Status epilepticus (SE) is associated with significantly higher morbidity and mortality than isolated seizures. Our objective was to identify clinical diagnoses and rhythmic and periodic ...electroencephalogram patterns (RPPs) associated with SE and seizures.
Retrospective cohort study.
Tertiary-care hospitals.
Twelve thousand four hundred fifty adult hospitalized patients undergoing continuous electroencephalogram (cEEG) monitoring in selected participating sites in the Critical Care EEG Monitoring Research Consortium database (February 2013 to June 2021).
Not applicable.
We defined an ordinal outcome in the first 72 hours of cEEG: no seizures, isolated seizures without SE, or SE (with or without isolated seizures). Composite groups included isolated seizures or SE (AnySz) and no seizure or isolated seizures. In this cohort (mean age: 60 ± 17 yr), 1,226 patients (9.8%) had AnySz and 439 patients (3.5%) had SE. In a multivariate model, factors independently associated with SE were cardiac arrest (9.2% with SE; adjusted odds ratio, 8.8 6.3-12.1), clinical seizures before cEEG (5.7%; 3.3 2.5-4.3), brain neoplasms (3.2%; 1.6 1.0-2.6), lateralized periodic discharges (LPDs) (15.4%; 7.3 5.7-9.4), brief potentially ictal rhythmic discharges (BIRDs) (22.5%; 3.8 2.6-5.5), and generalized periodic discharges (GPDs) (7.2%; 2.4 1.7-3.3). All above variables and lateralized rhythmic delta activity (LRDA) were also associated with AnySz. Factors disproportionately increasing odds of SE over isolated seizures were cardiac arrest (7.3 4.4-12.1), clinical seizures (1.7 1.3-2.4), GPDs (2.3 1.4-3.5), and LPDs (1.4 1.0-1.9). LRDA had lower odds of SE compared with isolated seizures (0.5 0.3-0.9). RPP modifiers did not improve SE prediction beyond RPPs presence/absence ( p = 0.8).
Using the largest existing cEEG database, we identified specific predictors of SE (cardiac arrest, clinical seizures prior to cEEG, brain neoplasms, LPDs, GPDs, and BIRDs) and seizures (all previous and LRDA). These findings could be used to tailor cEEG monitoring for critically ill patients.
The major advances in critical care EEG have been the development of rapid response EEG, major revision of the American Clinical Neurophysiology Society's (ACNS) standardized critical care EEG ...terminology, and the commencement of treatment trials on rhythmic and periodic patterns (RPPs) that do not qualify as seizures.
Rapid response EEG (rEEG) has proven an important supplement to full montage continuous EEG monitoring (cEEG). This EEG can be applied in a few minutes and provides excellent ability to exclude seizures, selecting those where conversion to cEEG would have the greatest diagnostic yield. Once cEEG has been commenced, the durations required to adequately exclude seizures have been refined. The ACNS provided major revision and expansion to the standardized critical care EEG terminology, which paved the way for determining with great accuracy the RPPs that are associated with seizures and that are capable of causing neurologic symptoms and/or secondary neuronal injury. The current limitations to multicenter treatment trials of these patterns have been highlighted.
Novel methods of EEG in critical care have been expanding access to all patients where clinically indicated. Standardized EEG terminology has provided the framework to determine what patterns in which presenting causes warrant treatment vs. those that do not.
Outcome trials in patients with type 2 diabetes mellitus have demonstrated reduced hospitalizations for heart failure (HF) with sodium-glucose co-transporter-2 inhibitors. However, few of these ...patients had HF, and those that did were not well-characterized. Thus, the effects of sodium-glucose co-transporter-2 inhibitors in patients with established HF with reduced ejection fraction, including those with and without type 2 diabetes mellitus, remain unknown.
DEFINE-HF (Dapagliflozin Effects on Biomarkers, Symptoms and Functional Status in Patients with HF with Reduced Ejection Fraction) was an investigator-initiated, multi-center, randomized controlled trial of HF patients with left ventricular ejection fraction ≤40%, New York Heart Association (NYHA) class II-III, estimated glomerular filtration rate ≥30 mL/min/1.73m
, and elevated natriuretic peptides. In total, 263 patients were randomized to dapagliflozin 10 mg daily or placebo for 12 weeks. Dual primary outcomes were (1) mean NT-proBNP (N-terminal pro b-type natriuretic peptide) and (2) proportion of patients with ≥5-point increase in HF disease-specific health status on the Kansas City Cardiomyopathy Questionnaire overall summary score, or a ≥20% decrease in NT-proBNP.
Patient characteristics reflected stable, chronic HF with reduced ejection fraction with high use of optimal medical therapy. There was no significant difference in average 6- and 12-week adjusted NT-proBNP with dapagliflozin versus placebo (1133 pg/dL (95% CI 1036-1238) vs 1191 pg/dL (95% CI 1089-1304),
=0.43). For the second dual-primary outcome of a meaningful improvement in Kansas City Cardiomyopathy Questionnaire overall summary score or NT-proBNP, 61.5% of dapagliflozin-treated patients met this end point versus 50.4% with placebo (adjusted OR 1.8, 95% CI 1.03-3.06, nominal
=0.039). This was attributable to both higher proportions of patients with ≥5-point improvement in Kansas City Cardiomyopathy Questionnaire overall summary score (42.9 vs 32.5%, adjusted OR 1.73, 95% CI 0.98-3.05), and ≥20% reduction in NT-proBNP (44.0 vs 29.4%, adjusted OR 1.9, 95% CI 1.1-3.3) by 12 weeks. Results were consistent among patients with or without type 2 diabetes mellitus, and other prespecified subgroups (all
values for interaction=NS).
In patients with heart failure and reduced ejection fraction, use of dapagliflozin over 12 weeks did not affect mean NT-proBNP but increased the proportion of patients experiencing clinically meaningful improvements in HF-related health status or natriuretic peptides. Benefits of dapagliflozin on clinically meaningful HF measures appear to extend to patients without type 2 diabetes mellitus.
URL: https://www.clinicaltrials.gov. Unique identifier: NCT02653482.
Heart failure (HF) is a complex disease associated with multisystem organ failure, recurrent hospital admissions, and increased mortality. Acute decompensated heart failure (ADHF) increases central ...venous pressure (CVP) with resultant hepatic congestion, and this relationship has prognostic significance. The gold standard method of measuring CVP, right heart catheterization, is invasive and costly, prompting further investigation into more accurate non‐invasive assessments in HF patients, including liver elastography. Liver elastography relies on imaging techniques to assess liver stiffness measurements (LSM), with high values equating to increased stiffness. While this was developed to assess fibrosis in liver disease, LSM also reflect increased CVP and hepatic congestion. Multiple studies involving ADHF patients, find that increased LSM are independently predictive of increased cardiac events, all‐cause mortality, and worse post‐operative outcome after both acute HF exacerbation and left ventricular assist device (LVAD) placement. In this review, we discuss the role of LSM as a surrogate for CVP and their applications in determining prognosis in both the ADHF and LVAD populations.
Since March, 2013, an avian-origin influenza A H7N9 virus has caused severe pneumonia in China. The aim of this study was to investigate the pathogenesis of this new virus in human beings.
We ...obtained ex-vivo cultures of the human bronchus, lung, nasopharynx, and tonsil and in-vitro cultures of primary human alveolar epithelial cells and peripheral blood monocyte-derived macrophages. We compared virus tropism and induction of proinflammatory cytokine responses of two human influenza A H7N9 virus isolates, A/Shanghai/1/2013 and A/Shanghai/2/2013; a highly pathogenic avian influenza H5N1 virus; the highly pathogenic avian influenza H7N7 virus that infected human beings in the Netherlands in 2003; the 2009 pandemic influenza H1N1 virus, and a low pathogenic duck H7N9 virus that was genetically different to the human disease causing A H7N9 viruses.
Both human H7N9 viruses replicated efficiently in human bronchus and lung ex-vivo cultures, whereas duck/H7N9 virus failed to replicate in either. Both human A H7N9 viruses infected both ciliated and non-ciliated human bronchial epithelial cells and replicated to higher titres than did H5N1 (p<0.0001 to 0.0046) and A/Shanghai/1/2013 replicated to higher titres than did H7N7 (p=0.0002-0.01). Both human A H7N9 viruses predominantly infected type II alveolar epithelial cells and alveolar macrophages in the human lung and replicated to higher titres than did H5N1 (p<0.0001 to 0.0078); A/Shanghai/1/2013 replicated to higher titres than did H1N1 (p=0.0052-0.05) and H7N7 (p=0.0031-0.0151). Human H7N9 viruses were less potent inducers of proinflammatory cytokines compared with H5N1 virus.
Collectively, the results suggest that the novel H7N9 viruses are better adapted to infect and replicate in the human conducting and lower airways than are other avian influenza viruses, including H5N1, and pose an important pandemic threat.
Area of Excellence Scheme of the University Grants Committee (AoE/M-12/96), Hong Kong Special Administrative Region.
The novel pandemic influenza H1N1 (H1N1pdm) virus of swine origin causes mild disease but occasionally leads to acute respiratory distress syndrome and death. It is important to understand the ...pathogenesis of this new disease in humans. We compared the virus tropism and host-responses elicited by pandemic H1N1pdm and seasonal H1N1 influenza viruses in ex vivo cultures of human conjunctiva, nasopharynx, bronchus, and lung, as well as in vitro cultures of human nasopharyngeal, bronchial, and alveolar epithelial cells. We found comparable replication and host-responses in seasonal and pandemic H1N1 viruses. However, pandemic H1N1pdm virus differs from seasonal H1N1 influenza virus in its ability to replicate in human conjunctiva, suggesting subtle differences in its receptor-binding profile and highlighting the potential role of the conjunctiva as an additional route of infection with H1N1pdm. A greater viral replication competence in bronchial epithelium at 33°C may also contribute to the slight increase in virulence of the pandemic influenza virus. In contrast with highly pathogenic influenza H5N1 virus, pandemic H1N1pdm does not differ from seasonal influenza virus in its intrinsic capacity for cytokine dysregulation. Collectively, these results suggest that pandemic H1N1pdm virus differs in modest but subtle ways from seasonal H1N1 virus in its intrinsic virulence for humans, which is in accord with the epidemiology of the pandemic to date. These findings are therefore relevant for understanding transmission and therapy.
3,3′,5,5′-Tetrabromobisphenol-A (TBBPA) is an important brominated flame retardant in epoxy, vinyl esters and polycarbonate resins. Previous studies have already shown the occurrence of its Phase II ...metabolites, TBBPA-glucuronide and sulfate conjugates, in human urine, after oral administration of TBBPA. The main objective of this work is to examine correlations among level of TBBPA in human blood and those of its Phase II metabolites in human urine. Four water-soluble TBBPA conjugates were synthesized, purified and characterized. An analytical protocol using solid-phase extraction and liquid chromatography–electrospray tandem mass spectrometry (SPE-LC-MS/MS) quantification was developed for the simultaneous analysis of these glucuronide and sulfate conjugates in human urine samples. TBBPA and its Phase II metabolites in paired human plasma and urine samples collected randomly from 140 voluntary donors in Hong Kong SAR, China, were determined. One or more TBBPA conjugates were detected in all of the urine samples, with concentration ranging from 0.19 to 127.24μgg−1-creatinine. TBBPA was also quantified in >85% of the plasma and urine samples. Strong correlations were observed between TBBPA content in plasma and the total amount of TBBPA-related compounds in urine.
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•The first report on the synthesis & purification of Phase II metabolites of TBBPA.•Reveals correlations among TBBPA and its metabolites in human plasma and urine.•Contributes to the establishment of convenient TBBPA population exposure markers.
Hexanucleotide repeat expansion in C9orf72 represents the most common genetic cause of familial and sporadic behavioural variant frontotemporal dementia. Previous studies show that some C9orf72 ...carriers with behavioural variant frontotemporal dementia exhibit distinctive atrophy patterns whereas others show mild or undetectable atrophy despite severe behavioural impairment. To explore this observation, we examined intrinsic connectivity network integrity in patients with or without the C9orf72 expansion. We studied 28 patients with behavioural variant frontotemporal dementia, including 14 C9orf72 mutation carriers (age 58.3 ± 7.7 years, four females) and 14 non-carriers (age 60.8 ± 6.9 years, four females), and 14 age- and sex-matched healthy controls. Both patient groups included five patients with comorbid motor neuron disease. Neuropsychological data, structural brain magnetic resonance imaging, and task-free functional magnetic resonance imaging were obtained. Voxel-based morphometry delineated atrophy patterns, and seed-based intrinsic connectivity analyses enabled group comparisons of the salience, sensorimotor, and default mode networks. Single-patient analyses were used to explore network imaging as a potential biomarker. Despite contrasting atrophy patterns in C9orf72 carriers versus non-carriers, patient groups showed topographically similar connectivity reductions in the salience and sensorimotor networks. Patients without C9orf72 expansions exhibited increases in default mode network connectivity compared to controls and mutation carriers. Across all patients, behavioural symptom severity correlated with diminished salience network connectivity and heightened default mode network connectivity. In C9orf72 carriers, salience network connectivity reduction correlated with atrophy in the left medial pulvinar thalamic nucleus, and this region further showed diminished connectivity with key salience network hubs. Single-patient analyses revealed salience network disruption and default mode network connectivity enhancement in C9orf72 carriers with early-stage or slowly progressive symptoms. The findings suggest that patients with behavioural variant frontotemporal dementia with or without the C9orf72 expansion show convergent large-scale network breakdowns despite distinctive atrophy patterns. Medial pulvinar degeneration may contribute to the behavioural variant frontotemporal dementia syndrome in C9orf72 carriers by disrupting salience network connectivity. Task-free functional magnetic resonance imaging shows promise in detecting early-stage disease in C9orf72 carriers and may provide a unifying biomarker across diverse anatomical variants.
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