of risk in individuals.

Heritability of Recurrent Exertional Rhabdomyolysis in Standardbred and Thoroughbred Racehorses Derived From SNP Genotyping Data.

Recurrent exertional rhabdomyolysis (RER) in Thoroughbred and Standardbred racehorses is characterized by episodes of muscle rigidity and cell damage that often recur upon strenuous exercise. The objective was to evaluate the importance of genetic factors in RER by obtaining an unbiased estimate of heritability in cohorts of unrelated Thoroughbred and Standardbred racehorses. Four hundred ninety-one Thoroughbred and 196 Standardbred racehorses were genotyped with the 54K or 74K SNP genotyping arrays. Heritability was calculated from genome-wide SNP data with a mixed linear and Bayesian model, utilizing the standard genetic relationship matrix (GRM). Both the mixed linear and Bayesian models estimated heritability of RER in Thoroughbreds to be approximately 0.34 and in Standardbred racehorses to be approximately 0.45 after adjusting for disease prevalence and sex. To account for potential differences in the genetic architecture of the underlying causal variants, heritability estimates were adjusted based on linkage disequilibrium weighted kinship matrix, minor allele frequency and variant effect size, yielding heritability estimates that ranged between 0.41-0.46 (Thoroughbreds) and 0.39-0.49 (Standardbreds). In conclusion, between 34-46% and 39-49% of the variance in RER susceptibility in Thoroughbred and Standardbred racehorses, respectively, can be explained by the SNPs present on these 2 genotyping arrays, indicating that RER is moderately heritable. These data provide further rationale for the investigation of genetic mutations associated with RER susceptibility.

Evidence of positive selection for a glycogen synthase (GYS1) mutation in domestic horse populations.

A dominantly inherited gain-of-function mutation in the glycogen synthase (GYS1) gene, resulting in excess skeletal muscle glycogen, has been identified in more than 30 horse breeds. This mutation is associated with the disease Equine Polysaccharide Storage Myopathy Type 1, yet persists at high frequency in some breeds. Under historical conditions of daily work and limited feed, excess muscle glycogen may have been advantageous, driving the increase in frequency of this allele. Fine-scale DNA sequencing in 80 horses and genotype assays in 279 horses revealed a paucity of haplotypes carrying the mutant allele when compared with the wild-type allele. Additionally, we found increased linkage disequilibrium, measured by relative extended haplotype homozygosity, in haplotypes carrying the mutation compared with haplotypes carrying the wild-type allele. Coalescent simulations of Belgian horse populations demonstrated that the high frequency and extended haplotype associated with the GYS1 mutation were unlikely to have arisen under neutrality or due to population demography. In contrast, in Quarter Horses, elevated relative extended haplotype homozygosity was associated with multiple haplotypes and may be the result of recent population expansion or a popular sire effect. These data suggest that the GYS1 mutation underwent historical selection in the Belgian, but not in the Quarter Horse.

Comparison of plasma l-lactate between jugular and cephalic veins in healthy and systemically ill horses using a point-of-care device.

OBJECTIVE: To compare plasma l-lactate (LAC) values between samples collected from jugular and cephalic venipuncture in healthy horses and systemically ill horses. DESIGN: Prospective, experimental study. SETTING: Large animal university teaching hospital. ANIMALS: Thirty healthy adult university-owned horses and 43 client-owned horses presenting to the large animal hospital for elective surgical procedures or for emergent medical evaluation of systemic illness. INTERVENTIONS: Blood samples were collected from the jugular vein (JV) and cephalic vein (CV) and placed in EDTA blood tubes prior to any medical therapy. LAC values were obtained with a handheld lactate meter at the time of blood collection. MEASUREMENTS AND MAIN RESULTS: LAC was higher in CV samples than JV samples in healthy horses (P < 0.001); however, all values were within the normal reference range. Similarly, LAC was higher in CV samples than JV samples in systemically ill horses (P < 0.001), but the median JV value was within normal reference range (1.9 mmol/L [17.1 mg/dL]), while the median CV value was outside the normal reference range (2.9 mmol/L [26.1 mg/dL]). CONCLUSIONS: The CV is an alternative venipuncture site for assessing plasma LAC if the JV is not accessible or to preserve the JV for subsequent catheterization. However, in ill horses, the CV value may be outside the reference range when the corresponding JV value would have been within the reference range.