HLA-A01 and HLA-B27 Supertypes, but Not HLA Homozygocity, Correlate with Clinical Outcome among Patients with Non-Small Cell Lung Cancer Treated with Pembrolizumab in Combination with Chemotherapy.

Introduction: Maximal heterozygosity on the human leukocyte antigen (HLA) loci has been found to be associated with improved survival and development of immune-related adverse events (irAEs) among NSCLC patients treated with immunotherapy. Here, we investigated the effect of germline HLA-I/-II on clinical outcomes among NSCLC patients treated with first-line pembrolizumab in combination with chemotherapy.

Method: We prospectively recruited patients with NSCLC who were commencing first-line pembrolizumab in combination with chemotherapy.

Predictive value of a comprehensive atrial assessment with cardiac magnetic resonance in non-ischemic cardiomyopathy: keep it simple.

Cardiac magnetic resonance (CMR) can provide a multi-parametric evaluation of left atrial (LA) size and function. A complete CMR-based LA assessment might improve the risk stratification of patients with non-ischemic dilated cardiomyopathy (DCM). We performed a comprehensive CMR-based evaluation of LA size and function, in order to assess the prognostic impact of specific LA parameters in DCM.

Disease-specific therapy for the treatment of the cardiovascular manifestations of Fabry disease: a systematic review.

Objective: The cardiovascular manifestations of Fabry disease are common and represent the leading cause of death. Disease-specific therapy, including enzyme replacement therapy (ERT) and chaperone therapy (migalastat), is recommended for patients exhibiting cardiovascular involvement, but its efficacy for modulating cardiovascular disease expression and optimal timing of initiation remains to be fully established. We therefore aimed to systematically review and evaluate the effectiveness of disease-specific therapy compared with placebo, and to no intervention, for the cardiovascular manifestations of Fabry disease.

Inflammatory Fabry Cardiomyopathy Demonstrated Using Simultaneous [F]-FDG PET-CMR.

Using hybridized [F]-fluorodeoxyglucose positron emission tomography with cardiac magnetic resonance, we identify active myocardial inflammation and demonstrate its relationship with late gadolinium enhancement, in Fabry disease. We demonstrate that late gadolinium enhancement represents, at least in part, active myocardial inflammation and identify an early inflammatory phenotype that may represent a therapeutic window before irreversible tissue injury and adaptation occur. ().

mRNA is downregulated by miR-155 in regulatory T cells, and reduced blood levels are associated with poor prognosis in metastatic melanoma patients.

Cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) is an immune checkpoint expressed in regulatory T (Treg) cells and activated T lymphocytes. Despite its potential as a treatment strategy for melanoma, CTLA-4 inhibition has limited efficacy. Using data from The Cancer Genome Atlas (TCGA) melanoma database and another dataset, we found that decreased mRNA was associated with a poorer prognosis in metastatic melanoma.

Rationale and design of a randomised trial of trientine in patients with hypertrophic cardiomyopathy.

Aims: Hypertrophic cardiomyopathy (HCM) is characterised by left ventricular hypertrophy (LVH), myocardial fibrosis, enhanced oxidative stress and energy depletion. Unbound/loosely bound tissue copper II ions are powerful catalysts of oxidative stress and inhibitors of antioxidants. Trientine is a highly selective copper II chelator.

The journal of cardiovascular computed tomography: A year in review: 2022.

This review aims to summarize key articles published in the Journal of Cardiovascular Computed Tomography (JCCT) in 2022, focusing on those that had the most scientific and educational impact. The JCCT continues to expand; the number of submissions, published manuscripts, cited articles, article downloads, social media presence, and impact factor continues to grow. The articles selected by the Editorial Board of the JCCT in this review highlight the role of cardiovascular computed tomography (CCT) to detect subclinical atherosclerosis, assess the functional relevance of stenoses, and plan invasive coronary and valve procedures.

Identification of TP53 mutations in circulating tumour DNA in high grade serous ovarian carcinoma using next generation sequencing technologies.

Plasma circulating tumour DNA (ctDNA) has been suggested to be a viable biomarker of response to treatment in patients with high grade serous ovarian carcinoma (HGSOC). TP53 mutations are present in more than 90% of HGSOCs but somatic variants are distributed across all exonic regions of the gene, requiring next generation sequencing (NGS) technologies for mutational analysis. In this study, we compared the suitability of the Accel (Swift) and Oncomine (ThermoFisher) panels for identification of TP53 mutations in ctDNA of HGSOC patients (N = 10).

The gestational diabetes future diabetes prevention study (GODDESS): A partially randomised feasibility controlled trial.

Objectives: To assess the feasibility of an ante- and post-natal lifestyle intervention for women with gestational diabetes mellitus (GDM) to reduce type 2 diabetes risk.

Design: A partially randomised patient preference feasibility trial.

Setting: Diabetes antenatal clinics in two inner-London hospitals, UK.

Validated Model for Prediction of Adverse Cardiac Outcome in Patients With Fabry Disease.

Background: The cardiac manifestations of Fabry disease are the leading cause of death, but risk stratification remains inadequate. Identifying patients who are at risk of adverse cardiac outcome may facilitate more evidence-based treatment guidance. Contemporary cardiovascular cardiac magnetic resonance biomarkers have become widely adopted, but their prognostic value remains unclear.

Symptoms of Anxiety and Depression Are Independently Associated With Impaired Awareness of Hypoglycemia in Type 1 Diabetes.

Objective: We tested the hypothesis that impaired awareness of hypoglycemia (IAH) is independently associated with symptoms of anxiety and depression in type 1 diabetes.

Research Design And Methods: In this cross-sectional observational study in 950 adults with type 1 diabetes, associations were examined using multiple regression models, adjusting for sociodemographic and clinical characteristics.

Results: Prevalence for probable anxiety, depression, and IAH were 9.

Let there be light! The meteoric rise of cardiac imaging.

Imaging plays a central role in modern cardiovascular practice. It is a field characterised by exciting technological advances that have shaped our understanding of pathology and led to major improvements in patient diagnosis and care. The UK has played a key international role in the development of this subspecialty and is the current home to many of the leading global centres in multimodality cardiovascular imaging.

The Journal of cardiovascular computed tomography: A year in review 2021.

This review aims to summarize original articles published in the Journal of Cardiovascular Computed Tomography (JCCT) for the year 2021, focusing on those that had the most scientific and educational impact. The JCCT continues to expand; the number of submissions, published manuscripts, cited articles, article downloads, social media presence, and impact factor continues to increase. The articles selected by the Editorial Board of the JCCT in this review focus on coronary artery disease, coronary physiology, structural heart disease, and technical advances in cardiovascular CT.

Geometric differences of the mitral valve apparatus in atrial and ventricular functional mitral regurgitation.

Background: Functional mitral regurgitation (FMR) occurs in patients with annular dilation (atrial, aFMR) or patients with left ventricular (LV) disease (ventricular, vFMR). Meticulous understanding of the mechanisms underpinning regurgitation is crucial to optimize therapeutic strategies.

Methods: Patients with moderate-severe FMR were identified from a registry of patients referred for transcatheter mitral valve intervention.

Copper chelation in patients with hypertrophic cardiomyopathy.

Background: Disturbances of copper (Cu) homeostasis can lead to hypertrophic cardiac phenotypes (eg, Wilson's disease). We previously identified abnormal Cu homeostasis in patients with hypertrophic cardiomyopathy (HCM) and, therefore, hypothesised that Cu-selective chelation with trientine dihydrochloride may slow or reverse disease progression in HCM. The aim of this study was, therefore to explore the clinical efficacy, safety and tolerability of trientine in HCM.

Analysis of Circulating Tumour Cells in Early-Stage Uveal Melanoma: Evaluation of Tumour Marker Expression to Increase Capture.

(1) Background: The stratification of uveal melanoma (UM) patients into prognostic groups is critical for patient management and for directing patients towards clinical trials. Current classification is based on clinicopathological and molecular features of the tumour. Analysis of circulating tumour cells (CTCs) has been proposed as a tool to avoid invasive biopsy of the primary tumour.

Detection of clinical progression through plasma ctDNA in metastatic melanoma patients: a comparison to radiological progression.

Background: The validity of circulating tumour DNA (ctDNA) as an indicator of disease progression compared to medical imaging in patients with metastatic melanoma requires detailed evaluation.

Methods: Here, we carried out a retrospective ctDNA analysis of 108 plasma samples collected at the time of disease progression. We also analysed a validation cohort of 66 metastatic melanoma patients monitored prospectively after response to systemic therapy.

Isolation and Quantification of Plasma Circulating Tumor DNA from Melanoma Patients.

In recent years, circulating tumor DNA (ctDNA) has emerged as a promising prognostic and monitoring biomarker of various cancers, including melanoma. However, sensitive methods are required for its preservation, isolation, and detection. Here we describe a sensitive method for plasma ctDNA isolation using a column-based extraction kit, followed by quantification using a single mutational target with a droplet digital PCR system.

Unraveling an Unusual Phenocopy of Hypertrophic Cardiomyopathy: MELAS Syndrome.

The mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome is an uncommon cause of cardiac hypertrophy, fibrosis, and dysfunction. It shares similar features to numerous other causes of left ventricular hypertrophy, and therefore, because of its rarity, may not be immediately considered as a diagnosis. Prompt recognition of clinical and cardiac imaging features may expedite diagnosis and management.

The Prognostic Impact of Circulating Tumour DNA in Melanoma Patients Treated with Systemic Therapies-Beyond Mutant Detection.

In this study, we evaluated the predictive value of circulating tumour DNA (ctDNA) to inform therapeutic outcomes in metastatic melanoma patients receiving systemic therapies. We analysed 142 plasma samples from metastatic melanoma patients prior to commencement of systemic therapy: 70 were treated with BRAF/MEK inhibitors and 72 with immunotherapies. Patient-specific droplet digital polymerase chain reaction assays were designed for ctDNA detection.

Neo-LVOT and Transcatheter Mitral Valve Replacement: Expert Recommendations.

With the advent of transcatheter mitral valve replacement (TMVR), the concept of the neo-left ventricular outflow tract (LVOT) was introduced and remains an essential component of treatment planning. This paper describes the LVOT anatomy and provides a step-by-step computed tomography methodology to segment and measure the neo-LVOT while discussing the current evidence and outstanding challenges. It also discusses the technical and hemodynamic factors that play a major role in assessing the neo-LVOT.