Clinical recognition of primary mitochondrial disorders (PMD) is difficult due to the clinical and genetic heterogeneity. Whereas lactate has low sensitivity and specificity, in structured clinical studies growth differentiation factor 15 (GDF15) has shown promise with elevations in mitochondrial DNA (mtDNA)-related PMD, but its specificity has been questioned. In a tertiary care hospital-wide study, medical records were retrospectively reviewed from 418 cases where GDF15 levels were obtained by clinicians.
View Article and Find Full Text PDFBackground: Oxygen therapy is commonly administered to patients with acute cardiovascular conditions during hospitalisation. Both hypoxaemia and hyperoxia can cause harm, making it essential to maintain oxygen saturation (SpO) within a target range. Traditionally, oxygen administration is manually controlled by nursing staff, guided by intermittent pulse oximetry readings.
View Article and Find Full Text PDFTo explore how nurses experience facilitators and barriers to the use of video-consultations for home-monitoring of patients with cardiac disease. A systematic literature search in PubMed, CINAHL, Scopus, and Web of Science was undertaken, inclusion criteria were qualitative data published between 2013 and 2023 written in English, Norwegian, Swedish, or Danish. Ten studies were included in the qualitative synthesis conducted as described by Braun and Clarke.
View Article and Find Full Text PDFThe recognition of glycine as an endogenous ligand at the allosteric activation site of the NMDA-type glutamatergic receptor led to the assumption that the excess glycine in nonketotic hyperglycinemia would result in overactivation of these receptors, and of the proposed use of inhibitors such as dextromethorphan or ketamine as a therapeutic agent. Years later it was recognized that these same receptors have an alternative endogenous activator d-serine, which is markedly decreased in nonketotic hyperglycinemia. This may result in underactivation of these NMDA-type glutamatergic receptors, challenging the earlier hypothesis.
View Article and Find Full Text PDFThe diagnosis of mitochondrial disorders is complex. Rapid whole genome sequencing is a first line test for critically ill neonates and infants allowing rapid diagnosis and treatment. Standard genomic technology and bioinformatic pipelines still have an incomplete diagnostic yield requiring complementary approaches.
View Article and Find Full Text PDFBackground And Aims: Overtesting of low-risk patients with suspect chronic coronary syndrome (CCS) is widespread. The acoustic-based coronary artery disease (CAD)-score has superior rule-out capabilities when added to pre-test probability (PTP). FILTER-SCAD tested whether providing a CAD-score and PTP to cardiologists was superior to PTP alone in limiting testing.
View Article and Find Full Text PDFBackground: Coronary tortuosity (CorT) is frequently observed in invasive angiography, though its aetiology and clinical significance remain ambiguous. Prior research has indicated possible links between CorT and factors such as hypertension, age, and calcium scores in the left anterior descending (LAD) artery. The aim of this study was to examine and optimize the usage of coronary computed tomography angiography (CCTA) with vessel tracking to explore these associations.
View Article and Find Full Text PDFPatients with long-standing inflammatory bowel disease (IBD) face an increased risk of developing colitis-associated cancer (CAC). Although IBD-induced prolonged inflammation seems to be involved in CAC pathogenesis, the specific molecular changes that contribute remain unknown. Here, we applied digital spatial RNA profiling, RNAscope, and imaging mass cytometry to examine paired uninflamed, inflamed, and early dysplastic mucosa of patients with IBD.
View Article and Find Full Text PDFBackground: Decentralised and evidence-informed health systems rely on managers and practitioners at all levels having sufficient 'decision space' to make timely locally informed and relevant decisions. Our objectives were to understand decision spaces in terms of constraints and enablers and outline opportunities through which to expand them in an understudied rural context in South Africa.
Methods: This study examined decision spaces within Mpumalanga Province, using data and insights generated through a participatory action research process with local communities and health system stakeholders since 2015, which was combined with published documents and research team participant observation to produce findings on three core domains at three levels of the health system.
Introduction: Intravenous loop diuretics have been a key component in treating pulmonary oedema since the 1960s and have a Class 1 recommendation in the 2021 guidelines for acute heart failure (AHF). While the diuretic effect of loop diuretics is well established, it remains unclear how furosemide influences pulmonary congestion and cardiac filling pressures in the hyperacute phase before significant diuresis occurs.
Methods: This was a prospective study of adult patients with AHF and objective signs of pulmonary congestion admitted to the cardiac ward.
J Inherit Metab Dis
September 2024
Nonketotic hyperglycinemia due to deficient glycine cleavage enzyme activity causes a severe neonatal epileptic encephalopathy. Current therapies based on mitigating glycine excess have only limited impact. An animal model with postnatal phenotyping is needed to explore new therapeutic approaches.
View Article and Find Full Text PDFBackground: Acute heart failure is a public health concern. This study systematically reviewed randomized clinical trials (RCTs) to evaluate vasodilators in acute heart failure.
Methods: The search was conducted across the databases of Medline, Embase, Latin American and the Caribbean Literature on Health Sciences, Web of Science, and the Cochrane Central Register of Controlled Trials.
Pathogenic ACAD9 variants cause complex I deficiency. Patients presenting in infancy unresponsive to riboflavin have high mortality. A six-month-old infant presented with riboflavin unresponsive lactic acidosis and life-threatening cardiomyopathy.
View Article and Find Full Text PDFWe recently used phase-contrast magnetic resonance imaging (PC-MRI) to demonstrate an attenuated postprandial blood flow response in the superior mesenteric artery (SMA) in patients with Parkinson's disease compared to age- and sex-matched healthy controls. Since both groups showed substantial inter-individual variations, we extended the cohort of controls with a group of young individuals to investigate possible age-related effects. Seventeen healthy young subjects aged < 30 years and 17 elderly subjects aged > 50 years underwent serial PC-MRI to measure the postprandial blood flow response in the SMA after ingestion of a standardized liquid test meal (∼400 kcal).
View Article and Find Full Text PDFAim: We aim to describe the behavioral phenotype of children and adolescents with the good to intermediate attenuated form of non-ketotic hyperglycinemia (NKH) and to explore associations between the behavioral phenotype and age, sex, plasma glycine levels and drug treatment.
Method: Parents of children with attenuated NKH completed questionnaires assessing maladaptive behavior, adaptive behavior, social communication, speech/language development and motor development in addition to demographic and medical questions.
Results And Interpretation: Twelve children, age 6 to 21y, functioned at mild to severe intellectual disability levels.
Introduction: Acute heart failure (AHF) is a critical, costly condition with high mortality rates, affecting millions annually. Despite advances in cardiovascular care, AHF treatment lacks robust evidence. AHF commonly manifests with sudden heart failure symptoms such as pulmonary congestion, and the pathophysiology involves fluid overload.
View Article and Find Full Text PDFUnlabelled: Nonketotic hyperglycinemia due to deficient glycine cleavage enzyme activity causes a severe neonatal epileptic encephalopathy. Current therapies based on mitigating glycine excess have only limited impact. An animal model with postnatal phenotyping is needed to explore new therapeutic approaches.
View Article and Find Full Text PDFBackground Coronary artery calcium (CAC) has prognostic value for major adverse cardiovascular events (MACE) in asymptomatic individuals, whereas its role in symptomatic patients is less clear. Purpose To assess the prognostic value of CAC scoring for MACE in participants with stable chest pain initially referred for invasive coronary angiography (ICA). Materials and Methods This prespecified subgroup analysis from the Diagnostic Imaging Strategies for Patients With Stable Chest Pain and Intermediate Risk of Coronary Artery Disease (DISCHARGE) trial, conducted between October 2015 and April 2019 across 26 centers in 16 countries, focused on adult patients with stable chest pain referred for ICA.
View Article and Find Full Text PDFImportance: The effectiveness and safety of computed tomography (CT) and invasive coronary angiography (ICA) in different age groups is unknown.
Objective: To determine the association of age with outcomes of CT and ICA in patients with stable chest pain.
Design, Setting, And Participants: The assessor-blinded Diagnostic Imaging Strategies for Patients With Stable Chest Pain and Intermediate Risk of Coronary Artery Disease (DISCHARGE) randomized clinical trial was conducted between October 2015 and April 2019 in 26 European centers.
Like allopathic healthcare workers, healers are also exposed to patients' blood and body fluids. A widespread practice is the traditional "injection," in which the healer performs subcutaneous incisions to rub herbs directly into the bloodied skin, resulting in 1,500 blood exposures over their lifetime. We tested the impact of healer-led PPE training, staffed by trained traditional healers who reported using PPE during each risky clinical encounter vs.
View Article and Find Full Text PDFBackground: We examined obstructive and nonobstructive plaque volumes in populations with subclinical and clinically manifested coronary artery disease (CAD) using quantitative computed tomography (QCT).
Methods: 855 participants with CAD (274 asymptomatic individuals, 254 acute chest pain patients without acute coronary syndrome (ACS), and 327 patients with ACS) underwent QCT of proximal coronary segments to assess participant-level plaque volumes of dense calcium, fibrous, fibrofatty, and necrotic core tissue.
Results: Nonobstructive (<50% stenosis) plaque volumes were greater than obstructive plaque volumes, irrespective of population (all p<0.