Comparison of skeletal scintigraphy and standing 18 F-NaF positron emission tomography for imaging of the fetlock in 33 Thoroughbred racehorses.

This retrospective, methods comparison study aimed to compare skeletal scintigraphy and 18 F-NaF positron emission tomography (PET) for the detection of abnormalities in the fetlocks of Thoroughbred racehorses. Thirty-three horses (72 limbs) imaged with both scintigraphy and 18 F-NaF PET, for investigation of lameness or poor performance related to the fetlock, were included. Seven observers, including experienced racetrack practitioners, surgery and imaging residents, and a board-certified veterinary radiologist, independently reviewed all data for evidence of increased radiopharmaceutical uptake in 10 different regions of interest. The interobserver agreement was higher for PET (Kappa-weighted (K-w) 0.73 (0.51-0.84)) (median (range)) than for scintigraphy (0.61 (0.40-0.77)) (P < 0.0001). When scintigraphy and PET were compared, the agreement was fair (K-w 0.29). More sites of increased uptake were identified using PET compared with scintigraphy. Agreement between the two modalities was higher for the palmar/plantar metacarpal/metatarsal condylar regions (K-w 0.59) than for the proximal sesamoid bones (K-w 0.25). Increased radiopharmaceutical uptake was detected in the medial proximal sesamoid bone in 6.9% and 22.2% of limbs with scintigraphy and PET, respectively. The high interobserver agreement for PET, despite the recent introduction of this technique, demonstrates the ease of clinical interpretation of PET scans. The higher number of lesions detected with PET compared with scintigraphy can be explained by the higher spatial resolution and cross-sectional nature of this modality. Study findings supported using PET in a clinical population of racehorses, in particular for the assessment of the proximal sesamoid bones.

Investigation of high gamma-glutamyltransferase syndrome in California Thoroughbred racehorses.

BACKGROUND: Increases in serum gamma-glutamyltransferase (GGT) activity have been reported in Thoroughbred (TB) racehorses and associated with maladaptation to training but the underlying etiology remains unknown. HYPOTHESIS/OBJECTIVES: Classify the etiology of high GGT syndrome in racing TBs by assessment of pancreatic enzymes, vitamin E concentrations, and both a candidate gene and whole genome association study. We hypothesized that a genetic variant resulting in antioxidant insufficiency or pancreatic dysfunction would be responsible for high GGT syndrome in TBs. ANIMALS: A total of 138 California racing TBs. Amylase: n = 31 affected (serum GGT activity ≥60 IU/L), n = 52 control (serum GGT activity <40 IU/L). Lipase: n = 19 affected, n = 35 control. Serum α-tocopherol concentrations: n = 32 affected, n = 46 control. Genome-wide association study (GWAS): 36 affected, 58 control. Whole genome sequencing: n = 5 affected, n = 5 control. METHODS: Biochemical and vitamin analytes were compared among cohorts. A GWAS was performed and a subset of TBs underwent whole genome sequencing to interrogate candidate genes and positional genetic regions. RESULTS: Serum lipase and amylase activity and α-tocopherol concentrations did not differ between groups. No genetic variants were identified in 2 candidate genes (UGT1A1 and GGT1) that associated with the phenotype. Four single nucleotide polymorphisms (SNPs) approached a suggestive association with the phenotype (P = 2.15 × 10-5 ), defining a 100 kb region on chromosome 5 surrounding cluster of differentiation 1a (CD1A1), a transmembrane gene related to the major histocompatibility complex. CONCLUSIONS AND CLINICAL IMPORTANCE: An underlying genetic etiology may exist for high GGT syndrome in racing TBs, similar to genetic disorders in humans.

Longitudinal monitoring of fetlock lesions in Thoroughbred racehorses using standing 18F-sodium fluoride positron emission tomography.

OBJECTIVE: To assess the repeatability of equine 18F-sodium fluoride (18F-NaF) positron emission tomography (PET) findings, and to evaluate the ability of PET to monitor the progression of areas of increased radiopharmaceutical uptake (IRU) in the fetlocks of Thoroughbred racehorses. ANIMALS: 25 racehorses with clinical signs related to fetlock injuries. PROCEDURES: This study is a prospective, longitudinal clinical study. Twenty-five racehorses (54 fetlocks) underwent three 18F-NaF PET scans 6 weeks apart. The first 18F-NaF PET scan was performed at the start of a 12-week period of rest from racing (lay-up). Areas of IRU in the fetlock joints were quantified using maximal standardized uptake values (SUVmax) and were graded by 2 experienced observers. Statistical comparisons were made between scans to detect changes in IRU grade and SUVmax over time. RESULTS: Standing PET findings were repeatable, with 131/149 (88%) areas of IRU identified on the initial scans seen again at the 6-week follow-up scan. The palmar/plantar condyles were the sites most commonly presenting with IRU, followed by the proximal sesamoid bones. Overall, 65% of fetlocks demonstrated improvement in IRU grade during the 12-week period of rest from racing. Areas of higher IRU grade took longer to resolve than the lower graded areas. CLINICAL RELEVANCE: Standing PET findings in the racehorse fetlock were repeatable. The SUV-based grading system may be helpful when determining appropriate lay-up duration for Thoroughbred racehorses. PET may be used to monitor areas of the fetlock involved in catastrophic breakdown injuries in Thoroughbred racehorses.

Impact of antithrombin III and enoxaparin dosage adjustment on prophylactic anti-Xa concentrations in trauma patients at high risk for venous thromboembolism: a randomized pilot trial.

The impact of antithrombin III activity (AT-III) on prophylactic enoxaparin anti-factor Xa concentration (anti-Xa) is unknown in high-risk trauma patients. So too is the optimal anti-Xa-adjusted enoxaparin dosage. This prospective, randomized, pilot study sought to explore the association between AT-III and anti-Xa goal attainment and to preliminarily evaluate two enoxaparin dosage adjustment strategies in patients with subprophylactic anti-Xa. Adult trauma patients with Risk Assessment Profile (RAP) ≥ 5 prescribed enoxaparin 30 mg subcutaneously every 12 h were eligible. AT-III and anti-Xa were drawn 8 h after the third enoxaparin dose and compared between patients with anti-Xa ≥ 0.1 IU/mL (goal; control group) or anti-Xa < 0.1 IU/mL (subprophylactic; intervention group). The primary outcome was difference in baseline AT-III. Subsequently, intervention group patients underwent 1:1 randomization to either enoxaparin 40 mg every 12 h (up to 50 mg every 12 h if repeat anti-Xa < 0.1 IU/mL) (enox12) or enoxaparin 30 mg every 8 h (enox8) with repeat anti-Xa assessments. The proportion of patients achieving goal anti-Xa after dosage adjustment were compared. A total of 103 patients were included. Anti-Xa was subprophylactic in 50.5%. Baseline AT-III (median [IQR]) was 87% [80-98%] in control patients versus 82% [71-96%] in intervention patients (p = 0.092). Goal trough anti-Xa was achieved on first assessment in 38.1% enox12 versus 50% enox8 patients (p = 0.67), 84.6% versus 53.3% on second assessment (p = 0.11), and 100% vs. 54.5% on third trough assessment (p = 0.045). AT-III activity did not differ between high-risk trauma patients with goal and subprophylactic enoxaparin anti-Xa concentrations, although future investigation is warranted. Enoxaparin dose adjustment rather than frequency adjustment may be associated with a higher proportion of patients achieving goal anti-Xa over time.

FGFR and PTEN signaling interact during lens development to regulate cell survival.

Lens epithelial cells express many receptor tyrosine kinases (RTKs) that stimulate PI3K-AKT and RAS-RAF-MEK-ERK intracellular signaling pathways. These pathways ultimately activate the phosphorylation of key cellular transcription factors and other proteins that control proliferation, survival, metabolism, and differentiation in virtually all cells. Among RTKs in the lens, only stimulation of fibroblast growth factor receptors (FGFRs) elicits a lens epithelial cell to fiber cell differentiation response in mammals. Moreover, although the lens expresses three different Fgfr genes, the isolated removal of Fgfr2 at the lens placode stage inhibits both lens cell survival and fiber cell differentiation. Phosphatase and tensin homolog (PTEN), commonly known as a tumor suppressor, inhibits ERK and AKT activation and initiates both apoptotic pathways, and cell cycle arrest. Here, we show that the combined deletion of Fgfr2 and Pten rescues the cell death phenotype associated with Fgfr2 loss alone. Additionally, Pten removal increased AKT and ERK activation, above the levels of controls, in the presence or absence of Fgfr2. However, isolated deletion of Pten failed to stimulate ectopic fiber cell differentiation, and the combined deletion of Pten and Fgfr2 failed to restore differentiation-specific Aquaporin0 and DnaseIIß expression in the lens fiber cells.

Clinical evaluation of the locking compression plate for fetlock arthrodesis in six thoroughbred racehorses.

OBJECTIVE: To report use of a locking compression plate (LCP) for fetlock arthrodesis in Thoroughbred racehorses after catastrophic disruption of the suspensory apparatus. STUDY DESIGN: Retrospective case study. ANIMALS: Racing Thoroughbreds (n=6) with a catastrophic breakdown injury of the suspensory apparatus. METHODS: Medical records (2004-2006) of horses that had fetlock arthrodesis using an LCP were reviewed. Preoperative recorded variables were: age, gender, affected limb, injury type and occurrence, limb support used and time to surgery. Recorded surgical variables were: implants used and cost, surgery time, and anesthetic recovery method. Postoperative recorded variables included: treatment, physical status, complications, and outcome. RESULTS: Of 6 Thoroughbred racehorses that had LCP arthrodesis, 4 were sound for breeding purposes the next year and 2 horses were euthanatized (1 at 16 days, 1 at 68 days) because of proximal interphalangeal joint (PIJ) luxation. No surgical complications were associated with implant application. Postoperative complications were similar to those reported for other arthrodesis techniques. CONCLUSIONS: LCP is a viable option for fetlock arthrodesis in Thoroughbred racehorses after catastrophic suspensory apparatus disruption. CLINICAL RELEVANCE: Adequate fetlock stability can be achieved with an LCP, and although the repair is likely more stable it is approximately 3 times more expensive than using a limited contact dynamic compression plate (LC-DCP) with cortical screws.

A clinical evaluation of a headless, titanium, variable-pitched, tapered, compression screw for repair of nondisplaced lateral condylar fractures in thoroughbred racehorses.

OBJECTIVE: To report clinical evaluation of headless compression screws for repair of metacarpal/metatarsal (MC/MT3) condylar fractures in horses. STUDY DESIGN: Retrospective case study. SAMPLE POPULATION: Racing Thoroughbreds (n=16) with nondisplaced lateral condylar fractures of MC/MT 3. METHODS: Medical records (1999-2004) of horses with nondisplaced longitudinal fractures of the lateral condyle of MC/MT3 were reviewed. Pre-operative variables retrieved were: patient age, gender, limb involvement, injury occurrence, fracture length, and width, evidence of palmar comminution and degenerative joint disease, number of pre-injury starts, and pre-injury earnings. Post-operative variables retrieved were: surgical complications, surgical time, number of race starts, and post-operative earnings. RESULTS: MC3 (n=11) and MT3 (5) nondisplaced longitudinal fractures of the lateral condyle were repaired with Acutrak Equine (AE) screws. Left front limb fractures were most common (8) followed by left hind (5) and right front (3). Nine fractures occurred during training and 7 during racing; 4 fractures had palmar comminution. No surgical complications occurred. Of 15 horses that returned to training, 11 (73%) raced 306+/-67 days after injury and had greater mean (+/-SD) post-injury earnings/start ($5290.00+/-$8124.00) than pre-injury ($4971.00+/-$2842.00). Screw removal was not required in any horse. CONCLUSION: The AE screw is a viable option for repair of nondisplaced lateral condylar MC/MT3 fractures in Thoroughbred racehorses. CLINICAL RELEVANCE: Adequate stability of nondisplaced lateral condylar fractures can be achieved with a headless tapered compression screw while avoiding impingement on the collateral ligaments and joint capsule of the fetlock joint.