Drug repurposing of cyclin-dependent kinase inhibitors for neutrophilic acute respiratory distress syndrome and psoriasis.

BACKGROUND: Neutrophilic inflammation, characterized by dysregulated neutrophil activation, triggers a variety of inflammatory responses such as chemotactic infiltration, oxidative bursts, degranulation, neutrophil extracellular traps (NETs) formation, and delayed turnover. This type of inflammation is pivotal in the pathogenesis of acute respiratory distress syndrome (ARDS) and psoriasis. Despite current treatments, managing neutrophil-associated inflammatory symptoms remains a significant challenge. AIM OF REVIEW: This review emphasizes the role of cyclin-dependent kinases (CDKs) in neutrophil activation and inflammation. It aims to highlight the therapeutic potential of repurposing CDK inhibitors to manage neutrophilic inflammation, particularly in ARDS and psoriasis. Additionally, it discusses the necessary precautions for the clinical application of these inhibitors due to potential off-target effects and the need for dose optimization. KEY SCIENTIFIC CONCEPTS OF REVIEW: CDKs regulate key neutrophilic functions, including chemotactic responses, degranulation, NET formation, and apoptosis. Repurposing CDK inhibitors, originally developed for cancer treatment, shows promise in controlling neutrophilic inflammation. Clinical anticancer drugs, palbociclib and ribociclib, have demonstrated efficacy in treating neutrophilic ARDS and psoriasis by targeting off-label pathways, phosphoinositide 3-kinase (PI3K) and phosphodiesterase 4 (PDE4), respectively. While CDK inhibitors offer promising therapeutic benefits, their clinical repurposing requires careful consideration of off-target effects and dose optimization. Further exploration and clinical trials are necessary to ensure their safety and efficacy in treating inflammatory conditions.

Early predictive values of clinical assessments for ARDS mortality: a machine-learning approach.

Acute respiratory distress syndrome (ARDS) is a devastating critical care syndrome with significant morbidity and mortality. The objective of this study was to evaluate the predictive values of dynamic clinical indices by developing machine-learning (ML) models for early and accurate clinical assessment of the disease prognosis of ARDS. We conducted a retrospective observational study by applying dynamic clinical data collected in the ARDSNet FACTT Trial (n = 1000) to ML-based algorithms for predicting mortality. In order to compare the significance of clinical features dynamically, we further applied the random forest (RF) model to nine selected clinical parameters acquired at baseline and day 3 independently. An RF model trained using clinical data collected at day 3 showed improved performance and prognostication efficacy (area under the curve [AUC]: 0.84, 95% CI: 0.78-0.89) compared to baseline with an AUC value of 0.72 (95% CI: 0.65-0.78). Mean airway pressure (MAP), bicarbonate, age, platelet count, albumin, heart rate, and glucose were the most significant clinical indicators associated with mortality at day 3. Thus, clinical features collected early (day 3) improved performance of integrative ML models with better prognostication for mortality. Among these, MAP represented the most important feature for ARDS patients' early risk stratification.

Clinical Profile and Course of Patients with Acute Respiratory Distress Syndrome due to COVID-19 in a Middle-Income Region in Mexico.

Introduction: COVID-19 leads to severe clinical complications that culminate in respiratory failure and acute respiratory distress syndrome (ARDS). Despite reports of some comorbidities that contribute to the development of COVID-19-mediated ARDS, there is great variation in mortality rates among critical COVID-19 patients in the world. To date, no studies have described the incidence and comorbidities associated with ARDS due to COVID-19 in the northeastern region of Mexico. Aim of the study: To describe patients diagnosed with ARDS due to COVID-19 in the northeastern region of Mexico, as well as its variations in comparison with other regions of the country. Material and Methods: We conducted a prospective and observational study in a tertiary care center in Northeastern Mexico. All patients diagnosed with SARS-CoV-2 infection and requiring management in the intensive care unit were included. We developed a database that was updated daily with the patients' demographic information, pre-existing diseases, disease severity, and clinical variables. Results: The incidence of ARDS secondary to COVID-19 in HRAEV was high in comparison with other reports. Diabetes mellitus was the risk factor most associated with COVID-19-mediated ARDS. Conclusion: Based on our findings and those previously reported in the literature, there are differences that we discuss between northeastern and central Mexico, and analyze other areas evaluated around the world.

Longitudinal Assessment of ROX and HACOR Scores to Predict Non-Invasive Ventilation Failure in Patients with SARS-CoV-2 Pneumonia.

Introduction: NIV (Non-invasive ventilation) and HFNC (High Flow nasal cannula) are being used in patients with acute respiratory failure. HACOR score has been exclusively calculated for patients on NIV, on other hand ROX index is being used for patients on HFNC. This is first study where ROX index has been used in patients on NIV to predict failure. Aim of the study: This study investigates the comparative diagnostic performance of HACOR score and ROX index to predict NIV failure. Methods: We performed a retrospective cohort study of non-invasively ventilated COVID-19 patients admitted between 1st April 2020 to 15th June 2021 to ICU of a tertiary care teaching hospital located in Central India. We assessed factors responsible for NIV failure, and whether these scores HACOR/ROX index have discriminative capacity to predict risk of invasive mechanical ventilation. Results: Of the 441 patients included in the current study, 179 (40.5%) recovered, while remaining 262 (59.4%) had NIV failure. On multivariable analysis, ROX index > 4.47 was found protective for NIV-failure (OR 0.15 (95% CI 0.03-0.23; p<0.001). Age > 60 years and SOFA score were other significant independent predictors of NIV-failure. The AUC for prediction of failure rises from 0.84 to 0.94 from day 1 to day 3 for ROX index and from 0.79 to 0.92 for HACOR score in the same period, hence ROX score was non-inferior to HACOR score in current study. DeLong's test for two correlated ROC curves had insignificant difference expect day-1 (D1: 0.03 to 0.08; p=3.191e-05, D2: -0.002 to 0.02; p = 0.2671, D3: -0.003 to 0.04; p= 0.1065). Conclusion: ROX score of 4.47 at day-3 consists of good discriminatory capacity to predict NIV failure. Considering its non-inferiority to HACOR score, the ROX score can be used in patients with acute respiratory failure who are on NIV.

COVID-19 Related Acute Respiratory Distress Syndrome versus Classical Acute Respiratory Distress Syndrome Patients: Inflammatory Biomarkers as Predictors of Mortality in Pulmonary Septic Shock.

Introduction and Objectives: Coronavirus disease-2019 (COVID-19)-related severe acute respiratory distress syndrome (ARDS) differs pathophysiological from other pulmonary septic shock-related ARDS. Thus, we assessed whether all-cause in-hospital mortality differs for severe COVID-19-related and classical severe ARDS and which inflammatory biomarkers can predict mortality among these patients. Material and Methods: This single-center, retrospective, observational cohort study included pulmonary septic shock patients (n = 114) with COVID-19-related and classical severe ARDS admitted in the Intensive Care Unit. Results: Patients with a mean age of 73 (IQR 62-82), predominantly male (63%), were divided into two groups based on outcomes: survivors (n = 50) and non-survivors (n = 64). COVID-19-related severe ARDS (n = 48) accounts for 75% of deaths. Present comorbidities like heart disease (p = 0.043), neurologic disorders (p = 0.018), and liver disease (p = 0.038) were associated with in-hospital mortality, as well. Regarding inflammatory biomarkers, the AUC/c-statistic was 0.656 (95% CI: 0.53-0.759) for leukocytes, 0.613 (95% CI: 0.509-0.717) C-reactive protein (CRP) and 0.651 (95% CI: 0.548-0.753) for procalcitonin in predicting all-cause in-hospital mortality among patients with pulmonary septic shock and severe ARDS. Conclusion: Patients with pulmonary septic shock and with COVID-19-related severe ARDS had a higher incidence of in-hospital mortality than those with classical severe ARDS. The high value of leukocytes, C-reactive protein, and procalcitonin were predictive for all-cause in-hospital mortality in patients with pulmonary septic shock and ARDS. Infection with COVID-19 was an independent predictor of in-hospital mortality in the presence of ARDS.

Definition and management of right ventricular injury in adult patients receiving extracorporeal membrane oxygenation for respiratory support using the Delphi method: a PRORVnet study. Expert position statements.

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

A novel extracellular vesicle paradigm for the treatment of COVID-19 induced acute respiratory distress syndrome (ARDS).

Efficacy of mesenchymal stem cells (MSCs) for treatment of acute respiratory distress syndrome (ARDS) suggests bioactive bone marrow MSC extracellular vesicles (BM-MSC EVs) may be effective. A patient with severe COVID-19 associated ARDS who was presumed to expire was treated with a BM-MSC EV preparation (14 doses over two months) as a rescue treatment for refractory COVID ARDS. Near complete reversal of lung inflammation and fibrosis (per computed tomography), near complete restoration of mobility, hospital discharge (3 months) with resumption of normal activities of daily living (one year) and return to work occurred. No adverse events occurred despite repeated dosing of investigational product, highlighting safety of this potential therapy for ARDS.

A Retrospective Comparison of Clinical and Laboratory Aspects of Patients With COVID-19-Related Acute Respiratory Distress Syndrome (ARDS) and Non-COVID-19-Related ARDS.

AIM/OBJECTIVE: This study investigated demographic characteristics, hemodynamic values, respiratory datas, laboratory values ​​such as biochemistry and blood gas, and treatment approaches of coronavirus disease 2019 (COVID-19)-related and non-COVID-19-related acute respiratory distress syndrome (ARDS) patients hospitalized in the intensive care unit (ICU). BACKGROUND: Determining the differences and similarities between COVID-19-related ARDS (CARDS) patients and non-COVID-19-related ARDS (NCARDS) patients will be useful to better understand these two diseases. MATERIALS AND METHODS: A total of 32 NCARDS patients who were followed and treated in the ICU for various reasons between January 2015 and December 2020 and 32 CARDS patients who were followed and treated in the ICU for various reasons between March 2020 and December 2020 were examined retrospectively. Age, gender, comorbidities, Glasgow Coma Scale (GCS), Acute Physiology and Chronic Health Evaluation (APACHE) II Score, blood pressure, heart rate, saturation, laboratory results, arterial blood gas (ABG) values, length of stay in the ICU, intubation, the number of days till the patient was extubated, the treatments applied, admission to the service, and mortality were evaluated. RESULTS: In the comparison between the two groups, the demographic data of the patients, the number of days intubated and extubated, APACHE II scores, and ICU length of stay were not statistically different. Values of positive end-expiratory pressure (PEEP), first hospitalization GCS, first hospitalization hemoglobin (Hgb), albumin at first admission, alanine aminotransferase (ALT) at first admission, and steroid use were found to be significantly different in patients with CARDS (p < 0.001). The median of PEEP values (p = 0.04), first admission GCS values (p = 0.04), first admission Hgb values (p = 0.005), albumin values at the first admission (p = 0.03), ALT values (p = 0.03), and the rate of steroid use (p = 0.001) of CARDS patients were significantly higher than those of NCARDS patients. The median of the first hospitalization heart rate values (p = 0.009), first hospitalization saturation values (p = 0.001), and first admission neutrophil values (p = 0.03) in NCARDS patients were significantly higher than that of CARDS patients. There was no significant difference between the two groups in terms of mortality, sedation use, inotropic support, C-reactive protein (CRP), and procalcitonin values. CONCLUSIONS: CARDS and NCARDS have clinical and laboratory similarities and differences. Therefore, there should be differences in our follow-up and treatment approach to these two disease groups.

Leptospirosis-Associated Acute Respiratory Distress Syndrome (ARDS) in Pregnancy: A Rare Presentation.

Leptospirosis, a zoonotic disease caused by spirochetes of the genus Leptospira, poses unique challenges in pregnancy due to its varied clinical presentation and potential adverse outcomes for both mother and fetus. We present a case of a 24-year-old primigravida at 35 weeks of gestation who presented with fever, dyspnea, and abdominal pain, and was ultimately diagnosed with leptospirosis complicated by acute respiratory distress syndrome (ARDS). Prompt initiation of antibiotic therapy, supportive care, and timely delivery via emergency cesarean section led to favorable maternal and neonatal outcomes. This case report underscores the importance of considering leptospirosis in pregnant patients presenting with similar symptoms, particularly in endemic regions, and highlights the critical role of multidisciplinary management in optimizing outcomes.

Flecainide-Induced Acute Respiratory Distress Syndrome: A Case Report.

Flecainide is an antiarrhythmic drug that rarely causes lung injury. We present a case of flecainide-induced lung injury (FILI) that resulted in acute respiratory distress syndrome (ARDS) and resolved after flecainide discontinuation and corticosteroid treatment. FILI has been shown to occur days to two years after treatment initiation. Our presented case shows that FILI can occur after at least five years of therapy and is the first to show lung injury after a period of flecainide cessation and subsequent re-initiation. Clinical impacts may be large, as flecainide becomes more commonplace in medical pharmacopeia.

PD-L1 and PD-1 Are Associated with Clinical Outcomes and Alveolar Immune Cell Activation in ARDS.

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

Integrative multi-omics analysis unravels the host response landscape and reveals a serum protein panel for early prognosis prediction for ARDS.

BACKGROUND: The multidimensional biological mechanisms underpinning acute respiratory distress syndrome (ARDS) continue to be elucidated, and early biomarkers for predicting ARDS prognosis are yet to be identified. METHODS: We conducted a multicenter observational study, profiling the 4D-DIA proteomics and global metabolomics of serum samples collected from patients at the initial stage of ARDS, alongside samples from both disease control and healthy control groups. We identified 28-day prognosis biomarkers of ARDS in the discovery cohort using the LASSO method, fold change analysis, and the Boruta algorithm. The candidate biomarkers were validated through parallel reaction monitoring (PRM) targeted mass spectrometry in an external validation cohort. Machine learning models were applied to explore the biomarkers of ARDS prognosis. RESULTS: In the discovery cohort, comprising 130 adult ARDS patients (mean age 72.5, 74.6% male), 33 disease controls, and 33 healthy controls, distinct proteomic and metabolic signatures were identified to differentiate ARDS from both control groups. Pathway analysis highlighted the upregulated sphingolipid signaling pathway as a key contributor to the pathological mechanisms underlying ARDS. MAP2K1 emerged as the hub protein, facilitating interactions with various biological functions within this pathway. Additionally, the metabolite sphingosine 1-phosphate (S1P) was closely associated with ARDS and its prognosis. Our research further highlights essential pathways contributing to the deceased ARDS, such as the downregulation of hematopoietic cell lineage and calcium signaling pathways, contrasted with the upregulation of the unfolded protein response and glycolysis. In particular, GAPDH and ENO1, critical enzymes in glycolysis, showed the highest interaction degree in the protein-protein interaction network of ARDS. In the discovery cohort, a panel of 36 proteins was identified as candidate biomarkers, with 8 proteins (VCAM1, LDHB, MSN, FLG2, TAGLN2, LMNA, MBL2, and LBP) demonstrating significant consistency in an independent validation cohort of 183 patients (mean age 72.6 years, 73.2% male), confirmed by PRM assay. The protein-based model exhibited superior predictive accuracy compared to the clinical model in both the discovery cohort (AUC: 0.893 vs. 0.784; Delong test, P < 0.001) and the validation cohort (AUC: 0.802 vs. 0.738; Delong test, P = 0.008). INTERPRETATION: Our multi-omics study demonstrated the potential biological mechanism and therapy targets in ARDS. This study unveiled several novel predictive biomarkers and established a validated prediction model for the poor prognosis of ARDS, offering valuable insights into the prognosis of individuals with ARDS.

Unmasking Negative Pressure Pulmonary Edema Following Hanging: A Case Series.

Pulmonary edema is a rare mechanism of death that develops after partial hanging, a potential complication that physicians should consider early in the management of these patients. This case series discusses the presentation, evaluation, and treatment course of three patients who had attempted suicide by hanging and were admitted to the hospital. These patients were admitted to the intensive care unit after being stabilized and supportive treatment was provided. In all the cases, a radiological scan of the chest revealed diffuse infiltrates consistent with pulmonary edema on both sides, features of which were also noted during a diagnostic bronchoscopy. After providing the best intensive care in the hospital, two patients clinically improved, and one patient succumbed to cardiac arrest. As most patients will be brought dead to the hospital following hanging, negative pressure pulmonary edema remains underdiagnosed. Thus, this case series enumerates the possible etiologies of negative pressure pulmonary edema and its contribution to death following suicidal hanging.

Correlation between worsening pneumonitis and right ventricular systolic function in critically ill patients with COVID-19.

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

Diagnostic accuracy of lung ultrasound in diagnosis of ARDS and identification of focal or non-focal ARDS subphenotypes: a systematic review and meta-analysis.

BACKGROUND: Acute respiratory distress syndrome (ARDS) is a life-threatening respiratory condition with high mortality rates, accounting for 10% of all intensive care unit admissions. Lung ultrasound (LUS) as diagnostic tool for acute respiratory failure has garnered widespread recognition and was recently incorporated into the updated definitions of ARDS. This raised the hypothesis that LUS is a reliable method for diagnosing ARDS. OBJECTIVES: We aimed to establish the accuracy of LUS for ARDS diagnosis and classification of focal versus non-focal ARDS subphenotypes. METHODS: This systematic review and meta-analysis used a systematic search strategy, which was applied to PubMed, EMBASE and cochrane databases. Studies investigating the diagnostic accuracy of LUS compared to thoracic CT or chest radiography (CXR) in ARDS diagnosis or focal versus non-focal subphenotypes in adult patients were included. Quality of studies was evaluated using the QUADAS-2 tool. Statistical analyses were performed using "Mada" in Rstudio, version 4.0.3. Sensitivity and specificity with 95% confidence interval of each separate study were summarized in a Forest plot. RESULTS: The search resulted in 2648 unique records. After selection, 11 reports were included, involving 2075 patients and 598 ARDS cases (29%). Nine studies reported on ARDS diagnosis and two reported on focal versus non-focal ARDS subphenotypes classification. Meta-analysis showed a pooled sensitivity of 0.631 (95% CI 0.450-0.782) and pooled specificity of 0.942 (95% CI 0.856-0.978) of LUS for ARDS diagnosis. In two studies, LUS could accurately differentiate between focal versus non-focal ARDS subphenotypes. Insufficient data was available to perform a meta-analysis. CONCLUSION: This review confirms the hypothesis that LUS is a reliable method for diagnosing ARDS in adult patients. For the classification of focal or non-focal subphenotypes, LUS showed promising results, but more research is needed.

Electrical Impedance Tomography, Artificial Intelligence, and Variable Ventilation: Transforming Respiratory Monitoring and Treatment in Critical Care.

BACKGROUND: Electrical Impedance Tomography (EIT), combined with variable ventilation strategies and Artificial Intelligence (AI), is poised to revolutionize critical care by transitioning from reactive to predictive approaches. This integration aims to enhance patient outcomes through personalized interventions and real-time monitoring. METHODS: this narrative review explores the principles and applications of EIT, variable ventilation, and AI in critical care. EIT impedance sensing creates dynamic images of internal physiology, aiding the management of conditions like Acute Respiratory Distress Syndrome (ARDS). Variable ventilation mimics natural breathing variability to improve lung function and minimize ventilator-induced lung injury. AI enhances EIT through advanced image reconstruction techniques, neural networks, and digital twin technology, offering more accurate diagnostics and tailored therapeutic interventions. CONCLUSIONS: the confluence of EIT, variable ventilation, and AI represents a significant advancement in critical care, enabling a predictive, personalized approach. EIT provides real-time insights into lung function, guiding precise ventilation adjustments and therapeutic interventions. AI integration enhances EIT diagnostic capabilities, facilitating the development of personalized treatment plans. This synergy fosters interdisciplinary collaborations and sets the stage for innovative research, ultimately improving patient outcomes and advancing the future of critical care.

Polyuria in COVID-19 Patients Undergoing Extracorporeal Membrane Oxygenation.

Background: The COVID-19 pandemic caused an unprecedented number of patients requiring veno-venous extracorporeal membrane oxygenation (VV ECMO) therapy. Clinical polyuria was observed at our ECMO center during the pandemic. This study aims to investigate the incidence, potential causes, and implications of polyuria in COVID-19 patients undergoing VV ECMO therapy. Methods: Here, 68 SARS-CoV-2 positive patients receiving VV ECMO were stratified into the following two groups: polyuria (PU), characterized by an average urine output of ≥3000 mL/day within seven days following initiation, and non-polyuria (NPU), defined by <3000 mL/day. Polyuria in ECMO patients occurred in 51.5% (n = 35) within seven days after ECMO initiation. No significant difference in mortality was observed between PU and NPU groups (60.0% vs. 60.6%). Differences were found in the fluid intake (p < 0.01) and balance within 24 h (p = 0.01), creatinine (p < 0.01), plasma osmolality (p = < 0.01), lactate (p < 0.01), urea (p < 0.01), and sodium levels (p < 0.01) between the groups. Plasma osmolality increased (p < 0.01) after ECMO initiation during the observation period. Results: Diuresis and plasma osmolality increased during VV ECMO treatment, while mortality was not affected by polyuria. Conclusions: Polyuria does not appear to impact mortality. Further investigations are warranted to elucidate its underlying mechanisms and clinical implications in the context of VV ECMO therapy and COVID-19 management.

Five sessions of hyperbaric oxygen for critically ill patients with COVID-19-induced ARDS: A randomised, open label, phase II trial.

BACKGROUND: Few treatment options exist for patients with COVID-19-induced acute respiratory distress syndrome (ARDS). Data on the benefits and harms of hyperbaric oxygen treatment (HBOT) for this condition is limited. OBJECTIVE: To evaluate benefits and harms of HBOT in patients with COVID-19 induced ARDS. METHODS: In this open-label trial conducted at three hospitals in Sweden and Germany, patients with moderate to severe ARDS and at least two risk factors for unfavourable outcome, were randomly assigned (1:1) to medical oxygen 100 %, 2·4 Atmospheres absolute (ATA), 80 min (HBOT) adjuvant to best practice or to best practice alone (Control). Randomisation was stratified by sex and site. The primary endpoint was ICU admission by Day 30. RESULTS: Between June 4, 2020, and Dec 1, 2021, 34 subjects were randomised to HBOT (N = 18) or Control (N = 16). The trial was prematurely terminated for futility. There was no statistically significant difference in ICU admission, 5 (50 %) in Control vs 13 (72 %) in HBOT. OR 2·54 [95 % CI 0·62-10·39], p = 0·19. HARMS: 102 adverse events (AEs) were recorded. 16 (94 %) subjects in the HBOT group and 14 (93 %) in the control group had at least one AE. Three serious adverse events (SAEs), were at least, possibly related to HBOT. All deaths were unlikely related to HBOT. CONCLUSIONS: HBOT did not reduce ICU admission or mortality in patients with COVID-19-induced ARDS. The trial cannot conclude definitive benefits or harms. Treating COVID-19-induced ARDS with HBOT is feasible with a favourable harms profile.

Trimethoprim-sulfamethoxazole acute respiratory distress syndrome requiring lung transplantation.

Trimethoprim-sulfamethoxazole (TMP-SMX) acute respiratory distress syndrome (ARDS) is a rare, but severe complication of a commonly prescribed antibiotic. TMP-SMX typically affects young, otherwise well patients with a specific human leukocyte antigen type (HLA-B*07:02 and HLA-C*07:02). The condition is poorly understood with a unique pathological appearance and mechanism that remains unclear. Mortality rate is greater than one third. We describe the case of a previously well 18-year-old woman treated with a prolonged course of TMP-SMX for a complex urinary tract infection who developed rapidly progressive respiratory failure requiring prolonged intensive care admission, extra-corporeal membranous oxygenation, and eventual lung transplantation. No targeted treatment exists, further research is required to better understand disease pathogenetic mechanisms and potential therapeutic interventions.

The impact of positive end-expiratory pressure on right ventricular function in patients with moderate-to-severe ARDS: a prospective paired-design study.

Objective: To determine the effects of varying positive end-expiratory pressures (PEEPs) on right ventricular function, hemodynamics, oxygenation, and the incidence of acute cor pulmonale (ACP) in patients with moderate-to-severe acute respiratory distress syndrome (ARDS). Methods: This prospective paired-design study involved patients with moderate-to-severe ARDS in the ICU. Participants received lung-protective ventilation and hemodynamic monitoring. During the study, mechanical ventilation was administered with PEEPs of 5 cmH2O, 10 cmH2O, and 15 cmH2O, while maintaining an end-inspiratory plateau pressure ≤ 30 cmH2O. Various assessments, including transthoracic echocardiography, cardiac output measurement, and blood gas analysis, were conducted at baseline and after 1 h of ventilation at each PEEP. Subsequently, variations in ventilation oxygenation, echocardiographic parameters, and hemodynamic indicators under different PEEPs were analyzed to explore the potential effects of PEEP on right ventricular function and hemodynamics, as well as the incidence of ACP. Results: A total of 317 ARDS patients were screened. Among them, 104 met the diagnostic criteria for moderate-to-severe ARDS, and 52 completed the study. The baseline PEEP of these 52 participants, acquired before commencement, was 11.5 ± 1.7 cmH2O, and the incidence of ACP was 25.0% (13/52). Intensive care unit mortality, overall hospital mortality, and 28-day mortality rates were 19.2% (10/52), 21.2% (11/52), and 32.7% (17/52), respectively. During the study, ACP incidences at PEEPs of 5 cmH2O, 10 cmH2O, and 15 cmH2O were 17.3% (9/52), 21.2% (11/52), and 38.5% (20/52), respectively. Meanwhile, the PaO2/FiO2 ratio improved with increasing PEEP, reaching 162.0 (140.9, 174.0), 171.0 (144.0, 182.0), and 176.5 (151.0, 196) mmHg at PEEPs of 5 cmH2O, 10 cmH2O, and 15 cmH2O, respectively. In addition, higher PEEPs were associated with a slight increase in PaCO2, showing statistically significant differences compared to moderate and low PEEPs. Compared to a PEEP of 5 cmH2O or 10 cmH2O, right ventricular function exhibited substantial changes at 15 cmH2O PEEP, manifested as increased pulmonary artery systolic pressure, enlarged right ventricular end-diastolic area, and decreased tricuspid annular plane systolic excursion, all with significant differences. Conversely, variations in left ventricular end-diastolic area and ejection fraction were not statistically significant. In terms of hemodynamics, increasing PEEP resulted in a decline in cardiac index (CI), with statistically significant differences between different PEEPs. Specifically, compared to the value at a PEEP of 5 cmH2O, the CI at a PEEP of 15 cmH2O decreased by 14.3% (2.63 [2.20, 2.95] vs. 3.07 [2.69, 3.67], p < 0.001). The decline in the stroke volume index with PEEP was more obvious (22.1 [18.4, 27.1] vs. 27.0 [24.2, 33.0], p < 0.001), reaching 18.1%. Additionally, both end-diastolic volume index and extravascular lung water index decreased significantly with increasing PEEP, while the pulmonary vascular permeability index remained unaffected. Conclusion: Different PEEPs can affect the incidence of ACP in patients with moderate-to-severe ARDS. High PEEP improves oxygenation and reduces extravascular lung water without significantly affecting the pulmonary vascular permeability index and left ventricular systolic function. Nevertheless, it can cause right ventricular dilation, as well as substantial declines in right ventricular systolic function and CI, thereby causing ACP.