Prognostic non-invasive biomarkers for all-cause mortality in non-alcoholic fatty liver disease: A systematic review and meta-analysis.

Background: Non-alcoholic fatty liver disease (NAFLD) represents a growing public health concern, with patients having higher risk of morbidity and mortality. It has a considerably high prevalence in the general population, estimated 20%-40% in Europe, and is asymptomatic until late in the disease course. It is therefore important to identify and validate tools that predict hard outcomes such as mortality for use in clinical practice in risk-stratifying NAFLD patients.

Diverging mental health after Brexit: Evidence from a longitudinal survey.

This study analyses the changes in mental health in the UK that occurred as a result of the 2016 referendum on UK membership of the EU (Brexit). Using the Household Longitudinal Study, we compare the levels of self-reported mental distress, mental functioning and life satisfaction be-fore and after the referendum. A linear fixed effects analysis revealed an overall decrease in mental health post-referendum with higher levels of mental distress, and a decline in the SF-12 Mental Component Summary score.

[Frozen shoulder: A long-lasting and misunderstood clinical problem].

Frozen shoulder (FS), also known as adhesive capsulitis, is a painful inflammatory fibrotic disease of the glenohumeral joint capsule. While it's frequently self-limiting, patients can be symptomatic for years. The clinical course is often divided into three phases: the freezing phase with predominantly pain, the frozen phase with mainly stiffness, and the thawing phase during which the complaints slowly resolve.

Dengue NS1 induces phospholipase A enzyme activity, prostaglandins, and inflammatory cytokines in monocytes.

Introduction: Dengue virus (DENV) NS1 is a non-structural secretory protein associated with severe disease and known to cause vascular leak leading to dengue haemorrhagic fever (DHF). As phospholipases A (PLA) enzymes, platelet activating factor, and leukotrienes are elevated in dengue, we sought to investigate whether NS1 potentially contributes to disease pathogenesis by inducing PLAs.

Methods: THP-1 cells and primary human monocytes of healthy adults (n = 6) were co-cultured with DENV1 NS1, LPS and media alone.

Functional and quality of life outcomes of localised prostate cancer treatments (Prostate Testing for Cancer and Treatment [ProtecT] study).

Objective: To investigate the functional and quality of life (QoL) outcomes of treatments for localised prostate cancer and inform treatment decision-making.

Patients And Methods: Men aged 50-69 years diagnosed with localised prostate cancer by prostate-specific antigen testing and biopsies at nine UK centres in the Prostate Testing for Cancer and Treatment (ProtecT) trial were randomised to, or chose one of, three treatments. Of 2565 participants, 1135 men received active monitoring (AM), 750 a radical prostatectomy (RP), 603 external-beam radiotherapy (EBRT) with concurrent androgen-deprivation therapy (ADT) and 77 low-dose-rate brachytherapy (BT, not a randomised treatment).

Cost-Effectiveness of Antihypertensive Deprescribing in Primary Care: a Markov Modelling Study Using Data From the OPTiMISE Trial.

Background: Deprescribing of antihypertensive medications for older patients with normal blood pressure is recommended by some clinical guidelines, where the potential harms of treatment may outweigh the benefits. This study aimed to assess the cost-effectiveness of this approach.

Methods: A Markov patient-level simulation was undertaken to model the effect of withdrawing one antihypertensive compared with usual care, over a life-time horizon.

2022 American College of Rheumatology/European Alliance of Associations for Rheumatology Classification Criteria for Eosinophilic Granulomatosis with Polyangiitis.

Objective: To develop and validate revised classification criteria for eosinophilic granulomatosis with polyangiitis (EGPA).

Methods: Patients with vasculitis or comparator diseases were recruited into an international cohort. The study proceeded in five phases: (1) identification of candidate criteria items using consensus methodology, (2) prospective collection of candidate items present at the time of diagnosis, (3) data-driven reduction of the number of candidate items, (4) expert panel review of cases to define the reference diagnosis and (5) derivation of a points-based risk score for disease classification in a development set using least absolute shrinkage and selection operator logistic regression, with subsequent validation of performance characteristics in an independent set of cases and comparators.

2022 American College of Rheumatology/European Alliance of Associations for Rheumatology classification criteria for granulomatosis with polyangiitis.

Objective: To develop and validate revised classification criteria for granulomatosis with polyangiitis (GPA).

Methods: Patients with vasculitis or comparator diseases were recruited into an international cohort. The study proceeded in five phases: (1) identification of candidate criteria items using consensus methodology, (2) prospective collection of candidate items present at the time of diagnosis, (3) data-driven reduction of the number of candidate items, (4) expert panel review of cases to define the reference diagnosis and (5) derivation of a points-based risk score for disease classification in a development set using least absolute shrinkage and selection operator logistic regression, with subsequent validation of performance characteristics in an independent set of cases and comparators.

2022 American College of Rheumatology/European Alliance of Associations for Rheumatology classification criteria for microscopic polyangiitis.

Objective: To develop and validate classification criteria for microscopic polyangiitis (MPA).

Methods: Patients with vasculitis or comparator diseases were recruited into an international cohort. The study proceeded in five phases: (1) identification of candidate items using consensus methodology, (2) prospective collection of candidate items present at the time of diagnosis, (3) data-driven reduction of the number of candidate items, (4) expert panel review of cases to define the reference diagnosis and (5) derivation of a points-based risk score for disease classification in a development set using least absolute shrinkage and selection operator logistic regression, with subsequent validation of performance characteristics in an independent set of cases and comparators.

2022 American College of Rheumatology/European Alliance of Associations for Rheumatology Classification Criteria for Microscopic Polyangiitis.

Objective: To develop and validate classification criteria for microscopic polyangiitis (MPA).

Methods: Patients with vasculitis or comparator diseases were recruited into an international cohort. The study proceeded in 5 phases: 1) identification of candidate items using consensus methodology, 2) prospective collection of candidate items present at the time of diagnosis, 3) data-driven reduction of the number of candidate items, 4) expert panel review of cases to define the reference diagnosis, and 5) derivation of a points-based risk score for disease classification in a development set using least absolute shrinkage and selection operator logistic regression, with subsequent validation of performance characteristics in an independent set of cases and comparators.

2022 American College of Rheumatology/European Alliance of Associations for Rheumatology Classification Criteria for Eosinophilic Granulomatosis With Polyangiitis.

Objective: To develop and validate revised classification criteria for eosinophilic granulomatosis with polyangiitis (EGPA).

Methods: Patients with vasculitis or comparator diseases were recruited into an international cohort. The study proceeded in 5 phases: 1) identification of candidate criteria items using consensus methodology, 2) prospective collection of candidate items present at the time of diagnosis, 3) data-driven reduction of the number of candidate items, 4) expert panel review of cases to define the reference diagnosis, and 5) derivation of a points-based risk score for disease classification in a development set using least absolute shrinkage and selection operator logistic regression, with subsequent validation of performance characteristics in an independent set of cases and comparators.

2022 American College of Rheumatology/European Alliance of Associations for Rheumatology Classification Criteria for Granulomatosis With Polyangiitis.

Objective: To develop and validate revised classification criteria for granulomatosis with polyangiitis (GPA).

Methods: Patients with vasculitis or comparator diseases were recruited into an international cohort. The study proceeded in 5 phases: 1) identification of candidate criteria items using consensus methodology, 2) prospective collection of candidate items present at the time of diagnosis, 3) data-driven reduction of the number of candidate items, 4) expert panel review of cases to define the reference diagnosis, and 5) derivation of a points-based risk score for disease classification in a development set using least absolute shrinkage and selection operator logistic regression, with subsequent validation of performance characteristics in an independent set of cases and comparators.

A guide to debridement, antibiotics, and implant retention.

Debridement, antibiotics, and implant retention (DAIR) is an alternative management strategy for the treatment of periprosthetic joint infection (PJI). While infection eradication rates are lower with DAIR, the benefits including decreased morbidity, improved functional outcomes, and decreased cost may justify the risks when considering this form of treatment compared to traditional one or two stage exchange arthroplasty. Implant longevity in the setting of a successful DAIR is similar to matched patients who have not experienced a PJI.

INTEnsive ambulance-delivered blood pressure Reduction in hyper-ACute stroke Trial (INTERACT4): study protocol for a randomized controlled trial.

Background: Early pre-hospital initiation of blood pressure (BP) lowering could improve outcomes for patients with acute stroke, by reducing hematoma expansion in intracerebral hemorrhage (ICH), and time to reperfusion treatment and risk of intracranial hemorrhage in ischemic stroke (IS). We present the design of the fourth INTEnsive ambulance-delivered blood pressure Reduction in hyper-ACute stroke Trial (INTERACT4).

Methods: A multi-center, ambulance-delivered, prospective, randomized, open-label, blinded endpoint (PROBE) assessed trial of pre-hospital BP lowering in 3116 hypertensive patients with suspected acute stroke at 50+ sites in China.

Neurophysiological characteristics in the periventricular/periaqueductal gray correlate with pain perception, sensation, and affect in neuropathic pain patients.

The periventricular/periaqueductal gray (PAG/PVG) is critical for pain perception and is associated with the emotional feelings caused by pain. However, the electrophysiological characteristics of the PAG/PVG have been little investigated in humans with chronic pain. The present study analyzed the oscillatory characteristics of local field potentials (LFPs) in the PAG/PVG of eighteen neuropathic pain patients.

A Randomized, double-blind, dose ranging clinical trial of intravenous FDY-5301 in acute STEMI patients undergoing primary PCI.

Background: Ischemia-reperfusion injury remains a major clinical problem in patients with ST-elevation myocardial infarction (STEMI), leading to myocardial damage despite early reperfusion by primary percutaneous coronary intervention (PPCI). There are no effective therapies to limit ischemia-reperfusion injury, which is caused by multiple pathways activated by rapid tissue reoxygenation and the generation of reactive oxygen species (ROS). FDY-5301 contains sodium iodide, a ubiquitous inorganic halide and elemental reducing agent that can act as a catalytic anti-peroxidant.

Immunogenicity and Safety of a 3-Antigen Hepatitis B Vaccine vs a Single-Antigen Hepatitis B Vaccine: A Phase 3 Randomized Clinical Trial.

Importance: There is a need for improved immunogenicity of hepatitis B virus (HBV) vaccines among young adults with risk of infection.

Objectives: To demonstrate manufacturing equivalence of a 3-antigen (3A) HBV vaccine, evaluate noninferiority of seroprotection rate (SPR) of 3A-HBV vs single-antigen (1A) HBV after 2 and 3 vaccine doses, and compare safety and reactogenicity between 3A-HBV and 1A-HBV vaccines.

Design, Setting, And Participants: This phase 3, double-blinded, randomized clinical trial included healthy adults aged 18 to 45 years randomized to 1 of three 3A-HBV groups or 1 control group receiving 1A-HBV.

CRISPR-Cas Gene Perturbation and Editing in Human Induced Pluripotent Stem Cells.

Directing the fates of human pluripotent stem cells (hPSC) to generate a multitude of differentiated cell types allows the study of the genetic regulation of human development and disease. The translational potential of hPSC is maximized by exploiting CRISPR to silence or activate genes with spatial and temporal precision permanently or reversibly. Here, we summarize the increasingly refined and diverse CRISPR toolkit for the latter forms of gene perturbation in hPSC and their downstream applications.

Application of CRISPR-Cas9 Editing for Virus Engineering and the Development of Recombinant Viral Vaccines.

CRISPR-Cas technology, discovered originally as a bacterial defense system, has been extensively repurposed as a powerful tool for genome editing for multiple applications in biology. In the field of virology, CRISPR-Cas9 technology has been widely applied on genetic recombination and engineering of genomes of various viruses to ask some fundamental questions about virus-host interactions. Its high efficiency, specificity, versatility, and low cost have also provided great inspiration and hope in the field of vaccinology to solve a series of bottleneck problems in the development of recombinant viral vaccines.