Vemurafenib for BRAF V600-Mutant Erdheim-Chester Disease and Langerhans Cell Histiocytosis: Analysis of Data From the Histology-Independent, Phase 2, Open-label VE-BASKET Study.

Importance: The histiocytic neoplasms Erdheim-Chester disease (ECD) and Langerhans cell histiocytosis (LCH) are highly enriched for BRAF V600 mutations and have been previously shown to be responsive to treatment with vemurafenib, an inhibitor of the BRAF V600 kinase. However, the long-term efficacy and safety of prolonged vemurafenib use in these patients are not defined. Here we analyze the final efficacy and safety data for vemurafenib in patients with ECD and LCH enrolled in the VE-BASKET study.

Tenofovir Alafenamide Fumarate: A New Tenofovir Prodrug for the Treatment of Chronic Hepatitis B Infection.

Tenofovir alafenamide fumarate (TAF), a new prodrug of tenofovir and a potential successor of tenofovir disoproxil fumarate (TDF), has been approved in the United States and Europe for treating adolescents and adults with chronic hepatitis B infection. TAF is formulated to deliver the active metabolite to target cells more efficiently than TDF at lower doses, thereby reducing systemic exposure to tenofovir. In patients with chronic hepatitis B, TAF appears to be as effective as TDF, with lower bone and renal toxicity.

Downregulation of mucosal mast cell activation and immune response in diarrhoea-irritable bowel syndrome by oral disodium cromoglycate: A pilot study.

Background And Goal: Diarrhoea-predominant irritable bowel syndrome (IBS-D) exhibits intestinal innate immune and mucosal mast cell (MC) activation. MC stabilisers have been shown to improve IBS symptoms but the mechanism is unclear. Our primary aim was to investigate the effect of oral disodium cromoglycate (DSCG) on jejunal MC activation and specific innate immune signalling pathways in IBS-D, and secondarily, its potential clinical benefit.

Validation of psychometric properties and development of response criteria for the psoriasis symptoms and signs diary (PSSD): results from a phase 3 clinical trial.

Purpose: The Psoriasis Symptoms and Signs Diary (PSSD) is a patient-reported instrument that assesses severity of six symptoms (itch, skin tightness, burning, stinging, and pain) and five signs (dryness, cracking, scaling, shedding/flaking, redness, and bleeding) of psoriasis.

Materials And Methods: PSSD symptoms and signs summary scores (range, 0-100) were derived based on individual item scores (0-10 [absent-worst imaginable]). Using Psoriasis Area and Severity Index [PASI], Investigator's Global Assessment [IGA] and Dermatology Life Quality Index [DLQI]) data from the NAVIGATE trial of patients with moderate-to-severe psoriasis, analyses were conducted to further validate the PSSD (7-day recall version) and establish criteria for clinically meaningful improvements (CMIs).

Weight decrease improves live birth rates in obese women undergoing IVF: a pilot study.

Obese women have lower pregnancy rates than normal-weight women undergoing assisted reproductive treatment. We conducted a pilot study to evaluate whether a 12-week diet and exercise intervention before an IVF cycle would influence pregnancy rates in obese women. Forty-one patients were enrolled in this study.

A polymorphism in the CYP17A1 gene influences the therapeutic response to steroidogenesis inhibitors in Cushing's syndrome.

Context: Steroidogenesis inhibitors, such as ketoconazole (KTZ) and metyrapone (MTP), are used to lower hypercortisolism in patients with Cushing's syndrome (CS). Cortisol normalization is not reached in all patients taking these medications.

Objective: To test the hypothesis that variants in genes affecting steroidogenesis contribute to different responses to KTZ and/or MTP in patients with CS.

Depression and Anxiety Scores Are Associated with Amygdala Volume in Cushing's Syndrome: Preliminary Study.

Introduction: Cushing's syndrome (CS) has repeatedly been associated with hippocampal volume reductions, while little information is available on the amygdala, another structure rich in glucocorticoid receptors. The aim of the study was to analyze amygdala volume in patients with CS and its relationship with anxiety, depression, and hormone levels.

Material And Methods: 39 CS patients (16 active and 23 patients in remission) and 39 healthy controls matched for age, sex, and education level completed anxiety (STAI) and depression tests (BDI-II) and underwent a 3 Tesla brain MRI and endocrine testing.

MANAGEMENT OF ENDOCRINE DISEASE: Quality of life tools for the management of pituitary disease.

Background: In the last few years, quality of life (QoL) has become an outcome measure in patients with pituitary diseases.

Objective: To describe the available data on QoL impairment evaluated with questionnaires in patients with pituitary diseases.

Design: Critical review of the pertinent literature and pragmatic discussion of available information.

White matter involvement on DTI-MRI in Cushing's syndrome relates to mood disturbances and processing speed: a case-control study.

Purpose: Cushing's syndrome (CS) is an endocrine disorder due to prolonged exposure to cortisol. Recently, microstructural white matter (WM) alterations detected by diffusion tensor imaging (DTI) have been reported in CS patients, and related to depression, but other functional significances. remain otherwise unclear.

Impaired quality of life in patients with treated acromegaly despite long-term biochemically stable disease: Results from a 5-years prospective study.

Objective: Patients with acromegaly demonstrate impaired quality of life (QoL), but data on long-term QoL changes in treated acromegaly are limited. This study evaluates and identifies factors that influence QoL in patients with long-term biochemical remission.

Design: The study consists of a cross-sectional arm comparing QoL between patients with treated and controlled acromegaly and healthy controls; and a longitudinal arm assessing QoL changes in patients with biochemically stable disease during 5.

Serum hepatitis B core-related antigen is more accurate than hepatitis B surface antigen to identify inactive carriers, regardless of hepatitis B virus genotype.

Objectives: To investigate whether hepatitis B surface antigen (HBsAg) and hepatitis B core-related antigen (HBcrAg) levels are useful to identify inactive carriers among HBeAg-negative patients infected by different hepatitis B virus (HBV) genotypes.

Methods: In all, 202 consecutive HBeAg-negative patients with chronic hepatitis B, 135 inactive carriers and 67 with HBV activity, were prospectively followed for 1 year.

Results: In HBeAg-negative patients, HBsAg levels differed across the different genotypes (p <0.

Management of direct antiviral agent failures.

The current standard of care for patients with chronic hepatitis C virus (HCV) infection is a combination of direct-acting antiviral agents (DAAs). Most HCV patients treated with these drugs achieve viral elimination, but 1% to 15% fail to attain this objective. Treatment failures are usually related to relapse, and less often to on-treatment viral breakthrough.

Effectiveness and Safety of Entecavir or Tenofovir in a Spanish Cohort of Chronic Hepatitis B Patients: Validation of the Page-B Score to Predict Hepatocellular Carcinoma.

Background: Long-term antiviral therapy has resulted in viral suppression and biochemical response in chronic hepatitis B, although the risk of hepatocellular carcinoma has not been abolished. The Page-B score could be useful to estimate the probability of HCC.

Aims: To analyze the effectiveness and safety of entecavir or tenofovir for more than 4 years and the usefulness of Page-B score in the real-world setting.

Learning from patients: trainers' use of narratives for learning and teaching.

Background: There is a growing interest in how doctors learn from narratives about individual cases, reflected, for example, in the use of e-portfolios.

Aim: This study aimed to evaluate how GP trainers conceptualised 'learning from patients', and what use they currently made of narrative recounts in training.

Design & Setting: Thematic analysis (TA) and corpus-linguistic (CL) analysis, with data collected from a convenience sample of trainers in the UK, Ireland, and Spain.

Relative bioavailability of three formulations of galunisertib administered as monotherapy in patients with advanced or metastatic cancer.

Objective: Galunisertib (LY2157299 monohydrate), an inhibitor of the transforming growth factor β (TGFβ) pathway, is currently under investigation in several clinical trials involving multiple tumor types. The primary objective of this study was to assess relative bioavailability of two new galunisertib formulations developed using the roller compaction (RC) dry-milled (RCD) and RC slurry-milled (RCS) processes, compared with the existing formulation developed using the high-sheer wet granulation (HSWG) process. The secondary objective was to report the safety profile after a single dose of the three formulations.

Affective alterations in patients with Cushing's syndrome in remission are associated with decreased BDNF and cortisone levels.

Objective: Affective alterations and poorer quality of life often persist in patients with Cushing's syndrome (CS) in remission. Brain-derived neurotrophic factor (BDNF) regulates the hypothalamic-pituitary-adrenal axis (HPA) and is highly expressed in brain areas controlling mood and response to stress. Our aims were to assess affective alterations after long-term remission of CS and evaluate whether they are associated with serum BDNF, salivary cortisol (SalF) and/or cortisone (SalE) concentrations.

Cystatin-C and epicardial adipose tissue as noninvasive predictors of cardiovascular risk in acromegaly.

Background: Acromegaly (ACRO) is associated with elevated cardiovascular risk, although the prevalence of coronary artery disease (CAD) is unclear. Increased epicardial adipose tissue (EAT) and elevated cystatin-C (Cys-C) levels are cardiovascular risk factors, also related to the progression of CAD in several populations.

Aims: To measure the severity and extent of CAD in patients with ACRO and to determine whether either EAT or Cys-C reflect higher cardiovascular risk in patients with ACRO than in healthy controls.

Targeted proteomics in urinary extracellular vesicles identifies biomarkers for diagnosis and prognosis of prostate cancer.

Rapid and reliable diagnosis of prostate cancer (PCa) is highly desirable as current used methods lack specificity. In addition, identification of PCa biomarkers that can classify patients into high- and low-risk groups for disease progression at early stage will improve treatment decision-making. Here, we describe a set of protein-combination panels in urinary extracellular vesicles (EVs), defined by targeted proteomics and immunoblotting techniques that improve early non-invasive detection and stratification of PCa patients.

Red blood cell transfusion-transmitted acute hepatitis E in an immunocompetent subject in Europe: a case report.

Background: Acute hepatitis E in industrialized countries is usually related to intake or manipulation of undercooked or raw meat. Cases of transfusion-transmitted hepatitis E have rarely been documented in immunosuppressed patients, mainly after receiving frozen plasma.

Study Design And Methods: A 61-year-old man was admitted to hospital for jaundice.

Update on quality of life in patients with acromegaly.

In recent years, health-related quality of life (QoL) has been considered an important outcome for clinical management of acromegaly. Poor QoL has been described in acromegalic patients with active disease as well as after endocrine cure. It is known that acromegaly determines many physical problems and psychological dysfunctions that unavoidably impact on patients' QoL.

Reduced DNA methylation of FKBP5 in Cushing's syndrome.

FKBP5 encodes a co-chaperone of HSP90 protein that regulates intracellular glucocorticoid receptor sensitivity. When it is bound to the glucocorticoid receptor complex, cortisol binds with lower affinity to glucocorticoid receptor. Cushing's syndrome is associated with memory deficits, smaller hippocampal volumes, and wide range of cognitive impairments.

T2-weighted MRI signal predicts hormone and tumor responses to somatostatin analogs in acromegaly.

GH-secreting pituitary adenomas can be hypo-, iso- or hyper-intense on T2-weighted MRI sequences. We conducted the current multicenter study in a large population of patients with acromegaly to analyze the relationship between T2-weighted signal intensity on diagnostic MRI and hormonal and tumoral responses to somatostatin analogs (SSA) as primary monotherapy. Acromegaly patients receiving primary SSA for at least 3 months were included in the study.

Conflicting Interpretation of Genetic Variants and Cancer Risk by Commercial Laboratories as Assessed by the Prospective Registry of Multiplex Testing.

Purpose Massively parallel sequencing allows simultaneous testing of multiple genes associated with cancer susceptibility. Guidelines are available for variant classification; however, interpretation of these guidelines by laboratories and providers may differ and lead to conflicting reporting and, potentially, to inappropriate medical management. We describe conflicting variant interpretations between Clinical Laboratory Improvement Amendments-approved commercial clinical laboratories, as reported to the Prospective Registry of Multiplex Testing (PROMPT), an online genetic registry.