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Unplanned extubation is a rather common issue in the ICU. Surprisingly, as documented in this issue of the Journal by Kudela et al,[1][1] only a relatively small portion of subjects require re-intubation. This may mean that many individuals remain intubated longer than necessary. The main reasons

Sierra Leone is the country with highest maternal mortality and infections are the underlying cause in 11% of maternal deaths, but the real burden remains unknown. This study aims to determine the incidence and risk factors of surgical site infection (SSI) post-caesarean section (CS) in women admitted to Princess Christian Maternity Hospital (PCMH) in Freetown, Sierra Leone. A prospective case-control (1:3 ratio) study was implemented from 1 May 2018 to 30 April 2019 and 11 women presenting with suspected or confirmed infection post-CS were screened for inclusion as a case. For each case, three patients undergoing CS on the same day and admitted to the same ward, but not presenting with SSI, were selected as controls. The post-CS infection rate was 10.9%. Two hundred and fifty-four clinically confirmed cases were enrolled and matched with 762 control patients. By multivariable analysis, the risk factors for SSI were: being single (odds ratio (OR) 1.48, 95% confidence interval (CI) 1.36-1.66), low education level (OR 1.68, 95% CI 1.55-1.84), previous CS (OR 1.27, 95% CI 1.10-1.52), presenting with premature membranes rupture (OR 1.49, 95% CI 1.18-1.88), a long decision-incision time (OR 2.08, 95% CI 1.74-2.24) and a high missing post-CS antibiotic doses rate (OR 2.52, 95% CI 2.10-2.85). Copyright © The Author(s), 2020. Published by Cambridge University Press.

Background Persistent hypercapnia after COPD exacerbation is associated with excess mortality and early rehospitalization. High Flow Nasal cannula (HFNC), may be theoretically an alternative to long-term noninvasive ventilation (NIV), since physiological studies have shown a reduction in PaCO2 level after few hours of treatment. In this clinical study we assessed the acceptability of HFNC and its effectiveness in reducing the level of PaCO2 in patients recovering from an Acute Hypercapnic Respiratory Failure (AHRF) episode. We also hypothesized that the response in CO2 clearance is dependent on baseline level of hypercapnia. Methods Fifty COPD patients recovering from an acute exacerbation and with persistent hypercapnia, despite having attained a stable pH (i.e. pH > 7,35 and PaCO2 > 45 mmHg on 3 consecutive measurements), were enrolled and treated with HFNC for at least 8 h/day and during the nighttime Results HFNC was well tolerated with a global tolerance score of 4.0 ± 0.9. When patients were separated into groups with or without COPD/OSA overlap syndrome, the “pure” COPD patients showed a statistically significant response in terms of PaCO2 decrease (p = 0.044). In addition, the subset of patients with a lower pH at enrolment were those who responded best in terms of CO2 clearance (score test for trend of odds, p = 0.0038). Conclusions HFNC is able to significantly decrease the level of PaCO2 after 72 h only in “pure” COPD patients, recovering from AHRF. No effects in terms of CO2 reduction were found in those with overlap syndrome. The present findings will help guide selection of the best target population and allow a sample size calculation for future long-term randomized control trials of HFNC vs NIV. Trial registration This study is registered with www. clinicaltrials.gov with identifier number NCT03759457.

Introduction The Coronavirus 2(SARS-CoV-2) outbreak spread rapidly in Italy and the lack of intensive care unit(ICU) beds soon became evident, forcing the application of noninvasive respiratory support(NRS) outside the ICU, raising concerns over staff contamination. We aimed to analyse the safety of the hospital staff, the feasibility, and outcomes of NRS applied to patients outside the ICU. Methods In this observational study, data from 670 consecutive patients with confirmed COVID-19 referred to the Pulmonology Units in nine hospitals between March 1st and May 10th,2020 were analysed. Data were collected including medication, mode and usage of the NRS (i.e. high-flow nasal cannula (HFNC), continuous positive airway pressure (CPAP), noninvasive ventilation(NIV)), length of stay in hospital, endotracheal intubation(ETI) and deaths. Results Forty-two health-care workers (11.4%) tested positive for infection, but only three of them required hospitalisation. Data are reported for all patients (69.3% male), whose mean age was 68 (sd 13) years. The PaO2/FiO2 ratio at baseline was 152±79, and the majority of patients (49.3%) were treated with CPAP. The overall unadjusted 30-day mortality rate was 26.9% with 16%, 30%, and 30%, while the total ETI rate was 27% with 29%, 25% and 28%, for HFNC, CPAP, and NIV, respectively, and the relative probability to die was not related to the NRS used after adjustment for confounders. ETI and length of stay were not different among the groups. Mortality rate increased with age and comorbidity class progression. Conclusions The application of NRS outside the ICU is feasible and associated with favourable outcomes. Nonetheless, it was associated with a risk of staff contamination., In patients with Coronavirus 2 infection and Acute Respiratory Failure, we demonstrated that the utilization of noninvasive respiratory support delivered outside the ICU, was feasible and effective, but associated with a risk of staff contamination

Domiciliary non-invasive ventilation (NIV) effectively reduces arterial carbon dioxide pressure (PaCO2) in patients with stable hypercapnic chronic obstructive pulmonary disease, but a consistent percentage of them may remain hypercapnic. We hypothesised that extracorporeal CO2 removal (ECCO2R) may lower their PaCO2. Ten patients hypercapnic despite ≥6 months of NIV underwent a 24-hour trial of ECCO2R. Six patients completed the ECCO2R-trial with a PaCO2 drop ranging between 23% and 47%. Time to return to baseline after interruption ranged 48–96 hours. In four patients, mechanical events led to ECCO2R premature interruption, despite a decreased in PaCO2. This time window ‘free’ from hypercapnia might allow to propose the concept of ‘CO2 dialysis’.

The World Health Organization has recently defined the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection a pandemic. The infection, that may cause a potentially very severe respiratory disease, now called coronavirus disease 2019 (COVID-19), has airborne transmission via droplets. The rate of transmission is quite high, higher than common influenza. Healthcare workers are at high risk of contracting the infection particularly when applying respiratory devices such as oxygen cannulas or noninvasive ventilation. The aim of this article is to provide evidence-based recommendations for the correct use of “respiratory devices” in the COVID-19 emergency and protect healthcare workers from contracting the SARS-CoV-2 infection.

Chest imaging in patients with acute respiratory failure plays an important role in diagnosing, monitoring and assessing the underlying disease. The available modalities range from plain chest X-ray to computed tomography, lung ultrasound, electrical impedance tomography and positron emission tomography. Surprisingly, there are presently no clear-cut recommendations for critical care physicians regarding indications for and limitations of these different techniques.The purpose of the present European Respiratory Society (ERS) statement is to provide physicians with a comprehensive clinical review of chest imaging techniques for the assessment of patients with acute respiratory failure, based on the scientific evidence as identified by systematic searches. For each of these imaging techniques, the panel evaluated the following items: possible indications, technical aspects, qualitative and quantitative analysis of lung morphology and the potential interplay with mechanical ventilation. A systematic search of the literature was performed from inception to September 2018. A first search provided 1833 references. After evaluating the full text and discussion among the committee, 135 references were used to prepare the current statement.These chest imaging techniques allow a better assessment and understanding of the pathogenesis and pathophysiology of patients with acute respiratory failure, but have different indications and can provide additional information to each other.

Background and objective: Non invasive ventilation (NIV) is currently employed for weaning from invasive ventilation (IMV) in the acute setting but its use for weaning from prolonged ventilation is still occasional and not standardized. We wanted to evaluate whether a combined protocol of NIV and decannulation in tracheostomized patients needing prolonged mechanical ventilation was feasible and what would be the one-year outcome. Methods: We studied patients still dependent from invasive mechanical ventilation with the following inclusion criteria: a) tolerance of at least 8 h of unsupported breathing, b) progressive hypercapnia/acidosis after invasive ventilation discontinuation, c) good adaptation to NIV, d) favorable criteria for decannulation. These patients were switched from IMV to NIV and decannulated; then they were discharged on home NIV and followed-up for one year in order to evaluate survival and complications rate. Results: Data from patients consecutively admitted to a weaning unit were prospectively collected between 2005 and 2018. Out of 587 patients admitted over that period, 341 were liberated from prolonged mechanical ventilation. Fifty-one out of 147 unweaned patients (35%) were eligible for the protocol but only 46 were enrolled. After a mean length of stay of 35 days they were decannulated and discharged on domiciliary NIV. After one year, 38 patients were still alive (survival rate 82%) and 37 were using NIV with good adherence (only one patient was switched again to invasive ventilation). Conclusions: NIV applied to patients with failed weaning from prolonged IMV is feasible and can facilitate the decannulation process. Patients successfully completing this process show good survival rates and few complications. Keywords: Prolonged weaning, Non invasive ventilation, Tracheostomy decannulation, Survival, Respiratory mechanics, Rehabilitation

INTRODUCTION: Acute respiratory failure (ARF) frequently complicates severe community-acquired pneumonia (CAP) that together with sepsis increases patient mortality. The background of the noninvasive ventilation (NIV) use is to overcome an episode of ARF avoiding invasive mechanical ventilation (IMV) and its associated morbidity. EVIDENCE ACQUISITION: We performed a systematic review of the available English literature published up to December 2018 inclusive and focused on ARF in adult CAP population. Database searches identified 177 articles; of these, only 16 were retained for data extraction. EVIDENCE SYNTHESIS: After analyzing all data, we observed that uncertainties in the current literature do not allow firm and definitive recommendations concerning the early use of NIV in hypoxemic CAP patients. IMV still remains a standard of care for many cases of severe CAP. CONCLUSIONS: Nonetheless, NIV is part of our armamentarium and some optimally selected patients clearly benefit from its use. However, in this setting NIV can be considered a valid and useful strategy in some well-selected patients.

BackgroundWhile the role of acute non-invasive ventilation (NIV) has been shown to improve outcome in acute life-threatening hypercapnic respiratory failure in COPD, the evidence of clinical efficacy of long-term home NIV (LTH-NIV) for management of COPD is less. This document provides evidence-based recommendations for the clinical application of LTH-NIV in chronic hypercapnic COPD patients.Materials and methodsThe European Respiratory Society task force committee was composed of clinicians, methodologists and experts in the field of LTH-NIV. The committee developed recommendations based on the GRADE (Grading, Recommendation, Assessment, Development and Evaluation) methodology. The GRADE Evidence to Decision framework was used to formulate recommendations. A number of topics were addressed under a narrative format which provides a useful context for clinicians and patients.ResultsThe task force committee delivered conditional recommendations for four actionable PICO (target population-intervention-comparator-outcome) questions, 1) suggesting for the use of LTH-NIV in stable hypercapnic COPD; 2) suggesting for the use of LTH-NIV in COPD patients following a COPD exacerbation requiring acute NIV 3) suggesting for the use of NIV settings targeting a reduction in carbon dioxide and 4) suggesting for using fixed pressure support as first choice ventilator mode.ConclusionsManaging hypercapnia may be an important intervention for improving the health outcome of COPD patients with chronic respiratory failure. The task force conditionally supports the application of LTH-NIV to improve health outcome by targeting a reduction in carbon dioxide in COPD patients with persistent hypercapnic respiratory failure. These recommendations should be applied in clinical practice by practitioners that routinely care for chronic hypercapnic COPD patients.

In conclusion, this study, besides beingwell conducted and providing important clinical information, clarifies the issue that perception in medicine may be very misleading. Therefore, the patient and clinician, allied together, should never give up on the dream to liberate the patient from prolonged ventilation and recover a satisfactory quality of life

AMPA receptors (AMPARs) are tetrameric ligand-gated channels made up of combinations of GluA1-4 subunits encoded by GRIA1-4 genes. GluA2 has an especially important role because, following post-transcriptional editing at the Q607 site, it renders heteromultimeric AMPARs Ca2+-impermeable, with a linear relationship between current and trans-membrane voltage. Here, we report heterozygous de novo GRIA2 mutations in 28 unrelated patients with intellectual disability (ID) and neurodevelopmental abnormalities including autism spectrum disorder (ASD), Rett syndrome-like features, and seizures or developmental epileptic encephalopathy (DEE). In functional expression studies, mutations lead to a decrease in agonist-evoked current mediated by mutant subunits compared to wild-type channels. When GluA2 subunits are co-expressed with GluA1, most GRIA2 mutations cause a decreased current amplitude and some also affect voltage rectification. Our results show that de-novo variants in GRIA2 can cause neurodevelopmental disorders, complementing evidence that other genetic causes of ID, ASD and DEE also disrupt glutamatergic synaptic transmission., Genetic variants in ionotropic glutamate receptors have been implicated in neurodevelopmental disorders. Here, the authors report heterozygous de novo mutations in the GRIA2 gene in 28 individuals with intellectual disability and neurodevelopmental abnormalities associated with reduced Ca2+ transport and AMPAR currents.”

International audience; Both cholinesterases (AChE and BChE) and kinases, such as GSK-3α/β, are associated with the pathology of Alzheimer's disease. Two scaffolds, targeting AChE (tacrine) and GSK-3α/β (valmerin) simultaneously, were assembled, using copper(I)-catalysed azide alkyne cycloaddition (CuAAC), to generate a new series of multifunctional ligands. A series of eight multi-target directed ligands (MTDLs) was synthesized and evaluated in vitro and in cell cultures. Molecular docking studies, together with the crystal structures of three MTDL/TcAChE complexes, with three tacrine-valmerin hybrids allowed designing an appropriate linker containing a 1,2,3-triazole moiety whose incorporation preserved, and even increased, the original inhibitory potencies of the two selected pharmacophores toward the two targets. Most of the new derivatives exhibited nanomolar affinity for both targets, and the most potent compound of the series displayed inhibitory potencies of 9.5 nM for human acetylcholinesterase (hAChE) and 7 nM for GSK-3α/β. These novel dual MTDLs may serve as suitable leads for further development, since, in the micromolar range, they exhibited low cytotoxicity on a panel of representative human cell lines including the human neuroblastoma cell line SH-SY5Y. Moreover, these tacrine-valmerin hybrids displayed a good ability to penetrate the blood-brain barrier (BBB) without interacting with efflux pumps such as P-gp.

Background: Chest ultrasound (CUS) has been shown to be a sensitive and specific imaging modality for pneumothorax, pneumonia, and pleural effusions. However, the role of chest ultrasound in the diagnosis of thoracic tuberculosis (TB) is uncertain. We performed a systematic search in the medical literature to better define the potential role and value of chest ultrasound in diagnosing thoracic tuberculosis. Aim: To describe existing literature with regard to the diagnostic value of chest ultrasound in thoracic tuberculosis. Methods: MEDLINE, EMBASE, and Scopus databases were searched for relevant articles. We included studies that used chest ultrasound for the diagnosis or management of any form of thoracic tuberculosis, including pulmonary, pleural, mediastinal, and military forms. Results: We identified five main fields of chest ultrasound application: (1) Detection, characterization, and quantification of TB; (2) detection of residual pleural thickening after evacuation; (3) chest ultrasound-guided needle biopsy; (4) identification of pathologic mediastinal lymph nodes in children; and (5) identification of parenchymal ultrasound patterns. Effusion was also detected, in early stages, with signs of organization in 24–100% of patients. A low to moderate (10–23%), false negative rate was reported for chest ultrasound-guided needle biopsy. CUS was able to identify mediastinal lymph nodes in as many as 67% of patients with negative chest radiography. Conclusions: Very few studies with important methodological limitations analyze the role of chest ultrasound in the diagnosis of TB. The scarce available data suggests potential targets of future diagnostic or feasibility trials, such as the detection of tuberculosis–related pleural effusion, residual pleural thickening, lymphadenopathy, TB parenchymal patterns, or the use of CUS in biopsy guidance.

Non-invasive ventilation is standard therapy in the management of both hypoxaemic and hypercapnic respiratory failure of various causes. The evidence base for its use and when and how it should be used has been reviewed in two recent guidelines. In this Series paper, we look beyond the guidelines to what is happening in everyday clinical practice in the real world, how patient selection can be refined to maximise the chances of a successful outcome, and emerging alternative therapies. Real-world application of non-invasive ventilation diverges from guideline recommendations, particularly with regard to patient selection and timing of initiation. To improve patient outcomes education programmes need to stress these issues and the effectiveness of non-invasive ventilation that is delivered needs to be monitored by regular audit.

The theoretical description of the critical temperature Tc of a Fermi superfluid dates back to the work by Gor'kov and Melik-Barkhudarov (GMB), who addressed it for a weakly-coupled (dilute) superfluid in the BCS (weak-coupling) limit of the BCS-BEC crossover. The point made by GMB was that particle-particle (pairing) excitations, which are responsible for superfluidity to occur below Tc, and particle-hole excitations, which give rise to screening also in a normal system, get effectively disentangled from each other in the BCS limit, thus yielding a reduction by a factor 2.2 of the value of Tc obtained when neglecting screening effects. Subsequent work on this topic, aimed at extending the original GMB argument away from the BCS limit with diagrammatic methods, has kept this disentangling between pairing and screening throughout the BCS-BEC crossover, without realising that the conditions for it to be valid are soon violated away from the BCS limit. Here, we reconsider this problem from a more general perspective and argue that pairing and screening are intrinsically entangled with each other along the whole BCS-BEC crossover but for the BCS limit considered by GMB. We perform a detailed numerical calculation of the GMB diagrammatic contribution extended to the whole BCS-BEC crossover, where the full wave-vector and frequency dependence occurring in the repeated in-medium two-particle scattering is duly taken into account. Our numerical calculations are tested against analytic results available in both the BCS and BEC limits, and the contribution of the GMB diagrammatic term to the scattering length of composite bosons in the BEC limit is highlighted. We calculate Tc throughout the BCS-BEC crossover and find that it agrees quite well with Quantum Monte Carlo calculations and experimental data available in the unitarity regime., 21 pages, 11 figures

High-flow nasal cannula (HFNC) is a device able to deliver heated and humidified oxygen at high flows (up to 60L/minutes). Potential benefits of HFNC are several and include the improvement of lung mucociliary clearance, the washout of upper airway dead space, the generation of a low level of positive airway pressure (PEEP effect), the decrease in inspiratory resistance and at the same time the increase in expiratory resistance. The present review aimed to describe the evidence surrounding the use of HFNC in stable chronic obstructive pulmonary disease patients.

The use of noninvasive ventilation (NIV) has increased significantly in patients with acute respiratory failure (ARF) in order to prevent tracheal intubation and its complications. Unfortunately, NIV failure represents a frequent event, with rates that in some cases reach 40%. Mask intolerance, agitation, and delirium may lead to NIV failure, thus requiring endotracheal intubation. NIV failure rates are higher in patients without chronic obstructive pulmonary disease (COPD), and, when used in acute hypoxemic failure, its failure is associated with an increased mortality rate. The practice of sedation during NIV could be a valuable option for patients at risk of intubation. Sedation may decrease patient's discomfort and agitation which is often related to mask intolerance, without significant effects on respiratory drive, respiratory frequency, or hemodynamics. Sedation may also reduce transpulmonary pressure and the associated risk of exposing the patient to high tidal volume hence preventing ventilator-induced lung injury (VILI).

We describe an effective oxidation of diltiazem (DTZ)-like molecules (a class of prochiral sulfides with potential pharmacological properties) using m-chloroperbenzoic acid (MCPBA) as oxidant either in dichloromethane or methanol. An excellent diastereomeric excess of one sulfoxide has been observed “in the absence of any chiral auxiliary”. The stereochemistry of the two diastereomeric sulfoxides has been determined by TDDFT simulations of the experimental electronic circular dichroism (ECD) spectra. A computational DFT study of the reaction mechanism shows that the attack of MCPBA on the two sulfide enantiotopic faces affords two preliminary complexes M1 and M1′. M1 is more stable than M1′ by 3.3 and 3.5 kcal mol−1 in dichloromethane and methanol, respectively, and after equilibration its population must be dominant. Two diastereomeric pathways originate from M1 and M1′ and give two diastereomeric sulfoxides with R and S configurations at the new chiral sulfur, respectively. Since TS (the transition state originating from M1) is more stable than TS′ (the energy gap is 0.7 kcal mol−1 in dichloromethane or methanol), following the Curtin–Hammett principle, the favoured path is the pro-R channel (M1→TS→M2) affording the (Rc,Rs)-2a′ product species in agreement with the observed diastereoselectivity. The M1–M1′ and TS–TS′ energy gaps are actually determined by the difference in the hydrogen bond network that features the two species even if the approaching orientation of the two molecules is governed by the interactions between the π systems of oxidant and substrate aromatic rings. The diastereomeric ratio computed on the basis of the energy difference between TS and TS′ (0.7 kcal mol−1) is 63:37, which must be compared to the experimental value 9:1. When we consider free energy differences (2.4 kcal mol−1 in vacuum and 2.9 kcal mol−1 in solution) this theoretical ratio becomes 85:15 and 89:11, respectively, in excellent agreement with the experimental value 9:1.

Noninvasive positive-pressure ventilation (NPPV) to treat acute respiratory failure has expanded tremendously over the world in terms of the spectrum of diseases that can be successfully managed, the locations of its application and achievable goals.The turning point for the successful expansion of NPPV is its ability to achieve the same physiological effects as invasive mechanical ventilation with the avoidance of the life-threatening risks correlated with the use of an artificial airway.Cardiorespiratory arrest, extreme psychomotor agitation, severe haemodynamic instability, nonhypercapnic coma and multiple organ failure are absolute contraindications for NPPV. Moreover, pitfalls of NPPV reduce its rate of success; consistently, a clear plan of what to do in case of NPPV failure should be considered, especially for patients managed in unprotected setting. NPPV failure is likely to be reduced by the application of integrated therapeutic tools in selected patients handled by expert teams.In conclusion, NPPV has to be considered as a rational art and not just as an application of science, which requires the ability of clinicians to both choose case-by-case the best “ingredients” for a “successful recipe” (i.e.patient selection, interface, ventilator, interface,etc.) and to avoid a delayed intubation if the ventilation attempt fails.

AIM: To date non-invasive (NIV) mechanical ventilation use is not recommended in chronic obstructive pulmonary disease (COPD) patients with acute respiratory failure (ARF) and pH < 7.30 outside a 'protected environment'. We assessed NIV efficacy and feasibility in improving arterial blood gases (ABG) and in-hospital outcome in patients with ARF and severe respiratory acidosis (RA) admitted to an experienced rural medical ward. METHODS: This paper is a prospective pilot cohort study conducted in the General Medicine Ward of Budrio's District Hospital. Two hundred and seventy-two patients with ARF were admitted to our Department, 112, meeting predefined inclusion criteria (pH < 7.35, PaCO2 > 45 mmHg). Patients were divided according to the severity of acidosis into: group A (pH < 7.26), group B (7.26 ≤ pH < 7.30) and group C (7.30 ≤ pH < 7.35). ABG were assessed at admission, at 2-6 h, 24 h, 48 h and at discharge. RESULTS: Group A included 55 patients (24 men, mean age: 80.8 ± 8.3 years), group B 31 (12 men, mean age: 80.3 ± 9.4 years) and group C 26 (15 men, mean age: 78.6 ± 9.9 years). ABG improved within the first hours in 92/112 (82%) patients, who were all successfully discharged. Eighteen percent (20/112) of the patients died during the hospital stay, no significant difference emerged in mortality rate (MR) within the groups (23%, 16% and 8%, for groups A, B and C, respectively) and between patients with or without pneumonia: 8/29 (27%) versus 12/83 (14%). On multivariable analysis, only age and Glasgow Coma Scale had an impact on the clinical outcome. CONCLUSION: In a non-'highly protected' environment such as an experienced medical ward of a rural hospital, NIV is effective not only in patients with mild, but also with severe forms of RA. MR did not vary according to the level of initial pH.

Since its first application in the late 1980s, noninvasive ventilation (NIV) has been the first-line intervention for certain forms of acute respiratory failure. NIV may be delivered through the patient's mouth, nose, or both using noninvasive intermittent positive pressure ventilation or continuous positive airway pressure. When applied appropriately, NIV may reduce morbidity and mortality and may avert iatrogenic complications and infections associated with invasive mechanical ventilation. This article provides physicians and respiratory therapists with a comprehensive, practical guideline for using NIV in critical care. © 2015 Elsevier Inc.

Background Socio-economic, cultural and environmental factors are becoming increasingly important determinants of chronic obstructive pulmonary disease (COPD). We conducted a study to investigate socio-demographic, lifestyle and clinical factors, and to assess their role as predictors of acute events (mortality or hospitalization for respiratory causes) in a group of COPD patients. Methods Subjects were recruited among outpatients who were undertaking respiratory function tests at the Pneumology Unit of the Sant’Orsola-Malpighi Hospital, Bologna. Patients were classified according to the GOLD Guidelines. Results 229 patients with COPD were included in the study, 44 with Mild, 68 Moderate, 52 Severe and 65 Very Severe COPD (GOLD stage). Significant differences among COPD stage, in terms of smoking status and fragility index, were detected. COPD stage significantly affected the values of all clinical tests (spirometry and ABG analysis). Kaplan-Meier estimates showed a significant difference between survival curves by COPD stage with lower event-free probability in very severe COPD stage. Significant risk factors for acute events were: underweight (HR = 4.08; 95% CI 1.01–16.54), having two or more comorbidities (HR = 4.71; 95% CI 2.52–8.83), belonging to moderate (HR = 3.50; 95% CI 1.01–12.18) or very severe COPD stage (HR = 8.23; 95% CI 2.35–28.85). Conclusions Our findings indicate that fragility is associated with COPD stage and that comorbidities and the low body mass index are predictors of mortality or hospitalization. Besides spirometric analyses, FeNO measure and comorbidities, body mass index could also be considered in the management and monitoring of COPD patients.

Delivering synchronous assist during non-invasive ventilation (NIV) is challenging with flow- or pressure-controlled ventilators, especially in patients with chronic obstructive pulmonary disease (COPD). Neurally adjusted ventilatory assist (NAVA) uses diaphragm electrical activity (EAdi) to control the ventilator. We evaluated patient-ventilator interaction in patients with COPD during NIV with pressure support ventilation (PSV) and NAVA using a recently introduced automated analysis.Twelve COPD patients underwent three 30-minute trials: 1) PSV with dedicated NIV ventilator (NIV-PSVVision), 2) PSV with intensive care unit (ICU) ventilator (NIV-PSVServo-I), and 3) with NIV-NAVA. EAdi, flow, and airway pressure were recorded. Patient-ventilator interaction was evaluated by comparing airway pressure and EAdi waveforms with automated computer algorithms. The NeuroSync index was calculated as the percentage of timing errors between airway pressure and EAdi.The NeuroSync index was higher (larger error) for NIV-PSVVision (24 (IQR 15 to 30) %) and NIV-PSVServo-I (21 (IQR 15 to 26) %) compared to NIV-NAVA (5 (IQR 4 to 7) %; P0.001). Wasted efforts, trigger delays and cycling-off errors were less with NAVA (P0.05 for all). The NeuroSync index and the number of wasted efforts were strongly correlated (r2 = 0.84), with a drastic increase in wasted efforts after timing errors reach 20%.In COPD patients, non-invasive NAVA improves patient-ventilator interaction compared to PSV, delivered either by a dedicated or ICU ventilator. The automated analysis of patient-ventilator interaction allowed for an objective detection of patient-ventilator interaction during NIV. In addition, we found that progressive mismatch between neural effort and pneumatic timing is associated with wasted efforts.

Post-viral cough is a type of cough originating from upper respiratory tract infections that persists after the infection is resolved. Although it was hypothesized that bronchodilators might have a role in the management of post-viral cough, a clear demonstration of their efficacy is missing. Therefore, we tested the efficacy of a combination of a β-agonist and an anticholinergic agent in reducing post-viral cough with a randomized, double blind, placebo controlled clinical trial. Patients were treated for 10 days with either a nebulized combination of salbutamol 1.875 mg/0.5 mL and ipratropium bromide 0.375 mg/0.5 mL, or a placebo, and followed up for another 10 days. Daytime and nighttime cough severity and spirometry testing were assessed before starting treatment, after 10 and 20 days. Ninety-two patients were randomized to receive placebo (n = 46) or the active treatment (n = 46); nine of them (4 in the placebo group, 5 in the active treatment group) dropped out from the study. Daytime and nighttime cough severity were significantly reduced in both groups during the study period, but the reduction was more prominent in the active treatment group vs. placebo after 10 days of treatment (P = 0.003 for day cough; P = 0.061 for night cough), whereas at the end of follow-up period cough severity was comparable between the two groups. Small but significant increases in spirometric parameters were observed in the active treatment vs. placebo group, although at the end of follow-up these values returned to be comparable to placebo. The frequency of adverse events was not significantly different between the two groups of patients. We concluded that a combination of a β-agonist and an anticholinergic agent can effectively reduce post-viral cough, and can thus represent a valid option for this type of cough.

Il capitolo tratta diffusamente della disciplina della società in nome collettivo

Background No biological marker is currently available for evaluating pulmonary involvement and/or for monitoring the clinical course of sarcoidosis. The present pilot study focused on possible relationships between circulating plasma levels of surfactant protein type B (SP-B) and plasma receptor for advanced glycation end products (RAGE) and lung function abnormalities in patients with pulmonary sarcoidosis, since both SP-B and RAGE have been previously suggested as lung injury markers. The plasmatic levels of these two proteins were also investigated with respect to functional capacity, as assessed by a cardiopulmonary exercise test (CPET). Methods Thirty pulmonary sarcoidosis outpatients and fifteen volunteers (Control Group) underwent lung function tests and CPET. Resting SP-B and RAGE plasma levels were also determined. Patients were then categorized according to the severity of their pulmonary involvement, as assessed in terms of lung diffusion for carbon monoxide (DL CO) values. Results Group B showed SP-B levels higher and RAGE levels lower than Group A and Control Group (p < 0.01). Group A showed lower RAGE levels than Control Group (p < 0.01), whereas SP-B levels did not differ between these two groups. A significant univariate relationship was found between both SP-B and RAGE and several lung function data, particularly with DLCO (SP-B Vs DLCO: r: -0.437, p = 0.016; RAGE Vs DL CO: r: -0.451, p = 0.012). Conclusions Circulating plasma levels of SP-B and RAGE showed an opposite behavior in patients with pulmonary sarcoidosis. SP-B values are directly related to alveolar unit damage, supporting a possible role of SP-B as a marker of disease severity in these patients. Differently, RAGE decreases in severe sarcoidosis, suggesting more complex underlying mechanisms.

Background: Lung diffusion for carbon monoxide (DLCO) has been shown to associate with the risk of pulmonary arterial hypertension development and, most likely, with right ventricular (RV) myocardial dysfunction in sarcoidosis patients. Besides its known role as a marker of left ventricular dysfunction, experimental evidence suggests a role of NT-proAtrial Natriuretic Peptide (NT-proANP) also in modulating pulmonary circulation. We therefore investigated possible relationships between NT-proANP, lung diffusion impairment and RV dysfunction. Methods: Thirty-two pulmonary sarcoidosis outpatients and eighteen volunteers underwent full clinical assessment, including full lung function tests and Doppler echocardiography integrated with tissue Doppler imaging (TDI) study. Resting circulating NT-proBNP and NT-proANP plasma levels were also determined. Results: NT-proANP and RV-myocardial performance index (RV-MPI) were significantly higher in those patients with the greatest DL CO impairment, whereas no differences were found for NT-proBNP values. At multivariable analysis, only DLCO (β: - 0.496; standard error: 3.38; p = 0.000) and RV-MPI (β: 0.373; standard error: 6.56; p = 0.031) remained significantly associated with NT-proANP levels. Conclusions: Our finding may support a key role of NT-proANP in the complex mechanisms underlying modulation of lung function. An early increase in pulmonary vascular resistance may stimulate NT-proANP increase, thus explaining its association with signs of early RV myocardial dysfunction. This hypothesis warrants further confirmation. © 2012 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.

The mechanisms leading to patient/ventilator asynchrony has never been systematically assessed. We studied the possible association between asynchrony and respiratory mechanics in patients ready to be enrolled for a home non-invasive ventilatory program. Secondarily, we looked for possible differences in the amount of asynchronies between obstructive and restrictive patients and a possible role of asynchrony in influencing the tolerance of non-invasive ventilation (NIV). METHODS: The respiratory pattern and mechanics of 69 consecutive patients with chronic respiratory failure were recorded during spontaneous breathing. After that patients underwent non-invasive ventilation for 60 minutes with a "dedicated" NIV platform in a pressure support mode during the day. In the last 15 minutes of this period, asynchrony events were detected and classified as ineffective effort (IE), double triggering (DT) and auto-triggering (AT). RESULTS: The overall number of asynchronies was not influenced by any variable of respiratory mechanics or by the underlying pathologies (that is, obstructive vs restrictive patients). There was a high prevalence of asynchrony events (58% of patients). IEs were the most frequent asynchronous events (45% of patients) and were associated with a higher level of pressure support. A high incidence of asynchrony events and IE were associated with a poor tolerance of NIV. CONCLUSIONS: Our study suggests that in non-invasively ventilated patients for a chronic respiratory failure, the incidence of patient-ventilator asynchronies was relatively high, but did not correlate with any parameters of respiratory mechanics or underlying disease

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Noninvasive mechanical ventilation (NIV) has become a standard of care in select patients with both hypercapnic and non-hypercapnic acute respiratory failure (ARF). Consequent to the increasing use of NIV, new interfaces of different designs, shapes, sizes, and materials have been proposed for clinical use in recent years. The aim of this report is to examine the most relevant physiological aspects related to the choice of interface with particular emphasis on the problems related to dead space and air leaks that may affect the synchrony between the patient and the machine, ultimately determining the patient's compliance and therefore NIV success.

OBJECTIVE: To determine the effects of different tracheotomy tube sizes on diaphragm effort and weanability indices. METHODS: Ten tracheotomized and difficult to wean subjects were randomized to 2 T-piece trials, with different tracheotomy tube diameters: inner diameters 8 mm and 6.5 mm. Diaphragm pressure-time product per min. (PTP(di/min)), lung compliance and resistance (C(L) and R(L)), breathing pattern, tension-time index of the diaphragm (TT(di)), and the ratio of breathing frequency to tidal volume (f/V(T)) were recorded. In an in vitro model, the flow-pressure relationship was measured using the 2 tracheotomy tubes and 2 endotracheal tubes of the same diameter. RESULTS: The use of a smaller diameter resulted in an increase of PTP(di) (337.63 ± 194.35 cm H(2)O · s/min vs 263.28 ± 156.23 cm H(2)O · s/min for 6.5 mm and 8 mm, respectively, P = .004) and R(L) (16.74 ± 8.10 cm H(2)O · s/min vs 11.72 ± 7.88 cm H(2)O · s/min, respectively, P = .008). Both weanability indices were also significantly higher using the smaller tube: f/V(T) 93.32 ± 20.91 vs 77.06 ± 19.26 for 6.5 mm and 8 mm, respectively, P < .02; TT(di) 0.09 ± 0.052 vs 0.08 ± 0.04, respectively, P < .02. In vitro measurements confirmed that the resistances were higher with the smaller diameter and similar between the tracheotomy tubes and the endotracheal tubes of the same diameters. CONCLUSIONS: In tracheotomized difficult to wean subjects the decrease of the tracheotomy tube size was associated with an increased PTP(di), f/V(T), and TT(di), that were otherwise normal, using a higher diameter. The in vitro study showed that the resistances increased similarly for tracheotomy tube and endotracheal tube, decreasing the diameter and increasing the flows.

To analyse the relation between results of the Aging Males' Symptoms (AMS) questionnaire for aging males, and of quality of life (QOL) questionnaire SF-12 and cardiovascular risk factors.1,927 men aged 55-85 years were interviewed by 56 general practitioners. During the interview the men were asked to fill in the AMS scale and the QOL questionnaire SF-12.Of 1,927 men 1,806 men filled correctly the AMS questionnaire. The mean SF-12 mental index was respectively 55.9 in men with a total AMS score indicating no impairment, 50.9 mild, 42.8 moderate, and 32.8 severe impairment. The corresponding values for the physical index were 51.2, 46.7, 40.8 and 32.3. A history of diabetes was associated with an increased risk of reporting moderate/severe impairment: in relation to the total AMS score the odds ratio, (OR), of moderate/severe impairment in comparison with no impairment was 1.6 (95%CI 1.2-2.1). A history of myocardial infarction and hypertension increased the risk (respectively OR 1.4 (95%CI 1.1-18) and 1.7 (95%CI 1.2-2.4)).This study shows that higher AMS scores are associated with lower SF-12 indices and suggests that elevated values of the AMS score are associated with cardiovascular risk factors or diseases.

The BCS-BEC crossover is studied in a systematic way in the broken-symmetry phase between zero temperature and the critical temperature. This study bridges two regimes where quantum and thermal fluctuations are, respectively, important. The theory is implemented on physical grounds, by adopting a fermionic self-energy in the broken-symmetry phase that represents fermions coupled to superconducting fluctuations in weak coupling and to bosons described by the Bogoliubov theory in strong coupling. This extension of the theory beyond mean field proves important at finite temperature, to connect with the results in the normal phase. The order parameter, the chemical potential, and the single-particle spectral function are calculated numerically for a wide range of coupling and temperature. This enables us to assess the quantitative importance of superconducting fluctuations in the broken-symmetry phase over the whole BCS-BEC crossover. Our results are relevant to the possible realizations of this crossover with high-temperature cuprate superconductors and with ultracold fermionic atoms in a trap., 21 pages, 15 figures

Predictions for the chemical potential and the excitation gap recently obtained by our diagrammatic theory for the BCS-BEC crossover in the superfluid phase are compared with novel Quantum Monte Carlo results at zero temperature now available in the literature. A remarkable agreement is found between the results obtained by the two approaches, Comment: 3 pages, 2 figures