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Background: Acute respiratory distress syndrome (ARDS) remains a significant challenge in critical care, with high mortality rates despite advancements in treatment. Venovenous extracorporeal membrane oxygenation (VV-ECMO) is employed as salvage therapy for refractory cases. However, some patients may continue to experience persistent severe hypoxemia despite being treated with VV-ECMO. To achieve this, moderate hypothermia and short-acting selective β1-blockers have been proposed. Methods: Using a swine model of severe ARDS treated with VV-ECMO, this study investigated the efficacy of moderate hypothermia or β-blockade in improving arterial oxygen saturation (SaO2) three hours after VV-ECMO initiation. Primary endpoints included the ratio of VV-ECMO flow to cardiac output and arterial oxygen saturation before VV-ECMO start (H0) and three hours after ECMO start (H3). Secondary safety criteria encompassed hemodynamics and oxygenation parameters. Results: Twenty-two male pigs were randomized into three groups: control (n = 6), hypothermia (n = 9) and β-blockade (n = 7). At H0, all groups demonstrated similar hemodynamic and respiratory parameters. Both moderate hypothermia and β-blockade groups exhibited a significant increase in the ratio of VV-ECMO flow to cardiac output at H3, resulting in improved SaO2. At H3, despite a decrease in oxygen delivery and consumption in the intervention groups compared to the control group, oxygen extraction ratios across groups remained unchanged and lactate levels were normal. Conclusions: In a swine model of severe ARDS treated with VV-ECMO, both moderate hypothermia and β-blockade led to an increase in the ratio of VV-ECMO flow to cardiac output resulting in improved arterial oxygen saturation without any impact on tissue perfusion. [ABSTRACT FROM AUTHOR]

Background: By controlling hypercapnia, respiratory acidosis, and associated consequences, extracorporeal CO2 removal (ECCO2R) has the potential to facilitate ultra-protective lung ventilation (UPLV) strategies and to decrease injury from mechanical ventilation. We convened a meeting of European intensivists and nephrologists and used a modified Delphi process to provide updated insights into the role of ECCO2R in acute respiratory distress syndrome (ARDS) and to identify recommendations for a future randomized controlled trial. Results: The group agreed that lung protective ventilation and UPLV should have distinct definitions, with UPLV primarily defined by a tidal volume (VT) of 4–6 mL/kg predicted body weight with a driving pressure (ΔP) ≤ 14–15 cmH2O. Fourteen (93%) participants agreed that ECCO2R would be needed in the majority of patients to implement UPLV. Furthermore, 10 participants (majority, 63%) would select patients with PaO2:FiO2 > 100 mmHg (> 13.3 kPa) and 14 (consensus, 88%) would select patients with a ventilatory ratio of > 2.5–3. A minimum CO2 removal rate of 80 mL/min delivered by continuous renal support machines was suggested (11/14 participants, 79%) for this objective, using a short, double-lumen catheter inserted into the right internal jugular vein as the preferred vascular access. Of the participants, 14/15 (93%, consensus) stated that a new randomized trial of ECCO2R is needed in patients with ARDS. A ΔP of ≥ 14–15 cmH2O was suggested by 12/14 participants (86%) as the primary inclusion criterion. Conclusions: ECCO2R may facilitate UPLV with lower volume and pressures provided by the ventilator, while controlling respiratory acidosis. Since recent European Society of Intensive Care Medicine guidelines on ARDS recommended against the use of ECCO2R for the treatment of ARDS outside of randomized controlled trials, new trials of ECCO2R are urgently needed, with a ΔP of ≥ 14–15 cmH2O suggested as the primary inclusion criterion. [ABSTRACT FROM AUTHOR]

Background: A combination of prone positioning (PP) and venovenous extracorporeal membrane oxygenation (VV-ECMO) is safe, feasible, and associated with potentially improved survival for severe acute respiratory distress syndrome (ARDS). However, whether ARDS patients, especially non-COVID-19 patients, placed in PP before VV-ECMO should continue PP after a VV-ECMO connection is unknown. This study aimed to test the hypothesis that early use of PP during VV-ECMO could increase the proportion of patients successfully weaned from ECMO support in severe ARDS patients who received PP before ECMO. Methods: In this prospective observational study, patients with severe ARDS who were treated with VV-ECMO were divided into two groups: the prone group and the supine group, based on whether early PP was combined with VV-ECMO. The proportion of patients successfully weaned from VV-ECMO and 60-day mortality were analyzed before and after propensity score matching. Results: A total of 165 patients were enrolled, 50 in the prone and 115 in the supine group. Thirty-two (64%) and 61 (53%) patients were successfully weaned from ECMO in the prone and the supine groups, respectively. The proportion of patients successfully weaned from VV-ECMO in the prone group tended to be higher, albeit not statistically significant. During PP, there was a significant increase in partial pressure of arterial oxygen (PaO2) without a change in ventilator or ECMO settings. Tidal impedance shifted significantly to the dorsal region, and lung ultrasound scores significantly decreased in the anterior and posterior regions. Forty-five propensity score-matched patients were included in each group. In this matched sample, the prone group had a higher proportion of patients successfully weaned from VV-ECMO (64.4% vs. 42.2%; P = 0.035) and lower 60-day mortality (37.8% vs. 60.0%; P = 0.035). Conclusions: Patients with severe ARDS placed in PP before VV-ECMO should continue PP after VV-ECMO support. This approach could increase the probability of successful weaning from VV-ECMO. Trial Registration: ClinicalTrials.Gov: NCT04139733. Registered 23 October 2019. [ABSTRACT FROM AUTHOR]

Type 2 alveolar epithelial (AT2) cells of the lung are fundamental in regulating alveolar inflammation in response to injury. Impaired mitochondrial long-chain fatty acid β-oxidation (mtLCFAO) in AT2 cells is assumed to aggravate alveolar inflammation in acute lung injury (ALI), yet the importance of mtLCFAO to AT2 cell function needs to be defined. Here we show that expression of carnitine palmitoyltransferase 1a (CPT1a), a mtLCFAO rate limiting enzyme, in AT2 cells is significantly decreased in acute respiratory distress syndrome (ARDS). In mice, Cpt1a deletion in AT2 cells impairs mtLCFAO without reducing ATP production and alters surfactant phospholipid abundance in the alveoli. Impairing mtLCFAO in AT2 cells via deleting either Cpt1a or Acadl (acyl-CoA dehydrogenase long chain) restricts alveolar inflammation in ALI by hindering the production of the neutrophilic chemokine CXCL2 from AT2 cells. This study thus highlights mtLCFAO as immunometabolism to injury in AT2 cells and suggests impaired mtLCFAO in AT2 cells as an anti-inflammatory response in ARDS. Impaired mitochondrial long-chain fatty acid β-oxidation (mtLCFAO) in type 2 alveolar epithelial (AT2) cells is thought to aggravate alveolar inflammation in acute lung injury. Here, the authors show that the mtLCFAO rate limiting enzyme CPT1a is decreased in AT2 cells in acute respiratory distress syndrome, highlighting the role of mtLCFAO in immunometabolism in this context. [ABSTRACT FROM AUTHOR]

Purpose: Nowadays, it is largely accepted that albumin should not be used in hypoalbuminemia or for nutritional purpose. The most discussed indication of albumin at present is the resuscitation in shock states, especially distributive shocks such as septic shock. The main evidence-based indication is also liver disease. In this review, we provided updated evidence-based instruction for definite and potential indications of albumin administration in clinical practice, with appropriate dosing and duration. Methods: Data collection was carried out until November 2023 by search of electronic databases including PubMed, Google Scholar, Scopus, and Web of Science. GRADE system has been used to determine the quality of evidence and strength of recommendations for each albumin indication. Results: A total of 165 relevant studies were included in this review. Fluid replacement in plasmapheresis and liver diseases, including hepatorenal syndrome, spontaneous bacterial peritonitis, and large-volume paracentesis, have a moderate to high quality of evidence and a strong recommendation for administering albumin. Moreover, albumin is used as a second-line and adjunctive to crystalloids for fluid resuscitation in hypovolemic shock, sepsis and septic shock, severe burns, toxic epidermal necrolysis, intradialytic hypotension, ovarian hyperstimulation syndrome, major surgery, non-traumatic brain injury, extracorporeal membrane oxygenation, acute respiratory distress syndrome, and severe and refractory edema with hypoalbuminemia has a low to moderate quality of evidence and weak recommendation to use. Also, in modest volume paracentesis, severe hyponatremia in cirrhosis has a low to moderate quality of evidence and a weak recommendation. Conclusion: Albumin administration is most indicated in management of cirrhosis complications. Fluid resuscitation or treatment of severe and refractory edema, especially in patients with hypoalbuminemia and not responding to other treatments, is another rational use for albumin. Implementation of evidence-based guidelines in hospitals can be an effective measure to reduce inappropriate uses of albumin. [ABSTRACT FROM AUTHOR]

Background: Central nervous system (CNS) injury following initiation of veno-venous extracorporeal membrane oxygenation (VV-ECMO) is common. An acute decrease in partial pressure of arterial carbon dioxide (PaCO2) following VV-ECMO initiation has been suggested as an etiological factor, but the challenges of diagnosing CNS injuries has made discerning a relationship between PaCO2 and CNS injury difficult. Methods: We conducted a prospective cohort study of adult patients undergoing VV-ECMO for acute respiratory failure. Arterial blood gas measurements were obtained prior to initiation of VV-ECMO, and at every 2–4 h for the first 24 h. Neuroimaging was conducted within the first 7–14 days in patients who were suspected of having neurological injury or unable to be examined because of sedation. We collected blood biospecimens to measure brain biomarkers [neurofilament light (NF-L); glial fibrillary acidic protein (GFAP); and phosphorylated-tau 181] in the first 7 days following initiation of VV-ECMO. We assessed the relationship between both PaCO2 over the first 24 h and brain biomarkers with CNS injury using mixed methods linear regression. Finally, we explored the effects of absolute change of PaCO2 on serum levels of neurological biomarkers by separate mixed methods linear regression for each biomarker using three PaCO2 exposures hypothesized to result in CNS injury. Results: In our cohort, 12 of 59 (20%) patients had overt CNS injury identified on head computed tomography. The PaCO2 decrease with VV-ECMO initiation was steeper in patients who developed a CNS injury (− 0.32%, 95% confidence interval − 0.25 to − 0.39) compared with those without (− 0.18%, 95% confidence interval − 0.14 to − 0.21, P interaction < 0.001). The mean concentration of NF-L increased over time and was higher in those with a CNS injury (464 [739]) compared with those without (127 [257]; P = 0.001). GFAP was higher in those with a CNS injury (4278 [11,653] pg/ml) compared with those without (116 [108] pg/ml; P < 0.001). The mean NF-L, GFAP, and tau over time in patients stratified by the three thresholds of absolute change of PaCO2 showed no differences and had no significant interaction for time. Conclusions: Although rapid decreases in PaCO2 following initiation of VV-ECMO were slightly greater in patients who had CNS injuries versus those without, data overlap and absence of relationships between PaCO2 and brain biomarkers suggests other pathophysiologic variables are likely at play. [ABSTRACT FROM AUTHOR]

The prone position is an immediately available and easily implemented procedure that was introduced more than 50 years ago as a method for improvement of gas exchange in patients with acute respiratory distress syndrome (ARDS). In the meantime, a survival advantage could also be shown in patients with severe ARDS, which led to the recommendation of the prone position for treatment of severe ARDS by expert consensus and specialist society guidelines. The continuing coronavirus disease 2019 (COVID-19) pandemic moved the prone position to the forefront of medicine, including the widespread implementation of the prone position for awake, spontaneously breathing nonintubated patients with acute hypoxemic respiratory insufficiency. The survival advantage is possible due to a reduction of the ventilator-associated lung damage. In this article, the physiological effects, data on clinical results, practical considerations and open questions with respect to the prone position are discussed. [ABSTRACT FROM AUTHOR]

The role of programmed death ligand 1 (PD-L1) has been extensively investigated in adaptive immune system. However, increasing data show that innate immune responses are also affected by the immune checkpoint molecule. It has been demonstrated that regulation of PD-L1 signaling in macrophages may be a potential therapeutic method for acute respiratory distress syndrome (ARDS). However, the PD-L1 expression pattern in local macrophages and whole lung tissues remains mysterious, hindering optimization of the potential treatment program. Therefore, we aim to determine the PD-L1 expression pattern during ARDS. Our findings show that PD-L1 levels are markedly increased in lipopolysaccharide (LPS)-stimulated lung tissues, which might be attributable to an increase in the gene expression by immune cells, including macrophages and neutrophils. In vitro experiments are performed to explore the mechanism involved in LPS-induced PD-L1 production. We find that PD-L1 generation is controlled by transcription factors early growth response 1 (Egr-1) and CCAAT/enhancer binding protein delta (C/EBPδ). Strikingly, PD-L1 production is enhanced by phosphoinositide-3 kinase (PI3K)–protein kinase B (AKT) signaling pathway via up-regulation of Egr-1 and C/EBPδ expressions. Additionally, we observe that expressions of Egr-1 and C/EBPδ mutually reinforce each other. Moreover, we observe that PD-L1 is protective for ARDS due to its regulatory role in macrophage-associated inflammatory response. In summary, during LPS-induced ARDS, PD-L1 expression, which is beneficial for the disease, is increased via the PI3K-AKT1-Egr-1/C/EBPδ signaling pathway, providing theoretical basis for application of methods controlling PD-L1 signaling in macrophages for ARDS treatment in clinic. [ABSTRACT FROM AUTHOR]

Sepsis-induced acute respiratory distress syndrome (ARDS) poses a grave danger to life, resulting from sepsis-induced multi-organ failure. Although ferroptosis, a form of iron-dependent lipid peroxidative cell death, has been associated with sepsis-induced ARDS, the specific mechanisms are not fully understood. In this study, we utilized WGCNA, PPI, friends analysis, and six machine learning techniques (Lasso, SVM, RFB, XGBoost, AdaBoost, and LightGBM) to pinpoint STAT3 as a potential diagnostic marker. A significant increase in monocyte and neutrophil levels was observed in patients with sepsis-induced ARDS, as revealed by immune infiltration analyses, when compared to controls. Moreover, there was a positive correlation between STAT3 expression and the level of infiltration. Single-cell analysis uncovered a notable disparity in B-cell expression between sepsis and sepsis-induced ARDS. Furthermore, in vitro experiments using LPS-treated human bronchial epithelial cells (BEAS-2B) and THP1 cells demonstrated a significant increase in STAT3 phosphorylation expression. Additionally, the inhibition of STAT3 phosphorylation by Stattic effectively prevented LPS-induced ferroptosis in both BEAS-2B and THP1 cells. This indicates that the activation of STAT3 phosphorylation promotes ferroptosis in human bronchial epithelial cells in response to LPS. In summary, this research has discovered and confirmed STAT3 as a potential biomarker for the diagnosis and treatment of sepsis-induced ARDS. [ABSTRACT FROM AUTHOR]

Galectin-3 is a multifunctional protein that is involved in various physiological and pathological events. Emerging evidence suggests that galectin-3 also plays a critical role in the pathogenesis of pulmonary diseases. Galectin-3 can be produced and secreted by various cell types in the lungs, and the overexpression of galectin-3 has been found in acute lung injury/acute respiratory distress syndrome (ALI/ARDS), pulmonary hypertension (PH), pulmonary fibrosis diseases, lung cancer, lung infection, chronic obstructive pulmonary disease (COPD), and asthma. Galectin-3 exerts diverse effects on the inflammatory response, immune cell activation, fibrosis and tissue remodeling, and tumorigenesis in these pulmonary disorders, and genetic and pharmacologic modulation of galectin-3 has therapeutic effects on the treatment of pulmonary illnesses. In this review, we summarize the structure and function of galectin-3 and the underlying mechanisms of galectin-3 in pulmonary disease pathologies; we also discuss preclinical and clinical evidence regarding the therapeutic potential of galectin-3 inhibitors in these pulmonary disorders. Additionally, targeting galectin-3 may be a very promising therapeutic approach for the treatment of pulmonary diseases. [ABSTRACT FROM AUTHOR]

The article discusses the relationship between acute kidney injury (AKI) and acute respiratory distress syndrome (ARDS) in critically ill patients. The study analyzed data from 10 randomized controlled trials conducted in the United States between 1996 and 2018. The authors found that AKI occurred in approximately 43.7% of patients with ARDS, with a higher incidence of AKI stage 3 and acute kidney disease (AKD) in patients with more severe AKI. The study also found that AKI was associated with higher mortality rates at 28 and 90 days. However, the study has some limitations, including the lack of consideration for certain variables and the heterogeneity of ARDS and AKI subphenotypes. Further research is needed to better understand the relationship between AKI and ARDS and to identify strategies for improving outcomes. [Extracted from the article]

Purpose: Human herpesviruses, particularly cytomegalovirus (CMV) and herpes simplex virus (HSV), frequently reactivate in critically ill patients, including those with acute respiratory distress syndrome (ARDS) related to coronavirus disease 2019 (COVID-19). The clinical interpretation of pulmonary herpesvirus reactivation is challenging and there is ongoing debate about its association with mortality and benefit of antiviral medication. We aimed to quantify the incidence and pathogenicity of pulmonary CMV and HSV reactivations in critically ill COVID-19 patients. Methods: Mechanically ventilated COVID-19 patients seropositive for CMV or HSV were included in this observational cohort study. Diagnostic bronchoscopy with bronchoalveolar lavage was performed routinely and analyzed for alveolar viral loads and inflammatory biomarkers. Utilizing joint modeling, we explored the dynamic association between viral load trajectories over time and mortality. We explored alveolar inflammatory biomarker dynamics between reactivated and non-reactivated patients. Results: Pulmonary reactivation (> 104 copies/ml) of CMV occurred in 6% of CMV-seropositive patients (9/156), and pulmonary reactivation of HSV in 37% of HSV-seropositive patients (63/172). HSV viral load dynamics prior to or without antiviral treatment were associated with increased 90-day mortality (hazard ratio [HR] 1.24, 95% confidence interval [CI] 1.04–1.47). The alveolar concentration of several inflammatory biomarkers increased with HSV reactivation, including interleukin (IL)-6, IL-1β, granulocyte colony stimulating factor (G-CSF), and tumor necrosis factor (TNF). Conclusion: In mechanically ventilated COVID-19 patients, HSV reactivations are common, while CMV reactivations were rare. HSV viral load dynamics prior to or without antiviral treatment are associated with mortality. Alveolar inflammation is elevated after HSV reactivation. [ABSTRACT FROM AUTHOR]

Purpose: Awake prone positioning has been reported to reduce endotracheal intubation in patients with coronavirus disease 2019 (COVID-19)-related acute hypoxemic respiratory failure (AHRF). However, it is still unclear whether using the awake prone positioning for longer periods can further improve outcomes. Methods: In this randomized, open-label clinical trial conducted at 12 hospitals in China, non-intubated patients with COVID-19-related AHRF were randomly assigned to prolonged awake prone positioning (target > 12 h daily for 7 days) or standard care with a shorter period of awake prone positioning. The primary outcome was endotracheal intubation within 28 days after randomization. The key secondary outcomes included mortality and adverse events. Results: In total, 409 patients were enrolled and randomly assigned to prolonged awake prone positioning (n = 205) or standard care (n = 204). In the first 7 days after randomization, the median duration of prone positioning was 12 h/d (interquartile range [IQR] 12–14 h/d) in the prolonged awake prone positioning group vs. 5 h/d (IQR 2–8 h/d) in the standard care group. In the intention-to-treat analysis, intubation occurred in 35 (17%) patients assigned to prolonged awake prone positioning and in 56 (27%) patients assigned to standard care (relative risk 0.62 [95% confidence interval (CI) 0.42–0.9]). The hazard ratio (HR) for intubation was 0.56 (0.37–0.86), and for mortality was 0.63 (0.42–0.96) for prolonged awake prone positioning versus standard care, within 28 days. The incidence of pre-specified adverse events was low and similar in both groups. Conclusion: Prolonged awake prone positioning of patients with COVID-19-related AHRF reduces the intubation rate without significant harm. These results support prolonged awake prone positioning of patients with COVID-19-related AHRF. [ABSTRACT FROM AUTHOR]

Purpose: Although noninvasive ventilation (NIV) may reduce reintubation in patients with acute hypoxemic respiratory failure following abdominal surgery, this strategy has not been specifically assessed in patients with obesity. Methods: We conducted a post hoc analysis of a multicenter randomized controlled trial comparing NIV delivered via facial mask to standard oxygen therapy among patients with obesity and acute hypoxemic respiratory failure within 7 days after abdominal surgery. The primary outcome was reintubation within 7 days. Secondary outcomes were invasive ventilation-free days at day 30, intensive care unit (ICU)-acquired pneumonia and 30-day survival. Results: Among 293 patients with hypoxemic respiratory failure following abdominal surgery, 76 (26%) patients had obesity and were included in the intention-to-treat analysis. Reintubation rate was significantly lower with NIV (13/42, 31%) than with standard oxygen therapy (19/34, 56%) within 7 days (absolute difference: − 25%, 95% confidence interval (CI) − 49 to − 1%, p = 0.03). NIV was associated with significantly more invasive ventilation-free days compared with standard oxygen therapy (27.1 ± 8.6 vs 22.7 ± 11.1 days; p = 0.02), while fewer patients developed ICU-acquired pneumonia (1/42, 2% vs 6/34, 18%; p = 0.04). The 30-day survival was 98% in the NIV group (41/42) versus 85% in the standard oxygen therapy (p = 0.08). In patients with body mass index (BMI) < 30 kg/m2, no significant difference was observed between NIV (36/105, 34%) and standard oxygen therapy (47/109, 43%, p = 0.03). An interaction test showed no statistically significant difference between the two subsets (BMI ≥ 30 kg/m2 and BMI < 30 kg/m2). Conclusions: Among patients with obesity and hypoxemic respiratory failure following abdominal surgery, use of NIV compared with standard oxygen therapy reduced the risk of reintubation within 7 days, contrary to patients without obesity. However, no interaction was found according to the presence of obesity or not, suggesting either a lack of power to conclude in the non-obese subgroup despite existing differences, or that the statistical difference found in the overall sample was driven by a large effect in the obese subsets. [ABSTRACT FROM AUTHOR]

The article discusses the limitations of evidence-based medicine in the critical care environment and the need for personalized medicine. It highlights the challenges faced by critical care physicians in making decisions based on available evidence, such as the vast amount of literature, outdated information, and the difficulty in conducting high-quality trials. The article also emphasizes the importance of expert judgment and experience in making ad-hoc decisions when evidence is lacking. It suggests that a deeper understanding of disease mechanisms and the development of more targeted therapies may lead to more effective personalized medicine in the future. [Extracted from the article]

Purpose: Severe Pneumocystis jirovecii pneumonia (PJP) requiring intensive care has been the subject of few prospective studies. It is unclear whether delayed curative antibiotic therapy may impact survival in these severe forms of PJP. The impact of corticosteroid therapy combined with antibiotics is also unclear. Methods: This multicentre, prospective observational study involving 49 adult intensive care units (ICUs) in France was designed to evaluate the severity, the clinical spectrum, and outcomes of patients with severe PJP, and to assess the association between delayed curative antibiotic treatment and adjunctive corticosteroid therapy with mortality. Results: We included 158 patients with PJP from September 2020 to August 2022. Their main reason for admission was acute respiratory failure (n = 150, 94.9%). 12% of them received antibiotic prophylaxis for PJP before ICU admission. The ICU, hospital, and 6-month mortality were 31.6%, 35.4%, and 40.5%, respectively. Using time-to-event analysis with a propensity score-based inverse probability of treatment weighting, the initiation of curative antibiotic treatment after 96 h of ICU admission was associated with faster occurrence of death [time ratio: 6.75; 95% confidence interval (95% CI): 1.48–30.82; P = 0.014]. The use of corticosteroids for PJP was associated with faster occurrence of death (time ratio: 2.48; 95% CI 1.01–6.08; P = 0.048). Conclusion: This study showed that few patients with PJP admitted to intensive care received prophylactic antibiotic therapy, that delay in curative antibiotic treatment was common and that both delay in curative antibiotic treatment and adjunctive corticosteroids for PJP were associated with accelerated mortality. [ABSTRACT FROM AUTHOR]

Purpose: The development of acute kidney injury (AKI) after the acute respiratory distress syndrome (ARDS) reduces the chance of organ recovery and survival. The purpose of this study was to examine the AKI rate and attributable mortality in ARDS patients. Methods: We performed an individual patient-data analysis including 10 multicenter randomized controlled trials conducted over 20 years. We employed a Super Learner ensemble technique, including a time-dependent analysis, to estimate the adjusted risk of AKI. We calculated the mortality attributable to AKI using an inverse probability of treatment weighting estimator integrated with the Super Learner. Results: There were 5148 patients included in this study. The overall incidence of AKI was 43.7% (n = 2251). The adjusted risk of AKI ranged from 38.8% (95% confidence interval [CI], 35.7 to 41.9%) in ARMA, to 55.8% in ROSE (95% CI, 51.9 to 59.6%). 37.1% recovered rapidly from AKI, with a significantly lower recovery rate in recent trials (P < 0.001). The 90-day excess in mortality attributable to AKI was 15.4% (95% CI, 12.8 to 17.9%). It decreased from 25.4% in ARMA (95% CI, 18.7 to 32%), to 11.8% in FACTT (95% CI, 5.5 to 18%) and then remained rather stable over time. The 90-day overall excess in mortality attributable to acute kidney disease was 28.4% (95% CI, 25.3 to 31.5%). Conclusions: The incidence of AKI appears to be stable over time in patients with ARDS enrolled in randomized trials. The development of AKI remains a significant contributing factor to mortality. These estimates are essential for designing future clinical trials for AKI prevention or treatment. [ABSTRACT FROM AUTHOR]

This article provides information on the use of facemask noninvasive ventilation (NIV) in various clinical settings. NIV allows for positive airway pressure without the need for intubation, providing respiratory support while avoiding the negative effects of invasive mechanical ventilation. The article discusses the set-up and ventilatory settings for facemask NIV, as well as its indications and monitoring. It also highlights the limitations and contraindications of this technique. The information presented in the article is based on research and clinical experience. [Extracted from the article]

Objectives: To identify the prevalence and associated factors of cognitive dysfunction, 1 year after ICU discharge, among adult patients, and it´s relation with quality of life. Methods: Multicenter, prospective cohort study including ICUs of 10 tertiary hospitals in Brazil, between May 2014 and December 2018. The patients included were 452 adult ICU survivors (median age 60; 47.6% women) with an ICU stay greater than 72 h. Results: At 12 months after ICU discharge, a Montreal Cognitive Assessment (tMOCA) telephone score of less than 12 was defined as cognitive dysfunction. At 12 months, of the 452 ICU survivors who completed the cognitive evaluation 216 (47.8%) had cognitive dysfunction. In multivariable analyses, the factors associated with long-term (1-year) cognitive dysfunction were older age (Prevalence Ratio–PR = 1.44, P < 0.001), absence of higher education (PR = 2.81, P = 0.005), higher comorbidities on admission (PR = 1.089; P = 0.004) and delirium (PR = 1.13, P < 0.001). Health-related Quality of life (HRQoL), assessed by the mental and physical dimensions of the SF-12v2, was significantly better in patients without cognitive dysfunction (Mental SF-12v2 Mean difference = 2.54; CI 95%, − 4.80/− 0.28; p = 0.028 and Physical SF-12v2 Mean difference = − 2.85; CI 95%, − 5.20/− 0.50; P = 0.018). Conclusions: Delirium was found to be the main modifiable predictor of long-term cognitive dysfunction in ICU survivors. Higher education consistently reduced the probability of having long-term cognitive dysfunction. Cognitive dysfunction significantly influenced patients' quality of life, leading us to emphasize the importance of cognitive reserve for long-term prognosis after ICU discharge. [ABSTRACT FROM AUTHOR]

Background: The survival benefit of venovenous extracorporeal membrane oxygenation (VV-ECMO) in adult patients with severe acute respiratory distress syndrome (ARDS) remains controversial. This study aimed to investigate the efficiency and potential prognostic factors of VV-ECMO for severe ARDS in adults by evaluating our institutional experience and results. Materials and methods: This research studied ARDS patients receiving VV-ECMO between June 2011 and May 2023. The inclusion criteria were PaO2/FiO2 < 100 mmHg at FiO2 of 1.0. Retrospective data was analyzed to identify factors associated with successful ECMO weaning and hospital discharge survival. Results: A total of 18 patients were included in this study, with 7 cases (38.9%) successfully weaned from ECMO and 5 cases (27.8%) surviving hospital discharge. The overall complication rate was 77.8%. After treatment with VV ECMO, there were statistically significant improvements in both PaO2 and PaCO2 (P < 0.05). Patients in the successful weaning group had a lower pTB value, less accumulative volume of sodium bicarbonate during ECMO, and lower accumulative volume of intravenous immunoglobulin in the hospital compared to the unsuccessful weaning group (all P < 0.05). Furthermore, compared to the non-survivors, the survivors had less severe acidosis, higher mean arterial pressure before ECMO, a lower level of pCr, and a lower pTB value during ECMO (all P < 0.05). Conclusion: ECMO can effectively promote oxygenation and carbon dioxide (CO2) removal in patients with severe ARDS. Early initiation of ECMO with appropriate management could benefit in reducing comorbidities and mortality. [ABSTRACT FROM AUTHOR]

In this review, we aimed to comprehensively summarize current literature on pathophysiology, relevance, diagnosis and treatment of fluid accumulation in patients with sepsis/septic shock. Fluid accumulation syndrome (FAS) is defined as fluid accumulation (any degree, expressed as percentage from baseline body weight) with new onset organ-failure. Over the years, many studies have described the negative impact of FAS on clinically relevant outcomes. While the relationship between FAS and ICU outcomes is well described, uncertainty exists regarding its diagnosis, monitoring and treatment. A stepwise approach is suggested to prevent and treat FAS in patients with septic shock, including minimizing fluid intake (e.g., by limiting intravenous fluid administration and employing de-escalation whenever possible), limiting sodium and chloride administration, and maximizing fluid output (e.g., with diuretics, or renal replacement therapy). Current literature implies the need for a multi-tier, multi-modal approach to de-resuscitation, combining a restrictive fluid management regime with a standardized early active de-resuscitation, maintenance fluid reduction (avoiding fluid creep) and potentially using physical measures such as compression stockings. Trial registration: Not applicable. [ABSTRACT FROM AUTHOR]

Background: Iliacus muscle abscess is an uncommon but potentially life-threatening condition that can present with nonspecific symptoms, posing diagnostic challenges. This case report highlights the importance of considering iliopsoas abscess in patients presenting with fever and hip pain, especially in the absence of obvious risk factors or penetrating trauma. The novelty of this case lies in its atypical presentation mimicking a respiratory viral infection and musculoskeletal injury, impeding accurate diagnosis and appropriate management. Case Presentation: A previously healthy 21-year-old female who had a mechanical fall 3 weeks prior presented with fever, right hip pain, and respiratory symptoms, initially suggestive of a respiratory infection and musculoskeletal injury. However, initial investigations revealing a markedly high C-reactive protein (CRP) concentration prompted further computed tomography (CT) imaging of her abdomen and pelvis, which uncovered an iliopsoas abscess presumably stemming from antecedent trauma. Subsequent CT guided aspiration along with culture-sensitive antibiotics led to successful treatment and resolution of her symptoms. Conclusions: This case emphasizes the importance of considering iliopsoas abscess as a possible differential, even in young patients without typical risk factors. Markedly elevated inflammatory markers such as CRP concentrations can serve as a vital indicator, directing attention towards the possibility of septicemia or the presence of an occult abscess, facilitating prompt imaging and accurate diagnosis. [ABSTRACT FROM AUTHOR]

Context: Critically ill patients, especially those with respiratory failure associated with multiple comorbidities, are at risk of recurrent ICU admission and consuming a significant portion of medical resources. Aim: To study the risk factors and common etiologies of readmission among surviving patients with acute respiratory failure in Mansoura University's respiratory intensive care unit during the year 2023. Settings and design: This was a retrospective cohort study. Patients and methods: This study included all patients with acute respiratory failure who were admitted to Mansoura University's respiratory intensive care unit (RICU), from January 2023 to December 2023. Deceased patients after initial admission or those with incomplete data were not included in the study. All data related to patient's demographics, type of respiratory failure, type of respiratory support, associated comorbidities, length of ICU stay, and causes of readmission were collected from the registration system database. Results: Eight-hundred-thirty (830) cases that were admitted to the Mansoura University's RICU with respiratory failure in the year 2023 were enrolled in the study, and 84 cases (10.1%) of them were readmitted. COPD exacerbation was the most common cause of readmission (35.7%) followed by pneumonia (21.4%) and OSA exacerbation (20.2%). Results showed that the significant independent predictors of readmission were being male [AOR (95% CI): 1.8 (1.01–3.1), p: 0.046], having organ failure (renal/liver) [AOR (95% CI): 29.9 (7.9–113.4), p ≤ 0.001], and length of ICU stay more than 12 days [AOR (95% CI): 4.8 (2.6–8.6), p ≤ 0.001]. Also, the type of respiratory failure and the type of respiratory support received were significantly associated with readmission in the univariate analysis; however, they were insignificant in the multivariate analysis. Conclusion: The rate of readmission was not high (only 10.3%). The most common causes of readmission were COPD exacerbation, followed by pneumonia and OSA exacerbation, respectively. Type of respiratory failure, male gender, the presence of other organ failure, and length of ICU stay are significant independent predictors of readmission in Mansoura University's RICU during the year 2023. Therefore, higher-risk individuals should receive attention and careful assessment before discharge from the ICU to reduce the rate of readmission. Trial registration: ClinicalTrials.gov identifier: NCT06291636. [ABSTRACT FROM AUTHOR]

Background: Patients with COVID-19 often experience severe long-term sequelae. This study aimed to assess resilience and Quality of Life (QoL) of patients who underwent mechanical ventilation due to COVID-19, one year after discharge. Methods: This cross-sectional study enrolled patients who received mechanical ventilation for severe COVID-19 and were assessed one-year post-discharge. Participants completed a structured questionnaire via telephone comprising the Connor-Davidson Resilience Scale (CD-RISC) and the Post-COVID-19 Functional Status scale (PCFS). To establish the association between QoL and resilience, Spearman correlations were calculated between the PCFS and the CD-RISC. Linear regression models were adjusted to evaluate which factors were associated with QoL, with the total score of PCFS as the dependent variable. Results: A total of 225 patients were included in the analysis. The CD-RISC had a median score of 83 (IQR 74–91). The PCFS results showed that 61.3% (n = 138) of the patients were able to resume their daily activities without limitations. Among them, 37.3% (n = 84) were classified as Grade 0 and 24% (n = 54) as Grade 1. Mild and moderate functional limitations were found in 33.7% of the patients, with 24.8% (n = 56) classified as Grade 2 and 8.8% (n = 20) as Grade 3. Severe functional limitations (Grade 4) were observed in 4.8% (n = 11) of the patients. High CD-RISC scores were associated with lower levels of PCFS score (p < 0.001). Conclusions: In this cohort of critically ill patients who underwent mechanical ventilation due to COVID-19, 38% of patients experienced a significant decline in their QoL one year after hospital discharge. Finally, a high level of resilience was strongly associated with better QoL one year after discharge. [ABSTRACT FROM AUTHOR]

Background: The recruitment-to-inflation ratio (R/I) has been recently proposed to bedside assess response to PEEP. The impact of PEEP on ventilator-induced lung injury depends on the extent of dynamic strain reduction. We hypothesized that R/I may reflect the potential for lung recruitment (i.e. recruitability) and, consequently, estimate the impact of PEEP on dynamic lung strain, both assessed through computed tomography scan. Methods: Fourteen lung-damaged pigs (lipopolysaccharide infusion) underwent ventilation at low (5 cmH2O) and high PEEP (i.e., PEEP generating a plateau pressure of 28–30 cmH2O). R/I was measured through a one-breath derecruitment maneuver from high to low PEEP. PEEP-induced changes in dynamic lung strain, difference in nonaerated lung tissue weight (tissue recruitment) and amount of gas entering previously nonaerated lung units (gas recruitment) were assessed through computed tomography scan. Tissue and gas recruitment were normalized to the weight and gas volume of previously ventilated lung areas at low PEEP (normalized-tissue recruitment and normalized-gas recruitment, respectively). Results: Between high (median [interquartile range] 20 cmH2O [18–21]) and low PEEP, median R/I was 1.08 [0.88–1.82], indicating high lung recruitability. Compared to low PEEP, tissue and gas recruitment at high PEEP were 246 g [182–288] and 385 ml [318–668], respectively. R/I was linearly related to normalized-gas recruitment (r = 0.90; [95% CI 0.71 to 0.97) and normalized-tissue recruitment (r = 0.69; [95% CI 0.25 to 0.89]). Dynamic lung strain was 0.37 [0.29–0.44] at high PEEP and 0.59 [0.46–0.80] at low PEEP (p < 0.001). R/I was significantly related to PEEP-induced reduction in dynamic (r = − 0.93; [95% CI − 0.78 to − 0.98]) and global lung strain (r = − 0.57; [95% CI − 0.05 to − 0.84]). No correlation was found between R/I and and PEEP-induced changes in static lung strain (r = 0.34; [95% CI − 0.23 to 0.74]). Conclusions: In a highly recruitable ARDS model, R/I reflects the potential for lung recruitment and well estimates the extent of PEEP-induced reduction in dynamic lung strain. [ABSTRACT FROM AUTHOR]

Influenza A virus subtype H1N1 can cause severe acute respiratory distress syndrome and death in young children and elderly individuals. H1N1 initiates inflammatory responses that aim to contain and eliminate microbial invaders. Various lipid mediators (LMs) are biosynthesized and play a critical role in fighting viruses during inflammation; thus, by profiling the LMs in patients, researchers can obtain mechanistic insights into diseases, such as the pathways disrupted. To date, the relationship between molecular alterations in LMs and the pathogenesis of H1N1 influenza in children is poorly understood. Here, we employed a targeted liquid chromatography coupled with tandem mass spectrometry (LC‒MS/MS) to profile LMs in serum from children with H1N1 influenza (H1N1 children) and recovered children. We found that 22 LM species were altered in H1N1 children with mild symptoms. Analysis of the LM profiles of recovered children revealed a decrease in the levels of thromboxane B2 (TxB2) and thromboxane B3 (TxB3) and an increase in the levels of other 8 altered LM species associated with H1N1 influenza, including cytochrome P450 (CYP) enzyme-derived dihydroxyeicosatrienoic acids (DiHETrEs) and hydroxyeicosatetraenoic acids (HETEs) from arachidonic acid (AA), and epoxyoctadecamonoenoic acids (EpOMEs) from linoleic acid (LA). Taken together, the results of this study revealed that serum LMs change dynamically in H1N1 children with mild symptoms. The dramatically altered LMs in H1N1 children could serve as a basis for potential therapeutics or adjuvants against H1N1 influenza. [ABSTRACT FROM AUTHOR]

Background: During the first COVID-19 pandemic wave, COVID-19-associated pulmonary aspergillosis (CAPA) has been reported in up to 11–28% of critically ill COVID-19 patients and associated with increased mortality. As new SARS-CoV-2 variants emerged, the characteristics of critically ill COVID-19 patients have evolved, particularly in the era of Omicron. The purpose of this study is to investigate the characteristics of CAPA in the era of new variants. Methods: This is a prospective multicenter observational cohort study conducted in France in 36 participating intensive care units (ICU), between December 7th, 2021 and April 26th 2023. Diagnosis criteria of CAPA relied on European Confederation of Medical Mycology (ECMM)/International Society for Human & Animal Mycology (ISHAM) consensus criteria. Results: 566 patients were included over the study period. The prevalence of CAPA was 5.1% [95% CI 3.4–7.3], and rose to 9.1% among patients who required invasive mechanical ventilation (IMV). Univariable analysis showed that CAPA patients were more frequently immunosuppressed and required more frequently IMV support, vasopressors and renal replacement therapy during ICU stay than non-CAPA patients. SAPS II score at ICU admission, immunosuppression, and a SARS-CoV-2 Delta variant were independently associated with CAPA in multivariable logistic regression analysis. Although CAPA was not significantly associated with day-28 mortality, patients with CAPA experienced a longer duration of mechanical ventilation and ICU stay. Conclusion: This study contributes valuable insights into the prevalence, characteristics, and outcomes of CAPA in the era of Delta and Omicron variants. We report a lower prevalence of CAPA (5.1%) among critically-ill COVID-19 patients than previously reported, mainly affecting intubated-patients. Duration of mechanical ventilation and ICU stay were significantly longer in CAPA patients. [ABSTRACT FROM AUTHOR]

Background: Duchenne muscular dystrophy (DMD) is a neuromuscular disorder with progressive decline of pulmonary function increasing the risk of early mortality. The aim of this study was to explore the respiratory-related comorbidities, and the effect of these comorbidities and treatments on life expectancy and causes of death. Methods: All male patients living in Sweden with DMD, born and deceased 1970–2019, were included. Data regarding causes of death were collected from the Cause of Death Registry and cross-checked with the medical records along with diagnostics and relevant clinical features. Results: Hundred and twenty nine patients were included with a median lifespan of 24.3 years. Acute respiratory failure accounted for 63.3% of respiratory-related causes of death. 70.1% suffered at least one pneumonia, with first episode at a median age of 17.8 years. Hypoventilation was found in 73.0% with onset at 18.1 years. 60.5% had their first pneumonia before established hypoventilation. Age at onset of hypoventilation showed a strong correlation with age at first pneumonia. First pneumonia and scoliosis non-treated with scoliosis surgery increased the risk of dying of respiratory-related causes. In 10% of the patients, first pneumonia resulted in acute tracheostomy or early death. Patients treated with assisted ventilation had higher life expectancy compared to untreated patients. Conclusions: Our results highlight the importance of identifying subclinical hypoventilation in a timely manner and the importance of an active treatment regime upon clinical signs of pneumonia. [ABSTRACT FROM AUTHOR]

Neurofibromatosis type 1 (NF1) is a multisystem neurocutaneous disorder. Scoliosis and dural ectasia are features of the associated mesodermal dysplasia. Lateral thoracic meningoceles can develop in NF1 and progressively enlarge due to cerebrospinal fluid (CSF) pulsations. Large meningoceles can cause compressive symptoms in the thorax. We are reporting a case of a NF1 presenting with acute onset respiratory distress, who also had chronic orthostatic headaches. CT chest showed unruptured enlarging bilateral lateral thoracic meningoceles causing lung compression. MRI of the brain and spine showed features of CSF hypotension, explaining the headaches. CSF hypotension with unruptured meningoceles is extremely rare. Management of the condition is challenging since surgical removal is prone to complications due to underlying mesodermal abnormalities. Cystoperitoneal shunting to relieve lung compression may worsen CSF hypotension. A shunt with a programmable valve allowed controlled drainage and successfully relieved lung compression without worsening of orthostatic headaches in our case. [ABSTRACT FROM AUTHOR]

Purpose: Severe acute respiratory distress syndrome (ARDS) with PaO2/FiO2 < 80 mmHg is a life-threatening condition. The optimal management strategy is unclear. The aim of this meta-analysis was to compare the effects of low tidal volumes (Vt), moderate Vt, prone ventilation, and venovenous extracorporeal membrane oxygenation (VV-ECMO) on mortality in severe ARDS. Methods: We performed a frequentist network meta-analysis of randomised controlled trials (RCTs) with participants who had severe ARDS and met eligibility criteria for VV-ECMO or had PaO2/FiO2 < 80 mmHg. We applied the Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) methodology to discern the relative effect of interventions on mortality and the certainty of the evidence. Results: Ten RCTs including 812 participants with severe ARDS were eligible. VV-ECMO reduces mortality compared to low Vt (risk ratio [RR] 0.77, 95% confidence interval [CI] 0.59–0.99, moderate certainty) and compared to moderate Vt (RR 0.75, 95% CI 0.57–0.98, low certainty). Prone ventilation reduces mortality compared to moderate Vt (RR 0.78, 95% CI 0.66–0.93, high certainty) and compared to low Vt (RR 0.81, 95% CI 0.63–1.02, moderate certainty). We found no difference in the network comparison of VV-ECMO compared to prone ventilation (RR 0.95, 95% CI 0.72–1.26), but inferences were based solely on indirect comparisons with very low certainty due to very wide confidence intervals. Conclusions: In adults with ARDS and severe hypoxia, both VV-ECMO (low to moderate certainty evidence) and prone ventilation (moderate to high certainty evidence) improve mortality relative to low and moderate Vt strategies. The impact of VV-ECMO versus prone ventilation remains uncertain. [ABSTRACT FROM AUTHOR]

This document discusses the importance of timing and order in the management of acute respiratory distress syndrome (ARDS). ARDS is a common condition in intensive care units and is associated with a high risk of death. The document highlights the need for a standardized approach to the diagnosis, severity assessment, and treatment of ARDS, taking into account the timing of interventions. The authors argue that a sequential and time-sensitive approach to ARDS management can lead to improved outcomes and reduced mortality rates. They propose specific benchmarks and interventions to be implemented within the first 24 hours of ARDS management. Standardizing therapy can ensure consistent and evidence-based treatments while allowing for individualization based on patient characteristics. [Extracted from the article]

Background: Cerebral microbleeds (CMBs) have been described in critically ill patients with respiratory failure, acute respiratory distress syndrome (ARDS), or sepsis. This scoping review aimed to systematically summarize existing literature on critical illness–associated CMBs. Methods: Studies reporting on adults admitted to the intensive care unit for respiratory failure, ARDS, or sepsis with evidence of CMBs on magnetic resonance imaging were included for review following a systematic search across five databases (MEDLINE, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), Scopus, and Web of Science) and a two-stage screening process. Studies were excluded if patients' CMBs were clearly explained by another process of neurological injury. Results: Forty-eight studies reporting on 216 critically ill patients (mean age 57.9, 18.4% female) with CMBs were included. Of 216, 197 (91.2%) patients developed respiratory failure or ARDS, five (2.3%) patients developed sepsis, and 14 (6.5%) patients developed both respiratory failure and sepsis. Of 211 patients with respiratory failure, 160 (75.8%) patients had coronavirus disease 2019. The prevalence of CMBs among critically ill patients with respiratory failure or ARDS was 30.0% (111 of 370 patients in cohort studies). The corpus callosum and juxtacortical area were the most frequently involved sites for CMBs (64.8% and 41.7% of all 216 patients, respectively). Functional outcomes were only reported in 48 patients, among whom 31 (64.6%) were independent at discharge, four (8.3%) were dependent at discharge, and 13 (27.1%) did not survive until discharge. Cognitive outcomes were only reported in 11 of 216 patients (5.1%), all of whom showed cognitive deficits (nine patients with executive dysfunction and two patients with memory deficits). Conclusions: Cerebral microbleeds are commonly reported in patients with critical illness due to respiratory failure, ARDS, or sepsis. CMBs had a predilection for the corpus callosum and juxtacortical area, which may be specific to critical illness–associated CMBs. Functional and cognitive outcomes of these lesions are largely unknown. [ABSTRACT FROM AUTHOR]

During the COVID-19 pandemic, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infected millions of people worldwide, with acute respiratory distress syndrome (ARDS) being the most common severe condition of pulmonary involvement. Despite its involvement in the lungs, SARS-CoV-2 causes multiple extrapulmonary manifestations, including manifestations in the musculoskeletal system. Several cases involving bone, joint, muscle, neurovascular and soft tissues were reported shortly after pandemic onset. Even after the acute infection has resolved, many patients experience persistent symptoms and a decrease in quality of life, a condition known as post-COVID syndrome or long COVID. COVID-19 vaccines have been widely available since December 2020, preventing millions of deaths during the pandemic. However, adverse reactions, including those involving the musculoskeletal system, have been reported in the literature. Therefore, the primary goal of this article is to review the main imaging findings of SARS-CoV-2 involvement in the musculoskeletal system, including acute, subacute, chronic and postvaccination manifestations. [ABSTRACT FROM AUTHOR]

This study determined whether compared to conventional mechanical ventilation (MV), extracorporeal membrane oxygenation (ECMO) is associated with decreased hospital mortality or fibrotic changes in patients with COVID-19 acute respiratory distress syndrome. A cohort of 72 patients treated with ECMO and 390 with conventional MV were analyzed (February 2020–December 2021). A target trial was emulated comparing the treatment strategies of initiating ECMO vs no ECMO within 7 days of MV in patients with a PaO2/FiO2 < 80 or a PaCO2 ≥ 60 mmHg. A total of 222 patients met the eligibility criteria for the emulated trial, among whom 42 initiated ECMO. ECMO was associated with a lower risk of hospital mortality (hazard ratio [HR], 0.56; 95% confidence interval [CI] 0.36–0.96). The risk was lower in patients who were younger (age < 70 years), had less comorbidities (Charlson comorbidity index < 2), underwent prone positioning before ECMO, and had driving pressures ≥ 15 cmH2O at inclusion. Furthermore, ECMO was associated with a lower risk of fibrotic changes (HR, 0.30; 95% CI 0.11–0.70). However, the finding was limited due to relatively small number of patients and differences in observability between the ECMO and conventional MV groups. [ABSTRACT FROM AUTHOR]

Normally aerated lung tissue on computed tomography (CT) is correlated with static respiratory system compliance (Crs) at zero end-expiratory pressure. In clinical practice, however, patients with acute respiratory failure are often managed using elevated PEEP levels. No study has validated the relationship between lung volume and tissue and Crs at the applied positive end-expiratory pressure (PEEP). Therefore, this study aimed to demonstrate the relationship between lung volume and tissue on CT and Crs during the application of PEEP for the clinical management of patients with acute respiratory distress syndrome due to COVID-19. Additionally, as a secondary outcome, the study aimed to evaluate the relationship between CT characteristics and Crs, considering recruitability using the recruitment-to-inflation ratio (R/I ratio). We analyzed the CT and respiratory mechanics data of 30 patients with COVID-19 who were mechanically ventilated. The CT images were acquired during mechanical ventilation at PEEP level of 15 cmH2O and were quantitatively analyzed using Synapse Vincent system version 6.4 (Fujifilm Corporation, Tokyo, Japan). Recruitability was stratified into two groups, high and low recruitability, based on the median R/I ratio of our study population. Thirty patients were included in the analysis with the median R/I ratio of 0.71. A significant correlation was observed between Crs at the applied PEEP (median 15 [interquartile range (IQR) 12.2, 15.8]) and the normally aerated lung volume (r = 0.70 [95% CI 0.46–0.85], P < 0.001) and tissue (r = 0.70 [95% CI 0.46–0.85], P < 0.001). Multivariable linear regression revealed that recruitability (Coefficient = − 390.9 [95% CI − 725.0 to − 56.8], P = 0.024) and Crs (Coefficient = 48.9 [95% CI 32.6–65.2], P < 0.001) were significantly associated with normally aerated lung volume (R-squared: 0.58). In this study, Crs at the applied PEEP was significantly correlated with normally aerated lung volume and tissue on CT. Moreover, recruitability indicated by the R/I ratio and Crs were significantly associated with the normally aerated lung volume. This research underscores the significance of Crs at the applied PEEP as a bedside-measurable parameter and sheds new light on the link between recruitability and normally aerated lung. [ABSTRACT FROM AUTHOR]

Background: Previous retrospective research has shown that maintaining prone positioning (PP) for an average of 40 h is associated with an increase of survival rates in intubated patients with COVID-19-related acute respiratory distress syndrome (ARDS). This study aims to determine whether a cumulative PP duration of more than 32 h during the first 2 days of intensive care unit (ICU) admission is associated with increased survival compared to a cumulative PP duration of 32 h or less. Methods: This study is an ancillary analysis from a previous large international observational study involving intubated patients placed in PP in the first 48 h of ICU admission in 149 ICUs across France, Belgium and Switzerland. Given that PP is recommended for a 16-h daily duration, intensive PP was defined as a cumulated duration of more than 32 h during the first 48 h, whereas standard PP was defined as a duration equal to or less than 32 h. Patients were followed-up for 90 days. The primary outcome was mortality at day 60. An Inverse Probability Censoring Weighting (IPCW) Cox model including a target emulation trial method was used to analyze the data. Results: Out of 2137 intubated patients, 753 were placed in PP during the first 48 h of ICU admission. The intensive PP group (n = 79) had a median PP duration of 36 h, while standard PP group (n = 674) had a median of 16 h during the first 48 h. Sixty-day mortality rate in the intensive PP group was 39.2% compared to 38.7% in the standard PP group (p = 0.93). Twenty-eight-day and 90-day mortality as well as the ventilator-free days until day 28 were similar in both groups. After IPCW, there was no significant difference in mortality at day 60 between the two-study groups (HR 0.95 [0.52–1.74], p = 0.87 and HR 1.1 [0.77–1.57], p = 0.61 in complete case analysis or in multiple imputation analysis, respectively). Conclusions: This secondary analysis of a large multicenter European cohort of intubated patients with ARDS due to COVID-19 found that intensive PP during the first 48 h did not provide a survival benefit compared to standard PP. [ABSTRACT FROM AUTHOR]

Background: The presence of nucleated red blood cells (NRBCs) in the peripheral blood of critically ill patients is associated with poor outcome. Evidence regarding the predictive value of NRBCs in patients with SARS-CoV-2-induced acute respiratory distress syndrome (ARDS) remains elusive. The aim of this study was to evaluate the predictive validity of NRBCs in these patients. Methods: Daily NRBC values of adult patients with SARS-CoV-2-induced ARDS were assessed and their predictive validity for mortality was statistically evaluated. A cut-off level based on the patient's maximum NRBC value during ICU stay was calculated and further specified according to Youden's method. Based on this cut-off value, further analyses such as logistic regression models and survival were performed. Results: 413 critically ill patients with SARS-CoV-2-induced ARDS were analyzed. Patients who did not survive had significantly higher NRBC values during their ICU stay compared to patients who survived (1090/µl [310; 3883] vs. 140/µl [20; 500]; p < 0.0001). Patients with severe ARDS (n = 374) had significantly higher NRBC values during ICU stay compared to patients with moderate ARDS (n = 38) (490/µl [120; 1890] vs. 30/µl [10; 476]; p < 0.0001). A cut-off level of NRBC ≥ 500/µl was found to best stratify risk and was associated with a longer duration of ICU stay (12 [8; 18] vs. 18 [13; 27] days; p < 0.0001) and longer duration of mechanical ventilation (10 [6; 16] vs. 17 [12; 26] days; p < 0.0001). Logistic regression analysis with multivariate adjustment showed NRBCs ≥ 500/µl to be an independent risk factor of mortality (odds ratio (OR) 4.72; 95% confidence interval (CI) 2.95–7.62, p < 0.0001). Patients with NRBC values below the threshold of 500/µl had a significant survival advantage over those above the threshold (median survival 32 [95% CI 8.7–43.3] vs. 21 days [95% CI 18.2–23.8], log-rank test, p < 0.05). Patients who once reached the NRBC threshold of ≥ 500/µl during their ICU stay had a significantly increased long-term mortality (median survival 489 days, log-rank test, p = 0.0029, hazard ratio (HR) 3.2, 95% CI 1.2–8.5). Conclusions: NRBCs predict mortality in critically ill patients with SARS-CoV-2-induced ARDS with high prognostic power. Further studies are required to confirm the clinical impact of NRBCs to eventually enhance decision making. [ABSTRACT FROM AUTHOR]

The 2019 coronavirus (COVID-19) can generate acute respiratory distress syndrome (ARDS), requiring advanced management within the Intensive Care Unit (ICU) using invasive mechanical ventilation (IMV However, managing this phenomenon has seen learning and improvements through direct experience. Therefore, this study aims were to describe the assessment of the different IMV variables in patients with post-COVID-19 hospitalized in the ICU and their relation with mortality. Observational and retrospective study. The sample was divided into two, the surviving group (SG) and the non-surviving group (NSG). Clinical data were extracted from the electronic clinical file and the respiratory therapist record sheet. The following information was obtained: Patient medical history: gender, age, co-morbidities, arterial gases, days on IMV, and IMV parameters. Out of a total of 101 patients, the total mortality was 32%. There was a significant decrease in respiratory rate (RR) (29.12 ± 4.24–26.78 ± 3.59, p = 0.006), Driving pressure (DP) (11.33 ± 2.39–9.67 ± 1.84, p = 0.002), Ventilatory rate (VR) (2.26 ± 0.66–1.89 ± 0.45, p = 0.001) and a significant rise in Static compliance (Cest) (35.49 ± 8.64–41.45 ± 9.62, p = 0.003) and relation between Arterial oxygen pressure/Inspirated oxygen fraction (PaO2/FiO2) (201.5 ± 53.98- 227.8 ± 52.11, p = 0.008) after 72 h of IMV, within the NSG compared to the SG. Apart from these points, multi-morbidity (HR = 3.208, p = 0.010) and DP (HR = 1.228, p = 0.030) and VR variables (HR = 2.267, p = 0.027) had more death probabilities. The results of this study indicate that there was a significant increase in RR, DP, VR, and CO2 and a significant drop in Cest and PaO2/FiO2 among the NSG compared with the SG. Apart from this, the DP and VR variables, multi-morbidity and being male. have more possibility of death. [ABSTRACT FROM AUTHOR]

Background: Protective ventilation seems crucial during early Acute Respiratory Distress Syndrome (ARDS), but the optimal duration of lung protection remains undefined. High driving pressures (ΔP) and excessive patient ventilatory drive may hinder lung recovery, resulting in self-inflicted lung injury. The hidden nature of the ΔP generated by patient effort complicates the situation further. Our study aimed to assess the feasibility of an extended lung protection strategy that includes a stepwise protocol to control the patient ventilatory drive, assessing its impact on lung recovery. Methods: We conducted a single-center randomized study on patients with moderate/severe COVID-19-ARDS with low respiratory system compliance (CRS < 0.6 (mL/Kg)/cmH2O). The intervention group received a ventilation strategy guided by Electrical Impedance Tomography aimed at minimizing ΔP and patient ventilatory drive. The control group received the ARDSNet low-PEEP strategy. The primary outcome was the modified lung injury score (mLIS), a composite measure that integrated daily measurements of CRS, along with oxygen requirements, oxygenation, and X-rays up to day 28. The mLIS score was also hierarchically adjusted for survival and extubation rates. Results: The study ended prematurely after three consecutive months without patient enrollment, attributed to the pandemic subsiding. The intention-to-treat analysis included 76 patients, with 37 randomized to the intervention group. The average mLIS score up to 28 days was not different between groups (P = 0.95, primary outcome). However, the intervention group showed a faster improvement in the mLIS (1.4 vs. 7.2 days to reach 63% of maximum improvement; P < 0.001), driven by oxygenation and sustained improvement of X-ray (P = 0.001). The intervention group demonstrated a sustained increase in CRS up to day 28 (P = 0.009) and also experienced a shorter time from randomization to room-air breathing (P = 0.02). Survival at 28 days and time until liberation from the ventilator were not different between groups. Conclusions: The implementation of an individualized PEEP strategy alongside extended lung protection appears viable. Promising secondary outcomes suggested a faster lung recovery, endorsing further examination of this strategy in a larger trial. Clinical trial registration This trial was registered with ClinicalTrials.gov (number NCT04497454) on August 04, 2020. [ABSTRACT FROM AUTHOR]

Currently there is a lack of randomized trial data examining the use of the antiviral nirmatrelvir/ritonavir in paediatric patients with SARS-CoV-2 infection. This target trial emulation study aims to address this gap by evaluating the use of nirmatrelvir/ritonavir in non-hospitalized paediatric patients aged 12–17 years with SARS-CoV-2 Omicron variant infection. Among paediatric patients diagnosed between 16th March 2022 and 5th February 2023, exposure was defined as outpatient nirmatrelvir/ritonavir treatment within 5 days of symptom onset or COVID-19 diagnosis. Primary outcome was 28 day all-cause mortality or all-cause hospitalization, while secondary outcomes were 28 day in-hospital disease progression, 28 day COVID-19-specific hospitalization, multisystem inflammatory syndrome in children (MIS-C), acute liver injury, acute renal failure, and acute respiratory distress syndrome. Overall, 49,378 eligible paediatric patients were included. Nirmatrelvir/ritonavir treatment was associated with reduced 28 day all-cause hospitalization (absolute risk reduction = 0.23%, 95%CI = 0.19%–0.31%; relative risk = 0.66, 95%CI = 0.56–0.71). No events of mortality, in-hospital disease progression, or adverse clinical outcomes were observed among nirmatrelvir/ritonavir users. The findings confirmed the effectiveness of nirmatrelvir/ritonavir in reducing all-cause hospitalization risk among non-hospitalized pediatric patients with SARS-CoV-2 Omicron variant infection. In this target trial emulation study, the authors evaluate effectiveness of nirmatrelvir/ritonavir in non-hospitalized paediatric patients aged 12–17 years with SARS-CoV-2 Omicron infection and show reduced risks of 28 day all-cause mortality or hospitalization associated with the treatment. [ABSTRACT FROM AUTHOR]

Patients with acute exacerbation of lung fibrosis with usual interstitial pneumonia (EUIP) pattern are at increased risk for ventilator-induced lung injury (VILI) and mortality when exposed to mechanical ventilation (MV). Yet, lack of a mechanical model describing UIP-lung deformation during MV represents a research gap. Aim of this study was to develop a constitutive mathematical model for UIP-lung deformation during lung protective MV based on the stress–strain behavior and the specific elastance of patients with EUIP as compared to that of acute respiratory distress syndrome (ARDS) and healthy lung. Partitioned lung and chest wall mechanics were assessed for patients with EUIP and primary ARDS (1:1 matched based on body mass index and PaO2/FiO2 ratio) during a PEEP trial performed within 24 h from intubation. Patient's stress–strain curve and the lung specific elastance were computed and compared with those of healthy lungs, derived from literature. Respiratory mechanics were used to fit a novel mathematical model of the lung describing mechanical-inflation-induced lung parenchyma deformation, differentiating the contributions of elastin and collagen, the main components of lung extracellular matrix. Five patients with EUIP and 5 matched with primary ARDS were included and analyzed. Global strain was not different at low PEEP between the groups. Overall specific elastance was significantly higher in EUIP as compared to ARDS (28.9 [22.8–33.2] cmH2O versus 11.4 [10.3–14.6] cmH2O, respectively). Compared to ARDS and healthy lung, the stress/strain curve of EUIP showed a steeper increase, crossing the VILI threshold stress risk for strain values greater than 0.55. The contribution of elastin was prevalent at lower strains, while the contribution of collagen was prevalent at large strains. The stress/strain curve for collagen showed an upward shift passing from ARDS and healthy lungs to EUIP lungs. During MV, patients with EUIP showed different respiratory mechanics, stress–strain curve and specific elastance as compared to ARDS patients and healthy subjects and may experience VILI even when protective MV is applied. According to our mathematical model of lung deformation during mechanical inflation, the elastic response of UIP-lung is peculiar and different from ARDS. Our data suggest that patients with EUIP experience VILI with ventilatory setting that are lung-protective for patients with ARDS. [ABSTRACT FROM AUTHOR]

Acute Respiratory Distress Syndrome (ARDS) is a critical form of Acute Lung Injury (ALI), challenging clinical diagnosis and severity assessment. This study evaluates the potential utility of various hematological markers in burn-mediated ARDS, including Neutrophil-to-Lymphocyte Ratio (NLR), Mean Platelet Volume (MPV), MPV-to-Lymphocyte Ratio (MPVLR), Platelet count, and Platelet Distribution Width (PDW). Employing a retrospective analysis of data collected over 12 years, this study focuses on the relationship between these hematological markers and ARDS diagnosis and severity in hospitalized patients. The study establishes NLR as a reliable systemic inflammation marker associated with ARDS severity. Elevated MPV and MPVLR also emerged as significant markers correlating with adverse outcomes. These findings suggest these economical, routinely measured markers can enhance traditional clinical criteria, offering a more objective approach to ARDS diagnosis and severity assessment. Hematological markers such as NLR, MPV, MPVLR, Platelet count, and PDW could be invaluable in clinical settings for diagnosing and assessing ARDS severity. They offer a cost-effective, accessible means to improve diagnostic accuracy and patient stratification in ARDS. However, further prospective studies are necessary to confirm these findings and investigate their integration with other diagnostic tools in diverse clinical settings. [ABSTRACT FROM AUTHOR]

Cytokine-mediated systemic inflammation after open thoracoabdominal aortic aneurysm (TAAA) repairs plays a pivotal role in disrupting circulatory homeostasis, potentially leading to organ dysfunction. The bioactive form of adrenomedullin (bio-ADM) is a peptide hormone with immunomodulatory and vasomotor effects, making it a potential diagnostic agent in these cases. This retrospective, bicentric study, conducted between January 2019 and December 2022, recruited 36 elective open TAAA repair patients in two German centres. Serum and plasma samples were collected at multiple time points to measure bio-ADM levels. The primary objective was to evaluate the association of bio-ADM levels with the onset of acute respiratory distress syndrome (ARDS), with secondary endpoints focusing on mortality and SIRS-related morbidity. Results showed a significant association between postoperative bio-ADM levels (12–48 h after surgery) and the onset of ARDS (p <.001), prolonged ventilation (p =.015 at 12h after surgery), atrial fibrillation (p <.001), and mortality (p =.05 at 24h). The biomarker was also strongly associated with sepsis (p =.01 at 12 h) and multi-organ dysfunction syndrome (MODS) (p =.02 at 24 h after surgery). The study underscores the potential utility of bio-ADM as a diagnostic tool for identifying patients at risk of postoperative complications following open TAAA repairs. [ABSTRACT FROM AUTHOR]

Administering sodium bicarbonate (NaHCO3) to patients with respiratory acidosis breathing spontaneously is contraindicated because it increases carbon dioxide load and depresses pulmonary ventilation. Nonetheless, several studies have reported salutary effects of NaHCO3 in patients with respiratory acidosis but the underlying mechanism remains uncertain. Considering that such reports have been ignored, we examined the ventilatory response of unanesthetized dogs with respiratory acidosis to hypertonic NaHCO3 infusion (1 N, 5 mmol/kg) and compared it with that of animals with normal acid-base status or one of the remaining acid-base disorders. Ventilatory response to NaHCO3 infusion was evaluated by examining the ensuing change in PaCO2 and the linear regression of the PaCO2 vs. pH relationship. Strikingly, PaCO2 failed to increase and the ΔPaCO2 vs. ΔpH slope was negative in respiratory acidosis, whereas PaCO2 increased consistently and the ΔPaCO2 vs. ΔpH slope was positive in the remaining study groups. These results cannot be explained by differences in buffering-induced decomposition of infused bicarbonate or baseline levels of blood pH, PaCO2, and pulmonary ventilation. We propose that NaHCO3 infusion improved the ventilatory efficiency of animals with respiratory acidosis, i.e., it decreased their ratio of total pulmonary ventilation to carbon dioxide excretion (VE/VCO2). Such exclusive effect of NaHCO3 infusion in animals with respiratory acidosis might emanate from baseline increased VD/VT (dead space/tidal volume) caused by bronchoconstriction and likely reduced pulmonary blood flow, defects that are reversed by alkali infusion. Our observations might explain the beneficial effects of NaHCO3 reported in patients with acute respiratory acidosis. [ABSTRACT FROM AUTHOR]

Purpose: Oxidative stress is proposed to be critical in acute lung disease, but methods to monitor radicals in lungs are lacking. Our goal is to develop low-frequency electron paramagnetic resonance (EPR) methods to monitor radicals that contribute to the disease. Procedures: Free radicals generated in a lipopolysaccharide-induced mouse model of acute respiratory distress syndrome reacted with cyclic hydroxylamines CPH (1-hydroxy-3-carboxy-2,2,5,5-tetramethylpyrrolidine hydrochloride) and DCP-AM-H (4-acetoxymethoxycarbonyl-1-hydroxy-2,2,5,5-tetramethylpyrrolidine-3-carboxylic acid), which were converted into the corresponding nitroxide radicals, CP• and DCP•. The EPR signals of the nitroxide radicals in excised lungs were imaged with a 1 GHz EPR spectrometer/imager that employs rapid scan technology. Results: The small numbers of nitroxides formed by reaction of the hydroxylamine with superoxide result in low signal-to-noise in the spectra and images. However, since the spectral properties of the nitroxides are known, we can use prior knowledge of the line shape and hyperfine splitting to fit the noisy data, yielding well-defined spectra and images. Two-dimensional spectral-spatial images are shown for lung samples containing (4.5 ± 0.5) ×1014 CP• and (9.9 ± 1.0) ×1014 DCP• nitroxide spins. These results suggest that a probe that accumulates in cells gives a stronger nitroxide signal than a probe that is more easily washed out of cells. Conclusion: The nitroxide radicals in excised mouse lungs formed by reaction with hydroxylamine probes CPH and DCP-AM-H can be imaged at 1 GHz. [ABSTRACT FROM AUTHOR]

Purpose: Patients with hyper- vs. hypo-inflammatory subphenotypes of acute respiratory distress syndrome (ARDS) exhibit different clinical outcomes. Inflammation increases the production of reactive oxygen species (ROS) and increased ROS contributes to the severity of illness. Our long-term goal is to develop electron paramagnetic resonance (EPR) imaging of lungs in vivo to precisely measure superoxide production in ARDS in real time. As a first step, this requires the development of in vivo EPR methods for quantifying superoxide generation in the lung during injury, and testing if such superoxide measurements can differentiate between susceptible and protected mouse strains. Procedures: In WT mice, mice lacking total body extracellular superoxide dismutase (EC-SOD) (KO), or mice overexpressing lung EC-SOD (Tg), lung injury was induced with intraperitoneal (IP) lipopolysaccharide (LPS) (10 mg/kg). At 24 h after LPS treatment, mice were injected with the cyclic hydroxylamines 1-hydroxy-3-carboxy-2,2,5,5-tetramethylpyrrolidine hydrochloride (CPH) or 4-acetoxymethoxycarbonyl-1-hydroxy-2,2,5,5-tetramethylpyrrolidine-3-carboxylic acid (DCP-AM-H) probes to detect, respectively, cellular and mitochondrial ROS – specifically superoxide. Several probe delivery strategies were tested. Lung tissue was collected up to one hour after probe administration and assayed by EPR. Results: As measured by X-band EPR, cellular and mitochondrial superoxide increased in the lungs of LPS-treated mice compared to control. Lung cellular superoxide was increased in EC-SOD KO mice and decreased in EC-SOD Tg mice compared to WT. We also validated an intratracheal (IT) delivery method, which enhanced the lung signal for both spin probes compared to IP administration. Conclusions: We have developed protocols for delivering EPR spin probes in vivo, allowing detection of cellular and mitochondrial superoxide in lung injury by EPR. Superoxide measurements by EPR could differentiate mice with and without lung injury, as well as mouse strains with different disease susceptibilities. We expect these protocols to capture real-time superoxide production and enable evaluation of lung EPR imaging as a potential clinical tool for subphenotyping ARDS patients based on redox status. [ABSTRACT FROM AUTHOR]

Background: The COVID-19 pandemic served as a reminder of the limited treatments available for acute respiratory distress syndrome (ARDS). The pandemic has highlighted the need to identify different clinical phenotypes of ARDS and investigate various interventions and treatments, both new and old. Case Presentation: We present a patient with severe ARDS secondary to COVID-19 who rapidly deteriorated despite neuromuscular blockade and prone ventilation. He was aggressively managed using a combination of high frequency oscillatory ventilation (HFOV), high dose methylprednisolone, TPE, and direct instillation of liquid surfactant. He had an excellent clinical response and ultimately discharged to inpatient rehabilitation, then home, totally independent. Conclusion: Relatively few effective treatment options exist for ARDS. Our patient's response to a combination of interventions that have fallen out of clinical practice serves as a reminder that research is needed to help identify distinct phenotypes so that clinical trials can be designed to investigate interventions and treatments specific to the different phenotypes. [ABSTRACT FROM AUTHOR]

Objectives: Patients with severe stroke are at high risk of developing acute respiratory distress syndrome (ARDS), but this severe complication was often under-diagnosed and rarely explored in stroke patients. We aimed to investigate the prevalence, early predictors, and outcomes of ARDS in severe stroke. Methods: This prospective study included consecutive patients admitted to neurological intensive care unit (neuro-ICU) with severe stroke, including acute ischemic stroke, intracerebral hemorrhage, and subarachnoid hemorrhage. The incidence of ARDS was examined, and baseline characteristics and severity scores on admission were investigated as potential early predictors for ARDS. The in-hospital mortality, length of neuro-ICU stay, the total cost in neuro-ICU, and neurological functions at 90 days were explored. Results: Of 140 patients included, 35 (25.0%) developed ARDS. Over 90% of ARDS cases occurred within 1 week of admission. Procalcitonin (OR 1.310 95% CI 1.005–1.707, P = 0.046) and PaO2/FiO2 on admission (OR 0.986, 95% CI 0.979–0.993, P < 0.001) were independently associated with ARDS, and high brain natriuretic peptide (OR 0.994, 95% CI 0.989–0.998, P = 0.003) was a red flag biomarker warning that the respiratory symptoms may be caused by cardiac failure rather than ARDS. ARDS patients had longer stays and higher expenses in neuro-ICU. Among patients with ARDS, 25 (62.5%) were moderate or severe ARDS. All the patients with moderate to severe ARDS had an unfavorable outcome at 90 days. Conclusions: ARDS is common in patients with severe stroke, with most cases occurring in the first week of admission. Procalcitonin and PaO2/FiO2 on admission are early predictors of ARDS. ARDS worsens both short-term and long-term outcomes. The conflict in respiratory support strategies between ARDS and severe stroke needs to be further studied. [ABSTRACT FROM AUTHOR]

Respiratory syncytial virus (RSV) infection represents one of the most common infections during childhood, with significant morbidity and mortality in newborns and in the early years of life. RSV is a common infection throughout all age groups, largely undetected and underestimated in adults, with a disproportionately high impact in older individuals. RSV infection has a wide range of clinical presentations, from asymptomatic conditions to acute pneumonia and severe life-threatening respiratory distress, including exacerbations of underlying chronic conditions. Overall, the incidence of RSV infections requiring medical attention increases with age, and it is highest among persons ≥ 70 years of age. As a consequence of a combination of an aging population, immunosenescence, and the related increased burden of comorbidities, high-income countries are at risk of developing RSV epidemics. The standard of care for RSV-infected patients remains supportive, including fluids, antipyretics, and oxygen support when needed. There is an urgent need for antivirals and preventive strategies in this population, particularly in individuals at higher risk of severe outcomes following RSV infection. In this review, we describe prevention and treatment strategies for RSV illnesses, with a deep focus on the novel data on vaccination that has become available (Arexvy, GSK, and Abrysvo, Pfizer) for older adults. [ABSTRACT FROM AUTHOR]

Background: ALI/ARDS is a syndrome of acute onset characterized by progressive hypoxemia and noncardiogenic pulmonary edema as the primary clinical manifestations. Necroptosis is a form of programmed cell necrosis that is precisely regulated by molecular signals. This process is characterized by organelle swelling and membrane rupture, is highly immunogenic, involves extensive crosstalk with various cellular stress mechanisms, and is significantly implicated in the onset and progression of ALI/ARDS. Methods: The current body of literature on necroptosis and ALI/ARDS was thoroughly reviewed. Initially, an overview of the molecular mechanism of necroptosis was provided, followed by an examination of its interactions with apoptosis, pyroptosis, autophagy, ferroptosis, PANOptosis, and NETosis. Subsequently, the involvement of necroptosis in various stages of ALI/ARDS progression was delineated. Lastly, drugs targeting necroptosis, biomarkers, and current obstacles were presented. Conclusion: Necroptosis plays an important role in the progression of ALI/ARDS. However, since ALI/ARDS is a clinical syndrome caused by a variety of mechanisms, we emphasize that while focusing on necroptosis, it may be more beneficial to treat ALI/ARDS by collaborating with other mechanisms. [ABSTRACT FROM AUTHOR]