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1. Impact of a multidisciplinary management team on clinical outcome in ICU patients affected by Gram-negative bloodstream infections: a pre-post quasi-experimental study

Author: Matteo Rinaldi, Milo Gatti, Tommaso Tonetti, Domenico Nocera, Simone Ambretti, Andrea Berlingeri, Giacomo Nigrisoli, Elisabetta Pierucci, Antonio Siniscalchi, Federico Pea, Pierluigi Viale, and Maddalena Giannella
Subjects: Multidisciplinary management team, Critically ill patients, Gram-negative bacteraemia, Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract: Abstract Background Bloodstream infections (BSIs) by Gram-negative pathogens play a major role in intensive care patients, both in terms of prevalence and severity, especially if multi-drug resistant pathogens are involved. Early appropriate antibiotic therapy is therefore a cornerstone in the management of these patients, and growing evidence shows that implementation of a multidisciplinary team may improve patients’ outcomes. Our aim was to evaluate the clinical and microbiological impact of the application of a multidisciplinary team on critically ill patients. Methods Pre-post study enrolling critically ill patients with Gram negative bloodstream infection in intensive care unit. In the pre-intervention phase (from January until December 2018) patients were managed with infectious disease consultation on demand, in the post-intervention phase (from January until December 2022) patients were managed with a daily evaluation by a multidisciplinary team composed of intensivist, infectious disease physician, clinical pharmacologist and microbiologist. Results Overall, 135 patients were enrolled during the study period, of them 67 (49.6%) in the pre-intervention phase and 68 (50.4%) in the post-intervention phase. Median age was 67 (58–75) years, sex male was 31.9%. Septic shock, the need for continuous renal replacement therapy and mechanical ventilation at BSI onset were similar in both groups, no difference of multidrug-resistant organisms (MDRO) prevalence was observed. In the post-phase, empirical administration of carbapenems decreased significantly (40.3% vs. 62.7%, p = 0.02) with an increase of appropriate empirical therapy (86.9% vs. 55.2%, p
Published: 2024
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2. Current knowledge gaps in extracorporeal respiratory support

Author: Tommaso Tonetti, Alberto Zanella, David Pérez-Torres, Giacomo Grasselli, and V. Marco Ranieri
Subjects: V-V ECMO, Acute respiratory failure, Gas exchange, Lung protective ventilation, Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract: Abstract Extracorporeal life support (ECLS) for acute respiratory failure encompasses veno-venous extracorporeal membrane oxygenation (V-V ECMO) and extracorporeal carbon dioxide removal (ECCO2R). V-V ECMO is primarily used to treat severe acute respiratory distress syndrome (ARDS), characterized by life-threatening hypoxemia or ventilatory insufficiency with conventional protective settings. It employs an artificial lung with high blood flows, and allows improvement in gas exchange, correction of hypoxemia, and reduction of the workload on the native lung. On the other hand, ECCO2R focuses on carbon dioxide removal and ventilatory load reduction (“ultra-protective ventilation”) in moderate ARDS, or in avoiding pump failure in acute exacerbated chronic obstructive pulmonary disease. Clinical indications for V-V ECLS are tailored to individual patients, as there are no absolute contraindications. However, determining the ideal timing for initiating extracorporeal respiratory support remains uncertain. Current ECLS equipment faces issues like size and durability. Innovations include intravascular lung assist devices (ILADs) and pumpless devices, though they come with their own challenges. Efficient gas exchange relies on modern oxygenators using hollow fiber designs, but research is exploring microfluidic technology to improve oxygenator size, thrombogenicity, and blood flow capacity. Coagulation management during V-V ECLS is crucial due to common bleeding and thrombosis complications; indeed, anticoagulation strategies and monitoring systems require improvement, while surface coatings and new materials show promise. Moreover, pharmacokinetics during ECLS significantly impact antibiotic therapy, necessitating therapeutic drug monitoring for precise dosing. Managing native lung ventilation during V-V ECMO remains complex, requiring a careful balance between benefits and potential risks for spontaneously breathing patients. Moreover, weaning from V-V ECMO is recognized as an area of relevant uncertainty, requiring further research. In the last decade, the concept of Extracorporeal Organ Support (ECOS) for patients with multiple organ dysfunction has emerged, combining ECLS with other organ support therapies to provide a more holistic approach for critically ill patients. In this review, we aim at providing an in-depth overview of V-V ECMO and ECCO2R, addressing various aspects of their use, challenges, and potential future directions in research and development.
Published: 2023
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3. Successful Versus Failed Transition From Controlled Ventilation to Pressure Support Ventilation in COVID-19 Patients: A Retrospective Cohort Study

Author: Melisa Polo Friz, MD, Emanuele Rezoagli, MD, Bijan Safaee Fakhr, MD, Gaetano Florio, MD, Eleonora Carlesso, MS, Riccardo Giudici, MD, Clarissa Forlini, MD, Francesca Tardini, MD, Thomas Langer, MD, Matteo Laratta, MD, Giampaolo Casella, MD, Andrea Forastieri Molinari, MD, Alessandro Protti, MD, Maurizio Cecconi, MD, Luca Cabrini, MD, Emanuela Biagioni, MD, Angela Berselli, MD, Lucia Mirabella, MD, Tommaso Tonetti, MD, Edoardo De Robertis, MD, Domenico Luca Grieco, MD, Massimo Antonelli, MD, Giuseppe Citerio, MD, Roberto Fumagalli, MD, Giuseppe Foti, MD, Alberto Zanella, MD, Giacomo Grasselli, MD, Giacomo Bellani, MD, for the COVID-19 Lombardy ICU Network, Amedeo Guzzardella, Luigi Vivona, Vittorio Scaravilli, Sebastiano Colombo, Alessio Cacioppola, Matteo Brioni, Clarissa Forlini, Francesca Tardini, Thomas Langer, Matteo Laratta, Giampaolo Casella, Maria Marsili, Serena Stropeni, Valentina Cordolcini, Francesco Crimella, Alessandro Santini, Massimiliano Greco, Michele Ferrari, Giacomo Iapichino, Paolo Severgnini, Davide Maraggia, Dario Gasberti, Alessandro Motta, Irene Coloretti, Stefano Busani, Martina Tosi, Ilenia Gatto, Carlo Montalto, Alberto Biondo, Ziad Algamain, Valentina Alaimo, Livio Tullo, Francesco Paolo Padovano, Giacinto Pizzilli, Irene Cavalli, Rachele Simonte, Davide Valeri, Gennaro DePascale, Simone Carelli, Valentina Noseda, Giacomo Cimicchi, Gaia Ottonello, Rossano Ghedin, Francesco Giacalone, Tiziana Bove, Francesco Meroi, Sara Scapol, Laura Pistidda, Angela Muretti, Savino Spadaro, Gaetano Scaramuzzo, Gioconda Ferraro, Giuseppe Gagliardi, Giovanni Sabbatini, Angelo Pezzi, Gabriele Sales, Giorgia Montrucchio, Andrea Carsetti, Federico Longhini, Maria Vargas, Plinio Calligaro, Ilaria Mariani, Vanessa Zambelli, Beatrice Noè, and Filippo Serra
Subjects: Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract: OBJECTIVES:. In patients with COVID-19 respiratory failure, controlled mechanical ventilation (CMV) is often necessary during the acute phases of the disease. Weaning from CMV to pressure support ventilation (PSV) is a key objective when the patient’s respiratory functions improve. Limited evidence exists regarding the factors predicting a successful transition to PSV and its impact on patient outcomes. DESIGN:. Retrospective observational cohort study. SETTING:. Twenty-four Italian ICUs from February 2020 to May 2020. PATIENTS:. Mechanically ventilated ICU patients with COVID-19-induced respiratory failure. INTERVENTION:. The transition period from CMV to PSV was evaluated. We defined it as “failure of assisted breathing” if the patient returned to CMV within the first 72 hours. MEASUREMENTS AND MAIN RESULTS:. Of 1260 ICU patients screened, 514 were included. Three hundred fifty-seven patients successfully made the transition to PSV, while 157 failed. Pao2/Fio2 ratio before the transition emerged as an independent predictor of a successful shift (odds ratio 1.00; 95% CI, 0.99–1.00; p = 0.003). Patients in the success group displayed a better trend in Pao2/Fio2, Paco2, plateau and peak pressure, and pH level. Subjects in the failure group exhibited higher ICU mortality (hazard ratio 2.08; 95% CI, 1.42–3.06; p < 0.001), an extended ICU length of stay (successful vs. failure 21 ± 14 vs. 27 ± 17 d; p < 0.001) and a longer duration of mechanical ventilation (19 ± 18 vs. 24 ± 17 d, p = 0.04). CONCLUSIONS:. Our study emphasizes that the Pao2/Fio2 ratio was the sole independent factor associated with a failed transition from CMV to PSV. The unsuccessful transition was associated with worse outcomes.
Published: 2024
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4. Long-term outcome of COVID-19 patients treated with helmet noninvasive ventilation vs. high-flow nasal oxygen: a randomized trial

Author: Teresa Michi, Chiara Mattana, Luca S. Menga, Maria Grazia Bocci, Melania Cesarano, Tommaso Rosà, Maria Rosaria Gualano, Jonathan Montomoli, Savino Spadaro, Matteo Tosato, Elisabetta Rota, Francesco Landi, Salvatore L. Cutuli, Eloisa S. Tanzarella, Gabriele Pintaudi, Edoardo Piervincenzi, Giuseppe Bello, Tommaso Tonetti, Paola Rucci, Gennaro De Pascale, Salvatore M. Maggiore, Domenico Luca Grieco, Giorgio Conti, Massimo Antonelli, and for the Gemelli COVID-ICU study group
Subjects: COVID-19, Noninvasive ventilation, Helmet, High-flow nasal oxygen, Acute respiratory failure, Patient self-inflicted lung injury (P-SILI), Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract: Abstract Background Long-term outcomes of patients treated with helmet noninvasive ventilation (NIV) are unknown: safety concerns regarding the risk of patient self-inflicted lung injury and delayed intubation exist when NIV is applied in hypoxemic patients. We assessed the 6-month outcome of patients who received helmet NIV or high-flow nasal oxygen for COVID-19 hypoxemic respiratory failure. Methods In this prespecified analysis of a randomized trial of helmet NIV versus high-flow nasal oxygen (HENIVOT), clinical status, physical performance (6-min-walking-test and 30-s chair stand test), respiratory function and quality of life (EuroQoL five dimensions five levels questionnaire, EuroQoL VAS, SF36 and Post-Traumatic Stress Disorder Checklist for the DSM) were evaluated 6 months after the enrollment. Results Among 80 patients who were alive, 71 (89%) completed the follow-up: 35 had received helmet NIV, 36 high-flow oxygen. There was no inter-group difference in any item concerning vital signs (N = 4), physical performance (N = 18), respiratory function (N = 27), quality of life (N = 21) and laboratory tests (N = 15). Arthralgia was significantly lower in the helmet group (16% vs. 55%, p = 0.002). Fifty-two percent of patients in helmet group vs. 63% of patients in high-flow group had diffusing capacity of the lungs for carbon monoxide
Published: 2023
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5. Changes in upper airways microbiota in ventilator-associated pneumonia

Author: Laura Alagna, Leonardo Mancabelli, Federico Magni, Liliane Chatenoud, Gabriele Bassi, Silvia Del Bianco, Roberto Fumagalli, Francesca Turroni, Davide Mangioni, Guglielmo M. Migliorino, Christian Milani, Antonio Muscatello, Giovanni Nattino, Edoardo Picetti, Riccardo Pinciroli, Sandra Rossi, Tommaso Tonetti, Alessia Vargiolu, Alessandra Bandera, Marco Ventura, Giuseppe Citerio, and Andrea Gori
Subjects: Ventilator-associated pneumonia, VAP, Upper airways microbiota, 16S-rRNA microbial profiling, Cohort study, Mechanical ventilation, Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract: Abstract Background The role of upper airways microbiota and its association with ventilator-associated pneumonia (VAP) development in mechanically ventilated (MV) patients is unclear. Taking advantage of data collected in a prospective study aimed to assess the composition and over-time variation of upper airway microbiota in patients MV for non-pulmonary reasons, we describe upper airway microbiota characteristics among VAP and NO-VAP patients. Methods Exploratory analysis of data collected in a prospective observational study on patients intubated for non-pulmonary conditions. Microbiota analysis (trough 16S-rRNA gene profiling) was performed on endotracheal aspirates (at intubation, T0, and after 72 h, T3) of patients with VAP (cases cohort) and a subgroup of NO-VAP patients (control cohort, matched according to total intubation time). Results Samples from 13 VAP patients and 22 NO-VAP matched controls were analyzed. At intubation (T0), patients with VAP revealed a significantly lower microbial complexity of the microbiota of the upper airways compared to NO-VAP controls (alpha diversity index of 84 ± 37 and 160 ± 102, in VAP and NO_VAP group, respectively, p-value
Published: 2023
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6. Comparative Impact of an Optimized PK/PD Target Attainment of Piperacillin-Tazobactam vs. Meropenem on the Trend over Time of SOFA Score and Inflammatory Biomarkers in Critically Ill Patients Receiving Continuous Infusion Monotherapy for Treating Documented Gram-Negative BSIs and/or VAP

Author: Milo Gatti, Matteo Rinaldi, Tommaso Tonetti, Antonio Siniscalchi, Pierluigi Viale, and Federico Pea
Subjects: piperacillin-tazobactam, meropenem, continuous infusion, critically ill patients, gram-negative infections, SOFA score, Therapeutics. Pharmacology, RM1-950
Abstract: (1) Background: The advantage of using carbapenems over beta-lactam/beta-lactamase inhibitor combinations in critically ill septic patients still remains a debated issue. We aimed to assess the comparative impact of an optimized pharmacokinetic/pharmacodynamic (PK/PD) target attainment of piperacillin-tazobactam vs. meropenem on the trend over time of both Sequential Organ Failure Assessment (SOFA) score and inflammatory biomarkers in critically ill patients receiving continuous infusion (CI) monotherapy with piperacillin-tazobactam or meropenem for treating documented Gram-negative bloodstream infections (BSI) and/or ventilator-associated pneumonia (VAP). (2) Methods: We performed a retrospective observational study comparing critically ill patients receiving targeted treatment with CI meropenem monotherapy for documented Gram-negative BSIs or VAP with a historical cohort of critical patients receiving CI piperacillin-tazobactam monotherapy. Patients included in the two groups were admitted to the general and post-transplant intensive care unit in the period July 2021–September 2023 and fulfilled the same inclusion criteria. The delta values of the SOFA score between the baseline of meropenem or piperacillin-tazobactam treatment and those at 48-h (delta 48-h SOFA score) or at 7-days (delta 7-days SOFA) were selected as primary outcomes. Delta 48-h and 7-days C-reactive protein (CRP) and procalcitonin (PCT), microbiological eradication, resistance occurrence, clinical cure, multi-drug resistant colonization at 90-day, ICU, and 30-day mortality rate were selected as secondary outcomes. Univariate analysis comparing primary and secondary outcomes between critically ill patients receiving CI monotherapy with piperacillin-tazobactam vs. meropenem was carried out. (3) Results: Overall, 32 critically ill patients receiving CI meropenem monotherapy were compared with a historical cohort of 43 cases receiving CI piperacillin-tazobactam monotherapy. No significant differences in terms of demographics and clinical features emerged at baseline between the two groups. Optimal PK/PD target was attained in 83.7% and 100.0% of patients receiving piperacillin-tazobactam and meropenem, respectively. No significant differences were observed between groups in terms of median values of delta 48-h SOFA (0 points vs. 1 point; p = 0.89) and median delta 7-days SOFA (2 points vs. 1 point; p = 0.43). Similarly, no significant differences were found between patients receiving piperacillin-tazobactam vs. meropenem for any of the secondary outcomes. (4) Conclusion: Our findings may support the contention that in critically ill patients with documented Gram-negative BSIs and/or VAP, the decreases in the SOFA score and in the inflammatory biomarkers serum levels achievable with CI piperacillin-tazobactam monotherapy at 48-h and at 7-days may be of similar extent and as effective as to those achievable with CI meropenem monotherapy provided that optimization on real-time by means of a TDM-based expert clinical pharmacological advice program is granted.
Published: 2024
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7. Could an Optimized Joint Pharmacokinetic/Pharmacodynamic Target Attainment of Continuous Infusion Piperacillin-Tazobactam Be a Valuable Innovative Approach for Maximizing the Effectiveness of Monotherapy Even in the Treatment of Critically Ill Patients with Documented Extended-Spectrum Beta-Lactamase-Producing Enterobacterales Bloodstream Infections and/or Ventilator-Associated Pneumonia?

Author: Milo Gatti, Matteo Rinaldi, Tommaso Tonetti, Antonio Siniscalchi, Pierluigi Viale, and Federico Pea
Subjects: piperacillin-tazobactam, continuous infusion, critically ill patients, Gram-negative infections, joint PK/PD target attainment, expert clinical pharmacological advice, Therapeutics. Pharmacology, RM1-950
Abstract: (1) Background: Piperacillin-tazobactam represents the first-line option for treating infections caused by full- or multi-susceptible Enterobacterales and/or Pseudomonas aeruginosa in critically ill patients. Several studies reported that attaining aggressive pharmacokinetic/pharmacodynamic (PK/PD) targets with beta-lactams is associated with an improved microbiological/clinical outcome. We aimed to assess the relationship between the joint PK/PD target attainment of continuous infusion (CI) piperacillin-tazobactam and the microbiological/clinical outcome of documented Gram-negative bloodstream infections (BSI) and/or ventilator-associated pneumonia (VAP) of critically ill patients treated with CI piperacillin-tazobactam monotherapy. (2) Methods: Critically ill patients admitted to the general and post-transplant intensive care unit in the period July 2021–September 2023 treated with CI piperacillin-tazobactam monotherapy optimized by means of a real-time therapeutic drug monitoring (TDM)-guided expert clinical pharmacological advice (ECPA) program for documented Gram-negative BSIs and/or VAP were retrospectively retrieved. Steady-state plasma concentrations (Css) of piperacillin and of tazobactam were measured, and the free fractions (f) were calculated according to respective plasma protein binding. The joint PK/PD target was defined as optimal whenever both the piperacillin fCss/MIC ratio was >4 and the tazobactam fCss/target concentration (CT) ratio was > 1 (quasi-optimal or suboptimal whenever only one or none of the two weas achieved, respectively). Multivariate logistic regression analysis was performed for testing variables potentially associated with microbiological outcome. (3) Results: Overall, 43 critically ill patients (median age 69 years; male 58.1%; median SOFA score at baseline 8) treated with CI piperacillin-tazobactam monotherapy were included. Optimal joint PK/PD target was attained in 36 cases (83.7%). At multivariate analysis, optimal attaining of joint PK/PD target was protective against microbiological failure (OR 0.03; 95%CI 0.003–0.27; p = 0.002), whereas quasi-optimal/suboptimal emerged as the only independent predictor of microbiological failure (OR 37.2; 95%CI 3.66–377.86; p = 0.002). (4) Conclusion: Optimized joint PK/PD target attainment of CI piperacillin-tazobactam could represent a valuable strategy for maximizing microbiological outcome in critically ill patients with documented Gram-negative BSI and/or VAP, even when sustained by extended-spectrum beta-lactamase (ESBL)-producing Enterobacterales. In this scenario, implementing a real-time TDM-guided ECPA program may be helpful in preventing failure in attaining optimal joint PK/PD targets among critically ill patients. Larger prospective studies are warranted to confirm our findings.
Published: 2023
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8. Expert clinical pharmacological advice may make an antimicrobial TDM program for emerging candidates more clinically useful in tailoring therapy of critically ill patients

Author: Milo Gatti, Pier Giorgio Cojutti, Michele Bartoletti, Tommaso Tonetti, Amedeo Bianchini, Stefania Ramirez, Giacinto Pizzilli, Simone Ambretti, Maddalena Giannella, Rita Mancini, Antonio Siniscalchi, Pierluigi Viale, and Federico Pea
Subjects: Expert clinical pharmacological advice program, Critically ill patients, Personalized antimicrobial therapy, Dosing adjustments, Transplant ICU, General ICU, Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract: Abstract Background Therapeutic drug monitoring (TDM) may represent an invaluable tool for optimizing antimicrobial therapy in septic patients, but extensive use is burdened by barriers. The aim of this study was to assess the impact of a newly established expert clinical pharmacological advice (ECPA) program in improving the clinical usefulness of an already existing TDM program for emerging candidates in tailoring antimicrobial therapy among critically ill patients. Methods This retrospective observational study included an organizational phase (OP) and an assessment phase (AP). During the OP (January–June 2021), specific actions were organized by MD clinical pharmacologists together with bioanalytical experts, clinical engineers, and ICU clinicians. During the AP (July–December 2021), the impact of these actions in optimizing antimicrobial treatment of the critically ill patients was assessed. Four indicators of performance of the TDM-guided real-time ECPA program were identified [total TDM-guided ECPAs July–December 2021/total TDM results July–December 2020; total ECPA dosing adjustments/total delivered ECPAs both at first assessment and overall; and turnaround time (TAT) of ECPAs, defined as optimal ( 48 h)]. Results The OP allowed to implement new organizational procedures, to create a dedicated pathway in the intranet system, to offer educational webinars on clinical pharmacology of antimicrobials, and to establish a multidisciplinary team at the morning bedside ICU meeting. In the AP, a total of 640 ECPAs were provided for optimizing 261 courses of antimicrobial therapy in 166 critically ill patients. ECPAs concerned mainly piperacillin–tazobactam (41.8%) and meropenem (24.9%), and also other antimicrobials had ≥ 10 ECPAs (ceftazidime, ciprofloxacin, fluconazole, ganciclovir, levofloxacin, and linezolid). Overall, the pre–post-increase in TDM activity was of 13.3-fold. TDM-guided dosing adjustments were recommended at first assessment in 61.7% of ECPAs (10.7% increases and 51.0% decreases), and overall in 45.0% of ECPAs (10.0% increases and 35.0% decreases). The overall median TAT was optimal (7.7 h) and that of each single agent was always optimal or quasi-optimal. Conclusions Multidisciplinary approach and timely expert interpretation of TDM results by MD Clinical Pharmacologists could represent cornerstones in improving the cost-effectiveness of an antimicrobial TDM program for emerging TDM candidates.
Published: 2022
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9. Circulating extracellular particles from severe COVID-19 patients show altered profiling and innate lymphoid cell-modulating ability

Author: Dorian Forte, Roberto Maria Pellegrino, Sara Trabanelli, Tommaso Tonetti, Francesca Ricci, Mara Cenerenti, Giorgia Comai, Pierluigi Tazzari, Tiziana Lazzarotto, Sandra Buratta, Lorena Urbanelli, Ghazal Narimanfar, Husam B. R. Alabed, Cristina Mecucci, Gaetano La Manna, Carla Emiliani, Camilla Jandus, Vito Marco Ranieri, Michele Cavo, Lucia Catani, and Francesca Palandri
Subjects: COVID-19, SARS-CoV-2, extracellular vesicles and particles, innate lymphoid cells, type 2 innate lymphoid cell, lipidomic, Immunologic diseases. Allergy, RC581-607
Abstract: IntroductionExtracellular vesicles (EVs) and particles (EPs) represent reliable biomarkers for disease detection. Their role in the inflammatory microenvironment of severe COVID-19 patients is not well determined. Here, we characterized the immunophenotype, the lipidomic cargo and the functional activity of circulating EPs from severe COVID-19 patients (Co-19-EPs) and healthy controls (HC-EPs) correlating the data with the clinical parameters including the partial pressure of oxygen to fraction of inspired oxygen ratio (PaO2/FiO2) and the sequential organ failure assessment (SOFA) score.MethodsPeripheral blood (PB) was collected from COVID-19 patients (n=10) and HC (n=10). EPs were purified from platelet-poor plasma by size exclusion chromatography (SEC) and ultrafiltration. Plasma cytokines and EPs were characterized by multiplex bead-based assay. Quantitative lipidomic profiling of EPs was performed by liquid chromatography/mass spectrometry combined with quadrupole time-of-flight (LC/MS Q-TOF). Innate lymphoid cells (ILC) were characterized by flow cytometry after co-cultures with HC-EPs or Co-19-EPs.ResultsWe observed that EPs from severe COVID-19 patients: 1) display an altered surface signature as assessed by multiplex protein analysis; 2) are characterized by distinct lipidomic profiling; 3) show correlations between lipidomic profiling and disease aggressiveness scores; 4) fail to dampen type 2 innate lymphoid cells (ILC2) cytokine secretion. As a consequence, ILC2 from severe COVID-19 patients show a more activated phenotype due to the presence of Co-19-EPs.DiscussionIn summary, these data highlight that abnormal circulating EPs promote ILC2-driven inflammatory signals in severe COVID-19 patients and support further exploration to unravel the role of EPs (and EVs) in COVID-19 pathogenesis.
Published: 2023
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10. Real-Time TDM-Based Expert Clinical Pharmacological Advice Program for Attaining Aggressive Pharmacokinetic/Pharmacodynamic Target of Continuous Infusion Meropenem in the Treatment of Critically Ill Patients with Documented Gram-Negative Infections Undergoing Continuous Veno-Venous Hemodiafiltration

Author: Milo Gatti, Matteo Rinaldi, Tommaso Tonetti, Antonio Siniscalchi, Pierluigi Viale, and Federico Pea
Subjects: meropenem, continuous infusion, continuous veno-venous hemodiafiltration, continuous renal replacement therapy, Gram-negative infections, PK/PD target attainment, Therapeutics. Pharmacology, RM1-950
Abstract: (1) Objectives: to describe the pharmacokinetic/pharmacodynamic (PK/PD) profile of continuous infusion (CI) meropenem in critical patients with documented Gram-negative infections undergoing continuous veno-venous hemodiafiltration (CVVHDF) and to assess the relationship with microbiological outcome. (2) Methods: Data were retrospectively retrieved for patients admitted to the general and the post-transplant intensive care units in the period October 2022–May 2023 who underwent CVVHDF during treatment with CI meropenem optimized by means of a real-time therapeutic drug monitoring (TDM)-based expert clinical pharmacological advice (ECPA) program for documented Gram-negative infections. Steady-state meropenem plasma concentrations were measured, and the free fractions (fCss) were calculated. Meropenem total clearance (CLtot) was calculated at each TDM assessment, and the impact of CVVHDF dose intensity and of residual diuresis on CLtot was investigated by means of linear regression. Optimal meropenem PK/PD target attainment was defined as an fCss/MIC ratio > 4. The relationship between meropenem PK/PD target attainment and microbiological outcome was assessed. (3) Results: A total of 24 critical patients (median age 68 years; male 62.5%) with documented Gram-negative infections were included. Median (IQR) meropenem fCss was 19.9 mg/L (17.4–28.0 mg/L). Median (IQR) CLtot was 3.89 L/h (3.28–5.29 L/h), and median (IQR) CVVHDF dose intensity was 37.4 mL/kg/h (33.8–44.6 mL/kg/h). Meropenem dosing adjustments were provided in 20 out of 24 first TDM assessments (83.3%, all decreases) and overall in 26 out of the 51 total ECPA cases (51.0%). Meropenem PK/PD target attainment was always optimal, and microbiological eradication was achieved in 90.5% of assessable cases. (4) Conclusion: the real-time TDM-guided ECPA program was useful in attaining aggressive PK/PD targeting with CI meropenem in critically ill patients undergoing high-intensity CVVHDF and allowed microbiological eradication in most cases with dosing regimens ranging between 125 and 500 mg q6h over 6 h.
Published: 2023
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11. Individualized positive end-expiratory pressure guided by end-expiratory lung volume in early acute respiratory distress syndrome: study protocol for the multicenter, randomized IPERPEEP trial

Author: Domenico Luca Grieco, Salvatore Maurizio Maggiore, Giacomo Bellani, Savino Spadaro, Elena Spinelli, Tommaso Tonetti, Luca S. Menga, Marco Pozzi, Denise Battaglini, Rosa Di Mussi, Andrea Bruni, Andrea De Gaetano, Carmine Giovanni Iovino, Matteo Brioni, Francesco Mojoli, Giuseppe Foti, Carlo Aberto Volta, Paolo Pelosi, Paolo Navalesi, Salvatore Grasso, V. Marco Ranieri, Massimo Antonelli, and the IPERPEEP study group
Subjects: Acute respiratory distress syndrome, Positive end-expiratory pressure, Mechanical ventilation, Ventilator-induced lung injury, Medicine (General), R5-920
Abstract: Abstract Background In acute respiratory distress syndrome (ARDS), response to positive end-expiratory pressure (PEEP) is variable according to different degrees of lung recruitability. The search for a tool to individualize PEEP based on patients’ individual response is warranted. End-expiratory lung volume (EELV) assessment by nitrogen washing-washout aids bedside estimation of PEEP-induced alveolar recruitment and may therefore help titrate PEEP on patient’s individual recruitability. We designed a randomized trial to test whether an individualized PEEP setting protocol driven by EELV measurement may improve a composite clinical outcome in patients with moderate-to-severe ARDS (IPERPEEP trial). Methods IPERPEEP is an open-label, multicenter, randomized trial that will be conducted in 10 intensive care units in Italy and will enroll 132 ARDS patients showing PaO2/FiO2 ratio ≤ 150 mmHg within 24 h from endotracheal intubation while on mechanical ventilation with PEEP 5 cmH2O. To standardize lung volumes at study initiation, all patients will undergo mechanical ventilation with tidal volume of 6 ml/kg of predicted body weight and PEEP set to obtain a plateau pressure within 28 and 30 cmH2O for 30 min (EXPRESS PEEP). Afterwards, a 5-step decremental PEEP trial will be conducted (EXPRESS PEEP to PEEP 5 cmH2O), and EELV will be measured at each step. Recruitment-to-inflation ratio will be calculated for each PEEP range from EELV difference. Patients will be then randomized to receive mechanical ventilation with PEEP set according to the optimal recruitment observed in the PEEP trial (IPERPEEP arm) trial or to achieve a plateau pressure of 28–30 cmH2O (control arm, EXPRESS strategy). In both groups, tidal volume size, use of prone positioning and neuromuscular blocking agents, and weaning from PEEP and from mechanical ventilation will be standardized. The primary endpoint of the study is a composite clinical outcome incorporating in-ICU mortality, 60-day ventilator-free days, and serum interleukin-6 concentration over the course of the initial 72 h of treatment. Discussion The IPERPEEP study is a randomized trial powered to elucidate whether an individualized PEEP setting protocol based on bedside assessment of lung recruitability can improve a composite clinical outcome during moderate-to-severe ARDS. Trial registration ClinicalTrials.gov NCT04012073 . Registered 9 July 2019.
Published: 2022
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12. Extracorporeal carbon dioxide removal for treatment of exacerbated chronic obstructive pulmonary disease (ORION): study protocol for a randomised controlled trial

Author: Tommaso Tonetti, Lara Pisani, Irene Cavalli, Maria Laura Vega, Elisa Maietti, Claudia Filippini, Stefano Nava, and V. Marco Ranieri
Subjects: Acute exacerbations of chronic obstructive pulmonary disease, COPD, Extracorporeal CO2 removal, ECCO2R, Non-invasive ventilation, NIV, Medicine (General), R5-920
Abstract: Abstract Background Hypercapnic exacerbations are severe complications of chronic obstructive pulmonary disease (COPD), characterized by negative impact on prognosis, quality of life and healthcare costs. The present standard of care for acute exacerbations of COPD is non-invasive ventilation; when it fails, the use of invasive mechanical ventilation is inevitable, but is associated with extremely poor prognosis. Extracorporeal circuits designed to remove CO2 (ECCO2R) may enhance the efficacy of NIV to remove CO2 and avoid the worsening of respiratory acidosis, which inevitably leads to failure of non-invasive ventilation. Although the use of ECCO2R for acute exacerbations of COPD is steadily increasing, solid evidence on its efficacy and safety is scarce, thus the need for a randomized controlled trial. Methods multicenter randomized controlled unblinded clinical trial including 284 (142 per arm) patients with acute hypercapnic respiratory failure caused by exacerbation of COPD, requiring respiratory support with NIV. The primary outcome is event free survival at 28 days, a composite outcome defined by survival in absence of prolonged mechanical ventilation, severe hypoxemia, septic shock and second episode of COPD exacerbation. Secondary outcomes are incidence of endotracheal intubation and tracheostomy, intensive care and hospital length-of-stay and 90-day mortality. Discussion Acute exacerbations of COPD represent a significant burden in terms of prognosis, quality of life and healthcare costs. Lack definite evidence despite increasing use of ECCO2R justifies a randomized trial to evaluate whether patients with acute hypercapnic acidosis not responsive to NIV should undergo invasive mechanical ventilation (with all serious related risks) or be treated with ECCO2R to avoid invasive ventilation but be exposed to possible adverse events of ECCO2R. Owing to its pragmatic nature, sample size and composite primary outcome, this trial aims at providing valuable answers to relevant questions for clinical treatment of acute exacerbations of COPD. Trial registration ClinicalTrials.gov , NCT04582799 . Registered 12 October 2020, .
Published: 2021
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13. The lower respiratory tract microbiome of critically ill patients with COVID-19

Author: Paolo Gaibani, Elisa Viciani, Michele Bartoletti, Russell E. Lewis, Tommaso Tonetti, Donatella Lombardo, Andrea Castagnetti, Federica Bovo, Clara Solera Horna, Marco Ranieri, Pierluigi Viale, Maria Carla Re, and Simone Ambretti
Subjects: Medicine, Science
Abstract: Abstract COVID-19 infection may predispose to secondary bacterial infection which is associated with poor clinical outcome especially among critically ill patients. We aimed to characterize the lower respiratory tract bacterial microbiome of COVID-19 critically ill patients in comparison to COVID-19-negative patients. We performed a 16S rRNA profiling on bronchoalveolar lavage (BAL) samples collected between April and May 2020 from 24 COVID-19 critically ill subjects and 24 patients with non-COVID-19 pneumonia. Lung microbiome of critically ill patients with COVID-19 was characterized by a different bacterial diversity (PERMANOVA on weighted and unweighted UniFrac Pr(> F) = 0.001) compared to COVID-19-negative patients with pneumonia. Pseudomonas alcaligenes, Clostridium hiranonis, Acinetobacter schindleri, Sphingobacterium spp., Acinetobacter spp. and Enterobacteriaceae, characterized lung microbiome of COVID-19 critically ill patients (LDA score > 2), while COVID-19-negative patients showed a higher abundance of lung commensal bacteria (Haemophilus influenzae, Veillonella dispar, Granulicatella spp., Porphyromonas spp., and Streptococcus spp.). The incidence rate (IR) of infections during COVID-19 pandemic showed a significant increase of carbapenem-resistant Acinetobacter baumannii (CR-Ab) infection. In conclusion, SARS-CoV-2 infection and antibiotic pressure may predispose critically ill patients to bacterial superinfection due to opportunistic multidrug resistant pathogens.
Published: 2021
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14. Prone position in intubated, mechanically ventilated patients with COVID-19: a multi-centric study of more than 1000 patients

Author: Thomas Langer, Matteo Brioni, Amedeo Guzzardella, Eleonora Carlesso, Luca Cabrini, Gianpaolo Castelli, Francesca Dalla Corte, Edoardo De Robertis, Martina Favarato, Andrea Forastieri, Clarissa Forlini, Massimo Girardis, Domenico Luca Grieco, Lucia Mirabella, Valentina Noseda, Paola Previtali, Alessandro Protti, Roberto Rona, Francesca Tardini, Tommaso Tonetti, Fabio Zannoni, Massimo Antonelli, Giuseppe Foti, Marco Ranieri, Antonio Pesenti, Roberto Fumagalli, Giacomo Grasselli, and PRONA-COVID Group
Subjects: COVID-19, Mechanical ventilation, Prone positioning, Refractory hypoxemia, Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract: Abstract Background Limited data are available on the use of prone position in intubated, invasively ventilated patients with Coronavirus disease-19 (COVID-19). Aim of this study is to investigate the use and effect of prone position in this population during the first 2020 pandemic wave. Methods Retrospective, multicentre, national cohort study conducted between February 24 and June 14, 2020, in 24 Italian Intensive Care Units (ICU) on adult patients needing invasive mechanical ventilation for respiratory failure caused by COVID-19. Clinical data were collected on the day of ICU admission. Information regarding the use of prone position was collected daily. Follow-up for patient outcomes was performed on July 15, 2020. The respiratory effects of the first prone position were studied in a subset of 78 patients. Patients were classified as Oxygen Responders if the PaO2/FiO2 ratio increased ≥ 20 mmHg during prone position and as Carbon Dioxide Responders if the ventilatory ratio was reduced during prone position. Results Of 1057 included patients, mild, moderate and severe ARDS was present in 15, 50 and 35% of patients, respectively, and had a resulting mortality of 25, 33 and 41%. Prone position was applied in 61% of the patients. Patients placed prone had a more severe disease and died significantly more (45% vs. 33%, p
Published: 2021
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15. Sustained oxygenation improvement after first prone positioning is associated with liberation from mechanical ventilation and mortality in critically ill COVID-19 patients: a cohort study

Author: Gaetano Scaramuzzo, Lorenzo Gamberini, Tommaso Tonetti, Gianluca Zani, Irene Ottaviani, Carlo Alberto Mazzoli, Chiara Capozzi, Emanuela Giampalma, Maria Letizia Bacchi Reggiani, Elisabetta Bertellini, Andrea Castelli, Irene Cavalli, Davide Colombo, Federico Crimaldi, Federica Damiani, Maurizio Fusari, Emiliano Gamberini, Giovanni Gordini, Cristiana Laici, Maria Concetta Lanza, Mirco Leo, Andrea Marudi, Giuseppe Nardi, Raffaella Papa, Antonella Potalivo, Emanuele Russo, Stefania Taddei, Guglielmo Consales, Iacopo Cappellini, Vito Marco Ranieri, Carlo Alberto Volta, Claude Guerin, Savino Spadaro, and The ICU-RER COVID-19 Collaboration
Subjects: COVID19, Prone positioning, Ventilatory free days, ICU, Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract: Abstract Background Prone positioning (PP) has been used to improve oxygenation in patients affected by the SARS-CoV-2 disease (COVID-19). Several mechanisms, including lung recruitment and better lung ventilation/perfusion matching, make a relevant rational for using PP. However, not all patients maintain the oxygenation improvement after returning to supine position. Nevertheless, no evidence exists that a sustained oxygenation response after PP is associated to outcome in mechanically ventilated COVID-19 patients. We analyzed data from 191 patients affected by COVID-19-related acute respiratory distress syndrome undergoing PP for clinical reasons. Clinical history, severity scores and respiratory mechanics were analyzed. Patients were classified as responders (≥ median PaO2/FiO2 variation) or non-responders (
Published: 2021
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16. Use of critical care resources during the first 2 weeks (February 24–March 8, 2020) of the Covid-19 outbreak in Italy

Author: Tommaso Tonetti, Giacomo Grasselli, Alberto Zanella, Giacinto Pizzilli, Roberto Fumagalli, Simone Piva, Luca Lorini, Giorgio Iotti, Giuseppe Foti, Sergio Colombo, Luigi Vivona, Sandra Rossi, Massimo Girardis, Vanni Agnoletti, Anselmo Campagna, Giovanni Gordini, Paolo Navalesi, Annalisa Boscolo, Alessandro Graziano, Ilaria Valeri, Andrea Vianello, Danilo Cereda, Claudia Filippini, Maurizio Cecconi, Franco Locatelli, Michele Bartoletti, Maddalena Giannella, Pierluigi Viale, Massimo Antonelli, Stefano Nava, Antonio Pesenti, V. Marco Ranieri, and the COVID-19 Northern Italian ICU Network
Subjects: COVID-19, Acute respiratory failure, ICU, Non-invasive ventilation, Rationing, Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract: Abstract Background A Covid-19 outbreak developed in Lombardy, Veneto and Emilia-Romagna (Italy) at the end of February 2020. Fear of an imminent saturation of available ICU beds generated the notion that rationing of intensive care resources could have been necessary. Results In order to evaluate the impact of Covid-19 on the ICU capacity to manage critically ill patients, we performed a retrospective analysis of the first 2 weeks of the outbreak (February 24–March 8). Data were collected from regional registries and from a case report form sent to participating sites. ICU beds increased from 1545 to 1989 (28.7%), and patients receiving respiratory support outside the ICU increased from 4 (0.6%) to 260 (37.0%). Patients receiving respiratory support outside the ICU were significantly older [65 vs. 77 years], had more cerebrovascular (5.8 vs. 13.1%) and renal (5.3 vs. 10.0%) comorbidities and less obesity (31.4 vs. 15.5%) than patients admitted to the ICU. PaO2/FiO2 ratio, respiratory rate and arterial pH were higher [165 vs. 244; 20 vs. 24 breath/min; 7.40 vs. 7.46] and PaCO2 and base excess were lower [34 vs. 42 mmHg; 0.60 vs. 1.30] in patients receiving respiratory support outside the ICU than in patients admitted to the ICU, respectively. Conclusions Increase in ICU beds and use of out-of-ICU respiratory support allowed effective management of the first 14 days of the Covid-19 outbreak, avoiding resource rationing.
Published: 2020
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17. Factors influencing liberation from mechanical ventilation in coronavirus disease 2019: multicenter observational study in fifteen Italian ICUs

Author: Lorenzo Gamberini, Tommaso Tonetti, Savino Spadaro, Gianluca Zani, Carlo Alberto Mazzoli, Chiara Capozzi, Emanuela Giampalma, Maria Letizia Bacchi Reggiani, Elisabetta Bertellini, Andrea Castelli, Irene Cavalli, Davide Colombo, Federico Crimaldi, Federica Damiani, Alberto Fogagnolo, Maurizio Fusari, Emiliano Gamberini, Giovanni Gordini, Cristiana Laici, Maria Concetta Lanza, Mirco Leo, Andrea Marudi, Giuseppe Nardi, Irene Ottaviani, Raffaella Papa, Antonella Potalivo, Emanuele Russo, Stefania Taddei, Carlo Alberto Volta, V. Marco Ranieri, and the ICU-RER COVID-19 Collaboration
Subjects: Coronavirus disease 2019, Intensive care, Mechanical ventilation, Outcomes, mortality, Respiration, artificial, ARDS, Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract: Abstract Background A large proportion of patients with coronavirus disease 2019 (COVID-19) develop severe respiratory failure requiring admission to the intensive care unit (ICU) and about 80% of them need mechanical ventilation (MV). These patients show great complexity due to multiple organ involvement and a dynamic evolution over time; moreover, few information is available about the risk factors that may contribute to increase the time course of mechanical ventilation. The primary objective of this study is to investigate the risk factors associated with the inability to liberate COVID-19 patients from mechanical ventilation. Due to the complex evolution of the disease, we analyzed both pulmonary variables and occurrence of non-pulmonary complications during mechanical ventilation. The secondary objective of this study was the evaluation of risk factors for ICU mortality. Methods This multicenter prospective observational study enrolled 391 patients from fifteen COVID-19 dedicated Italian ICUs which underwent invasive mechanical ventilation for COVID-19 pneumonia. Clinical and laboratory data, ventilator parameters, occurrence of organ dysfunction, and outcome were recorded. The primary outcome measure was 28 days ventilator-free days and the liberation from MV at 28 days was studied by performing a competing risks regression model on data, according to the method of Fine and Gray; the event death was considered as a competing risk. Results Liberation from mechanical ventilation was achieved in 53.2% of the patients (208/391). Competing risks analysis, considering death as a competing event, demonstrated a decreased sub-hazard ratio for liberation from mechanical ventilation (MV) with increasing age and SOFA score at ICU admission, low values of PaO2/FiO2 ratio during the first 5 days of MV, respiratory system compliance (CRS) lower than 40 mL/cmH2O during the first 5 days of MV, need for renal replacement therapy (RRT), late-onset ventilator-associated pneumonia (VAP), and cardiovascular complications. ICU mortality during the observation period was 36.1% (141/391). Similar results were obtained by the multivariate logistic regression analysis using mortality as a dependent variable. Conclusions Age, SOFA score at ICU admission, CRS, PaO2/FiO2, renal and cardiovascular complications, and late-onset VAP were all independent risk factors for prolonged mechanical ventilation in patients with COVID-19. Trial registration NCT04411459
Published: 2020
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18. Pulmonary embolism in patients with coronavirus disease-2019 (COVID-19) pneumonia: a narrative review

Author: Yasser Sakr, Manuela Giovini, Marc Leone, Giacinto Pizzilli, Andreas Kortgen, Michael Bauer, Tommaso Tonetti, Gary Duclos, Laurent Zieleskiewicz, Samuel Buschbeck, V. Marco Ranieri, and Elio Antonucci
Subjects: SARS-CoV-2, COVID-19, Pulmonary embolism, Thromboprophylaxis, Venous thromboembolism, Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract: Abstract Background Preliminary reports have described significant procoagulant events in patients with coronavirus disease-2019 (COVID-19), including life-threatening pulmonary embolism (PE). Main text We review the current data on the epidemiology, the possible underlying pathophysiologic mechanisms, and the therapeutic implications of PE in relation to COVID-19. The incidence of PE is reported to be around 2.6–8.9% of COVID-19 in hospitalized patients and up to one-third of those requiring intensive care unit (ICU) admission, despite standard prophylactic anticoagulation. This may be explained by direct and indirect pathologic consequences of COVID-19, complement activation, cytokine release, endothelial dysfunction, and interactions between different types of blood cells. Conclusion Thromboprophylaxis should be started in all patients with suspected or confirmed COVID-19 admitted to the hospital. The use of an intermediate therapeutic dose of low molecular weight (LMWH) or unfractionated heparin can be considered on an individual basis in patients with multiple risk factors for venous thromboembolism, including critically ill patients admitted to the ICU. Decisions about extending prophylaxis with LMWH after hospital discharge should be made after balancing the reduced risk of venous thromboembolism (VTE) with the risk of increased bleeding events and should be continued for 7–14 days after hospital discharge or in the pre-hospital phase in case of pre-existing or persisting VTE risk factors. Therapeutic anticoagulation is the cornerstone in the management of patients with PE. Selection of an appropriate agent and correct dosing requires consideration of underlying comorbidities.
Published: 2020
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19. Impact of Maximizing Css/MIC Ratio on Efficacy of Continuous Infusion Meropenem Against Documented Gram-Negative Infections in Critically Ill Patients and Population Pharmacokinetic/Pharmacodynamic Analysis to Support Treatment Optimization

Author: Pier Giorgio Cojutti, Milo Gatti, Matteo Rinaldi, Tommaso Tonetti, Cristiana Laici, Chiara Mega, Antonio Siniscalchi, Maddalena Giannella, Pierluigi Viale, and Federico Pea
Subjects: css/MIC ratio, efficacy, population pharmacokinetics, pharmacodynamics, continuous infusion meropenem, critically ill patients, Therapeutics. Pharmacology, RM1-950
Abstract: Introduction: optimal treatment of Gram-negative infections in critically ill patients is challenged by changing pathophysiological conditions, reduced antimicrobial susceptibility and limited therapeutic options. The aim of this study was to assess the impact of maximizing Css/MIC ratio on efficacy of continuous infusion (CI) meropenem in treating documented Gram-negative infections in critically ill patients and to perform a population pharmacokinetic/pharmacodynamic analysis to support treatment optimization.Materials and Methods: Classification and regression tree (CART) analysis was used to identify whether a cutoff of steady-state meropenem concentration (Css)-to-minimum inhibitory concentration (MIC) (Css/MIC) ratio correlated with favorable clinical outcome. A non-parametric approach with Pmetrics was used for pharmacokinetic analysis and covariate evaluation. The probability of target attainment (PTA) of the identified Css/MIC ratio was calculated by means of Monte Carlo simulations. Cumulative fraction of response (CFRs) were calculated against common Enterobacterales, P. aeruginosa and A. baumannii as well.Results: a total of 74 patients with 183 meropenem Css were included. CART analysis identified a Css/MIC ratio ≥4.63 as cutoff value significantly associated with favorable clinical outcomes. Multivariate regression analysis confirmed the association [OR (95%CI): 20.440 (2.063–202.522); p < 0.01]. Creatinine clearance (CLCR) was the only covariate associated with meropenem clearance. Monte Carlo simulations showed that, across different classes of renal function, dosages of meropenem ranging between 0.5 and 2 g q6h over 6 h (namely by CI) may grant PTAs of Css/MIC ratios ≥4.63 against susceptible pathogens with an MIC up to the EUCAST clinical breakpoint of 2 mg/L. The CFRs achievable with these dosages were very high (>90%) against Enterobacterales across all the classes of renal function and against P. aeruginosa among patients with CLCR < 30 ml/min/1.73 m2, and quite lower against A. baumannii.Discussion: our findings suggest that Css/MIC ratio ≥4.63 may be considered the pharmacodynamic target useful at maximizing the efficacy of CI meropenem in the treatment of Gram-negative infections in critically ill patients. Dosages ranging between 0.5 g q6h and 2 g q6h by CI may maximize the probability of favorable clinical outcome against meropenem-susceptible Gram-negative pathogens among critically ill patients having different degrees of renal function.
Published: 2021
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20. Dynamic Arterial Elastance to Predict Mean Arterial Pressure Decrease after Reduction of Vasopressor in Septic Shock Patients

Author: Paolo Persona, Tommaso Tonetti, Ilaria Valeri, Emanuele Pivetta, Francesco Zarantonello, Tommaso Pettenuzzo, Alessandro De Cassai, and Paolo Navalesi
Subjects: dynamic elastance, PPV/SVV, septic shock, haemodynamic monitoring, Science
Abstract: After fluid status optimization, norepinephrine infusion represents the cornerstone of septic shock treatment. De-escalation of vasopressors should be considered with caution, as hypotension increases the risk of mortality. In this prospective observational study including 42 patients, we assess the role of dynamic elastance (EaDyn), i.e., the ratio between pulse pressure variation and stroke volume variation, which can be measured noninvasively by the MostCare monitoring system, to predict a mean arterial pressure (MAP) drop > 10% 30 min after norepinephrine reduction. Patients were divided into responders (MAP falling > 10%) and non-responders (MAP falling < 10%). The receiver-operating-characteristic curve identified an area under the curve of the EaDyn value to predict a MAP decrease > 10% of 0.84. An EaDyn cut-off of 0.84 predicted a MAP drop > 10% with a sensitivity of 0.71 and a specificity of 0.89. In a multivariate logistic regression, EaDyn was significantly and independently associated with MAP decrease (OR 0.001, 95% confidence interval 0.00001–0.081, p < 0.001). The nomogram model for the probability of MAP decrease > 10% showed a C-index of 0.90. In conclusion, in a septic shock cohort, EaDyn correlates well with the risk of decrease of MAP > 10% after norepinephrine reduction.
Published: 2022
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21. Antiviral activity of interferon-based combination therapy in critically ill patients with COVID-19: Preliminary observations

Author: Paolo Gaibani, Tommaso Tonetti, Michele Bartoletti, Maria Carla Re, PierLuigi Viale, and V. Marco Ranieri
Subjects: COVID-19, Lopinavir/ritonavir, Hydroxychloroquine, Interferon β-1a, Microbiology, QR1-502
Published: 2021
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22. WSES consensus conference guidelines: monitoring and management of severe adult traumatic brain injury patients with polytrauma in the first 24 hours

Author: Edoardo Picetti, Sandra Rossi, Fikri M. Abu-Zidan, Luca Ansaloni, Rocco Armonda, Gian Luca Baiocchi, Miklosh Bala, Zsolt J. Balogh, Maurizio Berardino, Walter L. Biffl, Pierre Bouzat, Andras Buki, Marco Ceresoli, Randall M. Chesnut, Osvaldo Chiara, Giuseppe Citerio, Federico Coccolini, Raul Coimbra, Salomone Di Saverio, Gustavo P. Fraga, Deepak Gupta, Raimund Helbok, Peter J. Hutchinson, Andrew W. Kirkpatrick, Takahiro Kinoshita, Yoram Kluger, Ari Leppaniemi, Andrew I. R. Maas, Ronald V. Maier, Francesco Minardi, Ernest E. Moore, John A. Myburgh, David O. Okonkwo, Yasuhiro Otomo, Sandro Rizoli, Andres M. Rubiano, Juan Sahuquillo, Massimo Sartelli, Thomas M. Scalea, Franco Servadei, Philip F. Stahel, Nino Stocchetti, Fabio S. Taccone, Tommaso Tonetti, George Velmahos, Dieter Weber, and Fausto Catena
Subjects: Traumatic brain injury, Polytrauma, Bleeding, Hemorrhage, Monitoring, Management, Surgery, RD1-811, Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract: Abstract The acute phase management of patients with severe traumatic brain injury (TBI) and polytrauma represents a major challenge. Guidelines for the care of these complex patients are lacking, and worldwide variability in clinical practice has been documented in recent studies. Consequently, the World Society of Emergency Surgery (WSES) decided to organize an international consensus conference regarding the monitoring and management of severe adult TBI polytrauma patients during the first 24 hours after injury. A modified Delphi approach was adopted, with an agreement cut-off of 70%. Forty experts in this field (emergency surgeons, neurosurgeons, and intensivists) participated in the online consensus process. Sixteen recommendations were generated, with the aim of promoting rational care in this difficult setting.
Published: 2019
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23. Assignment of ASA-physical status relates to anesthesiologists’ experience: a survey-based national-study

Author: Alessandro De Cassai, Annalisa Boscolo, Tommaso Tonetti, Irina Ban, and Carlo Ori
Subjects: anesthesiology, asa-physical scale, asa-score, questionnaires and surveys, Anesthesiology, RD78.3-87.3
Abstract: Background The American Society of Anesthesiologists physical status (ASA-PS) is a grading system adopted worldwide by anesthesiologists to classify the overall health status of patients. Its importance is demonstrated not only by its routine use in clinical practice, but also by its deployment in other healthcare-related environments. However, a weak/moderate inter-rater reliability for ASA-PS has been previously shown, and although definitions and clinical examples of each class are provided by ASA, doubts remain on the individual factors influencing assignment to an ASA-PS class. The aim of this study was to investigate whether and how an anesthesiologist’s experience affects classification into a specific ASA-PS class. Methods An online survey presenting eight fictitious patients was administered to a group of Italian anesthesiologists and residents. Respondents were asked to assign each of the eight patients to a specific ASA-PS class. Anesthesiologists were subdivided into five classes according to years of experience as an anesthesiologist. Results Six hundred one surveys were correctly completed. The highest mean number of correct answers was obtained by residents (3.95 ± 1.13), with the number decreasing progressively with increasing work experience. The lowest value was recorded in the most experienced group (3.13 ± 1.25). Inter-rater reliability was weak/moderate in all experience level groups (k = 0.38). Conclusions Low inter-reliability of the ASA-PS and the experience-dependence of the anesthesiologist in assigning classifications must be taken into account when evaluating a patient, particularly in settings where wide differences in experience are present.
Published: 2019
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24. Erector spinae plane block as a multiple catheter technique for open esophagectomy: a case report

Author: Alessandro De Cassai, Tommaso Tonetti, Helmut Galligioni, and Carlo Ori
Subjects: Anesthesiology, RD78.3-87.3
Abstract: Background and objective: Erector spinae plane block is a valid technique to provide simultaneously analgesia for combined thoracic and abdominal surgery. Case report: A patient underwent open esophagectomy followed by reconstructive esophagogastroplasty but refused thoracic epidural analgesia; a multi-modal analgesia with a multiple erector spinae plane block was then planned. Three erector spinae plane catheters (T5 and T10 on the right side and T9 on the left side) for continuous analgesia were placed before surgery. During the first 48 h pain was never reported in the thoracic area but the patient reported multiple times to feel a pain well localized in epigastrium, but never localized in any other abdominal quadrant. Discussion: Erector spinae plane block is a valid technique to provide analgesia simultaneously for combined thoracic and abdominal surgery and could be a valid alternative strategy if the use of epidural analgesia is contraindicated. Resumo: Justificativa e objetivo: O bloqueio do plano do eretor da espinha é uma técnica válida para fornecer analgesia em cirurgias combinadas, torácica e abdominal, de modo simultâneo. Relato de caso: Um paciente foi submetido à esofagectomia aberta seguida de esofagogastroplastia reconstrutiva, mas recusou analgesia peridural torácica; uma analgesia multimodal com o bloqueio dos múltiplos segmentos do eretor da espinha foi então planejada. Três cateteres foram colocados no plano do eretor da espinha (T5 e T10 no lado direito e T9 no lado esquerdo) para analgesia contínua antes da cirurgia. Durante as primeiras 48 horas, não houve queixa de dor na área torácica, mas várias vezes o paciente relatou sentir uma dor bem localizada no epigástrio, mas nunca localizada em nenhum outro quadrante abdominal. Discussão: O bloqueio do plano do eretor da espinha é uma técnica válida para fornecer analgesia de modo simultâneo em cirurgias combinadas — torácica e abdominal — e pode ser uma estratégia alternativa também válida nos casos em que o uso de analgesia peridural for contraindicado. Keywords: Erector spinae plane block, Regional anesthesia, Esophagectomy, Palavras-chave: Bloqueio do plano do eretor da espinha, Anestesia regional, Esofagectomia
Published: 2019
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25. Regional physiology of ARDS

Author: Luciano Gattinoni, Tommaso Tonetti, and Michael Quintel
Subjects: Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract: Abstract The acute respiratory distress (ARDS) lung is usually characterized by a high degree of inhomogeneity. Indeed, the same lung may show a wide spectrum of aeration alterations, ranging from completely gasless regions, up to hyperinflated areas. This inhomogeneity is normally caused by the presence of lung edema and/or anatomical variations, and is deeply influenced by the gravitational forces. For any given airway pressure generated by the ventilator, the pressure acting directly on the lung (i.e., the transpulmonary pressure or lung stress) is determined by two main factors: 1) the ratio between lung elastance and the total elastance of the respiratory system (which has been shown to vary widely in ARDS patients, between 0.2 and 0.8); and 2) the lung size. In severe ARDS, the ventilatable parenchyma is strongly reduced in size (‘baby lung’); its resting volume could be as low as 300 mL, and the total inspiratory capacity could be reached with a tidal volume of 750–900 mL, thus generating lethal stress and strain in the lung. Although this is possible in theory, it does not explain the occurrence of ventilator-induced lung injury (VILI) in lungs ventilated with much lower tidal volumes. In fact, the ARDS lung contains areas acting as local stress multipliers and they could multiply the stress by a factor ~ 2, meaning that in those regions the transpulmonary pressure could be double that present in other parts of the same lung. These ‘stress raisers’ widely correspond to the inhomogenous areas of the ARDS lung and can be present in up to 40% of the lung. Although most of the literature on VILI concentrates on the possible dangers of tidal volume, mechanical ventilation in fact delivers mechanical power (i.e., energy per unit of time) to the lung parenchyma, which reacts to it according to its anatomical structure and pathophysiological status. The determinants of mechanical power are not only the tidal volume, but also respiratory rate, inspiratory flow, and positive end-expiratory pressure (PEEP). In the end, decreasing mechanical power, increasing lung homogeneity, and avoiding reaching the anatomical limits of the ‘baby lung’ should be the goals for safe ventilation in ARDS.
Published: 2017
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26. Assessment of a PK/PD Target of Continuous Infusion Beta-Lactams Useful for Preventing Microbiological Failure and/or Resistance Development in Critically Ill Patients Affected by Documented Gram-Negative Infections

Author: Milo Gatti, Pier Giorgio Cojutti, Renato Pascale, Tommaso Tonetti, Cristiana Laici, Alessio Dell’Olio, Antonio Siniscalchi, Maddalena Giannella, Pierluigi Viale, and Federico Pea
Subjects: PK/PD target attainment, beta-lactams, continuous infusion, critically ill patients, microbiological failure, resistance development, Therapeutics. Pharmacology, RM1-950
Abstract: Background: Emerging data suggest that more aggressive beta-lactam PK/PD targets could minimize the occurrence of microbiological failure and/or resistance development. This study aims to assess whether a PK/PD target threshold of continuous infusion (CI) beta-lactams may be useful in preventing microbiological failure and/or resistance development in critically ill patients affected by documented Gram-negative infections. Methods: Patients admitted to intensive care units from December 2020 to July 2021 receiving continuous infusion beta-lactams for documented Gram-negative infections and having at least one therapeutic drug monitoring in the first 72 h of treatment were included. A receiver operating characteristic (ROC) curve analysis was performed using the ratio between steady-state concentration and minimum inhibitory concentration (Css/MIC) ratio as the test variable and occurrence of microbiological failure as the state variable. Area under the curve (AUC) and 95% confidence interval (CI) were calculated. Independent risk factors for the occurrence of microbiological failure were investigated using logistic regression. Results: Overall, 116 patients were included. Microbiological failure occurred in 26 cases (22.4%). A Css/MIC ratio ≤ 5 was identified as PK/PD target cut-off with sensitivity of 80.8% (CI 60.6–93.4%) and specificity of 90.5% (CI 74.2–94.4%), and with an AUC of 0.868 (95%CI 0.793–0.924; p < 0.001). At multivariate regression, independent predictors of microbiological failure were Css/MIC ratio ≤ 5 (odds ratio [OR] 34.54; 95%CI 7.45–160.11; p < 0.001) and Pseudomonas aeruginosa infection (OR 4.79; 95%CI 1.11–20.79; p = 0.036). Conclusions: Early targeting of CI beta-lactams at Css/MIC ratio > 5 during the treatment of documented Gram-negative infections may be helpful in preventing microbiological failure and/or resistance development in critically ill patients.
Published: 2021
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27. Synergistic Effect of Static Compliance and D-dimers to Predict Outcome of Patients with COVID-19-ARDS: A Prospective Multicenter Study

Author: Tommaso Tonetti, Giacomo Grasselli, Paola Rucci, Francesco Alessandri, Alessio Dell’Olio, Annalisa Boscolo, Laura Pasin, Nicolò Sella, Chiara Mega, Rita Maria Melotti, Massimo Girardis, Stefano Busani, Giacomo Bellani, Giuseppe Foti, Domenico Luca Grieco, Vittorio Scaravilli, Alessandro Protti, Thomas Langer, Luciana Mascia, Francesco Pugliese, Maurizio Cecconi, Roberto Fumagalli, Stefano Nava, Massimo Antonelli, Arthur S. Slutsky, Paolo Navalesi, Antonio Pesenti, and Vito Marco Ranieri
Subjects: acute respiratory distress syndrome, COVID-19, D-dimer, static compliance, mechanical ventilation, Biology (General), QH301-705.5
Abstract: The synergic combination of D-dimer (as proxy of thrombotic/vascular injury) and static compliance (as proxy of parenchymal injury) in predicting mortality in COVID-19-ARDS has not been systematically evaluated. The objective is to determine whether the combination of elevated D-dimer and low static compliance can predict mortality in patients with COVID-19-ARDS. A “training sample” (March–June 2020) and a “testing sample” (September 2020–January 2021) of adult patients invasively ventilated for COVID-19-ARDS were collected in nine hospitals. D-dimer and compliance in the first 24 h were recorded. Study outcome was all-cause mortality at 28-days. Cut-offs for D-dimer and compliance were identified by receiver operating characteristic curve analysis. Mutually exclusive groups were selected using classification tree analysis with chi-square automatic interaction detection. Time to death in the resulting groups was estimated with Cox regression adjusted for SOFA, sex, age, PaO2/FiO2 ratio, and sample (training/testing). “Training” and “testing” samples amounted to 347 and 296 patients, respectively. Three groups were identified: D-dimer ≤ 1880 ng/mL (LD); D-dimer > 1880 ng/mL and compliance > 41 mL/cmH2O (LD-HC); D-dimer > 1880 ng/mL and compliance ≤ 41 mL/cmH2O (HD-LC). 28-days mortality progressively increased in the three groups (from 24% to 35% and 57% (training) and from 27% to 39% and 60% (testing), respectively; p < 0.01). Adjusted mortality was significantly higher in HD-LC group compared with LD (HR = 0.479, p < 0.001) and HD-HC (HR = 0.542, p < 0.01); no difference was found between LD and HD-HC. In conclusion, combination of high D-dimer and low static compliance identifies a clinical phenotype with high mortality in COVID-19-ARDS.
Published: 2021
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28. Sharing Mechanical Ventilator: In Vitro Evaluation of Circuit Cross-Flows and Patient Interactions

Author: Sebastiano Maria Colombo, Michele Battistin, Eleonora Carlesso, Luigi Vivona, Fabio Carfagna, Carlo Valsecchi, Gaetano Florio, Luca Carenzo, Tommaso Tonetti, Vito Marco Ranieri, Maurizio Cecconi, Antonio Pesenti, Giacomo Grasselli, and Alberto Zanella
Subjects: COVID-19, SARS-CoV2 infection, cross-flow dynamics, shared ventilation, sharing mechanical ventilator, two patients one ventilator, Chemical technology, TP1-1185, Chemical engineering, TP155-156
Abstract: During the COVID-19 pandemic, a shortage of mechanical ventilators was reported and ventilator sharing between patients was proposed as an ultimate solution. Two lung simulators were ventilated by one anesthesia machine connected through two respiratory circuits and T-pieces. Five different combinations of compliances (30–50 mL × cmH2O−1) and resistances (5–20 cmH2O × L−1 × s−1) were tested. The ventilation setting was: pressure-controlled ventilation, positive end-expiratory pressure 15 cmH2O, inspiratory pressure 10 cmH2O, respiratory rate 20 bpm. Pressures and flows from all the circuit sections have been recorded and analyzed. Simulated patients with equal compliance and resistance received similar ventilation. Compliance reduction from 50 to 30 mL × cmH2O−1 decreased the tidal volume (VT) by 32% (418 ± 49 vs. 285 ± 17 mL). The resistance increase from 5 to 20 cmH2O × L−1 × s−1 decreased VT by 22% (425 ± 69 vs. 331 ± 51 mL). The maximal alveolar pressure was lower at higher compliance and resistance values and decreased linearly with the time constant (r² = 0.80, p < 0.001). The minimum alveolar pressure ranged from 15.5 ± 0.04 to 16.57 ± 0.04 cmH2O. Cross-flows between the simulated patients have been recorded in all the tested combinations, during both the inspiratory and expiratory phases. The simultaneous ventilation of two patients with one ventilator may be unable to match individual patient’s needs and has a high risk of cross-interference.
Published: 2021
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29. Effects of regional perfusion block in healthy and injured lungs

Author: Barbara Cambiaghi, Francesco Vasques, Onnen Mörer, Christian Ritter, Tommaso Mauri, Nils Kunze-Szikszay, Karin Holke, Francesca Collino, Giorgia Maiolo, Francesca Rapetti, Elias Schulze-Kalthoff, Tommaso Tonetti, Günter Hahn, Michael Quintel, and Luciano Gattinoni
Subjects: Pulmonary embolism, Lung injury, Ventilator-induced lung injury, Experimental animal model, Pulmonary circulation, Computed tomography (CT), Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract: Abstract Background Severe hypoperfusion can cause lung damage. We studied the effects of regional perfusion block in normal lungs and in the lungs that had been conditioned by lavage with 500 ml saline and high V T (20 ml kg−1) ventilation. Methods Nineteen pigs (61.2 ± 2.5 kg) were randomized to five groups: controls (n = 3), the right lower lobe block alone (n = 3), lavage and high V T (n = 4), lung lavage, and high V T plus perfusion block of the right (n = 5) or left (n = 4) lower lobe. Gas exchange, respiratory mechanics, and hemodynamics were measured hourly. After an 8-h observation period, CT scans were obtained at 0 and 15 cmH2O airway pressure. Results Perfusion block did not damage healthy lungs. In conditioned lungs, the left perfusion block caused more edema in the contralateral lung (777 ± 62 g right lung vs 484 ± 204 g left; p
Published: 2017
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30. The future of mechanical ventilation: lessons from the present and the past

Author: Luciano Gattinoni, John J. Marini, Francesca Collino, Giorgia Maiolo, Francesca Rapetti, Tommaso Tonetti, Francesco Vasques, and Michael Quintel
Subjects: Mechanical ventilation, Acute respiratory distress syndrome, Ventilator-induced lung injury, Mechanical power, Extracorporeal membrane oxygenation, Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract: Abstract The adverse effects of mechanical ventilation in acute respiratory distress syndrome (ARDS) arise from two main causes: unphysiological increases of transpulmonary pressure and unphysiological increases/decreases of pleural pressure during positive or negative pressure ventilation. The transpulmonary pressure-related side effects primarily account for ventilator-induced lung injury (VILI) while the pleural pressure-related side effects primarily account for hemodynamic alterations. The changes of transpulmonary pressure and pleural pressure resulting from a given applied driving pressure depend on the relative elastances of the lung and chest wall. The term ‘volutrauma’ should refer to excessive strain, while ‘barotrauma’ should refer to excessive stress. Strains exceeding 1.5, corresponding to a stress above ~20 cmH2O in humans, are severely damaging in experimental animals. Apart from high tidal volumes and high transpulmonary pressures, the respiratory rate and inspiratory flow may also play roles in the genesis of VILI. We do not know which fraction of mortality is attributable to VILI with ventilation comparable to that reported in recent clinical practice surveys (tidal volume ~7.5 ml/kg, positive end-expiratory pressure (PEEP) ~8 cmH2O, rate ~20 bpm, associated mortality ~35%). Therefore, a more complete and individually personalized understanding of ARDS lung mechanics and its interaction with the ventilator is needed to improve future care. Knowledge of functional lung size would allow the quantitative estimation of strain. The determination of lung inhomogeneity/stress raisers would help assess local stresses; the measurement of lung recruitability would guide PEEP selection to optimize lung size and homogeneity. Finding a safety threshold for mechanical power, normalized to functional lung volume and tissue heterogeneity, may help precisely define the safety limits of ventilating the individual in question. When a mechanical ventilation set cannot be found to avoid an excessive risk of VILI, alternative methods (such as the artificial lung) should be considered.
Published: 2017
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31. Correction to: Factors influencing liberation from mechanical ventilation in coronavirus disease 2019: multicenter observational study in fifteen Italian ICUs

Author: Lorenzo Gamberini, Tommaso Tonetti, Savino Spadaro, Gianluca Zani, Carlo Alberto Mazzoli, Chiara Capozzi, Emanuela Giampalma, Maria Letizia Bacchi Reggiani, Elisabetta Bertellini, Andrea Castelli, Irene Cavalli, Davide Colombo, Federico Crimaldi, Federica Damiani, Alberto Fogagnolo, Maurizio Fusari, Emiliano Gamberini, Giovanni Gordini, Cristiana Laici, Maria Concetta Lanza, Mirco Leo, Andrea Marudi, Giuseppe Nardi, Irene Ottaviani, Raffaella Papa, Antonella Potalivo, Emanuele Russo, Stefania Taddei, Carlo Alberto Volta, V. Marco Ranieri, and the ICU-RER COVID-19 Collaboration
Subjects: Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract: An amendment to this paper has been published and can be accessed via the original article.
Published: 2020
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32. Central venous line placement and ultrasound probe damage: A word of caution

Author: Alessandro De Cassai and Tommaso Tonetti
Subjects: Medical technology, R855-855.5
Published: 2019
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33. Environmental Contamination by SARS-CoV-2 During Noninvasive Ventilation in COVID-19

Author: Alessio, Dell'Olio, Caterina, Vocale, Alessandra, Primavera, Lara, Pisani, Salvatore, Altavilla, Greta, Roncarati, Fabio, Tumietto, Pierluigi, Viale, Maria Carla, Re, Tiziana, Lazzarotto, Stefano, Nava, V Marco, Ranieri, and Tommaso, Tonetti
Subjects: Pulmonary and Respiratory Medicine, General Medicine, Critical Care and Intensive Care Medicine
Abstract: Environmental contamination by SARS-CoV-2 from patients with COVID-19 undergoing noninvasive ventilation (NIV) in the ICU is still under investigation. This study set out to investigate the presence of SARS-CoV-2 on surfaces near subjects receiving NIV in the ICU under controlled conditions (ie, use of dual-limb circuits, filters, adequate room ventilation).This was a single-center, prospective, observational study in the ICU of a tertiary teaching hospital. Four surface sampling areas, at increasing distance from subject's face, were identified; and each one was sampled at fixed intervals: 6, 12, and 24 h. The presence of SARS-CoV-2 was detected with real-time reverse transcriptase-polymerase-chain-reaction (RT-PCR) test on environmental swabs; the RT-PCR assay targeted the SARS-CoV-2 virus nucleocapsid N1 and N2 genes and the human RNase P gene as internal control.In a total of 256 collected samples, none were positive for SARS-CoV-2 genetic material, whereas 21 samples (8.2%) tested positive for RNase P, thus demonstrating the presence of genetic material unrelated to SARS-CoV-2.Our data show that application of NIV in an appropriate environment and with correct precautions leads to no sign of surface environmental contamination. Accordingly, our data support the idea that use of NIV in the ICU is safe both for health care workers and for other patients.
Published: 2022

34. Weaning from mechanical ventilation in intensive care units across 50 countries (WEAN SAFE): a multicentre, prospective, observational cohort study

Author: Tài, Pham, Leo, Heunk, Giacomo, Bellani, Fabiana, Madotto, Irene, Aragao, Gaëtan, Beduneau, Ewan C, Goligher, Giacomo, Grasselli, Jon Henrik, Laake, Jordi, Mancebo, Oscar, Peñuela, Lise, Piquilloud, Antonio, Pesenti, Hannah, Wunsch, Frank, van Haren, Laurent, Brochard, John G, Laffey, Abrough, Fekri, P Acharya, Subhash, Amin, Pravin, Arabi, Yaseen, Aragao, Irene, Bauer, Philippe, Beduneau, Gaëtan, Beitler, Jeremy, Berkius, Johan, Bugedo, Guillermo, Camporota, Luigi, Cerny, Vladimir, Cho, Young-Jae, Clarkson, Kevin, Estenssoro, Elisa, Goligher, Ewan, Grasselli, Giacomo, Gritsan, Alexey, Mohammadreza Hashemian, Seyed, Hermans, Greet, M Heunks, Leo, Jovanovic, Bojan, Kurahashi, Kiyoyasu, Henrik Laake, Jon, Matamis, Dimitrio, Moerer, Onnen, Molnar, Zsolt, Ozyilmaz, Ezgi, Panka, Bernardo, Papali, Alfred, Peñuelas, Óscar, Perbet, Sébastien, Piquilloud, Lise, Qiu, Haibo, Abdel Razek, Assem, Rittayamai, Nuttapol, Roldan, Rollin, Serpa Neto, Ary, Szuldrzynski, Konstanty, Talmor, Daniel, Tomescu, Dana, Van Haren, Frank, Villagomez, Asisclo, Ali Zeggwagh, Amine, Abe, Toshikazu, Aboshady, Abdelrhman, Acampo-de Jong, Melanie, Acharya, Subhash, Adderley, Jane, Adiguzel, Nalan, Kumar Agrawal, Vijay, Aguilar, Gerardo, Aguirre, Gaston, Aguirre-Bermeo, Hernan, Ahlström, Björn, Akbas, Türkay, Akker, Mustafa, Al Sadeh, Ghamdan, Alamri, Sultan, Algaba, Angela, Ali, Muneeb, Aliberti, Anna, Manuel Allegue, Jose, Alvarez, Diana, Amador, Joaquin, H Andersen, Finn, Ansari, Sharique, Apichatbutr, Yutthana, Apostolopoulou, Olympia, Arellano, Daniel, Arica, Mestanza, Arikan, Huseyin, Arinaga, Koichi, Arnal, Jean-Michel, Asano, Kengo, Asín-Corrochano, Marta, Milagrito Avalos Cabrera, Jesu, Avila Fuentes, Silvia, Aydemir, Semih, Aygencel, Gulbin, Azevedo, Luciano, Bacakoglu, Feza, Badie, Julio, Baedorf Kassis, Elia, Bai, Gabriela, Balaraj, Govindan, Ballico, Bruno, Banner-Goodspeed, Valerie, Banwarie, Preveen, Barbieri, Rosella, Baronia, Arvind, Barrett, Jonathan, Barrot, Loïc, Emilio Barrueco-Francioni, Jesu, Barry, Jeffrey, Bawangade, Harshal, Beavis, Sarah, Beck, Eduardo, Beehre, Nina, Belenguer Muncharaz, Alberto, Bellani, Giacomo, Belliato, Mirko, Bellissima, Agrippino, Beltramelli, Rodrigo, Ben Souissi, Asma, Benitez-Cano, Adela, Benlamin, Mohamed, Benslama, Abdellatif, Bento, Lui, Benvenuti, Daniela, Bernabe, Laura, Bersten, Andrew, Berta, Giacomo, Bertini, Pietro, Bertram-Ralph, Elliot, Besbes, Mohamed, Roberto Bettini, Lisandro, Beuret, Pascal, Bewley, Jeremy, Bezzi, Marco, Bhakhtiani, Lakshay, Bhandary, Rakesh, Bhowmick, Kaushik, Bihari, Shailesh, Bissett, Bernie, Blythe, David, Bocher, Simon, Boedjawan, Narain, M Bojanowski, Christine, Boni, Elisa, Boraso, Sabrina, Borelli, Massimo, Borello, Silvina, Borislavova, Margarita, J Bosma, Karen, Bottiroli, Maurizio, Boyd, Owen, Bozbay, Suha, Briva, Arturo, Brochard, Laurent, Bruel, Cédric, Bruni, Andrea, Buehner, Ulrike, Bulpa, Pierre, Burt, Karen, Buscot, Mathieu, Buttera, Stefania, Cabrera, Jorge, Caccese, Roberta, Caironi, Pietro, Canchos Gutierrez, Ivan, Canedo, Nancy, Cani, Alma, Cappellini, Iacopo, Carazo, Jesu, Pablo Cardonnet, Lui, Carpio, David, Carriedo, Demetrio, Carrillo, Ramón, Carvalho, João, Caser, Eliana, Castelli, Antonio, Castillo Quintero, Manuel, Castro, Heloisa, Catorze, Nuno, Cengiz, Melike, Cereijo, Enrique, Ceunen, Helga, Chaintoutis, Christo, Chang, Youjin, Chaparro, Gustavogcha, Chapman, Carmel, Chau, Simon, Eugenia Chavez, Cecilia, Chelazzi, Cosimo, Chelly, Jonathan, Chemouni, Frank, Chen, Kai, Chena, Ariel, Chiarandini, Paolo, Chilton, Phil, Chiumello, Davide, Chou-Lie, Yvette, Chudeau, Nicola, Cinel, Ismail, Cinnella, Gilda, Clark, Michele, Clark, Thoma, Clementi, Stefano, Coaguila, Lui, Jaspe Codecido, Alexi, Collins, Amy, Colombo, Riccardo, Conde, Juan, Consales, Guglielmo, Cook, Tim, Coppadoro, Andrea, Cornejo, Rodrigo, Cortegiani, Andrea, Coxo, Cristina, Neville Cracchiolo, Andrea, Crespo Ramirez, Mónica, Crova, Philippe, Cruz, José, Cubattoli, Lucia, Çukurova, Zafer, Curto, Francesco, Czempik, Piotr, D'Andrea, Rocco, da Silva Ramos, Fernando, Dangers, Laurence, Danguy des Déserts, Marc, Danin, Pierre-Eric, Dantas, Fabianne, Daubin, Cédric, Dawei, Wu, de Haro, Candelaria, de Jesus Montelongo, Felipe, De Mendoza, Diego, de Pablo, Raúl, De Pascale, Gennaro, De Rosa, Silvia, Decavèle, Maxen, Declercq, Pierre-Loui, Deicas, Alberto, Del Carmen Campos Moreno, María, Dellamonica, Jean, Delmas, Benjamin, Demirkiran, Oktay, Demirkiran, Hilmi, Dendane, Tarek, di Mussi, Rossella, Diakaki, Chrysi, Diaz, Anatilde, Diaz, Willy, Dikmen, Yalim, Dimoula, Aikaterini, Doble, Patricia, Doha, Nagwa, Domingos, Guilherme, Dres, Martin, Dries, David, Duggal, Abhijit, Duke, Graeme, Dunts, Pavel, Dybwik, Knut, Dykyy, Maksym, Eckert, Philippe, Efe, Serdar, Elatrous, Souheil, Elay, Gülseren, S Elmaryul, Abubaker, Elsaadany, Mohamed, Elsayed, Hany, Elsayed, Samar, Emery, Malo, Ena, Sébastien, Eng, Kevin, A Englert, Joshua, Erdogan, Elif, Ergin Ozcan, Perihan, Eroglu, Ege, Escobar, Miguel, Esen, Figen, Esen Tekeli, Arzu, Esquivel, Alejandro, Esquivel Gallegos, Helbert, Ezzouine, Hanane, Facchini, Alberto, Faheem, Mohammad, Fanelli, Vito, Fernanda Farina, Maria, Fartoukh, Muriel, Fehrle, Lutz, Feng, Feng, Feng, Yufeng, Fernandez, Irene, Fernandez, Borja, Lorena Fernandez-Rodriguez, Maria, Ferrando, Carlo, João Ferreira da Silva, Maria, Ferreruela, Mireia, Ferrier, Janet, Jesús Flamm Zamorano, Matia, Flood, Laura, Floris, Leda, Fluckiger, Martin, Forteza, Catalina, Fortunato, Antonella, Frans, Eric, Frattari, Antonella, Fredes, Sebastian, Frenzel, Tim, Fumagalli, Roberto, Andres Furche, Mariano, Fusari, Maurizio, Fysh, Edward, Luis Galeas-Lopez, Juan, Galerneau, Louis-Marie, Garcia, Analía, Fernanda Garcia, María, Garcia, Elisabet, Garcia Olivares, Pablo, Garlicki, Jaroslaw, Garnero, Aude, Garofalo, Eugenio, Gautam, Prabha, Gazenkampf, Andrey, Gelinotte, Stéphanie, Gelormini, Domenico, Ghrenassia, Etienne, Giacomucci, Angelo, Giannoni, Robert, Gigante, Andrea, Glober, Nancy, Gnesin, Paolo, Gollo, Yari, Gomaa, Dina, Gomero Paredes, Rosita, Gomes, Rui, Alejandro Gomez, Raúl, Gomez, Oscar, Gomez, Aroa, Gondim, Louise, Gonzalez, Manuel, Gonzalez, Isabel, Gonzalez-Castro, Alejandro, Gordillo Romero, Orlando, Gordo, Federico, Gouin, Philippe, Graf Santos, Jerónimo, Grainne, Rooney, Grando, Matilde, Granov Grabovica, Sanja, Grasso, Salvatore, Grasso, Rinaldo, Grimmer, Lisa, Grissom, Colin, Gu, Qing, Guan, Xiang-Dong, Guarracino, Fabio, Guasch, Neu, Guatteri, Luca, Gueret, Renaud, Guérin, Claude, Guerot, Emmanuel, Guitard, Pierre-Gilda, Gül, Fethi, Gumus, Ayca, Gurjar, Mohan, Gutierrez, Patricia, Hachimi, Abdelhamid, Hadzibegovic, Adi, Hagan, Samantha, Hammel, Clare, Han Song, Joo, Hanlon, Gabrielle, Heines, Serge, Henriksson, Johanna, Herbrecht, Jean-Etienne, Omar Heredia Orbegoso, Gabriel, Hermon, Andrew, Hernandez, Rosana, Hernandez, Carmen, Herrera, Lui, Herrera-Gutierrez, Manuel, Heunks, Leo, Hidalgo, Juan, Hill, Dianne, Holmquist, Dagmar, Homez, Marcela, Hongtao, Xia, Hormis, Anil, Horner, Daniel, Carmen Hornos, M, Hou, Meihong, House, Stacy, Housni, Brahim, Hugill, Keith, Humphreys, Sally, Humbert, Loui, Hunter, Stephanie, Hwa Young, Lee, Iezzi, Nicola, Ilutovich, Santiago, Inal, Volkan, Innes, Richard, Ioannides, Panagioti, Antonio Iotti, Giorgio, Ippolito, Mariachiara, Irie, Hiromasa, Iriyama, Hiroki, Itagaki, Taiga, Izura, Javier, Izza, Santiago, Jabeen, Rakhshanda, Jamaati, Hamidreza, Jamadarkhana, Sunil, Jamoussi, Amira, Jankowski, Milosz, Alberto Jaramillo, Lui, Jeon, Kyeongman, Jeong Lee, Seok, Jeswani, Deepak, Jha, Simant, Jiang, Liangyan, Jing, Chen, Jochmans, Sébastien, Anders Johnstad, Bror, Jongmin, Lee, Joret, Aurélie, Junhasavasdikul, Detajin, Teresa Jurado, Maria, Kam, Elisa, Kamohara, Hidenobu, Kane, Caroline, Kara, Iskender, Karakurt, Sait, Karnjanarachata, Cherdkiat, Kataoka, Jun, Katayama, Shinshu, Kaushik, Shuchi, Kelebek Girgin, Nermin, Kerr, Kathryn, Kerslake, Ian, Khairnar, Prakash, Khalid, Abidi, Khan, Akram, K Khanna, Ashish, Khorasanee, Reza, Kienhorst, Dieneke, Kirakli, Cenk, Knafelj, Rihard, Kol Kol, Mark, Kongpolprom, Napplika, Kopitko, Csaba, Korkmaz Ekren, Pervin, Kubisz-Pudelko, Agnieszka, Kulcsar, Zoltan, Kumasawa, Junji, Kuriyama, Akira, Kutchak, Fernanda, Labarca, Eduardo, Labat, Françoise, Laborda, César, Alberto Laca Barrera, Manuel, Lagache, Laurie, Landaverde Lopez, Antonio, Lanspa, Michael, Lascari, Valeria, Le Meur, Matthieu, Hwan Lee, Su, Ju Lee, Young, Lee, Jinwoo, Lee, Won-Yeon, Lee, Jarone, Legernaes, Terje, Leiner, Tamaa, Lemiale, Virginie, Leonor, Tiago, M Lepper, Philipp, Li, Dahuan, Li, Hongbin, Li, Oleg, Raquel Lima, Ana, Lind, Dan, Litton, Edward, Liu, Ning, Liu, Ling, Liu, Jialin, Llitjos, Jean-Françoi, Llorente, Beatriz, Lopez, Rodolfo, Elizabeth Lopez, Claudia, Lopez Nava, Claudia, Lovazzano, Pablo, Lu, Min, Lucchese, Francesca, Lugano, Manuela, Lugo Goytia, Gustavo, Luo, Hua, Lynch, Ceri, Macheda, Sebastiano, Hugo Madrigal Robles, Victor, Maurizio Maggiore, Salvatore, Magret Iglesias, Mònica, Malaga, Peter, Mallapura Maheswarappa, Harish, Malpartida, Guillermo, Malyarchikov, Andrey, Mansson, Helena, Manzano, Anaid, Marey, Ismael, Marin, Nathalie, Del Carmen Marin, Maria, Markman, Eliana, Martin, Felix, Martin, Alex, Martin Dal Gesso, Cristina, Martinez, Felipe, Martínez-Fidalgo, Conchita, Martin-Loeches, Ignacio, Mas, Arantxa, Masaaki, Sakuraya, Maseda, Emilio, Massa, Eleni, Mattsson, Anna, Maugeri, Jessica, Mccredie, Victoria, Mccullough, Jame, Mcguinness, Shay, Mckown, Andrew, Medve, László, Mei, Chengqing, Mellado Artigas, Ricard, Mendes, Vitor, Khalaf Ebraheim Mervat, Mohamed, Michaux, Isabelle, Mikhaeil, Michael, Milagros, Olga, Milet, Igor, Teresa Millan, Maria, Minwei, Zhang, Mirabella, Lucia, Mishra, Sanghamitra, Mistraletti, Giovanni, Mochizuki, Katsunori, Moghal, Arif, Mojoli, Francesco, Molin, Alexandre, Montiel, Raquel, Montini, Luca, Monza, Gianmario, Mora Aznar, Maria, Morakul, Sunthiti, Morales, Maria, Moreno Torres, Daniel, Rolando Morocho Tutillo, Diego, Motherway, Catherine, Mouhssine, Doumiri, Mouloudi, Eleni, Muñoz, Tapia, Munoz de Cabo, Carlo, Mustafa, Mohamed, Muthuchellappan, Radhakrishnan, Muthukrishnan, Muraleekrishnan, Muttini, Stefano, Nagata, Isao, Nahar, Dick, Nakanishi, Misuzu, Nakayama, Izumi, Antonio Namendys-Silva, Silvio, Nanchal, Rahul, Nandakumar, Sivakumar, Nasi, Alessandra, Nasir, Kamal, Navalesi, Paolo, Naz Aslam, Tayyba, Nga Phan, Thuy, Nichol, Alistair, Niiyama, Shuhei, Nikolakopoulou, Sofia, Nikolic, Elena, Nitta, Kenichi, Noc, Marko, Nonas, Stephanie, Nseir, Saad, Nur Soyturk, Ayse, Obata, Yukako, Oeckler, Richard, Oguchi, Moe, Ohshimo, Shinichiro, Oikonomou, Marina, Ojados, Agueda, Teresa Oliveira, Maria, Oliveira Filho, Wilson, Oliveri, Carlo, Olmos, Aitor, Omura, Kazuya, Cristina Orlandi, Maria, Orsenigo, Francesca, Ortiz-Ruiz De Gordoa, Laura, Ota, Kei, Ovalle Olmos, Rainier, Öveges, Nándo, Oziemski, Peter, Ozkan Kuscu, Ozlem, Özyilmaz, Ezgi, Pachas Alvarado, Fernando, Pagella, Gonzalo, Palaniswamy, Vijayanand, Luis Palazon Sanchez, Eugenio, Palmese, Salvatore, Pan, Guojun, Pan, Wensen, Papanikolaou, Metaxia, Papavasilopoulou, Theonymfi, Parekh, Ameet, Parke, Rachael, J Parrilla, Francisco, Parrilla, Dácil, Pasha, Taha, Pasin, Laura, Patão, Lui, Patel, Mayur, Patel, Grisma, Kumar Pati, Basanta, Patil, Jayaprakash, Pattnaik, Saroj, Paul, Daniel, Pavesi, Maurizio, Alejandra Pavlotsky, Vanesa, Paz, Graciela, Paz, Enrique, Pecci, Elisabetta, Pellegrini, Carlo, Gabriela Peña Padilla, Andrea, Perchiazzi, Gaetano, Pereira, Tiago, Pereira, Vera, Perez, Manuel, Perez Calvo, Cesar, Perez Cheng, Meisy, Perez Maita, Ronald, Pérez-Araos, Rodrigo, Perez-Teran, Purificación, Perez-Torres, David, Perkins, Gavin, Persona, Paolo, Petnak, Tananchai, Petrova, Marina, Pham, Tai, Philippart, Françoi, Picetti, Edoardo, Pierucci, Elisabetta, Piervincenzi, Edoardo, Pinciroli, Riccardo, Pintado, Maria-Consuelo, Piraino, Thoma, Piras, Stephanie, Piras, Claudio, Pirompanich, Pattarin, Pisani, Luigi, Platas, Enrique, Plotnikow, Gustavo, Porras, Willy, Porta, Virginia, Portilla, Mariana, Portugal, José, Povoa, Pedro, Prat, Gwenael, Pratto, Romina, Preda, Gabriel, Prieto, Isidro, Prol-Silva, Estefania, Pugh, Richard, Qi, Yupeng, Qian, Chuanyun, Qin, Tiehe, Qu, Hongping, Quintana, Teobaldo, Quispe Sierra, Rosari, Quispe Soto, Rocio, Rabbani, Raihan, Rabee, Mohamed, Rabie, Ahmed, Augusta Rahe Pereira, Maria, Rai, Ashish, Raj Ashok, Sundar, Rajab, Mostafa, Ramdhani, Navin, Ramey, Elizabeth, Ranieri, Marco, Rathod, Darshana, Ray, Banambar, Mahmud Redwanul Huq, Shihan, Regli, Adrian, Reina, Rosa, Resano Sarmiento, Natalia, Reynaud, Faustine, Rialp, Gemma, Ricart, Pilar, Rice, Todd, Richardson, Angu, Rieder, Marcelo, Rinket, Martin, Rios, Fernando, Risso Vazquez, Alejandro, Riva, Ivano, Rivette, Monaly, Roca, Oriol, Roche-Campo, Ferran, Rodriguez, Covadonga, 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Maseda, Eleni Massa, Anna Mattsson, Jessica Maugeri, Victoria McCredie, James McCullough, Shay McGuinness, Andrew McKown, László Medve, Chengqing Mei, Ricard Mellado Artigas, Vitor Mendes, Mohamed Khalaf Ebraheim Mervat, Isabelle Michaux, Michael Mikhaeil, Olga Milagros, Igor Milet, Maria Teresa Millan, Zhang Minwei, Lucia Mirabella, Sanghamitra Mishra, Giovanni Mistraletti, Katsunori Mochizuki, Arif Moghal, Francesco Mojoli, Alexandre Molin, Raquel Montiel, Luca Montini (ORCID:0000-0003-4602-5134), Gianmario Monza, Maria Mora Aznar, Sunthiti Morakul, Maria Morales, Daniel Moreno Torres, Diego Rolando Morocho Tutillo, Catherine Motherway, Doumiri Mouhssine, Eleni Mouloudi, Tapia Muñoz, Carlos Munoz de Cabo, Mohamed Mustafa, Radhakrishnan Muthuchellappan, Muraleekrishnan Muthukrishnan, Stefano Muttini, Isao Nagata, Dick Nahar, Misuzu Nakanishi, Izumi Nakayama, Silvio Antonio Namendys-Silva, Rahul Nanchal, Sivakumar Nandakumar, Alessandra Nasi, Kamal Nasir, Paolo Navalesi, Tayyba Naz 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Elizabeth Stevenson, Kristian Strand, Maria Teresa Strano, Slavenka Straus, Chenliang Sun, Rongqing Sun, Venkat Sundaram, Tai SunPark, Elisabeth Surlemont, Yuda Sutherasan, Zsuzsanna Szabo, Christopher Tainter, Akihiro Takaba, Mandy Tallott, Tamasato Tamasato, Zhanhong Tang, Viratch Tangsujaritvijit, Leandro Taniguchi, Daisuke Taniguchi, Fabio Tarantino, Krittika Teerapuncharoen, Susana Temprano, Pierpaolo Terragni, Nicolas Terzi, Anand Thakur, Pongdhep Theerawit, Arnaud W Thille, Matt Thomas, Poungrat Thungtitigul, Martial Thyrault, Nejla Tilouch, Karina Timenetsky, Juna Tirapu, Manuel Todeschini, Roser Tomas, Christian Tomaszewski, Tommaso Tonetti, Alexandre Tonnelier, John Trinder, Konlawij Trongtrakul, Jonathon Truwit, Betty Tsuei, Aiman Tulaimat, Sema Turan, Melda Turkoglu, Sanjeev Tyagi, Alejandro Ubeda, Federica Vagginelli, María Florencia Valenti, Imma Vallverdu, Alisha Van Axel, Ingrid van den Hul, Hans van der Hoeven, Nardo Van Der Meer, Marc Vanhoof, Mónica 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Tao, Yuan, Boyun, Yuangtrakul, Nadwipa, Yumoto, Tetsuya, Yun, Xie, Zakalik, Graciela, Zaki, Ahmad, Zalba-Etayo, Begoña, Zambon, Massimo, Zang, Bin, Zani, Gianluca, Zarka, Jonathan, Maria Zerbi, Simone, Zerman, Avsar, Zetterquist, Harald, Zhang, Jiuzhi, Zhang, Hongwen, Zhang, Wei, Zhang, Guoxiu, Zhang, Weixin, Zhao, Hongsheng, Zheng, Jia, Zhu, Bin, Zumaran, Ronald, Pham, Tài, Madotto, Fabiana, Goligher, Ewan C, Laake, Jon Henrik, Mancebo, Jordi, Peñuelas, Oscar, Pesenti, Antonio, Wunsch, Hannah, van Haren, Frank, Laffey, John G, Fekri Abrough, Subhash P Acharya, Pravin Amin, Yaseen Arabi, Irene Aragao, Philippe Bauer, Gaëtan Beduneau, Jeremy Beitler, Johan Berkius, Guillermo Bugedo, Luigi Camporota, Vladimir Cerny, Young-Jae Cho, Kevin Clarkson, Elisa Estenssoro, Ewan Goligher, Giacomo Grasselli, Alexey Gritsan, Seyed Mohammadreza Hashemian, Greet Hermans, Leo M Heunks, Bojan Jovanovic, Kiyoyasu Kurahashi, Jon Henrik Laake, Dimitrios Matamis, Onnen Moerer, Zsolt Molnar, Ezgi Ozyilmaz, Bernardo Panka, Alfred Papali, Óscar Peñuelas, Sébastien Perbet, Lise Piquilloud, Haibo Qiu, Assem Abdel Razek, Nuttapol Rittayamai, Rollin Roldan, Ary Serpa Neto, Konstanty Szuldrzynski, Daniel Talmor, Dana Tomescu, Frank Van Haren, Asisclo Villagomez, Amine Ali Zeggwagh, Toshikazu Abe, Abdelrhman Aboshady, Melanie Acampo-de Jong, Subhash Acharya, Jane Adderley, Nalan Adiguzel, Vijay Kumar Agrawal, Gerardo Aguilar, Gaston Aguirre, Hernan Aguirre-Bermeo, Björn Ahlström, Türkay Akbas, Mustafa Akker, Ghamdan Al Sadeh, Sultan Alamri, Angela Algaba, Muneeb Ali, Anna Aliberti, Jose Manuel Allegue, Diana Alvarez, Joaquin Amador, Finn H Andersen, Sharique Ansari, Yutthana Apichatbutr, Olympia Apostolopoulou, Daniel Arellano, Mestanza Arica, Huseyin Arikan, Koichi Arinaga, Jean-Michel Arnal, Kengo Asano, Marta Asín-Corrochano, Jesus Milagrito Avalos Cabrera, Silvia Avila Fuentes, Semih Aydemir, Gulbin Aygencel, Luciano Azevedo, Feza Bacakoglu, Julio Badie, Elias Baedorf Kassis, Gabriela Bai, Govindan Balaraj, Bruno Ballico, Valerie Banner-Goodspeed, Preveen Banwarie, Rosella Barbieri, Arvind Baronia, Jonathan Barrett, Loïc Barrot, Jesus Emilio Barrueco-Francioni, Jeffrey Barry, Harshal Bawangade, Sarah Beavis, Eduardo Beck, Nina Beehre, Alberto Belenguer Muncharaz, Giacomo Bellani, Mirko Belliato, Agrippino Bellissima, Rodrigo Beltramelli, Asma Ben Souissi, Adela Benitez-Cano, Mohamed Benlamin, Abdellatif Benslama, Luis Bento, Daniela Benvenuti, Laura Bernabe, Andrew Bersten, Giacomo Berta, Pietro Bertini, Elliot Bertram-Ralph, Mohamed Besbes, Lisandro Roberto Bettini, Pascal Beuret, Jeremy Bewley, Marco Bezzi, Lakshay Bhakhtiani, Rakesh Bhandary, Kaushik Bhowmick, Shailesh Bihari, Bernie Bissett, David Blythe, Simon Bocher, Narain Boedjawan, Christine M Bojanowski, Elisa Boni, Sabrina Boraso, Massimo Borelli, Silvina Borello, Margarita Borislavova, Karen J Bosma, Maurizio Bottiroli, Owen Boyd, Suha Bozbay, Arturo Briva, Laurent Brochard, Cédric Bruel, Andrea Bruni, Ulrike Buehner, Pierre Bulpa, Karen Burt, Mathieu Buscot, Stefania Buttera, Jorge Cabrera, Roberta Caccese, Pietro Caironi, Ivan Canchos Gutierrez, Nancy Canedo, Alma Cani, Iacopo Cappellini, Jesus Carazo, Luis Pablo Cardonnet, David Carpio, Demetrio Carriedo, Ramón Carrillo, João Carvalho, Eliana Caser, Antonio Castelli, Manuel Castillo Quintero, Heloisa Castro, Nuno Catorze, Melike Cengiz, Enrique Cereijo, Helga Ceunen, Christos Chaintoutis, Youjin Chang, Gustavogcha Chaparro, Carmel Chapman, Simon Chau, Cecilia Eugenia Chavez, Cosimo Chelazzi, Jonathan Chelly, Frank Chemouni, Kai Chen, Ariel Chena, Paolo Chiarandini, Phil Chilton, Davide Chiumello, Yvette Chou-Lie, Nicolas Chudeau, Ismail Cinel, Gilda Cinnella, Michele Clark, Thomas Clark, Stefano Clementi, Luis Coaguila, Alexis Jaspe Codecido, Amy Collins, Riccardo Colombo, Juan Conde, Guglielmo Consales, Tim Cook, Andrea Coppadoro, Rodrigo Cornejo, Andrea Cortegiani, Cristina Coxo, Andrea Neville Cracchiolo, Mónica Crespo Ramirez, Philippe Crova, José Cruz, Lucia Cubattoli, Zafer Çukurova, Francesco Curto, Piotr Czempik, Rocco D'Andrea, Fernando da Silva Ramos, Laurence Dangers, Marc Danguy des Déserts, Pierre-Eric Danin, Fabianne Dantas, Cédric Daubin, Wu Dawei, Candelaria de Haro, Felipe de Jesus Montelongo, Diego De Mendoza, Raúl de Pablo, Gennaro De Pascale, Silvia De Rosa, Maxens Decavèle, Pierre-Louis Declercq, Alberto Deicas, María Del Carmen Campos Moreno, Jean Dellamonica, Benjamin Delmas, Oktay Demirkiran, Hilmi Demirkiran, Tarek Dendane, Rossella di Mussi, Chrysi Diakaki, Anatilde Diaz, Willy Diaz, Yalim Dikmen, Aikaterini Dimoula, Patricia Doble, Nagwa Doha, Guilherme Domingos, Martin Dres, David Dries, Abhijit Duggal, Graeme Duke, Pavel Dunts, Knut Dybwik, Maksym Dykyy, Philippe Eckert, Serdar Efe, Souheil Elatrous, Gülseren Elay, Abubaker S Elmaryul, Mohamed Elsaadany, Hany Elsayed, Samar Elsayed, Malo Emery, Sébastien Ena, Kevin Eng, Joshua A Englert, Elif Erdogan, Perihan Ergin Ozcan, Ege Eroglu, Miguel Escobar, Figen Esen, Arzu Esen Tekeli, Alejandro Esquivel, Helbert Esquivel Gallegos, Hanane Ezzouine, Alberto Facchini, Mohammad Faheem, Vito Fanelli, Maria Fernanda Farina, Muriel Fartoukh, Lutz Fehrle, Feng Feng, Yufeng Feng, Irene Fernandez, Borja Fernandez, Maria Lorena Fernandez-Rodriguez, Carlos Ferrando, Maria João Ferreira da Silva, Mireia Ferreruela, Janet Ferrier, Matias Jesús Flamm Zamorano, Laura Flood, Leda Floris, Martin Fluckiger, Catalina Forteza, Antonella Fortunato, Eric Frans, Antonella Frattari, Sebastian Fredes, Tim Frenzel, Roberto Fumagalli, Mariano Andres Furche, Maurizio Fusari, Edward Fysh, Juan Luis Galeas-Lopez, Louis-Marie Galerneau, Analía Garcia, María Fernanda Garcia, Elisabet Garcia, Pablo Garcia Olivares, Jaroslaw Garlicki, Aude Garnero, Eugenio Garofalo, Prabha Gautam, Andrey Gazenkampf, Stéphanie Gelinotte, Domenico Gelormini, Etienne Ghrenassia, Angelo Giacomucci, Robert Giannoni, Andrea Gigante, Nancy Glober, Paolo Gnesin, Yari Gollo, Dina Gomaa, Rosita Gomero Paredes, Rui Gomes, Raúl Alejandro Gomez, Oscar Gomez, Aroa Gomez, Louise Gondim, Manuel Gonzalez, Isabel Gonzalez, Alejandro Gonzalez-Castro, Orlando Gordillo Romero, Federico Gordo, Philippe Gouin, Jerónimo Graf Santos, Rooney Grainne, Matilde Grando, Sanja Granov Grabovica, Salvatore Grasso, Rinaldo Grasso, Lisa Grimmer, Colin Grissom, Qing Gu, Xiang-Dong Guan, Fabio Guarracino, Neus Guasch, Luca Guatteri, Renaud Gueret, Claude Guérin, Emmanuel Guerot, Pierre-Gildas Guitard, Fethi Gül, Ayca Gumus, Mohan Gurjar, Patricia Gutierrez, Abdelhamid Hachimi, Adi Hadzibegovic, Samantha Hagan, Clare Hammel, Joo Han Song, Gabrielle Hanlon, Serge Heines, Johanna Henriksson, Jean-Etienne Herbrecht, Gabriel Omar Heredia Orbegoso, Andrew Hermon, Rosana Hernandez, Carmen Hernandez, Luis Herrera, Manuel Herrera-Gutierrez, Leo Heunks, Juan Hidalgo, Dianne Hill, Dagmar Holmquist, Marcela Homez, Xia Hongtao, Anil Hormis, Daniel Horner, M Carmen Hornos, Meihong Hou, Stacy House, Brahim Housni, Keith Hugill, Sally Humphreys, Louis Humbert, Stephanie Hunter, Lee Hwa Young, Nicolas Iezzi, Santiago Ilutovich, Volkan Inal, Richard Innes, Panagiotis Ioannides, Giorgio Antonio Iotti, Mariachiara Ippolito, Hiromasa Irie, Hiroki Iriyama, Taiga Itagaki, Javier Izura, Santiago Izza, Rakhshanda Jabeen, Hamidreza Jamaati, Sunil Jamadarkhana, Amira Jamoussi, Milosz Jankowski, Luis Alberto Jaramillo, Kyeongman Jeon, Seok Jeong Lee, Deepak Jeswani, Simant Jha, Liangyan Jiang, Chen Jing, Sébastien Jochmans, Bror Anders Johnstad, Lee Jongmin, Aurélie Joret, Detajin Junhasavasdikul, Maria Teresa Jurado, Elisa Kam, Hidenobu Kamohara, Caroline Kane, Iskender Kara, Sait Karakurt, Cherdkiat Karnjanarachata, Jun Kataoka, Shinshu Katayama, Shuchi Kaushik, Nermin Kelebek Girgin, Kathryn Kerr, Ian Kerslake, Prakash Khairnar, Abidi Khalid, Akram Khan, Ashish K Khanna, Reza Khorasanee, Dieneke Kienhorst, Cenk Kirakli, Rihard Knafelj, Mark Kol Kol, Napplika Kongpolprom, Csaba Kopitko, Pervin Korkmaz Ekren, Agnieszka Kubisz-Pudelko, Zoltan Kulcsar, Junji Kumasawa, Akira Kuriyama, Fernanda Kutchak, Eduardo Labarca, Françoise Labat, César Laborda, Manuel Alberto Laca Barrera, Laurie Lagache, Antonio Landaverde Lopez, Michael Lanspa, Valeria Lascari, Matthieu Le Meur, Su Hwan Lee, Young Ju Lee, Jinwoo Lee, Won-Yeon Lee, Jarone Lee, Terje Legernaes, Tamaas Leiner, Virginie Lemiale, Tiago Leonor, Philipp M Lepper, Dahuan Li, Hongbin Li, Oleg Li, Ana Raquel Lima, Dan Lind, Edward Litton, Ning Liu, Ling Liu, Jialin Liu, Jean-François Llitjos, Beatriz Llorente, Rodolfo Lopez, Claudia Elizabeth Lopez, Claudia Lopez Nava, Pablo Lovazzano, Min Lu, Francesca Lucchese, Manuela Lugano, Gustavo Lugo Goytia, Hua Luo, Ceri Lynch, Sebastiano Macheda, Victor Hugo Madrigal Robles, Salvatore Maurizio Maggiore, Mònica Magret Iglesias, Peter Malaga, Harish Mallapura Maheswarappa, Guillermo Malpartida, Andrey Malyarchikov, Helena Mansson, Anaid Manzano, Ismael Marey, Nathalie Marin, Maria Del Carmen Marin, Eliana Markman, Felix Martin, Alex Martin, Cristina Martin Dal Gesso, Felipe Martinez, Conchita Martínez-Fidalgo, Ignacio Martin-Loeches, Arantxa Mas, Sakuraya Masaaki, Emilio Maseda, Eleni Massa, Anna Mattsson, Jessica Maugeri, Victoria McCredie, James McCullough, Shay McGuinness, Andrew McKown, László Medve, Chengqing Mei, Ricard Mellado Artigas, Vitor Mendes, Mohamed Khalaf Ebraheim Mervat, Isabelle Michaux, Michael Mikhaeil, Olga Milagros, Igor Milet, Maria Teresa Millan, Zhang Minwei, Lucia Mirabella, Sanghamitra Mishra, Giovanni Mistraletti, Katsunori Mochizuki, Arif Moghal, Francesco Mojoli, Alexandre Molin, Raquel Montiel, Luca Montini (ORCID:0000-0003-4602-5134), Gianmario Monza, Maria Mora Aznar, Sunthiti Morakul, Maria Morales, Daniel Moreno Torres, Diego Rolando Morocho Tutillo, Catherine Motherway, Doumiri Mouhssine, Eleni Mouloudi, Tapia Muñoz, Carlos Munoz de Cabo, Mohamed Mustafa, Radhakrishnan Muthuchellappan, Muraleekrishnan Muthukrishnan, Stefano Muttini, Isao Nagata, Dick Nahar, Misuzu Nakanishi, Izumi Nakayama, Silvio Antonio Namendys-Silva, Rahul Nanchal, Sivakumar Nandakumar, Alessandra Nasi, Kamal Nasir, Paolo Navalesi, Tayyba Naz Aslam, Thuy Nga Phan, Alistair Nichol, Shuhei Niiyama, Sofia Nikolakopoulou, Elena Nikolic, Kenichi Nitta, Marko Noc, Stephanie Nonas, Saad Nseir, Ayse Nur Soyturk, Yukako Obata, Richard Oeckler, Moe Oguchi, Shinichiro Ohshimo, Marina Oikonomou, Agueda Ojados, Maria Teresa Oliveira, Wilson Oliveira Filho, Carlo Oliveri, Aitor Olmos, Kazuya Omura, Maria Cristina Orlandi, Francesca Orsenigo, Laura Ortiz-Ruiz De Gordoa, Kei Ota, Rainier Ovalle Olmos, Nándo Öveges, Peter Oziemski, Ozlem Ozkan Kuscu, Ezgi Özyilmaz, Fernando Pachas Alvarado, Gonzalo Pagella, Vijayanand Palaniswamy, Eugenio Luis Palazon Sanchez, Salvatore Palmese, Guojun Pan, Wensen Pan, Metaxia Papanikolaou, Theonymfi Papavasilopoulou, Ameet Parekh, Rachael Parke, Francisco J Parrilla, Dácil Parrilla, Taha Pasha, Laura Pasin, Luis Patão, Mayur Patel, Grisma Patel, Basanta Kumar Pati, Jayaprakash Patil, Saroj Pattnaik, Daniel Paul, Maurizio Pavesi, Vanesa Alejandra Pavlotsky, Graciela Paz, Enrique Paz, Elisabetta Pecci, Carlos Pellegrini, Andrea Gabriela Peña Padilla, Gaetano Perchiazzi, Tiago Pereira, Vera Pereira, Manuel Perez, Cesar Perez Calvo, Meisy Perez Cheng, Ronald Perez Maita, Rodrigo Pérez-Araos, Purificación Perez-Teran, David Perez-Torres, Gavin Perkins, Paolo Persona, Tananchai Petnak, Marina Petrova, Tai Pham, François Philippart, Edoardo Picetti, Elisabetta Pierucci, Edoardo Piervincenzi, Riccardo Pinciroli, Maria-Consuelo Pintado, Thomas Piraino, Stephanie Piras, Claudio Piras, Pattarin Pirompanich, Luigi Pisani, Enrique Platas, Gustavo Plotnikow, Willy Porras, Virginia Porta, Mariana Portilla, José Portugal, Pedro Povoa, Gwenael Prat, Romina Pratto, Gabriel Preda, Isidro Prieto, Estefania Prol-Silva, Richard Pugh, Yupeng Qi, Chuanyun Qian, Tiehe Qin, Hongping Qu, Teobaldo Quintana, Rosari Quispe Sierra, Rocio Quispe Soto, Raihan Rabbani, Mohamed Rabee, Ahmed Rabie, Maria Augusta Rahe Pereira, Ashish Rai, Sundar Raj Ashok, Mostafa Rajab, Navin Ramdhani, Elizabeth Ramey, Marco Ranieri, Darshana Rathod, Banambar Ray, Shihan Mahmud Redwanul Huq, Adrian Regli, Rosa Reina, Natalia Resano Sarmiento, Faustine Reynaud, Gemma Rialp, Pilar Ricart, Todd Rice, Angus Richardson, Marcelo Rieder, Martin Rinket, Fernando Rios, Alejandro Risso Vazquez, Ivano Riva, Monaly Rivette, Oriol Roca, Ferran Roche-Campo, Covadonga Rodriguez, Gabriel Rodriguez, Daniel Rodriguez Gonzalez, Xandra Yanina Rodriguez Tucto, Angela Rogers, María Elena Romano, Linda Rørtveit, Alastair Rose, Damien Roux, Anahita Rouze, Paolo Nahuel Rubatto Birri, Wang Ruilan, Aldana Ruiz Robledo, Antonio Luis Ruiz-Aguilar, Tomohito Sadahiro, Ignacio Saez, Judith Sagardia, Rajnish Saha, Rohit Saha, Narongkorn Saiphoklang, Shigeki Saito, Maie Salem, Gabriele Sales, Patricia Salgado, Srinivas Samavedam, Mhamed Sami Mebazaa, Line Samuelsson, Nandyelly San Juan Roman, Patricia Sanchez, Jesus Sanchez-Ballesteros, Yazcitk Sandoval, Emanuele Sani, Martin Santos, Carla Santos, Masamitsu Sanui, Lakshmikanthcharan Saravanabavan, Sema Sari, Agnes Sarkany, Bertrand Sauneuf, Monica Savioli, Hilal Sazak, Riccardo Scano, Francis Schneider, Frédérique Schortgen, Marcus J Schultz, Gabriele Leonie Schwarz, Faruk Seçkin Yücesoy, Andrew Seely, Frederik Seiler, Yasemin Seker Tekdos, Kim Seok Chan, Luca Serano, Wojciech Serednicki, Mariano Setten, Asim Shah, Bhagyesh Shah, You Shang, Pradeep Shanmugasundaram, Konstantin Shapovalov, Eman Shebl, Takuya Shiga, Nobuaki Shime, Phil Shin, Jack Short, Chen Shuhua, Sughrat Siddiqui, Juan Ignacio Silesky Jimenez, Daniel Silva, Betania Silva Sales, Koen Simons, Brit Ågot Sjøbø, David Slessor, Jakub Smiechowicz, Nathan Smischney, Paul Smith, Tim Smith, Mark Smith, Sarah Snape, Lindi Snyman, Filiep Soetens, Kyung Sook Hong, Miguel Ángel Sosa Medellin, Giovanna Soto, Xavier Souloy, Elsa Sousa, Stefania Sovatzis, Didem Sozutek, Savino Spadaro, Marco Spagnoli, Martin Spångfors, Nick Spittle, Mike Spivey, Andrew Stapleton, Branislava Stefanovic, Lorraine Stephenson, Elizabeth Stevenson, Kristian Strand, Maria Teresa Strano, Slavenka Straus, Chenliang Sun, Rongqing Sun, Venkat Sundaram, Tai SunPark, Elisabeth Surlemont, Yuda Sutherasan, Zsuzsanna Szabo, Christopher Tainter, Akihiro Takaba, Mandy Tallott, Tamasato Tamasato, Zhanhong Tang, Viratch Tangsujaritvijit, Leandro Taniguchi, Daisuke Taniguchi, Fabio Tarantino, Krittika Teerapuncharoen, Susana Temprano, Pierpaolo Terragni, Nicolas Terzi, Anand Thakur, Pongdhep Theerawit, Arnaud W Thille, Matt Thomas, Poungrat Thungtitigul, Martial Thyrault, Nejla Tilouch, Karina Timenetsky, Juna Tirapu, Manuel Todeschini, Roser Tomas, Christian Tomaszewski, Tommaso Tonetti, Alexandre Tonnelier, John Trinder, Konlawij Trongtrakul, Jonathon Truwit, Betty Tsuei, Aiman Tulaimat, Sema Turan, Melda Turkoglu, Sanjeev Tyagi, Alejandro Ubeda, Federica Vagginelli, María Florencia Valenti, Imma Vallverdu, Alisha Van Axel, Ingrid van den Hul, Hans van der Hoeven, Nardo Van Der Meer, Marc Vanhoof, Mónica Vargas-Ordoñez, Rosanna Vaschetto, Ettore Vascotto, Maria Vatsik, Ana Vaz, Antonia Vazquez-Sanchez, Sara Ventura, Jan Wytze Vermeijden, Anxela Vidal, Jocyelle Vieira, Bruno Vilela Costa Pinto, Ana Villagra, Cristina Villegas Succar, Ole Georg Vinorum, Giovanni Vitale, Ramesh Vj, Ana Vochin, Guillaume Voiriot, Carlo Alberto Volta, Magnus von Seth, Maazouzi Wajdi, Don Walsh, Shouhong Wang, Gabriel Wardi, Nils Christian Ween-Velken, Bi-Lin Wei, Dolf Weller, Deborah Welsh, Ingeborg Welters, Michael Wert, Simon Whiteley, Elizabeth Wilby, Erin Williams, Karen Williams, Antoinette Wilson, Jadwiga Wojtas, Jin Won Huh, David Wrathall, Christopher Wright, Jian-Feng Wu, Guo Xi, Zheng-Jiang Xing, Hongyang Xu, Kotaro Yamamoto, Jie Yan, Julio Yáñez, Xiaobo Yang, Elliot Yates, Ozlem Yazicioglu Mocin, Zhenglong Ye, Fatma Yildirim, Norifumi Yoshida, Hector Higo Leon Yoshido, Bo Young Lee, Rongguo Yu, Gong Yu, Tao Yu, Boyun Yuan, Nadwipa Yuangtrakul, Tetsuya Yumoto, Xie Yun, Graciela Zakalik, Ahmad Zaki, Begoña Zalba-Etayo, Massimo Zambon, Bin Zang, Gianluca Zani, Jonathan Zarka, Simone Maria Zerbi, Avsar Zerman, Harald Zetterquist, Jiuzhi Zhang, Hongwen Zhang, Wei Zhang, Guoxiu Zhang, Weixin Zhang, Hongsheng Zhao, Jia Zheng, Bin Zhu, and Ronald Zumaran
Abstract: Background: Current management practices and outcomes in weaning from invasive mechanical ventilation are poorly understood. We aimed to describe the epidemiology, management, timings, risk for failure, and outcomes of weaning in patients requiring at least 2 days of invasive mechanical ventilation. Methods: WEAN SAFE was an international, multicentre, prospective, observational cohort study done in 481 intensive care units in 50 countries. Eligible participants were older than 16 years, admitted to a participating intensive care unit, and receiving mechanical ventilation for 2 calendar days or longer. We defined weaning initiation as the first attempt to separate a patient from the ventilator, successful weaning as no reintubation or death within 7 days of extubation, and weaning eligibility criteria based on positive end-expiratory pressure, fractional concentration of oxygen in inspired air, and vasopressors. The primary outcome was the proportion of patients successfully weaned at 90 days. Key secondary outcomes included weaning duration, timing of weaning events, factors associated with weaning delay and weaning failure, and hospital outcomes. This study is registered with ClinicalTrials.gov, NCT03255109. Findings: Between Oct 4, 2017, and June 25, 2018, 10 232 patients were screened for eligibility, of whom 5869 were enrolled. 4523 (77·1%) patients underwent at least one separation attempt and 3817 (65·0%) patients were successfully weaned from ventilation at day 90. 237 (4·0%) patients were transferred before any separation attempt, 153 (2·6%) were transferred after at least one separation attempt and not successfully weaned, and 1662 (28·3%) died while invasively ventilated. The median time from fulfilling weaning eligibility criteria to first separation attempt was 1 day (IQR 0-4), and 1013 (22·4%) patients had a delay in initiating first separation of 5 or more days. Of the 4523 (77·1%) patients with separation attempts, 2927 (64·7%) had a short wean (≤1 d
Published: 2023

35. Management of the Potential Lung Donor

Author: Ashwini, Arjuna, Anna Teresa, Mazzeo, Tommaso, Tonetti, Rajat, Walia, and Luciana, Mascia
Subjects: Pulmonary and Respiratory Medicine, Time Factors, Tissue and Organ Procurement, Humans, Surgery, Lung, Tissue Donors, Lung Transplantation
Abstract: The use of donor management protocols has significantly improved recovery rates; however, the inherent instability of lungs after death results in low utilization rates of potential donor lungs. Donor lungs are susceptible to direct trauma, aspiration, neurogenic edema, ventilator-associated barotrauma, and ventilator-associated pneumonia. After irreversible brain injury and determination of futility of care, the goal of medical management of the donor shifts to maintaining hemodynamic stability and maximizing the likelihood of successful organ recovery.
Published: 2022

36. Phenotypes of Patients with COVID-19 Who Have a Positive Clinical Response to Helmet Noninvasive Ventilation

Author: Domenico Luca Grieco, Luca S. Menga, Melania Cesarano, Savino Spadaro, Maria Maddalena Bitondo, Cecilia Berardi, Tommaso Rosà, Filippo Bongiovanni, Salvatore Maurizio Maggiore, Massimo Antonelli, Jonathan Montomoli, Giulia Falò, Tommaso Tonetti, Salvatore L. Cutuli, Gabriele Pintaudi, Eloisa S. Tanzarella, Edoardo Piervincenzi, Antonio M. Dell’Anna, Luca Delle Cese, Simone Carelli, Maria Grazia Bocci, Luca Montini, Giuseppe Bello, Daniele Natalini, Gennaro De Pascale, Matteo Velardo, Carlo Alberto Volta, V. Marco Ranieri, Giorgio Conti, Riccardo Maviglia, Giovanna Mercurio, Paolo De Santis, Mariano Alberto Pennisi, Gian Marco Anzellotti, Flavia Torrini, Carlotta Rubino, Tony C. Morena, Veronica Gennenzi, Stefania Postorino, Joel Vargas, Nicoletta Filetici, Donatella Settanni, Miriana Durante, Laura Cascarano, Mariangela Di Muro, Roberta Scarascia, Martina Murdolo, Alessandro Mele, Serena Silva, Carmelina Zaccone, Francesca Pozzana, Alessio Maccaglia, Martina Savino, Antonella Potalivo, Francesca Ceccaroni, Angela Scavone, Gianmarco Lombardi, and Teresa Michi
Subjects: Male, Pulmonary and Respiratory Medicine, medicine.medical_specialty, 2019-20 coronavirus outbreak, Coronavirus disease 2019 (COVID-19), Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), MEDLINE, Critical Care and Intensive Care Medicine, Respiratory Rate, Internal medicine, Settore MED/41 - ANESTESIOLOGIA, Intubation, Intratracheal, Humans, Medicine, Aged, Noninvasive Ventilation, business.industry, Oxygen Inhalation Therapy, COVID-19, Middle Aged, Phenotype, Respiratory Function Tests, Treatment Outcome, Italy, Female, Noninvasive ventilation, business, Phenotypes of Patients with COVID-19
Published: 2022

37. Co-infection and ICU-acquired infection in COIVD-19 ICU patients: a secondary analysis of the UNITE-COVID data set

Author: Conway Morris, Andrew, Kohler, Katharina, De Corte, Thomas, Ercole, Ari, De Grooth, Harm-Jan, Elbers, Paul W G, Povoa, Pedro, Morais, Rui, Koulenti, Despoina, Jog, Sameer, Nielsen, Nathan, Jubb, Alasdair, Cecconi, Maurizio, De Waele, Jan, Marco, Bezzi, Alicia, Gira, Philipp, Eller, Tarikul, Hamid, Injamam Ull Haque, Wim De Buyser, Antonella, Cudia, Daniel De Backer, Pierre, Foulon, Vincent, Collin, Jan De Waele, Jolien Van Hecke, Elisabeth De Waele, Claire Van Malderen, Jean-Baptiste, Mesland, Patrick, Biston, Michael, Piagnerelli, Lionel, Haentjens, Nicolas De Schryver, Jan Van Leemput, Philippe, Vanhove, Pierre, Bulpa, Viktoria, Ilieva, David, Katz, Alexandra, Binnie, Anna, Geagea, Fernando, Tirapegui, Gustavo, Lago, Jerónimo, Graf, Rodrigo, Perez-Araos, Patricio, Vargas, Felipe, Martinez, Eduardo, Labarca, Daniel Molano Franco, Daniela, Parra-Tanoux, Luis Felipe Reyes, David, Yepes, Filip, Periš, Sanda Stojanović Stipić, Cynthia Vanessa Campozano Burgos, Paulo Roberto Navas Boada, Jose Luis Barberan Brun, Juan Pablo Paredes Ballesteros, Gamal, Abdelnasser, Ahmed, Hammouda, Omar, Elmandouh, Ahmed, Azzam, Aliae Mohamed Hussein, Islam, Galal, Ahmed, K Awad, Mohammed, A Azab, Maged, Abdalla, Hebatallah, Assal, Mostafa, Alfishawy, Sherief, Ghozy, Samar, Tharwat, Abdullah, Eldaly, Anneli, Ellervee, Veronika, Reinhard, Anne, Chrisment, Chrystelle, Poyat, Julio, Badie, Fernando Berdaguer Ferrari, Björn, Weiss, Clara, Schellenberg, Julius, J Grunow, Marco, Lorenz, Stefan, J Schaller, Peter, Spieth, Marc, Bota, Falk, Fichtner, Kristina, Fuest, Tobias, Lahmer, Johannes, Herrmann, Patrick, Meybohm, Nikolaos, Markou, Georgia, Vasileiadou, Evangelia, Chrysanthopoulou, Panagiotis, Papamichalis, Ioanna, Soultati, Sameer, Jog, Kushal, Kalvit, Sheila Nainan Myatra, Ivan, Krupa, Aisa, Tharwat, Alistair, Nichol, Aine, Mccarthy, Ata, Mahmoodpoor, Tommaso, Tonetti, Paolo, Isoni, Savino, Spadaro, Carlo Alberto Volta, Lucia, Mirabella, Alberto, Noto, Gaetano, Florio, Amedeo, Guzzardella, Chiara, Paleari, Federica, Baccanelli, Marzia, Savi, Massimo, Antonelli, Gennaro De Pascale, San, Luca, Barbara, Vaccarini, Giorgia, Montrucchio, Gabriele, Sales, Donadello, Katia, Leonardo, Gottin, Marta, Nizzero, Enrico, Polati, De Rosa, Silvia, Demet, Sulemanji, Abdurraouf, Abusalama, Muhammed, Elhadi, Montelongo De FelipeJesus, Daniel Rodriguez Gonzalez, Victor Hugo Madrigal Robles, Nancy, Canedo, Alejandro Esquivel Chavez, Tarek, Dendane, Bart, Grady, Ben de Jong, Eveline van der Heiden, Patrick, Thoral, Bas van den Bogaard, Peter, E Spronk, Sefanja, Achterberg, Melanie, Groeneveld, Ralph K, L So, Calvin de Wijs, Harm, Scholten, Albertus, Beishuizen, Alexander, D Cornet, Auke, C Reidinga, Hetty, Kranen, Roos, Mensink, Spaarne, Gasthuis, Sylvia den Boer, Marcel de Groot, Oliver, Beck, Carina, Bethlehem, Bas van Bussel, Tim, Frenzel, Celestine de Jong, Rob, Wilting, Jozef, Kesecioglu, Jannet, Mehagnoul-Schipper, Datonye, Alasia, Ashok, Kumar, Ahad, Qayyum, Muhammad, Rana, Mustafa Abu Jayyab, Rosario Quispe Sierra, Aaron Mark Hernandez, José de Almeida, Lúcia, Taborda, Mónica, Anselmo, Tiago, Ramires, Catarina, Silva, Carolina, Roriz, Rui, Morais, Pedro, Póvoa, Patricia, Patricio, André, Pinto, Maria Lurdes Santos, Vasco, Costa, Pedro, Cunha, Celina, Gonçalves, Sandra, Nunes, João, Camões, Diana, Adrião, Ana, Oliveira, Ali, Omrani, Muna Al Maslamani, Abdurrahmaan Suei Elbuzidi, Bara Mahmoud Al Qudah, Abdel Rauof Akkari, Mohamed, Alkhatteb, Anas, Baiou, Ahmed, Husain, Mohamed, Alwraidat, Ibrahim Abdulsalam Saif, Dana, Bakdach, Amna, Ahmed, Mohamed, Aleef, Awadh, Bintaher, Cristina, Petrisor, Evgeniy, Popov, Ksenia, Popova, Mariia, Dementienko, Boris, Teplykh, Alexey, Pyregov, Liubov, Davydova, Belskii, Vladislav, Elena, Neporada, Ivan, Zverev, Svetlana, Meshchaninova, Dmitry, Sokolov, Elena, Gavrilova, Irina, Shlyk, Igor, Poliakov, Marina, Vlasova, Ohoud, Aljuhani, Amina, Alkhalaf, Felwa Bin Humaid, Yaseen, Arabi, Ahmed, Kuhail, Omar, Elrabi, Madihah, E Ghannam, Ng Teng Fong, Amit, Kansal, Vui Kian Ho, Jensen, Ng, Raquel Rodrígez García, Xiana Taboada Fraga, Mª Del Pilar García-Bonillo, Antonio, Padilla-Serrano, Marta Martin Cuadrado, Carlos, Ferrando, Ignacio, Catalan-Monzon, Laura, Galarza, Fernando, Frutos-Vivar, Jorge, Jimenez, Carmen, Rodríguez-Solis, Enric, Franquesa-Gonzalez, Guillermo Pérez Acosta, Luciano Santana Cabrera, Juan Pablo Aviles Parra, Francisco Muñoyerro Gonzalez, Maria Del Carmen Lorente Conesa, Ignacio Yago Martinez Varela, Orville Victoriano Baez Pravia, Maria Cruz Martin Delgado, Carlos Munoz de Cabo, Ana-Maria, Ioan, Cesar, Perez-Calvo, Arnoldo, Santos, Ane, Abad-Motos, Javier, Ripolles-Melchor, Belén Civantos Martin, Santiago Yus Teruel, Juan Higuera Lucas, Aaron Blandino Ortiz, Raúl de Pablo Sánchez, Jesús Emilio Barrueco-Francioni, Lorena Forcelledo Espina, José, M Bonell-Goytisolo, Iñigo, Salaverria, Antonia Socias Mir, Emilio, Rodriguez-Ruiz, Virginia Hidalgo Valverde, Patricia Jimeno Cubero, Francisca Arbol Linde, Nieves Cruza Leganes, Juan Maria Romeu, Pablo, Concha, José Angel Berezo-Garcia, Virginia, Fraile, Cristina, Cuenca-Rubio, David, Pérez-Torres, Ainhoa, Serrano, Clara Martínez Valero, Andrea Ortiz Suner, Leire, Larrañaga, Noemi, Legaristi, Gerardo, Ferrigno, Safa, Khlafalla, Rosita, Bihariesingh-Sanchit, Hallands, Sjukhus, Frank, Zoerner, Jonathan, Grip, Kristina, Kilsand, Johan, Mårtensson, Jonas, Österlind, Akademiska, Sjukhuset, Magnus von Seth, Västerviks, Sjukhus, Johan, Berkius, Samuele, Ceruti, Andrea, Glotta, Seval, Izdes, Işıl Özkoçak Turan, Ahmet, Cosar, Burcin, Halacli, Necla, Dereli, Mehmet, Yilmaz, Türkay, Akbas, Gülseren, Elay, Selin, Eyüpoğlu, Yelíz, Bílír, Kemal Tolga Saraçoğlu, Ebru, Kaya, Ayca Sultan Sahin, Pervin Korkmaz Ekren, Tuğçe, Mengi, Kezban Ozmen Suner, Yakup, Tomak, Ahmet, Eroglu, Asad, Alsabbah, Katie, Hanlon, Kevin, Gervin, Sean, Mcmahon, Samantha, Hagan, Caroline, V Higenbottam, Randeep, Mullhi, Lottie, Poulton, Tomasz, Torlinski, Allen, Gareth, Nick, Truman, Gopal, Vijayakumar, Chris, Hall, Alasdair, Jubb, Lenka, Cagova, Nicola, Jones, Sam, Graham, Nicole, Robin, Amanda, Cowton, Adrian, Donnelly, Natalia, Singatullina, Melanie, Kent, Carole, Boulanger, Zoë, Campbell, Elizabeth, Potter, Natalie, Duric, Tamas, Szakmany, Royal, Brompton, Orinta, Kviatkovske, Nandor, Marczin, Caroline, Ellis, Rajnish, Saha, Chunda, Sri-Chandana, John, Allan, Lana, Mumelj, Harish, Venkatesh, Vera Nina Gotz, Anthony, Cochrane, Barbara, Ficial, Shruthi, Kamble, Nuttha, Lumlertgul, Christopher, Oddy, Susan, Jain, Giulia Beatrice Crapelli, Aikaterini, Vlachou, David, Golden, Sweyn, Garrioch, Jeremy, Henning, Gupta, Loveleena, Miriam, Davey, Lina, Grauslyte, Erika, Salciute-Simene, Martin, Cook, Danny, Barling, Phil, Broadhurst, Sarah, Purvis, Michael, Spivey, Benjamin, Shuker, Irina, Grecu, Daniel, Harding, James, T Dean, Nathan, D Nielsen, Sama, Al-Bayati, Mohammed, Al-Sadawi, Mariane, Charron, Peter, Stubenrauch, Jairo, Santanilla, Catherine, Wentowski, Dorothea, Rosenberger, Polikseni, Eksarko, Randeep, Jawa, Intensive care medicine, ACS - Microcirculation, ACS - Diabetes & metabolism, AII - Infectious diseases, Conway Morris, Andrew [0000-0002-3211-3216], Kohler, Katharina [0000-0003-1919-0193], De Corte, Thomas [0000-0001-5011-6640], Ercole, Ari [0000-0001-8350-8093], De Grooth, Harm-Jan [0000-0002-7499-076X], Elbers, Paul WG [0000-0003-0447-6893], Povoa, Pedro [0000-0002-7069-7304], Morais, Rui [0000-0003-4114-6949], Koulenti, Despoina [0000-0003-4364-2612], Jog, Sameer [0000-0002-1134-1260], Nielsen, Nathan [0000-0002-3131-7540], Jubb, Alasdair [0000-0001-5593-866X], Cecconi, Maurizio [0000-0002-4376-6538], De Waele, Jan [0000-0003-1017-9748], Apollo - University of Cambridge Repository, UCL - SSS/DDUV/GECE - Génétique cellulaire, UCL - (SLuc) Service de soins intensifs, Conway Morris A., Kohler K., De Corte T., Ercole A., De Grooth H.-J., Elbers P.W.G., Povoa P., Morais R., Koulenti D., Jog S., Nielsen N., Jubb A., Cecconi M., De Waele J., Bezzi M., Gira A., Eller P., Hamid T., Haque I.U., De Buyser W., Cudia A., De Backer D., Foulon P., Collin V., Van Hecke J., De Waele E., Van Malderen C., Mesland J.-B., Piagnerelli M., Haentjens L., De Schryver N., Van Leemput J., Vanhove P., Bulpa P., Ilieva V., Katz D., Geagea A., Binnie A., Tirapegui F., Lago G., Graf J., Perez-Araos R., Vargas P., Martinez F., Labarca E., Franco D.M., Parra-Tanoux D., Reyes L.F., Yepes D., Peris F., Stipic S.S., Burgos C.V.C., Boada P.R.N., Brun J.L.B., Ballesteros J.P.P., Hammouda A., Elmandouh O., Azzam A., Hussein A.M., Galal I., Awad A.K., Azab M.A., Abdalla M., Assal H., Alfishawy M., Ghozy S., Tharwat S., Eldaly A., Reinhard V., Chrisment A., Poyat C., Badie J., Ferrari F.B., Weiss B., Kuhn K.F., Grunow J.J., Lorenz M., Schaller S., Spieth P., Bota M., Fichtner F., Fuest K., Lahmer T., Herrmann J., Meybohm P., Markou N., Vasileiadou G., Chrysanthopoulou E., Papamichalis P., Soultati I., Kalvit K., Myatra S.N., Krupa I., Tharwat A., Nichol A., McCarthy A., Mahmoodpoor A., Tonetti T., Isoni P., Spadaro S., Volta C.A., Mirabella L., Noto A., Florio G., Guzzardella A., Paleari C., Baccanelli F., Savi M., Antonelli M., Vaccarini B., Montrucchio G., Sales G., Donadello K., Gottin L., Polati E., De Rosa S., Sulemanji D., Abusalama A., Elhadi M., De Jesus M.F., Gonzalez D.R., Canedo N., Chavez A.E., Dendane T., Grady B., de Jong B., van der Heiden E., Thoral P., van den Bogaard B., Spronk P.E., Achterberg S., Groeneveld M., So R.K.L., de Wijs C., Scholten H., Beishuizen A., Cornet A.D., Reidinga A.C., Kranen H., Mensink R., Boer S., de Groot M., Beck O., Bethlehem C., van Bussel B., Frenzel T., de Jong C., Wilting R., Kesecioglu J., Mehagnoul-Schipper J., Alasia D., Kumar A., Qayyum A., Rana M., Jayyab M.A., Sierra R.Q., Hernandez A.M., Taborda L., Ramires T., Silva C., Roriz C., Patricio P., Santos M.L., Costa V., Cunha P., Goncalves C., Nunes S., Camoes J., Adriao D., Oliveira A., Omrani A., Al Maslamani M., elbuzidi A.S., Al qudah B.M., Akkari A.R., Alkhatteb M., Baiou A., Husain A., Alwraidat M., Saif I.A., Bakdach D., Ahmed A., Aleef M., Bintaher A., Petrisor C., Popov E., Popova K., Dementienko M., Teplykh B., Pyregov A., Davydova L., Vladislav B., Neporada E., Zverev I., Meshchaninova S., Sokolov D., Gavrilova E., Shlyk I., Poliakov I., B?aco?a M., Aljuhani O., Alkhalaf A., Humaid F.B., Arabi Y., Kuhail A., Elrabi O., Alghnam M., Kansal A., Ho V.K., Ng J., Garcia R.R., Fraga X.T., del Pilar Garcia-Bonillo M., Padilla-Serrano A., Cuadrado M.M., Ferrando C., Catalan-Monzon I., Galarza L., Frutos-Vivar F., Jimenez J., Rodriguez-Solis C., Franquesa-Gonzalez E., Acosta G.P., Cabrera L.S., Parra J.P.A., Gonzalez F.M., del Carmen Lorente Conesa M., Varela I.Y.M., Pravia O.V.B., Delgado M.C.M., de Cabo C.M., Ioan A.-M., Perez-Calvo C., Santos A., Abad-Motos A., Ripolles-Melchor J., Martin B.C., Teruel S.Y., Lucas J.H., Ortiz A.B., de Pablo Sanchez R., Barrueco-Francioni J.E., Espina L.F., Bonell-Goytisolo J.M., Salaverria I., Mir A.S., Rodriguez-Ruiz E., Valverde V.H., Cubero P.J., Linde F.A., Leganes N.C., Romeu J.M., Concha P., Berezo-Garcia J.A., Fraile V., Cuenca-Rubio C., Perez-Torres D., Serrano A., Valero C.M., Suner A.O., Larranaga L., Legaristi N., Ferrigno G., Khlafalla S., Bihariesingh-Sanchit R., Zoerner F., Grip J., Kilsand K., Osterlind J., von Seth M., Berkius J., Ceruti S., Glotta A., Izdes S., Turan I.O., Cosar A., Halacli B., Dereli N., Yilmaz M., Akbas T., Elay G., Eyupoglu S., Bilir Y., Saracoglu K.T., Kaya E., Sahin A.S., Ekren P.K., Mengi T., Suner K.O., Tomak Y., Eroglu A., Alsabbah A., Hanlon K., Gervin K., McMahon S., Hagan S., Higenbottam C.V., Mullhi R., Poulton L., Torlinski T., Gareth A., Truman N., Vijayakumar G., Hall C., Cagova L., Jones N., Graham S., Robin N., Cowton A., Donnelly A., Singatullina N., Kent M., Boulanger C., Campbell Z., Potter E., Duric N., Szakmany T., Kviatkovske O., Marczin N., Ellis C., Saha R., Sri-Chandana C., Allan J., Mumelj L., Venkatesh H., Gotz V.N., Cochrane A., Lumlertgul N., Ficial B., Jain S., Crapelli G.B., Vlachou A., Golden D., Garrioch S., Henning J., Loveleena G., Davey M., Grauslyte L., Salciute-Simene E., Cook M., Barling D., Broadhurst P., Purvis S., Michael S., Shuker B., Grecu I., Harding D., Dean J.T., Nielsen N.D., Al-Bayati S., Al-Sadawi M., Charron M., Stubenrauch P., Santanilla J., Wentowski C., Rosenberger D., Eksarko P., and Jawa R.
Subjects: Adult, Coronavirus Disease 2019 (COVID-19), Critical Illness, Intensive Care Unit, Pneumonia, Viral, NCT04836065, Adrenal Cortex Hormone, Critical Care and Intensive Care Medicine, co-infection, COVID-19 Testing, Adrenal Cortex Hormones, Anti-Bacterial Agent, Medicine and Health Sciences, Pneumonia, Bacterial, Humans, Pandemics, Pandemic, Coinfection, Research, Other Research Radboud Institute for Health Sciences [Radboudumc 0], respiratory failure, COVID-19, Anti-Bacterial Agents, Intensive Care Units, NCT, ICU, Critical Illne, Coronavirus Disease 2019 (COVID-19), co-infection, ICU, respiratory failure, Human
Abstract: Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347, BACKGROUND: The COVID-19 pandemic presented major challenges for critical care facilities worldwide. Infections which develop alongside or subsequent to viral pneumonitis are a challenge under sporadic and pandemic conditions; however, data have suggested that patterns of these differ between COVID-19 and other viral pneumonitides. This secondary analysis aimed to explore patterns of co-infection and intensive care unit-acquired infections (ICU-AI) and the relationship to use of corticosteroids in a large, international cohort of critically ill COVID-19 patients. METHODS: This is a multicenter, international, observational study, including adult patients with PCR-confirmed COVID-19 diagnosis admitted to ICUs at the peak of wave one of COVID-19 (February 15th to May 15th, 2020). Data collected included investigator-assessed co-infection at ICU admission, infection acquired in ICU, infection with multi-drug resistant organisms (MDRO) and antibiotic use. Frequencies were compared by Pearson's Chi-squared and continuous variables by Mann-Whitney U test. Propensity score matching for variables associated with ICU-acquired infection was undertaken using R library MatchIT using the "full" matching method. RESULTS: Data were available from 4994 patients. Bacterial co-infection at admission was detected in 716 patients (14%), whilst 85% of patients received antibiotics at that stage. ICU-AI developed in 2715 (54%). The most common ICU-AI was bacterial pneumonia (44% of infections), whilst 9% of patients developed fungal pneumonia; 25% of infections involved MDRO. Patients developing infections in ICU had greater antimicrobial exposure than those without such infections. Incident density (ICU-AI per 1000 ICU days) was in considerable excess of reports from pre-pandemic surveillance. Corticosteroid use was heterogenous between ICUs. In univariate analysis, 58% of patients receiving corticosteroids and 43% of those not receiving steroids developed ICU-AI. Adjusting for potential confounders in the propensity-matched cohort, 71% of patients receiving corticosteroids developed ICU-AI vs 52% of those not receiving corticosteroids. Duration of corticosteroid therapy was also associated with development of ICU-AI and infection with an MDRO. CONCLUSIONS: In patients with severe COVID-19 in the first wave, co-infection at admission to ICU was relatively rare but antibiotic use was in substantial excess to that indication. ICU-AI were common and were significantly associated with use of corticosteroids. Trial registration ClinicalTrials.gov: NCT04836065 (retrospectively registered April 8th 2021)., European Society of Intensive Care Medicine ACM is supported by a Clinician Scientist Fellowship from the Medical Research Council (MR/V006118/1)
Published: 2022

38. Increased duration and similar outcomes of V-V ECLS in patients with COVID-19 ARDS compared to non-COVID ARDS: Single center experience

Author: Maria Benedetto, Giulia Piccone, Massimo Baiocchi, Elisa Cerchierini, Marco Adversi, Agostino Rossi, Alessio Dell'Olio, Daniela Di Luca, Andrea Castelli, V. Marco Ranieri, and Tommaso Tonetti
Subjects: Biomaterials, Biomedical Engineering, Medicine (miscellaneous), Bioengineering, General Medicine
Abstract: Veno-venous extracorporeal life support (V-V ECLS or V-V ECMO) has been adopted as a rescue support in severe cases of COVID-19 ARDS. Initial reports on the use of V-V ECLS in COVID-19 patients reported very high mortality rates (57%-94%), but subsequent studies showed much lower rates (30%-40%). The aim of this study is to analyze demographic features, clinical course and outcomes of COVID-19 treated with V-V ECLS during the Italian 'third wave', in which the alpha variant was prevalent in the country.Single-center, retrospective observational study conducted at the ECLS referral center of a teaching hospital in Italy from January 1st, 2021 and October 31st, 2021.Between January and October 2021, 18 consecutive adult patients who underwent V-V ECLS for severe ARDS due to COVID-19 were enrolled. Thirteen patients (72.2%) were male, and their median age was 50 years; the median P/F ratio before V-V ECLS initiation was 43 mm Hg (IQR, 40; 56), and the median RESP score was 0.5 (IQR, -2.25; 1.0). The mortality rate at 90 days was 55.6, compared to 55.7% in non-COVID patients in our center (p 0.05); the median duration of ECLS was 29 days (IQR, 11; 32), compared to 10 days (IQR, 8; 15), in non-COVID patients (p = 0.004). Incidence of complications was high.In patients with COVID-19 ARDS receiving V-V ECLS, unadjusted mortality was similar to pre-pandemic V-V ECLS cases, while the duration of ECLS was almost three times longer and with frequent complications. This could be partly explained by the selection of very sick patients at the baseline that evolved to multiorgan failure during the course of ECLS.
Published: 2022

39. A descriptive pharmacokinetic/pharmacodynamic analysis of continuous infusion ceftazidime-avibactam for treating DTR gram-negative infections in a case series of critically ill patients undergoing continuous veno-venous haemodiafiltration (CVVHDF)

Author: Milo Gatti, Matteo Rinaldi, Paolo Gaibani, Antonio Siniscalchi, Tommaso Tonetti, Maddalena Giannella, Pierluigi Viale, and Federico Pea
Subjects: Critical Care and Intensive Care Medicine
Published: 2023

40. Corrigendum to: 'Development and validation of a prediction model for severe respiratory failure in hospitalized patients with SARS-CoV-2 infection: a multicentre cohort study (PREDI-CO study)' Clinical Microbiology and Infection 26 (2020) 1545–1553

Author: Michele Bartoletti, Maddalena Giannella, Luigia Scudeller, Sara Tedeschi, Matteo Rinaldi, Linda Bussini, Giacomo Fornaro, Renato Pascale, Livia Pancaldi, Zeno Pasquini, Filippo Trapani, Lorenzo Badia, Caterina Campoli, Marina Tadolini, Luciano Attard, Massimo Puoti, Marco Merli, Cristina Mussini, Marianna Menozzi, Marianna Meschiari, Mauro Codeluppi, Francesco Barchiesi, Francesco Cristini, Annalisa Saracino, Alberto Licci, Silvia Rapuano, Tommaso Tonetti, Paolo Gaibani, Vito M. Ranieri, and Pierluigi Viale
Subjects: Microbiology (medical), Infectious Diseases, General Medicine
Published: 2023

41. Extracorporeal CO 2 Removal During Renal Replacement Therapy to Allow Lung-Protective Ventilation in Patients With COVID-19-Associated Acute Respiratory Distress Syndrome

Author: Francesco, Alessandri, Tommaso, Tonetti, Laura, Pistidda, Stefano, Busani, Cristian, Borrazzo, Vito, Fanelli, Mauro, Polzoni, Ornella, Piazza, Luca, Lorini, Sergio, Cattaneo, Davide, Ricci, Andrea, Zanoni, Massimo, Girardis, Pierpaolo, Terragni, Michele, Tempesta, Marina, Di Luca, Francesco, Pugliese, and V Marco, Ranieri
Subjects: Biomaterials, Biomedical Engineering, Biophysics, Bioengineering, General Medicine
Abstract: The aim of this retrospective multicenter observational study is to test the feasibility and safety of a combined extracorporeal CO 2 removal (ECCO 2 R) plus renal replacement therapy (RRT) system to use an ultraprotective ventilator setting while maintaining (1) an effective support of renal function and (2) values of pH within the physiologic limits in a cohort of coronavirus infectious disease 2019 (COVID-19) patients. Among COVID-19 patients admitted to the intensive care unit of 9 participating hospitals, 27 patients with acute respiratory distress syndrome (ARDS) and acute kidney injury (AKI) requiring invasive mechanical ventilation undergoing ECCO 2 R-plus-RRT treatment were included in the analysis. The treatment allowed to reduce V T from 6.0 ± 0.6 mL/kg at baseline to 4.8 ± 0.8, 4.6 ± 1.0, and 4.3 ± 0.3 mL/kg, driving pressure (ΔP) from 19.8 ± 2.5 cm H 2 O to 14.8 ± 3.6, 14.38 ± 4.1 and 10.2 ± 1.6 cm H 2 O after 24 hours, 48 hours, and at discontinuation of ECCO 2 R-plus-RRT (T3), respectively ( p0.001). PaCO 2 and pH remained stable. Plasma creatinine decreased over the study period from 3.30 ± 1.27 to 1.90 ± 1.30 and 1.27 ± 0.90 mg/dL after 24 and 48 hours of treatment, respectively ( p0.01). No patient-related events associated with the extracorporeal system were reported. These data show that in patients with COVID-19-induced ARDS and AKI, ECCO 2 R-plus-RRT is effective in allowing ultraprotective ventilator settings while maintaining an effective support of renal function and values of pH within physiologic limits.
Published: 2022

42. The clinical spectrum of pulmonary thromboembolism in patients with coronavirus disease-2019 (COVID-19) pneumonia: A European case series

Author: Andreas Kortgen, Samuel Buschbeck, Marc Leone, V. Marco Ranieri, Yasser Sakr, Giacinto Pizzilli, Tommaso Tonetti, Laurent Zieleskiewicz, Manuela Giovini, Gary Duclos, Elio Antonucci, Michael Bauer, Sakr Y., Giovini M., Leone M., Pizzilli G., Kortgen A., Bauer M., Tonetti T., Duclos G., Zieleskiewicz L., Buschbeck S., Ranieri V.M., Antonucci E., Jena University Hospital [Jena], Microbes évolution phylogénie et infections (MEPHI), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), University of Bologna/Università di Bologna, Technische Universität Dresden = Dresden University of Technology (TU Dresden), Service Anesthésie et Réanimation [Hôpital Nord - APHM], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital Nord [CHU - APHM], Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), and Assistance Publique - Hôpitaux de Marseille (APHM)
Subjects: medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), Critical Care and Intensive Care Medicine, medicine.disease_cause, Article, 03 medical and health sciences, 0302 clinical medicine, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Internal medicine, Medicine, [SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, In patient, Thromboprophylaxis, ComputingMilieux_MISCELLANEOUS, Coronavirus, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, SARS-CoV-2, business.industry, Pulmonary embolism, COVID-19, 030208 emergency & critical care medicine, medicine.disease, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Pneumonia, 030228 respiratory system, Concomitant, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Thromboprophylaxi, Complication, business, Venous thromboembolism
Abstract: Purpose To describe the clinical characteristics and outcomes of coronavirus disease-2019 (COVID-19)-associated pulmonary thromboembolism (PTE). Materials and methods A case series of five patients, representing the clinical spectrum of COVID-19 associated PTE. Patients were admitted to four hospitals in Germany, Italy, and France. Infection with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) was confirmed using a real-time reverse transcription polymerase chain reaction test. Results The onset of PTE varied from 2 to 4 weeks after the occurrence of the initial symptoms of SARS-CoV-2 infection and led to deterioration of the clinical picture in all cases. PTE was the primary reason for hospital admission after a 2-week period of self-isolation at home (1 patient) and hospital readmission after initial uncomplicated hospital discharge (2 patients). Three of the patients had no past history of clinically relevant risk factors for venous thromboembolism (VTE). Severe disease progression was associated with concomitant increases in IL-6, ferritin, and D-Dimer levels. The outcome from PTE was related to the extent of vascular involvement, and associated complications. Conclusion PTE is a potential life-threatening complication, which occurs frequently in patients with COVID-19. Intermediate therapeutic dose of anticoagulants and extend thromboprophylaxis are necessary after meticulous risk-benefit assessment., Highlights • Pulnonary thromboembolism (PTE) is a frequent life-threatening complication in patients with coronavirsus disease-2019 (COVID-19). • The onset of PTE varies from 2 to 4 weeks after the occurrence of the initial symptoms and may occur during home self-isolation or after hospital discharge of primarily uncomplicated hospital admission. • PTE may occur in patients without clinically relevant past history of risk factors for venous thromboembolism and in those receiving standard prophylactic anticoagulation. • Intermediate therapeutic dose of anticoagulants and extend thromboprophylaxis are necessary in these patients after meticulous risk-benefit assessment.
Published: 2021

43. Pathophysiology of COVID-19-associated acute respiratory distress syndrome: a multicentre prospective observational study

Author: Letizia Di Meglio, Antonio Pesenti, Amedeo Guzzardella, Marco Di Laudo, Claudia Filippini, Lorenzo Querci, Franco Locatelli, Massimo Antonelli, Vittorio Scaravilli, Arthur S. Slutsky, Alfredo Lissoni, Giacomo Bellani, Luca Carsana, Stefano Nava, V. Marco Ranieri, Carmen Seccafico, Jean Louis Vincent, Gianpaolo Carrafiello, Chiara Rizzuto, Francesco Monteduro, Maurizio Cecconi, Roberto Fumagalli, Domenico Luca Grieco, N Rossi, John G. Laffey, Massimo Girardis, Alberto Zanella, Gennaro De Pascale, Giacinto Pizzilli, Tommaso Tonetti, Carlo Valsecchi, Giacomo Grasselli, Ezio Lanza, Alessandro Protti, Francesca Bevilacqua, Fabiana Madotto, Thomas Langer, Maurizio Zompatori, Grasselli G., Tonetti T., Protti A., Langer T., Girardis M., Bellani G., Laffey J., Carrafiello G., Carsana L., Rizzuto C., Zanella A., Scaravilli V., Pizzilli G., Grieco D.L., Di Meglio L., de Pascale G., Lanza E., Monteduro F., Zompatori M., Filippini C., Locatelli F., Cecconi M., Fumagalli R., Nava S., Vincent J.-L., Antonelli M., Slutsky A.S., Pesenti A., Ranieri V.M., Lissoni A., Rossi N., Guzzardella A., Valsecchi C., Madotto F., Bevilacqua F., Di Laudo M., Querci L., Seccafico C., Grasselli, G, Tonetti, T, Protti, A, Langer, T, Girardis, M, Bellani, G, Laffey, J, Carrafiello, G, Carsana, L, Rizzuto, C, Zanella, A, Scaravilli, V, Pizzilli, G, Grieco, D, Di Meglio, L, de Pascale, G, Lanza, E, Monteduro, F, Zompatori, M, Filippini, C, Locatelli, F, Cecconi, M, Fumagalli, R, Nava, S, Vincent, J, Antonelli, M, Slutsky, A, Pesenti, A, and Ranieri, V
Subjects: Male, Pulmonary and Respiratory Medicine, ARDS, medicine.medical_specialty, Computed Tomography Angiography, Dead space, Pulmonary compliance, Pathophysiology, law.invention, Fibrin Fibrinogen Degradation Products, 03 medical and health sciences, 0302 clinical medicine, covid-19, acute respiratory distress syndrome, sars-cov-2, law, Settore MED/41 - ANESTESIOLOGIA, Correspondence, medicine, Humans, Prospective Studies, 030212 general & internal medicine, Respiratory system, Lung, Pandemics, Aged, Respiratory Distress Syndrome, SARS-CoV-2, business.industry, COVID-19, Articles, COVID-19, ARDS, D-dimer, compliance, Middle Aged, medicine.disease, Respiration, Artificial, Intensive care unit, 030228 respiratory system, Cohort, Emergency medicine, Female, Observational study, business
Abstract: Background: Patients with COVID-19 can develop acute respiratory distress syndrome (ARDS), which is associated with high mortality. The aim of this study was to examine the functional and morphological features of COVID-19-associated ARDS and to compare these with the characteristics of ARDS unrelated to COVID-19. Methods: This prospective observational study was done at seven hospitals in Italy. We enrolled consecutive, mechanically ventilated patients with laboratory-confirmed COVID-19 and who met Berlin criteria for ARDS, who were admitted to the intensive care unit (ICU) between March 9 and March 22, 2020. All patients were sedated, paralysed, and ventilated in volume-control mode with standard ICU ventilators. Static respiratory system compliance, the ratio of partial pressure of arterial oxygen to fractional concentration of oxygen in inspired air, ventilatory ratio (a surrogate of dead space), and D-dimer concentrations were measured within 24 h of ICU admission. Lung CT scans and CT angiograms were done when clinically indicated. A dataset for ARDS unrelated to COVID-19 was created from previous ARDS studies. Survival to day 28 was assessed. Findings: Between March 9 and March 22, 2020, 301 patients with COVID-19 met the Berlin criteria for ARDS at participating hospitals. Median static compliance was 41 mL/cm H2O (33–52), which was 28% higher than in the cohort of patients with ARDS unrelated to COVID-19 (32 mL/cm H2O [25–43]; p
Published: 2020

44. Clinical and organizational factors associated with mortality during the peak of first COVID-19 wave

Author: Greco, Massimiliano, De Corte, Thomas, Ercole, Ari, Antonelli, Massimo, Azoulay, Elie, Citerio, Giuseppe, Morris, Andy Conway, De Pascale, Gennaro, Duska, Frantisek, Elbers, Paul, Einav, Sharon, Forni, Lui, Galarza, Laura, Girbes, Armand R J, Grasselli, Giacomo, Gusarov, Vitaly, Jubb, Alasdair, Kesecioglu, Jozef, Lavinio, Andrea, Delgado, Maria Cruz Martin, Mellinghoff, Johannes, Myatra, Sheila Nainan, Ostermann, Marlies, Pellegrini, Mariangela, Povoa, Pedro, Schaller, Stefan J, Teboul, Jean-Louis, Wong, Adrian, De Waele, Jan J, Cecconi, Maurizio, Marco, Bezzi, Alicia, Gira, Philipp, Eller, Tarikul, Hamid, Injamam Ull Haque, Wim De Buyser, Antonella, Cudia, Daniel De Backer, Pierre, Foulon, Vincent, Collin, Jan De Waele, Jolien Van Hecke, Elisabeth De Waele, Claire Van Malderen, Jean-Baptiste, Mesland, Patrick, Biston, Michael, Piagnerelli, Lionel, Haentjens, Nicolas De Schryver, Jan Van Leemput, Philippe, Vanhove, Pierre, Bulpa, Viktoria, Ilieva, David, Katz, Alexandra, Binnie, Anna, Geagea, Fernando, Tirapegui, Gustavo, Lago, Jerónimo, Graf, Rodrigo, Perez-Araos, Patricio, Vargas, Felipe, Martinez, Eduardo, Labarca, Daniel Molano Franco, Daniela, Parra-Tanoux, Luis Felipe Reyes, David, Yepes, Filip, Periš, Sanda Stojanović Stipić, Cynthia Vanessa Campozano Burgos, Paulo Roberto Navas Boada, Jose Luis Barberan Brun, Juan Pablo Paredes Ballesteros, Gamal, Abdelnasser, Ahmed, Hammouda, Omar, Elmandouh, Ahmed, Azzam, Aliae Mohamed Hussein, Islam, Galal, Awad, Ahmed K., Azab, Mohammed A., Maged, Abdalla, Hebatallah, Assal, Mostafa, Alfishawy, Sherief, Ghozy, Samar, Tharwat, Abdullah, Eldaly, Anneli, Ellervee, Veronika, Reinhard, Anne, Chrisment, Chrystelle, Poyat, Julio, Badie, Fernando Berdaguer Ferrari, Björn, Weiss, Clara, Schellenberg, Grunow, Julius J., Marco, Lorenz, Schaller, Stefan J., Peter, Spieth, Marc, Bota, Falk, Fichtner, Kristina, Fuest, Tobias, Lahmer, Johannes, Herrmann, Patrick, Meybohm, Nikolaos, Markou, Georgia, Vasileiadou, Evangelia, Chrysanthopoulou, Panagiotis, Papamichalis, Ioanna, Soultati, Sameer, Jog, Kushal, Kalvit, Sheila Nainan Myatra, Ivan, Krupa, Aisa, Tharwat, Alistair, Nichol, Aine, Mccarthy, Ata, Mahmoodpoor, Tommaso, Tonetti, Paolo, Isoni, Savino, Spadaro, Carlo Alberto Volta, Lucia, Mirabella, Alberto, Noto, Gaetano, Florio, Amedeo, Guzzardella, Chiara, Paleari, Federica, Baccanelli, Marzia, Savi, Massimo, Antonelli, Gennaro De Pascale, San, Luca, Barbara, Vaccarini, Giorgia, Montrucchio, Gabriele, Sales, Donadello, Katia, Leonardo, Gottin, Marta, Nizzero, Enrico, Polati, De Rosa, Silvia, Demet, Sulemanji, Abdurraouf, Abusalama, Muhammed, Elhadi, Montelongo De FelipeJesus, Daniel Rodriguez Gonzalez, Victor Hugo Madrigal Robles, Nancy, Canedo, Alejandro Esquivel Chavez, Tarek, Dendane, Bart, Grady, Ben de Jong, Eveline van der Heiden, Patrick, Thoral, Bas van den Bogaard, Spronk, Peter E., Sefanja, Achterberg, Melanie, Groeneveld, Ralph K. L., So, Calvin de Wijs, Harm, Scholten, Albertus, Beishuizen, Cornet, Alexander D., Reidinga, Auke C., Hetty, Kranen, Roos, Mensink, Spaarne, Gasthuis, Sylvia den Boer, Marcel de Groot, Oliver, Beck, Carina, Bethlehem, Bas van Bussel, Tim, Frenzel, Celestine de Jong, Rob, Wilting, Jozef, Kesecioglu, Jannet, Mehagnoul-Schipper, Datonye, Alasia, Ashok, Kumar, Ahad, Qayyum, Muhammad, Rana, Mustafa Abu Jayyab, Rosario Quispe Sierra, Aaron Mark Hernandez, José de Almeida, Lúcia, Taborda, Mónica, Anselmo, Tiago, Ramires, Catarina, Silva, Carolina, Roriz, Rui, Morais, Pedro, Póvoa, Patricia, Patricio, André, Pinto, Maria Lurdes Santos, Vasco, Costa, Pedro, Cunha, Celina, Gonçalves, Sandra, Nunes, João, Camões, Diana, Adrião, Ana, Oliveira, Ali, Omrani, Muna Al Maslamani, Abdurrahmaan Suei elbuzidi, Bara Mahmoud Al qudah, Abdel Rauof Akkari, Mohamed, Alkhatteb, Anas, Baiou, Ahmed, Husain, Mohamed, Alwraidat, Ibrahim Abdulsalam Saif, Dana, Bakdach, Amna, Ahmed, Mohamed, Aleef, Awadh, Bintaher, Cristina, Petrisor, Evgeniy, Popov, Ksenia, Popova, Mariia, Dementienko, Boris, Teplykh, Alexey, Pyregov, Liubov, Davydova, Belskii, Vladislav, Elena, Neporada, Ivan, Zverev, Svetlana, Meshchaninova, Dmitry, Sokolov, Elena, Gavrilova, Irina, Shlyk, Igor, Poliakov, Marina, Vlasova, Ohoud, Aljuhani, Amina, Alkhalaf, Felwa Bin Humaid, Yaseen, Arabi, Ahmed, Kuhail, Omar, Elrabi, Ghannam, Madihah E., Ng Teng Fong, Amit, Kansal, Vui Kian Ho, Jensen, Ng, Raquel Rodrígez García, Xiana Taboada Fraga, Mª del Pilar García-Bonillo, Antonio, Padilla-Serrano, Marta Martin Cuadrado, Carlos, Ferrando, Ignacio, Catalan-Monzon, Laura, Galarza, Fernando, Frutos-Vivar, Jorge, Jimenez, Carmen, Rodríguez-Solis, Enric, Franquesa-Gonzalez, Guillermo Pérez Acosta, Luciano Santana Cabrera, Juan Pablo Aviles Parra, Francisco Muñoyerro Gonzalez, Maria del Carmen Lorente Conesa, Ignacio Yago Martinez Varela, Orville Victoriano Baez Pravia, Maria Cruz Martin Delgado, Carlos Munoz de Cabo, Ana-Maria, Ioan, Cesar, Perez-Calvo, Arnoldo, Santos, Ane, Abad-Motos, Javier, Ripolles-Melchor, Belén Civantos Martin, Santiago Yus Teruel, Juan Higuera Lucas, Aaron Blandino Ortiz, Raúl de Pablo Sánchez, Jesús Emilio Barrueco-Francioni, Lorena Forcelledo Espina, Bonell-Goytisolo, José M., Iñigo, Salaverria, Antonia Socias Mir, Emilio, Rodriguez-Ruiz, Virginia Hidalgo Valverde, Patricia Jimeno Cubero, Francisca Arbol Linde, Nieves Cruza Leganes, Juan Maria Romeu, Pablo, Concha, José Angel Berezo-Garcia, Virginia, Fraile, Cristina, Cuenca-Rubio, David, Pérez-Torres, Ainhoa, Serrano, Clara Martínez Valero, Andrea Ortiz Suner, Leire, Larrañaga, Noemi, Legaristi, Gerardo, Ferrigno, Safa, Khlafalla, Rosita, Bihariesingh-Sanchit, Hallands, Sjukhus, Frank, Zoerner, Jonathan, Grip, Kristina, Kilsand, Johan, Mårtensson, Jonas, Österlind, Akademiska, Sjukhuset, Magnus von Seth, Västerviks, Sjukhus, Johan, Berkius, Samuele, Ceruti, Andrea, Glotta, Seval, Izdes, Işıl Özkoçak Turan, Ahmet, Cosar, Burcin, Halacli, Necla, Dereli, Mehmet, Yilmaz, Türkay, Akbas, Gülseren, Elay, Selin, Eyüpoğlu, Yelíz, Bílír, Kemal Tolga Saraçoğlu, Ebru, Kaya, Ayca Sultan Sahin, Pervin Korkmaz Ekren, Tuğçe, Mengi, Kezban Ozmen Suner, Yakup, Tomak, Ahmet, Eroglu, Asad, Alsabbah, Katie, Hanlon, Kevin, Gervin, Sean, Mcmahon, Samantha, Hagan, Higenbottam, Caroline V., Randeep, Mullhi, Lottie, Poulton, Tomasz, Torlinski, Allen, Gareth, Nick, Truman, Gopal, Vijayakumar, Chris, Hall, Alasdair, Jubb, Lenka, Cagova, Nicola, Jones, Sam, Graham, Nicole, Robin, Amanda, Cowton, Adrian, Donnelly, Natalia, Singatullina, Melanie, Kent, Carole, Boulanger, Zoë, Campbell, Elizabeth, Potter, Natalie, Duric, Tamas, Szakmany, Royal, Brompton, Orinta, Kviatkovske, Nandor, Marczin, Caroline, Ellis, Rajnish, Saha, Chunda, Sri-Chandana, John, Allan, Lana, Mumelj, Harish, Venkatesh, Vera Nina Gotz, Anthony, Cochrane, Barbara, Ficial, Shruthi, Kamble, Nuttha, Lumlertgul, Christopher, Oddy, Susan, Jain, Giulia Beatrice Crapelli, Aikaterini, Vlachou, David, Golden, Sweyn, Garrioch, Jeremy, Henning, Gupta, Loveleena, Miriam, Davey, Lina, Grauslyte, Erika, Salciute-Simene, Martin, Cook, Danny, Barling, Phil, Broadhurst, Sarah, Purvis, Michael, Spivey, Benjamin, Shuker, Irina, Grecu, Daniel, Harding, Dean, James T., Nielsen, Nathan D., Sama, Al-Bayati, Mohammed, Al-Sadawi, Mariane, Charron, Peter, Stubenrauch, Jairo, Santanilla, Catherine, Wentowski, Dorothea, Rosenberger, Polikseni, Eksarko, and Randeep Jawa, Greco, Massimiliano [0000-0003-1003-4637], De Corte, Thomas [0000-0001-5011-6640], Ercole, Ari [0000-0001-8350-8093], Antonelli, Massimo [0000-0003-3007-1670], Azoulay, Elie [0000-0002-8162-1508], Citerio, Giuseppe [0000-0002-5374-3161], Morris, Andy Conway [0000-0002-3211-3216], De Pascale, Gennaro [0000-0002-8255-0676], Duska, Frantisek [0000-0003-1559-4078], Elbers, Paul [0000-0003-0447-6893], Einav, Sharon [0000-0001-8963-9633], Forni, Lui [0000-0002-0617-5309], Galarza, Laura [0000-0002-4658-748X], Girbes, Armand RJ [0000-0002-0711-0494], Grasselli, Giacomo [0000-0002-1735-1400], Gusarov, Vitaly [0000-0002-2900-1459], Jubb, Alasdair [0000-0001-5593-866X], Kesecioglu, Jozef [0000-0002-3007-8445], Lavinio, Andrea [0000-0002-8832-918X], Delgado, Maria Cruz Martin [0000-0002-7468-4594], Mellinghoff, Johannes [0000-0002-5455-8953], Myatra, Sheila Nainan [0000-0001-6761-163X], Ostermann, Marlies [0000-0001-9500-9080], Pellegrini, Mariangela [0000-0001-5668-7399], Povoa, Pedro [0000-0002-7069-7304], Schaller, Stefan J [0000-0002-6683-9584], Teboul, Jean-Louis [0000-0002-5748-7820], Wong, Adrian [0000-0003-4968-7328], De Waele, Jan J [0000-0003-1017-9748], Cecconi, Maurizio [0000-0002-4376-6538], Apollo - University of Cambridge Repository, Intensive care medicine, ACS - Diabetes & metabolism, AII - Infectious diseases, Greco, M, De Corte, T, Ercole, A, Antonelli, M, Azoulay, E, Citerio, G, Morris, A, De Pascale, G, Duska, F, Elbers, P, Einav, S, Forni, L, Galarza, L, Girbes, A, Grasselli, G, Gusarov, V, Jubb, A, Kesecioglu, J, Lavinio, A, Delgado, M, Mellinghoff, J, Myatra, S, Ostermann, M, Pellegrini, M, Povoa, P, Schaller, S, Teboul, J, Wong, A, De Waele, J, Cecconi, M, UCL - SSS/DDUV/GECE - Génétique cellulaire, UCL - (SLuc) Service de soins intensifs, investigators, ESICM UNITE-COVID, Girbes, Armand R. J. [0000-0002-0711-0494], Schaller, Stefan J. [0000-0002-6683-9584], and De Waele, Jan J. [0000-0003-1017-9748]
Subjects: Adult, Anestesi och intensivvård, Anesthesiology and Intensive Care, Original, SARS-CoV-2, Critical Illness, Other Research Radboud Institute for Health Sciences [Radboudumc 0], ACUTE KIDNEY INJURY, COVID-19, CORONAVIRUS DISEASE 2019, Pneumonia, Acute Kidney Injury, Critical Care and Intensive Care Medicine, Respiration, Artificial, Surge capacity, Critical care, Intensive Care Units, Settore MED/41 - ANESTESIOLOGIA, Medicine and Health Sciences, Humans, CRITICALLY-ILL PATIENTS
Abstract: Purpose To accommodate the unprecedented number of critically ill patients with pneumonia caused by coronavirus disease 2019 (COVID-19) expansion of the capacity of intensive care unit (ICU) to clinical areas not previously used for critical care was necessary. We describe the global burden of COVID-19 admissions and the clinical and organizational characteristics associated with outcomes in critically ill COVID-19 patients. Methods Multicenter, international, point prevalence study, including adult patients with SARS-CoV-2 infection confirmed by polymerase chain reaction (PCR) and a diagnosis of COVID-19 admitted to ICU between February 15th and May 15th, 2020. Results 4994 patients from 280 ICUs in 46 countries were included. Included ICUs increased their total capacity from 4931 to 7630 beds, deploying personnel from other areas. Overall, 1986 (39.8%) patients were admitted to surge capacity beds. Invasive ventilation at admission was present in 2325 (46.5%) patients and was required during ICU stay in 85.8% of patients. 60-day mortality was 33.9% (IQR across units: 20%-50%) and ICU mortality 32.7%. Older age, invasive mechanical ventilation, and acute kidney injury (AKI) were associated with increased mortality. These associations were also confirmed specifically in mechanically ventilated patients. Admission to surge capacity beds was not associated with mortality, even after controlling for other factors. Conclusions ICUs responded to the increase in COVID-19 patients by increasing bed availability and staff, admitting up to 40% of patients in surge capacity beds. Although mortality in this population was high, admission to a surge capacity bed was not associated with increased mortality. Older age, invasive mechanical ventilation, and AKI were identified as the strongest predictors of mortality. Correction in: Intensive Care Medicine, vol. 48, issue 8, pages 1130-1131.DOI: 10.1007/s00134-022-06801-2
Published: 2022

45. Reply to Barahona-Correa

Author: Tommaso, Tonetti, V Marco, Ranieri, Paolo, Navalesi, Stefano, Nava, and Arthur S, Slutsky
Subjects: Oxygen, Respiratory Distress Syndrome, Oxygen Inhalation Therapy, Humans, Hypoxia
Published: 2022

46. Individualized positive end-expiratory pressure guided by end-expiratory lung volume in early acute respiratory distress syndrome: study protocol for the multicenter, randomized IPERPEEP trial

Author: Luca Grieco, Domenico, Maurizio Maggiore, Salvatore, Bellani, Giacomo, Spadaro, Savino, Spinelli, Elena, Tonetti, Tommaso, S Menga, Luca, Pozzi, Marco, Battaglini, Denise, Di Mussi, Rosa, Bruni, Andrea, De Gaetano, Andrea, Giovanni Iovino, Carmine, Brioni, Matteo, Mojoli, Francesco, Foti, Giuseppe, Aberto Volta, Carlo, Pelosi, Paolo, Navalesi, Paolo, Grasso, Salvatore, Marco Ranieri, V, Antonelli, Massimo, Study Group, Iperpeep, Domenico Luca Grieco, Salvatore Maurizio Maggiore, Giacomo Bellani, Savino Spadaro, Elena Spinelli, Tommaso Tonetti, Luca S Menga, Marco Pozzi, Denise Battaglini, Rosa Di Mussi, Andrea Bruni, Andrea De Gaetano, Carmine Giovanni Iovino, Matteo Brioni, Francesco Mojoli, Giuseppe Foti, Carlo Aberto Volta, Paolo Pelosi, Paolo Navalesi, Salvatore Grasso, V Marco Ranieri, Massimo Antonelli (ORCID:0000-0003-3007-1670), IPERPEEP study group, Luca Grieco, Domenico, Maurizio Maggiore, Salvatore, Bellani, Giacomo, Spadaro, Savino, Spinelli, Elena, Tonetti, Tommaso, S Menga, Luca, Pozzi, Marco, Battaglini, Denise, Di Mussi, Rosa, Bruni, Andrea, De Gaetano, Andrea, Giovanni Iovino, Carmine, Brioni, Matteo, Mojoli, Francesco, Foti, Giuseppe, Aberto Volta, Carlo, Pelosi, Paolo, Navalesi, Paolo, Grasso, Salvatore, Marco Ranieri, V, Antonelli, Massimo, Study Group, Iperpeep, Domenico Luca Grieco, Salvatore Maurizio Maggiore, Giacomo Bellani, Savino Spadaro, Elena Spinelli, Tommaso Tonetti, Luca S Menga, Marco Pozzi, Denise Battaglini, Rosa Di Mussi, Andrea Bruni, Andrea De Gaetano, Carmine Giovanni Iovino, Matteo Brioni, Francesco Mojoli, Giuseppe Foti, Carlo Aberto Volta, Paolo Pelosi, Paolo Navalesi, Salvatore Grasso, V Marco Ranieri, Massimo Antonelli (ORCID:0000-0003-3007-1670), and IPERPEEP study group
Abstract: Background: In acute respiratory distress syndrome (ARDS), response to positive end-expiratory pressure (PEEP) is variable according to different degrees of lung recruitability. The search for a tool to individualize PEEP based on patients' individual response is warranted. End-expiratory lung volume (EELV) assessment by nitrogen washing-washout aids bedside estimation of PEEP-induced alveolar recruitment and may therefore help titrate PEEP on patient's individual recruitability. We designed a randomized trial to test whether an individualized PEEP setting protocol driven by EELV measurement may improve a composite clinical outcome in patients with moderate-to-severe ARDS (IPERPEEP trial). Methods: IPERPEEP is an open-label, multicenter, randomized trial that will be conducted in 10 intensive care units in Italy and will enroll 132 ARDS patients showing PaO2/FiO2 ratio ≤ 150 mmHg within 24 h from endotracheal intubation while on mechanical ventilation with PEEP 5 cmH2O. To standardize lung volumes at study initiation, all patients will undergo mechanical ventilation with tidal volume of 6 ml/kg of predicted body weight and PEEP set to obtain a plateau pressure within 28 and 30 cmH2O for 30 min (EXPRESS PEEP). Afterwards, a 5-step decremental PEEP trial will be conducted (EXPRESS PEEP to PEEP 5 cmH2O), and EELV will be measured at each step. Recruitment-to-inflation ratio will be calculated for each PEEP range from EELV difference. Patients will be then randomized to receive mechanical ventilation with PEEP set according to the optimal recruitment observed in the PEEP trial (IPERPEEP arm) trial or to achieve a plateau pressure of 28-30 cmH2O (control arm, EXPRESS strategy). In both groups, tidal volume size, use of prone positioning and neuromuscular blocking agents, and weaning from PEEP and from mechanical ventilation will be standardized. The primary endpoint of the study is a composite clinical outcome incorporating in-ICU mortality, 60-day ventilator-free days
Published: 2022

47. How important is obesity as a risk factor for respiratory failure, intensive care admission and death in hospitalised COVID-19 patients? Results from a single Italian centre

Author: Matteo Rottoli, Alessandra Cascavilla, Paolo Bernante, Francesca Balsamo, Sara K. Tedeschi, Michele Bartoletti, Vito Marco Ranieri, Silvia Garelli, Gilberto Poggioli, Pierluigi Viale, Lamberto Manzoli, Angela Belvedere, Elena Rosselli Del Turco, Tommaso Tonetti, Maddalena Giannella, Uberto Pagotto, Stefano Ianniruberto, Rottoli M., Bernante P., Belvedere A., Balsamo F., Garelli S., Giannella M., Cascavilla A., Tedeschi S., Ianniruberto S., Del Turco E.R., Tonetti T., Ranieri V.M., Poggioli G., Manzoli L., Pagotto U., Viale P., and Bartoletti M.
Subjects: Male, Endocrinology, Diabetes and Metabolism, Comorbidity, Logistic regression, Body Mass Index, law.invention, 0302 clinical medicine, Endocrinology, Risk Factors, Retrospective Studie, law, education.field_of_study, General Medicine, Middle Aged, Intensive care unit, Hospitalization, Intensive Care Units, Italy, 030220 oncology & carcinogenesis, Female, Coronavirus Infections, Respiratory Insufficiency, Human, Adult, medicine.medical_specialty, Logistic Model, Intensive Care Unit, Pneumonia, Viral, Population, 030209 endocrinology & metabolism, NO, Betacoronavirus, 03 medical and health sciences, Internal medicine, medicine, Humans, Obesity, Risk factor, education, Pandemics, Proportional Hazards Models, Retrospective Studies, Aged, COVID-19 - obesity - outcomes - respiratory failure - death - ICU admission - BMI, Pandemic, Betacoronaviru, SARS-CoV-2, Coronavirus Infection, Proportional hazards model, business.industry, Risk Factor, COVID-19, Retrospective cohort study, Logistic Models, Respiratory failure, Proportional Hazards Model, business, Body mass index
Abstract: Objective: Specific comorbidities and old age create a greater vulnerability to severe Coronavirus Disease 19 (COVID-19). While obesity seems to aggravate the course of disease, the actual impact of the BMI and the cutoff which increases illness severity are still under investigation. The aim of the study was to analyze whether the BMI represented a risk factor for respiratory failure, admission to the intensive care unit (ICU) and death. Research design and methods: A retrospective cohort study of 482 consecutive COVID-19 patients hospitalised between March 1 and April 20, 2020. Logistic regression analysis and Cox proportion Hazard models including demographic characteristics and comorbidities were carried out to predict the endpoints within 30 days from the onset of symptoms. Results: Of 482 patients, 104 (21.6%) had a BMI ≥ 30 kg/m2. At logistic regression analysis, a BMI between 30 and 34.9 kg/m2 significantly increased the risk of respiratory failure (OR: 2.32; 95% CI: 1.31–4.09, P = 0.004) and admission to the ICU (OR: 4.96; 95% CI: 2.53–9.74, P 2 (OR: 12.1; 95% CI: 3.25–45.1, P Conclusions: Obesity is a strong, independent risk factor for respiratory failure, admission to the ICU and death among COVID-19 patients. A BMI ≥ 30 kg/m2 identifies a population of patients at high risk for severe illness, whereas a BMI ≥ 35 kg/m2 dramatically increases the risk of death.
Published: 2020

48. Clinical implications of microvascular CT scan signs in COVID-19 patients requiring invasive mechanical ventilation

Author: Giorgia Dalpiaz, Lorenzo Gamberini, Aldo Carnevale, Savino Spadaro, Carlo Alberto Mazzoli, Sara Piciucchi, Davide Allegri, Chiara Capozzi, Ersenad Neziri, Maurizio Bartolucci, Francesco Muratore, Francesca Coppola, Antonio Poerio, Emanuela Giampalma, Luca Baldini, Tommaso Tonetti, Iacopo Cappellini, Davide Colombo, Gianluca Zani, Lorenzo Mellini, Vanni Agnoletti, Federica Damiani, Giovanni Gordini, Cristiana Laici, Giuliano Gola, Antonella Potalivo, Jonathan Montomoli, Vito Marco Ranieri, Emanuele Russo, Stefania Taddei, Carlo Alberto Volta, Gaetano Scaramuzzo, Dalpiaz G., Gamberini L., Carnevale A., Spadaro S., Mazzoli C.A., Piciucchi S., Allegri D., Capozzi C., Neziri E., Bartolucci M., Muratore F., Coppola F., Poerio A., Giampalma E., Baldini L., Tonetti T., Cappellini I., Colombo D., Zani G., Mellini L., Agnoletti V., Damiani F., Gordini G., Laici C., Gola G., Potalivo A., Montomoli J., Ranieri V.M., Russo E., Taddei S., Volta C.A., and Scaramuzzo G.
Subjects: Male, Acute respiratory distress syndrome, SARS-CoV-2, Chest Radiology, Novel coronavirus disease 2019, COVID-19, General Medicine, Length of Stay, Middle Aged, Respiration, Artificial, NO, Intensive Care Units, Pulmonary perfusion, Mechanical ventilation, Italy, Microvessels, Thoracic imaging, Humans, Radiology, Nuclear Medicine and imaging, Female, Prospective Studies, Tomography, X-Ray Computed, Lung, Aged
Abstract: Purpose COVID-19-related acute respiratory distress syndrome (ARDS) is characterized by the presence of signs of microvascular involvement at the CT scan, such as the vascular tree in bud (TIB) and the vascular enlargement pattern (VEP). Recent evidence suggests that TIB could be associated with an increased duration of invasive mechanical ventilation (IMV) and intensive care unit (ICU) stay. The primary objective of this study was to evaluate whether microvascular involvement signs could have a prognostic significance concerning liberation from IMV. Material and methods All the COVID-19 patients requiring IMV admitted to 16 Italian ICUs and having a lung CT scan recorded within 3 days from intubation were enrolled in this secondary analysis. Radiologic, clinical and biochemical data were collected. Results A total of 139 patients affected by COVID-19 related ARDS were enrolled. After grouping based on TIB or VEP detection, we found no differences in terms of duration of IMV and mortality. Extension of VEP and TIB was significantly correlated with ground-glass opacities (GGOs) and crazy paving pattern extension. A parenchymal extent over 50% of GGO and crazy paving pattern was more frequently observed among non-survivors, while a VEP and TIB extent involving 3 or more lobes was significantly more frequent in non-responders to prone positioning. Conclusions The presence of early CT scan signs of microvascular involvement in COVID-19 patients does not appear to be associated with differences in duration of IMV and mortality. However, patients with a high extension of VEP and TIB may have a reduced oxygenation response to prone positioning. Trial Registration: NCT04411459 Supplementary Information The online version contains supplementary material available at 10.1007/s11547-021-01444-7.
Published: 2022

49. Protective ventilation in patients with acute respiratory distress syndrome related to COVID-19: always, sometimes or never?

Author: Vito Marco Ranieri, Tommaso Tonetti, Chiara Mega, Irene Cavalli, Mega, Chiara, Cavalli, Irene, Ranieri, Vito Marco, and Tonetti, Tommaso
Subjects: medicine.medical_specialty, ARDS, Coronavirus disease 2019 (COVID-19), Acute respiratory distress, mechanical ventilation, Critical Care and Intensive Care Medicine, Positive-Pressure Respiration, coronavirus disease 2019, lung protective ventilation, Tidal Volume, medicine, Humans, In patient, Intensive care medicine, Lung, Respiratory Distress Syndrome, SARS-CoV-2, business.industry, acute respiratory distress syndrome, coronavirus disease 2019, lung protective ventilation, mechanical ventilation, RESPIRATORY SYSTEM: Edited by Giacomo Grasselli, COVID-19, Lung protective ventilation, acute respiratory distress syndrome, medicine.disease, Protective ventilation, medicine.anatomical_structure, Low tidal volume, business
Abstract: Purpose of review To review current evidence on the pathophysiology of COVID-19-related acute respiratory distress syndrome (ARDS) and on the implementation of lung protective ventilation. Recent findings Although multiple observations and physiological studies seem to show a different pathophysiological behaviour in COVID-19-ARDS compared with 'classical' ARDS, numerous studies on thousands of patients do not confirm these findings and COVID-19-ARDS indeed shares similar characteristics and interindividual heterogeneity with ARDS from other causes. Although still scarce, present evidence on the application of lung protective ventilation in COVID-19-ARDS shows that it is indeed consistently applied in ICUs worldwide with a possible signal towards better survival at least in one study. The levels of positive end-expiratory pressure (PEEP) usually applied in these patients are higher than in 'classical' ARDS, proposing once again the issue of PEEP personalization in hypoxemic patients. In the absence of robust evidence, careful evaluation of the patient is needed, and empiric settings should be oriented towards lower levels of PEEP. Summary According to the present evidence, a lung protective strategy based on low tidal volume and plateau pressures is indicated in COVID-19-ARDS as in ARDS from other causes; however, there are still uncertainties on the appropriate levels of PEEP.
Published: 2022

50. High-Flow Nasal Oxygen for Severe Hypoxemia: Oxygenation Response and Outcome in Patients with COVID-19

Author: Giacomo Grasselli, Massimo Antonelli, Chiara Mega, Antonio Pesenti, Roberto Dongilli, Paolo Navalesi, Paola Rucci, Luca S Menga, Laura Pasin, Nicolò Sella, Domenico Luca Grieco, Alessio Dell'Olio, Lara Pisani, V. Marco Ranieri, Giacinto Pizzilli, Tommaso Tonetti, Annalisa Boscolo, Arthur S. Slutsky, and Stefano Nava
Subjects: Pulmonary and Respiratory Medicine, Male, ARDS, Coronavirus disease 2019 (COVID-19), medicine.medical_treatment, mechanical ventilation, Critical Care and Intensive Care Medicine, Severe hypoxemia, Settore MED/41 - ANESTESIOLOGIA, medicine, Intubation, Humans, Hypoxia, Aged, Mechanical ventilation, Respiratory Distress Syndrome, business.industry, COVID-19, HFNO, noninvasive ventilation, Respiration, Oxygen Inhalation Therapy, Patient Acuity, Oxygenation, Creative commons, Middle Aged, medicine.disease, Treatment Outcome, Noninvasive ventilation, Female, Italy, Respiration, Artificial, Anesthesia, Artificial, High flow, business
Abstract: RATIONALE The "Berlin definition" of acute respiratory distress syndrome (ARDS) does not allow inclusion of patients receiving high-flow nasal oxygen (HFNO). However, several articles proposed that criteria for defining ARDS should be broadened to allow inclusion of patients receiving HFNO. OBJECTIVE To compare the proportion of patients fulfilling ARDS criteria during HFNO and soon after intubation, and 28-day mortality between patients treated exclusively with HFNO and patients transitioned from HFNO to IMV. METHODS From previously published studies we analyzed COVID-19 patients who had PaO2/FiO2 ≤300 while treated with HFNO ≥40 L/min, or NIV with PEEP ≥5 cmH2O (comparator). In patients transitioned from HFNO/NIV to invasive mechanical ventilation (IMV), we compared ARDS severity during HFNO/NIV and soon after IMV. We compared 28-day mortality in patients treated exclusively with HFNO/NIV vs. transitioned to IMV. MEASUREMENTS AND MAIN RESULTS We analyzed 184 and 131 patients receiving HFNO or NIV, respectively. 112 HFNO, and 69 NIV patients transitioned to IMV. 104 (92.9%) HFNO patients and 66 (95.7%) NIV patients continued to have PaO2/FiO2 ≤300 under IMV. 28-day mortality in patients who remained on HFNO was 4.2% (3/72) while in patients transitioned from HFNO to IMV it was 28.6% (32/112) (p
Published: 2022

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