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The precise link between inflammation and pathogenesis of myelodysplastic syndrome (MDS) is yet to be fully established. We developed a novel method to measure ASC/NLRP3 protein specks which are specific for the NLRP3 inflammasome only. We combined this with cytokine profiling to characterise various inflammatory markers in a large cohort of patients with lower risk MDS in comparison to healthy controls and patients with defined autoinflammatory disorders (AIDs). The ASC/NLRP3 specks were significantly elevated in MDS patients compared to healthy controls (p < 0.001) and these levels were comparable to those found in patients with AIDs. The distribution of protein specks positive only for ASC was different to ASC/NLRP3 ones suggesting that other ASC-containing inflammasome complexes might be important in the pathogenesis of MDS. Patients with MDS-SLD had the lowest levels of interleukin (IL)-1β, tumour necrosis factor (TNF), IL-23, IL-33, interferon (IFN) γ and IFN-α2, compared to other diagnostic categories. We also found that inflammatory cytokine TNF was positively associated with MDS progression to a more aggressive form of disease and IL-6 and IL-1β with time to first red blood cell transfusion. Our study shows that there is value in analysing inflammatory biomarkers in MDS, but their diagnostic and prognostic utility is yet to be fully validated., (© 2024 The Authors. British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.)

Introduction: Native hip dislocations are defined as traumatic dislocations of the hip, typically high-energy and associated with polytrauma. The majority of these injuries occur following motor vehicle accidents (MVAs). Due to the inherent stability of the hip joint, a significant force is required to cause dislocation. It is critical that such injuries are managed and reduced in a timely manner. We evaluated the current practice in a major trauma centre (MTC) in Cardiff and gathered information from emergency departments (EDs) in Wales and MTCs around the United Kingdom (UK)., Methods: We did an evaluation of the current practice with a retrospective audit of all traumatic native hip dislocations presenting to the MTC at Cardiff from August 2018 to February 2021. Data was obtained from Trauma Audit and Research Network (TARN), medical records, radiology and theatre management systems. An online survey was developed and disseminated to EDs in Wales and MTCs across the UK., Results: There were 15 traumatic hip dislocation cases over the period evaluated. Sixty percent of cases were due to MVA. Eighty-six percent of patients had an associated fracture, with one Pipkin type IV fracture dislocation. The mean time to reduction from injury was 532 minutes (240-804 minutes), with 28.6% reduced within 6 hours and 71.4% reduced within 12 hours. Two patients had reduction performed in the ED (mean time to reduction, 275 minutes). There was one occurrence of avascular necrosis (AVN) and one of chondrolysis at the follow-up. The response rate to the survey was 80% and 83% in Wales and MTCs nationally, respectively. The majority (82%) of departments did not have an established pathway in place for managing traumatic native hip dislocations with a preference for reduction in the operating theatre., Conclusion: Native hip dislocations are rare, high-energy injuries associated with significant morbidity. The available evidence suggests time to reduction is imperative in reducing the risk of future complications. The establishment of a pathway to guide management and having a mechanism to perform reductions in the ED may produce significant reductions in this time, impacting outcomes., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Jawad et al.)