Relationship between pruritus and sleep in participants with primary biliary cholangitis in the Phase 2b GLIMMER trial.

Background: Cholestatic pruritus and fatigue are debilitating conditions associated with primary biliary cholangitis (PBC) and can significantly impact patients' quality of life. Pruritus in PBC often worsens at night and patients frequently report sleep disturbance, which contributes to cognitive symptoms and fatigue. Linerixibat is an ileal bile acid transporter inhibitor in clinical development for the treatment of pruritus associated with PBC and was recently assessed versus placebo in the Phase 2b GLIMMER trial.

Statistical analysis of actigraphy data with generalised additive models.

There is a growing interest in the use of physical activity data in clinical studies, particularly in diseases that limit mobility in patients. High-frequency data collected with digital sensors are typically summarised into actigraphy features aggregated at epoch level (e.g.

A randomised, double-blind, placebo-controlled study of the LAG-3-depleting monoclonal antibody GSK2831781 in patients with active ulcerative colitis.

Background: Selective depletion of T cells expressing LAG-3, an immune checkpoint receptor that is upregulated on activated T cells, has been investigated in pre-clinical models as a potential therapeutic approach in inflammatory and autoimmune diseases where activated T cells are implicated.

Aims: GSK2831781, a depleting monoclonal antibody that specifically binds LAG-3 proteins, may deplete activated LAG-3 cells in ulcerative colitis (UC).

Methods: Patients with moderate to severe UC were randomised to GSK2831781 or placebo.

Randomized Trial of the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of GSK2831781 in Healthy Japanese and White Participants.

This study investigated ethnic differences in the safety, tolerability, pharmacokinetics, and pharmacodynamics of GSK2831781, an anti-lymphocyte activation gene 3 (LAG3) monoclonal antibody, in healthy participants, and determined local tolerability and bioavailability following subcutaneous (SC) administration. A double-blind, randomized study of (A) single intravenous (IV) doses of GSK2831781 450 mg or placebo in Japanese and White participants; and (B) single SC doses of GSK2831781 150 or 450 mg, or placebo in White participants, was conducted. Blood samples for analyses were collected before dosing and over 112 days after dosing.

Genomics Integration Into Nephrology Practice.

Rationale & Objective: The etiology of kidney disease remains unknown in many individuals with chronic kidney disease (CKD). We created the Mayo Clinic Nephrology Genomics Clinic to improve our ability to integrate genomic and clinical data to identify the etiology of unexplained CKD.

Study Design: Retrospective study.

Health care practitioners' experience-based opinions on providing care after a positive newborn screen for Pompe disease.

The addition of Pompe disease (PD) and other conditions with later-onset forms to newborn screening (NBS) in the United States (US) has been controversial. NBS technology cannot discern infantile-onset PD (IOPD) from later-onset PD (LOPD) without clinical follow-up. This study explores genetic health care practitioners' (HCPs) experiences and challenges providing NBS patient care throughout the US and their resultant opinions on NBS for PD.

Identification of Genetic Causes of Focal Segmental Glomerulosclerosis Increases With Proper Patient Selection.

Objective: To increase the likelihood of finding a causative genetic variant in patients with a focal segmental glomerulosclerosis (FSGS) lesion, clinical and histologic characteristics were analyzed.

Patients And Methods: Individuals 18 years and older with an FSGS lesion on kidney biopsy evaluated at Mayo Clinic from November 1, 1999, through October 31, 2019, were divided into 4 groups based on clinical and histologic characteristics: primary FSGS, secondary FSGS with known cause, secondary FSGS without known cause, and undetermined FSGS. A targeted gene panel and a customized gene panel retrieved from exome sequencing were performed.

Left atrial strain by speckle tracking predicts atrial fibrosis in patients undergoing heart transplantation.

Aims: In patients with heart failure (HF), chronically raised left ventricular (LV) filling pressures lead to progressive left atrial (LA) dysfunction and fibrosis. We aimed to assess the correlation of LA reservoir strain (peak atrial longitudinal strain, PALS) by speckle tracking echocardiography (STE) and LA fibrosis assessed by myocardial biopsy in patients undergoing heart transplantation (HTx).

Methods And Results: Forty-eight patients with advanced HF [mean age 51.

Opinions of adults affected with later-onset lysosomal storage diseases regarding newborn screening: A qualitative study.

Lysosomal storage diseases (LSDs) are a heterogeneous group of conditions causing substrate accumulation leading to progressive organ damage. Newborn screening (NBS) for several LSDs has become available in recent years due to advances in technology and treatment availability. While early initiation of treatment is lifesaving for those with infantile presentations, controversy continues regarding diagnosis of milder, later-onset diseases in infancy, including creation of pre-symptomatic populations of 'patients-in-waiting', the potential for medicalization, stigmatization, and/or discrimination.

Expanding insurance coverage for in vitro fertilisation with preimplantation genetic testing: putting the cart before the horse.

Madison Kilbride recently argued that insurance (eg, Centers for Medicare & Medicaid Services (CMS)) should cover in vitro fertilisation with preimplantation genetic testing (IVF-PGT) services for couples at high risk of having a child affected with a genetic condition. She argues that IVF-PGT meets CMS's definition of 'medically necessary care', where such care includes 'services or supplies needed to diagnose or treat an illness, injury, condition, disease or its symptoms'. Kilbride argues that IVF-PGT satisfies this definition in two ways: as a diagnostic tool and as a treatment.

Modelling and forecasting art movements with CGANs.

Conditional generative adversarial networks (CGANs) are a recent and popular method for generating samples from a probability distribution conditioned on latent information. The latent information often comes in the form of a discrete label from a small set. We propose a novel method for training CGANs which allows us to condition on a sequence of continuous latent distributions , …, .

The Role of Urinary Calcium and Chitotriosidase in a Cohort of Chronic Sarcoidosis Patients.

Background: Calcium metabolism alterations are quite common in sarcoidosis and have been correlated with disease activity.

Objectives: The aim of the study was to investigate the clinical significance of calcium metabolism alterations in patients with chronic sarcoidosis. We paid particular attention to associations with specific disease phenotypes and chitotriosidase (CTO) expression.

Left Atrial Fractional Shortening: A Simple and Practical "Strain" for Everyone.

Background: The function of the left atrium (LA) is reduced in many cardiac diseases even with normal size. The assessment of its compliance could represent an added value in an echocardiographic report in case the gold standard technique (speckle-tracking echocardiography [STE]) is not available. We sought to test a simple and quick method as surrogate of STE: the dynamic measurement of the LA anteroposterior diameter (APD) that we called LA fractional shortening (LAFS).

ACUTE HF score, a multiparametric prognostic tool for acute heart failure: A real-life study.

Background: Acute heart failure (AHF) is the first cause of hospitalization for over-65 individuals, associated with high mortality and readmission rate. The aim of this study was to assess the prognostic value of a multiparametric score combining clinical, biochemical and echocardiographic indexes in AHF for clinical practice.

Methods: 830 patients hospitalized for AHF were enrolled.

Prognosis and Risk Stratification of Patients With Advanced Heart Failure (from PROBE).

In recent years, many prognostic scores have been developed for advanced chronic heart failure (CHF), but none of them is comprised of first- and second level echocardiographic indexes. The aim was to create a new prognostic echocardiographic score for patients with advanced CHF. Patients with advanced CHF were analyzed by standard, 3D, and speckle tracking echocardiography and followed prospectively for 2 ± 0.

Left atrial, ventricular and atrio-ventricular strain in patients with subclinical heart dysfunction.

Arterial hypertension (AH) and diabetes mellitus (DM) are the most common causes of heart deterioration because of their high prevalence in the population. The aim of this study was to evaluate peak left atrial (LA), longitudinal strain (PALS), left ventricular (LV), longitudinal  strain (LS) and global atrial-ventricular strain (GAVS), by speckle-tracking echocardiography (STE), in asymptomatic patients with AH or/and DM and normal LA, LV size and ejection fraction (EF), to analyze their capability to detect early subclinical dysfunction. We enrolled 162 patients affected by AH and/or DM with normal indexed LA volume, LV end-diastolic diameter and a LVEF > 52% (females) or > 54% (males) (60 hypertensives, 52 diabetics and 50 both) and 60 healthy controls.

Left heart longitudinal deformation analysis in mitral regurgitation.

In mitral regurgitation (MR), left atrium (LA) and left ventricle (LV) undergo remodeling even if the patient is asymptomatic. The aim of our study was to identify the best echo index that correlates with MR severity in asymptomatic patients affected by MR. We enrolled 150 MR patients (50: mild, 50: moderate, 50: severe), asymptomatic for exertional dyspnea and 50 healthy controls.

The Italian National External Quality Assessment Program in Cytogenetics: 4 years of activity (2013-2016) following the introduction of poor performance criteria.

Background: Italian External Quality Assessment (IEQA) Program in Cytogenetics, established in 2001 by the Istituto Superiore di Sanità (ISS), covers both Constitutional and Oncohaematological diagnosis. In 2013, performance criteria were defined and adopted. In this paper, we present the data from the first 4 years of activity (2013-2016) following the introduction of performance criteria.

Newborn screening for Pompe disease: impact on families.

Pompe disease (PD) is an autosomal recessive lysosomal storage disorder causing progressive glycogen accumulation in muscles, with variability in age of onset and severity. For infantile-onset PD (IOPD), initiation of early treatment can be life-saving; however, current newborn screening (NBS) technology cannot distinguish IOPD from late-onset PD (LOPD) without clinical workup. Therefore, families of LOPD infants diagnosed by NBS may now spend years or even decades aware of their illness before symptoms appear, creating a pre-symptomatic awareness phase with which the medical community has little experience.

Self-Recovery Superhydrophobic Surfaces: Modular Design.

Superhydrophobicity, the enhanced hydrophobicity of surfaces decorated with textures of suitable size, is associated with a layer of gas trapped within surface roughness. The reduced liquid/solid contact makes superhydrophobicity attractive for many technological applications. This gas layer, however, can break down with the liquid completely wetting the surface.

The Psychosocial Impact of Carrying a Debated Variant in the GLA Gene.

The clinical significance of the c.427G>A (p.A143T) variant in GLA is a topic of debate within the lysosomal storage disease community.

Radiological contribution to the diagnosis of early postoperative complications after lung resection for primary tumor: a revisional study.

In the post-operative course of the interventions of lung resection for primary tumor, complications of different nature and severity can arise, recognizing different pathogenetic mechanisms and differing according to the type of resection performed and to the time elapsed after surgery. The low diagnostic accuracy of chest radiography requires a thorough knowledge of the radiologist about all radiographic findings, both normal and pathological, which can be found in the immediate post-operative period (within 30 days after surgery). This article aims to describe the incidence, the clinical features and the radiological aspects of immediate complications following pulmonary resections, with specific reference to those in which the diagnostic imaging provides a fundamental contribution.

Patients' perspectives on newborn screening for later-onset lysosomal storage diseases.

Lysosomal storage diseases (LSDs) are an individually rare but collectively common group of hereditary, progressive, multi-systemic disorders. Recent technological advances have brought newborn screening (NBS) for LSDs to attention in the United States. However, many LSD symptoms present in later childhood or adulthood, with a wide spectrum of severity.

Validation of a method for noninvasive prenatal testing for fetal aneuploidies risk and considerations for its introduction in the Public Health System.

Objective: The aim of this study was to validate noninvasive prenatal testing (NIPT) for fetal aneuploidies by whole-genome massively parallel sequencing (MPS).

Methods: MPS was performed on cell-free DNA (cfDNA) isolated from maternal plasma in two groups: a first set of 186 euploid samples and a second set of 195 samples enriched of aneuploid cases (n = 69); digital PCR for fetal fraction (FF) assessment was performed on 178/381 samples. Cases with <10 × 10 reads (n = 54) were excluded for downstream data analysis.