Consistent FFP2-masking as part of reducing viral respiratory infections on medical wards for allogeneic hematopoietic stem cell transplantation.

Patients undergoing allogenic hematopoietic stem cell transplantation (allo-HSCT) are highly susceptible to infections. The consequent use of masks on wards for allo-HSCT has been controversial in the past decades and was not common before the COVID-19 pandemic. We retrospectively compared incidence and outcomes of viral respiratory infections during allo-HSCT on our specialized ward between 01/2018 and 09/2020 to the era of FFP2 masking between 10/2020 and 10/2022 covering similar seasons of the year. Each group consisted of 150 matched patients. The usage of FFP2 masks reduced the incidence of viral respiratory infections from 22.1 to 2.1% (p < 0.005). This reduced the time on ward from a median of 26 days to 23.5 days (p = 0.002). It also resulted in less use of CT-scans (p = 0.003) and bronchoalveolar lavage procedures (p = 0.057). Median time to proof of infection was 21 days after admission in both groups. No difference was detected in progression free survival, hospital survival or non-relapse mortality (p = 0.78). Our retrospective results indicate that FFP2 masks worn by patients and hospital staff may help to significantly reduce the incidence of viral respiratory infections, including COVID-19, shorten the in-hospital time, and reduce costs without affecting survival.

Biomechanical analysis of cadaveric wrists before and after MOTEC wrist arthroplasty using a hexapod robot.

This study compares wrist motion, biomechanical behaviour and radiographic parameters before and after total wrist arthroplasty using a fourth-generation spherical articulation prosthesis. A total of 10 cadaveric specimens were assessed using a hexapod Stewart platform robot. After arthroplasty, there were significant increases in both stiffness and phase angle of wrist motion across all planes of motion assessed. In three specimens, a sudden increase in moment was observed on load/displacement curves. Radiographically, carpal height increased by 14%, and the centre of rotation was displaced 11.1 mm proximally, 4.6 mm dorsally and 3.9 mm radially. This stretched the musculotendinous units, tightening the joint, while increasing the moment arm of the wrist flexors and decreasing the moment arm of the extensors, potentially important in the development of postoperative flexion contractures. Possible alterations in technique and/or implant design are considered to assist surgeons in achieving optimal clinical and survivorship outcomes.

Predicting Psoriatic Arthritis in Psoriasis Patients - A Swiss Registry Study.

Background: Psoriatic arthritis (PsA) is a prevalent comorbidity among patients with psoriasis, heavily contributing to their burden of disease, usually diagnosed several years after the diagnosis of psoriasis. Objectives: To investigate the predictability of psoriatic arthritis in patients with psoriasis and to identify important predictors. Methods: Data from the Swiss Dermatology Network on Targeted Therapies (SDNTT) involving patients treated for psoriasis were utilized. A combination of gradient-boosted decision trees and mixed models was used to classify patients based on their diagnosis of PsA or its absence. The variables with the highest predictive power were identified. Time to PsA diagnosis was visualized with the Kaplan-Meier method and the relationship between severity of psoriasis and PsA was explored through quantile regression. Results: A diagnosis of psoriatic arthritis was registered at baseline of 407 (29.5%) treatment series. 516 patients had no registration of PsA, 257 patients had PsA at inclusion, and 91 patients were diagnosed with PsA after inclusion. The model's AUROCs was up to 73.7%, and variables with the highest discriminatory power were age, PASI, physical well-being, and severity of nail psoriasis. Among patients who developed PsA after inclusion, significantly more first treatment series were classified in the PsA-group, compared to those with no PsA registration. PASI was significantly correlated with the median burden/severity of PsA (P = .01). Conclusions: Distinguishing between patients with and without PsA based on clinical characteristics is feasible and even predicting future diagnoses of PsA is possible. Patients at higher risk can be identified using important predictors of PsA.

When is a network adequate? consumer perspectives on network adequacy definitions.

OBJECTIVES: Most Americans have insurance that uses managed care arrangements. Regulators have long sought to ensure access to care through network adequacy regulations. However, consumers have largely been excluded from conversations about network adequacy. To our knowledge, our study is the first to assess consumer preferences for various definitions of network adequacy including those aimed at supporting health equity and reducing disparities. STUDY DESIGN: We fielded a large and demographically diverse survey of US adults (N = 4008) from June 30 to July 2, 2023. The survey queried respondents about their perceptions of what adequate provider networks look like in the abstract. METHODS: Analyses were conducted using ordinary least squares regression with survey weights as well as t tests. RESULTS: Consumers were overwhelmingly supportive of standard definitions of adequacy focused on the number of providers and travel distance. Majorities also favored more expansive, health equity-focused definitions such as public transportation access, cultural competency, and lesbian, gay, bisexual, and transgender (LGBT+)-inclusive care. Being a woman; having higher levels of education, worse health, and recent experiences with the medical system; and ease of completing administrative tasks were relatively consistent positive predictors of supporting more expansive definitions. More controversial definitions saw effects of partisanship and LGBT+ identification. Rurality, insurance status, education, and recent experiences with the medical system affected perceptions of reasonable appointment wait times and travel distances. CONCLUSIONS: Our findings indicate that consumers have broad conceptions of network adequacy. Future work should assess consumer trade-offs in resource-constrained settings as well as perceptions of providers and carriers.

Hearing impairment amongst people with Osteogenesis Imperfecta in Germany.

INTRODUCTION: Hearing impairment concerns a relevant percentage of individuals with Osteogenesis Imperfecta (OI). When looking at the current literature, the percentage of affected individuals with OI varies greatly from 32 to 58% of patients having mild OI and 21% to 27% of patients having moderate to severe OI. Little is known about the German population with OI. METHOD: The goal of this study was to detect how many patients with OI, who visited the annual meeting of the German Association for Osteogenesis Imperfecta in 2023, proved to have a hearing impairment. In this prospective, cross-sectional study, each included individual obtained ear microscopy, audiometry, stapedius reflexes, tympanometry, and OAEs. Furthermore, each patient was asked a set of questions concerning the medical history. RESULTS: Of the included patients, 33% had hearing impairment. A significant difference was found for the mean air-bone gap (ABG) as well as the hearing threshold of the right ears. The difference was found between OI type III and IV (p = 0.0127) for the mean ABG and OI type I and IV (p = 0.0138) as well as III and IV (p = 0.0281) for the hearing threshold. Spearman's rank correlation showed a high correlation between age and hearing threshold. Of the patients between 40 and 50 years old, 56% had hearing loss. CONCLUSION: Hearing loss in individuals with OI is still a relevant problem, especially age-related in OI type I. Audiometry should be performed at least when individuals experience subjective hearing loss. The implementation of a screening starting at 40 years should be discussed and studied.

Rapid effects of plastic pollution on coastal sediment metabolism in nature.

While extensive research has explored the effects of plastic pollution, ecosystem responses remain poorly quantified, especially in field experiments. In this study, we investigated the impact of polyester pollution, a prevalent plastic type, on coastal sediment ecosystem function. Strips of polyester netting were buried into intertidal sediments, and effects on sediment oxygen consumption and polyester additive concentrations were monitored over 72-days. Our results revealed a rapid reduction in the magnitude and variability of sediment oxygen consumption, a crucial ecosystem process, potentially attributed to the loss of the additive di(2-ethylhexyl) phthalate (DEHP) from the polyester material. DEHP concentrations declined by 89% within the first seven days of deployment. However, effects on SOC dissipated after 22 days, indicating a short-term impact and a quick recovery by the ecosystem. Our study provides critical insights into the immediate consequences of plastic pollution on ecosystem metabolism in coastal sediments, contributing to a nuanced understanding of the temporal variation of plastic pollution's multifaceted impacts. Additionally, our research sheds light on the urgent need for comprehensive mitigation strategies to preserve marine ecosystem functionality from plastic pollution impacts.

Prevalence and clinical impact of topical corticosteroid phobia among patients with chronic hand eczema-Findings from the Danish Skin Cohort.

BACKGROUND: Topical corticosteroid phobia (TOPICOP) is associated with poor treatment adherence and is common among patients with skin disease. Knowledge about corticosteroid phobia and treatment adherence among patients with chronic hand eczema (CHE) is limited. OBJECTIVES: To investigate patient-reported outcomes regarding topical corticosteroids (TCSs), and their impact on treatment adherence in patients with CHE. METHODS: Patients with CHE from the Danish Skin Cohort answered a questionnaire including the TOPICOP scale and Medication Adherence Report Scale. Response rate was 69.2%. RESULTS: Of 927 with CHE, 75.5% totally or almost agreed that TCS damage the skin, 48.9% totally or almost agreed that TCS would affect their future health and 36.3% reported some degree of fear of TCS although they were unaware of any TCS-associated risks. Most patients (77.9%) always or often stop treatment as soon as possible, whereas 54.8% always or often wait as long as possible before starting treatment. Overall, 38.8% reported that they had taken less medicine than prescribed and 54.0% had stopped treatment throughout a period. Treatment adherence decreased with increasing corticosteroid phobia (P = .004). LIMITATIONS: TOPICOP has not been validated in patients with CHE. CONCLUSIONS: Corticosteroid phobia is common among patients with CHE and negatively associated with treatment adherence.

Emerging Adjuvant Thrombolytic Therapies for Acute Ischemic Stroke Reperfusion.

Thrombolytic therapies for acute ischemic stroke are widely available but only result in recanalization early enough, to be therapeutically useful, in 10% to 30% of cases. This large gap in treatment effectiveness could be filled by novel therapies that can increase the effectiveness of thrombus clearance without significantly increasing the risk of harm. This focused update will describe the current state of emerging adjuvant treatments for acute ischemic stroke reperfusion. We focus on new treatments that are designed to (1) target different components that make up a stroke thrombus, (2) enhance endogenous fibrinolytic systems, (3) reduce stagnant blood flow, and (4) improve recanalization of distal thrombi and postendovascular thrombectomy.

Genome sequence of Heterobasidion occidentale, a fungus that causes annosus root and butt rot among conifer trees in North America.

We report an annotated draft genome of Heterobasidion occidentale, a fungus (Basidiomycota, Agaricomycetes) that has pathogenic and saprophytic lifestyles. This fungus belongs to the H. annosum (Fr.) Bref. sensu lato species complex that comprises several root rot pathogens. Heterobasidion occidentale causes annosus root and butt rot primarily in true fir (Abies spp.) and spruce (Picea spp.) species throughout western North America.

Transradial Transcapitate Perilunotriquetral Coalition Fracture Dislocation.

Perilunate fracture dislocations (PLFDs) are uncommon, usually resulting from high-energy trauma. Several classification systems describe the patterns of injury seen, but there is still significant variation and patterns of injury that do not fit within these classifications continue to be described. Carpal coalitions are rare, mostly asymptomatic, and are, as a result, usually identified incidentally. We describe the case of a transradial transcapitate PLFD in a patient with a Minnaar Type 3 lunotriquetral coalition. Radiographic, clinical, and patient-reported outcomes are reported. When presented with a rare anatomical variation in the context of a complex injury, the importance of managing these complex injuries according to principles is highlighted.

Antithrombotic properties of Tafamidis: An additional protective effect for transthyretin amyloid cardiomyopathy patients.

INTRODUCTION: Tafamidis is a molecular chaperone that stabilizes the transthyretin (TTR) homo-tetramer, preventing its dissociation and consequent deposition as amyloid fibrils in organ tissues. Tafamidis reduces mortality and the incidence of hospitalization for cardiovascular causes in patients with TTR amyloid (ATTR) cardiomyopathy. As ATTR cardiomyopathy is associated with a high risk of thromboembolic complications, we hypothesized that tafamidis may have a direct ancillary anti-thrombotic effect. METHODS: Primary human aortic endothelial cells (HAECs) were treated with tafamidis at clinically relevant concentrations and with plasma of patients, before and after the initiation of treatment with tafamidis. The expression of TF was induced by incubation with Tumor Necrosis Factor α (TNFα). Intracellular expression of tissue factor (TF) was measured by western blot. TF activity was measured by a colorimetric assay. Gene expressions of TF were measured by quantitative polymerase chain reaction. RESULTS: Treatment with tafamidis dose-dependently reduced the expression and activity of TNFα-induced TF. This effect was confirmed in cells treated with patients' plasma. Signal Transducer and Activator of Transcription 3 (STAT3) phosphorylation was significantly inhibited by tafamidis. Incubation of HAECs with tafamidis and the STAT3 activator colivelin partially rescued the expression of TF. CONCLUSIONS: Treatment with tafamidis lowers the thrombotic potential in human primary endothelial cells by reducing TF expression and activity. This previously unknown off-target effect may provide a novel mechanistic explanation for the lower number of thromboembolic complications in ATTR cardiomyopathy patients treated with tafamidis.

Fluoroscopy-only guided transcatheter patent foramen ovale closure: the importance of pre-procedural echocardiography.

Objectives: Percutaneous closure of a patent foramen ovale (PFO) to prevent recurrent paradoxical thromboembolic events has become the standard of care. However, it remains uncertain if transesophageal echocardiography (TOE) guidance improves procedural success with an existing comprehensive pre-procedural TOE. The aim of the study was to compare the effectiveness of percutaneous PFO closure guided by fluoroscopy (FS) only vs TOE plus FS. Methods: Consecutive patients undergoing percutaneous PFO closure between February 2017 and April 2023 were analyzed. Based on pre-procedural echocardiography, patients were scheduled either for an FS-only or TOE/FS-guided procedure. The primary-endpoint was effective PFO-closure (residual-shunt grade 0/1 at 6-month follow-up). The secondary-endpoints included procedural safety/efficacy and major adverse cardiovascular events during hospital stay and at the 6-month follow-up. Results: Two hundred-three patients (mean age 51.8 ± 12.5 years, 39.4% women, Risk of Paradoxical Embolism score = 7 [IQR = 6-7]) underwent PFO closure with FS-only guidance (88 patients, 43.3%) or TOE/FS guidance (115 patients, 56.7%). The main indications for PFO closure were cryptogenic stroke (179 patients, 88.2%) and peripheral embolism (13 patients, 6.4%). At baseline, a right-to-left shunt of grade 2 or higher was present in 199 patients (98%). The procedure time in the FS group was shorter (13 minutes in the FS group vs 16.5 minutes in the TOE/FS group, P = .002). The immediate procedural success was 99.5%. At 6 months, effective closure was achieved in 195 patients (96.1% [FS group: 97.7% vs TOE/FS group 97.8%, P = .29]). The rates of atrial fibrillation and recurrent thromboembolic events were not different among the procedural strategies (3.9% [P = .47] and 0.5% [P = .43]). Conclusions: After comprehensive pre-procedural echocardiography workup, PFO closure with FS guidance only seems equally safe and effective as TOE/FS guidance. A standardized pre-procedural echocardiography protocol facilitates procedural planning with excellent echocardiographic and clinical outcomes.

Refinement of cryo-EM 3D maps with a self-supervised denoising model: crefDenoiser.

Cryogenic electron microscopy (cryo-EM) is a pivotal technique for imaging macromolecular structures. However, despite extensive processing of large image sets collected in cryo-EM experiments to amplify the signal-to-noise ratio, the reconstructed 3D protein-density maps are often limited in quality due to residual noise, which in turn affects the accuracy of the macromolecular representation. Here, crefDenoiser is introduced, a denoising neural network model designed to enhance the signal in 3D cryo-EM maps produced with standard processing pipelines. The crefDenoiser model is trained without the need for `clean' ground-truth target maps. Instead, a custom dataset is employed, composed of real noisy protein half-maps sourced from the Electron Microscopy Data Bank repository. Competing with the current state-of-the-art, crefDenoiser is designed to optimize for the theoretical noise-free map during self-supervised training. We demonstrate that our model successfully amplifies the signal across a wide variety of protein maps, outperforming a classic map denoiser and following a network-based sharpening model. Without biasing the map, the proposed denoising method leads to improved visibility of protein structural features, including protein domains, secondary structure elements and modest high-resolution feature restoration.

Identification of potent and reversible piperidine carboxamides that are species-selective orally active proteasome inhibitors to treat malaria.

Malaria remains a global health concern as drug resistance threatens treatment programs. We identified a piperidine carboxamide (SW042) with anti-malarial activity by phenotypic screening. Selection of SW042-resistant Plasmodium falciparum (Pf) parasites revealed point mutations in the Pf_proteasome ß5 active-site (Pfß5). A potent analog (SW584) showed efficacy in a mouse model of human malaria after oral dosing. SW584 had a low propensity to generate resistance (minimum inoculum for resistance [MIR] >109) and was synergistic with dihydroartemisinin. Pf_proteasome purification was facilitated by His8-tag introduction onto ß7. Inhibition of Pfß5 correlated with parasite killing, without inhibiting human proteasome isoforms or showing cytotoxicity. The Pf_proteasome_SW584 cryoelectron microscopy (cryo-EM) structure showed that SW584 bound non-covalently distal from the catalytic threonine, in an unexplored pocket at the ß5/ß6/ß3 subunit interface that has species differences between Pf and human proteasomes. Identification of a reversible, species selective, orally active series with low resistance propensity provides a path for drugging this essential target.

Multinational Drug Survival Study of Omalizumab in Patients With Chronic Urticaria and Potential Predictors for Discontinuation.

Importance: Treating patients with chronic urticaria using omalizumab has been shown to be safe and effective in randomized clinical trials. Multinational studies on long-term omalizumab performance in chronic urticaria in clinical practice settings are lacking, especially on drug survival. Drug survival, which refers to the length of time that patients are treated with a specific drug, is a comprehensive outcome covering effectiveness, safety, and patient and physician preferences. Furthermore, little is known about the reasons and potential predictors for omalizumab discontinuation. Objective: To investigate omalizumab drug survival as well as reasons and potential predictors for discontinuation in a large, diverse population. Design, Setting, and Participants: This international multicenter cohort study was conducted at 14 Urticaria Centers of Reference and Excellence in 10 countries, including all patients with chronic urticaria from these centers who were ever treated with omalizumab. Main Outcomes and Measures: Drug survival analysis was performed to assess time to discontinuation. Patient characteristics and treatment protocols were investigated by Cox regression analysis to identify potential predictors for omalizumab discontinuation. Results: In 2325 patients with chronic urticaria who started omalizumab between June 2009 and July 2022, the mean (SD) age of the cohort was 42 (6) years, and 1650 participants (71%) were female. Overall omalizumab survival rates decreased from 76% to 39% after 1 to 7 years, respectively (median survival time, 3.3 [95 % CI, 2.9-4.0] years), primarily due to discontinuation from well-controlled disease in 576 patients (65%). Ineffectiveness and adverse effects were reasons for discontinuation in a far smaller proportion of patients, totaling 164 patients (18%) and 31 patients (4%), respectively. Fast treatment response was associated with higher rates of omalizumab discontinuation due to well-controlled disease (hazard ratio, 1.45 [95% CI, 1.20-1.75]), and disease duration of more than 2 years was associated with lower rates of discontinuation due to well-controlled disease (HR, 0.81 [95% CI, 0.67-0.98]). Immunosuppressive cotreatment at the start of omalizumab and autoimmune disease was associated with a higher risk for discontinuation due to ineffectiveness (HR, 1.65 [95% CI, 1.12-2.42]). The presence of spontaneous wheals (HR, 0.62 [95% CI, 0.41-0.93]) and access to higher dosages (HR, 0.40 [95% CI, 0.27-0.58) were both associated with a lower risk for discontinuation of omalizumab due to ineffectiveness. Conclusion and Relevance: This multinational omalizumab drug survival cohort study demonstrated that treatment of chronic urticaria with omalizumab in a clinical setting is effective and safe, and well-controlled disease is the main reason for treatment discontinuation. These findings on omalizumab drug survival rates and reasons and potential predictors for discontinuation may guide patients and physicians in clinical decision-making and expectation management. These results may call for the identification of biomarkers for chronic urticaria remission in complete responders to omalizumab treatment.

Covert actions of epidural stimulation on spinal locomotor circuits.

Spinal circuitry produces the rhythm and patterning of locomotion. However, both descending and sensory inputs are required to initiate and adapt locomotion to the environment. Spinal cord injury (SCI) disrupts descending controls of the spinal cord, producing paralysis. Epidural stimulation (ES) is a promising clinical therapy for motor control recovery and is capable of reactivating the lumbar spinal locomotor networks, yet little is known about the effects of ES on locomotor neurons. Previously, we found that both sensory afferent pathways and serotonin exert mixed excitatory and inhibitory actions on lumbar interneurons involved in the generation of the locomotor rhythm, identified by the transcription factor Shox2. However, after chronic complete SCI, sensory afferent inputs to Shox2 interneurons become almost exclusively excitatory and Shox2 interneurons are supersensitive to serotonin. Here, we investigated the effects of ES on these SCI-induced changes. Inhibitory input from sensory pathways to Shox2 interneurons was maintained and serotonin supersensitivity was not observed in SCI mice that received daily sub-motor threshold ES. Interestingly, the effects of ES were maintained for at least three weeks after the ES was discontinued. In contrast, the effects of ES were not observed in Shox2 interneurons from mice that received ES after the establishment of the SCI-induced changes. Our results demonstrate mechanistic actions of ES at the level of identified spinal locomotor circuit neurons and the effectiveness of early treatment with ES on preservation of spinal locomotor circuitry after SCI, suggesting possible therapeutic benefits prior to the onset of motor rehabilitation.

Putting Health care Where the Kids Are: US Public Attitudes About School-Based Health Centers.

BACKGROUND: School-based health centers (SBHCs) have been shown to offer substantial benefits to students but we know little about how the public thinks about them. We sought to assess US public attitudes about SBHCs and the provision of 7 health service lines-primary care, preventive care, vaccinations, preventive dental care, preventive vision care, mental health care, and nutrition counseling. METHODS: We administered a national online survey (N = 4196) of US adults using Lucid, a large, internet-based, opt-in panel to assess public attitudes about SBHCs as well as 7 commonly offered health services in SBHCs. We then used t-tests and weighted linear regression models to carry out our study objectives. RESULTS: Unadjusted analysis revealed that more than 2 in 3 respondents supported SBHCs in general as well as the provision of all health services in SBHCs. Regression analysis indicated that ideology, partisanship, and trust in public school principals served as consistent predictors of attitudes when controlling for demographic and health characteristics. The provision of vaccinations stood out as particularly controversial. Subanalysis of parents found even higher levels of support as well as a more subdued role of ideology and partisanship. CONCLUSIONS: The US public broadly supports the provision of health services in SBHCs. Our results should inform policymakers, advocates, and providers seeking to improve access to health care among school-aged children, particularly for underserved populations. Increasing knowledge about SBHCs and providing stable funding should be a priority. In the immediate future, SBHCs may offer an important buffer against ongoing Medicaid disenrollments.

Optimal Control of Collective Electrotaxis in Epithelial Monolayers.

Epithelial monolayers are some of the best-studied models for collective cell migration due to their abundance in multicellular systems and their tractability. Experimentally, the collective migration of epithelial monolayers can be robustly steered e.g. using electric fields, via a process termed electrotaxis. Theoretically, however, the question of how to design an electric field to achieve a desired spatiotemporal movement pattern is underexplored. In this work, we construct and calibrate an ordinary differential equation model to predict the average velocity of the centre of mass of a cellular monolayer in response to stimulation with an electric field. We use this model, in conjunction with optimal control theory, to derive physically realistic optimal electric field designs to achieve a variety of aims, including maximising the total distance travelled by the monolayer, maximising the monolayer velocity, and keeping the monolayer velocity constant during stimulation. Together, this work is the first to present a unified framework for optimal control of collective monolayer electrotaxis and provides a blueprint to optimally steer collective migration using other external cues.

Tumour necrosis is a valuable histopathological prognostic parameter in melanomas of the vulva and vagina.

Vulvar and vaginal melanomas (VVMs) are rare and aggressive malignancies with limited prognostic models available and there is no standard reporting protocol. VVMs were selected from six tertiary Canadian hospitals from 2000-2021, resected from patients aged ≥18 years, with 6 months or longer follow-up data, and confirmation of melanocytic differentiation by at least two immunohistochemical markers. Cases were reviewed by pathologists to identify histological biomarkers. Survival outcomes were tested with Kaplan-Meier log-rank, univariate Cox, and multivariate Cox regression. There were 79 VVMs with median follow-up at 26 months. Univariate analysis revealed that tumour necrosis, tumour ulceration, positive lymph nodes, and metastasis at diagnosis were significantly associated with disease-specific mortality, progression, and metastasis. Multivariate analysis identified tumour necrosis as an independent prognostic factor for disease-specific mortality (HR 4.803, 95% CI 1.954-11.803, p<0.001), progression (HR 2.676, 95% CI 1.403-5.102, p=0.003), and time-to-metastasis for non-metastatic patients at diagnosis (HR 3.761, 95%CI 1.678-8.431, p=0.001). Kaplan-Meier survival analyses demonstrated that tumour necrosis was a poor prognostic factor for disease-specific, progression-free, and metastasis-free survival (p<0.001 for all comparisons). Vaginal melanomas displayed decreased survival compared to vulvar or clitoral melanomas. This study identifies tumour necrosis as an independent prognostic factor for VVMs. Vaginal melanomas specifically showed worse survival outcomes compared to vulvar or clitoral melanomas, consistent with previously reported findings in the literature, emphasising the importance of differentiating between these primary tumour epicentres for prognostication and treatment planning in the care of genital melanoma patients.