European Journal of Clinical Investigation

BACKGROUND: The fundamental role of the renin-angiotensin-aldosterone system in the pathophysiology of chronic kidney disease, congestive heart failure, hypertension and proteinuria is well established in pre-clinical and clinical studies. Mineralocorticoid receptor antagonists are among the primary options for renin-angiotensin-aldosterone system blockage, along with angiotensin-converting enzyme inhibitors and angiotensin receptor blockers. METHODS: In this narrative review, we aim to evaluate the efficiency and safety of mineralocorticoid receptor antagonists in kidney transplant recipients, including the potential underlying pathophysiology...

BACKGROUND: Due to medical and surgical advancements, the population of adult patients with congenital heart disease (ACHD) is growing. Despite successful therapy, ACHD patients face structural sequalae, placing them at increased risk for heart failure and arrhythmias. Left and right ventricular function are important predictors for adverse clinical outcomes. In acquired heart disease it has been shown that echocardiographic deformation imaging is of superior prognostic value as compared to conventional parameters as ejection fraction...

BACKGROUND: Cytometric analysis has been commonly used to delineate distinct cell subpopulations among peripheral blood mononuclear cells by the differential expression of surface receptors. This capability has reached its apogee with high-dimensional approaches such as mass cytometry and spectral cytometry that include simultaneous assessment of 20-50 analytes. Unfortunately, this approach also engenders significant complexity with analytical and interpretational pitfalls. METHODS: Here, we demonstrate a complementary approach with restricted-dimensionality to assess cell-type specific intracellular molecular expression levels at exceptional levels of precision...

BACKGROUND: High-altitude pulmonary oedema (HAPE) is a form of noncardiogenic pulmonary oedema. Studies have found that long noncoding RNA (lncRNA) plays an important role in HAPE. ANRIL is significant in pulmonary illnesses, which implies that alterations in ANRIL expression levels may be involved in the beginning and development of HAPE. However, the specific mechanism is indistinct. The present study is meant to explore the effect and mechanism of ANRIL on hypoxic-induced injury of pulmonary microvascular endothelial cells (PMEVCs)...

BACKGROUND: Short but impactful, the two-decade story of gene editing allowed a significant breakthrough in the treatment of haematological malignancies. However, despite different generations of chimeric antigen receptor T (CAR T), such a successful therapy has not yet been replicated in solid tumours and non-oncological diseases. METHODS: This narrative review discusses how CAR T therapy still faces challenges in overcoming the complexity of the solid tumour microenvironment and the concerns that its long-term activity raises about potential unknown and unpredictable consequences in non-oncological diseases...

BACKGROUND: Robotic gastrectomy is increasingly utilized for gastric cancer, but high morbidity remains a concern. Myosteatosis or low skeletal muscle density reflecting fatty infiltration, associates with complications after other cancer surgeries but has not been evaluated for robotic gastrectomy. METHODS: This retrospective study analysed 381 patients undergoing robotic gastrectomy for gastric cancer from September 2019 to October 2022. Myosteatosis was quantified on preoperative computed tomography (CT) images at lumbar 3 (L3)...

BACKGROUND: Defects of mitophagy, the selective form of autophagy for mitochondria, are commonly observed in several cardiovascular diseases and represent the main cause of mitochondrial dysfunction. For this reason, mitophagy has emerged as a novel and potential therapeutic target. METHODS: In this review, we discuss current evidence about the biological significance of mitophagy in relevant preclinical models of cardiac and vascular diseases, such as heart failure, ischemia/reperfusion injury, metabolic cardiomyopathy and atherosclerosis...

BACKGROUND: The prevalence of cancer patients with concomitant cardiovascular (CV) disease is on the rise due to improved cancer prognoses. The aim of this study is to evaluate the long-term outcomes of cancer patients referred to a cardiology department (CD) via primary care using e-consultation. METHODS: We analysed data from cancer patients with prior referrals to a CD between 2010 and 2021 (n = 6889) and compared two care models: traditional in-person consultations and e-consultations...

BACKGROUND: Oestrogen deficiency increases bone resorption, contributing to osteoporosis development. Yet, the mechanisms mediating the effects of oestrogen on osteoclasts remain unclear. This study aimed to elucidate the early metabolic alteration induced by RANKL, the essential cytokine in osteoclastogenesis and 17-beta-oestradiol (E2 ) on osteoclast progenitor cells, using RAW 264.7 macrophage cell line and primary bone marrow-derived macrophages as biological models. RESULTS: This research demonstrated that, in osteoclast precursors, RANKL stimulates complex I activity, oxidative phosphorylation (OXPHOS) and mitochondria-derived ATP production as early as 3 h of exposure...

PURPOSE: The purpose of this research is to demonstrate echinacoside promotes osteogenesis and angiogenesis and inhibits osteoclast formation. METHODS: We conducted a cell experiment in vitro to study how echinacoside affects angiogenesis, osteogenesis and osteoclast formation. We used polymerase chain reaction and Western blotting to detect the expression levels of proteins and genes related to angiogenesis, osteogenesis and osteoclast formation. We established a bone fracture model with rats to test angiogenesis, osteogenesis and osteoclast formation of echinacoside...

BACKGROUND: Limited data are available on patients with chronic lung disease (CLD) presenting with acute myocardial infarction (AMI). We aimed to analyse baseline characteristics, treatment and outcome of those patients enrolled in the Swiss nationwide prospective AMIS Plus registry. METHODS: All AMI patients enrolled between January 2002 and December 2021 with data on CLD, as defined in the Charlson Comorbidity Index, were included. The primary endpoints were in-hospital mortality and major adverse cardiac and cerebrovascular events (MACCE), defined as all-cause death, reinfarction and cerebrovascular events...

BACKGROUND: Prolactin (PRL) is a pituitary hormone promoting lactation in response to the suckling reflex. Beyond its well-known effects, novel tissue-specific and metabolic functions of PRL are emerging. AIMS: To dissect PRL as a critical mediator of whole-body gluco-insulinemic sensitivity. METHODS: PubMed-based search with the following terms 'prolactin', 'glucose metabolism', 'type 2 diabetes mellitus', 'type 1 diabetes mellitus', 'gestational diabetes mellitus' was performed...

BACKGROUND: Elevated factor XI (FXI) has been shown to predispose to thromboembolism. We investigated whether it is associated with left ventricular thrombus (LVT) formation, its recurrence and subsequent thromboembolic events. METHODS: In 54 patients with prior LVT of unknown origin, who stopped anticoagulation and 54 controls, we determined FXI, along with plasma clot permeability (Ks ), fibrinolysis time (CLT), endogenous thrombin potential (ETP), von Willebrand factor (vWF) and fibrinolysis proteins...

BACKGROUND: High-intensity focused ultrasound (HIFU) emerged as a novel approach for the treatment of localized prostate cancer (PCa). However, prospective studies on HIFU-related outcomes and predictors of treatment failure (TF) remain scarce. MATERIALS AND METHODS: We conducted a multinational prospective cohort study among patients undergoing HIFU therapy for localized, low- to intermediate-risk PCa. Follow-up data on serial prostate specific antigen (PSA), multi-parametric magnetic resonance imaging (mpMRI), targeted/systematic biopsies, adverse events and functional outcomes were collected...

BACKGROUND: Genetic diagnosis of inborn errors of immunity (IEI) is complex due to the large number of genes involved and their molecular features. Missense variants have been reported as the most common cause of IEI. However, the frequency of copy number variants (CNVs) may be underestimated since their detection requires specific quantitative techniques. At this point, the use of Next Generation Sequencing (NGS) is acquiring relevance. METHODS: In this article, we present our experience in the genetic diagnosis of IEI based on three diagnostic algorithms that allowed the detection of single nucleotide variants (SNVs) and CNVs...

BACKGROUND: Substantial focus has been placed on atrial fibrillation (AF) treatment and associated stroke prevention rather than preventing AF itself. We employed Mendelian randomization (MR) approach to examine the causal relationships between 50 modifiable risk factors (RFs) and AF. METHODS: Instrumental variables for genetically predicted exposures were derived from corresponding genome-wide association studies (GWASs). Summary-level statistical data for AF were obtained from a GWAS meta-analysis (discovery dataset, N = 1,030,836) and FinnGen (validation dataset, N = 208,594)...

BACKGROUND: Disturbances in habitual sleep have been associated with multiple age-associated diseases. However, the biological mechanisms underpinning these associations remain largely unclear. We assessed the possible involvement of the circulating immune system by determining the associations between sleep traits and white blood cell counts using multivariable-adjusted linear regression and Mendelian randomization. METHODS: Cross-sectional multivariable-adjusted linear regression analyses were done using participants within the normal range of total white blood cell counts (>4...

BACKGROUND: Osteosarcoma (OS) is a primary bone malignancy that mostly affects young people, characterized by high metastatic potential, and a marked chemoresistance that is responsible for disease relapse in most patients. Therefore, it is necessary to identify novel molecules to setup targeted strategies to improve the clinical outcome. The enzyme nicotinamide N-methyltransferase (NNMT) catalyses the N-methylation of nicotinamide and other analogs, playing a crucial role in the biotransformation of drugs and xenobiotics...

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OBJECTIVE: To assess the characteristics and financial conflicts of interest of presenters, panellists and moderators at haematology and oncology workshops held jointly with or hosted by the US FDA. SETTING: We included information on all publicly available haematology or oncology FDA workshop agendas held between 1 January 2018 and 31 December 2022. EXPOSURE: General and research payments reported on Open Payments, industry funding to patient advocacy organizations reported on their webpages or 990 tax forms and employment in both pharmaceutical and regulatory settings...