Citations

Abstract Purpose Although the Woven EndoBridge (WEB) device is increasingly used for the treatment of wide-neck intracranial aneurysms, including in the acute rupture setting, comparative evidence assessing the impact of rupture status remains limited. This study compared angiographic, safety, and clinical outcomes between ruptured and unruptured intracranial aneurysms treated with WEB. Methods We conducted a retrospective analysis of prospectively collected data from the multicenter cohort registry WorldWideWEB, including consecutive adult patients with intracranial aneurysms treated with the WEB. Patients were stratified into groups of ruptured and unruptured aneurysms. Propensity score matching was used to balance baseline characteristics between both groups. Retreatment rate was the primary outcome. Secondary outcomes included mRS, safety events (thromboembolic complications) and angiographic outcomes (periprocedurally and last follow-up). Results Among 1,220 patients, 342 (28.0%) presented with ruptured aneurysms. There was no significant difference in the rate of thromboembolic complications between groups (11.8% vs 5.9%, p = 0.056). At follow-up, adequate occlusion was lower (82.2% vs 93.3%, p < 0.002) and functional outcomes were worse (mRS ≥2 in 34.1% vs 21.9%, p = 0.012) among patients with ruptured aneurysms. Periprocedural adequate occlusion (53.3% vs 53.8%, p>0.9) and retreatment rates (11.8% vs 7.1%, p = 0.14) did not differ between groups after matching. Conclusion Ruptured aneurysms demonstrated expected inferior follow-up functional and angiographic outcomes when compared with unruptured aneurysms, but no difference in retreatment rate and procedural safety. These findings support WEB as a safe and effective treatment option for appropriately selected ruptured intracranial aneurysms in routine clinical practice.

Abstract Objectives Dravet syndrome (DS) is a drug‐resistant developmental and epileptic encephalopathy, often requiring three or more antiseizure medications (ASMs). Consequently, the therapeutic landscape is highly complex, combining DS‐specific agents (stiripentol, STP; cannabidiol, CBD; fenfluramine, FFA), non‐specific ASMs, and non‐pharmacologic options such as dietary therapy or neuromodulation. In addition, recognition of patients' changing needs across the lifespan, together with the essential contribution of caregiver education to effective treatment oversight—including awareness of potential drug–drug interactions and adverse events—emphasizes the value of an integrated and forward‐looking approach. A consensus initiative was developed to guide clinicians in the management of patients with DS, with a particular focus on STP‐containing regimens. Methods Based on a literature review and clinical vignette discussions, a nominal group of five international DS experts developed 38 statements across six themes: (i) general principles, (ii) guiding physicians to empower families, (iii) STP as add‐on to specific and non‐specific Dravet ASMs, (iv) FFA in regimens containing STP, (v) CBD in regimens containing STP, and (vi) patient follow‐up during treatment initiation. Statements were scored on a 9‐point Likert scale (1 = strongly disagree, 9 = strongly agree) first by the nominal group and then by an international panel of 59 DS clinicians. Consensus was defined as ≥75% rating ≥7 and/or a median ≥8. Results Thirty‐four of the 38 statements (89%) reached consensus among both the nominal group and the international panel; one did not reach consensus in either, and three reached consensus only among the nominal group. Both panels agreed on the importance of involving families in treatment decisions and follow‐up, as well as on key aspects of polytherapy management, including ASM initiation, treatment adjustments, and adverse event management. Significance This international consensus integrates evidence and clinical expertise to establish shared principles that address a long‐standing gap in the polytherapeutic management of Dravet syndrome. Plain Language Summary Dravet syndrome is a rare and severe form of epilepsy that begins in early childhood, with seizures that often persist throughout life. Because the disease is highly drug resistant, most patients are treated with polytherapy, making clinical management complex for clinicians. This consensus brings together published evidence and expert experience to provide practical guidance on the management of polytherapy in Dravet syndrome, supporting clinicians in optimizing patient care.

Abstract Radiotherapy is an established treatment for low-grade primary cutaneous B-cell lymphoma. Recommendations on its use differ internationally, which prompted our group to conduct this analysis. Twenty-two institutions participated in this international study. Patient eligibility required a diagnosis of limited (T1/T2) primary cutaneous marginal zone or follicle center lymphoma treated with radiotherapy between 1995 and 2023. Data were collected retrospectively until February 2024 within the framework of the International Lymphoma Radiation Oncology Group. Overall, 535 patients were analyzed. Predominant locations were the head (40%) and trunk (36%). Radiotherapy had a median dose of 24 Gy in fractions of 2 Gy. Complete responses were observed in 91% at a median time of 3.6 months following radiotherapy. There was no statistically significant difference between treatments ≤4 Gy and &gt;4 Gy for complete or overall response rates (P = .077 and P = .056, respectively). However, there was an inferior duration of local control with ≤4 Gy (5-year local control 73% ± 12% vs 96% ± 2%; P&lt; .001). Radiation dose was the main prognostic factor in the univariate and multivariable Cox analysis; however, higher doses did not translate into an overall survival benefit. Toxicities rarely exceeded grade 2 but were more frequent in the &gt;4 Gy group. Radiotherapy remains an effective treatment option for indolent skin lymphoma with low toxicity. High response rates are observed with low doses of ≤4 Gy. In comparison to conventional doses, these treatments have a shorter duration of local control but a favorable toxicity profile.

Abstract One of the most significant unmet clinical challenges in paediatric oncology is the development of novel therapeutic strategies for recurrent medulloblastoma (R-MB). MYC-driven MBs are defined as classically cold tumours with a low incidence of infiltrating immune cells, resulting in a therapeutic challenge. The identification of cell-cell interactions between tumour and immune cells may provide insight into critical intercellular communications and manipulations occurring within the tumour immune microenvironment (TME). We hypothesised that the key cell-cell interactions in MYC-driven primary and recurrent MB may reveal dominant immune-suppressive mechanisms and uncover targetable therapeutic vulnerabilities. Paired primary-recurrent bulk RNA-sequencing data, confirmed myeloid cells as the most infiltrating immune cell type in group3-MB and group4-MB. Comprehensive spatial phenotypic and cell-cell communication analyses corroborated this discovery, validating an increased incidence of macrophages in the matched-recurrent tumours. Subsequently, we used innovative algorithms for 10X MB single-cell data to predict interactions between tumour-cell ligands and immune-cell receptors within the TME; macrophages emerged as the core immune-cells involved in interactions throughout the TMEs, with the most significant ligand-receptor interaction and inflammatory response between MIF and CD74. In-depth immunohistochemistry analyses of primary and recurrent group3 and group4 tumours, and exhaustive tissue microarrays demonstrated expression of both CD74 and MIF, with limited expression of CD74 within the brain. To investigate the therapeutic potential of CD74, we developed recurrent, immune competent MYC-driven medulloblastoma mouse models. Comprehensive deconvolution analysis confirmed the TME integrity of our models to mirror that of the human disease. Locoregional delivery and repeat dosing of a bioactive-CD74 peptide demonstrated complete tumour clearance in our immune-competent mouse models of primary and recurrent MB, demonstrating the significant therapeutic potential of targeting the CD74-MIF axis in MYC-driven primary and recurrent MB. Key cellular interactions and therapeutic vulnerabilities within the tumour microenvironment of MYC-driven medulloblastoma (MB) have been identified, highlighting the CD74-MIF axis as a target for next-generation immunotherapies.

Abstract Background Hydrocephalus, the abnormal buildup of cerebrospinal fluid (CSF) in the brain’s ventricles, makes pediatric neurosurgery difficult. Endoscopic Third Ventriculostomy (ETV) and Ventriculoperitoneal Shunting (VPS) are the basic treatments, however unsuccessful ETV management is disputed. This study aims to compare RE-ETV with VPS in pediatric hydrocephalus patients after unsuccessful ETV. Methods A comprehensive literature review was performed using PubMed, Embase, and Cochrane Library. The review covered pediatric RE-ETV or VPS trials following ETV failure. Success rates, complications, failure timings, and reoperation rates were extracted. The Cochrane Collaboration’s risk of bias instrument (RoB 2.0) and Critical Appraisal Skills Programme (CASP) were utilized to assess quality of studies. Results 40 articles were chosen for comprehensive full-text evaluation. Nine publications specifically addressing the topic of Re-ETV and/or VPS placement after the failure of original ETV were identified as acceptable for the review. A data set of 663 patients was assessed. Re-ETV was carried out in 220 patients (33.18%) and VPS Placement was done in 443 patients (66.81%). The primary ETV failure rates ranged from 16.6% to 60.89%. There was a larger failure rate of Re-ETV (74.98%) compared to VPS (22.26%) showing that VPS is often more effective as a secondary intervention. The presence of bleeding during primary ETV suggested more benefit from VPS placement rather than Re-ETV (p &lt; 0.05). Conclusions VPS is more commonly employed than RE-ETV in pediatric patients after unsuccessful ETV. Although RE-ETV provides a less invasive technique, it has a greater failure rate. However, owing to inadequate evidence on VPS failure post-ETV, additional research is recommended. Future research should concentrate on enhancing the evidence foundation to aid clinical decision-making in treating hydrocephalus post-ETV failure.

Abstract As a group of diverse co-authors working in the fields of clinical radiology and oncology, we have first-hand experience of the systems that impact medical careers. Women remain underrepresented in most spaces and often face a complex set of obstacles exacerbated by additional protected characteristics such as race, disability and sexual orientation. The impact of flexible working and care giving responsibilities on career development as well as leadership opportunities further widens the gap between under- and overrepresented groups. In this commentary we describe the intersectional challenges faced by women in our specialties and the challenge of navigating these spaces to achieve career success. We explore the various forms of discrimination and its impact on representation in medicine. Potential strategies and solutions aimed at promoting a more equitable specialty are also highlighted.

ABSTRACT Objective To describe the practice patterns of point‐of‐care ultrasound (POCUS) and compare its usage across subgroups (adult vs. paediatric practitioners, physicians vs. nurse practitioners [NPs], high income [HI] vs. low and middle ‐income [LMI] countries). Methods Survey distributed via the Society of Critical Care Medicine in May–June 2024. Respondents reported the percentage of eligible patients in the past year for whom POCUS was used for vascular access and diagnostic purposes. Responses (0%, < 25%, 25%–50%, 50%–75%, > 75%) were converted into binary categories (> 50% use) and compared across subgroups using logistic regression. Results The survey was completed by 503 respondents from 39 countries (6% response rate): 77.7% from HI countries, 20.9% paediatric practitioners and 18.3% Nurse Practitioner (NPs)/Physician assistants (PAs). POCUS was commonly used for vascular access, and similar usage was found among NP/PAs, physicians, and adult and paediatric practitioners. Practitioners from LMI countries were less likely to use POCUS for vascular access. Basic diagnostic applications, such as assessing pleural effusion (72.5%) and left ventricular function (69.2%), were more commonly used than advanced applications like pulmonary artery pressure measurement (22%). Physicians were more likely than NPs (for some indications), and adult practitioners were more likely than paediatric practitioners (for most indications) to use POCUS for diagnostic purposes. Practitioners in LMI countries reported higher use of diagnostic applications than practitioners in HI countries. Conclusions POCUS is widely adopted in critical care but is less accepted for diagnostic use among paediatric practitioners and NP/PAs. Diagnostic utilisation is higher in LMI countries, while procedural use is lower. Impact Statement Point‐of‐care ultrasound (POCUS) is increasingly used in intensive care units to guide diagnosis and procedures. Despite its importance, little is known about how consistently it is used by different types of clinicians around the world. This international survey of critical care practitioners from 39 countries shows that POCUS is widely used, particularly for procedures, but diagnostic use remains uneven. Paediatric clinicians and advanced practice providers report lower diagnostic use, while clinicians in low‐ and middle‐income countries report higher diagnostic adoption. These findings highlight opportunities to improve access to training and support broader, more equitable use of POCUS in critical care.

Abstract Rare Mendelian disorders affect 300-400 million people globally. Although genetic testing has become widely adopted, gene-specific evidence for tailored variant interpretation remains scattered across resources. We present Gene Portals, a framework for gene-centered multimodal knowledge bases that co-localize expert-harmonized clinical data, functional assays, population variation, structural annotations and gene-specific ACMG/AMP specifications within a single resource. A modular interface integrates this unified evidence with VCEP-refined ACMG specifications to enable automated gene-specific variant classification, infer molecular mechanisms, and support cross-gene analyses. We demonstrate the framework’s utility across five Gene portals spanning eleven neurodevelopmental disorder-associated genes, integrating data from 4,423 individuals with 2,838 unique variants, 36,149 ClinVar submissions, and 1,044 expert-curated molecular readouts. By organizing evidence that is otherwise dispersed across multiple sources into a unified, queryable framework, the SCN, GRIN, CACNA1A, SATB2 and SLC6A1 Gene Portals became widely used community resources and provide an extensible template for standardized rare-disease variant interpretation and mechanism-aware discovery.