B-type natriuretic peptide clinical activation in aortic stenosis : impact on long-term survival

Objectives : This study was conducted to define the association between serum B-type natriuretic peptide (BNP) activation and survival after the diagnosis of aortic stenosis (AS).Background : In AS, the link between BNP levels and clinical outcome is in dispute. Failure to account for the normal shifting of BNP ranges with aging in men and women, not using hard endpoints (survival), and not enrolling large series of patients have contributed to the uncertainty.Methods : A program of prospective measurement of BNP levels with Doppler echocardiographic AS assessment during the same episode of care was conducted. BNP ratio (measured BNP/maximal normal BNP value specific to age and sex) >1 defined BNP clinical activation.Results : In 1,953 consecutive patients with at least moderate AS (aortic valve area 1.03 ± 0.26 cm2; mean gradient 36 ± 19 mm Hg), median BNP level was 252 pg/ml (interquartile range: 98 to 592 pg/ml); BNP ratio 2.46 (interquartile range 1.03 to 5.66); ejection fraction (EF) 57% ± 15%, and symptoms present in 60% of patients. After adjustment for all survival determinants, BNP clinical activation (BNP ratio >1) independently predicted mortality after diagnosis (p 2 (HR: 0.56; 95% CI: 0.47 to 0.66; p < 0.0001).Conclusions : In this large series of patients with AS, BNP clinical activation was associated with excess long-term mortality incrementally and independently of all baseline characteristics. Higher mortality with higher BNP clinical activation, even in asymptomatic patients, emphasizes the importance of appropriate clinical interpretation of BNP levels in managing patients with AS

Association of atrial fibrillation and obstructive sleep apnea.

BACKGROUND: Obstructive sleep apnea (OSA) is associated with recurrent atrial fibrillation (AF) after electrocardioversion. OSA is highly prevalent in patients who are male, obese, and/or hypertensive, but its prevalence in patients with AF is unknown. METHODS AND RESULTS: We prospectively studied consecutive patients undergoing electrocardioversion for AF (n=151) and consecutive patients without past or current AF referred to a general cardiology practice (n=312). OSA was diagnosed with the Berlin questionnaire, which is validated to identify patients with OSA. We also assessed its accuracy compared with polysomnography in a sample of the study population. Groups were compared with the 2-tailed t, Wilcoxon, and chi2 tests. Logistic regression modeled the association of AF and OSA after adjustment for relevant covariates. Patients in each group had similar age, gender, body mass index, and rates of diabetes, hypertension, and congestive heart failure. The questionnaire performed with 0.86 sensitivity, 0.89 specificity, and 0.97 positive predictive value in our sample. The proportion of patients with OSA was significantly higher in the AF group than in the general cardiology group (49% versus 32%, P=0.0004). The adjusted odds ratio for the association between AF and OSA was 2.19 (95% CI 1.40 to 3.42, P=0.0006). CONCLUSIONS: The novel finding of this study is that a strong association exists between OSA and AF, such that OSA is strikingly more prevalent in patients with AF than in high-risk patients with multiple other cardiovascular diseases. The coinciding epidemics of obesity and AF underscore the clinical importance of these results

Recurrent Granuloma Gluteale Infantum Secondary to Fecal Overflow Incontinence

Granuloma gluteale infantum is a rare pediatric dermatological disorder of uncertain etiology. Suggested causes include fluorinated corticosteroids, Candida albicans, and irritant contact dermatitis. We present the case of a 3-year-old boy with recurrent episodes of granuloma gluteale infantum which resolved with treatment of his fecal overflow incontinence. As each recurrence correlated with a relapse of overflow incontinence, in this case the cause was irritant contact dermatitis from the liquid stool. This is the first reported case of recurrent granuloma gluteale infantum

Neuropsychological Changes in a Prospectively Followed Cohort of Intravenous Drug Users with and without HIV

We followed a cohort of 223 intravenous drug users (99 HIV and 124 HIV+) for up to 3.5 years, examining change in performance over time as a function of HIV status, disease severity, and neurological signs and symptoms. Analyses were performed by applying generalized estimating equations (GEE) to regression analyses with repeated measures, and controlled for age, education, and length of substance use. None of the subjects had AIDS at baseline. There were 147 men (85 HIV+ and 62 HIV) and 76 women (39 HIV+ and 37 HIV). Memory performance was worse in the HIV+ than HIV− women. In the men, performance on the memory, executive, language, and attention factors improved significantly overtime, but this improvement was attenuated in the HIV men for the attention and orientation factors. In the HIV+ women. AIDS was associated with worsening performance on attention tests. The presence or onset of clinically significant neurological findings was associated with poorer language and motor speed performance. In the HIV+ men, memory performance was worse when the CD4 count fell below 200: it declined over time in men with AIDS but not in those without. A learning effect for language was attenuated in men who developed AIDS. The presence or development of a clinically significant neurological sign was associated with poorer memory, executive, language, attention, and motor speed performance. Our findings parallel those that we previously reported in a prospectively followed cohort of gay men. In combination, our studies of gay men and IDU cohorts suggest that (a) HIV can affect cognition early, even when the patient is medically asymptomatic; (b) cognitive difficulties worsen as the severity of HIV infection increases; and (c) the advent of clinically significant neurologic signs is associated with progression to more severe cognitive deficits. Our data suggest that the neurological and neuropsychological changes are both manifestations of the central effect of HIV on the CNS

Risk of Human Immunodeficiency Virus Type 1-Related Neurologic Disease in a Cohort of Intravenous Drug Users

Background: Although the proportion of cases of acquired immunodeficiency syndrome related to intravenous drug use has increased dramatically over the past decade, there has been no longitudinal examination of primary neurologic disease in this group. Objective: To study the development of neurologic disease in human immunodeficiency virus (HIV)—negative and HIV-positive men and women who were intravenous drug users over a 3.5-year period. Design: Prospective observational cohort study. Setting: Subjects were recruited from an infectious disease clinic at a New York City Hospital or from a methadone maintenance program. Participants: Ninety-nine HIV-negative (62 men and 37 women) and 124 HIV-positive (85 men and 39 women) intravenous drug users volunteered. Main Outcome Measure: The development of clinically significant manifestations in six neurologic domains. Results: With multivariate adjustment for current and past substance abuse, age, education, and head injury, we examined the odds of developing HIV-related neurologic disease. Extrapyramidal signs and reduced motor ability became increasingly apparent over time in HIV-infected men as their CD4 cell count declined and as the subjects developed the acquired immunodeficiency syndrome. Fewer neurologic signs were seen in the women. Conclusions: The impact of HIV infection among intravenous drug users parallels that in homosexual men and is independent of alcohol and other drug use

Nutrition for the ageing brain: towards evidence for an optimal diet

As people age they become increasingly susceptible to chronic and extremely debilitating brain diseases. The precise cause of the neuronal degeneration underlying these disorders, and indeed normal brain ageing remains however elusive. Considering the limits of existing preventive methods, there is a desire to develop effective and safe strategies. Growing preclinical and clinical research in healthy individuals or at the early stage of cognitive decline has demonstrated the beneficial impact of nutrition on cognitive functions. The present review is the most recent in a series produced by the Nutrition and Mental Performance Task Force under the auspice of the International Life Sciences Institute Europe (ILSI Europe). The latest scientific advances specific to how dietary nutrients and non-nutrient may affect cognitive ageing are presented. Furthermore, several key points related to mechanisms contributing to brain ageing, pathological conditions affecting brain function, and brain biomarkers are also discussed. Overall, findings are inconsistent and fragmented and more research is warranted to determine the underlying mechanisms and to establish dose-response relationships for optimal brain maintenance in different population subgroups. Such approaches are likely to provide the necessary evidence to develop research portfolios that will inform about new dietary recommendations on how to prevent cognitive decline

The epigenetic landscape of renal cancer

This is an accepted manuscript of an article published by Nature in Nature Reviews: Nephrology on 28/11/2016, available online: https://doi.org/10.1038/nrneph.2016.168 The accepted version of the publication may differ from the final published version.The majority of kidney cancers are associated with mutations in the von Hippel-Lindau gene and a small proportion are associated with infrequent mutations in other well characterized tumour-suppressor genes. In the past 15 years, efforts to uncover other key genes involved in renal cancer have identified many genes that are dysregulated or silenced via epigenetic mechanisms, mainly through methylation of promoter CpG islands or dysregulation of specific microRNAs. In addition, the advent of next-generation sequencing has led to the identification of several novel genes that are mutated in renal cancer, such as PBRM1, BAP1 and SETD2, which are all involved in histone modification and nucleosome and chromatin remodelling. In this Review, we discuss how altered DNA methylation, microRNA dysregulation and mutations in histone-modifying enzymes disrupt cellular pathways in renal cancers

Elaborative encoding through self-generation enhances outcomes with errorless learning: findings from the Skypekids memory study

Errorless learning has demonstrated efficacy in the treatment of memory impairment in adults and older adults with acquired brain injury. In the same population, use of elaborative encoding through supported self-generation in errorless paradigms has been shown to further enhance memory performance. However, the evidence base relevant to application of both standard and self-generation forms of errorless learning in children is far weaker. We address this limitation in the present study to examine recall performance in children with brain injury (n = 16) who were taught novel age-appropriate science and social science facts through the medium of Skype. All participants were taught these facts under conditions of standard errorless learning, errorless learning with self-generation, and trial-and-error learning after which memory was tested at 5-minute, 30-minute, 1-hour and 24-hour delays. Analysis revealed no main effect of time, with participants retaining most information acquired over the 24-hour testing period, but a significant effect of condition. Notably, self-generation proved more effective than both standard errorless and trial-and-error learning. Further analysis of the data revealed that severity of attentional impairment was less detrimental to recall performance under errorless conditions. This study extends the literature to provide further evidence of the value of errorless learning methods in children with ABI and the first demonstration of the effectiveness of self-generation when delivered via the Internet