Electroencephalogram Features Distinguish Cases of Cerebral Malaria Among Malawian Children With Fever and Coma.

Background: In febrile comatose patients living in malaria-endemic areas, overlapping symptoms and limited laboratory capacity make it difficult to distinguish parasitic, bacterial, and viral central nervous system infections. We evaluated electroencephalography (EEG) as a biomarker to differentiate the microbiologic etiology of pediatric febrile coma at a major referral center in Malawi.

Methods: This was a retrospective case-control study comparing EEG recordings of Malawian children with cerebral malaria to those with febrile coma of nonmalarial cause (bacterial meningitis, viral encephalitis, or unknown cause).

Aetiologies, neuroradiological features, and risk factors for mortality and long-term neurosequelae of febrile coma in Malawian children: a prospective cohort study.

Background: Children in febrile coma in Africa are frequently hospitalised, with poorer outcomes than those in high-income settings. Cerebral malaria is historically the most common cause of febrile coma. Due to limited diagnostic and radiological resources and a decrease in malaria prevalence, there might be under-recognition of non-malarial coma.

The aetiologies, mortality, and disability of non-traumatic coma in African children: a systematic review and meta-analysis.

Background: Non-traumatic coma in African children is a common life-threatening presentation often leading to hospital attendance. We aimed to estimate the distribution of non-traumatic coma causes and outcomes, including disease-specific outcomes, for which evidence is scarce.

Methods: We systematically reviewed MEDLINE, Embase, and Scopus databases from inception to Feb 6, 2024.

A multifaceted intervention to improve diagnosis and early management of hospitalised patients with suspected acute brain infections in Brazil, India, and Malawi: an international multicentre intervention study.

Background: Brain infections pose substantial challenges in diagnosis and management and carry high mortality and morbidity, especially in low-income and middle-income countries. We aimed to improve the diagnosis and early management of patients admitted to hospital (adults aged 16 years and older and children aged >28 days) with suspected acute brain infections at 13 hospitals in Brazil, India, and Malawi.

Methods: With hospital stakeholders, policy makers, and patient and public representatives, we co-designed a multifaceted clinical and laboratory intervention, informed by an evaluation of routine practice.

Reducing epilepsy diagnostic and treatment gaps: Standardized paediatric epilepsy training courses for health care professionals.

Aim: To evaluate improvement in knowledge and clinical behaviour among healthcare professionals after attendance at paediatric epilepsy training (PET) courses.

Method: Since 2005, 1-day PET courses have taught evidence-based paediatric epilepsy management to doctors and nurses in low-, middle-, and high-income countries. A cohort study was performed of 7528 participants attending 252 1-day PET courses between 2005 and 2020 in 17 low-, middle-, and high-income countries, and which gathered data from participants immediately after the course and then 6 months later.

Clinical predictors of encephalitis in UK adults-A multi-centre prospective observational cohort study.

Objectives: Encephalitis, brain inflammation and swelling, most often caused by an infection or the body's immune defences, can have devastating consequences, especially if diagnosed late. We looked for clinical predictors of different types of encephalitis to help clinicians consider earlier treatment.

Methods: We conducted a multicentre prospective observational cohort study (ENCEPH-UK) of adults (> 16 years) with suspected encephalitis at 31 UK hospitals.

Factors affecting ventriculoperitoneal shunt revision: a post hoc analysis of the British Antibiotic and Silver Impregnated Catheter Shunt multicenter randomized controlled trial.

Objective: The British Antibiotic and Silver Impregnated Catheter Shunt (BASICS) trial established level I evidence of the superiority of antibiotic-impregnated catheters in the prevention of infection of newly implanted ventriculoperitoneal shunts (VPSs). A wealth of patient, shunt, and surgery-specific data were collected from trial participants beyond that of the prespecified trial objectives.

Methods: This post hoc analysis of the BASICS survival data explores the impact of patient age, hydrocephalus etiology, catheter type, valve type, and previous external ventricular drain on the risk of infection or mechanical failure.

Brain injury in COVID-19 is associated with dysregulated innate and adaptive immune responses.

COVID-19 is associated with neurological complications including stroke, delirium and encephalitis. Furthermore, a post-viral syndrome dominated by neuropsychiatric symptoms is common, and is seemingly unrelated to COVID-19 severity. The true frequency and underlying mechanisms of neurological injury are unknown, but exaggerated host inflammatory responses appear to be a key driver of COVID-19 severity.

Proteome-wide Mendelian randomization identifies causal links between blood proteins and severe COVID-19.

In November 2021, the COVID-19 pandemic death toll surpassed five million individuals. We applied Mendelian randomization including >3,000 blood proteins as exposures to identify potential biomarkers that may indicate risk for hospitalization or need for respiratory support or death due to COVID-19, respectively. After multiple testing correction, using genetic instruments and under the assumptions of Mendelian Randomization, our results were consistent with higher blood levels of five proteins GCNT4, CD207, RAB14, C1GALT1C1, and ABO being causally associated with an increased risk of hospitalization or respiratory support/death due to COVID-19 (ORs = 1.

Viral capture sequencing detects unexpected viruses in the cerebrospinal fluid of adults with meningitis.

Objectives: Many patients with meningitis have no aetiology identified leading to unnecessary antimicrobials and prolonged hospitalisation. We used viral capture sequencing to identify possible pathogenic viruses in adults with community-acquired meningitis.

Methods: Cerebrospinal fluid (CSF) from 73 patients was tested by VirCapSeq-VERT, a probe set designed to capture viral targets using high throughput sequencing.

Aetiology and outcome of non-traumatic coma in African children: protocol for a systematic review and meta-analysis.

Background: Non-traumatic coma is a common acute childhood presentation to healthcare facilities in Africa and is associated with high morbidity and mortality. Historically, the majority of cases were attributed to cerebral malaria (CM). With the recent drastic reduction in malaria incidence, non-malarial coma is becoming a larger proportion of cases and determining the aetiology is diagnostically challenging, particularly in resource-limited settings.

A Systematic Evaluation of IgM and IgG Antibody Assay Accuracy in Diagnosing Acute Zika Virus Infection in Brazil: Lessons Relevant to Emerging Infections.

Accurate diagnostics underpin effective public health responses to emerging viruses. For viruses, such as Zika virus (ZIKV), where the viremia clears quickly, antibody-based (IgM or IgG) diagnostics are recommended for patients who present 7 days after symptom onset. However, cross-reactive antibody responses can complicate test interpretation among populations where closely related viruses circulate.

Neurological manifestations of SARS-CoV-2 infection in hospitalised children and adolescents in the UK: a prospective national cohort study.

Background: The spectrum of neurological and psychiatric complications associated with paediatric SARS-CoV-2 infection is poorly understood. We aimed to analyse the range and prevalence of these complications in hospitalised children and adolescents.

Methods: We did a prospective national cohort study in the UK using an online network of secure rapid-response notification portals established by the CoroNerve study group.

Guillain-Barré syndrome during the Zika virus outbreak in Northeast Brazil: An observational cohort study.

Objective: To determine the clinical phenotype of Guillain-Barré syndrome (GBS) after Zika virus (ZIKV) infection, the anti-glycolipid antibody signature, and the role of other circulating arthropod-borne viruses, we describe a cohort of GBS patients identified during ZIKV and chikungunya virus (CHIKV) outbreaks in Northeast Brazil.

Methods: We prospectively recruited GBS patients from a regional neurology center in Northeast Brazil between December 2014 and February 2017. Serum and CSF were tested for ZIKV, CHIKV, and dengue virus (DENV), by RT-PCR and antibodies, and serum was tested for GBS-associated antibodies to glycolipids.

Neurological disease in adults with Zika and chikungunya virus infection in Northeast Brazil: a prospective observational study.

Background: Since 2015, the arthropod-borne viruses (arboviruses) Zika and chikungunya have spread across the Americas causing outbreaks, accompanied by increases in immune-mediated and infectious neurological disease. The spectrum of neurological manifestations linked to these viruses, and the importance of dual infection, are not known fully. We aimed to investigate whether neurological presentations differed according to the infecting arbovirus, and whether patients with dual infection had a different disease spectrum or severity.

Methods of Inactivation of SARS-CoV-2 for Downstream Biological Assays.

The scientific community has responded to the coronavirus disease 2019 (COVID-19) pandemic by rapidly undertaking research to find effective strategies to reduce the burden of this disease. Encouragingly, researchers from a diverse array of fields are collectively working towards this goal. Research with infectious severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is undertaken in high-containment laboratories; however, it is often desirable to work with samples at lower-containment levels.

Silver-impregnated, antibiotic-impregnated or non-impregnated ventriculoperitoneal shunts to prevent shunt infection: the BASICS three-arm RCT.

Background: Insertion of a ventriculoperitoneal shunt to treat hydrocephalus is one of the most common neurosurgical procedures worldwide. Shunt infection affects up to 15% of patients, resulting in long hospital stays, multiple surgeries and reduced cognition and quality of life.

Objectives: The aim of this trial was to determine whether or not antibiotic-impregnated ventriculoperitoneal shunts (hereafter referred to as antibiotic shunts) (e.

TREM-1 activation is a potential key regulator in driving severe pathogenesis of enterovirus A71 infection.

Hand, foot and mouth disease (HFMD), caused by enterovirus A71 (EV-A71), presents mild to severe disease, and sometimes fatal neurological and respiratory manifestations. However, reasons for the severe pathogenesis remain undefined. To investigate this, infection and viral kinetics of EV-A71 isolates from clinical disease (mild, moderate and severe) from Sarawak, Malaysia, were characterised in human rhabdomyosarcoma (RD), neuroblastoma (SH-SY5Y) and peripheral blood mononuclear cells (PBMCs).

Implementation of cell-free DNA-based non-invasive prenatal testing in a National Health Service Regional Genetics Laboratory.

Background: Non-invasive prenatal testing (NIPT) for the detection of foetal aneuploidy through analysis of cell-free DNA (cfDNA) in maternal blood is offered routinely by many healthcare providers across the developed world. This testing has recently been recommended for evaluative implementation in the UK National Health Service (NHS) foetal anomaly screening pathway as a contingent screen following an increased risk of trisomy 21, 18 or 13. In preparation for delivering a national service, we have implemented cfDNA-based NIPT in our Regional Genetics Laboratory.

Terminal deoxynucleotidyl transferase promotes acute myeloid leukemia by priming FLT3-ITD replication slippage.

FLT3-internal tandem duplications (FLT3-ITDs) are prognostic driver mutations found in acute myeloid leukemia (AML). Although these short duplications occur in 25% of AML patients, little is known about the molecular mechanism underlying their formation. Understanding the origin of FLT3-ITDs would advance our understanding of the genesis of AML.

Molecular roulette: nucleophosmin mutations in AML are orchestrated through N-nucleotide addition by TdT.

Nucleophosmin (NPM1) is the most commonly mutated gene in acute myeloid leukemia (AML). AML with mutated NPM1 is recognized as a separate entity in the World Health Organization 2016 classification and carries a relatively favorable prognosis. NPM1 mutations are predominantly 4-bp duplications or insertions in the terminal exon that arise through an unknown mechanism.

Understanding parental perspectives on outcomes following paediatric encephalitis: A qualitative study.

Background: Encephalitis, characterised as inflammation of the brain tissue, is an important cause of acquired brain injury in children. Objective clinical outcomes vary significantly between affected patients, however they do not always correlate with quality of life as reported by parents. The aim of this study was to explore how parents experience and interpret outcomes in relation to their child who has been affected by encephalitis.

Antibiotic or silver versus standard ventriculoperitoneal shunts (BASICS): a multicentre, single-blinded, randomised trial and economic evaluation.

Background: Insertion of a ventriculoperitoneal shunt for hydrocephalus is one of the commonest neurosurgical procedures worldwide. Infection of the implanted shunt affects up to 15% of these patients, resulting in prolonged hospital treatment, multiple surgeries, and reduced cognition and quality of life. Our aim was to determine the clinical and cost-effectiveness of antibiotic (rifampicin and clindamycin) or silver shunts compared with standard shunts at reducing infection.

Subtype-specific regulatory network rewiring in acute myeloid leukemia.

Acute myeloid leukemia (AML) is a heterogeneous disease caused by a variety of alterations in transcription factors, epigenetic regulators and signaling molecules. To determine how different mutant regulators establish AML subtype-specific transcriptional networks, we performed a comprehensive global analysis of cis-regulatory element activity and interaction, transcription factor occupancy and gene expression patterns in purified leukemic blast cells. Here, we focused on specific subgroups of subjects carrying mutations in genes encoding transcription factors (RUNX1, CEBPα), signaling molecules (FTL3-ITD, RAS) and the nuclear protein NPM1).

Incidence, aetiology, and sequelae of viral meningitis in UK adults: a multicentre prospective observational cohort study.

Background: Viral meningitis is increasingly recognised, but little is known about the frequency with which it occurs, or the causes and outcomes in the UK. We aimed to determine the incidence, causes, and sequelae in UK adults to improve the management of patients and assist in health service planning.

Methods: We did a multicentre prospective observational cohort study of adults with suspected meningitis at 42 hospitals across England.