University College London Hospitals NHS Foundation Trust (UCLH) is an NHS foundation trust based in London, United Kingdom. It comprises University College Hospital, University College Hospital at Westmoreland Street, the UCH Macmillan Cancer Centre, the Royal National ENT and Eastman Dental Hospitals, the Hospital for Tropical Diseases, the National Hospital for Neurology and Neurosurgery, the Royal London Hospital for Integrated Medicine and the Royal National Throat, Nose and Ear Hospital.The Trust has an annual turnover of around £940 million and employs approximately 8,180 staff. Each year its hospitals treat over 500,000 outpatients appointments and admit over 100,000 patients. In partnership with University College London, UCLH has major research activities as part of the UCLH/UCL Biomedical Research Centre and the UCL Partners academic health science centre. Its hospitals are also major teaching centres and offer training for nurses, doctors and other health care professionals in partnership with City, University of London, King's College London, London South Bank University and UCL Medical School.
Background Emergency diagnosis of lung cancer is common and associated with worse prognosis. Aim To compare prediagnostic healthcare use between emergency-diagnosed patients and patients referred routinely or urgently. Design and setting Population-based linked English primary care, hospital admission, imaging, and cancer registration data were analysed for patients with lung cancer (2007-2018). Method Monthly prediagnosis rates of consultations (for any clinical reason and selected symptoms) and chest imaging by diagnostic route (emergency, routine referral, and urgent referral) were measured. Multivariable Poisson regression estimated route-specific event rates and inflection points. Results The study examined 4473 patients with lung cancer with features representative of the nationwide incident cohort, of whom 33% (n = 1491) were emergency diagnosed. Most (emergency diagnosis, n = 1473/1491; routine referral, n = 1023/1026; urgent referral, n = 1252/1259; and other, n = 684/697) had consulted in primary care in the year prediagnosis, independent of diagnostic route. Consultation and imaging rates increased from 5-and 4-months prediagnosis, respectively, with shorter diagnostic windows in emergency-diagnosed than referred route patients. Compared with emergency-diagnosed patients, referred route patients had higher prediagnostic consultations rates for cough (adjusted incidence rate ratio [aIRR] compared with emergencydiagnosed 1.90, 95% confidence interval [CI] = 1.58 to 2.30 for routinely and 1.94, 95% CI = 1.61 to 2.33 for urgently referred) and chest X-ray use (aIRR 1.91, 95% CI = 1.53 to 2.38 for routinely and 1.77, 95% CI = 1.42 to 2.21 for urgently referred). Conclusion Similar or shorter diagnostic windows suggest similar potential for earlier diagnosis among emergencydiagnosed and referred route patients alike. Earlier detection may be supported through improved management of nonspecific symptoms, timely follow-up of imaging, and greater access to chest computed tomography. Future research should measure missed diagnostic opportunities to identify clinical actions to further reduce emergency lung cancer diagnoses.
BACKGROUND:Superior semi-circular canal dehiscence syndrome is a disorder characterised by auditory and vestibular symptoms that can significantly impact quality of life, and yet it has no disease-specific quality of life instrument. METHOD:Thirty-six patients who underwent transmastoid superior semicircular canal resurfacing and plugging were included from an initial cohort of 60 surgically managed patients. A sub-cohort of 19 consecutive patients completed validated symptom and quality of life questionnaires before and after surgery. Of the 36 patients, 31 participated in a telephone semi-structured interview post-operatively. RESULTS:Following surgery, there was a statistically significant improvement in autophony index score (p = 0.02), symptom severity score (p < 0.001) and sound hypersensitivity (p = 0.01). Thematic analysis of telephone interviews suggested three main symptom themes: auditory hypersensitivity, dysequilibrium, headache and concentration difficulties. Dysequilibrium was found to persist post-operatively. CONCLUSION:Surgery improves overall symptoms and quality of life. However, important symptom themes may be overlooked using the outcome measures that are currently available. A unified disease-specific outcome measure is urgently required to better understand the impact of symptoms and measure treatment effects.
The thymus is essential for establishing T cell diversity early in life, but undergoes profound involution with age and has therefore traditionally been regarded as largely nonfunctional in adults1,2. Here we propose that preserving thymic functionality is integral to adult health and longevity. We developed a deep learning framework to quantify thymic health from routine radiographic images and evaluated its association with longevity and risk of major age-associated diseases in two large prospective cohorts of asymptomatic adults: the National Lung Screening Trial (n = 25,031) and the Framingham Heart Study (n = 2,581). In both cohorts, thymic health varied markedly across the population. In the National Lung Screening Trial, higher thymic health was consistently associated with lower all-cause mortality, reduced lung cancer incidence and lower cardiovascular mortality over 12 years of follow-up after adjustment for age, sex, smoking and comorbidities. In the independent Framingham Heart Study cohort, higher thymic health was significantly associated with reduced cardiovascular mortality, independent of age, sex and smoking. Thymic health was further linked to systemic inflammation and metabolic dysregulation, and associated with modifiable lifestyle factors including smoking, obesity and physical activity. Together, these findings reposition the thymus as a central regulator of immune-mediated ageing and disease susceptibility in adulthood, highlighting its potential as a target for preventive and regenerative strategies to promote healthy ageing and longevity.
ABSTRACT:Immunodeficiency-associated primary central nervous system lymphoma (ID-PCNSL) represents a clinicopathologically distinct PCNSL subtype, for which large studies and prognostic models are lacking. To address this gap, the International PCNSL Collaborative Group conducted a retrospective multicenter study, integrating clinical, radiological, and pathological data from 308 ID-PCNSL cases, diagnosed at 23 participating sites in 7 countries. Preexisting immunodeficiency included administration of immunosuppressants for transplantation (41.2%) or autoimmunity (36.7%) and HIV infection (21.7%). All tumors were diffuse large B-cell lymphomas, with Epstein-Barr virus (EBV) detected in 79.2%. Immune reconstitution together with rituximab and methotrexate-based chemotherapy was associated with the highest response rates and prolonged progression-free survival, irrespective of immunodeficiency subtype and EBV status. Survival outcomes were highly variable, with a 54-month median overall survival. Multivariable Cox regression identified age (per year increment; hazard ratio [HR], 1.05 (95% confidence interval [CI], 1.02-1.07); P< .001), Karnofsky performance status (KPS) <70 (HR, 3.10; 95% CI, 1.67-5.87; P< .001), and EBV positivity (HR, 3.26; 95% CI, 1.47-7.33; P = .004) as prognostic factors for overall survival. A prognostic score was developed based on the sum of these adverse variables (age >60 years, KPS <70, EBV positivity). Stratification by this score yielded median survival times of 135, 29, and 3 months in patients with up to 1, 2, and 3 unfavorable markers (P< .0001). It allowed improved prognostic stratification of ID-PCNSL as compared with the Memorial Sloan Kettering Cancer Center and International Extranodal Lymphoma Study Group models developed for immunocompetent PCNSL. Collectively, this large international cohort defines clinicobiological features of ID-PCNSL and introduces a prognostic system with potential to guide future management.
Radiotherapy (RT) is essential in pediatric cancer treatment and often requires complete immobility. In younger or noncompliant children, this is typically achieved through sedation or general anesthesia (GA), which raises concerns about acute complications and potential long-term neurodevelopmental effects. Despite widespread use, standardized anesthesia protocols for pediatric RT are lacking. To support the development of practice recommendations, the SIOPE Working Group on Pediatric Anesthesia in Radiation Therapy conducted a systematic literature review. Studies from Medline and Embase were reviewed (March-September 2024) according to PRISMA guidelines, focusing on sedation and GA in pediatric RT. Thirty-nine studies were included, mostly retrospective and of low to moderate quality. Considerable heterogeneity was observed in anesthetic techniques, staffing, and monitoring. Propofol-based sedation was most frequently reported, with favorable safety when delivered by experienced pediatric anesthetists. Complication rates varied widely and were often poorly defined. Additional concerns included long-term neurocognitive impact, vascular access, and procedural burden, especially in resource-limited settings. Evidence supports the safe use of sedation/GA in pediatric RT, but current literature is limited and inconsistent. Standardized protocols and prospective studies are urgently needed to better define safety, long-term outcomes, and staffing requirements.
