The Queen Elizabeth Hospital Birmingham is a major, 1,215 bed, tertiary NHS and military hospital in the Edgbaston area of Birmingham, situated very close to the University of Birmingham. The hospital, which cost £545 million to construct, opened on 16 June 2010, replacing the previous Queen Elizabeth Hospital and Selly Oak Hospital. It is one of the largest single-site hospitals in the United Kingdom and is part of one of the largest teaching trusts in England.It is named after Queen Elizabeth The Queen Mother, who was queen consort and wife of King George VI from 1936 until his death in 1952.The hospital provides a whole range of services including secondary services for its local population and regional and national services for the people of the West Midlands and beyond. The hospital has the largest solid organ transplantation programme in Europe. It has the largest renal transplant programme in the United Kingdom and it is a national specialist centre for liver, heart and lung transplantation, as well as cancer studies. The hospital has the largest single-floor critical care unit in the world with 100 beds, and is the home of the Royal Centre for Defence Medicine for military personnel injured in conflict zones. It is also a regional centre for trauma and burns. The hospital is served by University railway station which is a five-minute walk away.
Accurate registration of multi-stained whole-slide images (WSIs) enables the integration of complementary morphological and molecular information, improving both clinical diagnostic and prognostic analysis. It also enables efficient transfer of annotations between consecutive or re-stained slides, significantly reducing annotation time and cost, as well as three-dimensional tissue reconstruction. Despite its importance, WSI registration remains challenging due to variations in slide preparation across stains and complex tissue deformations. Existing methods are often tailored to specific staining modalities and fail to generalize across diverse settings, highlighting the need for a robust and generalizable cell-level multi-stain registration method. In this work, we introduce CORE, a novel coarse-to-fine framework for accurate cell-centric registration across six multimodal WSI datasets, encompassing 30 distinct staining types, including Hematoxylin & Eosin (H&E), periodic acid–Schiff (PAS), multiplex immunohistochemistry (mIHC), multiplex immunofluorescence (mIF) and Cyclic immunofluorescence (Cyc-IF). CORE first performs coarse global registration by extracting tissue masks through prompt-based segmentation to remove artifacts and non-tissue regions, followed by rigid alignment using tissue morphology and a pre-trained feature extractor. The resulting alignment is refined using a shape-aware point-set registration model applied to automatically detected nuclei centroids, enabling fine-grained rigid alignment. Finally, Coherent Point Drift (CPD) is used to estimate a non-linear displacement field for non-rigid cellular alignment. Using nuclei correspondences throughout the pipeline, CORE achieves accurate and robust cell-level alignment across modalities.Experimental results show that CORE consistently outperforms state-of-the-art methods in accuracy, robustness, and generalization across both bright-field and immunofluorescence WSIs.
This prospective phase 2 multicentre non-randomised parallel arm study of haploidentical peripheral blood stem cell (PBSC) transplantation with post-transplant cyclophosphamide (PTCy) recruited 77 patients: 50 received reduced-intensity conditioning (RIC) with PTCy post stem cell infusion while 27 underwent myeloablative conditioning (MAC) with PTCy given after lymphocyte but prior to infusion of CD34 selected stem cells. The primary end-point 1-year overall survival (OS) was 86% for RIC and 78% for MAC, meeting the pre-specified targets for efficacy. At 4 years, OS was 63% for RIC and 60% for MAC with low non-relapse mortality of RIC 18% and MAC 4%. Engraftment was faster in the MAC arm (median time to neutrophil and platelet engraftment 11 and 15 days; 21 and 24 days in the RIC arm). The economic analysis showed that MAC had higher initial transplant costs, RIC incurred greater post-transplant monitoring costs, resulting in higher overall costs (RIC £156 711, MAC £131 092). Quality of life (QoL) outcomes in both indicated significant post-transplant declines at 3 months but returned to baseline by 12 months. This study confirms the long-term safety of using PBSC with PTCy in haploidentical transplants, with a good quality of life and reasonable costs.
BACKGROUND:Fixation of the posterior malleolus in ankle fractures has evolved from simple size-based criteria to morphology-guided indications informed by computed tomography (CT). Direct posterior approaches now permit anatomic reduction of the posterior tibial plafond and restoration of syndesmotic stability. However, real-world functional outcomes and complication data from United Kingdom (UK) centres remain limited. OBJECTIVE:To describe patient-reported outcomes and complication patterns following morphology-guided posterior malleolus fixation for trimalleolar ankle fractures in a single National Health Service (NHS) teaching hospital. METHODS:We conducted a retrospective cohort study of patients with trimalleolar ankle fractures who underwent posterior malleolus fixation between 2020 and 2022. Functional outcome was assessed using the Olerud-Molander Ankle Score (OMAS). Scores were categorised as poor (<30), fair (30-59), good (60-79), very good (80-99), and excellent (≥100). Complications and reoperations were identified from electronic records. All summary data are reported as frequency (n) and percentage (%), and figures were generated directly from the clinical dataset. RESULTS:Thirty-nine patients contributed OMAS data. The median OMAS was 85, with an interquartile range of 27.5, indicating a distribution skewed towards higher function. Category distribution was poor in 2/39 (5.1%) patients, fair in 6/39 (15.4%), good in 8/39 (20.5%), very good in 16/39 (41.0%), and excellent in 7/39 (17.9%). Minor complications occurred in 10/39 patients (25.6%), most commonly pain in 2/39 (5.1%), post-traumatic arthritis requiring steroid injection in 2/39 (5.1%), and issues related to syndesmotic screws in 2/39 (5.1%). Seven patients (17.9%) underwent removal of metalwork. No deep infections or permanent neurological deficits were recorded. CONCLUSION:Morphology-guided posterior malleolus fixation in trimalleolar ankle fractures was associated with high functional scores and an acceptable complication profile in this single-centre series. These findings support contemporary practice that emphasises CT-based assessment and direct posterior fixation when morphology or instability indicates, while highlighting the need for further prospective studies with standardised reporting and long-term follow-up.
Background Free flap reconstruction is integral to the management of complex lower limb trauma, yet flap failure and return to theatre remain clinically significant challenges. Outcomes may vary according to injury timing and context. Methods A retrospective cohort study was conducted at a UK major trauma centre, including patients who underwent lower limb free flap reconstruction over a five-year period. Patients were categorised into three predefined groups: acute trauma reconstruction, closed fractures with delayed soft-tissue breakdown, and late elective reconstruction for infected metalwork. The primary outcome for acute trauma was any flap loss. A composite reconstruction outcome was used for the infected metalwork cohort. Descriptive and univariable statistical analyses were performed. Results Seventy patients underwent acute lower limb free flap reconstruction. Any flap loss occurred in five cases (7.1%), including four total and one partial flap loss. Return to theatre occurred in 31.4% of cases, with all flap losses occurring in patients requiring re-exploration. No flap losses were observed in patients with initially closed fractures who later developed soft-tissue breakdown (0/10). Nineteen patients underwent late elective free flap reconstruction for infected metalwork; partial or total flap loss occurred in 31.6%, and 57.9% achieved a satisfactory reconstruction using a predefined composite outcome. Conclusions Lower limb free flap reconstruction performed within a UK major trauma centre achieves flap survival rates comparable to published benchmarks despite managing complex injuries. Distinct biological contexts, including delayed breakdown and chronic infection, demonstrate differing outcome profiles, highlighting the importance of stratified analysis when evaluating reconstructive success.
Cascade screening enables effective secondary prevention and early treatment for Thoracic Aortic Disease (TAD) and increases survival. Despite guideline recommendations, the uptake of screening remains low. This study investigated individual and organisational barriers to screening participation. We performed clinician and public focus groups (n = 19 participants across 5 sessions), semi-structured interviews (4 clinicians) and a national patient/relative survey (n = 242 responses: 71 probands, 171 relatives). Behavioural theories guided data interpretation and thematic analysis. Data collection explored motivations, psychological and practical burdens, communication dynamics and attitudes towards screening and Decision Support Tools (DSTs). A national survey of TAD patients and their families provided quantitative context on demographics, genetic testing uptake and involvement in shared decision-making. Thematic analysis using the framework approach was applied to qualitative data. Qualitative analysis of focus groups, interviews and a national patient/relative survey (n = 242) identified significant barriers to TAD cascade screening, including fragmented services, inconsistent clinician knowledge and patient confusion regarding genetic testing pathways. Survey data showed low genetic testing uptake (47% survivors; 44% and 21% for first- and second-degree relatives). Conversely, key facilitators for a DST included user-friendliness, multi-modal accessibility, clear risk/benefit communication and the inherent value of reassurance with professional endorsement from healthcare providers. These would directly address observed psychological and practical burdens. Patient and family engagement in TAD cascade screening faces complex barriers, including psychological burdens and systemic issues, resulting in a substantial shared decision-making gap. User-centric, multi-modal Decision Support Tools, supported by enhanced clinician education and structured family communication, are vital for effective TAD prevention