Does timely reporting of preoperative CT scans influence outcomes for patients following emergency laparotomy?

Introduction: Timely preoperative computed tomography (CT) scans are important for patients requiring emergency laparotomy. United Kingdom guidelines state that a CT scan should be reported within 1h for 'critical' patients (will alter management at the time) and within 12h for 'urgent' patients (will alter management but not necessarily that day).

Methods: An observational study included patients who were added to the National Emergency Laparotomy Audit (NELA) at a National Health Service trust from 2014 to 2021.

Murine models of advanced maternal age: a systematic review and meta-analysis.

In Brief: Animal models have been developed to aid understanding of the increased incidence of adverse pregnancy complications observed in women of advanced maternal age (AMA). This systematic review of murine models of AMA demonstrates consistent effects of decreased litter size and fetal weight; this supports the future use of these models to determine pathophysiological mechanisms and test therapeutic strategies to improve poor pregnancy outcomes in AMA.

Abstract: Advanced maternal age (AMA; ≥35 years of age) is associated with an increased risk of adverse pregnancy outcomes.

Plasma S1P and Sphingosine are not Different Prior to Pre-Eclampsia in Women at High Risk of Developing the Disease.

Sphingolipids like sphingosine-1-phosphate (S1P) have been implicated in the pathophysiology of pre-eclampsia. We hypothesized that plasma S1P would be increased in women at high risk of developing pre-eclampsia who subsequently develop the disease. Low circulating placental growth factor (PlGF) is known to be associated with development of pre-eclampsia; so further, we hypothesized that increased S1P would be associated with concurrently low PlGF.

Sacroperineal Reconstruction With Inferior Gluteal Artery Perforator Flaps After Resection of Locally Advanced Primary and Recurrent Anorectal Malignancy.

Modern interdisciplinary concepts with involvement of various surgical specialties can considerably reduce perioperative morbidity after sacroperineal resection of locally advanced primary or recurrent anorectal malignancies. Resultant defects can represent a major challenge for reconstruction particularly with chemoradiotherapy. The aim is to assess the long-term outcomes of sacroperineal reconstruction using inferior gluteal artery perforator flaps.

Establishing a COVID-secure site for elective surgery during the COVID pandemic: An observational study.

Introduction: Maintaining timely and safe delivery of major elective surgery during the COVID-19 pandemic is essential to manage cancer and time-critical surgical conditions. Our NHS Trust established a COVID-secure elective site with a level 2 Post Anaesthetic Care Unit (PACU) facility. Patients requiring level 3 Intensive Care Unit admission were transferred to a non-COVID-secure site.

Comparing the surgical management of acute paediatric scrotal pain between adult urologists and general surgeons in the UK: an observational study.

Introduction: Acute scrotal pain is a common paediatric surgical emergency. Assessment and timely exploration are required to rule out testicular torsion (TT) and prevent unnecessary morbidity.

Methods: A retrospective observational cohort study was carried out at two district general hospitals in the UK for boys aged ≤16 years presenting with acute scrotal pain between January 2014 and October 2017 managed by adult general surgery (AGS) at one hospital and adult urology (AU) at the other.

Surgical training during the COVID-19 pandemic at a designated 'cold' site: are we meeting the challenge?

Introduction: There has been a marked reduction in surgical operative training opportunities during the COVID-19 pandemic. This may be improved by the establishment of 'cold' sites for NHS elective surgery. We investigated the training opportunities at a newly designated elective surgery cold site in the West Midlands, UK.

Complete response to neoadjuvant chemoradiotherapy in rectal cancer is associated with RAS/AKT mutations and high tumour mutational burden.

Background: Pathological complete response (pathCR) in rectal cancer is beneficial, as up to 75% of patients do not experience regrowth of the primary tumour, but it is poorly understood. We hypothesised that the changes seen in the pre-treatment biopsies of pathCR but not seen in residual tumour after chemoradiotherapy were the determinants of responsiveness.

Methods: Two groups of patients with either complete response (pathCR group, N = 24) or no response (poor response group, N = 24) were retrieved.

The molecular landscape of well differentiated retroperitoneal liposarcoma.

Well differentiated liposarcoma (WD-LPS) is a relatively rare tumour, with fewer than 50 cases occurring per year in the UK. These tumours are both chemotherapy- and radiotherapy-resistant and present a significant treatment challenge requiring radical surgery. Little is known of the molecular landscape of these tumours and no current targets for molecular therapy exist.

Detergent-free purification and reconstitution of functional human serotonin transporter (SERT) using diisobutylene maleic acid (DIBMA) copolymer.

Structure and function analysis of human membrane proteins in lipid bilayer environments is acutely lacking despite the fundame1ntal cellular importance of these proteins and their dominance of drug targets. An underlying reason is that detailed study usually requires a potentially destabilising detergent purification of the proteins from their host membranes prior to subsequent reconstitution in a membrane mimic; a situation that is exacerbated for human membrane proteins due to the inherent difficulties in overexpressing suitable quantities of the proteins. We advance the promising styrene maleic acid polymer (SMA) extraction approach to introduce a detergent-free method of obtaining stable, functional human membrane transporters in bilayer nanodiscs directly from yeast cells.

Clinical-grade whole-genome sequencing and 3' transcriptome analysis of colorectal cancer patients.

Background: Clinical-grade whole-genome sequencing (cWGS) has the potential to become the standard of care within the clinic because of its breadth of coverage and lack of bias towards certain regions of the genome. Colorectal cancer presents a difficult treatment paradigm, with over 40% of patients presenting at diagnosis with metastatic disease. We hypothesised that cWGS coupled with 3' transcriptome analysis would give new insights into colorectal cancer.

Evaluation of a bundle of care to reduce incisional surgical site infection after gastrointestinal surgery.

Background: Surgical site infection (SSI) is associated with morbidity, mortality and increased care costs; many SSIs are considered preventable. The aim of the present study was to test implementation of a pragmatic, evidence-based bundle designed to reduce incisional SSI after emergency laparotomy and elective major lower gastrointestinal surgery.

Method: This was a prospective before-and-after study.

Human placental uptake of glutamine and glutamate is reduced in fetal growth restriction.

Fetal growth restriction (FGR) is a significant risk factor for stillbirth, neonatal complications and adulthood morbidity. Compared with those of appropriate weight for gestational age (AGA), FGR babies have smaller placentas with reduced activity of amino acid transporter systems A and L, thought to contribute to poor fetal growth. The amino acids glutamine and glutamate are essential for normal placental function and fetal development; whether transport of these is altered in FGR is unknown.

A missense mutation of ErbB2 produces a novel mouse model of stillbirth associated with a cardiac abnormality but lacking abnormalities of placental structure.

Background: In humans, stillbirth describes the death of a fetus before birth after 28 weeks gestation, and accounts for approximately 2.6 million deaths worldwide annually. In high-income countries, up to half of stillbirths have an unknown cause and are described as "unexplained stillbirths"; this lack of understanding impairs efforts to prevent stillbirth.

Does declared surgeon specialist interest influence the outcome of emergency laparotomy?

Introduction: In the UK, general surgeons must demonstrate competency in emergency general surgery before obtaining a certificate of completion of training. Subsequently, many consultants develop focused elective specialist interests which may not mirror the breadth of procedures encountered during emergency practice. Recent National Emergency Laparotomy Audit analysis found that declared surgeon special interest impacted emergency laparotomy outcomes, which has implications for emergency general surgery service configuration.

Antenatal sildenafil citrate treatment increases offspring blood pressure in the placental-specific knockout mouse model of FGR.

Fetal growth restriction (FGR), where a fetus fails to reach its genetic growth potential, affects up to 8% of pregnancies and is a major risk factor for stillbirth and adulthood morbidity. There are currently no treatments for FGR, but candidate therapies include the phosphodiesterase-5 inhibitor sildenafil citrate (SC). Randomized clinical trials in women demonstrated no effect of SC on fetal growth in cases of severe early onset FGR; however, long-term health outcomes on the offspring are unknown.

Evidence of adaptation of maternofetal transport of glutamine relative to placental size in normal mice, and in those with fetal growth restriction.

Key Points: Fetal growth restriction (FGR) is a major risk factor for stillbirth and has significant impact upon lifelong health. A small, poorly functioning placenta, as evidenced by reduced transport of nutrients to the baby, underpins FGR. It remains unclear how a small but normal placenta differs from the small FGR placenta in terms of ability to transfer nutrients to the fetus.

Mechanisms Underpinning Adaptations in Placental Calcium Transport in Normal Mice and Those With Fetal Growth Restriction.

Fetal delivery of calcium, via the placenta, is crucial for appropriate skeletal mineralization. We have previously demonstrated that maternofetal calcium transport, per gram placenta, is increased in the placental specific insulin-like growth factor 2 knockout mouse (P0) model of fetal growth restriction (FGR) compared to wild type littermates (WTL). This effect was mirrored in wild-type (WT) mice comparing lightest vs.

Validation of epigenetic markers to identify colitis associated cancer: Results of module 1 of the ENDCAP-C study.

Background: Chronic inflammation caused by ulcerative colitis (UC) causes a pro-neoplastic drive in the inflamed colon, leading to a markedly greater risk of invasive malignancy compared to the general population. Despite surveillance protocols, 50% of cases proceed to cancer before neoplasia is detected. The Enhanced Neoplasia Detection and Cancer Prevention in Chronic Colitis (ENDCaP-C) trial is an observational multi-centre test accuracy study to ascertain the role of molecular markers in improving the detection of dysplasia.

Melatonin Increases Fetal Weight in Wild-Type Mice but Not in Mouse Models of Fetal Growth Restriction.

Fetal growth restriction (FGR) presents with an increased risk of stillbirth and childhood and adulthood morbidity. Melatonin, a neurohormone and antioxidant, has been suggested as having therapeutic benefit in FGR. We tested the hypothesis that melatonin would increase fetal growth in two mouse models of FGR which together represent a spectrum of the placental phenotypes in this complication: namely the endothelial nitric oxide synthase knockout mouse (eNOS) which presents with abnormal uteroplacental blood flow, and the placental specific knockout mouse (P0) which demonstrates aberrant placental morphology akin to human FGR.

Pomegranate Juice Supplementation Alters Utero-Placental Vascular Function and Fetal Growth in the eNOS Mouse Model of Fetal Growth Restriction.

The eNOS mouse provides a well-characterized model of fetal growth restriction (FGR) with altered uterine and umbilical artery function and reduced utero- and feto-placental blood flow. Pomegranate juice (PJ), which is rich in antioxidants and bioactive polyphenols, has been posited as a beneficial dietary supplement to promote cardiovascular health. We hypothesized that maternal supplementation with PJ will improve uterine and umbilical artery function and thereby enhance fetal growth in the eNOS mouse model of FGR.

The problem with using the birthweight:placental weight ratio as a measure of placental efficiency.

Introduction: The ratio of birthweight to placental weight (BW:PW) is often used as a measure of placental efficiency in humans and animals. However, ratios have properties that are known to lead to spurious results. An alternative approach is the use of residuals from regression, which reflect whether birthweight is higher or lower than expected for a given placental weight, given the population pattern.

A systematic review of epigenetic biomarkers in progression from non-dysplastic Barrett's oesophagus to oesophageal adenocarcinoma.

Objectives: The objective of this systematic review is to identify and summarise studies which examine epigenetic biomarkers in patients with Barrett's oesophagus (BO) and their association with progression to oesophageal adenocarcinoma (OADC). BO is a precursor lesion for OADC. There is no clinical test to predict patients who are likely to progress to OADC.

Discovery and Validation of Methylation Biomarkers for Ulcerative Colitis Associated Neoplasia.

Background And Aims: Ulcerative colitis (UC) is associated with a higher background risk of dysplasia and/or neoplasia due to chronic inflammation. There exist few biomarkers for identification of patients with dysplasia, and targeted biopsies in this group of patients are inaccurate in reliably identifying dysplasia. We aimed to examine the epigenome of UC dysplasia and to identify and validate potential biomarkers.