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During the coronavirus disease 2019 (COVID-19) pandemic, noninvasive respiratory support has played a central role in managing patients affected by moderate-to-severe acute hypoxemic respiratory failure, despite inadequate scientific evidence to support its usage. High-flow nasal cannula (HFNC) treatment has gained tremendous popularity because of its effectiveness in delivering a high fraction of humidified oxygen, which improves ventilatory efficiency and the respiratory pattern, as well as its reported high tolerability, ease of use, and application outside of ICUs. Nevertheless, the risk of infection transmission to health-care workers has raised some concerns about its use in the first wave of the pandemic outbreak, with controversial recommendations provided by different scientific societies. This narrative review provides an overview of the recent evidence on the physiologic rationale, risks, and benefits of using HFNC instead of conventional oxygen therapy and other types of noninvasive respiratory support devices, such as continuous positive airway pressure and noninvasive ventilation in patients affected by COVID-19 pneumonia with associated acute hypoxemic respiratory failure. It also summarizes the available evidence with regard to the clinical use of HFNC during the current pandemic and its reported outcomes, and highlights the risks of bioaerosol dispersion associated with HFNC use.

Purpose Pulmonary hamartoma is the most common benign tumor of the lung. We analyzed a 20-year historical series of patients with pulmonary hamartoma undergoing surgical resection, aiming to evaluate the characteristics, the outcomes, and the association between hamartoma and lung cancer. Methods It was a retrospective multicenter study including the data of all consecutive patients with pulmonary hamartoma undergoing surgical resection. The end-points were to evaluate: (i) the characteristics of hamartoma, (ii) outcomes, and (iii) whether hamartoma was a predictive factor for lung cancer development Results Our study population included 540 patients. Upfront surgical or endoscopic resection was performed in 385 (71%) cases while in the remaining 155 (29%) cases, the lesions were resected 20 ± 3.5 months later due to increase in size. In most cases, lung sparing resection was carried out including enucleation (n = 259; 48%) and wedge resection (n = 230; 43%) while 5 (1%) patients underwent endoscopic resection. Only two patients (0, 2%) had major complications. One patient (0.23%) had recurrence after endoscopic resection, while no cases of malignant degeneration were seen (mean follow-up:103.3 ± 93 months). Seventy-six patients (14%) had associated lung cancer, synchronous in 9 (12%) and metachronous in 67 (88%). Only age > 70-year-old (p = 0.0059) and smokers > 20 cigarettes/day (p Conclusion PH was a benign tumor, with no evidence of recurrence and/or of malignant degeneration after resection. The association between hamartoma and lung cancer was a spurious phenomenon due to common risk factors.

Background: High-flow nasal oxygen (HFNO) improves exercise capacity, oxygen saturation, and symptoms in patients with chronic obstructive pulmonary disease (COPD). Due to the need of electricity supply, HFNO has not been applied during free ambulation. Objective: We evaluated whether HFNO delivered during walking by a battery-supplied portable device was more effective than usual portable oxygen in improving exercise capacity in patients with COPD and severe exercise limitation. The effects on 6-min walking tests (6MWTs) were the primary outcome. Methods: After a baseline 6MWT, 20 stable patients requiring an oxygen inspiratory fraction (FiO2) 2. Walked distance, perceived dyspnea, pulse oximetry, and inspiratory capacity at end of the tests as well as patients’ comfort were compared between the tests. Results: As compared to baseline, walked distance improved significantly more in HFNO than in the control test (by 61.1 ± 37.8 and 39.7 ± 43.8 m, respectively, p = 0.01). There were no significant differences between the tests in dyspnea, peripheral oxygen saturation, or inspiratory capacity, but HFNO test was appreciated as more comfortable. Conclusion: In patients with COPD and severe exercise limitation, HFNO delivered by a battery-supplied portable device was more effective in improving walking distance than usual oxygen supplementation.

Introduction: Tracheostomy is a common procedure for management of tracheomalacia. However, the limitation to speak related to tracheostomy cannula could affect the quality of life. Objectives: we reported a new minimally invasive procedure to replace tracheostomy cannula with Montgomery T-tube to improve the ability of speaking. Methods: This is a single center study including all consecutive patients undergoing the replacement of standard tracheostomy cannula with T-tube for management of tracheomalacia. The end-points were to evaluate (a) the changes in Voice-related quality of Life (V-RQOL) before and after T-tube placement; and (b) the complications related to T-tube. Results: Eleven patients were included in the study. T-tube was placed using flexible bronchoscopy and laryngeal mask airway. A suture was inserted through the proximal end of T-tube. Once the stent was introduced with a clamp into the trachea, a traction was applied on the suture to facilitate the alignment of the upper end of the stent. The comparison of V-RQOL values before and after T-tube insertion showed a significant improvement in social/emotional (39.2±6.1 vs 66.8±1.9; P=.0001); physical functioning (21±5.7 vs 56.4±5.3; P=0.0001) and total V-RQOL scores (33.9+5.4 vs 61.3+6.1; P=0.0001). No complications were seen during the insertion of the stent. In two patients, T-tube was obstructed by mucus that resolved with aspiration using flexible bronchoscopy (mean follow-up: 18±10months). Conclusions: Our technique is simple and safe, not needing specific skills and/or cumbersome devices. The replacement of tracheostomy cannula with T-tube seems to improve the quality of voice without adding major complications.

Background Noninvasive ventilation (NIV) is indicated to treat respiratory acidosis due to exacerbation of chronic obstructive pulmonary disease (COPD). Recent nonrandomized studies also demonstrated some physiological effects of high-flow nasal therapy (HFNT) in COPD patients. We designed a prospective, unblinded, multicenter, randomized controlled trial to assess the noninferiority of HFNT compared to NIV with respect to the reduction of arterial partial pressure of carbon dioxide (PaCO2) in patients with hypercapnic acute respiratory failure with mild-to-moderate respiratory acidosis. Methods We will enroll adult patients with acute hypercapnic respiratory failure, as defined by arterial pH between 7.25 and 7.35 and PaCO2 ≥ 55 mmHg. Patients will be randomly assigned 1:1 to receive NIV or HFNT. NIV will be applied through a mask with a dedicated ventilator in pressure support mode. Positive end-expiratory pressure will be set at 3–5 cmH2O with inspiratory support to obtain a tidal volume between 6 and 8 ml/kg of ideal body weight. HFNT will be initially set at a temperature of 37 °C and a flow of 60 L/min. At 2 and 6 h we will assess arterial blood gases, vital parameters, respiratory rate, treatment intolerance and failure, need for endotracheal intubation, time spent under mechanical ventilation (both invasive and NIV), intensive care unit and hospital length of stay, and hospital mortality. Based on an α error of 5% and a β error of 80%, with a standard deviation for PaCO2 equal to 15 mmHg and a noninferiority limit of 10 mmHg, we computed a sample size of 56 patients. Considering potential drop-outs and nonparametric analysis, the final computed sample size was 80 patients (40 per group). Discussion HFNT is more comfortable than NIV in COPD patients recovering from an episode of exacerbation. If HFNT would not be inferior to NIV, HFNT could be considered as an alternative to NIV to treat COPD patients with mild-to-moderate respiratory acidosis. Trial registration ClinicalTrials.gov, NCT03370666. Registered on December 12, 2017. Electronic supplementary material The online version of this article (10.1186/s13063-019-3514-1) contains supplementary material, which is available to authorized users.

To evaluate whether pre-emptive skin analgesia using a lidocaine patch 5% would improve the effects of systemic morphine analgesia for controlling acute post-thoracotomy pain. Background: To evaluate whether pre-emptive skin analgesia using a lidocaine patch 5% would improve the effects of systemic morphine analgesia for controlling acute post-thoracotomy pain. Methods: This was a double-blind, placebo controlled, prospective study. Patients were randomly assigned to receive lidocaine 5% patch (lidocaine group) or a placebo (placebo group) three days before thoracotomy. Postoperative analgesia was induced in all cases with intravenous morphine analgesia. The intergroup differences were assessed in order to evaluate whether the lidocaine patch 5% would have effects on pain intensity when at rest and after coughing (primary end-point) on morphine consumption, on the recovery of respiratory function, and on peripheral painful pathways measured with N2 and P2 laser-evoked potential (secondary end-points). Results: A total of 90 patients were randomized, of whom 45 were allocated to the lidocaine group and 45 to the placebo group. Lidocaine compared with the placebo group showed a significant reduction in pain intensity both at rest (P = 0.013) and after coughing (P = 0.015), and in total morphine consumption (P = 0.001); and also showed a better recovery of flow expiratory volume in one second (P = 0.025) and of forced vital capacity (P = 0.037). The placebo group compared with the lidocaine group presented a reduction in amplitude of N2 (P = 0.001) and P2 (P = 0.03), and an increase in the latency of N2 (P = 0.023) and P2 (P = 0.025) laser-evoked potential. Conclusions: The preventive skin analgesia with lidocaine patch 5% seems to be a valid adjunct to intravenous morphine analgesia for controlling post-thoracotomy pain. However, our initial results should be corroborated/confirmed by larger studies.

During the COVID-19 pandemic, the need for noninvasive respiratory support devices has dramatically increased, sometimes exceeding hospital capacity. The full-face Decathlon snorkeling mask, EasyBreath (EB mask), has been adapted to deliver continuous positive airway pressure (CPAP) as an emergency respiratory interface. We aimed to assess the performance of this modified EB mask and to test its use during different gas mixture supplies. CPAP set at 5, 10, and 15 cmH2O was delivered to 10 healthy volunteers with a high-flow system generator set at 40, 80, and 120 L min−1 and with a turbine-driven ventilator during both spontaneous and loaded (resistor) breathing. Inspiratory CO2 partial pressure (PiCO2), pressure inside the mask, breathing pattern and electrical activity of the diaphragm (EAdi) were measured at all combinations of CPAP/flows delivered, with and without the resistor. Using the high-flow generator set at 40 L min−1, the PiCO2 significantly increased and the system was unable to maintain the target CPAP of 10 and 15 cmH2O and a stable pressure within the respiratory cycle; conversely, the turbine-driven ventilator did. EAdi significantly increased with flow rates of 40 and 80 L min−1 but not at 120 L min−1 and with the turbine-driven ventilator. EB mask can be safely used to deliver CPAP only under strict constraints, using either a high-flow generator at a flow rate greater than 80 L min−1, or a high-performance turbine-driven ventilator.

BACKGROUND: Survivors of coronavirus disease 2019 (COVID-19) associated pneumonia may show exercise-induced desaturation. We wondered whether these individuals show physiologic and symptom characteristics similar to individuals with chronic respiratory diseases with exercise-induced desaturation, namely COPD or interstitial lung diseases (ILD). We evaluated lung function, exercise capacity, and symptoms in these individuals compared with individuals with COPD or ILD and exercise-induced desaturation. METHODS: Survivors of COVID-19 associated pneumonia (study individuals), normoxemic at rest with exercise-induced desaturation, underwent assessment of dyspnea, dynamic lung volumes, carbon monoxide diffusion capacity, and the 6-min walk test. Data of individuals with COPD or with ILD and exercise-induced desaturation were also retrospectively analyzed. RESULTS: FVC was lower in individuals with COVID-19 or ILD than in those with COPD. Individuals who had COVID-19 walked < 70% of predicted and, as a whole, had a 6-min walk test performance similar to individuals with ILD but walked significantly less, showed more severe leg fatigue and dyspnea during exercise, and more exercise-induced desaturation than individuals with COPD. CONCLUSIONS: Survivors of COVID-19 associated pneumonia, who were normoxemic at rest with exercise-induced desaturation, had alterations in lung function, exercise capacity, and symptoms similar to individuals with ILD but more severe than individuals with COPD and exercise-induced desaturation.

We explore home use of a portable bi-level ventilation device among patients with severe chronic obstructive pulmonary disease (COPD), and describe changes in the patients’ physical activity levels, perceived dyspnea, anxiety and depression, as well as their satisfaction with the device, after one month of use. Methods. Forty patients with severe COPD and exertional dyspnea were instructed to use VitaBreath® device (Philips, Respironics) during efforts or activities of daily living for 4weeks, and agreed to answer questionnaires on anxiety, depression, dyspnea and physical activity. Results. Twenty-six (65%) patients used the VitaBreath® device for four weeks, while 14 patients (35%) stopped early for various reasons. Among patients who completed the 4-week course, no differences in dyspnea and physical activity were observed between baseline and follow-up (p-values 0.41 and 0.19, respectively). Thirteen (50%) and 15 (57%) patients experienced reduced anxiety and depression, respectively. Patients with greater functional impairment and less autonomy in activities of daily living tended to view the device more positively. Conclusion. Home use of portable bi-level positive-pressure ventilation devices by patients with COPD may alleviate disease-related anxiety and depression, particularly in more severe cases of COPD. Future portable device design should feature adjustable inspiratory/expiratory pressures.

Background We devised a new strategy using suture traction to facilitate the management of primary spontaneous pneumothorax during uniportal thoracoscopy. To test its validity, we compared the outcomes of our modified technique with those of conventional three-port thoracoscopy. Methods This retrospective study included all 43 consecutive patients with primary spontaneous pneumothorax undergoing thoracoscopy between January 2017 and December 2019. They were divided within two groups: uniportal thoracoscopy using suture traction ( n = 21) and conventional 3-port thoracoscopy ( n = 22). Postoperative pain, paresthesia, patient satisfaction, and surgical outcomes were compared to test the validity of our technique. Results There were no significant differences in operative time (47 ± 4.8 vs. 43 ± 7.9 min), number of staples used (2.5 ± 0.9 vs. 2.3 ± 0.6), postoperative drainage (235 ± 15 vs. 240 ± 19 mL), chest tube drainage time (3.2 ± 0.8 vs. 3.4 ± 1.8 days), and hospital stay (4.2 ± 1.2 vs. 4.3 ± 0.9 days). However, uniportal thoracoscopy was associated with less pain at 24 ( p = 0.01), 48 ( p = 0.02), and 72 h ( p = 0.03) postoperatively, less paresthesia at 24 ( p = 0.03), 48 ( p = 0.02), and 72 h ( p = 0.02) postoperatively, and greater patient satisfaction at 24 ( p = 0.04), 48 ( p = 0.02), and 72 h ( p = 0.02) postoperatively. Conclusions Our technique may facilitate the use of uniportal thoracoscopy for treatment of primary spontaneous pneumothorax, reducing neurological sequelae and improving patient satisfaction compared to the traditional three-port thoracoscopy.

Background: Assessment of intrinsic dynamic positive end-expiratory pressure (PEEPi,dyn) may be clinically important in stable patients with chronic obstructive pulmonary disease (COPD), but epidemiological data are scant. Objectives: The aim of our study was (i) to assess the PEEPi,dyn in a large population of stable patients with COPD and (ii) to evaluate the correlations with some noninvasive measurements routinely assessed. Method: Retrospective analysis of lung mechanics, dynamic volumes, arterial blood gases, dyspnoea by means of the Medical Research Council (MRC) scale, the COPD Assessment Test score, and maximal inspiratory/expiratory pressures in 87 hypercapnic and 62 normocapnic patients. Results: The mean PEEPi,dyn was significantly higher in hypercapnic than normocapnic patients (2.8 ± 2.2 vs. 1.9 ± 1.6 cm H2O, respectively, p = 0.0094). PEEPi,dyn did not differ according to Global Initiative for Chronic Obstructive Lung Disease stage, MRC score, or use or not of long-term oxygen therapy. There were significant although weak correlations between PEEPi,dyn and airway obstruction, hyperinflation, respiratory muscle function, arterial CO2 tension, and number of exacerbations/year. The transdiaphragmatic pressure was the strongest variable associated to PEEPi,dyn (R = 0.5713, p = 0.001). Conclusion: In stable patients with COPD, PEEPi,dyn is higher in hypercapnic patients and weakly correlated to noninvasive measures of lung and respiratory muscle function.

In recent years, high flow nasal cannula is being increasingly used. Most studies showed positive results when used in hypoxaemic respiratory failure. Its use in a patient with a large endobronchial mass has not yet being described. We report a patient who presented with hemoptysis and hypoxaemic respiratory failure second to a large mass obstructing the right main bronchus. High flow oxygen via nasal cannula was initiated with a quick improvement of the hemoptysis and the oxygen saturation. Thus, allowing the patient to be rapidly stabilized.

Objective: Sniff nasal inspiratory pressure (SNIP), a useful tool for the assessment of diaphragm function in patients with Amyotrophic Lateral Sclerosis (ALS), is usually performed together with l...

We reported the case of a 55-year-old man with a large tracheal lobular capillary haemangioma attached to posterior tracheal wall and successfully managed with arterial embolization followed by endoscopic resection using Harmonic™ ACE Plus. Because of the high risk of bleeding, Harmonic™ was used in this case due to its ability to cut and cauterize simultaneously. The instrument jaw repeatedly grasped the attachment point of tumor, and then the cavitation effect, created by the longitudinal vibration of the blade tip, separated it from the posterior tracheal wall, reducing the risk of perforation. Yet, the ultrasonic energy denatured proteins and coagulated the vessels, preventing the bleeding during resection. No complications occurred during and after the procedure. Twelve-month follow-up showed no recurrence.

Background: Noninvasive mechanical ventilation (NIV) is an effective treatment in patients with neuromuscular diseases (NMD) to improve symptoms, quality of life, and survival. Summary: NIV should be used early in the course of respiratory muscle involvement in NMD patients and its requirements may increase over time. Therefore, training on technical equipment at home and advice on problem solving are warranted. Remote monitoring of ventilator parameters using built-in ventilator software is recommended. Telemedicine may be helpful in reducing hospital admissions. Anticipatory planning and palliative care should be carried out to lessen the burden of care, to maintain or withdraw from NIV, and to guarantee the most respectful management in the last days of NMD patients’ life. Key Message: Long-term NIV is effective but challenging in NMD patients. Efforts should be made by health care providers in arranging a planned transition to home and end-of-life discussions for ventilator-assisted individuals and their families.

COVID-19 survivors are associated with acute respiratory failure (ARF) and show a high prevalence of impairment in physical performance. The present studied aimed to assess whether we may cluster these individuals according to an exercise test. The presented study is a retrospective analysis of 154 survivors who were admitted to two hospitals of Istituti Clinici Scientifici Maugeri network, Italy. Clinical characteristics, walked distance, heart rate (HR), pulse oximetry (SpO2), dyspnoea, and leg fatigue (Borg scale: Borg-D and Borg-F, respectively) while performing the six-minute walking test (6MWT) were entered into unsupervised clustering analysis. Multivariate linear regression identified variables that were informative for the set of variables used for cluster definition. Cluster 1 (C1: 86.4% of participants) and Cluster 2 (C2: 13.6%) were identified. Compared to C1, the individuals in C2 were significantly older, showed significantly higher increase in fatigue and in dyspnoea, greater reduction in SpO2, and a lower HRpeak during the test. The need of walking aids, time from admission to acute care hospitals, age, body mass index, endotracheal intubation, baseline HR and baseline Borg-D, and exercise-induced SpO2 change were significantly associated with the variables that were used for cluster definition. Different characteristics and physiological parameters during the 6MWT characterise survivors of COVID-19-associated ARF. These results may help in the management of the long-term effects of the disease.

ALS patients should discuss the issue of tracheostomy before the onset of terminal respiratory failure. While the process of shared decision-making is desirable, there are few data on the practical application of this real-life situation.To determine how a decision-making process is actually carried out, we analysed the episodes of acute respiratory failure preceding tracheostomy.We studied the charts of a group of ALS patients after tracheostomy. An interview focusing on the existence of anticipated directives was carried out. Tracheostomies were classified as planned or unplanned according to the presence of a decision plan.A total of 209 ALS patients were cared for during a three-year period. Of these patients, 34 (16%) were tracheotomised. In 38% of cases, tracheostomy was planned, 41% were unplanned, and 21% remained undiagnosed.A minority of ALS patients make a voluntary decision for tracheostomy before the procedure is conducted. The advising process of care still presents limits that have been thus far poorly addressed. In the future, we will need to develop guidelines for the timing and content of the shared-decision making process.

Objective The study aimed to evaluate whether high-flow oxygen therapy (HFOT) during training was more effective than oxygen in improving exercise capacity in hypoxemic chronic obstructive pulmonary disease (COPD). Methods A total of 171 patients with COPD and chronic hypoxemia were consecutively recruited in 8 rehabilitation hospitals in a randomized controlled trial. Cycle-ergometer exercise training was used in 20 supervised sessions at iso inspiratory oxygen fraction in both groups. Pre- and post-training endurance time (Tlim), 6-minute walking distance (6MWD), respiratory and limb muscle strength, arterial blood gases, Barthel Index, Barthel Dyspnea Index, COPD Assessment Test, Maugeri Respiratory Failure questionnaire, and patient satisfaction were evaluated. Results Due to 15.4% and 24.1% dropout rates, 71 and 66 patients were analyzed in HFOT and Venturi mask (V-mask) groups, respectively. Exercise capacity significantly improved after training in both groups with similar patient satisfaction. Between-group difference in post-training improvement in 6MWD (mean: 17.14 m; 95% CI = 0.87 to 33.43 m) but not in Tlim (mean: 141.85 seconds; 95% CI = −18.72 to 302.42 seconds) was significantly higher in HFOT. The minimal clinically important difference of Tlim was reached by 47% of patients in the V-mask group and 56% of patients in the HFOT group, whereas the minimal clinically important difference of 6MWD was reached by 51% of patients in the V-mask group and 69% of patients in the HFOT group, respectively. Conclusion In patients with hypoxemic COPD, exercise training is effective in improving exercise capacity. Impact Statement The addition of HFOT during exercise training is not more effective than oxygen through V-mask in improving endurance time, the primary outcome, whereas it is more effective in improving walking distance.

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

Herein, we report a new technique of middle lobe fixation using Hemopatch after thoracoscopic right upper lobectomy. A 3–0 atraumatic polypropylene suture is passed first through the Hemopatch, then two not-inflated lobes, and then again patch. The lung is half-inflated, and the Hemopatch is placed onto the surface of the two half-inflated lobes in a bridging manner over the fissure. The suture is then tied by a clip. This procedure was successfully applied in five consecutive patients after thoracoscopic right upper lobectomy for cancer. No complications occurred during and after operation.

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

High flow nasal cannula (HFNC) was shown to washout the anatomical dead space, permitting a higher fraction of minute ventilation to participate in gas pulmonary exchanges. Moreover, it is able to guarantee the desired inhaled oxygen fraction (FiO2) even at high level of patient's minute ventilation by minimizing the room air entrainment. The effect of HFNC has never been investigated on stable severe COPD patients in term of endurance capacity with standardised laboratory tests.We performed, in a randomized crossover study, two constant load exercise tests at the 75% of maximum workload achieved at a previous incremental exercise test on cycle-ergometer: with (HFNC-test) and without HFNC (Control-test). Both constant load tests were fulfilled at the same inhaled oxygen fraction (isoFiO2).The endurance time significantly increased in the HFNC-test compared to the Control-test (the mean difference between the two groups was 109 ± 104 s, p 0.015). At iso-time, HFNC-test showed a better oxygen saturation (95 ± 3% vs 89 ± 3%, respectively, p 0.005) either in the subgroup of patients who used supplemental oxygen and in the subgroup who did not. Moreover, a significantly lower dyspnea (median of 5.5 vs 10, respectively, p = 0.002) and leg fatigue score (median of 5 vs 9.5, p = 0.002) was recorded at iso-time during HFNC-test.HFNC may improve the exercise performance in severe COPD patients with ventilatory limitation. This effect is associated to an improvement of SaO2 and perceived symptoms at iso-time. In a Pulmonary Rehabilitation program HFNC may allow a given high intensity load to be sustained for a longer time with less symptoms.

Discussion about patients' end-of-life (E-o-L) preferences should be part of the routine practice. Using a semi-structured interview with a scenario-based decision, we performed a prospective multicentre study to elicit the patients' E-o-L preferences in very severe chronic obstructive pulmonary disease (COPD). We also checked their ability to retain this information and the respect of their decisions when they die. Forty-three out of ninety-one of the eligible patients completed the study. The choice of E-o-L practice was equally distributed among the three proposed options: endotracheal intubation (ETI), 'ceiling' non-invasive ventilation (NIV), and palliation of symptoms with oxygen and morphine. NIV and ETI were more frequently chosen by patients who already experienced them. ETI preference was also associated with the use of anti-depressant drugs and a low educational level, while a higher educational level and a previous discussion with a pneumologist significantly correlated with the preference for oxygen and morphine. Less than 50% of the patients retained a full comprehension of the options at 24 hours. About half of the patients who died in the follow-up period were not treated according to their wishes. In conclusion, in end-stage COPD more efforts are needed to improve communication, patients' knowledge of the disease and E-o-L practice.

Non-small-cell lung carcinomas (NSCLC) is the most common type of lung cancer and it has a poor prognosis, because overall survival after 5 years is 20-25% for all stages. Thus, it is extremely important to increase the survival rate in the early stages NSCLC by focusing on novel screening tests of cancer identifying specific biomarkers expression associated with a more accurate tumor staging and patient prognosis. In this study, we focused our attention on quantitative proteomics of three heavily glycosylated serum proteins: AMBP,α2 macroglobulin, and SERPINA1. In particular, we analyzed serum samples from 20 NSCLC lung adenocarcinoma cancer patients in early and advanced stages, and 10 healthy donors to obtain a relative quantification through the MRM analysis of these proteins that have shown to be markers of cancer development and progression. AMBP, α2 macroglobulin, and SERPINA1 were chosen because all of them possess endopeptidase inhibitor activity and play key roles in cancer. We observe a variation in the expression of these proteins linked to the stage of the disease. Therefore, we believe that proteins like α2 macroglobulin, αmicroglobulin/bikunin, and SERPINA1 could be useful biomarkers for early detection of lung cancer and in monitoring its evolution.

BACKGROUND: Humidification is a standard of care during invasive mechanical ventilation. Two types of devices are used for this purpose: heated humidifiers and heat-and-moisture exchangers (HME). AIM: To compare the short-term physiologic effects of an active HME, with those of heated humidifiers and HMEs in terms of respiratory effort, ventilatory pattern, and arterial blood gases during invasive mechanical ventilation. METHODS: We conducted a randomized crossover study with 3 different devices in 15 stable subjects who had a tracheostomy and were ventilator-dependent. Transdiaphragmatic pressure, ventilatory pattern, arterial blood gases, and dyspnea scale were recorded at baseline and at the end of a 20-min period with each device. RESULTS: Compared with heated humidifiers, the active HME was associated with higher diaphragmatic pressure-time product per minute (117.10 [interquartile range {IQR} 34.58–298.60]) versus 80.86 (IQR, 25.46–110.55) cm H2O×s/min, P = .01), higher PaCO2 (48.50 [IQR, 40.65–53.70] vs 39.60 [IQR, 37.50–49.95]) mm Hg, P = .02) and lower pH (7.41 [IQR, 7.36–7.49] vs 7.45 [IQR, 7.40–7.51], P = .030) without any significant difference in ventilatory pattern. A significantly worse dyspnea scale score (active HME, 3 (2–4) vs heated humidifiers: 4 (3–5); P = .009) was also observed. No significant differences were seen between active HME and HME. CONCLUSIONS: This study indicated that, compared with the heated humidifiers, the use of the active HME or the HME increased inspiratory effort, PaCO2, pH, and dyspnea in stable subjects who were tracheostomized and ventilator-dependent.

Background: The management of lung abscess may be a challenge in elderly patients undergoing chemotherapy and/or radiotherapy for previous malignancy. Herein, we reported a case series of elderly patients with previous lymphoma undergoing endoscopic treatment followed by pulmonary rehabilitation for lung abscess. Methods: Our study population included a consecutive series of elderly patients with previous lymphoma and lung abscess. Suppurative infection was refractory with specific antibiotic therapy. In all cases, drainage was endoscopically inserted in lung abscess via video-bronchoscopy. This strategy allowed performing daily therapy with the installation of gentamicin directly into the abscess cavity. All patients underwent a respiratory rehabilitation program to speed up convalescence and allow early discharge. Results: After positioning the catheter through a bronchoscopic route and subsequent washing with gentamicin, all the patients in our study showed an improvement in clinical conditions with resolution of fever within a few days of starting the procedure with normalization of blood tests (mean hospital length 7 &plusmn, 0.73 days). A follow-up chest computed tomography scan showed a resolution of lung abscess within a mean of 27 &plusmn, 1.53 days. Conclusions: Endoscopic treatment with a rehabilitation program may be a valuable strategy for the management of lung abscess that is refractory to standard antibiotic therapy. Further and larger studiesshould be done to confirm our results.

The aim of our study was to evaluate the prevalence and predictors of obstructive sleep apnea (OSA) in patients with chronic obstructive pulmonary disease (COPD) undergoing inpatient pulmonary rehabilitation programs (PRPs). A retrospective data review of consecutive stable patients with a known diagnosis of COPD, admitted for PRP between January 2007 and December 2013. Full overnight polysomnography (PSG) and Epworth Sleepiness Scale (ESS) were assessed in all patients. Out of 422 evaluated patients, 190 (45%) showed an Apnea Hypopnea Index (AHI) ≥ 15 events/hour and underwent OSA treatment. Patients with OSA were significantly younger and had a less severe airway obstruction as compared to patients without OSA. There were no significant differences in cardiac comorbidities nor in arterial blood gases. As expected, patients with OSA showed significantly more severe diurnal symptoms, as assessed by the ESS and higher body mass index (BMI). However, only 69 out of 190 patients with OSA (36.3%) showed an ESS10, whereas 25% of them had BMI ≤25 and 41% of them had a BMI30. In all, 68% of patients with OSA were discharged with continuous positive airway pressure (CPAP), 15% with Bilevel ventilation, and 17% without any ventilatory treatment. In conclusion, in the population studied, the combination of OSA and COPD was frequent. BMI and ESS values commonly considered cutoff values for the prediction of OSA in the general population may not be accurate in a subgroup of patients with COPD.

BACKGROUND: Until recently, it has been considered essential to maintain the use of a double-limb circuit in patients with amyotrophic lateral sclerosis (ALS) to avoid rebreathing expired air during invasive mechanical ventilation. Currently, life-sustaining home ventilators can work with a single, lighter circuit that is easier to manage. Our aim was to evaluate the effectiveness and safety of a single-limb circuit with intentional leaks (passive circuit) in comparison with a circuit with an expiratory valve (active circuit), in subjects with ALS who use invasive home ventilation. METHODS: We conducted a retrospective single-center study. The enrolled subjects were divided into 2 groups according to the type of exhalation port. The aim of the study was to compare arterial blood gases; nocturnal oxygen saturation recordings; and the occurrence of adverse events, both clinical and technical events. In addition, we compared the rate of mortality and unplanned hospital admissions that occurred within a year after discharge from the hospital. RESULTS: Forty-three subjects were included in our study: 23 who used a passive circuit and 20 who used an active circuit. No significant difference in nocturnal and diurnal gas exchanges was detected. The incidence of adverse events was significantly higher in the active circuit group (85% in active circuit vs 30% in passive circuit, P CONCLUSIONS: The passive circuit was shown to be as effective and safe as the active circuit during home invasive ventilation in the subjects with amyotrophic lateral sclerosis. A future randomized controlled study is necessary to confirm these results and to extend indications to other pathologies.

BACKGROUND: A recent study found that activation of disconnection and low-pressure alarms is common during mouthpiece ventilation and may represent a major limitation to its use. The aim of this bench study was: (1) to investigate the technical aspects that can influence the setting of the ventilator during mouthpiece ventilation and (2) to provide a practical setting strategy to avoid the alarm activation. METHODS: Eight life-support ventilators able to deliver volume controlled ventilation were tested in a bench study using a single-limb non-vented circuit configuration connected to a standard mouthpiece. Disconnection and apnea alarm were turned off or set at the least sensitive setting. The backup frequency was set at the lowest available level. Different tidal volumes (VT) (from 500 to 1,200 mL) were tested with the rectangular and descending flow shape. For each VT, we reported the maximum set inspiratory time (TI) that allowed preventing activation of the low-pressure alarm. The presence of auto-triggering was also surveyed. RESULTS: We found that a correct combination of VT and TI avoided the activation of disconnection and low-pressure alarms in all but 3 ventilators. One ventilator did not allow mouthpiece ventilation independently from the settings used. The inability to turn off the apnea alarm in two other ventilators led to the alarm going off in any tested conditions after 120 s without triggered breaths. Auto-triggering was seldom found and easily worked out, except for in one ventilator. CONCLUSIONS: An appropriate alarm setting and combination of VT and TI would allow the majority of the tested ventilators to be used for mouthpiece ventilation without alarm activation.

PURPOSE: Over the last two decades, noninvasive ventilation (NIV) has been proposed in various causes of acute respiratory failure (ARF) but some indications are debated. Current trends in NIV use are unknown. METHODS: Comparison of three multicenter prospective audits including all patients receiving mechanical ventilation and conducted in 1997, 2002, and 2011 in francophone countries. RESULTS: Among the 4132 patients enrolled, 2094 (51%) required ventilatory support for ARF and 2038 (49 %) for non-respiratory conditions. Overall NIV use was markedly increased in 2010/11 compared to 1997 and 2002 (37% of mechanically ventilated patients vs. 16% and 28%, P < 0.05). In 2010/11, the use of first-line NIV for ARF had reached a plateau (24% vs. 16% and 23%, P < 0.05) whereas pre-ICU and post-extubation NIV had substantially increased (11% vs. 4% and 11% vs. 7%, respectively, P < 0.05). First-line NIV remained stable in acute-on-chronic RF, continued to increase in cardiogenic pulmonary edema, but decreased in de novo ARF (16% in 2010/11 vs. 23% in 2002, P < 0.05). The NIV success rate increased from 56% in 2002 to 70% in 2010/11 and remained the lowest in de novo ARF. NIV failure in de novo ARF was associated with increased mortality in 2002 but not in 2010/11. Mortality decreased over time, and overall, NIV use was associated with a lower mortality. CONCLUSION: Increases in NIV use and success rate, an overall decrease in mortality, and a decrease of the adverse impact NIV failure has in de novo ARF suggest better patient selection and greater proficiency of staff in administering NIV. TRIAL REGISTRATION: Clinicaltrials.gov Identifier NCT01449331.

Ventilation with continuous positive airway pressure (CPAP) is the gold standard therapy for obstructive sleep apnea (OSA). However, it was recently suggested that a novel mode of ventilation, Bilevel-auto, could be equally effective in treating patients unable to tolerate CPAP. The aim of this study was to investigate the ability of Bilevel-auto to treat OSA patients whose nocturnal ventilatory disturbances are not completely corrected by CPAP.We enrolled 66 consecutive OSA patients, not responsive to (group A) or intolerant of (group B) CPAP treatment, after a full night of manual CPAP titration in a laboratory. Full polysomnography data and daytime sleepiness score were compared for each group in the three different conditions: basal, during CPAP, and during Bilevel-auto.The apnea-hypopnea index decreased significantly during CPAP in both groups; however, in the group A, there was a further significant improvement during Bilevel-auto. The same trend was observed for oxygenation indices, while the distribution and the efficiency of sleep did not differ following the switch from CPAP to Bilevel-auto.This study confirmed the role of Bilevel-auto as an effective therapeutic alternative to CPAP in patients intolerant of this latter mode of ventilation. Moreover, extending the use of Bilevel-auto to those OSA patients not responsive to CPAP, we showed a significantly better correction of nocturnal respiratory disturbances.

Objectives The aim of this study is to compare the accuracy of the standard visual scoring of computed tomography (CT) scans with a cloud-based quantitative CT analysis that uses the StratX software, to measure collateral ventilation and, thus, predict lobar atelectasis after valve treatment. Methods This is a retrospective, multicentre study of patients who had previously undergone valve treatment for severe heterogeneous emphysema and whose required fissure integrity ≥90% had been qualitatively scored by visual assessment of CT scans. For this study, all preprocedural CT scans were retrospectively analysed using the StratX software to provide quantitative scores of fissure integrity. The diagnostic accuracies of the visual and quantitative scores for predicting a target lobe volume reduction (TLVR) of ≥350 ml were calculated and statistically compared, as this level of volume reduction can be achieved only with sound fissure integrity. The clinical outcome of TLVR was also evaluated according to the minimal clinically important difference criteria. Results Eighty-three patients were included in the analysis. Of them, 65 of 83 (78%) patients presented with TLVR ≥350 ml. Visual scoring correctly identified the absence of collateral ventilation in 65 of 83 (78%) cases but failed in 18 of 83 (22%) cases. Of these 18 patients, quantitative analysis showed that 16 of 18 (89%) patients did not present completeness of the fissure. The diagnostic accuracy of the quantitative analysis was better than that of the visual analysis (96.4% vs 78.3%; P = 0.0003). Only patients having TLVR ≥350 ml met or exceeded the minimal clinically important difference criteria. Conclusions The quantitative analysis using the StratX software contributed a more objective and efficient evaluation of collateral ventilation that would have improved the selection of emphysematous patients for endobronchial valve treatment in the study population.

Background Noninvasive ventilation is used worldwide in many settings. Its effectiveness has been proven for common clinical conditions in critical care such as cardiogenic pulmonary edema and chronic obstructive pulmonary disease exacerbations. Since the first pioneering studies of noninvasive ventilation in critical care in the late 1980s, thousands of studies and articles have been published on this topic. Interestingly, some aspects remain controversial (e.g. its use in de-novo hypoxemic respiratory failure, role of sedation, self-induced lung injury). Moreover, the role of NIV has recently been questioned and reconsidered in light of the recent reports of new techniques such as high-flow oxygen nasal therapy. Methods We conducted a survey among leading experts on NIV aiming to 1) identify a selection of 10 important articles on NIV in the critical care setting 2) summarize the reasons for the selection of each study 3) offer insights on the future for both clinical application and research on NIV. Results The experts selected articles over a span of 26 years, more clustered in the last 15 years. The most voted article studied the role of NIV in acute exacerbation chronic pulmonary disease. Concerning the future of clinical applications for and research on NIV, most of the experts forecast the development of innovative new interfaces more adaptable to patients characteristics, the need for good well-designed large randomized controlled trials of NIV in acute “de novo” hypoxemic respiratory failure (including its comparison with high-flow oxygen nasal therapy) and the development of software-based NIV settings to enhance patient-ventilator synchrony. Conclusions The selection made by the experts suggests that some applications of NIV in critical care are supported by solid data (e.g. COPD exacerbation) while others are still waiting for confirmation. Moreover, the identified insights for the future would lead to improved clinical effectiveness, new comparisons and evaluation of its role in still “lack of full evidence” clinical settings. Electronic supplementary material The online version of this article (10.1186/s12871-017-0409-0) contains supplementary material, which is available to authorized users.

Symptoms, clinical course, functional and biological data during an exacerbation of chronic obstructive pulmonary disease (EXCOPD) have been investigated, but data on physiological changes of respiratory mechanics during a severe exacerbation with respiratory acidosis requiring noninvasive mechanical ventilation (NIMV) are scant. The aim of this study was to evaluate changes of respiratory mechanics in COPD patients comparing data observed during EXCOPD with those observed during stable state in the recovery phase. In 18 COPD patients having severe EXCOPD requiring NIMV for global respiratory failure, we measured respiratory mechanics during both EXCOPD (T0) and once the patients achieved a stable state (T1). The diaphragm and inspiratory muscles effort was significantly increased under relapse, as well as the pressure-time product of the diaphragm and the inspiratory muscle (PTPdi and PTPes). The resistive loads to breathe (i.e., PEEPi,dyn, compliance and inspiratory resistances) were also markedly increased, while the maximal pressures generated by the diaphragm and the inspiratory muscles, together with forced expired volumes were decreased. All these indices statistically improved but with a great intrasubject variability in stable condition. Moreover, tension-time index (TTdi) significantly improved from the EXCOPD state to the condition of clinical stability (0.156 ± 0.04 at T0 vs. 0.082 ± 0.02 at T1 p < 0.001). During an EXCOPD, the load/capacity of the respiratory pump is impaired, and although the patients exhibit a rapid shallow breathing pattern, this does not necessarily correlate with a TTdi ≥ 0.15. These changes are reverted once they recover from the EXCOPD, despite a large variability between patients.

Muscle quality is defined as muscle strength generated per unit muscle mass. If enzyme replacement therapy (ERT) has some effects on type II glycogenosis (GSDII) skeletal muscle pathology, we should be able to measure a change in strength and mass. We conducted a prospective study including 11 patients aged 54.2 ± 11.2 years, referring to a single institution and receiving ERT for ≥2 years. Median Walton score was 3 (2.5-6). Lower limb skeletal muscles were assessed by dynamometry and quantitative muscle MRI. Three segments (anterior thigh, posterior thigh, leg) were analysed separately. Clinical-MRI correlations were searched for at T0, T6/T8, and T18/24. Changes in lean and fat body composition were assessed by bioelectrical impedance analysis. We found that the anterior thigh showed the best therapeutic response, with an improvement in muscle quality (muscle mass: +7.5%, p = 0.035; strength: +45%, p = 0.002). BMI and lean body mass increased (p = 0.007). Patients with low BMI showed a better outcome. Intramuscular fat accumulation significantly progressed in spite of ERT (+3.7%, p = 0.001), especially in the poorly responsive posterior thigh muscles. Both clinical assessment and MRI revealed a definite improvement in the anterior thigh muscles. However, progression of intramuscular fat accumulation during ERT, as well as the limited responsiveness of posterior thigh muscles, suggests the necessity for early treatment intervention. The better outcome of patients with low BMI, if confirmed, may indicate that dietary protocols could be adopted as adjuvant measures to ERT in adult GSDII.

Mitochondria are highly specialized organelles and major players in fundamental aspects of cell physiology. In yeast, energy metabolism and coupling of mitochondrial activity to growth and survival is controlled by the protein kinase A pathway. In higher eukaryotes, modulation of the so-called A-kinase anchor protein (AKAP) complex regulates mitochondrial dynamics and activity, adapting the oxidative machinery and the metabolic pathway to changes in physiological demand. Protein kinases and phosphatases are assembled by AKAPs within transduction units, providing a mechanism to control signaling events at mitochondria and other target organelles. Ubiquitin-mediated proteolysis of signal transducers and effectors provides an additional layer of complexity in the regulation of mitochondria homeostasis. Genetic evidence indicates that alteration of one or more components of these biochemical pathways leads to mitochondrial dysfunction and human diseases. In this review, we focus on the emerging role of AKAP scaffolds and the proteasome pathway in the control of oxidative metabolism, organelle dynamics and the mitochondrial signaling network. These aspects are crucial elements for maintaining a proper energy balance and cellular lifespan.

PTPD1 is a cytosolic nonreceptor tyrosine phosphatase and a positive regulator of the Src-epidermal growth factor transduction pathway. We show that PTPD1 localizes along actin filaments and at adhesion plaques. PTPD1 forms a stable complex via distinct molecular modules with actin, Src tyrosine kinase, and focal adhesion kinase (FAK), a scaffold protein kinase enriched at adhesion plaques. Overexpression of PTPD1 promoted cell scattering and migration, short hairpin RNA-mediated silencing of endogenous PTPD1, or expression of PTPD1 mutants lacking either catalytic activity (PTPD1(C1108S)) or the FERM domain (PTPD1(Delta1-325)) significantly reduced cell motility. PTPD1 and Src catalytic activities were both required for epidermal growth factor-induced FAK autophosphorylation at its active site and for downstream propagation of ERK1/2 signaling. Our findings demonstrate that PTPD1 is a component of a multivalent scaffold complex nucleated by FAK at specific intracellular sites. By modulating Src-FAK signaling at adhesion sites, PTPD1 promotes the cytoskeleton events that induce cell adhesion and migration.

There is no consensus concerning the best system of humidification during long-term noninvasive mechanical ventilation (NIMV). In a technical pilot randomised crossover 12-month study, 16 patients with stable chronic hypercapnic respiratory failure received either heated humidification or heat and moisture exchanger. Compliance with long-term NIMV, airway symptoms, side-effects and number of severe acute pulmonary exacerbations requiring hospitalisation were recorded. Two patients died. Intention-to-treat statistical analysis was performed on 14 patients. No significant differences were observed in compliance with long-term NIMV, but 10 out of 14 patients decided to continue long-term NIMV with heated humidification at the end of the trial. The incidence of side-effects, except for dry throat (significantly more often present using heat and moisture exchanger), hospitalisations and pneumonia were not significantly different. In the present pilot study, the use heated humidification and heat and moisture exchanger showed similar tolerance and side-effects, but a higher number of patients decided to continue long-term noninvasive mechanical ventilation with heated humidification. Further larger studies are required in order to confirm these findings.

AKAP121 focuses distinct signaling events from membrane to mitochondria by binding and targeting cAMP-dependent protein kinase (PKA), protein tyrosine phosphatase (PTPD1), and mRNA. We find that AKAP121 also targets src tyrosine kinase to mitochondria via PTPD1. AKAP121 increased src-dependent phosphorylation of mitochondrial substrates and enhanced the activity of cytochrome c oxidase, a component of the mitochondrial respiratory chain. Mitochondrial membrane potential and ATP oxidative synthesis were enhanced by AKAP121 in an src- and PKA-dependent manner. Finally, siRNA-mediated silencing of endogenous AKAP121 drastically impaired synthesis and accumulation of mitochondrial ATP. These findings indicate that AKAP121, through its role in enhancing cAMP and tyrosine kinase signaling to distal organelles, is an important regulator in mitochondrial metabolism.

Compared with standard medical therapy (SMT), noninvasive ventilation (NIV) does not reduce the need for reintubation in unselected patients who develop respiratory failure after extubation. The goal of this study was to assess whether early application of NIV, immediately after extubation, is effective in preventing postextubation respiratory failure in an at-risk population.Multiple-center, randomized controlled study.Multiple hospitals.Ninety-seven consecutive patients with similar baseline characteristics, requiring48 hrs of mechanical ventilation and considered at risk of developing postextubation respiratory failure (i.e., patients who had hypercapnia, congestive heart failure, ineffective cough and excessive tracheobronchial secretions, more than one failure of a weaning trial, more than one comorbid condition, and upper airway obstruction).After a successful weaning trial, the patients were randomized to receive NIV foror = 8 hrs a day in the first 48 hrs or SMT. Primary outcome was the need for reintubation according to standardized criteria. Secondary outcomes were intensive care unit and hospital mortality, as well as time spent in the intensive care unit and in hospital.Compared with the SMT group, the NIV group had a lower rate of reintubation (four of 48 vs. 12 of 49; p = .027). The need for reintubation was associated with a higher risk of mortality (p.01). The use of NIV resulted in a reduction of risk of intensive care unit mortality (-10%, p.01), mediated by the reduction for the need of reintubation.NIV was more effective than SMT in preventing postextubation respiratory failure in a population considered at risk of developing this complication.

We reviewed data of 208 episodes of acute respiratory failure due to chronic obstructive pulmonary disease treated by non-invasive ventilation (NIV) in our Respiratory Intensive Care Unit (RICU) from its opening in 1992 to 1999.We assessed whether the rate of NIV success, the severity of the disease, and the associated costs changed in this period during which the staff and the equipment did not change.The failure rate was constant over the years (17.2% on average). The severity of the episodes of ARF, defined by pH and APACHE II at admission, worsened during the years. The statistical change point test allowed us to identify 1997 as the year of a significant change in the severity of admission pH and therefore to identify two different periods: 1992-1996 (mean pH = 7.25+/-0.07) and 1997-1999 (7.20+/-0.08; P0.001). In this latter period the risk of failure for a patient with a pH7.25 was threefold lower than in 1992-1996. In 1997-1999 an increasing number of episodes of ARF with a pH7.28 were treated in the Medical Ward (20% vs 60%). This allowed a significant reduction of daily cost per patient treated with NIV (558+/-8 Euros vs 470+/-14 Euros, respectively; P0.01).We conclude that, over time, experience with NIV may progressively allow more severely ill patients to be treated without changing the rate of success. The daily cost of NIV per patient can be reduced by treating less severely ill patients outside the RICU.

In Italy the birth rate decrease together with the continuous improvement of living conditions on one hand, and the health care progress on the other hand, led in recent years to an increasing number of patients with chronic mono- or multi-organ failures and in an extension of their life expectancy. However, the natural history of chronic failures has not changed and the inescapable disease's worsening at the end makes more rare remissions, increasing hospital admissions rate and length of stay. Thus, when the "end-stage" get close clinicians have to engage the patient and his relatives in an advance care planning aimed to share a decision making process regarding all future treatments and related ethical choices such as patient's best interests, rights, values, and priorities. A right approach to the chronic organ failures end-stage patients consists therefore of a careful balance between the new powers of intervention provided by the biotechnology and pharmacology (intensive care), both with the quality of remaining life supplied by physicians to these patients (proportionality and beneficence) and the effective resources rationing and allocation (distributive justice). However, uncertainty still marks the criteria used by doctors to assess prognosis of these patients in order to make decisions concerning intensive or palliative care. The integrated care pathway suggested in this position paper shared by nine Italian medical societies, has to be intended as a guide focused to identify end-stage patients and choosing for them the best care option between intensive treatments and palliative care.

The therapeutic options related to chronic organ failure are interconnected to the variability of human biological responses and the personal history and choices of the chronically ill patient on one hand, and with the variable human answers to therapies on the other hand. All these aspects may explain the small number and low quality of studies aimed to define the clinical criteria useful in identifying end-stage chronically ill patients, as highlighted through the 2012-2013 Medline survey performed by the task force. These results prevented the grading of scientific evidence. However, taking into account the evidence based medicine definition, the task force believes the clinical reasoning and the individual experience of clinicians as well as the patients and families preferences cannot be replaced "tout court" with a strict methodological research. Accordingly, the working method selected by the task force members was to draw up a set of clinical parameters based on the available scientific literature, submitting it to a peer review process carried out by an expert panel. This paper discusses a set of clinical parameters included in the clinical decision-making algorithm and shared by nine medical societies. For each chronic organ failure these clinical parameters should be intended not as a rigid cutoff system to make a choice between two selected care options (intensive vs palliative), rather as the starting point for a joint and careful consideration regarding the opportunity to adopt the clinical decision-making algorithm care proposed in Part I.

Background Pompe’s disease is a progressive myopathy caused by mutations in the lysosomal enzyme acid alphaglucosidase gene (GAA). A wide clinical variability occurs also in patients sharing the same GAA mutations, even within the same family. Methods For a large series of GSDII patients we collected some clinical data as age of onset of the disease, presence or absence of muscular pain, Walton score, 6-Minute Walking Test, Vital Capacity, and Creatine Kinase. DNA was extracted and tested for GAA mutations and some genetic polymorphisms able to influence muscle properties (ACE, ACTN3, AGT and PPARα genes). We compared the polymorphisms analyzed in groups of patients with Pompe disease clustered for their homogeneous genotype. Results We have been able to identify four subgroups of patients completely homogeneous for their genotype, and two groups homogeneous as far as the second mutation is defined “very severe” or “potentially less severe”. When disease free life was studied we observed a high significant difference between groups. The DD genotype in the ACE gene and the XX genotype in the ACTN3 gene were significantly associated to an earlier age of onset of the disease. The ACE DD genotype was also associated to the presence of muscle pain. Conclusions We demonstrate that ACE and ACTN3 polymorphisms are genetic factors able to modulate the clinical phenotype of patients affected with Pompe disease. Electronic supplementary material The online version of this article (doi:10.1186/s13023-014-0102-z) contains supplementary material, which is available to authorized users.

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

Mitochondria are now recognized as one of the main intracellular calcium-storing organelles which play a key role in the intracellular calcium signalling. Indeed, besides performing oxidative phosphorylation, mitochondria are able to sense and shape calcium (Ca(2+)) transients, thus controlling cytosolic Ca(2+) signals and Ca(2+)-dependent protein activity. It has been well established for many years that mitochondria have a huge capacity to accumulate calcium. While the physiological significance of this pathway was hotly debated until relatively recently, it is now clear that the ability of mitochondria in calcium handling is a ubiquitous phenomenon described in every cell system in which the issue has been addressed.In this chapter, we will review the molecular mechanisms involved in the regulation of mitochondrial calcium cycling in physiological conditions with particular regard to the role played by the mitochondrial Na(+)/Ca(2+) exchanger.