Diagnosis and management of vasospasm

An overview of the main features of cerebral vasospasm is provided in this report, highlighting the possible future direction of development in the diagnosis and management of this severe complication of aneurysmal subarachnoid hemorrhage

Is there a place for N-acetylcysteine in the treatment of septic shock?

Excessive inflammatory responses and impaired oxygen utilization because of microcirculatory failure are implicated in septic shock. Recent studies have pointed out some beneficial effects in the treatment of septic shock of several vasodilators that exert anti-inflammatory properties. In particular, the antioxidant N-acetylcysteine has been demonstrated to enhance cardiac performance, and to improve hepatosplanchnic perfusion and liver function in patients with established septic shock. These clinical observations may lead us to examine further the role of antioxidant agents in developing novel therapies for septic shock

Extracorporeal membrane oxygenation as "bridge" to lung transplantation: what remains in order to make it standard of care?

Since its introduction into clinical practice, lung transplantation (LTx) is gradually becoming a worldwide standard treatment for patients with a broad spectrum of end-stage respiratory diseases (1\u20133). From 1995 to 2010, more than 30,000 LTx have been performed, and it is worth noting that in recent years the number of LTx has been progressively increasing to more than 3,000/year in 2010, with a post-transplant graft half-life that went from 4.7 in the 1990s to 5.9 in the new millennium (4). However, the crude mortality rate of patients awaiting LTx is higher than mortality for other solid organs. Mortality rate in 2009 for patients on the waiting list for LTx was about 14.1% in North America (www.srtr.org) and 14.7% in Italy (www.airt.it). What are the reasons for these unacceptable mortality rates? First, patients have to wait for the graft longer than patients waiting for other organs because of the small number of lungs suitable for transplantation (5). Second is the lack of supportive therapies that are able to replace respiratory function when the primary pulmonary diseases evolve from \u201crespiratory insufficiency\u201d to \u201crespiratory failure,\u201d characterized by refractory hypoxemia and hypercapnia

A deep Natural Language Inference predictor without language-specific training data

In this paper we present a technique of NLP to tackle the problem of inference relation (NLI) between pairs of sentences in a target language of choice without a language-specific training dataset. We exploit a generic translation dataset, manually translated, along with two instances of the same pre-trained model - the first to generate sentence embeddings for the source language, and the second fine-tuned over the target language to mimic the first. This technique is known as Knowledge Distillation. The model has been evaluated over machine translated Stanford NLI test dataset, machine translated Multi-Genre NLI test dataset, and manually translated RTE3-ITA test dataset. We also test the proposed architecture over different tasks to empirically demonstrate the generality of the NLI task. The model has been evaluated over the native Italian ABSITA dataset, on the tasks of Sentiment Analysis, Aspect-Based Sentiment Analysis, and Topic Recognition. We emphasise the generality and exploitability of the Knowledge Distillation technique that outperforms other methodologies based on machine translation, even though the former was not directly trained on the data it was tested over.Comment: Conference: ICIAP202

Phosphoinositide 3-kinase γ-deficient hearts are protected from the PAF-dependent depression of cardiac contractility

Objectives: Following an ischemic insult, cardiac contractile recovery might be perturbed by the release of autacoids, like platelet-activating factor (PAF), that depress heart function by acting through G protein-coupled receptors (GPCRs). The signaling events downstream the PAF receptor that lead to the negative inotropic effect are still obscure. We thus investigated whether the GPCR-activated phosphoisositide 3-kinase γ (PI3Kγ) could play a role in the cardiac response to PAF. Methods: The negative inotropic effect of PAF was studied ex vivo, in isolated electrically driven atria and in Langendorff-perfused whole hearts derived from wild-type and PI3Kγ-null mice. Postischemic recovery of contractility was analyzed in normal and mutant whole hearts subjected to 30 min of ischemia and 40 min of reperfusion in the presence or absence of a PAF receptor antagonist. Results: While wild-type hearts stimulated with PAF showed increased nitric oxide (NO) production and a consequent decreased cardiac contractility, PI3Kγ-null hearts displayed reduced phosphorylation of nitric oxide synthase 3 (NOS3), blunted nitric oxide production and a complete protection from the PAF-induced negative inotropism. In addition, Langendorff-perfused PI3Kγ-null hearts showed a better contractile recovery after ischemia/reperfusion, a condition where PAF is known to be an important player in depressing contractility. In agreement with a role of PI3Kγ in this PAF-mediated signaling, postischemic contractile recovery in PI3Kγ-null mice appeared overlapping with that of normal hearts treated with the PAF receptor antagonist WEB 2170. Conclusion: These data indicate a novel PAF-dependent signaling pathway that, involving PI3Kγ and NOS3, contributes to postischemic contractile depressio

Novel aspinolide production by Trichoderma arundinaceum with a potential role in Botrytis cinerea antagonistic activity and plant defence priming

Harzianum A (HA), a trichothecene produced by Trichoderma arundinaceum, has recently been described to have antagonistic activity against fungal plant pathogens and to induce plant defence genes. In the present work, we have shown that a tri5 genedisrupted mutant that lacks HA production overproduces two polyketides, aspinolides B and C, which were not detected in the wild-type strain. Furthermore, four new aspinolides (D–G) were characterized. These compounds confirm that a terpene-polyketide cross-pathway exists in T. arundinaceum, and they may be responsible for the antifungal activity and the plant sensitization effect observed with the tri5- disrupted mutant. In addition, the molecular changes involving virulence factors in the phytopathogenic fungus Botrytis cinerea 98 (Bc98) during interaction with T. arundinaceum were investigated. The expression of genes involved in the production of botrydial by Bc98 was relatively repressed by HA, whereas other virulence genes of this pathogen were induced by the presence of T. arundinaceum, for example atrB and pg1 which encode for an ABC transporter and endopolygalacturonase 1 respectively. In addition, the interaction with Bc98 significantly repressed the production of HA by T. arundinaceum, indicating that a bidirectional transcriptional regulation is established between these two antagonistic fungi

Long-term home ventilation of children in Italy: A national survey.

BACKGROUND: Improved technology, as well as professional and parental awareness, enable many ventilator-dependent children to live at home. However, the profile of this growing population, the quality and adequacy of home care, and patients' needs still require thorough assessment. OBJECTIVES: To define the characteristics of Italian children receiving long-term home mechanical ventilation (HMV) in Italy. METHODS: A detailed questionnaire was sent to 302 National Health Service hospitals potentially involved in the care of HVM in children (aged <17 years). Information was collected on patient characteristics, type of ventilation, and home respiratory care. RESULTS: A total of 362 HMV children was identified. The prevalence was 4.2 per 100,000 (95% CI: 3.8-4.6), median age was 8 years (interquartile range 4-14), median age at starting mechanical ventilation was 4 years (1-11), and 56% were male. The most frequent diagnostic categories were neuromuscular disorders (49%), lung and upper respiratory tract diseases (18%), hypoxic (ischemic) encephalopathy (13%), and abnormal ventilation control (12%). Medical professionals with nurses (for 62% of children) and physiotherapists (20%) participated in the patients' discharge from hospital, though parents were the primary care giver, and in 47% of cases, the sole care giver. Invasive ventilation was used in 41% and was significantly related to young age, southern regional residence, longer time spent under mechanical ventilation, neuromuscular disorders, or hypoxic (ischemic) encephalopathy. CONCLUSIONS: Care and technical assistance of long-term HMV children need assessment, planning, and resources. A wide variability in pattern of HMV was found throughout Italy. An Italian national ventilation program, as well as a national registry, could be useful in improving the care of these often critically ill children

Tocilizumab in patients hospitalised with COVID-19 pneumonia: efficacy, safety, viral clearance, and antibody response from a randomised controlled trial (COVACTA)

Background: In COVACTA, a randomised, placebo-controlled trial in patients hospitalised with coronavirus disease-19 (COVID-19), tocilizumab did not improve 28-day mortality, but shortened hospital and intensive care unit stay. Longer-term effects of tocilizumab in patients with COVID-19 are unknown. Therefore, the efficacy and safety of tocilizumab in COVID-19 beyond day 28 and its impact on Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) clearance and antibody response in COVACTA were investigated. Methods: Adults in Europe and North America hospitalised with COVID-19 (N = 452) between April 3, 2020 and May 28, 2020 were randomly assigned (2:1) to double-blind intravenous tocilizumab or placebo and assessed for efficacy and safety through day 60. Assessments included mortality, time to hospital discharge, SARS-CoV-2 viral load in nasopharyngeal swab and serum samples, and neutralising anti-SARS-CoV-2 antibodies in serum. ClinicalTrials.gov registration: NCT04320615. Findings: By day 60, 24·5% (72/294) of patients in the tocilizumab arm and 25·0% (36/144) in the placebo arm died (weighted difference –0·5% [95% CI –9·1 to 8·0]), and 67·0% (197/294) in the tocilizumab arm and 63·9% (92/144) in the placebo arm were discharged from the hospital. Serious infections occurred in 24·1% (71/295) of patients in the tocilizumab arm and 29·4% (42/143) in the placebo arm. Median time to negative reverse transcriptase–quantitative polymerase chain reaction result in nasopharyngeal/oropharyngeal samples was 15·0 days (95% CI 14·0 to 21·0) in the tocilizumab arm and 21·0 days (95% CI 14·0 to 28·0) in the placebo arm. All tested patients had positive test results for neutralising anti–SARS-CoV-2 antibodies at day 60. Interpretation: There was no mortality benefit with tocilizumab through day 60. Tocilizumab did not impair viral clearance or host immune response, and no new safety signals were observed. Future investigations may explore potential biomarkers to optimize patient selection for tocilizumab treatment and combination therapy with other treatments. Funding: F. Hoffmann-La Roche Ltd and the US Department of Health and Human Services, Office of the Assistant Secretary for Preparedness and Response, Biomedical Advanced Research and Development Authority, under OT number HHSO100201800036C