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Introduction: Unlicensed cosmetic procedures, which come at increased risk of infection and potential surgical complications, have introduced new challenges in healthcare. Physicians should be aware of presentations that may arise secondary to these procedures.Case Report: We describe a case in which a previously healthy, 28-year-old female presented with new-onset seizures and acute respiratory distress syndrome (ARDS) in the setting of a recent cosmetic procedure with silicone injections to the gluteal region. The patient’s hospital course was complicated by altered mental status, respiratory failure, rapid hemodynamic compromise, and eventual death.Conclusion: In rare cases, one possible complication of cosmetic procedures is silicone embolism syndrome, which is characterized by pneumonitis, alveolar hemorrhage, and ARDS. The patient described in this report also experienced neurologic symptoms including seizure and altered mental status. This is a clinical diagnosis that relies upon thorough history-taking and detailed physical exam. Documentation on this phenomenon is limited, and medical management has not yet been standardized for this condition. Morbidity and mortality remain high.

Background: Since publication of the 2012 Berlin definition of acute respiratory distress syndrome (ARDS), several developments have supported the need for an expansion of the definition, including the use of high-flow nasal oxygen, the expansion of the use of pulse oximetry in place of arterial blood gases, the use of ultrasound for chest imaging, and the need for applicability in resource-limited settings. Methods: A consensus conference of 32 critical care ARDS experts was convened, had six virtual meetings (June 2021 to March 2022), and subsequently obtained input from members of several critical care societies. The goal was to develop a definition that would 1) identify patients with the currently accepted conceptual framework for ARDS, 2) facilitate rapid ARDS diagnosis for clinical care and research, 3) be applicable in resource-limited settings, 4) be useful for testing specific therapies, and 5) be practical for communication to patients and caregivers. Results: The committee made four main recommendations: 1) include high-flow nasal oxygen with a minimum flow rate of ⩾30 L/min; 2) use PaO2:FiO2 ⩽ 300 mm Hg or oxygen saturation as measured by pulse oximetry SpO2:FiO2 ⩽ 315 (if oxygen saturation as measured by pulse oximetry is ⩽97%) to identify hypoxemia; 3) retain bilateral opacities for imaging criteria but add ultrasound as an imaging modality, especially in resource-limited areas; and 4) in resource-limited settings, do not require positive end-expiratory pressure, oxygen flow rate, or specific respiratory support devices. Conclusions: We propose a new global definition of ARDS that builds on the Berlin definition. The recommendations also identify areas for future research, including the need for prospective assessments of the feasibility, reliability, and prognostic validity of the proposed global definition.

BackgroundSevere coccidioidomycosis presenting with respiratory failure is an uncommon manifestation of disease. Current knowledge of this condition is limited to case reports and small case series.MethodsA retrospective multicenter review of patients with coccidioidomycosis-associated acute respiratory distress syndrome (CA-ARDS) was conducted. It assessed clinical and laboratory variables at the time of presentation, reviewed the treatment course, and compared this cohort with a national database of patients with noncoccidioidomycosis ARDS. Survivors and nonsurvivors of coccidioidomycosis were also compared to determine prognostic factors.ResultsIn this study, CA-ARDS (n = 54) was most common in males, those of Hispanic ethnicity, and those with concurrent diabetes mellitus. As compared with the PETAL network database (Prevention and Early Treatment of Acute Lung Injury; n = 1006), patients with coccidioidomycosis were younger, had fewer comorbid conditions, and were less acidemic. The 90-day mortality was 15.4% for patients with coccidioidomycosis, as opposed to 42.6% (P < .0001) for patients with noncoccidioidomycosis ARDS. Patients with coccidioidomycosis who died, as compared with those who survived, were older, had higher APACHE II scores (Acute Physiology and Chronic Health Evaluation), and did not receive corticosteroid therapy.ConclusionsCA-ARDS is an uncommon but morbid manifestation of infection. When compared with a national database, the overall mortality appears favorable vs other causes of ARDS. Patients with CA-ARDS had a low overall mortality but required prolonged antifungal therapy. The utility of corticosteroids in this condition remains unconfirmed.

Background: There is accumulating evidence regarding the benefits of the 5-HT3 receptor antagonist ondansetron for the treatment of critical illness due to its potential anti-inflammatory effect. This study attempted to determine the potential targets and molecular mechanisms of ondansetron's action against critical illnesses. Methods: A bioinformatics analysis of network pharmacology was conducted to demonstrate screening targets and the signaling pathways of ondansetron action against the most common critical illnesses such as acute kidney injury (AKI), sepsis, and acute respiratory distress syndrome (ARDS). Experiments of LPS- stimulated rat neutrophilswith ondansetron treatmentwere conducted to further validate the relevant hypothesis. Results: A total of 198, 111, and 26 primary causal targets were identified fromthe data for the action of ondansetron against AKI, sepsis, and ARDS respectively. We found that the pathway of neutrophil extracellular traps (NETs) formation is statistically significantly involved in the action of ondansetron against these three critical illnesses. In the pathway of NETs formation, the common drug- disease intersection targets in these three critical illnesses were toll-like receptor 8(TLR8),mitogen-activated protein kinase-14 (MAPK14), nuclear factor kappa-B1 (NFKB1), neutrophil elastase (NE), andmyeloperoxidase (MPO). Considering these bioinformatics findings, we concluded that ondansetron anti-critical illness effects are mechanistically and pharmacologically implicated with suppression of neutrophils-associated inflammatory processes. It was also showed that after treatment of LPS-stimulated rat neutrophils with ondansetron, the key proteins NE, MPO, and Peptide Arginine Deaminase 4 (PAD4) in the NETs formation were significantly reduced, and the inflammatory factors IL-6, IL-1β, TNF-α, and chemokine receptor (CXCR4) were also significantly decreased. Conclusion: The excessive formation of NETsmay have important research value in the development and progression of critical illness. Ondansetron may reduce excessive inflammatory injury in critical diseases by reducing the formation of NETs via influencing the five targets: TLR8, NFKB1, MAPK14, NE, and MPO. Ondansetron and these primary predictive biotargets may potentially be used to treat critical illness in future clinical practice. [ABSTRACT FROM AUTHOR]

Purpose: Veno-venous extracorporeal membrane oxygenation (VV-ECMO) is an integral part of the management algorithm of patients with severe respiratory failure refractory to evidence-based conventional treatments. Right ventricular injury (RVI) pertaining to abnormalities in the dimensions and/or function of the right ventricle (RV) in the context of VV-ECMO significantly influences mortality. However, in the absence of a universally accepted RVI definition and evidence-based guidance for the management of RVI in this very high-risk patient cohort, variations in clinical practice continue to exist. Methods: Following a systematic search of the literature, an international Steering Committee consisting of eight healthcare professionals involved in the management of patients receiving ECMO identified domains and knowledge gaps pertaining to RVI definition and management where the evidence is limited or ambiguous. Using a Delphi process, an international panel of 52 Experts developed Expert position statements in those areas. The process also conferred RV-centric overarching open questions for future research. Consensus was defined as achieved when 70% or more of the Experts agreed or disagreed on a Likert-scale statement or when 80% or more of the Experts agreed on a particular option in multiple‐choice questions. Results: The Delphi process was conducted through four rounds and consensus was achieved on 31 (89%) of 35 statements from which 24 Expert position statements were derived. Expert position statements provided recommendations for RVI nomenclature in the setting of VV-ECMO, a multi-modal diagnostic approach to RVI, the timing and parameters of diagnostic echocardiography, and VV-ECMO settings during RVI assessment and management. Consensus was not reached on RV-protective driving pressure thresholds or the effect of prone positioning on patient-centric outcomes. Conclusion: The proposed definition of RVI in the context of VV-ECMO needs to be validated through a systematic aggregation of data across studies. Until further evidence emerges, the Expert position statements can guide informed decision-making in the management of these patients. [ABSTRACT FROM AUTHOR]

Background: Patients with severe respiratory failure due to COVID‐19 who are not under mechanical ventilation may develop severe hypoxemia when complicated with spontaneous pneumomediastinum (PM). These patients may be harmed by invasive ventilation. Alternatively, veno‐venous (V‐V) extracorporeal membrane oxygenation (ECMO) may be applied. We report on the efficacy of V‐V ECMO and invasive ventilation as initial advanced respiratory support in patients with COVID‐19 and acute respiratory failure due to spontaneous PM. Methods: This was a retrospective cohort study performed between March 2020 and January 2022. Enrolled patients had COVID‐19 and acute respiratory failure due to spontaneous PM and were not invasively ventilated. Patients were treated in the intensive care unit (ICU) with invasive ventilation (invasive ventilation group) or V‐V ECMO support (V‐V ECMO group) as the main therapeutic option. The primary outcomes were mortality and ICU discharge at 90 days after ICU admission. Results: Twenty‐two patients were included in this study (invasive ventilation group: 13 [59%]; V‐V ECMO group: 9 [41%]). The V‐V ECMO strategy was significantly associated with lower mortality (hazard ratio [HR] 0.33 [95% CI 0.12–0.97], p = 0.04). Five (38%) patients in the V‐V ECMO group were intubated and eight (89%) patients in the invasive ventilation group required V‐V ECMO support within 30 days from ICU admission. Three (33%) patients in the V‐V ECMO group were discharged from ICU within 90 days compared to one (8%) patient in the invasive ventilation group (HR 4.71 [95% CI 0.48–45.3], p = 0.18). Conclusions: Preliminary data suggest that V‐V ECMO without invasive ventilation may improve survival in COVID‐19‐related acute respiratory failure due to spontaneous PM. The study's retrospective design and limited sample size underscore the necessity for additional investigation and warrant caution. [ABSTRACT FROM AUTHOR]

Cognitive impairment is a severe complication of acute respiratory distress syndrome (ARDS). Emerging studies have revealed the effects of pyrrolidine dithiocarbamate (PDTC) on improving surgery-induced cognitive impairment. The major aim of the study was to investigate whether PDTC protected against ARDS-induced cognitive dysfunction and to identify the underlying mechanisms involved. The rat model of ARDS was established by intratracheal instillation of lipopolysaccharide (LPS), followed by treatment with PDTC. The cognitive function of rats was analyzed by the Morris Water Maze, and pro-inflammatory cytokines were assessed by quantitative real-time PCR, enzyme-linked immunosorbent assay, and western blot assays. A dual-luciferase reporter gene assay was performed to identify the relationship between miR-181c and its target gene, TAK1 binding protein 2 (TAB2). The results showed that PDTC improved cognitive impairment and alleviated neuroinflammation in the hippocampus in LPS-induced ARDS model. Furthermore, we demonstrated that miR-181c expression was downregulated in the hippocampus of the ARDS rats, which was restored by PDTC treatment. In vitro studies showed that miR-181c alleviated LPS-induced pro-inflammatory response by inhibiting TAB2, a critical molecule in the nuclear factor (NF)-κB signaling pathway. PDTC improves cognitive impairment in LPS-induced ARDS by regulating miR-181c/NF-κB axis-mediated neuroinflammation, providing a potential opportunity for the treatment of this disease. [ABSTRACT FROM AUTHOR]

Extracellular vesicles (EVs) represent a new axis of intercellular communication that can be harnessed for therapeutic purposes, as cell-free therapies. The clinical application of mesenchymal stromal cell (MSC)-derived EVs, however, is still in its infancy and faces many challenges. The heterogeneity inherent to MSCs, differences among donors, tissue sources, and variations in manufacturing conditions may influence the release of EVs and their cargo, thus potentially affecting the quality and consistency of the final product. We investigated the influence of cell culture and conditioned medium harvesting conditions on the physicochemical and proteomic profile of human umbilical cord MSC-derived EVs (hUCMSC-EVs) produced under current good manufacturing practice (cGMP) standards. We also evaluated the efficiency of the protocol in terms of yield, purity, productivity, and expression of surface markers, and assessed the biodistribution, toxicity and potential efficacy of hUCMSC-EVs in pre-clinical studies using the LPS-induced acute lung injury model. hUCMSCs were isolated from a cord tissue, cultured, cryopreserved, and characterized at a cGMP facility. The conditioned medium was harvested at 24, 48, and 72 h after the addition of EV collection medium. Three conventional methods (nanoparticle tracking analysis, transmission electron microscopy, and nanoflow cytometry) and mass spectrometry were used to characterize hUCMSC-EVs. Safety (toxicity of single and repeated doses) and biodistribution were evaluated in naive mice after intravenous administration of the product. Efficacy was evaluated in an LPS-induced acute lung injury model. hUCMSC-EVs were successfully isolated using a cGMP-compliant protocol. Comparison of hUCMSC-EVs purified from multiple harvests revealed progressive EV productivity and slight changes in the proteomic profile, presenting higher homogeneity at later timepoints of conditioned medium harvesting. Pooled hUCMSC-EVs showed a non-toxic profile after single and repeated intravenous administration to naive mice. Biodistribution studies demonstrated a major concentration in liver, spleen and lungs. HUCMSC-EVs reduced lung damage and inflammation in a model of LPS-induced acute lung injury. hUCMSC-EVs were successfully obtained following a cGMP-compliant protocol, with consistent characteristics and pre-clinical safety profile, supporting their future clinical development as cell-free therapies. [ABSTRACT FROM AUTHOR]

Mesenchymal stromal cells (MSCs) are attractive as a therapeutic modality in multiple disease conditions characterized by inflammation and vascular compromise. Logistically they are advantageous because they can be isolated from adult tissue sources, such as bone marrow (BM). The phase 2a START clinical trial determined BM-MSCs to be safe in patients with moderate-to-severe acute respiratory distress syndrome (ARDS). Herein, we examine a subset of the clinical doses of MSCs generated for the phase 2a START trial from three unique donors (1–3), where one of the donors' donated BM on two separate occasions (donor 3 and 3W). The main objective of this study was to correlate properties of the cells from the four lots with plasma biomarkers from treated patients and relevant to ARDS outcomes. To do this we evaluated MSC donor lots for (i) post-thaw viability, (ii) growth kinetics, (iii) metabolism, (iv) surface marker expression, (v) protein expression, (vi) immunomodulatory ability and (vii) their functional effects on regulating endothelial cell permeability. MSC-specific marker expression and protection of thrombin-challenged endothelial barrier permeability was similar among all four donor lots. Inter and intra-donor variability was observed in all the other in vitro assays. Furthermore, patient plasma ANG-2 and protein C levels at 6 hours post-transfusion were correlated to cell viability in an inter- and intra-donor dependent manner. These findings highlight the potential of donor dependent (inter-) and collection dependent (intra-) effects in patient biomarker expression. [ABSTRACT FROM AUTHOR]

BACKGROUND: Mechanical ventilation is a common life-saving procedure but can lead to serious complications, including ARDS and oxygen toxicity. Nonadherence to lung-protective ventilation guidelines is common. We hypothesized that a respiratory therapist-driven mechanical ventilation bundle could increase adherence to lung-protective ventilation and decrease the incidence of pulmonary complications in the ICU. METHODS: A respiratory therapist-driven protocol was implemented on August 1, 2018, in all adult ICUs of a Midwestern academic tertiary center. The protocol targeted low tidal volume, adequate PEEP, limiting oxygen, adequate breathing frequency, and head of the bed elevation. Adherence to lung-protective guidelines and clinical outcomes were retrospectively observed in adult subjects admitted to the ICU and on ventilation for ≥ 24 h between January 2011 and December 2019. RESULTS: We included 666 subjects; 68.5% were in the pre-intervention group and 31.5% were in the post-intervention group. After adjusting for body mass index and intubation indication, a significant increase in overall adherence to lung-protective ventilation guidelines was observed in the post-intervention period (adjusted odds ratio 2.48, 95% CI 1.73-3.56). Fewer subjects were diagnosed with ARDS in the post-intervention group (adjusted odds ratio 0.22, 95% CI 0.08-0.65) than in the pre-intervention group. There was no difference in the incidence of ventilator-associated pneumonia, ventilator-free days, ICU mortality, or death within 1 month of ICU discharge. CONCLUSIONS: A respiratory therapist-driven protocol increased adherence to lung-protective mechanical ventilation guidelines in the ICU and was associated with decreased ARDS incidence. [ABSTRACT FROM AUTHOR]

Background: Age as an eligibility criterion for V-V ECMO is widely debated and varies among healthcare institutions. We examined how age relates to mortality in patients undergoing V-V ECMO for ARDS. Methods: Systematic review and meta-regression of clinical studies published between 2015 and June 2024. Studies involving at least 6 ARDS patients treated with V-V ECMO, with specific data on ICU and/or hospital mortality and patient age were included. The search strategy was executed in PubMed, limited to English-language. COVID-19 and non-COVID-19 populations were analyzed separately. Meta-regressions of mortality outcomes on age were performed using gender, BMI, SAPS II, APACHE II, Charlson comorbidity index or SOFA as covariates. Results: In non-COVID ARDS, the meta-regression of 173 studies with 56,257 participants showed a significant positive association between mean age and ICU/hospital mortality. In COVID-19 ARDS, a significant relationship between mean age and ICU mortality, but not hospital mortality, was found in 103 studies with 21,255 participants. Sensitivity analyses confirmed these findings, highlighting a linear relationship between age and mortality in both groups. For each additional year of mean age, ICU mortality increased by 1.2% in non-COVID ARDS and 1.9% in COVID ARDS. Conclusions: The relationship between age and ICU mortality is linear and shows no inflection point. Consequently, no age cut-off can be recommended for determining patient eligibility for V-V ECMO. [ABSTRACT FROM AUTHOR]

Introduction: Acute Respiratory Distress Syndrome (ARDS) poses a significant health challenge due to its high incidence and mortality rates. The emergence of SARS-CoV-2 has added complexity, with evidence suggesting a correlation between COVID-19 induced ARDS and post-COVID symptoms. Understanding the underlying mechanisms of ARDS in COVID-19 patients is crucial for effective clinical treatment. Method: To investigate the potential role of ferroptosis in SARS-CoV-2 induced ARDS, we conducted a comprehensive analysis using bioinformatics methods. Datasets from the Gene Expression Omnibus (GEO) were utilized, focusing on COVID-19 patients with varying ARDS severity. We employed weighted gene co-expression network analysis (WGCNA), differential gene expression analysis, and single-cell sequencing to identify key genes associated with ferroptosis in ARDS. Hub genes were validated using additional GEO datasets and cell experiment. Result: The analysis discerned 916 differentially expressed genes in moderate/ severe ARDS patients compared to non-critical individuals. Weighted Gene Co-expression Network Analysis (WGCNA) unveiled two modules that exhibited a positive correlation with ARDS, subsequently leading to the identification of 15 hub genes associated with ferroptosis. Among the noteworthy hub genes were MTF1, SAT1, and TXN. Protein-protein interaction analysis, and pathway analysis further elucidated their roles. Immune infiltrating analysis highlighted associations between hub genes and immune cells. Validation in additional datasets confirmed the upregulation of MTF1, SAT1, and TXN in SARS-CoV-2-induced ARDS. This was also demonstrated by qRT-PCR results in the BEAS-2B cells vitro model, suggesting their potential as diagnostic indicators. Discussion: This study identifies MTF1, SAT1, and TXN as hub genes associated with ferroptosis in SARS-CoV-2-induced ARDS. These findings provide novel insights into the molecular mechanisms underlying ARDS in COVID-19 patients and offer potential targets for immune therapy and targeted treatment. Further experimental validation is warranted to solidify these findings and explore therapeutic interventions for ARDS in the context of COVID-19. [ABSTRACT FROM AUTHOR]

Background: Ventilation management may differ between COVID–19 ARDS (COVID–ARDS) patients and patients with pre–COVID ARDS (CLASSIC–ARDS); it is uncertain whether associations of ventilation management with outcomes for CLASSIC–ARDS also exist in COVID–ARDS. Methods: Individual patient data analysis of COVID–ARDS and CLASSIC–ARDS patients in six observational studies of ventilation, four in the COVID–19 pandemic and two pre–pandemic. Descriptive statistics were used to compare epidemiology and ventilation characteristics. The primary endpoint were key ventilation parameters; other outcomes included mortality and ventilator–free days and alive (VFD–60) at day 60. Results: This analysis included 6702 COVID–ARDS patients and 1415 CLASSIC–ARDS patients. COVID–ARDS patients received lower median VT (6.6 [6.0 to 7.4] vs 7.3 [6.4 to 8.5] ml/kg PBW; p < 0.001) and higher median PEEP (12.0 [10.0 to 14.0] vs 8.0 [6.0 to 10.0] cm H2O; p < 0.001), at lower median ΔP (13.0 [10.0 to 15.0] vs 16.0 [IQR 12.0 to 20.0] cm H2O; p < 0.001) and higher median Crs (33.5 [26.6 to 42.1] vs 28.1 [21.6 to 38.4] mL/cm H2O; p < 0.001). Following multivariable adjustment, higher ΔP had an independent association with higher 60–day mortality and less VFD–60 in both groups. Higher PEEP had an association with less VFD–60, but only in COVID–ARDS patients. Conclusions: Our findings show important differences in key ventilation parameters and associations thereof with outcomes between COVID–ARDS and CLASSIC–ARDS. Trial registration: Clinicaltrials.gov (identifier NCT05650957), December 14, 2022. [ABSTRACT FROM AUTHOR]

Severe COVID-19 cases often progress to life-threatening conditions such as acute respiratory distress syndrome (ARDS), sepsis, and multiple organ dysfunction syndrome (MODS). Gelsolin (GSN), an actin-binding protein with anti-inflammatory and immunomodulatory properties, is a promising therapeutic target for severe COVID-19. Plasma GSN levels are significantly decreased in critical illnesses, including COVID-19, correlating with dysregulated immune responses and poor outcomes. GSN supplementation may mitigate acute lung injury, ARDS, and sepsis, which share pathophysiological features with severe COVID-19, by scavenging actin, modulating cytokine production, enhancing macrophage phagocytosis, and stabilizing the alveolar-capillary barrier. Preliminary data indicate that recombinant human plasma GSN improves oxygenation and lung function in severe COVID-19 patients with ARDS. Although further research is needed to optimize GSN therapy, current evidence supports its potential to mitigate severe consequences of COVID-19 and improve patient outcomes. This review provides a comprehensive analysis of the biological characteristics, mechanisms, and therapeutic value of GSN in severe COVID-19. [ABSTRACT FROM AUTHOR]

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes virus-induced-senescence. There is an association between shorter telomere length (TL) in coronavirus disease 2019 (COVID-19) patients and hospitalization, severity, or even death. However, it remains unknown whether virus-induced-senescence is reversible. We aim to evaluate the dynamics of TL in COVID-19 patients 1 year after recovery from intensive care units (ICU). Longitudinal study enrolling 49 patients admitted to ICU due to COVID-19 (August 2020 to April 2021). Relative telomere length (RTL) quantification was carried out in whole blood by monochromatic multiplex real-time quantitative PCR (MMqPCR) assay at hospitalization (baseline) and 1 year after discharge (1-year visit). The association between RTL and ICU length of stay (LOS), invasive mechanical ventilation (IMV), prone position, and pulmonary fibrosis development at 1-year visit was evaluated. The median age was 60 years, 71.4% were males, median ICU-LOS was 12 days, 73.5% required IMV, and 38.8% required a prone position. Patients with longer ICU-LOS or who required IMV showed greater RTL shortening during follow-up. Patients who required pronation had a greater RTL shortening during follow-up. IMV patients who developed pulmonary fibrosis showed greater RTL reduction and shorter RTL at the 1-year visit. Patients with longer ICU-LOS and those who required IMV had a shorter RTL in peripheral blood, as observed 1 year after hospital discharge. Additionally, patients who required IMV and developed pulmonary fibrosis had greater telomere shortening, showing shorter telomeres at the 1-year visit. These patients may be more prone to develop cellular senescence and lung-related complications; therefore, closer monitoring may be needed. [ABSTRACT FROM AUTHOR]

Background and objective: COVID-19 has offered an opportunity to the clinicians to try and study various oxygenation enhancing maneuvers in the patients. These included lung protective measures and prone positioning of participants admitted to the ICU with acute respiratory distress syndrome. We aimed to identify the effects of early prone positioning on the length of stay, discharge rate, and frequency of tracheostomies in the ICU patients. Methodology: This retrospective study was conducted on critically ill patients needing mechanical ventilation with lung protective strategy, admitted to the Intensive Care Units of Al-Azhar University Hospitals between March 2020 to April 2022. All patients in the study were interpreted retrospectively by examining the patient's records. Group A (n = 39) included patients who had been early placed in prone positions within 24 h of intubation, and Group B (n = 31) included patients who had not been placed in prone positions. All patients received a lung protective strategy for ARDS. In both groups, PaO2, PaCO2, pH, SpO2, and PaO2/FiO2 ratio were checked initially and later every 24 h for 6 days. Data was evaluated for the total days of both hospital and ICU length of stay, number of successful discharges to home from the hospital, and the total number of tracheostomized patients. Results: After prone positioning, lower SOFA and APACHE II scores were noticed in the prone group. There was no significant difference in the rate of discharge between the two groups. We observed non-significant shorter hospital and ICU stays and higher frequency of tracheostomy procedures in the prone group. We noticed a significant improvement in PaO2/FiO2 ratios in the prone group starting from day 2 to day 6. We observed a significant improvement in PO2 in the prone group in comparison to the non-prone group. Conclusions: Early prone positioning of patients admitted to the ICU with acute respiratory distress syndrome during COVID-19 pandemic led to a significant improvement in both PaO2 and PaO2/FiO2 ratio with a non-significant decrease in both hospital and ICU length of stay as shown by the collected data over consecutive six days. [ABSTRACT FROM AUTHOR]

Even though much progress has been made to improve clinical outcomes, acute respiratory distress syndrome (ARDS) remains a significant cause of acute respiratory failure. Protective mechanical ventilation is the backbone of supportive care for these patients; however, there are still many unresolved issues in its setting. The primary goal of mechanical ventilation is to improve oxygenation and ventilation. The use of positive pressure, especially positive end-expiratory pressure (PEEP), is mandatory in this approach. However, PEEP is a double-edged sword. How to safely set positive end-inspiratory pressure has long been elusive to clinicians. We hereby propose a pressure–volume curve measurement-based method to assess whether injured lungs are recruitable in order to set an appropriate PEEP. For the most severe form of ARDS, extracorporeal membrane oxygenation (ECMO) is considered as the salvage therapy. However, the high level of medical resources required and associated complications make its use in patients with severe ARDS controversial. Our proposed protocol also attempts to propose how to improve patient outcomes by balancing the possible overuse of resources with minimizing patient harm due to dangerous ventilator settings. A recruitment-potential-oriented evaluation-based protocol can effectively stabilize hypoxemic conditions quickly and screen out truly serious patients. [ABSTRACT FROM AUTHOR]

As several recent studies have shown low mortality rates in burn injury induced ARDS early (≤7 days) after the burn, the Berlin criteria for the ARDS diagnosis in this setting may be disputed. Related to this issue, the present study investigated the incidence, trajectory and risk factors of early Acute Respiratory Distress Syndrome (ARDS) and outcome in burn patients, as per the Berlin criteria, along with the concurrent prevalence and influence of inhalation injury, and ventilator-acquired pneumonia (VAP). Over a 2.5-year period, burn patients with Total Burn Surface Area (TBSA) exceeding 10% admitted to a national burn center were included. The subgroup of interest comprised patients with more than 48 h of ventilatory support. This group was assessed for ARDS, inhalation injury, and VAP. Out of 292 admissions, 62 sustained burns > 10% TBSA. Of these, 28 (45%) underwent ventilatory support for over 48 h, almost all, 24 out of 28, meeting the criteria for ARDS early, within 7 days post-injury and with a P a O 2 /F i O 2 (PF) rat i o nadir at day 5. The mortality rate for this early ARDS group was under 10%, regardless of PF ratios (mean TBSA% 34,8%). Patients with concurrent inhalation injury and early ARDS showed significantly lower PF ratios (p < 0.001), and higher SOFA scores (p = 0.004) but without impact on mortality. Organ failure, indicated by SOFA scores, peaked early (day 3) and declined in the first week, mirroring PF ratio trends (p < 0.001). The low mortality associated with early ARDS in burn patients in this study challenges the Berlin criteria's for the early ARDS diagnosis, which for its validity relies on that higher mortality is linked to worsening PF ratios. The finding suggests alternative mechanisms, leading to the early ARDS diagnosis, such as the significant impact of inhalation injury on early PF ratios and organ failure, as seen in this study. The concurrence of early organ failure with declining PF ratios, supports, as expected, the hypothesis of trauma-induced inflammation/multi-organ failure mechanisms contributing to early ARDS. The study highlights the complexity in differentiating between the contributions of inhalation injury to early ARDS and the related organ dysfunction early in the burn care trajectory. The Berlin criteria for the ARDS diagnosis may not be fully applicable in the burn care setting, where the low mortality significantly deviates from that described in the original Berlin ARDS criteria publication but is as expected when considering the actual not very extensive burn injury sizes/Baux scores as in the present study. [Display omitted] • The study revealed that 45% of burn patients with ≥ 10% Total Burn Surface Area (TBSA) required ventilatory support ≥ 48 h. • Inhalation injury, when concurrent with early ARDS, significantly reduced the PaO2/FiO2 (PF) ratios, and increased the overall organ failure rate but did not primarily impact mortality. • A notable early peak in organ failure was observed on day 3, with subsequently a slow decline. This pattern mirrored the trends in PF ratios. • The findings challenge the Berlin criteria for early ARDS diagnosis in burn patients, particularly the link between higher mortality and worsening PF ratios. [ABSTRACT FROM AUTHOR]

Despite periodic changes in the clinical definition of ARDS, imaging of the lung remains a central component of its diagnostic identification. Several imaging modalities are available to the clinician to establish a diagnosis of the syndrome, monitor its clinical course, or assess the impact of treatment and management strategies. Each imaging modality provides unique insight into ARDS from structural and/or functional perspectives. This review will highlight several methods for lung imaging in ARDS, emphasizing basic operational and physical principles for the respiratory therapist. Advantages and disadvantages of each modality will be discussed in the context of their utility for clinical management and decision-making. [ABSTRACT FROM AUTHOR]

BACKGROUND: In recent years, acute lung injury (ALI) and ARDS have emerged as critical health concerns, drawing considerable attention from clinicians. The volume of published articles on ALI/ARDS is on the rise, indicating the expanding research interest in this field. However, the precise quantity and quality of studies on ALI/ARDS remain unclear. Consequently, we employed bibliometric and visual techniques to comprehensively analyze the patterns and focal points of these articles. METHODS: To investigate the characteristics of highly referenced papers on ALI/ARDS and offer insights into the progress and advancements in research on ALI/ARDS, we conducted a comprehensive search in the core Web of Science database for cited articles using the terms "ALI," "acute lung injury," "ARDS," or "acute respiratory distress syndrome." A total of 60,282 citations were retrieved by narrowing the scope to reviews, articles, and publications in English. From the obtained citations, we selected materials for analysis from the top 100 articles with the highest number of citations. Subsequently, the articles were visualized and analyzed using VOSviewer, CiteSpace, and bibliometric techniques. This analysis focused on identifying trends related to authors, journals, countries, institutions, collaborative networks, key words, and other relevant factors in the field of ALI/ARDS research. RESULTS: Among the top 100 cited articles, the highest and lowest number of citations were 6,957 and 451, respectively. The 100 articles were published between 1991-2020, with a peak in publications observed in 2004, 2005, and 2012 (no. = 7). Among 29 journals, The New England Journal of Medicine (no. = 21) had the highest number of publications, followed by the American Journal of Respiratory and Critical Care Medicine (no. = 14). Among the 29 countries represented in the top 100 cited articles, the United States (no. = 51) emerged as the leading country in the number of publications, followed by Canada (no. = 19) (there was some overlap in paper output between countries due to co-publication). The 3 predominant keywords identified in studies within the ALI/ARDS domain were ALI, mechanical ventilation, and PEEP. CONCLUSIONS: This study provides a historical perspective on the scientific advancements in ALI/ARDS research, highlighting the need for further investigation and development in specific areas within the field. Bibliometric analyses revealed that the United States is the predominant force in the field of ALI/ARDS, contributing significantly to its development. Through an examination of highly cited papers on ALI/ARDS, we have identified global research trends, assessed the quality of studies, and identified hot topics in the field of ALI/ARDS. [ABSTRACT FROM AUTHOR]

Background: The pneumonitis associated with coronavirus disease 2019 (COVID-19) infection impacts the right ventricle (RV). However, the association between the disease severity and right ventricular systolic function needs elucidation. Method: We conducted a retrospective study of 108 patients admitted to critical care with COVID-19 pneumonitis to examine the association between tricuspid annular plane systolic excursion (TAPSE) by transthoracic echocardiography as a surrogate for RV systolic function with PaO2/FiO2 ratio as a marker of disease severity and other respiratory parameters. Results: The median age was 59 years [51, 66], 33 (31%) were female, and 63 (58%) were mechanically ventilated. Echocardiography was performed at a median of 3 days [2, 12] following admission to critical care. The PaO2/FiO2 and TAPSE medians were 20.5 [14.4, 32.0] and 21 mm [18, 24]. There was a statistically significant, albeit weak, association between the increase in TAPSE and the worsening of the PaO2/FiO2 ratio (r2 = 0.041, p = 0.04). This association was more pronounced in the mechanically ventilated (r2 = 0.09, p = 0.02). TAPSE did not correlate significantly with FiO2, PaO2, PaCO2, pH, respiratory rate, or mechanical ventilation. Patients with a TAPSE ≥ 17 mm had a considerably worse PaO2/FiO2 ratio than a TAPSE < 17 mm (18.6 vs. 32.1, p = 0.005). The PaO2/FiO2 ratio predicted TAPSE (OR = 0.94, p = 0.004) with good area under the curve (0.72, p = 0.006). Moreover, a PaO2/FiO2 ratio < 26.7 (moderate pneumonitis) predicted TAPSE > 17 mm with reasonable sensitivity (67%) and specificity (68%). Conclusion: In patients admitted to critical care with COVID-19 pneumonitis, TAPSE increased as the disease severity worsened early in the course of the disease, especially in the mechanically ventilated. A TAPSE within the normal range is not necessarily reassuring in early COVID-19 pneumonitis. [ABSTRACT FROM AUTHOR]

Electrical Impedance Tomography (EIT) is a novel real-time lung imaging technology for personalized ventilation adjustments, indicating promising results in animals and humans. The present study aimed to assess its clinical utility for improved ventilation and oxygenation compared to traditional protocols. Comprehensive electronic database screening was done until 30th November, 2023. Randomized controlled trials, controlled clinical trials, comparative cohort studies, and assessments of EIT-guided PEEP titration and conventional methods in adult ARDS patients regarding outcome, ventilatory parameters, and P/F ratio were included. Our search retrieved five controlled cohort studies and two RCTs with 515 patients and overall reduced risk of mortality [RR = 0.68; 95% CI: 0.49 to 0.95; I2 = 0%], better dynamic compliance [MD = 3.46; 95% CI: 1.59 to 5.34; I2 = 0%] with no significant difference in PaO2/FiO2 ratio [MD = 6.5; 95%CI -13.86 to 26.76; I2 = 74%]. The required information size except PaO2/FiO2 was achieved for a power of 95% based on the 50% reduction in risk of mortality, 10% improved compliance as the cumulative Z-score of the said outcomes crossed the alpha spending boundary and did not dip below the inner wedge of futility. EIT-guided individualized PEEP titration is a novel modality; further well-designed studies are needed to substantiate its utility. Highlights: Question: Is the EIT-guided PEEP titration in ARDS universally beneficial and effective? Findings: This systematic review found better survivability, dynamic compliance, in ARDS patients, as the required information size was achieved for a power of 95%. There was no significant improvement in oxygenation and successful weaning incidence compared to conventional methods. However, the required information size for these contexts is yet to be achieved. Meaning: EIT-guided PEEP titration in ARDS patients showed promising results and warranted further clinical trials. [ABSTRACT FROM AUTHOR]

Transpulmonary pressure (PL) calculation requires esophageal pressure (PES) as a surrogate of pleural pressure (Ppl), but its calibration is a cumbersome technique. Central venous pressure (CVP) swings may reflect tidal variations in Ppl and could be used instead of PES, but the interpretation of CVP waveforms could be difficult due to superposition of heartbeat-induced pressure changes. Thus, we developed a digital filter able to remove the cardiac noise to obtain a filtered CVP (f-CVP). The aim of the study was to evaluate the accuracy of CVP and filtered CVP swings (ΔCVP and Δf-CVP, respectively) in estimating esophageal respiratory swings (ΔPES) and compare PL calculated with CVP, f-CVP and PES; then we tested the diagnostic accuracy of the f-CVP method to identify unsafe high PL levels, defined as PL>10 cmH2O. Twenty patients with acute respiratory failure (defined as PaO2/FiO2 ratio below 200 mmHg) treated with invasive mechanical ventilation and monitored with an esophageal balloon and central venous catheter were enrolled prospectively. For each patient a recording session at baseline was performed, repeated if a modification in ventilatory settings occurred. PES, CVP and airway pressure during an end-inspiratory and -expiratory pause were simultaneously recorded; CVP, f-CVP and PES waveforms were analyzed off-line and used to calculate transpulmonary pressure (PLCVP, PLf-CVP, PLPES, respectively). Δf-CVP correlated better than ΔCVP with ΔPES (r = 0.8, p = 0.001 vs. r = 0.08, p = 0.73), with a lower bias in Bland Altman analysis in favor of PLf-CVP (mean bias − 0.16, Limits of Agreement (LoA) -1.31, 0.98 cmH2O vs. mean bias − 0.79, LoA − 3.14, 1.55 cmH2O). Both PLf-CVP and PLCVP correlated well with PLPES (r = 0.98, p < 0.001 vs. r = 0.94, p < 0.001), again with a lower bias in Bland Altman analysis in favor of PLf-CVP (0.15, LoA − 0.95, 1.26 cmH2O vs. 0.80, LoA − 1.51, 3.12, cmH2O). PLf-CVP discriminated high PL value with an area under the receiver operating characteristic curve 0.99 (standard deviation, SD, 0.02) (AUC difference = 0.01 [-0.024; 0.05], p = 0.48). In mechanically ventilated patients with acute respiratory failure, the digital filtered CVP estimated ΔPES and PL obtained from digital filtered CVP represented a reliable value of standard PL measured with the esophageal method and could identify patients with non-protective ventilation settings. [ABSTRACT FROM AUTHOR]

Acute respiratory distress syndrome (ARDS)/acute lung injury (ALI) is a severe complication of sepsis characterized by acute respiratory distress, hypoxemia, and diffuse bilateral pulmonary infiltrates. The regulation of RIPK1 is an important part of the inflammatory response, and cIAP1/2 serves as the E3 ubiquitin ligase for RIPK1. In this study, we investigated the effect and mechanism of cIAP1/2 inhibition on sepsis-induced lung injury. Our results showed that cIAP1/2 inhibition can alleviate sepsis-induced lung injury and reduce the inflammatory response, which is accompanied by downregulation of RIPK1 phosphorylation and ubiquitination. Additionally, cIAP1/2 inhibition led to the up-regulation of programmed cell death, including apoptosis, necroptosis, and pyroptosis, and inhibiting these three cell death pathways can further reduce the inflammatory response, which is similar to the recently discovered programmed cell death pathway PANoptosis. Our findings suggest that cIAP1/2 and PANoptosis inhibition may be a new strategy for treating sepsis-induced lung injury and provide important references for further exploring the mechanism of sepsis-induced lung injury and identifying new therapeutic targets. [ABSTRACT FROM AUTHOR]