Diagnostic prediction models for bacterial meningitis in children with a suspected central nervous system infection: a systematic review and prospective validation study.

Objectives: Diagnostic prediction models exist to assess the probability of bacterial meningitis (BM) in paediatric patients with suspected meningitis. To evaluate the diagnostic accuracy of these models in a broad population of children suspected of a central nervous system (CNS) infection, we performed external validation.

Methods: We performed a systematic literature review in Medline to identify articles on the development, refinement or validation of a prediction model for BM, and validated these models in a prospective cohort of children aged 0-18 years old suspected of a CNS infection.

Biallelic variants in cause a novel autosomal recessive syndrome presenting with cardiac conduction defects and variable hypertrophic cardiomyopathy.

encodes for the Popeye domain-containing protein 2 which has an important role in cardiac pacemaking and conduction, due in part to its cAMP-dependent binding and regulation of TREK-1 potassium channels. Loss of in mice results in sinus pauses and bradycardia and morpholino knockdown of zebrafish results in atrioventricular (AV) block. We identified bi-allelic variants in in 4 families that presented with a phenotypic spectrum consisting of sinus node dysfunction, AV conduction defects and hypertrophic cardiomyopathy.

Granulocytes in cerebrospinal fluid of adults suspected of a central nervous system infection: a prospective study of diagnostic accuracy.

Purpose: Cerebrospinal fluid (CSF) granulocytes are associated with bacterial meningitis, but information on its diagnostic value is limited and primarily based on retrospective studies. Therefore, we assessed the diagnostic accuracy of CSF granulocytes.

Methods: We analyzed CSF granulocytes (index test) from all consecutive patients in two prospective cohort studies in the Netherlands.

Diagnostic accuracy of inflammatory markers in adults with suspected central nervous system infections.

Objectives: We aimed to determine diagnostic accuracy of inflammatory markers in plasma and cerebrospinal fluid (CSF) for the diagnosis of central nervous system (CNS) infections and specifically bacterial meningitis.

Methods: We analyzed 12 cytokines, chemokines, and acute phase reactants in CSF and plasma of 738 patients with suspected neurological infection included in a multicenter prospective cohort. We determined diagnostic accuracy for predicting any CNS infection and bacterial meningitis.

Diagnostic accuracy of clinical and laboratory characteristics in suspected non-surgical nosocomial central nervous system infections.

Background: The diagnosis of meningitis in non-surgical hospitalized patients is often difficult and diagnostic accuracy of clinical, laboratory, and radiological characteristics is unknown.

Aim: To assess diagnostic accuracy for individual clinical characteristics of patients suspected of non-surgical nosocomial central nervous system (CNS) infections.

Methods: In a prospective multi-centre cohort study in the Netherlands with adults suspected of CNS infections, consecutive patients who underwent a lumbar puncture for the suspicion of a non-surgical nosocomial CNS infection were included.

Predictors of unfavourable outcome in adults with suspected central nervous system infections: a prospective cohort study.

Suspected central nervous system (CNS) infections may pose a diagnostic challenge, and often concern severely ill patients. We aim to identify predictors of unfavourable outcome to prioritize diagnostics and treatment improvements. Unfavourable outcome was assessed on the Glasgow Outcome Scale at hospital discharge, defined by a score of 1 to 4.

Bacterial ribosomal RNA detection in cerebrospinal fluid using a viromics approach.

Background: In patients with central nervous system (CNS) infections identification of the causative pathogen is important for treatment. Metagenomic next-generation sequencing techniques are increasingly being applied to identify causes of CNS infections, as they can detect any pathogen nucleic acid sequences present. Viromic techniques that enrich samples for virus particles prior to sequencing may simultaneously enrich ribosomes from bacterial pathogens, which are similar in size to small viruses.

Seizures in adults with suspected central nervous system infection.

Background: Seizures can be part of the clinical presentation of central nervous system (CNS) infections. We describe patients suspected of a neurological infection who present with a seizure and study diagnostic accuracy of clinical and laboratory features predictive of CNS infection in this population.

Methods: We analyzed all consecutive patients presenting with a seizure from two prospective Dutch cohort studies, in which patients were included who underwent cerebrospinal fluid (CSF) examination because of the suspicion of a CNS infection.

Neurofilament light chain in central nervous system infections: a prospective study of diagnostic accuracy.

Diagnosing central nervous system (CNS) infections quickly is often difficult. Neurofilament light chain (NfL) is a component of the axonal cytoskeleton and identified as marker of neuronal damage in several CNS diseases. We evaluated the diagnostic accuracy of NfL for diagnosing CNS infections.

Sex steroid hormones are associated with mortality in COVID-19 patients: Level of sex hormones in severe COVID-19.

In patients with coronavirus disease 2019 (COVID-19), men are more severely affected than women. Multiple studies suggest that androgens might play a role in this difference in disease severity. Our objective was to assess the association between sex hormone levels and mortality in patients with severe COVID-19.

Anti-C5a antibody IFX-1 (vilobelimab) treatment versus best supportive care for patients with severe COVID-19 (PANAMO): an exploratory, open-label, phase 2 randomised controlled trial.

Background: Severe COVID-19 is characterised by inflammation and coagulation in the presence of complement system activation. We aimed to explore the potential benefit and safety of selectively blocking the anaphylatoxin and complement protein C5a with the monoclonal antibody IFX-1 (vilobelimab), in patients with severe COVID-19.

Methods: We did an exploratory, open-label, randomised phase 2 trial (part of the adaptive phase 2/3 PANAMO trial) of intravenous IFX-1 in adults with severe COVID-19 at three academic hospitals in the Netherlands.

Diagnostic accuracy of VIDISCA-NGS in patients with suspected central nervous system infections.

Objectives: Confirming the diagnosis in viral central nervous system (CNS) infections can be difficult with the currently available diagnostic tools. Virus discovery cDNA-amplified fragment length polymorphism next-generation sequencing (VIDISCA-NGS) is a promising viral metagenomic technique that enables the detection of all viruses in a single assay. We performed a retrospective study on the diagnostic accuracy of VIDISCA-NGS in cerebrospinal fluid (CSF) of individuals with suspected CNS infections.

Systematic review and validation of diagnostic prediction models in patients suspected of meningitis.

Objectives: Diagnostic prediction models have been developed to assess the likelihood of bacterial meningitis (BM) in patients presented with suspected central nervous system (CNS) infection. External validation in patients suspected of meningitis is essential to determine the diagnostic accuracy of these models.

Methods: We prospectively included patients who underwent a lumbar puncture for suspected CNS infection.

Viral Metagenomics on Cerebrospinal Fluid.

Identifying the causative pathogen in central nervous system (CNS) infections is crucial for patient management and prognosis. Many viruses can cause CNS infections, yet screening for each individually is costly and time-consuming. Most metagenomic assays can theoretically detect all pathogens, but often fail to detect viruses because of their small genome and low viral load.