Th17 plasticity and its changes associated with inflammatory bowel disease

CD4 T helper(Th) cell differentiation into distinct T cell subsets is critical to the normal function of the immune system. Until recently,the paradigm held that na?ve T cells differentiated into distinct subsets under the guidance of environmental cues(e.g.,cytokines) and that once polarized,these cells were committed to a particular functional state. However,the existence of transdifferentiated T cell populations,which express signature transcription factors and cytokines associated with more than one Th subset,challenges the immutability of T helper subsets and suggests that plasticity is a feature of multifaceted immune responses. How this process impacts immune dysregulation in diseases such as inflammatory bowel diseases(IBD) and the machinery that underlies this process is far from fully understood. Interleukin(IL)-17 secreting helper T(Th17) cells have been heavily implicated in tissue-specific immune pathology including murine models of IBD,human Crohn's disease and ulcerative colitis. Plasticity within this subset is suggested by the existence of IL-17 secreting cells,which,can also secrete interferon-γ,the signature cytokine for Th1 cells or,can co-express the anti-inflammatory transcription factor forkhead box p3,a signature transcription factor of regulatory T cells. In this review we mainly discuss evidence for Th17 plasticity,mechanisms,which govern it,and highlight the potential to therapeutically target this process in human IBD.

Monitoring osteoporosis therapy:Can FRAX help assessing success or failure in achieving treatment goals?

AIM: To assess:(1) Whether the World Health Organization fracture risk assessment tool(FRAX) can be used for monitoring osteoporosis patients receiving treatment as well as its clinical implications; and(2) The relation between fracture incidence and post-treatment FRAX.METHODS: Five hundred and seventy-nine osteoporotic women known to be adherent to the prescribed osteoporosis medication, had dual-energy X-ray absorptiometry scan and fracture probability calculated at baseline, 2 and 5-year of osteoporosis treatment. Those patients who responded to treatment and did not sustain a new low trauma fracture during the first 2 years, continued their treatment and were re-assessed 3-year later. The patient subgroup who did not achieve an improvement in their bone mineral density(BMD)or sustain any fracture within the first 2-year, had their osteoporosis treatment changed. Outcome measures included BMD and FRAX assessment calculated 3-year after commencing new osteoporosis treatment. RESULTS: There was a significant negative correlation between 10-year probability of major osteoporotic and hip fractures and BMD at the total proximal femur at 2-year of treatment(R =-0.449 and-0.479 respectively), and at 5-year(R =-0.489 and-0.594 respectively). At both 2 years and 5 years of treatment, the 10-year fracture probability showed significant correlation with the incidence of fracture(P < 0.01). On comparing fracture probability, there was a significant difference(P < 0.05) between the responders and non-responders to osteoporosis treatment.CONCLUSION: In women currently or previously treated for osteoporosis, the FRAX tool can be used to predict fracture probability. Osteoporosis treatment does not annul prediction of fractures. FRAX tool may be of value in guiding clinicians towards the need for continuation or withdrawal of treatment.

Blunt Abdominal Trauma Leading to Pancreatic Injury in Childhood. Delay in Diagnosis Leads to Poor Outcomes—A Case Presentation

This case report illustrates the difficulty in diagnosing paediatric patients with life threatening pancreatic injuries. A high index of suspicion is essential as late diagnosis significantly affects outcomes. A 9-year-old child presented with epigastric pain following an accident on his pushbike. The patient was examined in paediatric accident and emergency (A/E) and was discharged. He returned twice more to A/E and on the third visit, 5 days after the initial incident, a CT scan was performed. This showed a classical injury to the body of the pancreas with a collection in the lesser sac. The patient was transferred to the regional hepato-pancreato-biliary unit (HPB unit) and underwent surgery. Pancreatic injuries can be difficult to detect clinically and patients may be well on initial presentation with normal observations and routine bloods. Early CT scanning confirms the diagnosis and results in early specialist referral and better outcomes.