Objective: To clarify the link between germline variants in fumarate hydratase (FH), hereditary leiomyomatosis and renal cell cancer (HLRCC), and paraganglioma (PGL) and pheochromocytoma (PCC) we utilize a well-annotated hereditary cancer testing database.
Methods: Records of 120,061 patients receiving germline testing were obtained. FH variants were classified into 4 categories: autosomal dominant (AD) HLRCC variants, autosomal recessive (AR) fumarase deficiency (FMRD), variants, previously reported as PGL/PCC FH variants, and variants of unknown significance (VUS) not previously associated with PGL/PCC (NPP-VUS). Rates of PGL/PCC were compared with those with negative genetic testing.
Results: About 1.3% of individuals carried FH variants which were more common among individuals with PGL/PCC compared to those without (3.1% vs 1.3%, P < .0001). PGL/PCC rates were higher among individuals with PGL/PCC FH variants compared to those with negative genetic testing (22.2% vs 0.9%, P < .0001). Neither AD HLRCC variants (0.3% vs 0.9%, P = .35) nor AR FMRD variants (1.4% vs 0.9%, P = .19) carried an increased prevalence of PGL/PCC. An increased prevalence of PGL/PCC was detected in those with NPP-VUS (2.0% vs 0.9%, P = .0023).
Conclusions: Certain FH variants confer an increased risk of PGL/PCC, but not necessarily HLRCC. While universal screening for PGL/PCC among all individuals with FH variants does not appear warranted, it should be considered in select high-risk PGL/PCC FH variants.
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http://dx.doi.org/10.1016/j.urology.2022.11.053 | DOI Listing |
Infect Drug Resist
December 2024
Department of Cardiovascular Medicine, Showa University Fujigaoka Hospital, Yokohama, Japan.
Background: The emergence of the Omicron variant of severe acute respiratory syndrome coronavirus-2 has significantly altered the clinical features and severity of coronavirus disease 2019 (COVID-19).
Objective: This study aims to evaluate whether the clinical factors that previously predicted COVID-19 remain valid following the emergence of the Omicron variant.
Methods: This cross-sectional study was conducted at Showa University Fujigaoka Hospital from April 2022 to March 2023.
Front Cell Infect Microbiol
December 2024
Servicio de Microbiología, Hospital Universitario Ramón y Cajal, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Madrid, Spain.
Introduction: Murepavadin is an antimicrobial peptide (AMP) in clinical development that selectively targets LptD and whose resistance profile remains unknown. We aimed to explore genomic modifications and consequences underlying murepavadin and/or colistin susceptibility.
Methods: To define genomic mechanisms underlying resistance, we performed two approaches: 1) a genome-wide association study (GWAS) in a clinical collection (n=496), considering >0.
Int J Cardiol Congenit Heart Dis
September 2024
VPD Heart and Lung Research Institute, University of Cambridge, United Kingdom.
Pulmonary hypertension (PH) encompasses a group of conditions which ultimately lead to elevated pulmonary arterial pressure. PH is classified into five subgroups, of which Group 1 pulmonary arterial hypertension (PAH), is the most extensively studied. Numerous causal genes have been identified in PAH, most notably germline mutations in bone morphogenetic protein receptor type 2 () and the wider BMP pathway.
View Article and Find Full Text PDFDigit Health
December 2024
School of Computer Science, University of Birmingham, Birmingham, UK.
Objective: The study aims to present an active learning approach that automatically extracts clinical concepts from unstructured data and classifies them into explicit categories such as Problem, Treatment, and Test while preserving high precision and recall and demonstrating the approach through experiments using i2b2 public datasets.
Methods: Initially labeled data are acquired from a lexical-based approach in sufficient amounts to perform an active learning process. A contextual word embedding similarity approach is adopted using BERT base variant models such as ClinicalBERT, DistilBERT, and SCIBERT to automatically classify the unlabeled clinical concept into explicit categories.
Monogenic diabetes, formerly called Maturity-Onset Diabetes of the Young (MODY), involves single-gene mutations, typically with dominant inheritance, and has been associated with variants in 14 genes. Among these, mutations are the most common, and their diagnosis allows the use of alternative therapies, including sulfonylureas. In an earlier study, we described a variant displaying recessive transmission, p.
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