Imperial College Healthcare NHS Trust

Objective. Vulvar squamous cell carcinoma (VSCC) can be either HPV-dependent (HPVd) or HPV-independent (HPVi). HPVd VSCC typically occurs in younger women, has a more favorable prognosis, and develops from high-grade squamous intraepithelial lesions (HSIL). HPVi VSCC predominantly affects older women and arises within areas of chronic inflammation, particularly lichen sclerosis (LS). We utilized sequencing-based spatial transcriptomics to explore gene expression in a cohort of patients with HPVi and HPVd VSCC. Methods. We analysed gene expression in distinct areas (SCC, inflammation, LS, HSIL) from four early-stage VSCC cases (two HPVi, two HPVd) using the 10× Genomics Visium spatial transcriptomics platform. Cell-specific type expression was inferred using CIBERSORTx. Results. 28,183 Visium spots were detected; each contained an estimated 20-50 cells. Reads per spot ranged from 9903 to 68,527. More genes were upregulated in HPVd (N = 601) than HPVi (N = 72) with distinct differences in Keratin and Collagen genes between etiologies. Gene expression was strikingly similar between SCC and adjacent inflammatory areas, regardless of etiology. IL-17 signaling was upregulated in HPVd samples. Surprisingly , CIBERSORTx inferred significantly more CD45+ cells in HPVi tissues than HPVd, especially CD4+ resting memory and follicular helper T cells in SCC areas. Immune cells moved from resting states in the pre-invasive tissues to activated states in the SCC and peri-tumoral inflammatory area s. Conclusions. This study represents the first application of spatial transcriptomics in VSCC, with significantly more immune cells identified in HPVi SCC than in HPVd SCC. These data will act as a baseline for future studies.

Background The insertion of a tracheostomy is an established technique used to wean patients off ventilatory support, manage secretions in complex conditions, and as a potentially life-saving procedure to bypass upper airway obstruction. Life-threatening complications during aftercare are not uncommon and may be influenced by a lack of education of carers or healthcare providers of children and young people living with a tracheostomy. Education programmes designed and supported by the National Tracheostomy Safety Project are effective, but resources are not available to educate the workforce at scale. With the overarching aim of widening access to paediatric tracheostomy skills training, we present the protocol for the development and evaluation of a novel virtual reality (VR) training tool designed to simulate the emergency management of paediatric tracheostomy complications. Methods and discussion A multi-centre, non-inferiority educational interventional study with historical controls will be used to evaluate the novel VR training package. A group of 69 healthcare staff and students will have one week to use the educational intervention as often as necessary to learn paediatric emergency tracheostomy skills. The primary outcome measure is skill performance in simulation in a pre- and post-intervention structure within subjects. Participant performance will also be assessed using non-inferiority metrics against historical traditional educational control data. Secondary outcomes include knowledge gain, knowledge retention, usability, side effects, and participant satisfaction. To minimise the risk of cybersickness, teleportation was the preferred locomotion method for the user navigation within the VR environment. Trial registration Full registration of this study was completed at ClinicalTrials.gov. The registration number is NCT06350708 and was accepted on the 4th April 2024.

We report a 31-year-old man with diarrhea and tachycardia. Diagnostic workup confirmed raised free thyroid hormones with unsuppressed thyroid stimulating hormone (TSH). Laboratory assay and medication interference were excluded. Consistent with a high glycoprotein hormone α-subunit (α-GSU), the α-GSU:TSH molar ratio was increased. However, anterior pituitary panel testing also confirmed an isolated, raised follicle stimulating hormone (FSH) (17.3 IU/L; reference range, 1.7-8.0). Therefore, interpretation of α-GSU was limited given the co-existent elevated FSH. There was no pituitary lesion on magnetic resonance imaging (MRI) and stimulated TSH was 232% of baseline levels following thyrotropin-releasing hormone (TRH) stimulation, making a diagnosis of TSH-oma less likely. Genetic analysis revealed no pathogenic variants in the thyroid hormone receptor β gene. Due to the persistently elevated FSH, a follow-up pituitary MRI was arranged, which identified a nasopharyngeal mass on the floor of the sphenoid sinus, raising the possibility of ectopic pituitary tissue. The patient underwent endoscopic resection of this lesion, with subsequent normalization of free T4, TSH, and FSH within a few weeks. Histology confirmed a plurihormonal pituitary adenoma with staining for TSH, growth hormone, luteinizing hormone, and FSH. This case highlights the biochemical and radiological challenges of diagnosing ectopic TSH-secreting pituitary tumors.

Computer-assisted surgery is becoming essential in modern medicine to accurately plan, guide, and perform surgeries. Similarly, Digital Twin technology is expected to be instrumental in the future of surgery, owing to its capacity to virtually replicate patient-specific interventions whilst providing real-time updates to clinicians. This perspective introduces the term Digital Twin-Assisted Surgery and discusses its potential to improve surgical precision and outcome, along with key challenges for successful clinical translation.

Aims Outcome in pulmonary arterial hypertension (PAH) is determined by right ventricular (RV) function adaptation to increased afterload. Echocardiography is easily available to assist bedside evaluation of the RV. However, no agreement exists about the feasibility and most relevant measurements. We therefore examined the feasibility, quality, and clinical correlations of standard echocardiographic variables in the evaluation of PAH. Methods and results The present multicentric study collected echocardiographic examinations with centralized reading in 401 patients with prevalent PAH. Clinical variables, as World Health Organization (WHO) functional class (FC), 6 min walk distance (6MWD), brain natriuretic peptide (BNP)/NT-proBNP, invasive haemodynamics, the European Society of Cardiology (ESC)/European Respiratory Society (ERS) guidelines-derived four-strata score, and the United States Registry to Evaluate Early and Long-Term Pulmonary Arterial Hypertension Disease Management (REVEAL) 2.0 score, were also collected. Echocardiographic measurements showed variable degrees of dilation of the right heart as assessed by right atrial and RV areas, altered indices of systolic function such as tricuspid annular plane systolic excursion (TAPSE), fractional area change, or 2D strain, and derived estimates of RV to pulmonary artery (PA) coupling by referring these measurements to systolic PA pressure (sPAP). All these measurements were feasible. All measurements of right heart dimensions and function, particularly TAPSE/sPAP, were correlated with WHO-FC, 6MWD, BNP/NT-proBNP, invasive haemodynamics, and ESC/ERS and REVEAL 2.0 scores. Conclusion The present quality-controlled data from a network of PAH referral centres offer the background needed for further evaluation of the added value of echocardiography to currently recommended risk assessments in PAH.

Background Although mechanical thrombectomy (MT) represents the standard of care for ischemic stroke due to large‐vessel occlusion (LVO), the impact of sex on outcomes in tandem occlusions remains unclear. We investigated sex‐based differences in outcomes after MT for tandem occlusions. Methods This multicenter observational study included consecutive patients with tandem occlusion treated with MT across three stroke centers (2021–2023). Propensity score matching was performed. Primary outcomes were the 90‐day favorable functional outcome (mRS 0–2) and mRS score shift. Secondary outcomes included favorable recanalization, 24‐h early neurological improvement, and NIHSS median score. Safety outcomes were post‐MT intracerebral hemorrhage and 90‐day mortality. Results Of 635 patients (46.8% women), 289 women were matched to 289 men. There were no significant differences in primary, secondary, or safety outcomes between sexes. Subgroup analysis showed a lower rate of favorable 90‐day mRS scores in women with diabetes compared to men. Women not receiving emergent carotid treatment had higher rates of favourable outcomes. No significant sex differences were found in other subgroups. Conclusions Women with anterior circulation tandem occlusions treated with MT have similar outcomes to men. However, women with diabetes and those treated with intracranial MT alone exhibited sex‐specific differences. Further studies are needed to explore underlying mechanisms.

Guidance for venous leg ulceration (VLU) recommends compression therapy and early referral for specialist vascular assessment within two weeks. Few patients receive timely assessment and referral. Reasons for this are unclear. The aim of this work was to explore nurses' perceptions of the barriers and facilitators to early assessment of VLU and referral for specialist treatment. One‐to‐one semi‐structured interviews explored experiences caring for and referring patients with VLU to a vascular specialist. Maximum variation sampling and inductive thematic analysis were used. Eighteen nurses participated. Findings suggest junior nurses lack knowledge and confidence to care for VLU and often revert to a ‘task‐based’ approach, exacerbated by staff shortages and limited training. Because VLU occurs in the context of competing conditions and pressures, comprehensive assessments are missed, and the need for referral is not established or prioritised. Supporting patients to self‐manage is seen as a possible solution. Nurses reported disjointed pathways between primary and secondary care, compounded by poor MDT collaboration, ineffective communication systems and inadequate data sharing. Consequently, when the need for referral is established, communicating this between healthcare organisations is complex. Organisational and behavioural barriers impact nurses' ability to promote timely referral. Further exploration with patients and other healthcare professionals is needed.

Objective To provide up-to-date European Society of Urogenital Radiology (ESUR) guidelines for staging and follow-up of patients with ovarian cancer (OC). Methods Twenty-one experts, members of the female pelvis imaging ESUR subcommittee from 19 institutions, replied to 2 rounds of questionnaires regarding imaging techniques and structured reporting used for pre-treatment evaluation of OC patients. The results of the survey were presented to the other authors during the group’s annual meeting. The lexicon was aligned with the Society of American Radiology (SAR)-ESUR lexicon; a first draft was circulated, and then comments and suggestions from the other authors were incorporated. Results Evaluation of disease extent at diagnosis should be performed by chest, abdominal, and pelvic CT. The radiological report should map the disease with specific mention of sites that may preclude optimal cytoreductive surgery. For suspected recurrence, CT and [ ¹⁸ F]FDG PET-CT are both valid options. MRI can be considered in experienced centres, as an alternative to CT, considering the high costs and the need for higher expertise in reporting. Conclusions CT is the imaging modality of choice for preoperative evaluation and follow-up in OC patients. A structured radiological report, including specific mention of sites that may preclude optimal debulking, is of value for patient management. Key Points Question Guidelines were last published for ovarian cancer (OC) imaging in 2010; here, guidance on imaging techniques and reporting, incorporating advances in the field, are provided. Findings Structured reports should map out sites of disease, highlighting sites that limit cytoreduction. For suspected recurrence, CT and 18FDG PET-CT are options, and MRI can be considered. Clinical relevance Imaging evaluation of OC patients at initial diagnosis (mainly based on CT), using a structured report that considers surgical needs is valuable in treatment selection and planning.

Background We report our experience of patients with generalised myasthenia gravis (gMG) treated with efgartigimod, an neonatal Fc receptor antagonist, under the Early Access to Medicine Scheme (EAMS) in the UK. Methods Data from all UK patients treated with efgartigimod under the EAMS July 2022 to July 2023 were collected retrospectively. Efgartigimod was administered as per the ADAPT protocol (consisting of a treatment cycle of four infusions at weekly intervals with further cycles given according to clinical need). Results 48 patients with acetylcholine receptor antibody-positive gMG were treated in 12 centres. Most (75%) were female and most had a disease duration of over 10 years. The average MG-Activities of Daily Living (ADL) score at baseline was 11.2. Most (72.9%) patients had undergone thymectomy. 77.0% were taking prednisolone at baseline. All patients had used non-steroidal immunosuppressant treatments, the average number tried was 2.6 (range 1–6). 51% had received rituximab. 54.2% of patients required regular intravenous immunoglobulin/plasma exchange. 75% of patients had a mean reduction in the MG-ADL of≥2 points in the first cycle and this remained stable throughout the study. The mean intracycle reduction in the MG-ADL score in the first, second, third and fourth cycles were −4.6 to –3.9, −3.4 and −4.2, respectively. Side effects were generally mild. No rescue treatments were required. At the end of the study, 96% of patients remained on efgartigimod. Conclusion Efgartigimod is a safe and effective treatment for patients with refractory, treatment-resistant gMG.

Commutability is where the measurement response for a reference material (RM) is the same as for an individual patient sample with the same concentration of analyte measured using two or more measurement systems. Assessment of commutability is essential when the RM is used in a calibration hierarchy or to ensure that clinical measurements are comparable across different measurement procedures and at different times. The commutability of three new Standard Reference Materials ® (SRMs) for determining serum total 25-hydroxyvitamin D [25(OH)D], defined as the sum of 25-hydroxyvitamin D 2 [25(OH)D 2 ] and 25-hydroxyvitamin D 3 [25(OH)D 3 ], was assessed through an interlaboratory study. The following SRMs were assessed: (1) SRM 2969 Vitamin D Metabolites in Frozen Human Serum (Total 25-Hydroxyvitamin D Low Level), (2) SRM 2970 Vitamin D Metabolites in Frozen Human Serum (25-Hydroxyvitamin D 2 High Level), and (3) SRM 1949 Frozen Human Prenatal Serum. These SRMs represent three clinically relevant situations including (1) low levels of total 25(OH)D, (2) high level of 25(OH)D 2 , and (3) 25(OH)D levels in nonpregnant women and women during each of the three trimesters of pregnancy with changing concentrations of vitamin D-binding protein (VDBP). Twelve laboratories using 17 different ligand binding assays and eight laboratories using nine commercial and custom liquid chromatography–tandem mass spectrometry (LC–MS/MS) assays provided results in this study. Commutability of the SRMs with patient samples was assessed using the Clinical and Laboratory Standards Institute (CLSI) approach based on 95% prediction intervals or a pre-set commutability criterion and the recently introduced International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) approach based on differences in bias for the clinical and reference material samples using a commutability criterion of 8.8%. All three SRMs were deemed as commutable with all LC–MS/MS assays using both CLSI and IFCC approaches. SRM 2969 and SRM 2970 were deemed noncommutable for three and seven different ligand binding assays, respectively, when using the IFCC approach. Except for two assays, one or more of the three pregnancy levels of SRM 1949 were deemed noncommutable or inconclusive using different ligand binding assays and the commutability criterion of 8.8%. Overall, a noncommutable assessment for ligand binding assays is determined for these SRMs primarily due to a lack of assay selectivity related to 25(OH)D 2 or an increasing VDBP in pregnancy trimester materials rather than the quality of the SRMs. With results from 17 different ligand binding and nine LC–MS/MS assays, this study provides valuable knowledge for clinical laboratories to inform SRM selection when assessing 25(OH)D status in patient populations, particularly in subpopulations with low levels of 25(OH)D, high levels of 25(OH)D 2 , women only, or women who are pregnant. Graphical Abstract

Background The hippocampus is a key site of atrophy in Alzheimer’s disease (AD) and MRI derived estimates of hippocampal volume have been shown to be a robust biomarker of AD‐related neurodegeneration. However, its application at the individual level is limited by the lack of reference standards from large normative datasets that can be applied across a wide range of settings. We aimed to investigate the utility of hippocampal volume centile scores adjusted for age, sex and total intracranial volume (TIV) derived from a normative data from 101,457 participants across the life course, as a biomarker of neurodegeneration in AD. Methods BrainChart calculates age and sex adjusted centile scores for structural MRI metrics using a GAMLSS (Generalised Additive Models for Location Scale and Shape) approach and can be applied to individual datasets using an out‐of‐sample centile scoring approach that calculates study‐specific offsets (Bethlehem, Seidlitz, White et al. Nature 2022). Using this approach, we developed models for Freesurfer derived estimates of hippocampal volume additionally incorporating TIV as a co‐variate. This was then applied to 351 individuals with pathologically confirmed AD (median scan time prior to death 5.9 years) from the NACC dataset, as well as 110 amyloid‐PET positive patients from the ADNI‐3 cohort (MCI n=71, AD dementia n=39). Wilcoxon rank‐sum tests were used to assess differences between patient groups and cognitively normal controls from the relevant datasets. Spearman’s rank correlations were used to assess relationships with cognition (MMSE score). Results Median centile scores were reduced in all patient groups (pathologically confirmed AD cases left = 0.13, right =0.13; amyloid‐PET positive MCI cases left=0.12, right=0.16; and amyloid‐PET positive AD dementia left=0.01, right=0.02). This was significantly different to cognitively normal controls from both the NACC dataset (n=1400, cases left=0.52, right=0.52) and ADNI‐3 dataset (n=247, cases left=0.50, right=0.50), all to a significance level of p<0.0001. Hippocampal centile scores strongly predicted MMSE score in both cohorts (Spearmans’ Rho range 0.37‐0.41, p<0.001). Conclusion BrainChart age, sex and TIV adjusted hippocampal volume centile scores, derived from an extensive normative dataset, represent a method for objectively identifying neurodegeneration in AD that is interpretable at the individual level.

Background The administration of blood components and their alternatives can be lifesaving. Anaemia, bleeding and transfusion are all associated with poor peri‐operative outcomes. Considerable changes in the approaches to optimal use of blood components and their alternatives, driven by the findings of large randomised controlled trials and improved haemovigilance, have become apparent over the past decade. The aim of these updated guidelines is to provide an evidence‐based set of recommendations so that anaesthetists and peri‐operative physicians might provide high‐quality care. Methods An expert multidisciplinary, multi‐society working party conducted targeted literature reviews, followed by a three‐round Delphi process to produce these guidelines. Results We agreed on 12 key recommendations. Overall, these highlight the importance of organisational factors for safe transfusion and timely provision of blood components; the need for protocols that are targeted to different clinical contexts of major bleeding; and strategies to avoid the need for transfusion, minimise bleeding and manage anticoagulant therapy. Conclusions All anaesthetists involved in the care of patients at risk of major bleeding and peri‐operative transfusion should be aware of the treatment options and approaches that are available to them. These contemporary guidelines aim to provide recommendations across a range of clinical situations.

Infertility affects one-in-six couples, often necessitating in vitro fertilization treatment (IVF). IVF generates complex data, which can challenge the utilization of the full richness of data during decision-making, leading to reliance on simple ‘rules-of-thumb’. Machine learning techniques are well-suited to analyzing complex data to provide data-driven recommendations to improve decision-making. In this multi-center study (n = 19,082 treatment-naive female patients), including 11 European IVF centers, we harnessed explainable artificial intelligence to identify follicle sizes that contribute most to relevant downstream clinical outcomes. We found that intermediately-sized follicles were most important to the number of mature oocytes subsequently retrieved. Maximizing this proportion of follicles by the end of ovarian stimulation was associated with improved live birth rates. Our data suggests that larger mean follicle sizes, especially those >18 mm, were associated with premature progesterone elevation by the end of ovarian stimulation and a negative impact on live birth rates with fresh embryo transfer. These data highlight the potential of computer technologies to aid in the personalization of IVF to optimize clinical outcomes pending future prospective validation.

Although the key aspects of genetic evolution and their clinical implications in clear-cell renal cell carcinoma (ccRCC) are well documented, how genetic features coevolve with the phenotype and tumor microenvironment (TME) remains elusive. Here, through joint genomic–transcriptomic analysis of 243 samples from 79 patients recruited to the TRACERx Renal study, we identify pervasive nongenetic intratumor heterogeneity, with over 40% not attributable to genetic alterations. By integrating tumor transcriptomes and phylogenetic structures, we observe convergent evolution to specific phenotypic traits, including cell proliferation, metabolic reprogramming, and overexpression of putative cGAS–STING repressors amid high aneuploidy. We also uncover a coevolution between the tumor and the T-cell repertoire, as well as a longitudinal shift in the TME from an antitumor to an immunosuppressive state, linked to the acquisition of recurrently late ccRCC drivers 9p loss and SETD2 mutations. Our study reveals clinically relevant and hitherto underappreciated nongenetic evolution patterns in ccRCC. Significance Using joint genomic–transcriptomic analysis of 243 samples, we reveal recurrent patterns of nongenetic evolution in ccRCC not exclusively governed by genetic factors, including T-cell depletion, tumor T-cell receptor coevolution, potential cGAS–STING repression, and increased cell proliferation. These patterns can aid clinical management and guide novel treatment approaches.

Artificial Intelligence (AI) assists recruiting and job searching. Such systems can be biased against certain characteristics. This results in potential misrepresentations and consequent inequalities related to people with mental health disorders. Hence occupational and mental health bias in existing Natural Language Processing (NLP) models used in recruiting and job hunting must be assessed. We examined occupational bias against mental health disorders in NLP models through relationships between occupations, employability, and psychiatric diagnoses. We investigated Word2Vec and GloVe embedding algorithms through analogy questions and graphical representation of cosine similarities. Word2Vec embeddings exhibit minor bias against mental health disorders when asked analogies regarding employability attributes and no evidence of bias when asked analogies regarding high earning jobs. GloVe embeddings view common mental health disorders such as depression less healthy and less employable than severe mental health disorders and most physical health conditions. Overall, physical, and psychiatric disorders are seen as similarly healthy and employable. Both algorithms appear to be safe for use in downstream task without major repercussions. Further research is needed to confirm this. This project was funded by the London Interdisciplinary Social Science Doctoral Training Programme (LISS-DTP). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Introduction Peri‐operative allogeneic red blood cell transfusion is hypothesised to increase the risk of cancer recurrence following cancer surgery. However, previous data supporting this association are limited by residual confounding. We conducted an umbrella review (i.e. a systematic review of systematic reviews) to synthesise and evaluate the evidence between red blood cell transfusion and cancer recurrence. Methods We searched online databases for systematic reviews of red blood cell transfusion and cancer‐related outcomes. The AMSTAR 2 tool was used for quality assessment. The adequacy of confounding adjustment was judged according to a consensus‐derived framework. Results We included five relevant systematic views which included patient populations ranging from 2110 to 184,190. Two reviews reported cancer recurrence, and all reported an association with red blood cell transfusion. Three reviews reported positive associations between red blood cell transfusion and adverse outcomes including all‐cause mortality, recurrence‐free survival and cancer‐related mortality. According to AMSTAR 2, four reviews were rated as ‘critically low quality’ and one as ‘low quality’. There was variation in how systematic reviews assessed the risk of bias from confounding. Compared with our pre‐derived framework, we found a high likelihood of unmeasured confounding. Discussion Currently available evidence describes an association between peri‐operative red blood cell transfusion and cancer recurrence, but this is mostly of low to critically low quality, with minimal control for residual confounding. Further research, at low risk of bias, is required to provide definitive evidence and inform practice.

Background Limited data exist on the impact of polyvascular disease (PolyVD) on clinical outcomes in female patients undergoing transcatheter aortic valve replacement (TAVR). We therefore sought to investigate clinical outcomes in women with versus without PolyVD undergoing TAVR. Methods Female participants from the multicentre Women's International Transcatheter Aortic Valve Implantation (WIN‐TAVI) registry were categorized based on the presence or absence of PolyVD. The PolyVD population was defined as the presence of atherosclerotic disease affecting ≥ 2 arterial systems from coronary, cerebral, or lower limb peripheral vessels, whilst patients with either no atherosclerosis or atherosclerotic disease in one vascular system were included in the non‐PolyVD population. The primary endpoint was the Valve Academic Research Consortium‐2 consensus (VARC‐2) efficacy endpoint at 1 year, whilst secondary endpoints included VARC‐2 safety events, VARC‐2 major bleeding and major vascular complications. Cox regression analysis were computed adjusting for various cofounders. Results Among 996 participants, 543 (54.5%) had PolyVD, while 453 (45.5%) did not. Across the subgroups no differences in age was noted, whilst patients with PolyVD were more likely to have a history of hypercholesterolemia and a previous cardiac surgery. The incidence of the primary endpoint was higher in the PolyVD group (19.4%) compared to the non‐PolyVD group (13.3%, p log‐rank = 0.014), though the difference was attenuated after multivariable adjustments ( p = 0.093). Of note, no statistically significant differences concerning incident VARC‐2 safety events, VARC‐2 major bleeding and major vascular complications were noted according to PolyVD status. Conclusion PolyVD is a common comorbidity and is associated with elevated rates of adverse clinical events, but no increase in safety events, vascular complications, or bleeding among women undergoing TAVR.

Background and Purpose Embolization is the first-line treatment for dural arteriovenous fistulas (dAVF). The precipitating hydrophobic injectable liquid (PHIL) embolic agent is a non-adhesive copolymer with specific features and endovascular behavior. This study assessed its safety and efficacy in a prospective real-life cohort. Methods The PHIL-dAVF study was a prospective single-arm open-label observational multicenter study conducted between October 2017 and November 2019 in 14 European centers. Patients with a single intracranial dAVF intended for PHIL embolization were included. Previously partially treated or multiple dAVFs were excluded. Additional devices and embolic agents were permitted as complementary techniques or second-line strategies. Primary endpoints were functional outcome changes from baseline and complete cure rate at 3–6 months after the last embolization. Safety was assessed by adverse events (AE) incidence. Results A total of 67 patients (77 endovascular procedures; 70.1% men, mean age 61±14 years) were included. Most DAVFs were unruptured (71.6%), located in the transverse/sigmoid sinus (53.7%) and Cognard grade III or IV (56.7%). Sixty patients (89.6%) received one single embolization. Additional devices were used in 31.2% of procedures. Complete angiographic cure rate was 86.9% at the 3–6 month DSA follow-up after the last endovascular treatment. At least one AE was recorded in 37.3% of patients during follow-up, of which 52.9% were related to the procedure. The procedural rates of AE and serious AE were 32.5% and 15.6%, respectively. Five AEs were related to PHIL. Transient functional deterioration occurred in three patients (4.5%), all resolved by the last follow-up. Conclusion The PHIL-dAVF study provides evidence about the efficacy and safety of PHIL in the treatment of intracranial dAVFs, with outcomes comparable to existing liquid embolic agents reported in the literature.