Immunization of nonpregnant adults could help prevent invasive group B Streptococcus (GBS) infections, but adult immune responses have not been investigated. We defined capsular polysaccharide (CPS) ...and pilus island (PI) surface antigen distribution and expression and immune responses to GBS infection in nonpregnant adults. Prospective surveillance from 7 hospitals in Houston, Texas, USA, identified 102 adults with GBS bacteremia; 43% had skin/soft tissue infection, 16% bacteremia without focus, and 12% osteomyelitis. CPS-specific IgG was determined by ELISA and pilus-specific IgG by multiplex immunoassay. CPS types were Ia (24.5%), Ib (12.7%), II (9.8%), III (16.7%), IV (13.7%), and V (12.7%); 9.8% were nontypeable by serologic methods. Pili, expressed by 89%, were most often PI-2a. CPS and pilus-specific IgG increased during convalescence among patients with strains expressing CPS or PI. All GBS expressed CPS or PI; 79% expressed both. Increased antibodies to CPS and PI during recovery suggests that GBS bacteremia in adults is potentially vaccine preventable.
Wheat germ oil (WGO) is rich in α-tocopherol (vitamin E, VE), a vitamin that has long been suggested to exert hepatoprotective effects. In this study, this function of WGO-VE and its transcriptomics ...fingerprint were investigated in comparison with RRR−α-tocopherol and all-rac-α-tocopherol (nVE and sVE, respectively), in human liver cells treated with oleic acid (OA) to develop steatosis and lipotoxicity. Used in chemoprevention mode, all the VE formulations afforded significant reduction of the OA-induced steatosis and its consequent impact on lipotoxicity indicators, including ROS production and efflux (as H2O2), and apoptotic and necrotic cell death. A trend toward a better control of lipotoxicity was observed for WGO-VE and nVE compared to sVE.
Gene microarray data demonstrated that these effects of VE formulations were associated with significantly different responses of the cellular transcriptome to compensate for the modifications of OA treatment, including the downregulation of cellular homeostasis genes and the induction of genes associated with defects of liver cell metabolism, fibrosis and inflammation, liver disease and cancer. Ingenuity Pathway Analysis data showed that WGO-VE modulated genes associated with liver carcinogenesis and steatosis, whereas nVE modulated genes involved in liver cell metabolism and viability biofunctions; sVE did not significantly modulate any gene dataset relevant to such biofunctions.
In conclusion, WGO-VE prevents lipotoxicity in human liver cells modulating genes that differ from those affected by the natural or synthetic forms of pure VE. These differences can be captured by precision nutrition tools, reflecting the molecular complexity of this VE-rich extract and its potential in preventing specific cues of hepatocellular lipotoxicity.
Vitamin E; Alpha-tocopherol; Wheat germ oil; Lipotoxicity; NAFLD; NASH; Transcriptomics; Liver; Nutrigenomics; Human hepatocytes; Reactive oxygen species; Precision nutrition.
Background
Clinical data regarding use of newer antiseizure medications (ASMs) in an older population are limited. In randomized-controlled, placebo-controlled trials, older patients are ...under-represented, and protocols deviate markedly from routine clinical practice, limiting the external validity of results. Studies performed in a naturalistic setting are a useful complement to characterize the drug profile. Perampanel is a third-generation ASM and the first and only non-competitive alfa-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate receptor antagonist.
Objective
The aim of this study was to assess the effectiveness and tolerability of adjunctive perampanel over a 1‐year period in a population of older patients with epilepsy treated in a real-world setting.
Methods
Older (≥ 65 years of age) patients prescribed add-on perampanel at 12 Italian epilepsy centers were retrospectively identified. Seizure occurrence, adverse events (AEs), and drug withdrawal were analyzed. Effectiveness outcomes included the rates of seizure response (≥ 50% reduction in baseline monthly seizure frequency), seizure freedom, and treatment discontinuation. Safety and tolerability outcomes were the rate of treatment discontinuation due to AEs and the incidence of AEs.
Results
A total of 92 patients with a median age of 69 (range 65–88) years were included. The median daily dose of perampanel at 12 months was 6 mg (interquartile range 4–6 mg). At 12 months, 53 (57.6%) patients were seizure responders, and 22 (23.9%) patients were seizure free. Twenty (21.7%) patients discontinued perampanel; the reasons for treatment withdrawal were insufficient efficacy (
n
= 6/20; 30.0%), AEs (
n
= 12/20; 60.0%), and a combination of both (
n
= 2/20; 10%). The most common AEs included irritability (8.7%), somnolence (4.3%), and dizziness/vertigo (4.3%). The rate of behavioral and psychiatric AEs was higher in patients with history of psychiatric comorbidities (
p
= 0.044). There were no differences in the occurrence of behavioral and psychiatric AEs according to the concomitant use of levetiracetam (
p
= 0.776) and history of cognitive decline (
p
= 0.332).
Conclusions
Adjunctive perampanel was associated with improvement in seizure control and good tolerability in a real-life setting and can represent a viable therapeutic option in older patients with epilepsy.
Objective
To investigate changes in depressive and suicidality status and their relationship with seizure outcomes after the addition or substitution of another antiseizure medication (ASM) in adults ...with drug‐resistant focal epilepsy.
Methods
Seven hundred seventy consecutively enrolled patients were assessed and followed prospectively for seizure outcome and depressive status over a 6‐month period after starting treatment with a newly introduced ASM. The Neurological Disorders Depression Inventory for Epilepsy (NDDIE) was used to screen for depression and suicidality. Correlations of NDDIE results with clinical and treatment‐related variables were assessed by using a stepwise logistic regression model.
Results
At baseline, 50% of patients had a positive screening test result for depression and 13% had a positive screening test result for suicidal ideation. A psychiatric comorbidity at baseline was associated with a 2.3 times increased risk of an initially negative NDDIE screening result becoming positive at re‐assessment after 6 months. In addition, the number of ASMs taken at baseline correlated with an increased risk of a change in depression screening test results from negative to positive during follow‐up, whereas no association was identified with sociodemographic and epilepsy‐related variables, including seizure outcomes. Approximately 6% of patients who were initially negative at screening for suicidal ideation became positive at the 6‐month re‐assessment. The risk of switch from a negative to a positive screening test result for suicidal ideation was increased more than two‐fold in individuals who screened positive for depression at baseline, and was unrelated to the type of ASM introduced, sociodemographic variables, or seizure outcomes.
Significance
Almost 1 in 5 adults with drug‐resistant focal epilepsy who screen negative for depression become positive when re‐assessed 6 months after a treatment change. At re‐assessment 6 months later, 6.1% who screen initially negative for passive suicidal ideation become positive. These changes in screening status are independent of type of ASM introduced or seizure outcomes but correlate with psychiatric status at baseline.
•BRV proved to be useful and safe for the treatment of status epilepticus.•Time to seizures resolution appears shorter when it is administered in the early phases of status epilepticus.•The use of ...the BRV within 6 h from SE onset was independently associated to an early seizures’ resolution.•No severe treatment emergent adverse events were observed.
to evaluate the use, effectiveness, and adverse events of intravenous brivaracetam (BRV) in status epilepticus (SE).
a retrospective multicentric study involving 24 Italian neurology units was performed from March 2018 to June 2020. A shared case report form was used across participating centres to limit biases of retrospective data collection. Diagnosis and classification of SE followed the 2015 ILAE proposal. We considered a trial with BRV a success when it was the last administered drug prior the clinical and/or EEG resolution of seizures, and the SE did not recur during hospital observation. In addition, we considered cases with early response, defined as SE resolved within 6 h after BRV administration.
56 patients were included (mean age 62 years; 57 % male). A previous diagnosis of epilepsy was present in 21 (38 %). Regarding SE etiology classification 46 % were acute symptomatic, 18 % remote and 16 % progressive symptomatic. SE episodes with prominent motor features were the majority (80 %). BRV was administered as first drug after benzodiazepine failure in 21 % episodes, while it was used as the second or the third (or more) drug in the 38 % and 38 % of episodes respectively. The median loading dose was 100 mg (range 50−300 mg). BRV was effective in 32 cases (57 %). An early response was documented in 22 patients (39 % of the whole sample). The use of the BRV within 6 h from SE onset was independently associated to an early SE resolution (OR 32; 95 % CI 3.39–202; p = 0.002). No severe treatment emergent adverse events were observed.
BRV proved to be useful and safe for the treatment of SE. Time to seizures resolution appears shorter when it is administered in the early phases of SE.
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![[YIA] Cytoprotection effect...](http://api.summon.serialssolutions.com/2.0.0/image/issn/XR4PS5YY4K/0891-5849/small "[YIA] Cytoprotection effect of natural vitamin D in human liver cell lipotoxicity: a transcriptomics approach")
