Case Report: Lacosamide unmasking SCN5A-associated Brugada syndrome in a young female with epilepsy.

Background: Lacosamide is frequently used as a mono- or adjunctive therapy for the treatment of adults with epilepsy. Although lacosamide is known to act on both neuronal and cardiac sodium channels, potentially leading to cardiac arrhythmias, including Brugada syndrome (BrS), its adverse effects in individuals with genetic susceptibility are less understood. Case: We report a 33-year-old female with underlying epilepsy who presented to the emergency department with a four-day history of seizure clusters, and was initially treated with lacosamide therapy. During the intravenous lacosamide infusion, the patient developed sudden cardiac arrest caused by ventricular arrhythmias necessitating resuscitation. Of note, the patient had a family history of sudden cardiac death. Workup including routine laboratory results, 12-lead electrocardiogram (ECG), echocardiogram, and coronary angiogram was non-specific. However, a characteristic type 1 Brugada ECG pattern was identified by ajmaline provocation testing; thus, confirming the diagnosis of BrS. Subsequently, the genotypic diagnosis was confirmed by Sanger sequencing, which revealed a heterozygous mutation (c.2893C>T, p.Arg965Cys) in the SCN5A gene. Eventually, the patient underwent implantable cardioverter-defibrillator implantation and was discharged with full neurological recovery. Conclusion: This case highlights a rare but lethal adverse event associated with lacosamide treatment in patients with genetic susceptibility. Further research is warranted to investigate the interactions between lacosamide and SCN5A variants.

Basaloid tumors arising from seborrheic keratosis: Malignant basal cell carcinoma or benign basaloid follicular hamartomatous proliferation?

BACKGROUND: Basaloid tumors arising from seborrheic keratosis (SK) that resembled basal cell carcinoma (BCC) were infrequently observed in our patients. They also exhibited morphologic features similar to those of trichoblastoma or basaloid follicular hamartoma. METHODS: We retrospectively collected cases of SK with basaloid tumors from 2001 to 2017. Ten cases of BCC, five of nevus sebaceus with trichoblastoma, five of trichoblastoma, and five of trichoepithelioma were included as controls. Tumor-associated antigens Bcl-2, CD10, PHLDA1, and CK20 were tested. Antigenic markers CD34 and CD10 were used to analyze peritumoral stroma features and Ki-67 and pHH3 to measure the mitotic activity. RESULTS: Ten cases of SK with basaloid tumors were found and all located in non-sun-exposed areas, including five men and five women, with a mean age of 61 years. A distinct PHLDA1 staining was not observed. The staining patterns of basaloid tumor lobules associated with SK were similar to the benign control group. Bcl-2 staining in the tumor lobules was mostly negative. Peritumoral CD10 stain and CK20-positive Merkel cells in the lobules were observed and the mitotic counts were low. CONCLUSION: Basaloid tumors arising from SK are not always BCC. They were all benign follicular hamartomatous proliferation in this case series.

Zinc supplementation in patients with cirrhosis and hepatic encephalopathy: a systematic review and meta-analysis.

BACKGROUND: Low serum zinc level is associated with hepatic encephalopathy (HE), but the efficacy of zinc supplementation remains uncertain. This study aimed to investigate the effects of zinc supplementation on HE treatment in patients with cirrhosis. METHODS: We searched MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials (Cochrane CENTRAL) and Scopus from inception to December 2018; without publication date or language restrictions. Randomized controlled trials of zinc supplementation versus placebo or other treatment for the management of HE in adult patients with cirrhosis were selected. The primary outcome was the degree of HE as assessed by clinical signs or specialized psychometric tests. The secondary outcomes included serum ammonia levels, adverse events, or the length of hospital stay and costs. We carried out a meta-analysis with random effects model and summarized continuous outcomes using standardized mean differences (SMD) or mean differences (MD) with 95% confidence intervals (95% CI). The risk of bias was assessed using the Cochrane risk of bias tool, and the certainty of evidence for each outcome was evaluated with the Grading of Recommendations, Assessment, Development, and Evaluation approach. RESULTS: Four trials with 247 patients were included. In patients with cirrhosis who had mild HE (≤ grade II), the available evidence suggested that the combination treatment of zinc supplementation and lactulose over 3 to 6 months significantly improved performance in the number connection test (SMD: -0.97; 95% CI: - 1.75 to - 0.19; P = 0.01; moderate certainty), reported in three trials (n = 227). However, compared with lactulose therapy alone, additional zinc supplementation demonstrated no significant difference in the digit symbol test (SMD: 0.44; 95% CI: - 0.12 to 1.00; P = 0.12; very low certainty) or serum ammonia levels (MD: -10.86; 95% CI: - 25.73 to 4.01; P = 0.15; very low certainty), reported in two trials (n = 137). None of the included trials reported adverse events or effects on hospitalization. CONCLUSIONS: In conclusion, a combination of zinc supplementation and lactulose over 3 to 6 months may improve the number connection test in cirrhotic patients with low grade HE, compared with lactulose only. TRIAL REGISTRATION: PROSPERO: CRD42017080955 . Registered 23 November 2017.