Update on Blindness From Filler: Review of Prognostic Factors, Management Approaches, and a Century of Published Cases.

BACKGROUND: Vision loss secondary to aesthetic filler treatment is a rare but disastrous complication. OBJECTIVES: The aim was to update the published cases of blindness after filler injection that have occurred since our group published reviews of 98 cases in 2015 and an additional 48 cases in 2019. METHODS: A literature review was performed to identify all cases of visual complications caused by filler injection published between September 2018 and March 2023. The cases were analyzed independently and in combination with previously reviewed cases. Analyses are based on the number of cases with data available. RESULTS: 365 new cases of partial or complete vision loss after filler injection were identified. The sites that were highest risk were the nose (40.6%), forehead (27.7%), and glabella (19.0%). The filler injected was hyaluronic acid in 79.6% of cases. The most common associated signs were ptosis (56.2%), ophthalmoplegia (44.1%), pain (31.2%), and skin changes (73.2%). Stroke-like features were seen in 19.2% of cases. Of the cases reporting visual outcomes (318), 6.0% experienced complete vision recovery, 25.8% had partial improvement in visual acuity, and 68.2% had no vision recovery. Partially preserved visual acuity at onset was a significant predictor of visual improvement (p < .001). The three most common treatments were subcutaneous hyaluronidase at or near the filler site (70.1%), systemic steroids (57.3%), and intra-arterial thrombolytic therapy (56.0%). No treatments were significantly associated with visual improvement (p > .05). CONCLUSIONS: Although blindness and stroke from fillers is a rare complication, practitioners who inject filler should have a thorough knowledge of prevention and management strategies.

Patient experiences of Cytosponge: a qualitative study.

Objective: Cytosponge is a novel technology for oesophageal pathology diagnosis. Uses include diagnosis of Barrett's oesophagus and as a triage tool to prioritise upper gastrointestinal endoscopy. Patient experience is a key component of quality care. Previous work has developed endoscopy patient-reported experience measures. An appropriate tool to measure patient experience of Cytosponge is required. The aim of this work was to describe the patient experience of Cytosponge. Design/Method: Individuals aged 18 years or over, who had undergone Cytosponge from September 2020 to March 2021, were invited to participate in a semi-structured interview. Interviews were audio-recorded, transcribed verbatim and anonymised. Thematic analysis was undertaken. Themes were organised into two overarching areas relating to patient experiences and patient perceptions of the test. Results: 19 patients underwent interview (aged 37-80 years, 13 male). In terms of patient experiences of Cytosponge, five themes were identified: emotional reaction; expectations; environment and physical process; sensory experience; communication and information. All themes were present across all procedural phases, aside from sensory experience which was only present during the test. With regard to perception of the test, two major themes were identified: test novelty (encompassing patient awareness of the test and reaction to the new test) and trusting the test results. Conclusion: Patients must remain central to novel technologies such as Cytosponge. Measuring patient experience is essential to achieve that. This study demonstrates five major themes which describe the patient experience of this procedure. These have been used to adapt the Newcastle ENDOPREM for use in Cytosponge.

A systematic review of circulating predictive and prognostic biomarkers to aid the personalised use of radiotherapy in the radical treatment of patients with oesophageal cancer.

BACKGROUND: The availability of circulating biomarkers that are predictive of treatment response or prognostic of overall outcome could enable the personalised and adaptive use of radiotherapy (RT) in patients with oesophageal adenocarcinoma (OAC) and squamous cell carcinoma (OSCC). METHODS: A systematic review was carried out following Preferred Reporting Items for Systematic Reviews guidance. Medline, EMBASE, PubMed, Cochrane Library, CINAHL, Scopus and the Web of Science databases were searched for studies published between January 2005-February 2023 relating to circulating biomarkers evaluated in the context of neoadjuvant or definitive RT delivered for OAC/OSCC. Study quality was assessed using predefined criteria. RESULTS: A total of 3012 studies were screened and 57 subsequently included, across which 61 biomarkers were reported. A majority (43/57,75.4%) of studies were of Asian origin and retrospective (40/57, 70.2%), with most (52/57, 91.2%) biomarkers reported in the context of patients with OSCC. There was marked inter-study heterogeneity in patient populations, treatment characteristics, biomarker measurement and the cut points used to define biomarker positivity. Nevertheless, there is evidence for the prognostic and predictive value of circulating tumour DNA and numerous miRNAs in OAC and OSCC, as well as for the prognostic and predictive value of circulating levels of CYFRA21.1 in OSCC. CONCLUSIONS: There is consistent evidence for the potential predictive and prognostic value of a small number of biomarkers in OSCC and OAC, though these data are insufficient for translation to current clinical practice. Well-designed prospective studies are now required to validate their role in stratified and personalised RT treatment approaches.

SMAD4 and KCNQ3 alterations are associated with lymph node metastases in oesophageal adenocarcinoma.

Metastasis in oesophageal adenocarcinoma (OAC) is an important predictor of survival. Radiological staging is used to stage metastases in patients, and guide treatment selection, but is limited by the accuracy of the approach. Improvements in staging will lead to improved clinical decision making and patient outcomes. Sequencing studies on primary tumours and pre-cancerous tissue have revealed the mutational landscape of OAC, and increasingly cheap and widespread sequencing approaches offer the potential to improve staging assessment. In this work we present an analysis of lymph node metastases found by radiological and pathological sampling, identifying new roles of the genes SMAD4 and KCNQ3 in metastasis. Through transcriptomic analysis we find that both genes are associated with canonical Wnt pathway activity, but KCNQ3 is uniquely associated with changes in planar cell polaritiy associated with non-canonical Wnt signalling. We go on to validate our observations in KCNQ3 in cell line and xenograph systems, showing that overexpression of KCNQ3 reduces wound closure and the number of metastases observed. Our results suggest both genes as novel biomarkers of metastatic risk and offer new potential routes to drug targeting.

Deliberations of the Safety Task Force: Risk factors and treatment of adverse events associated with aesthetic injectables.

BACKGROUND: The growing popularity of aesthetic procedures involving fillers, biostimulators, and neurotoxins has prompted concerns about patient safety. To address these concerns, a global Safety Task Force (STF) was formed. AIMS: The inaugural STF meeting prioritized vascular compromise prevention and management, guiding clinical trial design and materials for future meetings, and collecting data from experts on current safety methods. METHODS: The STF was formed and consisted of 16 experts from nine different countries, with each possessing distinct expertise in various fields related to aesthetic injectables. Current safety data, protocols, knowledge gaps and future research priorities were discussed and voted upon. RESULTS: The establishment of a global database for tracking filler-related AEs was favored by 93% of participants. Discussions revolved around the database's scope, data standardization, and whether non-medical contributors should be included. Aspiration as a safety technique garnered support from 73% of participants. Approximately 43% of participants incorporate ultrasound in their injections, with divergent opinions on its impact and potential when used as a standard of practice versus in AE management. Most physicians on the task force incorporated cannula use for some of their injections (93%). There were varying perspectives on treatments for vascular adverse events (VAE), the primary causes, and the adoption of new protocols in the field. CONCLUSIONS: The STF meeting underscored the need for a coordinated effort to address complications related to HA fillers, including VAE management and hyaluronidase protocols. Reliable treatment endpoints were evaluated, but improved measurement methods are needed. Future meetings will focus on addressing delayed complications, furthering safety in this field.

Disentangling oncogenic amplicons in esophageal adenocarcinoma.

Esophageal adenocarcinoma is a prominent example of cancer characterized by frequent amplifications in oncogenes. However, the mechanisms leading to amplicons that involve breakage-fusion-bridge cycles and extrachromosomal DNA are poorly understood. Here, we use 710 esophageal adenocarcinoma cases with matched samples and patient-derived organoids to disentangle complex amplicons and their associated mechanisms. Short-read sequencing identifies ERBB2, MYC, MDM2, and HMGA2 as the most frequent oncogenes amplified in extrachromosomal DNAs. We resolve complex extrachromosomal DNA and breakage-fusion-bridge cycles amplicons by integrating of de-novo assemblies and DNA methylation in nine long-read sequenced cases. Complex amplicons shared between precancerous biopsy and late-stage tumor, an enrichment of putative enhancer elements and mobile element insertions are potential drivers of complex amplicons' origin. We find that patient-derived organoids recapitulate extrachromosomal DNA observed in the primary tumors and single-cell DNA sequencing capture extrachromosomal DNA-driven clonal dynamics across passages. Prospectively, long-read and single-cell DNA sequencing technologies can lead to better prediction of clonal evolution in esophageal adenocarcinoma.

Cancer Core Europe: Leveraging Institutional Synergies to Advance Oncology Research and Care Globally.

Cancer Core Europe brings together the expertise, resources, and interests of seven leading cancer institutes committed to leveraging collective innovation and collaboration in precision oncology. Through targeted efforts addressing key medical challenges in cancer and partnerships with multiple stakeholders, the consortium seeks to advance cancer research and enhance equitable patient care.

The Mutographs biorepository: A unique genomic resource to study cancer around the world.

Large-scale biorepositories and databases are essential to generate equitable, effective, and sustainable advances in cancer prevention, early detection, cancer therapy, cancer care, and surveillance. The Mutographs project has created a large genomic dataset and biorepository of over 7,800 cancer cases from 30 countries across five continents with extensive demographic, lifestyle, environmental, and clinical information. Whole-genome sequencing is being finalized for over 4,000 cases, with the primary goal of understanding the causes of cancer at eight anatomic sites. Genomic, exposure, and clinical data will be publicly available through the International Cancer Genome Consortium Accelerating Research in Genomic Oncology platform. The Mutographs sample and metadata biorepository constitutes a legacy resource for new projects and collaborations aiming to increase our current research efforts in cancer genomic epidemiology globally.