Gluten induces rapid reprogramming of natural memory αß and γδ intraepithelial T cells to induce cytotoxicity in celiac disease.

Celiac disease (CD) is an autoimmune disease in which intestinal inflammation is induced by dietary gluten. The means through which gluten-specific CD4+ T cell activation culminates in intraepithelial T cell (T-IEL)-mediated intestinal damage remain unclear. Here, we performed multiplexed single-cell analysis of intestinal and gluten-induced peripheral blood T cells from patients in different CD states and healthy controls. Untreated, active, and potential CD were associated with an enrichment of activated intestinal T cell populations, including CD4+ follicular T helper (TFH) cells, regulatory T cells (Tregs), and natural CD8+ αß and γδ T-IELs. Natural CD8+ αß and γδ T-IELs expressing activating natural killer cell receptors (NKRs) exhibited a distinct TCR repertoire in CD and persisted in patients on a gluten-free diet without intestinal inflammation. Our data further show that NKR-expressing cytotoxic cells, which appear to mediate intestinal damage in CD, arise from a distinct NKR-expressing memory population of T-IELs. After gluten ingestion, both αß and γδ T cell clones from this memory population of T-IELs circulated systemically along with gluten-specific CD4+ T cells and assumed a cytotoxic and activating NKR-expressing phenotype. Collectively, these findings suggest that cytotoxic T cells in CD are rapidly mobilized in parallel with gluten-specific CD4+ T cells after gluten ingestion.

Increased Patient Enrollment to a Randomized Surgical Trial Through Equipoise Polling of an Expert Surgeon Panel.

OBJECTIVE: To determine whether patients who learned the views of an expert surgeons' panel's assessment of equipoise between 2 alternative operative treatments had increased likelihood of consenting to randomization. BACKGROUND: Difficulty obtaining patient consent to randomization is an important barrier to conducting surgical randomized clinical trials, the gold standard for generating clinical evidence. METHODS: Observational study of the rate of patient acceptance of randomization within a 5-center randomized clinical trial comparing lumbar spinal decompression versus lumbar spinal decompression plus instrumented fusion for patients with symptomatic grade I degenerative lumbar spondylolisthesis with spinal stenosis. Eligible patients were enrolled in the trial and then asked to accept randomization. A panel of 10 expert spine surgeons was formed to review clinical information and images for individual patients to provide an assessment of suitability for randomization. The expert panel vote was disclosed to the patient by the patient's surgeon before the patient decided whether to accept randomization or not. RESULTS: Randomization acceptance among eligible patients without expert panel review was 40% (19/48) compared with 81% (47/58) among patients undergoing expert panel review (P < 0.001). Among expert-reviewed patients, randomization acceptance was 95% when all experts or all except 1 voted for randomization, 75% when 2 experts voted against randomization, and 20% with 3 or 4 votes against (P < 0.001 for trend). CONCLUSIONS: Patients provided with an expert panel's assessment of their own suitability for randomization were twice as likely to agree to randomization compared with patients receiving only their own surgeon's recommendation.

Orthopaedic Injuries in Equestrian Sports: A Current Concepts Review.

BACKGROUND: Despite the common nature of orthopaedic injuries in equestrian sports, there is no published review to specifically characterize orthopaedic injuries in equestrian athletes. PURPOSE: To characterize orthopaedic injury patterns in equine sports-related injuries and their treatment. STUDY DESIGN: Systematic review; Level of evidence, 4. METHODS: This review was performed through a PubMed, EMBASE, and Scopus query (from 1978 to June 2014) in the English literature using search terms "(equine-related OR equestrian-related OR horse-related OR equestrian OR equestrians) AND (injury OR injuries)." Only full-text studies reporting on orthopaedic injury patterns pertinent to equestrian sports in the United States (US) and the United Kingdom (UK) were included. Orthopaedic injuries were defined as those resulting in a fracture or dislocation. In all, 182 studies were excluded, leaving a total of 27 studies for evaluation. The studies included were analyzed for demographic and epidemiological data for orthopaedic injuries, including fractures and dislocations. Cranial and facial injuries were excluded from analysis. RESULTS: The majority of those injured in the US were female (64.5%). The leading cause of injury in the US was falling from a horse. The use of protective equipment seemed to vary widely, with helmet use ranging from less than 6% up to 66.7%. In the UK, fractures were found to account for 17.4% of reported injures, compared with 33.6% of injuries in the US. The majority of fractures in US riders occurred in the upper extremities (50.7%). CONCLUSION: This review helps characterize the epidemiology of equestrian injuries based on currently available data.