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1. Chromogranin B Protects Human Umbilical Endothelial Cells against Oxidative Stress

Author: Elena Grossini, Sakthipriyan Venkatesan, Mohammad Mostafa Ola Pour, Daniela Ferrante, Daniela Surico, Rosanna Vaschetto, Vincenzo Cantaluppi, and Mario Pirisi
Subjects: cardiovascular, granines, mitochondria, nitric oxide, oxidative stress, protection, Biology (General), QH301-705.5, Chemistry, QD1-999
Abstract: Chromogranin B (CgB) is involved in the control of the cardiovascular system through the regulation of catecholamine release. Whether CgB can exert direct actions on the endothelium has not yet been clarified. Here, we aimed to investigate the effects of CgB on cell viability, mitochondrial membrane potential, reactive oxygen species (ROS), glutathione (GSH), nitric oxide (NO) release, and the cytosolic calcium concentration ([Ca2+]c) in human vascular endothelial cells (HUVECs) cultured under both physiological and peroxidative conditions. In HUVECs, experiments were conducted to establish the proper concentration and timing of CgB stimulation. Thereafter, specific assays were used to evaluate the response of HUVECs cultured in physiologic or oxidative stress conditions to CgB in the presence or absence of β-adrenergic receptor agonists and antagonists and intracellular pathways blockers. Analysis of cell viability, mitochondrial membrane potential, and NO release revealed that CgB was able to cause increased effects in HUVECs cultured in physiological conditions. Additionally, the same analyses performed in HUVECs cultured with H2O2, showed protective effects exerted by CgB, which was also able to counteract ROS release and maintain GSH levels. Furthermore, CgB played a dual role on the [Ca2+]c depending on the physiological or peroxidative cell culturing conditions. In conclusion, our data provide new information about the direct role of CgB in the physiological regulation of endothelial function and highlight its potential as a protective agent against peroxidative conditions, such as those found in cardiovascular diseases.
Published: 2024
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2. Peri-partum respiratory management of pregnant women with neuro-muscular disorders: a prospective observational study (IT-NEUMA-Pregn study)

Author: Fabrizio Racca, Yaroslava Longhitano, Christian Zanza, Mario Giosuè Balzanelli, Gaetano Draisci, Paolo Augusto Stoia, Evelina Gollo, Mariella Maio, Claudia Grattarola, Marinella Astuto, Antonello Ciccarelli, Giulia Racca, Tatsiana Romenskaya, Benedetta Giordano, Alessandra Serraino, Valeria Ada Maria Sansone, Cesare Gregoretti, Giorgio Conti, Fabio Piccolella, and Rosanna Vaschetto
Subjects: Pregnancy, Neuromuscular diseases, Postoperative respiratory complications, Non-invasive ventilation, Mechanical cough device, Anesthesiology, RD78.3-87.3
Abstract: Abstract Background Pregnant women with neuromuscular diseases (NMDs) often display respiratory muscle impairment which increases the risk for pulmonary complications (PCs). The aim of this study was to identify pregnant NMDs patients with pulmonary risk factors and to apply in these women non-invasive ventilation (NIV) combined with mechanical insufflation-exsufflation (MI-E) in the peri-partum period. Methods We conducted a multicenter observational study on women with NMDs undergoing cesarean section or spontaneous labor in a network of 7 national hospitals. In these subjects we applied a protocol for screening and preventing PCs, and we evaluated PCs rate, maternal and neonatal outcome. Results Twenty-four patients out of the 94 enrolled pregnant women were at risk for PCs and were trained or retrained to use NIV and/or MI-E before delivery. After delivery, 17 patients required NIV with or without MI-E. Despite nine out of the 24 women at pulmonary risk developed postpartum PCs, none of them needed reintubation nor tracheostomy. In addition, the average birth weight and Apgar score were normal. Only one patient without pulmonary risk factors developed postpartum PCs. Conclusion This study showed the feasibility of applying a protocol for screening and treating pregnant NMDs women with pulmonary risk. Despite a PCs rate of 37% was observed in these patients, maternal and neonatal outcome were favorable.
Published: 2023
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3. A pragmatic, open-label, multi-center, randomized controlled clinical trial on the rotational use of interfaces vs standard of care in patients treated with noninvasive positive pressure ventilation for acute hypercapnic respiratory failure: the ROTAtional-USE of interface STUDY (ROTA-USE STUDY)

Author: Rosanna Vaschetto, Cesare Gregoretti, Lorenza Scotti, Nello De Vita, Annalisa Carlucci, Andrea Cortegiani, Claudia Crimi, Alessio Mattei, Raffaele Scala, Eduardo Rocca, Federico Longhini, Gianmaria Cammarota, Giovanni Misseri, Alberto Dal Molin, Sabino Scolletta, Stefano Nava, Salvatore Maurizio Maggiore, and Paolo Navalesi
Subjects: Noninvasive ventilation, Hypercapnic acute respiratory failure, Pressure ulcers, Rotational use of interfaces, Medicine (General), R5-920
Abstract: Abstract Background In the last decades, noninvasive ventilation (NIV) has been increasingly used to support patients with hypercapnic and hypoxemic acute respiratory failure. Pressure ulcers are a frequently observed NIV-related adverse effect, directly related to interface type and exposure time. Switching to a different interface has been proposed as a solution to improve patient comfort. However, large studies investigating the benefit of this strategy are not available. Thus, the aim of the ROTAtional-USE of interface STUDY (ROTA-USE STUDY) is to investigate whether a protocolized rotational use of interfaces during NIV is effective in reducing the incidence of pressure ulcers. Methods The ROTA-USE STUDY is a pragmatic, parallel arm, open-label, multicenter, spontaneous, non-profit, randomized controlled trial requiring non-significant risk medical devices, with the aim to determine whether a rotational strategy of NIV interfaces is associated with a lower incidence of pressure ulcers compared to the standard of care. In the intervention group, NIV mask will be randomly chosen and rotated every 6 h. In the control group, mask will be chosen according to the standard of care of the participating centers and changed in case of discomfort or in the presence of new pressure sores. In both groups, the skin underneath the mask will be inspected every 12 h for any possible damage by blinded assessors. The primary outcome is the proportion of patients developing new pressure sores at 36 h from randomization. The secondary outcomes are (i) onset of pressure sores measured at different time points, i.e., 12, 24, 36, 48, 60, 72, 84, and 96 h; (ii) number and stage of pressure sores and comfort measured at 12, 24, 36, 48, 60, 72, 84, and 96 h; and (iii) the economic impact of the protocolized rotational use of interfaces. A sample size of 239 subjects per group (intervention and control) is estimated to detect a 10% absolute difference in the proportion of patients developing pressure sores at 36 h. Discussion The development of pressure ulcers is a common side effect of NIV that negatively affects the patients’ comfort and tolerance, often leading to NIV failure and adverse outcomes. The ROTA-USE STUDY will determine whether a protocolized rotational approach can reduce the incidence, number, and severity of pressure ulcers in NIV-treated patients. Trial registration ClinicalTrials.gov NCT05513508. Registered on August 24, 2022.
Published: 2023
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4. Plasma Redox Balance in Advanced-Maternal-Age Pregnant Women and Effects of Plasma on Umbilical Cord Mesenchymal Stem Cells

Author: Elena Grossini, Carmen Imma Aquino, Sakthipriyan Venkatesan, Libera Troìa, Eleonora Tizzoni, Federica Fumagalli, Daniela Ferrante, Rosanna Vaschetto, Valentino Remorgida, and Daniela Surico
Subjects: aging, antioxidants, lipid peroxidation, nitric oxide, pregnancy, Biology (General), QH301-705.5, Chemistry, QD1-999
Abstract: Pregnancy at advanced maternal age (AMA) is a condition of potential risk for the development of maternal–fetal complications with possible repercussions even in the long term. Here, we analyzed the changes in plasma redox balance and the effects of plasma on human umbilical cord mesenchymal cells (hUMSCs) in AMA pregnant women (patients) at various timings of pregnancy. One hundred patients and twenty pregnant women younger than 40 years (controls) were recruited and evaluated at various timings during pregnancy until after delivery. Plasma samples were used to measure the thiobarbituric acid reactive substances (TBARS), glutathione and nitric oxide (NO). In addition, plasma was used to stimulate the hUMSCs, which were tested for cell viability, reactive oxygen species (ROS) and NO release. The obtained results showed that, throughout pregnancy until after delivery in patients, the levels of plasma glutathione and NO were lower than those of controls, while those of TBARS were higher. Moreover, plasma of patients reduced cell viability and NO release, and increased ROS release in hUMSCs. Our results highlighted alterations in the redox balance and the presence of potentially harmful circulating factors in plasma of patients. They could have clinical relevance for the prevention of complications related to AMA pregnancy.
Published: 2024
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5. The Role of New Morphological Parameters Provided by the BC 6800 Plus Analyzer in the Early Diagnosis of Sepsis

Author: Sara Sacchetti, Matteo Vidali, Teresa Esposito, Stefano Zorzi, Alessia Burgener, Lorenzo Ciccarello, Gianmaria Cammarota, Valentina Zanotti, Luca Giacomini, Mattia Bellan, Mario Pirisi, Ramon Simon Lopez, Umberto Dianzani, Rosanna Vaschetto, and Roberta Rolla
Subjects: affordable health care, early diagnosis, leukocyte parameters, morphological changes, Red Cell Distribution Width (RDW), sepsis, Medicine (General), R5-920
Abstract: Background: Late diagnosis of sepsis is associated with adverse consequences and high mortality rate. The aim of this study was to evaluate the diagnostic value of hematologic research parameters, that reflect the cell morphology of blood cells, available on the BC 6800 plus automated analyzer (Mindray) for the early detection of sepsis. Materials and Methods: A complete blood count (CBC) was performed by Mindray BC 6800 Plus Analyzer in 327 patients (223 with a confirmed diagnosis of sepsis following sepsis-3 criteria, 104 without sepsis), admitted at the Intensive Care Unit of the Novara’s Hospital (Italy) and in 56 patients with localized infection. Results: In univariate logistic regression, age, Hb, RDW, MO#, NMR, NeuX, NeuY, NeuZ, LymX, MonX, MonY, MonZ were associated with sepsis (p < 0.005). In multivariate analysis, only RDW, NeuX, NeuY, NeuZ, MonX and MonZ were found to be independent predictors of sepsis (p < 0.005). Morphological research parameters are confirmed to be predictors of sepsis even when analyzing the group with localized infection. Conclusions: In addition to already established biomarkers and basic CBC parameters, new morphological cell parameters can be a valuable aid in the early diagnosis of sepsis at no additional cost.
Published: 2024
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6. Point-of-care ultrasound training for residents in anaesthesia and critical care: results of a national survey comparing residents and training program directors’ perspectives

Author: Silvia Mongodi, Francesca Bonomi, Rosanna Vaschetto, Chiara Robba, Giulia Salve, Carlo Alberto Volta, Elena Bignami, Luigi Vetrugno, Francesco Corradi, Salvatore Maurizio Maggiore, Paolo Pelosi, and Francesco Mojoli
Subjects: Point-of-care ultrasound, Ultrasound education, Training, Residency school organization, Ultrasound curriculum, Teaching, Special aspects of education, LC8-6691, Medicine
Abstract: Abstract Background Point-of-care ultrasound (POCUS) has become an essential tool for anaesthesia and critical care physicians and dedicated training is mandatory. This survey describes the current state of Italian residency training programs through the comparison of residents’ and directors’ perspective. Methods Observational prospective cross-sectional study: 12-question national e-survey sent to Italian directors of anaesthesia and critical care residency programs (N = 40) and residents (N = 3000). Questions focused on POCUS teaching (vascular access, transthoracic echocardiography, focused assessment for trauma, transcranial Doppler, regional anaesthesia, lung and diaphragm ultrasound), organization (dedicated hours, teaching tools, mentors), perceived adequacy/importance of the training and limiting factors. Results Five hundred seventy-one residents and 22 directors completed the survey. Bedside teaching (59.4–93.2%) and classroom lessons (29.7–54.4%) were the most frequent teaching tools. Directors reported higher participation in research projects (p
Published: 2022
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7. Circulating Extracellular Vesicles in Subarachnoid Hemorrhage Patients: Characterization and Cellular Effects

Author: Elena Grossini, Teresa Esposito, Michela Viretto, Sakthipriyan Venkatesan, Ilaria Licari, Daniela Surico, Francesco Della Corte, Luigi Castello, Stefania Bruno, Marco Quaglia, Cristoforo Comi, Vincenzo Cantaluppi, and Rosanna Vaschetto
Subjects: subarachnoid hemorrhage, endothelial function, delayed cerebral ischemia, vasospasm, extracellular vesicles, Biology (General), QH301-705.5, Chemistry, QD1-999
Abstract: Circulating extracellular vesicles (EVs) may play a pathophysiological role in the onset of complications of subarachnoid hemorrhage (SAH), potentially contributing to the development of vasospasm (VP). In this study, we aimed to characterize circulating EVs in SAH patients and examine their effects on endothelial and smooth muscle cells (SMCs). In a total of 18 SAH patients, 10 with VP (VP), 8 without VP (NVP), and 5 healthy controls (HC), clinical variables were recorded at different time points. EVs isolated from plasma samples were characterized and used to stimulate human vascular endothelial cells (HUVECs) and SMCs. We found that EVs from SAH patients expressed markers of T-lymphocytes and platelets and had a larger size and a higher concentration compared to those from HC. Moreover, EVs from VP patients reduced cell viability and mitochondrial membrane potential in HUVECs and increased oxidants and nitric oxide (NO) release. Furthermore, EVs from SAH patients increased intracellular calcium levels in SMCs. Altogether, our findings reveal an altered pattern of circulating EVs in SAH patients, suggesting their pathogenic role in promoting endothelial damage and enhancing smooth muscle reactivity. These results have significant implications for the use of EVs as potential diagnostic/prognostic markers and therapeutic tools in SAH management.
Published: 2023
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8. Predictors of intubation and mortality in COVID-19 patients: a retrospective study

Author: Tiziana Cena, Gianmaria Cammarota, Danila Azzolina, Michela Barini, Simona Bazzano, Domenico Zagaria, Davide Negroni, Luigi Castello, Alessandro Carriero, Francesco Della Corte, and Rosanna Vaschetto
Subjects: COVID-19, Intubation, Factor risk, Mortality, Quantitative computerized tomography, Random forest, Anesthesiology, RD78.3-87.3, Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract: Abstract Background Estimating the risk of intubation and mortality among COVID-19 patients can help clinicians triage these patients and allocate resources more efficiently. Thus, here we sought to identify the risk factors associated with intubation and intra-hospital mortality in a cohort of COVID-19 patients hospitalized due to hypoxemic acute respiratory failure (ARF). Results We included retrospectively a total of 187 patients admitted to the subintensive and intensive care units of the University Hospital “Maggiore della Carità” of Novara between March 1st and April 30th, 2020. Based on these patients’ demographic characteristics, early clinical and laboratory variables, and quantitative chest computerized tomography (CT) findings, we developed two random forest (RF) models able to predict intubation and intra-hospital mortality. Variables independently associated with intubation were C-reactive protein (p < 0.001), lactate dehydrogenase level (p = 0.018) and white blood cell count (p = 0.026), while variables independently associated with mortality were age (p < 0.001), other cardiovascular diseases (p = 0.029), C-reactive protein (p = 0.002), lactate dehydrogenase level (p = 0.018), and invasive mechanical ventilation (p = 0.001). On quantitative chest CT analysis, ground glass opacity, consolidation, and fibrosis resulted significantly associated with patient intubation and mortality. The major predictors for both models were the ratio between partial pressure of arterial oxygen and fraction of inspired oxygen, age, lactate dehydrogenase, C-reactive protein, glycemia, CT quantitative parameters, lymphocyte count, and symptom onset. Conclusions Altogether, our findings confirm previously reported demographic, clinical, hemato-chemical, and radiologic predictors of adverse outcome among COVID-19-associated hypoxemic ARF patients. The two newly developed RF models herein described show an overall good level of accuracy in predicting intra-hospital mortality and intubation in our study population. Thus, their future development and implementation may help not only identify patients at higher risk of deterioration more effectively but also rebalance the disproportion between resources and demand.
Published: 2021
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9. Correction to: Effects of early extubation followed by noninvasive ventilation versus standard extubation on the duration of invasive mechanical ventilation in hypoxemic non-hypercapnic patients: a systematic review and individual patient data meta-analysis of randomized controlled trials

Author: Rosanna Vaschetto, Alessandro Pecere, Gavin D. Perkins, Dipesh Mistry, Gianmaria Cammarota, Federico Longhini, Miguel Ferrer, Renata Pletsch-Assunção, Michele Carron, Francesca Moretto, Haibo Qiu, Francesco Della Corte, Francesco Barone-Adesi, and Paolo Navalesi
Subjects: Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Published: 2021
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10. Noninvasive respiratory support outside the intensive care unit for acute respiratory failure related to coronavirus-19 disease: a systematic review and meta-analysis

Author: Gianmaria Cammarota, Teresa Esposito, Danila Azzolina, Roberto Cosentini, Francesco Menzella, Stefano Aliberti, Andrea Coppadoro, Giacomo Bellani, Giuseppe Foti, Giacomo Grasselli, Maurizio Cecconi, Antonio Pesenti, Michele Vitacca, Tom Lawton, V. Marco Ranieri, Sandro Luigi Di Domenico, Onofrio Resta, Antonio Gidaro, Antonella Potalivo, Giuseppe Nardi, Claudia Brusasco, Simonetta Tesoro, Paolo Navalesi, Rosanna Vaschetto, and Edoardo De Robertis
Subjects: Noninvasive ventilation, COVID-19, Intra-hospital mortality, Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract: Abstract Background Noninvasive respiratory support (NIRS) has been diffusely employed outside the intensive care unit (ICU) to face the high request of ventilatory support due to the massive influx of patients with acute respiratory failure (ARF) caused by coronavirus-19 disease (COVID-19). We sought to summarize the evidence on clinically relevant outcomes in COVID-19 patients supported by NIV outside the ICU. Methods We searched PUBMED®, EMBASE®, and the Cochrane Controlled Clinical trials register, along with medRxiv and bioRxiv repositories for pre-prints, for observational studies and randomized controlled trials, from inception to the end of February 2021. Two authors independently selected the investigations according to the following criteria: (1) observational study or randomized clinical trials enrolling ≥ 50 hospitalized patients undergoing NIRS outside the ICU, (2) laboratory-confirmed COVID-19, and (3) at least the intra-hospital mortality reported. Preferred Reporting Items for Systematic reviews and Meta-analysis guidelines were followed. Data extraction was independently performed by two authors to assess: investigation features, demographics and clinical characteristics, treatments employed, NIRS regulations, and clinical outcomes. Methodological index for nonrandomized studies tool was applied to determine the quality of the enrolled studies. The primary outcome was to assess the overall intra-hospital mortality of patients under NIRS outside the ICU. The secondary outcomes included the proportions intra-hospital mortalities of patients who underwent invasive mechanical ventilation following NIRS failure and of those with ‘do-not-intubate’ (DNI) orders. Results Seventeen investigations (14 peer-reviewed and 3 pre-prints) were included with a low risk of bias and a high heterogeneity, for a total of 3377 patients. The overall intra-hospital mortality of patients receiving NIRS outside the ICU was 36% [30–41%]. 26% [21–30%] of the patients failed NIRS and required intubation, with an intra-hospital mortality rising to 45% [36–54%]. 23% [15–32%] of the patients received DNI orders with an intra-hospital mortality of 72% [65–78%]. Oxygenation on admission was the main source of between-study heterogeneity. Conclusions During COVID-19 outbreak, delivering NIRS outside the ICU revealed as a feasible strategy to cope with the massive demand of ventilatory assistance. Registration PROSPERO, https://www.crd.york.ac.uk/prospero/ , CRD42020224788, December 11, 2020.
Published: 2021
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11. COVID-19 ARDS is characterized by higher extravascular lung water than non-COVID-19 ARDS: the PiCCOVID study

Author: Rui Shi, Christopher Lai, Jean-Louis Teboul, Martin Dres, Francesca Moretto, Nello De Vita, Tài Pham, Vincent Bonny, Julien Mayaux, Rosanna Vaschetto, Alexandra Beurton, and Xavier Monnet
Subjects: Transpulmonary thermodilution, Hemodynamic monitoring, Mechanical ventilation, SARS-CoV-2, Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract: Abstract Background In acute respiratory distress syndrome (ARDS), extravascular lung water index (EVLWi) and pulmonary vascular permeability index (PVPI) measured by transpulmonary thermodilution reflect the degree of lung injury. Whether EVLWi and PVPI are different between non-COVID-19 ARDS and the ARDS due to COVID-19 has never been reported. We aimed at comparing EVLWi, PVPI, respiratory mechanics and hemodynamics in patients with COVID-19 ARDS vs. ARDS of other origin. Methods Between March and October 2020, in an observational study conducted in intensive care units from three university hospitals, 60 patients with COVID-19-related ARDS monitored by transpulmonary thermodilution were compared to the 60 consecutive non-COVID-19 ARDS admitted immediately before the COVID-19 outbreak between December 2018 and February 2020. Results Driving pressure was similar between patients with COVID-19 and non-COVID-19 ARDS, at baseline as well as during the study period. Compared to patients without COVID-19, those with COVID-19 exhibited higher EVLWi, both at the baseline (17 (14–21) vs. 15 (11–19) mL/kg, respectively, p = 0.03) and at the time of its maximal value (24 (18–27) vs. 21 (15–24) mL/kg, respectively, p = 0.01). Similar results were observed for PVPI. In COVID-19 patients, the worst ratio between arterial oxygen partial pressure over oxygen inspired fraction was lower (81 (70–109) vs. 100 (80–124) mmHg, respectively, p = 0.02) and prone positioning and extracorporeal membrane oxygenation (ECMO) were more frequently used than in patients without COVID-19. COVID-19 patients had lower maximal lactate level and maximal norepinephrine dose than patients without COVID-19. Day-60 mortality was similar between groups (57% vs. 65%, respectively, p = 0.45). The maximal value of EVLWi and PVPI remained independently associated with outcome in the whole cohort. Conclusion Compared to ARDS patients without COVID-19, patients with COVID-19 had similar lung mechanics, but higher EVLWi and PVPI values from the beginning of the disease. This was associated with worse oxygenation and with more requirement of prone positioning and ECMO. This is compatible with the specific lung inflammation and severe diffuse alveolar damage related to COVID-19. By contrast, patients with COVID-19 had fewer hemodynamic derangement. Eventually, mortality was similar between groups. Trial registration number and date of registration ClinicalTrials.gov (NCT04337983). Registered 30 March 2020—Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT04337983 .
Published: 2021
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12. Effects of early extubation followed by noninvasive ventilation versus standard extubation on the duration of invasive mechanical ventilation in hypoxemic non-hypercapnic patients: a systematic review and individual patient data meta-analysis of randomized controlled trials

Author: Rosanna Vaschetto, Alessandro Pecere, Gavin D. Perkins, Dipesh Mistry, Gianmaria Cammarota, Federico Longhini, Miguel Ferrer, Renata Pletsch-Assunção, Michele Carron, Francesca Moretto, Haibo Qiu, Francesco Della Corte, Francesco Barone-Adesi, and Paolo Navalesi
Subjects: Noninvasive ventilation, Weaning, Hypoxemic acute respiratory failure, Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract: Abstract Background Usefulness of noninvasive ventilation (NIV) in weaning patients with non-hypercapnic hypoxemic acute respiratory failure (hARF) is unclear. The study aims to assess in patients with non-hypercapnic hARF, the efficacy of NIV after early extubation, compared to standard weaning. Methods In this individual patient data meta-analysis, we searched EMBASE, Medline and Cochrane Central Register of Controlled Trials to identify potentially eligible randomized controlled trials published from database inception to October 2020. To be eligible, studies had to include patients treated with NIV after early extubation and compared to conventional weaning in adult non-hypercapnic hARF patients. Anonymized individual patient data from eligible studies were provided by study investigators. Using one-step and two-step meta-analysis models we tested the difference in total days spent on invasive ventilation. Results We screened 1605 records. Six studies were included in quantitative synthesis. Overall, 459 participants (mean [SD] age, 62 [15] years; 269 [59%] males) recovering from hARF were included in the analysis (233 in the intervention group and 226 controls). Participants receiving NIV had a shorter duration of invasive mechanical ventilation compared to control group (mean difference, − 3.43; 95% CI − 5.17 to − 1.69 days, p
Published: 2021
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13. Intraoperative protective ventilation in patients undergoing major neurosurgical interventions: a randomized clinical trial

Author: Federico Longhini, Laura Pasin, Claudia Montagnini, Petra Konrad, Andrea Bruni, Eugenio Garofalo, Paolo Murabito, Corrado Pelaia, Valentina Rondi, Fabrizio Dellapiazza, Gianmaria Cammarota, Rosanna Vaschetto, Marcus J. Schultz, and Paolo Navalesi
Subjects: Mechanical ventilation, Postoperative pulmonary complications, Neurosurgery, Anesthesiology, RD78.3-87.3
Abstract: Abstract Background Post-operative pulmonary complications (PPC) can develop in up to 13% of patients undergoing neurosurgical procedures and may adversely affect clinical outcome. The use of intraoperative lung protective ventilation (LPV) strategies, usually including the use of a low Vt, low PEEP and low plateau pressure, seem to reduce the risk of PPC and are strongly recommended in almost all surgical procedures. Nonetheless, feasibility of LPV strategies in neurosurgical patients are still debated because the use of low Vt during LPV might result in hypercapnia with detrimental effects on cerebrovascular physiology. Aim of our study was to determine whether LPV strategies would be feasible compared with a control group in adult patients undergoing cranial or spinal surgery. Methods This single-centre, pilot randomized clinical trial was conducted at the University Hospital “Maggiore della Carità” (Novara, Italy). Adult patients undergoing major cerebral or spinal neurosurgical interventions with risk index for pulmonary post-operative complications > 2 and not expected to need post-operative intensive care unit (ICU) admission were considered eligible. Patients were randomly assigned to either LPV (Vt = 6 ml/kg of ideal body weight (IBW), respiratory rate initially set at 16 breaths/min, PEEP at 5 cmH2O and application of a recruitment manoeuvre (RM) immediately after intubation and at every disconnection from the ventilator) or control treatment (Vt = 10 ml/kg of IBW, respiratory rate initially set at 6–8 breaths/min, no PEEP and no RM). Primary outcomes of the study were intraoperative adverse events, the level of cerebral tension at dura opening and the intraoperative control of PaCO2. Secondary outcomes were the rate of pulmonary and extrapulmonary complications, the number of unplanned ICU admissions, ICU and hospital lengths of stay and mortality. Results A total of 60 patients, 30 for each group, were randomized. During brain surgery, the number of episodes of intraoperative hypercapnia and grade of cerebral tension were similar between patients randomized to receive control or LPV strategies. No difference in the rate of intraoperative adverse events was found between groups. The rate of postoperative pulmonary and extrapulmonary complications and major clinical outcomes were similar between groups. Conclusions LPV strategies in patients undergoing major neurosurgical intervention are feasible. Larger clinical trials are needed to assess their role in postoperative clinical outcome improvements. Trial registration registered on the Australian New Zealand Clinical Trial Registry ( www.anzctr.org.au ), registration number ACTRN12615000707561.
Published: 2021
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14. Early extubation with immediate non-invasive ventilation versus standard weaning in intubated patients for coronavirus disease 2019: a retrospective multicenter study

Author: Gianmaria Cammarota, Rosanna Vaschetto, Danila Azzolina, Nello De Vita, Carlo Olivieri, Chiara Ronco, Federico Longhini, Andrea Bruni, Davide Colombo, Claudio Pissaia, Federico Prato, Carlo Maestrone, Matteo Maestrone, Luigi Vetrugno, Tiziana Bove, Francesco Lemut, Elisa Taretto, Alessandro Locatelli, Nicoletta Barzaghi, Martina Cerrano, Enrico Ravera, Christian Zanza, Andrea Della Selva, Ilaria Blangetti, Francesco Salvo, Fabrizio Racca, Yaroslava Longhitano, Annalisa Boscolo, Ilaria Sguazzotti, Valeria Bonato, Francesca Grossi, Federico Crimaldi, Raffaella Perucca, Ester Boniolo, Federico Verdina, Gian Luca Vignazia, Erminio Santangelo, Riccardo Tarquini, Marta Zanoni, Antonio Messina, Matteo Marin, Paola Bacigalupo, Graziana Sileci, Nicolò Sella, Edardo De Robertis, Francesco Della Corte, and Paolo Navalesi
Subjects: Medicine, Science
Abstract: Abstract In patients intubated for hypoxemic acute respiratory failure (ARF) related to novel coronavirus disease (COVID-19), we retrospectively compared two weaning strategies, early extubation with immediate non-invasive ventilation (NIV) versus standard weaning encompassing spontaneous breathing trial (SBT), with respect to IMV duration (primary endpoint), extubation failures and reintubations, rate of tracheostomy, intensive care unit (ICU) length of stay and mortality (additional endpoints). All COVID-19 adult patients, intubated for hypoxemic ARF and subsequently extubated, were enrolled. Patients were included in two groups, early extubation followed by immediate NIV application, and conventionally weaning after passing SBT. 121 patients were enrolled and analyzed, 66 early extubated and 55 conventionally weaned after passing an SBT. IMV duration was 9 [6–11] days in early extubated patients versus 11 [6–15] days in standard weaning group (p = 0.034). Extubation failures [12 (18.2%) vs. 25 (45.5%), p = 0.002] and reintubations [12 (18.2%) vs. 22 (40.0%) p = 0.009] were fewer in early extubation compared to the standard weaning groups, respectively. Rate of tracheostomy, ICU mortality, and ICU length of stay were no different between groups. Compared to standard weaning, early extubation followed by immediate NIV shortened IMV duration and reduced the rate of extubation failure and reintubation.
Published: 2021
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15. Effect of Lactoferrin on Clinical Outcomes of Hospitalized Patients with COVID-19: The LAC Randomized Clinical Trial

Author: Erica Matino, Elena Tavella, Manuela Rizzi, Gian Carlo Avanzi, Danila Azzolina, Antonio Battaglia, Paolo Becco, Mattia Bellan, Giovanni Bertinieri, Massimo Bertoletti, Giuseppe Francesco Casciaro, Luigi Mario Castello, Umberto Colageo, Donato Colangelo, Davide Comolli, Martina Costanzo, Alessandro Croce, Davide D’Onghia, Francesco Della Corte, Luigi De Mitri, Valentina Dodaro, Filippo Givone, Alessia Gravina, Luca Grillenzoni, Graziano Gusmaroli, Raffaella Landi, Anna Lingua, Roberto Manzoni, Vito Marinoni, Bianca Masturzo, Rosalba Minisini, Marina Morello, Anna Nelva, Elena Ortone, Rita Paolella, Giuseppe Patti, Anita Pedrinelli, Mario Pirisi, Lidia Ravizzi, Eleonora Rizzi, Daniele Sola, Mariolina Sola, Nadir Tonello, Stelvio Tonello, Gigliola Topazzo, Aldo Tua, Piera Valenti, Rosanna Vaschetto, Veronica Vassia, Erika Zecca, Nicoletta Zublena, Paolo Manzoni, and Pier Paolo Sainaghi
Subjects: COVID-19, lactoferrin, randomized, placebo-controlled, multicenter, double-blind clinical trial, Nutrition. Foods and food supply, TX341-641
Abstract: As lactoferrin is a nutritional supplement with proven antiviral and immunomodulatory abilities, it may be used to improve the clinical course of COVID-19. The clinical efficacy and safety of bovine lactoferrin were evaluated in the LAC randomized double-blind placebo-controlled trial. A total of 218 hospitalized adult patients with moderate-to-severe COVID-19 were randomized to receive 800 mg/die oral bovine lactoferrin (n = 113) or placebo (n = 105), both given in combination with standard COVID-19 therapy. No differences in lactoferrin vs. placebo were observed in the primary outcomes: the proportion of death or intensive care unit admission (risk ratio of 1.06 (95% CI 0.63–1.79)) or proportion of discharge or National Early Warning Score 2 (NEWS2) ≤ 2 within 14 days from enrollment (RR of 0.85 (95% CI 0.70–1.04)). Lactoferrin showed an excellent safety and tolerability profile. Even though bovine lactoferrin is safe and tolerable, our results do not support its use in hospitalized patients with moderate-to-severe COVID-19.
Published: 2023
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16. Multicentre observational study on practice of prehospital management of hypotensive trauma patients: the SPITFIRE study protocol

Author: John B Holcomb, Tiziana Cena, David Lockey, Luca Montagnani, Simona Cavallo, Andrea Cortegiani, Lorenzo Gamberini, Carlo Coniglio, Marco Tartaglione, Valentina Chiarini, Cristian Lupi, Giovanni Gordini, Tobias Gauss, Aimone Giugni, Maria Teresa Strano, Luca Carenzo, Carlo Alberto Mazzoli, Silvia Cavagna, Davide Allegri, Giovanni Sbrana, Andrea Caglià, Jacopo Pernechele, Andrea Mina, Roberto Vacca, Roberto Gioachin, Valeria Bonato, Claudia Monge, Paolo Frisoni, Luca Nicora, Giovanna Zilio, Cristina Barbarino, Andrea Paoli, Giacomo Magagnotti, Andrea Spagna, Alberto Trincanato, Francesca Verginella, Marta Pescolderung, Stefania Armani, Adriano Valerio, Giulio Desiderio, Edoardo Picetti, Michela Ciminello, Christian Tosato, Yuri Ferrara, Stefano Barbadori, Silvia Pini, Andrea Vignali, Alberto Baratta, Davide Durì, Calogero Centonze, Matteo Ciccolini, Alessandra Spasiano, Tommaso Marzano, Guido Gambetti, Domenico Minniti, Michela Rauseo, Gilda Cinnella, Rosanna Vaschetto, Giacomo Iapichino, Fabio Genco, Antonio Iacono, Annalisa Deiana, Marco Vidili, Massimiliano Carta, Alessio Ficarella, and Flavia Baccari
Subjects: Medicine
Abstract: Introduction Major haemorrhage after injury is the leading cause of preventable death for trauma patients. Recent advancements in trauma care suggest damage control resuscitation (DCR) should start in the prehospital phase following major trauma. In Italy, Helicopter Emergency Medical Services (HEMS) assist the most complex injuries and deliver the most advanced interventions including DCR. The effect size of DCR delivered prehospitally on survival remains however unclear.Methods and analysis This is an investigator-initiated, large, national, prospective, observational cohort study aiming to recruit >500 patients in haemorrhagic shock after major trauma. We aim at describing the current practice of hypotensive trauma management as well as propose the creation of a national registry of patients with haemorrhagic shock. Primary objective: the exploration of the effect size of the variation in clinical practice on the mortality of hypotensive trauma patients. The primary outcome measure will be 24 hours, 7-day and 30-day mortality. Secondary outcomes include: association of prehospital factors and survival from injury to hospital admission, hospital length of stay, prehospital and in-hospital complications, hospital outcomes; use of prehospital ultrasound; association of prehospital factors and volume of first 24-hours blood product administration and evaluation of the prevalence of use, appropriateness, haemodynamic, metabolic and effects on mortality of prehospital blood transfusions. Inclusion criteria: age >18 years, traumatic injury attended by a HEMS team including a physician, a systolic blood pressure
Published: 2022
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17. 'War to the knife' against thromboinflammation to protect endothelial function of COVID-19 patients

Author: Gabriele Guglielmetti, Marco Quaglia, Pier Paolo Sainaghi, Luigi Mario Castello, Rosanna Vaschetto, Mario Pirisi, Francesco Della Corte, Gian Carlo Avanzi, Piero Stratta, and Vincenzo Cantaluppi
Subjects: COVID-19, Thrombosis, Thromboinflammation, Heparin, Plasma, Endothelial dysfunction, Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract: Abstract In this viewpoint, we summarize the relevance of thromboinflammation in COVID-19 and discuss potential mechanisms of endothelial injury as a key point for the development of lung and distant organ dysfunction, with a focus on direct viral infection and cytokine-mediated injury. Entanglement between inflammation and coagulation and resistance to heparin provide a rationale to consider other therapeutic approaches in order to preserve endothelial function and limit microthrombosis, especially in severe forms. These strategies include nebulized heparin, N-acetylcysteine, plasma exchange and/or fresh frozen plasma, plasma derivatives to increase the level of endogenous anticoagulants (tissue factor pathway inhibitor, activated protein C, thrombomodulin, antithrombin), dipyridamole, complement blockers, different types of stem cells, and extracellular vesicles. An integrated therapy including these drugs has the potential to improve outcomes in COVID-19.
Published: 2020
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18. High levels of circulating osteopontin in inflammatory lung disease regardless of SARS‐CoV‐2 infection

Author: Giuseppe Cappellano, Hugo Abreu, Davide Raineri, Lorenza Scotti, Luigi Castello, Rosanna Vaschetto, and Annalisa Chiocchetti
Subjects: Medicine (General), R5-920, Genetics, QH426-470
Published: 2021
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19. Isolated Central Nervous System Vasculitides in COVID-19: A Systematic Review of Case Reports and Series

Author: Domizia Vecchio, Francesca Moretto, Samuel Padelli, Francesca Grossi, Roberto Cantello, and Rosanna Vaschetto
Subjects: isolated cerebral vasculitides, primary central nervous system vasculitis, PCNSV, COVID-19, SARS-CoV-2, Medicine (General), R5-920, Medical physics. Medical radiology. Nuclear medicine, R895-920
Abstract: Cerebral vasculitides, both isolated or in systemic disorders, could be triggered by infections, and few cases have been associated to coronavirus disease 2019 (COVID-19). This study searched for publications in Pubmed, EMBASE, and Cochrane library databases for case reports and series of isolated central nervous system (CNS) vasculitides triggered by severe acute respiratory syndrome coronavirus-2. We included 12 studies (published from June 2020 to July 2022) and collected 39 adult patients (5/39 pathologically or radiologically proven, 34/39 suggestive for primary CNS vasculitis or PCNSV). All cases had a positive real-time polymerase chain reaction on a nasopharyngeal swab or a respiratory tract specimen. About the 85% of the included cases were males, and disease onset occurred later than 50 years old in all but three subjects. In total, 33/39 patients presented severe COVID-19 pneumonia, frequently requiring intensive care unit care. The most common neurological features were headache, obnubilation, and coma. PCNSV was suspected mainly on radiological findings, whereas the cerebrospinal fluid analysis was minimally altered. Magnetic resonance imaging showed vessel wall enhancement in 32/39 cases, generally with the concomitant presence of microbleeds, subarachnoid haemorrhages, and/or multiple ischemic lesions. Despite the severe respiratory and neurological disease course, most cases (93%) improved spontaneously or after a course of high-dose intravenous steroids with no need for immunosuppression. In conclusion, PCNSV could rarely relate to COVID-19 and independently from pulmonary disease severity. Adults with COVID-19-related PCNSV could have a favourable prognosis.
Published: 2022
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20. Comparisons of two diaphragm ultrasound-teaching programs: a multicenter randomized controlled educational study

Author: Eugenio Garofalo, Andrea Bruni, Corrado Pelaia, Giovanni Landoni, Alberto Zangrillo, Massimo Antonelli, Giorgio Conti, Daniele Guerino Biasucci, Giovanna Mercurio, Andrea Cortegiani, Antonino Giarratano, Luigi Vetrugno, Tiziana Bove, Francesco Forfori, Francesco Corradi, Rosanna Vaschetto, Gianmaria Cammarota, Marinella Astuto, Paolo Murabito, Valentina Bellini, Massimo Zambon, Federico Longhini, Paolo Navalesi, and Elena Bignami
Subjects: Diaphragm ultrasound, Diaphragm imaging, Learning, Education, Course, Training, Medical physics. Medical radiology. Nuclear medicine, R895-920
Abstract: Abstract Background This study aims to ascertain whether (1) an educational program is sufficient to achieve adequate Diaphragm Ultrasound (DUS) assessments on healthy volunteers and (2) combining a video tutorial with a practical session is more effective in making learners capable to obtain accurate DUS measurements, as opposed to sole video tutorial. Results We enrolledstep 1: 172 volunteers naïve to ultrasound. After watching a video tutorial, a questionnaire was administered and considered to be passed when at least 70% of the questions were correctly answered. Course participants who passed the theoretical test were randomized to either intervention or control group. Learners randomized to the interventional group underwent to a practical training, tutored by an expert, before accessing DUS examination. Participants randomized to the control group directly accessed DUS examination, without any practical training. DUS measurements by learners and tutors were recorded and checked for accuracy, according to predefined criteria. Detection of both acoustic windows and accurate DUS assessment was achieved by 83.7% learners of the intervention group while 3.5% only among controls (p
Published: 2019
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21. Is it feasible to collect exhaled breath condensate in COVID-19 patients undergoing noninvasive ventilatory support?

Author: Paola Pierucci, Rosanna Vaschetto, and Giovanna E. Carpagnano
Subjects: Medicine
Published: 2021
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22. Circulating Exosomes Are Strongly Involved in SARS-CoV-2 Infection

Author: Elettra Barberis, Virginia V. Vanella, Marco Falasca, Valeria Caneapero, Giuseppe Cappellano, Davide Raineri, Marco Ghirimoldi, Veronica De Giorgis, Chiara Puricelli, Rosanna Vaschetto, Pier Paolo Sainaghi, Stefania Bruno, Antonio Sica, Umberto Dianzani, Roberta Rolla, Annalisa Chiocchetti, Vincenzo Cantaluppi, Gianluca Baldanzi, Emilio Marengo, and Marcello Manfredi
Subjects: SARS-CoV-2, plasma exosomes, host-response, biomarkers, proteomics, Biology (General), QH301-705.5
Abstract: Knowledge of the host response to the novel coronavirus SARS-CoV-2 remains limited, hindering the understanding of COVID-19 pathogenesis and the development of therapeutic strategies. During the course of a viral infection, host cells release exosomes and other extracellular vesicles carrying viral and host components that can modulate the immune response. The present study used a shotgun proteomic approach to map the host circulating exosomes’ response to SARS-CoV-2 infection. We investigated how SARS-CoV-2 infection modulates exosome content, exosomes’ involvement in disease progression, and the potential use of plasma exosomes as biomarkers of disease severity. A proteomic analysis of patient-derived exosomes identified several molecules involved in the immune response, inflammation, and activation of the coagulation and complement pathways, which are the main mechanisms of COVID-19–associated tissue damage and multiple organ dysfunctions. In addition, several potential biomarkers—such as fibrinogen, fibronectin, complement C1r subcomponent and serum amyloid P-component—were shown to have a diagnostic feature presenting an area under the curve (AUC) of almost 1. Proteins correlating with disease severity were also detected. Moreover, for the first time, we identified the presence of SARS-CoV-2 RNA in the exosomal cargo, which suggests that the virus might use the endocytosis route to spread infection. Our findings indicate circulating exosomes’ significant contribution to several processes—such as inflammation, coagulation, and immunomodulation—during SARS-CoV-2 infection. The study’s data are available via ProteomeXchange with the identifier PXD021144.
Published: 2021
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23. Outcomes of COVID-19 patients treated with continuous positive airway pressure outside the intensive care unit

Author: Rosanna Vaschetto, Francesco Barone-Adesi, Fabrizio Racca, Claudio Pissaia, Carlo Maestrone, Davide Colombo, Carlo Olivieri, Nello De Vita, Erminio Santangelo, Lorenza Scotti, Luigi Castello, Tiziana Cena, Martina Taverna, Luca Grillenzoni, Maria Adele Moschella, Gianluca Airoldi, Silvio Borrè, Francesco Mojoli, Francesco Della Corte, Marta Baggiani, Sara Baino, Piero Balbo, Simona Bazzano, Valeria Bonato, Sara Carbonati, Federico Crimaldi, Veronica Daffara, Luca De Col, Matteo Maestrone, Mario Malerba, Federica Moroni, Raffaella Perucca, Mario Pirisi, Valentina Rondi, Daniela Rosalba, Letizia Vanni, Francesca Vigone, Paolo Navalesi, and Gianmaria Cammarota
Subjects: Medicine
Abstract: Aim We aimed to characterise a large population of coronavirus disease 2019 (COVID-19) patients with moderate-to-severe hypoxaemic acute respiratory failure (ARF) receiving continuous positive airway pressure (CPAP) outside the intensive care unit (ICU), and to ascertain whether the duration of CPAP application increased the risk of mortality for patients requiring intubation. Methods In this retrospective, multicentre cohort study, we included adult COVID-19 patients, treated with CPAP outside ICU for hypoxaemic ARF from 1 March to 15 April, 2020. We collected demographic and clinical data, including CPAP therapeutic goal, hospital length of stay and 60-day in-hospital mortality. Results The study included 537 patients with a median (interquartile range (IQR) age of 69 (60–76) years. 391 (73%) were male. According to the pre-defined CPAP therapeutic goal, 397 (74%) patients were included in the full treatment subgroup, and 140 (26%) in the do not intubate (DNI) subgroup. Median (IQR) CPAP duration was 4 (1–8) days, while hospital length of stay was 16 (9–27) days. 60-day in-hospital mortality was 34% (95% CI 0.304–0.384%) overall, and 21% (95% CI 0.169–0.249%) and 73% (95% CI 0.648–0.787%) for full treatment and DNI subgroups, respectively. In the full treatment subgroup, in-hospital mortality was 42% (95% CI 0.345–0.488%) for 180 (45%) CPAP failures requiring intubation, and 2% (95% CI 0.008–0.035%) for the remaining 217 (55%) patients who succeeded. Delaying intubation was associated with increased mortality (hazard ratio 1.093, 95% CI 1.010–1.184). Conclusions We described a large population of COVID-19 patients treated with CPAP outside ICU. Intubation delay represents a risk factor for mortality. Further investigation is needed for early identification of CPAP failures.
Published: 2021
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24. Assessing anaesthesiology and intensive care specialty physicians: An Italian language multisource feedback system.

Author: Luca Carenzo, Tiziana Cena, Fabio Carfagna, Valentina Rondi, Pier Luigi Ingrassia, Maurizio Cecconi, Claudio Violato, Francesco Della Corte, and Rosanna Vaschetto
Subjects: Medicine, Science
Abstract: BackgroundPhysician professionalism, including anaesthesiologists and intensive care doctors, should be continuously assessed during training and subsequent clinical practice. Multi-source feedback (MSF) is an assessment system in which healthcare professionals are assessed on several constructs (e.g., communication, professionalism, etc.) by multiple people (medical colleagues, coworkers, patients, self) in their sphere of influence. MSF has gained widespread acceptance for both formative and summative assessment of professionalism for reflecting on how to improve clinical practice.MethodsInstrument development and psychometric analysis (feasibility, reliability, construct validity via exploratory factor analysis) for MSF questionnaires in a postgraduate specialty training in Anaesthesiology and intensive care in Italy. Sixty-four residents at the Università del Piemonte Orientale (Italy) Anesthesiology Residency Program. Main outcomes assessed were: development and psychometric testing of 4 questionnaires: self, medical colleague, coworker and patient assessment.ResultsOverall 605 medical colleague questionnaires (mean of 9.3 ±1.9) and 543 coworker surveys (mean 8.4 ±1.4) were collected providing high mean ratings for all items (> 4.0 /5.0). The self-assessment item mean score ranged from 3.1 to 4.3. Patient questionnaires (n = 308) were returned from 31 residents (40%; mean 9.9 ± 6.2). Three items had high percentages of "unable to assess" (> 15%) in coworker questionnaires. Factor analyses resulted in a two-factor solution: clinical management with leadership and accountability accounting for at least 75% of the total variance for the medical colleague and coworker's survey with high internal consistency reliability (Cronbach's α > 0.9). Patient's questionnaires had a low return rate, a limited exploratory analysis was performed.ConclusionsWe provide a feasible and reliable Italian language MSF instrument with evidence of construct validity for the self, coworkers and medical colleague. Patient feedback was difficult to collect in our setting.
Published: 2021
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25. Metabolomics Diagnosis of COVID-19 from Exhaled Breath Condensate

Author: Elettra Barberis, Elia Amede, Shahzaib Khoso, Luigi Castello, Pier Paolo Sainaghi, Mattia Bellan, Piero Emilio Balbo, Giuseppe Patti, Diego Brustia, Mara Giordano, Roberta Rolla, Annalisa Chiocchetti, Giorgia Romani, Marcello Manfredi, and Rosanna Vaschetto
Subjects: breath analysis, metabolomics, COVID-19, GCxGC-MS, noninvasive analysis, Microbiology, QR1-502
Abstract: Infection from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can lead to severe respiratory tract damage and acute lung injury. Therefore, it is crucial to study breath-associated biofluids not only to investigate the breath’s biochemical changes caused by SARS-CoV-2 infection, but also to discover potential biomarkers for the development of new diagnostic tools. In the present study, we performed an untargeted metabolomics approach using a bidimensional gas chromatography mass spectrometer (GCxGC-TOFMS) on exhaled breath condensate (EBC) from COVID-19 patients and negative healthy subjects to identify new potential biomarkers for the noninvasive diagnosis and monitoring of the COVID-19 disease. The EBC analysis was further performed in patients with acute or acute-on-chronic cardiopulmonary edema (CPE) to assess the reliability of the identified biomarkers. Our findings demonstrated that an abundance of EBC fatty acids can be used to discriminate COVID-19 patients and that they may have a protective effect, thus suggesting their potential use as a preventive strategy against the infection.
Published: 2021
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26. Circulating Platelet-Derived Extracellular Vesicles Are a Hallmark of Sars-Cov-2 Infection

Author: Giuseppe Cappellano, Davide Raineri, Roberta Rolla, Mara Giordano, Chiara Puricelli, Beatrice Vilardo, Marcello Manfredi, Vincenzo Cantaluppi, Pier Paolo Sainaghi, Luigi Castello, Nello De Vita, Lorenza Scotti, Rosanna Vaschetto, Umberto Dianzani, and Annalisa Chiocchetti
Subjects: circulating biomarker, extracellular vesicles, platelets, COVID-19, Sars-Cov-2, Cytology, QH573-671
Abstract: Sars-Cov-2 infection causes fever and cough that may rapidly lead to acute respiratory distress syndrome (ARDS). Few biomarkers have been identified but, unfortunately, these are individually poorly specific, and novel biomarkers are needed to better predict patient outcome. The aim of this study was to evaluate the diagnostic performance of circulating platelets (PLT)-derived extracellular vesicles (EVs) as biomarkers for Sars-Cov-2 infection, by setting a rapid and reliable test on unmanipulated blood samples. PLT-EVs were quantified by flow cytometry on two independent cohorts of Sars-CoV-2+ (n = 69), Sars-Cov-2− (n = 62) hospitalized patients, and healthy controls. Diagnostic performance of PLT-EVs was evaluated by receiver operating characteristic (ROC) curve. PLT-EVs count were higher in Sars-Cov-2+ compared to Sars-Cov-2− patients or HC. ROC analysis of the combined cohorts showed an AUC = 0.79 and an optimal cut-off value of 1472 EVs/μL, with 75% sensitivity and 74% specificity. These data suggest that PLT-EVs might be an interesting biomarker deserving further investigations to test their predictive power.
Published: 2021
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27. Large-Scale Plasma Analysis Revealed New Mechanisms and Molecules Associated with the Host Response to SARS-CoV-2

Author: Elettra Barberis, Sara Timo, Elia Amede, Virginia V. Vanella, Chiara Puricelli, Giuseppe Cappellano, Davide Raineri, Micol G. Cittone, Eleonora Rizzi, Anita R. Pedrinelli, Veronica Vassia, Francesco G. Casciaro, Simona Priora, Ilaria Nerici, Alessandra Galbiati, Eyal Hayden, Marco Falasca, Rosanna Vaschetto, Pier Paolo Sainaghi, Umberto Dianzani, Roberta Rolla, Annalisa Chiocchetti, Gianluca Baldanzi, Emilio Marengo, and Marcello Manfredi
Subjects: SARS-CoV-2, biomarkers, metabolism, fatty acids, Biology (General), QH301-705.5, Chemistry, QD1-999
Abstract: The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread to nearly every continent, registering over 1,250,000 deaths worldwide. The effects of SARS-CoV-2 on host targets remains largely limited, hampering our understanding of Coronavirus Disease 2019 (COVID-19) pathogenesis and the development of therapeutic strategies. The present study used a comprehensive untargeted metabolomic and lipidomic approach to capture the host response to SARS-CoV-2 infection. We found that several circulating lipids acted as potential biomarkers, such as phosphatidylcholine 14:0_22:6 (area under the curve (AUC) = 0.96), phosphatidylcholine 16:1_22:6 (AUC = 0.97), and phosphatidylethanolamine 18:1_20:4 (AUC = 0.94). Furthermore, triglycerides and free fatty acids, especially arachidonic acid (AUC = 0.99) and oleic acid (AUC = 0.98), were well correlated to the severity of the disease. An untargeted analysis of non-critical COVID-19 patients identified a strong alteration of lipids and a perturbation of phenylalanine, tyrosine and tryptophan biosynthesis, phenylalanine metabolism, aminoacyl-tRNA degradation, arachidonic acid metabolism, and the tricarboxylic acid (TCA) cycle. The severity of the disease was characterized by the activation of gluconeogenesis and the metabolism of porphyrins, which play a crucial role in the progress of the infection. In addition, our study provided further evidence for considering phospholipase A2 (PLA2) activity as a potential key factor in the pathogenesis of COVID-19 and a possible therapeutic target. To date, the present study provides the largest untargeted metabolomics and lipidomics analysis of plasma from COVID-19 patients and control groups, identifying new mechanisms associated with the host response to COVID-19, potential plasma biomarkers, and therapeutic targets.
Published: 2020
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28. Osteopontin at the Crossroads of Inflammation and Tumor Progression

Author: Luigi Mario Castello, Davide Raineri, Livia Salmi, Nausicaa Clemente, Rosanna Vaschetto, Marco Quaglia, Massimiliano Garzaro, Sergio Gentilli, Paolo Navalesi, Vincenzo Cantaluppi, Umberto Dianzani, Anna Aspesi, and Annalisa Chiocchetti
Subjects: Pathology, RB1-214
Abstract: Complex interactions between tumor and host cells regulate systemic tumor dissemination, a process that begins early at the primary tumor site and goes on until tumor cells detach themselves from the tumor mass and start migrating into the blood or lymphatic vessels. Metastatic cells colonize the target organs and are capable of surviving and growing at distant sites. In this context, osteopontin (OPN) appears to be a key determinant of the crosstalk between cancer cells and the host microenvironment, which in turn modulates immune evasion. OPN is overexpressed in several human carcinomas and has been implicated in inflammation, tumor progression, and metastasis. Thus, it represents one of the most attracting targets for cancer therapy. Within the tumor mass, OPN is secreted in various forms either by the tumor itself or by stroma cells, and it can exert either pro- or antitumorigenic effects according to the cell type and tumor microenvironment. Thus, targeting OPN for therapeutic purposes needs to take into account the heterogeneous functions of the multiple OPN forms with regard to cancer formation and progression. In this review, we will describe the role of systemic, tumor-derived, and stroma-derived OPN, highlighting its pivotal role at the crossroads of inflammation and tumor progression.
Published: 2017
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29. Osteopontin in the Cerebrospinal Fluid of Patients with Severe Aneurysmal Subarachnoid Hemorrhage

Author: Maria Giulia Abate, Lorenza Moretto, Ilaria Licari, Teresa Esposito, Lorenzo Capuano, Carlo Olivieri, Arnaldo Benech, Matteo Brucoli, Gian Carlo Avanzi, Gianmaria Cammarota, Umberto Dianzani, Nausicaa Clemente, Gabriele Panzarasa, Giuseppe Citerio, Fabio Carfagna, Giuseppe Cappellano, Francesco Della Corte, and Rosanna Vaschetto
Subjects: osteopontin, subarachnoid hemorrhage, cerebrospinal fluid, inflammation, biomarker, Cytology, QH573-671
Abstract: Aneurysmal subarachnoid hemorrhage (SAH) is associated with high morbidity and mortality. In SAH patients, plasma osteopontin (OPN) has been shown to independently predict poor outcome. The aim of the study is to investigate, in a selected population with severe SAH, OPN time course in cerebrospinal fluid (CSF) and plasma during the first week after aneurism rupture, and OPN prognostic value. We included 44 patients with the following criteria: (1) age 18 and 80 years, (2) diagnosis of SAH from cerebral aneurysm rupture, (3) insertion of external ventricular drain. Plasma and CSF were sampled at day 1, 4, and 8. OPN levels, in CSF and plasma, displayed a weak correlation on day 1 and were higher, in CSF, in all time points. Only in poor prognosis patients, OPN levels in CSF significantly increased at day 4 and day 8. Plasma OPN at day 1 and 4 was predictor of poor outcome. In conclusion, plasma and CSF OPN displays a weak correlation, on day 1. The higher levels of OPN found in the CSF compared to plasma, suggest OPN production within the CNS after SAH. Furthermore, plasma OPN, at day 1 and 4, seems to be an independent predictor of poor outcome.
Published: 2019
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30. The Role of Osteopontin as a Diagnostic and Prognostic Biomarker in Sepsis and Septic Shock

Author: Luigi Mario Castello, Marco Baldrighi, Luca Molinari, Livia Salmi, Vincenzo Cantaluppi, Rosanna Vaschetto, Greta Zunino, Marco Quaglia, Mattia Bellan, Francesco Gavelli, Paolo Navalesi, Gian Carlo Avanzi, and Annalisa Chiocchetti
Subjects: Osteopontin, biomarkers, sepsis, Emergency Department, diagnosis, risk stratification, prognosis, Cytology, QH573-671
Abstract: Sepsis is a life-threatening organ dysfunction caused by a dysregulated host-response to infections. Osteopontin (OPN) is an extracellular matrix protein involved in the inflammatory response. Our aim was to evaluate the diagnostic and prognostic performance in sepsis of a single OPN determination in the Emergency Department (ED). We conducted a single-centre prospective observational study in an Italian ED where we enrolled 102 consecutive patients presenting with suspected infection and qSOFA ≥ 2. OPN plasma concentration was found to be an independent predictor of sepsis (OR = 1.020, 95% CI 1.002⁻1.039, p = 0.031) and the diagnostic receiver operating characteristic (ROC) curve resulted in an area under the curve (AUC) of 0.878. OPN levels were positively correlated to plasma creatinine (r = 0.401 with p = 0.0001), but this relation was not explained by the development of acute kidney injury (AKI), since no difference was found in OPN concentration between AKI and non-AKI patients. The analysis of 30-days mortality showed no significant difference in OPN levels between alive and dead patients (p = 0.482). In conclusion, a single determination of OPN concentration helped to identify patients with sepsis in the ED, but it was not able to predict poor prognosis in our cohort of patients.
Published: 2019
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31. Analysis of some sepsis markers: C-reactive protein, Procalcitonin, Osteopontin and suPAR

Author: Ilaria Crespi, Vesselina Kroumova, Elena Grossini, Maria Giuseppina Pellò, Marzia Tozzini, Giacomo Fortina, Silvia Valsecchi, Rosanna Vaschetto, Francesco Della Corte, and Annalisa Chiocchietti
Subjects: Sepsis, C-rective Protein, Procalcitonin, Osteopontin, suPAR, Microbiology, QR1-502
Abstract: Sepsis appears to be due to an uncontrolled pro and anti-inflammatory response leading to organ dysfunction until shock and death.Accuracy of diagnosis and appropriate treatment affect the outcome. Aim of the study was to investigate if the levels of Osteopontin (OPN) and Soluble Urokinase-type Plasminoge Activator Receptor (suPAR) might be early markers of sepsis and if these markers play a role in predicting the progression to septic shock. Methods:The levels of OPN, suPAR, C-reactive protein (CRP) and procalcitonin (PCT) were measured in patients at higher risk of infection. The samples were collected from the day of admission for the following fifteenth day. During recovery Sistemic Inflammatory Response Syndrome (SIRS) criteria, blood chemistry data, blood gas- analysis, lactate and diuresis were collected. Microbiological culture were performed according to the clinical condition. Results: 29 patients were enrolled in the study, including 14 subjects with positive blood cultures.The values of OPN, PCT, suPAR and CRP were significantly increased in patients with positive blood cultures than those with negative blood cultures.Analysing changes of the levels of OPN, suPAR, PCT and CRP in patients with septic shock, the values of OPN increased in advance to the clinical diagnosis of septic shock, while the values of suPAR and PCT slight delay compared to those OPN.The levels of CRP were independent from the onset of septic shock state. Conclusions: These preliminary data suggest that Osteopontin and suPAR can be used as early markers of sepsis and might be useful in monitoring of septic outcome to predict a possible evolution to septic shock.
Published: 2010
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32. Weaning from mechanical ventilation in intensive care units across 50 countries (WEAN SAFE): a multicentre, prospective, observational cohort study

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

33. Multicentre observational study on practice of prehospital management of hypotensive trauma patients: the SPITFIRE study protocol

Author: Tartaglione, Marco, Carenzo, Luca, Gamberini, Lorenzo, Lupi, Cristian, Giugni, Aimone, Mazzoli, Carlo Alberto, Chiarini, Valentina, Cavagna, Silvia, Allegri, Davide, Holcomb, John B, Lockey, David, Sbrana, Giovanni, Gordini, Giovanni, Coniglio, Carlo, SPITFIRE Study Collaborators: Luca Montagnani, Andrea Caglià, Jacopo Pernechele, Andrea Mina, Simona Cavallo, Roberto Vacca, Roberto Gioachin, Valeria Bonato, Claudia Monge, Paolo Frisoni, Luca Nicora, Giovanna Zilio, Cristina Barbarino, Andrea Paoli, Giacomo Magagnotti, Andrea Spagna, Alberto Trincanato, Francesca Verginella, Marta Pescolderung, Stefania Armani, Adriano Valerio, Giulio Desiderio, Edoardo Picetti, Michela Ciminello, Christian Tosato, Yuri Ferrara, Stefano Barbadori, Silvia Pini, Andrea Vignali, Alberto Baratta, Davide Durì, Calogero Centonze, Matteo Ciccolini, Alessandra Spasiano, Tommaso Marzano, Guido Gambetti, Domenico Minniti, Michela Rauseo, Gilda Cinnella, Tiziana Cena, Rosanna Vaschetto, Giacomo Iapichino, Tobias Gauss, Andrea Cortegiani, Fabio Genco, Antonio Iacono, Maria Teresa Strano, Annalisa Deiana, Marco Vidili, Massimiliano Carta, Alessio Ficarella, Flavia Baccari, Tartaglione, Marco, Carenzo, Luca, Gamberini, Lorenzo, Lupi, Cristian, Giugni, Aimone, Mazzoli, Carlo Alberto, Chiarini, Valentina, Cavagna, Silvia, Allegri, Davide, Holcomb, John B, Lockey, David, Sbrana, Giovanni, Gordini, Giovanni, Coniglio, Carlo, and SPITFIRE Study Collaborators: Luca Montagnani, Andrea Caglià, Jacopo Pernechele, Andrea Mina, Simona Cavallo, Roberto Vacca, Roberto Gioachin, Valeria Bonato, Claudia Monge, Paolo Frisoni, Luca Nicora, Giovanna Zilio, Cristina Barbarino, Andrea Paoli, Giacomo Magagnotti, Andrea Spagna, Alberto Trincanato, Francesca Verginella, Marta Pescolderung, Stefania Armani, Adriano Valerio, Giulio Desiderio, Edoardo Picetti, Michela Ciminello, Christian Tosato, Yuri Ferrara, Stefano Barbadori, Silvia Pini, Andrea Vignali, Alberto Baratta, Davide Durì, Calogero Centonze, Matteo Ciccolini, Alessandra Spasiano, Tommaso Marzano, Guido Gambetti, Domenico Minniti, Michela Rauseo, Gilda Cinnella, Tiziana Cena, Rosanna Vaschetto, Giacomo Iapichino, Tobias Gauss, Andrea Cortegiani, Fabio Genco, Antonio Iacono, Maria Teresa Strano, Annalisa Deiana, Marco Vidili, Massimiliano Carta, Alessio Ficarella, Flavia Baccari
Subjects: Emergency Medical Services, Adolescent, accident &amp, Hemorrhage, General Medicine, Shock, Hemorrhagic, intensive &amp, critical care, Observational Studies as Topic, emergency medicine, trauma management, Humans, Multicenter Studies as Topic, Prospective Studies, Hypotension
Abstract: IntroductionMajor haemorrhage after injury is the leading cause of preventable death for trauma patients. Recent advancements in trauma care suggest damage control resuscitation (DCR) should start in the prehospital phase following major trauma. In Italy, Helicopter Emergency Medical Services (HEMS) assist the most complex injuries and deliver the most advanced interventions including DCR. The effect size of DCR delivered prehospitally on survival remains however unclear.Methods and analysisThis is an investigator-initiated, large, national, prospective, observational cohort study aiming to recruit >500 patients in haemorrhagic shock after major trauma. We aim at describing the current practice of hypotensive trauma management as well as propose the creation of a national registry of patients with haemorrhagic shock. Primary objective: the exploration of the effect size of the variation in clinical practice on the mortality of hypotensive trauma patients. The primary outcome measure will be 24 hours, 7-day and 30-day mortality. Secondary outcomes include: association of prehospital factors and survival from injury to hospital admission, hospital length of stay, prehospital and in-hospital complications, hospital outcomes; use of prehospital ultrasound; association of prehospital factors and volume of first 24-hours blood product administration and evaluation of the prevalence of use, appropriateness, haemodynamic, metabolic and effects on mortality of prehospital blood transfusions. Inclusion criteria: age >18 years, traumatic injury attended by a HEMS team including a physician, a systolic blood pressure Ethics and disseminationThe study has been approved by the Ethics committee ‘Comitato Etico di Area Vasta Emilia Centro’. Data will be disseminated to the scientific community by abstracts submitted to international conferences and by original articles submitted to peer-reviewed journals.Trial registration numberNCT04760977.
Published: 2022

34. Intraoperative protective ventilation in patients undergoing major neurosurgical interventions: a randomized clinical trial

Author: Fabrizio Dellapiazza, Federico Longhini, Eugenio Garofalo, Petra Konrad, Rosanna Vaschetto, Paolo Navalesi, Laura Pasin, Paolo Murabito, Marcus J. Schultz, Claudia Montagnini, Gianmaria Cammarota, Valentina Rondi, Andrea Bruni, Corrado Pelaia, Intensive Care Medicine, ACS - Pulmonary hypertension & thrombosis, AII - Inflammatory diseases, ACS - Diabetes & metabolism, and ACS - Microcirculation
Subjects: Adult, Lung Diseases, Male, medicine.medical_specialty, Respiratory rate, medicine.medical_treatment, Neurosurgery, Pilot Projects, Neurosurgical Procedures, law.invention, Hospitals, University, Positive-Pressure Respiration, 03 medical and health sciences, Postoperative Complications, Mechanical ventilation, 0302 clinical medicine, Randomized controlled trial, Anesthesiology, 030202 anesthesiology, law, Humans, Medicine, Intubation, RD78.3-87.3, Adverse effect, Aged, Intraoperative Care, Postoperative pulmonary complications, business.industry, Research, Length of Stay, Middle Aged, Respiration, Artificial, Intensive care unit, Hospitalization, Clinical trial, Intensive Care Units, Anesthesiology and Pain Medicine, Italy, Anesthesia, Female, business, 030217 neurology & neurosurgery
Abstract: Background Post-operative pulmonary complications (PPC) can develop in up to 13% of patients undergoing neurosurgical procedures and may adversely affect clinical outcome. The use of intraoperative lung protective ventilation (LPV) strategies, usually including the use of a low Vt, low PEEP and low plateau pressure, seem to reduce the risk of PPC and are strongly recommended in almost all surgical procedures. Nonetheless, feasibility of LPV strategies in neurosurgical patients are still debated because the use of low Vt during LPV might result in hypercapnia with detrimental effects on cerebrovascular physiology. Aim of our study was to determine whether LPV strategies would be feasible compared with a control group in adult patients undergoing cranial or spinal surgery. Methods This single-centre, pilot randomized clinical trial was conducted at the University Hospital “Maggiore della Carità” (Novara, Italy). Adult patients undergoing major cerebral or spinal neurosurgical interventions with risk index for pulmonary post-operative complications > 2 and not expected to need post-operative intensive care unit (ICU) admission were considered eligible. Patients were randomly assigned to either LPV (Vt = 6 ml/kg of ideal body weight (IBW), respiratory rate initially set at 16 breaths/min, PEEP at 5 cmH2O and application of a recruitment manoeuvre (RM) immediately after intubation and at every disconnection from the ventilator) or control treatment (Vt = 10 ml/kg of IBW, respiratory rate initially set at 6–8 breaths/min, no PEEP and no RM). Primary outcomes of the study were intraoperative adverse events, the level of cerebral tension at dura opening and the intraoperative control of PaCO2. Secondary outcomes were the rate of pulmonary and extrapulmonary complications, the number of unplanned ICU admissions, ICU and hospital lengths of stay and mortality. Results A total of 60 patients, 30 for each group, were randomized. During brain surgery, the number of episodes of intraoperative hypercapnia and grade of cerebral tension were similar between patients randomized to receive control or LPV strategies. No difference in the rate of intraoperative adverse events was found between groups. The rate of postoperative pulmonary and extrapulmonary complications and major clinical outcomes were similar between groups. Conclusions LPV strategies in patients undergoing major neurosurgical intervention are feasible. Larger clinical trials are needed to assess their role in postoperative clinical outcome improvements. Trial registration registered on the Australian New Zealand Clinical Trial Registry (www.anzctr.org.au), registration number ACTRN12615000707561.
Published: 2022

35. One-Year Follow up of Noninvasive Respiratory Support in General Wards

Author: Francesca Moretto, Martina Fracazzini, Federico Verdina, Daniela Ferrante, Sara Baino, Francesca Grossi, Luigi Castello, Gianmaria Cammarota, Piero Balbo, Pier Paolo Sainaghi, Mauro Campanini, Mario Pirisi, Giuseppe Patti, Alberto Dal Molin, Francesco Della Corte, Paolo Navalesi, and Rosanna Vaschetto
Subjects: Pulmonary and Respiratory Medicine, General Medicine, Critical Care and Intensive Care Medicine
Abstract: Noninvasive respiratory support (NRS) has been used to treat acute respiratory failure outside the ICU, but existing data have left many knowledge gaps for managing NRS in general wards. The primary objective of this study was to describe indications, duration of treatment, and outcomes of subjects treated with NRS outside the ICU. The secondary objective was to compare outcomes based on age80 or ≥ 80 y.This retrospective observational study was conducted at Maggiore della Carità University Hospital in Novara, Italy, and included all patients treated with noninvasive ventilation (NIV) or CPAP outside the ICU from November 2017 to October 2018, with 1 year of follow-up.Of the 570 treatments performed, 383 subjects were analyzed, 136 NIV and 247 CPAP. Subjects' median (interquartile range [IQR]) age was 79 (72-85) y, and the main diagnoses of respiratory failure were cardiogenic pulmonary edema in 128 subjects (33%), pneumonia in 99 (26%), and COPD exacerbation in 52 (14%), with a median (IQR) treatment duration of 38 (16-74) h. Rapid response team visits lasted a median (IQR) 3 (2-6) d. Interface-related pressure lesions occurred in 13% of the subjects, in no case leading to definitive treatment discontinuation. Compared with the subjects ≥ 80 y old, the younger subjects had a median (IQR) longer hospitalization (16 [10-24] d vs 13 [9-20] d;In a real-life setting outside the ICU, NIV and CPAP managed by a rapid response team with a daily visit in collaboration with ward staff highly experienced in NRS allowed us to treat the subjects without major complications. Post-discharge 1-year mortality was higher in the subjects ≥ 80 y old treated with NIV for acute hypercapnic respiratory failure.
Published: 2022

36. The Role of Lung Ultrasound Monitoring in Early Detection of Ventilator-Associated Pneumonia in COVID-19 Patients: A Retrospective Observational Study

Author: Silvia Mongodi, Nello De Vita, Giulia Salve, Silvia Bonaiti, Francesco Daverio, Margherita Cavagnino, Gilda Siano, Alessandro Amatu, Giuseppe Maggio, Valeria Musella, Catherine Klersy, Rosanna Vaschetto, Belaid Bouhemad, and Francesco Mojoli
Subjects: lung ultrasound, lung monitoring, ventilator-associated pneumonia, nosocomial infection, arborescent air bronchogram, lung ultrasound score, aeration quantification, aeration monitoring, General Medicine, respiratory tract diseases
Abstract: Specific lung ultrasound signs combined with clinical parameters allow for early diagnosis of ventilator-associated pneumonia in the general ICU population. This retrospective cohort study aimed to determine the accuracy of lung ultrasound monitoring for ventilator-associated pneumonia diagnosis in COVID-19 patients. Clinical (i.e., clinical pulmonary infection score) and ultrasound (i.e., presence of consolidation and a dynamic linear–arborescent air bronchogram, lung ultrasound score, ventilator-associated lung ultrasound score) data were collected on the day of the microbiological sample (pneumonia-day) and 48 h before (baseline) on 55 bronchoalveolar lavages of 33 mechanically-ventilated COVID-19 patients who were monitored daily with lung ultrasounds. A total of 26 samples in 23 patients were positive for ventilator-associated pneumonia (pneumonia cases). The onset of a dynamic linear–arborescent air bronchogram was 100% specific for ventilator-associated pneumonia. The ventilator-associated lung ultrasound score was higher in pneumonia-cases (2.5 (IQR 1.0 to 4.0) vs. 1.0 (IQR 1.0 to 1.0); p < 0.001); the lung ultrasound score increased from baseline in pneumonia-cases only (3.5 (IQR 2.0 to 6.0) vs. −1.0 (IQR −2.0 to 1.0); p = 0.0001). The area under the curve for clinical parameters, ventilator-associated pneumonia lung ultrasound score, and lung ultrasound score variations were 0.472, 0.716, and 0.800, respectively. A newly appeared dynamic linear–arborescent air bronchogram is highly specific for ventilator-associated pneumonia in COVID-19 patients. A high ventilator-associated pneumonia lung ultrasound score (or an increase in the lung ultrasound score) orients to ventilator-associated pneumonia.
Published: 2022
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37. Delayed Neurological Sequelae Successfully Treated with Adjuvant, Prolonged Hyperbaric Oxygen Therapy: Review and Case Report

Author: Luca Martani, Andrea Giovanniello, Gerardo Bosco, Luca Cantadori, Francesca Calissi, Dany Furfaro, Massimo Pedrazzini, Rosanna Vaschetto, Enrico Mario Camporesi, and Matteo Paganini
Subjects: Oxygen, Carbon Monoxide Poisoning, Hyperbaric Oxygenation, Health, Toxicology and Mutagenesis, Public Health, Environmental and Occupational Health, Disease Progression, Oxygen Inhalation Therapy, Humans, hyperbaric oxygen treatment, carbon monoxide
Abstract: Carbon Monoxide (CO) intoxication is still a leading cause of mortality and morbidity in many countries. Due to the problematic detection in the environment and subtle symptoms, CO intoxication usually goes unrecognized, and both normobaric and hyperbaric oxygen (HBO) treatments are frequently administered with delay. Current knowledge is mainly focused on acute intoxication, while Delayed Neurological Sequelae (DNS) are neglected, especially their treatment. This work details the cases of two patients presenting a few weeks after CO intoxication with severe neurological impairment and a characteristic diffused demyelination at the brain magnetic resonance imaging, posing the diagnosis of DNS. After prolonged treatment with hyperbaric oxygen, combined with intravenous corticosteroids and rehabilitation, the clinical and radiological features of DNS disappeared, and the patients’ neurological status returned to normal. Such rare cases should reinforce a thorough clinical follow-up for CO intoxication victims and promote high-quality studies.
Published: 2022

38. 'War to the knife' against thromboinflammation to protect endothelial function of COVID-19 patients

Author: Marco Quaglia, Mario Pirisi, Gian Carlo Avanzi, Pier Paolo Sainaghi, Rosanna Vaschetto, Gabriele Guglielmetti, Piero Stratta, Luigi Mario Castello, Francesco Della Corte, and Vincenzo Cantaluppi
Subjects: Pneumonia, Viral, Complement, Inflammation, 030204 cardiovascular system & hematology, Pharmacology, Critical Care and Intensive Care Medicine, Thrombomodulin, 03 medical and health sciences, Anticoagulation, Plasma, 0302 clinical medicine, Tissue factor pathway inhibitor, Viewpoint, medicine, Humans, Endothelial dysfunction, Pandemics, 030304 developmental biology, 0303 health sciences, Thromboinflammation, business.industry, Heparin, Antithrombin, lcsh:Medical emergencies. Critical care. Intensive care. First aid, Endothelial Cells, COVID-19, Thrombosis, lcsh:RC86-88.9, Extracellular vesicles, medicine.disease, Fresh frozen plasma, medicine.symptom, business, Coronavirus Infections, Protein C, medicine.drug
Abstract: In this viewpoint, we summarize the relevance of thromboinflammation in COVID-19 and discuss potential mechanisms of endothelial injury as a key point for the development of lung and distant organ dysfunction, with a focus on direct viral infection and cytokine-mediated injury. Entanglement between inflammation and coagulation and resistance to heparin provide a rationale to consider other therapeutic approaches in order to preserve endothelial function and limit microthrombosis, especially in severe forms. These strategies include nebulized heparin, N-acetylcysteine, plasma exchange and/or fresh frozen plasma, plasma derivatives to increase the level of endogenous anticoagulants (tissue factor pathway inhibitor, activated protein C, thrombomodulin, antithrombin), dipyridamole, complement blockers, different types of stem cells, and extracellular vesicles. An integrated therapy including these drugs has the potential to improve outcomes in COVID-19.
Published: 2020

39. Predicted Effects of Stopping COVID-19 Lockdown on Italian Hospital Demand

Author: Francesco Della Corte, Consuelo R. Nava, Matteo Paganini, Jordy Bollon, Francesco Barone-Adesi, Rosanna Vaschetto, Nello De Vita, and Luca Ragazzoni
Subjects: 2019-20 coronavirus outbreak, medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), surge capacity, Hospital bed, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), law.invention, 03 medical and health sciences, 0302 clinical medicine, law, Intensive care, 0502 economics and business, Humans, Medicine, 030212 general & internal medicine, Pandemics, intensive care, Health Services Needs and Demand, Surge Capacity, business.industry, Brief Report, pandemic, 05 social sciences, Public Health, Environmental and Occupational Health, COVID-19, Intensive care unit, Hospitals, Confidence interval, Hospitalization, Intensive Care Units, Italy, Quarantine, Emergency medicine, 050211 marketing, business
Abstract: Objectives:Italy has been one of the first countries to implement mitigation measures to curb the coronavirus disease 2019 (COVID-19) pandemic. There is currently a debate on when and how such measures should be loosened. To forecast the demand for hospital intensive care unit (ICU) and non-ICU beds for COVID-19 patients from May to September, we developed 2 models, assuming a gradual easing of restrictions or an intermittent lockdown.Methods:We used a compartmental model to evaluate 2 scenarios: (A) an intermittent lockdown; (B) a gradual relaxation of the lockdown. Predicted ICU and non-ICU demand was compared with the peak in hospital bed use observed in April 2020.Results:Under scenario A, while ICU demand will remain below the peak, the number of non-ICU will substantially rise and will exceed it (133%; 95% confidence interval [CI]: 94-171). Under scenario B, a rise in ICU and non-ICU demand will start in July and will progressively increase over the summer 2020, reaching 95% (95% CI: 71-121) and 237% (95% CI: 191-282) of the April peak.Conclusions:Italian hospital demand is likely to remain high in the next months. If restrictions are reduced, planning for the next several months should consider an increase in health-care resources to maintain surge capacity across the country.
Published: 2020

40. Clinical Outcomes in Patients Aged 80 Years or Older Receiving Non-Invasive Respiratory Support for Hypoxemic Acute Respiratory Failure Consequent to COVID-19

Author: Andrea Vianello, Nello De Vita, Lorenza Scotti, Gabriella Guarnieri, Marco Confalonieri, Valeria Bonato, Beatrice Molena, Carlo Maestrone, Gianluca Airoldi, Carlo Olivieri, Pier Paolo Sainaghi, Federico Lionello, Giovanna Arcaro, Francesco Della Corte, Paolo Navalesi, Rosanna Vaschetto, Vianello, Andrea, De Vita, Nello, Scotti, Lorenza, Guarnieri, Gabriella, Confalonieri, Marco, Bonato, Valeria, Molena, Beatrice, Maestrone, Carlo, Airoldi, Gianluca, Olivieri, Carlo, Paolo Sainaghi, Pier, Lionello, Federico, Arcaro, Giovanna, Della Corte, Francesco, Navalesi, Paolo, and Vaschetto, Rosanna
Subjects: COVID-19, acute respiratory failure, non-invasive respiratory support, octogenarian patients, surgical procedures, operative, technology, industry, and agriculture, General Medicine, equipment and supplies, neoplasms
Abstract: As the clinical outcome of octogenarian patients hospitalised for COVID-19 is very poor, here we assessed the clinical characteristics and outcomes of patients aged 80 year or older hospitalised for COVID-19 receiving non-invasive respiratory support (NIRS). A multicentre, retrospective, observational study was conducted in seven hospitals in Northern Italy. All patients aged ≥80 years with COVID-19 associated hypoxemic acute respiratory failure (hARF) undergoing NIRS between 24 February 2020, and 31 March 2021, were included. Out of 252 study participants, 156 (61.9%) and 163 (64.6%) died during hospital stay and within 90 days from hospital admission, respectively. In this case, 228 (90.5%) patients only received NIRS (NIRS group), while 24 (9.5%) were treated with invasive mechanical ventilation (IMV) after NIRS failure (NIRS+IMV group). In-hospital mortality did not significantly differ between NIRS and NIRS+IMV group (61.0% vs. 70.8%, respectively; p = 0.507), while survival probability at 90 days was significantly higher for NIRS compared to NIRS+IMV patients (0.379 vs. 0.147; p = 0.0025). The outcome of octogenarian patients with COVID-19 receiving NIRS is quite poor. Caution should be used when considering transition from NIRS to IMV after NIRS failure.
Published: 2022

41. High-Flow Versus VenturiMask Oxygen Therapy to Prevent Reintubation in Hypoxemic Patients after Extubation: A Multicenter Randomized Clinical Trial

Author: Salvatore Maurizio Maggiore, Samir Jaber, Domenico Luca Grieco, Jordi Mancebo, Spyros Zakynthinos, Alexandre Demoule, Jean-Damien Ricard, Paolo Navalesi, Rosanna Vaschetto, Sami Hraiech, Kada Klouche, Jean-Pierre Frat, Virginie Lemiale, Vito Fanelli, Gerald Chanques, Daniele Natalini, Eleni Ischaki, Danielle Reuter, Indalecio Morán, Béatrice La Combe, Federico Longhini, Andrea De Gaetano, V. Marco Ranieri, Laurent J. Brochard, Massimo Antonelli, Yassir Aarab, Elie Azoulay, Fouad Belafia, Guillaume Berquier, Matthieu Conseil, Andrea Costamagna, Laurence Dangers, Audrey De Jong, Julie Delemazure, Francesco Della Corte, Ivan Dell’Atti, Stèphane Gaudry, Francesca Grossi, Giovanni Carmine Iovino, Sylvain Jean-Baptiste, Mohammed Laissi, Romaric Larcher, Matthieu Le Meur, Clèment Leclaire, Paula Andrea Lopez, Sotirios M. Malachias, Marilena Matteo, Julienne Mayaux, Jonathan Messika, Clement Monet, Elise Morawiec, Laurent Papazian, Francisco Parrilla, Laura Platon, Damien Roux, Maria Teresa Santantonio, Juan Carlos Suarez, Eloisa Sofia Tanzarella, Flavia Toni, Luigi Vetrugno, University 'G. d'Annunzio' of Chieti-Pescara [Chieti], SS Annunziata Hospital, Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Hôpital Saint Eloi (CHRU Montpellier), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Università cattolica del Sacro Cuore = Catholic University of the Sacred Heart [Roma] (Unicatt), Hospital de la Santa Creu i Sant Pau, National and Kapodistrian University of Athens (NKUA), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Neurophysiologie Respiratoire Expérimentale et Clinique (UMRS 1158), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Hôpital Louis Mourier - AP-HP [Colombes], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Università degli Studi di Padova = University of Padua (Unipd), Università degli Studi del Piemonte Orientale - Amedeo Avogadro (UPO), University Hospital 'Maggiore della Carità' [Novara, Italy], Hôpital Nord [CHU - APHM], Centre d'études et de recherche sur les services de santé et la qualité de vie (CEReSS), Aix Marseille Université (AMU), Hôpital Lapeyronie [Montpellier] (CHU), Centre hospitalier universitaire de Poitiers (CHU Poitiers), CIC - Poitiers, Université de Poitiers-Centre hospitalier universitaire de Poitiers (CHU Poitiers)-Direction Générale de l'Organisation des Soins (DGOS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hopital Saint-Louis [AP-HP] (AP-HP), Università degli studi di Torino = University of Turin (UNITO), Azienda Ospedalerio - Universitaria Città della Salute e della Scienza di Torino = University Hospital Città della Salute e della Scienza di Torino, Sorbonne Université (SU), Università degli Studi 'Magna Graecia' di Catanzaro = University of Catanzaro (UMG), Instituto di Analisi dei Sistemi ed Informatica, CNR (IASI), University of Bologna/Università di Bologna, St. Michael's Hospital, and University of Toronto
Subjects: Pulmonary and Respiratory Medicine, acute respiratory failure, [SDV]Life Sciences [q-bio], weaning, Oxygen Inhalation Therapy, noninvasive ventilation, oxygen therapy, Respiratory failure, High-flow nasal oxygen, Critical Care and Intensive Care Medicine, Oxygen, Mechanical ventilation, Noninvasive ventilation, Weaning, nasal high-flow oxygen, Settore MED/41 - ANESTESIOLOGIA, Airway Extubation, Intubation, Intratracheal, Humans, Respiratory Insufficiency
Abstract: International audience; Rationale: When compared with VenturiMask after extubation, high-flow nasal oxygen provides physiological advantages. Objectives: To establish whether high-flow oxygen prevents endotracheal reintubation in hypoxemic patients after extubation, compared with VenturiMask. Methods: In this multicenter randomized trial, 494 patients exhibiting PaO2:FiO2 ratio ⩽ 300 mm Hg after extubation were randomly assigned to receive high-flow or VenturiMask oxygen, with the possibility to apply rescue noninvasive ventilation before reintubation. High-flow use in the VenturiMask group was not permitted. Measurements and Main Results: The primary outcome was the rate of reintubation within 72 hours according to predefined criteria, which were validated a posteriori by an independent adjudication committee. Main secondary outcomes included reintubation rate at 28 days and the need for rescue noninvasive ventilation according to predefined criteria. After intubation criteria validation (n = 492 patients), 32 patients (13%) in the high-flow group and 27 patients (11%) in the VenturiMask group required reintubation at 72 hours (unadjusted odds ratio, 1.26 [95% confidence interval (CI), 0.70-2.26]; P = 0.49). At 28 days, the rate of reintubation was 21% in the high-flow group and 23% in the VenturiMask group (adjusted hazard ratio, 0.89 [95% CI, 0.60-1.31]; P = 0.55). The need for rescue noninvasive ventilation was significantly lower in the high-flow group than in the VenturiMask group: at 72 hours, 8% versus 17% (adjusted hazard ratio, 0.39 [95% CI, 0.22-0.71]; P = 0.002) and at 28 days, 12% versus 21% (adjusted hazard ratio, 0.52 [95% CI, 0.32-0.83]; P = 0.007). Conclusions: Reintubation rate did not significantly differ between patients treated with VenturiMask or high-flow oxygen after extubation. High-flow oxygen yielded less frequent use of rescue noninvasive ventilation. Clinical trial registered with www.clinicaltrials.gov (NCT02107183).
Published: 2022

42. Bronchoscopy during COVID-19 pandemic, ventilatory strategies and procedure measures

Author: Paolo Donato, Rosanna Vaschetto, Giuseppe Failla, Piero Candoli, Nicola Facciolongo, Alessio Mattei, Teresa Renda, Mario Salio, Raffaele Scala, Thomas Galasso, Roberto Piro, Paolo Solidoro, Michele Mondoni, Filippo Patrucco, Giovanni Ferrari, and Piero Emilio Balbo
Subjects: Bronchoscopy, Cannula, Continuous Positive Airway Pressure, Humans, Infectious Disease Transmission, Patient-to-Professional, Pandemics, Respiratory Insufficiency, SARS-CoV-2, COVID-19, Noninvasive Ventilation, Tracheostomy, medicine.medical_specialty, Infectious Disease Transmission, Sedation, medicine.medical_treatment, Atelectasis, medicine.disease_cause, Patient-to-Professional, medicine, Continuous positive airway pressure, Intensive care medicine, medicine.diagnostic_test, business.industry, General Medicine, medicine.disease, Prone position, Breathing, medicine.symptom, business, Airway, Nasal cannula
Abstract: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has changed bronchoscopy practices worldwide. Bronchoscopy is a high-risk aerosol-generating procedure with a potential for direct SARS-CoV-2 exposure and hospital-acquired infection. Current guidelines about personal protective equipment and environment considerations represent key competencies to minimize droplets dispersion and reduce the risk of transmission. Different measures should be put in field based on setting, patient's clinical characteristics, urgency and indications of bronchoscopy. The use of this technique in SARS-CoV-2 patients is reported primarily for removal of airway plugs and for obtaining microbiological culture samples. In mechanically ventilated patients with SARS-CoV-2, bronchoscopy is commonly used to manage complications such as hemoptysis, atelectasis or lung collapse when prone positioning, physiotherapy or recruitment maneuvers have failed. Further indications are represented by assistance during percutaneous tracheostomy. Continuous positive airway pressure, non-invasive ventilation support and high flow nasal cannula oxygen are frequently used in patient affected by Coronavirus Disease-2019 (COVID-19): management of patients' airways and ventilation strategies differs from bronchoscopy indications, patient's clinical status and in course or required ventilatory support. Sedation is usually administered by the pulmonologist (performing the bronchoscopy) or by the anesthetist depending on the complexity of the procedure and the level of sedation required. Finally, elective bronchoscopy for diagnostic indications during COVID-19 pandemic should be carried on respecting rigid standards which allow to minimize potential viral transmission, independently from patient's COVID-19 status. This narrative review aims to evaluate the indications, procedural measures and ventilatory strategies of bronchoscopy performed in different settings during COVID-19 pandemic.
Published: 2021

43. Evolution Over Time of Ventilatory Management and Outcome of Patients With Neurologic Disease

Author: Tejerina E. E., Pelosi P., Robba C., Penuelas O., Muriel A., Barrios D., Frutos-Vivar F., Raymondos K., Du B., Thille A. W., Rios F., Gonzalez M., Del-Sorbo L., Marin M. D. C., Valle Pinheiro B., Soares M. A., Nin N., Maggiore S. M., Bersten A., Amin P., Cakar N., Young Suh G., Abroug F., Jibaja M., Matamis D., Ali Zeggwagh A., Sutherasan Y., Anzueto A., Esteban A, Fernando Ríos, Damian Violi, Marisol Rodríguez-Goñi, Roger Lamoglie, Fernando Villarejo, Norberto Tiribelli, Santiago Ilutovich, Matías Brizuela, Mariana Monllau, Fernando Saldarini, Silvina Borello, Alberto Marino, Mauricio Vinzio, Karina Bonasegla, Julián Hernández, María Belén Yapur, María Eugenia González, Sebastián E Mare, Judith Sagardía, Marco Bezzi, Cecilia Pereyra, Julian Strati, Daniel Vargas, Claudia Diaz, Pablo Gómez, Marcelo Palavecino, Graciela Elizabeth, Aguilera García, M Eugenia, Luis Pablo Cardonnet, Lisandro Betttini, Hernán Nuñez, Lucas Vallejo, Fernando Fernández, Jorge Arroyo, Daniel Duarte, Gerardo Filippa, Cayetano Galetti, Hernan Nunia, Fernando Lambert, Elisa Estenssoro, Marina Busico, Javier Horacio Álvarez, Alejandro Raimondi, Gustavo Badariotti, Martín Lugaro, Fernando Lipovestky, Alan Javier Zazu, Hugo Capponcelli, Patricia Vogl, Cristina Orlandi, Alejandro Gómez, Gustavo Jannello, Alejandro Risso, Leticia Rapetti, Guillermo Chiappero, Juan Domingo Fernández, Rodrigo E Gómez-Paz, Marcos Juan Zec, Pascual Valdez, Jorgelina Guyon, Ariel Chena, Sergio Lasdica, Martin Deheza, Schimdt Alejandra, Francisco Criado, Norma Beatriz Márquez, Pablo Desmery, José Luis Scapellato, Gonzalo Javier Ríos, Cristian Casabella, Jasmin Board, Andrew Davies, Andrew Bersten, Elisha Matheson, Amy Waters, John Santamaria, Jennifer Holmes, Cartan Costello, Manoj K Saxena, John Myburgh, Ellen Kinkel, Forbes McGain, Claire Cattigan, Allison Bone, Ian Seppelt, Leonie Weisbrodt, Cheryl Cuzner, Christopher MacIsaac, Deborah Barge, Tania Caf, Cameron Knott, Graeme Duke, Imogen Mitchell, Helen Rodgers, Rachel Whyte, Elisha Fulton, Alistair Nichol, Hergen Buscher, Priya Nair, Claire Reynolds, Simon J G Hockley, Ian Moore, Katherine Davidson, David Milliss, Raju Pusapati, Helen Wong, Jason Fletcher, Julie Smith, Paul Goldrick, Dianne Stephens, Jane Thomas, Anders Aneman, Sutrisno Gunawan, Tom Cowlam, George Lukas, Rick McAllister, Minka Springham, Joanne Sutton, Jeff Presneill, Tony Sutherland, Dianne Hill, Howard Connor, Jenny Dennett, Tim Coles, Freddy Sandy, Sando Chavarria, Marcelo Choque, Ronald Pairumani, Juan Guerra, Marco Antônio Soares Reis, José Carlos Versiani, Eduardo Fonseca Sad, Maria Aparecida Braga, Dinalva Aparecida Gomes, Fernando Antônio Botoni, Maurício Meireles Góes, Frederico Costa Val Barros, Rogério de Castro Pereira, Hugo Urbano, Valéria de Carvalho Magela, Aline Camile Yehia, Bruno Bonaccorsi Fernandino, Marco Antônio Ribeiro Leão, Rovílson Lara, Rubens Altair Amaral de Pádua, Janine Dias Alves, Aloísio Marques do Nascimento, Bruno do Valle Pinheiro, Carlos Alberto Studart Gomes, Marcelo Alcântara Holanda, Frederico Rodrigues Anselmo, Niall Ferguson, Neill Adhikari, Robert Fowler, Cheromi Sittambalam, Mehar-Un-Nisa Raja, Nicole Marinoff, Lauralyn McIntryre, Shawna Reddie, Laura Jones, Irene Watpool, Jeffrey Singh, Madison Dennis, Andrea Matte, Marc Lipkus, Ryan Albert, Andrew Steel, Emily Stern, Michael Miletin, Antonio Raso, Robyn Klages, Jan Friedrich, Orla Smith, Laura Wilson, Deborah Cook, Mark Bailey, Sangeeta Mehta, Stephen Lapinsky, Hannah Mathers, Cheryl Ethier, Stephanie Lubchansky, Samer Haj-Bakri, Dietrich Henzler, Lisa Julien, Luis Soto-Román, Juan Carlos Maurelia, César Antonio Maquilon, Luis Soto-Germani, Bin Du, Yan Kang, Bo Wang, Fachun Zhou, Fang Xu, Haibo Qiu, Yi Yang, Qingyuan Zhan, Bing Sun, Zhenjie Hu, Bin Yu, Xi Zhu, Yu Bai, Gang Li, Yi Li, Geng Zhang, Jianbiao Meng, Xiaobo Huang, Hong Pu, Daxing Yu, Chuanyun Qian, Wei Zhang, Yongjie Yin, Debiao Song, Yunxuan Yue, Zhengxuan Lv, Chengmin Yu, Qunmei Yao, Xue Wang, Yuan Xu, Wei He, Mian Chen, Zhihua Hu, Dongpo Jiang, Jian Huang, Wei Yu, Juanxian Gu, Yangong Chao, Zhixiang Li, Zhicheng Zhang, Wanxia Li, Zhenyang He, Jianguo Li, Chang Liu, Tiehe Qin, Shouhong Wang, Feng Li, Jun Jin, Jianhong Fu, Hongyang Xu, Hongyuan Lin, Jianying Guo, Yalin Liu, Jinghua Wang, Maoqin Li, Jiaqiong Li, Lei Chen, Qing Song, Liang Pan, Xianyao Wan, Jiuzhi Zhang, Weihai Yao, Yuhong Guo, Pang Wing Yan, Kelly Choy, Kwan Ming Chit, Patricia Leung, Chau Chin Man, Marco González, Ricardo Buitrago, Marcela Granados, Guillermo Ortiz, Cesar Enciso, Mario Gómez, Bladimir Alejandro Gil, Juan Pablo Sedano, Luis Fernando Castro Castro, Carlo Alberto Acosta, Marco Gonzalez, Francisco Molina, Camilo Pizarro, Mario Villabon, Carmelo Dueñas, Carlos Andrés Díaz, Nelson Fonseca, Rubén Camargo, Juan David Uribe, Hans-Henrik Bülow, Simona Beniczky, Jens Brushoj, Mikkel Præst, Birgitte Viebaek, Sine Wichman, Anette Mortensen, Susanne Andi Iversen, Bo Broberg, Edgard Luna, Manuel Jibaja, Leonardo Pazmiño, Katty Trelles, Fabricio Picoita, Gustavo Paredes, Vanesa Ramírez, Guillermo Falconí, Cristian Cevallos, Boris Villamagua, Marco Escobar, Freddy Sánchez, Miguel Llano, Miguel Lazcano, Ramiro Puetate, José Miguel Guerrero, Mijail Játiva, Myriam Montalvo, Franklin Villegas, Luis González Zambrano, Ronnie Mantilla, Gina Quinde, Andrea Gimenez, Luis Gonzalez Mosquera, Henry Caballero, María Fernanda García, Marcelo Ochoa, Soraya Puertas, Jackeline Coello, Mario Acosta, Medhat Soliman, Arnaud W Thille, Achille Kouatchet, Alain Mercat, Laurent Brochard, François Collet, Guillaume Marcotte, Pascal Beuret, Jean-Christophe M Richard, Gaëtan Bedunaeu, Pierre-Gildas Guitard, Fabien Soulis, Frédéric Bellec, Philippe Berger, Dorothée Carpentier, Benoit Veber, Salem Ould Zein, Géraldine Dessertaine, C Canevet, Fabien Grelon, Konstantinos Raymondos, Rolf Dembinski, Rolf Rossaint, Steffen Weber-Carstens, Christian Putensen, Maximillian Ragaller, Michael Quintel, Winfried Schubert, Thomas Bein, Heinrich Paulus, Walter Brandt, Lutz Pfeiffer, Silke Frenzel, Thoralf Kerner, P Kruska, Leila Eckholt, Joachim Hartung, Harald Fritz, Monika Holler, Johannes Busch, Andreas Viehöfer, Jens Buettner, Jörn Schlechtweg, Achim Lunkeit, Roland Schneider, Maria Wussow, Nils Marquardt, Christian Frenkel, Falk Hildebrandt, Tumbass Volker, Thomas Lipp, Cezar Mihailescu, Thomas Moellhoff, Thomas Steinke, Oliver Franke, Marcus Ruecker, Markus Schappacher, Steffen Appel, Heinz Kerger, Andreas Schwartz, Jan Dittmann, Jörg Haberkorn, Wolfgang Baier, Walter Seyde, Dimitros Matamis, Eleni Antoniadou, Pertsas Evangelos, Maria Giannakou, Zoltan Szentkereszty, Zsolt Molnar, Pravin Amin, Farhad N Kapadia, Nagarajan Ramakrishnan, Deepak Govil, Anitha Shenoy, Umesh G, Samir Sahu, Sheila Nainan Myatra, Subhash Kumar Todi, Sanjay Dhanuka, Mayur Patel, P Samaddar, Dhruva Chaudhry, Vivek Joshi, Srinivas Samavedam, Ankur Devendra Bhavsar, Prachee Sathe, Sujoy Mukherjee, Salvatore Maurizio Maggiore, Francesco Idone, Federica Antonicelli, Paolo Navalesi, Rosanna Vaschetto, Arianna Boggero, Rosalba Tufano, Michele Iannuzzi, Edoardo De Robertis, Romano Tetamo, Andrea Neville Cracchiolo, Antonio Braschi, Francesco Mojoli, Ilaria Curro', Mirko Belliato, Chiara Verga, Marta Ferrari, Erika Mannelli, Valerio Mangani, Giorgio Tulli, Francesca Frigieri, Armando Pedulla', Monica Rocco, Giorgia Citterio, Di Russo, Gaetano Perchiazzi, Loredana Pitagora, Antonio Pesenti, Michela Bombino, Davide Chiumello, Federica Tallarini, Serena Azzari, Antonina Pigna, Ivano Aprile, Marco Adversi, Antonio Corcione, Marianna Esposito, Annunziata Mattei, Vito Marco Ranieri, Rosario Urbino, Ilaria Maria Mastromauro, Antonino Giarratano, Maurizio Raineri Santi, Ambrogio Sansone, Younsuck Koh, Moo Suk Park, Je Hyeong Kim, Kyung Chan Kim, Hye Sook Choi, Yun Seong Kim, Jin Hwa Lee, Myung-Goo Lee, Won-Yeon Lee, Jin Young An, Gee Young Suh, Ki-Suck Jung, Asisclo J Villagómez Ortiz, César Cruz Lozano, Zalatiel Maycotte Luna, José Francisco López Baca, José Elizalde, Guillermo Cueto Robledo, Mario Alonso Treviño Salinas, Ricardo Martinez Zubieta, Claudia Olvera-Guzman, Marco Montes De Oca, Silvio A Ñamendys-Silva, José Salvador Martínez Cano, Jose Angel Baltazar Torres, Gustavo Morales Muñoz, Antonio Villa Delgado, Javier Ladape Martinez, Amine Ali Zeggwagh, Tarek Dendane, Abderrahim Azzouzi, Ahmed Sbihi, Wajdi Maazouzi, Mourad Amor, Charki Haimeur, Michael A Kuiper, Matty Koopmans, Uli Strauch, Dennis Bergmans, Serge Heines, Sylvia den Boer, Bas M Kors, Peter van der Voort, Paul J Dennesen, Bert Beishuizen, Ingrid van den Hul, Erna Alberts, Harry P P M Gelissen, Eduard Bootsma, Auke Reidinga, Kim Heus, Diane Mackle, Paul Young, Rachael Parke, Eileen Gilder, Jodi Brown, Lynette Newby, Catherine Simmonds, Jan Mehrtens, Seton Henderson, Tony Williams, Judi Tai, Chantal Hogan, Mary La Pine, John Durning, Sheree Gare, Troy Browne, Shirley Nelson, Jennifer Goodson, Julio Osorio, Chabu Coronado, Rollin Roldán Mori, Rosa Luz López Martínez, Adam Mikstacki, Barbara Tamowicz, Rui Moreno, Eduardo Almeida, Joana Silvestre, Heloisa Castro, Irene Aragão, Susana Alves Ferreira, Nelson Barros, Filomena Faria, Carlos André Correia Casado, Fausto Fialho Moura, Paulo Marcal, Ricardo Matos, Edward Nicolayenko, Mikhail Kirov, Andrey Yaroshetskiy, Andrei Piontek, Valery Subbotin, Yaseen Arabi, Olivia Dulfo, Chafrina Marie Olay, Edgardo E Tabhan, Nicolas Nin, Alfonso Muñoz, César Aragón, Ana Villagrá, Ainhoa Rosselló, Joan Maria Raurich, María Garitacelaya, Miguel Ángel González-Gallego, Francisco Ortuño, Miguel Fernández-Vivas, David Freire, Francisco Guerrero, Francisco Manzano, Juan Carlos, Alfredo Padrón, Pedro Rosa, Rafael Morales, Liliana Caipe, Maurizio Bottiroli, José María Nicolás, Marta Ugalde, Javier Ruiz, Lucia Capilla, Guillermo Muñiz, Jesús Sánchez-Ruiz, Javier Cebrián, Begoña Balerdi, Elena Parreño, Alvaro van Bommel, César Pérez-Calvo, Irene Dot, Javier Blanco, Raquel Manzanedo, José J Blanco, Daniel Fontaneda, Raúl González, Javier Díaz Domínguez, Alfonso Moreno, Antonio Reyes, Ian Carrasco, Itziar Mintegui, Rosa Sebastián, Javier García-Alonso, Carolina Lorencio, Josep Maria Sirvent, Patricia Jimeno, Miguel León, Pedro Galdos, Nuria Alonso, Julia López-Díaz, María Victoria de la Torre, Jorge Vidal Hernández, Nicolás Zamboschi, Francisco Lucena, Gemma Rialp, Raquel Montoiro, Victoria Goñi, María Ángeles Pena, Antonio Maestre, Marc Fabra, Jacinto Baena, Eva Benveniste, Susana Temprano, Jesús Sánchez, Carmen Campos, Sara Cabañes, María Elena Pérez-Losada, José Claudio Leo, Enrique Piacentini, María Del Carmen de la Torre, Laura Álvarez-Montero, Fernando Sánchez, Antonio Viñuales, Bernabé Álvarez, Javier Castañeda, Ángela Alonso, María Isabel Ruiz, Pedro Jesús Domínguez, Marcos Delgado, Eugenio Palazón, Antonio García-Jiménez, Rosa Álvaro, Clara Laplaza Eva Regidor, Enrique Maraví, José María Quiroga, Amalia Martínez de la Gandara, Cecilia Carbayo, María Luisa Navarrete, Manuel Valledor, Raquel Yano, José María Gutiérrez, Javier González-Robledo, Amparo Ferrandiz, Alberto Belenguer, Lidón Mateu, Laura Sayagues, María José Tolón, Nieves Franco, Elena Gallego, Félix Lacoma, Patricia Albert, Vicente Arraez, Mar Gobernado, Susana Moradillo, Carolina Gímenez-Esparza, Teresa Sánchez de Dios, Carlos Marian Crespo, Cecilia Hermosa, Federico Gordo, Genis Carrasco, María Ángeles Alonso, Alejandro Algora, Raúl de Pablo, Sofía García, Ana Carolina Caballero, José María Montón, Teresa Mut, Eva Manteiga, Alejandro de la Serna, Ana Esther Trujillo, Rafael Blancas, Inmaculada Vallverdú, José Manuel Serrano, Miquel Ferrer, Juan Diego Jiménez, Carlos Gallego, Dolores Vila, Luis Marina, Valentín Parra, Juan Ramón Cortés, Chen Chin-Ming, Ai-Chin Cheng, Fekri Abroug, Besbes Mohamed, Imed Chouchene, Mounir Bouaziz, Stambouli Neji, Islem Ouanes, Ayed Samia, Nahit Cakar, Ismail Kati, Ali Aydım Altunkan, Remzi Iscimen, Zafer Dogan, Bilge Çetin, Tayfun Adanir, Sabriye Guvenc, Unase Büyükkoçak, Antonio Anzueto, Ashley Ellis, Gary Kinasewitz, Allan Walkey, Phil Alkana, Gregory A Schmidt, Susan Gillen, Kathleen Lilli, Jennifer Twombley, Denice Wells, Larry Welder, Alejandro Arroliga, Alfredo Vasquez-Sandoval, Vincent John Scott, Craig Cernosek, Christopher Spradley, Dimple Tejwani, Sindhaghatta Venkatram, Gilda Diaz-Fuentes, Amber Monson, Anthony Saleh, Madhav Gudi, George Liziamma, Mohamed A Saad, Crissie De Spirito, Bryan Beatty, Samir Vermani, Crissie Despirito, Zaza Cohen, Amee Patrawalla, Samir Abdelhadi, Rupesh Vakil, Steven Y Chang, Brian Sherman, Rosanna Del Giudice, John Oropell, Timothy D Girard, Cayce Strength, Joyce Okahashi, Leanne Boehm, Matthew Kirchner, Erwin J Oei, Sebastian Circo, Nelson Medina, Mohammed Al-Jagbeer, V J Cardenas Jr, Smyth Smith, Shelby Sutton, Marcela Canola-Mazo, Tim Houlihan, Yogeet Kaur, Travis Parry, Craig A Piquette, Kerry Canady, Rahul Nanchal, Dana K Soetaert, Maria Del Mar Torres-Perez, Carlos Robles-Arias, William Rodriguez-Cintron, Mark Tidswell, Jennifer Germain, Lori-Ann Kozikowski, Erin Braden, Geneva Tatem, Javier Hurtado, Alberto Deicas, Daniel Weiss, Marta Beron, Román Garrido, Cristina Santos, Mario Cancela, Raúl Lombardi, Pedro Alzugaray, Jorge Gerez, Silvia Mareque, Graciela Franca, Oscar Cluzet, Edgardo Nuñez, Julio Pontet, Sergio Cáceres, Elias Caragna, Alberto Soler, Frank Torres, Gastón Pittini, Gabriel D Empaire, Stevens Salva, Fernando Pérez, Clara Pacheco, Zoraida Parra, Ingrid Von der Osten, Luis Williams, José Salinas, Do Danh Quynh, Pham Thi Van Anh, Nguyen Huu Hoang, Nghuyen Ba Tuan, RS: NUTRIM - R2 - Liver and digestive health, MUMC+: MA Arts Assistenten IC (9), Intensive Care, MUMC+: MA Medische Staf IC (9), Tejerina E.E., Pelosi P., Robba C., Penuelas O., Muriel A., Barrios D., Frutos-Vivar F., Raymondos K., Du B., Thille A.W., Rios F., Gonzalez M., Del-Sorbo L., Marin M.D.C., Valle Pinheiro B., Soares M.A., Nin N., Maggiore S.M., Bersten A., Amin P., Cakar N., Young Suh G., Abroug F., Jibaja M., Matamis D., Ali Zeggwagh A., Sutherasan Y., Anzueto A., Esteban A, and Fernando Ríos, Damian Violi, Marisol Rodríguez-Goñi, Roger Lamoglie, Fernando Villarejo, Norberto Tiribelli, Santiago Ilutovich, Matías Brizuela, Mariana Monllau, Fernando Saldarini, Silvina Borello, Alberto Marino, Norberto Tiribelli, Mauricio Vinzio, Karina Bonasegla, Julián Hernández, María Belén Yapur, María Eugenia González, Sebastián E Mare, Judith Sagardía, Marco Bezzi, Cecilia Pereyra, Julian Strati, Daniel Vargas, Claudia Diaz, Pablo Gómez, Marcelo Palavecino, Graciela Elizabeth, Aguilera García, M Eugenia, Luis Pablo Cardonnet, Lisandro Betttini, Hernán Nuñez, Lucas Vallejo, Fernando Fernández, Jorge Arroyo, Daniel Duarte, Gerardo Filippa, Cayetano Galetti, Hernan Nunia, Fernando Lambert, Elisa Estenssoro, Marina Busico, Fernando Villarejo, Javier Horacio Álvarez, Alejandro Raimondi, Gustavo Badariotti, Martín Lugaro, Fernando Lipovestky, Alan Javier Zazu, Hugo Capponcelli, Patricia Vogl, Cristina Orlandi, Alejandro Gómez, Gustavo Jannello, Alejandro Risso, Leticia Rapetti, Guillermo Chiappero, Juan Domingo Fernández, Rodrigo E Gómez-Paz, Marcos Juan Zec, Pascual Valdez, Jorgelina Guyon, Ariel Chena, Sergio Lasdica, Martin Deheza, Schimdt Alejandra, Francisco Criado, Norma Beatriz Márquez, Pablo Desmery, José Luis Scapellato, Gonzalo Javier Ríos, Cristian Casabella, Jasmin Board, Andrew Davies, Andrew Bersten, Elisha Matheson, Amy Waters, John Santamaria, Jennifer Holmes, Cartan Costello, Manoj K Saxena, John Myburgh, Ellen Kinkel, Forbes McGain, Claire Cattigan, Allison Bone, Ian Seppelt, Leonie Weisbrodt, Cheryl Cuzner, Christopher MacIsaac, Deborah Barge, Tania Caf, Cameron Knott, Graeme Duke, Imogen Mitchell, Helen Rodgers, Rachel Whyte, Elisha Fulton, Jasmin Board, Andrew Davies, Alistair Nichol, Hergen Buscher, Priya Nair, Claire Reynolds, Simon J G Hockley, Ian Moore, Katherine Davidson, David Milliss, Raju Pusapati, Helen Wong, Jason Fletcher, Julie Smith, Paul Goldrick, Dianne Stephens, Jane Thomas, Anders Aneman, Sutrisno Gunawan, Tom Cowlam, George Lukas, Rick McAllister, Minka Springham, Joanne Sutton, Jeff Presneill, Tony Sutherland, Dianne Hill, Howard Connor, Jenny Dennett, Tim Coles, Freddy Sandy, Sando Chavarria, Marcelo Choque, Ronald Pairumani, Juan Guerra, Marco Antônio Soares Reis, José Carlos Versiani, Eduardo Fonseca Sad, Maria Aparecida Braga, Dinalva Aparecida Gomes, Fernando Antônio Botoni, Maurício Meireles Góes, Frederico Costa Val Barros, Rogério de Castro Pereira, Hugo Urbano, Valéria de Carvalho Magela, Aline Camile Yehia, Bruno Bonaccorsi Fernandino, Marco Antônio Ribeiro Leão, Rovílson Lara, Rovílson Lara, Rubens Altair Amaral de Pádua, Janine Dias Alves, Aloísio Marques do Nascimento, Bruno do Valle Pinheiro, Carlos Alberto Studart Gomes, Marcelo Alcântara Holanda, Frederico Rodrigues Anselmo, Niall Ferguson, Neill Adhikari, Robert Fowler, Cheromi Sittambalam, Mehar-Un-Nisa Raja, Nicole Marinoff, Lauralyn McIntryre, Shawna Reddie, Laura Jones, Irene Watpool, Jeffrey Singh, Madison Dennis, Andrea Matte, Marc Lipkus, Ryan Albert, Andrew Steel, Emily Stern, Michael Miletin, Antonio Raso, Robyn Klages, Jan Friedrich, Orla Smith, Laura Wilson, Deborah Cook, Mark Bailey, Sangeeta Mehta, Stephen Lapinsky, Hannah Mathers, Cheryl Ethier, Stephanie Lubchansky, Samer Haj-Bakri, Dietrich Henzler, Lisa Julien, Luis Soto-Román, Juan Carlos Maurelia, César Antonio Maquilon, Luis Soto-Germani, Bin Du, Yan Kang, Bo Wang, Fachun Zhou, Fang Xu, Haibo Qiu, Yi Yang, Qingyuan Zhan, Bing Sun, Zhenjie Hu, Bin Yu, Xi Zhu, Yu Bai, Gang Li, Yi Li, Geng Zhang, Jianbiao Meng, Xiaobo Huang, Hong Pu, Bin Du, Daxing Yu, Chuanyun Qian, Wei Zhang, Yongjie Yin, Debiao Song, Yunxuan Yue, Zhengxuan Lv, Chengmin Yu, Qunmei Yao, Xue Wang, Yuan Xu, Wei He, Mian Chen, Zhihua Hu, Dongpo Jiang, Jian Huang, Wei Yu, Juanxian Gu, Yangong Chao, Zhixiang Li, Zhicheng Zhang, Wanxia Li, Zhenyang He, Jianguo Li, Chang Liu, Tiehe Qin, Shouhong Wang, Feng Li, Jun Jin, Jianhong Fu, Hongyang Xu, Hongyuan Lin, Jianying Guo, Yalin Liu, Jinghua Wang, Maoqin Li, Jiaqiong Li, Lei Chen, Qing Song, Liang Pan, Xianyao Wan, Jiuzhi Zhang, Weihai Yao, Yuhong Guo, Pang Wing Yan, Kelly Choy, Kwan Ming Chit, Patricia Leung, Chau Chin Man, Marco González, Ricardo Buitrago, Marcela Granados, Guillermo Ortiz, Cesar Enciso, Mario Gómez, Bladimir Alejandro Gil, Juan Pablo Sedano, Luis Fernando Castro Castro, Carlo Alberto Acosta, Marco Gonzalez, Francisco Molina, Camilo Pizarro, Mario Villabon, Carmelo Dueñas, Carlos Andrés Díaz, Nelson Fonseca, Rubén Camargo, Juan David Uribe, Hans-Henrik Bülow, Simona Beniczky, Jens Brushoj, Mikkel Præst, Birgitte Viebaek, Sine Wichman, Anette Mortensen, Susanne Andi Iversen, Bo Broberg, Edgard Luna, Manuel Jibaja, Leonardo Pazmiño, Katty Trelles, Fabricio Picoita, Gustavo Paredes, Vanesa Ramírez, Guillermo Falconí, Cristian Cevallos, Boris Villamagua, Marco Escobar, Freddy Sánchez, Miguel Llano, Miguel Lazcano, Ramiro Puetate, José Miguel Guerrero, Mijail Játiva, Myriam Montalvo, Franklin Villegas, Luis González Zambrano, Ronnie Mantilla, Gina Quinde, Andrea Gimenez, Luis Gonzalez Mosquera, Henry Caballero, María Fernanda García, Marcelo Ochoa, Soraya Puertas, Jackeline Coello, Mario Acosta, Medhat Soliman, Arnaud W Thille, Achille Kouatchet, Alain Mercat, Laurent Brochard, François Collet, Guillaume Marcotte, Pascal Beuret, Jean-Christophe M Richard, Gaëtan Bedunaeu, Pierre-Gildas Guitard, Fabien Soulis, Frédéric Bellec, Philippe Berger, Dorothée Carpentier, Benoit Veber, Salem Ould Zein, Géraldine Dessertaine, C Canevet, Fabien Grelon, Konstantinos Raymondos, Rolf Dembinski, Rolf Rossaint, Steffen Weber-Carstens, Christian Putensen, Maximillian Ragaller, Michael Quintel, Winfried Schubert, Thomas Bein, Heinrich Paulus, Walter Brandt, Lutz Pfeiffer, Silke Frenzel, Thoralf Kerner, P Kruska, Leila Eckholt, Joachim Hartung, Harald Fritz, Monika Holler, Johannes Busch, Andreas Viehöfer, Jens Buettner, Jörn Schlechtweg, Achim Lunkeit, Roland Schneider, Maria Wussow, Nils Marquardt, Christian Frenkel, Falk Hildebrandt, Tumbass Volker, Thomas Lipp, Cezar Mihailescu, Thomas Moellhoff, Thomas Steinke, Oliver Franke, Marcus Ruecker, Markus Schappacher, Steffen Appel, Heinz Kerger, Andreas Schwartz, Jan Dittmann, Jörg Haberkorn, Wolfgang Baier, Walter Seyde, Dimitros Matamis, Eleni Antoniadou, Pertsas Evangelos, Maria Giannakou, Zoltan Szentkereszty, Zsolt Molnar, Pravin Amin, Farhad N Kapadia, Nagarajan Ramakrishnan, Deepak Govil, Anitha Shenoy, Umesh G, Samir Sahu, Sheila Nainan Myatra, Subhash Kumar Todi, Sanjay Dhanuka, Mayur Patel, P Samaddar, Dhruva Chaudhry, Vivek Joshi, Srinivas Samavedam, Ankur Devendra Bhavsar, Prachee Sathe, Sujoy Mukherjee, Salvatore Maurizio Maggiore, Francesco Idone, Federica Antonicelli, Paolo Navalesi, Rosanna Vaschetto, Arianna Boggero, Rosalba Tufano, Michele Iannuzzi, Edoardo De Robertis, Romano Tetamo, Andrea Neville Cracchiolo, Antonio Braschi, Francesco Mojoli, Ilaria Curro', Mirko Belliato, Chiara Verga, Marta Ferrari, Erika Mannelli, Valerio Mangani, Giorgio Tulli, Francesca Frigieri, Armando Pedulla', Monica Rocco, Giorgia Citterio, Di Russo, Gaetano Perchiazzi, Loredana Pitagora, Antonio Pesenti, Michela Bombino, Davide Chiumello, Federica Tallarini, Serena Azzari, Antonina Pigna, Ivano Aprile, Marco Adversi, Antonio Corcione, Marianna Esposito, Annunziata Mattei, Vito Marco Ranieri, Rosario Urbino, Ilaria Maria Mastromauro, Antonino Giarratano, Maurizio Raineri Santi, Ambrogio Sansone, Younsuck Koh, Moo Suk Park, Je Hyeong Kim, Kyung Chan Kim, Hye Sook Choi, Yun Seong Kim, Jin Hwa Lee, Myung-Goo Lee, Won-Yeon Lee, Jin Young An, Gee Young Suh, Ki-Suck Jung, Asisclo J Villagómez Ortiz, César Cruz Lozano, Zalatiel Maycotte Luna, José Francisco López Baca, José Elizalde, Guillermo Cueto Robledo, Mario Alonso Treviño Salinas, Ricardo Martinez Zubieta, Claudia Olvera-Guzman, Marco Montes De Oca, Silvio A Ñamendys-Silva, José Salvador Martínez Cano, Jose Angel Baltazar Torres, Gustavo Morales Muñoz, Antonio Villa Delgado, Javier Ladape Martinez, Amine Ali Zeggwagh, Tarek Dendane, Abderrahim Azzouzi, Ahmed Sbihi, Wajdi Maazouzi, Mourad Amor, Charki Haimeur, Michael A Kuiper, Matty Koopmans, Uli Strauch, Dennis Bergmans, Serge Heines, Sylvia den Boer, Bas M Kors, Peter van der Voort, Paul J Dennesen, Bert Beishuizen, Ingrid van den Hul, Erna Alberts, Harry P P M Gelissen, Eduard Bootsma, Auke Reidinga, Jasmin Board, Andrew Davies, Kim Heus, Diane Mackle, Paul Young, Rachael Parke, Eileen Gilder, Jodi Brown, Lynette Newby, Catherine Simmonds, Jan Mehrtens, Seton Henderson, Tony Williams, Judi Tai, Chantal Hogan, Mary La Pine, John Durning, Sheree Gare, Troy Browne, Shirley Nelson, Jennifer Goodson, Julio Osorio, Chabu Coronado, Rollin Roldán Mori, Rosa Luz López Martínez, Adam Mikstacki, Barbara Tamowicz, Rui Moreno, Eduardo Almeida, Joana Silvestre, Heloisa Castro, Irene Aragão, Susana Alves Ferreira, Nelson Barros, Filomena Faria, Carlos André Correia Casado, Fausto Fialho Moura, Paulo Marcal, Ricardo Matos, Edward Nicolayenko, Mikhail Kirov, Andrey Yaroshetskiy, Andrei Piontek, Valery Subbotin, Yaseen Arabi, Olivia Dulfo, Chafrina Marie Olay, Edgardo E Tabhan, Nicolas Nin, Alfonso Muñoz, César Aragón, Ana Villagrá, Ainhoa Rosselló, Joan Maria Raurich, María Garitacelaya, Miguel Ángel González-Gallego, Francisco Ortuño, Miguel Fernández-Vivas, David Freire, Francisco Guerrero, Francisco Manzano, Juan Carlos, Alfredo Padrón, Pedro Rosa, Rafael Morales, Liliana Caipe, Maurizio Bottiroli, José María Nicolás, Marta Ugalde, Javier Ruiz, Lucia Capilla, Guillermo Muñiz, Jesús Sánchez-Ruiz, Javier Cebrián, Begoña Balerdi, Elena Parreño, Alvaro van Bommel, César Pérez-Calvo, Irene Dot, Javier Blanco, Raquel Manzanedo, José J Blanco, Daniel Fontaneda, Raúl González, Javier Díaz Domínguez, Alfonso Moreno, Antonio Reyes, Ian Carrasco, Itziar Mintegui, Rosa Sebastián, Javier García-Alonso, Carolina Lorencio, Josep Maria Sirvent, Patricia Jimeno, Miguel León, Pedro Galdos, Nuria Alonso, Julia López-Díaz, María Victoria de la Torre, Jorge Vidal Hernández, Nicolás Zamboschi, Francisco Lucena, Gemma Rialp, Raquel Montoiro, Victoria Goñi, María Ángeles Pena, Antonio Maestre, Marc Fabra, Jacinto Baena, Eva Benveniste, Susana Temprano, Jesús Sánchez, Carmen Campos, Sara Cabañes, María Elena Pérez-Losada, José Claudio Leo, Enrique Piacentini, María Del Carmen de la Torre, Laura Álvarez-Montero, Fernando Sánchez, Antonio Viñuales, Bernabé Álvarez, Javier Castañeda, Ángela Alonso, María Isabel Ruiz, Pedro Jesús Domínguez, Marcos Delgado, Eugenio Palazón, Antonio García-Jiménez, Rosa Álvaro, Clara Laplaza Eva Regidor, Enrique Maraví, José María Quiroga, Amalia Martínez de la Gandara, Cecilia Carbayo, María Luisa Navarrete, Manuel Valledor, Raquel Yano, José María Gutiérrez, Javier González-Robledo, Amparo Ferrandiz, Alberto Belenguer, Lidón Mateu, Laura Sayagues, María José Tolón, Nieves Franco, Elena Gallego, Félix Lacoma, Patricia Albert, Vicente Arraez, Mar Gobernado, Susana Moradillo, Carolina Gímenez-Esparza, Teresa Sánchez de Dios, Carlos Marian Crespo, Cecilia Hermosa, Federico Gordo, Genis Carrasco, María Ángeles Alonso, Alejandro Algora, Raúl de Pablo, Sofía García, Ana Carolina Caballero, José María Montón, Teresa Mut, Eva Manteiga, Alejandro de la Serna, Ana Esther Trujillo, Rafael Blancas, Inmaculada Vallverdú, José Manuel Serrano, Miquel Ferrer, Juan Diego Jiménez, Carlos Gallego, Dolores Vila, Luis Marina, Valentín Parra, Juan Ramón Cortés, Chen Chin-Ming, Ai-Chin Cheng, Fekri Abroug, Besbes Mohamed, Imed Chouchene, Mounir Bouaziz, Stambouli Neji, Islem Ouanes, Ayed Samia, Nahit Cakar, Ismail Kati, Ali Aydım Altunkan, Remzi Iscimen, Zafer Dogan, Bilge Çetin, Tayfun Adanir, Sabriye Guvenc, Unase Büyükkoçak, Antonio Anzueto, Ashley Ellis, Gary Kinasewitz, Allan Walkey, Phil Alkana, Gregory A Schmidt, Susan Gillen, Kathleen Lilli, Jennifer Twombley, Denice Wells, Larry Welder, Alejandro Arroliga, Alfredo Vasquez-Sandoval, Vincent John Scott, Craig Cernosek, Christopher Spradley, Dimple Tejwani, Sindhaghatta Venkatram, Gilda Diaz-Fuentes, Amber Monson, Anthony Saleh, Madhav Gudi, George Liziamma, Mohamed A Saad, Crissie De Spirito, Bryan Beatty, Samir Vermani, Crissie Despirito, Zaza Cohen, Amee Patrawalla, Samir Abdelhadi, Rupesh Vakil, Steven Y Chang, Brian Sherman, Rosanna Del Giudice, John Oropell, Timothy D Girard, Cayce Strength, Joyce Okahashi, Leanne Boehm, Matthew Kirchner, Ashley Ellis, Gary Kinasewitz, Erwin J Oei, Sebastian Circo, Nelson Medina, Mohammed Al-Jagbeer, V J Cardenas Jr, Smyth Smith, Shelby Sutton, Marcela Canola-Mazo, Tim Houlihan, Yogeet Kaur, Travis Parry, Craig A Piquette, Kerry Canady, Rahul Nanchal, Dana K Soetaert, Maria Del Mar Torres-Perez, Carlos Robles-Arias, William Rodriguez-Cintron, Mark Tidswell, Jennifer Germain, Lori-Ann Kozikowski, Erin Braden, Geneva Tatem, Javier Hurtado, Alberto Deicas, Daniel Weiss, Marta Beron, Román Garrido, Cristina Santos, Mario Cancela, Raúl Lombardi, Pedro Alzugaray, Jorge Gerez, Silvia Mareque, Graciela Franca, Oscar Cluzet, Edgardo Nuñez, Julio Pontet, Sergio Cáceres, Elias Caragna, Alberto Soler, Frank Torres, Gastón Pittini, Gabriel D Empaire, Stevens Salva, Fernando Pérez, Clara Pacheco, Zoraida Parra, Ingrid Von der Osten, Luis Williams, José Salinas, Do Danh Quynh, Pham Thi Van Anh, Nguyen Huu Hoang, Nghuyen Ba Tuan
Subjects: Male, medicine.medical_treatment, pulmonary complications, RESPIRATORY-DISTRESS-SYNDROME, Critical Care and Intensive Care Medicine, CASE-FATALITY, 0302 clinical medicine, Risk Factors, Brain Injuries, Traumatic, Multicenter Studies as Topic, Hospital Mortality, Prospective Studies, Simplified Acute Physiology Score, Stroke, POPULATION, Age Factors, ANEURYSMAL SUBARACHNOID HEMORRHAGE, Middle Aged, Hemorrhagic Stroke, Intensive Care Units, Observational Studies as Topic, Anesthesia, Breathing, Female, medicine.symptom, Ventilator Weaning, Cohort study, Adult, TRAUMATIC BRAIN-INJURY, Pressure support ventilation, mechanical ventilation, prognosis factors, ACUTE LUNG INJURY, 03 medical and health sciences, medicine, Humans, Aged, Ischemic Stroke, Mechanical ventilation, Noninvasive Ventilation, business.industry, MORTALITY, neurologic patients, Organ dysfunction, 030208 emergency & critical care medicine, Length of Stay, medicine.disease, TRENDS, Respiration, Artificial, 030228 respiratory system, Etiology, NEUROCRITICAL CARE, Nervous System Diseases, Tracheotomy, business
Abstract: OBJECTIVES: To describe the changes in ventilator management over time in patients with neurologic disease at ICU admission and to estimate factors associated with 28-day hospital mortality. DESIGN: Secondary analysis of three prospective, observational, multicenter studies. SETTING: Cohort studies conducted in 2004, 2010, and 2016. PATIENTS: Adult patients who received mechanical ventilation for more than 12 hours. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Among the 20,929 patients enrolled, we included 4,152 (20%) mechanically ventilated patients due to different neurologic diseases. Hemorrhagic stroke and brain trauma were the most common pathologies associated with the need for mechanical ventilation. Although volume-cycled ventilation remained the preferred ventilation mode, there was a significant (p < 0.001) increment in the use of pressure support ventilation. The proportion of patients receiving a protective lung ventilation strategy was increased over time: 47% in 2004, 63% in 2010, and 65% in 2016 (p < 0.001), as well as the duration of protective ventilation strategies: 406 days per 1,000 mechanical ventilation days in 2004, 523 days per 1,000 mechanical ventilation days in 2010, and 585 days per 1,000 mechanical ventilation days in 2016 (p < 0.001). There were no differences in the length of stay in the ICU, mortality in the ICU, and mortality in hospital from 2004 to 2016. Independent risk factors for 28-day mortality were age greater than 75 years, Simplified Acute Physiology Score II greater than 50, the occurrence of organ dysfunction within first 48 hours after brain injury, and specific neurologic diseases such as hemorrhagic stroke, ischemic stroke, and brain trauma. CONCLUSIONS: More lung-protective ventilatory strategies have been implemented over years in neurologic patients with no effect on pulmonary complications or on survival. We found several prognostic factors on mortality such as advanced age, the severity of the disease, organ dysfunctions, and the etiology of neurologic disease.
Published: 2021

44. Predictors of intubation and mortality in COVID-19 patients: a retrospective study

Author: Simona Bazzano, Michela Barini, Rosanna Vaschetto, Davide Negroni, Gianmaria Cammarota, Francesco Della Corte, Luigi Mario Castello, Alessandro Carriero, Tiziana Cena, Domenico Zagaria, and Danila Azzolina
Subjects: Mechanical ventilation, medicine.medical_specialty, business.industry, medicine.medical_treatment, Quantitative computerized tomography, COVID-19, Retrospective cohort study, Factor risk, Anesthesiology, Fraction of inspired oxygen, Intensive care, Internal medicine, Cohort, Medicine, Intubation, Population study, Original Article, Mortality, business, Random forest
Abstract: Background Estimating the risk of intubation and mortality among COVID-19 patients can help clinicians triage these patients and allocate resources more efficiently. Thus, here we sought to identify the risk factors associated with intubation and intra-hospital mortality in a cohort of COVID-19 patients hospitalized due to hypoxemic acute respiratory failure (ARF). Results We included retrospectively a total of 187 patients admitted to the subintensive and intensive care units of the University Hospital “Maggiore della Carità” of Novara between March 1st and April 30th, 2020. Based on these patients’ demographic characteristics, early clinical and laboratory variables, and quantitative chest computerized tomography (CT) findings, we developed two random forest (RF) models able to predict intubation and intra-hospital mortality. Variables independently associated with intubation were C-reactive protein (p < 0.001), lactate dehydrogenase level (p = 0.018) and white blood cell count (p = 0.026), while variables independently associated with mortality were age (p < 0.001), other cardiovascular diseases (p = 0.029), C-reactive protein (p = 0.002), lactate dehydrogenase level (p = 0.018), and invasive mechanical ventilation (p = 0.001). On quantitative chest CT analysis, ground glass opacity, consolidation, and fibrosis resulted significantly associated with patient intubation and mortality. The major predictors for both models were the ratio between partial pressure of arterial oxygen and fraction of inspired oxygen, age, lactate dehydrogenase, C-reactive protein, glycemia, CT quantitative parameters, lymphocyte count, and symptom onset. Conclusions Altogether, our findings confirm previously reported demographic, clinical, hemato-chemical, and radiologic predictors of adverse outcome among COVID-19-associated hypoxemic ARF patients. The two newly developed RF models herein described show an overall good level of accuracy in predicting intra-hospital mortality and intubation in our study population. Thus, their future development and implementation may help not only identify patients at higher risk of deterioration more effectively but also rebalance the disproportion between resources and demand.
Published: 2021

45. Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Author: Labeau, Sonia O, Afonso, Elsa, Benbenishty, Julie, Blackwood, Bronagh, Boulanger, Carole, Brett, Stephen J, Calvino-Gunther, Silvia, Chaboyer, Wendy, Coyer, Fiona, Deschepper, Mieke, François, Guy, Honore, Patrick M, Jankovic, Radmilo, Khanna, Ashish K, Llaurado-Serra, Mireia, Lin, Frances, Rose, Louise, Rubulotta, Francesca, Saager, Leif, Williams, Ged, Blot, Stijn I, Dritan, Muzha, Antoni Margarit Ribas, Fernando, Lipovesty, Cecilia, Loudet, Fiona, Coyer, Philipp, Eller, Nafseen, Mostafa, Patrick, M Honoré, Vanesa Mercado Telleria, Jasmina, Smajic, Paula Cristina Nogueira, Khalid Mahmood Khan Nafees, Romuald, Hentchoya, Louise, Rose, Javiera, Soledad, Frances, Lin, Yenny, Cardenas, Amylkar Garay Reyes, Alan, Sustic, Meropi, Mpouzika, Tamas, Vymazal, Hanne Irene Jensen, Hernan, Aguirre-Bermeo, Liivi, Maddison, Maija, Valta, Silvia, Calvino-Gunther, Frank, Bloos, Faustina Excel Adipa, Vasilios, Koulouras, Judy, Enamorado, Zsuzsann, Ágoston, Hrönn, Birgisdóttir, Amit, Gupta, Mohan, Gurjar, Bram, Kilapong, Seyed Mohammadreza Hashemian, Ignacio, Martin-Loeches, Julie, Benbenishty, Andrea, Cortegiani, Kelly, Fletcher, Yoshiro, Hayashi, Wangari, Waweru-Siika, Khalid, Abidi, Sang-Min, Lee, Burhan, Hadri, Mihails, Dolgusevs, Fayez François Abillama, Tomas, Jovaisa, Cyril, Thix, Muhammed, Elhadi, Basri Mat Nor, Shanti, Ratnam, Mohd Zulfakar Mazlan, Sundaresan, Maiyalagan, Luis, Sánchez-Hurtado, Adrian, Belii, Mendsaikhan, Naranpurev, Prabha, Gautam, Dylan De Lange, Rachael, Parke, Rose Ekama Ilesanmi, Mirjana, Shosholcheva, Antonija, Petosic, Ranveig, Lind, Madiha Hashmi Ffarcsi, Javier, Bogarin, Aaron Mark Hernandez, Malgorzata, Mikaszewska-Sokolewicz, Bruno, Sousa, Dana, Tomescu, Dorel, Sandesc, Theogene, Twagirumugabe, Vitaly, Gusarov, Maie, Ebaid, Radmilo, Jankovic, Gari, Slobodianiuk, Andrea, Martonova, Rihard, Knafelj, Mervyn, Mer, Emilio, Maseda, Bernardo, Panka, Joerg, C Schefold, Eva, Joelsson-Alm, Konlawij, Trongtrakul, Lorna, Merritt-Charles, Lamia Ouanes Besbes, Yalım, Dikmen, Lesia, Zgrzheblovska, Mark, Fielding, Francesca, Rubulotta, Ashish, K Khanna, Leif, Saager, Ingrid von der Osten, Alban, Greca, Alma, Cani, Nordian, Xhindi, Genci, Hyska, Antonio Margarit Ribas, Susana, Pinto, Paulo, Alves, Romina, Esposito, Emanuel, Valgolio, John Thomas Sanchez Minope, Antonio, Abdala, Maria, Ayala, Silvina, Bravo, Ana, Bantar, Patricia, Delgado, Gustavo, Badariotti, Fernando, Lipovestky, Ana, Diaz, Pablo, Saul, Mariano, Setten, Alejandra, Aucapina, Ysica, Acosta, Victor, Gonzalez, Luis, Camputaro, Fernando, Baccaro, Robert, Villa, Marcela, Mastantuono, Emiliano, Dean, Oscar Fernández Rostello, Patricia, Brizuela, Julio Ricardo Bartoli, Matias, Guereschi, Cristian, Quiroga, Sofia, Putruele, Paula, Villegas, Veronica, Curilen, Ruben, Fernandez, Mariangeles Gabriela Nocheretti, Rosana Gabriela Escalante, Cecilia Inés Loudet, Silvia, Fernandez, Ana Laura Gonzalez, Gustavo Andres Alvarez, Federico, Iglesias, Silvia, Chaparro, Graciela, Zakalik, Gonzalo, Pagella, Matías, Baini, Pierina Arias Campos, Ignacio, Sabbag, Armando, Schmukler, Imelda Perdomo Fonseca, Gonzalo Martín Alvarez, Mario, Ramirez, Fernando, Tapia, Carlos Alejandro Bascary, Graciela Del Valle Gimenez, Fernando Pablo Bertoletti, Esteban, Milioto, Pablo Julio Maldonaldo Bonsignore, Maria Alejandra Fernandez, Julie, Smith, Tim, Chimunda, Lorraine, Thompson, Teena, Maguire, Wendy, Chaboyer, Stacey, Watts, Marion, Mitchell, Madeleine, Powell, India, Lye, Leanne, Parsons, Nerilee, Baker, Claire, Reynolds, Amy, Thompson, Kristy, Masters, Kellie, Sosnowski, Lynette, Morrison, Gavin, D Leslie, Ramanathan, Lakshmanan, Alexis, Tabah, Wendy, Brown, Sharon, McDowell-Skaines, Andrea, Mclucas, Chris, Smith, Mandy, Tallot, Sarah, Jones, Michelle, Barakat-Johnson, Thomas, Leong, Rand, Butcher, Kerrie, Martin, Philipp, Douschan, Dirk von Lewinski, René, Schmutz, Uta, Kolussi, Fatema, Salman, Zainab, Ateya, Koen De Decker, Niels Van Regenmortel, Anita, Jans, Patricia, Wijnands, Stefano, Coremans, Patrick, M Honore, David De Bels, Tanja, Depuydt, Caroline, Paillet, Luc-Marie, Jacquet, Walter, Swinnen, Francis, Hannes, Matthia, Mergeay, Stijn Van de Velde, Silvie, Allaert, Pieter, Hoste, Christophe, Borin, Sandrine, Balon, Vincent, Fraipont, Patrick, Biston, Nicolas De Schryver, Thierry, Dugernier, Ilse Van Cotthem, Angelica Olivetto de Almeida, Silvia Angelica Jorge, Delmiro, Becker, Raysa Cristina Schmidt, Evellyn, Oliveira, Aline, Ramalho, Eliane, Mazocoli, Audrey, Fioretti, Elaine, Barros, Leticia, Serpa, Suzana, Bianchini, Ticiane, Campanili, Taís, Pantaleao, Paulo Carlos Garcia, Ana Lucia Vitti Ronchini, Rayanne, Santos, Nurulhuda Binti, A Manap, Sean, Bagshaw, Dominic, Carney, Jon, Davidow, Ella, Rokosh, Andréa Maria Laizner, Samantha, Smith, Megan, Mcquirter, Betty Star Kampayana, René, Favre, Martin, Sills, Julie, Dallaire, Cathy, Becker, Sherissa, Microys, Bonnie, Bowes, Jennifer, Lajeunesse, Rishi, Ghosh, Jacqueline, Baptiste-Savoie, Rose, 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Michael, Isanan, Marta, Tubacka, Przemyslaw, Jasiewicz, Miroslaw, Czuczwar, Michal, Borys, Aleksandra, Gutysz-Wojnicka, Lidia, Glinka, Ryszard, Gawda, Jan, Bilawicz, Paula, Cabrita, João, Vieira, Margarida Ferreira Figueiredo, Cristiana Mota Pinheiro, Nelson, Antunes, Laura, Pedro, Fatima, Ferreira, Isabel, Parente, Maria, Varela, Fatima, Fernandes, Claudia, Martins, Abel, Viveiros, Raquel, Cavaco, Clara Santa Rita, Sofia, Dias, Ana Margarida Feranandes, Pedro, Silva, Catarina, Nunes, João, Cabral, Filpe, Pires, Hilaryano, Ferreira, Jacinta, Santos, Vitor Manuel Vaz Pinto, Bruno Miguel Bispo, Amelia, Ferreira, Elena, Molinos, Estevão, Lafuente, Ricardo, Gregorio, Humberto, Costa, Ângela, Lima, Susana, Ferreira, Vanda, Seromenho, Eulália, Luis, Idália, Valerio, Helena, Cesar, Ana, Tavares, Ahmed Subhy Alsheikhly, Saeed, Mahmood, Catalin Traian Guran, Alida, Moise, Daniela Carmen Filipescu, Mihail, Luchian, Mihai, Popescu, Monica Adriana Scutariu, Cristina, Petrisor, Natalia, Hagau, 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Slobodianiuk, Daria, Rabarova, Danca, Lančaričová, Janko, Vlaovic, Matjaž, Groznik, Milica, Lukic, Janja, Perme, Maja, Sostaric, Nejc, Umek, Tomislav, Mirkovic, Simon, Dolenc, Misa, Fister, Nika, Zorko, Andrej, Markota, Nomhle Princess Yeni, Phumele, Jali, Shelley, Schmollgruber, Muhommed Ridwaan Syed, Nivisha, Parag, Robert, Wise, Maria, Galiana, José Alejandro Navarro, Ana María De Pablo, Patricia, Albert, Pilar, Martinez, Yolanda, Mendiara, Barbara, Garcia, Ana Alabart Llinas, Marilyn, Riveiro, Elisabet, Gallart, Alba, Riera, Miquel, Sanz, Swagotika, Salo, Miguel Angel Gimenez Lajara, Montserrat Venturas Nieto, Rosa, Garcia, José Manuel Garcia Pena, Maria Carmen Gorgolas, Maria Aranzazu Isasi, Rafael, Sierra, Federico, Gordo, Isabel, Conejo, Vicent, Salvà-Costa, Carolina, Garzón-Tovar, Sara, Lospitao, Rafael, Gonzalez, Pedro, Gutierrez, Mercè, Girona, Jordi, Adamuz, Pablo Garcia Olivares, José Peral Gutierrez de Ceballos, Celia, Tirado, Irene De Wit, Ana Belén Curto Polo, Maria Del Mar Diaz Salcedo, Javier, Ripolles-Melchor, Eugenio, Martinez-Hurtado, Jorge Duerto Alvarez, María Luisa Bravo Arcas, Juan Ignacio Torres Gonzalez, Ana Belén Sánchez de la Ventana, Pablo Lopez-Arcas Calleja, Raquel Garcia Alvarez, Purificacion Sanchez Zamora, Alvaro Ortega Guerrero, Rosario, Cosano, Jonathan, Perez-Vacas, Margarita, Campos-Perez, Emma Moreno Barreiro, Losune Cano Sanchez, Monica Garcia Diaz, Raquel, Jimenez, Lorena Del Rio Cabajo, Daniel Sancho Muriel, Helena Fernandez Alonso, Ana Wensell Fernández, Isabel Santín Piñan, Guillermo Muñiz Albaiceta, Maria Cristina Iglesias Fernandez, Francisco Javier Saenz Abos, Pablo, Monedero, Ramon Molina Chueca, Lydia Gallego Aguirre, Silvia Call Manosa, Carmen Partera Luque, Neus, Calpe, Monica Recio Losilla, Meritxell Tapia Fores, Olga, Farre, Oscar, Fernandez, M Del Rosario Villar Redondo, Donaldo, S Arteta Arteta, Maria Angeles Hurtado Sanchez, Cristina Paños Espinosa, Laura Martinez Reyes, Laura Claramunt Domenech, Carmen Velasco Guillén, Josep Trenado Alvarez, Mercedes Del Cotillo, Jesus Emilio Barrueco-Francioni, Belen Burgos Conde, Maria Pilar Sogues Blanco, Maria Luisa Blasco, Ana Isabel Clement, Clara, Hurtado, Luz Coronado Sanz, David, Perez-Torres, Estefanía, Prol-Silva, Jorge, Pereira, Iván Areán González, Anastasio Espejo Cano, Cesar Rodriguez Nuñez, Inmaculada Lorenzo Fernadez, Alejandra Azahara Marguello Fernandez, Rosa Del Bosque Diez, Badiola, Hilario, Begoña, Zalba-Etayo, Ana, Pascual-Bielsa, Preveen, Banwarie, Dick, Nahar, Alisha van Axel, Naraindath, N Boedjawan, Erika Backlund Jansson, Ann-Sofie, Malvemyr, Lotta, Johansson, Ulla, Sandberg, Catarina, Tingsvik, Gunilla, Mattsson, Gun, Löf, Martin, Spångfors, Mona, Ringdal, Sebastian, Geijer, Lotti, Orvelius, Mia, Hylen, Caroline, Lagerhäll, Eva, Åkerman, Viveca Hamback Hellkvist, Ulrica, Mickelsson, Ewa, Wahlbom, Ing-Marie, Larsson, Ewa, Wallin, Filippo, Boroli, Solenne, Ory, Margaret Lynn Jong, Alexander, Dullenkopf, Martin, Lang, Yvan, Fleury, Marianne, Maus, Nawfel, Ben-Hamouda, Anne, Fishman, Mei Yu Hsu, Shu Chuan Chang, Konlawij, Trongtratul, Chaiwut, Sawawiboon, Sunthiti, Morakul, Bodin, Khwannimit, Keevan, Singh, Dale, Ventour, Dianne, Figaro-Barclay, Sasha, Sankar-Maharaj, Mhamed Sami Mebazaa, Salma, Kamoun, Souheil, Elatrous, Lamia, Besbes, Fekri, Abroug, Walid, Naija, Youssef Zied Elhechmi, Walid, Sellami, Zied, Hajjej, Takoua, Merhabene, Imen, Talik, Ozlem Ozkan Kuscu, Ozcengiz, Dilek, Avşar, Zerman, Hayriye Cankar Dal, Sema, Turan, Semih, Aydemir, Hakan, Yilmaz, Duygu Kayar Calili, Seval, İzdes, Melike, Cengiz, Ayça, Gümüş, Banu, Taşdemir, Ali, Kağnıcı, Mustafa, Ay, Serap Avcı Ay, Gulbahar, Caliskan, Turkay, Akbas, Abidin Oner Balbay, Serdar, Efe, Volkan, Inal, Gülseren, Elay, Pınar, Karabacak, Boğaç, Özserezli, Evren, Şentürk, Oktay, Demirkiran, Suha, Bozbay, Elif, Erdogan, Mustafa, Akker, Nebia, Peker, Asu, Ozgultekin, Sibel Ocak Serin, Can, Turan, Gulsah, Karaoren, Senay, Goksu, Sait, Karakurt, Huseyin, Arikan, Fethi, Gül, İsmail, Cinel, Iskender, Kara, Hasan Nabi Undar, Yesim Serife Bayraktar, Jale Bengi Çelik, Murat Emre Tokur, Demet Tok Aydin, İsmail, Yildiz, Beysim, Özcan, Başar, Erdivanli, Ahmet, Eroglu, Devrim, Akdağ, Nurdan, Ünlü, Adonis, Dungca, Ashwaq, Ali, Bindu, Thankamma, Paul Eric Reyes, Sini, John, Ajitha, Rajendran, Fatima Kasem El Ahmad, Kathleen Ann Smiley, Susanna, Hojden, Mia Thorning Miller, Vishnu Das Sasidharan Nair, Maria Gracia San Antonio, Khaled Al Qawasmeh, Sabah Abu Shawish, Hilary, Twiggs, Ines, Rosado, Volodymyr, Babych, Faye, Morren, Charlotte, Young, Nicola, Vaughan-Jones, Stephanie, Harris, Karen, Burns, Carmel, Georgiev, Rosina, Shayamano, Ian, Kerslake, Peter, Creber, Ana, Vochin, Catherine, O'Brien, Paul, Caddell, Samantha, Hagan, Mandy, Hughes, Tomasz, Torlinski, James, Sherwin, Santhana, Kannan, Amber, Markham, Richard, Lebon, Jason, Cupitt, Julius, Cranshaw, Nigel, White, Victoria, Marriott, Wendy, Milner, Casiano Barrera Groba, Joao, Azoia, Petra, 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A.S., Goller, S., Afonso, E., Larina, E., Labeau, Sonia O. 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[0000-0003-2145-0345], Apollo - University of Cambridge Repository, Critical Care, Labeau S.O., Afonso E., Benbenishty J., Blackwood B., Boulanger C., Brett S.J., Calvino-Gunther S., Chaboyer W., Coyer F., Deschepper M., Francois G., Honore P.M., Jankovic R., Khanna A.K., Llaurado-Serra M., Lin F., Rose L., Rubulotta F., Saager L., Williams G., Blot S.I., Muzha D., Ribas A.M., Lipovesty F., Loudet C., Eller P., Mostafa N., Telleria V.M., Smajic J., Nogueira P.C., Nafees K.M.K., Hentchoya R., Soledad J., Cardenas Y., Reyes A.G., Sustic A., Mpouzika M., Vymazal T., Jensen H.I., Aguirre-Bermeo H., Maddison L., Valta M., Bloos F., Adipa F.E., Koulouras V., Enamorado J., Agoston Z., Birgisdottir H., Gupta A., Gurjar M., Kilapong B., Hashemian S.M., Martin-Loeches I., Cortegiani A., Fletcher K., Hayashi Y., Waweru-Siika W., Abidi K., Lee S.-M., Hadri B., Dolgusevs M., Abillama F.F., Jovaisa T., Thix C., Elhadi M., Nor B.M., Ratnam S., Mazlan M.Z., Maiyalagan S., Sanchez-Hurtado L., Belii A., 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Goksu S., Karakurt S., Arikan H., Gul F., Cinel I., Kara I., Undar H.N., Bayraktar Y.S., Celik J.B., Tokur M.E., Aydin D.T., Yildiz I., Ozcan B., Erdivanli B., Eroglu A., Akdag D., Unlu N., Dungca A., Ali A., Thankamma B., Reyes P.E., John S., Rajendran A., Ahmad F.K.E., Smiley K.A., Hojden S., Miller M.T., Das Sasidharan Nair V., Antonio M.G.S., Qawasmeh K.A., Shawish S.A., Twiggs H., Rosado I., Babych V., Morren F., Young C., Vaughan-Jones N., Harris S., Burns K., Georgiev C., Shayamano R., Kerslake I., Creber P., Vochin A., O'Brien C., Caddell P., Hagan S., Hughes M., Torlinski T., Sherwin J., Kannan S., Markham A., Lebon R., Cupitt J., Cranshaw J., White N., Marriott V., Milner W., Groba C.B., Azoia J., Polgarova P., George S., Kapoor R., Lynch C., Fox N., Cranmer K., Llewellym T., Matthews K., Maltby L., Ibao J., Boulton K., Jarman R., Baxter K., Raj A.S., Moghal A., White J., Barrowcliffe S., Pulletz M., Ganeshalingam V., Baruah R., Baker H., Woods J., Ei P.P., Ogbeide V., Hayden P., Hughes J., Balasubramanian M., Salberg A., Saha R., Holmquist D., Derbyshire C., Smith N., Stones E., Ademokun J., Legorburo M.S., North S., Brett C., Jaundoo H., Craig J., Whiteley S., Howcroft C., Wilby L., Delve P., Shaw D., Williams K., Welters I.D., McMullen J., Brett S., Flores L., Trueman-Dawkins T., Templeton M., Adams J., Prowle J., Byers H., McDonnell A., Rose B.O., Reece-Anthony R., Mendes L., Vizcaychipi M., Bull R., Lacaden G., Santiago E., Delgado C.C., Farnell-Ward S., Thorpe E., Somerville J., Williams A., Cummings D., Derrick H., Brumwell S., Randell C., McCann N., Aves E., Berry G., Szakmany T., Gunter U., Pulak P., Sarkar N., Wright K., Gomes V., Jones J., Palfrey R., Camsooksai J., Lewis A., Eneas A., Tridente A., Barr L., Thomas B., Parkin E., Horner D., Frey C., Bench S., Baumber R., Broadhurst P., Jackson M., Williams L., Clark M., Paddle J., Bean S., Buckley S., Palfreeman C., Liu S., Allison N., Attwood B., Parsons P., Houghton V., Turner S.J., Higgins D., Bielskute E., Horrigan N., Jacob R., Habgood K., Zaki A., Collins A., Lord J., Ramiro C., Kubisz-Pudelko A., Kotze M., Williams H., Iovenko I., Tsarev A., Briva A., Mendez G., Napolitano L., Teig M., Rodriguez G.E., Ben-Jacob T., Potestio C., Eng T., Mahanes D., Khanna A., Duggal A., Nananmori M., Lois M., Karamchandani K., Bealer C., Barefield C., Terry D., Fivecoat P., Idowu O., Cata J., Clesi T., Peterson J., Hatton K., Dhaliwal J., Mueller D., Tao J., Eltorai A.S., Pastores S.M., Remor N., Salazar J., Barkas D., Joffe A., Barnes C., Sona C., Schallom M., Short J., Lorenzo J., Von Der Osten I., Borkowska M., Demarre L., Pleitinckx V., Xing C., Debue A.-S., Goller S., Larina E., Labeau, S. O., Blackwood, B., Brett, S. J., Deschepper, M., Francois, G., Honore, P. M., Khanna, A. K., Williams, G., Blot, S. I., Ribas, A. M., Telleria, V. M., Nogueira, P. C., Nafees, K. M. K., Reyes, A. G., Jensen, H. I., Adipa, F. E., Agoston, Z., Hashemian, S. M., Lee, S. -M., Abillama, F. F., Nor, B. M., Mazlan, M. Z., Sanchez-Hurtado, L., De lange, D., Ilesanmi, R. E., Ffarcsi, M. H., Hernandez, A. M., Schefold, J. C., Besbes, L. O., Minope, J. T. S., Rostello, O. F., Bartoli, J. R., Nocheretti, M. G., Escalante, R. G., Loudet, C. I., Gonzalez, A. L., Alvarez, G. A., Campos, P. A., Fonseca, I. P., Alvarez, G. M., Bascary, C. A., del Valle Gimenez, G., Bertoletti, F. P., Bonsignore, P. J. M., Fernandez, M. A., Leslie, G. D., Mclucas, A., Jacquet, L. -M., de Almeida, A. O., Jorge, S. A., Schmidt, R. C., Garcia, P. C., Ronchini, A. L. V., Manap, N. B. A., Laizner, A. M., Mcquirter, M., Kampayana, B. S., Sepulveda, M. I., Zamorano, M. J. F., Zhao, R. H., Hu, L. P., Jiao, Q. F., Wang, H. Y., Xia, C. J., Insu, L., Zhu, J. Y., Zhu, J. F., Huang, R. F., Wang, L. L., Song, J. H., Liu, X. M., Li, Z. S., Li, L. C., Zeng, J. M., Hu, X. C., Wang, R. X., Tak, P. S., Ho, S. W., Jiang, Q. X., Huang, L. P., Liu, X. L., Jiang, J. H., Gong, Y. Y., Lei, D. H., Bi, A. P., Zhao, H. M., Cao, Z. Q., Wu, S. F., Tian, X. F., Feng, Z. X., Liu, X. Z., Jiang, Z. X., Wang, G. X., Hu, R. L., Li, X. Q., Yu, Z. J., Yang, Y. X., Gama, L. M. S., Hernandez, J. S., Ochoa, M. -E., Reyes, A. J. G., Filipovic-Grcic, I., Vukovic, A., Pecenkovic, S., Suput, A., Radivojevic, R. C., Culjak, H., Adam, V. N., Pedersen, K. R., Kjaergard, I. E., Kodal, A. M., Hansen, T. C. B., Pedersen, A. S. B., Thomsen, T. D., Frandsen, T. M., Bliksted, I. A., Tamayo, L. M., Tutillo, D. R. M., Hurtado, C. V., Garcia, M. F., Kutimets, M., Lofqvist, C., Sakki, J. -K., Valta, M. A., Plantefeve, G., Deserts, M. D., Gunther, S. C., Timsit, J. -F., Farkas, J. -C., Bosl, K., Schuppel, S., Stubner, A., Osei, I. P., Kusi-Appiah, A. -C., Yakubu, Y. H., Patsiou, E. -C., Stalika, K. M. M., Enamorado, J. E., Jonasdottir, R. J., Lestari, M. I., Finn, D. O. C. R., Mcpherson, S., Ghioldi, D. M., Bruno, A. V., Maggiore, S. M., Volta, C. A., Taibi, M. R., Tranello, F. P., Giusti, G. D., Martin, M. A., Correia, M. C., Kim, J. H., Kim, K. C., Bae, J. -M., Park, S. Y., Park, T. S., Lee, H. B., Kim, S. C., Chee, H. K., Huh, J. W., Sim, Y. S., Ahn, J. -J., Kang, B. J., Lee, W. -Y., Lee, S. J., Feghaly, M. E., Belkhair, W. A., Tababa, O. W. E., Alkhumsi, S. I. R., Alshrif, A. I., Aboufray, A. A., Triki, A. R., Zahra, H. B., Al-Alawi, M. M. S., Ghula, M. A. A., Bahrin, L. K. K., Deva, S. R., Rahim, A. H. A., Hassan, W. N. W., Ismail, W. N. W., Ali, M. N., Khoo, T. M., Samat, N. M., Tong, J. M. G., Adib, N. A. N., Nor, M. B. M., Sulaiman, S. R., Foong, K. W., Hua, N. P., Zermeno, J. M., Nava, C. L. L., Nandyelly, S. J. R., Sanchez-Hurtado, L. A., Nava, L. P. A., Herrera, J. G., de Anda, G. F. V., Namendys-Silva, S. A., Romero-Gonzalez, J. P., Sosa, M. A., de Molina Serrano, J. I. R., Iburrigarro, S. R., Padilla, N. R. C., Pineda, A. A. V., Villafuerte, M. V. E., Herrera, M. O. G., Subedi, N. B., Pathak, S. D., Vermeijden, J. W., Gerritsen, R. T., Fijen, J. -W., Adejumo, P. O., Sankey, B. J., Olsen, B. F., Jensen, K. D., Johansen, B. F., Finnstrom, I. J., Skorstad, E. M., Lunde, G. A., Akselsen, G. R., Monstad, K. R., Hogvall, L., Malmin, S. K., Andersen, M. H., Hargott, R. F., de Jesus Ortiz, A., Cabral, D. M. B., Rivas, J. C., Moreira, M. L., Ellazar, C. G., Cerezo, F. D., Palo, J. E., Aperocho, C. A. J., Figueiredo, M. F., Pinheiro, C. M., Rita, C. S., Feranandes, A. M., Pinto, V. M. V., Bispo, B. M., Lima, A., Alsheikhly, A. S., Guran, C. T., Filipescu, D. C., Scutariu, M. A., Ebaid, M. S., Velickovic, D., Rajkovic, M., Stanojevic, M., Turcan, A., Lancaricova, D., Yeni, N. P., Syed, M. R., Navarro, J. A., De Pablo, A. M., Llinas, A. A., Lajara, M. A. G., Nieto, M. V., Pena, J. M. G., Gorgolas, M. C., Isasi, M. A., Salva-Costa, V., Garzon-Tovar, C., Olivares, P. G., de Ceballos, J. P. G., Polo, A. B. C., del Mar Diaz Salcedo, M., Alvarez, J. D., Arcas, M. L. B., Gonzalez, J. I. T., de la Ventana, A. B. S., Calleja, P. L. -A., Alvarez, R. G., Zamora, P. S., Guerrero, A. O., Barreiro, E. M., Sanchez, L. C., Diaz, M. G., Muriel, D. S., Alonso, H. F., Fernandez, A. W., Pinan, I. S., Albaiceta, G. M., Fernandez, M. C. I., Abos, F. J. S., Chueca, R. M., Aguirre, L. G., Manosa, S. C., Luque, C. P., Losilla, M. R., Fores, M. T., del Rosario Villar Redondo, M., Arteta Arteta, D. S., Sanchez, M. A. H., Espinosa, C. P., Reyes, L. M., Domenech, L. C., Guillen, C. V., Alvarez, J. T., del Cotillo, M., Barrueco-Francioni, J. E., Conde, B. B., Blanco, M. P. S., Blasco, M. L., Clement, A. I., Sanz, L. C., Gonzalez, I. A., Cano, A. E., Nunez, C. R., Fernadez, I. L., Fernandez, A. A. M., Boedjawan, N. N., Jansson, E. B., Malvemyr, A. -S., Lof, G., Spangfors, M., Lagerhall, C., Akerman, E., Hellkvist, V. H., Larsson, I. -M., Jong, M. L., Hsu, M. Y., Chang, S. C., Mebazaa, M. S., Elhechmi, Y. Z., Kuscu, O. O., Dal, H. C., Calili, D. K., Izdes, S., Gumus, A., Tasdemir, B., Kagnici, A., Ay, S. A., Balbay, A. O., Ozserezli, B., Senturk, E., Serin, S. O., Gul, F., Cinel, I., Undar, H. N., Bayraktar, Y. S., Celik, J. B., Tokur, M. E., Aydin, D. T., Yildiz, I., Ozcan, B., Akdag, D., Unlu, N., Reyes, P. E., Ahmad, F. K. E., Smiley, K. A., Miller, M. T., Antonio, M. G. S., Qawasmeh, K. A., Shawish, S. A., Groba, C. B., Raj, A. S., Ei, P. P., Legorburo, M. S., Welters, I. D., Mcmullen, J., Mcdonnell, A., Rose, B. O., Delgado, C. C., Mccann, N., Turner, S. J., Rodriguez, G. E., Eltorai, A. S., Pastores, S. M., Demarre, L., and Debue, A. -S.
Subjects: Male, Original, medicine.medical_treatment, artificial, Critical Care and Intensive Care Medicine, Medical and Health Sciences, Pressure ulcer, law.invention, Decubitus epidemiology, ICU, Morbidity, Mortality, Outcome, Pressure injury, Risk factors, Adult, Aged, Hospital Mortality, Humans, Patient Discharge, Prevalence, Risk Factors, Intensive Care Units, Respiration, Artificial, 0302 clinical medicine, decubitus epidemiology, pressure injury, pressure ulcer, outcome, risk factors, morbidity, mortality, law, Medicine and Health Sciences, adults, Medicine, Simplified Acute Physiology Score, icu, ziekenhuissterfte, Immunodeficiency, intensive care, European Society of Intensive Care Medicine (ESICM) Trials Group Collaborators, mannen, volwassenen, COST, Intensive care unit, STATE, ULCERS, Underweight, medicine.symptom, Life Sciences & Biomedicine, Human, medicine.medical_specialty, risicofactoren, Decubitus epidemiology, ICU, Pressure injury, Pressure ulcer, Outcome, Risk factors, Morbidity, Mortality, pressure injuries, Intensive Care Unit, prevalentie, NO, 1117 Public Health and Health Services, DecubICUs Study Team, 03 medical and health sciences, Critical Care Medicine, Anesthesiology, General & Internal Medicine, Health Sciences, ouderen, Mechanical ventilation, Science & Technology, business.industry, decubitus, Risk Factor, 030208 emergency & critical care medicine, 1103 Clinical Sciences, Odds ratio, medicine.disease, Emergency & Critical Care Medicine, Confidence interval, 030228 respiratory system, Emergency medicine, kunstmatige ademhaling, RISK-FACTORS, business, respiration
Abstract: Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347, Funder: Flemish Society for Critical Care Nurses, Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score < 19, ICU stay > 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat.
Published: 2021
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46. COVID-19 ARDS is characterized by higher extravascular lung water than non-COVID-19 ARDS: the PiCCOVID study

Author: Xavier Monnet, Francesca Moretto, Rui Shi, Vincent Bonny, Christopher Lai, Rosanna Vaschetto, Jean-Louis Teboul, Alexandra Beurton, Martin Dres, Julien Mayaux, Tài Pham, Nello De Vita, dres, martin, Hôpital Bicêtre, Pôle des Cardiopathies Congénitales du Nouveau-Né à L'adulte - Centre Constitutif Cardiopathies Congénitales Complexes M3C, Groupe Hospitalier Paris Saint-Joseph, Hôpital Marie-Lannelongue, Inserm U999, Université Paris-Saclay, Groupe de recherche clinique CARMAS (Cardiovascular and Respiratory Manifestations of Acute lung injury and Sepsis) (CARMAS), CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Henri Mondor, Neurophysiologie Respiratoire Expérimentale et Clinique (UMRS 1158), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), University Hospital 'Maggiore della Carità' [Novara, Italy], Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Université Paris-Saclay, Service de Pneumologie et Réanimation Médicale [CHU Pitié-Salpêtrière] (Département ' R3S '), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Neurophysiologie Respiratoire Expérimentale et Clinique, Gestionnaire, Hal Sorbonne Université, Hypertension pulmonaire : physiopathologie et innovation thérapeutique (HPPIT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Università degli Studi del Piemonte Orientale - Amedeo Avogadro (UPO), Université de Versailles Saint-Quentin-en-Yvelines - UFR Sciences de la santé Simone Veil (UVSQ Santé), and Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)
Subjects: Male, ARDS, medicine.medical_specialty, [SDV]Life Sciences [q-bio], medicine.medical_treatment, Thermodilution, Pulmonary Edema, 030204 cardiovascular system & hematology, Lung injury, Critical Care and Intensive Care Medicine, Severity of Illness Index, Capillary Permeability, 03 medical and health sciences, Mechanical ventilation, 0302 clinical medicine, Hemodynamic monitoring, Internal medicine, Intensive care, medicine, Extracorporeal membrane oxygenation, Humans, 030212 general & internal medicine, Transpulmonary thermodilution, Diffuse alveolar damage, Lung, Monitoring, Physiologic, Respiratory Distress Syndrome, RC86-88.9, SARS-CoV-2, business.industry, Research, Hemodynamics, COVID-19, Medical emergencies. Critical care. Intensive care. First aid, Oxygenation, Middle Aged, Prognosis, medicine.disease, [SDV] Life Sciences [q-bio], medicine.anatomical_structure, Extravascular Lung Water, Cardiology, business
Abstract: Background In acute respiratory distress syndrome (ARDS), extravascular lung water index (EVLWi) and pulmonary vascular permeability index (PVPI) measured by transpulmonary thermodilution reflect the degree of lung injury. Whether EVLWi and PVPI are different between non-COVID-19 ARDS and the ARDS due to COVID-19 has never been reported. We aimed at comparing EVLWi, PVPI, respiratory mechanics and hemodynamics in patients with COVID-19 ARDS vs. ARDS of other origin. Methods Between March and October 2020, in an observational study conducted in intensive care units from three university hospitals, 60 patients with COVID-19-related ARDS monitored by transpulmonary thermodilution were compared to the 60 consecutive non-COVID-19 ARDS admitted immediately before the COVID-19 outbreak between December 2018 and February 2020. Results Driving pressure was similar between patients with COVID-19 and non-COVID-19 ARDS, at baseline as well as during the study period. Compared to patients without COVID-19, those with COVID-19 exhibited higher EVLWi, both at the baseline (17 (14–21) vs. 15 (11–19) mL/kg, respectively, p = 0.03) and at the time of its maximal value (24 (18–27) vs. 21 (15–24) mL/kg, respectively, p = 0.01). Similar results were observed for PVPI. In COVID-19 patients, the worst ratio between arterial oxygen partial pressure over oxygen inspired fraction was lower (81 (70–109) vs. 100 (80–124) mmHg, respectively, p = 0.02) and prone positioning and extracorporeal membrane oxygenation (ECMO) were more frequently used than in patients without COVID-19. COVID-19 patients had lower maximal lactate level and maximal norepinephrine dose than patients without COVID-19. Day-60 mortality was similar between groups (57% vs. 65%, respectively, p = 0.45). The maximal value of EVLWi and PVPI remained independently associated with outcome in the whole cohort. Conclusion Compared to ARDS patients without COVID-19, patients with COVID-19 had similar lung mechanics, but higher EVLWi and PVPI values from the beginning of the disease. This was associated with worse oxygenation and with more requirement of prone positioning and ECMO. This is compatible with the specific lung inflammation and severe diffuse alveolar damage related to COVID-19. By contrast, patients with COVID-19 had fewer hemodynamic derangement. Eventually, mortality was similar between groups. Trial registration number and date of registration ClinicalTrials.gov (NCT04337983). Registered 30 March 2020—Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT04337983.
Published: 2021

47. Lung Ultrasound for Daily Monitoring and Management of ARDS Patients

Author: Belaid Bouhemad, Andrea Colombo, Silvia Bonaiti, Erminio Santangelo, Silvia Mongodi, Francesco Mojoli, Anita Orlando, Andrea Stella, and Rosanna Vaschetto
Subjects: Pulmonary and Respiratory Medicine, medicine.medical_specialty, ARDS, business.industry, Medicine, Radiology, Critical Care and Intensive Care Medicine, business, medicine.disease, Lung ultrasound
Published: 2019

48. Is it feasible to collect exhaled breath condensate in COVID-19 patients undergoing noninvasive ventilatory support?

Author: Rosanna Vaschetto, Giovanna Elisiana Carpagnano, and Paola Pierucci
Subjects: Pulmonary and Respiratory Medicine, medicine.medical_specialty, 2019-20 coronavirus outbreak, Future studies, Coronavirus disease 2019 (COVID-19), business.industry, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), 03 medical and health sciences, 0302 clinical medicine, 030228 respiratory system, Respiratory failure, Correspondence, medicine, Medicine, Exhaled breath condensate, In patient, 030212 general & internal medicine, Intensive care medicine, business
Abstract: The article recently published by Hjembaek-Brandt et al. focused on humidification during the collection of Exhaled Breath Condensate (EBC) in invasively mechanically ventilated (IMV) patients [1]. Indeed, in the current guidelines it is still unclear the standard humidification setting and technique that should be used [2, 3]. In some studies the EBC has been performed with active humidification (AH) on [4] while others removed it before collection [5]. Hjembaek-brandt demonstrated that diverse settings of AH may remarkably vary the amount of sample collected. The authors concluded that the EBC collection should be performed in no humidification (H-), turning off the humidifier 10 min before starting the exam [1].
Published: 2021

49. Effects of early extubation followed by noninvasive ventilation versus standard extubation on the duration of invasive mechanical ventilation in hypoxemic non-hypercapnic patients: a systematic review and individual patient data meta-analysis of randomized controlled trials

Author: Francesco Barone-Adesi, Federico Longhini, Renata Pletsch-Assunção, Gavin D. Perkins, Paolo Navalesi, Miguel Ferrer, Francesco Della Corte, Dipesh Mistry, Francesca Moretto, Alessandro Pecere, Haibo Qiu, Gianmaria Cammarota, Michele Carron, and Rosanna Vaschetto
Subjects: Time Factors, medicine.medical_treatment, MEDLINE, Weaning, Critical Care and Intensive Care Medicine, law.invention, 03 medical and health sciences, 0302 clinical medicine, Hypoxemic acute respiratory failure, Noninvasive ventilation, Randomized controlled trial, law, Humans, Medicine, 030212 general & internal medicine, Hypoxia, Randomized Controlled Trials as Topic, Mechanical ventilation, RC86-88.9, business.industry, Research, Correction, Medical emergencies. Critical care. Intensive care. First aid, Odds ratio, medicine.disease, Respiration, Artificial, Pneumonia, 030228 respiratory system, Meta-analysis, Anesthesia, Airway Extubation, Breathing, business, Ventilator Weaning
Abstract: Background Usefulness of noninvasive ventilation (NIV) in weaning patients with non-hypercapnic hypoxemic acute respiratory failure (hARF) is unclear. The study aims to assess in patients with non-hypercapnic hARF, the efficacy of NIV after early extubation, compared to standard weaning. Methods In this individual patient data meta-analysis, we searched EMBASE, Medline and Cochrane Central Register of Controlled Trials to identify potentially eligible randomized controlled trials published from database inception to October 2020. To be eligible, studies had to include patients treated with NIV after early extubation and compared to conventional weaning in adult non-hypercapnic hARF patients. Anonymized individual patient data from eligible studies were provided by study investigators. Using one-step and two-step meta-analysis models we tested the difference in total days spent on invasive ventilation. Results We screened 1605 records. Six studies were included in quantitative synthesis. Overall, 459 participants (mean [SD] age, 62 [15] years; 269 [59%] males) recovering from hARF were included in the analysis (233 in the intervention group and 226 controls). Participants receiving NIV had a shorter duration of invasive mechanical ventilation compared to control group (mean difference, − 3.43; 95% CI − 5.17 to − 1.69 days, p p = 0.024), a reduced risk of ventilatory associated pneumonia (odds ratio, 0.24; 95% CI 0.08 to 0.71, p = 0.014), a reduction of time spent in ICU (time ratio, 0.81; 95% CI 0.68 to 0.96, p = 0.015) and in-hospital (time ratio, 0.81; 95% CI 0.69 to 0.95, p = 0.010), with no difference in ICU mortality. Conclusions Although primary studies are limited, using an individual patient data metanalysis approach, NIV after early extubation appears useful in reducing total days spent on invasive mechanical ventilation. Trial registration The protocol was registered to PROSPERO database on 12/06/2019 and available at PROSPERO website inserting the study code i.e., CRD42019133837.
Published: 2021

50. Circulating Platelet-Derived Extracellular Vesicles Are a Hallmark of Sars-Cov-2 Infection

Author: Umberto Dianzani, Roberta Rolla, Rosanna Vaschetto, Beatrice Vilardo, Pier Paolo Sainaghi, Chiara Puricelli, Marcello Manfredi, Lorenza Scotti, Davide Raineri, Nello De Vita, Luigi Mario Castello, Vincenzo Cantaluppi, Mara Giordano, Giuseppe Cappellano, and Annalisa Chiocchetti
Subjects: Blood Platelets, Male, 0301 basic medicine, ARDS, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), 030204 cardiovascular system & hematology, Flow cytometry, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Predictive Value of Tests, medicine, Humans, Platelet, lcsh:QH301-705.5, Aged, Aged, 80 and over, Sars-Cov-2, medicine.diagnostic_test, Receiver operating characteristic, circulating biomarker, business.industry, Communication, Case-control study, COVID-19, General Medicine, Middle Aged, medicine.disease, 030104 developmental biology, lcsh:Biology (General), Case-Control Studies, Predictive value of tests, Immunology, platelets, Biomarker (medicine), Female, business, extracellular vesicles, Biomarkers
Abstract: Sars-Cov-2 infection causes fever and cough that may rapidly lead to acute respiratory distress syndrome (ARDS). Few biomarkers have been identified but, unfortunately, these are individually poorly specific, and novel biomarkers are needed to better predict patient outcome. The aim of this study was to evaluate the diagnostic performance of circulating platelets (PLT)-derived extracellular vesicles (EVs) as biomarkers for Sars-Cov-2 infection, by setting a rapid and reliable test on unmanipulated blood samples. PLT-EVs were quantified by flow cytometry on two independent cohorts of Sars-CoV-2+ (n = 69), Sars-Cov-2− (n = 62) hospitalized patients, and healthy controls. Diagnostic performance of PLT-EVs was evaluated by receiver operating characteristic (ROC) curve. PLT-EVs count were higher in Sars-Cov-2+ compared to Sars-Cov-2− patients or HC. ROC analysis of the combined cohorts showed an AUC = 0.79 and an optimal cut-off value of 1472 EVs/μL, with 75% sensitivity and 74% specificity. These data suggest that PLT-EVs might be an interesting biomarker deserving further investigations to test their predictive power.
Published: 2021

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