2024 Eastern publications

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    Cancer Precision-Prevention trial of Metformin in adults with Li Fraumeni syndrome (MILI) undergoing yearly MRI surveillance: a randomised controlled trial protocol
    (BioMed Central, 2024-02-03) Dixon-Zegeye, M.; Shaw, R.; Collins, L.; Perez-Smith, K.; Ooms, A.; Qiao, M.; Pantziarka, P.; Izatt, L.; Tischkowitz, M.; Harrison, R. E.; George, A.; Woodward, E. R.; Lord, S.; Hawkes, L.; Evans, D. G.; Franklin, J.; Hanson, H.; Blagden, S. P.
    BACKGROUND: Li-Fraumeni syndrome (LFS) is a rare autosomal dominant disease caused by inherited or de novo germline pathogenic variants in TP53. Individuals with LFS have a 70-100% lifetime risk of developing cancer. The current standard of care involves annual surveillance with whole-body and brain MRI (WB-MRI) and clinical review; however, there are no chemoprevention agents licensed for individuals with LFS. Preclinical studies in LFS murine models show that the anti-diabetic drug metformin is chemopreventive and, in a pilot intervention trial, short-term use of metformin was well-tolerated in adults with LFS. However, metformin's mechanism of anticancer activity in this context is unclear. METHODS: Metformin in adults with Li-Fraumeni syndrome (MILI) is a Precision-Prevention phase II open-labelled unblinded randomised clinical trial in which 224 adults aged = 16 years with LFS are randomised 1:1 to oral metformin (up to 2 mg daily) plus annual MRI surveillance or annual MRI surveillance alone for up to 5 years. The primary endpoint is to compare cumulative cancer-free survival up to 5 years (60 months) from randomisation between the intervention (metformin) and control (no metformin) arms. Secondary endpoints include a comparison of cumulative tumour-free survival at 5 years, overall survival at 5 years and clinical characteristics of emerging cancers between trial arms. Safety, toxicity and acceptability of metformin; impact of metformin on quality of life; and impact of baseline lifestyle risk factors on cancer incidence will be assessed. Exploratory end-points will evaluate the mechanism of action of metformin as a cancer preventative, identify biomarkers of response or carcinogenesis and assess WB-MRI performance as a diagnostic tool for detecting cancers in participants with LFS by assessing yield and diagnostic accuracy of WB-MRI. DISCUSSION: Alongside a parallel MILI study being conducted by collaborators at the National Cancer Institute (NCI), MILI is the first prevention trial to be conducted in this high-risk group. The MILI study provides a unique opportunity to evaluate the efficacy of metformin as a chemopreventive alongside exploring its mechanism of anticancer action and the biological process of mutated P53-driven tumourigenesis. TRIAL REGISTRATION: ISRCTN16699730. Registered on 28 November 2022. URL: https://www.isrctn.com/ EudraCT/CTIS number 2022-000165-41.
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    Progressive unilateral facial asymmetry in a young girl
    (Elsevier, 2024-12-01) Bagri, N. K.; Al Julandani, D. A.; Osborne, N. J. R.; Charman, C. R.; Ramanan, A. V.
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    UK Transfusion Laboratory Collaborative: Minimum standards for staff qualifications, training, competency and the use of information technology in hospital transfusion laboratories 2023
    (Wiley, 2024-02-01) Dowling, K.; Davies, J.; Narayan, S.; Tuckley, V.; Robbie, C.; Ward, C.; Subramaniam, C.; Whitham, C.; Tomlinson, T.; Stephens, G.; Thomson, A.; Carty, S.; Capps-Jenner, A.; Willis, D.
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    The characteristics and predictors of mortality in periprosthetic fractures around the knee
    (British Editorial Society of Bone and Joint Journal, 2024-02-01) Nasser, Aahh; Sidhu, M.; Prakash, R.; Mahmood, A.; Osman, K.; Chauhan, G. S.; Nandra, R.; Dewan, V.; Davidson, J.; Al-Azzawi, M.; Smith, C.; Gawad, M.; Palaiologos, I.; Cuthbert, R.; Wignadasan, W.; Banks, D.; Archer, J.; Odeh, A.; Moores, T.; Tahir, M.; Brooks, M.; Biring, G.; Jordan, S.; Elahi, Z.; Shaath, M.; Veettil, M.; De, C.; Handford, C.; Bansal, M.; Bawa, A.; Mattar, A.; Tandra, V.; Daadipour, A.; Taha, A.; Gangoo, S.; Srinivasan, S.; Tarisai, M.; Budair, B.; Subbaraman, K.; Khan, F.; Gomindes, A.; Samuel, A.; Kang, N.; Kapur, K.; Mainwaring, E.; Bridgwater, H.; Lo, A.; Ahmed, U.; Khaleeq, T.; El-Bakoury, A.; Rashed, R.; Hosny, H.; Yarlagadda, R.; Keenan, J.; Hamed, A.; Riemer, B.; Qureshi, A.; Gupta, V.; Waites, M.; Bleibleh, S.; Westacott, D.; Phillips, J.; East, J.; Huntley, D.; Masud, S.; Mirza, Y.; Mishra, S.; Dunlop, D.; Khalefa, M.; Balakumar, B.; Thibbaiah, M.; Payton, O.; Berstock, J.; Deano, K.; Sarraf, K. M.; Logishetty, K.; Lee, G.; Subbiah-Ponniah, H.; Shah, N.; Venkatesan, A.; Cheseldene-Culley, J.; Ayathamattam, J.; Tross, S.; Randhawa, S.; Mohammed, F.; Ali, R.; Bird, J.; Khan, K.; Akhtar, M. A.; Brunt, A.; Roupakiotis, P.; Subramanian, P.; Bua, N.; Hakimi, M.; Bitar, S.; Al Najjar, M.; Radhakrishnan, A.; Gamble, C.; James, A.; Gilmore, C.; Dawson, D.; Sofat, R.; Antar, M.; Raghu, A.; Heaton, S.; Tawfeek, W.; Charles, C.; Burnand, H.; Duffy, S.; Taylor, L.; Magill, L.; Perry, R.; Pettitt, M.; Okoth, K.; Pinkney, T.
    AIMS: Periprosthetic fractures (PPFs) around the knee are challenging injuries. This study aims to describe the characteristics of knee PPFs and the impact of patient demographics, fracture types, and management modalities on in-hospital mortality. METHODS: Using a multicentre study design, independent of registry data, we included adult patients sustaining a PPF around a knee arthroplasty between 1 January 2010 and 31 December 2019. Univariate, then multivariable, logistic regression analyses were performed to study the impact of patient, fracture, and treatment on mortality. RESULTS: Out of a total of 1,667 patients in the PPF study database, 420 patients were included. The in-hospital mortality rate was 6.4%. Multivariable analyses suggested that American Society of Anesthesiologists (ASA) grade, history of peripheral vascular disease (PVD), history of rheumatic disease, fracture around a loose implant, and cerebrovascular accident (CVA) during hospital stay were each independently associated with mortality. Each point increase in ASA grade independently correlated with a four-fold greater mortality risk (odds ratio (OR) 4.1 (95% confidence interval (CI) 1.19 to 14.06); p = 0.026). Patients with PVD have a nine-fold increase in mortality risk (OR 9.1 (95% CI 1.25 to 66.47); p = 0.030) and patients with rheumatic disease have a 6.8-fold increase in mortality risk (OR 6.8 (95% CI 1.32 to 34.68); p = 0.022). Patients with a fracture around a loose implant (Unified Classification System (UCS) B2) have a 20-fold increase in mortality, compared to UCS A1 (OR 20.9 (95% CI 1.61 to 271.38); p = 0.020). Mode of management was not a significant predictor of mortality. Patients managed with revision arthroplasty had a significantly longer length of stay (median 16 days; p = 0.029) and higher rates of return to theatre, compared to patients treated nonoperatively or with fixation. CONCLUSION: The mortality rate in PPFs around the knee is similar to that for native distal femur and neck of femur fragility fractures. Patients with certain modifiable risk factors should be optimized. A national PPF database and standardized management guidelines are currently required to understand these complex injuries and to improve patient outcomes.
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    Rapid genome sequencing for infantile-onset epilepsy within a national health-care setting
    (Elsevier, 2024-02-01) Robinson, H. K.; Stals, K.; Hill, S.; Parrish, A.; Baple, E. L.