The Common Carotid Artery in the Ultrasound Evaluation of Giant Cell Arteritis.

OBJECTIVES: Vascular ultrasound is commonly used to diagnose giant cell arteritis (GCA). Most protocols include the temporal arteries and axillary arteries, but it is unclear which other arteries should be included. This study investigated whether inclusion of intima media thickness (IMT) of the common carotid artery (CCA) in the ultrasound evaluation of GCA improves the accuracy of the examination. METHODS: We formed a fast-track clinic to use ultrasound to rapidly evaluate patients with suspected GCA. In this cohort study, patients referred for new concern for GCA received a vascular ultrasound for GCA with the temporal arteries and branches, the axillary artery, and CCA. RESULTS: We compared 57 patients with GCA and 86 patients without GCA. Three patients with GCA had isolated positive CCA between 1 and 1.49 mm, and 21 patients without GCA had isolated positive CCA IMT. At the 1.5-mm CCA cutoff, 4 patients without GCA had positive isolated CCA, and 1 patient with GCA had a positive isolated CCA. The sensitivity of ultrasound when adding carotid arteries to temporal and axillary arteries was 84.21% and specificity 65.12% at an intima media thickness (IMT) cutoff of ≥1 mm and 80.70% and 87.21%, respectively, at a cutoff of ≥1.5 mm. CONCLUSION: Measurement of the CCA IMT rarely contributed to the diagnosis of GCA and increased the rate of false-positive results. Our data suggest that the CCA should be excluded in the initial vascular artery ultrasound protocol for diagnosing GCA. If included, an IMT cutoff of higher than 1.0 mm should be used.

The Usefullness of Subclavian Artery Ultrasound Assessment in Giant Cell Arteritis Evaluation.

OBJECTIVE: Vascular ultrasound has been increasingly used to diagnose giant cell arteritis (GCA). The temporal and axillary arteries are commonly evaluated. However, the usefulness of including the subclavian artery remains unclear. This study investigated whether inclusion of the subclavian artery in addition to the temporal and axillary arteries in the ultrasound evaluation of GCA improves the accuracy of the examination beyond ultrasonography of the temporal and axillary arteries alone. METHODS: We formed a fast-track clinic to use ultrasound to rapidly evaluate patients with suspected GCA. In this cohort study, patients referred for new concern for GCA received a vascular ultrasound for GCA. Subclavian intima-media thickness (IMT) cutoffs of 1.0 and 1.5 mm were retrospectively assessed. RESULTS: Two hundred thirty-seven patients were referred to the fast-track clinic from November 2017 to August 2021. One hundred sixty-eight patients received an ultrasound for concern for new GCA. With a subclavian IMT cutoff of 1.5 mm, inclusion of the subclavian artery did not identify any patients with GCA who were not otherwise found to have positive temporal and/or axillary artery examinations, and at this cutoff, there was 1 false-positive result. A subclavian IMT cutoff of 1.0 mm identified several subjects diagnosed with GCA who had otherwise negative ultrasounds, but most subjects with an isolated subclavian IMT greater than 1.0 mm had false-positive results, and the specificity of this cutoff was poor. CONCLUSION: Inclusion of the subclavian artery in the ultrasound assessment of GCA at 2 different cutoffs rarely contributed to the accurate diagnosis of GCA and increased the rate of false-positive results.

Vascular Ultrasound for Giant Cell Arteritis: Establishing a Protocol Using Vascular Sonographers in a Fast-Track Clinic in the United States.

OBJECTIVE: We developed a fast-track clinic (FTC) to expedite the evaluation of patients suspected of having giant cell arteritis (GCA) using vascular ultrasound. Though FTCs have demonstrated efficacy in Europe, no protocolized clinic in the United States has been developed. This study introduces a new FTC model unique to the United States, using vascular sonographers, and describes the protocols used to develop reliable findings. We evaluate clinical outcomes using vascular ultrasound and temporal artery biopsy (TAB). METHODS: A retrospective review included all subjects referred to the University of Washington FTC aged 50 years old or older who received both ultrasound and TAB between November 2017 and November 2019. Ultrasound was performed by a vascular sonographer trained in GCA detection. Ultrasound results were read by a vascular surgeon and reviewed by four rheumatologists certified in musculoskeletal ultrasound who had completed a course in vascular ultrasound use in GCA and large-vessel vasculitis. RESULTS: A total of 43 subjects underwent both vascular ultrasound and TAB. Six subjects had both positive ultrasound and TAB results. There were also seven positive ultrasound results in patients with negative TAB results, most due to detection of large-vessel GCA (LV-GCA). All 29 subjects with negative ultrasound results had negative TAB results. CONCLUSION: This is the first study in the United States to demonstrate a reliable FTC protocol using vascular sonographers. This protocol demonstrated good agreement between ultrasound and TAB and allowed for the detection of additional cases of LV-GCA by vascular ultrasound. Vascular ultrasound improved the rate of GCA diagnosis primarily by detecting additional cases of LV-GCA.

Physical activity recommendations for cancer survivors living with bony metastases: views of oncologic healthcare providers.

PURPOSE: The potential of physical activity to improve function and quality of life of an individual with advanced cancer is now established. The purpose of this survey of oncologic healthcare providers (OHPs) is to understand their attitude towards physical activity for individuals living with bony metastases and to assess requirements to confidently provide physical activity recommendations. METHODS: A web-based survey administered through Qualtrics™ included questions on participant demographics and attitude questions ranked on a Likert scale. Eligibility was a physician or nurse practitioner currently providing care in the cancer care system of a public healthcare system in Canada. 338 participants were identified and invited to participate in this survey. RESULTS: The response rate was 34.6%. The majority of OHPs believed physical activity is important (89%) and safe (82%) in individuals living with bony metastases. OHPs agreed that these individuals looked to them for physical activity recommendations (74%) and that these recommendations would be followed (58%). Yet, 86% of OHPs felt they required more information before they could recommend physical activity to individuals living with bony metastases, and less than half (43%) of OHPs felt confident enough to prescribe physical activity. CONCLUSIONS: OHPs agree that physical activity for individuals living with bony metastatic cancer is beneficial and safe. However, OHPs are not confident in their ability to recommend physical activity to this population. IMPLICATIONS FOR CANCER SURVIVORS: There is a need to create physical activity guidelines for individuals living with bony metastases and improve access to rehabilitation services.

The U.S. Veterans Health Administration national giant cell arteritis (GCA) database cohort: incident ophthalmic complications in biopsy-negative GCA patients.

INTRODUCTION/OBJECTIVES: This study aimed to identify the incidence of ophthalmic complications of giant cell arteritis (GCA) among subjects with negative temporal artery biopsy (TAB) and to determine if duration of prednisone exposure relative to GCA diagnosis was associated with ophthalmic complications in TAB-negative subjects. METHOD: The U.S. Veterans Health Administration (VHA) national database was queried for subjects between 1999 and 2017 with ICD-9/-10 diagnosis code for GCA, procedure code for TAB, and ICD-9/-10 diagnosis code for blindness, anterior or posterior ischemic optic neuropathy, or branch or central retinal artery occlusion. Pharmacy data regarding prednisone dispensation were collected. A Cox proportional hazard model was performed using ophthalmic complication by 1 year as the outcome variable in TAB-negative subjects, adjusting for age, TAB length, TAB laterality, and prednisone dose relative to GCA diagnosis date. RESULTS: Incident ophthalmic complication occurred by 1 year in 9.6% with positive TAB and in 6.2% with negative TAB. The majority of complications occurred within the first month for both groups. Compared to a reference group of prednisone initiation 0-14 days prior to GCA diagnosis, ophthalmic complications in TAB-negative subjects were significantly higher when prednisone initiation was delayed 14-28 days after GCA diagnosis. CONCLUSIONS: A substantial number of TAB-negative subjects accrued an incident ICD-9/-10 code for ophthalmologic complication within a year after diagnosis, most occurring within the first month. Delaying prednisone initiation 14-28 days after GCA diagnosis in TAB-negative subjects led to a 3.5-fold higher rate of ophthalmic events occurring by 1 year. Key Points • This study provides an incidence rate of ophthalmic complication by one year in biopsy-negative subjects suspected of having GCA. • Delaying prednisone initiation 14-28 days after GCA diagnosis in TAB-negative GCA subjects led to a 3.5-fold higher rate of ophthalmic events occurring by 1 year.

Ultrasound-guided adductor canal block: a cadaver study investigating the effect of a thigh tourniquet.

BACKGROUND: Placement of local anaesthetic within the adductor canal using ultrasonography is an alternative to femoral nerve blocks for postoperative pain relief after knee joint replacement surgery. However, the effect of an inflated thigh tourniquet on the distribution of local anaesthetic within the adductor canal is unknown. The aim of this cadaveric study was to compare the distribution of radio-opaque dye within the adductor canal in the presence or absence of an inflated thigh tourniquet. METHODS: Bilateral ultrasound-guided adductor canal blocks were performed on the thawed lower limbs of five fresh frozen human cadavers. The left and right lower cadaver limbs were randomised to receive or not receive a thigh tourniquet inflated to 300 mm Hg for 1 h. X-rays with iohexol radio-opaque dye were obtained in four views, and fiducial markers inserted as reference points. Virtual editing technology was used to recreate outlines representing the distribution of the radio-opaque dye and superimpose these on anatomical images. RESULTS: Radio-opaque dye was distributed on the medial aspect of the thighs with entire and well circumscribed margins. The majority of the radio-opaque dye was confined within the adductor canal. Superior-inferior dye distribution was 315 mm [95% confidence intervals (CI) 289-342] and 264 mm (95% CI 239-289) in the presence and absence of an inflated thigh tourniquet, respectively (diff 95% CI -80.46 to -22.22, P=0.0081). Image analysis using the recreated radio-opaque outlines suggested that the most proximal point of the radio-opaque dye was 100 mm (95% CI 82-117) or 117 mm (95% CI 62-171) below the inguinal ligament in the presence and absence of an inflated thigh tourniquet, respectively (diff 95% CI -38 to 72, P=0.456). CONCLUSIONS: Application and inflation of thigh tourniquets significantly increased the combined superior-inferior dye distribution within the adductor canal of cadaveric limbs. There was insufficient evidence to suggest significant proximal spread of 25 ml of local anaesthetic to involve the motor branches of the femoral nerve. In some patients, the local anaesthetic may reach the popliteal fossa in close approximation to the sciatic nerve.

Markers of the p53 pathway further refine molecular profiling in high-risk endometrial cancer: A TransPORTEC initiative.

BACKGROUND: The morphological classification of high-risk endometrial cancer is of limited prognostic value. Recent attempts to stratify tumours according to molecular signatures have shown considerable promise. Here we attempted to further refine molecular classifications using markers of the p53 pathway. METHODS: We analysed the expression of p53 as well as three downstream markers of the p53 pathway, p21, mdm2 and phospho-p63 (pp63), by immunohistochemistry in a series of 114 endometrial cancers (86 endometrioid, 28 non-endometrioid subtype) with high-risk features (such as high tumour grade and deep myometrial invasion) and correlated results with clinical outcome. The Cancer Genome Atlas (TCGA) data were used to analyse TP63 mutations and copy-number alterations using cBioPortal. TP53 was silenced in two endometrial cancer cell lines to study its effect on p21 and p63. RESULTS: About half of the tumours showed a p53 mutant phenotype and there was a strong negative correlation with p21 expression. Being marker positive for pp63 or mdm2 was associated with a significantly increased likelihood of dying, [hazard ratios 5.93 (95% CI 2.37-7.27) and 7.48 (95% CI 3.04-9.39), respectively]. These findings were seen in both p53 wildtype and p53 mutant tumours. Only 11% of TCGA endometrial cancers had a functional TP63 alteration. Upon silencing of TP53, p21 expression was decreased in one cell line, but no effects on p63 were observed. CONCLUSION: Markers of the p53 pathway improve stratification of endometrial cancers and provide novel insights into the role of this pathway in the disease.

Treatment of septic arthritis of the coxofemoral joint in 12 foals.

OBJECTIVE: To describe the clinical signs, surgical treatment, and outcome of septic arthritis of the coxofemoral joint in foals. STUDY DESIGN: Retrospective clinical study. SAMPLE POPULATION: Foals (n = 12) with confirmed sepsis of the coxofemoral joint. METHODS: Lameness was localized to the coxofemoral joint based on physical examination. Sepsis was confirmed by cytological analysis of synovial fluid obtained under ultrasonographic guidance, during general anesthesia or standing sedation. Intra-articular analgesia was used as an adjunct diagnostic modality in 2 foals. Surgical lavage of the affected joint was performed via arthroscopy or needle lavage, with repeated lavage performed in 7 foals. RESULTS: Synovial fluid contained 4.4 to 173 × 109 /L white blood cells (WBCs), and 38-63 g/L total protein. Cultures were positive in 10/12 foals. Isolated organisms included Salmonella spp., Streptococcus spp., Rhodococcus spp., Enterococcus spp., Escherichia spp., Staphylococcus spp., Acinetobacter spp., Methicillin-resistant Staphylococcus aureus and Bacillus spp. Ten foals were discharged from hospital (83%). One of these was euthanized 15 days later due to chronic intestinal salmonellosis and renal failure, and 9 foals survived with no residual lameness detected 1 year after discharge from hospital. CONCLUSIONS: Sepsis of the coxofermoral joint can be effectively treated with a combination of arthroscopic lavage and the use of systemic and local antimicrobials.

Loss of Rearranged L-Myc Fusion (RLF) results in defects in heart development in the mouse.

Recently we reported that Rearranged L-Myc Fusion, RLF, acts as an epigenetic modifier maintaining low levels of DNA methylation at CpG island shores and enhancers across the genome. Here we focus on the phenotype of Rlf null mutant mice generated via an ENU mutagenesis screen, to identify genes required for epigenetic regulation. RLF is expressed in a range of fetal mouse tissues, including the fetal heart. Comprehensive timed-mating studies are consistent with our previously reported findings that Rlf homozygous mutant mice rarely survive to adulthood, with the majority dying shortly after birth. Histological analysis of two independent Rlf ENU mutant lines at E11.5-E14.5 showed heart defects resembling those present in humans with Left Ventricular Non-Compaction (LVNC). In situ hybridisation analysis localized expression of Rlf to the endocardium and epicardium of embryonic and postnatal hearts, and transiently to cardiomyocytes during heart looping and early chamber formation stages. RNA-seq analysis of Rlf mutant hearts highlighted defective NOTCH pathway signalling, recently describe as one cause of LVNC. This study provides the first evidence that RLF is required for normal heart development in the mouse. The heart morphological defects present at high penetrance in Rlf mutants are consistent with features of LVNC in humans, and molecular analysis identified attenuated JAGGED 1 expression and NOTCH signalling as likely contributors to these defects. Our study highlights the importance of RLF-dependent epigenetic modifications to DNA for maintaining correct gene regulatory network and intercellular signalling interactions during heart chamber and septal development. Further investigations are needed to define the biochemical role of RLF in the developing heart, and whether RLF mutations are a cause of heart defects in humans.

Tamoxifen in men: a review of adverse events.

Tamoxifen is an off-label option to treat men for breast cancer, infertility, and idiopathic gynecomastia. Lately, tamoxifen has been proposed as a treatment to prevent gynecomastia in prostate cancer patients receiving antiandrogen therapy. We reviewed the adverse events (AEs) reported in studies of men prescribed tamoxifen for these conditions to better understand its side-effect profile. We searched PubMed for randomized controlled trials (RCTs) that included safety data of tamoxifen treatment in men with prostate cancer, breast cancer, infertility, and idiopathic gynecomastia. Non-RCTs were also reviewed. The results demonstrate that the AE profile in tamoxifen-treated male populations varied. Excluding breast events, gastrointestinal, and cardiovascular problems were the most commonly reported AEs in prostate cancer patients, whereas more psychiatric disorders were reported in male breast cancer patients. Few AEs have been documented in men receiving tamoxifen for infertility and idiopathic gynecomastia. Less than 5% of men withdrew from tamoxifen therapy because of toxicity. This suggests that for most men, tamoxifen is well-tolerated. Of those who discontinued tamoxifen, the majority were male breast cancer patients, and cardiovascular events were the most common reason for stopping tamoxifen treatment. Unfortunately, in many cases, the reasons for withdrawing tamoxifen were unspecified. Based on the available evidence, tamoxifen's AE profile appears to vary depending upon which male population is treated. Also, the frequency at which AEs occur varies - less AEs in men with infertility and idiopathic gynecomastia compared to men with prostate cancer or breast cancer. Long-term studies that rigorously document the side-effect profile of tamoxifen in men are lacking.

The antimicrobial activity of honey against common equine wound bacterial isolates.

Delayed healing associated with distal limb wounds is a particular problem in equine clinical practice. Recent studies in human beings and other species have demonstrated the beneficial wound healing properties of honey, and medical grade honey dressings are available commercially in equine practice. Equine clinicians are reported to source other non-medical grade honeys for the same purpose. This study aimed to assess the antimicrobial activity of a number of honey types against common equine wound bacterial pathogens. Twenty-nine honey products were sourced, including gamma-irradiated and non-irradiated commercial medical grade honeys, supermarket honeys, and honeys from local beekeepers. To exclude contaminated honeys from the project, all honeys were cultured aerobically for evidence of bacterial contamination. Aerobic bacteria or fungi were recovered from 18 products. The antimicrobial activity of the remaining 11 products was assessed against 10 wound bacteria, recovered from the wounds of horses, including methicillin resistant Staphylococcus aureus and Pseudomonas aeruginosa. Eight products were effective against all 10 bacterial isolates at concentrations varying from <2% to 16% (v/v). Overall, the Scottish Heather Honey was the best performing product, and inhibited the growth of all 10 bacterial isolates at concentrations ranging from <2% to 6% (v/v). Although Manuka has been the most studied honey to date, other sources may have valuable antimicrobial properties. Since some honeys were found to be contaminated with aerobic bacteria or fungi, non-sterile honeys may not be suitable for wound treatment. Further assessment of gamma-irradiated honeys from the best performing honeys would be useful.

Dynamic ventrorostral displacement of the dorsal laryngeal mucosa in horses.

The objectives of this report were to describe the occurrence and features of dynamic ventrorostral displacement of the dorsal laryngeal mucosa (VRDDLM) in a group of Thoroughbred horses presented for investigation of poor performance and/or abnormal respiratory noise. Records from 600, dynamic, endoscopic examinations of the upper respiratory tract of horses were reviewed. Horses with VRDDLM were identified as those in which the dorsal laryngeal mucosa progressively obscured the interarytenoid notch and dorsoaxial portion of the corniculate processes of the arytenoid cartilages during high-speed exercise. The condition was recognised in 12 horses. Concurrent abnormalities of the respiratory tract of eight horses were also identified and included, axial deviation of the aryepiglottic folds, vocal cord prolapse, unilateral and bilateral ventromedial luxation of the apex of the corniculate process of the arytenoid cartilage, and intermittent dorsal displacement of the soft palate. VRDDLM is a rare abnormality of the upper portion of the respiratory tract of horses that may be associated with abnormal respiratory noise and potentially poor performance. The significance of the condition is not known, but the presence of this condition in combination with other, obstructive diseases of the equine airway warrants further investigation.

Comparison of dynamic and resting endoscopy of the upper portion of the respiratory tract in 57 Thoroughbred yearlings.

REASONS FOR PERFORMING THE STUDY: Endoscopic examination of Thoroughbred (TB) yearlings is performed routinely to determine the suitability of horses for racing and to ensure that the conditions of sale are satisfied. However, previous research has demonstrated that resting endoscopic examination can be inaccurate in the diagnosis of functional pathology of the upper portion of the respiratory tract (URT). OBJECTIVES: To investigate the feasibility of performing dynamic overground endoscopy in a group of TB yearlings and to compare the results of resting and dynamic endoscopic examination of the URT. STUDY DESIGN: Prospective cohort study. METHODS: Resting (pre- and post exercise) and exercising endoscopy was performed on 57 TB yearlings at a single training yard. Observed abnormalities were recorded and graded. The results of resting and dynamic examination were compared. RESULTS: Dynamic overground endoscopy was well tolerated and was performed with few complications. Laryngeal asymmetry (29 cases) was the most common abnormality identified at rest, while intermittent dorsal displacement of the soft palate (IDDSP; 19 cases) was the most common at exercise. Significant variation in laryngeal function and variation in the occurrence of IDDSP was noted between examinations. Other potentially significant pathology that was not noted at rest but was present during exercise included collapse of the apex of the corniculate process, pharyngeal collapse and cricotracheal ligament collapse. The occurrence of IDDSP at exercise was significantly associated with epiglottic structure grade>2 and a recent history of respiratory tract infection. CONCLUSIONS: Dynamic overground endoscopy is safe and potentially useful when assessing URT function in TB yearlings. Significant variations in the results of endoscopy at rest and during exercise were identified, which indicate that resting endoscopy may not be sufficient to predict the occurrence of pathology during exercise. POTENTIAL RELEVANCE: Dynamic overground endoscopic examination could be considered a suitable means of assessing URT function in TB yearlings and may provide additional pertinent information to that obtained during standard resting examination.

Evoked otoacoustic emissions: an alternative test of auditory function in horses.

REASONS FOR PERFORMING STUDY: Deafness has been reported in horses due to a variety of causes and objective auditory assessment has been performed with brainstem auditory evoked potential testing. Evoked otoacoustic emission (OAE) tests are widely used in human patients for hearing screening, detecting partial hearing loss (including frequency-specific hearing loss) and monitoring cochlear outer hair cell function over time. OAE tests are noninvasive, quick and affordable. Two types of OAE are commonly used clinically: transient evoked OAEs (TEOAEs) and distortion product OAEs (DPOAEs). Detection of OAEs has not been reported and OAE testing has not been evaluated for auditory assessment in horses. OBJECTIVES: To investigate whether TEOAEs and DPOAEs can be recorded in horses, and to evaluate the use of human OAE screening protocols in horses with apparently normal hearing. METHODS: Sixteen systemically healthy horses with normal behavioural responses to sound were included. OAE testing was performed during general anaesthesia using commercially available equipment and the final outcome for each ear for the TEOAE test (after a maximum of 3 runs) and the DPOAE test (after one run) were compared. RESULTS: TEOAEs and DPOAEs can be recorded in horses. Using the chosen TEOAE protocol, 96% of ears achieved a pass. Seventy percent of ears passed DPOAE testing, despite all of these ears passing TEOAE testing. CONCLUSIONS: Using the chosen stimulus and analysis protocols, TEOAEs were recorded from most ears; however, a smaller proportion of ears passed the DPOAE protocol, suggesting that this may be overly stringent and require further optimisation in horses. POTENTIAL RELEVANCE: OAE testing is rapid and easily performed in anaesthetised horses. It provides frequency-specific information about outer hair cell function, and is a promising tool for audiological assessment in the horse; however, it has not been assessed in conscious or sedated animals.

Surgical treatment of septic physitis in 17 foals.

OBJECTIVE: To document the progression and outcome after surgical curettage of septic physes in foals. STUDY DESIGN: Case series of 17 foals, aged <9 weeks, with septic physitis. METHODS: All foals were treated surgically with curettage of physeal lesions. Combinations of systemic antibiotics, intravenous regional perfusion of antibiotic and antibiotic-impregnated polymethylmethacrylate beads were used as adjunct medical treatments. Tissue removed from the physis of three foals during surgery was sent for pathological analysis. RESULTS: At follow-up, 15 of the 17 foals were alive. In the two foals with septic physitis of the distal tibia, the condition was bilateral. Eight foals had concurrent septic arthritis of the joint adjacent to the growth plate, but this did not affect outcome. Referring veterinarians of the foals were contacted at least 9 months post-surgery and all reported excellent functional, and good to excellent cosmetic, outcomes. Pathological examination of the septic physeal tissue showed that normal growth plate had been replaced by inflammatory tissue. CONCLUSION AND CLINICAL RELEVANCE: Septic physitis in foals may be treated using surgical curettage in selected cases. Removal of septic material might be expected to expedite resolution of infection, especially important in immunologically challenged neonates, where septic tissue may act as a reservoir for seeding of infection to other sites.

Association of owner-reported noise with findings during dynamic respiratory endoscopy in Thoroughbred racehorses.

REASONS FOR PERFORMING STUDY: To determine the association between owner-reported noise and findings during dynamic respiratory endoscopy (DRE) in a large case series. HYPOTHESIS: The sensitivity of owner-reported noise for dynamic upper respiratory tract obstructions in horses is low, and the specificity is high. METHODS: One hundred horses underwent DRE for the investigation of abnormal respiratory noise and/or poor performance. The association of abnormal noise with findings during DRE was evaluated. RESULTS: Eighty-five horses underwent DRE for the investigation of abnormal respiratory noise. Of these, 82% were found to have one or more obstructive upper respiratory tract abnormalities during DRE. Forty-eight percent of horses reported to gurgle, rattle or make a rough noise were diagnosed with solitary palatal dysfunction. A further 24% with this history showed palatal dysfunction in combination with an additional abnormality. Twenty-seven percent of horses with a history of whistling or roaring showed some degree of recurrent laryngeal neuropathy. Seven percent of horses with a history of whistling or roaring had vocal cord collapse as a solitary condition, whereas 40% had vocal cord collapse and another abnormality. The sensitivity of abnormal respiratory noise for any obstruction of the upper portion of the respiratory tract was high (84%), while the specificity was low (25%). Characteristic owner reported noise patterns showed moderate to low sensitivity for specific conditions. Whistling and roaring showed the highest specificity (≥80%) for laryngeal dysfunction. CONCLUSION: Diagnosis of upper respiratory tract obstructions based solely on owner-reported noise and performance history may result in incomplete diagnoses. CLINICAL RELEVANCE: DRE should be performed in horses with abnormal respiratory noise to rule out complex conditions of the upper portion of the respiratory tract.

Dynamic respiratory endoscopy in 67 Thoroughbred racehorses training under normal ridden exercise conditions.

REASONS FOR PERFORMING STUDY: There are potential advantages to imaging the upper portion of the respiratory tract (URT) of horses during ridden exercise. With the advent of a wireless endoscope, this is now possible. However, there has been no detailed validation of the technique and findings have not been compared to ridden speed. OBJECTIVES: To assess the combined use of a Dynamic Respiratory Scope (DRS) and global positioning system (GPS) receiver for examining the URT of a group of Thoroughbred racehorses randomly selected from a single flat racehorse training establishment. METHODS: Horses were selected randomly from a population of Thoroughbred horses in training at the same training yard. Endoscopic images of the URT were recorded during a ridden exercise test on an 'all-weather-gallop' and were reviewed post testing. Speed was measured using a wrist mounted GPS receiver. RESULTS: A total of 67 (34%) of the 195 horses in training were examined. Endoscopic findings included: normal URT function (44 cases); dorsal displacement of the soft palate (DDSP) (13 cases); laryngeal asymmetry (4 cases); and axial deviation of the aryepiglottic folds (3 cases). Maximum speed obtained by individual horses ranged from 41.8-56.3 km/h. Ridden speed was variably affected by DDSP. CONCLUSIONS: The DRS provides a safe effective system for imaging the equine URT during ridden exercise at speed. The abnormalities of the URT identified were similar to those observed during treadmill endoscopy studies reported in the literature. The effect of URT abnormalities on ridden speed requires further investigation. POTENTIAL RELEVANCE: This technique can be used to diagnose common causes of URT associated with poor performance in horses during normal training. This has substantial implications for future clinical diagnosis and treatment of URT pathology.

Fractures of the cervical vertebral odontoid in four horses and one pony.

Four horses and one pony, ranging in age from one to 11 years, were diagnosed with two different types of odontoid peg fractures. Their clinical signs included reluctance to move the neck and head, dullness, and abnormalities of gait. Radiography was essential for the diagnosis, and the method of treatment varied depending on the severity of the neurological signs, the intended use of the horse, and financial constraints. Optimal treatment requires a technique that allows decompression, anatomical alignment, and stabilisation of the odontoid fracture. If the clinical (neurological) signs are not too severe and the animal shows signs of feeling peripheral pain, conservative treatment can be applied, as is common practice in human surgery. All except the pony made a full recovery.

Frequent activating FGFR2 mutations in endometrial carcinomas parallel germline mutations associated with craniosynostosis and skeletal dysplasia syndromes.

Endometrial carcinoma is the most common gynecological malignancy in the United States. Although most women present with early disease confined to the uterus, the majority of persistent or recurrent tumors are refractory to current chemotherapies. We have identified a total of 11 different FGFR2 mutations in 3/10 (30%) of endometrial cell lines and 19/187 (10%) of primary uterine tumors. Mutations were seen primarily in tumors of the endometrioid histologic subtype (18/115 cases investigated, 16%). The majority of the somatic mutations identified were identical to germline activating mutations in FGFR2 and FGFR3 that cause Apert Syndrome, Beare-Stevenson Syndrome, hypochondroplasia, achondroplasia and SADDAN syndrome. The two most common somatic mutations identified were S252W (in eight tumors) and N550K (in five samples). Four novel mutations were identified, three of which are also likely to result in receptor gain-of-function. Extensive functional analyses have already been performed on many of these mutations, demonstrating they result in receptor activation through a variety of mechanisms. The discovery of activating FGFR2 mutations in endometrial carcinoma raises the possibility of employing anti-FGFR molecularly targeted therapies in patients with advanced or recurrent endometrial carcinoma.