Purpose: To investigate the presence of ESR1 mutation in primary oestrogen-receptor positive breast cancer (ER+BC) treated with extended (>4 weeks) neoadjuvant (pre-surgical) aromatase inhibitor (NAI) therapy and to identify patients who may gain less benefit from aromatase inhibition (AI) alone based upon on-treatment changes in gene expression. Experimental Design: We evaluated ER, progesterone receptor and Ki67 by immunostaining, ESR1 mutations by droplet-digital-PCR and expression of over...
4h
Purpose: To determine if FDG PET can expand eligibility in biomarker selected clinical trials by providing a means to quantitate response in patients with non-assessable disease by RECIST. Experimental Design: SUMMIT (NCT01953926) is a multicenter phase II "basket" trial of neratinib. Patients had advanced ERBB2 (HER2)-mutant solid tumors, ≥1 measurable lesion, preferably defined unidimensionally by RECIST v1.1, or alternatively metabolically by PET Response Criteria (PRC). The primary aim was to...
4h
Purpose: Previous studies have suggested that higher circulating 25-hydroxyvitamin D [25(OH)D] levels are associated with decreased colorectal cancer (CRC) risk and improved survival. However, the influence of vitamin D status on disease progression and patient survival remains largely unknown for patients with advanced or metastatic CRC. Experimental design: We prospectively collected blood samples in 1,041 patients with previously untreated advanced or metastatic CRC participating in a randomized...
4h
Purpose: Activation of NFE2L2 has been linked to chemoresistance in cell line models. Recently, somatic mutations which activate NFE2L2, including mutations in NFE2L2,KEAP1, or CUL3,have been found to be associated with poor outcomes in patients with non-small cell lung cancer (NSCLC). However, the impact of these mutations on chemoresistance remains incompletely explored. Experimental Design: We investigated the effect of Keap1 deletion on chemoresistance in cell lines from Trp53-based mouse models...
4h
PURPOSE: While patients with advanced-stage non-small cell lung cancers (NSCLCs) harboring MET exon 14 skipping mutations (METex14) often benefit from MET tyrosine kinase inhibitor (TKI) treatment, clinical benefit is limited by primary and acquired drug resistance. The molecular basis for this resistance remains incompletely understood. METHODS: Targeted sequencing analysis was performed on cell-free circulating tumor DNA obtained from 289 patients with advanced-stage METex14-mutated NSCLC. RESULTS:...
4h
Purpose: The outgrowth of antigen negative variants is a significant challenge for adoptive therapy with T cells that target a single specificity. Chimeric antigen receptors (CARs) are typically designed with one or two scFvs that impart antigen specificity fused to activation and costimulation domains of T cell signaling molecules. We designed and evaluated the function of CARs with up to three specificities for overcoming tumor escape using Designed Ankyrin Repeat Proteins (DARPins) rather than...
4h
Background: Patients with 1p/19q co-deleted low grade glioma (LGG) have longer overall survival and better treatment response than patients with 1p/19q intact tumors. Therefore, it is relevant to know the 1p/19q status. To investigate whether the 1p/19q status can be assessed prior to tumor resection, we developed a machine learning algorithm to predict the 1p/19q status of presumed LGG based on preoperative magnetic resonance imaging (MRI). Methods: Preoperative brain MRI scans from 284 patients...
4h
Purpose: Acute myeloid leukemia (AML) is a highly aggressive form of leukemia that results in poor survival outcomes. Currently, diagnosis and prognosis are based on invasive single-point bone marrow biopsies (iliac crest). There is currently no AML-specific non-invasive imaging method to detect disease, including in extramedullary organs, representing an unmet clinical need. About 85-90% of human myeloid leukemia cells express CD33 cell surface receptors, highlighting CD33 as an ideal candidate...
4h
FDA Approval Summary: Tagraxofusp-erzs For Treatment of Blastic Plasmacytoid Dendritic Cell Neoplasm
Tagraxofusp-erzs (Elzonris, Stemline) is a cytotoxin that targets CD123-expressing cells. On December 21, 2018, FDA approved tagraxofusp-erzs for the treatment of blastic plasmacytoid dendritic cell neoplasms (BPDCN) in adult and pediatric patients 2 years and older. Approval was based on the response rate in a single-arm trial, Study STML-401-0114; the pivotal cohort included 13 patients with treatment-naïve BPDCN who received tagraxofusp-erzs monotherapy. The complete response or clinical complete...
4h
Genetic robustness, the preservation of evolved phenotypes against genotypic mutations, is one of the central concepts in evolution. In recent years a large body of work has focused on the origins, mechanisms, and consequences of robustness in a wide range of biological systems. In particular, research on ncRNAs studied the ability of sequences to maintain folded structures against single-point mutations. In these studies, the structure is merely a reference. However, recent work revealed evidence...
4h
A highly conserved internal stem-loop (ISL) of U6 snRNA is important for the function of the spliceosome. U6 ISL contains a 1x2 nucleotide internal loop that folds and unfold during spliceosomal assembly and activation. This internal loop coordinates magnesium ions needed for catalysis. The 1x2 loop consists of a C67•A79 base pair that forms an additional hydrogen bond upon protonation, C67•A+79, and uracil (U80) that coordinates the catalytically essential magnesium ion(s). We designed a series...
4h
Eating more nuts is associated with less weight gain over time, according to an observational study in the BMJ Nutrition, Prevention & Health. Two of the...
5h
High-intensity surveillance for patients who've had colorectal adenomas removed at screening is associated with moderate clinical benefits while still being cost-effective, suggests a...
7h
See what's happening over at NEJM Group: NEJM Primary Care/Hospitalist Page: Images in Clinical Medicine: A 60-year-old woman with a history of...
7h
Liver fibrosis represents a serious global health-care problem and is the outcome of many chronic liver diseases, cirrhosis, hepatitis, and toxin accumulation. The present study aimed to evaluate the antifibrotic curative effect of Dunaliella salina (D. salina) on thioacetamide- (TAA-) induced liver fibrosis in rats. Liver fibrosis was induced by TAA (200mg/kg; i.p.) twice per week for 6 weeks. D. salina was given orally (100 and 200 mg/kg) and silymarin was given orally (100 mg/kg) daily, for 4 weeks...
5h
Microphthalmia-associated transcription factor (MITF) is a key regulator for the development and function of melanocytes in skin, eye, and plumage pigmentations. Thus, the MITF was selected as a candidate gene associated with plumage coloration in ducks. This study analyzed the mRNA expression, promoter methylation, and polymorphisms in the MITF gene in ducks with different plumage colors (Putian Black, Putian White, Liancheng White, and Longsheng Jade-green). No expression of the MITF melanin-specific...
17h
Lovastatin Enhances Cytotoxicity of Temozolomide via Impairing Autophagic Flux in Glioblastoma Cells
Drug resistance to temozolomide (TMZ) contributes to the majority of tumor recurrence and treatment failure in patients with glioblastoma multiforme (GBM). Autophagy has been reported to play a role in chemoresistance in various types of cancer, including GBM. The anticancer effect of statins is arousing great research interests and has been demonstrated to modulate autophagic function. In this study, we investigated the combinational effects of lovastatin and TMZ on treating U87 and U251 GBM cell...
17h
Hospital-acquired Infections (HAIs) surveillance, defined as the systematic collection of data related to a certain health event, is considered an essential dimension for a prevention HAI program to be effective. In recent years, new automated HAI surveillance methods have emerged with the wide adoption of electronic health records (EHR). Here we present the validation results against the gold standard of HAIs diagnosis of the InNoCBR system deployed in the Ourense University Hospital Complex (Spain)....
21h
Introduction. Low muscle strength is common and important in geriatric syndromes including frailty and sarcopenia. The epidemiology of grip strength of older people under long-term care facilities has been little explored. Purpose. The aim of this study was to assess handgrip strength of older women and men covered by institutional care and to analyse the associations between HGS and mobility, leg strength, flexibility, and postural balance. Materials and Methods. This is a cross-sectional study...
22h
Exp Clin Endocrinol DiabetesDOI: 10.1055/a-0998-8035 Background Subacute thyroiditis (SAT) is a rare inflammatory disease that presents diagnostic challenges. The underlying pathophysiology and prediction of outcomes are elusive. We investigated the long-term follow-up of SAT for up to 30 years and determined predictors for later hypothyroidism. Methods SAT outcome data from 127 patients (age: 47.6 ± 11.0 yrs., BMI: 24.7±4.8 kg/m²) were analyzed retrospectively. Patients with pre-existing and...
5h
Exp Clin Endocrinol DiabetesDOI: 10.1055/a-1001-2244 Objective Secretagogin, a Ca2+ binding protein, is one of the most abundant proteins in pancreatic β-cells and is critical for maintaining the structural integrity and signaling competence of β-cells. This study seeks to assess the concentrations of plasma secretagogin in participants with prediabetes (pre-DM) and newly diagnosed type 2 diabetes (T2DM) and to explore its relationship to parameters of glucose and lipid metabolism, first-phase insulin...
5h
Clinical and Molecular Characteristics of GNAS Inactivation Disorders Observed in 18 Korean Patients
Exp Clin Endocrinol DiabetesDOI: 10.1055/a-1001-3575 Background The GNAS gene on chromosome 20q13.3 is a complex, imprinted locus regulated in a tissue-specific manner. GNAS inactivation disorders are a heterogeneous group of rare disorders caused by mutations and methylation defects. These are divided into pseudohypoparathyroidism (PHP) types 1A and 1B, pseudo-pseudohypoparathyroidism (PPHP), and progressive osseous heteroplasia (POH), depending on the presence or absence of hormone resistance,...
5h
Exp Clin Endocrinol DiabetesDOI: 10.1055/a-1008-9223 Background The single nucleotide polymorphism in TCF7L2 rs7903146 is associated with an increased risk of type 2 diabetes mellitus and gestational diabetes mellitus. Mechanisms by which this mutation acts, and its impact on the clinical course of the diseases remain unclear. Here we investigated the clinical impact of the T risk allele in women with gestational diabetes mellitus. Methods We genotyped the C/T polymorphism in 164 Caucasian women...
5h
Exp Clin Endocrinol DiabetesDOI: 10.1055/a-1008-9110 Background High-fat-diet induces pancreatic β-cell compensatory proliferation, and impairments in pancreatic β-cell proliferation and function can lead to defects in insulin secretion and diabetes. NFATc3 is important for HFD-induced adipose tissue inflammation. But it is unknown whether NFATc3 is required for β cell compensatory growth in mice fed with HFD. Methods NFATc3 mRNA and protein expression levels were quantified by RT-qPCR and Western...
5h
AJP Rep 2019; 09: e302-e309DOI: 10.1055/s-0039-1697655 Objective This study aims to investigate accuracy of group beta Streptococcus (GBS) rectovaginal cultures at 35 to 37 weeks in predicting intrapartum colonization. Study Design Institutional review board (IRB) approved prospective cohort study of 302 women from October 2015 to May 2017. Patients had the following tests for GBS: first trimester urine culture, rectovaginal culture at 35 to 37 weeks, and intrapartum rectovaginal...
5h
J reconstr MicrosurgDOI: 10.1055/s-0039-1697904 Background Although lipedema is often clinically distinguished from lymphedema, there is considerable overlap between the two entities. The purpose of this study was to evaluate lymphoscintigraphic findings in patients with lipedema to better characterize lymphatic flow in this patient population. Methods Patients with lipedema receiving lymphoscintigraphy between January 2015 and October 2017 were included. Patient demographics,...
5h
J reconstr MicrosurgDOI: 10.1055/s-0039-1697646 Background In elderly patients, complex soft tissue defects are increasingly observed due to the prolonged life expectancy and accompanying comorbidities. The aim of this study is to evaluate whether free tissue transfer is safe in very old patients without additional risk and complications. Methods All patients older than 65 years undergoing free tissue transfer between November 2007 and September 2016 were reviewed in a retrospective...
5h
Abstract Objective To characterise the burden of voice disorders in teachers in a UK population, compare it with non‐teachers; and identify groups of teachers who may be particularly at risk of developing a voice problem. Design Questionnaire based survey of primary, secondary teachers and non‐teachers. Questions consisted of general demographics, VHI‐10 and questions relating to voice problems. Methods Distribution of questionnaires to teachers and non‐teachers and statistical analysis...
6h
Objectives(1) To assess the changes in the salt content of sauces in the UK in the past 10 years; (2) to compare the salt content of sauces in China with equivalent products sold in the UK and (3) to calculate the proportion of sauce products meeting the salt targets set by the UK Department of Health (DoH). DesignCross-sectional surveys from the nutrition information panels of sauces. SettingMajor retailers in London, Beijing and Shijiazhuang operating at data collection times. Main outcome measureSalt...
6h
ObjectiveTo investigate whether the introduction of a named general practitioner (GP, family physician) improved patients’ healthcare for patients aged 75 and over in England. SettingRandom sample of 27 500 patients aged 65 to 84 in 2012 within 139 English practices from the Clinical Practice Research Datalink linked with Hospital Episode Statistics. DesignProspective cohort approach, measuring patients’ GP consultations and emergency hospital admissions 2 years before/after the intervention. Patients...
11h
ObjectivesObstetric ultrasound is an important part of antenatal care in Vietnam, although there are great differences in access to antenatal care and ultrasound services across the country. The aim of this study was to explore Vietnamese health professionals’ experiences and views of obstetric ultrasound in relation to clinical management, resources and skills. DesignA cross-sectional questionnaire study was performed as part of the CROss Country UltraSound study. SettingHealth facilities (n=29)...
23h
Socioeconomic status (SES) is a major determinant of health. We studied the Index of Multiple Deprivation Rank of 473 families with individuals with pathogenic autosomal copy number variants (CNVs) and known inheritance status. The IMDR distribution of families with pathogenic CNVs was significantly different from the general population. Families with inherited CNVs were significantly more likely to be living in areas of higher deprivation when compared with families that had individuals with de...
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In this issue, Meester and colleagues use microsimulation modeling to assess the cost-effectiveness of high- and low-intensity surveillance colonoscopy in patients with adenomas. The editorialists discuss the findings, unanswered questions about the benefit of surveillance, and the issue of optimal resource use.
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Background:Surveillance of patients with colorectal adenomas has limited long-term evidence to support current practice.Objective:To compare the lifetime benefits and costs of high- versus low-intensity surveillance.Design:Microsimulation model.Data Sources:U.S. cancer registry, cost data, and published literature.Target Population:U.S. patients aged 50, 60, or 70 years with low-risk adenomas (LRAs) (1 to 2 small adenomas) or high-risk adenomas (HRAs) (3 to 10 small adenomas or ≥1 large adenoma)...
6h
Description:The Kidney Disease: Improving Global Outcomes (KDIGO) 2018 clinical practice guideline for the prevention, diagnosis, evaluation, and treatment of hepatitis C virus (HCV) infection in chronic kidney disease (CKD) is an extensive update of KDIGO's 2008 guideline on HCV infection in CKD. This update reflects the major advances since the introduction of direct-acting antivirals (DAAs) in the management of HCV infection in the CKD population.Methods:The KDIGO work group tasked with developing...
6h
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