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Upadhya P, H S S, R H, Mahesh Babu V, Balasoupramaniane K, Nadaf Z. Approach to mechanical ventilation: a simplified approach for a pulmonologist. Monaldi Arch Chest Dis 2025. [PMID: 40491383 DOI: 10.4081/monaldi.2025.3476] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2025] [Indexed: 06/11/2025] Open
Abstract
Mechanical ventilation is a critical intervention for patients with respiratory failure, providing essential support for oxygenation and ventilation while reducing the work of breathing. It operates through key breath-phase variables: triggering (breath initiation), targeting (flow or pressure delivery), and cycling (ending inspiration). Various ventilation modes, including invasive and non-invasive methods, are tailored to patient needs. Non-invasive ventilation and high-flow nasal cannula are first-line options in acute respiratory distress, whereas invasive mechanical ventilation is necessary for severe cases. Optimal ventilatory strategies aim to prevent complications such as barotrauma, volutrauma, and dynamic hyperinflation by carefully adjusting parameters like tidal volume, respiratory rate, and positive end-expiratory pressure. One major challenge in mechanical ventilation is patient-ventilator dyssynchrony, where the patient's respiratory efforts do not align with the ventilator's cycles, leading to increased work of breathing and discomfort. Dyssynchrony can occur during the trigger, target, or cycle phases, requiring waveform analysis and ventilator adjustments to optimize synchrony. Weaning from mechanical ventilation follows a structured process involving readiness assessment, spontaneous breathing trials, and extubation. Successful weaning depends on maintaining stable respiratory function, with close monitoring to prevent post-extubation failure. Identifying and managing ventilatory complications, optimizing patient comfort, and ensuring an individualized approach to ventilator management are key to improving patient outcomes. This review provides a comprehensive understanding of mechanical ventilation, its principles, common challenges, and weaning strategies to guide effective clinical decision-making.
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Affiliation(s)
- Pratap Upadhya
- Pulmonary Medicine, Jawaharlal Nehru Institute of Postgraduate Medical Education and Research, Puducherry
| | - Sanjana H S
- Neonatology, All India Institute of Medical Sciences, Nagpur
| | - Harshith R
- Pulmonary Medicine and Critical Care, Ramaiah Medical College Hospital, Bangalore
| | | | - Karthik Balasoupramaniane
- Pulmonary Medicine, Jawaharlal Nehru Institute of Postgraduate Medical Education and Research, Puducherry
| | - Zeenathaalam Nadaf
- Pulmonary Medicine, Jawaharlal Nehru Institute of Postgraduate Medical Education and Research, Puducherry
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Lambour A, Zerbib Y, Mercado P, Kontar L, Cagny BD, Maizel J, Slama M, Brault C. Lung recruitment maneuver improves right and left ventricular function in patients with acute respiratory distress syndrome. BMC Pulm Med 2025; 25:274. [PMID: 40450243 DOI: 10.1186/s12890-025-03735-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2025] [Accepted: 05/19/2025] [Indexed: 06/03/2025] Open
Affiliation(s)
- Alexis Lambour
- Medical Intensive Care Department, Amiens-Picardie University Hospital, 1 rue du Professeur Christian Cabrol, Amiens, 80000, France
| | - Yoann Zerbib
- Medical Intensive Care Department, Amiens-Picardie University Hospital, 1 rue du Professeur Christian Cabrol, Amiens, 80000, France
- MP3CV Laboratory, UR 7517, Jules Verne University of Picardie, Amiens, France
| | - Pablo Mercado
- Medical Intensive Care Department, Amiens-Picardie University Hospital, 1 rue du Professeur Christian Cabrol, Amiens, 80000, France
- Departamento de Paciente Crítico, Clínica Alemana de Santiago, Facultad de Medicina, Clínica Alemana - Universidad del Desarrollo, Santiago, Chile
| | - Loay Kontar
- Medical Intensive Care Department, Amiens-Picardie University Hospital, 1 rue du Professeur Christian Cabrol, Amiens, 80000, France
| | - Bertrand De Cagny
- Medical Intensive Care Department, Amiens-Picardie University Hospital, 1 rue du Professeur Christian Cabrol, Amiens, 80000, France
| | - Julien Maizel
- Medical Intensive Care Department, Amiens-Picardie University Hospital, 1 rue du Professeur Christian Cabrol, Amiens, 80000, France
- MP3CV Laboratory, UR 7517, Jules Verne University of Picardie, Amiens, France
| | - Michel Slama
- Medical Intensive Care Department, Amiens-Picardie University Hospital, 1 rue du Professeur Christian Cabrol, Amiens, 80000, France
- MP3CV Laboratory, UR 7517, Jules Verne University of Picardie, Amiens, France
| | - Clément Brault
- Medical Intensive Care Department, Amiens-Picardie University Hospital, 1 rue du Professeur Christian Cabrol, Amiens, 80000, France.
- MP3CV Laboratory, UR 7517, Jules Verne University of Picardie, Amiens, France.
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Xu J, Hu H, Jiang H, Wei Q, Zhang H, Lu Q. The therapeutic mechanisms of quercetin on inflammatory diseases: an update. Inflammopharmacology 2025:10.1007/s10787-025-01795-x. [PMID: 40448820 DOI: 10.1007/s10787-025-01795-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2025] [Accepted: 05/12/2025] [Indexed: 06/02/2025]
Abstract
Bioactive compounds derived from medicinal plants have become a significant source of drugs for inflammatory diseases treatment, particularly those caused by immune system abnormalities. Quercetin, a flavonol found in a wide variety of herbs, fruits, and vegetables, has garnered attention for its diverse biological properties, including anti-inflammatory, anticancer, and antiviral activities. Numerous in vivo and ex vivo studies have validated quercetin's role in treating inflammatory diseases through multiple pathways, mainly involving anti-oxidative stress, modulation of metabolism, intestinal flora, apoptosis, endoplasmic reticulum stress, and macrophage polarization, indicating it a promising pharmaceutical candidate for managing inflammatory and autoimmune conditions. We aimed to systematically review quercetin's anti-inflammatory activity and the mechanisms of action across various inflammatory diseases in the digestive, respiratory, endocrine, neurological, and osteoarticular systems. By summarizing the therapeutic potential of quercetin in these multifaceted conditions, this review seeks to provide a solid foundation for future clinical research and application strategies involving quercetin.
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Affiliation(s)
- Jie Xu
- School of Life Sciences, Beijing University of Chinese Medicine, Beijing, 102488, China
| | - Haikun Hu
- School of Life Sciences, Beijing University of Chinese Medicine, Beijing, 102488, China
| | - Haixu Jiang
- School of Chinese Pharmacy, Beijing University of Chinese Medicine, Beijing, China
| | - Qiuzhu Wei
- School of Life Sciences, Beijing University of Chinese Medicine, Beijing, 102488, China
| | - Honglin Zhang
- School of Life Sciences, Beijing University of Chinese Medicine, Beijing, 102488, China
| | - Qingyi Lu
- School of Life Sciences, Beijing University of Chinese Medicine, Beijing, 102488, China.
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Ahn JH, Hong SB, Lim CM, Huh JW. High Tidal Volume Variability Is Associated With Worse Outcomes in Patients With ARDS. Respir Care 2025. [PMID: 40425034 DOI: 10.1089/respcare.12930] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/29/2025]
Abstract
Background: The impact of spontaneous breathing during mechanical ventilation on the outcome of ARDS has yet to be established. This study aimed to evaluate the effect of tidal volume variability on ventilator-free days in mechanically ventilated subjects with ARDS using high-resolution tidal volume data collected through patient monitors. Methods: This single-center, retrospective cohort study included adult subjects with ARDS who received mechanical ventilation in our medical ICU between April 2018 and July 2019. The study subjects' expiratory tidal volume data during the first 7 days of mechanical ventilation were collected every 2 s from the patient monitors. The subjects were divided equally into 3 groups according to the coefficient of variation (CV) of all collected normalized tidal volume values. Results: A total of 108 subjects with ARDS were categorized into the low, intermediate, and high CV groups (each number = 36). Baseline characteristics of the 3 groups were comparable except for a lower PaO2/FIO2 in the low CV group (130 ± 50 mm Hg vs 160 ± 57 mm Hg vs 158 ± 50 mm Hg, P = .03). On average, 222,776 tidal volume data points were collected per subject during the first 7 days of mechanical ventilation. The CVs of tidal volume were 17% ± 3%, 26% ± 2%, and 38% ± 8% in each group, respectively. The number of ventilator-free days was significantly lower in the high CV group than in the intermediate CV group (0 [interquartile range or IQR, 0-2.5] days vs 16 [IQR, 0-21.5] days, P = .004 after Bonferroni correction). After adjusting in the zero-inflated negative binomial model, high CV was significantly associated with fewer ventilator-free days compared with intermediate CV (odds ratio, 11.1, 95% CI [2.3-52.7], P = .002). Conclusions: Based on the high-resolution tidal volume data from the patient monitors, high tidal volume variability during the first 7 days of mechanical ventilation in subjects with ARDS was associated with fewer ventilator-free days.
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Affiliation(s)
- Jee Hwan Ahn
- Drs. Ahn, Hong, Lim, and Huh are affiliated with Department of Pulmonary and Critical Care Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
| | - Sang-Bum Hong
- Drs. Ahn, Hong, Lim, and Huh are affiliated with Department of Pulmonary and Critical Care Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
| | - Chae-Man Lim
- Drs. Ahn, Hong, Lim, and Huh are affiliated with Department of Pulmonary and Critical Care Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
| | - Jin Won Huh
- Drs. Ahn, Hong, Lim, and Huh are affiliated with Department of Pulmonary and Critical Care Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
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Mitrou I, Dimopoulos G, Dakou K, Koufargyris P, Damoraki G, Gkavogianni T, Giamarellos-Bourboulis EJ. Interactions of Probiotics with the Immune Cells of Patients with COVID-19 Pneumonia. J Innate Immun 2025; 17:277-286. [PMID: 40424990 PMCID: PMC12112972 DOI: 10.1159/000545873] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2024] [Accepted: 04/10/2025] [Indexed: 05/29/2025] Open
Abstract
INTRODUCTION In severe COVID-19, excessive cytokine release may be driven by SARS-CoV-2. We investigated the modulatory effect of probiotics taking into consideration direct interaction with the immune gut cells. METHODS Fifty-five patients with confirmed COVID-19 infection were classified by the presence of acute respiratory distress syndrome (ARDS) or not. Peripheral blood mononuclear cells (PBMCs) were isolated and stimulated with lipopolysaccharide (LPS), a preparation of four probiotics (LactoLevure® containing Saccharomyces boulardii, Bifidobacterium lactis BB-12, Lactobacillus acidophilus LA-5, and L. plantarum) and/or recombinant human interferon-gamma (rhIFNγ) and tocilizumab. Cytokine concentrations were measured in cell supernatants. Gene expression of Toll-like receptors 2 (TLR2) and 4 (TLR4) was performed by quantitative real-time polymerase chain reaction (RT-PCR). Results were associated with the level of viremia. RESULTS Probiotics decreased tumor necrosis factor-alpha (TNFα) production by the PBMCs of both ARDS and non-ARDS patients. LPS stimulated the production of interleukin (IL)-1β, IL-6 in non-ARDS patients. IL-6 production was maintained in the presence of probiotics. rhIFNγ enhanced LPS-stimulated cytokine production by PBMCs; this was not the case when PBMCs were stimulated by probiotics. Probiotics upregulated TLR2 and LPS downregulated TLR4 in the PBMCs of patients with ARDS. PBMCs from patients with viremia had more cytokine production by probiotic stimulation. CONCLUSION Probiotics interact with the immune system of COVID-19 patients by modulating the production of TNFα, IL-1β, and IL-6 in an IFNγ-independent mechanism.
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Affiliation(s)
- Ioannis Mitrou
- Fourth Department of Internal Medicine, National and Kapodistrian University of Athens Medical School, Athens, Greece
| | - George Dimopoulos
- Third Department of Critical Care Medicine, National and Kapodistrian University of Athens Medical School, Athens, Greece
| | | | - Panagiotis Koufargyris
- Fourth Department of Internal Medicine, National and Kapodistrian University of Athens Medical School, Athens, Greece
| | - Georgia Damoraki
- Fourth Department of Internal Medicine, National and Kapodistrian University of Athens Medical School, Athens, Greece
| | - Theologia Gkavogianni
- Fourth Department of Internal Medicine, National and Kapodistrian University of Athens Medical School, Athens, Greece
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Morris PE. Translating Recent ARDS Criteria and Practice Guidelines Into Effective Clinical Interventions. Respir Care 2025. [PMID: 40420486 DOI: 10.1089/respcare.13168] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/28/2025]
Affiliation(s)
- Peter E Morris
- Dr. Morris is affiliated with Division of Pulmonary, Allergy and Critical Care Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA
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Haudebourg AF, Chantelot L, Nemlaghi S, Haudebourg L, Labedade P, Boujelben MA, Voiriot G, Mekontso Dessap A, Fartoukh M, Carteaux G. Factors influencing the transition phase in acute respiratory distress syndrome: an observational cohort study. Ann Intensive Care 2025; 15:71. [PMID: 40415127 DOI: 10.1186/s13613-025-01484-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2025] [Accepted: 05/05/2025] [Indexed: 05/27/2025] Open
Abstract
BACKGROUND Protective ventilation during the acute phase of ARDS and weaning from mechanical ventilation are well-established in current guidelines. However, the intermediate transition phase between these stages remains poorly characterized. OBJECTIVES To describe the transition phase in moderate-to-severe ARDS and evaluate the factors associated with neuromuscular blockade (NMBA) weaning failure and pressure support ventilation (PSV) failure. METHODS This bicentric observational cohort study included patients with moderate-to-severe ARDS requiring NMBA continuous infusion within 72 h post-intubation. The transition phase was defined as the 72 h following the first NMBA weaning attempt. The main endpoints were the rates of NMBA reintroduction and PSV failure. Secondary outcomes included predictive factors for NMBA weaning failure and PSV failure and the impact of tidal volume on patient outcomes. MAIN RESULTS A total of 196 patients were included. NMBA weaning failure occurred in 74 (38%) patients. COVID-19 (OR 3.98 [1.95-8.41], p < 0.001), pH (OR 0.50 [0.30-0.79], p = 0.004), PaO2/FiO2 ratio (OR 0.92 [0.87-0.97], p = 0.007), and high or low driving pressure before first NMBA weaning attempt (< 12 or ≥ 14 cmH2O) (OR 2.77 [1.16-7.14], p = 0.027) were significantly associated with NMBA reintroduction. PSV was initiated in 147 (75%) patients, with a failure rate of 57%, occurring after a median of 9 h [6-24]. Tidal volume (OR 1.28 [1.06-1.56], p = 0.012) was significantly associated with PSV failure. During PSV, 43% of patients exhibited high tidal volumes (> 8 mL/kg PBW). NMBA weaning failure was associated with fewer ventilator-free days and increased mortality at day 28. PSV failure was associated with fewer ventilator-free days. CONCLUSION The transition phase represents a high-risk period in ARDS, with significant failure rates for NMBA weaning and PSV trials that may influence patient outcomes. The transition phase therefore represents a critical area for future research to optimize management during this vulnerable period.
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Affiliation(s)
- Anne-Fleur Haudebourg
- Service de Médecine Intensive Réanimation, Assistance Publique-Hôpitaux de Paris, CHU Henri Mondor-Albert Chenevier, 51, Avenue du Maréchal de Lattre de Tassigny, Créteil Cedex, 94010, France.
- Faculté de Santé, Groupe de Recherche Clinique CARMAS, Université Paris Est-Créteil, Créteil, 94010, France.
- INSERM U955, Institut Mondor de Recherche Biomédicale, Créteil, F-94010, France.
- Service de Médecine Intensive Réanimation, CHU Henri Mondor, 1, rue Gustave Eiffel, Créteil Cedex, 94010, France.
| | - Louise Chantelot
- Service de Médecine Intensive Réanimation, Assistance Publique-Hôpitaux de Paris, CHU Henri Mondor-Albert Chenevier, 51, Avenue du Maréchal de Lattre de Tassigny, Créteil Cedex, 94010, France
| | - Safaa Nemlaghi
- Service de Médecine Intensive Réanimation, Assistance Publique-Hôpitaux de Paris, CHU Henri Mondor-Albert Chenevier, 51, Avenue du Maréchal de Lattre de Tassigny, Créteil Cedex, 94010, France
| | - Luc Haudebourg
- Service de Réanimation médicale et infectieuse, Assistance Publique-Hôpitaux de Paris, Hôpital Bichat-Claude Bernard, 46, rue Henri Huchard, Paris, 75018, France
| | - Pascale Labedade
- Service de Médecine Intensive Réanimation, Assistance Publique-Hôpitaux de Paris, CHU Henri Mondor-Albert Chenevier, 51, Avenue du Maréchal de Lattre de Tassigny, Créteil Cedex, 94010, France
- Faculté de Santé, Groupe de Recherche Clinique CARMAS, Université Paris Est-Créteil, Créteil, 94010, France
- INSERM U955, Institut Mondor de Recherche Biomédicale, Créteil, F-94010, France
| | - Mohamed Ahmed Boujelben
- Service de Médecine Intensive Réanimation, Assistance Publique-Hôpitaux de Paris, CHU Henri Mondor-Albert Chenevier, 51, Avenue du Maréchal de Lattre de Tassigny, Créteil Cedex, 94010, France
- Faculté de Santé, Groupe de Recherche Clinique CARMAS, Université Paris Est-Créteil, Créteil, 94010, France
| | - Guillaume Voiriot
- Service de Médecine Intensive Réanimation, Assistance Publique-Hôpitaux de Paris, Hôpital Tenon, 4, rue de la Chine, Paris, 75020, France
| | - Armand Mekontso Dessap
- Service de Médecine Intensive Réanimation, Assistance Publique-Hôpitaux de Paris, CHU Henri Mondor-Albert Chenevier, 51, Avenue du Maréchal de Lattre de Tassigny, Créteil Cedex, 94010, France
- Faculté de Santé, Groupe de Recherche Clinique CARMAS, Université Paris Est-Créteil, Créteil, 94010, France
- INSERM U955, Institut Mondor de Recherche Biomédicale, Créteil, F-94010, France
| | - Muriel Fartoukh
- Service de Médecine Intensive Réanimation, Assistance Publique-Hôpitaux de Paris, Hôpital Tenon, 4, rue de la Chine, Paris, 75020, France
| | - Guillaume Carteaux
- Service de Médecine Intensive Réanimation, Assistance Publique-Hôpitaux de Paris, CHU Henri Mondor-Albert Chenevier, 51, Avenue du Maréchal de Lattre de Tassigny, Créteil Cedex, 94010, France
- Faculté de Santé, Groupe de Recherche Clinique CARMAS, Université Paris Est-Créteil, Créteil, 94010, France
- INSERM U955, Institut Mondor de Recherche Biomédicale, Créteil, F-94010, France
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van Vliet R, Melger JWJ, Paulus F, Bem RA, Blokpoel RGT, Schultz MJ, van Meenen DMP, Kneyber MCJ. Practice of ventilation in critically ill pediatric patients: protocol for an international, long-term, observational study, and results of the pilot feasibility study. CRITICAL CARE SCIENCE 2025; 37:e20250398. [PMID: 40435034 PMCID: PMC12094694 DOI: 10.62675/2965-2774.20250398] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/19/2024] [Accepted: 01/02/2025] [Indexed: 06/01/2025]
Abstract
OBJECTIVE This manuscript describes the protocol of an investigator-initiated, international, multicenter, long-term, prospective observational study named PRactice of VENTilation in PEDiatric Patients (PRoVENT-PED), designed to investigate the epidemiology, respiratory support practices and outcomes of critically ill pediatric patients. DESIGN Data will be collected biannually over 10 years during predefined 4-week intervals, with an additional optional period to accommodate data collection during an epidemic or pandemic. The specific focus of PRoVENT-PED will evolve as the study progresses, initially emphasizing collecting detailed ventilator data from invasively ventilated patients. In later phases, the focus will shift to noninvasive respiratory support and typical aspects of respiratory support, like patient-ventilator asynchronies, weaning practices, and rescue therapies, as extracorporeal support. PRoVENT-PED includes patients under 18 years of age, admitted to a participating intensive care unit, and receiving respiratory support. The endpoints vary with the focus in each phase but will always include a set of key settings and ventilation parameters and related outcomes. If applicable, potentially modifiable factors and associations with outcomes will be studied. The pilot feasibility study demonstrated that the electronic capturing system effectively collects all necessary data within a reasonable time limit, with little missing data. CONCLUSION PRoVENT-PED is a 10-year, international, multicenter study focused on collecting data on respiratory support practices in critically ill pediatric patients. Its scope evolves from invasive to noninvasive ventilatory support, ultimately encompassing patient-ventilator asynchronies, weaning practices, and rescue therapies.
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Affiliation(s)
- Relin van Vliet
- Amsterdam University Medical CentersDepartment of Intensive CareAmsterdamThe NetherlandsDepartment of Intensive Care, Amsterdam University Medical Centers - Amsterdam, The Netherlands.
| | - Jonathan Willem Jochem Melger
- Amsterdam University Medical CentersDepartment of Intensive CareAmsterdamThe NetherlandsDepartment of Intensive Care, Amsterdam University Medical Centers - Amsterdam, The Netherlands.
| | - Frederique Paulus
- Amsterdam University Medical CentersDepartment of Intensive CareAmsterdamThe NetherlandsDepartment of Intensive Care, Amsterdam University Medical Centers - Amsterdam, The Netherlands.
| | - Reinout Alexander Bem
- Amsterdam University Medical CentersDepartment of Intensive CareAmsterdamThe NetherlandsDepartment of Intensive Care, Amsterdam University Medical Centers - Amsterdam, The Netherlands.
| | - Robert Gorge Theodoor Blokpoel
- University Medical Center GroningenBeatrix Children's HospitalDivision of Paediatric Critical Care MedicineGroningenThe NetherlandsDepartment of Paediatrics, Division of Paediatric Critical Care Medicine, Beatrix Children's Hospital, University Medical Center Groningen - Groningen, The Netherlands.
| | - Marcus Josephus Schultz
- Amsterdam University Medical CentersDepartment of Intensive CareAmsterdamThe NetherlandsDepartment of Intensive Care, Amsterdam University Medical Centers - Amsterdam, The Netherlands.
| | - David Michael Paul van Meenen
- Amsterdam University Medical CentersDepartment of AnesthesiologyAmsterdamThe NetherlandsDepartment of Anesthesiology, Amsterdam University Medical Centers - Amsterdam, The Netherlands.
| | - Martin Christiaan Jacques Kneyber
- University Medical Center GroningenBeatrix Children's HospitalDivision of Paediatric Critical Care MedicineGroningenThe NetherlandsDepartment of Paediatrics, Division of Paediatric Critical Care Medicine, Beatrix Children's Hospital, University Medical Center Groningen - Groningen, The Netherlands.
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Schultz MJ, Battaglini D, Nasa P. Classifying ARDS by dynamic or static oxygenation impairment or are other approaches needed for greater value. Thorax 2025:thorax-2025-223490. [PMID: 40393721 DOI: 10.1136/thorax-2025-223490] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/05/2025] [Indexed: 05/22/2025]
Affiliation(s)
- Marcus J Schultz
- Intensive Care Medicine, Amsterdam UMC Locatie AMC, Amsterdam, The Netherlands
| | - Denise Battaglini
- Anaesthesia and Intensive Care, IRCCS Ospedale Policlinico San Martino, Genoa, Liguria, Italy
| | - Prashant Nasa
- Department of Critical Care Medicine and Anaesthesia, New Cross Hospital, Wolverhampton, UK
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Bai Y, Chen S, Yang H, Huang X, Xia J, Zhan Q. Dynamic oxygenation subgroup bringing new insights in ARDS: more predictive of outcomes and response to PEEP than static PaO 2/FiO 2. Thorax 2025:thorax-2024-222360. [PMID: 40393717 DOI: 10.1136/thorax-2024-222360] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2024] [Accepted: 04/15/2025] [Indexed: 05/22/2025]
Abstract
BACKGROUND Acute respiratory distress syndrome (ARDS) is a rapidly evolving condition. Dynamic assessments using patient trajectories may provide novel insights into disease heterogeneity. The primary objective of this study was to develop and validate dynamic oxygenation subgroups of ARDS based on longitudinal arterial oxygen tension/fractional inspired oxygen (PaO2/FiO2) ratios from the day of ARDS diagnosis to day 3. The secondary objective was to determine whether these dynamic physiological subgroups are more effective in predicting patient outcomes and treatment response than the Berlin criteria-defined static oxygenation subgroups. METHODS We used group-based trajectory modelling to construct longitudinal oxygenation subgroups over the first 3 days following ARDS diagnosis, based on five ARDS databases. Additionally, we compared these longitudinal subgroups with static Berlin criteria-defined mild, moderate and severe subgroups in terms of clinical characteristics, outcomes and positive end-expiratory pressure (PEEP) responses. RESULTS A total of 814 and 2505 patients with ARDS were included in the training cohort (Chinese ARDS Database) and validation cohorts (FACTT, SAILS, ALVEOLI and MIMIC-IV), respectively. We derived three longitudinal oxygenation subgroups: group 1 (n=406, 49.88%), group 2 (n=302, 37.10%) and group 3 (n=106, 13.02%). The PaO2/FiO2 of the three subgroups exhibited the following trends over time: persistently low, gradually increasing and rapidly improving. The mortality differences across the three longitudinal subgroups (62.59% vs 35.79% vs 17.39%) were significantly greater than those in Berlin criteria-defined subgroups (57.53% vs 41.34% vs 32.18%; χ²=55.65 vs 13.45, p=0.001 for heterogeneity comparison). Additionally, treatment heterogeneity (high vs low PEEP) was more pronounced in longitudinal subgroups (interaction p=0.001) compared with Berlin subgroups (interaction p=0.72). The longitudinal subgroup exhibited variations in patient demographics, PaO2/FiO2 development trajectory and PEEP treatment response, compared with the subgroup defined by the Berlin criteria. CONCLUSIONS We identified three longitudinal oxygenation subgroups of ARDS that were more predictive of prognosis and response to PEEP than the subgroups defined by static PaO2/FiO2 ratios in the ARDS Berlin criteria.
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Affiliation(s)
- Yu Bai
- National Center for Respiratory Medicine; State Key Laboratory of Respiratory Health and Multimorbidity; National Clinical Research Center for Respiratory Diseases; Institute of Respiratory Medicine, Chinese Academy of Medical Sciences; Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital, Beijing, China
| | - Shengsong Chen
- Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
| | - Haopu Yang
- Tsinghua University School of Medicine, Beijing, China
| | - Xu Huang
- National Center for Respiratory Medicine; State Key Laboratory of Respiratory Health and Multimorbidity; National Clinical Research Center for Respiratory Diseases; Institute of Respiratory Medicine, Chinese Academy of Medical Sciences; Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital, Beijing, China
| | - Jingen Xia
- National Center for Respiratory Medicine; State Key Laboratory of Respiratory Health and Multimorbidity; National Clinical Research Center for Respiratory Diseases; Institute of Respiratory Medicine, Chinese Academy of Medical Sciences; Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital, Beijing, China
| | - Qingyuan Zhan
- National Center for Respiratory Medicine; State Key Laboratory of Respiratory Health and Multimorbidity; National Clinical Research Center for Respiratory Diseases; Institute of Respiratory Medicine, Chinese Academy of Medical Sciences; Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital, Beijing, China
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Huang J, An H, Cheng L, Li W, Zhang K, Su D. Roles of oral anticoagulant use on the risk of 28-day mortality and in-hospital mortality in patients with acute respiratory distress syndrome. Front Pharmacol 2025; 16:1565312. [PMID: 40438607 PMCID: PMC12117219 DOI: 10.3389/fphar.2025.1565312] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2025] [Accepted: 04/25/2025] [Indexed: 06/01/2025] Open
Abstract
Aim This study was to investigate the association between oral anticoagulant use and 28-day mortality and in-hospital mortality in patients with acute respiratory distress syndrome (ARDS). Methods A total of 1754 ARDS patients were identified in database from 2008 to 2022 in this cohort study. Univariable and multivariable cox regression models were applied to assess the associations of oral anticoagulant use with the risk of 28-day mortality and in-hospital mortality. Propensity score matching (PSM) was performed in ARDS patients according to whether they were taking oral anticoagulants or not to control potential bias. Subgroup analysis was performed according to severity of ARDS (mild, moderate, and severe), and comorbidities (atrial fibrillation, sepsis, and AKI). Hazards ratio (HR) and respective confidence interval (CI) were presented. Results In total, 7758 patients not receiving oral anticoagulant and 905 patients receiving oral anticoagulant. The reduced risk of 28-day mortality in ARDS patients was identified in those undergoing oral anticoagulant use (HR = 0.32, 95%CI: 0.24-0.44). Oral anticoagulant use was associated with reduced risk of in-hospital mortality (HR = 0.27, 95%CI: 0.20-0.37). After adjusting for the respective confounding factors, the associations of Warfarin with decreased risk of 28-day and in-hospital mortality were not significant (P > 0.05). Conclusion Oral anticoagulant was related to decreased risk of 28-day/in-hospital mortality in patients with ARDS. Warfarin and novel oral anticoagulants showed no significant difference on 28-day/in-hospital mortality in patients with ARDS.
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Affiliation(s)
- Jiayang Huang
- Department of Pharmacy, Shenzhen People’s Hospital (The Second Clinical Medical College, Jinan University, The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, China
| | - Huijie An
- Department of Pharmacy, General Hospital of Southern Theatre Command, PLA, Guangzhou, China
| | - Lin Cheng
- Department of Pharmacy, Shenzhen People’s Hospital (The Second Clinical Medical College, Jinan University, The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, China
| | - Wangsheng Li
- Department of Pharmacy, The Third People’s Hospital of Longgang District Shenzhen, Shenzhen, China
| | - Ke Zhang
- Department of Pharmacy, Shaoxing People’s Hospital, Shaoxing, China
| | - Dan Su
- Health Management Center, Shenzhen University General Hospital, Shenzhen, China
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12
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Xu S, Cui M, Wang R. Rs9839776 Genetic Variant of lncRNA SOX2OT Contributes to Susceptibility of Acute Kidney Injury in Sepsis Patients via Regulating SOX2OT/miR-9-5p Axis. J Inflamm Res 2025; 18:6077-6089. [PMID: 40357380 PMCID: PMC12068393 DOI: 10.2147/jir.s508476] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2024] [Accepted: 03/14/2025] [Indexed: 05/15/2025] Open
Abstract
Purpose Single nucleotide polymorphisms (SNPs) are commonly found in lncRNA, and can regulate its expression. The study examined the genotype and allele distributions of rs9839776 polymorphism in lncRNA SOX2OT in sepsis patients with acute kidney injury (AKI), as well as its expression changes. The function of SOX2OT in AKI cell model was also elucidated. Patients and Methods Serum SOX2OT levels were examined via qRT-PCR in 450 septic patients including 202 cases with AKI and 248 without. Genotyping of rs9839776 polymorphism was completed via Taqman real-time PCR. HK-2 cells were treated with LPS to mimic AKI, the cell viability, apoptosis and inflammatory response were evaluated after regulating SOX2OT levels. The function and pathways enriched by the downstream target genes were explored via GO and KEGG analysis. Results Rs9839776 CC genotype carriers were commonly observed in sepsis patients with AKI, and presented reduced levels of SOX2OT. Serum SOX2OT was lowly expressed in AKI patients, which can distinguish AKI patients from sepsis ones. In vitro, SOX2OT alleviated LPS-induced AKI via mediating cell proliferation, apoptosis and inflammatory response, which was reversed by miR-9-5p. GO and KEGG analysis uncovered significant links of miR-9-5p target genes with cytoskeleton in muscle cells, cell adhesion molecules and prolactin signaling pathway. Conclusion The CC genotype of rs9839776 polymorphism in SOX2OT could affect the susceptibility of AKI for sepsis patients, and its-mediated SOX2OT downregulation may serve as a biomarker for AKI. The underlying mechanism might be related to the mediation of the SOX2OT/miR-9-5p axis.
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Affiliation(s)
- Shuying Xu
- Department of Emergency, Binzhou Medical University Hospital, Binzhou, Shandong, People’s Republic of China
| | - Mingli Cui
- Department of Cardiovascular Medicine, Binzhou Medical University Hospital, Binzhou, Shandong, People’s Republic of China
| | - Ruixia Wang
- Department of Emergency, Binzhou Medical University Hospital, Binzhou, Shandong, People’s Republic of China
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13
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Alenezi FK, Mahida RY, Bangash MN, Patel J, Thickett D, Parekh D. Incidence of major adverse kidney events after ICU admission in COVID-19 and non-COVID-19 ARDS patients. BMJ Open 2025; 15:e094887. [PMID: 40328653 PMCID: PMC12056615 DOI: 10.1136/bmjopen-2024-094887] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/10/2024] [Accepted: 04/17/2025] [Indexed: 05/08/2025] Open
Abstract
OBJECTIVES To compare the incidence and drivers of major adverse kidney events (MAKEs) between COVID-19 and non-COVID-19 acute respiratory distress syndrome (ARDS) patients, with a focus on long-term kidney outcomes. DESIGN Retrospective cohort study. SETTING Single-centre intensive care unit in the Midlands, UK. PARTICIPANTS 708 ARDS patients (458 COVID-19, 250 non-COVID-19). PRIMARY AND SECONDARY OUTCOME MEASURES The primary outcome was MAKE at 365 days (MAKE-365), defined as new renal replacement therapy (RRT), estimated glomerular filtration rate (eGFR) <75% of baseline or all-cause mortality. Secondary analyses examined non-mortality MAKE components. RESULTS The incidence of MAKE-365 was significantly higher in the non-COVID-19 group compared with the COVID-19 group (66% vs 39%, p<0.001), primarily driven by increased RRT initiation, followed by mortality and eGFR decline (p=0.055). Independent predictors of MAKE-365 included lower eGFR and elevated bilirubin in both groups. Age (p<0.001) and diabetes (p=0.041) were additional predictors in the COVID-19 cohort, while lower albumin (p=0.002) was significant in the non-COVID-19 group. Excluding mortality, RRT and eGFR decline remained significant drivers of MAKE outcomes in the non-COVID-19 cohort. CONCLUSIONS Non-COVID-19 ARDS patients face a greater risk of MAKE-365 and adverse kidney outcomes due to higher RRT requirements and mortality rates. These findings underscore the importance of tailored interventions and long-term nephrology follow-up, particularly for patients with reduced eGFR, elevated bilirubin and comorbidities like diabetes and hypoalbuminaemia.
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Affiliation(s)
- Faraj K Alenezi
- King Saud bin Abdulaziz University for Health Sciences College of Applied Medical Sciences, Riyadh, Saudi Arabia
- King Abdullah International Medical Research Center, Riyadh, Saudi Arabia
- Institute of Inflammation and Ageing, University of Birmingham College of Medical and Dental Sciences, Birmingham, UK
| | - Rahul Y Mahida
- Institute of Inflammation and Ageing, University of Birmingham College of Medical and Dental Sciences, Birmingham, UK
| | - Mansoor N Bangash
- Critical Care Unit, University Hospital of Birmingham NHS Foundation Trust, Birmingham, UK
| | - Jaimin Patel
- Institute of Inflammation and Ageing, University of Birmingham College of Medical and Dental Sciences, Birmingham, UK
| | - David Thickett
- Institute of Inflammation and Ageing, University of Birmingham College of Medical and Dental Sciences, Birmingham, UK
| | - Dhruv Parekh
- Institute of Inflammation and Ageing, University of Birmingham College of Medical and Dental Sciences, Birmingham, UK
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14
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Dei Cas A, Aldigeri R, Eletto E, Ticinesi A, Nouvenne A, Prati B, Vazzana A, Antonini M, Moretti V, Balestreri E, Spigoni V, Fantuzzi F, Schirò S, Ruffini L, Sverzellati N, Meschi T, Bonadonna R. Hyperglycemia in the diabetic range, but not previous diagnosis of diabetes mellitus, is an independent indicator of poor outcome in patients hospitalized for severe COVID-19. Acta Diabetol 2025:10.1007/s00592-025-02507-1. [PMID: 40314776 DOI: 10.1007/s00592-025-02507-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/24/2025] [Accepted: 03/29/2025] [Indexed: 05/03/2025]
Abstract
AIMS Diabetes mellitus (DM) and hyperglycemia are associated with poor outcome(s) in COVID-19 hospitalized patients, but their independent impact on prognosis remains unclear. We aimed to assess the impact of DM and hyperglycemia on COVID-19 outcomes. METHODS Clinical data/records from COVID-19 patients admitted to the Parma University-Hospital (February 23rd to March 31st, 2020) were retrieved and analysed (NCT04550403). Fasting plasma glucose (FPG), inflammatory markers and the main biochemical variables were collected at admission. Patients underwent chest high-resolution CT and arterial blood gas analysis to determine the PaO2/FiO2 ratio (P/F ratio). The primary outcome was a composite of intensive care unit admission and/or death. RESULTS Among 756 subjects, 143 (19%) had DM. These patients were older with higher comorbidity rates. The primary outcome occurred in 61.5% DM patients versus 43.4% without DM (p < 0.001). In multivariable analysis (accuracy UC = 0.93), older age, cardiovascular and kidney diseases, FPG ≥ 126 mg/dl, C-reactive protein, and P/F ratio, but not previous DM, were independent risk indicators. CONCLUSIONS DM indicated poor COVID-19 outcomes, but not when adjusted for other clinical variables/comorbities, suggesting that its impact was mostly driven by concomitant factors. The independent role of fasting hyperglycemia points to the need for further research on its contribution to COVID-19.
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Affiliation(s)
- Alessandra Dei Cas
- Endocrinology and Metabolic Diseases, Azienda Ospedaliero-Universitaria of Parma, Via Gramsci 14, 43126, Parma, Italy
- Department of Medicine and Surgery, University of Parma, Parma, Italy
| | - Raffaella Aldigeri
- Endocrinology and Metabolic Diseases, Azienda Ospedaliero-Universitaria of Parma, Via Gramsci 14, 43126, Parma, Italy
- Department of Medicine and Surgery, University of Parma, Parma, Italy
| | - Elisa Eletto
- Endocrinology and Metabolic Diseases, Azienda Ospedaliero-Universitaria of Parma, Via Gramsci 14, 43126, Parma, Italy
| | - Andrea Ticinesi
- Department of Medicine and Surgery, University of Parma, Parma, Italy
- Department of Care Continuity and Multicomplexity, Azienda Ospedaliero-Universitaria of Parma, Parma, Italy
| | - Antonio Nouvenne
- Department of Medicine and Surgery, University of Parma, Parma, Italy
- Department of Care Continuity and Multicomplexity, Azienda Ospedaliero-Universitaria of Parma, Parma, Italy
| | - Beatrice Prati
- Department of Care Continuity and Multicomplexity, Azienda Ospedaliero-Universitaria of Parma, Parma, Italy
| | - Angela Vazzana
- Endocrinology and Metabolic Diseases, Azienda Ospedaliero-Universitaria of Parma, Via Gramsci 14, 43126, Parma, Italy
| | - Monica Antonini
- Endocrinology and Metabolic Diseases, Azienda Ospedaliero-Universitaria of Parma, Via Gramsci 14, 43126, Parma, Italy
| | - Valentina Moretti
- Endocrinology and Metabolic Diseases, Azienda Ospedaliero-Universitaria of Parma, Via Gramsci 14, 43126, Parma, Italy
| | - Emanuela Balestreri
- Endocrinology and Metabolic Diseases, Azienda Ospedaliero-Universitaria of Parma, Via Gramsci 14, 43126, Parma, Italy
| | - Valentina Spigoni
- Department of Medicine and Surgery, University of Parma, Parma, Italy
| | - Federica Fantuzzi
- Department of Medicine and Surgery, University of Parma, Parma, Italy
| | - Silvia Schirò
- Department of Medicine and Surgery, University of Parma, Parma, Italy
| | - Livia Ruffini
- Nuclear Medicine, Azienda Ospedaliero-Universitaria of Parma, Parma, Italy
| | - Nicola Sverzellati
- Department of Medicine and Surgery, University of Parma, Parma, Italy
- Radiological Sciences, Azienda Ospedaliero-Universitaria of Parma, Parma, Italy
| | - Tiziana Meschi
- Department of Medicine and Surgery, University of Parma, Parma, Italy
- Department of Care Continuity and Multicomplexity, Azienda Ospedaliero-Universitaria of Parma, Parma, Italy
| | - Riccardo Bonadonna
- Endocrinology and Metabolic Diseases, Azienda Ospedaliero-Universitaria of Parma, Via Gramsci 14, 43126, Parma, Italy.
- Department of Medicine and Surgery, University of Parma, Parma, Italy.
- Endocrinology, Diabetology and Metabolic Diseases, University of Verona and University Hospital of Verona, Verona, Italy.
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15
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Kelly-Hedrick M, Liu S, Hatfield J, Soto AL, Bartlett AM, Heo HJ, O’Callaghan E, Arulraja E, Kaplan S, Ohnuma T, Krishnamoorthy V, Colton K, Komisarow J. Management of traumatic brain injury and acute respiratory distress syndrome-What evidence exists? A scoping review. J Intensive Care Soc 2025; 26:205-222. [PMID: 39834359 PMCID: PMC11742134 DOI: 10.1177/17511437241311398] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/22/2025] Open
Abstract
Introduction Up to 20% of patients with traumatic brain injury (TBI) develop acute respiratory distress syndrome (ARDS), which is associated with increased odds of mortality. Guideline-based treatment for ARDS includes "lung protective" ventilation strategies, some of which are in opposition to "brain protective" strategies used for ventilation with patients with TBI. We conducted a scoping review of ventilation management strategies with clinical outcomes among patients with TBI and ARDS. Methods We searched three databases (MEDLINE, Embase, Web of Science) using a systematic search strategy. We included any studies of patients with TBI and ARDS with ventilation strategies including PEEP, oxygenation, prone positioning, recruitment maneuvers, pulmonary vasodilators (e.g., nitric oxide), high frequency oscillatory ventilation (HFOV), and extracorporeal membrane oxygenation (ECMO). All clinical outcomes were included. Extracted data included details about sample (age, gender), study design, inclusion/exclusion criteria, intervention details, and outcomes. Results The search returned 10,514 articles, 35 of which met final inclusion criteria. Interventions studied included ECMO (n = 13 articles), HFOV (n = 4), PEEP interventions (n = 3), prone positioning (n = 3), vasodilators (n = 4), and other lung recruitment maneuvers (n = 9). No randomized controlled trials were identified; studies were mostly case reports (n = 18/35, 51%) and series (n = 7/35, 20%), with some cohort studies (n = 5/35, 14%) and non-randomized experimental trials (n = 5/35, 14%), all at single institutions. Outcomes included physiologic changes (e.g., change in cerebrodynamics or hemodynamics with intervention) and clinical outcomes such as mortality, complications, or neurologic recovery. Five studies (14%) included pediatric patients. Discussion In this scoping review of ventilatory strategies for patients with concurrent TBI and ARDS, we found variation in heterogeneity of study design, interventions, and outcomes. Studies were mostly case report/series and observational studies, seriously limiting our ability to draw conclusions about effectiveness of interventions. Targeted areas of further research are discussed.
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Affiliation(s)
- Margot Kelly-Hedrick
- Critical Care and Perioperative Population Health Research (CAPER) Program, Department of Anesthesiology, Duke University, Durham, NC, USA
- Duke University School of Medicine, Durham, NC, USA
| | - Sunny Liu
- Critical Care and Perioperative Population Health Research (CAPER) Program, Department of Anesthesiology, Duke University, Durham, NC, USA
- Duke University School of Medicine, Durham, NC, USA
| | - Jordan Hatfield
- Critical Care and Perioperative Population Health Research (CAPER) Program, Department of Anesthesiology, Duke University, Durham, NC, USA
- Department of Neurosurgery, Duke University, Durham, NC, USA
| | | | | | - Helen J. Heo
- Duke University School of Medicine, Durham, NC, USA
| | | | | | - Samantha Kaplan
- Duke University Medical Center Library and Archives, Durham, NC, USA
| | - Tetsu Ohnuma
- Critical Care and Perioperative Population Health Research (CAPER) Program, Department of Anesthesiology, Duke University, Durham, NC, USA
- Anesthesiology, Duke University, Durham, NC, USA
| | - Vijay Krishnamoorthy
- Critical Care and Perioperative Population Health Research (CAPER) Program, Department of Anesthesiology, Duke University, Durham, NC, USA
- Anesthesiology, Duke University, Durham, NC, USA
- Population Health Sciences, Duke University, Durham, NC, USA
| | | | - Jordan Komisarow
- Critical Care and Perioperative Population Health Research (CAPER) Program, Department of Anesthesiology, Duke University, Durham, NC, USA
- Department of Neurosurgery, Duke University, Durham, NC, USA
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16
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Li W, Zhou H, Zou Y. An interpretable machine learning model for predicting mortality risk in adult ICU patients with acute respiratory distress syndrome. Front Med (Lausanne) 2025; 12:1580345. [PMID: 40351465 PMCID: PMC12061690 DOI: 10.3389/fmed.2025.1580345] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2025] [Accepted: 04/10/2025] [Indexed: 05/14/2025] Open
Abstract
Background Acute respiratory distress syndrome (ARDS) is a clinical syndrome triggered by pulmonary or extra-pulmonary factors with high mortality and poor prognosis in the ICU. The aim of this study was to develop an interpretable machine learning predictive model to predict the risk of death in patients with ARDS in the ICU. Methods The datasets used in this study were obtained from two independent databases: Medical Information Mart for Intensive Care (MIMIC) IV and eICU Collaborative Research Database (eICU-CRD). This study used eight machine learning algorithms to construct predictive models. Recursive feature elimination with cross-validation is used to screen features, and cross-validation-based Bayesian optimization is used to filter the features used to find the optimal combination of hyperparameters for the model. The Shapley additive explanations (SHAP) method is used to explain the decision-making process of the model. Results A total of 5,732 patients with severe ADRS were included in this study for analysis, of which 1,171 patients (20.4%) did not survive. Among the eight models, XGBoost performed the best; AUC-ROC was 0.887 (95% CI: 0.863-0.909) and AUPRC was 0.731 (95% CI: 0.673-0.783). Conclusion We developed a machine learning-based model for predicting the risk of death of critically ill ARDS patients in the ICU, and our model can effectively identify high-risk ARDS patients at an early stage, thereby supporting clinical decision-making, facilitating early intervention, and improving patient prognosis.
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Affiliation(s)
- Wanyi Li
- Tianjin Children’s Hospital (Children’s Hospital of Tianjin University), Tianjin, China
| | - Hangyu Zhou
- College of Statistics, Shanxi University of Finance and Economics, Taiyuan, Shanxi, China
| | - Yingxue Zou
- Tianjin Children’s Hospital (Children’s Hospital of Tianjin University), Tianjin, China
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17
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Zhao Q, Lai J, Jiang Y, Cui E, Chang H, Pan R, Li P, Shao JZ, Zheng J, Chen Y. Lactiplantibacillus plantarum -derived extracellular vesicles alleviate acute lung injury by inhibiting ferroptosis of macrophages. J Nanobiotechnology 2025; 23:307. [PMID: 40269965 PMCID: PMC12016285 DOI: 10.1186/s12951-025-03405-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2024] [Accepted: 04/15/2025] [Indexed: 04/25/2025] Open
Abstract
Despite considerable advancements in understanding the mechanisms of ALI, the therapeutic options available in clinical practice remain predominantly supportive, highlighting the urgent need for innovative treatments. In this study, we investigated the potential protective benefits of extracellular vehicles from the probiotic strain Lactiplantibacillus plantarum (LpEVs) in ALI mouse model. We revealed that LpEVs administration attenuated LPS-induced ALI, as evidenced by reduced lung pathology, decreased inflammatory markers, and mitigated ferroptosis. In vitro experiments demonstrated that LpEVs restrained ferroptosis and promoted a shift towards an anti-inflammatory macrophage phenotype. Moreover, LpEVs increased the expression of NRF2, resulting in the promotion of HO1 and strengthening anti-ferroptotic System Xc-/GPX4 axis. Our analysis revealed that LpEVs alleviated ALI through the suppression of macrophages ferroptosis by delivering cbn-let-7 targeting ferroptosis-related gene Acsl4. These findings propose LpEVs as a promising therapeutic approach for preventing and treating ALI, highlighting the potential of leveraging probiotic-derived biomolecules to develop novel therapeutic strategies.
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Affiliation(s)
- Qiong Zhao
- Department of Genetic and Metabolic Disease, The Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, 310052, China
- College of Life Sciences, Key Laboratory for Cell and Gene Engineering of Zhejiang Province, Zhejiang University, Hangzhou, 310052, China
| | - Jingbo Lai
- Department of Genetic and Metabolic Disease, The Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, 310052, China
- College of Life Sciences, Key Laboratory for Cell and Gene Engineering of Zhejiang Province, Zhejiang University, Hangzhou, 310052, China
| | - Yang Jiang
- Department of Genetic and Metabolic Disease, The Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, 310052, China
- College of Life Sciences, Key Laboratory for Cell and Gene Engineering of Zhejiang Province, Zhejiang University, Hangzhou, 310052, China
| | - Enhai Cui
- Department of Respiratory and Critical Care Medicine, Affiliated Huzhou Hospital, Huzhou Central Hospital, Zhejiang University School of Medicine, Huzhou, Zhejiang, 313000, China
| | - Hui Chang
- Department of Genetic and Metabolic Disease, The Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, 310052, China
- College of Life Sciences, Key Laboratory for Cell and Gene Engineering of Zhejiang Province, Zhejiang University, Hangzhou, 310052, China
| | - Ruolang Pan
- Zhejiang Provincial Key Laboratory of Cell-Based Drug and Applied Technology Development, Institute for Cell-Based Drug Development of Zhejiang Province, Hangzhou, China
| | - Ping Li
- Key Laboratory for Food Microbial Technology of Zhejiang Province, Zhejiang Gongshang University, Hangzhou, China
| | - Jian-Zhong Shao
- College of Life Sciences, Key Laboratory for Cell and Gene Engineering of Zhejiang Province, Zhejiang University, Hangzhou, 310052, China
| | - Jing Zheng
- Department of Genetic and Metabolic Disease, The Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, 310052, China.
| | - Ye Chen
- Department of Genetic and Metabolic Disease, The Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, 310052, China.
- College of Life Sciences, Key Laboratory for Cell and Gene Engineering of Zhejiang Province, Zhejiang University, Hangzhou, 310052, China.
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18
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Zhang R, Du H, Liu Z, Lei Y, Hu H, Zheng J, Yang P, Zhao D. Macrophage Notch1 Participates in LPS-Induced Acute Lung Injury via Regulating CCR5 Expression in Mice. FRONT BIOSCI-LANDMRK 2025; 30:37430. [PMID: 40302346 DOI: 10.31083/fbl37430] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2025] [Revised: 03/22/2025] [Accepted: 03/27/2025] [Indexed: 05/02/2025]
Abstract
BACKGROUND As pivotal immunoregulatory sentinels in pulmonary defense systems, alveolar macrophages (AMs) play dual roles in mediating inflammatory responses and tissue repair processes during various phases of inflammatory cascades. The present investigation focuses on elucidating the regulatory influence of Notch pathway activation within AM populations on the pathophysiological mechanisms underlying acute lung injury (ALI) development. METHODS To investigate the regulatory roles of Notch intracellular domain (NICD) and C-C chemokine receptor type 5 (CCR5) in pulmonary inflammation, an ALI model was established through lipopolysaccharide (LPS) administration. Complementary studies used macrophage-specific Notch1 knockout mice and immortalized bone marrow-derived macrophages (iBMDMs). Molecular profiling of CCR5 and inflammatory mediators was performed through real-time quantitative reverse transcription PCR (qRT-PCR) and immunofluorescence staining. Functional assessments of macrophage migration were carried out using scratch wound healing assays and transwell migration assays. RESULTS In the LPS-induced ALI model, pulmonary tissues exhibited elevated expression of both NICD and CCR5. Conversely, Notch1 knockout mice attenuated CCR5 expression, reduced macrophage infiltration and downregulated transcription of pro-inflammatory mediators compared to wild-type controls (p < 0.05). Lung injury was milder in the Notch1-deficient mice model compared to wild mice (p < 0.05). In vitro experiments demonstrated that inhibiting the Notch pathway in macrophages reduced CCR5 expression and attenuated CCL5-induced macrophage migration. CONCLUSION Notch signaling regulates macrophage infiltration and the inflammatory response by modulating CCR5 expression in ALI induced by LPS.
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Affiliation(s)
- Ruiyu Zhang
- Department of Pediatrics, Zhongnan Hospital of Wuhan University, 430071 Wuhan, Hubei, China
| | - Hui Du
- Department of Pediatrics, Zhongnan Hospital of Wuhan University, 430071 Wuhan, Hubei, China
| | - Zhi Liu
- Department of Pediatrics, Zhongnan Hospital of Wuhan University, 430071 Wuhan, Hubei, China
| | - Yuxi Lei
- Department of Pediatrics, Zhongnan Hospital of Wuhan University, 430071 Wuhan, Hubei, China
| | - Huizhi Hu
- Department of Pediatrics, Zhongnan Hospital of Wuhan University, 430071 Wuhan, Hubei, China
| | - Junwen Zheng
- Department of Pediatrics, Zhongnan Hospital of Wuhan University, 430071 Wuhan, Hubei, China
| | - Pu Yang
- Department of Pediatrics, Zhongnan Hospital of Wuhan University, 430071 Wuhan, Hubei, China
- Children's Digital Health and Data Center of Wuhan University, 430071 Wuhan, Hubei, China
| | - Dongchi Zhao
- Department of Pediatrics, Zhongnan Hospital of Wuhan University, 430071 Wuhan, Hubei, China
- Children's Digital Health and Data Center of Wuhan University, 430071 Wuhan, Hubei, China
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19
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Karnan N, Jancic P, Dumic I, Amadi E, Kommineni V, Stojsavljevic J, Shiari A, Hart M, Jabr R, Nordstrom CW. Severe Anaplasmosis with Multi-Organ Failure in a Patient with Splenectomy: A Case Report. Infect Dis Rep 2025; 17:38. [PMID: 40277965 PMCID: PMC12026683 DOI: 10.3390/idr17020038] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/17/2025] [Revised: 04/15/2025] [Accepted: 04/17/2025] [Indexed: 04/26/2025] Open
Abstract
BACKGROUND Anaplasma phagocytophilum is an emerging tick-borne zoonotic pathogen that typically causes mild infections, which are often successfully managed in outpatient settings. Immunosuppression associated with splenectomy is a well-documented risk factor for severe infections from pathogens such as Babesia microti and encapsulated bacteria. However, splenectomy has not previously been identified as a risk factor for severe anaplasmosis. CASE PRESENTATION This report describes a rare case of severe anaplasmosis complicated by multiorgan failure in a patient who had undergone splenectomy several decades earlier. The clinical course was notable for pneumonia, acute respiratory distress syndrome, acute kidney injury, rhabdomyolysis, atrial fibrillation, and possible myocarditis. Despite the severity of the presentation, prompt initiation of doxycycline led to recovery, albeit with a significantly prolonged hospital stay. CONCLUSIONS Patients with splenectomy might be more likely to develop a serious form of Anaplasmosis infection such as multiorgan failure. Clinicians in tick-borne endemic areas should be aware that non-specific symptoms can indicate anaplasmosis.
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Affiliation(s)
- Nithin Karnan
- Department of Hospital Medicine, Mayo Clinic Health System, Eau Claire, WI 54703, USA; (N.K.); (P.J.); (E.A.); (V.K.); (J.S.); (C.W.N.)
| | - Predrag Jancic
- Department of Hospital Medicine, Mayo Clinic Health System, Eau Claire, WI 54703, USA; (N.K.); (P.J.); (E.A.); (V.K.); (J.S.); (C.W.N.)
| | - Igor Dumic
- Department of Hospital Medicine, Mayo Clinic Health System, Eau Claire, WI 54703, USA; (N.K.); (P.J.); (E.A.); (V.K.); (J.S.); (C.W.N.)
- Mayo Clinic College of Medicine and Science, Rochester, MN 55905, USA; (A.S.); (M.H.); (R.J.)
| | - Emeka Amadi
- Department of Hospital Medicine, Mayo Clinic Health System, Eau Claire, WI 54703, USA; (N.K.); (P.J.); (E.A.); (V.K.); (J.S.); (C.W.N.)
- Mayo Clinic College of Medicine and Science, Rochester, MN 55905, USA; (A.S.); (M.H.); (R.J.)
| | - Vishnu Kommineni
- Department of Hospital Medicine, Mayo Clinic Health System, Eau Claire, WI 54703, USA; (N.K.); (P.J.); (E.A.); (V.K.); (J.S.); (C.W.N.)
- Mayo Clinic College of Medicine and Science, Rochester, MN 55905, USA; (A.S.); (M.H.); (R.J.)
| | - Jelena Stojsavljevic
- Department of Hospital Medicine, Mayo Clinic Health System, Eau Claire, WI 54703, USA; (N.K.); (P.J.); (E.A.); (V.K.); (J.S.); (C.W.N.)
- Mayo Clinic College of Medicine and Science, Rochester, MN 55905, USA; (A.S.); (M.H.); (R.J.)
| | - Aryan Shiari
- Mayo Clinic College of Medicine and Science, Rochester, MN 55905, USA; (A.S.); (M.H.); (R.J.)
- Department of Pulmonary and Critical Care Medicine, Mayo Clinic Health System, Eau Claire, WI 54703, USA
| | - Melissa Hart
- Mayo Clinic College of Medicine and Science, Rochester, MN 55905, USA; (A.S.); (M.H.); (R.J.)
- Department of Pathology, Mayo Clinic Health System, Eau Claire, WI 54703, USA
| | - Ra’ed Jabr
- Mayo Clinic College of Medicine and Science, Rochester, MN 55905, USA; (A.S.); (M.H.); (R.J.)
- Department of Infectious Disease, Mayo Clinic Health System, Eau Claire, WI 54703, USA
| | - Charles W. Nordstrom
- Department of Hospital Medicine, Mayo Clinic Health System, Eau Claire, WI 54703, USA; (N.K.); (P.J.); (E.A.); (V.K.); (J.S.); (C.W.N.)
- Mayo Clinic College of Medicine and Science, Rochester, MN 55905, USA; (A.S.); (M.H.); (R.J.)
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20
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Casas-Aparicio G, Caballero-Islas AE, León-Ortiz A, Escamilla-Illescas D, Rueda-Escobedo Y, Ascención-López C, Hernández-Quino D, Flores-Vargas A, Sosa-Chombo J, Tolentino-de La Mora A, Saucedo-Pruneda A, Piten-Isidro E. Early Driving Pressure Is Associated with Major Adverse Kidney Events at 30 Days in ARDS Patients with SARS-CoV-2. J Clin Med 2025; 14:2783. [PMID: 40283616 PMCID: PMC12027899 DOI: 10.3390/jcm14082783] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2025] [Revised: 04/05/2025] [Accepted: 04/11/2025] [Indexed: 04/29/2025] Open
Abstract
Background: Major adverse kidney events (MAKEs), including death, persistent AKI (pAKI), and renal replacement therapy, are more common in SARS-CoV-2-related ARDS. Invasive mechanical ventilation (IMV), systemic inflammation, and hemodynamic changes drive this risk. This study examines early IMV settings and urinary kidney biomarkers (UKBs) to better understand the development of MAKEs at 30 days. Methods: This prospective, cross-sectional cohort study was conducted in a single center between September and October 2021. This study included adults (≥18 years) diagnosed with ARDS due to SARS-CoV-2, requiring IMV within the first 6 h of admission. Exclusion criteria included a history of chronic kidney disease (CKD) and pregnant women. Initial mechanical ventilator settings were recorded after compliance-guided PEEP titration, and urine samples were collected for the analysis of UKBs at the same time. Our primary and secondary endpoints were to assess risk factors associated with MAKEs at 30 days and pAKI, respectively. Results: The cohort included 45 patients, with a median age of 57.75 (±18.64) years. In total, 32 (71%) developed MAKEs and 22 (48.8%) developed pAKI. MAKEs were associated with older age (adjusted odds ratio (aORs) = 1.23 95% CI: 1.00-1.22; p = 0.038) and higher driving pressure (ΔP) (aORs = 1.62, 95% CI:1.01-2.60, p = 0.043). Only urinary neutrophil gelatinase-associated lipocalin (uNGal) > 40 ng/mL was associated with pAKI (aORs = 8.54, 95% CI:1.75-41.65, p = 0.008). Conclusions: Early ventilator settings, particularly higher ΔP, play a critical role in the development of MAKEs. uN-Gal could enhance the early detection of pAKI, providing opportunities for timely interventions.
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Affiliation(s)
- Gustavo Casas-Aparicio
- Coordinación de Nefrología, Instituto Nacional de Enfermedades Respiratorias “Ismael Cosío Villegas”, Calzada de Tlalpan 4502, Ciudad de México 14080, Mexico; (A.E.C.-I.); (A.L.-O.)
- Departamento de Investigación en Enfermedades Infecciosas, Instituto Nacional de Enfermedades Respiratorias “Ismael Cosío Villegas”, Calzada de Tlalpan 4502, Ciudad de México 14080, Mexico;
| | - Adrián E. Caballero-Islas
- Coordinación de Nefrología, Instituto Nacional de Enfermedades Respiratorias “Ismael Cosío Villegas”, Calzada de Tlalpan 4502, Ciudad de México 14080, Mexico; (A.E.C.-I.); (A.L.-O.)
| | - Antonio León-Ortiz
- Coordinación de Nefrología, Instituto Nacional de Enfermedades Respiratorias “Ismael Cosío Villegas”, Calzada de Tlalpan 4502, Ciudad de México 14080, Mexico; (A.E.C.-I.); (A.L.-O.)
| | - David Escamilla-Illescas
- Dirección de Medicina, Fundación Clínica Médica Sur. Puente de Piedra 29, Col. Toriello Guerra, Ciudad de México 14040, Mexico;
| | - Yovanna Rueda-Escobedo
- Departamento de Enseñanza, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Calzada de Tlalpan 4502, Col. Sección XVI, Ciudad de Mexico 14080, Mexico;
| | - Carlos Ascención-López
- Facultad de Medicina Benemérita Universidad Autónoma de Puebla, Heroica Puebla de Zaragoza 72420, Mexico; (C.A.-L.); (D.H.-Q.)
| | - Diana Hernández-Quino
- Facultad de Medicina Benemérita Universidad Autónoma de Puebla, Heroica Puebla de Zaragoza 72420, Mexico; (C.A.-L.); (D.H.-Q.)
| | - Aimee Flores-Vargas
- Médico Adscrito a la Subdirección de Atención Médica de Neumología, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Calzada de Tlalpan 4502, Col. Sección XVI, Ciudad de Mexico 14080, Mexico; (A.F.-V.); (J.S.-C.); (A.S.-P.)
| | - Jesús Sosa-Chombo
- Médico Adscrito a la Subdirección de Atención Médica de Neumología, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Calzada de Tlalpan 4502, Col. Sección XVI, Ciudad de Mexico 14080, Mexico; (A.F.-V.); (J.S.-C.); (A.S.-P.)
| | - Abraham Tolentino-de La Mora
- Departamento de Investigación en Tabaquismo y EPOC, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Calzada de Tlalpan 4502, Col. Sección XVI, Ciudad de México 14080, Mexico;
| | - Ana Saucedo-Pruneda
- Médico Adscrito a la Subdirección de Atención Médica de Neumología, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Calzada de Tlalpan 4502, Col. Sección XVI, Ciudad de Mexico 14080, Mexico; (A.F.-V.); (J.S.-C.); (A.S.-P.)
| | - Elvira Piten-Isidro
- Departamento de Investigación en Enfermedades Infecciosas, Instituto Nacional de Enfermedades Respiratorias “Ismael Cosío Villegas”, Calzada de Tlalpan 4502, Ciudad de México 14080, Mexico;
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21
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Bardají-Carrillo M, Martín-Fernández M, López-Herrero R, Priede-Vimbela JM, Arroyo-Hernantes I, Cobo-Zubia R, Prieto-Utrera R, Gómez-Sánchez E, Villar J, Tamayo E. Chest radiographs in acute respiratory distress syndrome: an Achilles' heel of the Berlin criteria? Front Med (Lausanne) 2025; 12:1554752. [PMID: 40313553 PMCID: PMC12043692 DOI: 10.3389/fmed.2025.1554752] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2025] [Accepted: 03/31/2025] [Indexed: 05/03/2025] Open
Abstract
Background Despite the high mortality and economic burden associated with the acute respiratory distress syndrome (ARDS), the role of chest radiograph (CXR) in ARDS diagnosis and prognosis remains uncertain. The purpose of this study is to elucidate clinical characteristics that distinguish ARDS patients from those without ARDS, especially in patients where CXRs are indicative of ARDS. Methods Secondary analysis of a prospective observational study with 454 postoperative septic patients under mechanical ventilation (MV). Patients were stratified in two groups depending on whether they met the Berlin criteria for ARDS. Primary outcome was identification of clinical characteristics differentiating patients with ARDS confirmed by CXR from non-ARDS patients. Secondary outcome was 60-day in-hospital mortality of postoperative sepsis-induced ARDS. Results One hundred thirty-nine patients (30.6%) had CXRs compatible with ARDS, although ARDS was confirmed in only 45 patients (9.9%). Emergency surgery (OR 6.6), abdominal source of infection (OR 6.0), pneumonia (OR 8.2), and higher lactate (OR 3.9) were clinical features associated with ARDS development confirmed by CXR. ARDS was an independent risk factor for 60-day mortality (OR 1.8). Conclusion Although CXR criteria for ARDS diagnosis could be replaced in future definitions, its importance for ARDS diagnosis should not be underestimated.
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Affiliation(s)
- Miguel Bardají-Carrillo
- BioCritic, Group for Biomedical Research in Critical Care Medicine, Valladolid, Spain
- Anesthesiology and Critical Care, Clinical University Hospital of Valladolid, Valladolid, Spain
- CIBER de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, Madrid, Spain
| | - Marta Martín-Fernández
- BioCritic, Group for Biomedical Research in Critical Care Medicine, Valladolid, Spain
- CIBER de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, Madrid, Spain
- Department of Medicine, Toxicology and Dermatology, University of Valladolid, Valladolid, Spain
| | - Rocío López-Herrero
- BioCritic, Group for Biomedical Research in Critical Care Medicine, Valladolid, Spain
- Anesthesiology and Critical Care, Clinical University Hospital of Valladolid, Valladolid, Spain
- CIBER de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, Madrid, Spain
- Department of Surgery, University of Valladolid, Valladolid, Spain
| | - Juan M. Priede-Vimbela
- BioCritic, Group for Biomedical Research in Critical Care Medicine, Valladolid, Spain
- Anesthesiology and Critical Care, Clinical University Hospital of Valladolid, Valladolid, Spain
- CIBER de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, Madrid, Spain
| | - Irene Arroyo-Hernantes
- BioCritic, Group for Biomedical Research in Critical Care Medicine, Valladolid, Spain
- Department of Research and Innovation, Clinical University Hospital of Valladolid (HCUV), SACYL/IECSCYL, Valladolid, Spain
| | - Rosa Cobo-Zubia
- BioCritic, Group for Biomedical Research in Critical Care Medicine, Valladolid, Spain
| | - Rosa Prieto-Utrera
- BioCritic, Group for Biomedical Research in Critical Care Medicine, Valladolid, Spain
| | - Esther Gómez-Sánchez
- BioCritic, Group for Biomedical Research in Critical Care Medicine, Valladolid, Spain
- Anesthesiology and Critical Care, Clinical University Hospital of Valladolid, Valladolid, Spain
- CIBER de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, Madrid, Spain
- Department of Surgery, University of Valladolid, Valladolid, Spain
| | - Jesús Villar
- CIBER de Enfermedades Respiratorias, Instituto de Salud Carlos III, Madrid, Spain
- Research Unit at Hospital Universitario Dr. Negrín, Fundación Canaria Instituto de Investigación Sanitaria de Canarias, Las Palmas de Gran Canaria, Spain
- Li Ka Shing Knowledge Institute at St. Michael's Hospital, Toronto, ON, Canada
- Faculty of Health Sciences, Universidad del Atlántico Medio, Las Palmas de Gran Canaria, Spain
| | - Eduardo Tamayo
- BioCritic, Group for Biomedical Research in Critical Care Medicine, Valladolid, Spain
- Anesthesiology and Critical Care, Clinical University Hospital of Valladolid, Valladolid, Spain
- CIBER de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, Madrid, Spain
- Department of Surgery, University of Valladolid, Valladolid, Spain
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22
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Lim EHT, van de Beek D, de Bruin S, Rückinger S, Thielert C, Guo R, Burnett BP, Brouwer MC, Zerbib R, Chong C, Riedemann NC, Vlaar AP. Regional comparison of efficacy and safety for vilobelimab in critically ill, invasively mechanically ventilated COVID-19 patients. BMJ Open Respir Res 2025; 12:e002206. [PMID: 40250846 PMCID: PMC12010313 DOI: 10.1136/bmjresp-2023-002206] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2023] [Accepted: 04/01/2025] [Indexed: 04/20/2025] Open
Abstract
BACKGROUND Vilobelimab, a first in class C5a-specific monoclonal antibody, improved 28-day and 60-day mortality in intubated COVID-19 patients in PANAMO, a phase 3 randomised, double-blind, placebo-controlled multicentre study. All-cause mortality was pre-specified to be analysed pooling by region (western Europe, South America, South Africa/Russia). METHODS Critically ill, invasively mechanically ventilated COVID-19 patients were randomised in a 1:1 ratio within 48 hours of intubation to receive vilobelimab treatment (six, 800 mg intravenous infusions) or placebo on top of standard of care. We analysed the efficacy and safety of vilobelimab based on prespecified geographic regions. RESULTS 368 patients were randomised and analysed: 177 in the vilobelimab group and 191 in the placebo group. In western Europe (n=209), 28-day all-cause mortality was significantly lower in the vilobelimab group (21%) compared with placebo (37%) (HR 0.51 (95% CI: 0.30, 0.87), p=0.014). In South America (n=126), mortality was similar between groups (40% vs 37%; HR 0.94 (95% CI: 0.53, 1.67), p=0.83). In South Africa/Russia (n=33), mortality was 69% in the vilobelimab group and 87% in the placebo group (HR 0.62 (95% CI: 0.28, 1.38), p=0.25). Within the Brazilian subpopulation (n=74), a significant age imbalance between the vilobelimab and placebo group was detected (median 53.5 years in the vilobelimab group vs 44.5 years in the placebo group). Occurrence of treatment-emergent adverse events between regions was similar. CONCLUSION The most apparent 28-day all-cause mortality benefit for vilobelimab was in western Europe. Age imbalance between treatment groups in Brazil may have resulted in a lower efficacy signal for vilobelimab in South America compared with other regions. Overall, vilobelimab demonstrated a favourable safety profile and reduced mortality in critically ill, intubated COVID-19 patients, with regional variations influencing outcomes.
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Affiliation(s)
- Endry H T Lim
- Department of Intensive Care Medicine, Amsterdam UMC Location AMC, Amsterdam, Noord-Holland, Netherlands
- Department of Neurology, Amsterdam UMC Location AMC, Amsterdam, Noord-Holland, Netherlands
| | - Diederik van de Beek
- Department of Neurology, Amsterdam UMC Location AMC, Amsterdam, Noord-Holland, Netherlands
| | - Sanne de Bruin
- Department of Intensive Care Medicine, Amsterdam UMC Location AMC, Amsterdam, Noord-Holland, Netherlands
| | | | | | - Renfeng Guo
- InflaRx Pharmaceuticals Inc, Ann Arbor, Michigan, USA
| | | | - Matthijs C Brouwer
- Department of Neurology, Amsterdam UMC Location AMC, Amsterdam, Noord-Holland, Netherlands
| | | | | | | | - Alexander P Vlaar
- Department of Intensive Care Medicine, Amsterdam UMC Location AMC, Amsterdam, Noord-Holland, Netherlands
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23
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Lin H, Ren Y, Cui J, Guo J, Wang M, Wang L, Su X, Qiao X. Nomogram risk prediction model for acute respiratory distress syndrome following acute kidney injury. Front Med (Lausanne) 2025; 12:1563425. [PMID: 40270504 PMCID: PMC12014638 DOI: 10.3389/fmed.2025.1563425] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2025] [Accepted: 03/28/2025] [Indexed: 04/25/2025] Open
Abstract
Background Acute respiratory distress syndrome (ARDS), a severe form of respiratory failure, can be precipitated by acute kidney injury (AKI), leading to a significant increase in mortality among affected patients. This study aimed to identify the risk factors for ARDS and construct a predictive nomogram. Methods We conducted a retrospective analysis of 1,241 AKI patients admitted to the Second Hospital of Shanxi Medical University from August 25, 2016, to December 31, 2023. The patients were divided into a study cohort (1,012 cases, including 108 with ARDS) and a validation cohort (229 cases, including 23 with ARDS). Logistic regression analysis was employed to identify the risk factors for ARDS, which were subsequently incorporated into the development of a nomogram. The predictive performance of the nomogram was assessed by AUC, calibration plots, and decision curve analyses, with external validation also performed. Results Six risk factors were identified and included in the nomogram: older age (OR = 1.020; 95%CI = 1.005-1.036), smoking history (OR = 1.416; 95%CI = 1.213-1.811), history of diabetes mellitus (OR = 1.449; 95%CI = 1.202-1.797), mean arterial pressure (MAP; OR = 1.165; 95%CI = 1.132-1.199), higher serum uric acid levels (OR = 1.002; 95%CI = 1.001-1.004), and higher AKI stage [(stage 1: reference), (stage 2: OR = 11.863; 95%CI = 4.850-29.014), (stage 3: OR = 41.398; 95%CI = 30.840-52.731)]. The AUC values were 0.951 in the study cohort and 0.959 in the validation cohort. Calibration and decision curve analyses confirmed the accuracy and clinical utility of the nomogram. Conclusion The nomogram, which integrates age, smoking history, diabetes mellitus history, MAP, and AKI stage, predicts the risk of ARDS in patients with AKI. This tool may aid in early detection and facilitate clinical decision-making.
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Affiliation(s)
- Hui Lin
- Department of Nephrology, Second Hospital of Shanxi Medical University, Taiyuan, China
- Shanxi Kidney Disease Institute, Taiyuan, China
- Kidney Research Center of Shanxi Medical University, Taiyuan, China
| | - Yilin Ren
- Department of Nephrology, Second Hospital of Shanxi Medical University, Taiyuan, China
- Shanxi Kidney Disease Institute, Taiyuan, China
- Kidney Research Center of Shanxi Medical University, Taiyuan, China
| | - Jing Cui
- Department of Endocrinology, Air Force Medical Center, Beijing, China
| | - Junnan Guo
- Department of Nephrology, Second Hospital of Shanxi Medical University, Taiyuan, China
- Shanxi Kidney Disease Institute, Taiyuan, China
- Kidney Research Center of Shanxi Medical University, Taiyuan, China
| | - Mengzhu Wang
- Department of Nephrology, Second Hospital of Shanxi Medical University, Taiyuan, China
- Shanxi Kidney Disease Institute, Taiyuan, China
- Kidney Research Center of Shanxi Medical University, Taiyuan, China
| | - Lihua Wang
- Department of Nephrology, Second Hospital of Shanxi Medical University, Taiyuan, China
- Shanxi Kidney Disease Institute, Taiyuan, China
- Kidney Research Center of Shanxi Medical University, Taiyuan, China
| | - Xiaole Su
- Department of Nephrology, Second Hospital of Shanxi Medical University, Taiyuan, China
- Shanxi Kidney Disease Institute, Taiyuan, China
- Kidney Research Center of Shanxi Medical University, Taiyuan, China
| | - Xi Qiao
- Department of Nephrology, Second Hospital of Shanxi Medical University, Taiyuan, China
- Shanxi Kidney Disease Institute, Taiyuan, China
- Kidney Research Center of Shanxi Medical University, Taiyuan, China
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Nosaka N, Borges V, Martinon D, Crother TR, Arditi M, Shimada K. Hypothermia protects against ventilator-induced lung injury by limiting IL-1β release and NETs formation. BIORXIV : THE PREPRINT SERVER FOR BIOLOGY 2025:2024.09.02.610778. [PMID: 40236184 PMCID: PMC11996356 DOI: 10.1101/2024.09.02.610778] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 04/17/2025]
Abstract
Although mechanical ventilation is a critical intervention for acute respiratory distress syndrome (ARDS), it can trigger an IL-1β-associated complication known as ventilator-induced lung injury. In mice, we found that LPS and high-volume ventilation, LPS-HVV, leads to hypoxemia with neutrophil extracellular traps (NETs) formation in the alveoli. Furthermore, Il1r1 -/- LPS-HVV mice did not develop hypoxemia and had reduced NETs, indicating that IL-1R1 signaling is important for NETs formation and hypoxemia. Therapeutic hypothermia (TH) is known to reduce the release of inflammatory mediators. In LPS-HVV mice, TH (32 °C body temperature) prevented hypoxemia development, reducing albumin leakage, IL-1β, gasdermin D (GSDMD) and NETs formation. We also observed that LPS-primed macrophages, when stimulated at 32°C with ATP or nigericin, release less IL-1β associated with reduced GSDMD cleavage. Thus, hypothermia is an important modulating factor in the NLRP3 inflammasome activation, IL-1β release and NETs formation, preventing LPS-HVV-induced acute respiratory failure.
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Gacouin A, Maamar A, Terzi N, Tadié JM. Association of obesity on short- and long-term survival in patients with moderate to severe pneumonia-related ARDS: a retrospective cohort study. BMC Pulm Med 2025; 25:153. [PMID: 40181311 PMCID: PMC11969934 DOI: 10.1186/s12890-025-03614-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2024] [Accepted: 03/20/2025] [Indexed: 04/05/2025] Open
Abstract
BACKGROUND The incidence of obesity among patients admitted to the intensive care unit (ICU) is increasing, and pneumonia remains the leading cause of acute respiratory distress syndrome (ARDS). The association of obesity on both short- and long-term outcomes in patients with pneumonia-induced ARDS has been the subject of only limited research. METHODS We conducted a retrospective analysis of a prospective cohort consisting of ARDS patients who had microbiologically confirmed pneumonia and a PaO2/FiO2 ratio ≤ 150 mmHg. Patients were assessed for mortality at 28 days, 90 days, and at 1 year from the diagnosis of ARDS and compared between obese defined by a body mass index (BMI) ≥ 30 kg.m2 and non-obese patients. Models were adjusted for age, sex, COPD, coronary artery disease, immunodepression, severity score and acute kidney injury on admission to the ICU, severity of ARDS (PaO2/FiO2 ratio ≤ 100 mmHg), severe hypercapnia (PaCO2 ≥ 50 mmHg), ventilatory ratio and plateau pressure the first day of ARDS, influenza, COVID-19, pneumocystosis, and bacteria involved in pneumonia. We also investigated the continuous spectrum of BMI on the risk of mortality. RESULTS Of 603 patients, 227 patients (37.6%) were obese. Obesity was associated with female gender (p = 0.009), hypertension (p < 0.001), diabetes mellitus (p < 0.001), COVID-19 pneumonia (p = 0.008), and PaO2/FiO2 ratio ≤ 100 mmHg (p = 0.006). Obesity was independently associated with lower mortality at 28 days (adjusted Odds Ratio (OR) 0.55, 95% confident interval (CI) 0.33-0.90, p = 0.02) but not at 90 days (adjusted OR 0.70, 95% CI 0.45-1.09, p = 0.11) nor at 1 year from the diagnosis of ARDS (adjusted OR 0.73, 95% CI 0.47-1.13, p = 0.16). Mortality at 28 days was significantly lower in obese patients than in non-obese patients when propensity score matching was used (15.2% versus 22%, p = 0.04). BMI was also independently associated with lower mortality at 28 days (p = 0.038) but not with mortality at 90 days (p = 0.12) and 1 year (p = 0.12). CONCLUSION Our results suggest that in patients with pneumonia-related ARDS, obesity is independently associated with better survival at 28 days but not at 90 days and 1 year from the diagnosis of ARDS.
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Affiliation(s)
- Arnaud Gacouin
- CHU Rennes, Maladies Infectieuses Et Réanimation Médicale, 35033, Rennes, France.
- Faculté de Médecine, Université Rennes1, 35043, Biosit, Rennes, France.
- Inserm-CIC-1414, Faculté de Médecine, Université Rennes I, IFR 140, 35033, Rennes, France.
| | - Adel Maamar
- CHU Rennes, Maladies Infectieuses Et Réanimation Médicale, 35033, Rennes, France
- Faculté de Médecine, Université Rennes1, 35043, Biosit, Rennes, France
| | - Nicolas Terzi
- CHU Rennes, Maladies Infectieuses Et Réanimation Médicale, 35033, Rennes, France
- Faculté de Médecine, Université Rennes1, 35043, Biosit, Rennes, France
- Inserm-CIC-1414, Faculté de Médecine, Université Rennes I, IFR 140, 35033, Rennes, France
| | - Jean-Marc Tadié
- CHU Rennes, Maladies Infectieuses Et Réanimation Médicale, 35033, Rennes, France
- Faculté de Médecine, Université Rennes1, 35043, Biosit, Rennes, France
- Inserm-CIC-1414, Faculté de Médecine, Université Rennes I, IFR 140, 35033, Rennes, France
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Purbasari U, Prihartono NA, Helda, Antariksa B, Muljadi R, Mulyadi R, Eureka AN. The UTAMI score: a chest x-ray-based tool for predicting ICU admission in ARDS of pneumonia patients. Emerg Radiol 2025; 32:173-184. [PMID: 39985629 DOI: 10.1007/s10140-025-02315-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2024] [Accepted: 01/27/2025] [Indexed: 02/24/2025]
Abstract
PURPOSE This study proposes and evaluates the Universal Thorax ARDS Modification Index (UTAMI), a new method based on chest x-ray findings, for rapid ICU admission prediction in pneumonia with ARDS. Clinical and laboratory variables are analyzed to find potential predictors. METHOD A cross-sectional study at Fatmawati Central General Hospital (2022-2023) compared the diagnostic accuracy of UTAMI method against the gold standard for ARDS diagnosis; Berlin Definition. We analyzed 318 patients' data that were hospitalized for pneumonia. Clinical and laboratory predictors of ARDS were also analyzed. RESULTS Neutrophil levels, CRP, D-dimer, oxygen saturation, and respiratory rate can predict ARDS diagnosis according to the Berlin Definition. The patient cohort showed that those with moderate-severe ARDS were admitted to the ICU. With ARDS categorized as ARDS requiring ICU admission (ARDS ICU) and ARDS not requiring ICU admission, the UTAMI method requires only history of coronary artery disease (CAD), CRP, and oxygen saturation as key predictors. CRP was a predictor in both the Berlin Definition (PR 1.28) and the UTAMI method (PR 1.71). In the AUROC test, the Berlin Definition distinguished moderate-severe ARDS with 81.2% accuracy using chest radiographs, clinical and laboratory values. The UTAMI method, based solely on chest radiographs achieved 79.6% accuracy, showing fair discrimination against the gold standard. CONCLUSION UTAMI Score is a viable tool for predicting the risk of ARDS in pneumonia. Utilizing UTAMI method, ARDS can be predicted using only chest radiograph, making it easier for clinicians to be alerted earlier. Predicting ARDS ICU from UTAMI method requires only 3 variables; CAD comorbid, laboratory CRP and peripheral oxygen saturation.
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Affiliation(s)
- Utami Purbasari
- Department of Epidemiology, Faculty of Public Health, University of Indonesia, Kota Depok, Indonesia.
- Department of Radiology, Fatmawati General Hospital, South Jakarta, Indonesia.
| | | | - Helda
- Department of Epidemiology, Faculty of Public Health, University of Indonesia, Kota Depok, Indonesia
| | - Budhi Antariksa
- Department of Pulmonology, Faculty of Medicine, University of Indonesia, Kota Depok, Indonesia
| | - Rusli Muljadi
- Department of Radiology, Siloam Glen Eagles Hospital, Karawaci, Tangerang, Indonesia
| | - Rahmad Mulyadi
- Department of Radiology, Faculty of Medicine, University of Indonesia, Kota Depok, Indonesia
| | - Agnes Nina Eureka
- Department of Epidemiology, Faculty of Public Health, University of Indonesia, Kota Depok, Indonesia
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Laake JH, Hagen M, Aavitsland P, Buanes EA, Fjone KS, Kvåle R, Olsen BF, Hofsø K. COVID-19 in Norwegian ICUs 2020-2023: Patient characteristics, management, and outcomes-A nationwide prospective observational study. Acta Anaesthesiol Scand 2025; 69:e70027. [PMID: 40114460 DOI: 10.1111/aas.70027] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2025] [Revised: 03/10/2025] [Accepted: 03/11/2025] [Indexed: 03/22/2025]
Abstract
BACKGROUND During the COVID-19 pandemic, Norway experienced successive waves of hospital and intensive care unit (ICU) admissions, each with distinct characteristics, including patient demographics, medical therapies, vaccine coverage, respiratory failure management and mortality rates. The aim of this study was to analyse survival in a national cohort of adult COVID-19 patients admitted to Norwegian ICUs (March 2020-May 2023) and examine how patient characteristics and management strategies were associated with mortality across successive stages of the pandemic. METHODS Patients admitted to ICUs between 10 March 2020 and 5 May 2023, were identified via the Norwegian Intensive Care and Pandemic Registry. We included all adults (≥18 years) and analysed data on demographics, predefined risk factors, severity, patient management and outcomes. We quantified associations between patient demographics, risk factors and admission period with mortality and ICU length of stay (LOS). RESULTS The study included 2655 patients with confirmed COVID-19. Patients admitted from 2022 onwards were significantly older (median age >70) and had more predefined risk factors compared to those admitted during earlier periods (median age < 65 years). Management of respiratory failure shifted towards less frequent use of invasive mechanical ventilation. The crude 90-day mortality rate doubled from 21% (95% CI 14; 24) in the first half of 2020 to 43.5% (95% CI 31.1; 45.7) in the first half of 2023. ICU LOS decreased substantially from a median of 14.1 days (interquartile range [IQR] 6.8; 23.1) to 2.6 days (IQR 1.1; 5.0). The time period of admission, patient age, pre-defined risk factors and Simplified Acute Physiology Score (SAPS II) were significantly associated with mortality. Prolonged ICU LOS was primarily associated with respiratory support mode, age and higher SAPS II scores. CONCLUSION In this nationwide study of the COVID-19 pandemic in Norway, ICU mortality was significantly higher in later compared to earlier admission periods, largely explained by changes in case mix, such as older patients with more co-morbidities. While ICU therapies were modified over the course of the pandemic, their impact on survival cannot be determined from our analyses (NCT04601090). EDITORIAL COMMENT In this article, findings from Norway's national Intensive care database are presented for critically ill SARS-CoV-2 cases, including the different pandemic waves throughout the whole period. Characteristics and trends related to illness and ICU care are presented.
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Affiliation(s)
- Jon Henrik Laake
- Department of Anaesthesiology and Intensive Care Medicine, Division of Emergencies and Critical Care, Rikshospitalet Medical Centre, Oslo University Hospital, Oslo, Norway
- Department of Research and Development, Division of Emergencies and Critical Care, Oslo University Hospital, Oslo, Norway
| | - Milada Hagen
- Department of Public Health, Oslo Metropolitan University, Oslo, Norway
| | - Preben Aavitsland
- Norwegian Institute of Public Health, Oslo, Norway
- Pandemic Centre, University of Bergen, Bergen, Norway
| | - Eirik Alnes Buanes
- Department of Intensive Care, Haukeland University Hospital, Bergen, Norway
- Norwegian Intensive Care and Pandemic Registry, Haukeland University Hospital, Bergen, Norway
- Western Norway University of Applied Sciences, Bergen, Norway
| | - Kristina Struksnes Fjone
- Department of Research and Development, Division of Emergencies and Critical Care, Oslo University Hospital, Oslo, Norway
- Department of Public Health, Oslo Metropolitan University, Oslo, Norway
| | - Reidar Kvåle
- Department of Intensive Care, Haukeland University Hospital, Bergen, Norway
- Norwegian Intensive Care and Pandemic Registry, Haukeland University Hospital, Bergen, Norway
- University of Bergen, Bergen, Norway
| | - Brita Fosser Olsen
- Østfold Hospital Trust, Intensive and Postoperative Unit, Grålum, Norway
- Østfold University College, Faculty of Health and Welfare, Halden, Norway
| | - Kristin Hofsø
- Department of Postoperative and Critical Care Nursing, Division of Emergencies and Critical Care, Oslo University Hospital, Oslo, Norway
- Lovisenberg Diaconal University College, Oslo, Norway
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Lu Z, Yang J, Liu X, Wang J, Pan Y, Zhong J, Su X. Prognostic Value of Serum Interleukin-37 in Patients with Acute Respiratory Distress Syndrome. Immunol Invest 2025; 54:368-381. [PMID: 39698874 DOI: 10.1080/08820139.2024.2443253] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2024]
Abstract
BACKGROUND Acute respiratory distress syndrome (ARDS) is prominently characterized by uncontrolled inflammation and high mortality. The effect of interleukin-37 (IL-37) on the prognosis of ARDS remains unclear. METHODS This prospective cohort study detected and analyzed serum IL-37 levels on day 1 (baseline) in 128 patients with ARDS and 40 healthy controls, and on day 7 in patients with ARDS. Clinical and laboratory parameters were assayed. Survival status was tracked within 28-d of enrollment. RESULTS BaselineIL-37 concentration was lower in non-survivors (135.00 [87.75, 198.75] pg/mL) than in survivors (250.50 [173.25, 382.75] pg/mL) (p < .05). Non-survivors displayed a greater reduction in IL-37 levels from day 1-7 than survivors (49.87% vs. 40.09%) (p < .05). Baseline IL-37 levels were negatively associated with C-reactive protein, procalcitonin, and IL-6 levels. The area under the receiver operating characteristic curve of the baseline level and percentage decline in IL-37 was 0.755 and 0.809, respectively, for predicting 28-d mortality. Combining IL-37 with the acute physiology and chronic health evaluation II score further improved mortality prediction capability. Patients with ARDS with low IL-37 concentrations (<143.00 pg/mL) or a high percentage decline (≥44.76%) had a poorer survival rate than those with a high concentration or low percentage decline. The baseline IL-37 level and percentage decline independently predicted mortality in a univariate Cox regression model (p < .05). CONCLUSIONS A low IL-37 level or significantly declining rate predicts higher 28-d mortality in patients with ARDS, indicating that IL-37 may be a promising prognostic biomarker.
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Affiliation(s)
- Zhaohui Lu
- The First School of Clinical Medicine, Southern Medical University, Guangzhou, China
| | - Jie Yang
- The First School of Clinical Medicine, Southern Medical University, Guangzhou, China
| | - Xiaoguang Liu
- The First School of Clinical Medicine, Southern Medical University, Guangzhou, China
| | - Juan Wang
- Emergency Intensive Care Unit, Wuhu Hospital Affiliated with East China Normal University, Wuhu, China
| | - Youjun Pan
- Department of Critical Care Medicine, Wuhu Hospital Affiliated with East China Normal University, Wuhu, China
| | - Jinjin Zhong
- Department of Respiratory and Critical Care Medicine, Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School, Nanjing, China
| | - Xin Su
- The First School of Clinical Medicine, Southern Medical University, Guangzhou, China
- Department of Respiratory and Critical Care Medicine, Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School, Nanjing, China
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Mohammadi A, De Luca D, Gauda EB. Characteristics, triggers, treatments, and experimental models of neonatal acute respiratory distress syndrome. Am J Physiol Lung Cell Mol Physiol 2025; 328:L512-L525. [PMID: 39924963 DOI: 10.1152/ajplung.00312.2024] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2024] [Revised: 11/20/2024] [Accepted: 02/04/2025] [Indexed: 02/11/2025] Open
Abstract
Neonatal acute respiratory distress syndrome (NARDS) is a severe and potentially life-threatening form of lung injury recently defined by the International Neonatal ARDS Consensus. It is marked by extensive lung inflammation and damage to the alveolar epithelium and vascular endothelium. NARDS can be triggered by direct inflammatory exposures, such as pneumonia and aspiration, and indirect exposures, including sepsis, necrotizing enterocolitis, and chorioamnionitis. This review provides clinicians and researchers with the latest insights on NARDS. We adopt a cross-disciplinary approach to discuss the diagnostic criteria, pathobiology, triggers, epidemiology, and treatments of NARDS. In addition, we summarize existing clinical studies and advanced preclinical models that help address current knowledge gaps. Future research should focus on standardizing the Montreux consensus definition of NARDS in preclinical and clinical studies, identifying biomarkers, developing prediction models, and exploring novel therapies for affected infants.
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Affiliation(s)
- Atefeh Mohammadi
- Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada
- Division of Neonatology and Translational Medicine Program, The Hospital for Sick Children, Toronto, Ontario, Canada
| | - Daniele De Luca
- Division of Pediatrics and Neonatal Critical Care, "A. Béclère" Medical Center, Paris - Saclay University Hospitals, APHP, Paris, France
- Physiopathology and Therapeutic Innovation Unit-INSERM U999, Paris Saclay University, Paris, France
| | - Estelle B Gauda
- Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada
- Division of Neonatology and Translational Medicine Program, The Hospital for Sick Children, Toronto, Ontario, Canada
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Flora D, Adel M, Pauline G, Quentin Q, Valentin C, Benoit P, Jean-Marc T, Nicolas T, Arnaud G. Automatic continuous P 0.1 measurements during weaning from mechanical ventilation: a clinical study. Ann Intensive Care 2025; 15:47. [PMID: 40167952 PMCID: PMC11961779 DOI: 10.1186/s13613-025-01455-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2024] [Accepted: 03/08/2025] [Indexed: 04/02/2025] Open
Abstract
BACKGROUND In critically ill patients, weaning from mechanical ventilation (MV) includes spontaneous breathing trial (SBT) usually followed by a reventilation period in order to recover from the alveolar derecruitement induced by the SBT. The measurement of occlusion pressure during the first 100 ms of an airway occlusion (P0.1) one of the non-invasive tools available for estimating the respiratory drive, is a determinant of patient respiratory effort. This clinical study explores the use of non-invasive continuous monitoring of occlusion pressure automatically calculated by ventilators in the first 100 ms of airway occlusion (P0.1 vent) during SBT and reventilation periods. The study aimed to investigate patient or respirator factors influencing P0.1 vent as well as the association of P0.1 vent values with extubation success or failure. PATIENTS AND METHODS This prospective observational study, conducted from February 2022 to April 2023, included adult patients intubated for more than 24 h and screened for extubation weaning. SBTs were performed for one hour with zero pressure support and zero end-expiratory pressure (PS0 ZEEP). Reventilation followed for an hour with pressure support (8-12 cmH2O) and PEEP (5 cmH2O). Data included patient characteristics, ventilator parameters and extubation outcomes. RESULTS The study involved 224 measurements from 212 patients, with 157 successful extubations, 46 extubation failures at day 7 and 21 SBT failures. P0.1 vent mean values were significantly higher for extubation failures and SBT failures compared to successful extubations (p < 0.001). Delta P0.1 vent ((P0.1 vent reventilation - P0.1 vent SBT)/ P0.1 vent SBT) was significantly different according to whether extubation was a success or a failure: 0.21 (0.02-0.62) cm H2O vs. P0.1 vent vs. 1.12 (0.54-2.38) cm H2O; p < 0.0001 respectively. Values significantly differed in both the SBT and the reventilation periods whether or not patients had previous ARDS: 1.08 (0.70; 2.02) cmH2O vs. 0.80 (0.54; 1.28) cmH2O respectively (p = 0.003). Noteworthy, P0.1 vent values were influenced by airway humidification systems (0.92 (0.57; 1.54) cmH2O with humidification vs. 1.27 (0.91; 2.24) cmH2O without, p = 0.003). CONCLUSION The delta of P0.1vent values between SBT and reventilation are higher for patients who fail extubation, especially for those who had ARDS. While elevated P0.1 vent values were associated with extubation failure, the overlap in values limits its usefulness as a reliable predictor.
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Affiliation(s)
- Delamaire Flora
- Maladies Infectieuses et Réanimation Médicale, CHU de Rennes, Rennes, F-35033, France.
- Université de Rennes 1, Faculté de Médecine, Rennes, F-35043, France.
| | - Maamar Adel
- Maladies Infectieuses et Réanimation Médicale, CHU de Rennes, Rennes, F-35033, France
- Université de Rennes 1, Faculté de Médecine, Rennes, F-35043, France
| | - Guillot Pauline
- Maladies Infectieuses et Réanimation Médicale, CHU de Rennes, Rennes, F-35033, France
- Université de Rennes 1, Faculté de Médecine, Rennes, F-35043, France
| | - Quelven Quentin
- Maladies Infectieuses et Réanimation Médicale, CHU de Rennes, Rennes, F-35033, France
- Université de Rennes 1, Faculté de Médecine, Rennes, F-35043, France
| | - Coirier Valentin
- Maladies Infectieuses et Réanimation Médicale, CHU de Rennes, Rennes, F-35033, France
- Université de Rennes 1, Faculté de Médecine, Rennes, F-35043, France
| | - Painvin Benoit
- Maladies Infectieuses et Réanimation Médicale, CHU de Rennes, Rennes, F-35033, France
- Université de Rennes 1, Faculté de Médecine, Rennes, F-35043, France
| | - Tadie Jean-Marc
- Maladies Infectieuses et Réanimation Médicale, CHU de Rennes, Rennes, F-35033, France
- Université de Rennes 1, Faculté de Médecine, Rennes, F-35043, France
- Inserm-CIC-1414, Faculté de Médecine, Université de Rennes 1, IFR 140, Rennes, F-35033, France
| | - Terzi Nicolas
- Maladies Infectieuses et Réanimation Médicale, CHU de Rennes, Rennes, F-35033, France
- Université de Rennes 1, Faculté de Médecine, Rennes, F-35043, France
- Inserm-CIC-1414, Faculté de Médecine, Université de Rennes 1, IFR 140, Rennes, F-35033, France
| | - Gacouin Arnaud
- Maladies Infectieuses et Réanimation Médicale, CHU de Rennes, Rennes, F-35033, France
- Université de Rennes 1, Faculté de Médecine, Rennes, F-35043, France
- Inserm-CIC-1414, Faculté de Médecine, Université de Rennes 1, IFR 140, Rennes, F-35033, France
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Louart B, Muller L, Emond B, Boulet N, Roger C. Agreement between manual and automatic ultrasound measurement of the velocity-time integral in the left ventricular outflow tract in intensive care patients: evaluation of the AUTO-VTI® tool. J Clin Monit Comput 2025; 39:355-364. [PMID: 39287731 DOI: 10.1007/s10877-024-01215-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2024] [Accepted: 08/27/2024] [Indexed: 09/19/2024]
Abstract
Transthoracic echocardiography is widely used in intensive care unit (ICU) to manage patients with acute circulatory failure. Recently, automated ultrasound (US) measurement applications have been developed but their clinical performance has not been evaluated yet. The aim of this study was to assess the agreement between automated and manual measurements of the velocity-time integral in the left ventricular outflow tract (VTI-LVOT) using the auto-VTI® tool. This prospective, single-center, interventional study included ICU patients with acute circulatory failure. The examination involved two successive manual measurements of VTI-LVOT (mean of 3 consecutive heartbeats in regular sinus rhythm, and 5 heartbeats in irregular rhythm), followed by a measurement using auto-VTI® software. In patients receiving a fluid challenge, trending ability in detecting fluid responsiveness was also evaluated. Seventy patients were included between January 19, 2020, and September 24, 2020, at the Nîmes University Hospital. The feasibility of the auto-VTI® was 94%. The mean difference between the two methods was 11% with limits of agreement from - 19% to 42%. The proportion of agreement at the 15% difference threshold was 68% [58%; 80%]. The precision and least significant change measured for the manual measurement of VTI were 7.4 and 10.5%, respectively, and by inference for the automated method 28% and 40%. The new auto-VTI® tool, despite interesting feasibility, demonstrated an insufficient agreement with a systematic bias and an insufficient precision limiting its implementation in critically ill patients.Clinical trial registration: ClinicalTrials.gov identifier: NCT04360304.
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Affiliation(s)
- Benjamin Louart
- Department of Anesthesiology and Intensive Care, Pain and Emergency Medicine, Nîmes-Caremeau University Hospital, Place du Professeur Robert Debré, CEDEX 9, 30029, Nîmes, France.
| | - Laurent Muller
- Department of Anesthesiology and Intensive Care, Pain and Emergency Medicine, Nîmes-Caremeau University Hospital, Place du Professeur Robert Debré, CEDEX 9, 30029, Nîmes, France
| | - Baptiste Emond
- Department of Anesthesiology and Intensive Care, Pain and Emergency Medicine, Nîmes-Caremeau University Hospital, Place du Professeur Robert Debré, CEDEX 9, 30029, Nîmes, France
| | - Nicolas Boulet
- Department of Anesthesiology and Intensive Care, Pain and Emergency Medicine, Nîmes-Caremeau University Hospital, Place du Professeur Robert Debré, CEDEX 9, 30029, Nîmes, France
| | - Claire Roger
- Department of Anesthesiology and Intensive Care, Pain and Emergency Medicine, Nîmes-Caremeau University Hospital, Place du Professeur Robert Debré, CEDEX 9, 30029, Nîmes, France
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Taenaka H, Matthay MA. Mechanisms of impaired alveolar fluid clearance. Anat Rec (Hoboken) 2025; 308:1026-1039. [PMID: 36688689 PMCID: PMC10564110 DOI: 10.1002/ar.25166] [Citation(s) in RCA: 8] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2022] [Revised: 12/09/2022] [Accepted: 01/04/2023] [Indexed: 01/24/2023]
Abstract
Impaired alveolar fluid clearance (AFC) is an important cause of alveolar edema fluid accumulation in patients with acute respiratory distress syndrome (ARDS). Alveolar edema leads to insufficient gas exchange and worse clinical outcomes. Thus, it is important to understand the pathophysiology of impaired AFC in order to develop new therapies for ARDS. Over the last few decades, multiple experimental studies have been done to understand the molecular, cellular, and physiological mechanisms that regulate AFC in the normal and the injured lung. This review provides a review of AFC in the normal lung, focuses on the mechanisms of impaired AFC, and then outlines the regulation of AFC. Finally, we summarize ongoing challenges and possible future research that may offer promising therapies for ARDS.
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Affiliation(s)
- Hiroki Taenaka
- Department of Medicine, Cardiovascular Research Institute, University of California, San Francisco, California, USA
- Department of Anesthesia, Cardiovascular Research Institute, University of California, San Francisco, California, USA
- Department of Anesthesiology and Intensive Care Medicine, Osaka University Graduate School of Medicine, Suita, Japan
| | - Michael A. Matthay
- Department of Medicine, Cardiovascular Research Institute, University of California, San Francisco, California, USA
- Department of Anesthesia, Cardiovascular Research Institute, University of California, San Francisco, California, USA
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Xuan W, Liang C, Yang S, Zheng L, Wu X, Zhang X. FABP4 expression in neutrophils as a predictor of sepsis and SI-ARDS based on BALF transcriptome and peripheral blood validation. Chin Med J (Engl) 2025:00029330-990000000-01499. [PMID: 40169352 DOI: 10.1097/cm9.0000000000003447] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2024] [Indexed: 04/03/2025] Open
Abstract
BACKGROUND The objective of this study is to delineate the differential gene expression patterns of neutrophils in bronchoalveolar lavage fluid (BALF) from patients with sepsis and those experiencing progression to sepsis-induced acute respiratory distress syndrome (SI-ARDS). Additionally, we aim to comprehensively profile the transcriptomic landscape of neutrophils in BALF from patients with sepsis and SI-ARDS, particularly focusing on cases caused by specific bacterial pathogens. METHODS Patients with confirmed sepsis (n = 14) or SI-ARDS (n = 11) were recruited. Besides, a control group consisting of patients with unrelated diseases (n = 7) who required bronchoscopy was also included (cohort 1). We collected the neutrophils in BALF from participants in cohort 1. To validate the identified differentially expressed genes (DEGs) and evaluate neutrophil apoptosis, an additional cohort (cohort 2) was recruited, consisting of 5 healthy controls, 10 patients with sepsis, and 10 patients with SI-ARDS. Peripheral blood neutrophils were collected from participants in cohort 2 for further analysis. DEGs between SI-ARDS patients and controls, sepsis patients and controls, as well as SI-ARDS patients and sepsis patients were identified. And, publicly available datasets were downloaded to compare with local results. Additionally, the DEGs were also identified between patients infected with drug-resistant Klebsiella pneumoniae and those infected with other bacterial pathogens. Furthermore, a third cohort (cohort 3) consisting of 57 sepsis patients and 46 SI-ARDS patients was recruited for investigating the prognostic significance of neutrophils in SI-ARDS. RESULTS In cohort 1, 8/14 of the septic patients and 6/11 of the SI-ARDS patients were affected by drug-resistant Klebsiella pneumonia. There were 9921 DEGs between sepsis patients and controls, 10,252 DEGs between SI-ARDS patients and controls, and 24 DEGs between SI-ARDS and sepsis patients in neutrophils from BALF. Notably, fatty acid-binding pro-tein 4 (FABP4) exhibited significant downregulation in SI-ARDS patients. In cohort 2, peripheral blood analysis confirmed consistent trends, demonstrating that FABP4 expression was decreased, which contributed to the attenuation of neutrophil apoptosis. And FABP4 inhibitor-induced apoptosis resistance was reversed by a phosphatidylinositol 3 kinase (PI3K)/protein kinase B (AKT) inhibitor. Furthermore, survival analysis revealed that SI-ARDS patients with low levels of neutrophil FABP4 expression exhibited poor survival. Additionally, 520 overlapping DEGs were identified between the sepsis and control group comparisons and the SI-ARDS and sepsis group comparisons. Among these overlapping DEGs, 85% were downregulated, predominantly targeting immune-related pathways, whereas a smaller subset was upregulated, mainly associated with metabolism. DEGs in neutrophils in BALF of SI-ARDS and controls notably overlapped with those in neutrophils in peripheral blood. Importantly, DEGs in sepsis/SI-ARDS caused by drug-resistant Klebsiella pneumoniae differed from DEGs in sepsis/SI-ARDS caused by other bacteria. Additionally, FABP4 expression consistently decreased, attenuating neutrophil apoptosis. CONCLUSIONS The downregulation of FABP4 in neutrophils was found to inhibit apoptosis through the activation of the PI3K/AKT signaling pathway. Importantly, the expression level of FABP4 in neutrophil emerged as a prognostic indicator for sepsis and SI-ARDS patients, suggesting its potential utility in clinical decision-making to address the challenges posed by this condition.
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Affiliation(s)
- Weixia Xuan
- Department of Pulmonary and Critical Care Medicine, China-Japan Friendship Hospital, Capital Medical University, Beijing 100000, China
- Department of Pulmonary and Critical Care Medicine, National Center for Respiratory Medicine, Center of Respiratory Medicine, National Clinical Research Center for Respiratory Diseases, China-Japan Friendship Hospital, Beijing 100000, China
- Department of Respiratory and Critical Care Medicine, Zhengzhou University People's Hospital, Henan Provincial People's Hospital, Zhengzhou, Henan 450003, China
| | - Chaofan Liang
- Department of Respiratory and Critical Care Medicine, Zhengzhou University People's Hospital, Henan Provincial People's Hospital, Zhengzhou, Henan 450003, China
| | - Shenying Yang
- Department of Respiratory and Critical Care Medicine, Zhengzhou University People's Hospital, Henan Provincial People's Hospital, Zhengzhou, Henan 450003, China
| | - Longcheng Zheng
- Department of Respiratory and Critical Care Medicine, People's Hospital of Henan University, People's Hospital of Henan Province, Zhengzhou, Henan 450003, China
| | - Xu Wu
- Department of Scientific Research, Hunan Provincial People's Hospital, The First Affiliated Hospital of Hunan Normal University, Changsha, Hunan 41000, China
| | - Xiaoju Zhang
- Department of Respiratory and Critical Care Medicine, Zhengzhou University People's Hospital, Henan Provincial People's Hospital, Zhengzhou, Henan 450003, China
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Fan Y, Moser J, Jongman RM, Borghuis T, Vonk JM, Timens W, van Meurs M, Pillay J, Burgess JK. Compositional changes of the lung extracellular matrix in acute respiratory distress syndrome. Am J Physiol Cell Physiol 2025; 328:C1279-C1292. [PMID: 40063067 DOI: 10.1152/ajpcell.01007.2024] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2024] [Revised: 01/13/2025] [Accepted: 03/04/2025] [Indexed: 04/04/2025]
Abstract
Acute respiratory distress syndrome (ARDS) is pathologically characterized by diffuse alveolar damage (DAD) and is associated with high morbidity and mortality rates. Although pulmonary injury initiates alveolar-capillary barrier damage in ARDS, remodeling of the extracellular matrix (ECM), which is pivotal for both tissue repair and organ recovery, may play a large role in persistent ARDS. This study investigated the compositional changes in the ECM in different DAD stages in ARDS. Paraffin-embedded lung sections collected during autopsy or from posttransplant lungs were obtained from patients with ARDS (n = 28) admitted to the University Medical Center Groningen between 2010 and 2020. Sections were stained histochemically, and immunohistochemically for collagen III α1 chain (Col IIIa1), IV α3 chain (Col IVa3), VI α1 chain (Col VIa1), periostin (PSTN), lumican (LUM), and fibronectin (FN). The sections were divided into 118 regions based on DAD stages (54 early vs. 64 advanced). The differences in the expression of selected proteins were compared between DAD stages or across ARDS duration (<7 days, 7-14 days, and >14 days). The fiber pattern of Col VIa1 was analyzed using CellProfiler. Higher tissue density, lower proportional areas of Col IIIa1, Col IVa3, and LUM, and more concentrated Col VIa1 fibers were observed in the advanced DAD stage than in the early DAD stage. Areas with higher proportions of total collagen and FN, and lower proportional areas of Col IIIa1, Col IVa3, and LUM were detected in lung regions from patients with ARDS >14-days duration. These findings revealed proportional changes in ECM components, strongly suggesting that dynamic changes in ECM proteins play a role in pathophysiology in ARDS during progression.NEW & NOTEWORTHY Our study revealed ECM protein compositional differences in lung parenchyma between stages of DAD. In advanced DAD, tissue density was higher, but collagen type III, type IV, and lumican were proportionally lower compared with early DAD. The organization of collagen type VI fibers was highly concentrated in advanced DAD. Our results indicate that both composition and organization of ECM were remodeled in advanced DAD, suggesting a role in manifesting acute respiratory distress syndrome.
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Affiliation(s)
- YiWen Fan
- Department of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
- Department of Critical Care, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
- Groningen Research Institute for Asthma and COPD, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
| | - Jill Moser
- Department of Critical Care, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
| | - Rianne M Jongman
- Department of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
- Department of Anesthesiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
| | - Theo Borghuis
- Department of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
| | - Judith M Vonk
- Groningen Research Institute for Asthma and COPD, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
- Department of Epidemiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
| | - Wim Timens
- Department of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
- Groningen Research Institute for Asthma and COPD, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
| | - Matijs van Meurs
- Department of Critical Care, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
| | - Janesh Pillay
- Department of Critical Care, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
- Groningen Research Institute for Asthma and COPD, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
| | - Janette K Burgess
- Department of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
- Groningen Research Institute for Asthma and COPD, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
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Di Bari S, Izzo F, Bresciani L, Mancarella G, Garattini S, Gasperin A, Di Trento D, Grimaldi A, Parente A, Marocco R, Carraro A, Kertusha B, Tieghi T, Del Borgo C, Vita S, Guardiani M, Pasquazzi C, Spagnoli A, Alunni Fegatelli D, Lichtner M. Effectiveness of early intervention and combination treatment with monoclonal antibodies and antivirals in oncohematological patients with SARS-CoV-2: a retrospective experience. Front Immunol 2025; 16:1524525. [PMID: 40226612 PMCID: PMC11985841 DOI: 10.3389/fimmu.2025.1524525] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2024] [Accepted: 03/10/2025] [Indexed: 04/15/2025] Open
Abstract
Patients with acute SARS-CoV-2 and pre-existing oncohematological conditions challenge clinicians due to a heightened risk for severe COVID-19 and forced deferral of cancer treatment. Different treatment approaches aim to either prevent the progression of mild disease ("early therapy") or to treat more severe COVID-19. Currently, there is limited evidence supporting the effectiveness of a tailored approach for oncohematological patients. We present a real-world experience from two university hospitals. In this retrospective study we recruited oncohematological patients hospitalized for SARS-CoV-2 pneumonia between March 2020 and June 2023 from two hospitals in Latium, Italy. Patients with COVID-19 pneumonia received either antiviral or monoclonal antibodies (MoAb) alone, a dual therapy (antiviral with MoAb) or a triple therapy (two different antivirals and MoAb). The study aimed to evaluate the practical management of hospitalized oncohematological patients with COVID-19. We focused on the impact in patients with COVID-19 related pneumonia of specific therapies, early treatment, and tixagevimab-cilgavimab prophylaxis on in-hospital mortality and viral clearance time. Overall, 101 patients were recruited, 76 (75.24%) patients developed pneumonia, and 16 (15.84%) patients died from any cause. While most patients (75,25%) did not receive "early therapy", those who did had a higher chance of survival (p=0.04). Furthermore, the pneumonia subgroup treated with early therapy demonstrated a higher survival rate as well (p=0.02). Out of the hospitalized patients triple therapy resulted in lower mortality (all patients survive in this group). This group also showed a significant reduction in the time to viral clearance from the first day of the evaluated therapy (6 days [IQR 4;9]), compared to patients treated with only remdesivir (17 days [IQR 8;37]) (p=0.03). Our findings demonstrate that early therapy significantly reduces in-hospital mortality, while triple therapy accelerates viral clearance in hospitalized patients. These results, in line with recent studies, underscore the critical importance of prompt treatment and a multitargeted pharmacological approach for optimizing outcomes in oncohematological patients with SARS-CoV-2. Future research, involving larger cohorts, should delve deeper into COVID-19 treatment strategies for this vulnerable population, with a particular emphasis on the elderly, who continue to experience high mortality rates.
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Affiliation(s)
- Silvia Di Bari
- Infectious Disease Unit, Sant’Andrea Hospital, Sapienza University of Rome, Rome, Italy
| | - Francesco Izzo
- Infectious Disease Unit, Santa Maria Goretti Hospital, Sapienza University of Rome, Latina, Italy
| | - Livia Bresciani
- Infectious Disease Unit, Sant’Andrea Hospital, Sapienza University of Rome, Rome, Italy
| | - Giulia Mancarella
- Infectious Disease Unit, Santa Maria Goretti Hospital, Sapienza University of Rome, Latina, Italy
| | - Silvia Garattini
- Infectious Disease Unit, Santa Maria Goretti Hospital, Sapienza University of Rome, Latina, Italy
| | - Andrea Gasperin
- Infectious Disease Unit, Santa Maria Goretti Hospital, Sapienza University of Rome, Latina, Italy
| | - Daniela Di Trento
- Infectious Disease Unit, Santa Maria Goretti Hospital, Sapienza University of Rome, Latina, Italy
| | - Alessandra Grimaldi
- Infectious Disease Unit, Santa Maria Goretti Hospital, Sapienza University of Rome, Latina, Italy
| | - Alberico Parente
- Infectious Disease Unit, Santa Maria Goretti Hospital, Sapienza University of Rome, Latina, Italy
| | - Raffaella Marocco
- Infectious Disease Unit, Santa Maria Goretti Hospital, Sapienza University of Rome, Latina, Italy
| | - Anna Carraro
- Infectious Disease Unit, Santa Maria Goretti Hospital, Sapienza University of Rome, Latina, Italy
| | - Blerta Kertusha
- Infectious Disease Unit, Santa Maria Goretti Hospital, Sapienza University of Rome, Latina, Italy
| | - Tiziana Tieghi
- Infectious Disease Unit, Santa Maria Goretti Hospital, Sapienza University of Rome, Latina, Italy
| | - Cosmo Del Borgo
- Infectious Disease Unit, Santa Maria Goretti Hospital, Sapienza University of Rome, Latina, Italy
| | - Serena Vita
- National Institute for Infectious Diseases Lazzaro Spallanzani, Rome, Italy
| | - Mariasilvia Guardiani
- Infectious Disease Unit, Santa Maria Goretti Hospital, Sapienza University of Rome, Latina, Italy
| | - Caterina Pasquazzi
- Infectious Disease Unit, Sant’Andrea Hospital, Sapienza University of Rome, Rome, Italy
| | - Alessandra Spagnoli
- Department of Public Health and Infectious Diseases, Sapienza University of Rome, Rome, Italy
| | - Danilo Alunni Fegatelli
- Department of Public Health and Infectious Diseases, Sapienza University of Rome, Rome, Italy
| | - Miriam Lichtner
- Infectious Disease Unit, Sant’Andrea Hospital, Sapienza University of Rome, Rome, Italy
- Department of Neuroscience, Mental Health, and Sense Organs, NESMOS, Sapienza University of Rome, Rome, Italy
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López-Olivencia M, de Pablo R, de Dios NP, García-Plaza S, Sáez-Noguero S, de la Fuente JS, Fortún J, Cuesta MCS. The adverse impact of cytomegalovirus infection on intensive care units outcomes in critically ill COVID-19 patients: a single-center prospective observational study. Infection 2025:10.1007/s15010-025-02499-8. [PMID: 40106092 DOI: 10.1007/s15010-025-02499-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2024] [Accepted: 02/23/2025] [Indexed: 03/22/2025]
Abstract
PURPOSE To assess the incidence and clinical impact of CMV infection in critically ill COVID-19 patients, examining ICU and hospital mortality, and length of hospital stay. METHODS In this single-center, prospective observational study (March 2020 - September 2022), 431 patients with COVID-19 pneumonia and moderate to severe ARDS were included. An active CMV surveillance protocol was implemented, analyzing CMV DNA in plasma and bronchoalveolar lavage (BAL). Clinical characteristics and outcomes were compared between CMV-COVID co-infected patients and those without CMV reactivation. RESULTS CMV-COVID co-infection was detected in 14.8% (64/431) of the cohort. Patients with CMV-COVID co-infection exhibited significantly higher ICU mortality (43.8% vs. 13.6%; p < 0.001) and hospital mortality (48.4% vs. 13.6%; p < 0.001) compared to patients without CMV. CMV infection was an independent predictor of hospital mortality (OR 4.91; 95% CI 2.76-8.75; p = 0.019). Earlier CMV reactivation was associated with an increased risk of hospital mortality (HR = 0.94; 95% CI: 0.90-0.98; p = 0.003). Additionally, CMV-COVID patients had a higher incidence of ICU-acquired infections and a prolonged hospital stay. CONCLUSIONS In critically ill patients with SARS-CoV-2 pneumonia, CMV infection was frequently observed, and associated with increased ICU and hospital mortality. CMV co-infection correlated with a higher incidence of ICU-acquired bacterial and fungal infections and prolonged hospital stays. This emphasizes the importance of early CMV monitoring upon ICU admission, as timely detection and intervention could potentially mitigate its impact on patient outcomes.
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Affiliation(s)
| | - Raúl de Pablo
- Department of Intensive Care Medicine, Ramón y Cajal University Hospital, Madrid, Spain.
- Department of Medicine and Medical Specialties, University of Alcalá, Madrid, Spain.
| | - Noemí Paredes de Dios
- Department of Intensive Care Medicine, Ramón y Cajal University Hospital, Madrid, Spain
| | - Susana García-Plaza
- Department of Intensive Care Medicine, Ramón y Cajal University Hospital, Madrid, Spain
| | - Sergio Sáez-Noguero
- Department of Intensive Care Medicine, Ramón y Cajal University Hospital, Madrid, Spain
| | | | - Jesús Fortún
- Department of Infectious Diseases, Ramón y Cajal University Hospital, Madrid, Spain
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Cheong I, Álvarez Vilariño FM, Gómez RA, Merlo PM, Tamagnone FM. Assessing Right Ventricular Performance During Prone Ventilation in ARDS Patients Using Speckle Tracking Echocardiography. JOURNAL OF CLINICAL ULTRASOUND : JCU 2025. [PMID: 40098527 DOI: 10.1002/jcu.23954] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/07/2024] [Revised: 01/01/2025] [Accepted: 02/01/2025] [Indexed: 03/19/2025]
Abstract
PURPOSE Acute respiratory distress syndrome (ARDS) frequently results in right ventricular (RV) dysfunction due to increased afterload and pulmonary vascular resistance. Among the standardized therapeutic strategies for ARDS management, protective ventilation and prone positioning in cases of severe oxygenation deterioration have proven effective, with prone positioning offering additional benefits, including improved RV function, enhanced physiological outcomes such as oxygenation and lung mechanics. This study aims to evaluate the impact of prone positioning on RV performance in ARDS patients using speckle tracking echocardiography (STE). METHODS This observational, retrospective, single-center study aimed to evaluate the effects of prone positioning on RV function in patients with ARDS requiring mechanical ventilation. The study included patients with ARDS of varying severities who were passively ventilated. Transthoracic echocardiography was performed to assess RV function, with a specific focus on RV global longitudinal strain (GLS) and RV free wall strain (RVFWS) in both supine and prone positions using STE. RESULTS Between August 2021 and April 2024, a total of 16 mechanically ventilated patients were included in the study. Regarding mechanical ventilation parameters, after applying the Bonferroni correction, there was a statistically significant increase in the PaO2/FiO2 ratio during the prone position (p = 0.004). Concerning echocardiographic variables, no statistically significant differences were found in left ventricular ejection fraction, basal RV diameter, RV/left ventricular end-diastolic area ratio, or the values of tricuspid annular tissue S' wave, TAPSE, and RV fractional area change. However, during the prone position, there was a significant decrease in RV GLS (p = 0.009) and RVFWS (p = 0.003). CONCLUSION This study provides preliminary insights into the impact of the prone position maneuver on RV systolic function in patients with ARDS, suggesting that strain measured by STE could serve as a sensitive marker for detecting subclinical RV dysfunction. Further research with larger sample sizes and prospective designs is needed to confirm and build upon these findings.
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Affiliation(s)
- Issac Cheong
- Department of Critical Care Medicine, Sanatorio de Los Arcos, Buenos Aires, Argentina
- Argentinian Critical Care Ultrasonography Association (ASARUC), Buenos Aires, Argentina
| | | | - Raúl Alejandro Gómez
- Department of Critical Care Medicine, Sanatorio de Los Arcos, Buenos Aires, Argentina
| | - Pablo Martín Merlo
- Argentinian Critical Care Ultrasonography Association (ASARUC), Buenos Aires, Argentina
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Flower L, Vozza EG, Bryant CE, Summers C. Role of inflammasomes in acute respiratory distress syndrome. Thorax 2025; 80:255-263. [PMID: 39884849 PMCID: PMC12015084 DOI: 10.1136/thorax-2024-222596] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2024] [Accepted: 01/10/2025] [Indexed: 02/01/2025]
Abstract
Acute respiratory distress syndrome (ARDS) is present in >10% of all people admitted to critical care and is associated with severe morbidity and mortality. Despite more than half a century since its first description, no efficacious pharmacological therapies have been developed, and little progress has been made in improving clinical outcomes. Neutrophils are the principal drivers of ARDS, with their priming and subsequent aberrant downstream functions, including interleukin (IL) 1β and IL-18 secretion, central to the disease pathogenesis. The dominant pathways through which IL-1β and IL-18 are believed to be elaborated are multimeric protein structures called inflammasomes that consist of sensor proteins, adaptor proteins and an effector enzyme. The inflammasome's initial activation depends on one of a variety of damage-associated (DAMP) or pathogen-associated (PAMP) molecular patterns. However, once activated, a common downstream inflammatory pathway is initiated regardless of the specific DAMP or PAMP involved. Several inflammasomes exist in humans. The nucleotide-binding domain leucine-rich repeat (NLR) family, pyrin domain-containing 3 (NLRP3), inflammasome is the best described in the context of ARDS and is known to be activated in both infective and sterile cases. The NLR family, caspase activation and recruitment domain-containing 4 (NLRC4) and absent in melanoma 2 (AIM2) inflammasomes have also been implicated in various ARDS settings, as have inflammasome-independent pathways. Further work is required to understand human biology as much of our knowledge is extrapolated from rodent experimental models. Experimental lung injury models have demonstrated beneficial responses to inflammasome, IL-1β and IL-18 blockade. However, findings have yet to be successfully translated into humans with ARDS, likely due to an underappreciation of the central role of the neutrophil inflammasome. A thorough understanding of inflammasome pathways is vital for critical care clinicians and researchers and for the development of beneficial therapies. In this review, we describe the central role of the inflammasome in the development of ARDS and its potential for immunomodulation, highlighting key areas for future research.
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Affiliation(s)
- Luke Flower
- Victor Phillip Dahdaleh Heart & Lung Research Institute, University of Cambridge, Cambridge, UK
- Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
| | - Emilio G Vozza
- Victor Phillip Dahdaleh Heart & Lung Research Institute, University of Cambridge, Cambridge, UK
| | - Clare E Bryant
- Victor Phillip Dahdaleh Heart & Lung Research Institute, University of Cambridge, Cambridge, UK
| | - Charlotte Summers
- Victor Phillip Dahdaleh Heart & Lung Research Institute, University of Cambridge, Cambridge, UK
- Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
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Şirin İ, Erdem AB, Uysal ŞB, Gedikaslan Ş. The Effect of Tidal Volumes of Mechanically Ventilated Patients on Lung Sliding Amplitude in Point-Of-Care Lung Ultrasound. JOURNAL OF CLINICAL ULTRASOUND : JCU 2025. [PMID: 40098375 DOI: 10.1002/jcu.23968] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/15/2025] [Revised: 01/31/2025] [Accepted: 02/09/2025] [Indexed: 03/19/2025]
Abstract
OBJECTIVES Several factors influencing lung sliding amplitude have been identified. However, the effect of tidal volume changes on lung sliding amplitude in the same patient remains unclear. In this study, we investigated the relationship between lung sliding amplitude, tidal volume, lung compliance, and mortality. METHODS This was a single-center, observational, and prospective study. Lung sliding amplitudes were measured at four points using ultrasound in patients connected to mechanical ventilators in the emergency department of a tertiary hospital. In patients in whom tidal volume adjustments were made, lung measurements were repeated. RESULTS A total of 46 patients who met the inclusion criteria between June 2024 and September 2024 were included in the study. After a reduction in tidal volume, lung sliding amplitudes in all four lung regions significantly decreased in the second measurement compared to the first (p < 0.001). There was a weak positive correlation between lung compliance and both right and left basal lung sliding amplitudes (rho: 0.397, rho: 0.298, respectively), which was statistically significant (p = 0.004 and p = 0.045, respectively). There was also a significant relationship between the initially measured right basal lung sliding amplitude and mortality (p = 0.029). CONCLUSION In patients receiving mechanical ventilation support, a reduction in tidal volume results in decreased lung sliding amplitude. There is a relationship between lung sliding amplitude measured in the basal lung regions and lung compliance. Lung sliding amplitude measured in the right basal region may be associated with mortality, but this association is not present in other lung regions.
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Affiliation(s)
- İlker Şirin
- Department of Emergency Medicine, Ankara Etlik City Hospital, Ankara, Turkey
| | - Ahmet Burak Erdem
- Department of Emergency Medicine, Ankara Etlik City Hospital, Ankara, Turkey
| | - Şerife Büşra Uysal
- Department of Emergency Medicine, Ankara Etlik City Hospital, Ankara, Turkey
| | - Şeyda Gedikaslan
- Department of Emergency Medicine, Ankara Etlik City Hospital, Ankara, Turkey
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Cui N, Wang J, Feng X, Zhang L, Yang Y. Deep vein thrombosis in severe community-acquired pneumonia patients undergoing thromboprophylaxis: Prevalence, risk factors, and outcome. Thromb J 2025; 23:23. [PMID: 40075406 PMCID: PMC11905501 DOI: 10.1186/s12959-025-00706-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2024] [Accepted: 02/27/2025] [Indexed: 03/14/2025] Open
Abstract
BACKGROUND Even with adherence to thromboprophylaxis recommended by guidelines, the incidence of deep vein thrombosis (DVT) remains high among patients with severe community-acquired pneumonia (SCAP). There is an urgent need to identify the risk factors for DVT in these patients to optimize preventive strategies. STUDY DESIGN AND METHODS We retrospectively enrolled 309 adults with SCAP admitted to Beijing Chao-Yang Hospital between 1 January 2015 and 30 June 2023. All patients received guideline-recommended thromboprophylaxis and lower extremity venous compression ultrasound scanning. Clinical characteristics, including demographic information, clinical history, vital signs, laboratory findings, treatments, complications, and outcomes, were analyzed for patients with and without DVT in these two cohorts. RESULTS Of the 309 patients, 110 (35.6%) developed 1ower extremity DVT. There was no significant difference in the incidence of DVT among the different prophylactic measures (P = 0.393). Multivariate logistic regression analysis showed an association between a history of VTE (OR, 13.388, 95% CI: 2.179 ~ 82.257; P = 0.005), bedridden time > 3 days (OR, 17.672, 95% CI: 5.686 ~ 54.929; P < 0.001), D-dimer levels ≥ 1.0 µg/mL (OR, 2.109, 95% CI: 1.018 ~ 4.372; P = 0.045), LDH levels ≥ 400 U/L (OR, 2.548, 95% CI: 1.308 ~ 4.965; P = 0.006), IMV (OR, 2.479, 95% CI: 1.233 ~ 4.986; P = 0.011) and the occurrence of DVT. A new prediction model, including history of VTE, bedridden time, D-dimer levels, LDH levels and IMV, showed a better performance in predicting DVT (AUC = 0.856; 95% CI: 0.766 ~ 0.921; sensitivity: 80.6%; specificity: 81.4%) than Padua prediction score (AUC = 0.666) and Caprini prediction score (AUC = 0.688) for patients with SCAP. The 30-day mortality and in-hospital mortality in the DVT group were significantly higher than those in the non-DVT group. CONCLUSIONS Even received guideline-recommended thromboprophylaxis, the prevalence of DVT among patients with SCAP remains unexpectedly high which is also associated with a poor prognosis. It is necessary to identify people at high risk of DVT early and refine the preventive strategies accordingly to improve patient outcomes.
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Affiliation(s)
- Na Cui
- Department of Respiratory and Critical Care Medicine, Beijing Institute of Respiratory Medicine and Beijing Chao-Yang Hospital, Capital Medical University, 8 Gongren Tiyuchang Nanlua, Chaoyang District, Beijing, 100020, People's Republic of China
| | - Jing Wang
- Department of Respiratory and Critical Care Medicine, Beijing Institute of Respiratory Medicine and Beijing Chao-Yang Hospital, Capital Medical University, 8 Gongren Tiyuchang Nanlua, Chaoyang District, Beijing, 100020, People's Republic of China
| | - Xiaokai Feng
- Department of Respiratory and Critical Care Medicine, Beijing Institute of Respiratory Medicine and Beijing Chao-Yang Hospital, Capital Medical University, 8 Gongren Tiyuchang Nanlua, Chaoyang District, Beijing, 100020, People's Republic of China
| | - Liming Zhang
- Department of Respiratory and Critical Care Medicine, Beijing Institute of Respiratory Medicine and Beijing Chao-Yang Hospital, Capital Medical University, 8 Gongren Tiyuchang Nanlua, Chaoyang District, Beijing, 100020, People's Republic of China.
| | - Yuanhua Yang
- Department of Respiratory and Critical Care Medicine, Beijing Institute of Respiratory Medicine and Beijing Chao-Yang Hospital, Capital Medical University, 8 Gongren Tiyuchang Nanlua, Chaoyang District, Beijing, 100020, People's Republic of China.
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Zhang J, Jiang S, Jiang J, Liu Y. Global research landscape on nanotechnology in acute lung injury: a bibliometric analysis. Front Digit Health 2025; 7:1472753. [PMID: 40103738 PMCID: PMC11913875 DOI: 10.3389/fdgth.2025.1472753] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2024] [Accepted: 02/14/2025] [Indexed: 03/20/2025] Open
Abstract
Background Acute lung injury is a common respiratory emergency that seriously affects the life, health and quality of life of patients, especially after the global COVID-19 pneumonia. The application of nanotechnology in acute lung injury is promising. In response to the knowledge explosion resulting from rapid publication growth, we applied bibliometric analysis to explore the research profile and thematic trends in the field. Methods Articles and reviews related to nanotechnology in acute lung injury from 2004 to 2023 were searched. Java-based Citespace, VOSviewer, and R software-based Bibiometrix were used to systematically evaluate publications by spatiotemporal distribution, author distribution, subject categories, topic distribution, references, and keywords. Results A total of 1,347 publications were included. The number of papers related to nanotechnology in acute lung injury has grown exponentially over the past 20 years. China was the most productive country out of all 53 countries, followed by the United States. The Chinese Academy of Sciences was the most productive institution with 76 papers. PARTICLE AND FIBRE TOXICOLOGY was the most productive journal. The top five high-frequency keywords were inflammation, oxidative stress, toxicity, in vitro, respiratory-distress-syndrome. And the top five emerging keywords were delivery, covid-19, extracellular vesicles, therapy, sars-cov-2. Drug delivery are the focus of current research. Two emerging research areas represented the development trends: novel nanocarriers with higher efficiency and lower biotoxicity, and the other is research related to impact of nanomaterials in the progression of acute lung injury. Conclusion The field of nanotechnology in acute lung injury has been in a period of rapid development in the last three years. Delivery,targeted delivery and exosm have been the focus of current research in this field. Two emerging research areas represented the development trends:novel nanocarriers with higher efficiency and lower biotoxicity such as extracellular vesicles, exosomes and solid lipid nanoparticles, and the other is research related to impact of nanomaterials in the progression of acute lung injury.
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Affiliation(s)
- Jian Zhang
- School of Medicine, Nankai University, Tianjin, China
- Department of Thoracic Surgery, The First Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Shasha Jiang
- Department of Thoracic Surgery, The First Medical Center of Chinese PLA General Hospital, Beijing, China
- Postgraduate School, Medical School of Chinese PLA, Beijing, China
| | - Jipeng Jiang
- Department of Thoracic Surgery, The First Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Yang Liu
- School of Medicine, Nankai University, Tianjin, China
- Department of Thoracic Surgery, The First Medical Center of Chinese PLA General Hospital, Beijing, China
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Dao CX, Dang TQ, Luong CQ, Manabe T, Nguyen MH, Pham DT, Pham QT, Vu TT, Truong HT, Nguyen HH, Nguyen CB, Khuong DQ, Dang HD, Nguyen TA, Pham TT, Bui GTH, Van Bui C, Nguyen QH, Tran TH, Nguyen TC, Vo KH, Vu LT, Phan NT, Nguyen PTH, Nguyen CD, Nguyen AD, Van Nguyen C, Nguyen BG, Do SN. Predictive validity of the sequential organ failure assessment score for mortality in patients with acute respiratory distress syndrome in Vietnam. Sci Rep 2025; 15:7406. [PMID: 40033012 PMCID: PMC11876689 DOI: 10.1038/s41598-025-92199-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2024] [Accepted: 02/25/2025] [Indexed: 03/05/2025] Open
Abstract
Evaluating the prognosis of ARDS patients using grading systems can enhance treatment decisions. This retrospective observational study evaluated the predictive accuracy of the SOFA score, APACHE II score, SpO2/FiO2 ratio, and PaO2/FiO2 ratio for mortality in ARDS patients in Vietnam. The study included 335 adult ARDS patients admitted to a central hospital from August 2015 to August 2023. Among them, 66.9% were male, the median age was 55 years, and 61.5% died in the hospital. The SOFA (AUROC: 0.651) and APACHE II scores (AUROC: 0.693) showed poor discriminatory ability for hospital mortality. The SpO2/FiO2 (AUROC: 0.595) and PaO2/FiO2 ratios (AUROC: 0.595) also displayed poor discriminatory ability. In multivariable analyses, after adjusting for the same set of confounding variables, the APACHE II score (adjusted OR: 1.152), SpO2/FiO2 ratio (adjusted OR: 0.985), and PaO2/FiO2 ratio (adjusted OR: 0.989) were independently associated with hospital mortality. Although the SOFA score (adjusted OR: 1.132) indicated a potential association with hospital mortality, it did not reach statistical significance (p = 0.081). However, a SOFA score of ≥ 10 emerged as an independent predictor (adjusted OR: 3.398) of hospital mortality. These findings emphasize the need for further studies to develop more accurate scoring systems for predicting outcomes in ARDS patients.
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Affiliation(s)
- Co Xuan Dao
- Center for Critical Care Medicine, Bach Mai Hospital, Hanoi, Vietnam
- Department of Emergency and Critical Care Medicine, Hanoi Medical University, No. 01, Ton That Tung Street, Dong Da District, Hanoi, 100000, Vietnam
- Department of Emergency and Critical Care Medicine, Faculty of Medicine, VNU University of Medicine and Pharmacy, Vietnam National University, Hanoi, Vietnam
| | - Tuan Quoc Dang
- Center for Critical Care Medicine, Bach Mai Hospital, Hanoi, Vietnam.
- Department of Emergency and Critical Care Medicine, Hanoi Medical University, No. 01, Ton That Tung Street, Dong Da District, Hanoi, 100000, Vietnam.
| | - Chinh Quoc Luong
- Department of Emergency and Critical Care Medicine, Hanoi Medical University, No. 01, Ton That Tung Street, Dong Da District, Hanoi, 100000, Vietnam
- Department of Emergency and Critical Care Medicine, Faculty of Medicine, VNU University of Medicine and Pharmacy, Vietnam National University, Hanoi, Vietnam
- Center for Emergency Medicine, Bach Mai Hospital, Hanoi, Vietnam
| | - Toshie Manabe
- Nagoya City University School of Data Science, Nagoya, Aichi, Japan
- Center for Clinical Research, Nagoya City University Hospital, Nagoya, Aichi, Japan
| | - My Ha Nguyen
- Department of Health Organization and Management, Faculty of Public Health, Thai Binh University of Medicine and Pharmacy, Thai Binh, Vietnam
| | - Dung Thi Pham
- Department of Nutrition and Food Safety, Faculty of Public Health, Thai Binh University of Medicine and Pharmacy, Thai Binh, Vietnam
| | - Quynh Thi Pham
- Department of Emergency and Critical Care Medicine, Hanoi Medical University, No. 01, Ton That Tung Street, Dong Da District, Hanoi, 100000, Vietnam
- Intensive Care Unit, University Medical Center Ho Chi Minh City, University of Medicine and Pharmacy at Ho Chi Minh City, Ho Chi Minh City, Vietnam
| | - Tai Thien Vu
- Department of Emergency and Critical Care Medicine, Hanoi Medical University, No. 01, Ton That Tung Street, Dong Da District, Hanoi, 100000, Vietnam
- Emergency Department, Thai Nguyen National Hospital, Thai Nguyen City, Thai Nguyen, Vietnam
| | - Hau Thi Truong
- Center for Critical Care Medicine, Bach Mai Hospital, Hanoi, Vietnam
- Department of Emergency and Critical Care Medicine, Hanoi Medical University, No. 01, Ton That Tung Street, Dong Da District, Hanoi, 100000, Vietnam
| | - Hai Hoang Nguyen
- Department of Emergency and Critical Care Medicine, Hanoi Medical University, No. 01, Ton That Tung Street, Dong Da District, Hanoi, 100000, Vietnam
- Emergency Department, Agriculture General Hospital, Hanoi, Vietnam
| | - Cuong Ba Nguyen
- Center for Critical Care Medicine, Bach Mai Hospital, Hanoi, Vietnam
| | - Dai Quoc Khuong
- Department of Emergency and Critical Care Medicine, Hanoi Medical University, No. 01, Ton That Tung Street, Dong Da District, Hanoi, 100000, Vietnam
- Center for Emergency Medicine, Bach Mai Hospital, Hanoi, Vietnam
| | - Hien Duy Dang
- Center for Critical Care Medicine, Bach Mai Hospital, Hanoi, Vietnam
| | - Tuan Anh Nguyen
- Department of Emergency and Critical Care Medicine, Hanoi Medical University, No. 01, Ton That Tung Street, Dong Da District, Hanoi, 100000, Vietnam
- Center for Emergency Medicine, Bach Mai Hospital, Hanoi, Vietnam
| | - Thach The Pham
- Center for Critical Care Medicine, Bach Mai Hospital, Hanoi, Vietnam
- Department of Emergency and Critical Care Medicine, Hanoi Medical University, No. 01, Ton That Tung Street, Dong Da District, Hanoi, 100000, Vietnam
- Department of Emergency and Critical Care Medicine, Faculty of Medicine, VNU University of Medicine and Pharmacy, Vietnam National University, Hanoi, Vietnam
| | - Giang Thi Huong Bui
- Center for Critical Care Medicine, Bach Mai Hospital, Hanoi, Vietnam
- Department of Emergency and Critical Care Medicine, Hanoi Medical University, No. 01, Ton That Tung Street, Dong Da District, Hanoi, 100000, Vietnam
| | - Cuong Van Bui
- Center for Critical Care Medicine, Bach Mai Hospital, Hanoi, Vietnam
- Department of Emergency and Critical Care Medicine, Hanoi Medical University, No. 01, Ton That Tung Street, Dong Da District, Hanoi, 100000, Vietnam
- Department of Emergency and Critical Care Medicine, Faculty of Medicine, VNU University of Medicine and Pharmacy, Vietnam National University, Hanoi, Vietnam
- Department of Intensive Care for Tropical Diseases, Bach Mai Institute for Tropical Medicine, Bach Mai Hospital, Hanoi, Vietnam
| | - Quan Huu Nguyen
- Department of Emergency and Critical Care Medicine, Hanoi Medical University, No. 01, Ton That Tung Street, Dong Da District, Hanoi, 100000, Vietnam
- Department of Emergency and Critical Care Medicine, Faculty of Medicine, VNU University of Medicine and Pharmacy, Vietnam National University, Hanoi, Vietnam
- Center for Emergency Medicine, Bach Mai Hospital, Hanoi, Vietnam
| | - Thong Huu Tran
- Department of Emergency and Critical Care Medicine, Hanoi Medical University, No. 01, Ton That Tung Street, Dong Da District, Hanoi, 100000, Vietnam
- Department of Emergency and Critical Care Medicine, Faculty of Medicine, VNU University of Medicine and Pharmacy, Vietnam National University, Hanoi, Vietnam
- Center for Emergency Medicine, Bach Mai Hospital, Hanoi, Vietnam
| | - Tan Cong Nguyen
- Center for Critical Care Medicine, Bach Mai Hospital, Hanoi, Vietnam
- Department of Emergency and Critical Care Medicine, Hanoi Medical University, No. 01, Ton That Tung Street, Dong Da District, Hanoi, 100000, Vietnam
- Department of Emergency and Critical Care Medicine, Faculty of Medicine, VNU University of Medicine and Pharmacy, Vietnam National University, Hanoi, Vietnam
| | - Khoi Hong Vo
- Department of Neuro Intensive Care and Emergency Neurology, Neurology Center, Bach Mai Hospital, Hanoi, Vietnam
- Department of Neurology, Hanoi Medical University, Hanoi, Vietnam
- Department of Neurology, Faculty of Medicine, VNU University of Medicine and Pharmacy, Vietnam National University, Hanoi, Vietnam
| | - Lan Tuong Vu
- Department of Emergency and Critical Care Medicine, Hanoi Medical University, No. 01, Ton That Tung Street, Dong Da District, Hanoi, 100000, Vietnam
- Center for Emergency Medicine, Bach Mai Hospital, Hanoi, Vietnam
| | - Nga Thu Phan
- Department of Health Organization and Management, Faculty of Public Health, Thai Binh University of Medicine and Pharmacy, Thai Binh, Vietnam
| | - Phuong Thi Ha Nguyen
- Department of Nutrition and Food Safety, Faculty of Public Health, Thai Binh University of Medicine and Pharmacy, Thai Binh, Vietnam
| | - Cuong Duy Nguyen
- Department of Emergency and Critical Care Medicine, Thai Binh University of Medicine and Pharmacy, Thai Binh, Vietnam
| | - Anh Dat Nguyen
- Department of Emergency and Critical Care Medicine, Hanoi Medical University, No. 01, Ton That Tung Street, Dong Da District, Hanoi, 100000, Vietnam
- Center for Emergency Medicine, Bach Mai Hospital, Hanoi, Vietnam
| | - Chi Van Nguyen
- Department of Emergency and Critical Care Medicine, Hanoi Medical University, No. 01, Ton That Tung Street, Dong Da District, Hanoi, 100000, Vietnam
- Center for Emergency Medicine, Bach Mai Hospital, Hanoi, Vietnam
| | - Binh Gia Nguyen
- Center for Critical Care Medicine, Bach Mai Hospital, Hanoi, Vietnam
- Department of Pre-Hospital Emergency Medicine, Faculty of Medicine, VNU University of Medicine and Pharmacy, Vietnam National University, Hanoi, Vietnam
| | - Son Ngoc Do
- Center for Critical Care Medicine, Bach Mai Hospital, Hanoi, Vietnam
- Department of Emergency and Critical Care Medicine, Hanoi Medical University, No. 01, Ton That Tung Street, Dong Da District, Hanoi, 100000, Vietnam
- Department of Emergency and Critical Care Medicine, Faculty of Medicine, VNU University of Medicine and Pharmacy, Vietnam National University, Hanoi, Vietnam
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Kilpatrick F, Kanhere H, Stranz C, Prasad S, Sundararajan K, Edwards S, Trochsler M, Reddi B. Outcomes of open versus minimally invasive oesophagectomy in an Australian quaternary referral centre: a historical case-matched study. ANZ J Surg 2025; 95:350-355. [PMID: 39688212 DOI: 10.1111/ans.19351] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2024] [Revised: 11/21/2024] [Accepted: 11/26/2024] [Indexed: 12/18/2024]
Abstract
BACKGROUND Oesophagectomy for surgical management of oesophageal carcinoma has previously been performed via an open approach (OE), with a change in recent years to a minimally invasive technique (MIO). We performed a retrospective study to compare the rates of post-operative complications between OE and MIO patients at our institution. Secondary outcomes included nodal yield and ICU LOS. METHODS This is a retrospective, observational, case-matched single centre study of 2-stage oesophagectomies for carcinoma from January 2011 to December 2021. Fourty-four MIO patients were matched by age to 44 OE patients. Post-operative pulmonary, cardiac and surgical complications were defined using the Esophagectomy Complications Consensus Group (ECCG) guidelines. RESULTS Baseline characteristics were similar for the two groups, with a higher ASA grade for patients undergoing MIO. There was no significant difference in post-operative pulmonary complication rates between the OE versus MIO groups (41% versus 55%, P = 0.29). There were more cardiac arrhythmias in the MIO group however this was not statistically significant (9.1% versus 22.7%, P = 0.08). Rate of re-operation was equal between the groups with no difference between rates of other surgical complications, ICU LOS or hospital LOS. Significantly higher nodal yield was achieved in the MIO group. Overall rate of Clavien-Dindo graded complications were similar (55% versus 66%, P = 0.28). CONCLUSIONS MIO was associated with higher lymph node yield, and comparable complication rates when compared to OE and does not significantly alter time spent in hospital.
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Affiliation(s)
- Fiona Kilpatrick
- Intensive Care Unit, Royal Adelaide Hospital, Adelaide, South Australia, Australia
| | - Harsh Kanhere
- Department of Surgery, Royal Adelaide Hospital, Adelaide, South Australia, Australia
- University of Adelaide, Adelaide, South Australia, Australia
| | - Conrad Stranz
- University of Adelaide, Adelaide, South Australia, Australia
| | - Shalvin Prasad
- University of Adelaide, Adelaide, South Australia, Australia
| | - Krishnaswamy Sundararajan
- Intensive Care Unit, Royal Adelaide Hospital, Adelaide, South Australia, Australia
- Discipline of Acute Care Medicine, The University of Adelaide, Adelaide, South Australia, Australia
| | - Suzanne Edwards
- School of Public Health, The University of Adelaide, Adelaide, South Australia, Australia
| | - Markus Trochsler
- Department of Surgery, QEH & Royal Adelaide Hospital, Adelaide, South Australia, Australia
| | - Benjamin Reddi
- Intensive Care Unit, Royal Adelaide Hospital, Adelaide, South Australia, Australia
- Discipline of Acute Care Medicine, The University of Adelaide, Adelaide, South Australia, Australia
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Mady AF, Hamido HM, Abdulrahman B, Mady AA, Aletreby AW, Abdalla AA, Gano JQ, Hashim Aletreby WT. Effect of Nebulized Furosemide on the Mortality of Adult, Mechanically Ventilated Acute Respiratory Distress Syndrome (ARDS) Patients: Protocol of a Randomized Clinical Trial (The ENHALE Trial). Cureus 2025; 17:e81006. [PMID: 40260371 PMCID: PMC12011351 DOI: 10.7759/cureus.81006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/22/2025] [Indexed: 04/23/2025] Open
Abstract
Background Acute respiratory distress syndrome (ARDS) affects a significant proportion of ICU patients and has a high mortality rate. The inflammation of the alveolar-capillary membrane is pathognomonic and characterized by increased capillary permeability and pulmonary edema. A safe, readily available anti-inflammatory agent delivered directly to the lungs could be a promising therapeutic approach. All these properties apply to nebulized furosemide. Objectives The primary objective of this study is to analyze 28-day all-cause ICU mortality while the secondary objectives include assessing hospital mortality, ICU and hospital length of stay (LOS), ventilator-free days at 28 days, successful extubation rate, and adverse events. Methods A double-blind, placebo-controlled, parallel-arm superiority RCT using an intention-to-treat (ITT) analysis to assess whether nebulized furosemide reduces mortality in adult mechanically ventilated ARDS patients will be employed. Results The results of descriptive and inferential analyses will be tabulated, and the significant results will be presented.
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Affiliation(s)
- Ahmed F Mady
- Anesthesiology and Intensive Care, Tanta University Hospitals, Tanta, EGY
- Critical Care Medicine, King Saud Medical City, Riyadh, SAU
| | - Hend M Hamido
- Critical Care Medicine, King Saud Medical City, Riyadh, SAU
| | | | - Anas A Mady
- College of Medicine, Alfaisal University College of Medicine, Riyadh, SAU
| | | | - Ahmed A Abdalla
- College of Medicine, Alfaisal University College of Medicine, Riyadh, SAU
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Meza-Fuentes G, Delgado I, Barbé M, Sánchez-Barraza I, Retamal MA, López R. Machine learning-based identification of efficient and restrictive physiological subphenotypes in acute respiratory distress syndrome. Intensive Care Med Exp 2025; 13:29. [PMID: 40024962 PMCID: PMC11872963 DOI: 10.1186/s40635-025-00737-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2024] [Accepted: 02/14/2025] [Indexed: 03/04/2025] Open
Abstract
INTRODUCTION Acute respiratory distress syndrome (ARDS) is a severe condition with high morbidity and mortality, characterized by significant clinical heterogeneity. This heterogeneity complicates treatment selection and patient inclusion in clinical trials. Therefore, the objective of this study is to identify physiological subphenotypes of ARDS using machine learning, and to determine ventilatory variables that can effectively discriminate between these subphenotypes in a bedside setting with high performance, highlighting potential utility for future clinical stratification approaches. METHODOLOGY A retrospective cohort study was conducted using data from our ICU, covering admissions from 2017 to 2021. The study included 224 patients over 18 years of age diagnosed with ARDS according to the Berlin criteria and undergoing invasive mechanical ventilation (IMV). Data on physiological and ventilatory variables were collected during the first 24 h IMV. We applied machine learning techniques to categorize subphenotypes in ARDS patients. Initially, we employed the unsupervised Gaussian Mixture Classification Model approach to group patients into subphenotypes. Subsequently, we applied supervised models such as XGBoost to perform root cause analysis, evaluate the classification of patients into these subgroups, and measure their performance. RESULTS Our models identified two ARDS subphenotypes with significant clinical differences and significant outcomes. Subphenotype Efficient (n = 172) was characterized by lower mortality, lower clinical severity and presented a less restrictive pattern with better gas exchange compared to Subphenotype Restrictive (n = 52), which showed the opposite. The models demonstrated high performance with an area under the ROC curve of 0.94, sensitivity of 94.2% and specificity of 87.5%, in addition to an F1 score of 0.85. The most influential variables in the discrimination of subphenotypes were distension pressure, respiratory frequency and exhaled carbon dioxide volume. CONCLUSION This study presents an approach to improve subphenotype categorization in ARDS. The generation of clustering and prediction models by machine learning involving clinical, ventilatory mechanics, and gas exchange variables allowed for more accurate stratification of patients. These findings have the potential to optimize individualized treatment selection and improve clinical outcomes in patients with ARDS.
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Affiliation(s)
- Gabriela Meza-Fuentes
- Instituto de Ciencias e Innovación en Medicina, Facultad de Medicina Clínica Alemana, Universidad del Desarrollo, Santiago, Chile
| | - Iris Delgado
- Centro de Epidemiología y Políticas de Salud, Facultad de Medicina, Clínica Alemana, Universidad del Desarrollo, Santiago, Chile
| | - Mario Barbé
- Instituto de Ciencias e Innovación en Medicina, Facultad de Medicina Clínica Alemana, Universidad del Desarrollo, Santiago, Chile
| | - Ignacio Sánchez-Barraza
- Instituto de Ciencias e Innovación en Medicina, Facultad de Medicina Clínica Alemana, Universidad del Desarrollo, Santiago, Chile
| | - Mauricio A Retamal
- Programa de Comunicación Celular en Cáncer, Facultad de Medicina Clínica Alemana, Universidad del Desarrollo, Santiago, Chile
| | - René López
- Grupo Intensivo, ICIM, Facultad de Medicina, Clínica Alemana Universidad del Desarrollo, Santiago, Chile.
- Departamento de Paciente Crítico, Clínica Alemana de Santiago, Santiago, Chile.
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Magloire C, Aghabekyan T, Morley NE, Turcan S, Sexton S, Khatoon D, Okoye C, McFarlane SI. Severe Acute Respiratory Distress Syndrome in Lyme Disease: A Case Report and Review of the Literature. Cureus 2025; 17:e81170. [PMID: 40276406 PMCID: PMC12021006 DOI: 10.7759/cureus.81170] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2025] [Accepted: 03/25/2025] [Indexed: 04/26/2025] Open
Abstract
While there are many etiologies of acute respiratory distress syndrome (ARDS), Lyme disease is not a known cause of this disorder, and there is a paucity of Lyme-associated ARDS cases reported in the medical literature. In this report, we present a case of a 70-year-old woman with ARDS requiring mechanical ventilation, who initially had recurrent negative infectious workups but was ultimately diagnosed with Lyme disease with positive Lyme serology and western blot. The patient, who is from the New York City metropolitan area, had no outdoor exposure, recent travel history, or sick contacts. She experienced a complicated intensive care unit (ICU) course, including septic shock requiring antibiotics, vasopressors, and multiple diagnostic tests. Ultimately, the patient recovered and was transferred to the medicine unit and subsequently discharged in stable condition. This case highlights a rare complication of Lyme disease and highlights the importance of considering rare etiologies in the differential diagnosis of ARDS with an unclear etiology.
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Affiliation(s)
- Chris Magloire
- Internal Medicine, State University of New York Downstate Health Sciences University, New York, USA
| | - Tigran Aghabekyan
- Internal Medicine, State University of New York Downstate Health Sciences University, New York, USA
| | - Nicholas E Morley
- Internal Medicine, State University of New York Downstate Medical Center, New York, USA
| | - Sava Turcan
- Anesthesiology, State University of New York Downstate Health Sciences University, New York, USA
| | - Shawn Sexton
- Anesthesiology, State University of New York Downstate Medical Center, New York, USA
| | - Dilruba Khatoon
- Anesthesiology, State University of New York Downstate Health Sciences University, New York, USA
| | - Chibuzo Okoye
- Critical Care Medicine, State University of New York Downstate Health Sciences University, New York, USA
| | - Samy I McFarlane
- Internal Medicine, State University of New York Downstate Health Sciences University, New York, USA
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Said MM, Schippers JR, Atmowihardjo L, Li Y, van der Plas MS, Bogaard HJ, Bos LDJ, Mathôt RAA, Aman J, Swart EL, Bartelink IH. Disease-Drug-Drug Interaction of Imatinib in COVID-19 ARDS: A Pooled Population Pharmacokinetic Analysis. CPT Pharmacometrics Syst Pharmacol 2025; 14:583-595. [PMID: 39985762 PMCID: PMC11919263 DOI: 10.1002/psp4.13299] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2023] [Revised: 11/29/2024] [Accepted: 12/13/2024] [Indexed: 02/24/2025] Open
Abstract
Prior pharmacokinetic (PK) analysis revealed that increased alpha-1-acid glycoprotein (AAG) levels are associated with decreased imatinib unbound fraction in coronavirus disease 2019 (COVID-19) patients. This study aimed to investigate the PK of total and unbound concentrations of imatinib and the metabolite N-desmethyl imatinib in hospitalized patients with different severities of COVID-19, and to assess the impact of critical illness and the potential drug-drug interaction with IL-6R inhibitors on imatinib exposure. Imatinib, N-desmethyl imatinib, and AAG were quantified from collected plasma samples. The PK data was further combined with previous data from COVID-19 patients and chronic myelogenous leukemia/gastrointestinal stromal tumor (CML/GIST) patients who received imatinib. A population PK analysis was conducted using a standard sequential approach. Unbound fraction in COVID-19 patients admitted to the intensive care unit (ICU) and treated with IL-6R inhibitors was significantly elevated compared to CML/GIST patients (4.66% vs. 3.54% [1.08%-8.51%]; p < 0.001), despite twofold increased AAG levels. Our findings on total and unbound concentration show that cotreatment with IL-6R inhibitor can lead to changes in metabolism and protein binding, suggesting similar implications for other highly protein bound drugs. Consequently, total concentrations may not accurately reflect unbound target site concentrations.
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Affiliation(s)
- Medhat M. Said
- Department of Pharmacy and Clinical PharmacologyAmsterdam UMC, Location VUmcAmsterdamThe Netherlands
- Cancer Center AmsterdamAmsterdamThe Netherlands
| | - Job R. Schippers
- Department of Pulmonary MedicineAmsterdam UMC, Location VUmcAmsterdamThe Netherlands
- Amsterdam Cardiovascular SciencesAmsterdamThe Netherlands
| | - Leila Atmowihardjo
- Amsterdam Institute for Infection and ImmunityAmsterdamThe Netherlands
- Department of Intensive CareAmsterdam UMC, Location AMCAmsterdamThe Netherlands
| | - Yingxue Li
- Department of Pharmacy and Clinical PharmacologyAmsterdam UMC, Location VUmcAmsterdamThe Netherlands
| | - Mick S. van der Plas
- Department of Pharmacy and Clinical PharmacologyAmsterdam UMC, Location VUmcAmsterdamThe Netherlands
| | - Harm J. Bogaard
- Department of Pulmonary MedicineAmsterdam UMC, Location VUmcAmsterdamThe Netherlands
- Amsterdam Cardiovascular SciencesAmsterdamThe Netherlands
| | - Lieuwe D. J. Bos
- Department of Pulmonary MedicineAmsterdam UMC, Location VUmcAmsterdamThe Netherlands
- Amsterdam Cardiovascular SciencesAmsterdamThe Netherlands
| | - Ron A. A. Mathôt
- Amsterdam Cardiovascular SciencesAmsterdamThe Netherlands
- Amsterdam Institute for Infection and ImmunityAmsterdamThe Netherlands
- Department of Pharmacy and Clinical PharmacologyAmsterdam UMC, Location AMCAmsterdamThe Netherlands
| | - Jurjan Aman
- Department of Pulmonary MedicineAmsterdam UMC, Location VUmcAmsterdamThe Netherlands
- Amsterdam Cardiovascular SciencesAmsterdamThe Netherlands
| | - Eleonora L. Swart
- Department of Pharmacy and Clinical PharmacologyAmsterdam UMC, Location VUmcAmsterdamThe Netherlands
- Cancer Center AmsterdamAmsterdamThe Netherlands
- Amsterdam Institute for Infection and ImmunityAmsterdamThe Netherlands
| | - Imke H. Bartelink
- Department of Pharmacy and Clinical PharmacologyAmsterdam UMC, Location VUmcAmsterdamThe Netherlands
- Cancer Center AmsterdamAmsterdamThe Netherlands
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Gangireddy S, Kambagiri P, Jindal A. Deciphering Oxygenation Metrics in ARDS: A Deep Dive into the OXIVA-CARDS Study. Indian J Crit Care Med 2025; 29:282. [PMID: 40110243 PMCID: PMC11915399 DOI: 10.5005/jp-journals-10071-24846] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/22/2025] Open
Abstract
Gangireddy S, Kambagiri P, Jindal A. Deciphering Oxygenation Metrics in ARDS: A Deep Dive into the OXIVA-CARDS Study. Indian J Crit Care Med 2025;29(3):282.
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Affiliation(s)
- Sathwik Gangireddy
- Department of Pediatrics, All India Institute of Medical Sciences (AIIMS), Raipur, Chhattisgarh, India
| | - Pratyusha Kambagiri
- Department of Pediatrics, All India Institute of Medical Sciences (AIIMS), Raipur, Chhattisgarh, India
| | - Atul Jindal
- Department of Pediatrics, All India Institute of Medical Sciences (AIIMS), Raipur, Chhattisgarh, India
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Costa A, Scalzulli E, Carmosino I, Ielo C, Bisegna ML, Martelli M, Breccia M. Clinical and biological advances of critical complications in acute myeloid leukemia. Leuk Lymphoma 2025; 66:400-419. [PMID: 39582141 DOI: 10.1080/10428194.2024.2425051] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2024] [Revised: 10/24/2024] [Accepted: 10/27/2024] [Indexed: 11/26/2024]
Abstract
Managing acute myeloid leukemia (AML) and its critical complications requires understanding the complex interplay between disease biology, treatment strategies, and patient characteristics. Complications like sepsis, acute respiratory failure (ARF), hyperleukocytosis, coagulopathy, tumor lysis syndrome (TLS) and central nervous system (CNS) involvement present unique challenges needing precise evaluation and tailored interventions. Venetoclax-induced TLS and differentiation syndrome (DS) from IDH1/IDH2 or menin inhibitors highlight the need for ongoing research and innovative approaches. As the microbiological landscape evolves and new therapeutic agents emerge, adapting strategies to mitigate harmful pharmacological interactions is crucial. Advances in understanding the genetic profiles of patients with hyperleukocytosis contribute to better-targeted therapeutic strategies. Effective AML management relies on collaborative efforts from hematologists, specialized services, and intensive care units (ICUs). This review analyzes recent data on critical AML complications, identifies areas for further investigation, and proposes ways to advance clinical research and enhance patient care strategies.
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Affiliation(s)
- Alessandro Costa
- Hematology Unit, Businco Hospital, Department of Medical Sciences and Public Health, University of Cagliari, Cagliari, Italy
| | - Emilia Scalzulli
- Hematology, Department of Translational and Precision Medicine, Az. Policlinico Umberto I-Sapienza University, Rome, Italy
| | - Ida Carmosino
- Hematology, Department of Translational and Precision Medicine, Az. Policlinico Umberto I-Sapienza University, Rome, Italy
| | - Claudia Ielo
- Hematology, Department of Translational and Precision Medicine, Az. Policlinico Umberto I-Sapienza University, Rome, Italy
| | - Maria Laura Bisegna
- Hematology, Department of Translational and Precision Medicine, Az. Policlinico Umberto I-Sapienza University, Rome, Italy
| | - Maurizio Martelli
- Hematology, Department of Translational and Precision Medicine, Az. Policlinico Umberto I-Sapienza University, Rome, Italy
| | - Massimo Breccia
- Hematology, Department of Translational and Precision Medicine, Az. Policlinico Umberto I-Sapienza University, Rome, Italy
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Morales FL, Xu F, Lee HA, Tejedor Navarro H, Bechel MA, Cameron EL, Kelso J, Weiss CH, Nunes Amaral LA. Open-source computational pipeline automatically flags instances of acute respiratory distress syndrome from electronic health records. MEDRXIV : THE PREPRINT SERVER FOR HEALTH SCIENCES 2025:2024.05.21.24307715. [PMID: 38826348 PMCID: PMC11142283 DOI: 10.1101/2024.05.21.24307715] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/04/2024]
Abstract
Physicians, particularly intensivists, face information overload and decision fatigue, underscoring the need for automated diagnostic tools. Acute Respiratory Distress Syndrome (ARDS) affects over 10% of critical care patients, with over 40% mortality rate, yet is only recognized in 30-70% of cases in clinical settings. We present a reproducible computational pipeline that automates ARDS adjudication in retrospective datasets of mechanically ventilated adults, implementing the Berlin Definition via natural language processing and classification algorithms. We used labeled chest imaging reports from two hospitals to train an XGBoost model to detect bilateral infiltrates, and a labeled subset of attending physician notes from one hospital to train another XGBoost model to detect a pneumonia diagnosis. Both models achieve high discriminative performance on test sets-an area under the receiver operating characteristic curve (AUROC) of 0.88 for adjudicating bilateral infiltrates on chest imaging reports, and an AUROC of 0.87 for detecting pneumonia on attending physician notes. We integrated these models with rule-based components and validated the entire pipeline on a subset of healthcare encounters from a third hospital (MIMIC-III). We find a sensitivity of 93.5% in adjudicating ARDS - far surpassing the 22.6% ARDS documentation rate we found for this cohort - along with a false positive rate of 17.4%. We conclude that our reproducible, automated pipeline holds promise for improving ARDS recognition and could aid clinical practice through real-time EHR integration.
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