Conscious prone positioning in nonintubated COVID-19 patients with acute respiratory distress syndrome: systematic review and meta-analysis.

OBJECTIVE: To systematically review the effect of the prone position on endotracheal intubation and mortality in nonintubated COVID-19 patients with acute respiratory distress syndrome. METHODS: We registered the protocol (CRD42021286711) and searched for four databases and gray literature from inception to December 31, 2022. We included observational studies and clinical trials. There was no limit by date or the language of publication. We excluded case reports, case series, studies not available in full text, and those studies that included children < 18-years-old. RESULTS: We included ten observational studies, eight clinical trials, 3,969 patients, 1,120 endotracheal intubation events, and 843 deaths. All of the studies had a low risk of bias (Newcastle-Ottawa Scale and Risk of Bias 2 tools). We found that the conscious prone position decreased the odds of endotracheal intubation by 44% (OR 0.56; 95%CI 0.40 - 0.78) and mortality by 43% (OR 0.57; 95%CI 0.39 - 0.84) in nonintubated COVID-19 patients with acute respiratory distress syndrome. This protective effect on endotracheal intubation and mortality was more robust in those who spent > 8 hours/day in the conscious prone position (OR 0.43; 95%CI 0.26 - 0.72 and OR 0.38; 95%CI 0.24 - 0.60, respectively). The certainty of the evidence according to the GRADE criteria was moderate. CONCLUSION: The conscious prone position decreased the odds of endotracheal intubation and mortality, especially when patients spent over 8 hours/day in the conscious prone position and treatment in the intensive care unit. However, our results should be cautiously interpreted due to limitations in evaluating randomized clinical trials, nonrandomized clinical trials and observational studies. However, despite systematic reviews with meta-analyses of randomized clinical trials, we must keep in mind that these studies remain heterogeneous from a clinical and methodological point of view.

Manufacturing, quality control, and GLP-grade preclinical study of nebulized allogenic adipose mesenchymal stromal cells-derived extracellular vesicles.

BACKGROUND: Human adipose stromal cells-derived extracellular vesicles (haMSC-EVs) have been shown to alleviate inflammation in acute lung injury (ALI) animal models. However, there are few systemic studies on clinical-grade haMSC-EVs. Our study aimed to investigate the manufacturing, quality control (QC) and preclinical safety of clinical-grade haMSC-EVs. METHODS: haMSC-EVs were isolated from the conditioned medium of human adipose MSCs incubated in 2D containers. Purification was performed by PEG precipitation and differential centrifugation. Characterizations were conducted by nanoparticle tracking analysis, transmission electron microscopy (TEM), Western blotting, nanoflow cytometry analysis, and the TNF-α inhibition ratio of macrophage [after stimulated by lipopolysaccharide (LPS)]. RNA-seq and proteomic analysis with liquid chromatography tandem mass spectrometry (LC-MS/MS) were used to inspect the lot-to-lot consistency of the EV products. Repeated toxicity was evaluated in rats after administration using trace liquid endotracheal nebulizers for 28 days, and respiratory toxicity was evaluated 24 h after the first administration. In vivo therapeutic effects were assessed in an LPS-induced ALI/ acute respiratory distress syndrome (ARDS) rat model. RESULTS: The quality criteria have been standardized. In a stability study, haMSC-EVs were found to remain stable after 6 months of storage at - 80°C, 3 months at - 20 °C, and 6 h at room temperature. The microRNA profile and proteome of haMSC-EVs demonstrated suitable lot-to-lot consistency, further suggesting the stability of the production processes. Intratracheally administered 1.5 × 108 particles/rat/day for four weeks elicited no significant toxicity in rats. In LPS-induced ALI/ARDS model rats, intratracheally administered haMSC-EVs alleviated lung injury, possibly by reducing the serum level of inflammatory factors. CONCLUSION: haMSC-EVs, as an off-shelf drug, have suitable stability and lot-to-lot consistency. Intratracheally administered haMSC-EVs demonstrated excellent safety at the tested dosages in systematic preclinical toxicity studies. Intratracheally administered haMSC-EVs improved the lung function and exerted anti-inflammatory effects on LPS-induced ALI/ARDS model rats.

[Pulse oximetric saturation/fraction of inspired oxygen and partial pressure of oxygen/fraction of inspired oxygen in diagnosing acute respiratory distress syndrome: which is better?]

Acute Respiratory Distress Syndrome (ARDS) is distinguished by hypoxemia, contributing to heightened morbidity, elevated mortality rates, and substantial healthcare expenses, thereby imposing a significant burden on patients and society. Presently, effective treatments for ARDS are lacking, emphasizing the pivotal role of early diagnosis and timely intervention in its successful management. The partial pressure of oxygen/fraction of inspired oxygen (PaO2/FiO2, P/F) has traditionally served as a crucial metric for assessing patient hypoxemia and disease severity. While relatively accurate, its reliance on advanced technical expertise and specific medical equipment conditions constrains its implementation in areas with underdeveloped medical standards, resulting in missed diagnoses and treatments for ARDS patients. Conversely, the Pulse oximetric saturation/fraction of inspired oxygen (SpO2/FiO2, S/F) has garnered increasing attention owing to its straightforward, non-invasive, and sustainable monitoring attributes. This article seeks to meticulously compare the correlation, accuracy, and clinical feasibility of S/F with P/F in ARDS diagnosis, so as to propose diagnostic indicators for more quickly and accurately assessing the oxygenation status of ARDS patients.

[Prone positioning ventilation therapy in acute respiratory distress syndrome: knowns and unknowns in clinical efficacy].

Prone positioning ventilation (PPV) is considered one of the essential therapeutic approaches in the management of acute respiratory distress syndrome (ARDS). Several randomized controlled clinical trials have demonstrated the efficacy of PPV in the treatment of patients with ARDS. However, it is not clear whether PPV treatment can reduce mortality in patients with veno-venous extracorporeal membrane oxygenation (VV-ECMO)-supported ARDS and corona virus disease 2019 (COVID-19)-associated ARDS. This review aims to discuss the known and unknown aspects of the mechanism of PPV for ARDS, the clinical efficacy of PPV for ARDS, VV-ECMO-supported ARDS, and COVID-19-related ARDS.

[Clinical value of the implication of extracorporeal carbon dioxide removal in patients with acute respiratory distress syndrome].

Extracorporeal carbon dioxide removal (ECCO2R) is a respiratory support technique based on extra-pulmonary gas exchange, which can effectively remove carbon dioxide generated in-vivo, reducing the requirements of respiratory support from mechanical ventilation. With improvements in extracorporeal life support technologies and increasing clinical experience, ECCO2R has potential value in clinical application with acute respiratory distress syndrome (ARDS). This review article discusses the principles of ECCO2R, its relevant indications for ARDS, clinical evidence, existing issues, and future directions, aiming to provide more references for the application in ARDS.

[The mechanical ventilation guided by electrical impedance tomography in acute respiratory distress syndrome].

Acute respiratory distress syndrome (ARDS) is a common and critical clinical condition characterized by diffuse damage to the lung interstitium, alveoli, and increased permeability of pulmonary blood vessels. CT can be used to assess the imaging features, severity, and prediction of ARDS, but it requires patient transportation to the CT room and is only a static examination. Electrical impedance tomography (EIT) is an increasingly widely used monitoring tool in clinical applications in recent years. It enables continuous real-time assessment of lung ventilation distribution at the bedside and has high clinical value in optimizing mechanical ventilation parameters for critically ill patients. This article introduces the basic principles of EIT and how to better utilize EIT technology to guide mechanical ventilation treatment for ARDS patients.

[The precision medicine for the treatment of acute respiratory distress syndrome is based on identification of phenotypes].

The acute respiratory distress syndrome (ARDS) is a heterogeneous syndrome characterized by distinct etiologies and complicated pathobiological mechanism. It is difficult to discriminate patients with unique biological features or individual response to specific therapy by traditional definition and subgrouping. Unfortunately, there are few clinical evidences supporting effective drug therapy to ARDS. The sub-phenotype or endotype of ARDS is related to potential mechanism of the syndrome, and is critical to personalized treatment of ARDS. An appropriate sub-phenotype of ARDS may be defined by data-driven assessment of the available data including clinical features, biological biomarkers and respiratory parameters of the patients. Latent class analysis or machine learning has potential to establish new sub-phenotype of ARDS stably, which is helpful to guide precision medicine approach.

[The value of point-of-care ultrasound in the diagnosis and management of acute respiratory distress syndrome].

Acute respiratory distress syndrome (ARDS) continues to cause significant morbidity and mortality worldwide. However, there are currently no corresponding specific medications. Lung, right heart, and diaphragm protective therapy is the cornerstone of ARDS management. Non-invasive, radiation-free, and transportation-free point-of-care ultrasound enables for real-time dynamic evaluation of the lung, right heart, and diaphragm. It is an essential tool for the diagnosis, monitoring, and clinical decision-making of ARDS patients. However, ultrasound has several limitations, and its clinical application must be carefully evaluated in conjunction with clinical symptoms and other monitoring techniques. Further research is needed to determine whether clinical decision-making based on point-of-care ultrasound examination can improve the prognosis of ARDS patients.

[Value of transnasal high-flow oxygen therapy and noninvasive ventilation in the management of acute respiratory distress syndrome].

Acute respiratory distress syndrome (ARDS) is one of the most common syndromes in the intensive care unit, with a high mortality and morbidity. Refractory hypoxia is the typical feature of ARDS, and improving hypoxia is the key to the treatment of ARDS. Due to the rapid progression of ARDS, invasive ventilation is usually used to improve hypoxia. But in recent years, with the extending of the understanding of ARDS and the development of non-invasive oxygen therapy, high flow nasal oxygen (HFNO) and non-invasive ventilation (NIV) are gradually used in ARDS. Therefore, we reviewed the role of HFNO and NIV in ARDS in this paper.

Potential application of mesenchymal stromal cells as a new therapeutic approach in acute respiratory distress syndrome and pulmonary fibrosis.

While the COVID-19 outbreak and its complications are still under investigation, post-inflammatory pulmonary fibrosis (PF) has already been described as a long-term sequela of acute respiratory distress syndrome (ARDS) secondary to SARS-CoV2 infection. However, therapeutical strategies for patients with ARDS and PF are still limited and do not significantly extend lifespan. So far, lung transplantation remains the only definitive treatment for end-stage PF. Over the last years, numerous preclinical and clinical studies have shown that allogeneic mesenchymal stromal cells (MSCs) might represent a promising therapeutical approach in several lung disorders, and their potential for ARDS treatment and PF prevention has been investigated during the COVID-19 pandemic. From April 2020 to April 2022, we treated six adult patients with moderate COVID-19-related ARDS in a late proliferative stage with up to two same-dose infusions of third-party allogeneic bone marrow-derived MSCs (BM-MSCs), administered intravenously 15 days apart. No major adverse events were registered. Four patients completed the treatment and reached ICU discharge, while two received only one dose of MSCs due to multiorgan dysfunction syndrome (MODS) and subsequent death. All four survivors showed improved gas exchanges (PaO2/FiO2 ratio > 200), contrary to the others. Furthermore, LDH trends after MSCs significantly differed between survivors and the deceased. Although further investigations and shared protocols are still needed, the safety of MSC therapy has been recurrently shown, and its potential in treating ARDS and preventing PF might represent a new therapeutic strategy.

Factors influencing the therapeutic failure of high-flow nasal cannula oxygen humidification in patients with interstitial pneumonia complicated by respiratory failure.

OBJECTIVE: The aim of this study was to explore the factors influencing the treatment failure of high-flow nasal cannula (HFNC) therapy in patients with interstitial pneumonia (IP) complicated by respiratory failure. PATIENTS AND METHODS: A total of 158 patients with IP and respiratory failure treated with HFNC in our hospital from January 2020 to August 2023 were selected as the study population. Based on treatment efficacy, they were categorized into the HFNC treatment failure group and the HFNC treatment success group. Clinical data were compared between the two groups. Multiple logistic regression analysis was employed to identify independent factors influencing treatment failure, and the predictive value of these factors for HFNC treatment failure was assessed using receiver operating characteristic (ROC) curve analysis. RESULTS: After 7 days of HFNC treatment, among the 158 patients with IP and respiratory failure, 25 (15.8%) declared treatment failure, while the remaining 133 (84.2%) showed treatment success. Patients in the HFNC treatment failure group had significantly higher age, duration of IP, pre-treatment respiratory rate, C-reactive protein (CRP), and controlling nutritional status (CONUT) scores compared to the HFNC treatment success group. The PaO2/FiO2 ratio, left ventricular ejection fraction, and Glasgow Coma Scale (GCS) were significantly lower in the HFNC treatment failure group (p<0.05). Multiple logistic regression analysis revealed that pre-treatment PaO2/FiO2 ratio, CRP, CONUT, and GCS scores were independent factors influencing HFNC treatment failure in patients with IP and respiratory failure (p<0.05). Lower PaO2/FiO2 ratio and GCS scores, and higher CRP and CONUT scores were associated with an increased risk of HFNC treatment failure. ROC curve analysis indicated that pre-treatment PaO2/FiO2 ratio, CRP, CONUT, and GCS scores in patients with IP and respiratory failure had a high predictive value for HFNC treatment failure (p<0.05). CONCLUSIONS: The HFNC failure rate in patients with IP and respiratory failure is 15.8%. Pre-treatment PaO2/FiO2 ratio, CRP, CONUT, and GCS scores are independent factors associated with HFNC treatment failure and warrant clinical attention.

Contribution of electrical impedance tomography to personalize positive end-expiratory pressure under ECCO2R.

Extracorporeal Carbon Dioxide Removal (ECCO2R) is used in acute respiratory distress syndrome (ARDS) patients to facilitate lung-protective ventilatory strategies. Electrical Impedance Tomography (EIT) allows individual, non-invasive, real-time, bedside, radiation-free imaging of the lungs, providing global and regional dynamic lung analyses. To provide new insights for future ECCO2R research in ARDS, we propose a potential application of EIT to personalize End-Expiratory Pressure (PEEP) following each reduction in tidal volume (VT), as demonstrated in an illustrative case. A 72-year-old male with COVID-19 was admitted to the ICU for moderate ARDS. Monitoring with EIT was started to determine the optimal PEEP value (PEEPEIT), defined as the intersection of the collapse and overdistention curves, after each reduction in VT during ECCO2R. The identified PEEPEIT values were notably low (< 10 cmH2O). The decrease in VT associated with PEEPEIT levels resulted in improved lung compliance, reduced driving pressure and a more uniform ventilation pattern. Despite current Randomized Controlled Trials showing that ultra-protective ventilation with ECCO2R does not improve survival, the applicability of universal ultra-protective ventilation settings for all patients remains a subject of debate. Inappropriately set PEEP levels can lead to alveolar collapse or overdistension, potentially negating the benefits of VT reduction. EIT facilitates real-time monitoring of derecruitment associated with VT reduction, guiding physicians in determining the optimal PEEP value after each decrease in tidal volume. This original description of using EIT under ECCO2R to adjust PEEP at a level compromising between recruitability and overdistention could be a crucial element for future research on ECCO2R.

Severe Community-Acquired Pneumonia: Noninvasive Mechanical Ventilation, Intubation, and HFNT.

Severe acute respiratory failure (ARF) is a major issue in patients with severe community-acquired pneumonia (CAP). Standard oxygen therapy is the first-line therapy for ARF in the less severe cases. However, respiratory supports may be delivered in more severe clinical condition. In cases with life-threatening ARF, invasive mechanical ventilation (IMV) will be required. Noninvasive strategies such as high-flow nasal therapy (HFNT) or noninvasive ventilation (NIV) by either face mask or helmet might cover the gap between standard oxygen and IMV. The objective of all the supporting measures for ARF is to gain time for the antimicrobial treatment to cure the pneumonia. There is uncertainty regarding which patients with severe CAP are most likely to benefit from each noninvasive support strategy. HFNT may be the first-line approach in the majority of patients. While NIV may be relatively contraindicated in patients with excessive secretions, facial hair/structure resulting in air leaks or poor compliance, NIV may be preferable in those with increased work of breathing, respiratory muscle fatigue, and congestive heart failure, in which the positive pressure of NIV may positively impact hemodynamics. A trial of NIV might be considered for select patients with hypoxemic ARF if there are no contraindications, with close monitoring by an experienced clinical team who can intubate patients promptly if they deteriorate. In such cases, individual clinician judgement is key to choose NIV, interface, and settings. Due to the paucity of studies addressing IMV in this population, the protective mechanical ventilation strategies recommended by guidelines for acute respiratory distress syndrome can be reasonably applied in patients with severe CAP.

Intravascular guide wire aspiration in a patient on extracorporeal membrane oxygenation: A case report.

RATIONALE: Guide wire aspiration during central venous catheter (CVC) insertion in a patient on extracorporeal membrane oxygenation (ECMO) is a very rare but dangerous complication. A guide wire aspirated inside the ECMO can cause thrombosis, the ECMO to break down or shut off, and unnecessary ECMO replacement. PATIENT CONCERNS: A 58-year-old man was scheduled for venovenous ECMO for acute respiratory distress syndrome. After his vital signs stabilized, we inserted a CVC. During CVC insertion, the guide wire was aspirated into the ECMO venous line. INTERVENTION: After confirming the guide wire inside the ECMO venous line, we replaced the entire ECMO circuit. OUTCOMES: ECMO was maintained for 57 days, and weaning was successful but the patient died 5 days afterward. LESSONS: Care must be taken when inserting a CVC using a guide wire in ECMO patients: the guide wire should not be inserted deeply, it should be secured during insertion, the ECMO venous cannula tip requires proper positioning, and ECMO flow should be temporarily reduced.

Overexpression of Wnt5a promoted the protective effect of mesenchymal stem cells on Lipopolysaccharide-induced endothelial cell injury via activating PI3K/AKT signaling pathway.

BACKGROUND: Lung endothelial barrier injury plays an important role in the pathophysiology of acute lung injury/acute respiratory distress syndrome (ALI/ARDS). Mesenchymal stem cells (MSCs) therapy has shown promise in ARDS treatment and restoration of the impaired barrier function. It has been reported that Wnt5a shows protective effects on endothelial cells. Therefore, the study aimed to investigate whether overexpression of Wnt5a could promote the protective effects of MSCs on Lipopolysaccharide (LPS)-induced endothelial cell injury. METHODS: To evaluate the protective effects of MSCs overexpressing Wnt5a, we assessed the migration, proliferation, apoptosis, and angiogenic ability of endothelial cells. We assessed the transcription of protective cellular factors using qPCR and determined the molecular mechanism using Western blot analysis. RESULTS: Overexpression of Wnt5a upregulated the transcription of protective cellular factors in MSCs. Co-culture of MSCWnt5a promoted endothelial migration, proliferation and angiogenesis, and inhibited endothelial cell apoptosis through the PI3K/AKT pathway. CONCLUSIONS: Overexpression of Wnt5a promoted the therapeutic effect of MSCs on endothelial cell injury through the PI3K/AKT signaling. Our study provides a novel approach for utilizing genetically modified MSCs in the transplantation therapy for ARDS.

Differences of respiratory mechanics in mechanical ventilation of acute respiratory distress syndrome between patients with COVID-19 and Influenza A.

BACKGROUND: Whether COVID-19-induced acute respiratory distress syndrome (ARDS) should be approached differently in terms of mechanical ventilation therapy compared to other virus-induced ARDS is debatable. Therefore, we aimed to ascertain whether the respiratory mechanical characteristics of COVID-19-induced ARDS differ from those of influenza A induced ARDS, in order to establish a rationale for mechanical ventilation therapy in COVID-19-induced ARDS. METHODS: This was a retrospective cohort study comparing patients with COVID-19-induced ARDS and influenza A induced ARDS. We included intensive care unit (ICU) patients with COVID-19 or Influenza A aged ≥ 19, who were diagnosed with ARDS according to the Berlin definition between January 2015 and July 2021. Ventilation parameters for respiratory mechanics were collected at specific times on days one, three, and seven after intubation. RESULTS: The median age of the 87 participants was 71.0 (62.0-78.0) years old, and 63.2% were male. The ratio of partial pressure of oxygen in arterial blood to the fractional of inspiratory oxygen concentration in COVID-19-induced ARDS was lower than that in influenza A induced ARDS during the initial stages of mechanical ventilation (influenza A induced ARDS 216.1 vs. COVID-19-induced ARDS 167.9, p = 0.009, day 1). The positive end expiratory pressure remained consistently higher in the COVID-19 group throughout the follow-up period (7.0 vs. 10.0, p < 0.001, day 1). COVID-19 and influenza A initially showed different directions for peak inspiratory pressure and dynamic compliance; however, after day 3, both groups exhibited similar directions. Dynamic driving pressure exhibited opposite trends between the two groups during mechanical ventilation. CONCLUSIONS: Respiratory mechanics show clear differences between COVID-19-induced ARDS and influenza A induced ARDS. Based on these findings, we can consider future treatment strategies for COVID-19-induced ARDS.