Acute kidney injury (AKI) is a major clinical concern in sickle cell disease (SCD). Clinical evidence suggests that red cell alarmins may cause AKI in SCD however the sterile inflammatory process involved has hitherto not been defined. We discovered that hemopexin deficiency in SCD is associated with a compensatory increase in alpha-1-microglobulin (A1M) resulting in up to 10-fold higher A1M/hemopexin ratio in SCD compared to health controls. The A1M/hemopexin ratio is associated with markers of hemolysis and AKI in both humans and mice with SCD. Studies in mice showed that excess heme is directed to the kidneys in SCD in a process involving A1M causing AKI while excess heme in controls is transported to the liver as expected. Using genetic and bone marrow chimeric tools, we confirmed that hemopexin deficiency promotes AKI in sickle mice under hemolytic stress. However, AKI was blocked when hemopexin deficiency in sickle mice was corrected with infusions of purified hemopexin prior to the induction of hemolytic stress. This study identifies acquired hemopexin deficiency as a risk factor of AKI in SCD and hemopexin replacement as a potential therapy.
Synovial infections (SI) are common in horses of all ages and can be associated with high rates of morbidity and mortality. Identifying factors influencing survival and return to function may be useful for management of affected individuals and determination of prognosis. The objectives of this study were to identify factors associated with survival and return to function of horses and foals with SI presented to an equine hospital. This study is a retrospective case series. Data were collected from medical records of all horses with SI that were presented to a single equine hospital between April 1st, 2008 and May 1st, 2017. Long–term follow up was obtained by a semi-structured telephone questionnaire of clinical outcomes and analysis of online race records. Univariate models were created using generalized linear and linear mixed models to assess factors associated with outcomes. Multivariable models were created using generalized linear and linear mixed models to determine factors significantly associated with outcomes. Of 186 horses presented with SI, 161/186 (86.6%) were treated and 145/161 (90.1%) survived to discharge. The majority of joints were treated with synovial lavage (93.8%). One hundred and twenty horses were included in the return to function analysis and 79 (65%) returned to function. Increasing number of days of treatment with systemic antimicrobials was associated with increased likelihood of survival for each horse (OR 1.15, 95% CI 1.04−1.27, P = 0.025) and when considering each individual synovial structure (OR 1.11, 95% CI 1.04−1.17, P = 0.004). Horses treated with doxycycline were less likely to return to function (OR 0.39, 95% CI 0.19−0.8, P = 0.031). The overall rate of survival of horses treated with SI is good. The likelihood of return to function is lower than for survival. The findings of this study, combined with relevant antimicrobial stewardship practices, can be used as a part of evidence-based decision-making when veterinarians are treating horses with SI.
Background: Grading of equine gastric ulcer syndrome (EGUS) is undertaken in clinical and research settings, but the reliability of EGUS grading systems is poorly understood. Hypothesis/Objectives: Investigate interobserver and intraobserver reliability of an established ordinal grading system and a novel visual analog scale (VAS), and assess the influence of observer experience. Animals: Sixty deidentified gastroscopy videos. Methods: Six observers (3 specialists and 3 residents) graded videos using the EGUS Council (EGUC) system and VAS. Observers graded the videos three 3 for each system, using a cross-over design with at least 1 week between each phase. The order of videos was randomized for each phase. Methods: Interobserver and intraobserver reliability were estimated using Gwet's agreement coefficient with ordinal weights applied (AC2) for the EGUC system and the intraclass correlation coefficient (ICC) for the VAS.
Summary Tumours of vascular origin are uncommon in horses. This report describes the surgical treatment of a large subcutaneous tumour in a Quarter Horse colt. The histopathological appearance of the mass was most consistent with a haemangioma. While these neoplasms of vascular origin are often difficult to characterise, it has been suggested that there is a continuum of types with some cases falling between the categories. Further classification of vascular tumours requires special stains and immunohistochemical techniques.
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