Analysis of shared common genetic risk between amyotrophic lateral sclerosis and epilepsy

Because hyper-excitability has been shown to be a shared pathophysiological mechanism, we used the latest and largest genome-wide studies in amyotrophic lateral sclerosis (n = 36,052) and epilepsy (n = 38,349) to determine genetic overlap between these conditions. First, we showed no significant genetic correlation, also when binned on minor allele frequency. Second, we confirmed the absence of polygenic overlap using genomic risk score analysis. Finally, we did not identify pleiotropic variants in meta-analyses of the 2 diseases. Our findings indicate that amyotrophic lateral sclerosis and epilepsy do not share common genetic risk, showing that hyper-excitability in both disorders has distinct origins

Disability uditiva in rapporto alla soglia audiometrica: Ipotesi sulla determinazione di insorgenza dell'indebolimento del senso dell'udito

Background. The term auditory disability (AD) means the presence of auditory symptoms due to hearing loss. Until now the audiometric threshold cut-off between the presence or absence of AD was not clear. Objectives. In this study we attempted to define the value of audiometric threshold that could be considered as the limit between the presence or absence of weakness of auditory function, considered as the threshold at the 95th percentile of subjects that did not report AD. Methods. The study group consisted of 1641 males, 891 normally hearing and 750 affected by noise-induced hearing loss (NIHL) Each subject was submitted to a questionnaire specifically created in order to determine the presence of AD. Results. Statistical analysis confirmed the reliability of answers to items. AD was present in 577 subjects, not all affected by NIHL. Audiometric threshold and age correlated significatively with the degree of AD. Conclusions. The results obtained allowed the audiometric threshold values to be determined at the 95th percentile of subjects who did not report AD, in relation to the average of frequencies normally used in hearing loss evaluation

Self-reported disability and handicap in individuals with noise-induced hearing loss

Noise-induced hearing loss (NIHL) is the cause of subjective problems that could be classified as auditory disability (AD) and auditory handicap (AH). The aim of the study was to determine the relationship between the degree of hearing loss due to NIHL and AD-AH by means of an 11-item questionnaire. The study group consisted of 750 males affected by NIHL and 891 normally hearing males. Each subject was submitted to pure-tone audiometry (PTA) and to a questionnaire that explored AD and AH. Results showed that only 60% of NIHL subjects reported AD and 50% reported AH. The most common AD complaint was reduced speech comprehension in noise. Changes in social relations were rarely reported among the AH items. A correlation was found between both AD and AH and PTA threshold. The severity of AD seems more related to PTA threshold rather than to ag

Blood acidification enhances carbon dioxide removal of membrane lung: An experimental study

Purpose: Extracorporeal CO2removal is an effective procedure to allow a protective ventilatory strategy in ARDS patients, but it is technically challenging due to the high blood flow required. Increasing the CO2transfer through the membrane lung (ML) may lower the demand of extracorporeal blood flow and consequently allow for a wider clinical application of this technique. Since only the dissolved CO2(5% of the total CO2content) is easily removed by the ML, we tested whether acidifying the blood entering the ML to convert bicarbonate ions towards dissolved CO2could enhance the CO2transfer though the ML. Methods: Six pigs were connected to an extracorporeal circuit comprising a ML. The extracorporeal blood flow was 500 ml/min, while the gas flow was 10 l/min. A 15-min continuous infusion of 0.5 N lactic acid was added to the extracorporeal blood flow before the ML at a rate of 1, 2 and 5 mEq/min. Between steps we waited for a reequilibration time of at least 30 min. Results: Acid infusion at 0, 1, 2 and 5 mEq/min increased pCO2(56.19 \uc2\ub1 7.92, 68.24 \uc2\ub1 11.73, 84.28 \uc2\ub1 11.17 and 136.66 \uc2\ub1 18.46 mmHg, respectively) and decreased pH (7.39 \uc2\ub1 0.05, 7.30 \uc2\ub1 0.05, 7.20 \uc2\ub1 0.05 and 6.91 \uc2\ub1 0.05, respectively). ML CO2removal increased 11, 23 and 70% during acid infusion at 1, 2 and 5 mEq/min, respectively. Conclusions: Blood acidification at the inlet of a ML with infusion of 1, 2 and 5 mEq/min of lactic acid can increase the CO2removal capacity of the ML up to 70%. \uc2\ua9 2009 Springer-Verlag

Interstitial pneumonia with autoimmune features: an additional risk factor for ARDS?

Abstract Background Interstitial pneumonia with autoimmune features (IPAF) identifies a recently recognized autoimmune syndrome characterized by interstitial lung disease and autoantibodies positivity, but absence of a specific connective tissue disease diagnosis or alternative etiology. We retrospectively reviewed the clinical presentation, diagnostic workup and management of seven critically ill patients who met diagnostic criteria for IPAF. We compared baseline characteristics and clinical outcome of IPAF patients with those of the population of ARDS patients admitted in the same period. Results Seven consecutive patients with IPAF admitted to intensive care unit for acute respiratory distress syndrome (ARDS) were compared with 78 patients with ARDS secondary to a known risk factor and with eight ARDS patients without recognized risk factors. Five IPAF patients (71%) survived and were discharged alive from ICU: Their survival rate was equal to that of patients with a known risk factor (71%), while the subgroup of patients without risk factors had a markedly lower survival (38%). According to the Berlin definition criteria, ARDS was severe in four IPAF patients and moderate in the remaining three. All had multiple organ dysfunction at presentation. The most frequent autoantibody detected was anti-SSA/Ro52. All patients required prolonged mechanical ventilation (median duration 49 days, range 10–88); four received extracorporeal membrane oxygenation and one received low-flow extracorporeal CO2 removal. All patients received immunosuppressive therapy. Conclusions This is the first description of a cohort of critical patients meeting the diagnostic criteria for IPAF presenting with ARDS. This diagnosis should be considered in any critically ill patient with interstitial lung disease of unknown origin. While management is challenging and level of support high, survival appears to be good and comparable to that of patients with ARDS associated with a known clinical insul

MOESM1 of Interstitial pneumonia with autoimmune features: an additional risk factor for ARDS?

Additional file 1. Electronic Supplementary Materia