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5. Mechanical Ventilator Milano (MVM): A Novel Mechanical Ventilator Designed for Mass Scale Production in Response to the COVID-19 Pandemic

Author

Galbiati, C., Abba, A., Agnes, P., Amaudruz, P., Arba, M., Ardellier-Desages, F., Badia, C., Batignani, G., Bellani, G., Bianchi, G., Bishop, D., Bocci, V., Bonivento, W., Bottino, B., Bouchard, M., Brice, S., Buccino, G., Bussino, S., Caminata, A., Capra, A., Caravati, M., Carlini, M., Carrozzi, L., Cela, J. M., Celano, B., Charette, C., Coelli, S., Constable, M., Cocco, V., Croci, G., Cudmore, S., Molin, A. Dal, D'Auria, S., D'Avenio, G., DeRuiter, J., De Cecco, S., De Lauretis, L., Del Tutto, M., Devoto, A., Dinon, T., Druszkiewicz, E., Fabbri, A., Ferroni, F., Fiorillo, G., Ford, R., Foti, G., Franco, D., Gabriele, F., Abia, P. Garcia, Giarratana, L. S., Givoletti, J., Givoletti, Mi., Gorini, G., Gramellini, E., Grosso, G., Guescini, F., Guetre, E., Hadden, T., Hall, J., Heavey, A., Hersak, G., Hessey, N., Ianni, An., Ienzi, C., Ippolito, V., Kendziora, C. L., King, M., Kittmer, A., Kochanek, I., Kruecken, R., La Commara, M., Leblond, G., Li, X., Lim, C., Lindner, T., Lombardi, T., Long, T., Lu, P., Lukhanin, G., Magni, G., Maharaj, R., Malosio, M., Mapelli, C., Maqueo, P., Margetak, P., Mari, S. M., Martin, L., Massacret, N., McDonald, A., Minuzzo, D., Mohayai, T. A., Tosatti, L. Molinari, Moretti, C., Muraro, A., Nati, F., Noble, A. J., Norrick, A., Olchanski, K., Palumbo, I., Paoletti, R., Paoli, N., Pearson, C., Pellegrino, C., Pesudo, V., Pocar, A., Pontesilli, M., Pordes, R., Pordes, S., Prini, A., Putignano, O., Raaf, J. L., Razeti, M., Razeto, A., Reed, D., Renshaw, A., Rescigno, M., Retiere, F., Rignanese, L. P., Rode, J., Romualdez, L. J., Santorelli, R., Sablone, D., Scapparone, E., Schaubel, T., Shaw, B., Slutsky, A. S., Smith, B., Smith, N. J. T., Spagnolo, P., Spinella, F., Stenzler, A., Steri, A., Stiaccini, L., Stoughton, C., Stringari, P., Tardocchi, M., Tartaglia, R., Testera, G., Tintori, C., Tonazzo, A., Tseng, J., Viscione, E., Vivaldi, F., Wada, M., Wang, H., Westerdale, S., Yue, S., and Zardoni, A.

Subjects
Physics - Medical Physics
Abstract

Presented here is the design of the Mechanical Ventilator Milano (MVM), a novel mechanical ventilator designed for rapid mass production in response to the COVID-19 pandemic to address the urgent shortage of intensive therapy ventilators in many countries, and the growing difficulty in procuring these devices through normal supply chains across borders. This ventilator is an electro-mechanical equivalent of the old and reliable Manley Ventilator, and is able to operate in both pressure-controlled and pressure-supported ventilation modes. MVM is optimized for the COVID-19 emergency, thanks to the collaboration with medical doctors in the front line. MVM is designed for large-scale production in a short amount of time and at a limited cost, as it relays on off-the-shelf components, readily available worldwide. Operation of the MVM requires only a source of compressed oxygen (or compressed medical air) and electrical power. Initial tests of a prototype device with a breathing simulator are also presented. Further tests and developments are underway. At this stage the MVM is not yet a certified medical device but certification is in progress.

Published
2020
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6. One-Dimensional Flow Spectra and Cumulative Energy from Two Pipe Facilities

Author

Zanoun, E. -S., Öngüner, Emir, Egbers, C., Bellani, G., and Talamelli, A.

Subjects
Physics - Fluid Dynamics
Abstract

Experiments have been conducted to assess the sizes and energy fractions of structure in fully developed turbulent pipe flow regime in two pipe facilities, ColaPipe at BTU Cottbus-Senftenberg, and CICLoPE at University of Bologna, for shear Reynolds number in the range $2.5\cdot{10^3}\le{\mathrm{Re_{\tau}}}\le{{3.7\cdot{10^4}}}$, utilizing a single hot-wire probe. Considerations are given to the spectra of the streamwise velocity fluctuations, and to large scale motions and their energy contents from the pipe near-wall to centerline. The analysis of the velocity fluctuations revealed a Reynolds-number dependent inner peak at a fixed wall normal location, however, an outer peak seems not to appear that might be attributed either to low Reynolds number effect or not high enough spatial resolution of hot-wire probe, motivating further study utilizing nanoscale probes. Sizes of the large scale, and very large scale structures were estimated to have wavelengths of 3$R$, and 20$R$ at high Reynolds number, srespectively. The fractional energy contents in wavelengths associated with the large scale motions at various wall normal locations showed maximum contribution to the turbulent kinetic energy near the outer limit of the logarithmic layer.

Published
2019

8. Ventilation distribution during changes in trunk inclination in ARDS patients

Author

Marrazzo, F, Spina, S, Zadek, F, Forlini, C, Bassi, G, Giudici, R, Bellani, G, Fumagalli, R, Langer, T, Marrazzo F., Spina S., Zadek F., Forlini C., Bassi G., Giudici R., Bellani G., Fumagalli R., Langer T., Marrazzo, F, Spina, S, Zadek, F, Forlini, C, Bassi, G, Giudici, R, Bellani, G, Fumagalli, R, Langer, T, Marrazzo F., Spina S., Zadek F., Forlini C., Bassi G., Giudici R., Bellani G., Fumagalli R., and Langer T.

Published
2024

9. Expiratory Muscle Activity Counteracts Positive End-Expiratory Pressure and Is Associated with Fentanyl Dose in Patients with Acute Respiratory Distress Syndrome

Author

Plens, G, Droghi, M, Alcala, G, Pereira, S, Wawrzeniak, I, Victorino, J, Crivellari, C, Grassi, A, Rezoagli, E, Foti, G, Costa, E, Amato, M, Bellani, G, Plens G. M., Droghi M. T., Alcala G. C., Pereira S. M., Wawrzeniak I. C., Victorino J. A., Crivellari C., Grassi A., Rezoagli E., Foti G., Costa E. L. V., Amato M. B. P., Bellani G., Plens, G, Droghi, M, Alcala, G, Pereira, S, Wawrzeniak, I, Victorino, J, Crivellari, C, Grassi, A, Rezoagli, E, Foti, G, Costa, E, Amato, M, Bellani, G, Plens G. M., Droghi M. T., Alcala G. C., Pereira S. M., Wawrzeniak I. C., Victorino J. A., Crivellari C., Grassi A., Rezoagli E., Foti G., Costa E. L. V., Amato M. B. P., and Bellani G.

Abstract

Rationale: Hypoxemia during mechanical ventilation might be worsened by expiratory muscle activity, which reduces end-expiratory lung volume through lung collapse. A proposed mechanism of benefit of neuromuscular blockade in acute respiratory distress syndrome (ARDS) is the abolition of expiratory efforts. This may contribute to the restoration of lung volumes. The prevalence of this phenomenon, however, is unknown. Objectives: To investigate the incidence and amount of end-expiratory lung impedance (EELI) increase after the administration of neuromuscular blocking agents (NMBAs), clinical factors associated with this phenomenon, its impact on regional lung ventilation, and any association with changes in pleural pressure. Methods: We included mechanically ventilated patients with ARDS monitored with electrical impedance tomography (EIT) who received NMBAs in one of two centers. We measured changes in EELI, a surrogate for end-expiratory lung volume, before and after NMBA administration. In an additional 10 patients, we investigated the characteristic signatures of expiratory muscle activity depicted by EIT and esophageal catheters simultaneously. Clinical factors associated with EELI changes were assessed. Measurements and Main Results: We included 46 patients, half of whom showed an increase in EELI of >10% of the corresponding Vt (46.2%; IQR, 23.9-60.9%). The degree of EELI increase correlated positively with fentanyl dosage and negatively with changes in end-expiratory pleural pressures. This suggests that expiratory muscle activity might exert strong counter-effects against positive end-expiratory pressure that are possibly aggravated by fentanyl. Conclusions: Administration of NMBAs during EIT monitoring revealed activity of expiratory muscles in half of patients with ARDS. The resultant increase in EELI had a dose-response relationship with fentanyl dosage. This suggests a potential side effect of fentanyl during protective ventilation.

Published
2024

10. The “ZEEP-PEEP test” to evaluate the response to positive end-expiratory pressure delivered by helmet: A prospective physiologic study

Author

Giani, M, Fumagalli, B, Cipulli, F, Rezoagli, E, Pozzi, M, Fumagalli, D, Fumagalli, L, Ferrari, K, Rona, R, Bellani, G, Lucchini, A, Foti, G, Giani M., Fumagalli B., Cipulli F., Rezoagli E., Pozzi M., Fumagalli D., Fumagalli L., Ferrari K., Rona R., Bellani G., Lucchini A., Foti G., Giani, M, Fumagalli, B, Cipulli, F, Rezoagli, E, Pozzi, M, Fumagalli, D, Fumagalli, L, Ferrari, K, Rona, R, Bellani, G, Lucchini, A, Foti, G, Giani M., Fumagalli B., Cipulli F., Rezoagli E., Pozzi M., Fumagalli D., Fumagalli L., Ferrari K., Rona R., Bellani G., Lucchini A., and Foti G.

Abstract

Introduction: The improvement in oxygenation after helmet application in hypoxemic patients may be explained by the alveolar recruitment obtained with positive end expiratory pressure (PEEP) or by the administration of a more accurate inspiratory fraction of oxygen (FiO2). We have designed the “ZEEP-PEEP test”, capable to distinguish between the FiO2-related or PEEP-related oxygenation improvement. Our primary aim was to describe the use of this test during helmet CPAP to assess the oxygenation improvement attributable to PEEP application. Material and methods: We performed a prospective physiological study including adult critically ill patients. Respiratory and hemodynamic parameters were recorded before helmet application (PRE step), after helmet application without PEEP (ZEEP step) and after the application of the PEEP valve (PEEP step), while maintaining a constant FiO2. We defined as “PEEP responders” patients showing a PaO2/FiO2 ratio improvement ≥10% after PEEP application. Results: 93 patients were enrolled. Compared to the PRE step, PaO2/FiO2 ratio was significantly improved during helmet CPAP both at ZEEP and PEEP step (189 ± 55, 219 ± 74 and 241 ± 82 mmHg, respectively, p < 0.01). Both PEEP responders (41%) and non-responders showed a significant improvement of PaO2/FiO2 ratio after the application of helmet at ZEEP, PEEP responders also showed a significant improvement of oxygenation after PEEP application (208 ± 70 vs 267 ± 85, p < 0.01). Conclusions: Helmet CPAP improved oxygenation. This improvement was not only due to the PEEP effect, but also to the increase of the effective inspired FiO2. Performing the ZEEP-PEEP test may help to identify patients who benefit from PEEP.

Published
2024

11. A non-invasive continuous and real-time volumetric monitoring in spontaneous breathing subjects based on bioimpedance—ExSpiron®Xi: a validation study in healthy volunteers

Author

Gatti, S, Rezoagli, E, Madotto, F, Foti, G, Bellani, G, Gatti S., Rezoagli E., Madotto F., Foti G., Bellani G., Gatti, S, Rezoagli, E, Madotto, F, Foti, G, Bellani, G, Gatti S., Rezoagli E., Madotto F., Foti G., and Bellani G.

Abstract

Tidal volume (TV) monitoring breath-by-breath is not available at bedside in non-intubated patients. However, TV monitoring may be useful to evaluate the work of breathing. A non-invasive device based on bioimpedance provides continuous and real-time volumetric tidal estimation during spontaneous breathing. We performed a prospective study in healthy volunteers aimed at evaluating the accuracy, the precision and the trending ability of measurements of ExSpiron®Xi as compared with the gold standard (i.e. spirometry). Further, we explored whether the differences between the 2 devices would be improved by the calibration of ExSpiron®Xi with a pre-determined tidal volume. Analysis accounted for the repeated nature of measurements within each subject. We enrolled 13 healthy volunteers, including 5 men and 8 women. Tidal volume, TV/ideal body weight (IBW) and respiratory rate (RR) measured with spirometer (TVSpirometer) and with ExSpiron®Xi (TVExSpiron) showed a robust correlation, while minute ventilation (MV) showed a weak correlation, in both non/calibrated and calibrated steps. The analysis of the agreement showed that non-calibrated TVExSpiron underestimated TVspirometer, while in the calibrated steps, TVExSpiron overestimated TVspirometer. The calibration procedure did not reduce the average absolute difference (error) between TVSpirometer and TVExSpiron. This happened similarly for TV/IBW and MV, while RR showed high accuracy and precision. The trending ability was excellent for TV, TV/IBW and RR. The concordance rate (CR) was >95% in both calibrated and non-calibrated measurements. The trending ability of minute ventilation was limited. Absolute error for both calibrated and not calibrated values of TV, TV/IBW and MV accounting for repeated measurements was variably associated with BMI, height and smoking status. Conclusions: Non-invasive TV, TV/IBW and RR estimation by ExSpiron®Xi was strongly correlated with tidal ventilation according to the g

Published
2024

14. Successful Versus Failed Transition From Controlled Ventilation to Pressure Support Ventilation in COVID-19 Patients: A Retrospective Cohort Study

Author

Polo Friz, M, Rezoagli, E, Safaee Fakhr, B, Florio, G, Carlesso, E, Giudici, R, Forlini, C, Tardini, F, Langer, T, Laratta, M, Casella, G, Forastieri Molinari, A, Protti, A, Cecconi, M, Cabrini, L, Biagioni, E, Berselli, A, Mirabella, L, Tonetti, T, De Robertis, E, Grieco, D, Antonelli, M, Citerio, G, Fumagalli, R, Foti, G, Zanella, A, Grasselli, G, Bellani, G, Polo Friz, Melisa, Rezoagli, Emanuele, Safaee Fakhr, Bijan, Florio, Gaetano, Carlesso, Eleonora, Giudici, Riccardo, Forlini, Clarissa, Tardini, Francesca, Langer, Thomas, Laratta, Matteo, Casella, Giampaolo, Forastieri Molinari, Andrea, Protti, Alessandro, Cecconi, Maurizio, Cabrini, Luca, Biagioni, Emanuela, Berselli, Angela, Mirabella, Lucia, Tonetti, Tommaso, De Robertis, Edoardo, Grieco, Domenico Luca, Antonelli, Massimo, Citerio, Giuseppe, Fumagalli, Roberto, Foti, Giuseppe, Zanella, Alberto, Grasselli, Giacomo, Bellani, Giacomo, Polo Friz, M, Rezoagli, E, Safaee Fakhr, B, Florio, G, Carlesso, E, Giudici, R, Forlini, C, Tardini, F, Langer, T, Laratta, M, Casella, G, Forastieri Molinari, A, Protti, A, Cecconi, M, Cabrini, L, Biagioni, E, Berselli, A, Mirabella, L, Tonetti, T, De Robertis, E, Grieco, D, Antonelli, M, Citerio, G, Fumagalli, R, Foti, G, Zanella, A, Grasselli, G, Bellani, G, Polo Friz, Melisa, Rezoagli, Emanuele, Safaee Fakhr, Bijan, Florio, Gaetano, Carlesso, Eleonora, Giudici, Riccardo, Forlini, Clarissa, Tardini, Francesca, Langer, Thomas, Laratta, Matteo, Casella, Giampaolo, Forastieri Molinari, Andrea, Protti, Alessandro, Cecconi, Maurizio, Cabrini, Luca, Biagioni, Emanuela, Berselli, Angela, Mirabella, Lucia, Tonetti, Tommaso, De Robertis, Edoardo, Grieco, Domenico Luca, Antonelli, Massimo, Citerio, Giuseppe, Fumagalli, Roberto, Foti, Giuseppe, Zanella, Alberto, Grasselli, Giacomo, and Bellani, Giacomo

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

17. Airway Closure in Patients With Cardiogenic Pulmonary Edema as a Cause of Driving Pressure Overestimation: The “Uncorking Effect”

Author

Pozzi, M, Raimondi Cominesi, D, Giani, M, Avalli, L, Foti, G, Brochard, L, Bellani, G, Rezoagli, E, Pozzi M., Raimondi Cominesi D., Giani M., Avalli L., Foti G., Brochard L. J., Bellani G., Rezoagli E., Pozzi, M, Raimondi Cominesi, D, Giani, M, Avalli, L, Foti, G, Brochard, L, Bellani, G, Rezoagli, E, Pozzi M., Raimondi Cominesi D., Giani M., Avalli L., Foti G., Brochard L. J., Bellani G., and Rezoagli E.

Abstract

Airway closure is an underestimated phenomenon reported in hypoxemic respiratory failure under mechanical ventilation, during cardiac arrest, and in patients who are obese. Because airway and alveolar pressure are not communicating, it leads to an overestimation of driving pressure and an underestimation of respiratory system compliance. Airway closure also favors denitrogenation atelectasis. To date, it has been described mainly in patients with ARDS and those with obesity. We describe three cases of airway closure in patients with hydrostatic pulmonary edema caused by cardiogenic shock, highlighting its resolution in a limited period of time (24 h) as pulmonary edema resolved. The waveforms show a biphasic reopening that we refer to as the "uncorking effect". The detection of airway closure may require setting positive end-expiratory pressure at or above the airway opening pressure to avoid the overestimation of driving pressure.

Published
2023

18. Efficacy and adverse events profile of videolaryngoscopy in critically ill patients: subanalysis of the INTUBE study

Author

Russotto, V, Lascarrou, J, Tassistro, E, Parotto, M, Antolini, L, Bauer, P, Szułdrzyński, K, Camporota, L, Putensen, C, Pelosi, P, Sorbello, M, Higgs, A, Greif, R, Grasselli, G, Valsecchi, M, Fumagalli, R, Foti, G, Caironi, P, Bellani, G, Laffey, J, Myatra, S, Russotto V., Lascarrou J. B., Tassistro E., Parotto M., Antolini L., Bauer P., Szułdrzyński K., Camporota L., Putensen C., Pelosi P., Sorbello M., Higgs A., Greif R., Grasselli G., Valsecchi M. G., Fumagalli R., Foti G., Caironi P., Bellani G., Laffey J. G., Myatra S. N., Russotto, V, Lascarrou, J, Tassistro, E, Parotto, M, Antolini, L, Bauer, P, Szułdrzyński, K, Camporota, L, Putensen, C, Pelosi, P, Sorbello, M, Higgs, A, Greif, R, Grasselli, G, Valsecchi, M, Fumagalli, R, Foti, G, Caironi, P, Bellani, G, Laffey, J, Myatra, S, Russotto V., Lascarrou J. B., Tassistro E., Parotto M., Antolini L., Bauer P., Szułdrzyński K., Camporota L., Putensen C., Pelosi P., Sorbello M., Higgs A., Greif R., Grasselli G., Valsecchi M. G., Fumagalli R., Foti G., Caironi P., Bellani G., Laffey J. G., and Myatra S. N.

Abstract

Background: Tracheal intubation is a high-risk procedure in the critically ill, with increased intubation failure rates and a high risk of other adverse events. Videolaryngoscopy might improve intubation outcomes in this population, but evidence remains conflicting, and its impact on adverse event rates is debated. Methods: This is a subanalysis of a large international prospective cohort of critically ill patients (INTUBE Study) performed from 1 October 2018 to 31 July 2019 and involving 197 sites from 29 countries across five continents. Our primary aim was to determine the first-pass intubation success rates of videolaryngoscopy. Secondary aims were characterising (a) videolaryngoscopy use in the critically ill patient population and (b) the incidence of severe adverse effects compared with direct laryngoscopy. Results: Of 2916 patients, videolaryngoscopy was used in 500 patients (17.2%) and direct laryngoscopy in 2416 (82.8%). First-pass intubation success was higher with videolaryngoscopy compared with direct laryngoscopy (84% vs 79%, P=0.02). Patients undergoing videolaryngoscopy had a higher frequency of difficult airway predictors (60% vs 40%, P<0.001). In adjusted analyses, videolaryngoscopy increased the probability of first-pass intubation success, with an OR of 1.40 (95% confidence interval [CI] 1.05-1.87). Videolaryngoscopy was not significantly associated with risk of major adverse events (odds ratio 1.24, 95% CI 0.95-1.62) or cardiovascular events (odds ratio 0.78, 95% CI 0.60-1.02). Conclusions: In critically ill patients, videolaryngoscopy was associated with higher first-pass intubation success rates, despite being used in a population at higher risk of difficult airway management. Videolaryngoscopy was not associated with overall risk of major adverse events. Clinical trial registration: NCT03616054.

Published
2023

19. Hospital Memories and Six-Month Psychological Outcome: A Prospective Study in Critical Ill Patients with COVID-19 Respiratory Failure

Author

Pozzi, M, Ripa, C, Meroni, V, Ferlicca, D, Annoni, A, Villa, M, Strepparava, M, Rezoagli, E, Piva, S, Lucchini, A, Bellani, G, Foti, G, Pozzi M., Ripa C., Meroni V., Ferlicca D., Annoni A., Villa M., Strepparava M. G., Rezoagli E., Piva S., Lucchini A., Bellani G., Foti G., Pozzi, M, Ripa, C, Meroni, V, Ferlicca, D, Annoni, A, Villa, M, Strepparava, M, Rezoagli, E, Piva, S, Lucchini, A, Bellani, G, Foti, G, Pozzi M., Ripa C., Meroni V., Ferlicca D., Annoni A., Villa M., Strepparava M. G., Rezoagli E., Piva S., Lucchini A., Bellani G., and Foti G.

Abstract

ICU survivors suffer from various long-term physical and psychological impairments. Memories from the critical illness may influence long-term psychological outcome. In particular, the role of ICU memories in COVID-19 critically ill patients is unknown. In a prospective observational study, we aimed to investigate patients' memories from the experience of critical illness and their association with a six-month psychological outcome involving quality of life evaluation. Patients' memories were investigated with ICU Memory tool, while psychological outcome and quality of life were evaluated by means of a battery of validated questionnaires during an in-person interview at the follow-up clinic. 149 adult patients were enrolled. 60% retained memories from pre-ICU days spent on a general ward, while 70% reported memories from the in-ICU period. Delusional memories (i.e., memories of facts that never happened) were reported by 69% of patients. According to a multivariable analysis, the lack of pre-ICU memories was an independent predictor of worse psychological outcomes in terms of anxiety, depression and Post-traumatic Stress Disorder (PTDS). Factors associated with long-term outcome in ICU survivors are not still fully understood and patients' experience during the day spent before ICU admission may be associated with psychological sequelae.

Published
2023

22. Timing of Prone Positioning during Venovenous Extracorporeal Membrane Oxygenation for Acute Respiratory Distress Syndrome

Author

Giani, M, Rezoagli, E, Guervilly, C, Rilinger, J, Duburcq, T, Petit, M, Textoris, L, Garcia, B, Wengenmayer, T, Bellani, G, Grasselli, G, Pesenti, A, Combes, A, Foti, G, Schmidt, M, Giani M., Rezoagli E., Guervilly C., Rilinger J., Duburcq T., Petit M., Textoris L., Garcia B., Wengenmayer T., Bellani G., Grasselli G., Pesenti A., Combes A., Foti G., Schmidt M., Giani, M, Rezoagli, E, Guervilly, C, Rilinger, J, Duburcq, T, Petit, M, Textoris, L, Garcia, B, Wengenmayer, T, Bellani, G, Grasselli, G, Pesenti, A, Combes, A, Foti, G, Schmidt, M, Giani M., Rezoagli E., Guervilly C., Rilinger J., Duburcq T., Petit M., Textoris L., Garcia B., Wengenmayer T., Bellani G., Grasselli G., Pesenti A., Combes A., Foti G., and Schmidt M.

Abstract

OBJECTIVES: To assess the association of timing to prone positioning (PP) during venovenous extracorporeal membrane oxygenation (V-V ECMO) with the probability of being discharged alive from the ICU at 90 days (primary endpoint) and the improvement of the respiratory system compliance (Cpl,rs). DESIGN: Pooled individual data analysis from five original observational cohort studies. SETTING: European extracorporeal membrane oxygenation (ECMO) centers. PATIENTS: Acute respiratory distress syndrome (ARDS) patients who underwent PP during ECMO. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Time to PP during V-V ECMO was explored both as a continuous and a categorical variable with Cox proportional hazard models. Three hundred patients were included in the analysis. The longer the time to PP during V-V ECMO, the lower the adjusted probability of alive ICU discharge (adjusted hazard ratio [HR] 0.90 for each day increase; 95% CI, 0.87-0.93). Two hundred twenty-three and 77 patients were included in the early PP (≤ 5 d) and late PP (> 5 d) groups, respectively. The cumulative 90-day probability of being discharged alive from the ICU was 61% in the early PP group vs 36% in the late PP group (log-rank test, p <0.001). This benefit was maintained after adjustment for confounders (adjusted HR, 2.52; 95% CI, 1.66-3.81; p <0.001). In the early PP group, PP was associated with a significant improvement of Cpl,rs (4 ± 9 mL/cm H2O vs 0 ± 12 in the late PP group, p=0.038). CONCLUSIONS: In a large cohort of ARDS patients on ECMO, early PP during ECMO was associated with a higher probability of being discharged alive from the ICU at 90 days and a greater improvement of Cpl,rs.

Published
2023

24. Reliability of Respiratory System Compliance Calculation during Assisted Mechanical Ventilation: A Retrospective Study

Author

Bastia, L, Amendolagine, L, Pozzi, F, Carenini, S, Cipolla, C, Curto, F, Bellani, G, Fumagalli, R, Chieregato, A, Bastia L., Amendolagine L., Pozzi F., Carenini S., Cipolla C., Curto F., Bellani G., Fumagalli R., Chieregato A., Bastia, L, Amendolagine, L, Pozzi, F, Carenini, S, Cipolla, C, Curto, F, Bellani, G, Fumagalli, R, Chieregato, A, Bastia L., Amendolagine L., Pozzi F., Carenini S., Cipolla C., Curto F., Bellani G., Fumagalli R., and Chieregato A.

Abstract

OBJECTIVES: To compare respiratory system compliance (Crs) calculation during controlled mechanical ventilation (MV) and, subsequently, during assisted MV. DESIGN: This is a single-center, retrospective, observational study. SETTING: This study was conducted on patients admitted to Neuro-ICU of Niguarda Hospital (tertiary referral hospital). PATIENTS: We analyzed every patient greater than or equal to 18 years old having a Crsmeasurement in controlled and in assisted MV within 60 minutes. Plateau pressure (Pplat) was considered reliable if it was deemed visually stable for at least 2 seconds. Interventions: Inspiratory pause was incorporated to detect Pplatin controlled and assisted MV. Calculation of Crsand driving pressure were achieved. MEASUREMENTS AND MAIN RESULTS: A total of 101 patients were studied. An acceptable agreement was found (Bland-Altman plot bias-3.9, level of agreement upper 21.6, lower-29.6). Crsin assisted MV was 64.1 (52.6-79.3) and in controlled MV it was 61.2 (50-71.2) mL/cm H2o (p = 0.006). No statistical difference was found in Crs(assisted vs controlled MV) when peak pressure was lower than Pplatnor when peak pressure was higher than Pplat. CONCLUSIONS: A Pplatvisually stable for at least 2 seconds leads to reliable Crscalculation during assisted MV.

Published
2023

25. Prognostic Performance of Bedside Lung Ultrasound Score (LUSS) and ROX Index in Hypoxemic Respiratory Failure Due to COVID-19

Author

Nova, A, Rezoagli, E, Eronia, N, Benini, A, Scognamiglio, A, Foti, G, Bellani, G, Nova A., Rezoagli E., Eronia N., Benini A., Scognamiglio A., Foti G., Bellani G., Nova, A, Rezoagli, E, Eronia, N, Benini, A, Scognamiglio, A, Foti, G, Bellani, G, Nova A., Rezoagli E., Eronia N., Benini A., Scognamiglio A., Foti G., and Bellani G.

Abstract

Background: Noninvasive ventilation, mainly helmet CPAP, was widely used during the COVID-19 pandemic, even outside of intensive care units. Both the ROX index and the LUS score (LUSS) have been proposed as tools to predict negative outcomes in patients with hypoxemia treated with noninvasive ventilation (NIV) outside of ICUs. We aim to evaluate whether the combination of LUSS with the ROX index improves the predictive performance of these indices in patients with hypoxemia due to COVID-19 pneumonia, treated with NIV outside of ICUs. Methods: This is a monocentric prospective observational study conducted at the university teaching hospital Fondazione IRCCS San Gerardo dei Tintori (Monza, Italy) from February to April 2021. LUSS and ROX were collected at the same time in noninvasively ventilated patients outside of the ICU. An LUS exam was performed by 3 emergency medicine attending physicians with at least 5 years’ experience in point-of-care ultrasonography using a 12-zone system. To evaluate the accuracy of the prognostic indices in predicting a composite outcome (endotracheal intubation and mortality), ROC curves were used. A logistic multivariable model was used to explore the predictors of the composite outcome of endotracheal intubation and in-hospital mortality. An unadjusted Kaplan–Meier analysis was used to explore the association with the composite outcome of survival without invasive mechanical ventilation at the 30-day follow-up by stratifying the 3 indices by their best cut-offs. Results: A total of 79 patients were included in the statistical analysis and stratified into 2 groups based on the presence of a negative outcome, which was reported in 24 patients out of 79 (30%). A great proportion of patients (66 patients—84%) were treated with helmet CPAP. All three indices (LUSS, ROX and LUSS/ROX) were independently associated with negative outcomes in the multivariable analyses. Although the comparison between the AUROC of LUSS or ROX versus LUSS/ROX di

Published
2023

26. Individual response in patient’s effort and driving pressure to variations in assistance during pressure support ventilation

Author

Docci, M, Rezoagli, E, Teggia-Droghi, M, Coppadoro, A, Pozzi, M, Grassi, A, Bianchi, I, Foti, G, Bellani, G, Docci M., Rezoagli E., Teggia-Droghi M., Coppadoro A., Pozzi M., Grassi A., Bianchi I., Foti G., Bellani G., Docci, M, Rezoagli, E, Teggia-Droghi, M, Coppadoro, A, Pozzi, M, Grassi, A, Bianchi, I, Foti, G, Bellani, G, Docci M., Rezoagli E., Teggia-Droghi M., Coppadoro A., Pozzi M., Grassi A., Bianchi I., Foti G., and Bellani G.

Abstract

Background: During Pressure Support Ventilation (PSV) an inspiratory hold allows to measure plateau pressure (Pplat), driving pressure (∆P), respiratory system compliance (Crs) and pressure-muscle-index (PMI), an index of inspiratory effort. This study aims [1] to assess systematically how patient’s effort (estimated with PMI), ∆P and tidal volume (Vt) change in response to variations in PSV and [2] to confirm the robustness of Crs measurement during PSV. Methods: 18 patients recovering from acute respiratory failure and ventilated by PSV were cross-randomized to four steps of assistance above (+ 3 and + 6 cmH2O) and below (-3 and -6 cmH2O) clinically set PS. Inspiratory and expiratory holds were performed to measure Pplat, PMI, ∆P, Vt, Crs, P0.1 and occluded inspiratory airway pressure (Pocc). Electromyography of respiratory muscles was monitored noninvasively from body surface (sEMG). Results: As PSV was decreased, Pplat (from 20.5 ± 3.3 cmH2O to 16.7 ± 2.9, P < 0.001) and ∆P (from 12.5 ± 2.3 to 8.6 ± 2.3 cmH2O, P < 0.001) decreased much less than peak airway pressure did (from 21.7 ± 3.8 to 9.7 ± 3.8 cmH2O, P < 0.001), given the progressive increase of patient’s effort (PMI from -1.2 ± 2.3 to 6.4 ± 3.2 cmH2O) in line with sEMG of the diaphragm (r = 0.614; P < 0.001). As ∆P increased linearly with Vt, Crs did not change through steps (P = 0.119). Conclusion: Patients react to a decrease in PSV by increasing inspiratory effort—as estimated by PMI—keeping Vt and ∆P on a desired value, therefore, limiting the clinician’s ability to modulate them. PMI appears a valuable index to assess the point of ventilatory overassistance when patients lose control over Vt like in a pressure-control mode. The measurement of Crs in PSV is constant—likely suggesting reliability—independently from the level of assistance and patient’s effort.

Published
2023

27. Safety and Effectiveness of Intensive Treatments Administered Outside the Intensive Care Unit to Hematological Critically Ill Patients: An Intensive Care without Walls Trial

Author

Vergnano, B, Signori, D, Benini, A, Calcinati, S, Bettini, F, Verga, L, Borin, L, Cavalca, F, Gambacorti-Passerini, C, Bellani, G, Foti, G, Vergnano B., Signori D., Benini A., Calcinati S., Bettini F., Verga L., Borin L. M., Cavalca F., Gambacorti-Passerini C., Bellani G., Foti G., Vergnano, B, Signori, D, Benini, A, Calcinati, S, Bettini, F, Verga, L, Borin, L, Cavalca, F, Gambacorti-Passerini, C, Bellani, G, Foti, G, Vergnano B., Signori D., Benini A., Calcinati S., Bettini F., Verga L., Borin L. M., Cavalca F., Gambacorti-Passerini C., Bellani G., and Foti G.

Abstract

Historically, the admission of hematological patients in the ICU shortly after the start of a critical illness is associated with better survival rates. Early intensive interventions administered by MET could play a role in the management of hematological critically ill patients, eventually reducing the ICU admission rate. In this retrospective and monocentric study, we evaluate the safety and effectiveness of intensive treatments administered by the MET in a medical ward frame. The administered interventions were mainly helmet CPAP and pharmacological cardiovascular support. Frequent reassessment by the MET at least every 8 to 12 h was guaranteed. We analyzed data from 133 hematological patients who required MET intervention. In-hospital mortality was 38%; mortality does not increase in patients not immediately transferred to the ICU. Only three patients died without a former admission to the ICU; in these cases, mortality was not related to the acute illness. Moreover, 37% of patients overcame the critical episode in the hematological ward. Higher SOFA and MEWS scores were associated with a worse survival rate, while neutropenia and pharmacological immunosuppression were not. The MET approach seems to be safe and effective. SOFA and MEWS were confirmed to be effective tools for prognostication.

Published
2023

28. Rare predicted loss-of-function variants of type I IFN immunity genes are associated with life-threatening COVID-19

Author

Matuozzo, D, Talouarn, E, Marchal, A, Zhang, P, Manry, J, Seeleuthner, Y, Zhang, Y, Bolze, A, Chaldebas, M, Milisavljevic, B, Gervais, A, Bastard, P, Asano, T, Bizien, L, Barzaghi, F, Abolhassani, H, Abou Tayoun, A, Aiuti, A, Alavi Darazam, I, Allende, L, Alonso-Arias, R, Arias, A, Aytekin, G, Bergman, P, Bondesan, S, Bryceson, Y, Bustos, I, Cabrera-Marante, O, Carcel, S, Carrera, P, Casari, G, Chaibi, K, Colobran, R, Condino-Neto, A, Covill, L, Delmonte, O, El Zein, L, Flores, C, Gregersen, P, Gut, M, Haerynck, F, Halwani, R, Hancerli, S, Hammarstrom, L, Hatipoglu, N, Karbuz, A, Keles, S, Kyheng, C, Leon-Lopez, R, Franco, J, Mansouri, D, Martinez-Picado, J, Metin Akcan, O, Migeotte, I, Morange, P, Morelle, G, Martin-Nalda, A, Novelli, G, Novelli, A, Palabiyik, F, Pan-Hammarstrom, Q, de Diego, R, Planas-Serra, L, Pleguezuelo, D, Prando, C, Pujol, A, Reyes, L, Riviere, J, Rodriguez-Gallego, C, Rojas, J, Rovere-Querini, P, Schluter, A, Shahrooei, M, Sobh, A, Soler-Palacin, P, Tandjaoui-Lambiotte, Y, Tipu, I, Tresoldi, C, Troya, J, van de Beek, D, Zatz, M, Zawadzki, P, Al-Muhsen, S, Alosaimi, M, Alsohime, F, Baris-Feldman, H, Butte, M, Constantinescu, S, Cooper, M, Dalgard, C, Fellay, J, Heath, J, Lau, Y, Lifton, R, Maniatis, T, Mogensen, T, von Bernuth, H, Lermine, A, Vidaud, M, Boland, A, Deleuze, J, Nussbaum, R, Kahn-Kirby, A, Mentre, F, Tubiana, S, Gorochov, G, Tubach, F, Hausfater, P, Al-Mulla, F, Anderson, M, Andreakos, E, Feldman, H, Belot, A, Biggs, C, Bogunovic, D, Bondarenko, A, Bousfiha, A, Brodin, P, Bustamante, C, Chakravorty, S, Christodoulou, J, Desai, M, Drolet, B, Baghdadi, J, Espinosa-Padilla, S, Froidure, A, Hagin, D, Henrickson, S, Hsieh, E, Husebye, E, Imai, K, Itan, Y, Jarvis, E, Karamitros, T, Kisand, K, Ku, C, Ling, Y, Lucas, C, Marodi, L, Milner, J, Mironska, K, Morio, T, Ng, L, O'Farrelly, C, Okada, S, Planas, A, Quintana-Murci, L, Renia, L, Resnick, I, Sancho-Shimizu, V, Sediva, A, Seppanen, M, Shcherbina, A, Slaby, O, Snow, A, Spaan, A, Tancevski, I, Tangye, S, Ramaswamy, S, Turvey, S, Uddin, F, Uddin, M, Vinh, D, Casanova, J, Vacher, Y, Gysembergh-Houal, A, Demerville, L, Chachoua, A, Abad, S, Abassi, R, Abdellaoui, A, Abdelmalek, A, Abdoul, H, Abergel, H, Abeud, F, Abgrall, S, Abisror, N, Adechian, M, Aderdour, N, Admane, H, Adnet, F, Afritt, S, Agostini, H, Aguilar, C, Agut, S, Aiello, T, Kaci, M, Oufella, H, Ajeenthiravasan, G, Alauzy, V, Alby-Laurent, F, Allard, L, Alyanakian, M, Borrero, B, Amam, S, Amrouche, L, Andronikof, M, Anglicheau, D, Anguel, N, Annane, D, Aounzou, M, Aparicio, C, Aratus, G, Arlet, J, Arzoine, J, Aslangul, E, Assefi, M, Aubry, A, Audiffred, L, Audureau, E, Auger, C, Auregan, J, Awotar, C, Milla, S, Azan, D, Azemar, L, Azzouguen, B, Elrufaai, M, Badsi, A, Bakouboula, P, Balcerowiak, C, Balde, F, Baldivia, E, Bangamingo, E, Baptiste, A, Baran-Marszak, F, Barau, C, Barget, N, Baronnet, F, Barthelemy, R, Baudel, J, Baudry, C, Baudry, E, Beaugerie, L, Belamri, A, Belaube, N, Belilita, R, Bellassen, P, Belmokhtar, R, Beltran, I, Benainous, R, Benallaoua, M, Benamouzig, R, Benbara, A, Benhida, J, Benkhelouf, A, Benlagha, J, Benmostafa, C, Benothmane, S, Bentifraouine, M, Berard, L, Bernier, Q, Berti, E, Bertier, A, Berton, L, Bessis, S, Beurton, A, Bianco, C, Bianquis, C, Bidar, F, Blanche, P, Blayau, C, Bleibtreu, A, Blin, E, Bloch-Queyrat, C, Boissier, M, Bollens, D, Bolzoni, M, Bompard, R, Bonnet, N, Bonnouvrier, J, Botha, S, Boucenna, W, Bouchama, F, Bouchaud, O, Bouchghoul, H, Boudjebla, T, Boudjema, N, Bouffard, C, Bougle, A, Bouguerra, M, Bouras, L, Bourcier, A, Durand, A, Bourrier, A, Bouscarat, F, Bouvry, D, Bouziri, N, Bouzrara, O, Bribier, S, Brugier, D, Brunel, M, Bui, E, Buisson, A, Bukreyeva, I, Bureau, C, Cadranel, J, Cailhol, J, Calin, R, Vega, C, Canavaggio, P, Cancella, M, Cantin, D, Cao, A, Carbillon, L, Carlier, N, Cassard, C, Castor, G, Cauchy, M, Cha, O, Chaigne, B, Challal, S, Champion, K, Chariot, P, Chas, J, Chauveau, S, Chauvin, A, Chauvin, C, Chavarot, N, Chebbout, K, Cherai, M, Cherubini, I, Chevalier, A, Chiarabini, T, Chinet, T, Chocron, R, Choinier, P, Chommeloux, J, Choquet, C, Choupeaux, L, Chousterman, B, Ciocan, D, Clarke, A, Clavere, G, Clavier, F, Clement, K, Clerc, S, Cohen, Y, Cohen, F, Cohen, A, Coilly, A, Colboc, H, Colin, P, Collet, M, Comarmond, C, Combacon, E, Combes, A, Comparon, C, Constantin, J, Cordel, H, Cordier, A, Costantini, A, Chalumeau, N, Couffignal, C, Coupeau, D, Creange, A, Lamarre, Y, Da Silveira, C, Kayani, S, De Castro, N, De Rycke, Y, Del Pozo, L, Delannoy, Q, Delay, M, Deleris, R, Delforge, J, Delphine, L, Demare, N, Demeret, S, Demoule, A, Deniau, A, Depret, F, Derolez, S, Derradji, O, Derridj, N, Descamps, V, Deschamps, L, Desconclois, C, Desnos, C, Desongins, K, Dhote, R, Diallo, B, Didier, M, Diemer, M, Diez, S, Djadi-Prat, J, Monnory, F, Djebara, S, Djebra, N, Djietcheu, M, Djillali, H, Djouadi, N, Donneger, S, Dos Santos, C, Dournon, N, Dres, M, Droctove, L, Drogrey, M, Dropy, M, Drouet, E, Dubosq, V, Dubreucq, E, Dubus, E, Duchemann, B, Duchenoy, T, Dudoignon, E, Dufau, R, Dumas, F, Duran, C, Duron, E, Durrbach, A, Duvivier, C, Ebstein, N, Khalifa, J, Elabbadi, A, Elie, C, Ernotte, G, Esling, A, Etienne, M, Eyer, X, Fartoukh, M, Fayali, T, Fermaut, M, Fiorentino, A, Fliss, S, Fournier, M, Fournier, B, Francois, H, Freynet, O, Frigout, Y, Fromont, I, Fuentes, A, Furet, T, Galand, J, Garnier, M, Gaubert, A, Gaudry, S, Gaugain, S, Gauthier, D, Gautier, M, Georgin-Lavialle, S, Geromin, D, Ghalayini, M, Ghaleh, B, Ghezal, M, Gibelin, A, Gimeno, L, Girard, B, Leprieur, B, Gomes, D, Gomes-Pires, E, Gouge, A, Gouja, A, Goulet, H, Goupil, S, De Bouille, J, Gras, J, Greffe, S, Grimaldi, L, Guedeney, P, Guidet, B, Guillo, M, Gulczynski, M, Hadjam, T, Haguenauer, D, Hammal, S, Hammoudi, N, Hanon, O, Harrois, A, Hautem, C, Hekimian, G, Heming, N, Hermine, O, Ho, S, Houllier, M, Huot, B, Huscenot, T, Saied, W, Ikherbane, G, Imarazene, M, Ingiliz, P, Iratni, L, Jaureguiberry, S, Jean-Marc, J, Jeyarajasingham, D, Jouany, P, Jouis, V, Jourdaine, C, Kafif, O, Kallala, R, Katsahian, S, Kelesyan, L, Keo, V, Ketz, F, Khamis, W, Khelili, E, Khellaf, M, Youkou, C, Kounis, I, Kpalma, G, Krause, J, Labbe, V, Lacombe, K, Lacorte, J, Lafont, A, Lafont, E, Lagha, L, Lamhaut, L, Lancelot, A, Landman, C, Lanternier, F, Larcheveque, C, Combe, C, Lassel, L, Laverdant, B, Lavergne, C, Lavillegrand, J, Lazureanu, P, Le Guennec, L, Leberre, L, Leblanc, C, Leboyer, M, Lecomte, F, Lecorre, M, Leenhardt, R, Lefebvre, M, Lefebvre, B, Legendre, P, Leger, A, Legros, L, Legrosse, J, Lehuunghia, S, Lemarec, J, Leporrier-Ext, J, Lesein, M, Lesur, H, Levy, V, Levy, A, Lopes, E, Lopes, A, Lopez, V, Lopinto, J, Lortholary, O, Louadah, B, Loze, B, Lucas, M, Lucasamichi, A, Luong, L, Magazimama-Ext, A, Maingret, D, Mameri, L, Manivet, P, Mansouri, C, Marcault, E, Marey, J, Marin, N, Marois, C, Martin, O, Martineau, L, Martinez-Lopez, C, Martyniuck, P, De Farcy, P, Marzouk, N, Masmoudi, R, Mebazaa, A, Mechai, F, Mecozzi, F, Mediouni, C, Megarbane, B, Meghadecha, M, Mejean, E, Mekinian, A, Abdelhadi, N, Mekni, R, Meliti, T, Lima, B, Meng, P, Merbah, S, Messani, F, Messaoudi, Y, Mewasing, B, Meziane, L, Michelot-Burger, C, Mignot, F, Minka, F, Miyara, M, Moine, P, Molina, J, Montegnies-Boulet, A, Monti, A, Montlahuc, C, Montout, A, Moores, A, Morbieu, C, Mortelette, H, Mouly, S, Muzaffar, R, Nacerddine, C, Nadal, M, Nadif, H, Nassarmadji, K, Natella, P, Ndingamondze, S, Neraal, S, Nguyen, C, N'Guyen, B, Larmurier, I, Nlomenyengue, L, Noel, N, Nunes, H, Omar, E, Ouazene, Z, Ouedraogo, E, Ouelaa, W, Oukhedouma, A, Amara, Y, Oya, H, Oziel, J, Padilla, T, Paillaud, E, Paiva, S, Parfait, B, Parize, P, Parizot, C, Parrot, A, Pavot, A, Peaudecerf, L, Pene, F, Pepin, M, Pernet, J, Pernin, C, Petit, M, Peyrony, O, Pietri, M, Pietri, O, De Chambrun, M, Pinson, M, Pintado, C, Pires, C, Planquette, B, Poirier, S, Pomel, A, Pons, S, Ponscarme, D, Pourcelot, A, Pourcher, V, Pouvaret, A, Prever, F, Previlon, M, Prevost, M, Provoost, M, Quemeneur, C, Rafat, C, Rami, A, Ranque, B, Raphael, M, Raphalen, J, Rastoin, A, Raux, M, Rebai, A, Reby, M, Regent, A, Regrag, A, Resche-Rigon, M, Ressaire, Q, Richard, C, Richard, M, Robert, M, Rohaut, B, Rolland-Debord, C, Ropers, J, Roque-Afonso, A, Rosso, C, Rousseaux, M, Rousseaux, N, Roux, S, Roux, L, Rouzaud, C, Rozes, A, Rubenstein, E, Sabate, J, Sabet, S, Sacleux, S, Kermanach, N, Saliba, F, Salmon, D, Savale, L, Savary, G, Sberro, R, Scemla, A, Schlemmer, F, Schwartz, M, Sedfi, S, Sefir-Kribel, S, Seksik, P, Sellier, P, Selves, A, Sembach, N, Semerano, L, Senat, M, Sene, D, Serris, A, Sese, L, Sghiouar, N, Sigaux, J, Siguier, M, Silvain, J, Simon, N, Simon, T, Skandri, L, Slimani, M, Snauwaert, A, Sokol, H, Soliman, H, Soltani, N, Soyer, B, Steg, G, Suarez, L, Szwebel, T, Taffame, K, Tantet, C, Tateo, M, Theodose, I, Thiebaud, P, Thomas, C, Tiercelet, K, Tisserand, J, Tomczak, C, Torelino, K, Touam-Ext, F, Toumi, L, Toury, G, Toy-Miou, M, Lien, O, Trandinh, A, Treluyer, J, Trinque, B, Truchot, J, Tunesi, S, Turpin, M, Turpin, A, Urbina, T, Narvaez, R, Uzunhan, Y, Vaittinadaayar, P, Valent, A, Valentian, M, Valin, N, Vallet, H, Vaz, M, Vazquezibarra, M, Vedie, B, Velly, L, Verstuyft, C, Viallette, C, Vicaut, E, Vignes, D, Vimpere, D, Virlouvet, M, Voiriot, G, Voisot, L, Weiss, E, Weiss, N, Winchenne, A, Yordanov, Y, Zafrani, L, Zaidan, M, Zaidi, W, Zak, C, Zarhrate-Ghoul, A, Zatout, O, Zeino, S, Zeitouni, M, Zemirli, N, Zerah, L, Zia, O, Ziol, M, Zolario, O, Zuber, J, Andrejak, C, Angoulvant, F, Bachelet, D, Bartoli, M, Basmaci, R, Behilill, S, Beluze, M, Benkerrou, D, Bhavsar, K, Bouadma, L, Bouchez, S, Bouscambert, M, Cervantes-Gonzalez, M, Chair, A, Coelho, A, D'Ortenzio, E, Debray, M, Deconinck, L, Deplanque, D, Descamps, D, Desvallee, M, Diallo, A, Diouf, A, Dorival, C, Dubos, F, Duval, X, Elharrar, B, Eloy, P, Enouf, V, Esperou, H, Esposito-Farese, M, Devouge, E, Gault, N, Gaymard, A, Ghosn, J, Gigante, T, Gilg, M, Guedj, J, Hoctin, A, Hoffmann, I, Houas, I, Hulot, J, Jaafoura, S, Kaguelidou, F, Kali, S, Khalil, A, Khan, C, Laouenan, C, Laribi, S, Le, M, Le Hingrat, Q, Le Mestre, S, Le Nagard, H, Lescure, F, Levy, Y, Lingas, G, Lucet, J, Malvy, D, Mambert, M, Meziane, A, Mouquet, H, Mullaert, J, Neant, N, Nguyen, D, Noret, M, Nseir, S, Papadopoulos, A, Paul, C, Peiffer-Smadja, N, Perpoint, T, Petrov-Sanchez, V, Peytavin, G, Pham, H, Picone, O, Puechal, O, Rabaud, C, Rosa-Calatrava, M, Rossignol, B, Rossignol, P, Roy, C, Schneider, M, Su, R, Tardivon, C, Tellier, M, Teoule, F, Terrier, O, Timsit, J, Tual, C, Van Der Werf, S, Vanel, N, Veislinger, A, Visseaux, B, Wiedemann, A, Yazdanpanah, Y, Alavoine, L, Behillil, S, Burdet, C, Charpentier, C, Dechanet, A, Ecobichon, J, Frezouls, W, Houhou, N, Lehacaut, J, Letrou, S, Lina, B, Manchon, P, Nouroudine, M, Piquard, V, Quintin, C, Thy, M, Vignali, V, Chahine, A, Waucquier, N, Migaud, M, Djossou, F, Mergeay-Fabre, M, 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S., Saliba F., Salmon D., Savale L., Savary G., Sberro R., Scemla A., Schlemmer F., Schwartz M., Sedfi S., Sefir-Kribel S., Seksik P., Sellier P., Selves A., Sembach N., Semerano L., Senat M. -V., Sene D., Serris A., Sese L., Sghiouar N., Sigaux J., Siguier M., Silvain J., Simon N., Simon T., Skandri L. I., Slimani M., Snauwaert A., Sokol H., Soliman H., Soltani N., Soyer B., Steg G., Suarez L., Szwebel T. -A., Taffame K., Tantet C., Tateo M., Theodose I., Thiebaud P., Thomas C., Tiercelet K., Tisserand J., Tomczak C., Torelino K., Touam-Ext F., Toumi L., Toury G., Toy-Miou M., Lien O. T. D. T., Trandinh A., Treluyer J. -M., Trinque B., Truchot J., Tunesi S., Turpin M., Turpin A., Urbina T., Narvaez R. U., Uzunhan Y., Vaittinadaayar P., Valent A., Valentian M., Valin N., Vallet H., Vaz M., Vazquezibarra M. -A., Vedie B., Velly L., Verstuyft C., Viallette C., Vicaut E., Vignes D., Vimpere D., Virlouvet M., Voiriot G., Voisot L., Weiss E., Weiss N., Winchenne A., Yordanov Y., Zafrani L., Zaidan M., Zaidi W., Zak C., Zarhrate-Ghoul A., Zatout O., Zeino S., Zeitouni M., Zemirli N., Zerah L., Zia O., Ziol M., Zolario O., Zuber J., Andrejak C., Angoulvant F., Bachelet D., Bartoli M., Basmaci R., Behilill S., Beluze M., Benkerrou D., Bhavsar K., Bouadma L., Bouchez S., Bouscambert M., Cervantes-Gonzalez M., Chair A., Coelho A., d'Ortenzio E., Debray M. -P., Deconinck L., Deplanque D., Descamps D., Desvallee M., Diallo A., Diouf A., Dorival C., Dubos F., Duval X., Elharrar B., Eloy P., Enouf V., Esperou H., Esposito-Farese M., Devouge E. F., Gault N., Gaymard A., Ghosn J., Gigante T., Gilg M., Guedj J., Hoctin A., Hoffmann I., Houas I., Hulot J. -S., Jaafoura S., Kaguelidou F., Kali S., Khalil A., Khan C., Laouenan C., Laribi S., Le M., Le Hingrat Q., Le Mestre S., Le Nagard H., Lescure F. -X., Levy Y., Lingas G., Lucet J. C., Malvy D., Mambert M., Meziane A., Mouquet H., Mullaert J., Neant N., Nguyen D., Noret M., Nseir S., Papadopoulos A., Paul C., Peiffer-Smadja N., Perpoint T., Petrov-Sanchez V., Peytavin G., Pham H., Picone O., Puechal O., Rabaud C., Rosa-Calatrava M., Rossignol B., Rossignol P., Roy C., Schneider M., Su R., Tardivon C., Tellier M. -C., Teoule F., Terrier O., Timsit J. -F., Tual C., Van Der Werf S., Vanel N., Veislinger A., Visseaux B., Wiedemann A., Yazdanpanah Y., Alavoine L., Behillil S., Burdet C., Charpentier C., Dechanet A., Ecobichon J. -L., Frezouls W., Houhou N., Lehacaut J., Letrou S., Lina B., Manchon P., Nouroudine M., Piquard V., Quintin C., Thy M., Vignali V., Chahine A., Waucquier N., Migaud M. -C., Djossou F., Mergeay-Fabre M., Lucarelli A., Demar M., Bruneau L., Gerardin P., Maillot A., Payet C., Laviolle B., Laine F., Paris C., Desille-Dugast M., Fouchard J., Pistone T., Perreau P., Gissot V., Goas C. L. E., Montagne S., Richard L., Chirouze C., Bouiller K., Desmarets M., Meunier A., Bourgeon M., Lefevre B., Jeulin H., Legrand K., Lomazzi S., Tardy B., Gagneux-Brunon A., Bertholon F., Botelho-Nevers E., Christelle K., Nicolas L., Roufai L., Amat K., Couffin-Cadiergues S., Hendou S., Foti G., Bellani G., Citerio G., Contro E., Pesci A., Valsecchi M. G., Cazzaniga M., Abad J., Accordino G., Achille C., Aguilera-Albesa S., Aguilo-Cucurull A., Ozkan E. A., Albisures J. A. R., Aldave J. C., Ramos M. A., Khan T. A., Aliberti A., Nadji S. A., Alkan G., AlKhater S. A., Allardet-Servent J., Alshahrani M. S., Alsina L., Amoura Z., Antoli A., Arrestier R., Aubart M., Auguet T., Avramenko I., Azot A., Bahram S., Bajolle F., Baldanti F., Baldolli A., Ballester M., Barrou B., Basso S., Bayhan G. I., Bezrodnik L., Bilbao A., Blanchard-Rohner G., Blanco I., Blandinieres A., Blazquez-Gamero D., Bloomfield M., Bolivar-Prados M., Borghesi A., Borie R., Botdhlo-Nevers E., Bousquet A., Boutolleau D., Bouvattier C., Boyarchuk O., Bravais J., Briones M. L., Brunner M. -E., Bruno R., Bueno M. R. P., Bukhari H., Bustamante J., Agra J. J. C., Capra R., Carapito R., Carrabba M., Casasnovas C., Caseris M., Cassaniti I., Castelle M., Castelli F., de Vera M. C., Castro M. V., Catherinot E., Celik J. B., Ceschi A., Chalumeau M., Charbit B., Cheng M. P., Clave P., Clotet B., Codina A., Comoli P., Corsico A. G., Sozeri B., Coskuner T., Cvetkovski A., Cyrus C., Dalmau D., Danion F., Darley D. R., Das V., Dauby N., Dauger S., De Munter P., de Pontual L., Dehban A., Delplancq G., Desguerre I., Di Sabatino A., Diehl J. -L., Dobbelaere S., Dominguez-Garrido E., Dubost C., Ekwall O., Bozdemir S. E., Elnagdy M. H., Emiroglu M., Endo A., Erdeniz E. H., Aytekin S. E., Lasa M. P. 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Y., Lampropoulou V., Le Bourgeois F., Leo Y. -S., Leung D., Levin M., Levy M., Levy R., Li Z., Lilleri D., Lima E. J. A. B., Linglart A., Lopez-Collazo E., Lorenzo-Salazar J. M., Louapre C., Lubetzki C., Lung K. -C., Luyt C. -E., Lye D. C., Magnone C., Marchioni E., Marioli C., Marjani M., Marques L., Pereira J. M., Pueyo D. M., Marzana I., Mata-Martinez C., Mathian A., Matos L. R. B., Matthews G. V., Mayaux J., McLaughlin-Garcia R., Meersseman P., Mege J. -L., Mekontso-Dessap A., Melki I., Meloni F., Meritet J. -F., Merlani P., Akcan O. M., Mezidi M., Millereux M., Million M., Mirault T., Mircher C., Mirsaeidi M., Mizoguchi Y., Modi B. P., Mojoli F., Moncomble E., Melian A. M., Martinez A. M., Morandeira F., Mordacq C., Mouly S. J., Munoz-Barrera A., Nafati C., Nagashima S., Nakagama Y., Neven B., Neves J. F., Ng Y. -Y., Nielly H., Medina Y. N., Cuadros E. N., Ocejo-Vinyals J. G., Okamoto K., Oualha M., Ouedrani A., Ozcelik T., Ozkaya-Parlakay A., Pagani M., Papadaki M., Parola P., Pascreau T., Paul S., Paz-Artal E., Pedraza S., Pellecer N. C. G., Pellegrini S., Perez-Fernandez X. L., Philippe A., Philippot Q., Picod A., Piralla A., Ploin D., Poissy J., Poncelet G., Poulakou G., Pouletty M. S., Pourshahnazari P., Qiu-Chen J. L., Quentric P., Rambaud T., Raoult D., Raoult V., Rebillat A. -S., Redin C., Resmini L., Ricart P., Richard J. -C., Rigo-Bonnin R., rivet N., Rocamora-Blanch G., Rodero M. P., Rodrigo C., Rodriguez L. A., Rodriguez-Palmero A., Romero C. S., Rothenbuhler A., Roux D., Rovina N., Rozenberg F., Ruch Y., Ruiz M., del Prado M. Y. R., Ruiz-Rodriguez J. C., Sabater-Riera J., Saks K., Salagianni M., Sanchez O., Sanchez-Montalva A., Sanchez-Ramon S., Schidlowski L., Schmidt J., Schmidt M., Schuetz C., Schweitzer C. E., Scolari F., Seijo L., Seminario A. G., Seng P., Senoglu S., Seppanen M., Llovich A. S., Siguret V., Siouti E., Smadja D. M., Smith N., Solanich X., Sole-Violan J., Soler C., Stella G. M., Stepanovskiy Y., Stoclin A., Taccone F., Taupin J. -L., Tavernier S. J., Tello L. V., Terrier B., Thiery G., Thorball C., Thorn K., Thumerelle C., Tolstrup M., Tomasoni G., Toubiana J., Alvarez J. T., Triantafyllia V., Trouillet-Assant S., Tsang O. T. Y., Tserel L., Tso E. Y. K., Tucci A., Oz S. K. T., Ursini M. V., Utsumi T., Vabres P., Valencia-Ramos J., Van Den Rym A. M., Vandernoot I., Velez-Santamaria V., Veliz S. P. Z., Vidigal M. C., Viel S., Villain C., Vilaire-Meunier M. E., Villar-Garcia J., Vincent A., Volokha A., Vuotto F., Wauters E., Wauters J., Wu A. K. L., Wu T. -C., Yahsi A., Yesilbas O., Yildiz M., Young B. E., Yukselmis U., Zecca M., Zuccaro V., Van Praet J., Lambrecht B. 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P., Schuurmans A., Schuurmans J., Sigaloff K., Slim M. A., Smeele P., Smit M., Stijnis C. S., Stilma W., Teunissen C., Thoral P., Tsonas A. M., Tuinman P. R., van der Valk M., Veelo D., Volleman C., de Vries H., Vught L. A., van Vugt M., Wouters D., Zwinderman A. H., Brouwer M. C., Wiersinga W. J., Vlaar A. P. J., Tompkins M. F., Alba C., Hupalo D. N., Rosenberger J., Sukumar G., Wilkerson M. D., Zhang X., Lack J., Oler A. J., Dobbs K., Danielson J. J., Biondi A., Bettini L. R., D'Angio' M., Beretta I., Imberti L., Sottini A., Quaresima V., Quiros-Roldan E., Rossi C., Meyts I., Zhang S. -Y., Puel A., Notarangelo L. D., Boisson-Dupuis S., Su H. C., Boisson B., Jouanguy E., Zhang Q., Abel L., and Cobat A.

Abstract

Background: We previously reported that impaired type I IFN activity, due to inborn errors of TLR3- and TLR7-dependent type I interferon (IFN) immunity or to autoantibodies against type I IFN, account for 15–20% of cases of life-threatening COVID-19 in unvaccinated patients. Therefore, the determinants of life-threatening COVID-19 remain to be identified in ~ 80% of cases. Methods: We report here a genome-wide rare variant burden association analysis in 3269 unvaccinated patients with life-threatening COVID-19, and 1373 unvaccinated SARS-CoV-2-infected individuals without pneumonia. Among the 928 patients tested for autoantibodies against type I IFN, a quarter (234) were positive and were excluded. Results: No gene reached genome-wide significance. Under a recessive model, the most significant gene with at-risk variants was TLR7, with an OR of 27.68 (95%CI 1.5–528.7, P = 1.1 × 10−4) for biochemically loss-of-function (bLOF) variants. We replicated the enrichment in rare predicted LOF (pLOF) variants at 13 influenza susceptibility loci involved in TLR3-dependent type I IFN immunity (OR = 3.70[95%CI 1.3–8.2], P = 2.1 × 10−4). This enrichment was further strengthened by (1) adding the recently reported TYK2 and TLR7 COVID-19 loci, particularly under a recessive model (OR = 19.65[95%CI 2.1–2635.4], P = 3.4 × 10−3), and (2) considering as pLOF branchpoint variants with potentially strong impacts on splicing among the 15 loci (OR = 4.40[9%CI 2.3–8.4], P = 7.7 × 10−8). Finally, the patients with pLOF/bLOF variants at these 15 loci were significantly younger (mean age [SD] = 43.3 [20.3] years) than the other patients (56.0 [17.3] years; P = 1.68 × 10−5). Conclusions: Rare variants of TLR3- and TLR7-dependent type I IFN immunity genes can underlie life-threatening COVID-19, particularly with recessive inheritance, in patients under 60 years old.

Published
2023

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

Author

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N., Crespo Ramirez M., Crova P., Cruz J., Cubattoli L., Cukurova Z., Curto F., Czempik P., D'Andrea R., da Silva Ramos F., Dangers L., Danguy des Deserts M., Danin P. -E., Dantas F., Daubin C., Dawei W., de Haro C., de Jesus Montelongo F., De Mendoza D., de Pablo R., De Pascale G., De Rosa S., Decavele M., Declercq P. -L., Deicas A., del Carmen Campos Moreno M., Dellamonica J., Delmas B., Demirkiran O., Demirkiran H., Dendane T., di Mussi R., Diakaki C., Diaz A., Diaz W., Dikmen Y., Dimoula A., Doble P., Doha N., Domingos G., Dres M., Dries D., Duggal A., Duke G., Dunts P., Dybwik K., Dykyy M., Eckert P., Efe S., Elatrous S., Elay G., Elmaryul A. S., Elsaadany M., Elsayed H., Elsayed S., Emery M., Ena S., Eng K., Englert J. A., Erdogan E., Ergin Ozcan P., Eroglu E., Escobar M., Esen F., Esen Tekeli A., Esquivel A., Esquivel Gallegos H., Ezzouine H., Facchini A., Faheem M., Fanelli V., Farina M. F., Fartoukh M., Fehrle L., Feng F., Feng Y., Fernandez I., Fernandez B., Fernandez-Rodriguez M. L., Ferrando C., Ferreira da Silva M. J., Ferreruela M., Ferrier J., Flamm Zamorano M. J., Flood L., Floris L., Fluckiger M., Forteza C., Fortunato A., Frans E., Frattari A., Fredes S., Frenzel T., Fumagalli R., Furche M. A., Fusari M., Fysh E., Galeas-Lopez J. L., Galerneau L. -M., Garcia A., Garcia M. F., Garcia E., Garcia Olivares P., Garlicki J., Garnero A., Garofalo E., Gautam P., Gazenkampf A., Gelinotte S., Gelormini D., Ghrenassia E., Giacomucci A., Giannoni R., Gigante A., Glober N., Gnesin P., Gollo Y., Gomaa D., Gomero Paredes R., Gomes R., Gomez R. A., Gomez O., Gomez A., Gondim L., Gonzalez M., Gonzalez I., Gonzalez-Castro A., Gordillo Romero O., Gordo F., Gouin P., Graf Santos J., Grainne R., Grando M., Granov Grabovica S., Grasso S., Grasso R., Grimmer L., Grissom C., Gu Q., Guan X. -D., Guarracino F., Guasch N., Guatteri L., Gueret R., Guerin C., Guerot E., Guitard P. -G., Gul F., Gumus A., Gurjar M., Gutierrez P., Hachimi A., Hadzibegovic A., Hagan S., Hammel C., Han Song J., Hanlon G., Heines S., Henriksson J., Herbrecht J. -E., Heredia Orbegoso G. O., Hermon A., Hernandez R., Hernandez C., Herrera L., Herrera-Gutierrez M., Hidalgo J., Hill D., Holmquist D., Homez M., Hongtao X., Hormis A., Horner D., Hornos M. C., Hou M., House S., Housni B., Hugill K., Humphreys S., Humbert L., Hunter S., Hwa Young L., Iezzi N., Ilutovich S., Inal V., Innes R., Ioannides P., Iotti G. A., Ippolito M., Irie H., Iriyama H., Itagaki T., Izura J., Izza S., Jabeen R., Jamaati H., Jamadarkhana S., Jamoussi A., Jankowski M., Jaramillo L. A., Jeon K., Jeong Lee S., Jeswani D., Jha S., Jiang L., Jing C., Jochmans S., Johnstad B. A., Jongmin L., Joret A., Junhasavasdikul D., Jurado M. T., Kam E., Kamohara H., Kane C., Kara I., Karakurt S., Karnjanarachata C., Kataoka J., Katayama S., Kaushik S., Kelebek Girgin N., Kerr K., Kerslake I., Khairnar P., Khalid A., Khan A., Khanna A. K., Khorasanee R., Kienhorst D., Kirakli C., Knafelj R., Kol M. K., Kongpolprom N., Kopitko C., Korkmaz Ekren P., Kubisz-Pudelko A., Kulcsar Z., Kumasawa J., Kuriyama A., Kutchak F., Labarca E., Labat F., Laborda C., Laca Barrera M. A., Lagache L., Landaverde Lopez A., Lanspa M., Lascari V., Le Meur M., Lee S. H., Lee Y. J., Lee J., Lee W. -Y., Legernaes T., Leiner T., Lemiale V., Leonor T., Lepper P. M., Li D., Li H., Li O., Lima A. R., Lind D., Litton E., Liu N., Liu L., Liu J., Llitjos J. -F., Llorente B., Lopez R., Lopez C. E., Lopez Nava C., Lovazzano P., Lu M., Lucchese F., Lugano M., Lugo Goytia G., Luo H., Lynch C., Macheda S., Madrigal Robles V. H., Maggiore S. M., Magret Iglesias M., Malaga P., Mallapura Maheswarappa H., Malpartida G., Malyarchikov A., Mansson H., Manzano A., Marey I., Marin N., Marin M. D. C., Markman E., Martin F., Martin A., Martin Dal Gesso C., Martinez F., Martinez-Fidalgo C., Martin-Loeches I., Mas A., Masaaki S., Maseda E., Massa E., Mattsson A., Maugeri J., McCredie V., McCullough J., McGuinness S., McKown A., Medve L., Mei C., Mellado Artigas R., Mendes V., Mervat M. K. E., Michaux I., Mikhaeil M., Milagros O., Milet I., Millan M. T., Minwei Z., Mirabella L., Mishra S., Mistraletti G., Mochizuki K., Moghal A., Mojoli F., Molin A., Montiel R., Montini L., Monza G., Mora Aznar M., Morakul S., Morales M., Moreno Torres D., Morocho Tutillo D. R., Motherway C., Mouhssine D., Mouloudi E., Munoz T., Munoz de Cabo C., Mustafa M., Muthuchellappan R., Muthukrishnan M., Muttini S., Nagata I., Nahar D., Nakanishi M., Nakayama I., Namendys-Silva S. A., Nanchal R., Nandakumar S., Nasi A., Nasir K., Navalesi P., Naz Aslam T., Nga Phan T., Nichol A., Niiyama S., Nikolakopoulou S., Nikolic E., Nitta K., Noc M., Nonas S., Nseir S., Nur Soyturk A., Obata Y., Oeckler R., Oguchi M., Ohshimo S., Oikonomou M., Ojados A., Oliveira M. T., Oliveira Filho W., Oliveri C., Olmos A., Omura K., Orlandi M. C., Orsenigo F., Ortiz-Ruiz De Gordoa L., Ota K., Ovalle Olmos R., Oveges N., Oziemski P., Ozkan Kuscu O., Pachas Alvarado F., Pagella G., Palaniswamy V., Palazon Sanchez E. L., Palmese S., Pan G., Pan W., Papanikolaou M., Papavasilopoulou T., Parekh A., Parke R., Parrilla F. J., Parrilla D., Pasha T., Pasin L., Patao L., Patel M., Patel G., Pati B. K., Patil J., Pattnaik S., Paul D., Pavesi M., Pavlotsky V. A., Paz G., Paz E., Pecci E., Pellegrini C., Pena Padilla A. G., Perchiazzi G., Pereira T., Pereira V., Perez M., Perez Calvo C., Perez Cheng M., Perez Maita R., Perez-Araos R., Perez-Teran P., Perez-Torres D., Perkins G., Persona P., Petnak T., Petrova M., Philippart F., Picetti E., Pierucci E., Piervincenzi E., Pinciroli R., Pintado M. -C., Piraino T., Piras S., Piras C., Pirompanich P., Pisani L., Platas E., Plotnikow G., Porras W., Porta V., Portilla M., Portugal J., Povoa P., Prat G., Pratto R., Preda G., Prieto I., Prol-Silva E., Pugh R., Qi Y., Qian C., Qin T., Qu H., Quintana T., Quispe Sierra R., Quispe Soto R., Rabbani R., Rabee M., Rabie A., Rahe Pereira M. A., Rai A., Raj Ashok S., Rajab M., Ramdhani N., Ramey E., Ranieri M., Rathod D., Ray B., Redwanul Huq S. M., Regli A., Reina R., Resano Sarmiento N., Reynaud F., Rialp G., Ricart P., Rice T., Richardson A., Rieder M., Rinket M., Rios F., Risso Vazquez A., Riva I., Rivette M., Roca O., Roche-Campo F., Rodriguez C., Rodriguez G., Rodriguez Gonzalez D., Rodriguez Tucto X. Y., Rogers A., Romano M. E., Rortveit L., Rose A., Roux D., Rouze A., Rubatto Birri P. N., Ruilan W., Ruiz Robledo A., Ruiz-Aguilar A. L., Sadahiro T., Saez I., Sagardia J., Saha R., Saiphoklang N., Saito S., Salem M., Sales G., Salgado P., Samavedam S., Sami Mebazaa M., Samuelsson L., San Juan Roman N., Sanchez P., Sanchez-Ballesteros J., Sandoval Y., Sani E., Santos M., Santos C., Sanui M., Saravanabavan L., Sari S., Sarkany A., Sauneuf B., Savioli M., Sazak H., Scano R., Schneider F., Schortgen F., Schultz M. J., Schwarz G. L., Seckin Yucesoy F., Seely A., Seiler F., Seker Tekdos Y., Seok Chan K., Serano L., Serednicki W., Setten M., Shah A., Shah B., Shang Y., Shanmugasundaram P., Shapovalov K., Shebl E., Shiga T., Shime N., Shin P., Short J., Shuhua C., Siddiqui S., Silesky Jimenez J. I., Silva D., Silva Sales B., Simons K., Sjobo B. A., Slessor D., Smiechowicz J., Smischney N., Smith P., Smith T., Smith M., Snape S., Snyman L., Soetens F., Sook Hong K., Sosa Medellin M. A., Soto G., Souloy X., Sousa E., Sovatzis S., Sozutek D., Spadaro S., Spagnoli M., Spangfors M., Spittle N., Spivey M., Stapleton A., Stefanovic B., Stephenson L., Stevenson E., Strand K., Strano M. T., Straus S., Sun C., Sun R., Sundaram V., SunPark T., Surlemont E., Sutherasan Y., Szabo Z., Tainter C., Takaba A., Tallott M., Tamasato T., Tang Z., Tangsujaritvijit V., Taniguchi L., Taniguchi D., Tarantino F., Teerapuncharoen K., Temprano S., Terragni P., Terzi N., Thakur A., Theerawit P., Thille A. W., Thomas M., Thungtitigul P., Thyrault M., Tilouch N., Timenetsky K., Tirapu J., Todeschini M., Tomas R., Tomaszewski C., Tonetti T., Tonnelier A., Trinder J., Trongtrakul K., Truwit J., Tsuei B., Tulaimat A., Turan S., Turkoglu M., Tyagi S., Ubeda A., Vagginelli F., Valenti M. F., Vallverdu I., Van Axel A., van den Hul I., van der Hoeven H., Van Der Meer N., Vanhoof M., Vargas-Ordonez M., Vaschetto R., Vascotto E., Vatsik M., Vaz A., Vazquez-Sanchez A., Ventura S., Vermeijden J. W., Vidal A., Vieira J., Vilela Costa Pinto B., Villagra A., Villegas Succar C., Vinorum O. G., Vitale G., Vj R., Vochin A., Voiriot G., Volta C. A., von Seth M., Wajdi M., Walsh D., Wang S., Wardi G., Ween-Velken N. C., Wei B. -L., Weller D., Welsh D., Welters I., Wert M., Whiteley S., Wilby E., Williams E., Williams K., Wilson A., Wojtas J., Won Huh J., Wrathall D., Wright C., Wu J. -F., Xi G., Xing Z. -J., Xu H., Yamamoto K., Yan J., Yanez J., Yang X., Yates E., Yazicioglu Mocin O., Ye Z., Yildirim F., Yoshida N., Yoshido H. H. L., Young Lee B., Yu R., Yu G., Yu T., Yuan B., Yuangtrakul N., Yumoto T., Yun X., Zakalik G., Zaki A., Zalba-Etayo B., Zambon M., Zang B., Zani G., Zarka J., Zerbi S. M., Zerman A., Zetterquist H., Zhang J., Zhang H., Zhang W., Zhang G., Zhao H., Zheng J., Zhu B., and Zumaran R.

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

30. Identifying Trauma Patients in Need for Emergency Surgery in the Prehospital Setting: The Prehospital Prediction of In-Hospital Emergency Treatment (PROPHET) Study

Author

Isgro, S, Giani, M, Antolini, L, Giudici, R, Valsecchi, M, Bellani, G, Chiara, O, Bassi, G, Latronico, N, Cabrini, L, Fumagalli, R, Chieregato, A, Sammartano, F, Sechi, G, Zoli, A, Pagliosa, A, Palo, A, Valoti, O, Carlucci, M, Benini, A, Foti, G, Isgro S., Giani M., Antolini L., Giudici R., Valsecchi M. G., Bellani G., Chiara O., Bassi G., Latronico N., Cabrini L., Fumagalli R., Chieregato A., Sammartano F., Sechi G., Zoli A., Pagliosa A., Palo A., Valoti O., Carlucci M., Benini A., Foti G., Isgro, S, Giani, M, Antolini, L, Giudici, R, Valsecchi, M, Bellani, G, Chiara, O, Bassi, G, Latronico, N, Cabrini, L, Fumagalli, R, Chieregato, A, Sammartano, F, Sechi, G, Zoli, A, Pagliosa, A, Palo, A, Valoti, O, Carlucci, M, Benini, A, Foti, G, Isgro S., Giani M., Antolini L., Giudici R., Valsecchi M. G., Bellani G., Chiara O., Bassi G., Latronico N., Cabrini L., Fumagalli R., Chieregato A., Sammartano F., Sechi G., Zoli A., Pagliosa A., Palo A., Valoti O., Carlucci M., Benini A., and Foti G.

Abstract

Prehospital field triage often fails to accurately identify the need for emergent surgical or non-surgical procedures, resulting in inefficient resource utilization and increased costs. This study aimed to analyze prehospital factors associated with the need for emergent procedures (such as surgery or interventional angiography) within 6 h of hospital admission. Additionally, our goal was to develop a prehospital triage tool capable of estimating the likelihood of requiring an emergent procedure following hospital admission. We conducted a retrospective observational study, analyzing both prehospital and in-hospital data obtained from the Lombardy Trauma Registry. We conducted a multivariable logistic regression analysis to identify independent predictors of emergency procedures within the first 6 h from admission. Subsequently, we developed and internally validated a triage score composed of factors associated with the probability of requiring an emergency procedure. The study included a total of 3985 patients, among whom 295 (7.4%) required an emergent procedure within 6 h. Age, penetrating injury, downfall, cardiac arrest, poor neurological status, endotracheal intubation, systolic pressure, diastolic pressure, shock index, respiratory rate and tachycardia were identified as predictors of requiring an emergency procedure. A triage score generated from these predictors showed a good predictive power (AUC of the ROC curve: 0.81) to identify patients requiring an emergent surgical or non-surgical procedure within 6 h from hospital admission. The proposed triage score might contribute to predicting the need for immediate resource availability in trauma patients.

Published
2023

31. Correction: Epidemiology and outcomes of early-onset AKI in COVID-19-related ARDS in comparison with non-COVID-19-related ARDS: insights from two prospective global cohort studies (Critical Care, (2023), 27, 1, (3), 10.1186/s13054-022-04294-5)

Author

McNicholas B. A., Mcnicholas, B, Rezoagli, E, Simpkin, A, Khanna, S, Suen, J, Yeung, P, Brodie, D, Bassi, G, Pham, T, Bellani, G, Fraser, J, Laffey, J, Al-Dabbous, T, Alfoudri, H, Shamsah, M, Alhadad, Q, Hanan, M, Elapavaluru, S, Berg, A, Horn, C, Abdelhalim, A, Amer, A, Elnaggar, C, Hassan, A, Abdelaziz, A, Abdelhalim, M, Orabi, Y, Alaraji, Z, Muhaisen, M, Almasri, L, Mustafa, D, Hamdan, S, Al-Saba'a, Y, Dalloul, Z, Alkahlout, M, Jaber, H, Aldabbourosama, O, Hussein, A, Emad, Z, Khaled, S, Mohamed, N, Hassanin, E, Hamdi, A, Ragab, A, Azizeldin, M, Mayasi, Y, Schroll, S, Meyer, D, Velazco, J, Ploskanych, L, Fikes, W, Bagewadi, R, Dao, M, White, H, Laviena, A, Ehlers, A, Shalabi-McGuire, M, Witt, T, Grazioli, L, Lorini, L, Grandin, E, Nunez, J, Reyes, T, O'Briain, D, Hunter, S, Ramanan, M, Affleck, J, Veerendra, H, Rai, S, Russell-Brown, J, Nourse, M, Joseph, M, Mitchell, B, Tenzer, M, Abe, R, Cho, H, Jeong, I, Rahman, N, Kakar, V, Sun, H, Hanley, A, Brozzi, N, Mehkri, O, Krishnan, S, Duggal, A, Houltham, S, Graf, J, Diaz, R, Orrego, R, Delgado, C, Gonzalez, J, Sanchez, M, Piagnerelli, M, Sarrazin, J, Zabert, G, Espinosa, L, Delgado, P, Delgado, V, Rincon, D, Yanten, A, Duque, M, Abouelmagd, K, Elhazmi, A, Al-Hudaib, A, Javidfar, J, Callahan, M, Dong, A, D'Orleans, C, Taufik, M, Wardoyo, E, Gunawan, M, Trisnaningrum, N, Irawany, V, Rayhan, M, Panigada, M, Pesenti, A, Zanella, A, Grasselli, G, Colombo, S, Martinet, C, Florio, G, Antonelli, M, Carelli, S, Grieco, D, Asaki, M, Hoshino, K, Salazar, L, Monsalve, M, Cosgrave, D, Atif, M, Qutishat, F, Laffey, C, Van Der Walt, M, Mccaffrey, J, Bone, A, Hakeem, Y, Winearls, J, Tallott, M, Thomson, D, Joubert, I, Arnold-Day, C, Piercy, J, van Zyl Smit, R, Miller, M, Seymour, L, van Heyningen, F, Teyangesikayi, G, Fredericks, D, Hssain, A, Aliudin, J, Alqahtani, A, Mohamed, K, Mohamed, A, Tan, D, Villanueva, J, Zaqout, A, Kurtzman, E, Ademi, A, Dobrita, A, El Aoudi, K, Segura, J, Giwangkancana, G, Ohshimo, S, Osatnik, J, Joosten, A, Torres, A, Yang, M, Motos, A, Luna, C, Arancibia, F, Williams, V, Noel, A, Luque, N, Fantini, M, Garcia, R, Alvarez, E, Greti, A, Ceccato, A, Sanchez, A, Vazquez, A, Roche-Campo, F, Franch-Llasat, D, Tuazon, D, Amato, M, Cassimiro, L, Pola, F, Ribeiro, F, Fonseca, G, Dalton, H, Desai, M, Osborn, E, Deeb, H, Arcadipane, A, Martucci, G, Panarello, G, Vitiello, S, Bianco, C, Occhipinti, G, Rossetti, M, Cuffaro, R, Cho, S, Whitman, G, El Sayed, M, Mokhtar, W, El-Shenawy, E, Shimizu, H, Moriyama, N, Kim, J, Kitamura, N, Gebauer, J, Yokoyama, T, Al-Fares, A, Buabbas, S, Alamad, E, Alawadhi, F, Alawadi, K, Khalefa, M, Al Ajeel, N, Aly, M, Al-Saleh, A, Naanouh, A, Elshourbgy, A, Gad, M, Elrazaz, R, Khadadah, I, Almumin, A, Altarakma, H, Albannay, H, Alsaleh, M, Radwan, M, Saadallah, I, Tanaka, H, Hashimoto, S, Yamazaki, M, Oh, T, Epler, M, Forney, C, Kruse, L, Feister, J, Williamson, J, Grobengieser, K, Gnall, E, Golden, S, Caroline, M, Shapiro, T, Karaj, C, Thome, L, Sher, L, Vanderland, M, Welch, M, Mcdermott, S, Brain, M, Mineall, S, Unwin, M, Chen, L, Trezise, T, Mckeon, L, Kimura, D, Brazzi, L, Sales, G, Montrucchio, G, Ogston, T, Nagpal, D, Fischer, K, Lorusso, R, van Bussell, B, De Piero, M, Mariani, S, Rangappa, R, Shetty, R, Rai, P, Ganesan, A, Esperatti, M, Fuentes, N, Gonzalez, M, Carton, E, Sen, A, Palacios, A, Rainey, D, Samoukoviv, G, Campisi, J, Durham, L, Neumann, E, Seefeldt, C, Falcucci, O, Emmrich, A, Guy, J, Johns, C, Potzner, K, Zimmermann, C, Espinal, A, Buchtele, N, Schwameis, M, Korhnfehl, A, Brock, R, Staudinger, T, Stecher, S, Barnikel, M, Anton, S, Pawlikowski, A, Zaaqoq, A, Galloway, L, Merley, C, Nichol, A, Csete, M, Quesada, L, Saba, I, Kasugai, D, Hiraiwa, H, Tanaka, T, Marwali, E, Purnama, Y, Dewayanti, S, Ardiyan, Juzar, D, Siagian, D, Chen, Y, Ogino, M, Nasa, P, Matthew, C, Majeed, N, Ratsep, I, Post, A, Sillaots, P, Krund, A, Lehiste, M, Lepik, T, Manetta, F, Mihelis, E, Sarmiento, I, Narasimhan, M, Varrone, M, Komats, M, Garcia-Diaz, J, Harmon, C, Satyapriya, S, Bhatt, A, Mokadam, N, Uribe, A, Gonzalez, A, Shi, H, Mckeown, J, Pasek, J, Fiorda, J, Echeverria, M, Moreno, R, Zakhary, B, Cavana, M, Cucino, A, Foti, G, Giani, M, Fumagalli, B, Chiumello, D, Castagna, V, Dell'Amore, A, Navalesi, P, Shum, H, Vuysteke, A, Usman, A, Acker, A, Smood, B, Mergler, B, Sertic, F, Subramanian, M, Sperry, A, Rizer, N, Burhan, E, Rasmin, M, Akmal, E, Sitompul, F, Lolong, N, Naivedh, B, Erickson, S, Barrett, P, Dean, D, Daugherty, J, Loforte, A, Khan, I, Quraishi, M, Desantis, O, So, D, Kandamby, D, Mandei, J, Natanael, H, Yudhalantang, E, Lantang, A, Wijaya, S, Jung, A, Ng, G, Ng, W, Ng, P, Fang, S, Tabah, A, Ratcliffe, M, Duroux, M, Alajeeli, A, Tarhabat, A, Adachi, S, Nakao, S, Blanco, P, Prieto, A, Sanchez, J, Nicholson, M, Butt, W, Serratore, A, Delzoppo, C, Janin, P, Yarad, E, Totaro, R, Coles, J, Pujo, B, Balk, R, Vissing, A, Kapania, E, Hays, J, Fox, S, Yantosh, G, Mishin, P, Yuliarto, S, Santoso, K, Djajalaksana, S, Fatoni, A, Fukuda, M, Liu, K, Pelosi, P, Battaglini, D, Jimenez, J, Bastos, D, Gaiao, S, Rusmawatiningtyas, D, Cho, Y, Lee, S, Kawasaki, T, Munshi, L, Sakiyalak, P, Nitayavardhana, P, Elagili, M, Salem, T, Seitz, T, Arora, R, Kent, D, Marino, D, Parwar, S, Cheng, A, Miller, J, Fujitani, S, Shimizu, N, Madhok, J, Owyang, C, Buscher, H, Reynolds, C, Maasikas, O, Aleksanbeljantsev, Mihnovits, V, Akimoto, T, Aizawa, M, Horibe, K, Onodera, R, Hodgson, C, Burrell, A, Young, M, George, T, Shekar, K, Mcguinness, N, Irvine, L, Flynn, B, Endo, T, Sugiyama, K, Shimizu, K, Fan, E, Exconde, K, Ichiba, S, Binnawara, M, Lussier, L, Lotz, G, Malfertheiner, M, Maier, L, Dreier, E, Kusumastuti, N, Mccloskey, C, Dabaliz, A, Elshazly, T, Smith, J, Szuldrzynski, K, Bielanski, P, Wille, K, Murthy, S, Parhar, K, Fiest, K, Codan, C, Shahid, A, Fayed, M, Evans, T, Gutierrez, A, Song, T, Rose, R, Bennett, S, Richardson, D, Peek, G, Arora, L, Rappapport, K, Rudolph, K, Sibenaller, Z, Stout, L, Walter, A, Herr, D, Vedadi, N, Bartlett, R, Thompson, S, Hoffman, J, Ying, X, Williams, B, Sanchez, E, Akwani, C, Kennedy, R, Elhadi, M, Griffee, M, Mone, M, Ciullo, A, Kida, Y, Roca, R, Riera, J, Contreras, S, Alegre, C, Kay, C, Fischer, I, Renner, E, Taniguci, H, Lee, J, Plotkin, D, Citarella, B, Merson, L, Hartley, E, Lubis, B, Ikeyama, T, Alhamad, A, Fathi, M, Hadhoud, M, Alhouri, H, Mechi, A, Alyasiri, M, Elsaid, M, Shahla, H, Bhaskar, B, Jung, J, Mcguinness, S, Eastwood, G, Marta, S, Guarracino, F, Gerle, S, Coxon, E, Claro, B, Eleisawy, M, Osama, H, Loverde, D, Patil, N, Parrini, V, Mcbride, A, Negaard, K, Ratsch, A, Uribe, J, Peris, A, Sanders, M, Emerson, D, Kamal, M, Faida, H, Povoa, P, Francis, R, Cherif, A, Joseph, S, Di Nardo, M, Heard, M, Kyle, K, Blackwell, R, Ouyahia, A, Biston, P, Jeong, H, Smith, R, Prawira, Y, Garcia, A, Salterain, N, Meyns, B, Elnasser, M, Moreno, M, Walia, R, Mehta, A, Schweda, A, Williams, M, Emadamkhatirah, Kim, K, Assad, A, Giraldo, E, Karolak, W, Balik, M, Pocock, E, 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A., Rezoagli E., Simpkin A. J., Khanna S., Suen J. Y., Yeung P., Brodie D., Bassi G. L., Pham T., Bellani G., Fraser J. F., Laffey J., Al-Dabbous T., Alfoudri H., Shamsah M., Alhadad Q., Hanan M., Elapavaluru S., Berg A., Horn C., Abdelhalim A. R. M. E., Amer A. E., Elnaggar C. O. R., Hassan A. A., Abdelaziz A., Abdelhalim M., Orabi Y. S. S. A., Alaraji Z. A., Muhaisen M. R., Almasri L., Mustafa D., Hamdan S., Al-Saba'a Y., Dalloul Z., Alkahlout M., Jaber H., Aldabbourosama O., Hussein A. A. R. M., Emad Z. K., Khaled S., Mohamed N., Hassanin E., Hamdi A., Ragab A., Azizeldin M. G., Mayasi Y., Schroll S., Meyer D., Velazco J., Ploskanych L., Fikes W., Bagewadi R., Dao M., White H., Laviena A. B., Ehlers A., Shalabi-McGuire M., Witt T., Grazioli L., Lorini L., Grandin E. W., Nunez J., Reyes T., O'Briain D., Hunter S., Ramanan M., Affleck J., Veerendra H. H., Rai S., Russell-Brown J., Nourse M., Joseph M., Mitchell B., Tenzer M., Abe R., Cho H. J., Jeong I. 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A., Aliudin J., Alqahtani A. -R., Mohamed K., Mohamed A., Tan D., Villanueva J., Zaqout A., Kurtzman E., Ademi A., Dobrita A., El Aoudi K., Segura J., Giwangkancana G., Ohshimo S., Osatnik J., Joosten A., Torres A., Yang M., Motos A., Luna C., Arancibia F., Williams V., Noel A., Luque N., Fantini M., Garcia R. N. J., Alvarez E. C., Greti A., Ceccato A., Sanchez A., Vazquez A. L., Roche-Campo F., Franch-Llasat D., Tuazon D., Amato M., Cassimiro L., Pola F., Ribeiro F., Fonseca G., Dalton H., Desai M., Osborn E., Deeb H., Arcadipane A., Martucci G., Panarello G., Vitiello S., Bianco C., Occhipinti G., Rossetti M., Cuffaro R., Cho S. -M., Whitman G., El Sayed M., Mokhtar W., El-Shenawy E., Shimizu H., Moriyama N., Kim J. -B., Kitamura N., Gebauer J., Yokoyama T., Al-Fares A., Buabbas S., Alamad E., Alawadhi F., Alawadi K., Khalefa M. A., Al Ajeel N. A. A., Aly M. F., Al-Saleh A., Naanouh A., Elshourbgy A. M., Gad M. Y., ElRazaz R. M., Khadadah I., Almumin A. M., Altarakma H., Albannay H., Alsaleh M. K., Radwan M. S. A., Saadallah I. A., Tanaka H., Hashimoto S., Yamazaki M., Oh T. -H., Epler M., Forney C., Kruse L., Feister J., Williamson J., Grobengieser K., Gnall E., Golden S., Caroline M., Shapiro T., Karaj C., Thome L., Sher L., Vanderland M., Welch M., McDermott S., Brain M., Mineall S., Unwin M., Chen L., Trezise T., McKeon L., Kimura D., Brazzi L., Sales G., Montrucchio G., Ogston T., Nagpal D., Fischer K., Lorusso R., van Bussell B., De Piero M. E., Mariani S., Rangappa R., Shetty R. M., Rai P. S., Ganesan A., Esperatti M., Fuentes N. A., Gonzalez M. E., Carton E. G., Sen A., Palacios A., Rainey D., Samoukoviv G., Campisi J., Durham L., Neumann E., Seefeldt C., Falcucci O., Emmrich A., Guy J., Johns C., Potzner K., Zimmermann C., Espinal A., Buchtele N., Schwameis M., Korhnfehl A., Brock R., Staudinger T., Stecher S. -S., Barnikel M., Anton S., Pawlikowski A., Zaaqoq A., Galloway L. A., Merley C., Nichol A., Csete M., Quesada L., Saba I., Kasugai D., Hiraiwa H., Tanaka T., Marwali E., Purnama Y., Dewayanti S. R., Juzar D. A., Siagian D., Chen Y. -S., Ogino M., Nasa P., Matthew C., Majeed N. A., Ratsep I., Post A. -M., Sillaots P., Krund A., Lehiste M. -H., Lepik T., Manetta F., Mihelis E., Sarmiento I. C., Narasimhan M., Varrone M., Komats M., Garcia-Diaz J., Harmon C., Satyapriya S. V., Bhatt A., Mokadam N. A., Uribe A., Gonzalez A., Shi H., McKeown J., Pasek J., Fiorda J., Echeverria M., Moreno R., Zakhary B., Cavana M., Cucino A., Foti G., Giani M., Fumagalli B., Chiumello D., Castagna V., Dell'Amore A., Navalesi P., Shum H. -P., Vuysteke A., Usman A., Acker A., Smood B., Mergler B., Sertic F., Subramanian M., Sperry A., Rizer N., Burhan E., Rasmin M., Akmal E., Sitompul F., Lolong N., Naivedh B., Erickson S., Barrett P., Dean D., Daugherty J., Loforte A., Khan I., Quraishi M. A., DeSantis O., So D., Kandamby D., Mandei J. M., Natanael H., YudhaLantang E., Lantang A., Wijaya S. O., Jung A., Ng G., Ng W. Y., Ng P. Y., Fang S., Tabah A., Ratcliffe M., Duroux M., Alajeeli A., Tarhabat A., Adachi S., Nakao S., Blanco P., Prieto A., Sanchez J., Nicholson M., Butt W., Serratore A., Delzoppo C., Janin P., Yarad E., Totaro R., Coles J., Pujo B., Balk R., Vissing A., Kapania E., Hays J., Fox S., Yantosh G., Mishin P., Yuliarto S., Santoso K. H., Djajalaksana S., Fatoni A. Z., Fukuda M., Liu K., Pelosi P., Battaglini D., Jimenez J. F. M., Bastos D., Gaiao S., Rusmawatiningtyas D., Cho Y. -J., Lee S. H., Kawasaki T., Munshi L., Sakiyalak P., Nitayavardhana P., Elagili M. B., Salem T. A. A., Seitz T., Arora R., Kent D., Marino D., Parwar S., Cheng A., Miller J., Fujitani S., Shimizu N., Madhok J., Owyang C., Buscher H., Reynolds C., Maasikas O., AleksanBeljantsev, Mihnovits V., Akimoto T., Aizawa M., Horibe K., Onodera R., Hodgson C., Burrell A., Young M., George T., Shekar K., McGuinness N., Irvine L., Flynn B., Endo T., Sugiyama K., Shimizu K., Fan E., Exconde K., Ichiba S., Binnawara M., Lussier L., Lotz G., Malfertheiner M., Maier L., Dreier E., Kusumastuti N. P., McCloskey C., Dabaliz A. -A., Elshazly T. B., Smith J., Szuldrzynski K. S., Bielanski P., Wille K., Murthy S., Parhar K. K. S., Fiest K. M., Codan C., Shahid A., Fayed M., Evans T., Garcia R., Gutierrez A., Song T., Rose R., Bennett S., Richardson D., Peek G., Arora L., Rappapport K., Rudolph K., Sibenaller Z., Stout L., Walter A., Herr D., Vedadi N., Bartlett R., Thompson S., Hoffman J., Ying X., Williams B., Sanchez E., Akwani C., Kennedy R., Elhadi M., Griffee M., Mone M., Ciullo A., Kida Y., Roca R. F., Riera J. I., Contreras S., Alegre C., Kay C., Fischer I., Renner E., Taniguci H., Lee J., Plotkin D., Citarella B. W., Merson L., Hartley E., Lubis B., Ikeyama T., Alhamad A., Fathi M., Hadhoud M. M., Alhouri H., Mechi A., Alyasiri M. S., Elsaid M. Z. A., Shahla H., Bhaskar B., Jung J. -S., McGuinness S., Eastwood G., Marta S. R., Guarracino F., Gerle S., Coxon E., Claro B., Eleisawy M., Osama H., Loverde D., Patil N., Parrini V., McBride A., Negaard K., Ratsch A., Uribe J. D., Peris A., Sanders M., Emerson D., Kamal M., Faida H., Povoa P., Francis R., Cherif A., Joseph S., Di Nardo M., Heard M., Kyle K., Blackwell R. A., Ouyahia A., Biston P., Jeong H. W., Smith R., Prawira Y., Garcia A. H., Salterain N., Meyns B., Elnasser M., Moreno M., Walia R., Mehta A., Schweda A., Williams M., EmadAmkhatirah, Kim K. H., Assad A., Giraldo E., Karolak W., Balik M., Pocock E., Gajkowski E., Masafumi K., Barrett N., Takeyama Y., Park S., Amin F., Andriyani F. M., Sudakevych S., Schnur J., Vera M., Cornejo R., Schwarz P., Mardini A. C., de Paula T., Neto A. S., Villoldo A., Colafranceschi A. S., Iglesias A. U., Granjean J., Melro L. M. G., Romualdo G. F., Gaia D., Souza H., Galas F., Mendiluce R. M., Sosa A., Martinez I., Kurosawa H., Almoshantaf M. B., Salgado J., Hugi-Mayr B., Charbonneau E., Barzilai V. S., Monteiro V., de Souza R. R., Harper M., Siddig N., Suzuki H., Adams C., Brieva J., Khamees A., Graige F., Supriatna M., Nyale G., Eltatar F. S., Fatani J., Baeissa H., Masri A. A. L., Rabie A., Hui M. Y., Yamane M., Jung H., Margaret A. M., Nacpil N., Ruck K., Bakken R., Jara C., Felton T., Tharwat S., Berra L., Shah B., Chakraborty A., Cardona M., Capatos G., Akkanti B., Orija A., Jain H., Ito A., Muftah M., Housni B., Aldhalia A., Low S., Iihara K., Chavez J., Ramanathan K., Naidoo K., Seppelt I., VanDyk M., MacDonald S., Hafez W., McGregor R., Siebenaler T., Flynn H., Lofton K., Aokage T., Kvirkvelia B., Shigemitsu K., Moscatelli A., Fiorentino G., Baumgaertel M., Mba S. E., Assy J., Hutahaean A., Roush H., Sichting K. A., Alessandri F., Burns D., Alkhubouli T. H., Nasrallah A., Salt G., Garabedian C. P., Millar J., Sim M., Mattke A., McAuley D., Tadili J., Frenzel T., Bar-Lavie Y., Ortiz A. B., Stone J., Attokaran A., Farquharson M., Patel B., Gunning D., Baillie K., Adem S., Watson P., Tamai K., Sajinadiyasa G. K., Kanyawati D., Salgado M., Sassine A., Yudo B., McCaul S., Lee B., Lee S. M., Afek A., Iwashita Y., Fadlalmola H., Semedi B. P., Mansour N. M., Metiva J., Van Belle N., Martin-Loeches I., Al-Sadawi M., Kirakli C., Shimaa A. -T., Abdurraouf A., Ivatt L., Moharam S., Woon C. Y., Kang H. M., Smith T., James E., Al-Rawas N., Almjersah A., Iwasaki Y., Ashour H., Embarek H., King-Chung K. C., Gudzenko V., Taccone F., Perdhana F., Lamarche Y., Ribeiro J. M., Bradic N., Van den Bossche K., Lansink O., Singh G., Debeuckelaere G., Stelfox H. T., Yi C., Elia J., Tribble T., Shankar S., Padmanabhan R., Hallinan B., Paoletti L., Leyva Y., Fykuda T., Badulak J., Koch J., Janowaik L., Hackman A., Hernandez D., Osofsky J., Donadello K., Lawang A., Fine J., Davidson B., Vazquez A. O. R., and Abdehaleem I.

Abstract

Following publication of the original article [1], the authors identified that the collaborating authors part of the collaborating author group CCCC Consortium was missing. The collaborating author group is available and included as Additional file 1 in this article.

Published
2023

32. Editorial: Lung monitoring in respiratory failure

Author

Rezoagli E., Chen L., Bellani G., Rezoagli, E, Chen, L, and Bellani, G

Subjects
non-invasive ventilation (NIV), prone position, surface electromyography (EMG), esophageal pressure (Pes), General Medicine, mechanical ventilation, spontaneous breathing trial (SBT), tracheal extubation
Published
2023

36. Hospital Memories and Six-Month Psychological Outcome: A Prospective Study in Critical Ill Patients with COVID-19 Respiratory Failure

Author

Pozzi M., Ripa C., Meroni V., Ferlicca D., Annoni A., Villa M., Strepparava M. G., Rezoagli E., Piva S., Lucchini A., Bellani G., Foti G., Pozzi, M, Ripa, C, Meroni, V, Ferlicca, D, Annoni, A, Villa, M, Strepparava, M, Rezoagli, E, Piva, S, Lucchini, A, Bellani, G, and Foti, G

Subjects
long-term outcome, psychological outcome, PIC syndrome, ARDS, COVID-19 pneumonia, M-PSI/08 - PSICOLOGIA CLINICA, MED/41 - ANESTESIOLOGIA, ICU memorie
Abstract

ICU survivors suffer from various long-term physical and psychological impairments. Memories from the critical illness may influence long-term psychological outcome. In particular, the role of ICU memories in COVID-19 critically ill patients is unknown. In a prospective observational study, we aimed to investigate patients' memories from the experience of critical illness and their association with a six-month psychological outcome involving quality of life evaluation. Patients' memories were investigated with ICU Memory tool, while psychological outcome and quality of life were evaluated by means of a battery of validated questionnaires during an in-person interview at the follow-up clinic. 149 adult patients were enrolled. 60% retained memories from pre-ICU days spent on a general ward, while 70% reported memories from the in-ICU period. Delusional memories (i.e., memories of facts that never happened) were reported by 69% of patients. According to a multivariable analysis, the lack of pre-ICU memories was an independent predictor of worse psychological outcomes in terms of anxiety, depression and Post-traumatic Stress Disorder (PTDS). Factors associated with long-term outcome in ICU survivors are not still fully understood and patients' experience during the day spent before ICU admission may be associated with psychological sequelae.

Published
2023

37. Microbiological models for accelerated development of secondary caries in vitro: Microbiological models simulating secondary caries

Author

Ionescu, A, Hahnel, S, Delvecchio, P, Ilie, N, Moldovan, M, Zambelli, V, Bellani, G, Brambilla, E, Ionescu A. C., Hahnel S., Delvecchio P., Ilie N., Moldovan M., Zambelli V., Bellani G., Brambilla E., Ionescu, A, Hahnel, S, Delvecchio, P, Ilie, N, Moldovan, M, Zambelli, V, Bellani, G, Brambilla, E, Ionescu A. C., Hahnel S., Delvecchio P., Ilie N., Moldovan M., Zambelli V., Bellani G., and Brambilla E.

Abstract

Objectives: The current study aimed to compare the efficacy of two in vitro microbiological models based on open and closed systems designed to obtain secondary caries in an accelerated and reproducible way. Methods: A conventional resin-based composite (RBC - Majesty ES-2; Kuraray, Japan) and a resin-modified glass-ionomer cement (RMGIC – Ionolux; VOCO, Germany) were used to restore standardized class II cavities (n = 4/tooth, cervical margin in dentin) in 16 human molars. The ability to produce secondary caries with Streptococcus mutans biofilms was tested using either an open-cycle or closed-cycle bioreactor (n = 8 specimens/model). Specimens were scanned before and after the biofilm exposure using micro-CT (Skyscan 1176, 9 µm resolution, 80 kV, 300 mA). Image reconstruction was performed, and demineralization depths (µm) were evaluated at the restoration margins and a distance of 1.0 mm. Results: Dentin demineralization could be observed in all specimens, and enamel demineralization in 50% of the specimens. The open system bioreactor produced lesions with significantly higher overall demineralization depths (p < .001). However, demineralization depths at a 1.0 mm distance from the restoration margins showed no difference between open and closed systems or materials. In the open system, significantly lower demineralization depths were observed in proximity to RMGIC than RBC (p < .001), which was not significantly different in the closed system (p = .382). Conclusions: Both systems produced in vitro secondary caries in an accelerated way. However, the open-cycle bioreactor system confirmed the caries-protective activity exerted by the RMGIC material in contrast to the RBC, better simulating materials’ clinical behavior. Clinical significance: The possibility of obtaining accelerated and reproducible secondary caries development in vitro is fundamental in testing the behavior of conventional and yet-to-come restorative dental materials. Such systems can provi

Published
2022

38. Unsupervised segmentation and quantification of COVID-19 lesions on computed Tomography scans using CycleGAN

Author

Connell, M, Xin, Y, Gerard, S, Herrmann, J, Shah, P, Martin, K, Rezoagli, E, Ippolito, D, Rajaei, J, Baron, R, Delvecchio, P, Humayun, S, Rizi, R, Bellani, G, Cereda, M, Connell M., Xin Y., Gerard S. E., Herrmann J., Shah P. K., Martin K. T., Rezoagli E., Ippolito D., Rajaei J., Baron R., Delvecchio P., Humayun S., Rizi R. R., Bellani G., Cereda M., Connell, M, Xin, Y, Gerard, S, Herrmann, J, Shah, P, Martin, K, Rezoagli, E, Ippolito, D, Rajaei, J, Baron, R, Delvecchio, P, Humayun, S, Rizi, R, Bellani, G, Cereda, M, Connell M., Xin Y., Gerard S. E., Herrmann J., Shah P. K., Martin K. T., Rezoagli E., Ippolito D., Rajaei J., Baron R., Delvecchio P., Humayun S., Rizi R. R., Bellani G., and Cereda M.

Abstract

Background: Lesion segmentation is a critical step in medical image analysis, and methods to identify pathology without time-intensive manual labeling of data are of utmost importance during a pandemic and in resource-constrained healthcare settings. Here, we describe a method for fully automated segmentation and quantification of pathological COVID-19 lung tissue on chest Computed Tomography (CT) scans without the need for manually segmented training data. Methods: We trained a cycle-consistent generative adversarial network (CycleGAN) to convert images of COVID-19 scans into their generated healthy equivalents. Subtraction of the generated healthy images from their corresponding original CT scans yielded maps of pathological tissue, without background lung parenchyma, fissures, airways, or vessels. We then used these maps to construct three-dimensional lesion segmentations. Using a validation dataset, Dice scores were computed for our lesion segmentations and other published segmentation networks using ground truth segmentations reviewed by radiologists. Results: The COVID-to-Healthy generator eliminated high Hounsfield unit (HU) voxels within pulmonary lesions and replaced them with lower HU voxels. The generator did not distort normal anatomy such as vessels, airways, or fissures. The generated healthy images had higher gas content (2.45 ± 0.93 vs 3.01 ± 0.84 L, P < 0.001) and lower tissue density (1.27 ± 0.40 vs 0.73 ± 0.29 Kg, P < 0.001) than their corresponding original COVID-19 images, and they were not significantly different from those of the healthy images (P < 0.001). Using the validation dataset, lesion segmentations scored an average Dice score of 55.9, comparable to other weakly supervised networks that do require manual segmentations. Conclusion: Our CycleGAN model successfully segmented pulmonary lesions in mild and severe COVID-19 cases. Our model's performance was comparable to other published models; however, our model is unique in its a

Published
2022

39. Monitoring Lung Injury Severity and Ventilation Intensity during Mechanical Ventilation

Author

Rezoagli, E, Laffey, J, Bellani, G, Rezoagli E., Laffey J. G., Bellani G., Rezoagli, E, Laffey, J, Bellani, G, Rezoagli E., Laffey J. G., and Bellani G.

Abstract

Acute respiratory distress syndrome (ARDS) is a severe form of respiratory failure burden by high hospital mortality. No specific pharmacologic treatment is currently available and its ventilatory management is a key strategy to allow reparative and regenerative lung tissue processes. Unfortunately, a poor management of mechanical ventilation can induce ventilation induced lung injury (VILI) caused by physical and biological forces which are at play. Different parameters have been described over the years to assess lung injury severity and facilitate optimization of mechanical ventilation. Indices of lung injury severity include variables related to gas exchange abnormalities, ventilatory setting and respiratory mechanics, ventilation intensity, and the presence of lung hyperinflation versus derecruitment. Recently, specific indexes have been proposed to quantify the stress and the strain released over time using more comprehensive algorithms of calculation such as the mechanical power, and the interaction between driving pressure (DP) and respiratory rate (RR) in the novel DP multiplied by four plus RR [(4 × DP) + RR] index. These new parameters introduce the concept of ventilation intensity as contributing factor of VILI. Ventilation intensity should be taken into account to optimize protective mechanical ventilation strategies, with the aim to reduce intensity to the lowest level required to maintain gas exchange to reduce the potential for VILI. This is further gaining relevance in the current era of phenotyping and enrichment strategies in ARDS.

Published
2022

40. Prone positioning during venovenous extracorporeal membrane oxygenation for acute respiratory distress syndrome: a pooled individual patient data analysis

Author

Giani, M, Rezoagli, E, Guervilly, C, Rilinger, J, Duburcq, T, Petit, M, Textoris, L, Garcia, B, Wengenmayer, T, Grasselli, G, Pesenti, A, Combes, A, Foti, G, Schmidt, M, Bellani, G, Martucci, G, Arcadipane, A, Lucchini, A, Garofalo, E, Belliato, M, Fanelli, V, Papazian, L, Forel, J, Hraiech, S, Roch, A, Prud'Homme, E, Luyt, C, Hekimian, G, Chommeloux, J, Pineton de Chambrun, M, Brechot, N, Staudacher, D, Supady, A, Biever, P, Zotzmann, V, Bemtgen, X, Sekandarzad, A, Kruger, K, Flugler, A, Parmentier-Decrucq, E, Poissy, J, Gaudet, A, Moussa, M, Vincentelli, A, Giani M., Rezoagli E., Guervilly C., Rilinger J., Duburcq T., Petit M., Textoris L., Garcia B., Wengenmayer T., Grasselli G., Pesenti A., Combes A., Foti G., Schmidt M., Bellani G., Martucci G., Arcadipane A., Lucchini A., Garofalo E., Belliato M., Fanelli V., Papazian L., Forel J. -M., Hraiech S., Roch A., Prud'homme E., Luyt C. E., Hekimian G., Chommeloux J., Pineton de Chambrun M., Brechot N., Staudacher D. L., Supady A., Biever P., Zotzmann V., Bemtgen X., Sekandarzad A., Kruger K., Flugler A., Parmentier-Decrucq E., Poissy J., Gaudet A., Moussa M. D., Vincentelli A., Giani, M, Rezoagli, E, Guervilly, C, Rilinger, J, Duburcq, T, Petit, M, Textoris, L, Garcia, B, Wengenmayer, T, Grasselli, G, Pesenti, A, Combes, A, Foti, G, Schmidt, M, Bellani, G, Martucci, G, Arcadipane, A, Lucchini, A, Garofalo, E, Belliato, M, Fanelli, V, Papazian, L, Forel, J, Hraiech, S, Roch, A, Prud'Homme, E, Luyt, C, Hekimian, G, Chommeloux, J, Pineton de Chambrun, M, Brechot, N, Staudacher, D, Supady, A, Biever, P, Zotzmann, V, Bemtgen, X, Sekandarzad, A, Kruger, K, Flugler, A, Parmentier-Decrucq, E, Poissy, J, Gaudet, A, Moussa, M, Vincentelli, A, Giani M., Rezoagli E., Guervilly C., Rilinger J., Duburcq T., Petit M., Textoris L., Garcia B., Wengenmayer T., Grasselli G., Pesenti A., Combes A., Foti G., Schmidt M., Bellani G., Martucci G., Arcadipane A., Lucchini A., Garofalo E., Belliato M., Fanelli V., Papazian L., Forel J. -M., Hraiech S., Roch A., Prud'homme E., Luyt C. E., Hekimian G., Chommeloux J., Pineton de Chambrun M., Brechot N., Staudacher D. L., Supady A., Biever P., Zotzmann V., Bemtgen X., Sekandarzad A., Kruger K., Flugler A., Parmentier-Decrucq E., Poissy J., Gaudet A., Moussa M. D., and Vincentelli A.

Abstract

Background: Prone positioning (PP) reduces mortality of patients with acute respiratory distress syndrome (ARDS). The potential benefit of prone positioning maneuvers during venovenous extracorporeal membrane oxygenation (ECMO) is unknown. The aim of this study was to evaluate the association between the use of prone positioning during extracorporeal support and ICU mortality in a pooled population of patients from previous European cohort studies. Methods: We performed a pooled individual patient data analysis of European cohort studies which compared patients treated with prone positioning during ECMO (Prone group) to “conventional” ECMO management (Supine group) in patients with severe ARDS. Results: 889 patients from five studies were included. Unadjusted ICU mortality was 52.8% in the Supine Group and 40.8% in the Prone group. At a Cox multiple regression analysis PP during ECMO was not significantly associated with a reduction of ICU mortality (HR 0.67 95% CI: 0.42–1.06). Propensity score matching identified 227 patients in each group. ICU mortality of the matched samples was 48.0% and 39.6% for patients in the Supine and Prone group, respectively (p = 0.072). Conclusions: In a large population of ARDS patients receiving venovenous extracorporeal support, the use of prone positioning during ECMO was not significantly associated with reduced ICU mortality. The impact of this procedure will have to be definitively assessed by prospective randomized controlled trials.

Published
2022

41. 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

Grieco, D, Maggiore, S, Bellani, G, Spadaro, S, Spinelli, E, Tonetti, T, Menga, L, Pozzi, M, Battaglini, D, Di Mussi, R, Bruni, A, De Gaetano, A, Iovino, C, Brioni, M, Mojoli, F, Foti, G, Volta, C, Pelosi, P, Navalesi, P, Grasso, S, Ranieri, V, Antonelli, M, Grieco D. L., Maggiore S. M., Bellani G., Spadaro S., Spinelli E., Tonetti T., Menga L. S., Pozzi M., Battaglini D., Di Mussi R., Bruni A., De Gaetano A., Iovino C. G., Brioni M., Mojoli F., Foti G., Volta C. A., Pelosi P., Navalesi P., Grasso S., Ranieri V. M., Antonelli M., Grieco, D, Maggiore, S, Bellani, G, Spadaro, S, Spinelli, E, Tonetti, T, Menga, L, Pozzi, M, Battaglini, D, Di Mussi, R, Bruni, A, De Gaetano, A, Iovino, C, Brioni, M, Mojoli, F, Foti, G, Volta, C, Pelosi, P, Navalesi, P, Grasso, S, Ranieri, V, Antonelli, M, Grieco D. L., Maggiore S. M., Bellani G., Spadaro S., Spinelli E., Tonetti T., Menga L. S., Pozzi M., Battaglini D., Di Mussi R., Bruni A., De Gaetano A., Iovino C. G., Brioni M., Mojoli F., Foti G., Volta C. A., Pelosi P., Navalesi P., Grasso S., Ranieri V. M., and Antonelli M.

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

42. Reliability of plateau pressure during patient-triggered assisted ventilation. Analysis of a multicentre database

Author

Bianchi, I, Grassi, A, Pham, T, Telias, I, Teggia Droghi, M, Vieira, F, Jonkman, A, Brochard, L, Bellani, G, Bianchi I., Grassi A., Pham T., Telias I., Teggia Droghi M., Vieira F., Jonkman A., Brochard L., Bellani G., Bianchi, I, Grassi, A, Pham, T, Telias, I, Teggia Droghi, M, Vieira, F, Jonkman, A, Brochard, L, Bellani, G, Bianchi I., Grassi A., Pham T., Telias I., Teggia Droghi M., Vieira F., Jonkman A., Brochard L., and Bellani G.

Abstract

Purpose: An inspiratory hold during patient-triggered assisted ventilation potentially allows to measure driving pressure and inspiratory effort. However, muscular activity can make this measurement unreliable. We aim to define the criteria for inspiratory holds reliability during patient-triggered breaths. Material and methods: Flow, airway and esophageal pressure recordings during patient-triggered breaths from a multicentre observational study (BEARDS, NCT03447288) were evaluated by six independent raters, to determine plateau pressure readability. Features of “readable” and “unreadable” holds were compared. Muscle pressure estimate from the hold was validated against other measures of inspiratory effort. Results: Ninety-two percent of the recordings were consistently judged as readable or unreadable by at least four raters. Plateau measurement showed a high consistency among raters. A short time from airway peak to plateau pressure and a stable and longer plateau characterized readable holds. Unreadable plateaus were associated with higher indexes of inspiratory effort. Muscular pressure computed from the hold showed a strong correlation with independent indexes of inspiratory effort. Conclusion: The definition of objective parameters of plateau reliability during assisted-breath provides the clinician with a tool to target a safer assisted-ventilation and to detect the presence of high inspiratory effort.

Published
2022

43. Bag valve resuscitator versus Mapleson C circuit during manual ventilation: A bench top study

Author

Giani, M, Lucchini, A, Moretto, L, Di Pierro, M, Lo Re, F, Mancini, P, Palano, S, Foti, G, Bellani, G, Bronco, A, Giani M., Lucchini A., Moretto L., Di Pierro M., Lo Re F., Mancini P. G., Palano S., Foti G., Bellani G., Bronco A., Giani, M, Lucchini, A, Moretto, L, Di Pierro, M, Lo Re, F, Mancini, P, Palano, S, Foti, G, Bellani, G, Bronco, A, Giani M., Lucchini A., Moretto L., Di Pierro M., Lo Re F., Mancini P. G., Palano S., Foti G., Bellani G., and Bronco A.

Abstract

Background: Manual ventilation is life saving in critically ill patients. The lack of airway pressure monitoring makes it operator and device dependent. In this bench top-study, we compared a self- inflating bag valve resuscitator and a Mapleson C circuit during manual ventilation performed by critical care nurses under normal and pathologic conditions, with a special focus on delivered positive end expiratory pressure (PEEP). Methods: Three different respiratory patterns (normal, restrictive and obstructive) were reproduced by a breathing simulator. Twenty nurses provided manual ventilation with a specific ventilatory pattern. Airway pressure, tidal volume and respiratory rate were recorded. Absolute value, error (difference between recorded and target values) and variability of PEEP were analysed. Results: 3820 breathing traces were analysed. PEEP error was significantly higher with Mapelson C (43.3% vs 5.9% respectively, p < 0.001). This finding was confirmed regardless of operator skill and scenario. PEEP was more variable with Mapelson C (p < 0.05 in all scenarios). Ventilation of obstructive patients with Mapelson C resulted in higher PEEP levels compared to the reference value. Conversely, in the restrictive setting, PEEP was lower. Difference between PEEP and the minimum pressure recorded during the respiratory cycle was significantly higher with Mapelson C (p < 0.05). Conclusions: Manual ventilation with a Mapleson C circuit delivered a less accurate and less stable PEEP level compared to a self-inflating bag valve resuscitator.

Published
2022

44. Bedside Selection of Positive End Expiratory Pressure by Electrical Impedance Tomography in Patients Undergoing Veno-Venous Extracorporeal Membrane Oxygenation Support: A Comparison between COVID-19 ARDS and ARDS from Other Etiologies

Author

Di Pierro, M, Giani, M, Bronco, A, Lembo, F, Rona, R, Bellani, G, Foti, G, Di Pierro M., Giani M., Bronco A., Lembo F. M., Rona R., Bellani G., Foti G., Di Pierro, M, Giani, M, Bronco, A, Lembo, F, Rona, R, Bellani, G, Foti, G, Di Pierro M., Giani M., Bronco A., Lembo F. M., Rona R., Bellani G., and Foti G.

Abstract

Background: The interest in protective ventilation strategies and individualized approaches for patients with severe illness on veno venous extracorporeal support has increased in recent years. Wide heterogeneity exists among patients with COVID-19 related acute respiratory distress syndrome (C-ARDS) and ARDS from other etiologies (NC-ARDS). EIT is a useful tool for the accurate analysis of regional lung volume distribution and allows for a tailored ventilatory setting. The aim of this work is to retrospectively describe the results of EIT assessments performed in patients C-ARDS and NC-ARDS undergoing V-V ECMO support. Methods: A clinical EIT-guided decremental PEEP trail was conducted for all patients included in the study and mechanically ventilated. Results: 12 patients with C-ARDS and 12 patients with NC-ARDS were included in the study for a total of 13 and 18 EIT evaluations, respectively. No significant differences in arterial blood gas, respiratory parameters, and regional ventilation before and after the EIT exam were recorded. The subset of patients with NC-ARDS whose EIT exam led to PEEP modification was characterized by a lower baseline compliance compared with the C-ARDS group: 18 (16–28) vs. 27 (24–30) (p = 0.04). Overdis-tension significantly increased at higher steps only for the NC-ARDS group. A higher percentage of overdistension was described in patients with NC-ARDS when compared with patients with C-ARDS. Conclusions: EIT is feasible in patients with COVID-19-associated ARDS on veno-venous extracorporeal support and may help in tailoring the PEEP setting. Overall, severe COVID-19-related ARDS presents respiratory characteristics similar to severe “classical” NC-ARDS. However, C-ARDS is associated with a lower risk of overdistension at a higher PEEP level compared with NC-ARDS.

Published
2022

45. PEEP Setting in ARDS

Author

Bellani, G, Rezoagli, E, Rezoagli E., Bellani G., Bellani, G, Rezoagli, E, Rezoagli E., and Bellani G.

Abstract

Positive end-expiratory pressure (PEEP) is a crucial element of ventilatory treatment for ARDS patients. PEEP increases end-expiratory lung volume (EELV), and may avoid derecruitment, but also cause alveolar overdistension, increased right afterload and dead space. Higher rather than lower levels of PEEP are suggested in moderate or severe ARDS in the latest guidelines. The strategies available for PEEP setting in ARDS include: PEEP/FiO2 combination tables, CO2 clearance, respiratory mechanichs (e.g. driving pressure, stress index) the measurement of transpulmonary pressure and lung imaging. The pathophysiological rationale and main clinical outcomes of the varius strategies are discussed.

Published
2022

46. Vignettes: Controlled Mechanical Ventilation

Author

Bellani, G, Pozzi, M, Rezoagli, E, Pozzi M., Bellani G., Rezoagli E., Bellani, G, Pozzi, M, Rezoagli, E, Pozzi M., Bellani G., and Rezoagli E.

Abstract

In the following two chapters (“Controlled modes of mechanical ventilation” and “Assisted modes of mechanical ventilation”) 24 clinical vignettes representing some figurative examples of two main clinical circumstances that physicians may face up in their daily clinical practice in the Intensive Care Unit about the ventilation management are collected.

Published
2022

47. Vignettes: Assisted Mechanical Ventilation

Author

Bellani, G, Pozzi, M, Rezoagli, E, Pozzi M., Bellani G., Rezoagli E., Bellani, G, Pozzi, M, Rezoagli, E, Pozzi M., Bellani G., and Rezoagli E.

Abstract

In this second chapter about clinical vignettes, we represented 14 noninvasive ventilation scenarios about assisted modes of mechanical ventilation, and we highlighted different approaches on lung monitoring and to how detect common ventilator asynchronies.

Published
2022

49. Correction to: The Intensive Care Global Study on Severe Acute Respiratory Infection (IC-GLOSSARI): a multicenter, multinational, 14-day inception cohort study

Author

Sakr, Yasser, Ferrer, Ricard, Reinhart, Konrad, Beale, Richard, Rhodes, Andrew, Moreno, Rui, Timsit, Jean Francois, Brochard, Laurent, Thompson, B. Taylor, Rezende, Ederlon, Chiche, Jean Daniel, Auer, J., Schatzl, G., Mach, K., Gruber, H., Schreurs, E., Vander Laenen, M., Ceunen, H., Wauters, J., Francois, G., Deschamps, P., Castanares, D., Debels, D., Pierrakos, C., Vincent, J. L., Taccone, F., Vymazal, T., Gornik, I., Vujiaklija Brajkovic, A., Medici, R., Nielsen, J., Bendtsen, A., Siegel, H., Suonsyrjä, T., Hraech, S., Daviaux, F., Guillot, M., Castelain, V., Losser, R-R., Novy, E., Bouadma, L., Misset, B., Philippart, F., Mallat, J., Zogheib, E., Miclo, M., Teboul, J-L., Anguel, N., Darmon, M., Pham, T., Barberet, G., Plantefeve, G., Floccard, B., Kheladze, Z., Bloos, F., Faltlhauser, A., Helmes, T., Zacharowski, K., Meybohm, P., Schwarzkopf, K., Christ, M., Baumgaertel, M., John, S., Nentwich, J., Deja, M., Goldmann, A., Gottschalk, A., Honig, F., Siepe, B., Goebel, U., Lehmke, J., Behrens, S., Fiedler, K., Sagoschen, I., Riessen, R., Haap, M., Simon, Ph., Kaisers, U., Behrens, S., Niesen, M., Jaschinski, U., Hoersch, S., Jung, A., Allgaeuer, S., Haake, H., Lange, A., Papanikolaou, M., Balla, M., Giannakou, M., Soultati, I., Nikos, G., Koulouras, V., Kyriazopoulos, G., Gkika, D., Vlachogianni, G., Psaroulis, K., Mouloudi, E., Massa, E., Nichol, A., Meany, E., Motherway, C., Bellani, G., Pota, V., Schiavone, V., Girardis, M., Busani, S., Petrucci, N., Di Pasquale, R., Mazzini, P., Molin, A., Pellerano, G., Volta, C., Spadaro, S., Guarracino, F., Savioli, M., Pellis, T., Chinellato, N., Gatta, A., Cecchini, F., Raineri, S. M., Cortegiani, A., Kekstas, G., Karosas, V., Anguseva, T., Mitrev, Z., Beck, O., Cimic, N., Janssen, G., Bormans, L., Kuiper, M., Koopmans, K., Den Boer, S., de Groot, M., Dennesen, P., van den Bosch, J., Kluge, G., Mikaszewska-Sokolewicz, M., Lazowski, T., Chruscikowski, M., Machon, J., Adamik, B., Kübler, A., Wieczorek, A., Afonso, S., Matos, R., Catorze, N., Araujo, A., Costa, Z., Pais-de-Lacerda, A., Martins, I., Cardiga, R., Fernandes, L., Serra, I., Martinho, A., Tomescu, D., Popescu, M., Scarlatescu, E., Stoica, R., Macri, A., Filipescu, D., Rupnik, E., Tomic, V., Sifrer, F., Sole Violan, J., Ferrer Agüero, J. M., Izura, J., Monedero, P., de Cabo, C. Muños, Aguilar, G., Belda, F. J., Blanquer, J., Nives Carbonell, E., Lopez-Delgado, J-C., Aragon, C., Joya, C., Ortiz-Leyba, C., Fernandez Gonzalez, C. J., de la Torre-Prados, M-V., Puerto-Morlan, A., Araujo Aguilar, P., Tomás Marsilla, J. I., Vera Aratcoz, P., Olmo, A., Ferrer Roca, R., Catalan, R. M., Garcia Olivares, P., Albis, A., Alvarez, M., Corcoles Gonzalez, V., Gutierrez Rubio, J. M., Montoiro Allue, R., Rubio Mateo-Sidron, J., Hobrok, M., Cecconi, M., Di Tomasso, N., Raj, A., Szakmany, T., Srinivasa, L., Mathew, S., Ferguson, A., Blahut-Zugaj, M., Watters, M., Henderson, S., Sim, M., Csabi, P., O’Neill, O., Nutt, C., Humphreys, S., Bhowmick, K., Donnelly, A., O’Kane, S., Garfield, M., Jha, R., Unni, N., Gordon, A., Rubulotta, F., Ravi, K., Lunch, G., Franco, F., Higgs, D., Strandvik, G., Jonas, A., Hopkins, Ph., Hurst, T., Bellini, A., Balogun, O., Srinivasan, R., Ostermann, M., Alexander, P., McCalman, K., Bedford, J., Fulop, M., Brescia, G., Strachan, J., Meyer, J., Stotz, M., Brett, S., Zand, F., Nikandish, R., Hashemian, S., Jamaati, H., Alsheikhly, A. S., Almekhlafi, G., Albarrak, M., Maghrabi, A., Salahuddin, N., Aisa, T., Atalan, H. K., Sungur, M., Hegazi, M., Bauer, P., Mukkera, S., Fried, J., Barger, M., Gueret, R., Gonzalez, C., Lovesio, C., Dellera, Ch., Barrios, D., Leite Mendes, C., Gottardo, P., Caser, E., Santos, C., Carvalho, A., Teixeira, C., Samaniego, W., Whittle, S., Molano, D., Rojas, A., Guerra, K., Villamagua, B., Salgado-Yepez, E., Morocho, D., Remache-Vargas, N., Ñamendys-Silva, S., Rodriguez, D., Dominguez, G., Barraza, G., Bermudez-Aceves, E., Sanchez-Hurtado, L. A., Baltazar-Torres, J. A., Quispe Sierra, R., Chavez, C., von Osten, I., Van Haren, C., Smalley, N., Kol, M., Wong, H., Smith, R., Yu, L., Wu, X., Chao, L., Zhai, Q., Wu, D., Zhang, X., Jing, X., Bigornia, R., Ikeda-Maquiling, Y., Robles, J., Palo, J. E., Nguyen, T., Dao, C., Dixit, S., Gurjar, M., Reddy, P., Pravin, A., Simran, S., Ramakrishnan, N., Shetty, R., Udwadia, F., Faraz, M., Indraratna, K., Rajasinhe, J., and IC-GLOSSARI Investigators and ESICM Trials Group

Published
2017
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50. Long-term physical impairments in survivors of COVID-19-associated ARDS compared with classic ARDS: A two-center study

Author

Piva, S, Pozzi, M, Bellani, G, Peli, E, Gitti, N, Lucchini, A, Bertoni, M, Goffi, A, Marshall, J, Calza, S, Rasulo, F, Foti, G, Latronico, N, Piva, Simone, Pozzi, Matteo, Bellani, Giacomo, Peli, Elena, Gitti, Nicola, Lucchini, Alberto, Bertoni, Michele, Goffi, Alberto, Marshall, John C, Calza, Stefano, Rasulo, Francesco A, Foti, Giuseppe, Latronico, Nicola, Piva, S, Pozzi, M, Bellani, G, Peli, E, Gitti, N, Lucchini, A, Bertoni, M, Goffi, A, Marshall, J, Calza, S, Rasulo, F, Foti, G, Latronico, N, Piva, Simone, Pozzi, Matteo, Bellani, Giacomo, Peli, Elena, Gitti, Nicola, Lucchini, Alberto, Bertoni, Michele, Goffi, Alberto, Marshall, John C, Calza, Stefano, Rasulo, Francesco A, Foti, Giuseppe, and Latronico, Nicola

Abstract

Purpose: This work aimed to compare physical impairment in survivors of classic ARDS compared with COVID-19-associated ARDS (CARDS) survivors.Material and methods: This is a prospective observational cohort study on 248 patients with CARDS and compared them with a historical cohort of 48 patients with classic ARDS. Physical performance was evaluated at 6 and 12 months after ICU discharge, using the Medical Research Council Scale (MRCss), 6-min walk test (6MWT), handgrip dynamometry (HGD), and fatigue severity score (FSS). We also assessed activities of daily living (ADLs) using the Barthel index.Results: At 6 months, patients with classic ARDS had lower HGD (estimated difference [ED]: 11.71 kg, p < 0.001; ED 31.9% of predicted value, p < 0.001), 6MWT distance (ED: 89.11 m, p < 0.001; ED 12.96% of predicted value, p = 0.032), and more frequent significant fatigue (OR 0.35, p = 0.046). At 12 months, patients with classic ARDS had lower HGD (ED: 9.08 kg, p = 0.0014; ED 25.9% of predicted value, p < 0.001) and no difference in terms of 6MWT and fatigue. At 12 months, patients with classic ARDS improved their MRCss (ED 2.50, p = 0.006) and HGD (ED: 4.13 kg, p = 0.002; ED 9.45% of predicted value, p = 0.005), while those with CARDS did not. Most patients in both groups regained independence in ADLs at 6 months. COVID-19 diagnosis was a significant independent predictor of better HGD (p < 0.0001) and 6MWT performance (p = 0.001), and lower prevalence of fatigue (p = 0.018).Conclusions: Both classic ARDS and CARDS survivors experienced long-term impairments in physical functioning, confirming that post-intensive care syndrome remains a major legacy of critical illness. Surprisingly, however, persisting disability was more common in survivors of classic ARDS than in CARDS survivors. In fact, muscle strength measured with HGD was reduced in survivors of classic ARDS compared to CARDS patients at both 6 and 12 months. The 6MWT was reduced and fatigue was more co

Published
2023

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