High-flow nasal oxygen versus conventional oxygen therapy in patients with COVID-19 pneumonia and mild hypoxaemia: a randomised controlled trial.

RATIONALE: In patients with COVID-19 pneumonia and mild hypoxaemia, the clinical benefit of high-flow nasal oxygen (HFNO) remains unclear. We aimed to examine whether HFNO compared with conventional oxygen therapy (COT) could prevent escalation of respiratory support in this patient population. METHODS: In this multicentre, randomised, parallel-group, open-label trial, patients with COVID-19 pneumonia and peripheral oxygen saturation (SpO2) ≤92% who required oxygen therapy were randomised to HFNO or COT. The primary outcome was the rate of escalation of respiratory support (ie, continuous positive airway pressure, non-invasive ventilation or invasive mechanical ventilation) within 28 days. Among secondary outcomes, clinical recovery was defined as the improvement in oxygenation (SpO2 ≥96% with fractional inspired oxygen (FiO2) ≤30% or partial pressure of arterial carbon dioxide/FiO2 ratio >300 mm Hg). RESULTS: Among 364 randomised patients, 55 (30.3%) of 181 patients assigned to HFNO and 70 (38.6%) of 181 patients assigned to COT underwent escalation of respiratory support, with no significant difference between groups (absolute risk difference -8.2% (95% CI -18% to +1.4%); RR 0.79 (95% CI 0.59 to 1.05); p=0.09). There was no significant difference in clinical recovery (69.1% vs 60.8%; absolute risk difference 8.2% (95% CI -1.5% to +18.0%), RR 1.14 (95% CI 0.98 to 1.32)), intensive care unit admission (7.7% vs 11.0%, absolute risk difference -3.3% (95% CI -9.3% to +2.6%)), and in hospital length of stay (11 (IQR 8-17) vs 11 (IQR 7-20) days, absolute risk difference -1.0% (95% CI -3.1% to +1.1%)). CONCLUSIONS: Among patients with COVID-19 pneumonia and mild hypoxaemia, the use of HFNO did not significantly reduce the likelihood of escalation of respiratory support. TRIAL REGISTRATION NUMBER: NCT04655638.

Bleeding during Learning Curve of Thoracoscopic Lobectomy: CUSUM Analysis Results.

BACKGROUND: The management of intraoperative bleeding during thoracoscopic lobectomy is challenging, especially for non-experienced surgeons. We evaluated intraoperative bleeding in relation to learning curve of thoracoscopic lobectomy, the strategies to face it, the outcomes, and the target case number for gaining the technical proficiency. METHODS: This was a retrospective single center study including consecutive patients undergoing thoracoscopic lobectomy for lung cancer. Based on cumulative sum analysis, patients were divided into early and late experience groups, and the differences on surgical outcomes, with particular focus on vascular injury, were statistically compared. RESULTS: Eight-three patients were evaluated. Cumulative sum charts showed a decreasing of operative time, blood loss, and hospital stay after the 49th, the 43th, and the 39th case, respectively. Early (n = 49) compared with late experience group (n = 34) was associated with higher conversion rate (p = 0.08), longer operative time (p <0.0001), greater blood loss (p <0.0001), higher transfusion rate (p = 0.01), higher postoperative air leak rate (p = 0.02), longer chest tube stay (p <0.0001), and hospitalization (p <0.0001). Six patients (7%) had intraoperative bleeding during early phase of learning curve, successfully treated by thoracoscopy in four cases. Patients with vascular injury (n = 6) compared with control group (n = 77) presented a longer operative time (p = 0.003), greater blood loss (p = 0.0001), and higher transfusion rate (p = 0.001); no significant differences were found regarding postoperative morbidity (p = 0.57), length of chest tube stay (p = 0.07), and hospitalization (p = 0.07). CONCLUSION: Technical proficiency was achieved after 50 procedures. All vascular injuries occurred in the early phase of learning curve; they were safely managed, without affecting surgical outcomes.

Long-term home noninvasive ventilation (LTHNIV) in restrictive thoracic diseases: the Italian snapshot.

Long-term home noninvasive ventilation (LTHNIV) in restrictive thoracic diseases was explored via the recently published international REINVENT ERS survey. The Italian subset of respondents (ITA-r), the highest above all participating nations, was analyzed and compared to non-Italian respondents (NO-ITA-r). The ITA-r represented 20% of the total answers examined. Ninety-four percent were physicians, whose half worked in a respiratory ICU (RICU). ITA-r mainly worked in community hospitals vs NO-ITA-r who are largely affiliated with university hospitals (p<0.0001). Amyotrophic lateral sclerosis (ALS) was considered the most common medical condition leading to NIV indication by both ITA-r and NO-ITA-r (93% vs 78%, p>0.5). A greater proportion of ITA-r considered MIP/MEP the most important test for NIV initiation as compared to NO-ITA-r (p<0.05). There was no significant difference for both ITA-r and NO-ITA-r as regards the other questions. This study illustrates Italian LTHNIV practices in patients with NMD and it shows some important differences with the other countries' practices but agreement in terms of goals to achieve, reasons to initiate NIV, and practices among the two communities.

Portable High-Flow Nasal Oxygen during Walking in Patients with Severe Chronic Obstructive Pulmonary Disease: A Randomized Controlled Trial.

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) <0.60 during exercise, randomly underwent 2 6MWT carrying a rollator, under either HFNO with a portable device (HFNO test) or oxygen supplementation by a Venturi mask (Control) at isoFiO2. 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.

Pulmonary Hamartoma Associated With Lung Cancer (PHALC Study): Results of a Multicenter Study.

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 < 0.0001) were the significant risk factors for lung cancer. 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.

Hemopatch to Fix Mobile Lobe after Thoracoscopic Lobectomy.

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.

Feasibility and clinical impact of out-of-ICU noninvasive respiratory support in patients with COVID-19-related pneumonia.

INTRODUCTION: The severe acute respiratory syndrome-coronavirus 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 and the feasibility and outcomes of NRS applied to patients outside the ICU. METHODS: In this observational study, data from 670 consecutive patients with confirmed coronavirus disease 2019 referred to pulmonology units in nine hospitals between March 1 and May 10, 2020 were analysed. Data collected included medication, mode and usage of 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: 42 (11.1%) healthcare workers tested positive for infection, but only three of them required hospitalisation. Data are reported for all patients (69.3% male), whose mean±sd age was 68±13 years. The arterial oxygen tension/inspiratory oxygen fraction ratio at baseline was 152±79, and the majority (49.3%) of patients were treated with CPAP. The overall unadjusted 30-day mortality rate was 26.9%, with 16%, 30% and 30% for HFNC, CPAP and NIV, respectively, while the total ETI rate was 27%, with 29%, 25% and 28%, respectively; the relative probability of death 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.

High flow nasal therapy versus noninvasive ventilation as initial ventilatory strategy in COPD exacerbation: a multicenter non-inferiority randomized trial.

BACKGROUND: The efficacy and safety of high flow nasal therapy (HFNT) in patients with acute hypercapnic exacerbation of chronic obstructive pulmonary disease (AECOPD) are unclear. Our aim was to evaluate the short-term effect of HFNT versus NIV in patients with mild-to-moderate AECOPD, with the hypothesis that HFNT is non-inferior to NIV on CO2 clearance after 2 h of treatment. METHODS: We performed a multicenter, non-inferiority randomized trial comparing HFNT and noninvasive ventilation (NIV) in nine centers in Italy. Patients were eligible if presented with mild-to-moderate AECOPD (arterial pH 7.25-7.35, PaCO2 ≥ 55 mmHg before ventilator support). Primary endpoint was the mean difference of PaCO2 from baseline to 2 h (non-inferiority margin 10 mmHg) in the per-protocol analysis. Main secondary endpoints were non-inferiority of HFNT to NIV in reducing PaCO2 at 6 h in the per-protocol and intention-to-treat analysis and rate of treatment changes. RESULTS: Seventy-nine patients were analyzed (80 patients randomized). Mean differences for PaCO2 reduction from baseline to 2 h were - 6.8 mmHg (± 8.7) in the HFNT and - 9.5 mmHg (± 8.5) in the NIV group (p = 0.404). By 6 h, 32% of patients (13 out of 40) in the HFNT group switched to NIV and one to invasive ventilation. HFNT was statistically non-inferior to NIV since the 95% confidence interval (CI) upper boundary of absolute difference in mean PaCO2 reduction did not reach the non-inferiority margin of 10 mmHg (absolute difference 2.7 mmHg; 1-sided 95% CI 6.1; p = 0.0003). Both treatments had a significant effect on PaCO2 reductions over time, and trends were similar between groups. Similar results were found in both per-protocol at 6 h and intention-to-treat analysis. CONCLUSIONS: HFNT was statistically non-inferior to NIV as initial ventilatory support in decreasing PaCO2 after 2 h of treatment in patients with mild-to-moderate AECOPD, considering a non-inferiority margin of 10 mmHg. However, 32% of patients receiving HFNT required NIV by 6 h. Further trials with superiority design should evaluate efficacy toward stronger patient-related outcomes and safety of HFNT in AECOPD. TRIAL REGISTRATION: The study was prospectively registered on December 12, 2017, in ClinicalTrials.gov (NCT03370666).

Intrinsic Dynamic Positive End-Expiratory Pressure in Stable Patients with Chronic Obstructive Pulmonary Disease.

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.

Hemoptysis due to a large endobronchial mass successful regression after the use of high flow nasal cannula.

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.

Proteomics analysis of human serum of patients with non-small-cell lung cancer reveals proteins as diagnostic biomarker candidates.

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.

Framework for patient-ventilator asynchrony during long-term non-invasive ventilation.

Episodes of patient-ventilator asynchrony (PVA) occur during acute and chronic non-invasive positive pressure ventilation (NIV). In long-term NIV, description and quantification of PVA is not standardised, thus limiting assessment of its clinical impact. The present report provides a framework for a systematic analysis of polygraphic recordings of patients under NIV for the detection and classification of PVA validated by bench testing. The algorithm described uses two different time windows: rate asynchrony and intracycle asynchrony. This approach should facilitate further studies on prevalence and clinical impact of PVA in long-term NIV.

European Respiratory Society guidelines on long-term home non-invasive ventilation for management of COPD.

BACKGROUND: While 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 METHODS: The 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. RESULTS: The 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. CONCLUSIONS: Managing 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.

Long-Term Ventilation in Neuromuscular Patients: Review of Concerns, Beliefs, and Ethical Dilemmas.

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.

Prevalence and Predictors of Obstructive Sleep Apnea in Patients with Chronic Obstructive Pulmonary Disease Undergoing Inpatient Pulmonary Rehabilitation.

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 ESS >10, whereas 25% of them had BMI ≤25 and 41% of them had a BMI <30. 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.

Changes of Respiratory Mechanics in COPD Patients from Stable State to Acute Exacerbations with Respiratory Failure.

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.

End-of-Life Discussion, Patient Understanding and Determinants of Preferences in Very Severe COPD Patients: A Multicentric Study.

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.

NCX3 regulates mitochondrial Ca(2+) handling through the AKAP121-anchored signaling complex and prevents hypoxia-induced neuronal death.

The mitochondrial influx and efflux of Ca(2+) play a relevant role in cytosolic and mitochondrial Ca(2+) homeostasis, and contribute to the regulation of mitochondrial functions in neurons. The mitochondrial Na(+)/Ca(2+) exchanger, which was first postulated in 1974, has been primarily investigated only from a functional point of view, and its identity and localization in the mitochondria have been a matter of debate over the past three decades. Recently, a Li(+)-dependent Na(+)/Ca(2+) exchanger extruding Ca(2+) from the matrix has been found in the inner mitochondrial membrane of neuronal cells. However, evidence has been provided that the outer membrane is impermeable to Ca(2+) efflux into the cytoplasm. In this study, we demonstrate for the first time that the nuclear-encoded NCX3 isoform (1) is located on the outer mitochondrial membrane (OMM) of neurons; (2) colocalizes and immunoprecipitates with AKAP121 (also known as AKAP1), a member of the protein kinase A anchoring proteins (AKAPs) present on the outer membrane; (3) extrudes Ca(2+) from mitochondria through AKAP121 interaction in a PKA-mediated manner, both under normoxia and hypoxia; and (4) improves cell survival when it works in the Ca(2+) efflux mode at the level of the OMM. Collectively, these results suggest that, in neurons, NCX3 regulates mitochondrial Ca(2+) handling from the OMM through an AKAP121-anchored signaling complex, thus promoting cell survival during hypoxia.

[Part I. End-stage chronic organ failures: a position paper on shared care planning. The Integrated Care Pathway]. / Parte I. Il percorso clinico e assistenziale nelle insufficienze croniche d'organo "end-stage".Documento di consenso per una pianificazione condivisa delle scelte di cura.

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.