Long-term treatment with Perampanel of Chinese patients with focal-onset seizures, especially in sleep-related epilepsy: a prospective real-world observational study.

Background: There is currently a lack of studies examining the long-term therapeutic effectiveness of the third-generation anti-sezure medication, perampanel (PER), for focal-onset seizures (FOS), particularly in Chinese patients with sleep-related epilepsy (SRE). Additionally, the appropriate dosage, plasma concentration, and the relationship between dose and plasma concentration of PER in Chinese patients are still uncertain. Methods: A prospective, single-center, 24-month observational study was conducted in patients diagnosed with FOS, with a focus on patients with SRE. Changes in seizure frequency from baseline, adverse events, and retention rates were analyzed at 12 and 24 months following the start of the treatment. Tolerability was evaluated based on adverse events and discontinuation profiles. PER plasma concentrations were used to assess dose-concentration-response relationships. Results: A total of 175 patients were included (median age: 25 years; range: 4-72 years; 53. 1% males and 46.9% females), with the SRE population accounting for 49. 1% (n = 86). The patients diagnosed with SRE showed considerably higher response rates than those who did not have this diagnosis (p = 0.025, odds ratio = 3.8). Additionally, the SRE group adhered better to PER treatment (r = 0.0009). Patients with a shorter duration of epilepsy (median: 3 years; range:2-7 years) demonstrated a more favorable therapeutic response to PER (p = 0.032). Throughout the administration of maintenance doses, among the entire FOS population, the concentration of PER (C0) ranged between 101.5 and 917.4 ng/mL (median, 232.0 ng/mL), and the mean plasma concentration of PER in the responders was 292.8 ng/mL. We revealed a linear relationship between PER dose and plasma concentration, regardless of whether PER was used as monotherapy or add-on therapy. The retention rates were 77.7% and 65. 1% at 12 and 24 months, respectively. Drug-related adverse events occurred in 45.0% of the patients and were mostly manageable. Conclusion: PER effectively reduced seizure frequency in Chinese patients with FOS, particularly in those with SRE, over a 24-month period. The treatment was well-tolerated and had a clear linear dose-plasma concentration relationship.

Effectiveness and safety of perampanel as adjunctive therapy among Chinese patients with focal-onset epilepsy: A real-world prospective observational study.

OBJECTIVE: Perampanel (PER) has previously been shown to be effective and tolerable when used as an adjunctive therapy for patients with focal-onset seizures (FOS). This study aimed to evaluate the effect of PER as adjunctive therapy for patients with FOS in the Chinese population under real-world conditions for 1 year. METHODS: A prospective, single-center, 1-year observational study was conducted at Huashan Hospital, enrolling both under age (≥4 years old) and adult patients with FOS. Response to PER was assessed at 3-, 6-, and 12-month checkpoints by analyzing the 50 % responder rate, the seizure-free rate, and reduction in seizure frequency. RESULTS: One hundred and eight patients (mean age: 26.6 years, 56.5 % males) with FOS were included, with seventy-six patients finishing the 1-year follow-up (retention rate: 70.4 %, mean PER dose: 4.3 mg/day). The seizure frequency was reduced significantly at 3, 6, and 12 months relative to baseline (p < 0.001 for each seizure type). At 12 months, the responder rate was 65.8 %, and the seizure-free rate was 39.5 %. A significantly higher responder rate was found in patients with focal to bilateral tonic-clonic seizures (p = 0.024), among which the percentage of patients with sleep-related epilepsy was significantly high (p = 0.045). Responders had a lower number of concomitant anti-seizure medications (ASMs) than the non-responders (p = 0.009). Drug-related adverse events (AEs) were reported in 37 % of patients, mostly mild or moderate, and the patients who experienced AEs had a higher daily dose of PER than those who did not (p = 0.026). CONCLUSION: Perampanel, an add-on therapy for focal-onset seizures, was found to be effective and tolerable in Chinese patients at 12 months.

Comparison of Lamotrigine and Oxcarbazepine Monotherapy Among Chinese Adult Patients With Newly-Diagnosed Focal-Onset Epilepsy: A Prospective Observational Study.

Objective: We performed a prospective cohort study to compare the efficacy, safety, effect on mood, and quality of life between lamotrigine (LTG) and oxcarbazepine (OXC) monotherapy among Chinese adult patients with newly-diagnosed focal-onset epilepsy (FOE) with or without secondarily generalized tonic-clonic seizures. Methods: We enrolled 106 adult patients with new-onset FOE, of whom 56 were in the OXC group and 50 in the LTG group. Their clinical characteristics were detailly recorded especially basic seizure frequency, seizure types, and drug-related adverse events. Efficacy was evaluated as seizure-free (no seizure for 6 months), effective (seizure reduction by more than 50%), and ineffective (seizure reduction by less than 50%). Both intention-to-treat and per-protocol analyses were performed. We also assessed their mood state with the Zung Self-rating Scale for anxiety (Z-SAS) and Zung Self-rating Scale for Depression (Z-SDS) and quality of life (QOL) with Quality of Life in Epilepsy (QOLIE-31) at their baseline visit, 3-month visits, and 6-month visit. Intra-group comparisons in each group and inter-group comparisons between the two groups were made. Correlation analysis and multiple regression analysis were also conducted. Results: Except for gender, the two groups were well matched in any other characteristics such as primary seizure frequency and seizure types. In terms of efficacy, 33 patients in the OXC group were evaluated as seizure-free and 15 as effective, while in the LTG group, 31 were seizure-free, and nine were effective. No significant differences could be observed in efficacy between the two groups (P = 0.429). Through multiple logistic regression analysis, we found that OXC monotherapy was more likely to predict a seizure-free state (OR = 1.76) than LTG, but the difference didn't reach statistical significance (P = 0.322) after correcting for other clinical variables. Both groups had adverse events such as fatigue, drowsiness, dizziness, rash, and gastrointestinal discomfort, most of which were mild and transient. In the OXC group, the scores of SAS (P = 0.067) and SDS (P = 0.004) reduced at the 6-month visit, while the score of QOLIE-31 significantly increased (P = 0.001). In the LTG group, a significant decrease in SAS and SDS scores and an increase in QOLIE-31 scores could be witnessed (All P < 0.001). The inter-group comparison showed that improvement of SAS and SDS in the LTG group was more evident than that in the OXC group, which was of statistical significance. Correlational analysis indicated that the improvement of mood and life quality scales in both groups was independent of baseline seizure frequency and treatment efficacy. Multiple linear regression analysis indicated that LTG monotherapy was the only independent factor that could predict a better SAS (P = 0.01) and SDS (P = 0.019) outcome. Conclusions: OXC and LTG are effective as monotherapy and can be considered first-line selection among adult patients with new-onset FOE. Most adverse events are mild, transient, and tolerable. The two drugs improve the mood state of patients, though LTG is superior to OXC in this respect. OXC and LTG have great power in enhancing patients' quality of life. The positive effect on the psychosocial well-being of epilepsy patients may be one of the intrinsic pharmacological properties of LTG and OXC.

Compound heterozygosity for novel variations of the NHLRC1 Gene in a family with Lafora disease.

PURPOSE: NHLRC1 gene mutations are present in a varied proportion of patients with Lafora disease (LD). Compound heterozygosity for novel variations of the gene has been reported in progressive Lafora myoclonic epilepsy of Lafora pedigree. METHODS: The clinical data of the cases were collected for diagnosis, and the genetic spectrum of the family was confirmed. For molecular diagnosis, whole-exome sequencing (WES) of the pedigree was performed. RESULTS: A novel biallelic compound heterozygous c.333dupC chr6-18122504 (p.(Gly112ArgfsTer44)) and c.612dupT chr6-18122225 (p.(Gly205Trpfs*29)) mutation in the NHLRC1 gene was identified in our progressive myoclonic epilepsy of Lafora pedigree. CONCLUSIONS: The genetic analysis was useful for the diagnosis of LD. Genetic analysis is recommended for patients and close relatives, and tissue biopsy is an alternative.

Iridium-Catalyzed B-H Bond Insertion Reactions Using Sulfoxonium Ylides as Carbene Precursors toward α-Boryl Carbonyls.

An iridium-catalyzed B-H bond insertion reaction between borane adducts and sulfoxonium ylides to afford α-boryl carbonyls has been developed. The starting materials are safe and readily available. In addition, analogues of sulfoxonium ylides, such as sulfonium salts and sulfonium ylides could also be amenable to the reaction.

Correction: Synthesis of indoles and quinazolines via additive-controlled selective C-H activation/annulation of N-arylamidines and sulfoxonium ylides.

Correction for 'Synthesis of indoles and quinazolines via additive-controlled selective C-H activation/annulation of N-arylamidines and sulfoxonium ylides' by Ruizhi Lai et al., Chem. Commun., 2019, 55, 4039-4042.

Synthesis of indoles and quinazolines via additive-controlled selective C-H activation/annulation of N-arylamidines and sulfoxonium ylides.

Selective synthesis of indole and quinazoline products was achieved through a precise control of the C-H activation/annulation by changing the additives from NaOAc to CuF2/CsOAc. This strategy constructs indole and quinazoline scaffolds efficiently, and hence is of great interest in pharmaceutical, agricultural and chemical industries.

Engineering human ventricular heart tissue based on macroporous iron oxide scaffolds.

Myocardial infarction (MI) is a primary cardiovascular disease threatening human health and quality of life worldwide. The development of engineered heart tissues (EHTs) as a transplantable artificial myocardium provides a promising therapy for MI. Since most MIs occur at the ventricle, engineering ventricular-specific myocardium is therefore more desirable for future applications. Here, by combining a new macroporous 3D iron oxide scaffold (IOS) with a fixed ratio of human pluripotent stem cell (hPSC)-derived ventricular-specific cardiomyocytes and human umbilical cord-derived mesenchymal stem cells, we constructed a new type of engineered human ventricular-specific heart tissue (EhVHT). The EhVHT promoted expression of cardiac-specific genes, ion exchange, and exhibited a better Ca2+ handling behaviors and normal electrophysiological activity in vitro. Furthermore, when patched on the infarcted area, the EhVHT effectively promoted repair of heart tissues in vivo and facilitated the restoration of damaged heart function of rats with acute MI. Our results show that it is feasible to generate functional human ventricular heart tissue based on hPSC-derived ventricular myocytes for the treatment of ventricular-specific myocardium damage. STATEMENT OF SIGNIFICANCE: We successfully generated highly purified homogenous human ventricular myocytes and developed a method to generate human ventricular-specific heart tissue (EhVHT) based on three-dimensional iron oxide scaffolds. The EhVHT promoted expression of cardiac-specific genes, ion exchange, and exhibited a better Ca2+ handling behaviors and normal electrophysiological activity in vitro. Patching the EhVHT on the infarct area significantly improved cardiac function in rat acute MI models. This EhVHT has a great potential to meet the specific requirements for ventricular damages in most MI cases and for screening drugs specifically targeting ventricular myocardium.