Characterizing sleep disorders in an autism-specific collection of electronic health records.

OBJECTIVE/BACKGROUND: Sleep problems are common in people on the autism spectrum. This study reviews one detailed approach to querying the electronic health record (EHR) in a large tertiary care center. PATIENTS/METHODS: We developed methods for identifying people on the autism spectrum and defined their sleep problems using the key words, "sleep" or "melatonin", or International Classification of Diseases (ICD) codes. We examined treatment responses of these individuals to melatonin supplementation. RESULTS: Sleep problems were documented in 86% of patients with ages ranging from 6 to 30 years old. Our specific keyword search yielded more patients with sleep diagnoses than ICD codes alone. About two-thirds of patients who received melatonin supplementation reported benefit from its use. CONCLUSIONS: Our study provides a framework for using deidentified medical records to characterize sleep, a common co-occurring condition, in people on the autism spectrum. Using specific keywords could be helpful in future work that queries the EHR.

A multi-centre cohort study investigating the outcome of synovial contamination or sepsis of the calcaneal bursae in horses treated by endoscopic lavage and debridement.

BACKGROUND: Previous studies investigating factors associated with survival following endoscopic treatment of contamination/sepsis of the calcaneal bursa are limited. OBJECTIVES: To investigate the factors associated with survival in horses with contamination/sepsis of the calcaneal bursae treated endoscopically and to describe the bacterial isolates involved in the synovial infections. STUDY DESIGN: Retrospective analysis of clinical records. METHODS: Medical records from 128 horses with contamination/sepsis of the calcaneal bursae treated by endoscopic lavage at seven equine hospitals were reviewed. A follow-up questionnaire was used to determine survival and return to athletic performance. Descriptive statistics and Cox proportional hazards survival models were used to determine factors associated with survival. RESULTS: Horses underwent one (n = 107), two (n = 19), or three (n = 2) surgeries. Survival to hospital discharge was 84.4%. Univariable survival analysis revealed that administration of systemic antimicrobials prior to referral was associated with reduced mortality (hazard ratio, [HR] 0.41, 95% CI 0.18-0.91, P = 0.03). Increased mortality was associated with bone fracture/osteomyelitis (HR 2.43, 95% CI 1.12-5.26, P = 0.03), tendon involvement (≥30% cross sectional area) (HR 3.78 95% CI 1.78-8.04, P = 0.001), duration of general anaesthesia (HR 1.01, 95% CI 1.00-1.02, P = 0.04), post-operative synoviocentesis (HR 3.18, 95% CI 1.36-7.43, P = 0.006) and post-operative wound dehiscence (HR 2.5, 95% CI 1.08-5.65, P = 0.04). Multivariable Cox proportional hazards model revealed reduced mortality after systemic antimicrobial administration prior to referral (HR 0.25, 95% CI 0.11-0.60, P = 0.002) and increased mortality with tendinous involvement (≥30% cross-sectional area) (HR 7.92, 95% CI 3.31-19.92, P<0.001). At follow-up (median 30 months, range 0.25-13 years, n = 70) 87.1% horses were alive, 7.1% had been euthanised due to the calcaneal injury and 5.7% had been euthanised for unrelated reasons. From 57 horses with athletic performance follow-up, 91.2% returned to the same/higher level of exercise, 5.3% to a lower level and 3.5% were retired due to persistent lameness of the affected limb. MAIN LIMITATIONS: Retrospective study and incomplete follow-up. CONCLUSION: Endoscopic treatment of contamination/sepsis of the calcaneal bursae has an 84% survival rate to hospital discharge. Tendinous involvement reduced survival whilst systemic antimicrobials administration prior to referral improved survival.

Histological examination of the interspinous ligament in horses with overriding spinous processes.

The equine interspinous ligament (ISL) consists of an oblique crossing arrangement of collagenous bundles which are thought to counteract the tensile and rotational forces of distraction between the spinous processes (SPs) in the caudal thoracic and cranial lumbar spine. The aim of this controlled histological study was to assess the structural anatomy and innervation of the ISL in horses with clinically significant overriding (dorsal) SPs (ORSPs) and to compare the findings with the ISL of normal horses. Samples of the ISL were obtained from 10 horses that underwent subtotal ostectomy for treatment of ORSPs. Control samples were obtained from horses without spinal pathology. Histological staining of ISL sections with haematoxylin and eosin was performed to assess the morphology of the ligaments and with Alcian blue-periodic acid-Schiff to determine the proteoglycan and glycosaminoglycan content. Immunohistochemistry for S100 was performed for quantitative evaluation of nerves within the ISL. The ISL in horses with ORSPs had an altered collagen fibre alignment and arrangement of the ligamentous layers when compared to healthy controls. A significant increase in fibrocartilaginous tissue with evidence of fibrocartilaginous metaplasia was detected (P=0.001). The number of nerves in the ISL samples was significantly higher in horses with ORSPs than in controls (P=0.017). Structural alterations of the ISL, including loss of fibre alignment and fibrocartilaginous metaplasia, are associated with ORSPs in the equine thoracolumbar spine. In addition, an increase in innervation of the ISL in horses with ORSPs, compared to normal, may explain the thoracolumbar pain experienced by some horses with ORSPs.

Olfactory bulb atrophy and caspase activation observed in the BACHD rat models of Huntington disease.

Olfactory dysfunction is observed in several neurological disorders, including Huntington disease (HD), and correlates with global cognitive performance, depression and degeneration of olfactory regions in the brain. Despite clear evidence demonstrating olfactory dysfunction in HD patients, only limited details are available in murine models and the underlying mechanisms are unknown. In order to determine if alterations in the olfactory bulb (OB) are observed in HD we assessed OB weight or area from 3 to 12 months of age in the BACHD transgenic lines (TG5 and TG9). A significant decrease in the OB was observed at 6 and 12 months of age compared to WT. We also detected increased mRNA and protein expression of mutant huntingtin (mHTT) in the OB of TG5 compared to TG9 at specific ages. Despite the higher expression of mHTT in the TG5 OBs, there was increased nuclear accumulation of mHTT in the OB of TG9 compared to WT and TG5 rats. As we observed atrophy of the OB in the BACHD rats we assessed for caspase activation, a known mechanism underlying the cell death observed in HD. We characterized caspase-3, -6, -8 and - 9 mRNA and protein expression levels in the OB of the BACHD transgenic lines at 3, 6 and 12 months of age. Alterations in caspase mRNA and protein expression were detected in the TG5 and TG9 lines. However, the changes observed in the mRNA and protein levels are in some cases discordant, suggesting that the caspase protein modifications detected may be more attributable to post-translational modifications. The caspase activation studies support that cell death may be increased in the rodent HD OB and further our understanding of the olfactory dysfunction and the role of caspases in the pathogenesis of HD.

Increased sclerostin associated with stress fracture of the third metacarpal bone in the Thoroughbred racehorse.

OBJECTIVES: The exact aetiology and pathogenesis of microdamage-induced long bone fractures remain unknown. These fractures are likely to be the result of inadequate bone remodelling in response to damage. This study aims to identify an association of osteocyte apoptosis, the presence of osteocytic osteolysis, and any alterations in sclerostin expression with a fracture of the third metacarpal (Mc-III) bone of Thoroughbred racehorses. METHODS: A total of 30 Mc-III bones were obtained; ten bones were fractured during racing, ten were from the contralateral limb, and ten were from control horses. Each Mc-III bone was divided into a fracture site, condyle, condylar groove, and sagittal ridge. Microcracks and diffuse microdamage were quantified. Apoptotic osteocytes were measured using TUNEL staining. Cathepsin K, matrix metalloproteinase-13 (MMP-13), HtrA1, and sclerostin expression were analyzed. RESULTS: In the fracture group, microdamage was elevated 38.9% (sd 2.6) compared with controls. There was no difference in the osteocyte number and the percentage of apoptotic cells between contralateral limb and unraced control; however, there were significantly fewer apoptotic cells in fractured samples (p < 0.02). Immunohistochemistry showed that in deep zones of the fractured samples, sclerostin expression was significantly higher (p < 0.03) than the total number of osteocytes. No increase in cathepsin K, MMP-13, or HtrA1 was present. CONCLUSION: There is increased microdamage in Mc-III bones that have fractured during racing. In this study, this is not associated with osteocyte apoptosis or osteocytic osteolysis. The finding of increased sclerostin in the region of the fracture suggests that this protein may be playing a key role in the regulation of bone microdamage during stress adaptation.Cite this article:Bone Joint Res 2018;7:94-102.

Predicted coreceptor usage at end-stage HIV disease in tissues derived from subjects on antiretroviral therapy with an undetectable plasma viral load.

HIV cure research is increasingly focused on anatomical tissues as sites for residual HIV replication during combined antiretroviral therapy (cART). Tissue-based HIV could contribute to low-level immune activation and viral rebound over the course of infection and could also influence the development of diseases, such as atherosclerosis, neurological disorders and cancers. cART-treated subjects have a decreased and irregular presence of HIV among tissues, which has resulted in a paucity of actual evidence concerning how or if HIV persists, replicates and evolves in various anatomical sites during therapy. In this study, we pooled 1806 HIV envelope V3 loop sequences from twenty-six tissue types (seventy-one total tissues) of six pre-cART subjects, four subjects with an unknown cART history who died with profound AIDS, and five subjects who died while on cART with an undetectable plasma viral load. A computational approach was used to assess sequences for their ability to utilize specific cellular coreceptors (R5, R5 and X4, or X4). We found that autopsied tissues obtained from virally suppressed cART+ subjects harbored both integrated and expressed viruses with similar coreceptor usage profiles to subjects with no or ineffective cART therapy (i.e., significant plasma viral load at death). The study suggests that tissue microenvironments provide a sanctuary for the continued evolution of HIV despite cART.

Structure and Innervation of the Equine Supraspinous and Interspinous Ligaments.

Pain related to the osseous thoracolumbar spine is common in the equine athlete, with minimal information available regarding soft tissue pathology. The aims of this study were to describe the anatomy of the equine SSL and ISL (supraspinous and interspinous ligaments) in detail and to assess the innervation of the ligaments and their myofascial attachments including the thoracolumbar fascia. Ten equine thoracolumbar spines (T15-L1) were dissected to define structure and anatomy of the SSL, ISL and adjacent myofascial attachments. Morphological evaluation included histology, electron microscopy and immunohistochemistry (S100 and Substance P) of the SSL, ISL, adjacent fascial attachments, connective tissue and musculature. The anatomical study demonstrated that the SSL and ISL tissues merge with the adjacent myofascia. The ISL has a crossing fibre arrangement consisting of four ligamentous layers with adipose tissue axially. A high proportion of single nerve fibres were detected in the SSL (mean = 2.08 fibres/mm2 ) and ISL (mean = 0.75 fibres/mm2 ), with the larger nerves located between the ligamentous and muscular tissue. The oblique crossing arrangement of the fibres of the ISL likely functions to resist distractive and rotational forces, therefore stabilizing the equine thoracolumbar spine. The dense sensory innervation within the SSL and ISL could explain the severe pain experienced by some horses with impinging dorsal spinous processes. Documentation of the nervous supply of the soft tissues associated with the dorsal spinous processes is a key step towards improving our understanding of equine back pain.

Prevalence and antimicrobial susceptibility of bacterial isolates from horses with synovial sepsis: A cross-sectional study of 95 cases.

Bacterial culture and antimicrobial susceptibility testing of septic synovial samples allows instigation of targeted antimicrobial therapy; however, bacterial culture takes more than 24 h and has low sensitivity. This study aimed to identify the most frequently cultured bacteria and their antimicrobial susceptibility profile from septic synovial samples in our referral equine hospital, to allow recommendations regarding appropriate initial antimicrobial therapy prior to culture results. Hospital records for all horses with synovial sepsis and a synovial sample submitted to the microbiology laboratory between 2004 and 2013 were retrieved (n= 379 samples). One horse had positive cultures from more than one synovial structure, and two horses had positive cultures obtained from repeat samples. Overall, 114 bacterial isolates were obtained. Gram-positive bacteria were isolated in 75% of cases, of which 22% were haemolytic Staphylococcus spp., and 52% were Staphylococcus aureus including two multidrug-resistant isolates. Gram-negative bacteria were isolated from 25% of cases. Anaerobic Clostridium spp. was isolated in 3% of cases. Of the first line antimicrobials, oxytetracycline and doxycycline were effective against 70-100% of the Gram-positive bacteria and 20-100% of the Gram-negative organisms, whilst trimethoprim-sulphamethoxazole and gentamicin efficacy ranged between 50% and 88% for both Gram-positive and Gram-negative bacteria. Of the equine protected antimicrobials, ceftiofur was effective against 70-90% of all bacterial isolates whilst 80% of isolates were susceptible to enrofloxacin. These results indicate that tetracyclines, trimethoprim-sulphamethoxazole or gentamicin may be suitable first-line antimicrobials for treatment of synovial sepsis cases while awaiting laboratory results, findings which support current recommendations for antimicrobial stewardship in equine medicine.

[Small Suture, Large Effect - Therapy of Esohypotropia Associated with Severe Myopia]. / Kleiner Faden, große Wirkung ­ Therapie der Esohypotropie bei hoher Myopie.

Purpose: To evaluate a dose-response relationship by using Yokoyama procedure we compared a group of inhomogeneous cases with esohypotropia (EHT) associated with high myopia. Methods: We did a retrospective analysis of 7 cases with EHT associated with high myopia, who underwent Yokoyama procedure between 2014 and 2015. Pre- and postoperative orthoptic measurements as well as measurements of axial length were recorded. Results: The average age ranged from 59.5 ± 2.8 (SD) years. The mean value of axial lengths was 32.7 ± 3.2 mm (29-36.4 mm). The angle of esotropia changed from 44.6 ± 35.2 prism dioptres (PD) to 11.4 ± 16.9 PD and the angle of hypotropia changed from 15.4 ± 4.7 to 2.2 ± 5.2 PD postoperatively. All patients underwent Yokoyama procedure with fornix incision, 3 patients with additional medial rectus recession. Abduction and supraduction improved after surgery. The average follow-up was 6 months, the postoperative outcomes were stable. Conclusion: The Yokoyama procedure with or without additional medial rectus recession is an effective surgical treatment of EHT associated with high myopia.

Severe Foot Lesions in Dairy Goats Associated with Digital Dermatitis Treponemes.

Treponeme-associated foot disease has been described in cattle with digital dermatitis and sheep with contagious ovine digital dermatitis. In this study, severe foot lesions in dairy goats associated with digital dermatitis treponemes (i.e. Treponema medium, Treponema phagedenis and Treponema pedis) were characterized macroscopically, radiographically and histologically. The main macroscopic foot lesion was of extensive solar ulceration with or without exophytic papilliform hyperkeratosis. Radiographically, the distal phalanx and distal sesamoid bones were severely damaged and remodelled. Histologically, the lesion was categorized as a chronic lymphoplasmacytic, suppurative and ulcerative pododermatitis. Immunohistochemistry identified the spirochaetal microorganisms located extracellularly in the superficial horn. Study limitations mean that the treponeme bacteria could not be considered the sole or causal agents in the cases described.

Lamellar pathology in horses with pituitary pars intermedia dysfunction.

REASONS FOR PERFORMING STUDY: Hoof lamellar pathology in horses with pituitary pars intermedia dysfunction (PPID) has not been described previously. OBJECTIVES: To describe the histomorphometry and pathological lesions in hoof lamellar tissue of animals that had PPID with or without concurrent laminitis, with reference to age-matched controls. We hypothesised that lamellar lesions consistent with laminitis would be associated with PPID, even in animals without current or historical laminitis. STUDY DESIGN: Prospective case-control study. METHODS: Mid-dorsal hoof histological sections were obtained post mortem from the forelimbs of 16 PPID-affected animals either with (n = 6) or without laminitis (n = 10) and 10 age- and breed-matched controls. Sections were examined by a blinded veterinary pathologist. The length and width of 10 primary epidermal lamellae were measured using image analysis software. The morphology and pathology of primary and secondary epidermal lamellae were then typed or graded in axial, middle and abaxial regions. Fasting serum insulin, plasma adrenocorticotropin and blood glucose concentration were measured from blood samples taken prior to euthanasia. RESULTS: All animals with PPID and laminitis had fasting hyperinsulinaemia (median 74.1 miu/l, interquartile range 49.9-349.5 miu/l) whereas PPID animals without laminitis had serum insulin concentrations below the upper limit of the reference range (<20 miu/l). Lamellar pathology in PPID animals with laminitis was variable in severity and unrelated to the reported duration of laminitis (range 2 months-5 years). Most lesions were located abaxially within the lamellar tissue and included increased length and width of the lamellae, chronic abnormal keratinisation, interlamellar epidermal bridging and cell death with more acute lamellar tearing in some cases. The lamellae of PPID animals without laminitis were normal referent to the relevant control group. CONCLUSIONS: Whether PPID and hyperinsulinaemia have a causal inter-relationship or not, it may only be the hyperinsulinaemia that is associated with lamellar morphological alteration and pathology consistent with laminitis.

Tumor Enucleation of Renal Cell Carcinoma in a Solitary Kidney.

We describe the case of a 57 year old man with a solitary kidney after undergoing resection of a Wilm's tumor as a child and a recent left partial colectomy who presents with an incidentally found clinical T1b renal mass. The patient underwent tumor enucleation and had no change in his renal function twelve days after surgery as compared to his preoperative baseline, highlighting the additional nephron-sparing associated with tumor enucleation as compared to partial nephrectomy that includes a gross margin of normal parenchyma.

Reactive oxygen species-mediated therapeutic response and resistance in glioblastoma.

Glioblastoma (GBM) resistance to therapy is the most common cause of tumor recurrence, which is ultimately fatal in 90% of the patients 5 years after initial diagnosis. A sub-population of tumor cells with stem-like properties, glioma stem cells (GSCs), is specifically endowed to resist or adapt to the standard therapies, leading to therapeutic resistance. Several anticancer agents, collectively termed redox therapeutics, act by increasing intracellular levels of reactive oxygen species (ROS). In this study, we investigated mechanisms underlying GSC response and resistance to cannabidiol (CBD), a non-toxic, non-psychoactive cannabinoid and redox modulator. Using primary GSCs, we showed that CBD induced a robust increase in ROS, which led to the inhibition of cell survival, phosphorylated (p)-AKT, self-renewal and a significant increase in the survival of GSC-bearing mice. Inhibition of self-renewal was mediated by the activation of the p-p38 pathway and downregulation of key stem cell regulators Sox2, Id1 and p-STAT3. Following CBD treatment, a subset of GSC successfully adapted, leading to tumor regrowth. Microarray, Taqman and functional assays revealed that therapeutic resistance was mediated by enhanced expression of the antioxidant response system Xc catalytic subunit xCT (SLC7A11 (solute carrier family 7 (anionic amino-acid transporter light chain), member 11)) and ROS-dependent upregulation of mesenchymal (MES) markers with concomitant downregulation of proneural (PN) markers, also known as PN-MES transition. This 'reprogramming' of GSCs occurred in culture and in vivo and was partially due to activation of the NFE2L2 (NRF2 (nuclear factor, erythroid 2-like)) transcriptional network. Using genetic knockdown and pharmacological inhibitors of SLC7A11, we demonstrated that combining CBD treatment with the inhibition of system Xc resulted in synergistic ROS increase leading to robust antitumor effects, that is, decreased GSC survival, self-renewal, and invasion. Our investigation provides novel mechanistic insights into the antitumor activity of redox therapeutics and suggests that combinatorial approaches using small molecule modulators of ROS offer therapeutic benefits in GBM.

Pathology of Natural Cases of Equine Endocrinopathic Laminitis Associated With Hyperinsulinemia.

Laminitis in equids is a clinical syndrome usually associated with systemic disease. Endocrinopathies recently have been recognized as the most common cause of laminitis, with hyperinsulinemia playing a key role. Descriptions of laminitis-associated lesions have been confusing due to the wide range of experimental models used, failure of adequate clinical documentation for naturally occurring cases, lack of separate analysis of inflammatory and endocrinopathic laminitis, and uncertainty regarding normal morphological variation of lamellae. In this study, lamellar morphology and pathology were described in 14 laminitic horses and ponies that had hyperinsulinemia (>20 mIU/l), with reference to 25 age- and breed-matched controls. The type and severity of lesions noted had no correlation with reported clinical duration and in at least some cases must have preceded it. Lesions were largely localized abaxially within the lamellar tissue and included apoptotic cell death, as well as lamellar fusion, hyperplasia, and partial replacement with aberrant keratin containing nucleated debris and proteinaceous lakes. The lesions resulted in irregular margins between the inner horn and the lamellar tissue. Acute separation originated from the abaxial region, with minimal associated inflammation. Axially, epidermal lamellar tapering was the most frequent morphological observation. The lesions in these chronic cases of laminitis were similar to those described in some inflammatory laminitis models and contained features seen in developmental phases of hyperinsulinemic models. These findings support the theory that repeated episodes of subclinical laminitis occur prior to clinical presentation. In addition, the pathology does not include extensive basement membrane failure seen in some inflammatory models.

Is anaesthesia of the deep branch of the lateral plantar nerve specific for the diagnosis of proximal metatarsal pain in the horse?

OBJECTIVES: To investigate the specificity of anaesthesia of the deep branch of the lateral plantar nerve (DB-LPN). METHODS: Twenty horses had DB-LPN anaesthesia performed by a single injection technique as part of a lameness investigation. The mechanical nociceptive threshold (NT) was measured using a handheld force meter at six points on the lateral aspect of the limb: before diagnostic anaesthesia (T0), and at 15 (T15) and 30 (T30) minutes post anaesthesia. Paired t-tests were performed and significance was set at p <0.05. In addition, ten cadaveric limbs were injected with 2.5 ml new methylene blue solution using a single injection technique to evaluate the extent of dye diffusion within the proximal metatarsal region. RESULTS: Compared with T0, there was a significant decrease in NT for all points combined at T15 (p = 0.008) and also at T30 (p = 0.007). There was a significant decrease in NT at T15 on the lateral third metatarsal bone (p = 0.012). At T30 there was a significant decrease in NT at the lateral sesamoid (p = 0.007), lateral third metatarsal bone (p = 0.031), and mid metatarsus (p = 0.033). Four out of 20 horses had a NT greater than 10 N at the lateral heel bulb at T30. In the cadaveric limbs, the total diffusion distance for all limbs (mean ± SD) was 70.4 ± 20.5 mm. Dye surrounded the DB-LPN in all limbs and the lateral plantar nerve (LPN) in nine out of 10 limbs. CLINICAL SIGNIFICANCE: Concurrent anaesthesia of the LPN is likely to occur when DB-LPN anaesthesia is performed using a single injection technique.

Predictors of CNS injury as measured by proton magnetic resonance spectroscopy in the setting of chronic HIV infection and CART.

The reasons for persistent brain dysfunction in chronically HIV-infected persons on stable combined antiretroviral therapies (CART) remain unclear. Host and viral factors along with their interactions were examined in 260 HIV-infected subjects who underwent magnetic resonance spectroscopy (MRS). Metabolite concentrations (NAA/Cr, Cho/Cr, MI/Cr, and Glx/Cr) were measured in the basal ganglia, the frontal white matter, and gray matter, and the best predictive models were selected using a bootstrap-enhanced Akaike information criterion (AIC). Depending on the metabolite and brain region, age, race, HIV RNA concentration, ADC stage, duration of HIV infection, nadir CD4, and/or their interactions were predictive of metabolite concentrations, particularly the basal ganglia NAA/Cr and the mid-frontal NAA/Cr and Glx/Cr, whereas current CD4 and the CPE index rarely or did not predict these changes. These results show for the first time that host and viral factors related to both current and past HIV status contribute to persisting cerebral metabolite abnormalities and provide a framework for further understanding neurological injury in the setting of chronic and stable disease.

Factors associated with survival to hospital discharge following endoscopic treatment for synovial sepsis in 214 horses.

REASONS FOR PERFORMING STUDY: To determine risk factors involved in survival to hospital discharge of cases of synovial sepsis. OBJECTIVES: Investigate pre-, intra- and post operative factors involved in short-term survival of horses undergoing endoscopic treatment for synovial sepsis. STUDY DESIGN: Retrospective case series. METHODS: Clinical data were obtained for horses (>6 months old) undergoing endoscopic surgery as part of management for synovial sepsis over a 7-year period in a single hospital population. Descriptive data were generated for pre-, intra- and post operative variables. Multivariable logistic regression analysis was used to develop 3 models related to presurgical, surgical and post surgical stages of management with outcome defined as survival to hospital discharge. RESULTS: Two hundred and fourteen horses were included. In Model 1 (preoperative variables), increased preoperative synovial fluid total protein (TP) was associated with nonsurvival (OR 0.88, 95% CI 0.83-0.94, P<0.001) whereas the presence of a wound on admission was associated with survival (OR 4.75, 95% CI 1.21-18.65, P = 0.02). Model 2 (intraoperative variables) revealed that factors associated with decreased survival were anaesthetic induction outside of normal working hours (OR 0.36, 95% CI 0.15-0.88 P = 0.02) and presence of moderate/severe synovial inflammation at surgery (OR 0.28, 95% CI 0.12-0.67, P = 0.004). Model 3 (post operative variables) showed that increased post operative synovial fluid TP (OR 0.94, 95% CI 0.90-0.98, P = 0.013) and undertaking more than one endoscopic surgery for treatment (OR 0.19, 95% CI 0.05-0.70, P = 0.005) were associated with nonsurvival. Cut-off values for predicting survival were 55-60 g/l for preoperative and 50-55 g/l for post operative TP measurements. CONCLUSIONS: This study has identified factors associated with altered likelihood of survival to hospital discharge following endoscopic surgery for synovial sepsis. Prognosis for survival to hospital discharge can be based on evidence from this study at the key stages of management of horses with synovial sepsis.

Outcome of horses with synovial structure involvement following solar foot penetrations in four UK veterinary hospitals: 95 cases.

REASONS FOR PERFORMING STUDY: The factors associated with outcome following solar foot penetration involving synovial structures treated using endoscopic lavage have not been described in the UK population. OBJECTIVES: To provide descriptive data on horses with synovial contamination or sepsis following solar penetration in 4 UK equine referral hospitals and to identify specific factors associated with the outcome. STUDY DESIGN: Retrospective case series. METHODS: Data were collected from 4 veterinary hospitals. Follow-up data were obtained via a telephone questionnaire. Two multivariable logistic regression models were generated. Model 1 included all horses with synovial contamination following foot penetration undergoing surgical treatment, with the outcome variable being euthanasia during hospitalisation. Model 2 included all horses surviving anaesthesia, with the outcome variable being failure to return to pre-injury athletic function. RESULTS: Ninety-five horses were included. Overall, 56% of horses survived to discharge and 36% of horses returned to pre-injury athletic function. Model 1 included penetration of the central frog sulcus (odds ratio [OR] 10, 95% confidence interval [CI] 1.9-51.8), concurrent distal phalanx involvement (OR 32, 95% CI 2.6-101.9), increasing days to presentation (OR 1.2, 95% CI 1.0-1.3) and hospital. Model 2 included increasing days to presentation (OR 1.1, 95% CI 1.1-1.6), breed (OR 32, 95% CI 2.2-135.4), more than one surgery (OR 5.6, 95% CI 1.0-32.7) and hospital. CONCLUSIONS AND POTENTIAL RELEVANCE: Synovial involvement following solar foot penetration has a guarded prognosis for survival to discharge and a poor prognosis for return to pre-injury athletic function. Penetration of the central sulcus of the frog and distal phalanx involvement are associated with euthanasia during hospitalisation. Delayed referral and hospitalisation are associated with both euthanasia and failure to return to pre-injury athletic function. Breed and more than one surgery are associated with failure to return to pre-injury athletic function. These data may assist veterinary surgeons and owners to make evidence-based decisions when managing cases with synovial involvement following solar foot penetration.

Neutrophil gelatinase-associated lipocalin: pathophysiology and clinical applications.

Neutrophil gelatinase-associated lipocalin (NGAL), a 25 kDa protein produced by injured nephron epithelia, is one of the most promising new markers of renal epithelial injury. In contrast to serum creatinine and urinary output, which are the measures of kidney function, NGAL is specifically induced in the damaged nephron and then released into blood and urine, where it can be readily measured. Careful proof-of-concept studies using defined animal models have uncovered the sources and trafficking of NGAL in acute kidney injury (AKI) and have addressed the contributions of renal and non-renal sources. Clinical studies indicate that NGAL, unlike creatinine, is a marker responsive to tissue stress and nephron injury, but less so to adaptive hemodynamic responses. In certain clinical settings, NGAL is an earlier marker compared with serum creatinine. In addition, clinical studies have shown that NGAL is a powerful predictor of poor clinical outcomes, which can be used to risk stratify patients when combined with serum creatinine. NGAL has important limitations, including its responsiveness in systemic inflammation, which is partially uncoupled from its response to kidney injury and which needs to be considered when interpreting NGAL results clinically. This review covers the biology and pathophysiology of NGAL and summarizes the results of the growing body of clinical studies that have addressed the utility of NGAL in the early diagnosis of AKI, in the distinction of intrinsic AKI and in the prognostic assessment of broad patient populations.