Lynch syndrome diagnostic testing pathways in endometrial cancers: a nationwide English registry-based study.

Background: For female patients with Lynch syndrome (LS), endometrial cancer (EC) is often their first cancer diagnosis. A testing pathway of somatic tumour testing triage followed by germline mismatch repair (MMR) gene testing is an effective way of identifying the estimated 3% of EC caused by LS.

Methods: A retrospective national population-based observational study was conducted using comprehensive national data collections of functional, somatic and germline MMR tests available via the English National Cancer Registration Dataset.

Ascertaining the prognostic role of cardiac resynchronisation therapy in cardiac sarcoidosis: A comparison with ischaemic cardiomyopathy.

Background: Cardiac Resynchronisation Therapy (CRT) has demonstrated short and long-term benefit in heart failure with reduced ejection fraction (HFrEF), including ischaemic (ICM) and non-ischaemic cardiomyopathy. However, there is a paucity of evidence regarding its role in cardiac sarcoidosis (CS).

Methods: Consecutive CS patients with CRT and baseline left ventricle ejection fraction (LVEF)≤40 referred to one specialist hospital in London between November 2008-March 2023 were retrospectively reviewed.

Swallowing and Aspiration: How to Evaluate and Treat Swallowing Disorders Associated with Aspiration Pneumonia in Older Persons.

Aspiration pneumonia (AP) is the most severe complication of oropharyngeal dysphagia (OD). It is highly underdiagnosed and undertreated among older patients hospitalized with community-acquired pneumonia (CAP). Our aim is to review the state of the art in the diagnosis and treatment of swallowing disorders associated with AP.

Prospective randomized evaluation of the sustained impact of assistive artificial intelligence on anesthetists' ultrasound scanning for regional anesthesia.

Objectives: Ultrasound-guided regional anesthesia (UGRA) relies on acquiring and interpreting an appropriate view of sonoanatomy. Artificial intelligence (AI) has the potential to aid this by applying a color overlay to key sonoanatomical structures.The primary aim was to determine whether an AI-generated color overlay was associated with a difference in participants' ability to identify an appropriate block view over a 2-month period after a standardized teaching session (as judged by a blinded assessor).

Neuropsychiatric prodromes and symptom timings in relation to disease onset and/or flares in SLE: results from the mixed methods international INSPIRE study.

Background: Neuropsychiatric symptoms in SLE and other systemic autoimmune rheumatic diseases (SARDs) are challenging to diagnose, attribute and manage. We investigated the timings of onset of a broad range of neuropsychiatric (NP) symptoms in relation to timing of SLE onset. In addition, we explored whether NP symptoms may be a prodrome to SARD onset and to subsequent flares.

How to auscultate for heart sounds in infants and children.

This article provides an introduction to performing cardiac auscultation in infants and children aged 0-16 years, with the aim of improving children's nurses' knowledge and confidence in this procedure. Nurses wishing to develop competence in cardiac auscultation can use this article as a guide to complement supervised practical experience; however, it is not intended to determine an individual's competence. • Cardiac auscultation is a component of a structured cardiac assessment rather than a standalone tool.

The potential of tendon autograft as meniscus substitution: Current concepts.

Meniscectomy is known to alter the mechanics, stability, and kinematics of the tibiofemoral joint, leading to early knee osteoarthritis (KOA). While several meniscal substitutions exist, such as meniscus allograft transplantation, collagen meniscus implants, and artificial substitutes, they often come with technical challenges, high costs, and risks, including allograft failure, infections, and disease transmission. Tendon autografts emerge as a promising option, offering safety, availability, biocompatibility, and a reduced risk of pathophoresis.

Enteroendocrine cell-derived peptide YY signalling is stimulated by pinolenic acid or Intralipid and involves coactivation of fatty acid receptors FFA1, FFA4 and GPR119.

Long chain fatty acids are sensed by enteroendocrine L cells that express free-fatty acid receptors, including FFA1, FFA4 and the acylethanolamine receptor GPR119. Here we investigated the acute effects of single or multiple agonism at these G protein-coupled receptors in intestinal mucosae where L cell-derived peptide YY (PYY) is anti-secretory and acts via epithelial Y receptors. Mouse ileal or colonic mucosae were mounted in Ussing chambers, voltage-clamped and the resultant short-circuit current (I) recorded continuously.

Brain PET Imaging in the Presurgical Evaluation of Drug-Resistant Focal Epilepsy.

Presurgical evaluation aims to localize the seizure onset zone (SOZ) for a tailored resection. Interictal [F]fluorodeoxyglucose PET is now an established test to lateralize and/or localize the SOZ, particularly if MR imaging is negative or if the noninvasive assessment shows discrepancies. PET can show hypometabolic areas associated with SOZ and the potential altered metabolic brain networks.

Racial disparities in prostate cancer in the UK and the USA: similarities, differences and steps forwards.

In the USA, Black men are approximately twice as likely to be diagnosed with and to die of prostate cancer than white men. In the UK, despite Black men having vastly different ancestral contexts and health-care systems from Black men in the USA, the lifetime risk of being diagnosed with prostate cancer is two-to-three times higher among Black British men than among white British men and Black British men are twice as likely to die of prostate cancer as white British men. Examination of racial disparities in prostate cancer in the USA and UK highlights systemic, socio-economic and sociocultural factors that might contribute to these differences.

Promise and Peril of a Genotype-First Approach to Mendelian Cardiovascular Disease.

Precision medicine, which among other aspects includes an individual's genomic data in diagnosis and management, has become the standard-of-care for Mendelian cardiovascular disease (CVD). However, early identification and management of asymptomatic patients with potentially lethal and manageable Mendelian CVD through screening, which is the promise of precision health, remains an unsolved challenge. The reduced costs of genomic sequencing have enabled the creation of biobanks containing in-depth genetic and health information, which have facilitated the understanding of genetic variation, penetrance, and expressivity, moving us closer to the genotype-first screening of asymptomatic individuals for Mendelian CVD.

Enzalutamide versus abiraterone acetate in the development of new-onset or worsening type 2 diabetes mellitus in patients with metastatic castration-resistant prostate cancer: EVADE study.

Purpose: To determine new-onset or worsening T2DM risk in patients with metastatic castration-resistant prostate cancer (mCRPC) receiving abiraterone acetate (AA) vs. enzalutamide (ENZA) in England.

Methods: Records of patients on AA and/or ENZA (2015-2021) were analysed retrospectively from UK- or England-wide databases and data sets.

Phase Ib Study of the Immunocytokine Simlukafusp Alfa (FAP-IL2v) in Combination with Cetuximab in Patients with Head and Neck Squamous Cell Carcinoma.

Purpose: This phase Ib trial evaluated fibroblast activation protein-α-targeted IL2 variant (FAP-IL2v), a novel immunocytokine engineered to minimize CD25-mediated toxicities, in combination with cetuximab, in patients with recurrent, unresectable, or metastatic head and neck squamous cell carcinoma (HNSCC).

Patients And Methods: Patients received FAP-IL2v either on a continuous weekly (QW) schedule or QW for 4 weeks and then every 2 weeks (Q2W). Cetuximab was dosed at QW or Q2W schedules.

Why regulation hurts: balancing the need to maintain standards with the mental health impact on public sector professionals.

Robust regulatory scrutiny is an unavoidable and necessary part of professional life for public sector professionals. Inspection and investigation can lead to poor mental health for individuals already working under pressure owing to increased workload and anticipation of poor outcomes. Although good regulation maintains standards and provides accountability to government and the public, regulators must face their obligation to understand the wider impact of their practices on the mental health of those they evaluate.

An update on autophagy disorders.

Macroautophagy is a highly conserved cellular pathway for the degradation and recycling of defective cargo including proteins, organelles, and macromolecular complexes. As autophagy is particularly relevant for cellular homeostasis in post-mitotic tissues, congenital disorders of autophagy, due to monogenic defects in key autophagy genes, share a common "clinical signature" including neurodevelopmental, neurodegenerative, and neuromuscular features, as well as variable abnormalities of the eyes, skin, heart, bones, immune cells, and other organ systems, depending on the expression pattern and the specific function of the defective proteins. Since the clinical and genetic resolution of EPG5-related Vici syndrome, the paradigmatic congenital disorder of autophagy, the widespread use of massively parallel sequencing has resulted in the identification of a growing number of autophagy-associated disease genes, encoding members of the core autophagy machinery as well as related proteins.