Manchester Royal Infirmary

RASopathies are clinically overlapping neurodevelopmental syndromes resulting from germline mutations in genes involved in the rat sarcoma/mitogen-activated protein kinases (RAS/MAPK) pathway. Historically, RASopathies have been described by clinical phenotypes, such as Noonan syndrome and Neurofibromatosis type I. There is emerging evidence of the association between Noonan syndrome spectrum disorders (NSSD) and systemic lupus erythematosus (SLE). Here, we present an SLE patient diagnosed with SOS1-associated Noonan Syndrome (c.806 T>C; p.Met269Thr) as part of a research study. Reviewing the literature, we identified further 16 cases of NSSD associated with SLE. Nine out of 16 cases (56%) had a confirmed molecular diagnosis, with pathogenic missense variants identified in KRAS, PTPN11, and SHOC2 genes, the majority in the last. Variants in SHOC2 are the cause of only a small proportion of all presentations of NSSD. Our case represents the first reported case of SLE in a patient with a SOS1 pathogenic variant. Compared to the general SLE population, SLE in the presence of NSSD develops at a younger age, with a similar prevalence among females and males, suggesting a contribution of the RAS/MAPK pathway in the development of SLE.

Computer-based learning (CBL) has emerged as a transformative approach in surgical education, with remote teaching (RT) and self-directed virtual teaching (SDVT) offering scalable and, flexible alternatives to traditional face-to-face instruction. This systematic review aims to qualitatively analyse the current evidence on RT and SDVT for surgical skill training. In July 2023, we conducted a structured search of PubMed, Cochrane Library, Scopus, and Web of Science. To enable a clear evaluation of CBL, particularly by examining retained knowledge, we included only randomized controlled trials (RCT) and prospective cohort studies. Data extraction followed a pretested Excel form, and qualitative synthesis adhered to PRISMA principles. Twenty seven studies (15 RCTs, 12 prospective cohorts) published between 2006 and 2023 met the inclusion criteria. Despite the heterogenicity of the included studies, key findings show that students completed RT achieved competency outcomes equivalent to traditional learning for basic suturing, knot-tying, and fundamental laparoscopic skills in most of the studies. SDVT matched traditional learning for basic tasks but underperformed in complex procedures. Hybrid models combining SDVT with real-time feedback enhanced learner autonomy, engagement and skill retention. Lastly, CBL modalities were well received by trainees, offering time- and cost advantages, as well as providing a teaching platform for low- and middle-income countries. CBL, through RT and SDVT, provides an effective adjunct to traditional surgical training, particularly for foundational technical skills. Integrating the flexibility of SDVT with synchronous feedback during RT can optimize psychomotor learning while maintaining instructional oversight. Future research should standardize outcome measures, assess long-term skill retention, and explore implementation in resource-limited settings.

Background/Objectives: This review is a concise summary of the current roles and indications for procalcitonin measurement in the management of patients with acute pancreatitis. Methods: The National Library of Medicine's PubMed database for the period 1 January 2000 to 27 November 2025 was interrogated using the keywords "procalcitonin" and "acute pancreatitis". Articles on gut dysbiosis in acute pancreatitis, procalcitonin and its role as a predictor of disease severity, a marker of pancreatic necrosis and a guide to antibiotic therapy in acute pancreatitis were retrieved. Results: Persistently elevated procalcitonin levels are indicators of disease severity and necrosis in acute pancreatitis. In the setting of acute pancreatitis with raised inflammatory markers, a procalcitonin level >1 ng/mL has evidentiary proof for use as an indicator for starting antibiotic therapy. Conclusions: In current practice, in patients with acute pancreatitis and raised inflammatory markers but without positive microbiological cultures, a procalcitonin level >1 ng/mL can be used as an indicator for starting antibiotic therapy.

Abstract Background Nocturnal hypoglycaemia (NH) is a common and challenging complication in Type 1 Diabetes (T1D), disrupting blood glucose control and sleep physiology. Its real-world impact on sleep architecture remains poorly characterised. Consumer wearables offer a way to examine these associations under free-living conditions, providing detailed insight into behavioural and physiological responses to nocturnal blood glucose fluctuations. This study aims to assess how wearable-derived sleep metrics and physiological features could be used as indicators of NH, including the effects of how low blood glucose levels fall during hypoglycaemic events and the associated pre-event changes. Methods We conducted a comparative observational analysis of paired continuous glucose monitoring (CGM) and Garmin smartwatch data collected over 12 weeks from 17 adults with T1D. Nights were categorised as normoglycaemia, hyperglycaemia, or hypoglycaemia Level 1 ( ≥ 3.1 and < 3.9 mmol/L), and hypoglycaemia Level 2 ( < 3.0 mmol/L). Thirteen sleep metrics, including total sleep time, wake after sleep onset (WASO), sleep-stage proportions, fragmentation indices, and physiological features such as heart rate, were compared using non-parametric tests. Pre-hypoglycaemic event analyses examined 60-minute and 15-minute windows preceding hypoglycaemia to identify early deviations in sleep and physiological metrics. Results Across 573 nights, 17.5% involved Level 1 and 7.3% Level 2 hypoglycaemia. Level 2 hypoglycaemia was associated with 31 minutes less wakefulness, 17–25 minutes more REM, and up to 74% more deep sleep compared with normo-glycaemic nights. Sleep efficiency increased during hypoglycaemic events despite greater fragmentation. Pre-hypoglycaemic episode analyses revealed shorter awake and light-sleep bouts, as well as a 9.8% higher heart rate, preceding Level 2 episodes. Conclusions Wearable-derived sleep and physiological signals reveal clear intraindividual changes both before and during NH. Our findings indicate that Level 2 episodes are associated with deeper sleep and reduced behavioural arousal, suggesting that CGM alarms may be less effective at waking individuals during level2 NH. By characterising pre-hypoglycaemic changes that differ based on hypoglycaemia level, this work provides preliminary evidence for personalised, wearable-based early-warning systems. Such approaches could help distinguish nocturnal hypoglycaemic events and support more effective alerting, particularly in settings with limited or no access to CGM. Author Summary Why was this study done? People with Type 1 Diabetes (T1D) frequently experience nocturnal hypoglycaemia (low blood glucose at night), a dangerous event that often goes unnoticed because individuals are less able to recognise symptoms or wake up during sleep. These events also disrupt sleep in ways that are not well characterised under real-world conditions. Limited access to continuous glucose monitoring (CGM), especially in low- and middle-income countries, highlights the need for affordable alternatives to ensure nighttime safety. What did we do and find? Using more than 500 nights of paired smartwatch and CGM data, we investigated how sleep features change when blood glucose levels fall overnight. We found that hypoglycaemic nights show distinct alterations in sleep architecture, including increased REM and deep sleep, and greater micro-fragmentation. A key finding was that Level 2 hypoglycaemia was associated with deeper sleep and reduced wakefulness. This pattern indicates that individuals may be less likely to awaken during more severe events, even when alarms are present. Pre-hypoglycaemic episode analysis revealed additional early-warning signals, such as shorter awake and light-sleep bouts and elevated heart rate, before level 2 hypoglycaemia occurred. What do these findings mean? Smartwatches can capture sleep-based changes that appear before and during nocturnal hypoglycaemia. Because deeper sleep during Level 2 episodes may reduce responsiveness to CGM alerts, these results suggest that current alarm approaches could be improved by incorporating sleep features alongside glucose data. Such sleep-informed detection may enhance the reliability of hypoglycaemia alerts, reduce missed events during deep sleep, and provide a foundation for low-cost early-warning systems in settings where CGM is unavailable or unaffordable. Further research is needed in larger and more diverse populations, but this work provides early evidence that wearable-derived sleep features can meaningfully strengthen nocturnal hypoglycaemia detection.

Peripheral arterial disease (PAD) is a chronic vascular condition characterized by narrowing or obstruction of arteries to the extremities, leading to symptoms such as intermittent claudication, rest pain, foot ulcers, and gangrene. Its severe form is known as critical limb ischaemia (CLI), which is characterized by rest pain, tissue loss, and reduced perfusion pressures. Most CLI patients have multiple medical comorbidities ranging from diabetes, hypertension, hypercholesterolemia, to ischaemic heart disease, chronic lung disease, and previous strokes. The most effective management of CLI requires a multidisciplinary approach that integrates expertise from vascular surgeons, endocrinologists, podiatrists, interventional radiologists, microbiologists, plastic surgeons, primary care physicians, and specialist nurses. This article explores the pivotal role of multidisciplinary team foot clinics (MDT foot clinics) in the holistic management of CLI, emphasizing their benefits in providing patient-centric care and better clinical outcomes with cost-effectiveness. The MDT foot clinics are the best approach to CLI management, as they provide diagnostic evaluations, wound care, infection control, long-term medical therapy, and referrals for any revascularization procedure, all in a single coordinated setup. These clinics also address barriers such as transportation challenges, high-frequency visits made by patients, distrust of healthcare systems, and expensive treatment options hence, providing a more patient-centered approach. Multiple studies have demonstrated that the introduction of these clinics has significantly reduced the rates of amputation and inpatient admissions and has improved treatment outcomes and limb salvage rates. In conclusion, the multidisciplinary approach is indeed the gold standard approach that paves a path to better outcomes in patients with CLI by delivering superior outcomes through comprehensive, integrated, and patient-centric care. This approach focusses on most, if not all, aspects of management, starting from treating the active disease symptoms, preventing the disease progression, and also enhancing the quality of life with regular follow-ups and continuous monitoring of patients, all in a community setup.

BackgroundSlow flow/no-reflow (SF/NR) can undermine effective reperfusion during primary percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI). Identifying patients at risk before device escalation may enable protocolized microvascular-protection strategies within STEMI systems of care.ObjectiveThis study aimed to determine the prevalence of SF/NR in STEMI treated with primary PCI, identify pre-PCI predictors, and assess short-term in-hospital outcomes associated with SF/NR.MethodsIn a prospective cohort at a high-volume tertiary center, we enrolled 226 consecutive STEMI patients treated between January 1, 2024, and December 31, 2024 (complete-case analysis). SF/NR was defined as final thrombolysis in myocardial infarction (TIMI) flow <3 in the absence of mechanical obstruction. Multivariable logistic regression estimated independent predictors (adjusted odds ratios (aORs) with 95% CIs). Discrimination was assessed using the area under the receiver operating characteristic curve (AUC) with bootstrap optimism correction. In-hospital outcomes included final TIMI 3 flow, ventricular arrhythmia, hemodynamic instability, heart failure, and death.ResultsSF/NR occurred in 65/226 patients (28.8%). Independent predictors were diabetes mellitus (aOR, 2.05; 95% CI, 1.07-3.91), TIMI thrombus grade 5 (aOR, 3.02; 95% CI, 1.55-5.87), and pre-PCI TIMI 0 flow (aOR, 3.85; 95% CI, 1.53-9.67); symptom-to-balloon time >6 h was not an independent predictor. Model discrimination was fair (AUC, 0.74; 95% CI, 0.67-0.81; optimism-corrected AUC, 0.73). Compared with patients without SF/NR, those with SF/NR had lower final TIMI 3 flow (43.1% vs 82.0%; difference, −38.9 percentage points; 95% CI, −51.0 to −26.8) and higher rates of ventricular arrhythmia (18.5% vs 5.6%; P = 0.004), hemodynamic instability (24.6% vs 8.6%; P = 0.002), heart failure (21.5% vs 9.3%; P = 0.01), and in-hospital mortality (7.7% vs 1.9%; P = 0.04).ConclusionsIn contemporary primary PCI for STEMI, SF/NR was common and associated more strongly with thrombus burden and absent antegrade flow, along with diabetes, than with delays >6 hours. A simple pre-PCI triad (diabetes, TIMI thrombus grade 5, and TIMI 0 flow) may help flag higher-risk cases and prompt early microvascular-protection measures; external validation is warranted prior to routine adoption.

Abstract Introduction Penile septal haematoma is a rare and underrecognised form of penile trauma characterised by bleeding within the inter-corporeal septum without rupture of the tunica albuginea. It often presents with subtle or delayed symptoms, making diagnosis and management challenging. Objective This review aims to synthesise current literature on penile septal haematoma, with a focus on clinical presentation, diagnostic modalities, and management strategies. A case report is presented to illustrate real-world diagnostic and therapeutic considerations. Methods A systematic review of PubMed and Google Scholar was conducted using keywords: “penile trauma,” “penile septal haematoma,” “intracavernous haematoma,” and “penile injury.” Relevant case reports and clinical studies were included. Additionally, a recent clinical case of penile septal haematoma managed conservatively is described, and relevant radiological features are discussed. Results Only a few cases of penile septal haematoma are described in the literature. Clinical signs are often atypical, lacking the classic features of penile fracture. MRI and ultrasound are critical for diagnosis, differentiating haematomas from neoplasms or Peyronie’s plaques. Management varies from conservative observation to surgical drainage. Our case involved a 34-year-old male with a penile septal haematoma post-intercourse, successfully managed conservatively with preserved erectile function. Conclusions Penile septal haematoma is a distinct and underdiagnosed condition. Increased awareness and early imaging can facilitate prompt diagnosis, reducing long-term complications such as fibrosis and erectile dysfunction. Further research is needed to determine optimal treatment pathways and long-term outcomes. Disclosure No

Abstract Introduction Surgical treatment of erectile dysfunction (ED), particularly inflatable penile prosthesis (IPP) implantation, is a key intervention for patients unresponsive to conservative therapies. Delivering this care efficiently within elective services is essential, especially as surgical backlogs and resource constraints challenge healthcare systems. Centralised tertiary centres often struggle with emergency care pressures, potentially impacting elective surgery throughput. This study evaluates theatre efficiency and patient outcomes in IPP surgery across two hospital models: a large tertiary centre and a dedicated elective “cold-site”. The standalone “cold-sites” were designed to deliver high-volume elective surgical care while being insulated from the demands of emergency care pressures. Objective To compare surgical delivery of inflatable penile prosthesis implantation and other andrology surgeries using theatre efficiency metrics between a tertiary and cold-site hospital setting, with emphasis on theatre utilisation, patient experience, and system-based delays. Methods A retrospective observational study analysed all full-day urology theatre sessions led by two high-volume andrology surgeons over two 18-month periods: Period 1 (Oct 2018–Feb 2020, tertiary centre) and Period 2 (Oct 2023–Feb 2025, cold-site hospital). These timeframes were selected to minimise COVID-19-related bias. Metrics included theatre utilisation, case volume, proportion of IPP/andrology cases, delays, cancellations, day-case rates, 30-day readmissions, and IPP-specific patient satisfaction scores. Results In Period 1 (tertiary centre), 71 theatre sessions were conducted with 202 cases and 67.3% being andrology-related. Theatre utilisation averaged 34.61%. In Period 2 (cold-site), 82 sessions were recorded with 340 cases, of which 79.9% were andrology procedures. Theatre utilisation improved to 81.2%, with a day case rate of 73.5%. Delayed starts occurred in 30 sessions (mean 21.8 minutes), and 19 sessions overran (mean 36.9 minutes). There were 32 on-the-day cancellations, and the 30-day readmission rate was 1.18%. Patient experience survey data for 61 IPP implantation patients during 2024 revealed strong satisfaction levels: * Pre-operative: 4.81 / 5 * Day of surgery: 4.73 / 5 * Post-operative: 4.58 / 5 These outcomes reflect a patient-centred care model enhanced by the cold-site's dedicated elective infrastructure. Conclusions Cold-site elective surgery delivery for erectile dysfunction, mainly IPP implantation, demonstrated markedly improved efficiency and patient satisfaction compared to a tertiary hospital setting. Higher throughput, better theatre utilisation, and reduced disruption from emergency pressures underpin these findings. The results support broader adoption of ring-fenced elective surgical pathways to improve access, efficiency, and patient experience in surgical management of erectile dysfunction. Disclosure No

Testosterone replacement therapy (TRT) remains controversial in men with a history of prostate cancer due to historical concerns regarding oncologic safety. This scoping review aimed to systematically map existing evidence on the safety and efficacy of TRT in men following definitive treatment for prostate cancer. A systematic search of PubMed, CENTRAL, and Embase identified 447 records, from which 12 studies met inclusion criteria. Most were retrospective cohort studies, with sample sizes ranging from 10 to 152 men. TRT was not associated with an increased risk of biochemical recurrence or cancer progression in any included study. Reported PSA kinetics remained within expected post-treatment parameters, and several studies showed lower recurrence rates in TRT groups compared to controls. TRT consistently increased total and/or free testosterone and improved hypogonadal symptoms. However, the evidence base is limited by retrospective designs, small sample sizes, heterogeneous outcome reporting, and a lack of long-term data. Despite these limitations, findings suggest TRT may be cautiously considered in selected men with stable disease and confirmed hypogonadism. High-quality prospective studies are needed to clarify safety in diverse and high-risk populations and inform future clinical guidelines.

AimTo ascertain the safety and feasibility of robotic simultaneous resection of synchronous colorectal cancer and liver metastases.MethodsA PRISMA-compliant systematic review with proportion meta-analysis was conducted. All retrospective or prospective observational studies including patients aged ≥ 18 with synchronous colorectal cancer and liver metastases undergoing robotic simultaneous resection were eligible. The outcomes included conversion to open, operative time, intraoperative blood loss, Clavien-Dindo ≥ III complications, 30-day mortality, anastomotic leak, R0 resection, and length of hospital stay.ResultsSeven eligible studies including 165 patients were identified. The mean age was 62.8years (95% CI: 60.5-65.2), mean body mass index was 26.5 (95% CI: 24.6-28.4), and 52.0% (95% CI: 37.9-66.1) were male. The mean operative time was 406.5min (95% CI: 358.2-454.7) and mean intraoperative blood loss was 150.0mL (95% CI: 124.5-175.6). Conversion to open occurred in 3.9% (95% CI: 1.0-6.8), Clavien-Dindo ≥ III complications in 9.3% (95% CI: 4.7-13.8), 30-day mortality in 0.9% (95% CI: 0.0-2.4), and anastomotic leak in 4.3% (95% CI: 0.9-7.6). R0 resection was achieved in 99.0% (95% CI: 97.5-100), and the mean length of hospital stay was 6.7days (95% CI: 5.5-7.9).ConclusionsSingle-arm meta-analysis suggests that robotic simultaneous resection of synchronous colorectal cancer and liver metastases may not only be feasible and safe but also may be advantageous in terms of conversion avoidance, complexity handling, and perioperative recovery. More studies with larger sample size are required to inform long-term oncological outcomes and selection criteria and to provide comparative evidence.