Responsive neurostimulation for focal motor status epilepticus.

No clear evidence-based treatment paradigm currently exists for refractory and super-refractory status epilepticus, which can result in significant mortality and morbidity. While patients are typically treated with antiepileptic drugs and anesthetics, neurosurgical neuromodulation techniques can also be considered. We present a novel case in which responsive neurostimulation was used to effectively treat a patient who had developed super-refractory status epilepticus, later consistent with epilepsia partialis continua, that was refractory to antiepileptic drugs, immunomodulatory therapies, and transcranial magnetic stimulation. This case demonstrates how regional therapy provided by responsive neurostimulation can be effective in treating super-refractory status epilepticus through neuromodulation of seizure networks.

HCV-Related Mortality Among HIV/HCV Co-infected Patients: The Importance of Behaviors in the HCV Cure Era (ANRS CO13 HEPAVIH Cohort).

Mortality among individuals co-infected with HIV and hepatitis C virus (HCV) is relatively high. We evaluated the association between psychoactive substance use and both HCV and non-HCV mortality in HIV/HCV co-infected patients in France, using Fine and Gray's competing-risk model adjusted for socio-demographic, clinical predictors and confounding factors, while accounting for competing causes of death. Over a 5-year median follow-up period, 77 deaths occurred among 1028 patients. Regular/daily cannabis use, elevated coffee intake, and not currently smoking were independently associated with reduced HCV-mortality (adjusted sub-hazard ratio [95% CI] 0.28 [0.10-0.83], 0.38 [0.15-0.95], and 0.28 [0.10-0.79], respectively). Obesity and severe thinness were associated with increased HCV-mortality (2.44 [1.00-5.93] and 7.25 [2.22-23.6] versus normal weight, respectively). Regular binge drinking was associated with increased non-HCV-mortality (2.19 [1.10-4.37]). Further research is needed to understand the causal mechanisms involved. People living with HIV/HCV co-infection should be referred for tobacco, alcohol and weight control interventions and potential benefits of cannabis-based therapies investigated.

Arrhythmias in congenital heart disease: a position paper of the European Heart Rhythm Association (EHRA), Association for European Paediatric and Congenital Cardiology (AEPC), and the European Society of Cardiology (ESC) Working Group on Grown-up Congenital heart disease, endorsed by HRS, PACES, APHRS, and SOLAECE.

The population of patients with congenital heart disease (CHD) is continuously increasing with more and more patients reaching adulthood. A significant portion of these young adults will suffer from arrhythmias due to the underlying congenital heart defect itself or as a sequela of interventional or surgical treatment. The medical community will encounter an increasing challenge as even most of the individuals with complex congenital heart defects nowadays become young adults. Within the past 20 years, management of patients with arrhythmias has gained remarkable progress including pharmacological treatment, catheter ablation, and device therapy. Catheter ablation in patients with CHD has paralleled the advances of this technology in pediatric and adult patients with structurally normal hearts. Growing experience and introduction of new techniques like the 3D mapping systems into clinical practice have been particularly beneficial for this growing population of patients with abnormal cardiac anatomy and physiology. Finally, device therapies allowing maintanence of chronotropic competence and AV conduction, improving haemodynamics by cardiac resynchronization, and preventing sudden death are increasingly used. For pharmacological therapy, ablation procedures, and device therapy decision making requires a deep understanding of the individual pathological anatomy and physiology as well as detailed knowledge on natural history and long-term prognosis of our patients. Composing expert opinions from cardiology and paediatric cardiology as well as from non-invasive and invasive electrophysiology this position paper was designed to state the art in management of young individuals with congenital heart defects and arrhythmias.

Protective effect of coffee consumption on all-cause mortality of French HIV-HCV co-infected patients.

BACKGROUND & AIMS: Coffee has anti-inflammatory and hepato-protective properties. In the general population, drinking ≥3cups of coffee/day has been associated with a 14% reduction in the risk of all-cause mortality. The aim of this study was to investigate the relationship between coffee consumption and the risk of all-cause mortality in patients co-infected with human immunodeficiency virus (HIV) and hepatitis C virus (HCV). METHODS: ANRS CO13 HEPAVIH is an ongoing French nationwide prospective cohort of patients co-infected with HIV-HCV collecting both medical and psychosocial/behavioural data (annual self-administered questionnaires). We used a Cox proportional hazards model to estimate the effect of elevated coffee consumption (≥3cups/day) at baseline on all-cause mortality during the cohort's five-year follow-up. RESULTS: Over a median [interquartile range] follow-up of 5.0 [3.9-5.9] years, 77 deaths occurred among 1,028 eligible patients (mortality rate 1.64/100 person-years; 95% confidence interval [CI] 1.31-2.05). Leading causes of death were HCV-related diseases (n=33, 43%), cancers unrelated to AIDS/HCV (n=9, 12%), and AIDS (n=8, 10%). At the first available visit, 26.6% of patients reported elevated coffee consumption. Elevated coffee consumption at baseline was associated with a 50% reduced risk of all-cause mortality (hazard ratio 0.5; CI 0.3-0.9; p=0.032), after adjustment for gender and psychosocial, behavioral and clinical time-varying factors. CONCLUSIONS: Drinking three or more cups of coffee per day halves all-cause mortality risk in patients co-infected with HIV-HCV. The benefits of coffee extracts and supplementing dietary intake with other anti-inflammatory compounds need to be evaluated in this population. LAY SUMMARY: Coffee has anti-inflammatory and hepato-protective properties but its effect on mortality risk has never been investigated in patients co-infected with human immunodeficiency virus (HIV) and hepatitis C virus (HCV). This study shows that elevated coffee consumption (≥3cups/day) halves all-cause mortality risk in patients co-infected with HIV-HCV. The benefits of coffee extracts and supplementing dietary intake with other anti-inflammatory compounds need to be evaluated in this population.

Brexanolone as adjunctive therapy in super-refractory status epilepticus.

OBJECTIVE: Super-refractory status epilepticus (SRSE) is a life-threatening form of status epilepticus that continues or recurs despite 24 hours or more of anesthetic treatment. We conducted a multicenter, phase 1/2 study in SRSE patients to evaluate the safety and tolerability of brexanolone (USAN; formerly SAGE-547 Injection), a proprietary, aqueous formulation of the neuroactive steroid, allopregnanolone. Secondary objectives included pharmacokinetic assessment and open-label evaluation of brexanolone response during and after anesthetic third-line agent (TLA) weaning. METHODS: Patients receiving TLAs for SRSE control were eligible for open-label, 1-hour brexanolone loading infusions, followed by maintenance infusion. After 48 hours of brexanolone infusion, TLAs were weaned during brexanolone maintenance. After 4 days, the brexanolone dose was tapered. Safety and functional status were assessed over 3 weeks of follow-up. RESULTS: Twenty-five patients received open-label study drug. No serious adverse events (SAEs) were attributable to study drug, as determined by the Safety Review Committee. Sixteen patients (64%) experienced ≥1 SAE. Six patient deaths occurred, all deemed related to underlying medical conditions. Twenty-two patients underwent ≥1 TLA wean attempt. Seventeen (77%) met the response endpoint of weaning successfully off TLAs before tapering brexanolone. Sixteen (73%) were successfully weaned off TLAs within 5 days of initiating brexanolone infusion without anesthetic agent reinstatement in the following 24 hours. INTERPRETATION: In an open-label cohort of limited size, brexanolone demonstrated tolerability among SRSE patients of heterogeneous etiologies and was associated with a high rate of successful TLA weaning. The results suggest the possible development of brexanolone as an adjunctive therapy for SRSE requiring pharmacological coma for seizure control. Ann Neurol 2017;82:342-352.

Significant reductions in alcohol use after hepatitis C treatment: results from the ANRS CO13-HEPAVIH cohort.

BACKGROUND AND AIMS: Few data exist on changes to substance use patterns before and after hepatitis C virus (HCV) treatment. We used longitudinal data of HIV-HCV co-infected individuals to examine whether receiving pegylated interferon (Peg-IFN)-based therapy irrespective of HCV clearance could modify tobacco, cannabis and alcohol use. DESIGN: A prospective cohort of HIV-HCV co-infected individuals was enrolled from 2006. Participants' clinical data were retrieved from medical records and socio-demographic and behavioural characteristics were collected by yearly self-administered questionnaires. SETTING: Data were collected across 17 hospitals in France. PARTICIPANTS: All HIV-HCV co-infected patients who initiated HCV treatment during follow-up and answered items regarding substance use in at least one yearly questionnaire (258 patients, 671 visits). INTERVENTION: HCV treatment consisted of Peg-IFN-based regimens. MEASUREMENTS: Four time-varying outcomes: hazardous alcohol use (Alcohol Use Disorders Identification Test-C > 3/4 for women/men), number of alcohol units/month, binge drinking, cannabis and tobacco use. Mixed models assessed the effect of HCV treatment status (not yet treated, treated and HCV-cleared, treated and HCV-chronic) on each outcome. FINDINGS: A significant decrease (more than 60% reduction) in both hazardous alcohol use and binge drinking and a reduction of 10 alcohol units/month was observed after HCV treatment (irrespective of HCV clearance). No significant effect of HCV treatment status was found on tobacco use and regular cannabis use, but HCV 'clearers' reported less non-regular use of cannabis. CONCLUSIONS: Hepatitis C virus (HCV) treatment appears to help HIV-HCV co-infected patients reduce alcohol use.

Sudden death caused by cardiac sarcoidosis in childhood.

This report describes an adolescent who presented with ventricular tachycardia (VT) originating from the right ventricular apex, with no apparent underlying cause. Cardiac sarcoidosis was identified only at postmortem examination after sudden death. There must be a high index of suspicion for subtle forms of primary myocardial abnormalities in such cases. Investigation for VT should include specific investigations for cardiac sarcoidosis when no other pathology has been identified and there are persistent conduction abnormalities on resting ECG.