bluuebunny/crossref_metadata_2025_split huggingface dataset:
O9: DETECTION OF RELEVANT GENE MUTATIONS IN GLIOMA USING PLASMA CELL FREE DNA
Authors: Ita M , Nolan Y , Toulouse A , Wang JH , Lim CH , O'sullivan MGJ , Kaar GF , Redmond HP 
Published: April 2021

Abstract

Background
Comprehensive molecular profiling of gliomas provide information essential for accurate biological classification beyond traditional histopathology. Genomic profiling utilizing tumour tissue samples inevitably involves obtaining tissues through potentially hazardous surgical procedures or stereotactic biopsies carrying risks of morbidity and mortality. Tissues from biopsies may also be insufficient or fail to capture a comprehensive picture of the tumours genetic profile due to tumour heterogeneity. In these contexts, complementary minimally invasive strategies are needed for molecular profiling of gliomas. Cell free DNA (cfDNA) has emerged as an easily accessible biomarker containing fragments of circulating tumour DNA (ctDNA) released into plasma through apoptosis. We explored its potential utility in genomic profiling of brain tumours.

Method
Plasma cfDNA from patients with radiographically suspected brain malignancies were extracted and quantified before planned surgical interventions. Cell free DNA was extracted using a QIAamp Circulating Nucleic Acid Kit (Qiagen), and was quantified (ng cfDNA/mL) using a DS-11 FX Spectrophotometer (DeNovix). Pathway focused profiling of somatic mutation status was performed using QBiomarker Somatic Mutation PCR Arrays for human brain cancers (Qiagen) through real time PCR (Roche).

Result
Somatic mutations in human brain cancer were evaluated in the following genes; BRAF, CTNNB1/beta-catenin, EGFR, IDH1, IDH2, KRAS, NF2, NRAS, PIK3CA, and PTEN. A total of 14 (70%) patients had greater than 1 somatic mutation detected in their plasma cfDNA.

Conclusion
We postulate that glioma derived circulating tumour DNA occur in plasma, and genomic analysis using cell free DNA may complement current methods of glioma genomic characterisation.

Take-home message
Glioma derived circulating tumour DNA occur in plasma.
O20: PREOPERATIVE INTRAVENOUS IRON THERAPY AND SURVIVAL AFTER COLORECTAL CANCER SURGERY: LONG TERM RESULTS FROM THE INTRAVENOUS IRON IN COLORECTAL CANCER-ASSOCIATED ANAEMIA (IVICA) TRIAL
Authors: Dickson EA , Keeler BD , Ng O , Kumar A , Brookes MJ , Acheson AG 
Published: April 2021

Abstract

Background
Intravenous iron is now the standard treatment to correct preoperative anaemia. However, iron may promote tumour growth and progression which could influence cancer recurrence and survival. We explore the long term postoperative outcomes of patients receiving oral (OI) or intravenous iron (IVI) as part of a randomised controlled trial.

Method
The multicentre IVICA trial randomised anaemic colorectal cancer patients in a 1:1 fashion to receive either OI or IVI prior to their elective operation. Follow up analysis of all patients was performed and Kaplan-Meier survival estimates and Cox proportional hazard models were used to compare groups. A pooled analysis comparing patients who did/did not achieve preoperative resolution of anaemia was also undertaken.
Result, Data were available for 106 of the 116 IVICA patients (OI n=55, IVI n=51). Median follow up was 61 months (IQR 38-68, [range 1-80]). Overall survival estimates at 3 and 5 years were 82%(95% CI 76-90) and 72%(58-83) respectively for OI and 75%(61-86) and 59%(45-72) for IVI, P=0.106. No significant difference in 5-year overall survival (HR 1.73, 95% CI 0.90-3.34 P=0.102) or disease-free survival (HR 1.50, 95% CI 0.83-2.73 P=0.182) was observed between groups. Those non-anaemic at operation demonstrated improved 5 year overall survival (HR 3.26 [1.01-10.58], P=0.05). Non-significant trends in improved disease-free survival (HR 2.29 [0.91-5.81], p=0.08) were observed for the non-anaemic group

Conclusion
Preoperative correction of anaemia confers a postoperative survival advantage following elective colorectal cancer surgery. Due to its superior efficacy intravenous iron is recommended as the treatment of choice for this anaemia.

Take-home message
Preoperative correction of anaemia, achieved most effectively with intravenous iron, may offer improved long term postoperative survival after colorectal cancer surgery.
O47: IKK-ALPHA AS A POTENTIAL NOVEL TARGET FOR TREATMENT OF COLORECTAL CANCER
Authors: Patel M , Quinn JA , Pennel KAF , Flanagan D , Horgan PG , McMillan DC , MacKay S , Sansom O , Edwards J 
Published: April 2021

Abstract

Introduction
There is substantial evidence linking NF-κB and cancer-related processes. The aim of this study was to investigate the role of IKKα, the main catalytic component of non-canonical NF-κB pathway in colorectal cancer (CRC).

Method
Immunohistochemistry and immunofluorescence was used to examine expression of IKKα in 1030 patients undergoing resection for stage I-III CRC. To assess IKKα inhibition, organoids were prepared from wild type (WT) mouse colon, mouse models of CRC (Apc and Apc.KRAS.pT53.TGFbR2 (AKPT)) and patient derived human organoids. These were treated with an IKKα inhibitor, SU1433 and organoid size and cell viability assessed.

Result
High cytoplasmic expression of IKKα was associated with increasing T stage (p=0.012), poor tumour differentiation (p=0.010), tumour necrosis (p=0.013) and low proliferation status (p=0.013). High punctate IKKα expression was associated with reduced CSS (HR1.20 95%CI 1.02-1.42, p&lt;0.001). Immunofluorescence showed IKKα was co-located with a Golgi-related structure. SU1433 did not significantly impact on WT (C57/B16) organoid viability up to a concentration of 1uM, however organoid size and cell viability was significantly reduced in a dose-dependent manner in organoids from both Apc and AKPT mouse models. A similar reduction was observed in patient derived human organoids.

Conclusion
Punctate IKKα expression was associated with poor cancer specific survival in CRC patients. The relationship between IKKα and the Golgi requires further investigation. Inhibition with SU1433, impacted on CRC mouse and patient derived human organoid size and cell viability. These results suggest that IKKα following further investigation could be employed as a novel therapeutic target in CRC.

Take-home message
IKKα is up-regulated in patients undergoing surgery for CRC, this is associated with poor survival outcome and inhibition of IKKα and has presented itself as a novel therapeutic target. The relationship between IKKα and the Golgi has raised interesting questions regarding the molecular behaviour of IKKα and this warrants further investigation.
O51: ARTIFICIAL INTELLIGENCE UTILIZING RECURRENT NEURAL NETWORKS TO CONTINUOUSLY MONITOR COMPOSITES OF SURGICAL EXPERTISE
Authors: Yilmaz R , Winkler-Schwartz A , Mirchi N , Reich A , Del Maestro R 
Published: April 2021

Abstract

Introduction
Many surgical adverse events occur secondary to technical errors related to poor bimanual skills, fatigue and lack of the required expertise. We developed AI algorithms to continuously assess surgical bimanual technical performance during virtual reality simulated surgical tasks. To our knowledge, this is the first attempt in surgery to train AI algorithms to continuously monitor and evaluate bimanual skills comprehensively.

Method
Fifty individuals from four expertise levels (14 experts/neurosurgeons, 14 senior residents, 10 junior residents, 12 medical students) performed two virtual reality simulated surgical tasks with haptic feedback: a subpial tumor resection 5 times and a complex, realistically simulated brain tumor operation once. Each task required complete tumor removal while minimizing bleeding and damage to surrounding tissues using a simulated ultrasonic aspirator and a bipolar. A recurrent neural network continually tracked individual bimanual performance utilizing 16 performance metrics generated every 0.2 seconds.

Result
The recurrent neural network algorithm was successfully trained using neurosurgeons and medical students' data, learning the composites of expertise comparing high and lower skill levels. The trained algorithm outlined and monitored technical skills every 0.2 second continuously organizing performance of each surgical task into three levels: ‘excellent’, ‘average’ and ‘poor’. The percentage time spent on each level was calculated and significant differences found between all four groups for ‘excellent’ and ‘poor’ levels.

Conclusion
AI-powered surgical simulators provide an advanced assessment and training tool. AI's ability to continuous assess bimanual technical skills during surgery may further define the composites necessary to train surgical expertise.

Abbrev
AI: artificial intelligence

Take-home message
By advanced artificial intelligence algorithms surgeon's bi-manual technical skills can be assessed continuously, time periods of poor performance which increase the possibility of errors in performance can be identified.
O54: GENDER REPRESENTATION IN EDITORIAL BOARDS OF INTERNATIONAL GENERAL SURGERY JOURNALS
Authors: Gallivan ER , Arshad SR , Skinner H , Burke JR , Young AL 
Published: April 2021

Abstract

Introduction
Despite women constituting over half of new UK doctors, and a similar proportion worldwide, gender disparity remains an issue throughout academic medicine. Surgery has shown particularly slow progress towards gender parity. This study aims to quantify gender representation within editorial boards of the top 25 general surgical journals.

Method
All surgical journals were collated using the SCImago Journal Rank (SJR) and Journal Impact Factor (JIF). Non general surgery journals were excluded. Journals were contacted requesting gender editorial team demographics. Editorial board data was collected via journal websites on 20th November 2019.

Result
The top 25 surgical journals were determined through SJR and JIF ranking methods. Editorial board data was publicly available for 31 of these 32 different surgical journals. This data was then examined. Women accounted for 18.4% (576/3135) of total editorial board positions. Women constituted 12.5% (5/40) of Editors-in-Chief positions, 31.6% (31/98) of Deputy Editors and 17.2% (416/2415) of general editorial board positions.

Conclusion
For the first time, gender disparity has been demonstrated within editorial boards of the most prominent general surgery journals. The implications of such significant gender disparity are wide reaching. Action should be taken to champion fair female representation, eliminate risk of bias and provide more visible female role models in academic surgery.

Take-home message
For the first time, this study demonstrates gender disparity in Editorial boards of major general surgery journals. Action should be taken to champion fair female representation, eliminate risk of bias and provide more visible female role models in academic surgery.
O63: POST-OPERATIVE ACUTE KIDNEY INJURY IN PATIENTS UNDERGOING MAJOR GASTROINTESTINAL SURGERY— AN OBSERVATIONAL COHORT STUDY AND EXTERNAL VALIDATION OF A PROGNOSTIC MODEL
Authors:   Collaborative STARSurg
Published: April 2021

Abstract

Introduction
Acute kidney injury (AKI) is well-recognised as a significant cause of morbidity and mortality. Due to limited evidence on the longer-term implications, this study aimed to explore the association of postoperative AKI one-year survival and renal function in patients undergoing major gastrointestinal and liver surgery.

Method
Patients undergoing major gastrointestinal surgery in the prospective Outcomes of Kidney Injury after Surgery (OAKS) study across UK and Ireland were followed up at one-year postoperatively. The primary outcome was survival at 1-year and secondary outcomes included the composite “Major Adverse Kidney Events” outcome at day 365 (MAKE-365), with respective multivariable Cox-regression and logistic regression analysis performed.

Result
Of 62.2% of OAKS patients (n=3,575/5,745) with 1-year follow-up, there were no significant differences compared to those without follow-up. Among the follow-up cohort, 8.0% (n=269) patients died. On univariate analysis, patients experiencing 7-day postoperative AKI had a significantly higher hazard of death between 30 to 365 days postoperatively (HR: 2.10, 95% CI: 1.50-2.94, p&lt;0.001) compared to patients who did not. This persisted on multivariable Cox-regression (HR: 1.67, 95% CI: 1.17-2.40, p=0.005). Furthermore, 9.1% (n=305) patients met the MAKE-365 endpoint. Multilevel logistic regression analysis demonstrated that the MAKE-365 endpoint was independently associated with both stage 1 (OR: 1.78, 95% CI: 1.22-2.61, p=0.003) and stage 2-3 7-day postoperative AKI (OR: 6.13, 95% CI: 3.97-9.45, p&lt;0.001).

Conclusion
Post-operative AKI is associated with significantly higher rate of 1-year mortality and MAKE-365 endpoints. Improved monitoring of these patients may be warranted to identify and facilitate potential avenues for intervention

Take-home message
Post-operative AKI is associated with significantly higher rate of 1-year mortality. Hence, early detection and improved monitoring of patients with AKI with improve long-term outcomes of these patients.
O72: SECONDARY PREVENTION OF CARDIOVASCULAR DISEASE IN PERIPHERAL ARTERY DISEASE PATIENTS
Authors: Rashid ST , Bangee S 
Published: April 2021

Abstract

Introduction
Peripheral artery disease (PAD) is associated with significant cardiovascular morbidity and mortality which can be reduced by the treatment of atherosclerotic risk factors. Recent research demonstrates that novel drugs can significantly enhance PAD outcomes. However, the uptake of these drugs is uncertain. We wished to audit current atherosclerotic management in PAD patients as well as their eligibility for newer drugs - PCSK 9 inhibitors, SGLT2 inhibitors, and DOAC drugs – in accordance with relevant guidelines and trials.

Method
100 PAD inpatients and outpatients seen at a teaching hospital in the UK within the month of March 2019 were assessed. Medications from PAD patients were recorded from hospital records and patient histories were assessed for secondary prevention of cardiovascular disease - lipids, blood pressure, diabetic control, and atherothrombotic prevention.

Result
showed that compliance with NICE guidelines had a wide range – from 19% of outpatients on correct lipid control to 89% of inpatients on optimal atherothrombotic management. Based on the best evidence of eligibility: 0 of 41 eligible patients were taking PCSK9 Inhibitors, 1 out of the 71 was on an SGLT 2 inhibitor and 6 of 98 patients were on Rivaroxaban.

Conclusion
This audit shows adherence to NICE guidelines is variable for secondary prevention of atherosclerosis in PAD patients. Furthermore, very few novel treatments had been prescribed for suitable patients. Overall, prescribing for PAD risk factor management can be significantly improved. A solution could be dedicating risk factor clinics led by nurses, pharmacists or physicians.

Take-home message
Steps need to be taken to prevent cardiovascular disease in peripheral arterial disease patients. Steps include improvements in the following of guidelines, exploration of novel treatments, and the introduction of special risk factor clinics focused on improving the prognosis of the patients.
O80: GREMLIN-1 PROMOTES TUMOURIGENESIS AND METASTASIS IN HER2 POSITIVE BREAST CANCER
Authors: Zabkiewicz C , Ye L , Hargest R 
Published: April 2021

Abstract

Introduction
HER2 over-expression denotes poor prognosis in breast cancers.Bone morphogenetic protein(BMP) signalling is known to interact with EGF signalling, co-regulating breast cancer progression.BMP antagonist Gremlin-1 may influence breast cancer disease progression, but this remains unexplored in HER2 positive breast cancers.

Method
GREM1 and HER2 expression, and clinical outcomes were examined in clinical cohorts.GREM1 overexpression or pEF control plasmid were transduced into BT474 HER2+breast cancer cells. In vitro function tests using BT474 pEF and BT474GREM1cells include 2D/3D growth, migration, and expression of epithelial to mesenchymal transition(EMT)markers. Signalling cascades were examined in BT474 treated with RhGremlin-1. In vivo, BALB/c nude mice underwent either mammary injection or intra-cardiac injection of BT474pEF or BT474GREM1 cells and disease burden assessed.

Result
GREM1 expression correlates with HER2 in breast tumours(p=0.03) and is higher in metastatic HER2 positive cancers (p = 0.04). HER2 positive patients with high GREM1 have poor survival(p = 0.0002). BT474GREM1cells have up-regulated markers of EMT compared to control. BT474 RhGremlin-1 treated cells have active AKT pathway signalling, independent of BMP signalling. In vitro, BT474GREM1cells significantly proliferate and migrate compared to control(p&lt;0.05 and p &lt; 0.001).This is confirmed in vivo, BT474GREM1 mice grew significantly larger mammary tumours(p&lt;0.05) and had more PETCT metastatic hotspots.

Conclusion
Gremlin-1 is correlated with poor outcomes in HER2 patients and promotes breast cancer cellular growth, migration and metastasis.Gremlin-1 is a novel area of research with potential as a prognostic biomarker and therapeutic target for personalised, effective, breast cancer outcomes.

Take-home message
BMP antagonists are gaining interest for their potential in breast cancer prognosis and therapeutics.This novel area of research shows BMP antagonist Gremlin-1 is of importance in HER2 positive breast cancers.
DRAGONS DEN
P4: EXTERNAL VALIDATION OF THE OUTCOMES AFTER KIDNEY INJURY IN SURGERY (OAKS) PROGNOSTIC SCORE TO PREDICT POSTOPERATIVE ACUTE KIDNEY INJURY IN PATIENTS UNDERGOING MAJOR ELECTIVE COLORECTAL SURGERY
Authors:   STARSurg Collaborative, EuroSurg Collaborative
Published: April 2021

Abstract

Background
Postoperative Acute Kidney Injury (AKI) is associated with significant morbidity and mortality following major gastrointestinal surgery. The Outcomes After Kidney injury in Surgery (OAKS) prognostic score risk stratifies patients undergoing major gastrointestinal surgeries for 7-day postoperative acute kidney injury (AKI). This study aimed to perform external validation of an international elective colorectal cohort.

Method
The Ileus MAnagement INternational (IMAGINE) audit (January to April 2018) included consecutive adults undergoing elective colorectal resection or stoma reversal across Europe and Australasia. Multivariate logistic regression was performed using data on 7-day AKI and the OAKS prognostic variables (age, sex, ASA grade, preoperative estimated glomerular filtration rate, planned open surgery, and preoperative use of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers). Discrimination and calibration (Hosmer–Lemeshow test) were assessed on prediction of patients at high-risk (&gt;20%) of postoperative AKI.

Result
Of 4046 patients included across 338 centres, 13.4% (n=542) developed 7-day AKI. The model discrimination was 0.67 (95% CI = 0.65-0.70), identifying high-risk patients with low sensitivity (0.28, 95% CI: 0.25-0.32) but high specificity (0.90, 95% CI = 0.89-0.91). Furthermore, the model demonstrated good calibration (p=0.518).

Conclusion
Discrimination of the OAKS score for patients at high-risk of postoperative AKI in this cohort is good, and remains consistent with the derivation cohort. High-risk patients identified may represent a feasible target for interventions aimed at mitigating AKI.

Take-home message
Prognostic risk scores may be helpful in predicting risk of postoperative acute kidney injury in patients undergoing major abdominal surgery.
P7: ACUTE KIDNEY INJURY AFTER ELECTIVE COLORECTAL SURGERY: RESULTS OF A NATIONAL CLOSED-LOOP AUDIT
Authors:   STARSurg Collaborative, EuroSurg Collaborative
Published: April 2021

Abstract

Introduction
The aim of this study was to re-audit the rates of acute kidney injury (AKI) after elective colorectal surgery, following local presentations of results.

Method
Outcomes After Kidney injury in Surgery (OAKS) and Ileus Management International (IMAGINE), were prospective multicentre audits on consecutive elective colorectal resections, in the UK and Ireland. These were performed over 3-month periods in 2015 and 2018 respectively. During the interim period, results were presented at participating centres to stimulate local quality improvement initiatives. Risk-adjusted 7-day postoperative AKI rates were calculated through multilevel logistic regression based on the OAKS prognostic score.

Result
Of the 4,917 patients included, 3,133 (63.7%) originated from OAKS and 1,784 (36.3%) from IMAGINE. On univariate analysis, there was no significant difference (p=0.737) in the 7-day AKI rate between OAKS (n=346, 11.8%) and IMAGINE (n=205, 11.5%). However, the risk-adjusted AKI rate in IMAGINE was significantly lower compared to OAKS (-1.8%, 95% CI: -2.3% to -1.3%, p&lt;0.001). Of 47 centres (40.1%) with a recorded local presentation, there was no significant difference in the subsequent AKI rate in IMAGINE (-0.7%, -2.0% to 0.6%, p=0.278).

Conclusion
Rates of AKI after elective colorectal surgery significantly reduced on re-audit. However, this may be related to increased awareness from participation or national quality improvement initiatives, rather than local presentation of results. Abbrev. AKI - Acute Kidney Injury, OAKS - Outcomes After Kidney injury in Surgery, IMAGINE - Ileus Management International

Take-home message
Risk-adjusted AKI rates significantly reduced on re-audit, however, this was most likely due to factors separate from the local presentation of initial results.
P8: A COMPARATIVE EVALUATION OF INTENSIVE OUT-OF-TERM AND CONVENTIONAL TERM-TIME MENTORING SCHEMES IN PREPARING MEDICAL STUDENTS FOR A CAREER IN SURGERY
Authors: Sawhney R , Ingram J , Smith J 
Published: April 2021

Abstract

Introduction
Mentoring schemes have been established to mitigate these concerns and improve interest in surgery among medical students; however, there is a paucity of research on whether conventional term-time (CTT) mentoring or more intensive out-of-term (IOT) mentoring is more meaningful in promoting surgical careers.

Method
Most surgical societies in the UK offer CTT schemes (ca. one-to-three mentoring during the academic year) to their members. In addition to this, a student-led surgical society piloted an IOT scheme (one-to-one mentoring during the summer break). Students completed a ten-point questionnaire at the end of the academic year evaluating the scheme(s) they participated in.

Result
Of the 35 students that completed a questionnaire, 74% participated in either CTT or IOT (1:1), and 26% participated in both. Students that participated in one scheme considered that scheme to be superior in increasing interest in surgery (CTT 69%; IOT 79%), while students that participated in both favoured IOT (78%). With regards to increasing preparedness for surgical careers, IOT was universally preferred. According to previously determined levels of engagement, maximum engagement was achieved by 61.5% of students in a single week of IOT, compared to only 7.7% of students after a full academic year of CTT.

Conclusion
IOT outperforms CTT with regards to boosting interest in surgery and preparedness for surgical careers. This suggests that introduction of IOT schemes nationally may be a valuable advance in the future of surgical mentoring.

Take-home message
Adopting an intensive out-of-term mentoring scheme has shown a positive outcome in terms of both increasing preparedness for, and interest in, surgical careers. This suggests implementing such time intensive schemes nationally could be a sensible future-step in surgical mentoring.