- Research Article
- 10.1016/s2352-4642(25)00380-3
Safety of in vivo gene therapy in children: mechanisms and management of liver injury.
- Jun 01, 2026
- The Lancet. Child & adolescent health
- Rebecca Jeyaraj + 9 more +9
Publications from 2021 to 2026
Showing 10 of 458 papers
Safety of in vivo gene therapy in children: mechanisms and management of liver injury.
SRS382 - A systematic review and meta-analysis of efficacy, safety and oncological outcomes of endoscopic mucosal resection (EMR), endoscopic submucosal dissection (ESD) and trans-minimally invasive surgery (TAMIS) for early rectal cancer
Abstract Introduction Minimally invasive techniques have transformed early rectal cancer treatment; yet the optimal approach is unclear. ESD, EMR, and TAMIS are increasingly being used, however, most studies only compare two of these techniques. This meta-analysis directly compares all three in efficacy, safety, and oncological performance. Methods PubMed, Scopus, and Medline were searched to identify relevant studies as of September 2024. Criteria included studies in adults with early rectal cancer treated by ESD, EMR, or TAMIS, reporting at least one outcome and specifying treatment type and cancer stage. Comprehensive Meta-Analysis v4 was used for analysis with heterogeneity assessed via I². Results A total of 127 studies encompassing 8915 patients were included (EMR = 3979, ESD = 4470, and TAMIS = 466). Mean procedural times were: overall 8.3 min (7.7–8.8), I² = 99%; EMR 7.5 (6.9–8.1), I² = 98%; ESD 32.6 (29.3–36), I² = 99%; TAMIS 101.6 (83.9–119.9), I² = 95%. En bloc resection: overall 87.1% (85.6–88.5), I² = 81%; EMR 86.5% (84.4–88.4), I² = 82%; ESD 87.2% (84.4–89.5), I² = 80%; TAMIS 94.1% (88.9–97), I² = 0%. R0 resection: overall 79.7% (78.6–80.8), I² = 80%—EMR 79.9% (78.3–81.5), I² = 85%; ESD 78.7% (77.1–80.3), I² = 76%; TAMIS 87.1% (82.8–90.4), I² = 42%. Conclusions Although EMR appears efficient, it demonstrated less favourable outcomes regarding en bloc resection. ESD showed favourable oncological outcomes while maintaining moderate procedural time. TAMIS is most time-intensive but yields the highest resection quality.
Read morePain and infection are the primary reasons for elective retrieval of bone-anchored implants.
Elective removal of bone-anchored hearing implants and epistheses is uncommon, limiting the understanding of the biological factors contributing to adverse reactions, implant success or failure. Therefore, the tissue-level response at the implant interface remains poorly understood. This study examined 21 explanted bone-anchored implants and interfacial tissues from 19 patients using a controlled retrieval protocol. The clinical data were correlated with histological, immunohistochemical, microbiological, and structural analyses. Pain (12/19) and infection (7/19) were the most common reasons for elective implant retrieval and in 5 cases occurred together. All explants, apart from one, showed significant osseointegration and maintained stability in situ, independent of their design characteristics. Staphylococcus aureus was isolated in five patients—four of whom reported pain even without overt infection. Staphylococcus epidermidis was detected in two patients: one with pain and infection and the other asymptomatic with a resolved infection. S. aureus colonization was associated with intense inflammation, marked by the presence of neutrophils, iNOS+ macrophages, CD3 + T-cells, and CD20 + B-cells. Pain and infection—often involving Staphylococcus species—are key drivers of implant retrieval. These findings emphasize the complex immune response at the implant site and the diagnostic value of analysing electively retrieved implants for improving patient outcomes.
Read moreQualitative and Quantitative Analysis of Circulating Net-Derived Chromatin and Nucleosomes in Severe Thermal and Traumatically Injured Patients.
This study evaluates the dynamic changes in the quantity and quality of neutrophil-derived cell-free DNA (cfDNA) in whole blood and plasma samples from severe thermal and traumatically injured patients. Neutrophil-derived cfDNA, a component of neutrophil extracellular traps (NETs), is released during immune responses to injury and infection. Excessive NET formation mediates inflammation, tissue damage, and coagulopathy. Increased cfDNA levels in burn and trauma patients are reported to be associated with poor clinical outcomes, indicating their potential as biomarkers for predicting sepsis and MODS. Blood samples were obtained from two cohorts of burns (n = 96) and trauma (n = 147) patients. Neutrophil-derived cfDNA was quantified in plasma by SYTOX Green fluorescence and the size of extracted DNA was measured by electrophoresis. A microfluidic assay was also performed to capture NET-derived chromatin from burn patients' fresh whole blood samples. Captured NETs were stained with SYTOX green and anti-citrullinated histone antibodies. Stimulated whole blood or isolated neutrophils from healthy controls were used to generate NETs as positive controls. Circulating cfDNA levels were significantly elevated in plasma from both burns (days 1-14 postinjury) and trauma patients (<1-72 hours) compared to healthy controls. Electrophoresis revealed a prominent nucleosome band (~150 base pairs) in both burns and trauma plasma, with nucleosome oligomers detected within ultra-early samples (<1-hour posttrauma). The density of nucleosome bands correlated with cfDNA concentrations. Microfluidic capture of circulating NET-derived chromatin demonstrated increased levels in whole blood from burns, particularly at day 1 postinjury. NET-derived chromatin, cfDNA, and nucleosomes are elevated following severe burns and trauma. The dynamic changes in cDNA support their contribution to inflammation and as a key biomarker.
Read moreOperative approaches and outcomes of nephroureterectomy for UTUC: a network meta-analysis.
LungDetectNet: a multi-task deep learning framework with enhanced detection and descriptive capabilities
Development of a Cystic Fibrosis Weight Management Programme: protocol for a co-design study
The resulting CF WMP will extend the usability of an NHS digital WMP to adults with CF, to better ensure it meets their needs, which have changed since the introduction of HEMT.
Read more29 Optimising Lung Cancer Adjuvant Treatment Pathways
Developing a Biocompatible Photopolymerized Nonisocyanate Polyurethane Resin for Orthopedic Surgical Guide Plates: Synthesis, Characterization, and In Vitro/In Vivo Biocompatibility
Orthopedic surgical guide plates require materials with excellent biocompatibility, mechanical adaptability, and reliable photopolymerization performance. This paper reports a photopolymerizable biocompatible nonisocyanate polyurethane (NIPU) resin designed for orthopedic surgical guide applications, which eliminates the use of toxic isocyanates and enhances clinical safety. Two structurally distinct NIPUs (NIPUA1 and NIPUA2) were synthesized by incorporating aliphatic ring and chain structures, followed by modification with methacrylic anhydride to impart photopolymerizability. Characterization showed that the NIPUA2 resin exhibited a 1.96-fold increase in both elongation at break and impact strength compared to that of NIPUA1, providing better resistance to intraoperative stress. With a viscosity below 600 mPa·s and a glass transition temperature of 134.74 °C, NIPUA2 also demonstrated good printability and sterilizability. Compared to a commercial resin (TRANS), both NIPUA1 and NIPUA2 showed excellent cytocompatibility with C2C12 myoblasts and MC3T3-E1 osteoblasts, as confirmed by CCK-8, live/dead staining, and flow cytometry assays, which indicated low apoptosis rates and normal cell cycles. In vivo experiments further revealed reduced muscle toxicity and inflammatory responses for the NIPUA resins. This study presents the NIPUA2 resin as a promising material, combining biocompatibility and favorable mechanical properties for orthopedic surgical guides.
Read morePerceptions of Plastic Surgery Training in the United Kingdom: A Mixed-Methods Trainee Survey
Background: Plastic surgery training in the United Kingdom (UK) is a highly competitive and evolving field. Recent reforms have aimed to standardise operative exposure, academic opportunities, and mentorship, yet the perspectives of current trainees remain underexplored.Objective: This study assessed UK plastic surgery trainees’ perceptions of their training quality, satisfaction, and preparedness for independent practice.Methods: A cross-sectional, anonymised online survey was distributed to UK plastic surgery trainees. The questionnaire included demographic items, views on training duration and fellowship structure, and satisfaction ratings across key domains of training using a five-point Likert scale. Free-text comments were thematically analysed to identify recurrent qualitative themes.Results: Fourteen trainees from multiple UK deaneries responded. Half reported three to four years of training (n = 7, 50%), and four (29%) had less than one year of training. Most respondents (n = 9, 64%) believed six years of training was sufficient to achieve key competencies, while two (14%) disagreed and three (21%) were uncertain. Opinions on fellowship structure were divided: seven (50%) supported integration within the six-year programme (5+1), six (43%) preferred a separate post-CCT (certificate of completion of training) fellowship (6+1), and one (7%) was unsure. Mean overall satisfaction was 3.2/5 (median = 3). Highest domain scores were supervisor involvement (mean = 3.5/5, n = 14) and case variety/hands-on opportunities (mean = 3.5/5, n = 14); lowest were research opportunities (mean = 2.9/5, n = 14) and work-life balance (mean = 3.0/5, n = 14). Qualitative responses highlighted five themes: limited operative exposure, inconsistent mentorship, regional variation, restricted research time, and the lasting impact of COVID-19.Conclusions: UK plastic surgery trainees report moderate satisfaction overall, with particular concern regarding research access and work-life balance. Qualitative feedback revealed recurring issues around mentorship and operative opportunities, consistent with national trainee trends.
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