Liver Fibrosis Assessed Via Noninvasive Tests Is Associated With Incident Heart Failure in a General Population Cohort.

Background & Aims: The aim of this study was to determine whether liver fibrosis is associated with heart failure in a general population cohort, and if genetic polymorphisms (PNPLA3 rs738409; TM6SF2 rs58542926), linked to increased risk of liver fibrosis and decreased risk of coronary artery disease, modify this association.

Methods: Using UK Biobank data, we prospectively examined the relationship between noninvasive fibrosis markers (nonalcoholic fatty liver disease [NAFLD] fibrosis score [NFS], Fibrosis-4 [FIB-4] and aspartate transaminase [AST] to platelet ratio index [APRI]) and incident hospitalization/death from heart failure (n = 413,860). Cox-regression estimated hazard ratios (HRs) for incident heart failure.

Thyroid dysfunction after immune checkpoint inhibitors in a single-centre UK pan-cancer cohort: A retrospective study.

Purpose: This study investigated thyroid dysfunction with immune checkpoint inhibitors (ICIs) in terms of proportions affected, risk factors, thyroid sequelae, and overall survival (OS).

Methods: Among patients with normal baseline free T4 (fT4) and thyroid stimulating hormone (TSH) receiving ICIs at a large cancer centre, proportions of hyperthyroidism/hypothyroidism were determined (any, subclinical [normal fT4, abnormal TSH], overt [abnormal fT4, abnormal TSH], isolated hyperthyroxinaemia/hypothyroxinaemia and secondary) with onset times and subsequent thyroid statuses. Associations of overt dysfunction with OS were estimated using Cox regression and methods robust to immortal time bias (time-dependent Cox regression and 3- and 6-month landmark analyses).

Prognostic and predictive value of non-steroidal anti-inflammatory drugs in the EORTC 1325/KEYNOTE-054 phase III trial of pembrolizumab versus placebo in resected high-risk stage III melanoma.

Background: Pain is common in patients with cancer. The World Health Organisation recommends paracetamol or non-steroidal anti-inflammatory drugs (NSAIDs) for mild pain and combined with other agents for moderate/severe pain. This study estimated associations of NSAIDs with recurrence-free survival (RFS), distant metastasis-free survival (DMFS) and the incidence of immune-related adverse events (irAEs) in high-risk patients with resected melanoma in the EORTC 1325/KEYNOTE-054 phase III clinical trial.

Gene of the month: cancer testis antigen gene 1b (NY-ESO-1).

Cancer testis antigen gene 1B (CTAG1B) and its associated gene product; New York oesophageal squamous carcinoma 1 (NY-ESO-1), represent a unique and promising target for cancer immunotherapy. As a member of the cancer testis antigen family (CTA), the protein's restricted expression pattern and ability to elicit spontaneous humoural and cellular immune responses has resulted in a plethora of novel modalities and approaches attempting to harness its immunotherapeutic anti-cancer potential. Here, we discuss the structure and function of CTAG1B/NY-ESO-1 in both health and disease, immunohistochemical detection, as well as the most promising advances in the development of associated anti-cancer therapies.

Prognostic and predictive value of metformin in the European Organisation for Research and Treatment of Cancer 1325/KEYNOTE-054 phase III trial of pembrolizumab versus placebo in resected high-risk stage III melanoma.

Background: Metformin is a commonly prescribed and well-tolerated medication. In laboratory studies, metformin suppresses BRAF wild-type melanoma cells but accelerates the growth of BRAF-mutated cells. This study investigated the prognostic and predictive value of metformin, including with respect to BRAF mutation status, in the European Organisation for Research and Treatment of Cancer 1325/KEYNOTE-054 randomised controlled trial.

The impact of non-alcoholic fatty liver disease and liver fibrosis on adverse clinical outcomes and mortality in patients with chronic kidney disease: a prospective cohort study using the UK Biobank.

Background: Chronic kidney disease (CKD) and non-alcoholic fatty liver disease (NAFLD) frequently co-exist. We assess the impact of having NAFLD on adverse clinical outcomes and all-cause mortality for people with CKD.

Methods: A total of 18,073 UK Biobank participants identified to have CKD (eGFR < 60 ml/min/1.

Social determinants of health derived from people with opioid use disorder: Improving data collection, integration and use with cross-domain collaboration and reproducible, data-centric, notebook-style workflows.

Deriving social determinants of health from underserved populations is an important step in the process of improving the well-being of these populations and in driving policy improvements to facilitate positive change in health outcomes. Collection, integration, and effective use of clinical data for this purpose presents a variety of specific challenges. We assert that combining expertise from three distinct domains, specifically, medical, statistical, and computer and data science can be applied along with provenance-aware, self-documenting workflow tools.

Child and adult adiposity and subtype-specific endometrial cancer risk: a multivariable Mendelian randomisation study.

Increased adiposity is a known risk factor for endometrial cancer (EC). This study aimed to disentangle the separate causal roles of child and adult adiposity on EC risk in adults, including endometrioid and non-endometrioid histological subtypes using multivariable Mendelian randomisation. These analyses employed genetic associations derived from UK Biobank as proxies for child and adult body size in 12,906 cases and 108,979 controls that participated in the Endometrial Cancer Association Consortium.

Brief Communication on the Impact of β-blockers on Outcomes in Patients Receiving Cancer Immunotherapy.

Preclinical studies show that β-adrenergic activation suppresses the immune system and reduces the effectiveness of cancer immunotherapy. As a result, there is considerable interest in using β-blockers (BBs), a cheap and safe class of medication, in combination with immunotherapy to improve outcomes in cancer. This study is a systematic review and meta-analysis of clinical studies.

Prognostic and predictive value of β-blockers in the EORTC 1325/KEYNOTE-054 phase III trial of pembrolizumab versus placebo in resected high-risk stage III melanoma.

Background: β-adrenergic receptors are upregulated in melanoma cells and contribute to an immunosuppressive, pro-tumorigenic microenvironment. This study investigated the prognostic and predictive value of β-adrenoreceptor blockade by β-blockers in the EORTC1325/KEYNOTE-054 randomised controlled trial.

Methods: Patients with resected stage IIIA, IIIB or IIIC melanoma and regional lymphadenectomy received 200 mg of adjuvant pembrolizumab (n = 514) or placebo (n = 505) every three weeks for one year or until recurrence or unacceptable toxicity.

Systematic review of the impact of non-alcoholic fatty liver disease on mortality and adverse clinical outcomes for individuals with chronic kidney disease.

Objectives: To investigate if non-alcoholic fatty liver disease (NAFLD) impacts mortality and adverse outcomes for individuals with chronic kidney disease (CKD).

Design: Systematic review.

Data Sources: PubMed, EMBASE and Web of Science were searched up to 1 February 2020 with no restriction on the earliest date.

Coffee Consumption and Kidney Function: A Mendelian Randomization Study.

Rationale & Objective: Chronic kidney disease (CKD) is a leading cause of morbidity and mortality worldwide, with limited strategies for prevention and treatment. Coffee is a complex mixture of chemicals, and consumption has been associated with mostly beneficial health outcomes. This work aimed to determine the impact of coffee consumption on kidney function.

Evaluating the effectiveness of the NHS Health Check programme in South England: a quasi-randomised controlled trial.

Objective: To evaluate uptake, risk factor detection and management from the National Health Service (NHS) Health Check (HC).

Design: This is a quasi-randomised controlled trial where participants were allocated to five cohorts based on birth year. Four cohorts were invited for an NHS HC between April 2011 and March 2015.

Coffee consumption and health: umbrella review of meta-analyses of multiple health outcomes.

 To evaluate the existing evidence for associations between coffee consumption and multiple health outcomes. Umbrella review of the evidence across meta-analyses of observational and interventional studies of coffee consumption and any health outcome. PubMed, Embase, CINAHL, Cochrane Database of Systematic Reviews, and screening of references.

2017 European guidelines for the management of genital herpes.

Genital herpes is one of the commonest sexually transmitted infections worldwide. Using the best available evidence, this guideline recommends strategies for diagnosis, management, and follow-up of the condition as well as for minimising transmission. Early recognition and initiation of therapy is key and may reduce the duration of illness or avoid hospitalisation with complications, including urinary retention, meningism, or severe systemic illness.

Coffee, including caffeinated and decaffeinated coffee, and the risk of hepatocellular carcinoma: a systematic review and dose-response meta-analysis.

Objectives: To examine the association between coffee, including caffeinated and decaffeinated coffee, with hepatocellular carcinoma (HCC) and assess the influence of HCC aetiology and pre-existing liver disease.

Design: We performed a systematic review and meta-analysis. We calculated relative risks (RRs) of HCC according to caffeinated and decaffeinated coffee consumption using a random-effects dose-response meta-analysis.

The Enhanced Liver Fibrosis (ELF) Panel: Analyte Stability Under Common Sample Storage Conditions Used in Clinical Practice.

Background: The enhanced liver fibrosis (ELF) blood test has recently been recommended by the National Institute for Health and Care Excellence to test for advanced fibrosis in nonalcoholic fatty liver disease. The ELF test involves calculating a score from the concentrations of serum biomarkers: tissue inhibitor of matrix metalloproteinases-1 (TIMP-1), aminoterminal propeptide of procollagen type III (P3NP), and hyaluronic acid (HA). Blood samples for the ELF score are often acquired in primary care and may be stored before analysis.