Royal London Hospital

Advanced tumors harboring SWI/SNF mutations are rare and aggressive. Often presenting in young patients, treatment options are limited. This phase II basket study (NCT02601950) assessed oral tazemetostat, an EZH2 inhibitor, at 800 mg twice daily (N = 129). Cohorts included malignant rhabdoid tumors (n = 32, Cohort 1), synovial sarcoma (n = 33, Cohort 2), INI1-negative tumors (n = 32, Cohort 3), renal medullary carcinoma (n = 14, Cohort 4), and poorly differentiated chordoma (n = 18, Cohort 7). Efficacy assessments used a 2-stage Green-Dahlberg design. Stage 1 futility was predefined as objective responses (complete/partial [CR/PR]) <5% (Cohorts 1, 3, 4, 7) or 16-week progression-free survival (PFS) <15% (Cohort 2). Sufficient clinical activity was declared in Stage 2 if ≥5 patients had a CR/PR (Cohorts 1,3,4,7) or ≥9 patients had a CR/PR, or stable disease (Cohort 2; primary endpoints). Responses were observed in malignant rhabdoid tumors (9%; n = 2 PR, n = 1 CR), INI1-negative tumors (9%; n = 3 PR, n = 0 CR), and poorly differentiated chordoma (6%; n = 1 PR, n = 0 CR) but not the remaining 2 cohorts (both 0%). 16-week PFS for synovial sarcoma was 15.2% (n = 5). Grade ≥3 treatment-related adverse events occurred in 10% of patients. Tazemetostat demonstrated preliminary antitumor activity in a subset of poor-prognosis cancers, underscoring the need for combination strategies when EZH2 signaling is not the sole disease driver.

Invasive conjunctival squamous cell carcinoma (CSCC) is an aggressive, ocular surface malignancy. The mean annual age-standardised incidence rate of 0.45 cases per million per year is increasing with an average annual percent rise of 4.5% and occurs mainly in over 65-year-olds in temperate climates but in a younger demographic in the tropics. Invasive CSCC can lead to vision loss either from the destructive effects of the tumour or side effects of therapy, facial disfigurement from radical surgery, and death from metastases. There is no standardised treatment and not all cases are referred to a specialist ocular oncology centre. Recent progress in cancer immunology and genetics has revolutionised the treatment of cutaneous and head and neck SCCs, which share some similarities to invasive CSCC. A better understanding of invasive CSCC and its preinvasive intraepithelial lesions is required to lead to the development of novel targeted and immunotherapies both for local tumour control, globe sparing alternatives and to prevent disseminated disease. This review aims to provide a comprehensive clinical overview of the current knowledge regarding CSSC, its epidemiology, pathogenesis, presentation, diagnosis, management, recent advances in targeted and immunotherapies for personalised treatment of this disease, and early diagnosis strategies to improve patient outcomes.

Abstract Fomite-mediated and airborne transmission pathways play a significant role in the dissemination of healthcare associated pathogens, contributing to the burden of hospital-acquired infections (HAIs). Effective infection prevention and control therefore require robust surveillance approaches capable of capturing the complexity of air and surface microbial communities present in healthcare settings. However, to date such approaches are not widely employed. In this study we used a rapid and low-biomass optimized metagenomic workflow to detect clinically relevant pathogens, characterise genetic signatures such as antimicrobial resistance and virulence determinants, and profile the wider airborne microbiome, including unculturable taxa) essential for HAI surveillance. Air samples were collected from multiple clinical and non-clinical areas across three multi-storey healthcare units within a UK hospital, alongside to surface samples from a haematology/oncology ward with a documented history of outbreaks. Following DNA extraction and enrichment optimised for low-biomass samples, sequencing was performed using the Oxford Nanopore Technologies MinIon long-read platform. Metagenomics data were analysed using an in-house developed bioinformatics pipeline. Metagenomic profiling revealed high bacterial taxonomic diversity across sampled environments, with limited overlap between the airborne and surface communities. Approximately 0.3% of bacterial reads harboured a large variety of antimicrobial resistance genes (ARGs), virulence factors (VFs) and mobile genetics elements (MGEs) across different hospital sample groups. Notably, critical and emerging pathogens were detected across ten wards and were associated with clinically significant resistance determinants, including multiple bla OXA subtypes, vanA gene clusters, and multidrug efflux pumps conferring resistance to eight important classes of antibiotics, including carbapenems, cephalosporins, penams, and vancomycin. In addition, several plasmid replicons implemented in horizontal gene transfer (HGT) were identified within these pathogens, indicating an increased potential for the emergence and dissemination of multi-drug resistance within hospital associated microbial communities. Our findings highlight the importance of using rapid metagenomics-based methodologies for environmental surveillance in healthcare settings. Correspondingly, this study revealed that hospital air and surface microbiomes comprise complex and dynamic microbial communities that harbour divers e of ARGs and VFs with the potential for rapid transmission across the surface-air interface, particularly in high-risk/vulnerable patient areas where outbreaks are more likely to occur.

SummaryTeenage and young adult (TYA) patients undergoing allogeneic stem cell transplant have distinct psychosocial needs, yet they are poorly represented in research and their outcomes are not well understood. This study uses prospectively collected data from the British Society of Blood and Marrow Transplantation and Cellular Therapy (BSBMTCT) registry to explore UK transplant practice and outcomes for TYA patients (aged 16–24) in this healthcare setting, alongside children (aged 1–15) and adults (aged 25–39), transplanted for acute leukaemia (including lymphoblastic, acute lymphoblastic leukaemia [ALL], and myeloid, acute myeloid leukaemia [AML]). Nine hundred and forty TYA patients, transplanted between 1999 and 2018, are included, representing 87% of all UK activity during the study period. On adjusted analyses, overall survival after transplant for ALL worsened from children, through TYA, to adults; survival for patients with AML was similar across age groups. Non‐relapse mortality was not significantly worse in TYA patients compared with children (p = 0.117 in ALL, p = 0.379 in AML). The risk of chronic graft‐versus‐host disease (GvHD) was strongly correlated with age, with rates in the TYA group much closer to those seen in adults. While a graft‐versus‐leukaemia effect may be suppressing relapse, the high rate of GvHD represents an unmet need in this group, who are at a crucial juncture in their personal, educational and social development.

[This corrects the article DOI: 10.7759/cureus.96126.].

BackgroundRecognising the medical and surgical complexity of certain patient populations, perioperative pathways are evolving to incorporate multidisciplinary team perspectives, alongside surgeons, in shared decision-making. We aimed to synthesise the evidence base for multidisciplinary team shared decision-making.MethodsWe performed a systematic literature review accessing bibliographic databases (MEDLINE (using OVID), EMBASE, PsycINFO, Web of Science, CINAHL, and ProQuest), the international prospective register for systematic reviews (PROSPERO), the International Standard Randomised Control Trial Number Registry, and the King’s Fund Library Database.ResultsOf 8727 citations, 271 were eligible for full-text review and 29 included in the final narrative synthesis. A wide variety of non-surgical healthcare professionals (e.g. anaesthetist, geriatrician, radiation oncologist, intensivist, specialist nurse, physiotherapist, psychologist, and social worker) and others (including peer support) participated in perioperative shared decision-making. Consultations were mainly structured sequentially or concomitantly with surgical consultations. Patients and clinicians generally responded positively to multidisciplinary team shared decision-making. Where measured, decisional quality was reported to have improved, and decisional conflict reduced. Studies of high-risk patients indicated that multidisciplinary team shared decision-making was more likely to result in non-operative management. We identified five features of these modes of multidisciplinary team shared decision-making consultation: identification of relevant experts required, expert multidisciplinary assessment, thorough consideration of alternative treatments, coordinated patient support, and additional consultation time.ConclusionsSome surgical populations, as a function of the complexity of their medical, surgical, or both condition(s), would benefit from multidisciplinary team shared decision-making. Further research is required to understand the optimal organisation of this approach and the impact on patient and systems outcomes.Systematic review protocolPROSPERO (CRD42025636328).

To compare the ALGO Smart Pump (ALGO), operating in Adaptive Pulsatile Aspiration (APA™) and Static modes, with the Penumbra ENGINE during in-vitro mechanical thrombectomy, and to determine whether adaptive pulsatile aspiration improves complete clot ingestion (CCI) and reduces aspiration time across catheters sizes and catheter-to-artery (C/A) ratios. Apre-specified integrative analysis of two previously completed in-vitro thrombectomy studies was conducted using astandardized middle cerebral artery occlusion model. Atotal of 720 thrombectomy procedures were performed by two experienced operators using twelve commercial catheters (six small-bore, six large-bore). Three aspiration modalities were tested: ALGO APA™, ALGO Static, and Penumbra ENGINE continuous aspiration (n = 30 per catheter-pump pairing). The primary endpoint was CCI; secondary endpoint was aspiration time. Outcome analysis included two-way ANOVA and Chi-squared tests, with catheter, operator, and C/A ratio terms. The ALGO demonstrated ahigher median CCI rate than Penumbra (81.4% vs. 56.1%, χ2(1) = 52.364, p < 0.001). Aspiration times were significantly shorter with ALGO, particularly in APA™ mode (43.8 s vs. 60.6 s, p < 0.001). Two-way ANOVA demonstrated significant interaction between catheter size and pump type (p < 0.001), with ALGO notably improving small-bore catheter performance. CCI correlated positively with catheter-to-artery (C/A) ratio across both systems, with ALGO maintaining higher success across all ratios. Adaptive pulsatile aspiration enhances clot ingestion efficiency and reduces aspiration time in an in-vitro thrombectomy model, particularly for smaller catheters. These findings support further translational studies on optimizing aspiration dynamics to enhance first-pass success in endovascular stroke therapy.

Nasal obstruction and epistaxis are common otorhinolaryngologic complaints with multiple etiologies ranging from benign anatomical variations and mucosal inflammation to severe neoplastic and vascular disorders. Clinical evaluation and nasal endoscopy are first-line diagnostic tools, with imaging reserved for selected indications. Imaging differentiates uncomplicated from complicated presentations, guiding management and surgical planning. Computed tomography (CT) is the primary modality for assessing sinonasal anatomical variants, bony pathology, and inflammatory or neoplastic disease. Magnetic resonance imaging (MRI) complements CT when soft tissue or intracranial extension is suspected. Imaging in epistaxis is not routinely indicated but is recommended in recurrent, severe, or posterior bleeding to detect underlying vascular lesions or tumors. CT angiography is preferred for vascular assessment and interventional planning. Implementing these recommendations can improve diagnostic accuracy, streamline patient management, and enhance surgical outcomes in patients presenting with nasal obstruction and epistaxis. KEY POINTS: Clinical history and nasal endoscopy should be the primary tools for initial assessment, with imaging reserved for inconclusive or persistent cases. CT is the preferred imaging modality for evaluating structural causes of nasal obstruction, especially prior to surgical intervention. Imaging in epistaxis is indicated mainly in severe, recurrent, or posterior bleeding to localize the source and guide treatment.