COLOFIT: Development and Internal-External Validation of Models Using Age, Sex, Faecal Immunochemical and Blood Tests to Optimise Diagnosis of Colorectal Cancer in Symptomatic Patients.

Background: Colorectal cancer (CRC) is the third most common cancer in the United Kingdom and the second largest cause of cancer death.

Aim: To develop and validate a model using available information at the time of faecal immunochemical testing (FIT) in primary care to improve selection of symptomatic patients for CRC investigations.

Methods: We included all adults (≥ 18 years) referred to Nottingham University Hospitals NHS Trust between 2018 and 2022 with symptoms of suspected CRC who had a FIT.

From promise to practice: CAR T and Treg cell therapies in autoimmunity and other immune-mediated diseases.

Autoimmune diseases, characterized by the immune system's attack on the body's own tissues, affect millions of people worldwide. Current treatments, which primarily rely on broad immunosuppression and symptom management, are often associated with significant adverse effects and necessitate lifelong therapy. This review explores the next generation of therapies for immune-mediated diseases, including chimeric antigen receptor (CAR) T cell and regulatory T cell (Treg)-based approaches, which offer the prospect of targeted, durable disease remission.

Host cell glycosylation selects for infection with CCR5- versus CXCR4-tropic HIV-1.

Human immunodeficiency virus type 1 (HIV-1) infection involves a selection bottleneck that leads to transmission of one or a few variants. C-C motif chemokine receptor 5 (CCR5) or C-X-C motif chemokine receptor 4 (CXCR4) can act as coreceptors for HIV-1 viral entry. However, initial infection mostly occurs via CCR5, despite abundant expression of CXCR4 on target cells.

Systematic review: Mortality associated with raised faecal immunochemical test and positive faecal occult blood results.

Background: Faecal haemoglobin (f-Hb) testing is used in colorectal cancer (CRC) screening and increasingly to guide the investigation in patients with symptoms suggestive of CRC. Studies have demonstrated increased mortality with raised f-Hb.

Aims: To assess the association of raised f-Hb with all-cause, non-CRC (any cause excluding CRC) and cause-specific mortality.

The Impact of the Covid-19 Pandemic on Annual Review of Competency Progression Outcomes Issued to General Surgical Trainees.

Background: The Covid-19 pandemic had a profound impact on surgical training. In this longitudinal cohort study, we quantify the effects of the pandemic on United Kingdom (UK) surgeons in higher specialty training by analyzing the Annual Review of Competency Progression (ARCP) Outcomes issued to them prior to, and during, the pandemic.

Methods: Anonymized records were provided from the UK training management system- the Intercollegiate Surgical Curriculum Programme (ISCP)- on the ARCP Outcomes of higher specialty trainees in General Surgery over the period between January 2017 and December 2022.

The effect of diabetes mellitus on perioperative outcomes after colorectal resection: a national cohort study.

Background: Diabetes mellitus is a significant modulator of postoperative outcomes and is an important risk factor in the patient selection process. We aimed to investigate the effect of diabetes mellitus and use of insulin on outcomes after colorectal resection using a national cohort.

Methods: Adults with a recorded colorectal resection in England between 2010 and 2020 were identified from Hospital Episode Statistics data linked to the Clinical Practice Research Database.

'Low' faecal immunochemical test (FIT) colorectal cancer: a 4-year comparison of the Nottingham '4F' protocol with FIT10 in symptomatic patients.

Aim: The aim of this work was to evaluate colorectal cancer (CRC) outcomes after 'low' (sub-threshold) faecal immunochemical test (FIT) results in symptomatic patients tested in primary care.

Method: This work comprised a retrospective audit of 35 289 patients with FIT results who had consulted their general practitioner with lower gastrointestinal symptoms and had subsequent CRC diagnoses. The Rapid Colorectal Cancer Diagnosis pathway was introduced in November 2017 to allow incorporation of FIT into clinical practice.

Temporal trends and patterns in initial opioid prescriptions after hospital discharge following colectomy in England over 10 years.

Background: While opioid analgesics are often necessary for the management of acute postoperative pain, appropriate prescribing practices are crucial to avoid harm. The aim was to investigate the changes in the proportion of people receiving initial opioid prescriptions after hospital discharge following colectomy, and describe trends and patterns in prescription characteristics.

Methods: This was a retrospective cohort study.

Regional variations and deprivation are linked to poorer access to laparoscopic and robotic colorectal surgery: a national study in England.

Background: Laparoscopic and now robotic colorectal surgery has rapidly increased in prevalence; however, little is known about how uptake varies by region and sociodemographics. The aim of this study was to quantify the uptake of minimally invasive colorectal surgery (MIS) over time and variations by region, sociodemographics and ethnicity.

Methods: Retrospective analysis of routinely collected healthcare data (Clinical Practice Research Datalink linked to Hospital Episode Statistics) for all adults having elective colorectal resectional surgery in England from 1 January 2006 to 31 March 2020.

The impact of urgency of umbilical hernia repair on adverse outcomes in patients with cirrhosis: a population-based cohort study from England.

Introduction: Umbilical hernia is common in patients with cirrhosis; however, there is a paucity of dedicated studies on postoperative outcomes in this group of patients. This population-based cohort study aimed to determine the outcomes after emergency and elective umbilical hernia repair in patients with cirrhosis.

Methods: Two linked electronic healthcare databases from England were used to identify all patients undergoing umbilical hernia repair between January 2000 and December 2017.

Host cell glycosylation selects for infection with CCR5- versus CXCR4-tropic HIV-1.

HIV-1 infection involves a selection bottleneck that leads to transmission of one or a few HIV variants, which nearly always use CCR5 as the coreceptor (R5 viruses) for viral entry as opposed to CXCR4 (X4 viruses). The host properties that drive this selection are not well understood and may hold keys to factors that govern HIV susceptibility. In this report, we identified SLC35A2, a transporter of UDP-galactose, as a candidate X4-specific restriction factor in CRISPR-knockout screens in primary target CD4 T cells.

Outcomes after emergency appendicectomy in patients with liver cirrhosis: a population-based cohort study from England.

Introduction: The mortality risk after appendicectomy in patients with liver cirrhosis is predicted to be higher than in the general population given the associated risk of perioperative bleeding, infections and liver decompensation. This population-based cohort study aimed to determine the 90-day mortality risk following emergency appendicectomy in patients with cirrhosis.

Methods: Adult patients undergoing emergency appendicectomy in England between January 2001 and December 2018 were identified from two linked primary and secondary electronic healthcare databases, the clinical practice research datalink and hospital episode statistics data.

Understanding colorectal cancer risk for symptomatic patients in primary care: A cohort study utilising faecal immunochemical tests and blood results in England.

Background: A faecal immunochemical tests (FIT) cut-off of ≥10 μg Hb/g faeces is now recommended in the UK as a gateway to urgent (suspected cancer) investigation for colorectal cancer (CRC), based on an expected CRC risk threshold of 3%.

Aims: To quantify the risk of CRC at FIT cut-offs by age, haemoglobin and platelet strata.

Methods: A cohort study of a symptomatic CRC pathway based on primary care FIT tests in Nottingham, UK (November 2017-2021) with 1-year follow-up.

Risk of osteopaenia, osteoporosis and osteoporotic fractures in patients with chronic pancreatitis: A systematic review and meta-analysis.

Background & Aims: Chronic pancreatitis results in irreversible pancreatic dysfunction and malnutrition which, alongside excess alcohol intake, can increase the risk of low bone density. Osteoporosis increases the risk of fractures and chronic bone pain, reduces quality of life, and poses considerable costs to healthcare. Despite this, there remains a paucity of literature evaluating bone health in this patient population.

Predictors of persistent postoperative opioid use following colectomy: a population-based cohort study from England.

This retrospective cohort study on adults undergoing colectomy from 2010 to 2019 used linked primary (Clinical Practice Research Datalink), and secondary (Hospital Episode Statistics) care data to determine the prevalence of persistent postoperative opioid use following colectomy, stratified by pre-admission opioid exposure, and identify associated predictors. Based on pre-admission opioid exposure, patients were categorised as opioid-naïve, currently exposed (opioid prescription 0-6 months before admission) and previously exposed (opioid prescription within 7-12 months before admission). Persistent postoperative opioid use was defined as requiring an opioid prescription within 90 days of discharge, along with one or more opioid prescriptions 91-180 days after hospital discharge.

Several cell-intrinsic effectors drive type I interferon-mediated restriction of HIV-1 in primary CD4 T cells.

Type I interferon (IFN) upregulates proteins that inhibit HIV within infected cells. Prior studies have identified IFN-stimulated genes (ISGs) that impede lab-adapted HIV in cell lines, yet the ISG(s) that mediate IFN restriction in HIV target cells, primary CD4 T cells, are unknown. Here, we interrogate ISG restriction of primary HIV in CD4 T cells by performing CRISPR-knockout screens with a custom library that specifically targets ISGs expressed in CD4 T cells.

Venous thromboembolism following colectomy for diverticular disease: an English population-based cohort study.

Aim: This study reports venous thromboembolism (VTE) rates following colectomy for diverticular disease to explore the magnitude of postoperative VTE risk in this population and identify high risk subgroups of interest.

Method: English national cohort study of colectomy patients between 2000 and 2019 using linked primary (Clinical Practice Research Datalink) and secondary (Hospital Episode Statistics) care data. Stratified by admission type, absolute incidence rates (IR) per 1000 person-years and adjusted incidence rate ratios (aIRR) were calculated for 30- and 90-day post-colectomy VTE.

Risk of Postoperative Venous Thromboembolism After Benign Colorectal Surgery: Systematic Review and Meta-analysis.

Background: Venous thromboembolism is a well-established preventable complication after colectomy. Specific guidance on venous thromboembolism prevention after colectomy for benign disease is limited.

Objective: This meta-analysis aimed to quantify the venous thromboembolism risk after benign colorectal resection and determine its variability.

Several cell-intrinsic effectors drive type I interferon-mediated restriction of HIV-1 in primary CD4 T cells.

Type I interferon (IFN) upregulates proteins that inhibit HIV within infected cells. Prior studies have identified IFN-stimulated genes (ISGs) that impede lab-adapted HIV in cell lines, yet the ISG(s) that mediate IFN restriction in HIV target cells, primary CD4 T cells, are unknown. Here, we interrogate ISG restriction of primary HIV in CD4 T cells.

Discovery of a polymer resistant to bacterial biofilm, swarming, and encrustation.

Innovative approaches to prevent catheter-associated urinary tract infections (CAUTIs) are urgently required. Here, we describe the discovery of an acrylate copolymer capable of resisting single- and multispecies bacterial biofilm formation, swarming, encrustation, and host protein deposition, which are major challenges associated with preventing CAUTIs. After screening ~400 acrylate polymers, poly(-butyl cyclohexyl acrylate) was selected for its biofilm- and encrustation-resistant properties.

The Impact of COVID-19 on Lung Cancer Incidence in England: Analysis of the National Lung Cancer Audit 2019 and 2020 Rapid Cancer Registration Datasets.

Background: The COVID-19 pandemic has caused significant disruption to health-care services and delivery worldwide. The impact of the pandemic and associated national lockdowns on lung cancer incidence in England have yet to be assessed.

Research Question: What was the impact of the first year of the COVID-19 pandemic on the incidence and presentation of lung cancer in England?

Study Design And Methods: In this retrospective observational study, incidence rates for lung cancer were calculated from The National Lung Cancer Audit Rapid Cancer Registration Datasets for 2019 and 2020, using midyear population estimates from the Office of National Statistics as the denominators.

Long-term adverse effects and healthcare burden of rectal cancer radiotherapy: systematic review and meta-analysis.

Background: As rectal cancer survival increases, more patients survive with potentially severe, long-term gastrointestinal and genitourinary complications from radiotherapy. The burden of these complications for patients and healthcare services is unclear, which this review aims to quantify.

Methods: Systematic search of Medline and Embase for randomized-controlled trials (RCTs) and multicentre observational studies published since 2000, reporting hospitalization/procedural intervention for long-term (>6 months post-treatment) gastrointestinal or genitourinary complications after radiotherapy and surgery for rectal cancer.