Search

We investigate the potential of surface plasmon polaritons at noble metal interfaces for surface-enhanced chiroptical sensing of dilute chiral drug solutions with nl volume. The high quality factor of surface plasmon resonances in both Otto and Kretschmann configurations enables the enhancement of circular dichroism differenatial absorption thanks to the large near-field intensity of such plasmonic excitations. Furthermore, the subwavelength confinement of surface plasmon polaritons is key to attain chiroptical sensitivity to small amounts of drug volumes placed around ≃100 nm by the metal surface. Our calculations focus on reparixin, a pharmaceutical molecule currently used in clinical studies for patients with community-acquired pneumonia, including COVID-19 and acute respiratory distress syndrome. Considering realistic dilute solutions of reparixin dissolved in water with concentration ≤ 5 mg/ml and nl volume, we find a circular-dichroism differential absorption enhancement factor of the order ≃20 and chirality-induced polarization distortion upon surface plasmon polariton excitation. Our results are relevant for the development of innovative chiroptical sensors capable of measuring the enantiomeric imbalance of chiral drug solutions with nl volume. [ABSTRACT FROM AUTHOR]

Background and Purpose: Fibrotic lung remodelling after a respiratory viral infection represents a debilitating clinical sequela. Studying or managing viral–fibrotic sequela remains challenging, due to limited therapeutic options and lack of understanding of mechanisms. This study determined whether protein disulfide isomerase A3 (PDIA3) and secreted phosphoprotein 1 (SPP1), which are associated with pulmonary fibrosis, can promote influenza‐induced lung fibrotic remodelling and whether inhibition of PDIA3 or SPP1 can resolve viral‐mediated fibrotic remodelling. Experimental Approach: A retrospective analysis of TriNetX data sets was conducted. Serum from healthy controls and influenza A virus (IAV)‐infected patients was analysed. An inhibitor of PDIA3, punicalagin, and a neutralizing antibody for SPP1 were administered in mice. Macrophage cells treated with macrophage colony‐stimulating factor (M‐CSF) were used as a cell culture model. Key Results: The TriNetX data set showed an increase in lung fibrosis and decline in lung function in flu‐infected acute respiratory distress syndrome (ARDS) patients compared with non‐ARDS patients. Serum samples revealed a significant increase in SPP1 and PDIA3 in influenza‐infected patients. Lung PDIA3 and SPP1 expression increased following viral infection in mouse models. Punicalagin administration 2 weeks after IAV infection in mice caused a significant decrease in lung fibrosis and improved oxygen saturation. Administration of neutralizing SPP1 antibody decreased lung fibrosis. Inhibition of PDIA3 decreased SPP1secretion from macrophages, in association with diminished disulfide bonds in SPP1. Conclusion and Implications: The PDIA3–SPP1 axis promotes post‐influenza lung fibrosis in mice and that pharmacological inhibition of PDIA3 or SPP1 can treat virus‐induced lung fibrotic sequela. [ABSTRACT FROM AUTHOR]

Acute respiratory distress syndrome (ARDS) is characterized by bilateral chest infiltration and acute hypoxic respiratory failure. ARDS carries significant morbidity and mortality despite advancements in medical management, calling for the development of novel therapeutic targets. Hypoxia‐inducible factor (HIF) is a heterodimeric protein involved in various essential pathways, including metabolic reprogramming, immune modulation, angiogenesis and cell cycle regulation. HIF is routinely degraded in homeostasis conditions via the prolyl hydroxylase domain/von Hippel–Lindau protein pathway. However, HIF is stabilized in ARDS via various mechanisms (oxygen‐dependent and independent) as an endogenous protective pathway and plays multifaceted roles in different cell populations. This review focuses on the functional role of HIF and its target genes during ARDS, as well as how HIF has evolved as a therapeutic target in current medical management. [ABSTRACT FROM AUTHOR]

The article discusses the impact of sociodemographic factors on sepsis recovery globally, emphasizing the disparities in healthcare facilities and personnel in low- to middle-income countries. It also highlights the importance of ensuring that solutions to sepsis are accessible beyond privileged areas. Additionally, it addresses the issue of sleep disruption in critically ill children in the PICU, attributing it to various factors such as chaotic surroundings, pain, medications, and caregiving, which can lead to cognitive impairment and other adverse effects. The article suggests that promoting sleep through interventions like increased light exposure and noise reduction can improve outcomes for patients recovering from critical illnesses. [Extracted from the article]

Machine learning (ML) tools for acute respiratory distress syndrome (ARDS) detection and prediction are increasingly used. Therefore, understanding risks and benefits of such algorithms is relevant at the bedside. ARDS is a complex and severe lung condition that can be challenging to define precisely due to its multifactorial nature. It often arises as a response to various underlying medical conditions, such as pneumonia, sepsis, or trauma, leading to widespread inflammation in the lungs. ML has shown promising potential in supporting the recognition of ARDS in ICU patients. By analyzing a variety of clinical data, including vital signs, laboratory results, and imaging findings, ML models can identify patterns and risk factors associated with the development of ARDS. This detection and prediction could be crucial for timely interventions, diagnosis and treatment. In summary, leveraging ML for the early prediction and detection of ARDS in ICU patients holds great potential to enhance patient care, improve outcomes, and contribute to the evolving landscape of precision medicine in critical care settings. This article is a concise definitive review on artificial intelligence and ML tools for the prediction and detection of ARDS in critically ill patients. [ABSTRACT FROM AUTHOR]

OBJECTIVES: Guillain-Barré syndrome (GBS) and myasthenia gravis (MG) are the most common causes of acute neuromuscular respiratory failure resulting in ICU admission. This synthetic narrative review summarizes the evidence for the prediction and management of acute neuromuscular respiratory failure due to GBS and MG. DATA SOURCES: We searched PubMed for relevant literature and reviewed bibliographies of included articles for additional relevant studies. STUDY SELECTION: English-language publications were reviewed. DATA EXTRACTION: Data regarding study methodology, patient population, evaluation metrics, respiratory interventions, and clinical outcomes were qualitatively assessed. DATA SYNTHESIS: No single tool has sufficient sensitivity and specificity for the prediction of acute neuromuscular respiratory failure requiring mechanical ventilation. Multimodal assessment, integrating history, examination maneuvers (single breath count, neck flexion strength, bulbar weakness, and paradoxical breathing) and pulmonary function testing are ideal for risk stratification. The Erasmus GBS Respiratory Insufficiency Score is a validated tool useful for GBS. Noninvasive ventilation can be effective in MG but may not be safe in early GBS. Airway management considerations are similar across both conditions, but dysautonomia in GBS requires specific attention. Extubation failure is common in MG, and early tracheostomy may be beneficial for MG. Prolonged ventilatory support is common, and good functional outcomes may occur even when prolonged ventilation is required. CONCLUSIONS: Multimodal assessments integrating several bedside indicators of bulbar and respiratory muscle function can aid in evidence-based risk stratification for respiratory failure among those with neuromuscular disease. Serial evaluations may help establish a patient's trajectory and to determine timing of respiratory intervention. [ABSTRACT FROM AUTHOR]

Background: A careful approach is required when providing nutritional support to patients with acute respiratory distress syndrome (ARDS). This study investigated whether implementing a multidisciplinary nutritional support team (NST) is associated with improved survival outcomes in patients with ARDS. Methods: In a nationwide population‐based cohort study, all adult patients admitted to the intensive care unit (ICU) in South Korea with a primary diagnosis of ARDS from January 1, 2017, to December 31, 2021, were included. The NST comprised four professionals (physicians, full‐time nurses, full‐time pharmacists, and full‐time clinical dietitians). Patients admitted to ICUs with and without the NST system were allocated to the NST and non‐NST groups, respectively. Results: The analysis comprised a total of 15,555 patients with ARDS. Among them, 6615 (42.5%) were in the NST group, and 8940 (57.5%) were in the non‐NST group. After adjusting for covariates in the multivariable logistic regression, the NST group showed a 19% lower 30‐day mortality than the non‐NST group (odds ratio: 0.81, 95% confidence interval: 0.75–0.87, p <.001). Furthermore, after adjusting for covariates in multivariable Cox regression, the NST group showed a 12% lower 1‐year all‐cause mortality than the non‐NST group (hazard ratio: 0.88, 95% confidence interval: 0.85–0.92, p <.001). Conclusions: NST implementation was associated with enhanced 30‐day and 1‐year survival rates in patients with ARDS. These findings indicate that nutritional support provided by the NST may influence the survival outcomes of patients with ARDS in the ICU. [ABSTRACT FROM AUTHOR]

Background: Comorbidities are similarly associated with short‐term mortality for COVID‐19, acute respiratory distress syndrome (ARDS) and sepsis in intensive care unit (ICU) patients, but their adjusted frequencies at admission are unknown. Thus, we aimed to evaluate the adjusted distribution, reported as odds ratios, of known risk factors (i.e., age, sex and comorbidities) for ICU admission between COVID‐19, sepsis and ARDS patients in this nationwide registry‐based study. Methods: In this cohort study, we included adult patients admitted to Swedish ICUs with COVID‐19 (n = 7382) during the pandemic and compared them to patients admitted to ICU with sepsis (n = 22,354) or ARDS (n = 2776) during a pre‐COVID‐19 period. The main outcomes were the adjusted odds for comorbidities, sex, and age in multivariable logistic regression on diagnostic categories in patients admitted to ICU, COVID‐19 or sepsis and COVID‐19 or ARDS. Results: We found that most comorbidities, as well as age, had a stronger association with sepsis admission than COVID‐19 admission with the exception of male sex, type 2 diabetes mellitus, and asthma that were more strongly associated with COVID‐19 admission, while no difference was seen for chronic renal failure and obesity. For COVID‐19 and ARDS admission most risk factors were more strongly associated with ARDS admission except for male sex, type 2 diabetes mellitus, chronic renal failure, and obesity which were more strongly associated with COVID‐19 admission, whereas hypertension, chronic obstructive pulmonary disease and asthma were not different. Conclusions: Patients admitted to ICU with sepsis or ARDS carry a heavier burden of comorbidity and high age than patients admitted with COVID‐19. This is likely caused by a combination of: (1) respiratory failure in COVID‐19 being less dependent on comorbidities than in other forms of ARDS, and the cause of critical illness in other infections causing sepsis and (2) COVID‐19 patients being deferred admission in situations where patients with the other syndromes were admitted. [ABSTRACT FROM AUTHOR]

Objective To compare the risk of severe maternal morbidity (SMM) from the delivery admission to 42 days' postdischarge among persons with sickle cell disease (SCD) to those without SCD. Study Design This retrospective cohort study included deliveries ≥20 weeks' gestation at an urban safety net hospital in Atlanta, GA from 2011 to 2019. The exposure was SCD diagnosis. The outcome was a composite of SMM from the delivery admission to 42 days' postdischarge. SMM indicators as defined by the Centers for Disease Control and Prevention were identified using the International Classification of Diseases, Ninth and Tenth Revisions (ICD-9/10) codes; transfusion of blood products and sickle cell crisis were excluded. Results Of N = 17,354 delivery admissions, n = 92 (0.53%) had SCD. Persons with SCD versus without SCD had an increased risk of composite SMM (15.22 vs. 2.29%, p < 0.001), acute renal failure (6.52 vs. 0.71%, p < 0.001), acute respiratory distress syndrome (4.35 vs. 0.17%, p < 0.001), puerperal cerebrovascular disorders (3.26 vs. 0.10%, p < 0.001), sepsis (4.35 vs. 0.42%, p < 0.01), air and thrombotic embolism (5.43 vs. 0.10%, p < 0.001), and ventilation (2.17 vs. 0.09%, p < 0.01). Ultimately, those with SCD had an approximately 6-fold higher incidence risk ratio of SMM, which remained after adjustment for confounders (adjusted incidence risk ratio [aIRR]: 5.96, 95% confidence interval [CI]: 3.4–9.19, p < 0.001). Persons with SCD in active vaso-occlusive crisis at the delivery admission had an approximately 9-fold higher risk of SMM up to 42 days' postdischarge compared with those with SCD not in crisis at the delivery admission (incidence: 25.71 vs. 8.77%, p < 0.05; aIRR: 8.92, 95% CI: 4.5–10.04, p < 0.05). Among those with SCD, SMM at the delivery admission was primarily related to renal and cerebrovascular events, whereas most postpartum SMM was related to respiratory events or sepsis. Conclusion SCD is significantly associated with an increased risk of SMM during the delivery admission and through 42 days' postdischarge. Active crisis at delivery further increases the risk of SMM. Key Points Sickle cell disease was associated with an approximately 6-fold increased risk of SMM. Active vaso-occlusive crisis at delivery was associated with an approximately 9-fold increased risk of SMM. 48% of SMM events in persons with SCD occurred postpartum and were respiratory- or sepsis-related. [ABSTRACT FROM AUTHOR]

Introduction: Prone position ventilation (PPV) of patients with adult respiratory distress syndrome (ARDS) supported with veno-venous extracorporeal membrane oxygenation (V-V ECMO) may improve oxygenation and alveolar recruitment and is recommended when extensive dorsal consolidations are present, but only few data regarding adverse events (AE) related to PPV in this group of patients have been published. Methods: Nationwide retrospective analysis of 68 COVID-19 patients admitted from March 2020 – December 2021 with severe ARDS and need of V-V ECMO support. The number of patients treated with PPV, number of PPV-events, timing, the time spent in prone position, number and causes of AE are reported. Causes to stop the PPV regimen and risk factors for AE were explored. Results: 44 out of 68 patients were treated with PPV, and 220 PPV events are evaluated. AE were identified in 99 out of 220 (45%) PPV events and occurred among 31 patients (71%). 1 fatal PPV related AE was registered. Acute supination occurred in 19 events (9%). Causes to stop the PPV regimen were almost equally distributed between effect (weaned from ECMO), no effect, death (of other reasons) and AE. Frequent causes of AE were pressures sores and ulcers, hypoxia, airway related and ECMO circuit related. Most AE occurred during patients first or second PPV event. Conclusions: PPV treatment was found to carry a high incidence of PPV related AE in these patients. Causes and preventive measures to reduce occurrence of PPV related AE during V-V ECMO support need further exploration. [ABSTRACT FROM AUTHOR]

Objectives: The aim of the study was to examine the incidence, baseline characteristics, and outcomes of Chimeric Antigen Receptor T-cell (CAR-T) therapy admissions in individuals who developed acute respiratory failure (ARF). The study utilized the National Inpatient Sample (NIS) database for the years 2017 to 2020. Methods: The study identified CAR-T cell therapy hospitalizations through the International Classification of Diseases, Tenth Revision, Procedure Coding System (ICD-10-PCS) codes. Patients with acute respiratory failure (ARF) were further classified using specific International Classification of Disease, Tenth Revision, Clinical Modification (ICD-10-CM) codes. Descriptive statistics were performed to analyze baseline characteristics, comorbidities, complications, and outcomes. Results: Analysis of the NIS Database identified 5545 CAR-T therapy admissions between 2017 and 2020, revealing a rising trend over time. In our study, we found that hypertension (39%), dyslipidemia (21.7%), and venous thromboembolism (13%) were the most frequently observed comorbidities in CAR-T cell therapy admissions. Acute respiratory failure (ARF) was reported in 7.1% of admissions, and they had higher all-cause in-hospital mortality than CAR-T cell therapy admissions without ARF (32.9% vs 1.3%, P < 0.001). ARF admissions that required invasive mechanical ventilation (IMV) also had higher all-cause in-hospital mortality compared to admissions not requiring IMV (48.9% vs 11.8%, P = 0.001). There was no difference in the mortality rate among admissions with non-Hodgkin's Lymphoma, Multiple Myeloma, and Leukemia that utilized CAR-T therapy. Conclusions: In this largest study to date, we illuminate the incidence and outcomes of CAR-T cell therapy admissions with ARF. Higher mortality rates were observed in CAR-T cell therapy admissions with ARF. The study emphasizes the crucial role of interdisciplinary collaboration in CAR-T patient management and calls for additional research to clarify ARF's etiology and inform effective management strategies. [ABSTRACT FROM AUTHOR]

Objective: The prone positioning (PP) strategy has been considered as a feasible treatment for intubated coronavirus disease 2019 (COVID-19) patients with acute respiratory distress syndrome (ARDS). However, the optimal duration of PP remains uncertain. This meta-analysis aims to assess the efficacy and safety of extended PP (EPP) on patients with ARDS due to COVID-19. Materials and methods: The Cochrane Library databases, Embase, and Pubmed were systematically searched from inception until September 21, 2023. The primary outcomes were the mortality and the change of PaO2:FiO2 ratio; the secondary outcome was the incidence of complications (pressure injuries, facial edema, loss of endotracheal tube, loss of vascular access, etc). The random effects model was used to analyze the data. Results: Eight studies were eligible for inclusion in the meta-analysis. All studies had a low risk of bias. Compared to the standard prone position group, EPP could improve the PaO2:FiO2 ratio (mean deviation [MD], 9.13; 95% confidence intervals [CI] 0.29-17.96; P =.04; χ2 = 1.12, I2 = 0%). No significant difference was found in the mortality (odds ratios [OR] 0.90; 95% CI 0.67-1.22; P =.49; χ2 = 5, I2 = 0%). However, patients treated with the EPP were associated with an increasing incidence rate of pressure injuries (OR 1.47; 95% CI 1.08-2.01; P =.01; χ2 = 4.37, I2 = 0%) compared to standard care. Conclusions: Our results demonstrated that the EPP could be an effective strategy to improve the PaO2:FiO2 ratio without detrimental effects on mortality in intubated patients with COVID-19. Given the limited number of randomized controlled trials (RCTs), further high-quality RCTs are needed to confirm the results. INPLASY registration number: INPLASY202390072 [ABSTRACT FROM AUTHOR]

Background: This study aimed to investigate the associations between dyscapnia, ventilatory variables, and mortality. We hypothesized that the association between mechanical power or ventilatory ratio and survival is mediated by dyscapnia. Methods: Patients with moderate or severe acute respiratory distress syndrome (ARDS), who received mechanical ventilation within the first 48 h after admission to the intensive care unit for at least 48 h, were included in this retrospective single-center study. Values of arterial carbon dioxide (PaCO2) were categorized into "hypercapnia" (PaCO2 ≥ 50 mm Hg), "normocapnia" (PaCO2 36-49 mmHg), and "hypocapnia" (PaCO2 ≤ 35 mm Hg). We used path analyses to assess the associations between ventilatory variables (mechanical power and ventilatory ratio) and mortality, where hypocapnia or hypercapnia were included as mediating variables. Results: Between December 2017 and April 2021, 435 patients were included. While there was a significant association between mechanical power and hypercapnia (BEM = 0.24 [95% CI: 0.15; 0.34], P <.01), there was no significant association between mechanical power or hypercapnia and ICU mortality. The association between mechanical power and intensive care unit (ICU) mortality was fully mediated by hypocapnia (BEM = −0.10 [95% CI: −0.19; 0.00], P =.05; BMO = 0.38 [95% CI: 0.13; 0.63], P <.01). Ventilatory ratio was significantly associated with hypercapnia (B = 0.23 [95% CI: 0.14; 0.32], P <.01). There was no significant association between ventilatory ratio, hypercapnia, and mortality. There was a significant effect of ventilatory ratio on mortality, which was fully mediated by hypocapnia (BEM = −0.14 [95% CI: −0.24; −0.05], P <.01; BMO = 0.37 [95% CI: 0.12; 0.62], P <.01). Conclusion: In mechanically ventilated patients with moderate or severe ARDS, the association between mechanical power and mortality was fully mediated by hypocapnia. Likewise, there was a mediating effect of hypocapnia on the association between ventilatory ratio and ICU mortality. Our results indicate that the debate on dyscapnia and outcome after ARDS should consider the impact of ventilatory variables. [ABSTRACT FROM AUTHOR]

Diffuse alveolar hemorrhage (DAH) is a morbid syndrome that occurs after autologous and allogeneic hematopoietic cell transplantation in children and adults. DAH manifests most often in the first few weeks following transplantation. It presents with pneumonia-like symptoms and acute respiratory failure, often requiring high levels of oxygen supplementation or mechanical ventilatory support. Hemoptysis is variably present. Chest radiographs typically feature widespread alveolar filling, sometimes with peripheral sparing and pleural effusions. The diagnosis is suspected when serial bronchoalveolar lavages return increasingly bloody fluid. DAH is differentiated from infectious causes of alveolar hemorrhage when extensive microbiological testing reveals no pulmonary pathogens. The cause is poorly understood, though preclinical and clinical studies implicate pretransplant conditioning regimens, particularly those using high doses of total-body-irradiation, acute graft-versus-host disease (GVHD), medications used to prevent GVHD, and other factors. Treatment consists of supportive care, systemic corticosteroids, platelet transfusions, and sometimes includes antifibrinolytic drugs and topical procoagulant factors. Therapeutic blockade of tumor necrosis factor-α showed promise in observational studies, but its benefit for DAH remains uncertain after small clinical trials. Even with these treatments, mortality from progression and relapse is high. Future investigational therapies could target the vascular endothelial cell biology theorized to contribute to alveolar bleeding and pathways that contribute to susceptibility, inflammation, cellular resilience, and tissue repair. This review will help clinicians navigate through the limited evidence to diagnose and treat DAH, counsel patients and families, and plan for future research. [ABSTRACT FROM AUTHOR]

Acute lung injury (ALI) or acute respiratory distress syndrome (ARDS) is a high-mortality disease caused by multiple disorders such as COVID-19, influenza, and sepsis. Current therapies mainly rely on the inhalation of nitric oxide or injection of pharmaceutical drugs (e.g., glucocorticoids); however, their toxicity, side effects, or administration routes limit their clinical application. In this study, pachypodol (Pac), a hydrophobic flavonol with anti-inflammatory effects, was extracted from Pogostemon cablin Benth and intercalated in liposomes (Pac@liposome, Pac-lipo) to improve its solubility, biodistribution, and bioavailability, aiming at enhanced ALI/ARDS therapy. Nanosized Pac-lipo was confirmed to have stable physical properties, good biodistribution, and reliable biocompatibility. In vitro tests proved that Pac-lipo has anti-inflammatory property and protective effects on endothelial and epithelial barriers in lipopolysaccharide (LPS)-induced macrophages and endothelial cells, respectively. Further, the roles of Pac-lipo were validated on treating LPS-induced ALI in mice. Pac-lipo showed better effects than did Pac alone on relieving ALI phenotypes: It significantly attenuated lung index, improved pulmonary functions, inhibited cytokine expression such as TNF-α, IL-6, IL-1β, and iNOS in lung tissues, alleviated lung injury shown by HE staining, reduced protein content and total cell number in bronchoalveolar lavage fluid, and repaired lung epithelial and vascular endothelial barriers. As regards the underlying mechanisms, RNA sequencing results showed that the effects of the drugs were associated with numerous immune- and inflammation-related signaling pathways. Molecular docking and western blotting demonstrated that Pac-lipo inhibited the activation of the TLR4-MyD88-NF-κB/MAPK signaling pathway. Taken together, for the first time, our new drug (Pac-lipo) ameliorates ALI via inhibition of TLR4-MyD88-NF-κB/MAPK pathway-mediated inflammation and disruption of lung barrier. These findings may provide a promising strategy for ALI treatment in the clinic. [Display omitted] [ABSTRACT FROM AUTHOR]

Sepsis is one of the major causes of morbidity and mortality in burn patients. However, the optimal timing of admission which can minimize the probability of sepsis is still unclear. This study aims to determine the optimal time period of admission for severely burned patients and find out the possible reasons for it. 185 victims to the Kunshan factory aluminum dust explosion accident, which happened on August 2nd, 2014, were studied. The optimal cutpoint for continuous variables in survival models was determined by means of the maximally selected rank statistic. Univariate and multivariate analyses were further conducted to verify that admission time was not a risk factor for sepsis. Subgroup analyses were performed to find out possible contributing factors for the result. The cutoff point for admission time was determined as seven hours, which was supported by the survival curve (p < 0.001). Multivariate analysis showed that, in our study population, delayed admission time was not a risk factor for sepsis (HR = 0.610, 95 %CI = 0.415 - 0.896, p = 0.012). Subgroup analyses showed that "Tracheotomy before admission" (p = 0.002), "Whole blood transfusion" (p < 0.001), "Hemodynamic instability before admission" (p = 0.02), "Has a burn department in the hospital" (p = 0.009), "Has a burn ICU in the hospital" (p < 0.001), "Acute heart failure (AHF)" (p = 0.05), "acute respiratory distress syndrome (ARDS)" (p = 0.05) and "GI bleeding" (p = 0.04) were all statistically significant. In our study population, we found that delayed admission time was not a risk factor associated with a reduced incidence of sepsis among severely burned patients. This might be attributed to variations in prehospital treatments (whole blood transfusion and tracheotomy), whether the hospital had a burn department/ICU, and certain complications (AHF, ARDS and GI bleeding). It can be inferred that early prehospital care plays a crucial role in reducing sepsis risk among severe burn patients. • Seven hours post-injury is key to reducing sepsis risk in severe burn cases. • Hospital facilities, especially burn units, crucially impact sepsis prognosis. • Complications such as AHF, ARDS, and GI bleeding significantly affect sepsis risk. [ABSTRACT FROM AUTHOR]

Limited data exist to guide oxygen administration during one-lung ventilation for thoracic surgery. We hypothesised that high intraoperative inspired oxygen fraction during lung resection surgery requiring one-lung ventilation is independently associated with postoperative pulmonary complications (PPCs). We performed this retrospective multicentre study using two integrated perioperative databases (Multicenter Perioperative Outcomes Group and Society of Thoracic Surgeons General Thoracic Surgery Database) to study adult thoracic surgical procedures using one-lung ventilation. The primary outcome was a composite of PPCs (atelectasis, acute respiratory distress syndrome, pneumonia, respiratory failure, reintubation, and prolonged ventilation >48 h). The exposure of interest was high inspired oxygen fraction (FiO 2), defined by area under the curve of a FiO 2 threshold > 80%. Univariate analysis and logistic regression modelling assessed the association between intraoperative FiO 2 and PPCs. Across four US medical centres, 141/2733 (5.2%) procedures conducted in 2716 patients (55% female; mean age 66 yr) resulted in PPCs. FiO 2 was univariately associated with PPCs (adjusted OR [aOR]: 1.17, 95% confidence interval [CI]: 1.04–1.33, P =0.012). Logistic regression modelling showed that duration of one-lung ventilation (aOR: 1.20, 95% CI: 1.03–1.41, P =0.022), but not the time-weighted average FiO 2 (aOR: 1.01, 95% CI: 1.00–1.02, P =0.165), was associated with PPCs. Our results do not support limiting the inspired oxygen fraction for the purpose of reducing postoperative pulmonary complications in thoracic surgery involving one-lung ventilation. [ABSTRACT FROM AUTHOR]

Pulmonary thromboembolismis a common cardiovascular disease, with high morbidity and mortality rates in hospitalized patients. Because of clotting disorders and hypoxemia caused by COVID-19, critically ill patients are highly susceptible to thrombotic complications. A study published in the Journal of the American Medical Association in 2022 showed that the incidence of venous thromboembolism(VTE) in critically ill COVID-19 patients was approximately 10%to 35%, whereas the incidence of VTE in autopsy cases was as high as 60%(JAMA Intern Med 182:1063-1070). Clinicians need increased awareness of VTE in COVID-19 patients, to reduce the risk of deep vein thrombosis and pulmonary thromboembolism and to be alert to life-threatening complications. [ABSTRACT FROM AUTHOR]

Systemic sclerosis (SSc) can lead to dyspnea and respiratory failure through multiple mechanisms, making a precise diagnosis particularly challenging, especially amid the current COVID-19 pandemic. In this report, we present a case involving a 26-year-old female who had previously undiagnosed SSc. She experienced acute respiratory failure necessitating orotracheal intubation. Following an extensive evaluation, the patient exhibited skin thickening, kidney failure, thrombocytopenia, microangiopathic anemia, and an antinuclear antibody with a nuclear fine speckled pattern at a titer of 1:320. A diagnosis of SSc complicated by scleroderma renal crisis (SRC) was established. The patient's condition improved after undergoing hemodialysis, receiving an angiotensin-converting enzyme inhibitor, and undergoing cyclophosphamide treatment. Subsequently, she demonstrated sustained improvement during a follow-up period of 20 months. [ABSTRACT FROM AUTHOR]

BACKGROUND: The use of prone position (PP) has been widespread during the COVID-19 pandemic. Whereas it has demonstrated benefits, including improved oxygenation and lung aeration, the factors influencing the response in terms of gas exchange to PP remain unclear. In particular, the association between baseline quantitative computed tomography (CT) scan results and gas exchange response to PP in invasively ventilated subjects with COVID-19 ARDS is unknown. The present study aimed to compare baseline quantitative CT results between subjects responding to PP in terms of oxygenation or CO2 clearance and those who did not. METHODS: This was a single-center, retrospective observational study including critically ill, invasively ventilated subjects with COVID-19-related ARDS admitted to the ICUs of Niguarda Hospital between March 2020-November 2021. Blood gas samples were collected before and after PP. Subjects in whom the PaO2 /FIO2 increase was ≥ 20 mm Hg after PP were defined as oxygen responders. CO2 responders were defined when the ventilatory ratio (VR) decreased during PP. Automated quantitative CT analyses were performed to obtain tissue mass and density of the lungs. RESULTS: One hundred twenty-five subjects were enrolled, of which 116 (93%) were O2 responders and 51 (41%) CO2 responders. No difference in quantitative CT characteristics and oxygen were observed between responders and non-responders (tissue mass 1,532 ± 396 g vs 1,654 ± 304 g, P = .28; density -544 ± 109 HU vs -562 ± 58 HU P = .42). Similar findings were observed when dividing the population according to CO2 response (tissue mass 1,551 ± 412 g vs 1,534 ± 377 g, P = .89; density -545 ± 123 HU vs -546 ± 94 HU, P = .99). CONCLUSIONS: Most subjects with COVID-19-related ARDS improved their oxygenation at the first pronation cycle. The study suggests that baseline quantitative CT scan data were not associated with the response to PP in oxygenation or CO2 in mechanically ventilated subjects with COVID-19-related ARDS. [ABSTRACT FROM AUTHOR]

Background: Hypoalbuminemia has been associated with an increased risk of in-hospital delirium. However, the relationship between serum albumin levels and the duration and severity of delirium is not well defined. Objective: To investigate the relationship between albumin levels and delirium duration and severity. Methods: Study data were from a randomized controlled trial involving adult intensive care unit patients (≥ 18 years old) admitted to 3 academic hospitals from 2009 to 2015 who had positive delirium screening results on the Confusion Assessment Method for the Intensive Care Unit–7. Delirium severity was defined by mean Confusion Assessment Method for the Intensive Care Unit–7 scores by day 8. Delirum duration was defined by the number of delirium-free and coma-free days by day 8. Serum albumin levels within 72 hours of intensive care unit admission were collected from electronic medical records. Results: The study included 237 patients (mean age, 60.3 years; female sex, 52.7%; receiving mechanical ventilation, 59.5%; acute respiratory failure or sepsis, 57.8%). Serum albumin levels were categorized as 3 g/dL or greater (n = 13), 2.5 to 2.99 g/dL (n = 142), and less than 2.5 g/dL (n = 82). After adjustment for demographic and clinical characteristics, no significant associations between albumin levels and delirium duration or severity were found. However, patients with normal albumin levels (≥3 g/dL) had shorter stays than did patients with hypoalbuminemia. Conclusion: In patients with delirium, higher albumin levels were associated with shorter hospital stays but not with delirium duration or severity. [ABSTRACT FROM AUTHOR]

The relationship between the PD-L1 (Programmed Death-Ligand 1)/PD-1 pathway, lung inflammation, and clinical outcomes in acute respiratory distress syndrome (ARDS) is poorly understood. We sought to determine whether PD-L1/PD-1 in the lung or blood is associated with ARDS and associated severity. We measured soluble PD-L1 (sPD-L1) in plasma and lower respiratory tract samples (ARDS1 [n = 59] and ARDS2 [n = 78]) or plasma samples alone (ARDS3 [n = 149]) collected from subjects with ARDS and tested for associations with mortality using multiple regression. We used mass cytometry to measure PD-L1/PD-1 expression and intracellular cytokine staining in cells isolated from BAL fluid (n = 18) and blood (n = 16) from critically ill subjects with or without ARDS enrolled from a fourth cohort. Higher plasma concentrations of sPD-L1 were associated with mortality in ARDS1, ARDS2, and ARDS3. In contrast, higher concentrations of sPD-L1 in the lung were either not associated with mortality (ARDS2) or were associated with survival (ARDS1). Alveolar PD-1POS T cells had more intracellular cytokine staining than PD-1NEG T cells. Subjects without ARDS had a higher ratio of PD-L1POS alveolar macrophages to PD-1POS T cells than subjects with ARDS. We conclude that sPD-L1 may have divergent cellular sources and/or functions in the alveolar versus blood compartments, given distinct associations with mortality. Alveolar leukocyte subsets defined by PD-L1 or PD-1 cell-surface expression have distinct cytokine secretion profiles, and the relative proportions of these subsets are associated with ARDS. [ABSTRACT FROM AUTHOR]

Rationale: Lung-protective strategies using low Vt and moderate positive end-expiratory pressure (PEEP) are considered best practice in critical care, but interventional trials have never been conducted in patients with acute brain injuries because of concerns about carbon dioxide control and the effect of PEEP on cerebral hemodynamics. Objectives: To test the hypothesis that ventilation with lower VT and higher PEEP compared to conventional ventilation would improve clinical outcomes in patients with acute brain injury. Methods: In this multicenter, open-label, controlled clinical trial, 190 adult patients with acute brain injury were assigned to receive either a lung-protective or a conventional ventilatory strategy. The primary outcome was a composite endpoint of death, ventilator dependency, and acute respiratory distress syndrome (ARDS) at Day 28. Neurological outcome was assessed at ICU discharge by the Oxford Handicap Scale and at 6 months by the Glasgow Outcome Scale. Measurements and Main Results: The two study arms had similar characteristics at baseline. In the lung-protective and conventional strategy groups, using an intention-to-treat approach, the composite outcome at 28 days was 61.5% and 45.3% (relative risk [RR], 1.35; 95% confidence interval [CI], 1.03–1.79; P = 0.025). Mortality was 28.9% and 15.1% (RR, 1.91; 95% CI, 1.06–3.42; P = 0.02), ventilator dependency was 42.3% and 27.9% (RR, 1.52; 95% CI, 1.01–2.28; P = 0.039), and incidence of ARDS was 30.8% and 22.1% (RR, 1.39; 95% CI, 0.85–2.27; P = 0.179), respectively. The trial was stopped after enrolling 190 subjects because of termination of funding. Conclusions: In patients with acute brain injury without ARDS, a lung-protective ventilatory strategy, as compared with a conventional strategy, did not reduce mortality, percentage of patients weaned from mechanical ventilation, or incidence of ARDS and was not beneficial in terms of neurological outcomes. Because of the early termination, these preliminary results require confirmation in larger trials. Clinical trial registered with (NCT01690819). [ABSTRACT FROM AUTHOR]

In order to evaluate the impact of olive activities on the population health in Fez rural, which is affected by air pollution, a retrospective study of acute respiratory infections (ARI) and chronic was studied (about ten years) in the commune of Ain Taoujdate (30 km of Fez center), known by its strong pollution particularly that of the air caused by industrial activity. Method using was the examination of medical records from 2004 to 2015. Analyzing the evolution of respiratory infections at Ain Taoujdate, we noticed a remarkable and repetitive increase, during olive tree campaign and in the spring (in each year), following the air pollution in the commune and abundance of pollen (pollinosis). Very high cases of pneumopathies recorded during the month of December 2004 and which reached 305 and 124 cases successively and which corresponds to the most important triturating activity during these twelve years of study. On the other hand the asthma crisis of Ain Taoujdate, shows a very large value in olive oil milling season. The main cause seems to be air pollution of Ain Taoujdate, since a large oil mill that releases a huge amount of fume is installed close to the population. Statistical analyzes using principal component analysis (PCA) and ascending hierarchical classification (HAC), were able to show an eventual correlation. This work excludes microbial infections; its limitation is the absence of air quality data and was the consequences to take stock of the impact of air pollution caused by oil mills on respiratory health. [ABSTRACT FROM AUTHOR]

Background: By 2023, COVID-19 had caused 6.8 million deaths in the United States. COVID-19 presents more severely in leukemia compared to solid tumors (OR 1.6, p<0.05). However, data on Acute Myeloid Leukemia (AML) and Myelodysplastic Syndrome (MDS) are limited. We investigated the mortality in AML and MDS patients with COVID-19. Methods: Data from the 2020-2021 National Inpatient Sample was used to conduct a cross-sectional analysis. We identified AML and MDS patients with COVID-19 hospitalizations through ICD-10 codes. Analysis was done by propensity matching and multivariate regression with a p-value of =0.05. Results: Of 28,028 AML admissions, 336 (1.2%) were admitted for COVID-19. AML-COVID-19 cohort had a lower hospitalization risk (aOR 0.3, p=0.000) and higher mortality (21.7% vs 8.7%; aOR 1.6, p=0.023) than AML patients admitted for other causes. AML patients post-HSCT (Hematopoietic Stem Cell Transplantation) had a higher risk of COVID-19 (20.2% vs 9.8%; aOR 2.6, p=0.000) and increased mortality (19.1% vs 6.7%; aOR 4.1, p=0.000) compared to other causes. Similarly, of 28,148 MDS patients, 769 (2.7%) were admitted for COVID-19. The MDS-COVID-19 cohort had a lower hospitalization risk (aOR 0.59, p=0.000) and higher mortality (19.6% vs 6.6%; aOR 2.2, p=0.000) compared to other causes. In MDS, HSCT did not alter the risk of COVID-19 hospitalizations (3% vs 3.9%; aOR 0.9, p=0.662), but these patients had higher mortality (17.4% vs 5.1%; aOR 4.0, p=0.032). Conclusion: COVID-19 hospitalization was low in AML and MDS but carried a high mortality risk. Post-HSCT, the mortality is high, warranting research into understanding the underlying factors. [ABSTRACT FROM AUTHOR]

Acute respiratory distress syndrome (ARDS) is a severe lung disease characterized by significant hypoxemia, which impairs the oxygen supply necessary for optimal lung function. This study aimed to investigate the effects of sodium propionate (SP), the primary end product of intestinal flora fermentation of dietary fiber, on lipopolysaccharide (LPS)-induced ARDS in rats. The rats were treated with SP, after which the lung wet/dry ratio, arterial partial oxygen pressure (PaO2), levels of pro- and anti-inflammatory cytokines, tight junction proteins ZO-1 and Occludin, as well as LC3 and phosphorylated PI3K (p-PI3K)/p-AKT/p-mTOR protein levels, were measured. Additionally, histopathological analysis was conducted. The results indicated that SP effectively alleviated arterial hypoxemia in rats and mitigated the pathological damage to both intestinal and lung tissues caused by LPS. Notably, SP significantly reduced the levels of inflammatory factors TNF-α and IL-6 in the blood and bronchoalveolar lavage fluid (BALF) of ARDS rats, while increasing the concentration of the anti-inflammatory factor IL-10. Furthermore, SP inhibited the activation of the PI3K/AKT/mTOR signaling pathway and enhanced the LC3II/LC3I ratio in lung tissue. Therefore, SP may improve LPS-induced ARDS in rats by inhibiting the activation of the PI3K/AKT/mTOR signaling pathway, promoting autophagy, decreasing the production and release of inflammatory markers, and reducing alveolar epithelial damage. [ABSTRACT FROM AUTHOR]

The Nipah Virus (NiV) was discovered in 1999 in the Sungai Nipah region of Malaysia. It is one of many emerging bat-borne zoonotic viruses that threaten global health security. The Pteropus fruit bats are identified as the natural reservoirs for the virus. NiV belongs to the family of Paramyxoviridae and is mostly present in locations surrounded by water, vegetation, and controlled or protected religious areas. To date, cases of NiV have been identified in Southeast Asian regions, with the highest number of cases in Bangladesh, totalling 305, with a fatality rate of 65%. The highest mortality has been observed in the Indian region, at 73%. NiV is an emerging zoonotic disease that needs to be focused on. The median incubation period is 9.5 days and the clinical features primarily lead to either progressive encephalitis or Acute Respiratory Distress Syndrome. The diagnosis is conducted in Bio-safety level 3 or level 4 labs through Polymerase chain reaction. Human nasal swabs, throat swabs, urine, blood, and cerebrospinal fluid (CSF) are collected for diagnostic purposes. At present, there is no approved treatment or vaccine for the prevention of the disease. However, research on a vaccine against NiV is being investigated, and a subunit vaccine with NiV-G protein is found to produce potential efficacy. An outbreak in Kerala, a state in India, led to the implementation of an action plan involving lead agencies to combat the sudden surge of the virus. In the current scenario, appropriate preventive strategies are more effective in controlling the virus. However, emphasis should be placed on affordable and efficient diagnostic methods, treatment options, and vaccines to better manage the virus, considering the highest fatality caused by the virus. [ABSTRACT FROM AUTHOR]

Background: Mesenchymal stem/stromal cells (MSCs) have attracted interest as a potential therapy given their anti-inflammatory and immunomodulatory properties. However, clinical trials using MSCs for acute respiratory distress syndrome (ARDS) have produced mixed and inconclusive data. In previous work, we performed a "head-to-head" comparison between different sources of MSCs and showed that each source had a unique genomic and proteomic "signature". Method: This study investigated which sources of MSC: bone marrow derived-MSCs (BM-MSCs), adipose tissue derived-MSCs (AD-MSCs) and umbilical cord derived-MSCs (UC-MSCs) would be the optimal candidate to be used as a therapy in an LPS-induced mouse model of ARDS. Immune cells assessment, tissue transcriptomics, animal survival, and endothelial-epithelial barrier assessment were used to evaluate their effects. Results: When comparing the three most commonly used MSC sources, we found that UC-MSCs exhibited greater efficacy compared to other MSCs in improving animal survival, mitigating epithelial/endothelial damage, decreasing lung inflammation via reducing neutrophil infiltration, T cell proliferation, and M1 polarization. Bulk RNA sequencing of lung tissue also showed that UC-MSCs have the capability to downregulate extracellular trap formation, by the downregulation of key genes like Elane and Padi4. Notably, treatment with UC-MSCs demonstrated a significant reduction in Fc-γ R mediated phagocytosis, which has been associated with monocyte pyroptosis and intense inflammation in the context of COVID-19. Conclusion: Our findings suggest that UC-MSCs are an optimal source of MSC to treat acute inflammatory conditions in the lungs, such as ARDS. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to evaluate the roles of galectin-3 and irisin as biomarkers in predicting severe outcomes in COVID-19 patients. Results: We analyzed serum levels of galectin-3 and irisin in 59 patients with severe COVID-19 and 30 healthy controls. Elevated galectin-3 levels were associated with increased risks of mortality, need for intensive care, and severe acute respiratory distress syndrome. The optimal cut-off value for galectin-3 was 13.47 ng/ml, with a sensitivity of 72.7% and specificity of 76.6%. Irisin levels did not differ significantly between survivors and non-survivors at admission or on the 3rd day post-admission, but approached significance on the 7th day. These findings suggest that galectin-3 could be a valuable prognostic biomarker for severe COVID-19 outcomes, while irisin's role remains to be clarified in further studies. [ABSTRACT FROM AUTHOR]

Background: The use of prehospital tranexamic acid (TXA) in patients with trauma has attracted considerable attention. This systematic review and meta-analysis aimed to provide the best evidence for clinicians. Methods: All related literature in PubMed, Embase, and the Cochrane Central Register of Controlled Trials (Central) databases were searched systematically from their establishment to July 1, 2023. The outcome measures included 24-hour and 28–30-day mortality and adverse events (multiple organ dysfunction syndrome, acute respiratory distress syndrome, thrombotic events, and infection events). The Revised Cochrane Risk of Bias Tool for Randomized Trials was used to evaluate the quality of the randomized controlled trials (RCTs). The Methodological Index for Nonrandomized Studies (MINORS) was used to evaluate the risk of bias in non-RCTs. The required information size was estimated using trial sequential analysis. The Grading of Recommendations, Assessment, Development, and Evaluation approach was used to evaluate the evidence quality. Results: Eleven studies (comprising 11,259 patients) were included; two of these were RCTs. The overall risks of bias were low in the RCTs. ROBINS-I risk of bias was Moderate in 3 studies, serious in 5 studies, and critical in 1 study. A significant reduction in 24-hour mortality was observed (odds ratio [OR], 0.82; 95% confidence interval [CI], 0.71–0.94). A subgroup analysis that included only RCTs revealed that prehospital TXA was associated with reduced 28–30-day mortality (OR, 0.80; 95% CI, 0.66–0.97) and increased risks of thromboembolism (OR, 1.22; 95% CI, 1.03–1.44) and infection (OR, 1.13; 95% CI, 1.00–1.28) events. The blood products for transfusion decreased by 2.3 units on average (weighted mean difference [WMD], − 2.30; 95%CI, − 3.59 to − 1.01). Conclusions: This updated systematic review showed that prehospital TXA reduced the 24-hour and 28–38-day mortality and blood transfusion but increased the risks of infection and thromboembolism in patients with trauma. Future RCTs with larger and more homogeneous samples will help verify our results. [ABSTRACT FROM AUTHOR]

Background: The success and failure of extubation of patients with acute respiratory failure is a very important issue for clinicians, and the failure of the ventilator often leads to possible complications, which in turn leads to a lot of doubts about the medical treatment in the minds of the people, so in order to increase the success of extubation success of the doctors to prevent the possible complications, the present study compared different time series algorithms and different activation functions for the training and prediction of extubation success or failure models. Methods: This study compared different time series algorithms and different activation functions for training and predicting the success or failure of the extubation model. Results: The results of this study using four validation methods show that the GRU model and Tanh's model have a better predictive model for predicting the success or failure of the extubation and better predictive result of 94.44% can be obtained using Holdout cross-validation validation method. Conclusion: This study proposes a prediction method using GRU on the topic of extubation, and it can provide the doctors with the clinical application of extubation to give advice for reference. [ABSTRACT FROM AUTHOR]

Background: Despite being essential in patients with acute respiratory distress syndrome (ARDS), mechanical ventilation (MV) may cause lung injury and hemodynamic instability. Mechanical power (MP) may describe the net injurious effects of MV, but whether it reflects the hemodynamic effects of MV is currently unclear. We hypothesized that MP is also associated with cardiac output (CO) and pulmonary blood flow (PBF). Methods: 24 anesthetized pigs with experimental acute lung injury were ventilated for 18 h according to one of three strategies: 1) Open lung approach (OLA), 2) ARDS Network high-PEEP/FIO2 strategy (HighPEEP), or 3) low-PEEP/FIO2 strategy (LowPEEP). Total MP was assessed as the sum of energy dissipated to overcome airway resistance and energy temporarily stored in the elastic lung tissue per minute. The distribution of pulmonary perfusion was determined by positron emission tomography. Regional PBF and MP, assessed in three iso-gravitational regions of interest (ROI) with equal lung mass (ventral, middle, and dorsal ROI), were compared between groups. Results: MP was higher in the LowPEEP than in the OLA group, while CO did not differ between groups. After 18 h, regional PBF did not differ between groups. During LowPEEP, regional MP was higher in the ventral ROI compared to OLA and HighPEEP groups (2. 5 ± 0. 3 vs. 1. 4 ± 0. 4 and 1. 6 ± 0. 3 J/min, respectively, P < 0. 001 each), and higher in the middle ROI compared to the OLA group (2. 5 ± 0. 4 vs. 1. 6 ± 0. 5 J/min, P = 0. 04). MP in the dorsal ROI did not differ between groups (1. 4 ± 0. 9 vs. 1. 4 ± 0. 5 vs. 1. 3 ± 0. 8 J/min, P = 0. 916). Total MP was independently associated with CO [0. 34 (0. 09, 0. 59), P = 0. 020]. Regional MP was positively associated with PBF irrespective of the regions [0. 52 (0. 14, 0. 76), P = 0. 01; 0. 49 (0. 10, 0. 74), P = 0. 016; 0. 64 (0. 32, 0. 83), P = 0. 001 for ventral, middle, and dorsal ROI, respectively]. Subgroup analysis revealed a significant association of MP and CO only in the OLA group as well as a significant association between MP with regional PBF only in the HighPEEP group. Conclusion: In this model of acute lung injury in pigs ventilated with either open lung approach, high, or low PEEP tables recommended by the ARDS network, MP correlated positively with CO and regional PBF, whereby these clinically relevant lung-protective ventilation strategies influenced the associations. [ABSTRACT FROM AUTHOR]

Objective: The lactate/albumin ratio (LAR) has been used as a novel prognostic indicator for aneurysmal subarachnoid hemorrhage, traumatic brain injury, sepsis, heart failure, and acute respiratory failure. However, its potential in predicting all-cause mortality in patients with ischemic stroke (IS) has not been evaluated. Therefore, this study aimed to elucidate the correlation between LAR and 28-day all-cause mortality in IS patients without reperfusion therapy. Methods: This retrospective cohort study used data from the Medical Information Mart for Intensive Care (MIMIC-IV) (v2.0) database. It included 568 IS adult patients admitted to the intensive care unit (ICU). The correlation between LAR and ICU 28-day all-cause mortality rate was analyzed using multiple COX regression analysis and Kaplan-Meier survival analysis. Restricted cubic spline (RCS) curves were used to assess the relationship between LAR and 28-day mortality. In addition, a subgroup analysis was performed to investigate the impact of other influencing factors on outcomes. The primary outcome was the ability of LAR to predict 28-day mortality in IS patients. Results: Among the 568 patients with IS, 370 survived (survival group) and 198 died (non-survival group) within 28 days of admission (mortality rate: 34.9%). A multivariate COX regression analysis indicated that LAR was an independent predictor of all-cause mortality within 28 days after admission for patients with IS (hazard ratio: 1.32; 95% confidence interval: 1.03-1.68; P = 0.025). We constructed a model that included LAR, age, race, sex, white blood cell count, Sequential Organ Failure Assessment (SOFA) score, and anion gap (AG) and established a prediction model with an area under the curve (AUC) value of 71.5% (95% confidence interval: 67.1%-75.8%). The optimal cuto value of LAR that separated the survival group and the non-survival group based on the Youden index was 0.55. The Kaplan-Meier survival curves plotted using this critical value showed that patients with LAR ≥ 0.55 had a significantly higher 28-day all-cause mortality rate than patients with LAR < 0.55 (P = 0.0083). Conclusion: LAR can serve as an independent predictor of all-cause mortality within 28 days after admission for patients with IS. [ABSTRACT FROM AUTHOR]

Background: Advancing age is associated with an increase in mortality among patients with acute respiratory distress syndrome (ARDS) due to coronavirus disease 2019 (COVID-19). This study aimed to determine risk factors for in-hospital mortality in patients over 60 years old with COVID-19-related ARDS (C-ARDS). Methods: This was an observational, analytical, retrospective study conducted on a cohort that included all patients aged 60 years or older diagnosed with COVID-ARDSwho were admitted to a high-complexity hospital in Bogotá, Colombia, between March 2020 and July 2021. Results: A total of 1563 patients were included in the analysis, with a median age of 73 years (interquartile range [IQR]: 67–80) and 811 deaths (51.8%). Independent risk factors for in-hospital mortality were identified as follows: patients aged 71–80 [OR 1.87 (95% CI 1.33–2.64)], age > 80 [OR 8.74 (95% CI 5.34–14.31)], lactate dehydrogenase (LDH) [OR 1.009 (95% CI 1.003–1.0015)], severe C-ARDS [OR 2.16 (95% CI 1.50–3.11)], use of invasive mechanical ventilation (IMV) [OR 12.94 (95% CI 9.52–17.60)], and use of steroids [OR 1.49 (95% CI 1.09–2.03)]. In patients over 80 years of age (n = 388), the primary risk factor associated with in-hospital mortality was the use of IMV (n = 76) [OR 6.26 (95% CI 2.67–14.69)], resulting in an in-hospital mortality rate of 89.4% (n = 68) when this therapy was implemented. Conclusions: The primary risk factors for in-hospital mortality in patients older than 60 years were age, the use of IMV, the severity of C-ARDS, use of steroids and elevated LDH values. Among patients older than 80 years, the main risk factor for in-hospital mortality was the use of IMV. In cases of C-ARDS in older patients, the decision to initiate IMV should always be individualized; therefore, the use of alternative oxygen delivery systems as the first-line approach can be considered. [ABSTRACT FROM AUTHOR]

In patients with sepsis, neutrophil apoptosis tends to be inversely proportional to the severity of sepsis, but its mechanism is not yet clear. This study aimed to explore the mechanism of fatty acid binding protein 4 (FABP4) regulating neutrophil apoptosis through combined analysis of gut microbiota and short-chain fatty acids (SCFAs) metabolism. First, neutrophils from bronchoalveolar lavage fluid (BALF) of patients with sepsis-induced acute respiratory distress syndrome (ARDS) were purified and isolated RNA was applied for sequencing. Then, the cecal ligation and puncture (CLP) method was applied to induce the mouse sepsis model. After intervention with differential SCFAs sodium acetate, neutrophil apoptosis and FABP4 expression were further analyzed. Then, FABP4 inhibitor BMS309403 was used to treat neutrophils. We found CLP group had increased lung injury score, lung tissue wet/dry ratio, lung vascular permeability, and inflammatory factors IL-1β, TNF-α, IL-6, IFN-γ, and CCL3 levels in both bronchoalveolar lavage fluid and lung tissue. Additionally, FABP4 was lower in neutrophils of ARDS patients and mice. Meanwhile, CLP-induced dysbiosis of gut microbiota and changes in SCFAs levels were observed. Further verification showed that acetic acids reduced neutrophil apoptosis and FABP4 expression via FFAR2. Besides, FABP4 affected neutrophil apoptosis through endoplasmic reticulum (ER) stress, and neutrophil depletion alleviated the promotion of ARDS development by BMS309403. Moreover, FABP4 in neutrophils regulated the injury of RLE-6TN through inflammatory factors. In conclusion, FABP4 affected by gut microbiota-derived SCFAs delayed neutrophil apoptosis through ER stress, leading to increased inflammatory factors mediating lung epithelial cell damage. [ABSTRACT FROM AUTHOR]

Background: Convalescent plasma (CP) reduced the mortality in COVID-19 induced ARDS (C-ARDS) patients treated in the CONFIDENT trial. As patients are immunologically heterogeneous, we hypothesized that clusters may differ in their treatment responses to CP. Methods: We measured 20 cytokines, chemokines and cell adhesion markers using a multiplex technique at the time of inclusion in the CONFIDENT trial in patients of centers having accepted to participate in this secondary study. We performed descriptive statistics, unsupervised hierarchical cluster analysis, and examined the association between the clusters and CP effect on day-28 mortality. Results: Of the 475 patients included in CONFIDENT, 391 (82%) were sampled, and 196/391 (50.1%) had been assigned to CP. We identified four sub-phenotypes representing 89 (22.8%), 178 (45.5%), 38 (9.7%), and 86 (22.0%) patients. The most contributing biomarkers in the principal component analysis were IL-1β, IL-12p70, IL-6, IFN-α, IL-17A, IFN-γ, IL-13, TFN-α, total IgG, and CXCL10. Sub-phenotype-1 displayed a lower immune response, sub-phenotype-2 a higher adaptive response, sub-phenotype-3 the highest innate antiviral, pro and anti-inflammatory response, and adhesion molecule activation, and sub-phenotype-4 a higher pro and anti-inflammatory response, migration protein and adhesion molecule activation. Sub-phenotype-2 and sub-phenotype-4 had higher severity at the time of inclusion. The effect of CP treatment on mortality appeared higher than standard care in each sub-phenotype, without heterogeneity between sub-phenotypes (p = 0.97). Conclusion: In patients with C-ARDS, we identified 4 sub-phenotypes based on their immune response. These sub-phenotypes were associated with different clinical profiles. The response to CP was similar across the 4 sub-phenotypes. Trial registration: Ethics Committee of the University Hospital of Liège CE 2020/239. Clinicaltrials.gov NCT04558476. Registered 2020-09-11, https://www.clinicaltrials.gov/study/NCT04558476. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusion Severe acute respiratory syndrome (ARDS) may require veno‐venous extracorporeal membrane oxygenation (V‐V ECMO). The aim of this study was to provide data on patient selection and outcome in a nationwide cohort study of patients with COVID‐19 associated ARDS supported with V‐V ECMO.We identified all patients with COVID‐19, who were supported with V‐V ECMO in Denmark from March 10, 2020, to December 31, 2021, and retrieved data on patients who were referred to‐ and accepted for ECMO, demographics, outcome data, and complications. Risk factors for mortality were analysed using multivariate Cox regression analysis.During the study period, 1836 patients were admitted to Danish intensive care units (ICUs). In the same period, there were 197 enquiries for ECMO of whom 118 patients were considered eligible. Overall, 71 patients were cannulated for ECMO; three patients were cannulated for veno‐arterial extracorporeal membrane oxygenation (V‐A ECMO) due to right sided heart failure and 68 patients were cannulated for V‐V ECMO. Two patients accepted for V‐V ECMO died during cannulation. The median age was 55 years (IQR 45–60) and 66% were males. The median duration of ECMO support was 13 days (IQR 7–21), mechanical ventilation median 26 days (IQR 14–42), ICU stay median 34 days (IQR 17–46), and length of hospital stay median 41 days (IQR 25–56). Ninety‐day mortality was 43%. Age of 60 years or more was associated with an increased risk of mortality. Pre‐existing hypertension was associated with a decreased risk of mortality.A nationwide, Danish cohort study of 68 COVID‐19 patients supported with V‐V ECMO, showed a 90‐day survival of 43%, which is in accordance with reports from comparable cohorts. Age of 60 years or more was associated with an increased risk of mortality. Pre‐existing hypertension was associated with a decreased risk of mortality. [ABSTRACT FROM AUTHOR]

Introduction: The COVID-19, triggered by the SARS-CoV-2 virus, has varied clinical manifestations, ranging from mild cases to severe forms such as fatal pneumonia and acute respiratory distress syndrome (ARDS). Disease severity is influenced by an exacerbated immune response, characterized by high proinflammatory cytokine levels. Inhibition of AKT can potentially suppress pathological inflammation, cytokine storm and platelet activation associated with COVID-19. In this study, we aimed to investigate the rs2494746 and rs1130214 variants in the AKT1 gene associated with severe COVID-19 outcomes. Methods: Peripheral blood samples and sociodemographic data from 508 individuals with COVID-19, measuring plasma cytokine concentrations using ELISA and genotyped the AKT1 variants. Results: The rs2494746-C allele was associated with severity, ICU admission, and death from COVID-19. The C allele at rs1130214 was linked to increased TNF and D-dimer levels. Moreover, both variants exhibited an increased cumulative risk of disease severity, ICU admission, and mortality caused by COVID-19. In the predictive analysis, the rs2494746 obtained an accuracy of 71%, suggesting a high probability of the test determining the severity of the disease. Discussion: Our findings contribute to understanding the influence of the AKT1 gene variants on the immunological damage in individuals infected with SARS-CoV-2. [ABSTRACT FROM AUTHOR]

Background: Extubation failure is a crucial issue for acute respiratory distress syndrome (ARDS). Ultrasound of the lung and diaphragm is individually valuable for predicting extubation outcomes. We aimed to determine whether combined lung and diaphragmatic ultrasound could improve the accuracy of predicting the extubation of ARDS patients. Methods: This was a prospective cohort study of ARDS patients who were ready for extubation. The lung ultrasound score (LUS), diaphragmatic displacement (DD), diaphragm thickening fraction (DTF), and diaphragmatic-rapid shallow breathing index (D-RSBI) were measured at the end of the spontaneous breathing trial. The primary outcome was extubation success. Logistic regression was used to combine these indicators, and the predictive performance of the single and combined indicators was evaluated through receiver operating characteristic (ROC) curves, the Hosmer–Lemeshow Ĉ‐test, and the Brier score. Multivariate logistic regression was used to determine the association between combined ultrasound indicators and extubation success. Results: This study enrolled 132 eligible patients from January 2019 to December 2022. A total of 71% (94/132) of patients were successfully extubated from mechanical ventilation. The combination of LUS and D-RSBI had the largest area under the ROC curves, the lowest Brier score, and the greatest calibration. After formula transformation, LUS + 2.43 × D-RSBI ≤ 14.273 was significantly associated with extubation success in ARDS patients. Conclusions: In ARDS patients receiving mechanical ventilation, the combination of LUS and D-RSBI was more accurate than a single parameter alone in predicting extubation outcomes. This combined approach could help refine extubation protocols in critical care. Clinical trial registration This study is registered online with the Chinese Clinical Trial Registry (ChiCTR), http://www.chictr.org.cn, ChiCTR1800019340 (Registration time: 2018/11/06). [ABSTRACT FROM AUTHOR]

Background: Malaria-associated acute lung injury/acute respiratory distress syndrome (MA-ALI/ARDS) is a fatal complication of Plasmodium falciparum infection that is partially triggered by macrophage recruitment and polarization. As reported, copper exposure increases the risk of malaria infection, and copper accumulation-induced cuproptosis triggers M1 macrophage polarization. It is thus hypothesized that cuproptosis could act as a critical mediator in the pathogenesis of MA-ALI/ARDS, but its underlying mechanism remains unclear. The present study aimed to explore the role of cuproptosis in the severity of murine MA-ALI/ARDS. Methods: We utilized an experimental model of MA-ALI/ARDS using female C57BL/6 mice with P. berghei ANKA infection, and treated these animals with the potent copper ion carrier disulfiram (DSF) or copper ion chelator tetrathiomolybdate (TTM). The RAW 264.7 macrophages, which were stimulated with infected red blood cells (iRBCs) in vitro, were also targeted with DSF-CuCl2 or TTM-CuCl2 to further investigate the underlying mechanism. Results: Our findings showed a dramatic elevation in the amount of copper and the expression of SLC31A1 (a copper influx transporter) and FDX1 (a key positive regulator of cuproptosis) but displayed a notable reduction in the expression of ATP7A (a copper efflux transporter) in the lung tissue of experimental MA-ALI/ARDS mice. Compared to the P. berghei ANKA-infected control group, mice that were administered DSF exhibited a remarkable increase in parasitemia/lung parasite burden, total protein concentrations in bronchoalveolar lavage fluid (BALF), lung wet/dry weight ratio, vascular leakage, and pathological changes in lung tissue. Strikingly, the experimental MA-ALI/ARDS mice with DSF treatment also demonstrated dramatically elevated copper levels, expression of SLC31A1 and FDX1, numbers of CD86+, CD68+, SLC31A1+-CD68+, and FDX1+-CD68+ macrophages, and messenger RNA (mRNA) levels of pro-inflammatory cytokines (tumor necrosis factor [TNF-α] and inducible nitric oxide synthase [iNOS]) in lung tissue, but showed a remarkable decrease in body weight, survival time, expression of ATP7A, number of CD206+ macrophages, and mRNA levels of anti-inflammatory cytokines (transforming growth factor beta [TGF-β] and interleukin 10 [IL-10]). In contrast, TTM treatment reversed these changes in the infected mice. Similarly, the in vitro experiment showed a notable elevation in the mRNA levels of SLC31A1, FDX1, CD86, TNF-α, and iNOS in iRBC-stimulated RAW 264.7 cells targeted with DSF-CuCl2, but triggered a remarkable decline in the mRNA levels of ATP7A, CD206, TGF-β, and IL-10. In contrast, TTM-CuCl2 treatment also reversed these trends in the iRBC-stimulated RAW 264.7 cells. Conclusions: Our data demonstrate that the activation of cuproptosis with DSF aggravated the severity of MA-ALI/ARDS by partially inducing M1 polarization of pulmonary macrophages, while inhibition of cuproptosis with TTM contrarily ameliorated the severity of MA-ALI/ARDS by promoting macrophage M2 polarization. Our findings suggest that blockage of cuproptosis could be a potential therapeutic strategy for treatment of MA-ALI/ARDS. [ABSTRACT FROM AUTHOR]

Background: Maintaining the patient awake and not intubated during the venovenous extracorporeal membrane oxygenation (VV ECMO) reduces the risk of ventilation-induced lung injury in patients with ARDS. Currently, there is a lack of data on outcomes and complications associated with the awake ECMO approach. Objectives: To evaluate outcomes and the occurrence of complications of awake ECMO approach guided by local safety protocol comprising ultrasound-guided cannulation, argatroban-based anticoagulation, respiratory support, and routine sedation targeted to reduce respiratory effort and keeping nurse-to-patient ratio of 1:1. Design: A single-center retrospective case series analysis. Methods: Consecutive patients with COVID-19-related acute respiratory distress syndrome (ARDS) (CARDS) treated by full awake VV ECMO approach from April 2019 to December 2023 were eligible. Results: Our center treated 10 patients (mean age 54.7 ± 11.6 years) with CARDS with an awake ECMO approach. The reasons for awake ECMO included the presence of barotrauma in six patients, a team consensus to prefer awake ECMO instead of mechanical ventilation in three patients, and the patient's refusal to be intubated in one case. Before ECMO, patients were severely hypoxemic, with a mean value of Horowitz index of 48.9 ± 9.1 mmHg and a mean respiratory rate of 28.8 ± 7.3 breaths per minute on high-flow nasal cannula or noninvasive ventilation support. The mean duration of awake VV ECMO was 558.0 ± 173.6 h. Seven patients (70%) were successfully disconnected from ECMO and fully recovered. Intubation from respiratory causes was needed in three patients (30%), all of whom died eventually. In total, three episodes of delirium, two episodes of significant bleeding, one pneumothorax requiring chest tube insertion, and one oxygenator acute exchange occurred throughout the 5580 h of awake ECMO. No complications related to cannula displacement or malposition occurred. Conclusion: The awake ECMO strategy guided by safety protocol appears to be a safe approach in conscious, severely hypoxemic, non-intubated patients with COVID-19-related ARDS. Plain language summary: Enhancing the safety and effectiveness of extracorporeal membrane oxygenation (ECMO) therapy in awake, spontaneously breathing patients with the most severe form of COVID-19-related acute respiratory distress syndrome (ARDS) Why Was the Study Done? Extracorporeal membrane oxygenation (ECMO) represents a life-saving therapeutic approach that ensures appropriate gas exchange in patients with the most severe form of respiratory failure – acute respiratory distress syndrome (ARDS). Typically, patients are connected to ECMO when already deeply sedated and mechanically ventilated. The awake ECMO approach (keeping the patient awake, not intubated, and breathing spontaneously during ECMO support) minimizes the risks associated with mechanical ventilation and provides several relevant physiological benefits. However, the awake ECMO approach is also associated with several significant risks, including delirium, bleeding, and cannula displacement. Published papers have reported relatively frequent complications and method failures. What Did the Researchers Do? To address safety concerns regarding the awake ECMO approach, we present a single-center retrospective analysis of ten COVID-19-related ARDS patients treated with the awake ECMO approach, guided by the local safety protocol. What Did the Researchers Find? The awake ECMO approach yielded success (i.e., the patient was not intubated for respiratory causes, was successfully disconnected from ECMO, and fully recovered in seven patients (70.0%), outperforming previously published efficacy ranges. Three patients were intubated due to the progression of respiratory failure and eventually died. The incidence of adverse events during the 5,580 hours of awake ECMO was considered low. No cannula displacement or malposition occurred despite routine active physiotherapy, including walking during ECMO treatment in three patients. What Do the Findings Mean? The general applicability of the study is limited by the low number of patients and the retrospective monocentric design. However, the presented data illustrate real-life clinical scenarios and could aid clinicians in managing severely hypoxemic but still conscious and cooperative patients. [ABSTRACT FROM AUTHOR]

Background: This study analyzed weaning characteristics and assessed the association of clinical and ultrasonographic indices—maximum inspiratory pressure (MIP), rapid shallow breathing index (RSBI), peak flow expiratory (PFE), diaphragm-thickening fraction (DTF), diaphragm thickness (DT), diaphragm excursion (DE), diaphragm-RSBI (D-RSBI), and lung ultrasound (LUS) patterns—with weaning failure. Methods: This retrospective cohort study included critically ill COVID-19 patients aged 18 and older who had been on invasive mechanical ventilation for at least 48 h and undergoing weaning. Exclusion criteria included absence of ultrasound assessments, neuromuscular diseases, and chronic cardio-respiratory dysfunction. Results: Among 61 patients, 44.3% experienced weaning failure, 27.9% failed the spontaneous breathing trial (SBT), 16.4% were re-intubated within 48 h, and 28% required tracheostomy. Weaning failure was associated with prolonged ventilation (29 vs. 7 days, p < 0.001), extended oxygen therapy, longer ICU stays, and higher ICU mortality. These patients had higher pressure support, lower oxygenation levels, a higher RSBI, and a lower MIP. While PEF, DTF, DE, and D-RSBI showed no significant differences, both right and left diaphragm thicknesses and the inspiratory thickness of the left diaphragm were reduced in failure cases. LUS scores were significantly higher before and after SBT in the failure group. Bivariate analysis identified RSBI [OR = 1.04 (95% CI = 1.01–1.07), p = 0.010], MIP [OR = 0.92 (95% CI = 0.86–0.99), p = 0.018], and LUS [OR = 1.15 (95% CI = 0.98–1.35), p = 0.025] as predictors of weaning failure; however, these associations were not confirmed in multivariate analysis. Conclusions: Ultrasound provides supplementary information during weaning, but no definitive association between ultrasound indices and weaning failure was confirmed in this study. [ABSTRACT FROM AUTHOR]

A cytokine storm is an intense inflammatory response characterized by the overproduction of proinflammatory cytokines, resulting in tissue damage, and organ dysfunction. Cytokines play a crucial role in various conditions, such as coronavirus disease, in which the immune system becomes overactive and releases excessive levels of cytokines, including interleukins, tumor necrosis factor-alpha (TNF-α), and interferon-gamma (IFN-γ). This anomalous response often leads to acute respiratory distress syndrome (ARDS), disseminated intravascular coagulation (DIC), and multiple organ injury (MOI). Glucosinolates are plant secondary metabolites predominantly found in Brassica vegetables, but are also present in other species, such as Moringa Adens and Carica papaya L. When catalyzed by the enzyme myrosinase, glucosinolates produce valuable products, including sulforaphane, phenethyl isothiocyanate, 6-(methylsulfinyl) hexyl isothiocyanate, erucin, goitrin, and moringin. These hydrolyzed products regulate proinflammatory cytokine production by inhibiting the nuclear factor kappa-light-chain-enhancer of activated B-cell (NF-κB) signaling pathway and stimulating the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway. This action can alleviate hyperinflammation in infected cells and modulate cytokine storms. In this review, we aimed to examine the potential role of glucosinolates in modulating cytokine storms and reducing inflammation in various conditions, such as coronavirus disease. Overall, we found that glucosinolates and their hydrolysis products can potentially attenuate cytokine production and the onset of cytokine storms in diseased cells. In summary, glucosinolates could be beneficial in regulating cytokine production and preventing complications related to cytokine storms. [ABSTRACT FROM AUTHOR]

The present study aimed to identify in patients with severe COVID-19 and acute respiratory distress syndrome (ARDS) the association between rs3804099 and rs3804100 (TLR2) and evaluate the expression of TLR-2 on the cell surface of innate and adaptive cells of patients' carriers of C allele in at least one genetic variant. We genotyped 1018 patients with COVID-19 and ARDS. According to genotype, a subgroup of 12 patients was selected to stimulate peripheral blood mononuclear cells (PBMCs) with spike and LPS + spike. We evaluated soluble molecules in cell culture supernatants. The C allele in TLR2 (rs3804099, rs3804100) is not associated with a risk of severe COVID-19; however, the presence of the C allele (rs3804099 or rs3804100) affects the TLR-2 ability to respond to a spike of SARS-CoV-2 correctly. The reference group (genotype TT) downregulated the frequency of non-switched TLR-2+ B cells in response to spike stimulus; however, the allele's C carriers group is unable to induce this regulation, but they produce high levels of IL-10, IL-6, and TNF-α by an independent pathway of TLR-2. Findings showed that TT genotypes (rs3804099 and rs3804100) affect the non-switched TLR-2+ B cell distribution. Genotype TT (rs3804099 and rs3804100) affects the TLR-2's ability to respond to a spike of SARS-CoV-2. However, the C allele had increased IL-10, IL-6, and TNF-α by stimulation with spike and LPS. [ABSTRACT FROM AUTHOR]

Influenza A virus (IAV) is known for causing seasonal epidemics ranging from flu to more severe outcomes like pneumonia, cytokine storms, and acute respiratory distress syndrome. The innate immune response and inflammasome activation play pivotal roles in sensing, preventing, and clearing the infection, as well as in the potential exacerbation of disease progression. This study examines the complex relationships between donor-specific characteristics and cytokine responses during H3N2 IAV infection using an ex vivo model. At 24 h post infection in 31 human lung explant tissue samples, key cytokines such as interleukin (IL)-6, IL-10, tumor necrosis factor-alpha (TNF-α), and interferon-gamma (IFN-γ) were upregulated. Interestingly, a history of lung cancer did not impact the acute immune response. However, cigarette smoking and programmed death-ligand 1 (PD-L1) expression on macrophages significantly increased IL-2 levels. Conversely, age inversely affected IL-4 levels, and diabetes mellitus negatively influenced IL-6 levels. Additionally, both diabetes mellitus and programmed cell death protein 1 (PD-1) expression on CD3+/CD4+ T cells negatively impacted TNF-α levels, while body mass index was inversely associated with IFN-γ production. Toll-like receptor 2 (TLR2) expression emerged as crucial in mediating acute innate and adaptive immune responses. These findings highlight the intricate interplay between individual physiological traits and immune responses during influenza infection, underscoring the importance of tailored and personalized approaches in IAV treatment and prevention. [ABSTRACT FROM AUTHOR]

Importance: Community-acquired pneumonia (CAP) results in approximately 1.4 million emergency department visits, 740 000 hospitalizations, and 41 000 deaths in the US annually. Observations: Community-acquired pneumonia can be diagnosed in a patient with 2 or more signs (eg, temperature >38 °C or ≤36 °C; leukocyte count <4000/μL or >10 000/μL) or symptoms (eg, new or increased cough or dyspnea) of pneumonia in conjunction with consistent radiographic findings (eg, air space density) without an alternative explanation. Up to 10% of patients with CAP are hospitalized; of those, up to 1 in 5 require intensive care. Older adults (≥65 years) and those with underlying lung disease, smoking, or immune suppression are at highest risk for CAP and complications of CAP, including sepsis, acute respiratory distress syndrome, and death. Only 38% of patients hospitalized with CAP have a pathogen identified. Of those patients, up to 40% have viruses identified as the likely cause of CAP, with Streptococcus pneumoniae identified in approximately 15% of patients with an identified etiology of the pneumonia. All patients with CAP should be tested for COVID-19 and influenza when these viruses are common in the community because their diagnosis may affect treatment (eg, antiviral therapy) and infection prevention strategies. If test results for influenza and COVID-19 are negative or when the pathogens are not likely etiologies, patients can be treated empirically to cover the most likely bacterial pathogens. When selecting empirical antibacterial therapy, clinicians should consider disease severity and evaluate the likelihood of a bacterial infection—or resistant infection—and risk of harm from overuse of antibacterial drugs. Hospitalized patients without risk factors for resistant bacteria can be treated with β-lactam/macrolide combination therapy, such as ceftriaxone combined with azithromycin, for a minimum of 3 days. Systemic corticosteroid administration within 24 hours of development of severe CAP may reduce 28-day mortality. Conclusions: Community-acquired pneumonia is common and may result in sepsis, acute respiratory distress syndrome, or death. First-line therapy varies by disease severity and etiology. Hospitalized patients with suspected bacterial CAP and without risk factors for resistant bacteria can be treated with β-lactam/macrolide combination therapy, such as ceftriaxone combined with azithromycin, for a minimum of 3 days. This Review summarizes current evidence on pathogenesis, epidemiology, diagnosis, and treatment of community-acquired pneumonia and focuses on adults without immune-compromising conditions. [ABSTRACT FROM AUTHOR]

Background: The Subglottic Cysts (SGCs) are a rare cause of respiratory distress in infants. Typical risk factors include male gender, extreme prematurity, gastro-oesophageal reflux and invasive ventilation, the latter being associated with mucosal damage and blockage of the subglottic cysts' ducts. We describe a case of acquired subglottic cysts in a premature infants presented with respiratory distress. Case presentation: A premature male infant was born at 25 weeks + 2 days with a history of monochorionic diamniotic twin pregnancy with twin-to-twin transfusion syndrome. During hospitalization, invasive mechanical ventilation was necessary for a total of 18 days; the patient was discharged at postmenstrual age of 40 weeks + 1 day in good condition. At 43 weeks post-menstrual age, he presented to our department with mixed stridor and worsening of respiratory dynamics. A laryngotracheoscopy evaluation was performed. The exam showed the presence of multiple SGCs causing an almost complete obstruction of the airway. Because of the significant reduction of the airway's patency, the child underwent a tracheotomy and thereafter cysts' removal using cold steel microinstruments. A better airway patency was restored although a slight glottic edema persisted. The histopathology confirmed the benign nature of the lesions. Successive controls showed a completely patent airway and absence of SGCs. Conclusion: In conclusion, SGCs should be considered in preterm infants with respiratory distress previously intubated, which cannot be explained by the most common causes. Early diagnosis and treatment are fundamental to reducing the morbidity and mortality associated with this disease. [ABSTRACT FROM AUTHOR]

The development of acute respiratory distress syndrome (ARDS) in sepsis is associated with substantial morbidity and mortality. However, the molecular pathogenesis underlying sepsis‐induced ARDS remains elusive. Neutrophil heterogeneity and dysfunction contribute to uncontrolled inflammation in patients with ARDS. A specific subset of neutrophils undergoing reverse transendothelial migration (rTEM), which is characterized by an activated phenotype, is implicated in the systemic dissemination of inflammation. Using single‐cell RNA sequencing (scRNA‐seq), it identified functionally activated neutrophils exhibiting the rTEM phenotype in the lung of a sepsis mouse model using cecal ligation and puncture. The prevalence of neutrophils with the rTEM phenotype is elevated in the blood of patients with sepsis‐associated ARDS and is positively correlated with disease severity. Mechanically, scRNA‐seq and proteomic analys revealed that inflamed endothelial cell (EC) released extracellular vesicles (EVs) enriched in karyopherin subunit beta‐1 (KPNB1), promoting abluminal‐to‐luminal neutrophil rTEM. Additionally, EC‐derived EVs are elevated and positively correlated with the proportion of rTEM neutrophils in clinical sepsis. Collectively, EC‐derived EV is identified as a critical regulator of neutrophil rTEM, providing insights into the contribution of rTEM neutrophils to sepsis‐associated lung injury. [ABSTRACT FROM AUTHOR]

Preclinical animal models are crucial for advancing the clinical management of acute respiratory distress syndrome (ARDS). However, there is a lack of positive findings from preclinical studies that translate into clinical practice. One possible reason for this is the inadequate optimization of positive end-expiratory pressure (PEEP) during injury development in animal models. Insufficient PEEP levels can lead to the inclusion of subjects with mild lung injury, resulting in erroneous conclusions. Therefore, it is important to prioritize PEEP optimization in preclinical ARDS models to achieve consistent and clinically relevant lung injury. A study conducted on an ovine model of ARDS found that optimizing PEEP during injury development can significantly alter injury levels and align them more accurately with clinical practice. Future preclinical studies should also incorporate clinically relevant adjunctive therapies to better replicate the complexity of ARDS in real-world scenarios. [Extracted from the article]

Acute lung injury (ALI) and its severe counterpart, acute respiratory distress syndrome (ARDS), are critical respiratory conditions with high mortality rates due primarily to acute and intense pulmonary inflammation. Despite significant research advances, effective pharmacological treatments for ALI and ARDS remain unavailable, highlighting an urgent need for therapeutic innovation. Notably, idiopathic pulmonary fibrosis (IPF) is a chronic, progressive disease characterized by the irreversible progression of fibrosis, which is initiated by repeated damage to the alveolar epithelium and leads to excessive extracellular matrix deposition. This condition is further complicated by dysregulated tissue repair and fibroblast dysfunction, exacerbating tissue remodeling processes and promoting progression to terminal pulmonary fibrosis. Similar to that noted for ALI and ARDS, treatment options for IPF are currently limited, with no specific drug therapy providing a cure. Histone deacetylase 3 (HDAC3), a notable member of the HDAC family with four splice variants (HD3a, -b, -g, and -d), plays multiple roles. HDAC3 regulates gene transcription through histone acetylation and adjusts nonhistone proteins posttranslationally, affecting certain mitochondrial and cytoplasmic proteins. Given its unique structure, HDAC3 impacts various physiological processes, such as inflammation, apoptosis, mitochondrial homeostasis, and macrophage polarization. This article explores the intricate role of HDAC3 in ALI/ARDS and IPF and evaluates its therapeutic potential the treatment of these severe pulmonary conditions. [ABSTRACT FROM AUTHOR]