A de novo GABRA2 missense mutation in severe early-onset epileptic encephalopathy with a choreiform movement disorder

Background

Early-onset epileptic encephalopathy (EOEE) is a severe convulsive disorder with a poor developmental prognosis. Although it has been associated with mutations in a number of genes, the fact that there is a large proportion of patients who remain undiagnosed suggests that there are many more still-unknown genetic causes of EOEE. Achieving a genetic diagnosis is important for understanding the biological basis of the disease, with its implications for treatment and family planning.

A novel 154-bp deletion in the human mitochondrial DNA control region in healthy individuals

The biological role of the mitochondrial DNA (mtDNA) control region in mtDNA replication remains unclear. In a worldwide survey of mtDNA variation in the general population, we have identified a novel large control region deletion spanning positions 16154 to 16307 (m.16154_16307del154). The population prevalence of this deletion is low, since it was only observed in 1 out of over 120,000 mtDNA genomes studied. The deletion is present in a nonheteroplasmic state, and was transmitted by a mother to her two sons with no apparent past or present disease conditions. The identification of this large deletion in healthy individuals challenges the current view of the control region as playing a crucial role in the regulation of mtDNA replication, and supports the existence of a more complex system of multiple or epigenetically-determined replication origins.     

Risk of COVID-19 and its complications in patients with atopic dermatitis undergoing dupilumab treatment—a population-based cohort study

The risk of coronavirus disease (COVID-19) infection and its complications among patients with atopic dermatitis (AD) treated by dupilumab is yet to be determined. We aimed to assess the risk of SARS-CoV-2 infection, COVID-19-associated hospitalization, and mortality among patients with AD treated by dupilumab. A population-based cohort study was conducted to compare AD patients treated by dupilumab (n?=?238) with those treated by prolonged systemic corticosteroids (≥?3 months; n?=?1,023), phototherapy (n?=?461), and azathioprine or mycophenolate mofetil (MMF; n?=?194) regarding the incidence of COVID-19 and its complications. The incidence rate of COVID-19, COVID-19-associated hospitalization, and mortality among patients treated by dupilumab was 70.1 (95% CI, 40.5–116.4), 5.0 (95% CI, 0.3–24.7), and 0.0 per 1,000 person-year, respectively. The use of dupilumab was not associated with an increased risk of SARS-CoV-2 infection [adjusted HR for dupilumab vs. prolonged systemic corticosteroids: 1.13 (95% CI, 0.61–2.09); dupilumab vs. phototherapy: 0.80 (95% CI, 0.42–1.53); dupilumab vs. azathioprine/MMF: 1.10 (95% CI, 0.45–2.65)]. Dupilumab was associated with a comparable risk of COVID-19-associated hospitalization [adjusted HR for dupilumab vs. prolonged systemic corticosteroids: 0.35 (95% CI, 0.05–2.71); dupilumab vs. phototherapy: 0.43 (95% CI, 0.05–3.98); dupilumab vs. azathioprine/MMF: 0.25 (95% CI, 0.02–2.74)]. When applicable, the risk of mortality was not elevated in patients with AD treated by dupilumab [HR for dupilumab vs. prolonged systemic corticosteroids: 0.04 (95% CI, 0.00–225.20)]. To conclude, dupilumab does not impose an increased risk of SARS-CoV-2 infection or COVID-19 complications in patients with AD. Dupilumab should be continued and considered as a safe drug for moderate-to-severe AD during the pandemic.

     

Pacemakers and defibrillators: recent and ongoing studies that impact the elderly

Since the first implantation of a cardiac pacemaker in the second half of the 20th century, there have been evolutionary and revolutionary advances in the technology developed for patients with heart rhythm disturbances. These advances, however, have instead failed to demonstrate that mimicry of physiology by a pacing system would deliver a longer and better life to its recipient. Indeed, we are just now in the process of developing a new paradigm in pacing that may finally deliver physiology to the hyperbolically named "physiologic pacing." This article will discuss the reasons for the discrepancy between the earlier studies and the more recent ones, as well as a review of implantable cardioverter-defibrillator trials, keeping in focus the special needs of aged heart rhythm device recipients.     

Measured body mass index in adolescence and the incidence of pancreatic cancer in a cohort of 720,000 Jewish men

Purpose

The increasing prevalence of adolescent obesity affects adult health. We investigated the association of adolescent overweight with pancreatic cancer incidence in a cohort of 720,927 Jewish Israeli men.

Methods

Body mass index (BMI) was measured during a general health examination at ages 16?C19 between the years 1967 and 1995. Overweight was defined as BMI????85th percentile of the reference US-CDC distribution in adolescence. Pancreatic cancer was identified by linkage with the Israel National Cancer Registry up to 2006.

Results

The mean follow-up period was 23.3?±?8.0?years. During 16.8 million person-years, 98 cases of pancreatic cancer were detected. Using Cox proportional hazards modeling, overweight in adolescence predicted an increased risk of pancreatic cancer [hazard ratio (HR)?=?2.09; 95% confidence interval (CI): 1.26?C3.50, p?=?0.005]. Compared with adolescents with ??normal?? range BMI Z-scores (?1 to +1), adolescents with Z-scores?>?1 showed significantly increased risk [HR, 2.28 (95% CI: 1.43?C3.64), p?=?0.001]. Lower education level (10 or less years of schooling vs. 11?C12?years) was also associated with increased risk of pancreatic cancer [HR 1.90 (95% CI: 1.27?C2.86, p?=?0.002)], whereas height, country of origin and immigration status were not.

Conclusions

Adolescent overweight is substantially associated with pancreatic cancer incidence in young to middle-aged adults. Applying our point estimates to the 16.8% prevalence of excess weight in Israeli adolescents in the past decade suggests a population fraction of 15.5% (95% CI: 4.2?C29.6%) for pancreatic cancer attributable to adolescent overweight in Israel.