NHS Grampian

A patient in his 20s presented with a change in the appearance of his left eye with evidence of relative afferent pupillary defect. Imaging revealed a giant frontoethmoidal osteoma, a benign sinonasal tumour, invading three-quarters of the orbit. Multidisciplinary discussion involving opthalmology, maxillofacial surgery, neurosurgery and otolaryngology resulted in the decision to attempt entirely endoscopic excision of this lesion, which was performed with successful outcomes. This case demonstrates how a sinonasal osteoma should be considered in the differential diagnosis for a patient presenting with proptosis or other eye signs suggestive of compression of the orbital compartment. This case report and literature review highlights the possibility of managing giant sinonasal osteomas with orbital extension through a completely endoscopic approach.

There has been an assumption in the literature that the three concepts of ideal body shape (personal ideal, cultural ideal, and the most attractive body shape) are effectively the same percept. To test this presumption, 554 participants completed either a between- or within-subjects condition using a matrix of 32 bodies varying in two dimensions: muscle and adiposity. Three separate groups of participants were recruited to the between-subjects design and made only one of these judgements, whilst participants in the within-subjects version completed all three of these judgments. These bodies are based on 3D scans of 221 women’s bodies and so accurately represent the change in size and shape caused by changing body composition. The participants also completed a set of psychometric questionnaires to index the degree to which external concepts of body image have been internalised. The results show that in both conditions, all three judgements collapse onto the same average preferred body shape, with low adiposity and relatively high muscularity. However, this masked systematic differences in responses between personal ideals and the other body judgements, which may be explained by a difference in how information directly related to oneself is processed relative to more abstract third person judgements.

UNC93B1 is a transmembrane domain protein mediating the signaling of endosomal Toll-like receptors (TLRs). We report five families harboring rare missense substitutions (I317M, G325C, L330R, R466S, and R525P) in UNC93B1 causing systemic lupus erythematosus (SLE) or chilblain lupus (CBL) as either autosomal dominant or autosomal recessive traits. As for a D34A mutation causing murine lupus, we recorded a gain of TLR7 and, to a lesser extent, TLR8 activity with the I317M (in vitro) and G325C (in vitro and ex vivo) variants in the context of SLE. Contrastingly, in three families segregating CBL, the L330R, R466S, and R525P variants were isomorphic with respect to TLR7 activity in vitro and, for R525P, ex vivo. Rather, these variants demonstrated a gain of TLR8 activity. We observed enhanced interaction of the G325C, L330R, and R466S variants with TLR8, but not the R525P substitution, indicating different disease mechanisms. Overall, these observations suggest that UNC93B1 mutations cause monogenic SLE or CBL due to differentially enhanced TLR7 and TLR8 signaling.

Background The ketogenic diet (KD) is a high fat, moderate protein and very low carbohydrate diet. It can be used as a medical treatment for drug‐resistant epilepsy (DRE), glucose transporter 1 deficiency syndrome and pyruvate dehydrogenase deficiency. The aim of this scoping review was to map the KD literature, with a focus on epilepsy and associated metabolic conditions, to summarise the current evidence‐base and identify any gaps. Methods This review was conducted using JBI scoping review methodological guidance and the PRISMA extension for scoping reviews reporting guidance. A comprehensive literature search was conducted in September 2021 and updated in February 2024 using MEDLINE, CINAHL, AMED, EmBASE, CAB Abstracts, Scopus and Food Science Source databases. Results The initial search yielded 2721 studies and ultimately, data were extracted from 320 studies that fulfilled inclusion criteria for the review. There were five qualitative studies, and the remainder were quantitative, including 23 randomised controlled trials (RCTs) and seven quasi‐experimental studies. The USA published the highest number of KD studies followed by China, South Korea and the UK. Most studies focused on the classical KD and DRE. The studies key findings suggest that the KD is efficacious, safe and tolerable. Conclusions There are opportunities available to expand the scope of future KD research, particularly to conduct high‐quality RCTs and further qualitative research focused on the child's needs and family support to improve the effectiveness of KDs.

This retrospective population-based analysis assessed variations in urgent healthcare use by children and young people (CYP) across UK nations (England, Scotland and Wales) between 2007 and 2017. The study focused on urgent hospital admissions, short stay urgent admissions (SSUA) and Emergency Department (ED) attendances among CYP aged <25 years, stratified by age groups and Index of Multiple Deprivation (IMD) quintile groups. A linear mixed model was used to assess trends in healthcare activity over time and across deprivation quintiles. Urgent admissions, SSUA and ED attendances increased across all deprivation quintiles in all studied nations. Increasing deprivation was consistently associated with higher urgent healthcare utilisation. In England, the rise in urgent admissions and SSUA for CYP was slower for CYP from the quintile of greatest deprivation compared those from the least deprived quintile (respective mean differences 0.69/1000/y [95% CI 0.53, 0.85] and 0.25/1000/y [0.07, 0.42]), leading to a narrowing in health inequality. Conversely, in Scotland, urgent admissions and SSUA increased more rapidly for CYP from all deprivation quintiles, widening health inequality. Understanding the differences we describe here could inform changes to NHS pathways of care across the UK which slow the rise in urgent healthcare use for CYP.

Objective To estimate the cost of paediatric asthma from a UK National Health Service (NHS) and societal perspective and explore determinants of these costs. Design Cost analysis based on data from a large clinical trial between 2017 and 2019. Case report forms recorded healthcare resource use and productivity losses attributable to asthma over a 12-month period. These were combined with national unit cost data to generate estimates of health service and indirect costs. Setting Asthma clinics in primary and secondary care in England and Scotland. Main outcome measures Cost per asthma attack stratified by highest level of care received. Total annual health service and indirect costs. Modelled effect of sex, age, severity, number of attacks and adherence on total annual costs. Results Of 506 children included in the analysis, 252 experienced at least one attack. The mean (SD) cost per attack was £297 (806) (median £46, IQR 40–138) and the mean total annual cost to the NHS was £1086 (2504) (median £462, IQR 296–731). On average, children missed 6 days of school and their carers missed 13 hours of paid work, contributing to a mean annual indirect cost of £412 (879) (median £30, IQR 0–477). Health service costs increased significantly with number of attacks and participant age (>11 years). Indirect costs increased with asthma severity and number of attacks but were found to be lower in older children. Conclusions Paediatric asthma imparts a significant economic burden on the health service, families and society. Efforts to improve asthma control may generate significant cost savings. Trial registration number ISRCTN 67875351.

Introduction Distractions in operating theatres prevent team members from concentrating on the complex tasks required for a successful operation. This can be a potential hazard to care for, and previously, correlations have been made between increased theatre distractions and adverse events. However, it remains unclear how frequently such events occur during routine care in theatres. The present study aims to quantify distractions and analyse any differences between staff groups, operative stages, and modes of operation. Methods A single-centre prospective study was conducted to assess disruptions in general surgical theatres. Events were recorded using a previously described categorization system on a proforma by a single researcher. The source and severity of distraction were recorded, as well as the mode of operation (elective/emergency), stage of operation, and staff team (scrubbed/floor). Results A total of 4,219 minutes of surgery were observed over four weeks, and 1,095 distraction events were recorded. Of the 14 elective and nine emergency procedures recorded, there was a mean of 54.8 distractions per procedure and a frequency of one distraction every three minutes and 51 seconds (15.6 hr⁻¹). Irrelevant communication relating to the patient's case was the most common source, accounting for 24.7% of all distractions. The most frequently disrupted stage of the procedure for scrubbed staff was during anastomosis/resection for both elective and emergency procedures, with 16.9 and 32.6 distractions occurring per hour, respectively. Scrubbed staff were significantly more susceptible to distraction in emergency procedures than the floor staff. Discussion Our study reflects previous assessments with irrelevant communications and emergency procedures yielding the highest prevalence of distraction. This investigation provides novel information about the different stages of general surgery and the frequency of distractions that occur.

Objectives: To evaluate the clinical effectiveness of long acting progestogens compared with the combined oral contraceptive pill in preventing recurrence of endometriosis related pain. Design: The PRE-EMPT (preventing recurrence of endometriosis) pragmatic, parallel group, open label, randomised controlled trial. Setting: 34 UK hospitals. Participants: 405 women of reproductive age undergoing conservative surgery for endometriosis. Interventions: Participants were randomised in a 1:1 ratio using a secure internet facility to a long acting progestogen (depot medroxyprogesterone acetate or levonorgestrel releasing intrauterine system) or the combined oral contraceptive pill. Main outcome measures: The primary outcome was pain measured three years after randomisation using the pain domain of the Endometriosis Health Profile 30 (EHP-30) questionnaire. Secondary outcomes (evaluated at six months, one, two, and three years) included the four core and six modular domains of the EHP-30, and treatment failure (further therapeutic surgery or second line medical treatment). Results: 405 women were randomised to receive a long acting progestogen (n=205) or combined oral contraceptive pill (n=200). At three years, there was no difference in pain scores between the groups (adjusted mean difference -0.8, 95% confidence interval -5.7 to 4.2, P=0.76), which had improved by around 40% in both groups compared with preoperative values (an average of 24 and 23 points for long acting progestogen and combined oral contraceptive pill groups, respectively). Most of the other domains of the EHP-30 also showed improvement at all time points compared with preoperative scores, without evidence of any differences between groups. Women randomised to a long acting progestogen underwent fewer surgical procedures or second line treatments compared with those randomised to the combined oral contraceptive pill group (73 v 97; hazard ratio 0.67, 95% confidence interval 0.44 to 1.00). Conclusions: Postoperative prescription of a long acting progestogen or the combined oral contraceptive pill results in similar levels of improvement in endometriosis related pain at three years, with both groups showing around a 40% improvement compared with preoperative levels. While women can be reassured that both options are effective, the reduced risk of repeat surgery for endometriosis and hysterectomy might make long acting reversible progestogens preferable for some. Trial registration: ISRCTN registry ISRCTN97865475.

Background Non-toxic approaches to enhance radiotherapy outcomes are beneficial, particularly in ageing populations. Based on preclinical findings showing that high-fibre diets sensitised bladder tumours to irradiation by modifying the gut microbiota, along with clinical evidence of prebiotics enhancing anti-cancer immunity, we hypothesised that dietary fibre and its gut microbiota modification can radiosensitise tumours via secretion of metabolites and/or immunomodulation. We investigated the efficacy of high-fibre diets combined with irradiation in immunoproficient C57BL/6 mice bearing bladder cancer flank allografts. Result Psyllium plus inulin significantly decreased tumour size and delayed tumour growth following irradiation compared to 0.2% cellulose and raised intratumoural CD8⁺ cells. Post-irradiation, tumour control positively correlated with Lachnospiraceae family abundance. Psyllium plus resistant starch radiosensitised the tumours, positively correlating with Bacteroides genus abundance and increased caecal isoferulic acid levels, associated with a favourable response in terms of tumour control. Psyllium plus inulin mitigated the acute radiation injury caused by 14 Gy. Psyllium plus inulin increased caecal acetate, butyrate and propionate levels, and psyllium alone and psyllium plus resistant starch increased acetate levels. Human gut microbiota profiles at the phylum level were generally more like mouse 0.2% cellulose profiles than high fibre profiles. Conclusion These supplements may be useful in combination with radiotherapy in patients with pelvic malignancy. C3P3Z-i-BEWcsPG8U_9P4fVideo Abstract

The 11th revision of the International Classification of Diseases and Related Health Problems (ICD-11) aims at improving the lives of persons with the lived experience of chronic pain by providing clearly defined and clinically useful diagnoses that can reduce stigma, facilitate communication, and improve access to pain management, among others. The aim of this study was to assess the perspective of people with chronic pain on these diagnoses. An international web-based survey was distributed among persons with the lived experience of chronic pain. After having seen an information video, participants rated the diagnoses on 8 endorsement scales (eg, diagnostic fit, stigma) that ranged from −5 to +5 with 0 representing the neutral point of no expected change. Overall ratings and differences between participants with chronic primary pain (CPP) and chronic secondary pain (CSP) were analyzed. N = 690 participants were included in the data analysis. The ratings on all endorsement scales were significantly higher than the neutral point of 0. The highest ratings were obtained for “openness” (2.95 ± 1.93) and “overall opinion” (1.87 ± 1.98). Participants with CPP and CSP did not differ in their ratings; however, those with CSP indicated an improved diagnostic fit of the new diagnoses, whereas participants with CPP rated the diagnostic fit of the new diagnoses similar to the fit of their current diagnoses. These results show that persons with the lived experience of chronic pain accept and endorse the new diagnoses. This endorsement is an important indicator of the diagnoses' clinical utility and can contribute to implementation and advocacy.

Chondrosarcoma is the second most common surgically treated primary bone sarcoma. Despite a large number of scientific papers in the literature, there is still significant controversy about diagnostics, treatment of the primary tumour, subtypes, and complications. Therefore, consensus on its day-to-day treatment decisions is needed. In January 2024, the Birmingham Orthopaedic Oncology Meeting (BOOM) attempted to gain global consensus from 300 delegates from over 50 countries. The meeting focused on these critical areas and aimed to generate consensus statements based on evidence amalgamation and expert opinion from diverse geographical regions. In parallel, periprosthetic joint infection (PJI) in oncological reconstructions poses unique challenges due to factors such as adjuvant treatments, large exposures, and the complexity of surgery. The meeting debated two-stage revisions, antibiotic prophylaxis, managing acute PJI in patients undergoing chemotherapy, and defining the best strategies for wound management and allograft reconstruction. The objectives of the meeting extended beyond resolving immediate controversies. It sought to foster global collaboration among specialists attending the meeting, and to encourage future research projects to address unsolved dilemmas. By highlighting areas of disagreement and promoting collaborative research endeavours, this initiative aims to enhance treatment standards and potentially improve outcomes for patients globally. This paper sets out some of the controversies and questions that were debated in the meeting. Cite this article: Bone Joint J 2024;106-B(5):425–429.

Background An improved understanding of which gastroesophageal adenocarcinoma (GOA) patients respond to both chemotherapy and immune checkpoint inhibitors (ICI) is needed. We investigated the predictive role and underlying biology of a 44-gene DNA damage immune response (DDIR) signature in patients with advanced GOA. Materials and methods Transcriptional profiling was carried out on pretreatment tissue from 252 GOA patients treated with platinum-based chemotherapy (three dose levels) within the randomized phase III GO2 trial. Cross-validation was carried out in two independent GOA cohorts with transcriptional profiling, immune cell immunohistochemistry and epidermal growth factor receptor (EGFR) fluorescent in situ hybridization (FISH) (n = 430). Results In the GO2 trial, DDIR-positive tumours had a greater radiological response (51.7% versus 28.5%, P = 0.022) and improved overall survival in a dose-dependent manner (P = 0.028). DDIR positivity was associated with a pretreatment inflamed tumour microenvironment (TME) and increased expression of biomarkers associated with ICI response such as CD274 (programmed death-ligand 1, PD-L1) and a microsatellite instability RNA signature. Consensus pathway analysis identified EGFR as a potential key determinant of the DDIR signature. EGFR amplification was associated with DDIR negativity and an immune cold TME. Conclusions Our results indicate the importance of the GOA TME in chemotherapy response, its relationship to DNA damage repair and EGFR as a targetable driver of an immune cold TME. Chemotherapy-sensitive inflamed GOAs could benefit from ICI delivered in combination with standard chemotherapy. Combining EGFR inhibitors and ICIs warrants further investigation in patients with EGFR-amplified tumours.