West Middlesex University Hospital

The detection of monogenic diabetes illustrates the potential of precision medicine, with treatments tailored to specific genes and diagnosis involving targeted genetic testing. Current detection criteria are derived from White populations. We investigated detection of monogenic diabetes in an unselected multiethnic cohort comprising 1,706 participants diagnosed with diabetes before the age of 30-years. Using broad biomarker criteria (triple pancreatic antibody negative and detectable C-peptide) to select for next generation sequencing of monogenic diabetes genes, we found a non-significantly different minimum cohort prevalence of monogenic diabetes of 2.1% in White, 2.0% in South Asian, 2.5% in African-Caribbean, and 3.6% in Mixed participants. The detection rate, however, varied significantly (17.7% in White, 5.3% in South Asian, 8.0% in African-Caribbean, and 15.2% in Mixed participants, p<0.001). Those without monogenic diabetes showed significant variations in BMI. No difference in phenotype of monogenic diabetes across ancestry groups was observed. Non-white ethnicity participants were significantly more likely to have undiagnosed monogenic diabetes than White with on average a 10-year duration before receiving a correct diagnosis. By applying ancestry-specific BMI cut-offs (White <30, South Asian <27, African-Caribbean and Mixed <35 kg/m2), the overall detection rate increased from 8.8 to 16%, reducing the number needed to test to identify one case from 11 to 6 and boosting detection rates to 39, 11, 9 and 26% in White, South Asian, African-Caribbean and Mixed-ethnicity participants, respectively. These findings were validated in an external real-world dataset. Applying broad biomarker criteria for initial selection, mitigates clinical biases leading to misclassification of monogenic diabetes in non-White ethnicities. However, further tailoring criteria with ethnic-specific BMI cut-offs doubled detection rates, improving cost-effectiveness by minimising unnecessary testing. Our study highlights the need to develop precision medicine approaches accounting for phenotypic variation across diverse populations, to ensure accurate diagnoses and cost-efficient healthcare provision.

Securing the appendiceal stump is a critical step in laparoscopic appendicectomy, the gold-standard treatment for managing acute appendicitis. Endoloops are widely used in appendiceal stump ligation owing to their simplicity and cost-effectiveness, but practice varies between surgeons in the use of one or two loops. This study aimed to compare outcomes between single and double endoloop closure and to explore surgeon perspectives. A mixed methods approach was used to compare the use of one or two endoloops. A retrospective cohort analysis included patients undergoing laparoscopic appendicectomy in a UK district general hospital between August 2023 and January 2025, comparing post-operative complications and operating time between single and double endoloop ligation. Overall complications were defined as any complications within the 30-day post-operative period while clinically relevant complications referred to intra-abdominal abscess, stump leak, or stump appendicitis. A focus group of operating surgeons was analysed thematically to explore decision-making factors. Among 191 patients included, 50 (26%) received a single endoloop and 141 (74%) received two. No statistically significant difference in clinically relevant 30-day complications was observed (12% vs. 9.9%; p = 0.07) with overlapping confidence intervals for all complication outcomes. Operative time was shorter in the single-endoloop group (84 ± 41.5 vs. 108.5 ± 31.9 min; p = 0.004). Thematic analysis identified three key influences on endoloop choice: perceived security through tradition, assessment of appendiceal base integrity, and training considerations. No statistically significant difference in clinically relevant post-operative complications was observed between single and double endoloop closure, although the study may be underpowered to detect rare events. Single endoloop closure was associated with a shorter operative time, which may be partly confounded by disease severity. Surgical decision-making remains influenced by training culture and tradition rather than evidence-based practice, and full standardisation is challenging given variability in case complexity and surgeon expertise.

Abstract Background Advanced therapies are crucial in Ulcerative Colitis(UC). Anti-TNFa agents recommended as first-line therapy1 are switched to second-line when patients lose response or develop adverse effects. In practice, vedolizumab2, JAK inhibitors(JAKi)3, and IL-12/23 inhibitors are used sequentially4, with IL-12/23 or JAKi often reserved for third-line therapy4. However, no comparative data exist for outcomes of third line agents. Methods We conducted a retrospective, international, multi-centre study that compared anti-IL12/23 and JAKi as third line therapy in UC patients with prior anti-TNFa and vedolizumab failure, between 01/2022 and 09/2025. The primary outcome was clinical response at week 12 defined as a decrease of SCCAI or pMayo score ≥3 points from baseline. The secondary outcomes were: clinical remission(SCCAI score≤2 or pMayo≤2), biochemical remission(faecal calprotectin<150 ug/g and CRP< 5mg/L) and endoscopic remission(UCEIS = 0 or Mayo = 0) at week 12, 24, 52. Treatment persistence and adverse events up to week 52 were documented. Statistical analyses were conducted using SPSS. This study received ethics approval. Results We recruited 178 participants from 8 tertiary centres. Patients were treated with mirikizumab, ustekinumab, upadacitinib, filgotinib and tofacitinib. The median age was 41.5 years(IQR 26), with a median disease duration of 8 years(IQR 8) and 46.6% were female. 58 patients received anti-IL12/23 and 120 received JAKi. Clinical response at week 12 was 56.3% in anti-IL12/23 versus 78.7% in JAKi(p = 0.005). Clinical remission at week 12 was 61.2% in anti-IL12/23 versus 75% in JAKi(p = 0.086). Biochemical remission was 50% and 61.8% in anti-IL12/23 and JAKi respectively(p = 0.43). Endoscopic remission was 40% in anti-IL12/23 versus 33.3% in JAKi (p = 0.61)(Figure 1). In the subgroup analysis (Figure 2), clinical remission at week 12 was higher for upadacitinib(81%) compared to filgotinib(64.3%) and tofacitinib (72.5%,p = 0.41), while among anti-IL12/23, ustekinumab presented higher clinical remission rates (67.5%), versus mirikizumab (33.3%,p = 0.57). Biochemical remission was similar among upadacitinib, filgotinib and tofacitinib (61.5%, 33.3% and 73.3% respectively, p = 0.23), and among anti-IL12/23 (20% with mirikizumab versus 63.6% with ustekinumab, p = 0.1). Treatment persistence at week 52 was 68.8% for ustekinumab, 76.3% for upadacitinib, 64.7% for filgotinib, 66.7% for tofacitinib. In the anti-IL12/23 cohort, 1 patient developed infectious endocarditis, while 2 cases of lymphoma and basal cell carcinoma were reported among JAKi. Conclusion JAKi demonstrated superior clinical response rates at week 12 as third line therapy versus anti-IL12/23, with upadacitinib achieving higher, but not statistically significant, remission rates.

Abstract Disclosure: E. Ssemmondo: None. Background: Multiple daily doses of hydrocortisone are traditionally used as glucocorticoid replacement in patients with adrenal insufficiency. The Endocrine Society guideline suggests 3-5mg of prednisolone as an alternative. Prednisone is a pro drug that is converted to prednisolone by first pass metabolism in the liver. We compared the metabolic profile of patients taking multiple doses of hydrocortisone before and after switching to a single daily dose of prednisolone 2-5mg. Methods: Patients with adrenal insufficiency were switched from multiple-daily dose hydrocortisone to once-daily low-dose prednisolone and followed up after 4 months. We assessed cardiovascular risk using weight, blood pressure, waist and hip circumference, lipid profile and C-reactive protein. Quality of life was assessed using a modified SF-36 questionnaire. Baseline and follow-up data were compared using a paired t-test. Results: Sixty-two participants were enrolled, of whom 48 completed the study. Eight (16.8%) had a diagnosis of primary adrenal insufficiency. The mean duration of glucocorticoid use was 11.4±8.6 years. After at least four months of prednisolone, we observed significant reductions in weight from 90.6 kg to 89.6 kg (p=0.007) and in systolic blood pressure (BP) of up to 6 mmHg (p=0.027). There was no difference in the waist to hip ratios between the two treatments (p=0.183). The use of prednisolone was associated with no change in total, LDL, HDL, or non-HDL cholesterol, triglycerides or CRP. Use of single-daily low-dose prednisolone demonstrated an increase in subjective energy and total quality of life scores (p=0.003 and p=0.019 respectively). Patients reported prednisolone to be more convenient compared to hydrocortisone (p=0.002). Conclusion: Single dose daily low-dose prednisolone is a safe and convenient alternative with a similar cardiovascular risk profile to multiple-daily dose hydrocortisone in patients with adrenal insufficiency. Additional improvements in weight, systolic blood pressure and subjective health scores offers advantages over hydrocortisone and would support larger prospective studies evaluating long-term health outcomes. Presentation: Sunday, July 13, 2025

Haemophagocytic lymphohistiocytosis (HLH) is a hyperinflammatory sepsis-like syndrome that accounts for 1% of maternal deaths in the United Kingdom (UK). In 2019, a UK-wide HLH network was developed to provide specialist advice for patients with HLH. Until September 2024, eight individuals had been referred to this service with HLH onset during pregnancy or within 6 months postpartum, and this article summarises their management. Shared themes were of postpartum predominance, with onset typically within a month of delivery, preceding infection, and underlying immune dysfunction. Common therapies included corticosteroids and the interleukin-1 receptor antagonist, anakinra. Most individuals required level 3 care, three were considered for extracorporeal membrane oxygenation, and one died. HLH should be included in the differential of maternal sepsis, given all cases presented with fever and organ dysfunction, particularly if there is ongoing deterioration despite antimicrobial therapy and/or without an identified source.

Abstract Our study highlights cognitive measures underlying post-stroke recovery using the ‘Birmingham Cognitive Screening’ (BCOS) program—the only dataset with comprehensive assessments of cognition, praxis, and stroke outcomes. We analysed 256 stroke patients tested for cognitive deficits, which uniquely included apraxia and the Barthel Index for daily living activities at subacute and chronic stages. Using step-wise multivariate linear regression, we identified significant predictive factors—praxis, language, orientation, and baseline independence—linked to improved daily activities, and validated our model with 4-fold cross-validation. This research underscores the vital role of specific cognitive measures including apraxia as key cognitive predictors for stroke recovery.

Abstract Background Vedolizumab is a gut-selective monoclonal antibody that is well-recognised for managing moderate and severe Crohn’s disease (CD) and Ulcerative Colitis (UC) [1]. Subcutaneous (SC) vedolizumab has been shown to be an effective and well-tolerated alternative to the intravenous (IV) form [2,3]. However, there remains a lack of data on real-world outcomes. This study evaluates the effectiveness and safety outcomes of switching from IV to SC vedolizumab in CD and UC. Methods We collected retrospective data from the electronic patient records at West Middlesex Hospital for all adults currently receiving vedolizumab for CD and UC between December 2017 and September 2024. This included patients’ demographics, disease epidemiology, current and previous biologic treatment, vedolizumab serum concentrations, and faecal calprotectin (FCP) levels. The primary endpoints were FCP and serum vedolizumab levels pre- and post-switch. The secondary endpoints were the development of adverse events and the need for rescue therapy post-switch. Results We included 105 patients with a median age of 59. Of these, 54.28% are males (n=57). 43 patients (40.95%) were switched to maintenance SC. Most patients were on the standard 8-weekly dosing regimen of intravenous vedolizumab pre-switch (88.37%, n=38), while the rest (n=5, 11.62%) were on an escalated 4-weekly regimen. More than half (n=23, 53.48%) of the patients were switched on a clinical basis, while the remainder (n=20, 46.51%) were switched due to patient preference. All the patients in the former group had low vedolizumab levels (< 15 mg/dl), and almost half (n=11) had associated active disease. In the low-level group switched to SC, UC constituted 52.17% (n=12) and CD was 47.82% (n=11). Ten patients (43.47%) had previously received anti-TNF-alpha. The median (IQR = Q3-Q1) pre-switch vedolizumab serum concentration level was 10 (5.5) mg/L, which almost tripled to 29.3 (15.6) mg/L after switching (12 to 52 weeks post-switch). The median faecal calprotectin (FCP) levels dropped from 357 (820) µg/g to 259 (493.5) µg/g post-switching to SC. The patients who remained on IV had a median vedolizumab level of 14.6 (11) mg/L and FCP of 263.5 (653.5) µg/g. None of the patients who were switched because of low levels sustained adverse effects compared to 5 patients (8.06%) in the IV group (mucocutaneous (n=2), joint (n=1) and fatigue (n=1) symptoms). Over the one-year follow-up period, one patient (4.34%) required rescue steroid therapy, compared to three (4.83%) in the IV group. Conclusion Implementing proactive subcutaneous switching of vedolizumab in a real-world setting correlates with higher levels confers improved clinical response, and has a good safety profile, reflecting clinical trial results.

Abstract Background Emergency bowel surgery presents an elevated risk of anastomotic leaks, attributed to factors such as comorbidities, sepsis, and inadequate pre-operative optimization. This heightened risk often results in a greater likelihood of stoma formation, which can lead to significant patient distress. This study aimed to assess the efficacy of Indocyanine Green (ICG) as a predictor for bowel resection and stoma requirement in emergency general surgery. Methods A systematic search was conducted on Embase and PubMed using the keywords: ICG, emergency, surgery, bowel, ischemia, and perfusion. Out of 266 articles identified, 32 original studies were included for analysis. Results A total of 308 individual cases were evaluated. Intra-operative visual findings were consistent with ICG perfusion results in 61% of cases (n=188). Two cases did not report ICG-intra-operative finding compatibility. In instances of discrepancy, ICG assessment led to altered surgical decisions in 47% (n=89) cases. Seven patients required further resection due to ongoing ischemia; notably, bowel resection was avoided in three patients despite ICG indicating poor perfusion. ICG predicted the bowel perfusion/viability in 302 cases, contributing to avoiding unnecessary resections in 21.7% (n=67) cases. Conclusion Our study showed that ICG can reliably indicate adequate bowel perfusion and therefore viability in 98% of emergency general surgery cases. ICG is a valuable predictor for the need for stoma formation in emergency surgical contexts. To explain the discrepancy between this result and reality, human decision-making bias is worth exploring.

Abstract Background In the early 2000s, the shift to laparoscopic surgery led to a significant decrease in appendicectomies performed by Core Surgical Trainees/Junior Clinical Fellows (CST/JCFs). Previously, CST/JCFs conducted 33% of open appendicectomies; however, this dropped to 8.7% by 2002. Alarmingly, by 2006, a district hospital reported that no CST/JCFs had conducted laparoscopic appendicectomies. This trend raises serious concerns regarding the diminishing opportunities for CST/JCFs to acquire essential experience in this critical surgical procedure. The current study assesses the training opportunities for CST/JCFs in minimally invasive surgery. Methods Emergency laparoscopic appendicectomy (ELA) in one University Hospital from September 2022 to August 2024 were identified retrospectively. Grade of the operating surgeon was categorized into Consultant, Registrar, or CST/JCF. Results Out of 574 identified ELAs, 572 were included after excluding two given missing digital notes. Documentation of the surgeon's level was ambiguous in 41 cases. The analysis revealed Consultants performed 52% (n=298) while CST/JCFs conducted only 11% (n=65). Among 126 paediatric cases, Consultants performed 64% (n=85), while CST/JCFs accounted for 10% (n=13). Conclusion The opportunity for CST/JCF to perform appendicectomy has significantly declined, affecting recruitment into higher surgical training programs that now mandate documented appendicectomy experience. Studies have shown no significant morbidity or mortality rates differences between appendicectomy performed by consultant/registrars and CST/JCF. CST/JCF involvement is crucial in fostering their competency in essential surgical skills and further national evaluation is required to assess quality of CST/JCF training.