Acute severe hepatitis outbreak in children: A perfect storm. What do we know, and what questions remain?

During the first half of 2022, the World Health Organization reported an outbreak of acute severe hepatitis of unknown aetiology (AS-Hep-UA) in children, following initial alerts from the United Kingdom (UK) where a cluster of cases was first observed in previously well children aged <6 years. Sporadic cases were then reported across Europe and worldwide, although in most countries incidence did not increase above the expected baseline. There were no consistent epidemiological links between cases, and microbiological investigations ruled out known infectious causes of hepatitis.

Diagnostic accuracy of serum ascites albumin gradient (SAAG) in a contemporary unselected medical cohort.

Objectives: To describe the different aetiologies of ascites and test the validity of serum ascites albumin gradient (SAAG) and cytology in a contemporary unselected medical cohort.

Methods: All adult patients admitted to Nottingham University Hospitals, UK, between 1 May 2013 and 30 April 2018 with new-onset radiologically-confirmed ascites were included. Data were analysed to determine the distribution of different aetiologies of ascites and the diagnostic accuracy of SAAG in portal hypertension and cytology in malignancy as underlying causes of ascites.

Physical activity is inversely associated with hepatic fibro-inflammation: A population-based cohort study using UK Biobank data.

Background & Aims: Physical activity (PA) is recommended in the management of non-alcoholic fatty liver disease (NAFLD) given its beneficial effects on liver fat and cardiometabolic risk. Using data from the UK Biobank population-cohort, this study examined associations between habitual PA and hepatic fibro-inflammation.

Methods: A total of 840 men and women aged 55-70 years were included in this cross-sectional study.

Mechanistic and Clinical Evidence Supports a Key Role for Cell Division Cycle Associated 5 (CDCA5) as an Independent Predictor of Outcome in Invasive Breast Cancer.

Background: Cell Division Cycle Associated 5 () plays a role in the phosphoinositide 3-kinase (PI3K)/AKT/mTOR signalling pathway involving cell division, cancer cell migration and apoptosis. This study aims to assess the prognostic and biological value of in breast cancer (BC).

Methods: The biological and prognostic value of were evaluated at mRNA ( = 5109) and protein levels ( = 614) utilizing multiple well-characterized early stage BC cohorts.

Time to focus on chronic liver diseases in the community: A review of primary care hepatology tools, pathways of care and reimbursement mechanisms.

Addressing primary care's low confidence in detecting and managing chronic liver disease is becoming increasingly important owing to the escalating prevalence of its common lifestyle-related metabolic risk factors - obesity, physical inactivity, smoking and alcohol consumption. Whilst liver blood testing is frequently carried out in the management of long-term conditions, its interpretation is not typically focused on specific liver disease risk. Educational steps for primary care should outline how liver fibrosis is the flag of pathological concern, encourage use of pragmatic algorithms such as fibrosis-4 index to differentiate between those requiring referral for further fibrosis risk assessment and those who can be managed in the community, and emphasise that isolated minor liver function test abnormalities are unreliable for estimating the risk of fibrosis progression.

Variability of noninvasive MRI and biological markers in compensated cirrhosis: insights for assessing disease progression.

Background: We annually monitored stable compensated cirrhosis (CC) patients to evaluate serial variation in blood serum, liver stiffness, and multiparametric magnetic resonance imaging (mpMRI) measures to provide reference change values (RCV) and sample size measures for future studies.

Methods: Patients were recruited from a prospectively followed CC cohort, with assessments at baseline and annually over three years. We report on blood markers, transient elastography liver stiffness measures (LSM) and noninvasive mpMRI (volume, T1 mapping, blood flow, perfusion) of the liver, spleen, kidneys, and heart in a stable CC group and a healthy volunteer (HV) group.

pMTL60000: A modular plasmid vector series for Parageobacillus thermoglucosidasius strain engineering.

Parageobacillus thermoglucosidasius is a promising chassis for producing chemicals and fuels. Here we designed, built and tested the pMTL60000 modular plasmids containing standardised Gram-positive and Gram-negative replicons, selectable markers and application-specific modules. The pMTL60000 modular plasmids were characterised with regard to transformation efficiency, segregational stability, copy number and compatibility.

Pulse oximeter measurement error of oxygen saturation in patients with SARS-CoV-2 infection stratified by smoking status.

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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.

Differential pulse oximetry readings between ethnic groups and delayed transfer to intensive care units.

Background: Pulse oximeters are widely used to monitor blood oxygen saturations, although concerns exist that they are less accurate in individuals with pigmented skin.

Aims: This study aimed to determine if patients with pigmented skin were more severely unwell at the period of transfer to intensive care units (ICUs) than individuals with White skin.

Methods: Using data from a large teaching hospital, measures of clinical severity at the time of transfer of patients with COVID-19 infection to ICUs were assessed, and how this varied by ethnic group.

Decreased renal perfusion during acute kidney injury in critical COVID-19 assessed by magnetic resonance imaging: a prospective case control study.

Background: Renal hypoperfusion has been suggested to contribute to the development of acute kidney injury (AKI) in critical COVID-19. However, limited data exist to support this. We aim to investigate the differences in renal perfusion, oxygenation and water diffusion using multiparametric magnetic resonance imaging in critically ill COVID-19 patients with and without AKI.

Therapeutic Management of Idiosyncratic Drug-Induced Liver Injury and Acetaminophen Hepatotoxicity in the Paediatric Population: A Systematic Review.

Introduction: Drug-induced liver injury (DILI) is a rare but serious adverse event that can progress to acute liver failure (ALF). The evidence for treatment of DILI in children is scarce.

Objective: We aimed to comprehensively review the available literature on the therapies for both acetaminophen overdose (APAP) and idiosyncratic DILI in the paediatric population.

Hyoscine butylbromide mode of action on bowel motility: From pharmacology to clinical practice.

Background: Hyoscine butylbromide (HBB) has been available for use as an antispasmodic since 1951 and is indicated for the treatment of abdominal pain associated with cramps. A previous review in 2007 summarized the evidence on the mode of action of HBB in vitro and in vivo in both animal and human studies. However, since then, novel publications have appeared within the literature and also our knowledge of what represents normal motility in humans has evolved.

Evaluating the Role of Antibiotics in Patients Admitted to Hospital With Decompensated Cirrhosis: Lessons From the ATTIRE Trial.

Introduction: Hospital-acquired infections (HAI) are common in cirrhosis with antibiotics frequently used to prevent infections, but their efficacy for this role is unknown. To investigate this, we used Albumin to Prevent Infection in Chronic Liver Failure (ATTIRE) data to evaluate whether antibiotic use in patients without infection prevented HAI.

Methods: In ATTIRE patients without infection at baseline grouped by antibiotic prescription or not, we studied HAI during trial treatment period and mortality, with propensity score matching to account for differences in disease severity.

A new framework for advancing in drug-induced liver injury research. The Prospective European DILI Registry.

Background & Aims: No multi-national prospective study of drug-induced liver injury (DILI) has originated in Europe. The design of a prospective European DILI registry, clinical features and short-term outcomes of the cases and controls is reported.

Methods: Patients with suspected DILI were prospectively enrolled in the United Kingdom, Spain, Germany, Switzerland, Portugal and Iceland, 2016-2021.

Development of Food Group Tree-Based Analysis and Its Association with Non-Alcoholic Fatty Liver Disease (NAFLD) and Co-Morbidities in a South Indian Population: A Large Case-Control Study.

Background: Non-alcoholic fatty liver disease (NAFLD) is a global problem growing in parallel to the epidemics of obesity and diabetes, with South Asians being particularly susceptible. Nutrition and behaviour are important modifiers of the disease; however, studies to date have only described dietary patterns and nutrients associated with susceptibility to NAFLD.

Methods: This cross-sectional case-control study included 993 NAFLD patients and 973 healthy controls from Trivandrum (India).

Proposal of minimum elements for screening and diagnosis of gastric cancer by an international Delphi consensus.

The World Endoscopy Organization Stomach and Duodenal Diseases Committee extracted minimum elements for screening and diagnosis of gastric cancer (GC) in aim to support countries that do not have national guidelines on screening and diagnosis of GC. Current national or international guidelines were collected worldwide and recommendations were classified according to the quality of evidence and were finalized through a modified Delphi method. The minimum elements consist of seven categories: [1] Extraction of high-risk patients of GC before esophagogastroduodenoscopy (EGD), [2] Patients who need surveillance of GC, [3] Method to ensure quality of EGD for detection of GC, [4] Individual GC risk assessment by EGD, [5] Extraction of high-risk patients of GC after EGD [6] Qualitative or differential diagnosis of GC by EGD, and [7] Endoscopic assessment to choose the therapeutic strategy for GC.

LiverScreen project: study protocol for screening for liver fibrosis in the general population in European countries.

Background: The development of liver cirrhosis is usually an asymptomatic process until late stages when complications occur. The potential reversibility of the disease is dependent on early diagnosis of liver fibrosis and timely targeted treatment. Recently, the use of non-invasive tools has been suggested for screening of liver fibrosis, especially in subjects with risk factors for chronic liver disease.

The Duration and Magnitude of Postdischarge Venous Thromboembolism Following Colectomy.

Objective: To assess the impact of current guidelines by reporting weekly postoperative postdischarge venous thromboembolism (VTE) rates.

Summary Background Data: Disparity exists between the postoperative thromboprophylaxis duration colectomy patients receive based on surgical indication, where malignant resections routinely receive 28 days extended thromboprophylaxis into the postdischarge period and benign resections do not.

Methods: English national cohort study of colectomy patients between 2010 and 2019 using linked primary (Clinical Practice Research Datalink) and secondary (Hospital Episode Statistics) care data.

Time trends in the incidence rates of venous thromboembolism following colorectal resection by indication and operative technique.

Aim: It is important for patient safety to assess if international changes in perioperative care, such as the focus on venous thromboembolism (VTE) prevention and minimally invasive surgery, have reduced the high post colectomy VTE risks previously reported. This study assesses the impact of changes in perioperative care on VTE risk following colorectal resection.

Method: This was a population-based cohort study of colectomy patients in England between 2000 and 2019 using a national database of linked primary (Clinical Practice Research Datalink) and secondary (Hospital Episode Statistics) care data.

Simultaneous determination of HCV genotype and NS5B resistance associated substitutions using dried serum spots from São Paulo state, Brazil.

Hepatitis C virus (HCV) is responsible for more than 180 million infections worldwide, and about 80 % of infections are reported in Low and Middle-income countries (LMICs). Therapy is based on the administration of interferon (INF), ribavirin (RBV) or more recently Direct-Acting Antivirals (DAAs). However, amino acid substitutions associated with resistance (RAS) have been extensively described and can contribute to treatment failure, and diagnosis of RAS requires considerable infrastructure, not always locally available.

Clinical effectiveness of short course oral prednisone for stricture prevention after semi-circumferential esophageal endoscopic submucosal dissection.

Esophageal strictures (ES) occur frequently after semi-circumferential endoscopic submucosal dissection (ESD) for the eradication of superficial esophageal neoplasms and negatively impact a patient's quality of life. Oral corticosteroids have been shown to be clinically effective, but the most appropriate drug, dose and duration is yet to be determined. The aim of the study was to investigate the clinical effectiveness and safety of 30 mg prednisone with a shortened tapering schedule on ES after semi-circumferential ESD.

Alcohol-related liver disease mortality and missed opportunities in secondary care: A United Kingdom retrospective observational study.

Introduction: Alcohol-related liver disease (ARLD) is a preventable cause of mortality. Historical epidemiological studies on ARLD often lack a detailed linked assessment of health-related contacts prior to death which limits understanding of opportunities for intervention. We aimed to analyse retrospective population-based data of all adult residents of Nottinghamshire dying from ARLD to determine the factors associated with delayed diagnosis of ARLD and the potential missed opportunities for interventions.