The Sheffield Children's Hospital is a healthcare facility for children in Broomhill, Sheffield, South Yorkshire, England. It is managed by the Sheffield Children's NHS Foundation Trust.
Reconstruction of finger defects remains challenging, especially when protective sensation and mobility are required. The distal dorsoulnar artery perforator free flap (DDUAPF) provides neuro-sensate soft tissue coverage with low donor morbidity. No systematic review has previously combined outcomes of the DDUAPF in digital reconstruction; this study addresses this gap, and highlights a potential modification. A systematic search of Pubmed, Medline, EBSCO was performed. Screening followed PRISMA guidelines and the review was registered on PROSPERO (CRD420241137681). Outcomes included flap survival, complications, donor morbidity, range of motion (ROM), and sensory recovery. Study quality was assessed using Critical-Appraisal-Skills-Programme (CASP) checklist and Risk-of-Bias-In-Non-randomised-Studies-of-Interventions (ROBINS-I). Ten studies involving 178 patients and 184 flaps were included. Mean age was 33.7 years. Indications included trauma, degloving, infection, burns and ischaemia. Average flap size was 12.3 cm2 (range 3- 71.5 cm2). Flap failure occurred in 0.5
BACKGROUND:Dravet syndrome is a severe developmental and epileptic encephalopathy caused primarily by SCN1A haploinsufficiency. Risks of sudden unexpected death in epilepsy and cognitive deficits are higher among patients with this syndrome than in the general population with epilepsy. The effects of zorevunersen, an antisense oligonucleotide designed to up-regulate NaV1.1 sodium channels, in patients with Dravet syndrome are not known. METHODS:We enrolled patients 2 to 18 years of age with Dravet syndrome who were receiving standard antiseizure medications in two phase 1-2a, open-label, multicenter studies (MONARCH and ADMIRAL). Patients were included in either a single-ascending-dose cohort, in which zorevunersen (10 to 70 mg) was administered on day 1 only, or a multiple-ascending-dose cohort, in which zorevunersen (20 to 70 mg) was administered two or three times in a 3-month period. Patients eligible for rollover to the two open-label extension studies (SWALLOWTAIL and LONGWING) continued to receive zorevunersen (≤45 mg) every 4 months. The safety and pharmacokinetics of zorevunersen were assessed in the primary analysis; clinical effects were also evaluated. RESULTS:A total of 81 patients were enrolled in the phase 1-2a studies. As of May 30, 2025, a total of 75 patients had entered the extension studies. Most adverse events were mild or moderate. The most common adverse event was post-lumbar puncture syndrome (in 25% of patients) in the phase 1-2a studies and was an elevated protein level in cerebrospinal fluid (in 45%) in the extension studies. One patient had suspected unexpected serious adverse reactions, 1 had an adverse event that led to study withdrawal, 2 died from sudden unexpected death in epilepsy, and 1 died from malnutrition. Patients who received 70 mg of zorevunersen (one, two, or three doses) in the phase 1-2a studies, followed by up to 45 mg in the extension studies, had a median change from baseline in convulsive-seizure frequency ranging from -58.82% to -90.91% across 1-month intervals during the first 20 months of the extension studies. The data supported improvements in overall clinical status, quality of life, and adaptive behavior with continued treatment for up to 36 months in the extension studies. CONCLUSIONS:The safety profile and initial clinical improvement support the continued development of zorevunersen as a potential disease-modifying treatment for Dravet syndrome. (Supported by Stoke Therapeutics; MONARCH and SWALLOWTAIL ClinicalTrials.gov numbers, NCT04442295 and NCT04740476, respectively; ADMIRAL and LONGWING ISRCTN Registry numbers, ISRCTN99651026 and ISRCTN12811235, respectively.).
Introduction In 2025, the Medicines and Healthcare products Regulatory Agency (MHRA) approved the use of teplizumab (a monoclonal anti-CD3 antibody) to delay progression from Stage 2 to Stage 3 Type 1 diabetes in the UK. Methods To address the need for clear guidance on managing patients eligible for teplizumab therapy, the British Society of Paediatric Endocrinology and Diabetes (BSPED) Type 1 diabetes Special Interest Group (SIG) and the Association of British Clinical Diabetologists (ABCD) assembled a group to review the clinical trial data and develop expert consensus guidelines on the approach to teplizumab infusions. Conclusion Here, we present recommendations on all aspects of teplizumab administration with evidence base where available. We highlight the safety considerations in individual's selection, screening, monitoring and treatment of potential common side effects.
OBJECTIVES:To conduct data-driven sensitivity analyses to evaluate whether refined definitions of childhood-onset systemic lupus erythematosus (cSLE) treat-to-target goals provide better protection against moderate-severe flares and new damage, compared with original consensus-derived targets. METHODS:The UK JSLE Cohort Study was utilized. Childhood-SLE target attainment was determined at each visit. Removal or transformation of cSLE target criteria ('variations') were investigated, for Childhood Lupus Low Disease Activity State (cLLDAS), cSLE Clinical Remission on Steroids (cCR) and cSLE Clinical Remission off Steroids (cCR-0). The impact of such variations on the hazards of subsequent moderate-severe flare and new damage was assessed, using Prentice-Williams-Peterson (PWP) models. Two-sided t-tests compared the hazard ratios (HRs) obtained from the PWP gap-time models for the original and varied cSLE target definitions. RESULTS:Two variations of cLLDAS demonstrated significantly better protection against moderate-severe flare, including transformation of SLEDAI-2K cut-off to ≤3 (HR 0.13 [0.09, 0.19], P < 0.001); and transformation of PGA cut-off to ≤0.25 (HR 0.14 [0.10, 0.20], P < 0.001). These variations in cLLDAS did not impact on the hazards of new damage. No variations of cCR and cCR-0 led to a significant improvement in hazards of moderate-severe flare/new damage (all P > 0.05). A modified version of cLLDAS, combining these two transformations was also assessed, demonstrating further improvement in protection against moderate-severe flare (HR 0.12 [0.08, 0.17], P < 0.001). CONCLUSIONS:Refining the cLLDAS definition by lowering the SLEDAI-2K cut-off to ≤3 and PGA to ≤0.25 may enhance protection against moderate-severe flare, but not new damage. No variations of cCR or cCR-0 showed significant improvement.
