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Background Although patients with AE-ILD and UIP pattern may experience severe acute respiratory failure requiring invasive MV, physiological data on lung mechanics during these events are lacking. We aimed to describe the physiological effect of lung protective ventilation in patients with AE-ILD-UIP and to compare it with primary ARDS.Methods Partitioned lung and chest wall mechanics were compared between patients AE-ILD-UIP and 1:1 matched primary ARDS (based on BMI and PaO2/FiO2 ratio) within a PEEP trial performed within 24 h from intubation and comprising three levels of PEEP [(ZEEP), 4–8 cmH2O (PEEPLOW) and PEEP titrated to achieve positive end-expiratory transpulmonary pressure (PL,EE) (PEEPTITRATED)]Results Ten patients with AE-ILD-UIP and 10 matched with primary ARDS were included. In AE-ILD-UIP median PL,EE at ZEEP was − 4.3 [-7.6 – -2.3] cmH2O and lung elastance (EL) 44 [40–51] cmH2O/L. At PEEPLOW, PL,EE remained negative and EL did not change (p = 0.995) versus ZEEP. At PEEPTITRATED, PL,EE increased to 0.8 [0.3–1.5] cmH2O and EL to 49 [59–43] (p = 0.004 and p LOW, respectively). ΔPL decreased at PEEPLOW (p = 0.018) and increased at PEEPTITRATED (p = 0.003). Differently than AE-ILD-UIP, in ARDS matched controls PEEP titration to obtain a positive PL,EE did not result in changes in EL and ΔPL.Conclusions In mechanically ventilated AE-ILD-UIP, lower PEEP levels did not impact on EL and ΔPL whereas, differently than in patients with primary ARDS, PEEP titrated to obtain a positive PL,EE worsened EL and ΔPL.

In a real-life cohort of patients with AHRF undergoing HFNO, ΔPnose showed excellent accuracy in predicting early failure, similar of that displayed by ROX. Giving that the decision to upgrade to NIV or MV was based on clinical variables, the high accuracy of ROX in predicting failure of HFNO is not surprising. The similar accuracy of ΔPnose (the only measurement that remained blinded to our clinical decision), strengthened the association with outcome, avoiding incorporation bias.

Noninvasive ventilation (NIV) still has high failure rate when used for de novo acute respiratory failure (ARF). Delirium may impact the outcome, however data regarding its incidence, timing of occurrence and clinical predictors in this subset of patients are scarce.Consecutive patients with de novo ARF subjected to NIV were recruited in 10 Italian Respiratory Intensive Care Units (RICUs) and Intensive Care Units (ICUs). Demographics and clinical features, including tolerance to interface and NIV setting were recorded on admission and during stay, whereas delirium onset and type was assessed by the Confusion Assessment Method for ICU (CAM-ICU)-7 scale and Richmond Agitation Sedation Scale (RASS) twice/per day up to a week. The association between clinical variables and the occurrence of delirium and its influence on NIV failure and other clinical outcomes were analyzed.Thirty-two out of 90 enrolled patients (36%) developed delirium over seven days upon admission; median time to onset was 48 hours (24-60). Older age (OR=2.7 [1.9-9], P=0.01), the presence of cancer OR=3.7 [2-5.4], P=0.002), sepsis (OR=1.7 [1.1-3.4], P=0.01), SOFA Score (OR=1.8 [1.1-3.1], P=0.01), low tolerance to interface (OR=3.2 [2.1-5], P=0.002), use of helmet (OR=1.9 [1.2-4.3] P=0.04), and higher PRE-DELIRIC (OR=3.5 [1.3-15], P=0.03) and BORG (OR=1.7 [1.1-4.6], P=0.02] scores were significantly associated with delirium. Delirium had high risk for NIV failure (HR=3.5 95% CI: [1.4-8.6], P=0.0002) and it significantly associated with longer RICU/ICU stay and higher mortality.Delirium onset in acute hypoxic patients undergoing NIV is frequent and negatively affects the outcome. Multiple related clinical factors should be addressed early on admission to prevent the delirium-related risk of NIV failure in these patients.

Despite new therapeutic perspectives, the presence of central airways occlusion (CAO) in patients with locally advanced non-small cell lung cancer (NSCLC) is associated with poor survival. There is no clear evidence on the clinical impact of interventional bronchoscopy as a part of an integrated treatment to cure these patients.This retrospective cohort study was conducted in two teaching hospitals over a 10 years period (January 2010-January 2020) comparing patients with NSCLC at stage IIIB and CAO at disease onset treated with chemotherapy/radiotherapy (standard therapy-ST) with those receiving interventional bronchoscopy plus ST (integrated treatment-IT). Primary outcome was 1-year survival. The onset of respiratory events, symptoms-free interval, hospitalization, need for palliation, and overall mortality served as secondary outcomes.A total of 100 patients were included, 60 in the IT and 40 in the ST group. Unadjusted Kaplan-Meier estimates showed greater effect of IT compared to ST on 1-year survival (HR = 2.1 95%CI[1.1-4.8], p = 0.003). IT showed a significantly higher survival gain over ST in those patients showing KRAS mutation (7.6 VS 0.8 months,0.0001), a lumen occlusion65% (6.6 VS 2.9 months,0.001), and lacking the involvement of left bronchus (7 VS 2.3 months,0.0001). Compared to ST, IT also showed a favorable difference in terms of new hospitalizations (p = 0.03), symptom-free interval (p = 0.02), and onset of atelectasis (p = 0.01).In patients with NSCLC stage IIIB and CAO, additional interventional bronchoscopy might impact on 1-year survival. Genetic and anatomic phenotyping might allow identifying those patients who may gain life expectancy from the endoscopic intervention.

Rehabilitation outcomes of difficult-to-wean tracheostomized patients have been reported in relatively small case studies and described for a limited time span. This study describes the characteristics and clinical outcomes of a large cohort of tracheostomized patients admitted to a specialized weaning unit over 10 years. We retrospectively analyzed data collected from January 2010 to December 2019 on difficult-to-wean tracheostomized patients who underwent comprehensive rehabilitation. Clinical characteristics collected at admission were the level of comorbidity (by the Cumulative Illness Rating Scale—CIRS) and the clinical severity (by the Simplified Acute Physiology Score—SAPS II). The proportions of patients weaned, decannulated, and able to walk; the change in autonomy level according to the Bristol Activities of Daily Living (BADL) Scale; and the setting of hospital discharge was assessed and compared in a consecutive 5-year time period (2010–2014 and 2015–2019) subgroup analysis. A total of 180 patients were included in the analysis. Patient anthropometry and preadmission clinical management in acute care hospitals were similar across years, but the categories of underlying diagnosis changed (p < 0.001) (e.g., chronic obstructive pulmonary disease—COPD—decreased), while the level of comorbidities increased (p = 0.003). The decannulation rate was 45.6%. CIRS and SAPS II at admission were both significant predictors of clinical outcomes. The proportion of patients whose gain in BADL score increased ≥ 2 points decreased over time. This study confirms the importance of rehabilitation in weaning units for the severely disabled subset of tracheostomized patients. Comorbidities and severity at admission are significantly associated with rehabilitation outcomes at discharge.

BACKGROUND/MATERIALS AND METHODS: This retrospective cohort study was conducted in two teaching hospitals over a 3-month period (March 2010-June 2020) comparing severe and critical COVID-19 patients admitted to Respiratory Intensive Care Unit for non-invasive respiratory support (NRS) and subjected to awake prone position (PP) with those receiving standard care (SC). Primary outcome was endotracheal intubation (ETI) rate. In-hospital mortality, time to ETI, tracheostomy, length of RICU and hospital stay served as secondary outcomes. Risk factors associated to ETI among PP patients were also investigated. RESULTS: A total of 114 patients were included, 76 in the SC and 38 in the PP group. Unadjusted Kaplan-Meier estimates showed greater effect of PP compared to SC on ETI rate (HR = 0.45 95% CI [0.2-0.9], p = 0.02) even after adjustment for baseline confounders (HR = 0.59 95% CI [0.3-0.94], p = 0.03). After stratification according to non-invasive respiratory support, PP showed greater significant benefit for those on High Flow Nasal Cannulae (HR = 0.34 95% CI [0.12-0.84], p = 0.04). Compared to SC, PP patients also showed a favorable difference in terms of days free from respiratory support, length of RICU and hospital stay while mortality and tracheostomy rate were not significantly different. CONCLUSIONS: Prone positioning in awake and spontaneously breathing Covid-19 patients is feasible and associated with a reduction of intubation rate, especially in those patients undergoing HFNC. Although our results are intriguing, further randomized controlled trials are needed to answer all the open questions remaining pending about the real efficacy of PP in this setting.

Introduction Chronic Critical Illness (chronic CI) is a condition associated to patients surviving an episode of acute respiratory failure (ARF). The prevalence and the factors associated with the development of chronic CI in the population admitted to a Respiratory Intensive Care Unit (RICU) have not yet been clarified. Methods An observational prospective cohort study was undertaken at the RICU of the University Hospital of Modena (Italy). Patients mechanically ventilated with ARF in RICU were enrolled. Demographics, severity scores (APACHEII, SOFA, SAPSII), and clinical condition (septic shock, pneumonia, ARDS) were recorded on admission. Respiratory mechanics and inflammatory-metabolic blood parameters were measured both on admission and over the first week of stay. All variables were tested as predictors of chronic CI through univariate and multivariate analysis. Results Chronic CI occurred in 33 out of 100 patients observed. Higher APACHEII, the presence of septic shock, diaphragmatic dysfunction (DD) at sonography, multidrug-resistant (MDR) bacterial infection, the occurrence of a second infection during stay, and a C-reactive protein (CRP) serum level inceasing 7 days over admission were associated with chronic CI. Septic shock was the strongest predictor of chronic CI (AUC = 0.92 p Conclusions Chronic CI is frequent in patients admitted to RICU and mechanically ventilated due to ARF. Infection-related factors seem to play a major role as predictors of this syndrome.

Background Although non-invasive mechanical ventilation (NIV) is the gold standard treatment for patients with acute exacerbation of COPD (AECOPD) developing respiratory acidosis, failure rates still range from 5% to 40%. Recent studies have shown that the onset of severe diaphragmatic dysfunction (DD) during AECOPD increases risk of NIV failure and mortality in this subset of patients. Although the imbalance between the load and the contractile capacity of inspiratory muscles seems the main cause of AECOPD-induced hypercapnic respiratory failure, data regarding the influence of mechanical derangement on DD in this acute phase are lacking. With this study, we investigate the impact of respiratory mechanics on diaphragm function in AECOPD patients experiencing NIV failure. Methods Twelve AECOPD patients with respiratory acidosis admitted to the Respiratory ICU of the University Hospital of Modena from 2017 to 2018 undergoing mechanical ventilation (MV) due to NIV failure were enrolled. Static respiratory mechanics and end-expiratory lung volume (EELV) were measured after 30 mins of volume control mode MV. Subsequently, transdiaphragmatic pressure (Pdi) was calculated by means of a sniff maneuver (Pdisniff) after 30 mins of spontaneous breathing trial. Linear regression analysis and Pearson's correlation coefficient served to assess associations. Results Average Pdisniff was 23.3 cmH2O (standard deviation 29 cmH2O) with 3 patients presenting bilateral diaphragm palsy. Pdisniff was directly correlated with static lung elastance (r=0.69, p=0.001) while inverse correlation was found with dynamic intrinsic PEEP (r=-0.73, p=0.007). No significant correlation was found with static intrinsic PEEP (r=-0.55, p=0.06), EELV (r=-0.4, p=0.3), airway resistance (r=-0.2, p=0.54), chest wall, and total elastance (r=-0-01, p=0.96 and r=0.3, p=0.36, respectively). Significant linear inverse correlation was found between Pdisniff and the ratio between Pdi assessed at tidal volume and Pdi sniff (r=-0.82, p=0.02). Conclusion The causes of extreme DD in AECOPD patients who experienced NIV failure might be predominantly mechanical, driven by a severe dynamic hyperinflation that overlaps on an elastic lung substrate favoring volume overload.

Background Excessive inspiratory effort could translate into self-inflicted lung injury, thus worsening clinical outcomes of spontaneously breathing patients with acute respiratory failure (ARF). Although esophageal manometry is a reliable method to estimate the magnitude of inspiratory effort, procedural issues significantly limit its use in daily clinical practice. The aim of this study is to describe the correlation between esophageal pressure swings (ΔPes) and nasal (ΔPnos) as a potential measure of inspiratory effort in spontaneously breathing patients with de novo ARF. Methods From January 1, 2021, to September 1, 2021, 61 consecutive patients with ARF (83.6% related to COVID-19) admitted to the Respiratory Intensive Care Unit (RICU) of the University Hospital of Modena (Italy) and candidate to escalation of non-invasive respiratory support (NRS) were enrolled. Clinical features and tidal changes in esophageal and nasal pressure were recorded on admission and 24 h after starting NRS. Correlation between ΔPes and ΔPnos served as primary outcome. The effect of ΔPnos measurements on respiratory rate and ΔPes was also assessed. Results ΔPes and ΔPnos were strongly correlated at admission (R2 = 0.88, p R2 = 0.94, p Pnos measurement did not result in significant change of respiratory rate and ΔPes. The correlation between measures at 24 h remained significant even after splitting the study population according to the type of NRS (high-flow nasal cannulas [R2 = 0.79, p R2 = 0.95, p Conclusions In a cohort of patients with ARF, nasal pressure swings did not alter respiratory mechanics in the short term and were highly correlated with esophageal pressure swings during spontaneous tidal breathing. ΔPnos might warrant further investigation as a measure of inspiratory effort in patients with ARF. Trial registration: NCT03826797. Registered October 2016.

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).

Lung fibrosis results from the synergic interplay between regenerative deficits of the alveolar epithelium and dysregulated mechanisms of repair in response to alveolar and vascular damage, which is followed by progressive fibroblast and myofibroblast proliferation and excessive deposition of the extracellular matrix. The increased parenchymal stiffness of fibrotic lungs significantly affects respiratory mechanics, making the lung more fragile and prone to non-physiological stress during spontaneous breathing and mechanical ventilation. Given their parenchymal inhomogeneity, fibrotic lungs may display an anisotropic response to mechanical stresses with different regional deformations (micro-strain). This behavior is not described by the standard stress-strain curve but follows the mechano-elastic models of "squishy balls", where the elastic limit can be reached due to the excessive deformation of parenchymal areas with normal elasticity that are surrounded by inelastic fibrous tissue or collapsed induration areas, which tend to protrude outside the fibrous ring. Increasing evidence has shown that non-physiological mechanical forces applied to fibrotic lungs with associated abnormal mechanotransduction could favor the progression of pulmonary fibrosis. With this review, we aim to summarize the state of the art on the relation between mechanical forces acting on the lung and biological response in pulmonary fibrosis, with a focus on the progression of damage in the fibrotic lung during spontaneous breathing and assisted ventilatory support.

Aims The aim of this study was to estimate a 48 hour prediction of moderate to severe respiratory failure, requiring mechanical ventilation, in hospitalized patients with COVID-19 pneumonia. Methods This was an observational prospective study that comprised consecutive patients with COVID-19 pneumonia admitted to hospital from 21 February to 6 April 2020. The patients’ medical history, demographic, epidemiologic and clinical data were collected in an electronic patient chart. The dataset was used to train predictive models using an established machine learning framework leveraging a hybrid approach where clinical expertise is applied alongside a data-driven analysis. The study outcome was the onset of moderate to severe respiratory failure defined as PaO2/FiO2 ratio Results A total of 198 patients contributed to generate 1068 usable observations which allowed to build 3 predictive models based respectively on 31-variables signs and symptoms, 39-variables laboratory biomarkers and 91-variables as a composition of the two. A fourth “boosted mixed model” included 20 variables was selected from the model 3, achieved the best predictive performance (AUC = 0.84) without worsening the FN rate. Its clinical performance was applied in a narrative case report as an example. Conclusion This study developed a machine model with 84% prediction accuracy, which is able to assist clinicians in decision making process and contribute to develop new analytics to improve care at high technology readiness levels.

Background: Noninvasive ventilation (NIV) still has high failure rate when used for acute respiratory failure (ARF). Delirium may impact the outcome, however data regarding its incidence, timing of occurrence and clinical predictors are lacking. Methods: Consecutive patients with ARF subjected to NIV were recruited in 9 Respiratory Intensive Care Units (July 2019-January 2020). Individuals with neurological impairment, established psychiatric or neurological disease, need for immediate intubation, and use of home-NIV were excluded. Demographics and clinical features, including tolerance to interface and NIV setting were recorded on admission, whereas delirium was assessed by the CAM-ICU7 Scale twice/per day up to a week. The impact of baseline variables on the occurrence of delirium and its influence on NIV outcome were analysed. Results: Thirty-two out of 92 enrolled patients (34,7%) developed delirium over 7 days upon admission; time to onset was 32.6 hours (SD=12.6). Sepsis (OR=2.9[1.2-14.5] p=0.01), SOFA score>7 (OR= 3.5[1.6-19.4] p=0.002), low tolerance to interface (OR=1.9[1.1-21.4] p=0.002), use of helmet (OR=4.2[1.7-29] p=0.001), and higher pre-DELIRIC (OR=1.8 [1.1-14]p=0.03) and BORG (OR=2.6[1.4-11.6]p=0.002] scores were significantly associated with delirium. Delirium was highly related with NIV failure (HR=3.5[1.4-8.5] p=0.01). Conclusion: The occurrence of delirium in patients undergoing acute NIV is relevant and negatively affects the outcome. Multiple related clinical factors should be addressed early on admission to prevent the risk of NIV failure in these patients.

Background Machine learning can assist clinicians in forecasting patients with COVID-19 who develop respiratory failure requiring mechanical ventilation. This analysis aimed to determine a 48 hours prediction of moderate to severe respiratory failure, as assessed with PaO2/FiO2 < 150 mmHg, in hospitalized patients with COVID-19 pneumonia. Methods This was an observational study that comprised all consecutive adult patients with COVID-19 pneumonia admitted to the Infectious Diseases Clinic of the University Hospital of Modena, Italy from 21 February to 6 April 2020. COVID-19 was confirmed with PCR positive nasopharyngeal swabs while the presence of pneumonia was radiologically confirmed. Patients received standard of care according to national guidelines for clinical management of SARS-CoV-2 infection. The patients' full medical history, demographic and epidemiological features, clinical data, complete blood count, coagulation, inflammatory and biochemical markers were routinely collected and aggregated in a clinically-oriented logical framework in order to build different datasets. The dataset was used to train a learning framework relying on Microsoft LightGBM and leveraging a hybrid approach, where clinical expertise is applied alongside a data-driven analysis. Shapley Additive exPlanations (SHAP) values were used to quantify the positive or negative impact of each variable included in the model on the predicted outcome. The study outcome was the onset of moderate to severe respiratory failure defined as PaO2/FiO2 ratio < 150 mmHg ([≥] 13.3 kPa) in at least one of two consecutive arterial blood gas analyses in the following 48 hours. Results A total of 198 patients contributed to generate 1068 valuable observations which allowed to build 3 prediction models based respectively on 31-variables signs and symptoms, 39-variables laboratory biomarkers and 91-variables as a composition of the two. A fourth boosted mixed model which included 20 variables was selected from the model 3, achieved the best predictive performance (AUC=0.84). Its clinical performance was applied in a narrative case report as an example. Conclusion This study developed a machine learning algorithm, with a 84% prediction accuracy, which is potentially able to assist clinicians in decision making process with therapeutic implications.

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

Background: No therapy is approved for COVID-19 pneumonia. The aim of this study was to assess the role of tocilizumab in reducing the risk of invasive mechanical ventilation and death in patients with severe COVID-19 pneumonia who received standard of care treatment. Methods: This retrospective, observational cohort study included adults (≥18 years) with severe COVID-19 pneumonia who were admitted to tertiary care centres in Bologna and Reggio Emilia, Italy, between Feb 21 and March 24, 2020, and a tertiary care centre in Modena, Italy, between Feb 21 and April 30, 2020. All patients were treated with the standard of care (ie, supplemental oxygen, hydroxychloroquine, azithromycin, antiretrovirals, and low molecular weight heparin), and a non-randomly selected subset of patients also received tocilizumab. Tocilizumab was given either intravenously at 8 mg/kg bodyweight (up to a maximum of 800 mg) in two infusions, 12 h apart, or subcutaneously at 162 mg administered in two simultaneous doses, one in each thigh (ie, 324 mg in total), when the intravenous formulation was unavailable. The primary endpoint was a composite of invasive mechanical ventilation or death. Treatment groups were compared using Kaplan-Meier curves and Cox regression analysis after adjusting for sex, age, recruiting centre, duration of symptoms, and baseline Sequential Organ Failure Assessment (SOFA) score. Findings: Of 1351 patients admitted, 544 (40%) had severe COVID-19 pneumonia and were included in the study. 57 (16%) of 365 patients in the standard care group needed mechanical ventilation, compared with 33 (18%) of 179 patients treated with tocilizumab (p=0·41; 16 [18%] of 88 patients treated intravenously and 17 [19%] of 91 patients treated subcutaneously). 73 (20%) patients in the standard care group died, compared with 13 (7%; p

Background: In patients developing de novorespiratory failure (DRF) a trial of non-invasive mechanical ventilation (NIV) might be offered in the appropriate clinical setting. Among the other potential predictors of NIV failure, the role of spontaneous breathing is still unexplored under this condition. Aim: To investigate the impact of trans-esophageal pressure (ΔPe) and dynamic transpulmonary pressure (ΔPtp) on NIV failure, as defined by the need for endotracheal intubation, in patients with DRF. Methods: 17 consecutive patients with DRF (P/F ratio Results: On admission average P/F ratio, HACOR score and ΔPtp were 129 (SD 47), 8.2 (SD 4) and 28.6 (SD 11) cmH20, respectively. ΔPes and ΔPes/ΔPtp ratio were significantly lower 2 hours following the onset of NIV start in those patients who succeeded as compared to those who failed. P/F ratio, HACOR score and ΔPtp differed later at 12-hour (see Figure). Conclusion: Pes monitoring during NIV might early identify patients with DRF at major risk for treatment failure.

Background: Chronic Critical Illness (CCI) is a condition associated to patients surviving an acute phase of disease although remaining dependent on mechanical ventilation (MV). The prevalence of CCI among patients with acute respiratory failure (ARF) undergoing MV and the underlying mechanisms have not been elucidated. Methods: We conducted an observational cohort study at our Respiratory Intensive Care Unit (RICU) of the University Hospital of Modena (Italy) from January 2014 to January 2016. Patients with ARF but without any advanced chronic lung disease undergoing MV were enrolled. We pre-specified the prevalence of CCI as the primary outcome; a sample size of 84 patients was analyzed. Diagnosis, clinical severity scores (APACHEII, SOFA, SAPSII, GCS) and conditions (septic shock, infections, ARDS) were recorded on admission. Inflammatory-metabolic blood parameters and their trends within the first days of stay were recorded. All these variables were tested as potential predictors of CCI. Results: CCI was identified in 37% of patients. APACHEII (RR= 2.1), SOFA (RR=1.8), SAPSII (RR=2.5), GCS (RR=2.6), septic shock (RR=15) and infections sustained by MDR bacteria (RR=6.8) were significantly associated with the development of CCI (p Conclusion: CCI is highly prevalent in patients with ARF admitted to a RICU. Severe infection and the persistence of inflammatory status are predictors of CCI development in this setting.

Background Ultrasound (US) evaluation of diaphragmatic dysfunction (DD) has proved to be a reliable technique in critical care. In this single-center prospective study, we investigated the impact of US-assessed DD on noninvasive ventilation (NIV) failure in patients with acute exacerbations of chronic obstructive pulmonary disease (AECOPD) and its correlation with the transdiaphragmatic pressure assessed using the invasive sniff maneuver (Pdi sniff). Methods A population of 75 consecutive patients with AECOPD with hypercapnic acidosis admitted to our respiratory intensive care unit (RICU) were enrolled. Change in diaphragm thickness (ΔTdi)

Purpose: Blunt traumatic chylothorax could be distinguished in CT (Computer Tomography) scan as low attenuated fluid, due to chylomicrons inside, however blood intermixture in chylous effusion could make densitomery higher and hide chylothorax, due to the possible presence of an underlying hemothorax. The objective of the study is to demonstrate the specificity of retrocrural space obliteration, as additional CT sign to quickly identify and treat chylothorax. Materials and Methods: This retrospective study was undertaken since May 2012 until May 2013 and included patients scheduled for MDCT (Multi Detector CT) scan before a thoracentesis procedure diagnostic for hemothorax and chylothorax. Were used as a controls, MDCT scans performed for thoracic or thoracic-abdominal trauma, or after a

Autophagy is the main cellular pathway for degradation of long-lived proteins and organelles and regulates cell fate in response to stress. Beclin 1 is a key regulator of this process. In some settings autophagy and apoptosis seem to be interconnected. Recent reports indicate that fibroblasts in idiopathic pulmonary fibrosis (IPF) acquire resistance to apoptosis. Here, we examined the expression of beclin 1, and of the anti apoptotic protein Bcl-2 in human IPF fibroblasts using immunohistochemistry and molecular biology in bioptic sections, in primary cultures of fibroblasts taken from patients with IPF and in fibroblast cell lines. Expression of beclin 1 in fibroblasts from IPF was down-regulated in comparison with fibroblasts from normal lungs while the anti-apoptotic protein Bcl-2 expression was over-expressed. Treatment of fibroblast cell cultures with cisplatin induced a significant increase in beclin 1 and caspase 3 protein levels but a reduction in Bcl-2 expression. These observations were confirmed by the analysis of acid compartments and transmission electron microscopy. Our results demonstrate a modified expression of the apoptotic beclin 1 Bcl-2 proteins in human IPF fibroblasts suggesting the existence of an autophagy/apoptosis system dysfunction.

Lymphocytes possess an independent cholinergic system. We assessed the expression of muscarinic cholinergic receptors in lymphocytes from 49 asthmatic children and 10 age matched controls using Western blot. We demonstrated that CD4+ and CD8+ T cells expressed M2 and M4 muscarinic receptors which density were significantly increased in asthmatic children in comparison with controls. M2 and M4 receptor increase was strictly related with IgE and fraction of exhaled nitric oxide (FeNO) measurements and with impairment in objective measurements of airway obstruction. Increased lymphocyte muscarinic cholinergic receptor expression may concur with lung cholinergic dysfunction and with inflammatory molecular framework in asthma.