bluuebunny/crossref_metadata_2025_split huggingface dataset:
O257: A Transcriptome Analysis of Primary Breast Cancer with Discordant Brain Metastasis Subtype
Authors: Daly Gordon R , McGrath Jason , Dowling Gavin P , Hegarty Aisling , Fallon Ramon , Cox Luke , Hill Arnold D K , Vareslija Damir , Young Leonie 
Published: March 2024

Abstract

Introduction
Brain metastasis (BM) occurs in 15-30% of breast cancer (BC) cases. In the era of personalised medicine, knowledge of the BM subtype is of increasing importance. However, there is often discordance between breast primary (BP) subtype and its BM. Improvements in stereotactic radiosurgery and neuroradiology have greatly reduced the number patients undergoing surgical resection. Therefore, identifying BM subtype poses a therapeutic challenge.

Methods
This study included 116 patients with breast cancer brain metastasis on CTRIAL-IE 09/07. Clinical subtype was evaluated using immunohistochemistry (IHC) results for oestrogen receptor (ER), progesterone receptor (PR) and HER2. 63 BP RNA sequencing (RNA-Seq) samples were analysed to identify differentially expressed genes in ER positive (ER+) primaries that subsequently lost ER in BM vs. ER+ primaries that retained ER.

Results
34 (29.3%) of BPs were ER+/HER2- vs. 19 (16.4%) brain metastases, 50 (43.1%) BPs were HER2+ vs. 60 (51.7%) metastases, 32 (27.6%) BPs were TNBC vs. 37 (31.9%) metastases. The most common receptor switches were loss of ER 20/62 (32.36%), loss of PR 17/30 (56.7%) and gain of HER2 11/65 (16.9%). RNA-Seq differential expression analysis of ER+ primary/ER- BM vs. ER+ primary/ER+ BM found ALB, CPA1, GOLGA8G were significantly underexpressed in patients that subsequently lost ER, conversely MUC2, AREG and HSPB1 were significantly overexpressed.

Conclusion
This study profiles receptor discordance between primary BC and its matched BM. Future studies of differentially expressed genes at a transcript level may predict BM subtype using primary RNA-Seq data and allow for a more tailored treatment approach.
O132: Impaired oxygen unloading from stored blood results in diffusion-limited oxygen release at tissues: evidence from twinned-circuit human kidney perfusion
Authors: Dumbill Richard , Rabcuka Julija , Fallon John , Knight Simon , Hunter James , Voyce Daniel , Barrett Jacob , Ellen Matt , Weissenbacher Annemarie , Ploeg Rutger , Coussios Constantin , Friend Peter , Swietach Pawel 
Published: March 2024

Abstract

Background
The storage lesion is a multifactorial degradation effect seen in units of banked blood, and results in an increase in the time-constant of oxygen-unloading from red cells (tau). We have previously shown the relevance of this effect in observational data from a recent clinical trial of prolonged normothermic kidney perfusion as a preservation technique ahead of transplantation. We sought direct confirmatory evidence for diffusion-limited oxygen release by stored red cells (RBCs) during normothermic kidney perfusion in a precisely controlled experimental setting.

Methods
A novel twinned-circuit kidney perfusion system using common, recirculated dialysis was developed, achieving physical separation of RBCs of two conditions whilst allowing non-cellular components of the perfusate to equilibrate throughout. Using human kidneys unsuitable for transplantation, perfusion was alternated between stored and rejuvenated RBCs (treated with PIPA solution) originating from the same donation, to manipulate oxygen-unloading whilst holding all non-RBC parameters constant, without interrupting blood flow.

Results
Tau improved with PIPA treatment (1.6 to 1.1s). Rejuvenated oxygen-unloading kinetics reversibly and significantly improved the kidney’s oxygen diffusion capacity and increased cortical oxygen tension by 60%. This supported observations from our clinical trial, where increased tau was strongly associated with restricted renal oxygen consumption.

Conclusions
We have confirmed that oxygen delivery to tissues can become diffusion-limited during normothermic perfusion with stored blood. This effect is reversible by treatment with PIPA solution. This has important implications for ex-vivo normothermic organ perfusion, and potentially for other scenarios such as major hemorrhage, elective surgery with high blood product utilisation, and paediatric transfusion.
O237: Conversion of human kidney tissue to Bombay type using FucOB enzyme
Authors: Walker-Panse Léonie , MacMillan Serena , Hosgood Sarah , Nicholson Michael 
Published: March 2024

Abstract

Introduction
The Bombay phenotype (Oh) is characterised by an absence of H antigen expression on red blood cells and vascular endothelium. The Oh phenotype is rare but most prevalent in the Indian subcontinent where it poses significant challenges in performing blood transfusions and kidney transplants, as Oh recipients can only receive from Oh blood type donors. The enzyme α-1,2-fucosidase (FucOB) derived from Akkermansia muciniphila bacteria has been shown to hydrolyse blood group H antigens. This study examined the efficiency of the FucOB enzyme on O type human kidney tissue to obtain Bombay phenotype.

Methods
H antigen removal was investigated in formalin-fixed paraffin embedded (FFPE) human kidney cortical biopsies from blood group O-type donors (n=8). Biopsies were incubated at 37OC for 1h with FucOB enzyme at concentrations 0µg/ml, 0.05µg/ml, 0.1µg/ml, 0.5µg/ml and 5µg/ml and inactive enzyme (iFucOB; 5µg/ml). Quantitative immunofluorescence was used to determine co-localisation of H antigen and vascular endothelium (Ulex).

Results
Increasing concentrations of FucOB progressively removed H antigen from FFPE sections of renal cortex. When compared to untreated control and iFucOB, a FucOB concentration of 5µg/ml caused 95% loss of H antigen expression on renal vascular endothelium (p&lt;0.0001; Friedman test with Dunn’s multiple comparisons test).

Conclusion
This is the first description of enzymatic cleavage of H antigen from human O-type kidney tissue. The next step is to deliver FucOB enzyme to human kidneys during normothermic machine perfusion. This strategy has the potential to dramatically increase the availability of ABO compatible kidneys from individuals with Bombay phenotype.
O241: A multi-omic systematic review of metabolites involved in predicting of the response to neoadjuvant therapy in locally advanced rectal cancer
Authors: Kler Aaron , Fok Matthew , Grundy Gabrielle , Sciacovelli Marco , Dunn Warwick , Vimalchandran Dale 
Published: March 2024

Abstract

Introduction
Locally advanced rectal cancer (LARC), treated with neoadjuvant chemoradiotherapy (NCRT), displays varying treatment responses. Despite extensive research in the "omics" fields, clinical practice lacks NCRT predictive biomarkers for LARC. Metabolomics, an emerging "omics" discipline, quantitatively assesses small metabolites' influence on the phenotype and has successfully identified biomarkers for cancer diagnosis, therapy, and prognosis, including colorectal cancer. Therefore, this systematic review aimed to identify metabolomic studies in LARC patients undergoing NCRT and elucidate treatment response-associated metabolic pathways.

Methods
A systematic review was performed using Pubmed, Web of Science, and Scopus, collating statistically significant metabolites from selected studies. Subsequently, pathway and enrichment analyses were performed using Metaboanalyst 5.0.

Results
Eight eligible studies examined 184 metabolites. Pathway analysis revealed fifteen significant metabolic pathways, notably emphasizing alanine and branched chain amino acid metabolism. Enrichment analysis confirmed the importance of alanine metabolism, alongside oxidative phosphorylation, gluconeogenesis, and glycolysis.

Discussion
In these pathways, paramount significance lies in their ability to generate ATP to meet increased energy demands via oxidative phosphorylation and gluconeogenesis, crucial in the context of NCRT. Furthermore, pathways proficient in neutralizing harmful reactive oxidation species, contributors to radiation-induced DNA damage, play a critical role in treatment response determination. In summary, the metabolomic landscape in LARC patients undergoing NCRT sheds light on pivotal pathways for predicting treatment response. These findings underscore the importance of energy metabolism and the attenuation of oxidative stress as promising avenues for further research and the development of LARC therapy predictive biomarkers.
O156: Post-operative surveillance following curative resection of colorectal cancer in an elderly population
Authors: Shekleton Florence , Baker William , Courtney Edward 
Published: March 2024

Abstract

Introduction
There are over 42,000 new cases of colorectal cancer in the UK each year with the highest incidence rates in those aged 85-89. Post-colorectal cancer surveillance aims to reduce cancer incidence and mortality, but its necessity and effectiveness remain debated especially in an elderly population. This study explores the relevance of computer tomography (CT) and colonoscopy surveillance in patients aged 75 and over who have undergone curative resection for colorectal cancer.

Methods
A retrospective analysis of prospectively collected data was conducted on patients aged 75 and over who had undergone surgical resection of colorectal cancer between November 2014 and August 2021. Data on demographics, treatment, survival, and surveillance were gathered from electronic patient records. The primary outcome was adherence to follow-up colonoscopy and CT-scan surveillance following surgery.

Results
A total of 417 patients underwent colorectal cancer surgery, with 334 included for analysis. Twelve-month CT surveillance showed normal results in 91.8% of cases, while 24-month CT surveillance demonstrated normal findings in 88.7%. Only 52.4% had colonoscopy follow-up, with 53.7% showing normal results, 42.3% demonstrated benign polyps, and 1.1% had histologically proven cancer. Reasons for not undergoing colonoscopy included patient preference (19.1%) and frailty (28.7%).

Conclusion
This study reinforces the notion that colonoscopy surveillance in patients over 75 may have limited benefits. In an aging population, benefits of surveillance in terms of early detection of recurrence must be balanced against the risks of harm from the procedure, availability of further management, cost-effectiveness, and patients’ preference.
O255: Is a low calorie "liver shrinking" diet predictive of long term weight loss and metabolic improvement after sleeve gastrectomy?
Authors: O’Brien James , Natarajan Madhavi , Bartlett David , Pring Chris 
Published: March 2024

Abstract

Introduction
Limited evidence exists regarding pre-operative “liver shrinking” diet, but a two-week period of low calorie diet (LCD) is mandated before bariatric surgery, with weight outcomes rarely measured. Longer periods of LCD can ameliorate obesity, diabetes and metabolic-associated-fatty-liver disease (MAFLD). Primary aim to determine if response to LCD is predictive of long-term weight loss. Secondary aim to determine if alteration in liver function, and MAFLD, correlate with weight change after diet/ in follow up.

Methodology
Patients undergoing sleeve gastrectomy recruited and weight, blood plasma and 16S rRNA faecal microbiome profile recorded at baseline, following two-week LCD and at six-months, with liver biopsy at surgery (6).

Results
First nine patients had median baseline BMI 47.3kg/m2, and 34.7 kg/m2 at 6-months (-12.3kg/m2). Median excess weight loss was 8.6% (6.35kg) after LCD and 47.57% (34.65kg) at 6-months. Spearman’s Rank Correlation was weakly positive (0.5) for absolute weight loss between LCD and follow up, and was 0.25 using excess weight loss (non-significant). Change in liver function and MAFLD grade did not correlate with weight loss following LCD and at 6-months.

Conclusions
Weight loss response to LCD correlated poorly with long-term weight loss (analysing by absolute/ excess weight). Liver health and MAFLD did not predict 6-month weight loss. A dramatic response to LCD may not manifest in longer term metabolic improvement after surgery. We will also report on faecal microbiome; it appears more complex mechanisms underpin weight change and response to dietary manipulation in the surgical cohort than can be extrapolated from population studies.
O104: The “At-Risk” Infrainguinal Bypass Graft: benefit of Duplex Ultrasound Surveillance and Institutional costs of failure
Authors: Stocco Fabio , Dhital Ketan , Kwan Jing Yi , Scott Julian , Bailey Marc , Coughlin Patrick 
Published: March 2024

Abstract

Introduction
The “Achilles heel” of infrainguinal surgical revascularisation (IISR) is that of restenosis. Duplex Ultrasound Surveillance (DUS) is undertaken to identify restenosis to permit intervention to maintain graft patency. We report the impact of DUS on outcomes focusing on patient- and treatment-associated costs.

Methods
Consecutive patients undergoing IISR at our Institution were assessed (January 2017 - December 2020). Data on DUS (1-, 6- and 12-month scans) were collated. Primary outcomes were mortality and major limb amputations (MLA) at 2-years post IISR. Grafts were defined “at-risk” if radiological evidence of significant graft stenosis or occlusion, with or without symptoms, was identified. Post IISR graft-specific Institutional costs for all patients were quantified.

Results
254 patients had IISR in the observed period (196 men, median age 70yrs). Of those, 194 (76%) entered DUS, and 109 (43%) completed it. In patients who completed DUS (vs incomplete vs none), mortality was 6.4%, (vs 26.5% vs 38% respectively; p &lt;0.001) and MLA rates were 6.4% (vs 12% vs 30%, p=0.174 and p&lt;0.001 respectively). Managing at-risk grafts led to additional 384 cross-sectional imaging requests, 284 outpatient reviews, 933 hospital admission days and 233 open and endovascular reinterventions with a total additional NHS cost of £ 1.348.518 in 2 years. Per-patient costs were £216 (per patient, per month) for the complete DUS group vs £348 in no DUS group.

Conclusion
The ongoing management of IISR is associated with significant costs. Enrolment in and completion of a DUS programme is associated with improved patient outcomes and a reduction in costs.
O202: Clinical characteristics and outcomes of traumatic brain injury in a high-volume tertiary hospital in India
Authors: Steinruecke Moritz , Nair Shalini , Venturini Sara , Hutchinson Peter , Kolias Angelos , Joseph Mathew 
Published: March 2024

Abstract

Background
Traumatic brain injury (TBI) is a common neurosurgical emergency but its epidemiological and clinical characteristics vary across country income levels. High-quality TBI data from low and lower-middle income countries are required to inform trials and public policy in these settings.

Methods
We performed a prospective cohort study of patients admitted to a high-volume tertiary hospital in Vellore, India following a TBI between 2013 and 2019. We collected data on patient characteristics and measured their outcomes using the Glasgow Outcome Scale-Extended (GOSE).

Results
We identified 3,172 patients (84% males) with a mean age of 35 years (SD = 18). Two-wheeler road traffic accidents caused 2,259/3,172 (71%) injuries, in which 13 (0.5%) patients were wearing a helmet. The median time from injury to admission was 3 hours (IQR = 2–7). 2,363/3,172 (75%) patients did not undergo surgery and 405/3,172 (13%) underwent decompressive craniectomy and haematoma evacuation. Inpatient mortality was 5.6% (median length of stay = 6 days [IQR = 4–10]) and overall mortality at discharge from follow-up (median = 6 months [IQR = 3–9]) was 18%. Inpatient deaths most frequently occurred within two days of admission (82/174 [47%]). 2,066/3,082 (67%) patients had upper- or lower-good recovery. The IMPACT (AUC = 83%, CI: 79–87%) and Rotterdam CT prognostic scores (AUC = 79%, CI: 75–83%) predicted inpatient mortality with good performance.

Conclusions
We describe the TBI population of a high-volume tertiary hospital in India, including inpatient mortality, medium-term functional status, and the performance of commonly used prognostic tools.
O216: RECOVER REALITY - Recover after injury or surgery to the brain and spine with virtual Reality: Feasibility Trial Results and Effectiveness Trial Protocol
Authors: Bolton William , Cooper Sara , Sinha Rohitashwa , Oluwaseyi1 Adebola , Stephenson Elisa , Ewan Seonaid , Hunsley Rachel , Kearton Victoria , Stevens David , Mathew Ryan 
Published: March 2024

Abstract

Aim
Neurorehabilitation is fundamental to improve outcomes for patients recovering from injury or surgery to the central nervous system. Access to neurorehabilitation is limited by resource shortages, the consequences of which are unfulfilled therapy needs, longer hospital stays and detrimental effects on quality of life. Virtual reality (VR) could be used to augment neurorehabilitation in a self-directed, safe, virtual environment. The aim of this study is to investigate the feasibility of a VR rehabilitation programme in an acute neurosurgical inpatient environment to improve neurorehabilitation.

Method
A single group, feasibility study was conducted in a tertiary UK neurosurgical department. Patients aged 16 and over who had undergone a neurosurgical intervention for brain tumours were eligible. Participants were offered a VR session at least once per day for the first 14 days post-surgery/injury or until discharge, whichever comes first, with reasons for non-engagement collected. Primary outcomes were feasibility outcomes, and secondary outcomes included rehabilitation engagement and length of stay.

Results
Thirty-five participants were recruited. One withdrew due to headaches. None of the VR applications failed but connectivity to accompanying tablet was latent in 50% of cases. Majority of patients were able to use VR from day 2 post-op or injury. The Hopkins Rehabilitation Engagement scale and Simulation Sickness Questionnaires were feasible instruments to measure outcomes.

Conclusions
Feasibility was confirmed in this study. A multi-centre, prospective, randomised, controlled, unblinded, parallel-group trial of virtual reality enhanced neurorehabilitation versus standard neurorehabilitation for improving recovery after neurotrauma or neurosurgery has now been designed.
O226: OTD is cytotoxic to A-375 melanoma cells without compromising fibroblast migratory wound healing function – a potential role in perioperative melanoma surgery
Authors: O'Callaghan Stephanie Kate , Foley Cathriona , Redmond Henry Paul 
Published: March 2024

Abstract

Introduction
Melanoma incidence is increasing with 325,000 new cases reported in 2020 worldwide and 57,000 deaths. High recurrence rates are associated with prolonged inflammation and subsequent immunosuppression post-operatively. Surgical adjuvants may play a role in mitigating these adverse immune responses while increasing the cytotoxicity of cancer cells. Our previous research demonstrated anti-inflammatory effects of 1,4,5-oxathiazinane-4,4-dioxide (OTD) on Human Dermal Fibroblasts (HDFs) by the reduction of cytokine production. This study evaluates its cytotoxicity on melanoma cells.

Methods
OTD treatments of 0.25mM, 0.5mM, 0.75mM, 1mM and 1.25mM were applied to A-375 primary melanoma cells in triplicate for 24h and an MTT assay assessed cell viability. The absorbance was measured at 570nm wavelength. Cell viability was expressed as a percentage of the control. Results were compared using one-way analysis of variance (ANOVA) with GraphPad Prism software.

Results
Application of OTD treatments demonstrated a cytotoxic effect on melanoma cells at all concentrations. Relative optical density (OD) value was compared for each concentration against the control. A significant difference in cytotoxicity, relative to untreated control, was observed for each concentration; 56.8% at 0.25mM OTD (p*** = 0.001) and 68 to 71.6% at 0.5mM to 1.25mM OTD (p****&lt;0.001).

Conclusion
OTD induces cytotoxicity in primary melanoma cells at all concentrations. Whereas our previous research demonstrated at 0.75mM it reduced inflammatory cytokine production in HDFs without adversely affecting migration. Therefore, OTD as a surgical adjuvant has the potential to be cytotoxic towards primary melanoma cells, reduce HDF inflammation and preserve migratory wound healing function.
O198: Cytosponge: Innovative technology in Barrett’s oesophagus surveillance
Authors: Khan Saadia , Brown Ayla , Ghoneima Ahmed , Bonner Clare , Farrah Nima , Hammett Felix , Sowemimo Sinmidele , Asarbakhsh Mariam , Saha Arin 
Published: March 2024

Abstract

Introduction
British Society of Gastroenterology guidance recommends oesophagogastroduodenoscopy (OGD) for Barrett’s oesophagus surveillance with quandrantic biopsies for every 2cm length of Barrett’s. The Covid pandemic led to delays in Barrett's surveillance and prolongation of surveillance intervals. This study assessed the potential role of Cytosponge, a novel cytology sampling device, in Barrett's surveillance.

Methodology
All patients due Barrett's surveillance in 2022/23 were identified and screened to assess suitability for Cytosponge. Cytology results and associated early clinical outcomes were assessed.

Results
193 patients (77%) were suitable for Cytosponge, and 175 of these (90%) did not require OGD. 18 patients (10%) required urgent OGD for inadequate cytology samples (3), cellular atypia (8), aberrant p53 (3) or dysplasia (4). 2 patients had high grade dysplasia on subsequent OGD, successfully treated with radiofrequency ablation. No diagnosis of oesophago-gastric cancer was made during the follow-up period. By July 2023, 282 patients with Barrett’s oesophagus had completed Cytosponge assessment; minimum follow-up was 4 months and no patients had developed ‘inter-test’ malignancy.

Conclusion
These data are promising and suggest that endoscopy and biopsy may not be required for all Barrett’s surveillance. Cytology samples alone may be sufficient to assess for epithelial dysplastic and neoplastic change in Barrett’s surveillance, with judicious utilisation of endoscopy resources where indicated and necessary. Patients who received a Cytosponge in 2022 will be due for endoscopic surveillance in 2024 – these data will provide valuable additional information about the role of Cytosponge in Barrett’s surveillance and whether endoscopy can be replaced altogether.