Gloucestershire Evidence & Research Repository

Recent Submissions

  • PublicationOpen Access
    Recommendations for contouring of gross tumour volume for locally advanced lung cancer using magnetic resonance imaging
    (Elsevier, 2026-03-15) Shiarli, Anna-Maria; Dubec, Michael; Ahmed, Merina; Asmussen, Jon; Bainbridge, Hannah; Belderbos, Jose; Brown, Sean; Bussink, Johan; Cobben, David; Geurts, Bram; Brown, Sean; Medical and Dental
    Background and purpose: The use of Magnetic Resonance imaging (MRI) for radiotherapy planning and guidance for locally advanced non-small cell lung cancer (LA NSCLC) is novel. The superior soft tissue definition of MRI compared to CT, may facilitate more accurate gross tumour volume (GTV) definition, with the goal of improving radiotherapy precision. This work aims to develop GTV contouring recommendations for NSCLC on MRI. Materials and methods: Two international training workshops on GTV delineation for LA NSCLC were attended by thoracic radiation oncologists and MR radiologists. Thoracic radiation oncology experts contoured nine cases of LA NSCLC, firstly, on mid-position 4D-CT with PET-CT guidance, and secondly on non-contrast MRI, registered with the CT and PET-CT. Consensus contours generated on CT and MRI were discussed and finalised during two international meetings. Results: Recommendations on GTV delineation for LA NSCLC for both the primary tumour and individual lymph node stations using thoracic MRI were produced and are provided in this document. Consensus contours generated on CT and MRI for specific clinical scenarios were demonstrated and challenges addressed. Conclusions: We provide the first set of consensus recommendations on GTV contouring on MRI for LA NSCLC through an international collaborative process between international experts in thoracic radiation oncology and MR radiology. This work provides an initial step towards standardisation of lung GTV delineation on MRI, which is necessary prior to any meaningful assessment of the benefits of MRI in GTV definition compared to current practice. Keywords: Lung cancer; Radiotherapy; Thoracic MRI.
  • PublicationOpen Access
    Role of Cardiac Magnetic Resonance (CMR) as a Diagnostic and Risk Stratification Tool for a Patient With Arrhythmic Mitral Valve Complex Phenotype and Tricuspid Annular Disjunction (TAD)
    (Springer Nature, 2026-02-28) Raslan, Mahmoud; Huang, Xi Na; Elmarzouky, Zeyad; Elmarzouky, Zeyad; Medical and Dental
    Arrhythmogenic mitral valve disease (AMVD) is a newly established entity that carries a high risk of developing ventricular arrhythmia ranging from premature ventricular contraction to sudden cardiac death. Therefore, there is an urgent need for risk prediction and stratification by using different imaging modalities. A 77-year-old patient presented with a syncopal episode. Physical examination was unremarkable. Resting electrocardiogram (ECG) was normal. Echocardiography showed mild systolic dysfunction and mild aortic stenosis. Seven days of Holter monitor recording demonstrated frequent episodes of polymorphic ventricular contraction and one episode of sinus bradycardia. Therefore, the patient was scheduled for cardiac magnetic resonance (CMR) which was successful in revealing the etiology of the presentation. Biannuli disjunction and mitral valve prolapse could be clearly visualized in our CMR study. Consequently, the patient was referred for an urgent clinical consultation by the electrophysiology heart team and implantable loop recorder. A review of the six-week recording showed further episodes of narrow complex tachycardia with rates up to 222 beats per minute (bpm) associated with one episode of pre-syncope. He was prescribed bisoprolol and scheduled for regular follow-up at the arrhythmia clinic. In our report, we present a case of AMVD when the definite diagnosis could not be revealed by using the echocardiography modality alone. However, CMR has been proven successful in establishing a diagnosis and unveiling the etiology of the presentation. Keywords: arrhythmogenic mitral valve complex; cardiac mri; mitral annular disjunction; mitral valve prolapse; tricuspid annular disjunction.
  • PublicationOpen Access
    Myeloproliferative neoplasms with concomitant chronic myeloid leukemia are associated with TKI resistance and poor outcomes
    (Springer Nature, 2026-03-27) Gagnon, Laura; Duminuco, Andrea; Stagno, Fabio; Sobas, Marta; Fominykh, Mikhail; Virchis, Andres; Nicolini, Franck-Emmanuel; Hildt, Julie; Bentley, Helen; Godfrey, Anna; Frewin, Rebecca; Frewin, Rebecca; Medical and Dental
    Chronic myeloid leukemia (CML) and Philadelphia (Ph)-negative myeloproliferative neoplasms (MPN) are generally distinct clonal disorders, with the co-occurrence of BCR::ABL1 rearrangement with concomitant Ph-negative MPN rarely reported. Here we describe the largest known international cohort of Ph-negative MPN and coexisting CML providing important insights into this rare clinical scenario. We performed an international, multicenter, retrospective analysis of patients with concomitant BCR::ABL1 rearrangement and Ph-negative MPN, identifying 61 cases from 30 centers in 7 countries, over a 29-year period (1996-2025). Thirty-one patients (50.8%) had Ph-negative MPN preceding CML, 18 patients (29.5%) had CML preceding Ph-negative MPN, and 12 patients (19.7%) had Ph-negative MPN and CML diagnosed simultaneously. We observed increased TKI resistance and myelofibrotic transformation, especially in patients initially diagnosed with Ph-negative MPN. In this group, 35.4% (n = 11) progressed to MF, 2 patients to blast-phase MPN, and 69.2% (n = 18) failed to achieve a complete cytogenetic response. The rare e1a2 BCR::ABL1 transcript was notably prevalent which is associated with TKI resistance and a more aggressive disease course in CML. We described superior survival in those with Ph-negative MPN preceding CML, with median OS not reached, compared with 277 months for CML preceding Ph-negative MPN and 100 months for those diagnosed simultaneously (p = 0.05).
  • PublicationOpen Access
    Biallelic variants in RNU2-2 cause a remarkably frequent developmental and epileptic encephalopathy
    (Springer Nature, 2026-03-30) Jackson, Adam; Blakes, Alexander; Alhaddad, Bader; Henry, Olivia; Delgado-Vega, Angelica; Wall, Elizabeth; Abdelhadi, Ola; Agrawal, Shakti; Bakur, Khadijah; Milhench, Alison; Milhench, Alison; Medical and Dental
    Neurodevelopmental disorders (NDDs) affect 2-4% of the population, are predominantly genetic and remain unsolved in ~50% of individuals. We show that rare biallelic variants in RNU2-2 are enriched and over-transmitted in individuals with unresolved NDDs. We define a recessive RNU2-2 syndrome, delineate its unique genetic architecture and show that it manifests clinically as a severe developmental and epileptic encephalopathy. We find that candidate biallelic variants are significantly correlated with reduced U2-2 abundance, implicating compromised transcript stability as a probable pathomechanism. We identify a decreased ratio of U2-2 to its paralog U2-1 as a potential diagnostic biomarker for this condition. We show that the recessive RNU2-2 syndrome is genetically, clinically and mechanistically distinct from the dominant RNU2-2 disorder. Within our cohort, the recessive RNU2-2 syndrome emerges as by far the most frequent recessive NDD, greatly disproportionate to the small genomic footprint of this non-protein-coding gene.
  • PublicationOpen Access
    Validating and updating the OHTS-EGPS model predicting 5-year glaucoma risk among patients with ocular hypertension using electronic medical records: a cohort study
    (NIHR Journals Library, 2026-03) Wright, David; Wu, Hangjian; King, Anthony; Montesano, Giovanni; Higgins, Bethany; Gazzard, Gus; Morgan, James; McNaught, Andrew; Sebastian, Rani; Ahmed, Faisal; McNaught, Andrew; Medical and Dental
    Background: Ocular hypertension, that is intraocular pressure > 21 mmHg, is a risk factor for glaucoma. A glaucoma risk predictor, the Ocular Hypertension Study-European Glaucoma Prevention Study model, is available. Objectives: (1) To validate and update the Ocular Hypertension Study-European Glaucoma Prevention Study risk prediction model in a United Kingdom population; (2) to assess the relative efficiency of alternative monitoring pathways according to glaucoma risk; (3) to determine the clinical and cost-effectiveness of treating people with ocular hypertension with intraocular pressure of 22 or 23 mmHg and (4) to elicit patient preferences for monitoring. Design: (1) Retrospective data analysis of electronic medical records of ocular hypertension patients attending hospital eye services. The influence of the Ocular Hypertension Study-European Glaucoma Prevention Study predictors and additional ocular and systematic factors was explored. Validation: the Ocular Hypertension Study-European Glaucoma Prevention Study prediction model was applied. Update: the model was refitted by re-estimating baseline hazard and regression coefficients. (2, 3) Predictor versus standard care, with deterministic and probabilistic sensitivity analyses. Subgroup analysis for people with 22-23 mmHg intraocular pressure. (4) Discrete choice experiment. Setting and participants: People with intraocular pressure 22-32 mmHg in either eye, at least four visual field tests, 5 years of follow-up, no significant ocular comorbidities. Data sourced from secondary clinical settings. Main outcome measures: Discriminative ability (c-index) and calibration (calibration slope) to predict conversion to glaucoma in 5 years. Quality-adjusted life-years, incremental cost-effectiveness ratio, preferences. Data sources: Electronic medical records of 10 hospitals in England. Results: (1) Of 9030 patients with ocular hypertension who fitted the inclusion criteria 1530 (16.9%) converted to glaucoma. The Ocular Hypertension Study-European Glaucoma Prevention Study model provided a pooled c-index of 0.61 (95% confidence interval: 0.60 to 0.63). The updated model had a pooled c-index of 0.67 (0.51 to 0.84). (2) In the economic model almost all (99%) patients were treated in the risk predictor strategy, and less than half (47%) in the standard care strategy. The risk predictor strategy produced higher costs, but also higher quality-adjusted life-years and is likely to be cost-effective compared with standard care. (3) Patients with ocular hypertension and intraocular pressure 22-23 mmHg had similar risk of conversion to the rest of the cohort. A treat-all strategy may not be cost-effective. (4) Three hundred and sixty patients were recruited from four NHS hospitals. Almost all respondents (92%) had experienced face-to-face monitoring at a hospital; fewer respondents had experienced virtual clinics (47%) or community optometrist monitoring (43%). Most patients preferred hospital-based monitoring services by health professionals rather than community-based by optometrists but patients with prior experience of community optometrist monitoring preferred it. Patients preferred options associated with lower risk of conversion and lower costs. Limitations: Insufficient data to evaluate influence of ethnicity or ocular factors such as optic disc and retinal anatomy. Conclusions: We validated the Ocular Hypertension Study-European Glaucoma Prevention Study predictor model in a large population with ocular hypertension achieving modest improvements. The use of a risk prediction tool is likely to be cost-effective. Reducing the risk of conversion was the most important preference for patients with ocular hypertension. Future work: Future work should address the influence of genetic or other ocular factors in disease progression, evaluation of effectiveness and cost-effectiveness of different models of eye care, and on how to avoid late glaucoma presentation.