RATIONALE:In intubated patients, occlusion maneuvers allow non-invasive assessment of inspiratory effort, respiratory drive and lung mechanics. OBJECTIVES:To assess the feasibility of occlusion maneuvers during noninvasive ventilation (NIV). METHODS:In this multicenter study, 60 hypoxemic patients underwent two randomized 1-hour NIV sessions with oro-nasal and full-face masks after extubation. End-expiratory and end-inspiratory occlusions measured expiratory occlusion pressure (Pocc), 100-ms airway-pressure drop (P0.1), and plateau pressure. Esophageal manometry, calibrated before extubation, provided reference values for inspiratory effort, assessed as esophageal pressure swing (ΔPes), and dynamic transpulmonary driving pressure (ΔPL,dyn = pressure support - ΔPes). Interface-specific conversion factors (K) translating Pocc into predicted ΔPes (K × Pocc) and predicted ΔPL,dyn (pressure support - predicted ΔPes) were derived through 100-interaction cross-validation (20-patient derivation set, 40-patient validation set). MAIN RESULTS:Pocc was measurable in all patients. Mean K was 0.71 with the oro-nasal mask and 0.80 with the full-face mask. Predicted ΔPes agreed with observed ΔPes (oro-nasal bias -0.41 cm H2O, 95% limits of agreement -2.3 to 1.5; full-face 0.09, -2.9 to 3.1), and predicted ΔPL,dyn agreed with observed ΔPL,dyn (oro-nasal bias 0.03, -2.9 to 2.9; full-face -0.04, -4.3 to 4.2). Predicted ΔPes identified observed ΔPes ≤ -10 cm H2O, with areas under the receiver-operating-characteristic curve of 0.98 (oro-nasal) and 0.97 (full-face). Ventilator-derived P0.1 did not precisely quantify respiratory drive, but values >2.7 cm H2O with the oro-nasal mask and >3 cm H2O with the full-face mask identified high drive with specificity >90%. Plateau pressure was unstable in 78% (oro-nasal) and 90% (full-face) of patients. More negative predicted ΔPes, higher predicted ΔPL,dyn, and lower predicted lung compliance (expiratory tidal volume/predicted ΔPL,dyn) were associated with subsequent re-intubation. CONCLUSION:During NIV, Pocc-derived parameters provide non-invasive estimates of inspiratory effort, lung stress and mechanics, whereas ventilator P0.1 and plateau pressure are less reliable.

Introduction. The new global definition of Acute Respiratory Distress Syndrome (ARDS) allows diagnosis in patients receiving High-Flow Nasal Cannula (HFNC) therapy at flow rates ≥30 L/min and supports the SpO2/FiO2 (S/F) ratio as an alternative to the PaO2/FiO2 (P/F) ratio. It also recognizes Lung Ultrasound (LUS) as an imaging modality equivalent to CT or chest X-ray for identifying bilateral opacities, emphasizing its value for dynamic bedside monitoring of disease progression and recovery. We report a case of Fat Embolism Syndrome (FES) evolving into moderate ARDS, managed exclusively with HFNC and monitored through an integrated ultrasonographic approach. Methods. A 16-year-old male was admitted to the Intensive Care Unit (ICU) for hypoxemia that developed after a post-traumatic diaphyseal femur fracture. On admission, on spontaneous ventilation before the initiation of HFNC, the S/F ratio was 224. Chest CT revealed bilateral alveolar infiltrates consistent with ARDS. HFNC was started (initial flow 55 L/min, FiO₂ 0.5), with serial monitoring of P/F and S/F ratios. A systematic 8-zone diagnostic lung ultrasound was also performed with a convex low frequency probe and the lung ultrasound computed for each zone. Results. Following HFNC initiation, oxygenation progressively improved. The P/F ratio increased from 138 to 262 mmHg, while the S/F ratio rose from 186 to 306, with parallel trajectories accompanying the gradual reduction of support (Figure 1) and the HFNC flow was decreased from 60 to 40 L/min in accordance with clinical and gasometric improvement. Lung ultrasound demonstrated a distinct interstitial pattern with multiple B-lines with a global LUS score of 14, consistent with CT and chest X-ray findings (Figure 2). The clinical course was favorable, with complete HFNC weaning by day 5 and discharge on day 6. Conclusions. Implementation of the new global definition is especially useful in post-traumatic ARDS in young patients, for whom a tube-sparing strategy is encouraged - and in resource-limited settings with restricted access to blood gas analysis and imaging. Benefits are also envisaged in terms of limiting serial arterial blood gas sampling and iatrogenic anemia in the ICU. This case exemplifies its practical application, showing how integrating HFNC, S/F ratio, and lung ultrasound enables early diagnosis and effective non-invasive management.

Positive end-expiratory pressure (PEEP) remains a cornerstone of acute respiratory distress syndrome management. However, randomized trials of PEEP strategies have yielded conflicting results, reflecting inter-individual heterogeneity. PEEP-induced alveolar recruitment enhances lung protection by redistributing tidal volume over a larger functional lung and reducing atelectrauma and bronchiolotrauma. Conversely, in poorly recruitable lungs, PEEP predominantly increases stress in already aerated regions, potentially exacerbating ventilator-induced lung injury and cardiovascular compromise. The net effect of PEEP reflects a patient-specific balance between recruitment and overdistension, shaped by hemodynamic tolerance. Clinical markers traditionally used for assessing PEEP response (gas exchange, compliance, and driving pressure), while informative at a population level, remain unreliable for clinical decision-making at the individual level. With the exception of specific subgroups (e.g., obesity), patients with PaO2/FiO2 > 200 mmHg are unlikely to have substantial alveolar collapse amenable to recruitment and can be managed with lower PEEP (e.g., 5–8 cmH2O) facilitating transition to assisted ventilation. In contrast, higher PEEP is more likely to benefit patients with PaO2/FiO2 ≤ 200 mmHg, in whom a physiologically grounded framework should begin with assessment of lung recruitability (e.g., computed tomography, gas recruitment indices). This should account for airway closure, since PEEP below the airway opening pressure does not modify lung volume and may confound respiratory mechanics interpretation. In patients with significant recruitability, PEEP titration should integrate global measures (plateau pressure, stress index) with regional monitoring (electrical impedance tomography, transpulmonary pressure) when available. Conversely, poorly recruitable patients are unlikely to benefit from higher PEEP and can be managed with lower levels.

Background. Major trauma is a recognized risk factor for Acute Respiratory Distress Syndrome (ARDS), resulting from direct lung injury (e.g. pulmonary contusions) or indirect mechanisms mediated by inflammation and endothelial dysfunction. Trauma-related risk factors include pulmonary injury, head trauma, hemorrhagic shock, massive transfusion, and long bone or pelvic fractures. Initial management relies on lung-protective mechanical ventilation with a tidal volume <6 mL/kg PBW and moderate PEEP. In cases of severe ARDS with refractory hypoxemia or hypercapnia, extracorporeal CO2 removal (ECCO2R) may serve as a rescue strategy, enabling CO2 clearance and allowing ultra-protective ventilation without substantially affecting oxygenation. Methods. A 30-year-old patient with multiple traumatic injuries was admitted and showing thoracic asymmetry and absent breath sounds on the right side, consistent with an extensive right pneumothorax. Imaging revealed multiple pulmonary contusions in both lungs, with fractures of the ribs, and sternal manubrium. After 7 days under mechanical ventilation, the patient developed severe ARDS (P/F 83). A single prone positioning attempt failed to improve oxygenation. A double lumen tracheostomy cannula was positioned to allow separate ventilation of the two lungs. Ultra-protective ventilation was set on the most injured side and enabling extracorporeal CO₂ removal during concurrent renal replacement therapy (Figure 1, AI generated). Results. Following surgical tracheostomy and insertion of a double-lumen cannula, differential lung ventilation was initiated, using ultra-protective settings (Vt≈3.5mL/kg PBW). This maintained expired minute volumes of 1.46L/min (right lung) and 5.28L/min (left lung). Simultaneously, ECCO2R was started via a dialysis-oxygenator circuit (blood flow ∼300mL/min; sweep gas flow 10L/min). In the first 48h, PaCO2 progressively decreased from 95 to 49mmHg, normalizing the pH (7.03→7.27) (Figure 2). PaO2 and the P/F ratio remained stable (155→120) despite ultra-protective ventilation and CO2 reduction, confirming preserved oxygenation efficiency. Following improved gas exchange, the patient began a ventilator weaning protocol and was transferred to the Physical and Rehabilitative Medicine Unit on day 45. Conclusions. The combination of differential lung ventilation and ECCO₂R during RRT allowed safe ventilation and effective CO₂ clearance in severe trauma-related ARDS refractory to conventional management. The treatment maintained stable oxygenation while improving ventilation–perfusion efficiency, suggesting feasibility and potential as a rescue strategy in selected patients.

Rationale: Conventional parameters to determine the success of spontaneous breathing trials (SBTs) may fail to detect impending respiratory distress. Objectives: To assess whether SBT-induced changes in respiratory system compliance, inspiratory effort, and respiratory drive measured as occlusion pressure during the first 100 milliseconds (P0.1), all assessed noninvasively through airway occlusions, are associated with extubation outcomes. Methods: We conducted a multicenter study on patients at high risk of extubation failure who successfully passed a 30-minute SBT on the basis of conventional parameters. The SBT was reproduced using a specific ventilator immediately before extubation to continuously monitor respiratory system compliance, inspiratory effort, and P0.1. Extubation failure was defined as reintubation within 72 hours. Measurements and Main Results: Forty-six (19%) of 238 extubated patients required reintubation. No differences in Vt or respiratory rate were observed between successfully extubated and reintubated patients at any time. In the success group, inspiratory effort and normalized compliance (i.e., scaled to predicted body weight) remained unchanged throughout the SBT. In the failure group, normalized compliance declined (1.0 [0.8-1.2] to 0.7 [0.6-0.9] ml/cm H2O/kg; P < 0.001), whereas inspiratory effort increased (12 [10-15] to 18 [15-20] cm H2O; P < 0.001) during the SBT. P0.1 increased in both groups but more markedly in reintubated patients (2 [1.5-2.4] to 3.2 [2.9-3.5] cm H2O; P < 0.001). SBT-induced normalized compliance reduction less than or equal to -0.2 ml/cm H2O/kg (less than or equal to -0.1; less than or equal to -0.2) and inspiratory effort increase >2 cm H2O (>1, >3) were the most accurate predictors of extubation failure (area under the curve, 0.90 [0.84-0.93]; sensitivity, 80%; specificity, 83%; area under the curve, 0.94 [0.90-0.97]; sensitivity, 89%; specificity, 93%, respectively). Conclusions: In high-risk patients, SBT-induced declines in respiratory system compliance and increases in inspiratory effort are associated with extubation failure. Clinical trial registered with www.clinicaltrials.gov (NCT05295186).

BACKGROUND:Pulmonary complications, including atelectasis and reintubation, are common after cardiac surgery and are associated with increased morbidity and mortality. Postoperative continuous positive airway pressure (CPAP) may reduce these risks, but its effectiveness remains uncertain. OBJECTIVES:To assess whether CPAP reduces the need for reintubation in hypoxaemic patients after cardiac surgery, and to evaluate its effect on other postoperative pulmonary complications. DESIGN:Multicentre, open-label, randomised clinical trial. The study was prematurely terminated due to funding constraints, leading to an underpowered sample. SETTING:Ten university-affiliated hospitals across Italy. PATIENTS:Adults undergoing cardiac surgery with cardiopulmonary bypass who developed a Pa O 2 /FiO 2 ratio 200 or less within 1 h of extubation. Exclusion criteria included severe COPD, previous mechanical ventilation and lack of consent. MAIN OUTCOME MEASURES:The primary endpoint was reintubation within 28 days of surgery. Secondary endpoints included atelectasis, pneumonia, sepsis, mortality and oxygenation. RESULTS:The incidence of reintubation was 10.8% (95% confidence interval [CI], 6.52 to 15.15) in the control group and 8.3% (95% CI, 4.51 to 12.16) in the treatment group ( P  = 0.3908). In contrast, the occurrence of atelectasis was significantly higher in the control group at 24.1% (95% CI, 18.20 to 30.07) compared with 14.2% (95% CI, 9.38 to 19.05) in the treatment group ( P  = 0.0110). At 48 h, the incidence of reintubation was significantly lower in the CPAP group 2.94% (95% CI, 0.60 to 5.28) compared with the control group, 7.39% (95% CI, 3.76 to 11.02), P  = 0.0425. No significant differences in pneumonia, sepsis or mortality were observed. CPAP significantly improved oxygenation ( P  < 0.0001). CONCLUSION:CPAP did not significantly reduce 28-day reintubation rates compared with oxygen therapy via Venturi mask. However, CPAP was associated with a significant reduction in atelectasis and early reintubation at 48 h. Further research is warranted to confirm these findings and compare CPAP with other noninvasive support strategies. TRIAL REGISTRATION:ClinicalTrials.gov Identifier: NCT01726140.

Pulmonary complications, including atelectasis and reintubation, are common after cardiac surgery and are associated with increased morbidity and mortality. Postoperative continuous positive airway pressure (CPAP) may reduce these risks, but its effectiveness remains uncertain. To assess whether CPAP reduces the need for reintubation in hypoxaemic patients after cardiac surgery, and to evaluate its effect on other postoperative pulmonary complications. Multicentre, open-label, randomised clinical trial. The study was prematurely terminated due to funding constraints, leading to an underpowered sample. Ten university-affiliated hospitals across Italy. Adults undergoing cardiac surgery with cardiopulmonary bypass who developed a P aO2/FiO2 ratio 200 or less within 1 h of extubation. Exclusion criteria included severe COPD, previous mechanical ventilation and lack of consent. The primary endpoint was reintubation within 28 days of surgery. Secondary endpoints included atelectasis, pneumonia, sepsis, mortality and oxygenation. The incidence of reintubation was 10.8% (95% confidence interval [CI], 6.52 to 15.15) in the control group and 8.3% (95% CI, 4.51 to 12.16) in the treatment group (P = 0.3908). In contrast, the occurrence of atelectasis was significantly higher in the control group at 24.1% (95% CI, 18.20 to 30.07) compared with 14.2% (95% CI, 9.38 to 19.05) in the treatment group (P = 0.0110). At 48 h, the incidence of reintubation was significantly lower in the CPAP group 2.94% (95% CI, 0.60 to 5.28) compared with the control group, 7.39% (95% CI, 3.76 to 11.02), P = 0.0425. No significant differences in pneumonia, sepsis or mortality were observed. CPAP significantly improved oxygenation (P < 0.0001). CPAP did not significantly reduce 28-day reintubation rates compared with oxygen therapy via Venturi mask. However, CPAP was associated with a significant reduction in atelectasis and early reintubation at 48 h. Further research is warranted to confirm these findings and compare CPAP with other noninvasive support strategies. ClinicalTrials.gov Identifier: NCT01726140

Rationale: It is unclear whether extracorporeal CO2 removal (ECCO2R) can reduce the rate of intubation or the total time on invasive mechanical ventilation (IMV) in adults experiencing an exacerbation of chronic obstructive pulmonary disease (COPD). Objectives: To determine whether ECCO2R increases the number of ventilator-free days within the first 5 days postrandomization (VFD-5) in exacerbation of COPD in patients who are either failing noninvasive ventilation (NIV) or who are failing to wean from IMV. Methods: This randomized clinical trial was conducted in 41 U.S. institutions (2018-2022) (ClinicalTrials.gov ID: NCT03255057). Subjects were randomized to receive either standard care with venovenous ECCO2R (NIV stratum: n = 26; IMV stratum: n = 32) or standard care alone (NIV stratum: n = 22; IMV stratum: n = 33). Measurements and Main Results: The trial was stopped early because of slow enrollment and enrolled 113 subjects of the planned sample size of 180. There was no significant difference in the median VFD-5 between the arms controlled by strata (P= 0.36). In the NIV stratum, the median VFD-5 for both arms was 5 days (median shift = 0.0; 95% confidence interval [CI]: 0.0-0.0). In the IMV stratum, the median VFD-5 in the standard care and ECCO2R arms were 0.25 and 2 days, respectively; median shift = 0.00 (95% confidence interval: 0.00-1.25). In the NIV stratum, all-cause in-hospital mortality was significantly higher in the ECCO2R arm(22% vs. 0%, P = 0.02) with no difference in the IMV stratum (17% vs. 15%, P= 0.73). Conclusions: In subjects with exacerbation of COPD, the use of ECCO2R compared with standard care did not improve VFD-5.

The effects of tracheostomy on outcome as well as on intra or post-operative complications is yet to be defined. Admission of patients with tracheostomy to rehabilitation facility is at higher risk of suboptimal care and increased mortality. The aim of the study was to investigate ICU mortality, clinical outcome and quality of life up to 12 months after ICU discharge in tracheostomized critically ill patients. This is a prospective, multi-center, cohort study endorsed by Italian Society of Anesthesia, Analgesia, Reanimation, and Intensive Care (SIAARTI Prot. n° 643/13) registered in Clinicaltrial.gov (NCT01899352). Patients admitted to intensive care unit (ICU) and requiring elective tracheostomy according to physician in charge decision were included in the study. The primary outcome was ICU mortality. Secondary outcomes included risk factors for ICU mortality, prevalence of mortality at follow-up, rate of discharge from the hospital and rehabilitation, quality of life, performance status, and management of tracheostomy cannula at 3-, 6, 12-months from the day of tracheostomy. 694 critically ill patients who were tracheostomized in the ICU were included. ICU mortality was 15.8%. Age, SOFA score at the day of the tracheostomy, and days of endotracheal intubation before tracheostomy were risk factors for ICU mortality. The regression tree analysis showed that SOFA score at the day of tracheostomy and age had a preeminent role for the choice to perform the tracheostomy. Of the 694 ICU patients with tracheostomy, 469 completed the 12-months follow-up. Mortality was 33.51% at 3-months, 45.30% at 6-months, and 55.86% at 12-months. Patients with tracheostomy were less likely discharged at home but at hospital facilities or rehabilitative structures; and quality of life of patients with tracheostomy was severely compromised at 3–6 and 12 months when compared with patients without tracheostomy. In patients admitted to ICU, tracheostomy is associated with high mortality, difficult rehabilitation, and decreased quality of life. The choice to perform a tracheostomy should be carefully weighed on family burden and health-related quality of life. Clinical trial registration: Clinicaltrial.gov (NCT01899352).

BACKGROUND AND OBJECTIVE:We hypothesize that lung ultrasound scores (LUS) can help stratify the cardiac risk of elderly patients undergoing orthopedic surgery for hip fracture, adding value to the Revised Cardiac Risk Index (RCRI), the American Society of Anesthesiologists Physical Status (ASA-PS) and the National Surgical Quality Improvement Program Myocardial infarction and Cardiac arrest (NSQIP-MICA). METHODS:Prospective, observational multicenter study of 11 Italian hospitals on patients aged >65 years with hip fractures needing urgent surgery. Subjects with major adverse cardiovascular events (MACE) in the previous 6 months or with ongoing acute heart failure were excluded. Trained anesthesiologists obtained preoperative LUS scores during preoperative evaluation. ROC curve analysis and comparison were used to evaluate test accuracy. RESULTS:A total of 877 patients were enrolled in the study period. 108 MACE events occurred in 98 patients, with an overall incidence of 11.2%. LUS score was higher in complicated than non-complicated patients, 11.6 ± 6.64 vs. 4.97 ± 4.90 (p < 0.001). Preoperative LUS score ≥8 showed both better AUC (0.78) and accuracy (0.76) in predicting MACE than the RCRI scores (p < 0.001), MICA scores (p = 0.001) and ASA classes (p < 0.001). LUS sensitivity was 0.71, specificity was 0.76, negative predictive value was 0.95. LUS score ≥8 showed an OR for MACE of 5.81[95% CI 3.55-9.69] at multivariate analysis. 91 patients (10.4%) experienced postoperative pneumonia showing a preoperative LUS score higher in the non-pneumonia group, p < 0.001. CONCLUSIONS:The preoperative LUS score, with its high negative predictive value, could improve patients' risk stratification when used alone or add further value to the RCRI score. REGISTRATION:Registered at clinicaltrials.gov as NCT04074876.

Rationale: Definitive guidelines for anticoagulation management during veno-venous extracorporeal membrane oxygenation (VV ECMO) are lacking, while bleeding complications continue to pose major challenges. Objectives: To describe anticoagulation modalities and bleeding events in adults receiving VV ECMO. Methods: International prospective observational study in 41 centers, from December 2018 to February 2021. Anticoagulation was recorded daily in terms of type, dosage, and monitoring strategy. Bleeding events were reported according to site, severity, and impact on mortality. Measurements and Main Results: The study cohort included 652 patients, and 8471 days on ECMO were analyzed. Unfractionated heparin (UFH) was the initial anticoagulant in 77% of patients, and the most used anticoagulant during the ECMO course (6221 days, 73%). Activated partial thromboplastin time (aPTT) was the most common test for monitoring coagulation (86% of days): the median value was 52 seconds (39-61), but dropped by 5.3 seconds after the first bleeding event (95% CI -7.4 to -3.2, p< 0.01). Bleeding occurred on 1202 days (16.5 %). Overall, 342 patients (52.5 %) experienced at least one bleeding event (one episode every 215 hours on ECMO), of which 10 (1.6%) were fatal. In a multiple penalized Cox proportional hazard model, higher aPTT was a potentially modifiable risk factor for the first episode of bleeding (for 20 seconds increase, hazard ratio 1.07). Conclusions: Anticoagulation during VV ECMO was a dynamic process, with frequent stopping in cases of bleeding, and restart according to the clinical picture. Future studies might explore lower aPTT targets to reduce the risk of bleeding.

BACKGROUND:Age as an eligibility criterion for V-V ECMO is widely debated and varies among healthcare institutions. We examined how age relates to mortality in patients undergoing V-V ECMO for ARDS. METHODS:Systematic review and meta-regression of clinical studies published between 2015 and June 2024. Studies involving at least 6 ARDS patients treated with V-V ECMO, with specific data on ICU and/or hospital mortality and patient age were included. The search strategy was executed in PubMed, limited to English-language. COVID-19 and non-COVID-19 populations were analyzed separately. Meta-regressions of mortality outcomes on age were performed using gender, BMI, SAPS II, APACHE II, Charlson comorbidity index or SOFA as covariates. RESULTS:In non-COVID ARDS, the meta-regression of 173 studies with 56,257 participants showed a significant positive association between mean age and ICU/hospital mortality. In COVID-19 ARDS, a significant relationship between mean age and ICU mortality, but not hospital mortality, was found in 103 studies with 21,255 participants. Sensitivity analyses confirmed these findings, highlighting a linear relationship between age and mortality in both groups. For each additional year of mean age, ICU mortality increased by 1.2% in non-COVID ARDS and 1.9% in COVID ARDS. CONCLUSIONS:The relationship between age and ICU mortality is linear and shows no inflection point. Consequently, no age cut-off can be recommended for determining patient eligibility for V-V ECMO.

Background: Since publication of the 2012 Berlin definition of acute respiratory distress syndrome (ARDS), several developments have supported the need for an expansion of the definition, including the use of high-flow nasal oxygen, the expansion of the use of pulse oximetry in place of arterial blood gases, the use of ultrasound for chest imaging, and the need for applicability in resource-limited settings. Methods: A consensus conference of 32 critical care ARDS experts was convened, had six virtual meetings (June 2021 to March 2022), and subsequently obtained input from members of several critical care societies. The goal was to develop a definition that would 1) identify patients with the currently accepted conceptual framework for ARDS, 2) facilitate rapid ARDS diagnosis for clinical care and research, 3) be applicable in resource-limited settings, 4) be useful for testing specific therapies, and 5) be practical for communication to patients and caregivers. Results: The committee made four main recommendations: 1) include high-flow nasal oxygen with a minimum flow rate of ⩾30 L/min; 2) use PaO2:FiO2 ⩽ 300 mm Hg or oxygen saturation as measured by pulse oximetry SpO2:FiO2 ⩽ 315 (if oxygen saturation as measured by pulse oximetry is ⩽97%) to identify hypoxemia; 3) retain bilateral opacities for imaging criteria but add ultrasound as an imaging modality, especially in resource-limited areas; and 4) in resource-limited settings, do not require positive end-expiratory pressure, oxygen flow rate, or specific respiratory support devices. Conclusions: We propose a new global definition of ARDS that builds on the Berlin definition. The recommendations also identify areas for future research, including the need for prospective assessments of the feasibility, reliability, and prognostic validity of the proposed global definition.

Dear Editor, SARS-CoV-2 infections are expected in ~ 10% of the vaccinated population (breakthrough infection) [1].Although early data showed that progression to critical illness was less likely among vaccinated than unvaccinated patients [2], recent data show that mortality in patients requiring admission to the intensive care unit (ICU) did not differ [3], or was higher [4, 5] in vaccinated than unvaccinated patients.This study sets up to test the hypothesis that when age, comorbidities, and pathophysiological conditions are considered, vaccines are effective to prevent deaths in patients requiring ICU admission for breakthrough infection.This prospective multicenter observational study enrolled patients from 27 ICUs in Italy (June 1st, 2021-June 31st, 2022).Entry criteria were age ≥ 18 and respiratory failure associated to coronavirus disease 2019 (COVID-19) with a P/F < 300.Exclusion criteria were (a) pre-existing limitations on the use of life-sustaining treatments; (b) no/ incomplete information on vaccination status.Study endpoint was hospital mortality.Age, comorbidities, arterial-to-inspiratory O 2 ratio (P/F), Simplified Acute Physiology Score (SAPS) II, and Sequential Organ

The definition of acute respiratory distress syndrome (ARDS) has a somewhat controversial history, with some even questioning the need for the term "ARDS." This controversy has been amplified by the coronavirus disease (COVID-19) pandemic given the marked increase in the incidence of ARDS, the relatively new treatment modalities that do not fit neatly with the Berlin definition, and the difficulty of making the diagnosis in resource-limited settings. We propose that attempts to revise the definition of ARDS should apply the framework originally developed by psychologists and social scientists and used by other medical disciplines to generate and assess definitions of clinical syndromes that do not have gold standards. This framework is structured around measures of reliability, feasibility, and validity. Future revisions of the definition of ARDS should contain the purpose, the methodology, and the framework for empirically testing any proposed definition. Attempts to revise critical illness syndromes' definitions usually hope to make them "better"; our recommendation is that future attempts use the same criteria used by other fields in defining what "better" means.