Vascular malformations occur during early vascular development resulting in abnormally formed vessels that can manifest as arterial, venous, capillary or lymphatic lesions, or in combination, and include local tissue overdevelopment. Vascular malformations are largely caused by sporadic somatic gene mutations. This article aims to review and discuss current molecular signaling pathways and therapeutic targets for vascular malformations and to classify vascular malformations according to the molecular pathways involved. A literature review was performed using Embase and Medline. Different MeSH terms were combined for the search strategy, with the aim of encompassing all studies describing the classification, pathogenesis, and treatment of vascular malformations. Major pathways involved in the pathogenesis of vascular malformations are vascular endothelial growth factor (VEGF), Ras/Raf/MEK/ERK, angiopoietin-TIE2, transforming growth factor beta (TGF-β), and PI3K/AKT/mTOR. These pathways are involved in controlling cellular growth, apoptosis, differentiation, and proliferation, and play a central role in endothelial cell signaling and angiogenesis. Many vascular malformations share similar aberrant molecular signaling pathways with cancers and inflammatory disorders. Therefore, selective anticancer agents and immunosuppressants may be beneficial in treating vascular malformations of specific mutations. The current classification systems of vascular malformations, including the International Society of the Study of Vascular Anomalies (ISSVA) classification, are primarily observational and clinical, and are not based on the molecular pathways involved in the pathogenesis of the condition. Several molecular pathways with potential therapeutic targets have been demonstrated to contribute to the development of various vascular anomalies. Classifying vascular malformations based on their molecular pathogenesis may improve treatment by determining the underlying nature of the condition and their potential therapeutic target.

Objective: Recently, studies have shown that sirolimus is clinically efficacious in the treatment of some low-flow vascular malformations (LFVM). This study aimed to assess the efficacy and safety of sirolimus in treating complex head and neck (H&N) LFVM that were challenging and/or refractory to standard treatment. Methods: Each patient had baseline and 6-months assessments consisting of clinical history and examination, quality of life (QoL) questionnaires, laboratory investigations, MRI and medical photography. Patients were followed up 1-week and then 1-monthly for 6-months. Wilcoxon signed-rank test was used to compare pre-and 6-months treatment in all 8 domains of RAND 36-Item Short Form Health Survey (SF-36), hospital anxiety and depression scale (HADS), and visual analog score for pain (VAS-P). P < 0.05 was considered significant. Results: Seven patients (median age 43 years, range 23-65 years) were recruited. Six patients completed the six-months course of therapy with 1 patient withdrawing due to intolerable side effects. All six patients reported reduction of swelling with and without other symptom improvement related to the vascular malformations while on treatment. However, at 1-month review after discontinuation of sirolimus, 5 patients reported return of initial symptoms. Overall, patients demonstrated an improvement in QoL six-months treatment but there was no statistical significance (P > 0.05) in all 8 domains of SF-36, HADS and VAS-P. Five patients demonstrated a minimum 10% decrease in lesion size six-months treatment (median 21%, range 13-40%). A Wilcoxon signed-rank test showed that sirolimus treatment did elicit a statistically significant change in lesion size in either direction (Z = -1.992, P = 0.046). The most common side effects found were dyslipidaemia (n-4) and mouth ulcers (n = 2). Conclusion: In our preliminary experience, sirolimus is effective and safe in treating patients with complex H&N LFVM. This provides an alternative treatment where standard treatment is challenging and/or refractory.

Background: Hip fractures remain a major health concern owing to the increasing elderly population and their association with significant morbidity and mortality. The effects of weekend admission on mortality have been studied since the late 1970s. Despite most studies showing that mortality rates are higher for patients admitted on a weekend, the characteristics of the admitted patients have remained unclear. We aim to investigate this ‘weekend effect’ at our hospital in patients presenting with a hip fracture. Methods: Patients undergoing acute hip fracture surgery were identified from the local National Hip Fracture Database. Patient demographics, fracture type, co-morbidities and admission blood parameters were examined. The outcome analysed was 30-day mortality. The data were analysed with regard to day of admission, i.e. weekday (Monday to Friday) or weekend (Saturday and Sunday). Results: A total of 894 patients were included. Results demonstrated that 30-day mortality was similar on the weekend compared with the weekday (6.96% versus 10.39%, OR 0.65, 95% CI 0.36–1.14, p = 0.128) for patients who sustained an acute hip fracture. The total number of deaths within 30 days was 85 (69 weekday versus 16 weekend). This remained non-significant after adjusting for several variables: age and sex only (OR = 0.65, 95% CI 0.37–1.16, p = 0.146), age, sex, and care variables (OR = 0.59, 95% CI 0.33–1.06, p = 0.080), age, sex, and blood test results (OR = 0.62, 95% CI 0.35–1.12, p = 0.111), and all covariates (OR = 0.69, 95% CI 0.29–1.62, p = 0.392). In the fully adjusted model, the following variables were independent predictors of mortality: sex (male) (OR = 1.93, 95% CI 1.11–3.35, p = 0.019) and ASA > 2 (OR = 2.6, 95% CI 1.11–6.11, p = 0.028) and age (1.08, 95% CI 1.04–1.13, p < 0.001). Conclusion: The evidence for a ‘weekend effect’ in patients with a hip fracture is absent in this study. However, we have shown other factors that are associated with increased mortality such as increased age, male sex and higher ASA grade. Level of evidence: Level 3.

Background: Tourniquet pressures used in upper limb surgery are commonly standardized at 250 mmHg. These higher tourniquet pressures have been associated with an increased risk of complications, such as neural compression injury and soft tissue damage. However, there has been limited consensus as to the use of lower tourniquet pressures and their efficacy. This systematic review and meta-analysis aims to examine the current evidence for the use of lower tourniquet pressures in upper limb surgery, comparing them to the standard tourniquet pressures of 250 mmHg and, in some cases, 300 mmHg. This study is registered on PROSPERO (CRD42024511501). The primary outcome was the adequacy and quality of the bloodless field achieved at lower pressures. Secondary outcomes were assessed when reported, including the operative time, pain, and complications. Methods: The databases Medline (via Ovid), Embase (via Ovid), Cochrane, Web of Science (Core Collection) and Scopus, ClinicalTrials.gov, EU Clinical Trials Register, and ISRCTN registry were searched from inception to January 2025. The inclusion criteria included patients undergoing upper limb surgery using regional or general anesthetic with the use of a pneumatic tourniquet. A total of 1994 studies were identified, of which 12 met the inclusion criteria for review and 8 studies were used in the meta-analysis. Risk of bias was assessed using the ROBINS-I and RoB-2 tools. Results: The sample size was 1427 patients with a mean age of 46.8 years. All studies showed a bloodless surgical field at lower tourniquet occlusion pressures. The meta-analysis showed the overall mean tourniquet inflation pressure, estimated using a random effects model, to be 169.3 mmHg with a 95% confidence interval of 144.9–193.6. However, the heterogeneity in the reported results is significant (p < 0.0001) and is a limitation to this review. Conclusions: This systematic review highlights the benefit of the use of a lower tourniquet pressure (below the standard 250 mmHg) to produce an adequate surgical field and influence procedural outcomes.