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Background: Postoperative hypoxemia and pulmonary complications remain a frequent event after on-pump cardiac surgery and mostly characterized by pulmonary atelectasis. Surfactant dysfunction or hyposecretion happens prior to atelectasis formation, and sigh represents the strongest stimulus for surfactant secretion. The role of sigh breaths added to conventional lung protective ventilation in reducing postoperative hypoxemia and pulmonary complications among cardiac surgery is unknown. Methods: The perioperative sigh ventilation in cardiac surgery (E-SIGHT) trial is a single-center, two-arm, randomized controlled trial. In total, 192 patients scheduled for elective cardiac surgery with cardiopulmonary bypass (CPB) and aortic cross-clamp will be randomized into one of the two treatment arms. In the experimental group, besides conventional lung protective ventilation, sigh volumes producing plateau pressures of 35 cmH2O (or 40 cmH2O for patients with body mass index > 35 kg/m2) delivered once every 6 min from intubation to extubation. In the control group, conventional lung protective ventilation without preplanned recruitment maneuvers is used. Lung protective ventilation (LPV) consists of low tidal volumes (6–8 mL/kg of predicted body weight) and positive end-expiratory pressure (PEEP) setting according to low PEEP/FiO2 table for acute respiratory distress syndrome (ARDS). The primary endpoint is time-weighted average SpO2/FiO2 ratio during the initial post-extubation hour. Main secondary endpoint is the severity of postoperative pulmonary complications (PPCs) computed by postoperative day 7. Discussion: The E-SIGHT trial will be the first randomized controlled trial to evaluate the impact of perioperative sigh ventilation on the postoperative outcomes after on-pump cardiac surgery. The trial will introduce and assess a novel perioperative ventilation approach to mitigate the risk of postoperative hypoxemia and PPCs in patients undergoing cardiac surgery. Also provide the basis for a future larger trial aiming at verifying the impact of sigh ventilation on postoperative pulmonary complications. Trial registration: ClinicalTrials.gov NCT06248320. Registered on January 30, 2024. Last updated February 26, 2024. [ABSTRACT FROM AUTHOR]

Objective: This Study aims to investigate the risk factors of hypoglycemia in neonates through meta-analysis. Method: PubMed, Embase, Cochrane library, and Web of science databases were searched for case-control studies on risk factors for neonatal hypoglycemia. The search was done up to 1st October 2023 and Stata 15.0 was used for data analysis. Results: A total of 12 published studies were included, including 991 neonates in the hypoglycemic group and 4388 neonates in the non-hypoglycemic group. Meta-analysis results suggested caesarean section [OR = 1.90 95%CI (1.23, 2.92)], small gestational age[OR = 2.88, 95%CI (1.59, 5.20)], gestational diabetes [OR = 1.65, 95%CI (1.11, 2.46)], gestational hypertension[OR = 2,79, 95%CI (1.78, 4.35)] and respiratory distress syndrome[OR = 5.33, 95%CI (2.22, 12.84)] were risk factors for neonatal hypoglycemia. Conclusion: Based on the current study, we found that caesarean section, small gestational age, gestational diabetes, gestational hypertension, respiratory distress syndrome are risk factors for neonatal hypoglycemia. PROSPERO registration number: CRD42023472974. [ABSTRACT FROM AUTHOR]

Background: SARS-CoV-2 pneumonia can cause significant long-term radiological changes, even resembling pulmonary fibrosis. However, the risk factors for these long-term effects are unknown. This study aims to assess radiological abnormalities and their possible risk factors six months after hospital discharge due to COVID-19 pneumonia. Material and methods: This cross-sectional study in a tertiary hospital included adults admitted for COVID-19 pneumonia from March 2020 to February 2021, who underwent high-resolution computed tomography (HRCT) scans of the chest six months after hospital discharge. The primary outcome was radiological abnormalities on HRCT, while the main explanatory variables were drawn from the patient's medical history along with the disease course, analytical indicators, and the treatment received during admission. Results: The 189 included patients had a mean age of 61.5 years; 70.9% were male, and hypertension was the main comorbidity (45%). About two-thirds (67.2%) presented acute respiratory distress syndrome (ARDS). Most (97.9%) received systemic corticosteroid therapy, and 81% presented pathological findings on HRCT, most commonly ground glass (63.5%), followed by bronchial dilatation (36%) and subpleural bands (25.4%). The multivariable analysis showed that age was the main risk factor, associated with most radiological changes. Other factors were the duration of corticosteroid therapy for ground glass (adjusted odds ratio [aOR] 1.020) as well as a longer stay in the intensive care unit (ICU) (aOR 1.290) and high levels of IL-6 for bronchial dilation (aOR 1.002). Conclusion: Radiological involvement of the lungs six months after COVID-19 pneumonia is frequent, especially ground glass. Elderly patients with prolonged ICU admission and a significant inflammatory response measured by IL-6 are more likely to present worse radiological evolution and are candidates for radiological follow-up after COVID-19 pneumonia. [ABSTRACT FROM AUTHOR]

Background: Coronavirus disease 2019 originated in China and swiftly spread worldwide, posing a significant threat to public health. Caused by SARS-CoV-2, it manifests as a flu-like illness that can escalate to Acute Respiratory Distress Syndrome, potentially resulting in fatalities. In countries where HIV/Leishmania infantum is endemic, the occurrence of concurrent SARS-CoV-2/HIV/Leishmania infantum infections is a reality, prompting inquiries into appropriate clinical management. Case presentation: We present the case of a 48-year-old woman who was hospitalized for 36 days across three different hospitals in the state of Pernambuco, Brazil. She was diagnosed with SARS-CoV-2/HIV/L. infantum coinfection. The patient exhibited severe COVID-19 symptoms, including fever, productive cough, and dyspnea. Throughout her hospitalization, she experienced oxygen saturation levels of ≤ 93%, along with fluctuations in blood pressure, respiratory rate, and heart rate. Her blood tests revealed lymphopenia, leukopenia, and neutropenia, while laboratory results indicated abnormal levels of d-dimer, AST, ALT, lactate dehydrogenase, ferritin, and C-reactive protein. A computed tomography scan revealed 75% involvement of the lung parenchyma with patchy ground-glass opacities. Conclusion: Against all odds, the patient was discharged. The leukopenia associated with HIV/L. infantum may have played a decisive role. Further studies are necessary to better understand diagnostic strategies and clinical management measures for HIV/L. infantum coinfected patients who are susceptible to SARS-CoV-2 infection. [ABSTRACT FROM AUTHOR]

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

Background: This study aimed to evaluate the role of platelet count (PLT) in the prognosis of patients with acute respiratory distress syndrome (ARDS). Methods: The data were extracted from the Medical Information Mart for Intensive Care database (version 2.2). Patients diagnosed with ARDS according to criteria from Berlin Definition and had the platelet count (PLT) measured within the first day after intensive care unit admission were analyzed. Based on PLT, ARDS patients were divided into four groups: PLT ≤ 100 × 109/L, PLT 101–200 × 109/L, PLT 201–300 × 109/L, and PLT > 300 × 109/L. The primary outcome was 28-day mortality. Survival probabilities were analyzed using Kaplan–Meier. Furthermore, the association between PLT and mortality in ARDS patients was assessed using a univariate and multivariable Cox proportional hazards model. Results: Overall, the final analysis included 3,207 eligible participants with ARDS. According to the Kaplan–Meier curves for 28-day mortality of PLT, PLT ≤ 100 × 109/L was associated with a higher incidence of mortality (P = 0.001), the same trends were observed in the 60-day (P = 0.001) and 90‐day mortality (P = 0.001). In the multivariate model adjusted for the potential factors, the adjusted hazard ratio at PLT 101–200 × 109/L group, PLT 201–300 × 109/L, and PLT > 300 × 109/L was 0.681 [95% confidence interval (CI): 0.576–0.805, P < 0.001], 0.733 (95% CI: 0.604–0.889, P = 0.002), and 0.787 (95% CI: 0.624–0.994, P = 0.044) compared to the reference group (PLT ≤ 100 × 109/L), respectively. Similar relationships between the PLT ≤ 100 × 109/L group and 28-day mortality were obtained in most subgroups. Conclusion: PLT appeared to be an independent predictor of mortality in critically ill patients with ARDS. [ABSTRACT FROM AUTHOR]

Background: Acute respiratory distress syndrome (ARDS) after cardiac surgery is a severe respiratory complication with high mortality and morbidity. Traditional clinical approaches may lead to under recognition of this heterogeneous syndrome, potentially resulting in diagnosis delay. This study aims to develop and external validate seven machine learning (ML) models, trained on electronic health records data, for predicting ARDS after cardiac surgery. Methods: This multicenter, observational cohort study included patients who underwent cardiac surgery in the training and testing cohorts (data from Nanjing First Hospital), as well as those patients who had cardiac surgery in a validation cohort (data from Shanghai General Hospital). The number of important features was determined using the sliding windows sequential forward feature selection method (SWSFS). We developed a set of tree-based ML models, including Decision Tree, GBDT, AdaBoost, XGBoost, LightGBM, Random Forest, and Deep Forest. Model performance was evaluated using the area under the receiver operating characteristic curve (AUC) and Brier score. The SHapley Additive exPlanation (SHAP) techinque was employed to interpret the ML model. Furthermore, a comparison was made between the ML models and traditional scoring systems. ARDS is defined according to the Berlin definition. Results: A total of 1996 patients who had cardiac surgery were included in the study. The top five important features identified by the SWSFS were chronic obstructive pulmonary disease, preoperative albumin, central venous pressure_T4, cardiopulmonary bypass time, and left ventricular ejection fraction. Among the seven ML models, Deep Forest demonstrated the best performance, with an AUC of 0.882 and a Brier score of 0.809 in the validation cohort. Notably, the SHAP values effectively illustrated the contribution of the 13 features attributed to the model output and the individual feature's effect on model prediction. In addition, the ensemble ML models demonstrated better performance than the other six traditional scoring systems. Conclusions: Our study identified 13 important features and provided multiple ML models to enhance the risk stratification for ARDS after cardiac surgery. Using these predictors and ML models might provide a basis for early diagnostic and preventive strategies in the perioperative management of ARDS patients. [ABSTRACT FROM AUTHOR]

Background: This study aims to evaluate the association of metabolic syndrome (MetS) with the risk of all-cause mortality in elderly patients with acute respiratory distress syndrome (ARDS). Methods: Elderly ARDS patients (≥ 65 years) enrolled from our hospital between January 2018 and July 2023 were divided into the MetS group or the non-MetS group. The outcomes were 28-day and 90-day all-cause mortality rates in the total population and two subgroups stratified by age (65–75 years and ≥ 75 years). Multivariate Cox regression was employed to assess the association of MetS with all-cause mortality, after controlling for potential cofounding factors. Results: A total of 946 patients were divided into the MetS group (n = 410) or the non-MetS group (n = 536). The 28-day and 90-day all-cause mortality rates were significantly higher for MetS group compared to non-MetS group in the total population and two subgroups (all P < 0.01). Multivariate Cox regression indicated that MetS was significantly associated with a higher risk of 90-day all-cause mortality in the total population (HR = 1.62, 95% CI: 1.22–2.15; P < 0.01), and subgroups of patients aged 65–75 years (HR = 1.52, 95% CI: 1.04–2.21; P = 0.03) and ≥ 75 years (HR = 1.90, 95% CI: 1.23–2.94; P < 0.01). Moreover, with each MetS criterion added from 0 to 1 to 2, 3, and 4 of 4 criteria, both 28-day and 90-day all-cause mortality rates significantly increased (both P < 0.01). Conclusion: MetS was associated with higher risks of 28-day and 90-day all-cause mortality in elderly patients with ARDS. [ABSTRACT FROM AUTHOR]

Introduction: Morbidly obese patients occasionally have respiratory problems owing to hypoventilation. Airway pressure release ventilation is one of the ventilation settings often used for respiratory management of acute respiratory distress syndrome. However, previous reports indicating that airway pressure release ventilation may become a therapeutic measure as ventilator management in morbid obesity with respiratory failure is limited. We report a case of markedly improved oxygenation in a morbidly obese patient after airway pressure release ventilation application. Case report: A 50s-year-old Asian man (body mass index 41 kg/m2) presented with breathing difficulties. The patient had respiratory failure with a PaO2/FIO2 ratio of approximately 100 and severe atelectasis in the left lung, and ventilator management was initiated. Although the patient was managed on a conventional ventilate mode, oxygenation did not improve. On day 11, we changed the ventilation setting to airway pressure release ventilation, which showed marked improvement in oxygenation with a PaO2/FIO2 ratio of approximately 300. We could reduce sedative medication and apply respiratory rehabilitation. The patient was weaned from the ventilator on day 29 and transferred to another hospital for further rehabilitation on day 31. Conclusion: Airway pressure release ventilation ventilator management in morbidly obese patients may contribute to improving oxygenation and become one of the direct therapeutic measures in the early stage of critical care. [ABSTRACT FROM AUTHOR]

Background: COVID-19 infections can result in severe acute respiratory distress syndrome (ARDS) requiring admission to the intensive care unit (ICU). Cardiovascular manifestation or exacerbation of cardiovascular diseases could be another complication. Cardiac arrhythmias including New-Onset Atrial Fibrillation (NOAF), have been observed in hospitalized patients with COVID-19 infections. In this analysis, we aimed to systematically compare the complications associated with NOAF in critically ill COVID-19 patients admitted to the ICU. Methods: MEDLINE, EMBASE, Web of Science, the Cochrane database, http://www.ClinicalTrials.gov, Google Scholar and Mendeley were searched for relevant publications based on COVID-19 patients with NOAF admitted to the ICU. Complications including in-hospital mortality, ICU mortality, patients requiring mechanical ventilation, acute myocardial infarction, acute kidney injury, renal replacement therapy and pulmonary embolism were assessed. This is a meta-analysis and the analytical tool which was used was the RevMan software version 5.4. Risk ratios (RR) and 95% confidence intervals (CIs) were used to represent the data post analysis. Results: In critically ill COVID-19 patients with NOAF admitted to the ICU, the risks of ICU mortality (RR: 1.39, 95% CI: 1.07 – 1.80; P = 0.01), in-hospital mortality (RR: 1.56, 95% CI: 1.20 – 2.04; P = 0.001), patients requiring mechanical ventilation (RR: 1.32, 95% CI: 1.04 – 1.66; P = 0.02) were significantly higher when compared to the control group without AF. Acute myocardial infarction (RR: 1.54, 95% CI: 1.31 – 1.81; P = 0.00001), the risk for acute kidney injury (RR: 1.31, 95% CI: 1.11 – 1.55; P = 0.002) and patients requiring renal replacement therapy (RR: 1.83, 95% CI: 1.60 – 2.09; P = 0.00001) were also significantly higher in patients with NOAF. Conclusions: Critically ill COVID-19 patients with NOAF admitted to the ICU were at significantly higher risks of developing complications and death compared to similar patients without AF. [ABSTRACT FROM AUTHOR]

The lung is a highly mechanical organ as it is exposed to approximately 109 strain cycles, (where strain is the length change of tissue structure per unit initial length), with an approximately 4% amplitude change during quiet tidal breathing or 107 strain cycles at a 25% amplitude during heavy exercises, sighs, and deep inspirations. These mechanical indices have been reported to become aberrant in lung diseases such as acute respiratory distress syndrome (ARDS), pulmonary hypertension, bronchopulmonary dysplasia (BPD), idiopathic pulmonary fibrosis (IPF), and asthma. Through recent innovations, various in vitro systems/bioreactors used to mimic the lung's mechanical strain have been developed. Among these, the Flexcell tension system which is composed of bioreactors that utilize a variety of programs in vitro to apply static and cyclic strain on different cell-types established as 2D monolayer cultures or cell-embedded 3D hydrogel models, has enabled the assessment of the response of different cells such as fibroblasts to the lung's mechanical strain in health and disease. Fibroblasts are the main effector cells responsible for the production of extracellular matrix (ECM) proteins to repair and maintain tissue homeostasis and are implicated in the excessive deposition of matrix proteins that leads to lung fibrosis. In this review, we summarise, studies that have used the Flexcell tension bioreactor to assess effects of the mechanical lung on the structure, function, and phenotype of lung fibroblasts in homeostatic conditions and abnormal environments associated with lung injury and disease. We show that these studies have revealed that different strain conditions regulate fibroblast proliferation, ECM protein production, and inflammation in normal repair and the diseased lung. [ABSTRACT FROM AUTHOR]

Background: Despite the significance and prevalence of acute respiratory distress syndrome (ARDS), its detection remains highly variable and inconsistent. In this work, we aim to develop an algorithm (ARDSFlag) to automate the diagnosis of ARDS based on the Berlin definition. We also aim to develop a visualization tool that helps clinicians efficiently assess ARDS criteria. Methods: ARDSFlag applies machine learning (ML) and natural language processing (NLP) techniques to evaluate Berlin criteria by incorporating structured and unstructured data in an electronic health record (EHR) system. The study cohort includes 19,534 ICU admissions in the Medical Information Mart for Intensive Care III (MIMIC-III) database. The output is the ARDS diagnosis, onset time, and severity. Results: ARDSFlag includes separate text classifiers trained using large training sets to find evidence of bilateral infiltrates in radiology reports (accuracy of 91.9%±0.5%) and heart failure/fluid overload in radiology reports (accuracy 86.1%±0.5%) and echocardiogram notes (accuracy 98.4%±0.3%). A test set of 300 cases, which was blindly and independently labeled for ARDS by two groups of clinicians, shows that ARDSFlag generates an overall accuracy of 89.0% (specificity = 91.7%, recall = 80.3%, and precision = 75.0%) in detecting ARDS cases. Conclusion: To our best knowledge, this is the first study to focus on developing a method to automate the detection of ARDS. Some studies have developed and used other methods to answer other research questions. Expectedly, ARDSFlag generates a significantly higher performance in all accuracy measures compared to those methods. [ABSTRACT FROM AUTHOR]

Background: Morphine relieves dyspnea in various clinical circumstances. Whether or not this applies to patients admitted to intensive care units (ICUs) for acute respiratory failure (ARF) is unknown. We evaluated the efficacy and safety of low-dose morphine on dyspnea in patients admitted to the ICU for ARF. Methods: In this single-center, double-blind, phase 2, randomized, controlled trial, we assigned non-intubated adults admitted to the ICU for ARF with severe dyspnea, defined by a visual analog scale for dyspnea (dyspnea-VAS) from zero (no dyspnea) to 100 mm (worst imaginable dyspnea) ≥40 mm, to receive a low dose of Morphine Hydrochloride (intravenous titration followed by subcutaneous relay) or Placebo. All patients received standard therapy, including etiological treatment and non-invasive respiratory support. Results: Twenty-two patients were randomized, 11 in each group. The average dyspnea (median [interquartile range]) over 24 hours did not significantly differ between the two groups (40 [25 – 43] mm in the Morphine group vs. 40 [36 – 49] mm in the Placebo group, p=0.411). Dyspnea-VAS was lower in the Morphine group than in the Placebo group at the end of intravenous titration (30 [11 – 30] vs. 35 [30 – 44], p=0.044) and four hours later (18 [10 – 29] vs. 50 [30 – 60], p=0.043). The cumulative probability of intubation was higher in the Morphine group than in the Placebo group (p=0.046) Conclusion: In this phase 2 pilot trial, morphine did not improve 24-hour average dyspnea in adult patients with ARF, even though it had a statistically significant immediate effect. Of concern, Morphine use was associated with a higher intubation rate. Trial registration: The protocol was declared on the ClinicalTrial.gov database (no. NCT04358133) and was published in September 2022. [ABSTRACT FROM AUTHOR]

Peripheral intravenous central catheter (PICC) is a common tool for intravenous infusion for children who need central venous access. Although it is safe for physicians and nurses to place, complications like infection, occlusion, phlebitis, and bleeding can occur. We report a 5-month-old infant who suffered respiratory failure caused by catheter malposition resulting in massive fluid infusion into the thoracic cavity. Point-of-care ultrasound (POCUS) was utilized to identify a massive pleural effusion that prompted urgent drainage. Complications related to PICC in pediatric patients are not common but difficult to immediately identify sometimes. Therefore, careful attention should be paid by physicians to identify and reduce the risk of complications associated with PICC. Thus, visual tools are strongly advised to enhance the safety of invasive procedures. [ABSTRACT FROM AUTHOR]

Background: Lung ultrasound (LUS) in an emerging technique used in the intensive care unit (ICU). The derivative LUS aeration score has been shown to have associations with mortality in invasively ventilated patients. This study assessed the predictive value of baseline and early changes in LUS aeration scores in critically ill invasively ventilated patients with and without ARDS (Acute Respiratory Distress Syndrome) on 30- and 90-day mortality. Methods: This is a post hoc analysis of a multicenter prospective observational cohort study, which included patients admitted to the ICU with an expected duration of ventilation for at least 24 h. We restricted participation to patients who underwent a 12-region LUS exam at baseline and had the primary endpoint (30-day mortality) available. Logistic regression was used to analyze the primary and secondary endpoints. The analysis was performed for the complete patient cohort and for predefined subgroups (ARDS and no ARDS). Results: A total of 442 patients were included, of whom 245 had a second LUS exam. The baseline LUS aeration score was not associated with mortality (1.02 (95% CI: 0.99 – 1.06), p = 0.143). This finding was not different in patients with and in patients without ARDS. Early deterioration of the LUS score was associated with mortality (2.09 (95% CI: 1.01 – 4.3), p = 0.046) in patients without ARDS, but not in patients with ARDS or in the complete patient cohort. Conclusion: In this cohort of critically ill invasively ventilated patients, the baseline LUS aeration score was not associated with 30- and 90-day mortality. An early change in the LUS aeration score was associated with mortality, but only in patients without ARDS. Trial registration: ClinicalTrials.gov, ID NCT04482621. [ABSTRACT FROM AUTHOR]

Mesenchymal stem and stromal cells (MSCs) hold potential to treat a broad range of clinical indications, but clinical translation has been limited to date due in part to challenges with batch-to-batch reproducibility of potential critical quality attributes (pCQAs) that can predict potency/efficacy. Here, we designed and implemented a microcarrier-microbioreactor approach to cell therapy manufacturing, specific to anchorage-dependent cells such as MSCs. We sought to assess whether increased control of the biochemical and biophysical environment had the potential to create product with consistent presentation and elevated expression of pCQAs relative to established manufacturing approaches in tissue culture polystyrene (TCPS) flasks. First, we evaluated total cell yield harvested from dissolvable, gelatin microcarriers within a microbioreactor cassette (Mobius Breez) or a flask control with matched initial cell seeding density and culture duration. Next, we identified 24 genes implicated in a therapeutic role for a specific motivating indication, acute respiratory distress syndrome (ARDS); expression of these genes served as our pCQAs for initial in vitro evaluation of product potency. We evaluated mRNA expression for three distinct donors to assess inter-donor repeatability, as well as for one donor in three distinct batches to assess within-donor, inter-batch variability. Finally, we assessed gene expression at the protein level for a subset of the panel to confirm successful translation. Our results indicated that MSCs expanded with this microcarrier-microbioreactor approach exhibited reasonable donor-to-donor repeatability and reliable batch-to-batch reproducibility of pCQAs. Interestingly, the baseline conditions of this microcarrier-microbioreactor approach also significantly improved expression of several key pCQAs at the gene and protein expression levels and reduced total media consumption relative to TCPS culture. This proof-of-concept study illustrates key benefits of this approach to therapeutic cell process development for MSCs and other anchorage-dependent cells that are candidates for cell therapies. [ABSTRACT FROM AUTHOR]

Background: End-expiratory lung volume (EELV) has been observed to decrease in acute respiratory distress syndrome (ARDS). Yet, research investigating EELV in patients with COVID-19 associated ARDS (CARDS) remains limited. It is unclear whether EELV could serve as a potential metric for monitoring disease progression and identifying patients with ARDS at increased risk of adverse outcomes. Study design and methods: This retrospective study included mechanically ventilated patients diagnosed with CARDS during the initial phase of epidemic control in Shanghai. EELV was measured using the nitrogen washout-washin technique within 48 h post-intubation, followed by regular assessments every 3–4 days. Chest CT scans, performed within a 24-hour window around each EELV measurement, were analyzed using AI software. Differences in patient demographics, clinical data, respiratory mechanics, EELV, and chest CT findings were assessed using linear mixed models (LMM). Results: Out of the 38 patients enrolled, 26.3% survived until discharge from the ICU. In the survivor group, EELV, EELV/predicted body weight (EELV/PBW) and EELV/predicted functional residual capacity (EELV/preFRC) were significantly higher than those in the non-survivor group (survivor group vs. non-survivor group: EELV: 1455 vs. 1162 ml, P = 0.049; EELV/PBW: 24.1 vs. 18.5 ml/kg, P = 0.011; EELV/preFRC: 0.45 vs. 0.34, P = 0.005). Follow-up assessments showed a sustained elevation of EELV/PBW and EELV/preFRC among the survivors. Additionally, EELV exhibited a positive correlation with total lung volume and residual lung volume, while demonstrating a negative correlation with lesion volume determined through chest CT scans analyzed using AI software. Conclusion: EELV is a useful indicator for assessing disease severity and monitoring the prognosis of patients with CARDS. [ABSTRACT FROM AUTHOR]

Background: Adherence with follow-up appointments after a pediatric intensive care unit (PICU) admission is likely a key component in managing post-PICU sequalae. However, prior work on PICU follow-up adherence is limited. The objective of this study is to identify hospitalization characteristics, discharge child health metrics, and follow-up characteristics associated with full adherence with recommended follow-up at a quaternary care center after a PICU admission due to respiratory failure. Methods: We conducted a retrospective cohort study of patients ≤ 18 years with respiratory failure admitted between 1/2013–12/2014 to a quaternary care PICU. Post-hospitalization full adherence with recommended follow-up in the two years post discharge (1/2013–3/2017) at the quaternary care center was quantified and compared by demographics, baseline child health metrics, hospitalization characteristics, discharge child health metrics, and follow-up characteristics in bivariate and multivariate analyses. Patients were dichotomized into being non-adherent with follow-up (patients who attended less than 100% of recommended appointments at the quaternary care center) and fully adherent (patients who attended 100% of recommended appointments at the quaternary care center). Results: Of 155 patients alive at hospital discharge, 140 (90.3%) were recommended to follow-up at the quaternary care center. Of the 140 patients with recommended follow-up at the quaternary care center, 32.1% were non-adherent with follow-up and 67.9% were fully adherent. In a multivariable logistic regression model, each additional recommended unique follow-up appointment was associated with lower odds of being fully adherent with follow-up (OR 0.74, 95% CI 0.60–0.91, p = 0.005), and each 10% increase in the proportion of appointments scheduled before discharge was associated with higher odds of being fully adherent with follow-up (OR 1.02, 95% CI 1.01–1.03, p = 0.004). Conclusions: After admission for acute respiratory failure, only two-thirds of children were fully adherent with recommended follow-up at a quaternary care center. Our findings suggest that limiting the recommended follow-up to only key essential healthcare providers and working to schedule as many appointments as possible before discharge could improve follow-up adherence. However, a better understanding of the factors that lead to non-adherence with follow-up appointments is needed to inform broader system-level approaches could help improve PICU follow-up adherence. [ABSTRACT FROM AUTHOR]

Background: Prior research has highlighted the involvement of a transcriptional complex comprising C-terminal binding protein 2 (CtBP2), histone acetyltransferase p300, and nuclear factor kappa B (NF-κB) in the transactivation of proinflammatory cytokine genes, contributing to inflammation in mice with acute respiratory distress syndrome (ARDS). Nonetheless, it remains uncertain whether the therapeutic targeting of the CtBP2-p300-NF-κB complex holds potential for ARDS suppression. Methods: An ARDS mouse model was established using lipopolysaccharide (LPS) exposure. RNA-Sequencing (RNA-Seq) was performed on ARDS mice and LPS-treated cells with CtBP2, p300, and p65 knockdown. Small molecules inhibiting the CtBP2-p300 interaction were identified through AlphaScreen. Gene and protein expression levels were quantified using RT-qPCR and immunoblots. Tissue damage was assessed via histological staining. Key findings: We elucidated the specific role of the CtBP2-p300-NF-κB complex in proinflammatory gene regulation. RNA-seq analysis in LPS-challenged ARDS mice and LPS-treated CtBP2-knockdown (CtBP2KD), p300KD, and p65KD cells revealed its significant impact on proinflammatory genes with minimal effects on other NF-κB targets. Commercial inhibitors for CtBP2, p300, or NF-κB exhibited moderate cytotoxicity in vitro and in vivo, affecting both proinflammatory genes and other targets. We identified a potent inhibitor, PNSC928, for the CtBP2-p300 interaction using AlphaScreen. PNSC928 treatment hindered the assembly of the CtBP2-p300-NF-κB complex, substantially downregulating proinflammatory cytokine gene expression without observable cytotoxicity in normal cells. In vivo administration of PNSC928 significantly reduced CtBP2-driven proinflammatory gene expression in ARDS mice, alleviating inflammation and lung injury, ultimately improving ARDS prognosis. Conclusion: Our results position PNSC928 as a promising therapeutic candidate to specifically target the CtBP2-p300 interaction and mitigate inflammation in ARDS management. [ABSTRACT FROM AUTHOR]

Background: COVID-19 is a new infectious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS CoV-2). Since the outbreak in December 2019, it has caused an unprecedented world pandemic, leading to a global human health crisis. Although SARS CoV-2 mainly affects the lungs, causing interstitial pneumonia and severe acute respiratory distress syndrome, a number of patients often have extensive clinical manifestations, such as gastrointestinal symptoms, cardiovascular damage and renal dysfunction. Purpose: This review article discusses the pathogenic mechanisms of cardiovascular damage in COVID-19 patients and provides some useful suggestions for future clinical diagnosis, treatment and prevention. Methods: An English-language literature search was conducted in PubMed and Web of Science databases up to 12th April, 2024 for the terms "COVID-19", "SARS CoV-2", "cardiovascular damage", "myocardial injury", "myocarditis", "hypertension", "arrhythmia", "heart failure" and "coronary heart disease", especially update articles in 2023 and 2024. Salient medical literatures regarding the cardiovascular damage of COVID-19 were selected, extracted and synthesized. Results: The most common cardiovascular damage was myocarditis and pericarditis, hypertension, arrhythmia, myocardial injury and heart failure, coronary heart disease, stress cardiomyopathy, ischemic stroke, blood coagulation abnormalities, and dyslipidemia. Two important pathogenic mechanisms of the cardiovascular damage may be direct viral cytotoxicity as well as indirect hyperimmune responses of the body to SARS CoV-2 infection. Conclusions: Cardiovascular damage in COVID-19 patients is common and portends a worse prognosis. Although the underlying pathophysiological mechanisms of cardiovascular damage related to COVID-19 are not completely clear, two important pathogenic mechanisms of cardiovascular damage may be the direct damage of the SARSCoV-2 infection and the indirect hyperimmune responses. [ABSTRACT FROM AUTHOR]

Background: The impact of chronic obstructive pulmonary disease (COPD) on outcome in perioperative organ injury (POI) has not yet been investigated sufficiently. Methods: This retrospective cohort study analysed data of surgical patients with POI, namely delirium, stroke, acute myocardial infarction, acute respiratory distress syndrome, acute liver injury (ALI), or acute kidney injury (AKI), in Germany between 2015 and 2019. We compared in-hospital mortality, hospital length of stay (HLOS) and perioperative ventilation time (VT) in patients with and without COPD. Results: We analysed the data of 1,642,377 surgical cases with POI of which 10.8% suffered from COPD. In-hospital mortality was higher (20.6% vs. 15.8%, p < 0.001) and HLOS (21 days (IQR, 12–34) vs. 16 days (IQR, 10–28), p < 0.001) and VT (199 h (IQR, 43–547) vs. 125 h (IQR, 32–379), p < 0.001) were longer in COPD patients. Within the POI examined, AKI was the most common POI (57.8%), whereas ALI was associated with the highest mortality (54.2%). Regression analysis revealed that COPD was associated with a slightly higher risk of in-hospital mortality (OR, 1.19; 95% CI:1.18–1.21) in patients with any POI. Conclusions: COPD in patients with POI is associated with higher mortality, longer HLOS and longer VT. Especially patients suffering from ALI are susceptible to the detrimental effects of COPD on adverse outcome. [ABSTRACT FROM AUTHOR]

Objective: This comparative analysis aimed to investigate the efficacy of Sivelestat Sodium Hydrate (SSH) combined with Ulinastatin (UTI) in the treatment of sepsis with acute respiratory distress syndrome (ARDS). Methods: A control group and an observation group were formed with eighty-four cases of patients with sepsis with ARDS, with 42 cases in each group. The control group was intravenously injected with UTI based on conventional treatment, and the observation group was injected with SSH based on the control group. Both groups were treated continuously for 7 days, and the treatment outcomes and efficacy of both groups were observed. The Murray Lung Injury Score (MLIS), Sequential Organ Failure Assessment (SOFA), and Acute Physiology and Chronic Health Evaluation II (APACHE II) were compared. Changes in respiratory function, inflammatory factors, and oxidative stress indicators were assessed. The occurrence of adverse drug reactions was recorded. Results: The total effective rate in the observation group (95.24%) was higher than that in the control group (80.95%) (P < 0.05). The mechanical ventilation time, intensive care unit (ICU) hospitalization time, and duration of antimicrobial medication in the observation group were shorter and multiple organ dysfunction syndrome incidence was lower than those in the control group (P < 0.05). The mortality rate of patients in the observation group (35.71%) was lower than that in the control group (52.38%), but there was no statistically significant difference between the two groups (P > 0.05). MLIS, SOFA, and APACHE II scores in the observation group were lower than the control group (P < 0.05). After treatment, respiratory function, inflammation, and oxidative stress were improved in the observation group (P < 0.05). Adverse reactions were not significantly different between the two groups (P > 0.05). Conclusion: The combination of SSH plus UTI improves lung injury and pulmonary ventilation function, and reduces inflammation and oxidative stress in patients with sepsis and ARDS. [ABSTRACT FROM AUTHOR]

Background: Limited evidence exists regarding the link between platelet count and 30-day in-hospital mortality in acute respiratory failure (ARF) patients. Thus, this study aims to investigate this association among ICU patients experiencing acute respiratory failure. Methods: We conducted a retrospective cohort study across multiple centers, utilizing data from the US eICU-CRD v2.0 database covering 22,262 patients with ARF in the ICU from 2014 to 2015. Our aim was to investigate the correlation between platelet count and 30-day in-hospital mortality using binary logistic regression, subgroup analyses, and smooth curve fitting. Results: The 30-day in-hospital mortality rate was 19.73% (4393 out of 22,262), with a median platelet count of 213 × 109/L. After adjusting for covariates, our analysis revealed an inverse association between platelet count and 30-day in-hospital mortality (OR = 0.99, 95% CI 0.99, 0.99). Subgroup analyses supported the robustness of these findings. Furthermore, a nonlinear relationship was identified between platelet count and 30-day in-hospital mortality, with the inflection point at 120 × 109/L. Below the inflection point, the effect size (OR) was 0.89 (0.87, 0.91), indicating a significant association. However, beyond this point, the relationship was not statistically significant. Conclusion: This study establishes a clear negative association between platelet count and 30-day in-hospital mortality among ICU patients with ARF. Furthermore, we have identified a nonlinear relationship with saturation effects, indicating that among ICU patients with acute respiratory failure, the lowest 30-day in-hospital mortality rate occurs when the baseline platelet count is approximately 120 × 109/L. [ABSTRACT FROM AUTHOR]

Background: Inflammation and endothelial barrier dysfunction are the major pathophysiological changes in acute respiratory distress syndrome (ARDS). Sphingosine-1-phosphate receptor 3 (S1PR3), a G protein-coupled receptor, has been found to mediate inflammation and endothelial cell (EC) integrity. However, the function of S1PR3 in ARDS has not been fully elucidated. Methods: We used a murine lipopolysaccharide (LPS)-induced ARDS model and an LPS- stimulated ECs model to investigate the role of S1PR3 in anti-inflammatory effects and endothelial barrier protection during ARDS. Results: We found that S1PR3 expression was increased in the lung tissues of mice with LPS-induced ARDS. TY-52156, a selective S1PR3 inhibitor, effectively attenuated LPS-induced inflammation by suppressing the expression of proinflammatory cytokines and restored the endothelial barrier by repairing adherens junctions and reducing vascular leakage. S1PR3 inhibition was achieved by an adeno-associated virus in vivo and a small interfering RNA in vitro. Both the in vivo and in vitro studies demonstrated that pharmacological or genetic inhibition of S1PR3 protected against ARDS by inhibiting the NF-κB pathway and improving mitochondrial oxidative phosphorylation. Conclusions: S1PR3 inhibition protects against LPS-induced ARDS via suppression of pulmonary inflammation and promotion of the endothelial barrier by inhibiting NF-κB and improving mitochondrial oxidative phosphorylation, indicating that S1PR3 is a potential therapeutic target for ARDS. [ABSTRACT FROM AUTHOR]

Aim: Acute respiratory distress syndrome or ARDS is an acute, severe form of respiratory failure characterised by poor oxygenation and bilateral pulmonary infiltrates. Advancements in signal processing and machine learning have led to promising solutions for classification, event detection and predictive models in the management of ARDS. Method: In this review, we provide systematic description of different studies in the application of Machine Learning (ML) and artificial intelligence for management, prediction, and classification of ARDS. We searched the following databases: Google Scholar, PubMed, and EBSCO from 2009 to 2023. A total of 243 studies was screened, in which, 52 studies were included for review and analysis. We integrated knowledge of previous work providing the state of art and overview of explainable decision models in machine learning and have identified areas for future research. Results: Gradient boosting is the most common and successful method utilised in 12 (23.1%) of the studies. Due to limitation of data size available, neural network and its variation is used by only 8 (15.4%) studies. Whilst all studies used cross validating technique or separated database for validation, only 1 study validated the model with clinician input. Explainability methods were presented in 15 (28.8%) of studies with the most common method is feature importance which used 14 times. Conclusion: For databases of 5000 or fewer samples, extreme gradient boosting has the highest probability of success. A large, multi-region, multi centre database is required to reduce bias and take advantage of neural network method. A framework for validating with and explaining ML model to clinicians involved in the management of ARDS would be very helpful for development and deployment of the ML model. [ABSTRACT FROM AUTHOR]

Background: Previously identified phenotypes of acute respiratory distress syndrome (ARDS) could not reveal the dynamic change of phenotypes over time. We aimed to identify novel clinical phenotypes in ARDS using trajectories of fluid balance, to test whether phenotypes respond differently to different treatment, and to develop a simplified model for phenotype identification. Methods: FACTT (conservative vs liberal fluid management) trial was classified as a development cohort, joint latent class mixed models (JLCMMs) were employed to identify trajectories of fluid balance. Heterogeneity of treatment effect (HTE) for fluid management strategy across phenotypes was investigated. We also constructed a parsimonious probabilistic model using baseline data to predict the fluid trajectories in the development cohort. The trajectory groups and the probabilistic model were externally validated in EDEN (initial trophic vs full enteral feeding) trial. Results: Using JLCMM, we identified two trajectory groups in the development cohort: Class 1 (n = 758, 76.4% of the cohort) had an early positive fluid balance, but achieved negative fluid balance rapidly, and Class 2 (n = 234, 24.6% of the cohort) was characterized by persistent positive fluid balance. Compared to Class 1 patients, patients in Class 2 had significantly higher 60-day mortality (53.5% vs. 17.8%, p < 0.001), and fewer ventilator-free days (0 vs. 20, p < 0.001). A significant HTE between phenotypes and fluid management strategies was observed in the FACTT. An 8-variables model was derived for phenotype assignment. Conclusions: We identified and validated two novel clinical trajectories for ARDS patients, with both prognostic and predictive enrichment. The trajectories of ARDS can be identified with simple classifier models. [ABSTRACT FROM AUTHOR]

Background: Acute respiratory distress syndrome (ARDS) is a severe and fatal disease. Although mesenchymal stem cell (MSC)-based therapy has shown remarkable efficacy in treating ARDS in animal experiments, clinical outcomes have been unsatisfactory, which may be attributed to the influence of the lung microenvironment during MSC administration. Extracellular vesicles (EVs) derived from endothelial cells (EC-EVs) are important components of the lung microenvironment and play a crucial role in ARDS. However, the effect of EC-EVs on MSC therapy is still unclear. In this study, we established lipopolysaccharide (LPS) - induced acute lung injury model to evaluate the impact of EC-EVs on the reparative effects of bone marrow-derived MSC (BM-MSC) transplantation on lung injury and to unravel the underlying mechanisms. Methods: EVs were isolated from bronchoalveolar lavage fluid of mice with LPS - induced acute lung injury and patients with ARDS using ultracentrifugation. and the changes of EC-EVs were analysed using nanoflow cytometry analysis. In vitro assays were performed to establish the impact of EC-EVs on MSC functions, including cell viability and migration, while in vivo studies were performed to validate the therapeutic effect of EC-EVs on MSCs. RNA-Seq analysis, small interfering RNA (siRNA), and a recombinant lentivirus were used to investigate the underlying mechanisms. Results: Compared with that in non-ARDS patients, the quantity of EC-EVs in the lung microenvironment was significantly greater in patients with ARDS. EVs derived from lipopolysaccharide-stimulated endothelial cells (LPS-EVs) significantly decreased the viability and migration of BM-MSCs. Furthermore, engrafting BM-MSCs pretreated with LPS-EVs promoted the release of inflammatory cytokines and increased pulmonary microvascular permeability, aggravating lung injury. Mechanistically, LPS-EVs reduced the expression level of isocitrate dehydrogenase 2 (IDH2), which catalyses the formation of α-ketoglutarate (α-KG), an intermediate product of the tricarboxylic acid (TCA) cycle, in BM-MSCs. α-KG is a cofactor for ten-eleven translocation (TET) enzymes, which catalyse DNA hydroxymethylation in BM-MSCs. Conclusions: This study revealed that EC-EVs in the lung microenvironment during ARDS can affect the therapeutic efficacy of BM-MSCs through the IDH2/TET pathway, providing potential strategies for improving the therapeutic efficacy of MSC-based therapy in the clinic. [ABSTRACT FROM AUTHOR]

Background: Acute respiratory distress syndrome (ARDS) is characterized by alveolar edema that can progress to septal fibrosis. Mechanical ventilation can augment lung injury, termed ventilator-induced lung injury (VILI). Connective tissue growth factor (CTGF), a mediator of fibrosis, is increased in ARDS patients. Blocking CTGF inhibits fibrosis and possibly vascular leakage. This study investigated whether neutralizing CTGF reduces pulmonary edema in VILI. Methods: Following LPS administration, rats were mechanically ventilated for 6 h with low (6 mL/kg; low VT) or moderate (10 mL/kg; mod VT) tidal volume and treated with a neutralizing CTGF antibody (FG-3154) or placebo lgG (vehicle). Control rats without LPS were ventilated for 6 h with low VT. Lung wet-to-dry weight ratio, FITC-labeled dextran permeability, histopathology, and soluble RAGE were determined. Results: VILI was characterized by reduced PaO2/FiO2 ratio (low VT: 540 [381–661] vs. control: 693 [620–754], p < 0.05), increased wet-to-dry weight ratio (low VT: 4.8 [4.6–4.9] vs. control: 4.5 [4.4–4.6], p < 0.05), pneumonia (low VT: 30 [0–58] vs. control: 0 [0–0]%, p < 0.05) and interstitial inflammation (low VT: 2 [1–3] vs. control: 1 [0–1], p < 0.05). FG-3154 did not affect wet-to-dry weight ratio (mod VT + FG-3154: 4.8 [4.7–5.0] vs. mod VT + vehicle: 4.8 [4.8–5.0], p > 0.99), extravasated dextrans (mod VT + FG-3154: 0.06 [0.04–0.09] vs. mod VT + vehicle: 0.04 [0.03–0.09] µg/mg tissue, p > 0.99), sRAGE (mod VT + FG-3154: 1865 [1628–2252] vs. mod VT + vehicle: 1885 [1695–2159] pg/mL, p > 0.99) or histopathology. Conclusions: 'Double hit' VILI was characterized by inflammation, impaired oxygenation, pulmonary edema and histopathological lung injury. Blocking CTGF does not improve oxygenation nor reduce pulmonary edema in rats with VILI. [ABSTRACT FROM AUTHOR]

Background: In patients with chronic obstructive pulmonary disease (COPD) and acute respiratory failure, approximately 10% of them are considered to be at high risk for prolonged mechanical ventilation (PMV, > 21 days). PMV have been identified as independent predictors of unfavorable outcomes. Our previous study revealed that patients aged 70 years older and COPD severity were at a significantly higher risk for PMV. We aimed to analyze the impact of comorbidities and their associated risks in patients with COPD who require PMV. Methods: The data used in this study was collected from Kaohsiung Medical University Hospital Research Database. The COPD subjects were the patients first diagnosed COPD (index date) between January 1, 2012 and December 31, 2020. The exclusion criteria were the patients with age less than 40 years, PMV before the index date or incomplete records. COPD and non-COPD patients, matched controls were used by applying the propensity score matching method. Results: There are 3,744 eligible patients with COPD in the study group. The study group had a rate of 1.6% (60 cases) patients with PMV. The adjusted HR of PMV was 2.21 (95% CI 1.44–3.40; P < 0.001) in the COPD patients than in non-COPD patients. Increased risks of PMV were found significantly for patients with diabetes mellitus (aHR 4.66; P < 0.001), hypertension (aHR 3.20; P = 0.004), dyslipidemia (aHR 3.02; P = 0.015), congestive heart failure (aHR 6.44; P < 0.001), coronary artery disease (aHR 3.11; P = 0.014), stroke (aHR 6.37; P < 0.001), chronic kidney disease (aHR 5.81 P < 0.001) and Dementia (aHR 5.78; P < 0.001). Conclusions: Age, gender, and comorbidities were identified as significantly higher risk factors for PMV occurrence in the COPD patients compared to the non-COPD patients. Beyond age, comorbidities also play a crucial role in PMV in COPD. [ABSTRACT FROM AUTHOR]

Background: Conventional Mechanical ventilation modes used for individuals suffering from acute respiratory distress syndrome have the potential to exacerbate lung injury through regional alveolar overinflation and/or repetitive alveolar collapse with shearing, known as atelectrauma. Animal studies have demonstrated that airway pressure release ventilation (APRV) offers distinct advantages over conventional mechanical ventilation modes. However, the methodologies for implementing APRV vary widely, and the findings from clinical studies remain controversial. This study (APRVplus trial), aims to assess the impact of an early pathophysiology-driven APRV ventilation approach compared to a low tidal volume ventilation (LTV) strategy on the prognosis of patients with moderate to severe ARDS. Methods: The APRVplus trial is a prospective, multicenter, randomized clinical trial, building upon our prior single-center study, to enroll 840 patients from at least 35 hospitals in China. This investigation plans to compare the early pathophysiology-driven APRV ventilation approach with the control intervention of LTV lung-protective ventilation. The primary outcome measure will be all-cause mortality at 28 days after randomization in the intensive care units (ICU). Secondary outcome measures will include assessments of oxygenation, and physiology parameters at baseline, as well as on days 1, 2, and 3. Additionally, clinical outcomes such as ventilator-free days at 28 days, duration of ICU and hospital stay, ICU and hospital mortality, and the occurrence of adverse events will be evaluated. Trial ethics and dissemination: The research project has obtained approval from the Ethics Committee of West China Hospital of Sichuan University (2019-337). Informed consent is required. The results will be submitted for publication in a peer-reviewed journal and presented at one or more scientific conferences. Trial registration: The study was registered at Clinical Trials.gov (NCT03549910) on June 8, 2018. [ABSTRACT FROM AUTHOR]

Background: The Berlin definition of acute respiratory distress syndrome (ARDS) includes only clinical characteristics. Understanding unique patient pathobiology may allow personalized treatment. We aimed to define and describe ARDS phenotypes/endotypes combining clinical and pathophysiologic parameters from a Canadian ARDS cohort. Methods: A cohort of adult ARDS patients from multiple sites in Calgary, Canada, had plasma cytokine levels and clinical parameters measured in the first 24 h of ICU admission. We used a latent class model (LCM) to group the patients into several ARDS subgroups and identified the features differentiating those subgroups. We then discuss the subgroup effect on 30 day mortality. Results: The LCM suggested three subgroups (n1 = 64, n2 = 86, and n3 = 30), and 23 out of 69 features made these subgroups distinct. The top five discriminating features were IL-8, IL-6, IL-10, TNF-a, and serum lactate. Mortality distinctively varied between subgroups. Individual clinical characteristics within the subgroup associated with mortality included mean PaO2/FiO2 ratio, pneumonia, platelet count, and bicarbonate negatively associated with mortality, while lactate, creatinine, shock, chronic kidney disease, vasopressor/ionotropic use, low GCS at admission, and sepsis were positively associated. IL-8 and Apache II were individual markers strongly associated with mortality (Area Under the Curve = 0.84). Perspective: ARDS subgrouping using biomarkers and clinical characteristics is useful for categorizing a heterogeneous condition into several homogenous patient groups. This study found three ARDS subgroups using LCM; each subgroup has a different level of mortality. This model may also apply to developing further trial design, prognostication, and treatment selection. [ABSTRACT FROM AUTHOR]

Background: Extracorporeal membrane oxygenation (ECMO) is a rescue therapy in patients with severe acute respiratory distress syndrome (ARDS) secondary to COVID-19. While bleeding and thrombosis complicate ECMO, these events may also occur secondary to COVID-19. Data regarding bleeding and thrombotic events in COVID-19 patients on ECMO are sparse. Methods: Using the COVID-19 Critical Care Consortium database, we conducted a retrospective analysis on adult patients with severe COVID-19 requiring ECMO, including centers globally from 01/2020 to 06/2022, to determine the risk of ICU mortality associated with the occurrence of bleeding and clotting disorders. Results: Among 1,248 COVID-19 patients receiving ECMO support in the registry, coagulation complications were reported in 469 cases (38%), among whom 252 (54%) experienced hemorrhagic complications, 165 (35%) thrombotic complications, and 52 (11%) both. The hazard ratio (HR) for Intensive Care Unit mortality was higher in those with hemorrhagic-only complications than those with neither complication (adjusted HR = 1.60, 95% CI 1.28–1.99, p < 0.001). Death was reported in 617 of the 1248 (49.4%) with multiorgan failure (n = 257 of 617 [42%]), followed by respiratory failure (n = 130 of 617 [21%]) and septic shock [n = 55 of 617 (8.9%)] the leading causes. Conclusions: Coagulation disorders are frequent in COVID-19 ARDS patients receiving ECMO. Bleeding events contribute substantially to mortality in this cohort. However, this risk may be lower than previously reported in single-nation studies or early case reports. Trial registration ACTRN12620000421932 (https://covid19.cochrane.org/studies/crs-13513201). Clinical Perspective: Coagulation disorders such as thrombotic or hemorrhagic events are frequent in COVID-19 ARDS patients receiving ECMO. While older age, pre-existing cardiac disease, and diabetes were independently associated with bleeding, prone positioning and a longer time from admission to ECMO were associated with a higher percentage of thrombotic events. A longer duration of ECMO was linked to an increased rate of combined hemorrhagic and thrombotic events. [ABSTRACT FROM AUTHOR]

Background: Recent advances on cardiorespiratory monitoring applied in ARDS patients undergoing invasive mechanical ventilation and noninvasive ventilatory support are available in the literature and may have potential prognostic implication in ARDS treatment. Main body: The measurement of oxygen saturation by pulse oximetry is a valid, low-cost, noninvasive alternative for assessing arterial oxygenation. Caution must be taken in patients with darker skin pigmentation, who may experience a greater incidence of occult hypoxemia. Dead space surrogates, which are easy to calculate, have important prognostic implications. The mechanical power, which can be automatically computed by intensive care ventilators, is an important parameter correlated with ventilator-induced lung injury and outcome. In patients undergoing noninvasive ventilatory support, the use of esophageal pressure can measure inspiratory effort, avoiding possible delays in endotracheal intubation. Fluid responsiveness can also be evaluated using dynamic indices in patients ventilated at low tidal volumes (< 8 mL/kg). In patients ventilated at high levels of positive end expiratory pressure (PEEP), the PEEP test represents a valid alternative to passive leg raising. There is growing evidence on alternative parameters for evaluating fluid responsiveness, such as central venous oxygen saturation variations, inferior vena cava diameter variations and capillary refill time. Conclusion: Careful cardiorespiratory monitoring in patients affected by ARDS is crucial to improve prognosis and to tailor treatment via mechanical ventilatory support. Keypoints: The SpO2/FiO2 ratio, corrected minute ventilation and ventilatory ratio are valid surrogates for estimating gas exchange in ARDS patients, and caution should be taken in patients with darker skin pigmentation and moderate–severe ARDS. Changes in esophageal pressure during noninvasive respiratory support and mechanical power must be carefully monitored to estimate PSILI and VILI in ARDS patients undergoing mechanical ventilation. The use of dynamic indexes of fluid responsiveness should be encouraged in ARDS patients. Pulse pressure variation and stroke volume variation have also been validated in mechanically ventilated patients with low tidal volume. A possible alternative to passive leg raising in a mechanically ventilated patient is the PEEP test. Two minimally invasive alternatives to predict fluid responsiveness are changes in central venous oxygen saturation and capillary refill time after a passive leg raising or a fluid challenge. [ABSTRACT FROM AUTHOR]

Background: The aim of this study is to determine the effectiveness of antenatal corticosteroid in reducing respiratory morbidity in babies born in the late preterm period. Methods: Two hundred and eighty-six pregnant women at risk of having a late preterm delivery were studied. One hundred and forty-three (143) served as the cases and were given 2 doses of 12 mg intramuscular dexamethasone 12 h apart, while 143 served as the controls and were given a similar quantity of placebo. The women were followed up prospectively and data were collected on the pregnant women and their newborns on a standardized form. The neonates were assessed for acute respiratory distress syndrome and transient tachypnea of the newborn based on clinical signs, symptoms, and chest x-ray results (when indicated). The primary outcome was the occurrence of neonatal respiratory morbidity. Results: The primary outcome occurred in 5 out of 130 infants (3.8%) in the dexamethasone group and 31 out of 122 (25.4%) in the placebo group (P value = 0.000003). Birth asphyxia, neonatal intensive care admission and need for active resuscitation at birth also occurred significantly less frequently in the dexamethasone group (P value 0.004, 0.009, 0.014 respectively). There were no significant group differences in the incidence of neonatal sepsis, neonatal jaundice, hypoglycemia and feeding difficulties. Conclusions: Administration of dexamethasone to women at risk for late preterm delivery significantly reduced the rate of neonatal respiratory complications, neonatal intensive care unit admission, and need for active resuscitation at birth. Trial registration: PACTR (www.pactr.org) Registration Number: PACTR202304579281358. The study was retrospectively registered on April 19, 2023. [ABSTRACT FROM AUTHOR]

Background: Children with advanced pulmonary disease due to cystic fibrosis (CF) are at risk of acute respiratory failure due to pulmonary exacerbations leading to their admission to pediatric intensive care units (PICU). The objectives of this study were to determine short and medium-term outcomes of children with CF admitted to PICU for acute respiratory failure due to pulmonary exacerbation and to identify prognosis factors. Methods: This retrospective monocentric study included patients less than 18 years old admitted to the PICU of a French university hospital between 2000 and 2020. Cox proportional hazard regression methods were used to determine prognosis factors of mortality or lung transplant. Results: Prior to PICU admission, the 29 patients included (median age 13.5 years) had a severe lung disease (median Forced Expiratory Volume in 1 s percentage predicted at 29%). Mortality rates were respectively 17%, 31%, 34%, 41% at discharge and at 3, 12 and 36 months post-discharge. Survival rates free of lung transplant were 34%, 32%, 24% and 17% respectively. Risk factors associated with mortality or lung transplant using the univariate analysis were female sex and higher pCO2 and chloride levels at PICU admission, and following pre admission characteristics: home respiratory and nutritional support, registration on lung transplant list and Stenotrophomonas Maltophilia bronchial colonization. Conclusion: Children with CF admitted to PICU for acute respiratory failure secondary to pulmonary exacerbations are at high risk of death, both in the short and medium terms. Lung transplant is their main chance of survival and should be considered early. [ABSTRACT FROM AUTHOR]

Sepsis, a prevalent critical condition in clinics, continues to be the leading cause of death from infections and a global healthcare issue. Among the organs susceptible to the harmful effects of sepsis, the lungs are notably the most frequently affected. Consequently, patients with sepsis are predisposed to developing acute lung injury (ALI), and in severe cases, acute respiratory distress syndrome (ARDS). Nevertheless, the precise mechanisms associated with the onset of ALI/ARDS remain elusive. In recent years, there has been a growing emphasis on the role of endothelial cells (ECs), a cell type integral to lung barrier function, and their interactions with various stromal cells in sepsis-induced ALI/ARDS. In this comprehensive review, we summarize the involvement of endothelial cells and their intricate interplay with immune cells and stromal cells, including pulmonary epithelial cells and fibroblasts, in the pathogenesis of sepsis-induced ALI/ARDS, with particular emphasis placed on discussing the several pivotal pathways implicated in this process. Furthermore, we discuss the potential therapeutic interventions for modulating the functions of endothelial cells, their interactions with immune cells and stromal cells, and relevant pathways associated with ALI/ARDS to present a potential therapeutic strategy for managing sepsis and sepsis-induced ALI/ARDS. [ABSTRACT FROM AUTHOR]

Highlights: LPS-induced ARDS rats and PMVECs have low Fcgr2b level and high Elk1 level; Fcgr2b overexpression mitigates LPS-induced ALI/ARDS in rats and PMVECs; Elk1 knockdown mitigates LPS-induced ALI/ARDS in rats and PMVECs; Elk1 represses Fcgr2b transcription by recruiting H3K9me3; Elk1/Fcgr2b axis aggravates LPS-induced ALI/ARDS in rats and PMVECs. Objective: Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are associated with significant mortality rates. The role of Fcgr2b in the pathogenesis of ALI/ARDS is not fully elucidated. This study aimed to investigate the functions of Fcgr2b in ALI/ARDS and explore its underlying mechanisms. Methods: Methods: In this study, rat models of ARDS and pulmonary microvascular endothelial cell (PMVEC) injury models were established through the administration of lipopolysaccharide (LPS). The expression levels of Fcgr2b and Elk1 were quantified in both LPS-induced ARDS rats and PMVECs. Subsequent gain- and loss-of-function experiments were conducted, followed by comprehensive assessments of lung tissue for pathomorphological changes, edema, glycogen storage, fibrosis, and infiltration of inflammatory cells. Additionally, bronchoalveolar lavage fluid was analyzed for T-helper 17 (Th17) cell infiltration, inflammatory response, and microvascular permeability to evaluate lung injury severity in ARDS models. Furthermore, the activity, cytotoxicity, apoptosis, and angiogenic potential of PMVECs were assessed to gauge cell injury. The interaction between Elk1 and Fcgr2b was also examined to confirm their regulatory relationship. Results: In the context of LPS-induced ARDS and PMVEC injury, Fcgr2b expression was markedly reduced, whereas Elk1 expression was elevated. Overexpression of Fcgr2b led to a decrease in Th17 cell infiltration and mitigated lung tissue damage in ARDS models, in addition to reducing LPS-induced injury in PMVECs. Elk1 was found to suppress Fcgr2b transcription through the recruitment of histone 3 lysine 9 trimethylation (H3K9me3). Knockdown of Elk1 diminished Th17 cell infiltration and lung tissue damage in ARDS models, and alleviated LPS-induced injury in PMVECs, effects that were reversed upon Fcgr2b upregulation. Conclusion: Elk1 negatively regulates Fcgr2b transcription, thereby augmenting the inflammatory response and exacerbating lung injury in LPS-induced ALI/ARDS. [ABSTRACT FROM AUTHOR]

Background: Acute respiratory distress syndrome (ARDS) is a common cause of respiratory failure in critically ill patients, and diffuse alveolar damage (DAD) is considered its histological hallmark. Sepsis is one of the most common aetiology of ARDS with the highest case-fatality rate. Identifying ARDS patients and differentiate them from other causes of acute respiratory failure remains a challenge. To address this, many studies have focused on identifying biomarkers that can help assess lung epithelial injury. However, there is scarce information available regarding the tissue expression of these markers. Evaluating the expression of elafin, RAGE, and SP-D in lung tissue offers a potential bridge between serological markers and the underlying histopathological changes. Therefore, we hypothesize that the expression of epithelial injury markers varies between sepsis and ARDS as well as according to its severity. Methods: We compared the post-mortem lung tissue expression of the epithelial injury markers RAGE, SP-D, and elafin of patients that died of sepsis, ARDS, and controls that died from non-pulmonary causes. Lung tissue was collected during routine autopsy and protein expression was assessed by immunohistochemistry. We also assessed the lung injury by a semi-quantitative analysis. Results: We observed that all features of DAD were milder in septic group compared to ARDS group. Elafin tissue expression was increased and SP-D was decreased in the sepsis and ARDS groups. Severe ARDS expressed higher levels of elafin and RAGE, and they were negatively correlated with PaO2/FiO2 ratio, and positively correlated with bronchopneumonia percentage and hyaline membrane score. RAGE tissue expression was negatively correlated with mechanical ventilation duration in both ARDS and septic groups. In septic patients, elafin was positively correlated with ICU admission length, SP-D was positively correlated with serum lactate and RAGE was correlated with C-reactive protein. Conclusions: Lung tissue expression of elafin and RAGE, but not SP-D, is associated with ARDS severity, but does not discriminate sepsis patients from ARDS patients. [ABSTRACT FROM AUTHOR]

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

Background: Conventional natural killer (cNK) cells play an important role in the innate immune response by directly killing infected and malignant cells and by producing pro- and anti-inflammatory cytokines. Studies on their role in malaria and its complications have resulted in conflicting results. Methods: Using the commonly used anti-NK1.1 depletion antibodies (PK136) in an in-house optimized experimental model for malaria-associated acute respiratory distress syndrome (MA-ARDS), the role of cNK cells was investigated. Moreover, flow cytometry was performed to characterize different NK cell populations. Results: While cNK cells were found to be dispensable in the development of MA-ARDS, the appearance of a NK1.1+ cell population was observed in the lungs upon infection despite depletion with anti-NK1.1. Detailed characterization of the unknown population revealed that this population consisted of a mixture of monocytes and macrophages that bind the anti-NK1.1 antibody in an aspecific way. This aspecific binding may occur via Fcγ receptors, such as FcγR4. In contrast, in vivo depletion using anti-NK1.1 antibodies was proved to be specific for cNK cells. Conclusion: cNK cells are dispensable in the development of experimental MA-ARDS. Moreover, careful flow cytometric analysis, with a critical mindset in relation to potential aspecific binding despite the use of commercially available Fc blocking reagents, is critical to avoid misinterpretation of the results. [ABSTRACT FROM AUTHOR]

Background: Despite vaccines' effectiveness in reducing COVID-19 infection rates and disease severity, their impact on critical patients presenting with acute respiratory failure is elusive. The aim of this study was to further investigate the influence of vaccination on mortality rates among severely ill COVID-19 patients experiencing acute respiratory failure. Methods: This retrospective cohort study was carried out at a tertiary medical center in Taiwan. From April to September 2022, patients who tested positive for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) through reverse transcription polymerase chain reaction (RT-PCR) and subsequently experienced acute respiratory failure were included in the study. Baseline characteristics, including vaccination history, along with information regarding critical illness and clinical outcomes, were gathered and compared between patients who received the vaccine and those who did not. Results: A total of 215 patients with COVID-19 exhibiting acute respiratory failure, as confirmed via RT‒PCR, were included in the analysis. Of this cohort, sixty-six (30.7%) patients died within 28 days. Neither administration of the vaccine nor achievement of primary series vaccination status had a significantly different effect on 28 day mortality, number of viral shedding events, acute respiratory distress syndrome (ARDS) incidence or other clinical outcomes. Patients who received the booster vaccine and completed the primary series showed a tendency of increased 28 days of ventilator-free status, though this difference was not statistically significant (p = 0.815). Conclusions: Vaccination status did not significantly influence mortality rates, the occurrence of ARDS, or the viral shedding duration in COVID-19 patients with acute respiratory failure. [ABSTRACT FROM AUTHOR]

Background: COVID-19-associated pulmonary aspergillosis (CAPA) is burdened by high mortality. Data are lacking about non-ICU patients. Aims of this study were to: (i) assess the incidence and prevalence of CAPA in a respiratory sub-intensive care unit, (ii) evaluate its risk factors and (iii) impact on in-hospital mortality. Secondary aims were to: (i) assess factors associated to mortality, and (ii) evaluate significant features in hematological patients. Materials and methods: This was a single-center, retrospective study of COVID-19 patients with acute respiratory failure. A cohort of CAPA patients was compared to a non-CAPA cohort. Among patients with CAPA, a cohort of hematological patients was further compared to another of non-hematological patients. Results: Three hundred fifty patients were included in the study. Median P/F ratio at the admission to sub-intensive unit was 225 mmHg (IQR 155–314). 55 (15.7%) developed CAPA (incidence of 5.5%). Eighteen had probable CAPA (37.3%), 37 (67.3%) possible CAPA and none proven CAPA. Diagnosis of CAPA occurred at a median of 17 days (IQR 12–31) from SARS-CoV-2 infection. Independent risk factors for CAPA were hematological malignancy [OR 1.74 (95%CI 0.75–4.37), p = 0.0003], lymphocytopenia [OR 2.29 (95%CI 1.12–4.86), p = 0.02], and COPD [OR 2.74 (95%CI 1.19–5.08), p = 0.014]. Mortality rate was higher in CAPA cohort (61.8% vs 22.7%, p < 0.0001). CAPA resulted an independent risk factor for in-hospital mortality [OR 2.92 (95%CI 1.47–5.89), p = 0.0024]. Among CAPA patients, age > 65 years resulted a predictor of mortality [OR 5.09 (95% CI 1.20–26.92), p = 0.035]. No differences were observed in hematological cohort. Conclusion: CAPA is a life-threatening condition with high mortality rates. It should be promptly suspected, especially in case of hematological malignancy, COPD and lymphocytopenia. [ABSTRACT FROM AUTHOR]

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

Background: Plasmodium ovale malaria is usually considered a tropical infectious disease associated with low morbidity and mortality. However, severe disease and death have previously been reported. Case presentation: A case of severe P. ovale malaria in a healthy Caucasian man with a triangle splenic infarction and clinical progression towards Acute Respiratory Distress Syndrome was reported despite a rapid response to oral chloroquine treatment with 24-h parasitaemia clearance. Conclusion: Plasmodium ovale malaria is generally considered as a benign disease, with low parasitaemia. However, severe disease and death have occasionally been reported. It is important to be aware that occasionally it can progress to serious illness and death even in immunocompetent individuals. [ABSTRACT FROM AUTHOR]

Introduction: EXO-CD24 are exosomes genetically manipulated to over-express Cluster of Differentiation (CD) 24. It consists of two breakthrough technologies: CD24, the drug, as a novel immunomodulator that is smarter than steroids without any side effects, and exosomes as the ideal natural drug carrier. Methods: A randomized, single blind, dose-finding phase IIb trial in hospitalized patients with mild to moderate Coronavirus disease 2019 (COVID-19) related Acute Respiratory Distress Syndrome (ARDS) was carried out in two medical centers in Athens. Patients received either 109 or 1010 exosome particles of EXO-CD24, daily, for five consecutive days and monitored for 28 days. Efficacy was assessed at day 7 among 91 patients who underwent randomization. The outcome was also compared in a post-hoc analysis with an income control group (n = 202) that fit the inclusion and exclusion criteria. Results: The mean age was 49.4 (± 13.2) years and 74.4% were male. By day 7, 83.7% showed improved respiratory signs and 64% had better oxygen saturation (SpO2) (p < 0.05). There were significant reductions in all inflammatory markers, most notably in C-reactive protein (CRP), lactate dehydrogenase (LDH), ferritin, fibrinogen and an array of cytokines. Conversely, levels of the anti-inflammatory cytokine Interleukin-10 (IL-10) were increased (p < 0.05). Of all the documented adverse events, none were considered treatment related. No drug-drug interactions were noted. Two patients succumbed to COVID-19. Post-hoc analysis revealed that EXO-CD24 patients exhibited greater improvements in clinical and laboratory outcomes compared to an observational income control group. Conclusions: EXO-CD24 presents a promising therapeutic approach for hyper-inflammatory state and in particular ARDS. Its unique combination of exosomes, as a drug carrier, and CD24, as an immunomodulator, coupled with inhalation administration, warrants further investigation in a larger, international, randomized, quadri-blind trial against a placebo. [ABSTRACT FROM AUTHOR]

Background: The coronavirus disease 2019 (COVID-19) pandemic has had a significant impact on global health and economies, resulting in millions of infections and deaths. This retrospective cohort study aimed to investigate the effect of antifibrotic agents (nintedanib and pirfenidone) on 1-year mortality in COVID-19 patients with acute respiratory failure. Methods: Data from 61 healthcare organizations in the TriNetX database were analyzed. Adult patients with COVID-19 and acute respiratory failure were included. Patients with a pre-existing diagnosis of idiopathic pulmonary fibrosis before their COVID-19 diagnosis were excluded. The study population was divided into an antifibrotic group and a control group. Propensity score matching was used to compare outcomes, and hazard ratios (HR) for 1-year mortality were calculated. Results: The antifibrotic group exhibited a significantly lower 1-year mortality rate compared to the control group. The survival probability at the end of the study was 84.42% in the antifibrotic group and 69.87% in the control group. The Log-Rank test yielded a p-value of less than 0.001. The hazard ratio was 0.434 (95% CI: 0.264–0.712), indicating a significant reduction in 1-year mortality in the antifibrotic group. Subgroup analysis demonstrated significantly improved 1-year survival in patients receiving nintedanib treatment and during periods when the Wuhan strain was predominant. Discussion: This study is the first to demonstrate a survival benefit of antifibrotic agents in COVID-19 patients with acute respiratory failure. Further research and clinical trials are needed to confirm the efficacy of these antifibrotic agents in the context of COVID-19 and acute respiratory failure. [ABSTRACT FROM AUTHOR]

Background: Short bowel syndrome (SBS) in adults is defined as having less than 180 to 200 cm of remaining small bowel. Many literature sources do not provide precise epidemiological data, and challenges in estimating the prevalence of SBS include its multifactorial etiology and varying definitions. The most common pathologies leading to SBS include Crohn disease, mesenteric ischemia, radiation enteritis, post-surgical adhesions, and post-operative complications. Case presentation: This article presents a clinical case of a 76-year-old Lithuanian patient who underwent parenteral nutrition for four months due to SBS. Before the following diagnosis, the patient had undergone two surgeries. During the hospitalization, life-threatening conditions such as stercoral peritonitis, septic shock, and acute respiratory failure, were observed and treated. As a result of SBS, hypoproteinemia and hypoalbuminemia developed, leading to the prescription of full parenteral nutrition. After correcting the malnutrition, a third surgery was performed, resulting in the discontinuation of parenteral nutrition and the resumption of a regular diet. Conclusions: Parenteral nutrition is the sole effective method for preserving the lives of patients with a short segment of the intestine. While on parenteral nutrition, patients can be prepared for reconstructive surgery. [ABSTRACT FROM AUTHOR]

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

Background: Cadmium and nickel exposure can cause oxidative stress, induce inflammation, inhibit immune function, and therefore has significant impacts on the pathogenesis and severity of many diseases. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can also provoke oxidative stress and the dysregulation of inflammatory and immune responses. This study aimed to assess the potential associations of cadmium and nickel exposure with the severity and clinical outcomes of patients with coronavirus disease 2019 (COVID-19). Methods: We performed a retrospective, observational, bicenter cohort analysis of patients with SARS-CoV-2 infection in Taiwan between June 2022 and July 2023. Cadmium and nickel concentrations in blood and urine were measured within 3 days of the diagnosis of acute SARS-CoV-2 infection, and the severity and clinical outcomes of patients with COVID-19 were analyzed. Results: A total of 574 patients were analyzed and divided into a severe COVID-19 group (hospitalized patients) (n = 252; 43.9%), and non-severe COVID-19 group (n = 322; 56.1%). The overall in-hospital mortality rate was 11.8% (n = 68). The severe COVID-19 patients were older, had significantly more comorbidities, and significantly higher neutrophil/lymphocyte ratio, C-reactive protein, and interleukin-6 than the non-severe COVID-19 patients (all p < 0.05). Blood and urine cadmium and urine nickel concentrations were significantly higher in the severe COVID-19 patients than in the non-severe COVID-19 patients. Among the severe COVID-19 patients, those in higher urine cadmium/creatinine quartiles had a significantly higher risk of organ failure (i.e., higher APACHE II and SOFA scores), higher neutrophil/lymphocyte ratio, lower PaO2/FiO2 requiring higher invasive mechanical ventilation support, higher risk of acute respiratory distress syndrome, and higher 60-, 90-day, and all-cause hospital mortality (all p < 0.05). Multivariable logistic regression models revealed that urine cadmium/creatinine was independently associated with severe COVID-19 (adjusted OR 1.643 [95% CI 1.060–2.547], p = 0.026), and that a urine cadmium/creatinine value > 2.05 μg/g had the highest predictive value (adjusted OR 5.349, [95% CI 1.118–25.580], p = 0.036). Conclusions: Urine cadmium concentration in the early course of COVID-19 could predict the severity and clinical outcomes of patients and was independently associated with the risk of severe COVID-19. [ABSTRACT FROM AUTHOR]

Benign mediastinal tumor is usually asymptomatic and exhibits uncomplicated clinical course. Posterior mediastinal schwannoma is common, but a huge benign tumor causing acute respiratory failure due to mass effect is unusual. We present a patient who suffered from acute respiratory failure due to huge mediastinal mass effect and improved after en bloc surgical resection. A 56-year-old woman had no history of systemic disease, but experienced general discomfort and malaise for several months. She was referred to our emergency department after developing sudden respiratory failure. Intubation was performed with ventilator support and she was admitted to the intensive care unit. Chest radiograph and computed tomography showed a huge mass over the left pleural cavity causing left lung, heart, and mediastinal compression. After en bloc resection, she was weaned off the ventilator successfully and was discharged at 24 days after the operation. Postoperative outpatient follow-up showed no symptoms. Mediastinal ancient schwannoma is a rare posterior mediastinal benign tumor. However, mass effect might lead to lethal complications. En bloc resection is necessary for curative treatment. [ABSTRACT FROM AUTHOR]