Normal pregnancy leads to profound maternal hemodynamic changes, including increased blood volume and vasodilatation. Several vasodilator mediators are implicated, including prostaglandins, carbon monoxide and nitric oxide (NO). Pre-eclampsia (PE) affects 3-10 % of pregnancies and is associated with increased maternal and perinatal morbidity and mortality. Around 8 % of pregnancies are complicated by intra-uterine growth restriction (IUGR), also associated with increased perinatal mortality and morbidity. PE and IUGR often co-exist. NO is essential for the formation of healthy endothelium, and in pregnancy promotes endovascular invasion by the cytotrophoblast. As interstitial trophoblasts invade the maternal spiral arteries in the uterine wall, they produce NO which acts on artery walls to create a low-resistance, high-caliber uteroplacental unit. If this process fails, the result is a high-resistance uteroplacental circulation. The hypoperfused and ischemic placenta releases antiangiogenic factors which mediate generalized endothelial dysfunction, oxidative stress and inflammatory mediators. It is these mediators that are implicated in both the fetal and maternal syndromes of PE and IUGR. Studies of NO and its modulator amino acids, including the precursors arginine and homoarginine and the NO synthesis inhibitor asymmetric dimethylarginine (ADMA), have investigated their role in both normal and pathological pregnancies. Many studies of PE (and, to a lesser extent, IUGR) have investigated maternal circulating ADMA, arginine and homoarginine levels. This article reviews and discusses the role of these amino acids in pregnancy. The results have shed some light on their role in these pathologies, but some of the findings have been conflicting and more research is needed. Nevertheless, therapeutic interventions that manipulate these guanidine-amino acids and their interactions hold real promise for the management of pregnancies complicated by PE and/or IUGR, and the results of ongoing studies are eagerly awaited.
Introduction The classification of soft tissue and bone neoplasms is experiencing a transformation as methods to detect gene fusions expand. Next-generation sequencing panels, anchored multiplex polymerase chain reaction systems and comprehensive RNA sequencing have all contributed to new histological categorisation. The EWSR1-NFATC2 is one such novel translocation found in a round cell sarcomas. These sarcoma sit within the WHO group of undifferentiated round and spindle cell sarcomas. They presents as either a primary bone or soft tissue tumour and exhibits distinctive histopathologic features. Methods This is a case study of a soft tissue mesenchymal tumour with the recently described gene fusion EWSR1-NFATC2. The case is described, with 3-month outcomes and considered in the most recent literature on this sarcoma subset (26 cases). Results This case study prompted a look at the current NHS paradigm for these emerging histopathologically distinctive sarcoma subgroups. At present the expertise with the sarcoma MDT, along with second opinion from other national MDTs is the format for subtype specific sarcoma management, informed by recent literature. Conclusion The EWSR1-NFATC2 fusion round cell sarcoma tumours are an example of a very recently emerged sarcoma subset which display oncological variance to the wider Ewing’s family. The novel literature guided the Southmead and Royal Marsden MDT opinions to proceed straight to surgical excision. The Authors recommend a national prospective database for rare sarcoma subsets, particularly those that appear to exhibit distinctive clinicopathology characteristics. The format could be through the RSTN collaborative, secure anonymised data collection can be collected through REDCap.
Introduction An important clinical question during the Covid -19 pandemic is the safety of steroid use. Guidelines published by rheumatology, physiotherapy, orthopaedic and pain medicine societies have advised on the restricted use of corticosteroids for musculoskeletal and rheumatic conditions. For clinicians across the specialities there is a challenge to safely conducting best practice, yet ensuring patients have access to the significant functional benefits of steroid injections. Methods The STING prospective service evaluation will collect data on steroid injections undertaken during this part of the pandemic. Clinicians will be able to input information on patient demographics, background Covid risk and steroid injection specifics. At follow up at 4-6 weeks complications and Covid specific outcomes will be recorded, as well as patient perceived symptom improvement. Each unit collecting data will have assigned collaborator(s), with a senior consultant validating the data. Data will be collected and managed using Research Electronic Data Capture (REDCap). Data collection and management will adhere to Caldicott II principles and GDPR. Results Results will be analysed through RedCap and compared to national Covid incidence. Local complication and patient reported outcomes will be compared between specialities, environments and steroid specifics (volume, location etc.). Conclusion A pan-speciality look at steroid injection use during the pandemic will be useful primarily to contribute to understanding the safety of steroid use. Secondarily to look at cross speciality differences in administration, PROMs and to appreciate patient groups who may be excluded from steroid treatment. Join the team! Head to RSTN to get involved.
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