bluuebunny/crossref_metadata_2025_split huggingface dataset:
O014 SIKs suppress tumourigenesis in colorectal cancer and can serve as prognostic biomarkers
Authors: Alcazaren L , Martin T , Jiang W , Ruge F 
Published: May 2023

Abstract

Introduction
Salt inducible kinases (SIKs) have a role in various biological process, including tumourigenesis in a tissue-dependent manner. However, their role in colorectal cancer (CRC) has yet to be established. We hypothesise that SIKs are differentially expressed in CRC, both promoting and preventing tumourigenesis.

Methods
SIK mRNA expression was determined within the Cardiff CRC cohort using reverse transcription-quantitative PCR and clinicopathological features were evaluated. Kaplan-Meier survival curves were created. SIK protein expression in CRC tissue were analysed using immunohistochemistry. SIK knockdown (KD) models were created to investigate the role of SIKs on barrier function and migration in vitro.

Results
Low SIK levels within CRC tissue were associated with poorer clinicopathological features. At the protein level, SIKs were downregulated in CRC tissue. Reduced expression of SIK2 and SIK3 were linked to poorly differentiated tumours. SIK KD induced different effects on cell barrier function, depending on the cell type. SIK KD increased cell migration in HT115 cells but reduced it in HRT18 cells.

Conclusion
Following translation, SIK expression was lower in CRC tumours than in normal tissue. Low SIK levels correlated to poorer clinicopathological characteristics, demonstrating their protective role in CRC. SIK loss contributed to cell-cell barrier dysregulation in vitro, revealing a possible mechanism of how SIKs regulate the metastatic potential of tumours. We demonstrate for the first time, the expression and role of all three SIKs in the tumourigenesis of CRC. This novel discovery has revealed possible therapeutic targets and biomarkers.
O015 CD34+ vascular stem cells play a key role in vein graft remodelling
Authors: Xu S , Smith A , Modarai B 
Published: May 2023

Abstract

Introduction
Venous conduits that are grafted into arterial circulation undergo neointima remodelling, causing excessive hyperplasia that contributes to early graft failure which a major drawback of surgical vein grafting. Stem cells expressing the CD34 surface protein have been postulated to have a key role in the process, but their involvement has not been studied.

Methods
A segment of the inferior vena cava of wild-type mice was interposition grafted into mice in which CD34-expressing cells were located through their genetically induced expression of tdTomato red marker protein (CD34-CreERT2xRosa26-tdTomato mice). This enabled us to determine whether CD34+ derived cells found in the vein after grafting originated from the donor mouse or from the host. Grafts were explanted 4wks after surgery and analysed by immunohistology and single cell RNA sequencing to resolve cell-level gene expression. Cells from vein grafts were also cultured in vitro and proliferation/differentiation assays were carried out on purified CD34+ cells.

Results
70% of cells in the vein graft neointima were derived from CD34+ graft lineage whereas there was no significant contribution of recipient-derived stem cells or bone marrow cells to the neointima. Vein graft neointima smooth muscle cells (SMC) are not stem cells derived. CD34+ stem cells differentiated predominantly into fibroblasts which induced vein SMC phenotype switching and proliferation.

Conclusion
The majority of CD34+ stem cells found in the neointima of veins, grafted into the arterial circulation were derived from the resident cell population. These cells
O036 Postoperative complications are predicted by surgery duration in the unilateral deep inferior epigastric perforator (DIEP) flap reconstruction: a retrospective cohort study
Authors: Shtarbanov P , Ioannidi L , Ghali S , Hamilton S , Ahmed Z , Nikkhah D 
Published: May 2023

Abstract

Introduction
Currently, one published study documented operative time (OT) as a predictor for postoperative outcomes in bilateral deep inferior epigastric perforator (DIEP) flap breast reconstructions. No literature has investigated this in unilateral DIEP flaps. We aimed to determine the relationship between unilateral OT, postoperative complications and length-of-stay (LOS).

Methods
Electronic hospital data of adult women that underwent elective immediate or delayed unilateral DIEP reconstruction at a tertiary centre in London, between 2021 to 2022, was retrospectively analysed. Patients were divided into four groups depending on OT quartiles to define a critical cut-off period. Data on extensive potential confounders was recorded and used in univariable and multivariable regression models. Further statistical analyses were performed where appropriate.

Results
The final cohort contained 66 patients. Through quartiles, the risk-adjusted cut-off OT was defined as 515 minutes. After risk-adjustment, operations &gt;515 minutes had a significantly higher overall complication rate than ≤515 minutes (HR: 2.16, p=0.032, 95% CI: 1.067, 4.38). No significant difference in mean ranks of LOS (p=0.16) was noted above the cut-off period. In patients that developed at least one complication type, no significant difference was observed in the unadjusted return-to-theatre rate between the two groups (HR: 0.86, p=0.82, 95% CI: 0.23, 3.24).

Conclusion
We confirmed OT was an independent predictor for postoperative complications in the DIEP flap and demonstrated this in unilateral reconstructions. Larger multicentre prospective studies are required to ascertain the significance of the OT effects, and to deduce the minimum OT threshold below which detriment to patient outcomes arises.
O037 VEGF-A: a potential prognostic biomarker for donor liver viability
Authors: Cheemungtoo G , Dobbins J , Mahendran B , Tingle S , Bates L , Figueiredo R , Amer A , Sen G , Hammond J , Talbot D , White S , Manas D , Wilson C 
Published: May 2023

Abstract

Introduction
Waitlist mortality for liver transplant recipients may be tackled by increasing graft utilisation from marginal donors. At present, there are no reliable methods of assessing the quality of potential donor grafts prior to post-transplantation complications such as early allograft dysfunction (EAD). This pilot study evaluates the validity of a patented biomarker panel on flush effluent samples collected on the backbench after organ retrieval.

Methods
All flush effluent samples were collected and stored with patient consent and ethical approval. Flush effluents were retrieved from cold-stored donor liver grafts on the backbench for both transplantation and research purposes. Meso Scale Diagnostics multiplex assays were used to quantify biomarker levels in each sample with a BCA protein assay for data normalisation. Graft utilisation was assessed as our primary outcome measure and post-operative EAD incidence was our secondary outcome.

Results
Thirteen donor livers were sampled, out of which 61.5% (n=8) were transplanted and 38.5% (n=5) were declined. Utilisation outcomes analysis demonstrated that only VEGF-A levels were significantly different between the transplanted and declined grafts (p&lt;0.001). EAD incidence was 37.5% (n=3) from the 8 transplant recipients. There was no statistical significance between each biomarker level and the development of EAD post-transplantation.

Conclusion
Liver flush effluents are a rich, novel source of protein biomarkers. Flush VEGF-A may be a prognostic biomarker for donor liver viability. Further evaluation is warranted for point of care testing.
O042 Enzymatic conversion of human blood group A kidneys to universal blood group O
Authors: MacMillan S , Hosgood S , Rahfeld P , Kizhakkedathu J , Macdonald S , Withers S , Nicholson M L 
Published: May 2023

Abstract

Introduction
The ABO blood group restriction on allocation of donor organs leads to waiting time disadvantages for individuals of more restrictive blood types. Here, we outline the first preclinical use of two enzymes from Flavonifractor plautii to convert human blood group A kidneys to universal blood group O.

Methods
Six pairs of human kidneys rejected for transplantation and offered for research were used to in this study with approval from the National Research Ethics committee and Research and Development Office (NRES: 15/NE/0408). Three pairs were perfused for 6 h using normothermic machine perfusion (NMP), and three pairs were perfused for 24 h using hypothermic machine perfusion (HMP), with one kidney per pair randomised to enzyme treatment. Cortical biopsies collected throughout perfusion were examined for antigen loss using immunofluorescence microscopy.

Results
After 2hrs of NMP, a significant loss of 83.4±10.2% blood group A antigen expression was observed compared to pre-treatment levels (p=0.012), while no significant changes were observed in control kidneys (p=0.999). For HMP, a maximal loss of 71.2±21.9% was observed after 6 h (p=0.066), with no decrease observed in the contralateral controls (p=0.977). Haemodynamic perfusion parameters were stable in both cohorts, with no significant difference between control vs treated kidneys.

Conclusion
Our results show a loss of 70-80% of blood group A antigens in as little as 2 h of NMP and 6 h of HMP. These approaches pave the way for the first clinical studies that could herald the start of a new era that transforms donor organ allocation in kidney transplantation.
O051 Combining sarcopenia and asa status to inform emergency laparotomy outcomes: could it be that simple?
Authors: Karolewski J , Ming Y J , Howley P , Holmes M , Gani J , Pockney P 
Published: May 2023

Abstract

Introduction
Emergency laparotomy mortality prediction tools are usually multipoint scoring systems such as NELA, ACS-NSQIP, and P-POSSUM. However, these tools are time consuming and complex to use. Sarcopenia on CT scans is correlated with mortality in emergency laparotomy patients and we explored the combination of this (as measured by PM:L3) with ASA as a simple and efficient tool to predict the outcome of Emergency Laparotomies.

Methods
A retrospective analysis was conducted across four hospitals, identifying 500 patients who underwent emergency laparotomies between 2016-2017 and had contemporaneous abdomino-pelvic CT scans. Radiological sarcopenia was measured using the PM:L3 ratio on a cross-sectional axial CT slice. PM:L3, NELA, ACS-NSQIP, and P-POSSUM, as well as simplified ASA (sASA) were retrospectively calculated and assessed as potential predictors of 30-, 90-, and 365-day mortality.

Results
ACS-NSQIP, NELA, P-POSSUM and PM:L3/sASA were each statistically significant predictors of 30-day, 90-day and 365-day mortality (p&lt;0.001). Logistic regression models of 30-, 90- and 365-day mortality containing just the two predictors PM:L3 and simplified ASA exhibited AUCs of 0.838, 0.805 and 0.775 respectively, which are comparable with the best currently used predictors ACS-NSQIP and NELA.

Conclusion
Combining PM:L3 with ASA scores appears to be a significant predictor of 30-, 90-, and 365-day mortality in emergency laparotomy patients in Australia. The results are comparable with some of the best performing widely used risk assessment tools and provide a more time-efficient and accessible method of performing risk assessments in Emergency Laparotomy patients.
O052 Erect chest X-ray is inadequately diagnostic and falsely reassuring in assessment of abdominal visceral perforation: a retrospective cohort study
Authors: Saji A P , Shah J , Hajibandeh S , Hajibandeh S 
Published: May 2023

Abstract

Introduction
Pneumoperitoneum refers to air in the abdominal cavity due to abdominal visceral perforation and can be visualised as air under the diaphragm on erect chest x-ray. This study aims to evaluate the accuracy of erect CXR in detecting the presence of abdominal visceral perforation.

Methods
A retrospective cohort study in a single centre was conducted between January 2014 and January 2020. The study population comprised of all patients with gastrointestinal perforation confirmed by assessment during emergency laparotomy. The outcome measure of this study was perforation detection rate, defined as detection of air under diaphragm in preoperative erect CXR confirmed by two independent qualified radiologists.

Results
A total of 219 patients were eligible for inclusion in this study. Among 219 patients with intraoperative evidence of abdominal visceral perforation, preoperative erect CXR showed air under diaphragm in 43 patients. The perforation detection rate was 20% (95% CI 15-26%). Subgroup analysis based on the level of perforation showed that the perforation detection rate was 32% (95% CI 21-43%) in patients with upper gastrointestinal perforation and 13% (95% CI 8-20%) in patients with lower gastrointestinal perforation.

Conclusion
Erect CXR can only detect the presence of abdominal visceral perforation in 20% of patients and does not provide any information about the level or cause of perforation. The time is to move away from the use of erect CXR in assessment of patients with acute abdominal pain. It is inadequately diagnostic and falsely reassuring. All patients with suspected perforation should have immediate CT scan.
O054 Return to pre-hospital residence following emergency laparotomy
Authors: Rugendyke A , Holmes M , Ming Y , Gani J S , Pockney P 
Published: May 2023

Abstract

Introduction
Poor outcomes following emergency laparotomy include death and the loss of independent living. A widely-held apprehension is the ‘salvage’ of a previously independent patient, only to render them reliant on long-term dependent care. We aimed to establish the proportion of patients who returned to their pre-hospital residence following emergency laparotomy, measured at discharge, 90 and 365 days.

Methods
Data was collected on all patients over 18 years of age who underwent emergency laparotomy across four Australian hospitals between 1 January 2018 and 31 December 2019. Data recorded included pre-hospital residence, discharge destination, mortality and place of residence at 90 and 365 days.

Results
782 patients underwent an emergency laparotomy during the study period. The mean age was 64 years (range 18-96). Prior to hospital admission, 95.5% of patients lived in their own home, while the remainder resided in supported living facilities. 7% of patients died during their hospital admission. Of those alive on discharge, 77.6% were discharged to their pre-hospital residence. At 90 days, mortality was 10.6% while 97.1% of surviving patients had returned to their pre-hospital residence. By 365 days, mortality was 17.0% while 98.0% of surviving patients had returned to their pre-hospital residence, and 94.0% were living in their own home.

Conclusion
Patients who survive 90 and 365 days following emergency laparotomy nearly all return to their pre-hospital residence, with only a small proportion of previously independent patients entering dependent care. This should inform shared decision-making regarding emergency laparotomy in the acute setting.
O063 Should the presence of a carotid web be an indication for carotid intervention? A 12-year single centre retrospective study
Authors: Erete L , Islam S , Glasgow S , Baker D 
Published: May 2023

Abstract

Introduction
Carotid webs are a rare form of focal fibromuscular dysplasia and a possible cause of ischaemic stroke. They are defined as an abnormal shelf-like projection of intimal fibrous tissue into the carotid bulb. We reviewed patients found to have carotid webs at our unit over a 12-year period.

Methods
Radiology reports of all cross-sectional imaging from 2010-2021 were searched for the phrase carotid web. Images were reviewed to confirm the finding. Patients with previous carotid intervention were excluded. Electronic patient records were reviewed to establish presenting symptoms, diagnosis, management and stroke recurrence.

Results
60 patients with carotid webs were identified. Ages ranged from 36-92 years. The gender ratio was 31 male:29 female. 29 patients had left-sided carotid webs, 22 right-sided and 9 bilateral. No patients had a pre-event diagnosis of fibromuscular dysplasia. 27 patients had an ischaemic intracerebral event - 18 in the territory relevant to the web location and nine in other territories. 1 patient was treated with thrombolysis, 1 with thrombectomy and 1 with thrombolysis and thrombectomy. None underwent carotid intervention. Of the 18 patients with a carotid web on the ipsilateral side to their ischaemic event, none had a repeat event recorded.

Conclusion
30% of patients had an ischaemic event corresponding to the territory supplied by a carotid artery with a web. Current management of carotid webs favours conservative management with antiplatelet therapy. However, these data suggest carotid intervention should be considered in selected patients where stroke symptoms correlate to the laterality of the carotid web.
O068 Magnesium, the anaesthetists’ friend during carotid endarterectomy (CEA)
Authors: Myers A , Baker D , Adedugbe I 
Published: May 2023

Abstract

Introduction
Magnesium can be used as an antihypertensive for CEA patients, with the added benefit of anti-arrhythmic and anti-convulsive effects without the negative chronotropic effect of classic antihypertensives. It however causes vasodilation and increased diuresis, possibly increasing post-operative vasopressor requirements. This study determines the postoperative haemodynamic impact of magnesium therapy on CEA patients.

Methods
A retrospective review of CEA patients’ medical records between April 2020 and December 2021 was undertaken. In our unit, the postoperative trigger for commencing vasopressors (metaraminol or noradrenaline) is a systolic blood pressure &lt;110 mmHg. A comparison of the postoperative vasopressor requirements in patients given intraoperative magnesium {5g IV infusion over 20 min if SBP &gt;170mmHg} with those not given magnesium therapy was made (using Chi-square test). A secondary outcome was to assess the development of new acute postoperative kidney injury (AKI) (eGFR &lt;60 ml/min/1.73m2).

Results
Of the 89 CEA patients; 8 had incomplete data and 65% were over 70 years old. The Surgical Outcome Risk Tool (SORT) score identified 44 (53%) patients as high risk (&gt;5% risk of perioperative mortality). There was no difference between the magnesium vs non-magnesium therapy groups postoperatively in vasopressor requirement. (p=0.38, X2=0.74) or AKI rates (n=14, 16.8%).

Conclusion
Organ perfusion and cardiac stability can be achieved perioperatively in CEA patients with magnesium therapy without increasing vasopressors requirement or renal impairment; making it a good first-line therapy for intraoperative hypertension.
O072 A 6-year cohort study assessing outcomes following calf fasciotomies at a single tertiary vascular trauma centre
Authors: Gnanasundaram A , Laloo R , Bailey M , Scott D 
Published: May 2023

Abstract

Introduction
Acute compartment syndrome (ACS) is a surgical emergency. Delayed diagnosis and fasciotomy can result in irreversible muscle necrosis causing permanent disability and major amputation. This study compared outcomes following prophylactic (Group1) versus therapeutic calf fasciotomies (Group2), as well as early (within 6 hours) versus delayed fasciotomies (&gt;6 hours) at a single tertiary vascular trauma centre.

Methods
All patients undergoing calf fasciotomies between 1st January 2017 and 31st November 2022 were identified from a prospectively collected vascular departmental database. The primary outcomes included foot drop, amputation and mortality while infection, wound debridement, neuropathic pain and negative-pressure dressing were secondary outcomes. Statistical analysis with SPSS was performed using Fisher's exact test.

Results
88 patients (65 men, 23 women) of median age (IQR) 67 (56-74) underwent calf fasciotomies. Of these, 43 (48.9%) were therapeutic (Median age=62) and 45 (51.1%) were prophylactic (Median age=67).Ischaemia was more prevalent among Group1 while trauma among Group2.There were no significant differences among outcomes between both groups apart from higher 30-day mortality rate (26.7% vs. 7.0%, p=0.014)and incidence of neuropathic pain (22.2% vs. 4.7%, p=0.027)in Group1 versus Group2.Most patients (79.5%) underwent early calf fasciotomy with no significant differences in primary and secondary outcomes between early and delayed fasciotomy groups. The delay was attributed to theatre unavailability (n=6) and on-going resuscitation (n=5).

Conclusion
Higher rates of neuropathic pain and 30-day mortality in group1 may be attributed to co-existing lower limb ischaemia. Further work is required to establish the impact of neuropathic pain. Pathways should be developed to ensure rapid access to theatres for patients with suspected ACS.
O080 Evaluation of patient post-operative outcomes after deep inferior epigastric perforator (DIEP) flap surgery
Authors: Shatskikh M , Coe L , McMahon M , Kennedy-Williams S , Hil A , Martin-Smith J 
Published: May 2023

Abstract

Introduction
The Deep Inferior Epigastric Perforator (DIEP) flap is considered the gold standard procedure for breast reconstruction. The long-term cosmetic outcomes of the reconstructed breast are unmatched by alternative reconstructive methods, however the donor site morbidity, including pain, scarring and extended recovery periods, require patients to consider their preferred option.

Methods
There is a paucity of data regarding return to pre-surgical activity timelines, and effect of reconstruction on psychosocial, sexual, and physical wellbeing. After obtaining audit approval, we utilized the Breast-QTM questionnaire to conduct a prospective cohort study. DIEP breast reconstruction patients in a tertiary referral, high-volume centre (N=26) were assessed prior to surgery and at 3 months post-operatively.

Results
An average of 20.3 days were lost to hospital admissions, follow-up, and post-operative recovery. Of employed patients, 68% had not yet returned to work. For those that did, an average of 6 weeks was required to feel well enough. Additionally, patients reported needing 4.8 weeks to drive again, 4.4 weeks to resume chores, 3.7 weeks to recommence childcare duties and 4.3 weeks to resume exercise. Comparing pre-operative and post-operative Rasch Transformed Scores, patients’ sexual wellbeing score decreased (58.3 to 52.2, p=0.09), while their psychosocial wellbeing score increased (62.1 to 66.7, p=0.16). Qualitatively, patients reported significant challenges impacting return to baseline, particularly involving abdominal scar site, size, and associated healing delays.

Conclusion
Ultimately, results of our work indicate the need for additional patient supports to improve outcomes, decrease the burden of recovery and time required to return to baseline.