Genomic profiling at a single center cracks the code in inborn errors of immunity.

Inborn errors of immunity (IEI) entail a diverse group of disorders resulting from hereditary or de novo mutations in single genes, leading to immune dysregulation. This study explores the clinical utility of next-generation sequencing (NGS) techniques in diagnosing monogenic immune defects. Eight patients attending the immunodeficiency clinic and with unclassified antibody deficiency were included in the analysis.

Diverting hepatic lipid fluxes with lifestyles revision and pharmacological interventions as a strategy to tackle steatotic liver disease (SLD) and hepatocellular carcinoma (HCC).

Steatotic liver disease (SLD) and Hepatocellular Carcinoma (HCC) are characterised by a substantial rewiring of lipid fluxes caused by systemic metabolic unbalances and/or disrupted intracellular metabolic pathways. SLD is a direct consequence of the interaction between genetic predisposition and a chronic positive energy balance affecting whole-body energy homeostasis and the function of metabolically-competent organs. In this review, we discuss how the impairment of the cross-talk between peripheral organs and the liver stalls glucose and lipid metabolism, leading to unbalances in hepatic lipid fluxes that promote hepatic fat accumulation.

Metabolic Syndrome and Cardiovascular Risk Factors in a Fishing Community in Southern Italy.

Background: Work organization and psychosocial factors influencing sleep patterns may be significant risk factors for developing obesity and metabolic syndrome (MetS). However, the impact on the health of working patterns in the fishing sector is not well characterized. The aim of the study is to determine the prevalence of MetS and its components in fishermen and to analyze occupational-specific risk factors contributing to metabolic alterations.

Changes in Angiogenesis and Bone Turnover Markers in Patients with Gaucher Disease Developing Osteonecrosis.

: Patients with Gaucher disease have a high risk of bone disease, with osteonecrosis representing the most debilitating complication. The pathogenesis of osteonecrosis has not been fully elucidated yet, and there is an unmet need for predictive biomarkers of bone complications. We aimed to assess the utility of angiogenesis and bone turnover biomarkers as predictors of osteonecrosis in Gaucher disease.

Immunoglobulin Replacement Therapy: Insights into Multiple Myeloma Management.

Immunoglobulin (Ig) replacement therapy (IgRT) consists of the administration of low-dose human polyclonal Igs for the treatment of primary and secondary hypogammaglobulinemia that are associated with recurrent infections and immune dysfunction. IgRT restores physiological antibody levels and induces an immunomodulatory effect by strengthening immune effector cells, thus reducing infections. Here, we describe the pharmacology of different Ig formulations with a particular focus on their mechanism of action as low-dose IgRT, including the direct anti-microbial effect and the immunomodulatory function.

Fabry disease Enzyme Enhancement on migalastat Study: FEES.

Background: There is limited information on the α-galactosidase A (α-Gal-A) in vivo response in Fabry patients receiving migalastat. In this single centre study, we evaluated changes from baseline in α-Gal A activity, lyso-Gb3 and other assessments in patients on migalastat.

Results: 79 patients were recruited (48 M:31F; median duration receiving migalastat 3.

Fabry App: the value of a portable technology in recording day-to-day patient monitored information in patients with Fabry disease.

Background: Fabry disease is a rare inherited disorder resulting from deficient α-galactosidase A enzyme activity. Common disease manifestations are sweating abnormalities, neuropathic pain, gastrointestinal symptoms and fatigue. Challenges are faced by health care professionals in evaluating symptom burden in the current clinical setting, and the demand for alternative methods for monitoring disease-specific symptoms has seen an acceleration in recent years.

European gay fathers via surrogacy: Parenting, social support, anti-gay microaggressions, and child behavior problems.

The present study investigated child behavior problems, parenting styles, coparenting, and couple relationship satisfaction in 67 European gay father families via surrogacy and 67 European heterosexual parent families via unassisted conception, all with children aged 1.5-10 years (M = 3.57 years, SD = 2.

Atrioventricular nodal reentry tachycardia treatment using CARTO 3 V7 activation mapping: a new era of slow pathway radiofrequency ablation is under coming.

Background: Slow pathway (SP) ablation is the cornerstone for atrioventricular nodal reentry tachycardia (AVNRT) treatment, and a low-voltage bridge offers a good target during mapping using low x-ray exposure. We aimed to assess a new tool to identify SP by activation mapping using the last CARTO3® version, i.e.

QFR-Based Virtual PCI or Conventional Angiography to Guide PCI: The AQVA Trial.

Background: Post-percutaneous coronary intervention (PCI) quantitative flow ratio (QFR) values ≥0.90 are associated with a low incidence of adverse events.

Objectives: The AQVA (Angio-based Quantitative Flow Ratio Virtual PCI Versus Conventional Angio-guided PCI in the Achievement of an Optimal Post-PCI QFR) trial aims to test whether a QFR-based virtual percutaneous coronary intervention (PCI) is superior to a conventional angiography-based PCI at obtaining optimal post-PCI QFR results.

Stress and Resilience Experiences during the Transition to Parenthood among Belgian Lesbian Mothers through Donor Insemination.

The present research explored parenting, stress, and resilience experiences among 16 Belgian, lesbian, first-time parental couples with donor-conceived children aged 3-72 months. In each couple, both mothers participated in a conjoint, semi-structured interview focused on their parenthood desire; the impact of stigmatization and social support from families of origin, friends, and institutions; and couple and family resources. Interviews were audio recorded, transcribed, and analyzed using Braun and Clarke's reflective thematic analysis.

Mental Health Disparities Between Lesbian Mothers and Heterosexual Parents: the Mediating Role of Positivity.

Introduction: Previous evidence has shown better mental health outcomes for lesbian mothers, in comparison with heterosexual parents. The present study explored the mediating role of positivity (i.e.

Radiographic Cortical Thickness Index Predicts Fragility Fracture in Gaucher Disease.

Background Patients with Gaucher disease (GD) have a high risk of fragility fractures. Routine evaluation of bone involvement in these patients includes radiography and repeated dual-energy x-ray absorptiometry (DXA). However, osteonecrosis and bone fracture may affect the accuracy of DXA.

Management and Outcomes in the Elderly with Non-ST-Elevation Acute Coronary Syndromes Admitted to Spoke Hospitals with No Catheterization Laboratory Facility.

Background: Contemporary guidelines advocate for early invasive strategy with coronary angiography in patients with non-ST-elevation acute coronary syndromes (NSTE-ACS). Still, the impact of an invasive strategy in older patients remains controversial and may be challenging in spoke hospitals with no catheterization laboratory (cath-lab) facility. Purpose: The purpose of this study was to analyse the characteristics and outcomes of patients ≥80 years old with NSTE-ACS admitted to spoke hospitals.

The desire for more children among Israeli lesbian, gay, and heterosexual couples who became parents through assisted reproduction.

The present online questionnaire-based study compared 72 lesbian mothers by donor insemination (within 36 families), 78 gay fathers by gestational surrogacy (within 39 families), and 72 heterosexual parents by assisted reproduction (without donated eggs and/or sperm; within 36 families), on their desire to have more children and their ideal number of children. All participants self-identified as cisgender, lived in Israel, and had a mean number of two children. The study also explored the predictors of participants' desire for more children.

Lipidomic Approaches to Study HDL Metabolism in Patients with Central Obesity Diagnosed with Metabolic Syndrome.

The metabolic syndrome (MetS) is a cluster of cardiovascular risk factors characterised by central obesity, atherogenic dyslipidaemia, and changes in the circulating lipidome; the underlying mechanisms that lead to this lipid remodelling have only been partially elucidated. This study used an integrated "omics" approach (untargeted whole serum lipidomics, targeted proteomics, and lipoprotein lipidomics) to study lipoprotein remodelling and HDL composition in subjects with central obesity diagnosed with MetS ( controls). Compared with healthy subjects, MetS patients showed higher free fatty acids, diglycerides, phosphatidylcholines, and triglycerides, particularly those enriched in products of lipogenesis.

Platelets from patients with visceral obesity promote colon cancer growth.

Several studies highlighted the importance of platelets in the tumor microenvironment due to their ability to interact with other cell types such as leukocytes, endothelial, stromal and cancer cells. Platelets can influence tumor development and metastasis formation through several processes consisting of the secretion of growth factors and cytokines and/or via direct interaction with cancer cells and endothelium. Patients with visceral obesity (VO) are susceptible to pro-thrombotic and pro-inflammatory states and to development of cancer, especially colon cancer.

The effects of sustained COVID-19 emergency and restrictions on the mental health of subjects with serious mental illness: A prospective study.

Few longitudinal studies have so far investigated the impact of sustained COVID-19 among people with pre-existing psychiatric disorders. We conducted a prospective study involving people with serious mental illness (n = 114) and healthy controls (n = 41) to assess changes in the Perceived Stress Scale, Generalized Anxiety Disorder Scale, Patient Health Questionnaire, and Specific Psychotic Experiences Questionnaire scores 18 months after the COVID-19 pandemic outset. Subjects underwent interviews with a mental health professional in April 2020 and at the end of the local third wave (October 2021).

Assisted Conception Socialization Self-Efficacy Among Israeli Lesbian, Gay, and Heterosexual Parent Families and its Association with Child Externalizing Problems.

This questionnaire-based study compared 36 Israeli lesbian mother families ( = 72 lesbian mothers) formed by donor insemination, 39 Israeli gay father families ( = 78 gay fathers) formed by gestational surrogacy, and 36 Israeli heterosexual parent families ( = 72 heterosexual parents) formed by assisted reproduction (without donated gametes), all with a target child aged 3-10 years. The families were examined for parents' assisted conception socialization self-efficacy, depression, negative and positive affect, life satisfaction, positivity, resilience, social support, and child externalizing problems. Multiple factors associated with child externalizing problems were also examined.

Transcriptional, epigenetic and metabolic signatures in cardiometabolic syndrome defined by extreme phenotypes.

Background: This work is aimed at improving the understanding of cardiometabolic syndrome pathophysiology and its relationship with thrombosis by generating a multi-omic disease signature.

Methods/results: We combined classic plasma biochemistry and plasma biomarkers with the transcriptional and epigenetic characterisation of cell types involved in thrombosis, obtained from two extreme phenotype groups (morbidly obese and lipodystrophy) and lean individuals to identify the molecular mechanisms at play, highlighting patterns of abnormal activation in innate immune phagocytic cells. Our analyses showed that extreme phenotype groups could be distinguished from lean individuals, and from each other, across all data layers.

Jaw involvement in Gaucher disease: a not-so-uncommon feature of a rare disease.

Gaucher disease is an inborn error of metabolism resulting from the deficiency of the enzyme glucocerebrosidase and consequent accumulation of glucocerebroside within the lysosomes of macrophages. The clinical presentation is very diverse, depending on the age of onset and the severity of the disease, and results from the progressive infiltration of lipid-laden cells in various organs. Common manifestations of Gaucher disease include enlarged liver and/or spleen (hepatosplenomegaly), bone marrow disease (pancytopenia) and bone abnormalities, which are extremely variable and can affect multiple skeletal sites.

In-depth phenotyping for clinical stratification of Gaucher disease.

Background: The Gaucher Investigative Therapy Evaluation is a national clinical cohort of 250 patients aged 5-87 years with Gaucher disease in the United Kingdom-an ultra-rare genetic disorder. To inform clinical decision-making and improve pathophysiological understanding, we characterized the course of Gaucher disease and explored the influence of costly innovative medication and other interventions. Retrospective and prospective clinical, laboratory and radiological information including molecular analysis of the GBA1 gene and comprising > 2500 variables were collected systematically into a relational database with banking of collated biological samples in a central bioresource.

Long-term outcome of catheter ablation for atrial fibrillation in patients with severe left atrial enlargement and reduced left ventricular ejection fraction.

Aims: Data regarding the efficacy of catheter ablation in heart failure patients with severely dilated left atrium and reduced left ventricular ejection fraction (LVEF) are scanty. We sought to assess the efficacy of catheter ablation in patients with reduced LVEF and severe left atrial (LA) enlargement, and to compare it to those patients with preserved left ventricular function and equally dilated left atrium.

Methods And Results: Three patient groups with paroxysmal or persistent atrial fibrillation (AF) undergoing a first pulmonary vein isolation (PVI) were considered: Group 1 included patients with normal or mildly abnormal LA volume (≤41 mL/m2) and normal LVEF; Group 2 included patients with severe LA enlargement (>48 mL/m2) and normal LVEF; and Group 3 included patients with severe LA enlargement and reduced LVEF.