Tunbridge Wells Hospital

Prostate-specific membrane antigen (PSMA) is upregulated in prostate cancer cells relative to other cells. The increased expression and enzymatic activity of PSMA in high-stage disease confers a selective advantage on such cells, contributing to their increased proliferation, the tendency to metastasize and the development of a castration-resistant phenotype. The decades of radiobiochemical advances in the development of PSMA targeting radiolabelled ligands has led to the subsequent FDA approval of a number of radiotracers and radiotherapeutics for clinical use. Novel developments in therapeutic advances using PSMA-based combinatorial approaches include PSMA-targeted antibody-drug conjugates and PSMA-targeted radionuclide payloads. Combining and sequencing some of these strategies with standard therapy options such as surgery, radiotherapy and androgen receptor pathway inhibitors could improve patient outcomes. Immunotherapy and chimeric antigen receptorT cell therapy are relevant to PSMA-based therapies as PSMA can serve as a specific target antigen for these treatments, enabling precise tumour recognition and enhanced efficacy of prostate cancer therapies.

HAVING just read Aneesa Malik's recent In Practice clinical article on dealing with wild pigeons in practice,1 I was disappointed to see that the most pain free and simple method of euthanasia was not mentioned. We have used the intracloacal route for many years now and found it to be remarkably stress free and humane. For this method, 2 ml of pentobarbitone seems to work very well for every pigeon, and I have found it far simpler than the complicated methods listed in the article. A quick literature review seems to support this method.

Metabolic bariatric surgery (MBS) is an effective treatment for paediatric obesity, yet the mechanisms underlying weight loss remain unclear. This systematic review and meta-analysis evaluated the short- and long-term effects of MBS on the paediatric metabolome to provide insights into metabolic pathways contributing to surgical outcomes. This prospectively registered systematic review (PROSPERO ID: CRD42024607784) adhered to PRISMA guidelines. Meta-analysis was undertaken on pre-defined post-operative weight and metabolic parameters in paediatric patients (aged 5- 19 years) following MBS. Outcomes were reported as weighted or standardised mean Difference with 95 percent confidence intervals from random effects modelling. Quality scoring and quantitative assessment of bias were performed. Results from 12 studies (451 patients, mean age 16.9 years) across five countries were included. The median follow-up was 12 months. Patients underwent Roux-en-Y gastric bypass (RYGB, n = 275) or laparoscopic sleeve gastrectomy (LSG, n = 140). Most studies used serum and urine assays; two included tissue biosamples. MBS was associated with significant long-term weight reduction, with a mean BMI decrease of -14.4 kg/m2 (95% CI: -17.5 to -11.3) and %TWL of 25% (95% CI: 18.6 to 32.2). Metabolic improvements included reduced cholesterol (-10 mg/dL), LDL (-14.6 mg/dL), triglycerides (-33.3 mg/dL), and increased HDL (+ 8.0 mg/dL). Significant enhancements were noted in glycaemic, pancreatic and insulin regulation, evidenced by decreased HOMA-IR (-4.1) and C-peptide (-1.8 ng/mL). Liver function parameters, ALT (-14.4 U/L), AST (-5.4 U/L), and GGT (-9.6 U/L) and inflammatory cytokines, IL-6 (-12.2 pg/mL) and TNF-α (-54 pg/mL) significantly declined following surgery. These findings demonstrate a distinct metabolic signature of MBS in adolescents, leading to substantial weight loss and improvements in cardiovascular, glycaemic, and liver health, alongside reduced systemic inflammation. These results underscore the efficacy of MBS as a therapeutic intervention for adolescents living with severe obesity, demonstrating a profound impact on the paediatric metabolome.Supplementary InformationThe online version contains supplementary material available at 10.1038/s41598-025-20078-7.

<h3></h3> SAPHO (Synovitis Acne Pustulosis Hyperostosis and Osteitis) syndrome is a rare autoinflammatory condition characterized by bone inflammation (aseptic osteitis) and skin manifestations, such as palmoplantar pustulosis, acne, and pustular psoriasis.¹ Due to its often subtle and variable presentation, SAPHO syndrome is frequently misdiagnosed, especially in patients with comorbid inflammatory bowel disease (IBD).² Since 1992, cases of SAPHO syndrome associated with IBD have been reported, though only a few paediatric cases have been documented.^{2 3} Here, we present a unique case of SAPHO syndrome developing in an adolescent with Crohn’s disease, highlighting the diagnostic and therapeutic challenges associated with overlapping autoimmune diseases. An 8-year-old girl was seen in the paediatric Gastroenterology clinic with symptoms of chronic diarrhoea, angular stomatitis. Her Faecal calprotectin was &gt;1800. Endoscopy and histology revealed multifocal Crohn’s disease-Stomach, Duodenum, ileum and Colon (Paris Classification A1b, L3 + L4a, B1, G0) After diagnosis, the patient achieved remission with Modulen and corticosteroids. However, maintenance therapy with azathioprine proved ineffective in maintaining clinical remission and Infliximab was initiated. Due to ongoing symptoms her IFX dose was increased to 10 mg/kg every 8 weeks, and azathioprine was discontinued. She maintained sustained clinical and biochemical remission after optimising the IFX therapy. At age 11, three years after her Crohn’s diagnosis, she developed psoriatic skin lesions, including palmar psoriasis and plaques on her knees, elbows, scalp, and legs. Dermatology initially suspected an anti-TNF-induced skin reaction; however, the diagnosis was revised to psoriasis, and topical therapy with steroid and emollients was started. Around the same period, she developed painful swelling at the medial end of the right clavicle, presenting with warmth, mild tenderness, and persistent erythema. Radiological studies revealed chronic recurrent multifocal osteomyelitis (CRMO) of the right sternoclavicular joint, fulfilling the Kahn criteria for a diagnosis of SAPHO syndrome.^{1 4} Due to her stable Crohn’s disease and the onset of SAPHO-related symptoms, infliximab was discontinued at age 12. However, as pain in her clavicles, knee, and elbow intensified, she received a Zolendronic acid infusion for symptom relief. With her Crohn’s disease in remission, she was switched to weekly subcutaneous methotrexate (15 mg/m²). Over the past two years, the patient has maintained a stable clinical course, with sustained clinical and biochemical remission of her Crohn’s disease and complete resolution of osteoarticular and dermatological manifestations. This case underscores the complexity of diagnosing and managing SAPHO syndrome in paediatric patients with Crohn’s disease. SAPHO syndrome can mimic anti-TNF skin reactions, adding diagnostic challenges in IBD patients.^{3 5} Methotrexate proved effective in managing SAPHO in this patient and may offer an effective alternative therapy allowing for sustained remission of both Crohn’s disease and SAPHO symptoms.³ Biologic swap could be considered to Adalimumab if Methotrexate alone does not provide adequate maintenance therapy for Crohn’s. Multidisciplinary collaboration and individualized therapy are essential in managing the intersecting pathways of autoinflammatory and autoimmune conditions in paediatric patients. <h3>References</h3> Chamot AM, Benhamou CL, Kahn MF, <i>et al</i>. Acne-pustulosis- hyperostosis-osteitis syndrome. Results of a national survey 85 cases. <i>Rev Rhum Mal Osteoartic</i>. 1987;<b>54</b>:187–196. Naves JE, Cabré E, Manosa M, Grados D, Olivé A, Domènech E. Asystematic review of SAPHO syndrome and inflammatory bowel disease association. <i>Dig Dis Sci</i>. 2013 Aug;<b>58</b>(8):2138–47. Marrani E, <i>et al</i>. SAPHO syndrome in pediatric patients with inflammatory bowel disease treated with infliximab. <i>Dig Liver Dis</i>. 2018. https://doi.org/10.1016/j.dld.2018.09.001 Kotilainen PM, Laxen FO, Manner IK, <i>et al</i>. An aseptic inflam- mation of the clavicle in a patient with Crohn’s disease. A potential manifestation of the SAPHO syndrome. <i>Scand J Rheumatol</i>. 1996;<b>25</b>:112–114. Rukavina I. SAPHO syndrome: a review. <i>J Child Orthop</i>. 2015 Feb;<b>9</b>(1):19–27.

Receiving a diagnosis of congenital anomalies in the first 1000 days of life can have significant implications for a family's emotional and mental wellbeing. We refer to this as different news. We evaluated a communications skills training to improve how healthcare professionals deliver different news using a train-the-trainer (Champions) model. We recruited 22 healthcare professionals from 6 NHS trusts in England and trained them as Champions. They delivered 17 training sessions to healthcare professional colleagues. Data were collected on knowledge, skills and attitudes to different news communication using a bespoke questionnaire and the Self-Efficacy Scale (SE-12) at pre-training, straight after training and four weeks post-training. We conducted 19 interviews with healthcare professionals, four managers and eight parents. Data were analysed using Framework analysis guided by the Theoretical Domains Framework. A total of 204 healthcare professionals completed pre-training questionnaires, 187 completed post-training questionnaires immediately after training, and 109 completed the questionnaires four weeks post-training. A total of 179 healthcare professionals completed the SE-12 scale immediately after training and 102 completed it at four weeks follow-up. The training improved healthcare professionals' confidence and skills to deliver different news. There were statistically significant differences in confidence levels between pre-/post-training SE-12 scores in delivering different news. Scores were significantly higher post-training. The estimated difference in mean scores post-training was 18.3 (95% confidence interval 15.7-20.9 p < 0.001), and one-month post-training 16.9 (95% confidence interval 13.7-20.2; p < 0.001) more than three times larger than the difference in SE-12 in the validation sample. There was a statistically significant difference between SE-12 scores for the Champions and the healthcare professionals they trained. SE-12 scores were higher for Champions and their improvement from pre-training was greater. Overall, participants reported that the training provided the skills to structure different news conversations, use the right language and pace the provision of information and support. The results suggest that the training equips healthcare professionals to deliver different news to families sensitively and compassionately which can potentially prevent mental ill-health across the life course.

This study aimed to explore the relationship between time below range (TBR), impaired awareness of hypoglycemia (IAH), and severe hypoglycemia (SH). This cross-sectional study analyzed data from individuals with diabetes using continuous glucose monitors (CGMs) in the Association of British Clinical Diabetologists audit. Hypoglycemia awareness was assessed via the Gold score (≥4 denoting IAH), and SH was defined as hypoglycemia requiring third-party assistance. Logistic regression was used to determine the association between TBR percentage (<70 mg/dL; 3.9 mmol/L) at first follow-up and follow-up Gold score and SH incidence. The Youden J index identified optimal TBR percentage cutoffs for detecting IAH and SH. The study included 15,777 participants, with follow-up TBR and SH data available for 5,029. The median TBR percentage was 4% (interquartile range 2-6.6%), with 42% meeting the recommended TBR of ≤4%. Adjusted for age, sex, and BMI, TBR was significantly associated with SH (P < 0.001) and IAH (P = 0.005). Optimal TBR cutoffs for identifying IAH and SH were 3.35% and 3.95%, yielding negative predictive value (NPV) values of 85% and 97%, respectively. Our findings support the international consensus recommending a TBR of <4% in type 1 diabetes, with high NPV values suggesting the utility of TBR in screening for SH.