Postpneumonectomy-Like Syndrome in an Infant With Right Lung Agenesis and Left Main Bronchus Hypoplasia

We report a 1-year-old child born with agenesis of the right lung who sustained an episode of acute respiratory failure related to a postpneumonectomy-like syndrome, with severe mediastinal shift and subsequent stretching and stenosis of the left main bronchus. The insertion of an expandable prosthesis in the right empty pleural space markedly improved the patient's clinical condition

A Local Signature of LTP-Like Plasticity Induced by Repetitive Paired Associative Stimulation

Repetitive paired associative stimulation (rPAS) repeatedly pairs electrical nerve stimulation (ENS) with transcranial magnetic stimulation (TMS) of the contralateral motor hand area (M1) at 5 Hz frequency. So far, there are only few studies concerning the effects of PAS on the modulation of EEG power. Hence, aim of the present study was to investigate rPAS long term after-effects on cortical excitability looking at EEG power spectra. In four experimental sessions, separated by 2 weeks interval, 12 awake subjects received rPAS of the right median nerve and left M1 at a fixed interval (ISI) of 25 ms (real condition), 5 Hz-TMS on left M1, 5 Hz-ENS, of the right median nerve, and rPAS with changing ISI (sham condition). We measured peak-to-peak MEP amplitude, evoked from the target muscle (right abductor pollicis brevis muscle) at rest and the absolute power (POW) in four frequency bands: \u3b1 (8-12 Hz), \u3b2 (13-30), \u3b8 (4-7) and \u3b4 (1-3), under rest conditions. All these parameters were evaluated in three detection blocks: baseline, immediately after and after 30' from the end of the conditioning protocol. Real rPAS induced a long-lasting homotopic cortical excitability modulation, as indexed by MEP amplitude increase, that was paralleled by a long-lasting reduction of \u3b1/\u3b2-POW and by a widespread \u3b8-\u3b4-POW modulation. rPAS applied over the sensory-motor cortex induced an LTP-like plasticity, as indexed by a robust reduction in the \u3b1/\u3b2 POW positively correlated with the MEP amplitude increase. rPAS25ms may be a useful tool for motor neurorehabilitation promoting a sensory-motor coupling within \u3b2 oscillations

Comparison of Direct Oral Anticoagulant Use for the Treatment of Non-Valvular Atrial Fibrillation in Pivotal Clinical Trials vs. the Real-World Setting: A Population-Based Study from Southern Italy

Patients enrolled into pivotal randomized controlled trials (RCTs) may differ substantially from those treated in a real-world (RW) setting, which may result in a different benefit\u2013risk profile. The aim of the study was to assess the external validity of pivotal RCT findings concerning direct oral anticoagulants (DOACs) for the treatment of nonvalvular atrial fibrillation (NVAF) by comparing patients recruited in RCTs to those treated with DOACs registered in a southern Italian local health unit (LHU) in the years 2013\u20132017. The Palermo LHU claims database was used to describe the baseline characteristics of incident DOAC users (washout > 1 year) with NVAF compared with those of enrolled patients in DOAC pivotal RCTs. In the RW, DOAC treatment discontinuation was calculated during the follow-up and compared with DOAC treatment discontinuation of enrolled patients in DOAC pivotal RCTs. Rates of effectiveness and safety outcomes during the follow-up were calculated in an unmatched and in a simulated RCT population, by matching individual incidental RW and RCT DOAC users (excluding edoxaban users) on age, sex, and CHADS2 score. Overall, 42,336 and 7092 incident DOAC users with NVAF were identified from pivotal RCTs and from the RW setting, respectively. In RCTs, DOAC use was more common among males (62.6%) compared with an almost equal sex distribution in the RW. RCT patients were younger (mean age \ub1 standard deviation: 70.7 \ub1 9.2 years) than RW patients (76.0 \ub1 8.6 years). Compared with RCTs, a higher proportion of RW dabigatran users (30.4% vs. 19.6%) and a lower proportion of RW apixaban (15.9% vs. 25.3%) and rivaroxaban (20.4% vs. 23.7%) users discontinued the treatment during the follow-up (p-value < 0.001). The rate of ischemic stroke was lower in RW high-dose dabigatran users (unmatched/-matched population: 0.40\u20130.11% per year) than in the Randomized Evaluation of Long- Term Anticoagulation Therapy (RE-LY) population (0.93% per year). Major bleeding rates were lower in RW users than in RCT users. In conclusion, except for dabigatran, a lower proportion of DOAC discontinuers was observed in the real-world than in pivotal RCT settings. This study provides reassurance to practicing physicians that DOAC use appears to be effective in stroke prevention and is likely safer in RW patients than in RCT enrolled patients. These results may be related to a lower burden of comorbidities despite more advanced age in the RW population compared to the pivotal RCT population

Design and baseline characteristics of the finerenone in reducing cardiovascular mortality and morbidity in diabetic kidney disease trial

Background: Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. Patients and Methods: The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate >= 25 mL/min/1.73 m(2) and albuminuria (urinary albumin-to-creatinine ratio >= 30 to <= 5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level alpha = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. Conclusions: FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

[The HEAT-PPCI study]

Background. La bivalirudina, in associazione con l\u2019uso selettivo degli inibitori della glicoproteina (GP) IIb/IIIa, rappresenta uno standard di cura riconosciuto nell\u2019angioplastica coronarica primaria (PPCI). Scopo dello studio \ue8 stato quello di confrontare la terapia antitrombotica con bivalirudina o eparina non frazionata nel corso di tale procedura. Metodi e risultati. Tra il 7 febbraio 2012 e il 20 novembre 2013, sono stati randomizzati 1829 pazienti su un totale di 1917 pazienti sottoposti ad angiografia d\u2019emergenza presso il nostro centro (pari al 97% dei pazienti afferiti consecutivamente), di cui 1812 inclusi nell\u2019analisi finale. 751 pazienti (83%) dei 905 inclusi nel gruppo bivalirudina e 740 pazienti (82%) dei 907 inclusi nel gruppo eparina sono stati sottoposti ad angioplastica coronarica. Il tasso di utilizzo degli inibitori della GP IIb/IIIa era sostanzialmente simile nei due gruppi (122 pazienti [13%] nel gruppo bivalirudina e 140 pazienti [15%] nel gruppo eparina). L\u2019endpoint primario di efficacia si \ue8 verificato in 79/905 pazienti (8.7%) del gruppo bivalirudina e in 52/907 pazienti (5.7%) del gruppo eparina (differenza di rischio assoluto 3.0%; rischio relativo [RR] 1.52, IC 95% 1.09-2.13, p=0.01). L\u2019\uadendpoint\uad primario di sicurezza si \ue8 verificato in 32/905 pazienti (3.5%) del gruppo bivalirudina e in 28/907 pazienti (3.1%) del gruppo eparina (differenza di rischio assoluto 0.4%; RR 1.15, IC 95% 0.70-1.89, p=0.59). Conclusioni. Rispetto alla bivalirudina, l\u2019eparina riduce l\u2019incidenza degli eventi ischemici avversi maggiori nel contesto della PPCI, a fronte di nessun incremento delle complicanze emorragiche. L\u2019uso sistematico di eparina, invece che di bivalirudina, si tradurrebbe in una sostanziale riduzione dei costi correlati al farmaco. [Lancet 2014;384:1849-58

Effects of grain-size composition examined in laboratory and numerical tests on artificial mud-flows

This paper deals with a laboratory and numerical research on mudflows performed in with the aim to study the interrelations between the grain-size composition of the mud and its rheological properties at different solid concentrations. Furthermore, the predicting capability of a new numerical model in reproducing the flow of viscous materials is evaluate

Tissue Factor Is Induced by Resistin in Human Coronary Artery Endothelial Cells by the NF-?B-Dependent Pathway

Objective: Atherosclerosis is characterized by endothelial inflammation and dysfunction. Adipose tissue has increasingly been recognized as an active endocrine organ secreting so-called adipokines. Among these, resistin – recently described, but not yet extensively studied – has been defined as a novel inflammatory marker in atherosclerosis. The pathophysiology underlying this interplay, however, remains to be fully characterized. The aim of the study is to determine whether resistin might affect prothrombotic characteristics of human coronary artery endothelial cells (HCAECs). Methods and Results: Incubation of HCAECs with resistin caused upregulation of tissue factor (TF) expression as demonstrated by FACS analysis. Moreover, TF activity was induced in a dose-dependent manner, as shown by real-time PCR and colorimetric assay. Resistin-induced TF expression was mediated by oxygen free radicals through the activation of the transcription factor nuclear factor-ĸB (NF-ĸB), as demonstrated by electrophoretic mobility shift assay and by suppression of TF expression by superoxide dismutase, catalase, and the NF-ĸB inhibitors PDTC and BAY 11-7082. Conclusions: These data confirm the hypothesis that resistin may contribute to atherothrombosis, exerting direct effects on HCAECs by promoting TF expression; thus, it represents an effector molecule able to induce a prothrombotic phenotype in cells present in the vessel wall