Walsall Healthcare NHS Trust

Abstract Background In this paper, we describe the role of Copy Number Variation (CNV) detection applications in Genome Sequencing data in the diagnosis of Loeys-Dietz syndrome type 4 in a large family, bringing a 30-year diagnostic odyssey to an end. Initially, a 38-year-old man was referred for clinical assessment due to a family history of Marfan syndrome. He had several clinical features indicative of Marfan's syndome. Linkage analysis performed in the family in 1990s was considered informative within a 4.3Mb locus on chromosome 15 including FBN1, supporting the clinical suspicion of Marfan syndrome. Methods A range of genomic tests in the next two decades, initially DHPLC and later sequencing and MLPA of FBN1, failed to identify a pathogenic variant in the family. Genome sequencing (GS) through the UK 100,000 Genomes Project (100kGP) was performed in the patient and his affected maternal aunt using 150bp paired-end reads. Results Reanalysis of the GS data using the SVRare application (1) identified a heterozygous 19,256bp deletion encompassing the last exon of TGFB2 with TCC microhomology seen at breakpoints. This finding, one of the smallest deletions involving TGFB2 described to date (2,3,4), was consistent with a diagnosis of Loeys-Dietz syndrome in the patient and his affected aunt. There have been a range of clinical benefits from a precise molecular diagnosis in this family. The aortic phenotype in this family was significant, with history of aortic surgery or dissection in at least five relatives. Predictive genetic testing has resulted in Loeys-Dietz syndrome type 4 being diagnosed in five further patients in this family. Conclusions Heterozygous loss-of-function variants in TGFB2 cause Loeys-Dietz syndrome type 4 (2) and there are overlapping features between this condition and Marfan syndrome. Precise molecular diagnosis of connective tissue disorders is crucial in appropriate management and surveillance, with a range of clinical benefits seen within this family.

Surgical attire and personal protective equipment (PPE) represent significant financial and environmental costs in dermatologic surgery. Evidence suggests that lower-resource approaches can maintain low surgical site infection (SSI) rates. To describe international PPE use and highlight opportunities to improve sustainability and reduce unnecessary expenditure while ensuring patient safety. A 16-item online questionnaire was developed in Google Forms, refined through colleague feedback, circulated in March 2025 via the British Society for Dermatological Surgery, the New Zealand Dermatological Society Inc., and the European Society for Micrographic Surgery, with one reminder sent. It collected demographic data and tailored questions for Mohs surgeons and those performing flap/graft repairs. Responses were obtained from 205 clinicians across 25 countries, predominantly from the UK (59.5%), New Zealand (13.7%), and the Netherlands (6.8%). Most were consultant dermatologists (79.5%); 42.0% were Mohs surgeons. Considerable variation was reported in glove type, attire, and mask use. For diagnostic biopsies, 40.0% used clean gloves, 63.9% sterile gloves, and 40.0% wore clean scrubs alone, while 26.3% operated in normal work clothes. For excisions with direct closure, 92% used sterile gloves, though over half wore only clean scrubs. Among Mohs surgeons, 20.9% used clean gloves for tumour extirpation and most (75.6%) wore clean scrubs alone. Reusable attire was limited, mainly scrubs and personal eyewear, while disposable caps and masks predominated. This international survey demonstrates variability in dermatologic surgical PPE, with single-use items remaining widespread despite limited evidence of benefit. Evidence-based standardisation could improve sustainability, reduce costs, and maintain excellent patient outcomes.

Medial epicondylitis is a chronic tendinopathic disorder involving the flexor-pronator origin of the medial elbow, characterised by pain and functional limitation related to repetitive loading and microtrauma. The condition exemplifies the broader spectrum of overuse injuries that result from cumulative strain exceeding the capacity for tendon repair. Diagnosis relies primarily on clinical evaluation, with imaging modalities used selectively to define the extent of pathology or to exclude alternative causes of medial elbow pain. Management follows a structured, stepwise approach, centred on conservative therapy, including rest, physiotherapy, and graduated strengthening programmes that are supported by adjunctive interventions when symptoms persist. Surgical management is considered only in cases of chronic, treatment-resistant disease. Growing recognition of this condition in both community and inpatient populations highlights its relevance to multidisciplinary care and underscores the value of coordinated management strategies that combine clinical assessment, rehabilitation, and targeted use of imaging to optimise outcomes.

The INS c.16 C > T (insulin p.Arg6Cys, R6C) variant was reported to cause autosomal dominant monogenic diabetes, yet its pathogenicity has been questioned. R6C preproinsulin exhibits impaired translocation into the endoplasmic reticulum (ER). We explored R6C pathogenicity using integrative clinical, genetic, and functional approaches.Homozygous INS R6C individuals presented early-onset insulin-treated diabetes, whereas heterozygous carriers showed variable or absent glycemic phenotypes. Population-level analysis revealed no significant enrichment of diabetes among heterozygotes. Heterozygous R6C patient’s induced pluripotent stem cell (iPSC)-derived pancreatic β cells exhibited minimal defects, while homozygous R6C β cells displayed preproinsulin accumulation and reduced insulin content and secretion. In vivo, homozygous R6C β cell transplants recapitulated insulin deficiency and responded poorly to GLP-1 receptor agonist. Homozygous R6C β cells had a gene signature of attenuated translation, translocation and ER related pathways.Our findings establish R6C as a recessive loss-of-function mutation, prompting a clinical reassessment of heterozygous R6C carriers. This study highlights the power of population genetic databases, patients’ iPSC-based modeling and multi-modal variant classification frameworks for dissecting the consequences of genetic variants in monogenic diabetes.

Abstract Aim The aim of the study was to evaluate the impact of preoperative GLP-1 agonist medication on postoperative weight-loss outcomes during the first 12 months after bariatric surgery. Method A retrospective, single-centre, cohort study was conducted. A total of 85 adult patients, who underwent primary bariatric surgery (Sleeve Gastrectomy, Roux-en-Y Gastric Bypass, Mini Gastric Bypass) between January and December 2023 and were started on GLP-1 agonists six months before surgery, were included. Patients were grouped based on preoperative use (n=36) or non-use (n=49) of GLP-1 agonists. Primary outcome assessed was the percentage of excess weight loss (%EWL) at 12 months post operative. Statistical analysis was performed using the Mann-Whitney U test. Results Patients using GLP-1 agonists demonstrated significantly greater preoperative excess body weight loss compared to non-users (12.64% vs 6.95%, p=0.015). However, at 12 months postoperative, no significant statistical differences in % EWL between groups, Sleeve Gastrectomy (55.6% vs 48.1%, p=0.148), Mini Gastric Bypass (53.53% vs 51.51%, p=0.356), or Roux-en-Y Gastric Bypass (61.9% vs 56.02%, p=0.148), was noted. Conclusions Although preoperative use of GLP-1 agonists offers in improved weight reduction in preoperative time, but it did not demonstrate any superior short term postoperative weight loss outcomes for bariatric surgery patients. A multi-centre, prospective study having larger sample size with long term follow up may be required to establish and measure long-term implications.

Hypertrophic pulmonary osteoarthropathy (HPOA) is a paraneoplastic syndrome characterised by digital clubbing, periostitis, and arthralgia, most commonly secondary to lung malignancy. This case report presents a man in his 60s with a long history of smoking and asbestos exposure who developed progressive wrist and ankle pain, limb swelling, and enlargement of the hands and feet over eight months. He was initially investigated for rheumatoid arthritis due to positive rheumatoid factor (RF) and anti-citrullinated peptide (anti-CCP) antibodies, but repeated chest X-rays were normal. A CT scan later revealed a left lower lobe lesion, and biopsy confirmed squamous cell carcinoma of the lung. This case underscores the importance of maintaining a high index of suspicion for paraneoplastic syndromes such as HPOA when unexplained arthropathy and digital clubbing occur, even in the absence of respiratory symptoms.

Objectives: We aimed to evaluate the management of lower urinary tract infections (LUTIs) in elderly inpatients, to determine the prevalence of inappropriate treatment of asymptomatic bacteriuria (ASB), and to assess the impact of targeted educational interventions on antibiotic prescribing accuracy.Settings: An acute general hospital in the East Midlands of the United Kingdom.Participants: A total of 77 patients aged 65 years and older who underwent urine culture for suspected lower urinary tract infection were included in the study.Design: This was a prospective case series of emergency hospital admissions collected over eight months in acute elderly medicine wards, with two educational interventions implemented during the second and third months of the study period.Methods: Data relating to demographics, catheterization status, presenting symptoms, urine dipstick usage, culture collection methods, and antibiotic prescription patterns were obtained from electronic and paper records as part of audit number 1688 registered at the hospital trust. Interventions included the display of an informational poster based on NICE guidelines and a dedicated educational teaching session for clinicians. In total, 19 patients were involved pre-intervention. A total of 58 patients were involved post-intervention. Among the post-intervention cohort, 32 patients were involved after the poster intervention, and 17 patients were involved following the teaching intervention. Several months following the intervention, nine patients were involved in the study.Results: Initial findings revealed suboptimal adherence to national guidelines, with 50% (n=5) of asymptomatic patients with negative cultures inappropriately prescribed antibiotics. Following the poster intervention, prescribing was found to be three-and-a-half times more appropriate for LUTIs than the pre-intervention period (OR=3.61, 95% CI: 1.08-12.03, Ꭓ2=4.56, p=0.033). Compared to the pre-intervention period, antibiotic prescribing was found to be five times more appropriate (OR=5.05, 95% CI: 0.96-26.66, Ꭓ2=3.91, p=0.048) after all educational interventions were implemented. Catheter-associated infections also showed a significant reduction, albeit with poor statistical correlation. Conclusion: Targeted educational interventions, including informational posters and teaching sessions, improved appropriate diagnosis and antibiotic prescribing for LUTIs and ASB in elderly hospitalized patients within the scope of this study.

Abstract Background Recurrent acute diverticulitis (AD) significantly impacts patient's quality of life and increases morbidity and healthcare costs. This study aims to assess risk factors for recurrence and the need for surgical and radiological intervention during one year from index presentation. Methods This multicentre study was performed in four UK hospitals. All patients presented with a CT scan confirmed colonic AD during 12 months were included. Patients were followed up for one year from the index presentation. Outcomes of interest were the patient factors associated with recurrent episodes of diverticulitis and the requirement for a radiological or surgical intervention, using both univariate and multivariate logistic regression. Statistical analysis was performed using R version 4.4. Results A total number of 542 patients were included; the median age was 62 (51–73) years, and 64.2% had Hinchey 1a AD. The recurrence rate over 1 year was 19.5%, with increased likelihood in patients with previous diverticulitis (P=0.006), Temperature ≥ 38°C on index admission (P=0.021), and LOS ≥ 3 days (P=0.009). Surgical and radiological intervention during follow-up was reported as 11.8% and 2%, respectively. Factors associated with increased likelihood of surgical intervention within 1 year were previous diagnosis of complicated diverticulitis (P=0.002), pyrexia(P=0.009) and hypotension(P=0.013) on index admission, CRP >300 (P=0.037), WCC ≥15(P=0.007), and Hinchey grades ≥ 2 (P=0.001). Conclusion High inflammatory markers, prolonged LOS and previous history of diverticulitis are associated with an increased risk of recurrence of diverticulitis. Treatment of acute diverticulitis must be tailored according to the patient's risk stratification.