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Background: Leptospirosis, a zoonotic disease prevalent in tropical regions, often leads to severe complications such as Weil's disease and acute respiratory distress syndrome (ARDS). This pioneering meta-analysis investigated the role of corticosteroids in treating severe leptospirosis, addressing a critical gap in the current clinical knowledge. Methods: We systematically reviewed studies from PubMed and Scopus, focusing on randomized controlled trials and observational cohort studies involving adult patients diagnosed with leptospirosis. Five studies comprising 279 participants met the inclusion criteria. Results: Although some studies suggest potential benefits, particularly for pulmonary complications, the evidence remains inconclusive due to the limited number of studies and their methodological limitations. Notably, while four of the five reviewed studies indicated a possible positive role of corticosteroids, the single randomized controlled trial showed no significant benefit, highlighting the need for more robust research. Conclusions: While the current evidence provides a basis for potential benefits, it is not sufficient to make definitive clinical recommendations. Further research is essential to clarify the role of corticosteroids in the treatment of severe leptospirosis, with the aim of improving patient outcomes and guiding clinical practices effectively. [ABSTRACT FROM AUTHOR]

Patient self-inflicted lung injury (P-SILI) is a major challenge for the ICU physician: although spontaneous breathing is associated with physiological benefits, in patients with acute respiratory distress syndrome (ARDS), the risk of uncontrolled inspiratory effort leading to additional injury needs to be assessed to avoid delayed intubation and increased mortality. In the present review, we analyze the available clinical and experimental evidence supporting the existence of lung injury caused by uncontrolled high inspiratory effort, we discuss the pathophysiological mechanisms by which increased effort causes P-SILI, and, finally, we consider the measurements and interpretation of bedside physiological measures of increased drive that should alert the clinician. The data presented in this review could help to recognize injurious respiratory patterns that may trigger P-SILI and to prevent it. [ABSTRACT FROM AUTHOR]

Background: The efficacy of veno-venous extracorporeal membrane oxygenation (VV-ECMO) as rescue therapy for refractory COVID-19-related ARDS (C-ARDS) is still debated. We describe the cohort of C-ARDS patients treated with VV-ECMO at our ECMO center, focusing on factors that may affect in-hospital mortality and describing the time course of lung mechanics to assess prognosis. Methods: We performed a prospective observational study in the intensive care unit at the "Città della Salute e della Scienza" University Hospital in Turin, Italy, between March 2020 and December 2021. Indications and management of ECMO followed the Extracorporeal Life Support Organization (ELSO) guidelines. Results: The 60-day in-hospital mortality was particularly high (85.4%). Non-survivor patients were more frequently treated with non-invasive ventilatory support and steroids before ECMO (95.1% vs. 57.1%, p = 0.018 and 73.2% vs. 28.6%, p = 0.033, respectively), while hypertension was the only pre-ECMO factor independently associated with in-hospital mortality (HR: 2.06, 95%CI: 1.06–4.00). High rates of bleeding (85.4%) and superinfections (91.7%) were recorded during ECMO, likely affecting the overall length of ECMO (18 days, IQR: 10–24) and the hospital stay (32 days, IQR: 24–47). Static lung compliance was lower in non-survivors (p = 0.031) and differed over time (p = 0.049), decreasing by 48% compared to initial values in non-survivors. Conclusions: Our data suggest the importance of considering NIS among the common ECMO eligibility criteria and changes in lung compliance during ECMO as a prognostic marker. [ABSTRACT FROM AUTHOR]

Background: During the COVID-19 pandemic, emergency departments were overcrowded with critically ill patients, and many providers were confronted with ethical dilemmas in assigning respiratory support to them due to scarce resources. Quick tools for evaluating patients upon admission were necessary, as many existing scores proved inaccurate in predicting outcomes. The ROX Index (RI), a rapid and straightforward scoring system reflecting respiratory status in acute respiratory failure patients, has shown promise in predicting outcomes for COVID-19 patients. The 24 h difference in the RI accurately gauges mortality and the need for invasive mechanical ventilation (IMV) among patients with COVID-19. Methods: Study design: Prospective cohort study. A total of 204 patients were admitted to the emergency department from May to August 2020. Data were collected from the clinical records. The RI was calculated at admission and 24 h later, and the difference was used to predict the association with mortality and the need for IMV, a logistic regression model was used to adjust for age, sex, presence of comorbidities, and disease severity. Finally, the data were analyzed using ROC. Results: The difference in respiratory RI between admission and 24 h is a good predictor for death (AUC 0.92) and for mechanic ventilation (AUC: 0.75). Each one-unit decrease in the RI difference at 24 h was associated with an odds ratio of 1.48 for the risk of death (95%CI: 1.31–1.67) and an odds ratio of 1.16 for IMV (95% IC: 1.1–1.23). Conclusions: The 24 h variation of RI is a good prediction tool to allow healthcare professionals to identify the patients who will benefit from invasive treatment, especially in low-resource settings. [ABSTRACT FROM AUTHOR]

This review examines respiratory complications in autoimmune rheumatic diseases within intensive care units (ICUs). The respiratory system, primarily affected in diseases like rheumatoid arthritis, systemic lupus erythematosus, and scleroderma, often leads to respiratory failure. Common manifestations include alveolar hemorrhage, interstitial fibrosis, and acute respiratory distress syndrome. Early recognition and treatment of non-malignant conditions are crucial to prevent rapid disease progression, with ICU mortality rates ranging from 30% to 60%. Delayed immunosuppressive or antimicrobial therapy may result in organ system failure. Collaboration with rheumatic specialists is vital for accurate diagnosis and immediate intervention. Mortality rates for rheumatic diseases in the ICU surpass those of other conditions, underscoring the need for specialized care and proactive management. The review emphasizes comprehensive assessments, distinguishing disease-related complications from underlying issues, and the importance of vigilant monitoring to enhance patient outcomes. [ABSTRACT FROM AUTHOR]

Background: High-flow nasal cannula (HFNC) therapy has emerged as a promising treatment modality for interstitial lung disease (ILD)-related respiratory failure. This systematic review aims to evaluate the efficacy and safety of HFNC therapy in patients with ILDs. Methods: A comprehensive literature search was conducted using major electronic databases to identify relevant studies investigating the use of HFNC therapy in ILD patients with respiratory failure. Outcome measures of interest included improvements in oxygenation, dyspnea relief, respiratory rate control, hospital length of stay, and mortality. Results: Twelve studies were analyzed with an overall population of 715 patients included. Idiopathic Pulmonary Fibrosis (IPF) was the most prevalent type of ILD. Evaluated clinical settings were acute (7 studies), chronic (2 studies), and end-stage (3 studies) ILDs. The HFNC as a support for acute respiratory failure seems not inferior to non-invasive ventilation while offering better comfort and patient's perception. Poor data are available about use in chronic/long-term or rehabilitative settings. In end of life/palliative care, an HFNC might improve quality of life. Despite the promising results, further research is warranted to establish optimal HFNC protocols, identify patient subgroups most likely to benefit, and explore long-term outcomes. Conclusions: Overall, the HFNC appears to be a valuable therapeutic option for managing respiratory failure in ILD patients, offering potential improvements in oxygenation and symptom relief. [ABSTRACT FROM AUTHOR]

Background: Acute respiratory distress syndrome (ARDS) presents a significant challenge in critical care settings, characterized by compromised gas exchange, necessitating in the most severe cases interventions such as veno-venous extracorporeal membrane oxygenation (vv-ECMO) when conventional therapies fail. Critically ill ARDS patients on vv-ECMO may experience several complications. Limited data exist comparing complication rates between COVID-19 and non-COVID-19 ARDS patients undergoing vv-ECMO. This retrospective observational study aimed to assess and compare complications in these patient cohorts. Methods: We retrospectively analyzed the medical records of all patients receiving vv-ECMO for ARDS between March 2020 and March 2022. We recorded the baseline characteristics, the disease course and complication (barotrauma, bleeding, thrombosis) before and after ECMO cannulation, and clinical outcomes (mechanical ventilation and ECMO duration, intensive care unit, and hospital lengths of stay and mortalities). Data were compared between COVID-19 and non-COVID-19 patients. In addition, we compared survived and deceased patients. Results: Sixty-four patients were included. COVID-19 patients (n = 25) showed higher rates of pneumothorax (28% vs. 8%, p = 0.039) with subcutaneous emphysema (24% vs. 5%, p = 0.048) and longer non-invasive ventilation duration before vv-ECMO cannulation (2 [1; 4] vs. 0 [0; 1] days, p = <0.001), compared to non-COVID-19 patients (n = 39). However, complication rates and clinical outcomes post-vv-ECMO were similar between groups. Survival analysis revealed no significant differences in pre-vv-ECMO complications, but non-surviving patients had a trend toward higher complication rates and more pleural effusions post-vv-ECMO. Conclusions: COVID-19 patients on vv-ECMO exhibit higher pneumothorax rates with subcutaneous emphysema pre-cannulation; post-cannulation complications are comparable to non-COVID-19 patients. [ABSTRACT FROM AUTHOR]

COVID-19 has been a challenging outbreak to face, with millions of deaths among the globe. Acute respiratory failure due to interstitial pneumonia was the leading cause of death other than prothrombotic activation and complications. Lung ultrasound (LUS) and point-of-care ultrasound (POCUS) are widely used not only to triage, to identify, and to monitor lungs involvement but also to assess hemodynamic status and thrombotic and hemorrhagic complications, mainly in critically ill patients. POCUS has gained growing consideration due to its bedside utilization, reliability, and reproducibility even in emergency settings especially in unstable patients. In this narrative review, we aim to describe LUS and POCUS utilization in COVID-19 infection based on the literature found on this topic. We reported the LUS patterns of COVID-19 pulmonary infection, the diagnostic accuracy with respect to CT lung scan, its prognostic value, the variety of scores and protocols proposed, and the utilization of POCUS to investigate the extra-lung complications. [ABSTRACT FROM AUTHOR]

Airway pressure release ventilation (APRV) is a protective mechanical ventilation mode for patients with acute respiratory distress syndrome (ARDS) that theoretically may reduce ventilator-induced lung injury (VILI) and ARDS-related mortality. However, there is no standard method to set and adjust the APRV mode shown to be optimal. Therefore, we performed a meta-regression analysis to evaluate how the four individual APRV settings impacted the outcome in these patients. Methods: Studies investigating the use of the APRV mode for ARDS patients were searched from electronic databases. We tested individual settings, including (1) high airway pressure (PHigh); (2) low airway pressure (PLow); (3) time at high airway pressure (THigh); and (4) time at low pressure (TLow) for association with PaO2/FiO2 ratio and ICU length of stay. Results: There was no significant difference in PaO2/FiO2 ratio between the groups in any of the four settings (PHigh difference −12.0 [95% CI −100.4, 86.4]; PLow difference 54.3 [95% CI −52.6, 161.1]; TLow difference −27.19 [95% CI −127.0, 72.6]; THigh difference −51.4 [95% CI −170.3, 67.5]). There was high heterogeneity across all parameters (PhHgh I2 = 99.46%, PLow I2 = 99.16%, TLow I2 = 99.31%, THigh I2 = 99.29%). Conclusions: None of the four individual APRV settings independently were associated with differences in outcome. A holistic approach, analyzing all settings in combination, may improve APRV efficacy since it is known that small differences in ventilator settings can significantly alter mortality. Future clinical trials should set and adjust APRV based on the best current scientific evidence available. [ABSTRACT FROM AUTHOR]

Advanced respiratory monitoring encompasses a diverse range of mini- or noninvasive tools used to evaluate various aspects of respiratory function in patients experiencing acute respiratory failure, including those requiring extracorporeal membrane oxygenation (ECMO) support. Among these techniques, key modalities include esophageal pressure measurement (including derived pressures), lung and respiratory muscle ultrasounds, electrical impedance tomography, the monitoring of diaphragm electrical activity, and assessment of flow index. These tools play a critical role in assessing essential parameters such as lung recruitment and overdistention, lung aeration and morphology, ventilation/perfusion distribution, inspiratory effort, respiratory drive, respiratory muscle contraction, and patient–ventilator synchrony. In contrast to conventional methods, advanced respiratory monitoring offers a deeper understanding of pathological changes in lung aeration caused by underlying diseases. Moreover, it allows for meticulous tracking of responses to therapeutic interventions, aiding in the development of personalized respiratory support strategies aimed at preserving lung function and respiratory muscle integrity. The integration of advanced respiratory monitoring represents a significant advancement in the clinical management of acute respiratory failure. It serves as a cornerstone in scenarios where treatment strategies rely on tailored approaches, empowering clinicians to make informed decisions about intervention selection and adjustment. By enabling real-time assessment and modification of respiratory support, advanced monitoring not only optimizes care for patients with acute respiratory distress syndrome but also contributes to improved outcomes and enhanced patient safety. [ABSTRACT FROM AUTHOR]

Acute respiratory distress syndrome (ARDS) is a well-defined clinical entity characterized by the acute onset of diffuse pulmonary injury and hypoxemia not explained by fluid overload. The COVID-19 pandemic brought about an unprecedented volume of patients with ARDS and challenged our understanding and clinical approach to treatment of this clinical syndrome. Unique to COVID-19 ARDS is the disruption and dysregulation of the pulmonary vascular compartment caused by the SARS-CoV-2 virus, which is a significant cause of hypoxemia in these patients. As a result, gas exchange does not necessarily correlate with respiratory system compliance and mechanics in COVID-19 ARDS as it does with other etiologies. The purpose of this review is to relate the mechanics of COVID-19 ARDS to its underlying pathophysiologic mechanisms and outline the lessons we have learned in the management of this clinic syndrome. [ABSTRACT FROM AUTHOR]

Background: The ability to predict a long duration of mechanical ventilation (MV) by clinicians is very limited. We assessed the value of machine learning (ML) for early prediction of the duration of MV > 14 days in patients with moderate-to-severe acute respiratory distress syndrome (ARDS). Methods: This is a development, testing, and external validation study using data from 1173 patients on MV ≥ 3 days with moderate-to-severe ARDS. We first developed and tested prediction models in 920 ARDS patients using relevant features captured at the time of moderate/severe ARDS diagnosis, at 24 h and 72 h after diagnosis with logistic regression, and Multilayer Perceptron, Support Vector Machine, and Random Forest ML techniques. For external validation, we used an independent cohort of 253 patients on MV ≥ 3 days with moderate/severe ARDS. Results: A total of 441 patients (48%) from the derivation cohort (n = 920) and 100 patients (40%) from the validation cohort (n = 253) were mechanically ventilated for >14 days [median 14 days (IQR 8–25) vs. 13 days (IQR 7–21), respectively]. The best early prediction model was obtained with data collected at 72 h after moderate/severe ARDS diagnosis. Multilayer Perceptron risk modeling identified major prognostic factors for the duration of MV > 14 days, including PaO2/FiO2, PaCO2, pH, and positive end-expiratory pressure. Predictions of the duration of MV > 14 days showed modest discrimination [AUC 0.71 (95%CI 0.65–0.76)]. Conclusions: Prolonged MV duration in moderate/severe ARDS patients remains difficult to predict early even with ML techniques such as Multilayer Perceptron and using data at 72 h of diagnosis. More research is needed to identify markers for predicting the length of MV. This study was registered on 14 August 2023 at ClinicalTrials.gov (NCT NCT05993377). [ABSTRACT FROM AUTHOR]

Introduction: Coronavirus disease 2019 (COVID-19) is a significant and novel cause of acute respiratory distress syndrome (ARDS). During the COVID-19 pandemic, there has been an increase in the incidence of cases involving pneumothorax and pneumomediastinum. However, the risk factors associated with poor outcomes in these patients remain unclear. Methods: This observational study collected clinical and imaging data from COVID-19 patients with PTX and/or PNM across five tertiary hospitals in central Italy between 1 March 2020 and 1 March 2022. This study also calculated the incidence of PTX and PNM and utilized multivariable regression analysis and Kaplan–Meier curve analysis to identify predictor factors for 28-day mortality and 3-day orotracheal intubation after PTX/PNM. This study also considered the impact of the three main variants of concern (VoCs) (alfa, delta, and omicron) circulating during the study period. Results: During the study period, a total of 11,938 patients with COVID-19 were admitted. This study found several factors independently associated with a higher risk of death in COVID-19 patients within 28 days of pulmonary barotrauma. These factors included a SOFA score ≥ 4 (OR 3.22, p = 0.013), vasopressor/inotropic therapy (OR 11.8, p < 0.001), hypercapnia (OR 2.72, p = 0.021), PaO2/FiO2 ratio < 150 mmHg (OR 10.9, p < 0.001), and cardiovascular diseases (OR 7.9, p < 0.001). This study also found that a SOFA score ≥ 4 (OR 3.10, p = 0.015), PCO2 > 45 mmHg (OR 6.0, p = 0.003), and P/F ratio < 150 mmHg (OR 2.9, p < 0.042) were factors independently associated with a higher risk of orotracheal intubation (OTI) within 3 days from PTX/PNM in patients with non-invasive mechanical ventilation. SARS-CoV-2 VoCs were not associated with 28-day mortality or the risk of OTI. The estimated cumulative probability of OTI in patients after pneumothorax was 44.0% on the first day, 67.8% on the second day, and 68.9% on the third day, according to univariable survival analysis. In patients who had pneumomediastinum only, the estimated cumulative probability of OTI was 37.5%, 46.7%, and 57.7% on the first, second, and third days, respectively. The overall incidence of PTX/PNM among hospitalized COVID-19 patients was 1.42%, which increased up to 4.1% in patients receiving invasive mechanical ventilation. Conclusions: This study suggests that a high SOFA score (≥4), the need for vasopressor/inotropic therapy, hypercapnia, and PaO2/FiO2 ratio < 150 mmHg in COVID-19 patients with pulmonary barotrauma are associated with higher rates of intubation, ICU admission, and mortality. Identifying these risk factors early on can help healthcare providers anticipate and manage these patients more effectively and provide timely interventions with appropriate intensive care, ultimately improving their outcomes. [ABSTRACT FROM AUTHOR]

Extracorporeal membrane oxygenation (ECMO) is a cardiac or pulmonary function support system that is used in cases of refractory organ failure in addition to conventional treatment. Currently, Level I evidence is not yet available, which reflects improved outcomes with ECMO in pregnant women, the use in pregnancy should be indicated in selected cases and only in specialized centers. We searched articles in the most important scientific databases from 2009 until 31 December 2023 consulting also the site ClinicalTrials.com to find out about studies that have been recently conducted or are currently ongoing. We matched the combination of the following keywords: "ECMO and pregnancy", "H1N1 and pregnancy", "COVID-19 and pregnancy", "ARDS and pregnancy", "ECMO and pregnancy AND (cardiac arrest)". We selected the following number of articles for each keyword combination: "ECMO and pregnancy" (665 articles); "ECMO and influenza H1N1" (384 articles); "pregnancy and influenza H1N1" (1006 articles); "pregnancy and ARDS" (2930 articles); "ECMO and pregnancy and ARDS and influenza H1N1" (24 articles); and "[ECMO and pregnancy AND (cardiac arrest)]" (74 articles). After careful inspection, only 43 papers fitted our scope. There are two types of ECMO: venous-venous (VV-ECMO) and venous-arterial (VA-ECMO). The first-one is necessary to cope with severe hypoxia: oxygen-depleted blood is taken from the venous circulation, oxygenated, and carbon dioxide removed from the extracorporeal circuit and returned to the same venous system. The VA-ECMO is a type of mechanical assistance to the circulatory system that allows to put the failing organ at rest by ensuring adequate oxygenation and systemic de-oxygenation, avoiding multi-organ failure. The main indications for ECMO support in pregnant women are cardiogenic shock, acute respiratory distress syndrome (ARDS), pulmonary embolism, and eclampsia. There are also fetal indications for ECMO, and they are fetal distress, hypoxic-ischemic encephalopathy (HIE), and twin-to-twin transfusion syndrome (TTTS). Until now, based on the outcomes of the numerous clinical studies conducted, ECMO has been shown to be a successful therapeutic strategy in cases where medical treatment has been unsuccessful. In well-selected pregnant patients, it appears to be safe and associated with a low risk of maternal and fetal complications. The aim of this review is to report the main properties of ECMO (VV and VA) and the indications for its use in pregnant women. [ABSTRACT FROM AUTHOR]

(1) Background: This retrospective study focused on severe acute respiratory distress syndrome (ARDS) patients treated with veno-venous (VV) extracorporeal membrane oxygenation (ECMO) and who inhaled nitric oxide (NO) for pulmonary arterial hypertension (PAH) and/or right ventricular failure (RV failure). (2) Methods: Out of 662 ECMO-supported patients, 366 received VV ECMO, including 48 who inhaled NO. We examined the NO's indications, dosing, duration, and the ability to lower PAH. We compared patients with and without inhaled NO in terms of mechanical ventilation duration, ECMO weaning, organ dysfunction, in-hospital mortality, and survival. (3) Results: Patients received 14.5 ± 5.5 ppm NO for 3 days with only one-third experiencing decreased pulmonary arterial pressure. They spent more time on VV ECMO, had a higher ECMO weaning failure frequency, and elevated severity scores (SAPS II and TIPS). A Kaplan–Meier analysis revealed reduced survival in the NO group. Multiple variable logistic regression indicated a twofold increased risk of death for ARDS patients on VV ECMO with NO. We observed no increase in continuous renal replacement therapy. (4) Conclusions: This study suggests that persistent PAH and/or RV failure is associated with poorer outcomes in severe ARDS patients on VV-ECMO, with an inhaled NO responder rate of only 30%, and it does not impact acute kidney failure rates. [ABSTRACT FROM AUTHOR]

The management of mechanical ventilation (MV) remains a challenge in intensive care units (ICUs). The digitalization of healthcare and the implementation of artificial intelligence (AI) and machine learning (ML) has significantly influenced medical decision-making capabilities, potentially enhancing patient outcomes. Acute respiratory distress syndrome, an overwhelming inflammatory lung disease, is common in ICUs. Most patients require MV. Prolonged MV is associated with an increased length of stay, morbidity, and mortality. Shortening the MV duration has both clinical and economic benefits and emphasizes the need for better MV weaning management. AI and ML models can assist the physician in weaning patients from MV by providing predictive tools based on big data. Many ML models have been developed in recent years, dealing with this unmet need. Such models provide an important prediction regarding the success of the individual patient's MV weaning. Some AI models have shown a notable impact on clinical outcomes. However, there are challenges in integrating AI models into clinical practice due to the unfamiliar nature of AI for many physicians and the complexity of some AI models. Our review explores the evolution of weaning methods up to and including AI and ML as weaning aids. [ABSTRACT FROM AUTHOR]

Background: Few data are available concerning the outcome of patients denied venovenous extracorporeal membrane oxygenation (VV-ECMO) relative to severe acute respiratory distress syndrome (ARDS) due to COVID-19. Methods: We compared the 90-day survival rate of consecutive adult patients for whom our center was contacted to discuss VV-ECMO indication. Three groups of patients were created: patients for whom VV-ECMO was immediately indicated (ECMO-indicated group), patients for whom VV-ECMO was not indicated at the time of the call (ECMO-not-indicated group), and patients for whom ECMO was definitely contraindicated (ECMO-contraindicated group). Results: In total, 104 patients were referred for VV-ECMO support due to severe COVID-19 ARDS. Among them, 32 patients had immediate VV-ECMO implantation, 28 patients had no VV-ECMO indication, but 1 was assisted thereafter, and 44 patients were denied VV-ECMO for contraindication. Among the 44 patients denied, 30 were denied for advanced age, 24 for excessive prior duration of mechanical ventilation, and 16 for SOFA score >8. The 90-day survival rate was similar for the ECMO-indicated group and the ECMO-not-indicated group at 62.1 and 61.9%, respectively, whereas it was significantly lower (20.5%) for the ECMO-contraindicated group. Conclusions: Despite a low survival rate, 50% of patients were at home 3 months after being denied for VV-ECMO for severe ARDS due to COVID-19. [ABSTRACT FROM AUTHOR]

The use of neuromuscular blocking agents (NMBAs) is common in the intensive care unit (ICU). NMBAs have been used in critically ill patients with lung diseases to optimize mechanical ventilation, prevent spontaneous respiratory efforts, reduce the work of breathing and oxygen consumption, and avoid patient–ventilator asynchrony. In patients with acute respiratory distress syndrome (ARDS), NMBAs reduce the risk of barotrauma and improve oxygenation. Nevertheless, current guidelines and evidence are contrasting regarding the routine use of NMBAs. In status asthmaticus and acute exacerbation of chronic obstructive pulmonary disease, NMBAs are used in specific conditions to ameliorate patient–ventilator synchronism and oxygenation, although their routine use is controversial. Indeed, the use of NMBAs has decreased over the last decade due to potential adverse effects, such as immobilization, venous thrombosis, patient awareness during paralysis, development of critical illness myopathy, autonomic interactions, ICU-acquired weakness, and residual paralysis after cessation of NMBAs use. The aim of this review is to highlight current knowledge and synthesize the evidence for the effects of NMBAs for critically ill patients with lung diseases, focusing on patient–ventilator asynchrony, ARDS, status asthmaticus, and chronic obstructive pulmonary disease. [ABSTRACT FROM AUTHOR]

Background: Mechanical ventilation is the main supportive treatment of severe cases of COVID-19-associated ARDS (C-ARDS). Weaning failure is common and associated with worse outcomes. We investigated the role of respiratory drive, assessed by monitoring the electrical activity of the diaphragm (EAdi), as a predictor of weaning failure. Methods: Consecutive, mechanically ventilated patients admitted to the ICU for C-ARDS with difficult weaning were enrolled. Blood gas, ventilator, and respiratory mechanic parameters, as well as EAdi, were recorded at the time of placement of EAdi catheter, and then after 1, 2, 3, 7, and 10 days, and compared between patients with weaning success and weaning failure. Results: Twenty patients were enrolled: age 66 (60–69); 85% males; PaO2/FiO2 at admission 148 (126–177) mmHg. Thirteen subjects (65%) were classified as having a successful weaning. A younger age (OR(95%CI): 0.02 (0.01–0.11) per year), a higher PaO2/FiO2 ratio (OR(95%CI): 1.10 (1.01–1.21) per mmHg), and a lower EAdi (OR(95%CI): 0.16 (0.08–0.34) per μV) were associated with weaning success. Conclusion: In critically ill patients with moderate–severe C-ARDS and difficult weaning from mechanical ventilation, a successful weaning was associated with a lower age, a higher oxygenation, and a lower respiratory drive, as assessed at the bedside via EAdi monitoring. [ABSTRACT FROM AUTHOR]

Background: Coronavirus disease 2019 (COVID-19) is the etiology of acute respiratory distress syndrome (ARDS). Extracorporeal membrane oxygenation (ECMO) is used to support gas exchange in patients who have failed conventional mechanical ventilation. However, there is no clear consensus on the timing of ECMO use in severe COVID-19 patients. Objective: The aim of this study is to compare the differences in pre-ECMO time and ECMO duration between COVID-19 survivors and non-survivors and to explore the association between them. Methods: PubMed, the Cochrane Library, Embase, and other sources were searched until 21 October 2022. Studies reporting the relationship between ECMO-related time and COVID-19 survival were included. All available data were pooled using random-effects methods. Linear regression analysis was used to determine the correlation between pre-ECMO time and ECMO duration. The meta-analysis was registered with PROSPERO under registration number CRD42023403236. Results: Out of the initial 2473 citations, we analyzed 318 full-text articles, and 54 studies were included, involving 13,691 patients. There were significant differences between survivors and non-survivors in the time from COVID-19 diagnosis (standardized mean difference (SMD) = −0.41, 95% confidence interval (CI): [−0.53, −0.29], p < 0.00001), hospital (SMD = −0.53, 95% CI: [−0.97, −0.09], p = 0.02) and intensive care unit (ICU) admission (SMD = −0.28, 95% CI: [−0.49, −0.08], p = 0.007), intubation or mechanical ventilation to ECMO (SMD = −0.21, 95% CI: [−0.32, −0.09], p = 0.0003) and ECMO duration (SMD = −0.18, 95% CI: [−0.30, −0.06], p = 0.003). There was no statistical association between a longer time from symptom onset to ECMO (hazard ratio (HR) = 1.05, 95% CI: [0.99, 1.12], p = 0.11) or time from intubation or mechanical ventilation (MV) and the risk of mortality (highest vs. lowest time groups odds ratio (OR) = 1.18, 95% CI: [0.78, 1.78], p = 0.42; per one-day increase OR = 1.14, 95% CI: [0.86, 1.52], p = 0.36; HR = 0.99, 95% CI: [0.95, 1.02], p = 0.39). There was no linear relationship between pre-ECMO time and ECMO duration. Conclusion: There are differences in pre-ECMO time between COVID-19 survivors and non-survivors, and there is insufficient evidence to conclude that longer pre-ECMO time is responsible for reduced survival in COVID-19 patients. ECMO duration differed between survivors and non-survivors, and the timing of pre-ECMO does not have an impact on ECMO duration. Further studies are needed to explore the association between pre-ECMO and ECMO time in the survival of COVID-19 patients. [ABSTRACT FROM AUTHOR]

Background: Prone position (PP) and the positive end-expiratory pressure (PEEP)-induced lung recruitment maneuver (LRM) are both efficient in improving oxygenation and prognosis in patients with ARDS. The synergistic effect of PP combined with PEEP-induced LRM in patients with ARDS remains unclear. We aim to explore the effects of PP combined with PEEP-induced LRM on prognosis in patients with moderate to severe ARDS and the predicting role of lung recruitablity. Methods: Patients with moderate to severe ARDS were consecutively enrolled. The patients were prospectively assigned to either the intervention (PP with PEEP-induced LRM) or control groups (PP). The clinical outcomes, respiratory mechanics, and electric impedance tomography (EIT) monitoring results for the two groups were compared. Lung recruitablity (recruitment-to-inflation ratio: R/I) was measured during the PEEP-induced LRM procedure and was used for predicting the response to LRM. Results: Fifty-eight patients were included in the final analysis, among which 28 patients (48.2%) received PEEP-induced LRM combined with PP. PEEP-induced LRM enhanced the effect of PP by a significant improvement in oxygenation (∆PaO2/FiO2 75.8 mmHg vs. 4.75 mmHg, p < 0.001) and the compliance of respiratory system (∆Crs, 2 mL/cmH2O vs. −1 mL/cmH2O, p = 0.02) among ARDS patients. Based on the EIT measurement, PP combined with PEEP-induced LRM increased the ventilation distribution mainly in the dorsal region (5.0% vs. 2.0%, p = 0.015). The R/I ratio was measured in 28 subjects. The higher R/I ratio was related to greater oxygenation improvement after LRM (Pearson's r = 0.4; p = 0.034). Conclusions: In patients with moderate to severe ARDS, PEEP-induced LRM combined with PP can improve oxygenation and dorsal ventilation distribution. R/I can be useful to predict responses to LRM. [ABSTRACT FROM AUTHOR]

Acute respiratory failure (ARF) is a challenging condition that clinicians, especially in emergency settings, have to face frequently. Especially in emergency settings, many underlying diseases can lead to ARF and life-threatening conditions have to be promptly assessed and correctly treated to avoid unfavorable outcomes. In recent years, point-of-care ultrasound (POCUS) gained growing consideration due to its bedside utilization, reliability and reproducibility even in emergency settings especially in unstable patients. Research on POCUS application to assess ARF has been largely reported mainly with observational studies showing heterogeneous results from many different applications. This narrative review describes the wide potentiality of POCUS to face airways and breathing life-threatening conditions such as upper airway management, pulmonary and pleural pathologies and diaphragm impairment. We conducted extensive research of the literature to report from major studies to case reports deemed useful in practical clinical utilization of POCUS in ARF. Due to the huge amount of the literature found, we focused on airways and breathing assessment trying to systematize the evidence according to clinical care of ARF in emergency settings. Further studies, possibly trials, should determine how POCUS is crucial in clinical practice in terms of standard of care improvements, patient safety and cost-benefit analysis. [ABSTRACT FROM AUTHOR]

Pulmonary circulation is crucial in the human circulatory system, facilitating the oxygenation of blood as it moves from the right heart to the lungs and then to the left heart. However, during critical illness, pulmonary microcirculation can be vulnerable to both intrapulmonary and extrapulmonary injuries. To assess these potential injuries in critically ill patients, critical point-of-care ultrasound can be used to quantitatively and qualitatively evaluate the right atrium, right ventricle, pulmonary artery, lung, pulmonary vein, and left atrium along the direction of blood flow. This assessment is particularly valuable for common ICU diseases such as acute respiratory distress syndrome (ARDS), sepsis, pulmonary hypertension, and cardiogenic pulmonary edema. It has significant potential for diagnosing and treating these conditions in critical care medicine. [ABSTRACT FROM AUTHOR]

Acute Respiratory Distress Syndrome (ARDS) is a sudden onset of lung injury characterized by bilateral pulmonary edema, diffuse inflammation, hypoxemia, and a low P/F ratio. Epithelial injury and endothelial injury are notable in the development of ARDS, which is more severe under mechanical stress. This review explains the role of alveolar epithelial cells and endothelial cells under physiological and pathological conditions during the progression of ARDS. Mechanical injury not only causes ARDS but is also a side effect of ventilator-supporting treatment, which is difficult to model both in vitro and in vivo. The development of lung organoids has seen rapid progress in recent years, with numerous promising achievements made. Multiple types of cells and construction strategies are emerging in the lung organoid culture system. Additionally, the lung-on-a-chip system presents a new idea for simulating lung diseases. This review summarizes the basic features and critical problems in the research on ARDS, as well as the progress in lung organoids, particularly in the rapidly developing microfluidic system-based organoids. Overall, this review provides valuable insights into the three major factors that promote the progression of ARDS and how advances in lung organoid technology can be used to further understand ARDS. [ABSTRACT FROM AUTHOR]

Prone positioning (PP) represents a therapeutic intervention with the proven capacity of ameliorating gas exchanges and ventilatory mechanics indicated in acute respiratory distress syndrome (ARDS). When PP is selectively applied to moderate-severe cases of ARDS, it sensitively affects clinical outcomes, including mortality. After the COVID-19 outbreak, clinical application of PP peaked worldwide and was applied in 60% of treated cases, according to large reports. Research on this topic has revealed many physiological underpinnings of PP, focusing on regional ventilation redistribution and the reduction of parenchymal stress and strain. However, there is a lack of evidence on biomarkers behavior in different phases and phenotypes of ARDS. Patients response to PP are, to date, decided on PaO2/FiO2 ratio improvement, whereas scarce data exist on biomarker tracking during PP. The purpose of this review is to explore current evidence on the clinical relevance of biomarkers in the setting of moderate-severe ARDS of different etiologies (i.e., COVID and non-COVID-related ARDS). Moreover, this review focuses on how PP may modulate biomarkers and which biomarkers may have a role in outcome prediction in ARDS patients. [ABSTRACT FROM AUTHOR]

Artificial intelligence (AI) can make intelligent decisions in a manner akin to that of the human mind. AI has the potential to improve clinical workflow, diagnosis, and prognosis, especially in radiology. Acute respiratory distress syndrome (ARDS) is a very diverse illness that is characterized by interstitial opacities, mostly in the dependent areas, decreased lung aeration with alveolar collapse, and inflammatory lung edema resulting in elevated lung weight. As a result, lung imaging is a crucial tool for evaluating the mechanical and morphological traits of ARDS patients. Compared to traditional chest radiography, sensitivity and specificity of lung computed tomography (CT) and ultrasound are higher. The state of the art in the application of AI is summarized in this narrative review which focuses on CT and ultrasound techniques in patients with ARDS. A total of eighteen items were retrieved. The primary goals of using AI for lung imaging were to evaluate the risk of developing ARDS, the measurement of alveolar recruitment, potential alternative diagnoses, and outcome. While the physician must still be present to guarantee a high standard of examination, AI could help the clinical team provide the best care possible. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic challenged the medical field to rapidly identify and implement new approaches to the diagnosis, treatment and prevention of SARS-CoV-2 infections. The scientific community also needed to rapidly initiate basic, translational, clinical and epidemiological studies to understand the pathophysiology of this new family of viruses, which continues to evolve with the emergence of new genetic variants. One of the earliest clinical observations that provided a framework for the research was the finding that, in contrast to most other respiratory viruses, children developed less severe acute and post-acute disease compared to adults. Although the clinical manifestations of SARS-CoV-2 infection changed with each new wave of the pandemic, which was dominated by evolving viral variants, the differences in severity between children and adults persisted. Comparative immunologic studies have shown that children mount a more vigorous local innate response characterized by the activation of interferon pathways and recruitment of innate cells to the mucosa, which may mitigate against the hyperinflammatory adaptive response and systemic cytokine release that likely contributed to more severe outcomes including acute respiratory distress syndrome in adults. In this review, the clinical manifestations and immunologic responses in children during the different waves of COVID-19 are discussed. [ABSTRACT FROM AUTHOR]

The emergence of the new SARS-CoV-2 in December 2019 caused a worldwide pandemic of the resultant disease, COVID-19. There was a massive surge in admissions to intensive care units (ICU), notably of patients with hypoxaemic acute respiratory failure. In these patients, optimal oxygen therapy was crucial. In this article, we discuss tracheal intubation to provide mechanical ventilation in patients with hypoxaemic acute respiratory failure due to SARS-CoV-2. We first describe the pathophysiology of respiratory anomalies leading to acute respiratory distress syndrome (ARDS) due to infection with SARS-CoV-2, and then briefly review management, focusing particularly on the ventilation strategy. Overall, the ventilatory management of ARDS due to SARS-CoV-2 infection is largely the same as that applied in ARDS from other causes, and lung-protective ventilation is recommended. The difference lies in the initial clinical presentation, with profound hypoxaemia often observed concomitantly with near-normal pulmonary compliance. [ABSTRACT FROM AUTHOR]

(1) Background: There is a marked proportion of spondylodiscitis patients who die during the early stage of the disease despite the applied therapy. This study investigates this early mortality and explores the associated risk factors. (2) Methods: We conducted a retrospective analysis of spondylodiscitis patients treated at our Level I spine center between 1 January 2018 and 31 December 2022. (3) Results: Among 430 patients, 32 (7.4%) died during their hospital stay, with a median time of 28.5 days (range: 2.0–84.0 days). Six of these patients (18.75%) did not undergo surgery due to dire clinical conditions or death prior to scheduled surgery. Identified causes of in-hospital death included multiorgan failure (n = 15), acute bone marrow failure (2), cardiac failure (4), liver failure (2), acute respiratory failure (2), acute renal failure (1), and concomitant oncological disease (1). In a simple logistic regression analysis, advanced age (p = 0.0006), diabetes mellitus (p = 0.0002), previous steroid medication (p = 0.0279), Charlson Comorbidity Index (p < 0.0001), and GFR level at admission (p = 0.0008) were significant risk factors for in-hospital death. In a multiple logistic regression analysis, advanced age (p = 0.0038), diabetes mellitus (p = 0.0002), and previous steroid medication (p = 0.0281) remained significant. (4) Conclusions: Despite immediate treatment, a subset of spondylodiscitis patients experience early mortality. Particular attention should be given to elderly patients and those with diabetes or a history of steroid medication, as they face an elevated risk of a rapidly progressing and fatal disease. [ABSTRACT FROM AUTHOR]

Severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2)-infection is associated with an extremely variable disease course. When interstitial pneumonia (IP) occurs, it can lead to acute respiratory distress syndrome and death. Serum Krebs von den Lungen-6 (KL-6) is an established marker of IP, but its role as a marker of SARS-CoV-2 pneumonia is debated. This bicentric study included 157 patients with SARS-CoV-2 pneumonia. The WHO Ordinal Scale for Clinical Improvement (0–10 points) was used to classify the clinical course. Serum samples were collected at admission, and on days 3 and 7 of hospitalization. KL-6 was measured by using automated chemiluminescence immunoassay. A total of 68 patients developed a severe SARS-CoV-2 pneumonia, 135 of them required oxygen, and 15 died during hospitalization. The patients requiring non-invasive ventilation, invasive ventilation, or extracorporeal membrane oxygenation had significantly higher serum KL-6 levels at admission. The serum KL-6 levels were tendentially higher in patients who died than in those who survived. Logistic regression identified serum KL-6 at a cut-off of 335 U/mL at admission as a significant predictor of severe SARS-CoV-2 pneumonia outcome. Serum KL-6 seems to be a candidate biomarker for the clinical routine to stratify patients with SARS-CoV-2 pneumonia for the risk of a severe disease outcome or death. [ABSTRACT FROM AUTHOR]

Considering the characteristics of coronavirus disease 2019 (COVID-19) acute respiratory distress syndrome (ARDS), we compared the clinical course and outcomes of patients with ARDS who received venovenous extracorporeal membrane oxygenation (VV ECMO) based on the etiology of ARDS. This retrospective single-center study included adult patients with severe ARDS necessitating VV ECMO during the COVID-19 pandemic. Among 45 patients who received VV ECMO, 21 presented with COVID-19. COVID-19 patients exhibited lower sequential organ failure assessment scores (9 [8–12.75] versus 8 [4–11.5], p = 0.033) but longer duration of VV ECMO support (10.5 days [3.25–29.25] versus 28 days [10.5–70.5] p = 0.018), which was accompanied by an weaning off rate from VV ECMO in 12/24 (50%) versus 12/21 (57.1%) and 28-day mortality in 9/24 [37.5%] versus 2/21 [9.5%] in non-COVID-19 and COVID-19 patients (p = 0.767, p = 0.040), respectively. Finally, in the adjusted Cox regression model for hospital mortality, the hazard ratio of COVID-19 was not significant (hazard ratio 0.350, 95% confidence interval 0.110–1.115, p = 0.076). Although the VV ECMO period was longer, COVID-19 did not significantly impact ECMO weaning off and mortality rates. Nonetheless, judicious patient selections based on risk factors should be followed. [ABSTRACT FROM AUTHOR]

Current studies agree on the impact of sleep and circadian rest–activity rhythm alterations in acute respiratory distress syndrome (ARDS) survivors. However, research on the duration of this impact is scarce. In this study, we evaluate the impact of ARDS on the sleep and circadian rest–activity rhythm of COVID-19 survivors twelve months after hospital discharge. This is a prospective study including COVID-19 survivors with and without ARDS during hospitalization. Data was collected four and twelve months after hospital discharge. The interventions included one-week wrist actigraphy and a home sleep apnea test (HSAT), and evaluations were conducted according to the Pittsburgh sleep quality index (PSQI), Epworth sleepiness scale (ESS), and insomnia severity index (ISI). Fifty-two patients were evaluated (ARDS = 31 and non-ARDS = 21); they had a median age of 49.0 [39.0;57.2] years and 53.8% were male. After twelve months, 91.3% presented poor sleep quality, 58.7% presented insomnia, 50% presented daytime somnolence, and 37% presented comorbid insomnia and obstructive sleep apnea (COMISA). No significant improvement was observed in relation to sleep or the circadian rest–activity rhythm between four and twelve months. A tendency of poor sleep quality, insomnia, daytime somnolence, and COMISA was observed. Finally, there was no significant impact on the circadian rest–activity rhythm between four and twelve months or between the groups. [ABSTRACT FROM AUTHOR]

Introduction: The objective of this study is to assess the failure of therapies with HFNO (high-flow nasal oxygen), CPAP, Bilevel, or combined therapy in patients with hypoxemic acute respiratory failure due to SARS-CoV-2 during their hospitalization. Methods: This was a retrospective and observational study of SARS-CoV-2-positive patients who required non-invasive respiratory support (NIRS) at the Reina Sofía General University Hospital of Murcia between March 2020 and May 2021. Results: Of 7355 patients, 197 (11.8%) were included; 95 of them failed this therapy (48.3%). We found that during hospitalization in the ward, the combined therapy of HFNO and CPAP had an overall lower failure rate and the highest treatment with Bilevel (p = 0.005). In the comparison of failure in therapy without two levels of airway pressure, HFNO, CPAP, and combined therapy of HFNO with CPAP, (35.6% of patients) presented with 24.2% failure, compared to those who had two levels of pressure with Bilevel and combined therapy of HFNO with Bilevel (64.4% of patients), with 75.8% associated failure (OR: 0, 374; CI 95%: 0.203–0.688. p = 0.001). Conclusions: The use of NIRS during conventional hospitalization is safe and effective in patients with respiratory failure secondary to SARS-CoV-2 infection. The therapeutic strategy of Bilevel increases the probability of failure, with the combined therapy strategy of CPAP and HFNO being the most promising option. [ABSTRACT FROM AUTHOR]

Background: The impact of serial imaging on the outcome of ICU patients has not been studied specifically in patients with high illness severity. Methods: The authors sought a relationship between the numbers of antero-posterior supine chest X-rays (CXR), computed tomography (CT) examinations, and outcome in a cohort of 292 patients with severe COVID-19 ARDS collected over 24 months in a high-volume ECMO center with established ultrasound and echocardiographic diagnostics. Of the patients, 172 (59%) were obese or morbidly obese, and 119 (41%) were treated with ECMO. Results: The median number of CXRs was eight per 14 days of the length of stay in the ICU. The CXR rate was not related to ICU survival (p = 0.37). Patients required CT scanning in 26.5% of cases, with no relationship to the outcome except for the better ICU survival of the ECMO patients without a need for a CT scan (p = 0.01). The odds ratio for survival associated with ordering a CT scan in an ECMO patient was 0.48, p = 0.01. The calculated savings for not routinely requesting a whole-body CT scan in every patient were 98.685 EUR/24 months. Conclusions: Serial imaging does not impact the survival rates of patients with severe ARDS. Extracorporeal membrane oxygenation patients who did not need CT scanning had significantly better ICU outcomes. [ABSTRACT FROM AUTHOR]

Objective: Our primary objective was to describe the baseline characteristics, main reasons for intensive care unit (ICU) admission, and interventions required in the ICU across patients who received CAR-T cell immunotherapy. The secondary objectives were to evaluate different outcomes (ICU mortality) across patients admitted to the ICU after having received CAR-T cell therapy. Materials and Methods. We performed a medical literature review, which included MEDLINE, Embase, and Cochrane Library, of studies published from the inception of the databases until 2022. We conducted a systematic review with meta-analyses of proportions of several studies, including CAR-T cell-treated patients who required ICU admission. Outcomes in the meta-analysis were evaluated using the random-effects model. Results: We included four studies and analyzed several outcomes, including baseline characteristics and ICU-related findings. CAR-T cell recipients admitted to the ICU are predominantly males (62% CI-95% (57–66)). Of the total CAR-T cell recipients, 4% CI-95% (3–5) die in the hospital, and 6% CI-95% (4–9) of those admitted to the ICU subsequently die. One of the main reasons for ICU admission is acute kidney injury (AKI) in 15% CI-95% (10–19) of cases and acute respiratory failure in 10% CI-95% (6–13) of cases. Regarding the interventions initiated in the ICU, 18% CI-95% (13–22) of the CAR-T recipients required invasive mechanical ventilation during their ICU stay, 23% CI-95% (16–30) required infusion of vasoactive drugs, and 1% CI-95% (0.1–3) required renal replacement therapy (RRT). 18% CI-95% (13–22) of the initially discharged patients were readmitted to the ICU within 30 days, and the mean length of hospital stay is 22 days CI-95% (19–25). The results paint a current state of matter in CAR-T cell recipients admitted to the ICU. Conclusions: To better understand immunotherapy-related complications from an ICU standpoint, acknowledge the deteriorating patient on the ward, reduce the ICU admission rate, advance ICU care, and improve the outcomes of these patients, a standard of care and research regarding CAR-T cell-based immunotherapies should be created. Studies that are looking from the perspective of intensive care are highly warranted because the available literature regarding this area is scarce. [ABSTRACT FROM AUTHOR]

(1) Background: Although Non-Invasive Ventilation (NIV) is effective in preventing mortality and endotracheal intubation in patients with Acute Respiratory Failure (ARF) linked to a neuromuscular disorder, its efficacy can be affected by patient intolerance. A High-Flow Nasal Cannula (HFNC) appears to have a significant advantage over NIV as far as patient tolerance is concerned. The aim of the study was to investigate HFNC's safety profile in a group of consecutive Neuromuscular Disease (NMD) patients intolerant to NIV who were admitted to an Intermediate Respiratory Care Unit (IRCU) for ARF. (2) Methods: The clinical course of nine NMD patients intolerant to NIV and switched to HFNC was reported. HFNC was provided during daytime hours and NIV during the night-time to the NIV-intolerant patients. HFNC was utilized 24 h a day in those patients who were intolerant of even nocturnal NIV. (3) Results: HFNC was simple to use and it was well tolerated by all of the patients. Three out of nine patients experienced treatment failure, consisting of the need for ETI and/or death during their IRCU stay. The remaining 6 had a favorable outcome. Treatment failure was linked to the utilization of HFNC 24 h a day. (4) Conclusion: HFNC during the daytime hours, together with nocturnal NIV, seems to be a safe therapeutic approach for NMD patients with ARF. A round-the-clock use of HFNC tends to be linked to a high likelihood of failure. [ABSTRACT FROM AUTHOR]

Nighttime and non-working days are characterized by a shortage of dedicated staff and available resources. Previous studies have highlighted that patients admitted during the weekend had higher mortality than patients admitted on weekdays ("weekend effect"). However, most studies have focused on specific conditions and controversial results were reported. We conducted an observational, monocentric, retrospective cohort study, based on data collected prospectively to evaluate the impact of the timing of NIV initiation on clinical outcomes in COPD patients with acute respiratory failure (ARF). A total of 266 patients requiring NIV with a time gap between diagnosis of ARF and NIV initiation <48 h were included. Interestingly, 39% of patients were not acidotic (pH = 7.38 ± 0.09 vs. 7.26 ± 0.05, p = 0.003) at the time of NIV initiation. The rate of NIV failure (need for intubation and/or all-cause in-hospital death) was similar among three different scenarios: "daytime" vs. "nighttime", "working" vs. "non-working days", "nighttime or non-working days" vs. "working days at daytime". Patients starting NIV during nighttime had a longer gap to NIV initiation compared to daytime (219 vs. 115 min respectively, p = 0.01), but this did not influence the NIV outcome. These results suggested that in a training center for NIV management, the failure rate did not increase during the "silent" hours. [ABSTRACT FROM AUTHOR]

(1) Background: SARS-COV2 infection has a clinical spectrum ranging from asymptomatic infection to COVID-19 with acute respiratory distress syndrome (ARDS). Although vitamin D deficiency is often found in patients with ARDS, its role in COVID-19 is not clear. The aim of this study was to explore a possible association between serum 25-hydroxyvitamin D levels and the severity of COVID-19 in hospitalised patients. (2) Methods: In this retrospective observational study, we analysed data from 763 patients hospitalised for COVID-19 in 2020 and 2021. Patients were included in the study if serum 25-hydroxyvitamin D was assessed 30 days before or after hospital admission. Vitamin D deficiency was defined as <50 nmol/L (<20 ng/mL). The primary outcome was COVID-19 severity. (3) Results: The overall median serum 25-hydroxyvitamin D level was 54 nmol/L (IQR 35–76); 47% of the patients were vitamin D deficient. Most patients had mild to moderate COVID-19 and no differences were observed between vitamin D deficient and non-deficient patients (81% vs. 84% of patients, respectively p = 0.829). (4) Conclusion: No association was found between serum 25-hydroxyvitamin D levels and COVID-19 severity in this large observational study conducted over 2 years of the pandemic. [ABSTRACT FROM AUTHOR]

Background: One of the main features of COVID-19 pneumonia is hypoxemic acute respiratory failure (ARF), often requiring ventilatory support. The influence of chest physiotherapy in patients with ARF is not extensively studied. The aim of the study was to analyze the short-time effects of chest physiotherapy using a 10 cm H2O threshold valve in patients with COVID-19 and ARF. Methods; Quasi-experimental cross-sectional study, in hospitalized patients from March to May 2020. The fractions of inspired oxygen, oxygen saturation, heart rate, respiratory rate and dyspnea were collected before and after the starting session (day 1) and after the 5th day of therapy. Results: The final sample size included 125 patients. Significant differences (p < 0.01) were found in the pre-post intervention SpO2/FiO2 ratio (250 ± 88.4 vs. 275.6 ± 97.5, p < 0.001), reaching 354.4 ± 110.2 after 5 days of therapy (p < 0.001 with respect to the baseline). The respiratory and heart rate dyspnea level did not change during the intervention. In patients needing FiO2 > 0.4, the SpO2/FiO2 ratio improvement was higher than in patients with milder severity (46.85 ± 77.69, p < 0.01). Conclusions: Chest physiotherapy with a 10 cm H2O threshold valve seems to be a safe and tolerated intervention with short-term improvement in oxygenation in patients with COVID-19 pneumonia. [ABSTRACT FROM AUTHOR]

Treatment of acute respiratory distress syndrome (ARDS) represents a severe complication of coronavirus disease 2019 (COVID-19) infection and is often challenging in intensive care treatment. Potential positive effects of intravenous cyclophosphamide have been reported in interstitial lung diseases (ILDs). However, there are no data on the use of high-dose cyclophosphamide in therapy-resistant COVID-19 ARDS. We report the case of a 32-year-old male patient admitted to the intensive care unit (ICU) of the Medical University of Vienna due to severe COVID-19 ARDS who required venovenous extracorporeal membrane oxygenation (ECMO) with a total runtime of 85 days. Despite all these therapeutic efforts, he remained in a condition of therapy-resistant ARDS. Unfortunately, the patient was denied for lung transplantation. However, a significant improvement in his respiratory condition was achieved after the administration of an intravenous regimen of cyclophosphamide and prednisolone. After a period of consecutive stabilization, the patient was transferred to the normal ward after 125 days of intensive care treatment. There is a substantial lack of therapeutic options in therapy-resistant ARDS. Our case report suggests that cyclophosphamide may represent a new treatment strategy in therapy-resistant ARDS. Due to its severe adverse effect profile, cyclophosphamide should be used after careful evaluation of a patient's general condition. [ABSTRACT FROM AUTHOR]

Background: A few prospective trials and case series have suggested that hyperbaric oxygen therapy (HBOT) may be efficacious for the treatment of severe COVID-19, but safety is a concern for critically ill patients. We present an interim analysis of the safety of HBOT via a randomized controlled trial (COVID-19-HBO). Methods: A randomized controlled, open-label, clinical trial was conducted in compliance with good clinical practice to explore the safety and efficacy of HBOT for severe COVID-19 in critically ill patients with moderate acute respiratory distress syndrome (ARDS). Between 3 June 2020, and 17 May 2021, 31 patients with severe COVID-19 and moderate-to-severe ARDS, a ratio of arterial oxygen partial pressure to fractional inspired oxygen (PaO2/FiO2) < 26.7 kPa (200 mmHg), and at least two defined risk factors for intensive care unit (ICU) admission and/or mortality were enrolled in the trial and randomized 1:1 to best practice, or HBOT in addition to best practice. The subjects allocated to HBOT received a maximum of five treatments at 2.4 atmospheres absolute (ATA) for 80 min over seven days. The subjects were followed up for 30 days. The safety endpoints were analyzed. Results: Adverse events (AEs) were common. Hypoxia was the most common adverse event reported. There was no statistically significant difference between the groups. Numerically, serious adverse events (SAEs) and barotrauma were more frequent in the control group, and the differences between groups were in favor of the HBOT in PaO2/FiO2 (PFI) and the national early warning score (NEWS); statistically, however, the differences were not significant at day 7, and no difference was observed for the total oxygen burden and cumulative pulmonary oxygen toxicity dose (CPTD). Conclusion: HBOT appears to be safe as an intervention for critically ill patients with moderate-to-severe ARDS induced by COVID-19. Clinical trial registration: NCT04327505 (31 March 2020) and EudraCT 2020-001349-37 (24 April 2020). [ABSTRACT FROM AUTHOR]

We hypothesize that (1) a significant pre-ECMO liver impairment, which is evident in the presence of pre-ECMO acute liver injury and a higher pre-ECMO MELD (model for end-stage liver disease) score, is associated with increased mortality; and (2) the requirement of veno-veno-arterial (V-VA) ECMO support is linked to a higher prevalence of pre-ECMO acute liver injury, a higher pre-ECMO MELD score, and increased mortality. We analyze 187 ECMO runs (42 V-VA and 145 veno-venous (V-V) ECMO) between January 2017 and December 2020. The SAPS II score is calculated at ICU admission; hepatic function and MELD score are assessed at ECMO initiation (pre-ECMO) and during the first five days on ECMO. SOFA, PRESERVE and RESP scores are calculated at ECMO initiation. Pre-ECMO cardiac failure, acute liver injury, ECMO type, SAPS II and MELD, SOFA, PRESERVE, and RESP scores are associated with mortality. However, only the pre-ECMO MELD score independently predicts mortality (p = 0.04). In patients with a pre-ECMO MELD score > 16, V-VA ECMO is associated with a higher mortality risk (p = 0.0003). The requirement of V-VA ECMO is associated with the development of acute liver injury during ECMO support, a higher pre-ECMO MELD score, and increased mortality. [ABSTRACT FROM AUTHOR]

Background: Reverse triggered breath (RTB) has been extensively described during assisted-controlled modes of ventilation. We aimed to assess whether RTB occurs during Pressure Support Ventilation (PSV) and Neurally Adjusted Ventilatory Assist (NAVA) at varying depths of propofol sedation. Methods: This is a retrospective analysis of a prospective crossover randomized controlled trial conducted in an Intensive Care Unit (ICU) of a university hospital. Fourteen intubated patients for acute respiratory failure received six trials of 25 minutes randomly applying PSV and NAVA at three different propofol infusions: awake, light, and deep sedation. We assessed the occurrence of RTBs at each protocol step. The incidence level of RTBs was determined through the RTB index, which was calculated by dividing RTBs by the total number of breaths triggered and not triggered. Results: RTBs occurred during both PSV and NAVA. The RTB index was greater during PSV than during NAVA at mild (1.5 [0.0; 5.3]% vs. 0.6 [0.0; 1.1]%) and deep (5.9 [0.7; 9.0]% vs. 1.7 [0.9; 3.5]%) sedation. Conclusions: RTB occurs in patients undergoing assisted mechanical ventilation. The level of propofol sedation and the mode of ventilation may influence the incidence of RTBs. [ABSTRACT FROM AUTHOR]

At present, the management of patients with acute respiratory distress syndrome (ARDS) largely focuses on ventilator settings to limit intrathoracic pressures by using low tidal volumes and on FiO2/PEEP relationships to maintain optimal gas exchange. Acute respiratory distress syndrome is a complex medical disorder that can develop in several primary acute disorders, has a rapid time course, and has several classifications that can reflect either the degree of hypoxemia, the extent of radiographic involvement, or the underlying pathogenesis. The identification of subtypes of patients with ARDS would potentially make precision medicine possible in these patients. This is a very difficult challenge given the heterogeneity in the clinical presentation, pathogenesis, and treatment responses in these patients. The analysis of large databases of patients with acute respiratory failure using statistical methods such as cluster analysis could identify phenotypes that have different outcomes or treatment strategies. However, clinical information available on presentation is unlikely to separate patients into groups that allow for secure treatment decisions or outcome predictions. In some patients, non-invasive positive pressure ventilation provides adequate support through episodes of acute respiratory failure, and the development of specialized units to manage patients with this support might lead to the better use of hospital resources. Patients with ARDS have capillary leak, which results in interstitial and alveolar edema. Early attention to fluid balance in these patients might improve gas exchange and alter the pathophysiology underlying the development of severe ARDS. Finally, more attention to the interaction of patients with ventilators through complex monitoring systems has the potential to identify ventilator dyssynchrony, leading to ventilator adjustments and potentially better outcomes. Recent studies with COVID-19 patients provide tentative answers to some of these questions. In addition, expert clinical investigators have analyzed the promise and difficulties associated with the development of precision medicine in patients with ARDS. [ABSTRACT FROM AUTHOR]

Acute respiratory distress syndrome (ARDS) is associated with a heterogeneous pattern of injury throughout the lung parenchyma that alters regional alveolar opening and collapse time constants. Such heterogeneity leads to atelectasis and repetitive alveolar collapse and expansion (RACE). The net effect is a progressive loss of lung volume with secondary ventilator-induced lung injury (VILI). Previous concepts of ARDS pathophysiology envisioned a two-compartment system: a small amount of normally aerated lung tissue in the non-dependent regions (termed "baby lung"); and a collapsed and edematous tissue in dependent regions. Based on such compartmentalization, two protective ventilation strategies have been developed: (1) a "protective lung approach" (PLA), designed to reduce overdistension in the remaining aerated compartment using a low tidal volume; and (2) an "open lung approach" (OLA), which first attempts to open the collapsed lung tissue over a short time frame (seconds or minutes) with an initial recruitment maneuver, and then stabilize newly recruited tissue using titrated positive end-expiratory pressure (PEEP). A more recent understanding of ARDS pathophysiology identifies regional alveolar instability and collapse (i.e., hidden micro-atelectasis) in both lung compartments as a primary VILI mechanism. Based on this understanding, we propose an alternative strategy to ventilating the injured lung, which we term a "stabilize lung approach" (SLA). The SLA is designed to immediately stabilize the lung and reduce RACE while gradually reopening collapsed tissue over hours or days. At the core of SLA is time-controlled adaptive ventilation (TCAV), a method to adjust the parameters of the airway pressure release ventilation (APRV) modality. Since the acutely injured lung at any given airway pressure requires more time for alveolar recruitment and less time for alveolar collapse, SLA adjusts inspiratory and expiratory durations and inflation pressure levels. The TCAV method SLA reverses the open first and stabilize second OLA method by: (i) immediately stabilizing lung tissue using a very brief exhalation time (≤0.5 s), so that alveoli simply do not have sufficient time to collapse. The exhalation duration is personalized and adaptive to individual respiratory mechanical properties (i.e., elastic recoil); and (ii) gradually recruiting collapsed lung tissue using an inflate and brake ratchet combined with an extended inspiratory duration (4–6 s) method. Translational animal studies, clinical statistical analysis, and case reports support the use of TCAV as an efficacious lung protective strategy. [ABSTRACT FROM AUTHOR]

Acute respiratory distress syndrome (ARDS) is a leading cause of disability and mortality worldwide, and while no specific etiologic interventions have been shown to improve outcomes, noninvasive and invasive respiratory support strategies are life-saving interventions that allow time for lung recovery. However, the inappropriate management of these strategies, which neglects the unique features of respiratory, lung, and chest wall mechanics may result in disease progression, such as patient self-inflicted lung injury during spontaneous breathing or by ventilator-induced lung injury during invasive mechanical ventilation. ARDS characteristics are highly heterogeneous; therefore, a physiology-based approach is strongly advocated to titrate the delivery and management of respiratory support strategies to match patient characteristics and needs to limit ARDS progression. Several tools have been implemented in clinical practice to aid the clinician in identifying the ARDS sub-phenotypes based on physiological peculiarities (inspiratory effort, respiratory mechanics, and recruitability), thus allowing for the appropriate application of personalized supportive care. In this narrative review, we provide an overview of noninvasive and invasive respiratory support strategies, as well as discuss how identifying ARDS sub-phenotypes in daily practice can help clinicians to deliver personalized respiratory support and potentially improve patient outcomes. [ABSTRACT FROM AUTHOR]

Background: Changing trunk inclination affects lung function in patients with ARDS. However, its impacts on PEEP titration remain unknown. The primary aim of this study was to assess, in mechanically ventilated patients with COVID-19 ARDS, the effects of trunk inclination on PEEP titration. The secondary aim was to compare respiratory mechanics and gas exchange in the semi-recumbent (40° head-of-the-bed) and supine-flat (0°) positions following PEEP titration. Methods: Twelve patients were positioned both at 40° and 0° trunk inclination (randomized order). The PEEP associated with the best compromise between overdistension and collapse guided by Electrical Impedance Tomography (PEEPEIT) was set. After 30 min of controlled mechanical ventilation, data regarding respiratory mechanics, gas exchange, and EIT parameters were collected. The same procedure was repeated for the other trunk inclination. Results: PEEPEIT was lower in the semi-recumbent than in the supine-flat position (8 ± 2 vs. 13 ± 2 cmH2O, p < 0.001). A semi-recumbent position with optimized PEEP resulted in higher PaO2:FiO2 (141 ± 46 vs. 196 ± 99, p = 0.02) and a lower global inhomogeneity index (46 ± 10 vs. 53 ± 11, p = 0.008). After 30 min of observation, a loss of aeration (measured by EIT) was observed only in the supine-flat position (−153 ± 162 vs. 27 ± 203 mL, p = 0.007). Conclusions: A semi-recumbent position is associated with lower PEEPEIT and results in better oxygenation, less derecruitment, and more homogenous ventilation compared to the supine-flat position. [ABSTRACT FROM AUTHOR]

Background: For moderate to severe acute respiratory distress syndrome (ARDS), lung-protective ventilation combined with prolonged and repeated prone position (PP) is recommended. For the most severe patients for whom this strategy failed, venovenous extracorporeal membrane oxygenation (vv-ECMO) allows a reduction in ventilation-induced lung injury and improves survival. Some aggregated data have suggested a benefit regarding survival in pursuing PP during vv-ECMO. The combination of PP and vv-ECMO has been also documented in COVID-19 studies, although there is scarce evidence concerning respiratory mechanics and gas exchange response. The main objective was to compare the physiological response of the first PP during vv-ECMO in two cohorts of patients (COVID-19-related ARDS and non-COVID-19 ARDS) regarding respiratory system compliance (CRS) and oxygenation changes. Methods: This was a single-center, retrospective, and ambispective cohort study in the ECMO center of Marseille, France. ECMO was indicated according to the EOLIA trial criteria. Results: A total of 85 patients were included, 60 in the non-COVID-19 ARDS group and 25 in the COVID-19-related ARDS group. Lung injuries of the COVID-19 cohort exhibited significantly higher severity with a lower CRS at baseline. Concerning the main objective, the first PP during vv-ECMO was not associated with a change in CRS or other variation in respiratory mechanic variables in both cohorts. By contrast, oxygenation was improved only in the non-COVID-19 ARDS group after a return to the supine position. Mean arterial pressure was higher during PP as compared with a return to the supine position in the COVID-19 group. Conclusion: We found distinct physiological responses to the first PP in vv-ECMO-supported ARDS patients according to the COVID-19 etiology. This could be due to higher severity at baseline or specificity of the disease. Further investigations are warranted. [ABSTRACT FROM AUTHOR]

Acute respiratory distress syndrome (ARDS) is a life-threatening lung condition that arises from multiple causes, including sepsis, pneumonia, trauma, and severe coronavirus disease 2019 (COVID-19). Given the heterogeneity of causes and the lack of specific therapeutic options, it is crucial to understand the genetic and molecular mechanisms that underlie this condition. The identification of genetic risks and pharmacogenetic loci, which are involved in determining drug responses, could help enhance early patient diagnosis, assist in risk stratification of patients, and reveal novel targets for pharmacological interventions, including possibilities for drug repositioning. Here, we highlight the basis and importance of the most common genetic approaches to understanding the pathogenesis of ARDS and its critical triggers. We summarize the findings of screening common genetic variation via genome-wide association studies and analyses based on other approaches, such as polygenic risk scores, multi-trait analyses, or Mendelian randomization studies. We also provide an overview of results from rare genetic variation studies using Next-Generation Sequencing techniques and their links with inborn errors of immunity. Lastly, we discuss the genetic overlap between severe COVID-19 and ARDS by other causes. [ABSTRACT FROM AUTHOR]

Introduction: Despite improved management of patients with COVID-19, we still ignore whether pharmacologic treatments and improved respiratory support have modified outcomes for intensive care unit (ICU) surviving patients of the three first consecutive waves (w) of the pandemic. The aim of this study was to evaluate whether developments in the management of ICU COVID-19 patients have positively impacted respiratory functional outcomes, quality of life (QoL), and chest CT scan patterns in ICU COVID-19 surviving patients at 3 months, according to pandemic waves. Methods: We prospectively included all patients admitted to the ICU of two university hospitals with acute respiratory distress syndrome (ARDS) related to COVID-19. Data related to hospitalization (disease severity, complications), demographics, and medical history were collected. Patients were assessed 3 months post-ICU discharge using a 6 min walking distance test (6MWT), a pulmonary function test (PFT), a respiratory muscle strength (RMS) test, a chest CT scan, and a Short Form 36 (SF-36) questionnaire. Results: We included 84 ARDS COVID-19 surviving patients. Disease severity, complications, demographics, and comorbidities were similar between groups, but there were more women in wave 3 (w3). Length of stay at the hospital was shorter during w3 vs. during wave 1 (w1) (23.4 ± 14.2 days vs. 34.7 ± 20.8 days, p = 0.0304). Fewer patients required mechanical ventilation (MV) during the second wave (w2) vs. during w1 (33.3% vs. 63.9%, p = 0.0038). Assessment at 3 months after ICU discharge revealed that PFTs and 6MWTs scores were worse for w3 > w2 > w1. QoL (SF-36) deteriorated (vitality and mental health) more for patients in w1 vs. in w3 (64.7 ± 16.3 vs. 49.2 ± 23.2, p = 0.0169). Mechanical ventilation was associated with reduced forced expiratory volume (FEV1), total lung capacity (TLC), diffusing capacity for carbon monoxide (DLCO), and respiratory muscle strength (RMS) (w1,2,3, p < 0.0500) on linear/logistic regression analysis. The use of glucocorticoids, as well as tocilizumab, was associated with improvements in the number of affected segments in chest CT, FEV1, TLC, and DLCO (p < 0.01). Conclusions: With better understanding and management of COVID-19, there was an improvement in PFT, 6MWT, and RMS in ICU survivors 3 months after ICU discharge, regardless of the pandemic wave during which they were hospitalized. However, immunomodulation and improved best practices for the management of COVID-19 do not appear to be sufficient to prevent significant morbidity in critically ill patients. [ABSTRACT FROM AUTHOR]