RESUMEN
BACKGROUND: Pulmonary fibrosis can develop after acute respiratory distress syndrome (ARDS). The hypothesis is we are able to measure phenotypes that lie at the origin of ARDS severity and fibrosis development. The aim is an accuracy study of prognostic circulating biomarkers. METHODS: A longitudinal study followed COVID-related ARDS patients with medical imaging, pulmonary function tests and biomarker analysis, generating 444 laboratory data. Comparison to controls used non-parametrical statistics; p < 0·05 was considered significant. Cut-offs were obtained through receiver operating curve. Contingency tables revealed predictive values. Odds ratio was calculated through logistic regression. RESULTS: Angiotensin 1-7 beneath 138 pg/mL defined Angiotensin imbalance phenotype. Hyper-inflammatory phenotype showed a composite index test above 34, based on high Angiotensin 1-7, C-Reactive Protein, Ferritin and Transforming Growth Factor-ß. Analytical study showed conformity to predefined goals. Clinical performance gave a positive predictive value of 95 % (95 % confidence interval, 82 %-99 %), and a negative predictive value of 100 % (95 % confidence interval, 65 %-100 %). Those severe ARDS phenotypes represented 34 (Odds 95 % confidence interval, 3-355) times higher risk for pulmonary fibrosis development (p < 0·001). CONCLUSIONS: Angiotensin 1-7 composite index is an early and objective predictor of ARDS evolving to pulmonary fibrosis. It may guide therapeutic decisions in targeted phenotypes.
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Angiotensina I , Fragmentos de Péptidos , Fibrosis Pulmonar , Humanos , Angiotensina I/sangre , Masculino , Femenino , Fibrosis Pulmonar/sangre , Fibrosis Pulmonar/diagnóstico , Fragmentos de Péptidos/sangre , Persona de Mediana Edad , Anciano , Estudios Longitudinales , Biomarcadores/sangre , COVID-19/sangre , COVID-19/complicaciones , COVID-19/diagnóstico , Síndrome de Dificultad Respiratoria/diagnóstico , Síndrome de Dificultad Respiratoria/sangreRESUMEN
Acute respiratory distress syndrome is a severe lung condition resulting from various causes, with life-threatening consequences that necessitate intensive care. The phenomenon can be modeled in preclinical models, notably through the use of lipopolysaccharide (LPS) instillation in mice. The phenotype induced closely recapitulates the human syndrome, including pulmonary edema, leukocyte infiltration, acute inflammation, impaired pulmonary function, and histological damage. However, the experimental designs using LPS instillations are extremely diverse in the literature. This highly complicates the interpretation of the induced phenotype chronology for future study design and hinders the proper identification of the optimal time frame to assess different readouts. Therefore, the definition of the treatment window in relation to the beginning of the disease onset also presents a significant challenge to address questions or test compound efficacy. In this context, the temporality of the different readouts usually measured in the model was evaluated in both normal and neutrophil-depleted male C57bl/6 mice using LPS-induction to assess the best window for proper readout evaluation with an optimal dynamic response range. Ventilation parameters were evaluated by whole-body plethysmography and neutrophil recruitment were evaluated in bronchoalveolar lavage fluids and in lung tissues directly. Imaging evaluation of myeloperoxidase along with activity in lung lysates and fluids were compared, along with inflammatory cytokines and lung extravasation by enzyme-linked immunoassays. Moreover, dexamethasone, the gold standard positive control in this model, was also administered at different times before and after phenotype induction to assess how kinetics affected each parameter. Overall, our data demonstrate that each readout evaluated in this study has a singular kinetic and highlights the key importance of the timing between ARDS phenotype and treatment administration and/or analysis. These findings also strongly suggest that analyzes, both in-life and post-mortem should be conducted at multiple time points to properly capture the dynamic phenotype of the LPS-ARDS model and response to treatment.
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Modelos Animales de Enfermedad , Lipopolisacáridos , Ratones Endogámicos C57BL , Fenotipo , Síndrome de Dificultad Respiratoria , Animales , Síndrome de Dificultad Respiratoria/tratamiento farmacológico , Síndrome de Dificultad Respiratoria/inducido químicamente , Síndrome de Dificultad Respiratoria/patología , Ratones , Masculino , Pulmón/patología , Pulmón/metabolismo , Pulmón/efectos de los fármacos , Líquido del Lavado Bronquioalveolar/química , Factores de Tiempo , Citocinas/metabolismo , Neutrófilos/metabolismoRESUMEN
OBJECTIVE: To investigate the application effect of early awake prone position in mild-to-moderate acute respiratory distress syndrome (ARDS) patients, and analyze the related factors affecting the prone position outcome. METHODS: A prospective cohort study was conducted. The mild-to-moderate ARDS patients admitted to the emergency department of Yingshang County People's Hospital from January 2020 to June 2023 were enrolled as the research subjects. According to the results of prone tolerance test, the patients were divided into awake prone position group and non-prone position group. All patients were given high flow nasal cannula (HFNC) according to the standard procedures. The patients in the awake prone position group received prone position treatment within 12 hours after admission, in addition to the standard treatment. This could be performed in several times, at least once a day, and at least 2 hours each time. In order to prolong the prone position as much as possible, the patients were allowed to move or keep a small angle side prone. The changes of oxygenation index (PaO2/FiO2) at 0, 24, 48, and 72 hours after admission, the rate of intensive care unit (ICU) transfer, the use rate and use time of non-invasive ventilation (NIV), the total hospital stay, and the daily prone position time and 2-hour ROX index [ratio of pulse oxygen saturation/fraction of inspired oxygen (SpO2/FiO2) and respiratory rate (RR)] of prone position patients were recorded. The successful termination of HFNC was defined as the successful prone position, and the failure of prone position was defined as switching to NIV or transferring to ICU. Subgroup analysis was performed, and the binary multivariate Logistic regression analysis was used to screen the influencing factors of the early awake prone position outcome. RESULTS: A total of 107 patients were finally enrolled, with 61 in the awake prone position group and 46 in the non-prone position group. Both groups showed a gradual increase in PaO2/FiO2 with prolonged admission time. The PaO2/FiO2 at 24 hours after admission in the awake prone position group was significantly higher than that at 0 hour [mmHg (1 mmHg ≈ 0.133 kPa): 191.94±17.86 vs. 179.24±29.27, P < 0.05], while the difference in the non-prone position group was only statistically significant at 72 hours (mmHg: 198.24±17.99 vs. 181.24±16.62, P < 0.05). Furthermore, the PaO2/FiO2 at 48 hours and 72 hours after admission in the awake prone position group was significantly higher than that in the non-prone position group. The use rate of NIV in the awake prone position group was significantly lower than that in the non-prone position group [36.1% (22/61) vs. 56.5% (26/46), P < 0.05]; Kaplan-Meier curve analysis further confirmed that the patients in the awake prone position group used NIV later, and the cumulative rate of NIV usage was significantly lower than that in the non-prone position group (Log-Rank test: χ 2 = 5.402, P = 0.020). Compared with the non-prone position group, the ICU transfer rate in the awake prone position group was significantly lowered [11.5% (7/61) vs. 28.3% (13/46), P < 0.05], and the HFNC time, NIV time, and total hospital stay were significantly shortened [HFNC time (days): 5.71±1.45 vs. 7.24±3.36, NIV time (days): 3.27±1.28 vs. 4.40±1.47, total hospital stay (days): 11 (7, 13) vs. 14 (10, 19), all P < 0.05]. Of the 61 patients who underwent awake prone positioning, 39 were successful, and 22 failed. Compared with the successful group, the patients in the failure group had a higher body mass index [BMI (kg/m2): 26.61±4.70 vs. 22.91±5.50, P < 0.05], lower PaO2/FiO2, proportion of asymptomatic hypoxemia and 2-hour ROX index of prone position [PaO2/FiO2 (mmHg): 163.73±24.73 vs. 185.69±28.87, asymptomatic hypoxemia proportion: 18.2% (4/22) vs. 46.2% (18/39), 2-hour ROX index of prone position: 5.75±1.18 vs. 7.21±1.45, all P < 0.05], and shorter daily prone positioning time (hours: 5.87±2.85 vs. 8.05±1.99, P < 0.05). Binary multivariate Logistic regression analysis showed that all these factors were influencing factors for the outcome of awake prone positioning (all P < 0.05), among which BMI [odds ratio (OR) = 1.447, 95% confidence interval (95%CI) was 1.105-2.063] and non-asymptomatic hypoxemia (OR = 13.274, 95%CI was 1.548-117.390) were risk factors for failure of prone position, while PaO2/FiO2 (OR = 0.831, 95%CI was 0.770-0.907), daily prone positioning time (OR = 0.482, 95%CI was 0.236-0.924), and 2-hour ROX index of prone position (OR = 0.381, 95%CI was 0.169-0.861) were protective factors. CONCLUSIONS: Early awake prone positioning in patients with mild-to-moderate ARDS supported by HFNC is safe and feasible, reducing the use rate and duration of NIV, lowering the ICU transfer rate, and shortening the hospital stay. High BMI and non-asymptomatic hypoxemia are risk factors for failed prone position, while higher PaO2/FiO2 and the ROX index within 2 hours of prone position (the patient's good response to prone position), and prolonged daily prone position can improve the success rate of prone position.
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Unidades de Cuidados Intensivos , Síndrome de Dificultad Respiratoria , Humanos , Posición Prona , Síndrome de Dificultad Respiratoria/terapia , Estudios Prospectivos , Vigilia , Tiempo de Internación , Ventilación no Invasiva/métodos , Masculino , FemeninoRESUMEN
IMPORTANCE: A time-limited trial (TLT) is a collaborative plan among clinicians, patients, and families to use life-sustaining therapy for a defined duration, after which the patient's response informs whether to continue care directed toward recovery or shift the focus toward comfort. TLTs are a promising approach to help navigate uncertainty in critical illness, yet little is known about their current use. OBJECTIVES: To characterize TLT use in patients with acute respiratory failure (ARF). DESIGN, SETTING, AND PARTICIPANTS: Prospective 12-month observational cohort study at an U.S. academic medical center of adult ICU patients with ARF receiving invasive mechanical ventilation for greater than or equal to 48 hours. MAIN OUTCOMES AND MEASURES: Primary exposure was TLT participation, identified by patients' ICU physician. Patient characteristics, care delivery elements, and hospital outcomes were extracted from the electronic medical record. RESULTS: Among 176 eligible patients, 36 (20.5%) participated in a TLT. Among 18 ICU attending physicians, nine (50%) participated in greater than or equal to 1 TLT (frequency 0-39% of patients cared for). Median TLT duration was 3.0 days (interquartile range [IQR], 3.0-4.5 d). TLT patients had a higher mean age (67.4 yr [sd, 12.0 yr] vs. 60.0 yr [sd, 16.0 yr]; p < 0.01), higher Charlson Comorbidity Index (5.1 [sd, 2.2] vs. 3.8 [sd, 2.6]; p < 0.01), and similar Sequential Organ Failure Assessment score (9.6 [sd, 3.3] vs. 9.5 [sd, 3.7]; p = 0.93), compared with non-TLT patients. TLT patients were more likely to die or be discharged to hospice (80.6% vs. 42.1%; p < 0.05) and had shorter ICU length of stay (median, 5.7 d [IQR, 4.0-9.0 d] vs. 10.3 d [IQR, 5.5-14.5 d]; p < 0.01). CONCLUSIONS AND RELEVANCE: In this study, approximately one in five patients with ARF participated in a TLT. Our findings suggest TLTs are used primarily in patients near end of life but with substantial physician variation, highlighting a need for evidence to guide optimal use.
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Unidades de Cuidados Intensivos , Insuficiencia Respiratoria , Humanos , Estudios Prospectivos , Femenino , Masculino , Persona de Mediana Edad , Anciano , Insuficiencia Respiratoria/terapia , Respiración Artificial , Estudios de Cohortes , Factores de Tiempo , Síndrome de Dificultad Respiratoria/terapia , Enfermedad CríticaRESUMEN
The COVID-19 pandemic has undeniably changed the way intensivists manage acute hypoxaemic respiratory failure. Paradigms had evolved particularly in the way we support patients with respiratory failure, and the adjunctive therapies which can be used. Many questions have been answered, and many more generated, from the last few years. For example, is COVID-19 acute respiratory failure and acute respiratory distress syndrome similar to non-COVID-19? How can we personalize therapy in patients with COVID-19, and what are some new statistical tools that we can use to aid in this approach? Is intubation and invasive mechanical ventilation the only way to support patients with acute respiratory failure, or can we turn to other modalities of respiratory support? And what about patients with the most severe form of respiratory failure, how can we support them? In this chapter, we explore the lessons learnt, identifying gaps and advances in knowledge in terms of the pathophysiology of acute respiratory failure, its prognostic factors, oxygen supports, and other therapies. We also touch on how physicians treating patients can tap on international networks to create a "whole that is more than the sum of its parts", and impart clinical insights on the management of acute respiratory failure. Finally, we highlight the importance of a cautious skepticism in our approach to both clinical medicine and evidence-based medicine, highlighting how evidence in a pandemic can rapidly evolve both within an ICU, and longitudinally around the world.
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COVID-19 , Respiración Artificial , Insuficiencia Respiratoria , SARS-CoV-2 , Humanos , COVID-19/complicaciones , COVID-19/terapia , Insuficiencia Respiratoria/terapia , Insuficiencia Respiratoria/virología , Respiración Artificial/métodos , Síndrome de Dificultad Respiratoria/terapia , Síndrome de Dificultad Respiratoria/virologíaRESUMEN
Objective: Acute respiratory distress syndrome (ARDS) presents a global health challenge, characterized by significant morbidity and mortality. However, the role of natural killer T (NKT) cells in human ARDS remains poorly understood. Therefore, this study explored the numerical and functional status of NKT cells in patients with ARDS, examining their clinical relevance and interactions with macrophages and fibroblasts during various stages of the syndrome. Methods: Peripheral blood from 40 ARDS patients and 30 healthy controls was analyzed, with paired samples of peripheral blood and bronchoalveolar lavage fluid (BALF) from seven ARDS patients. We measured levels of NKT cells, cytokines, CD69, programmed death-1 (PD-1), and annexin-V using flow cytometry, and extracellular matrix (ECM) protein expression using real-time PCR. Results: ARDS patients exhibited decreased circulating NKT cells with elevated CD69 expression and enhanced IL-17 production. The reduction in NKT cells correlated with PaO2/FiO2 ratio, albumin, and C-reactive protein levels. Proliferative responses to α-galactosylceramide (α-GalCer) were impaired, and co-culturing NKT cells with monocytes or T cells from ARDS patients resulted in a reduced α-GalCer response. Increased and activated NKT cells in BALF induced proinflammatory cytokine release by macrophages and ECM protein expression in fibroblasts. Conclusion: ARDS is associated with a numerical deficiency but functional activation of circulating NKT cells, showing impaired responses to α-GalCer and altered interactions with immune cells. The increase in NKT cells within BALF suggests their role in inducing inflammation and remodeling/fibrosis, highlighting the potential of targeting NKT cells as a therapeutic approach for ARDS.
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Células T Asesinas Naturales , Síndrome de Dificultad Respiratoria , Humanos , Síndrome de Dificultad Respiratoria/inmunología , Masculino , Femenino , Persona de Mediana Edad , Células T Asesinas Naturales/inmunología , Células T Asesinas Naturales/metabolismo , Líquido del Lavado Bronquioalveolar/inmunología , Líquido del Lavado Bronquioalveolar/citología , Adulto , Anciano , Macrófagos/inmunología , Macrófagos/metabolismo , Citocinas/metabolismo , Fibroblastos/metabolismo , Fibroblastos/inmunología , Activación de Linfocitos/inmunología , Antígenos de Diferenciación de Linfocitos T , Antígenos CD , Lectinas Tipo CRESUMEN
Introduction: In post-COVID survivors, transforming growth factor-beta-1 (TGF-ß1) might mediate fibroblast activation, resulting in persistent fibrosis. Methods: In this study, 82 survivors of COVID-19-associated ARDS were examined at 6- and 24-months post-ICU discharge. At 6-months, quantitative CT analysis of lung attenuation was performed and active TGF-ß1 was measured in blood and exhaled breath condensate (EBC). Results: At 6-months of ICU-discharge, patients with reduced DmCO/alveolar volume ratio exhibited higher plasma and EBC levels of active TGF-ß1. Plasma TGF-ß1 levels were elevated in dyspneic survivors and directly related to the high-attenuation lung volume. In vitro, plasma and EBC from survivors induced profibrotic changes in human primary fibroblasts in a TGF-ß receptor-dependent manner. Finally, at 6-months, plasma and EBC active TGF-ß1 levels discriminated patients who, 24-months post-ICU-discharge, developed gas exchange impairment. Discussion: TGF-ß1 pathway plays a pivotal role in the early-phase fibrotic abnormalities in COVID-19-induced ARDS survivors, with significant implications for long-term functional impairment.
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COVID-19 , SARS-CoV-2 , Sobrevivientes , Factor de Crecimiento Transformador beta1 , Humanos , COVID-19/inmunología , COVID-19/complicaciones , COVID-19/patología , Factor de Crecimiento Transformador beta1/metabolismo , Factor de Crecimiento Transformador beta1/sangre , Masculino , Femenino , Persona de Mediana Edad , Anciano , Pulmón/patología , Pulmón/metabolismo , Fibroblastos/metabolismo , Síndrome de Dificultad Respiratoria/etiología , Síndrome de Dificultad Respiratoria/metabolismo , FibrosisRESUMEN
BACKGROUND: The objective is to assess lung compliance and identify the optimal positive end-expiratory pressure (PEEP) levels in patients with tuberculosis-associated Acute Respiratory Distress Syndrome (TB-ARDS) compared to non-TB-ARDS patients. METHODS: This observational case-control study utilized electrical impedance tomography to evaluate lung mechanics in 20 TB-ARDS and 20 non-TB-ARDS patients. Participants underwent PEEP titration from 23 to 5 cm H2O in 2 cm H2O decrements. Lung compliance and the rates of hyperdistention and collapse were assessed at each PEEP level. RESULTS: Delta impedance values showed higher amounts in a PEEP range of 11-17 cm H2O and in patients with TB-ARDS (P > 0.05). In addition, both hyperdistention and collapse rates were nonsignificantly higher in TB-ARDS patients (P > 0.05), and the compromised levels of hyperdistention and collapse rates were at 15-17 cm H2O, indicating the most favorable PEEP level. CONCLUSIONS: The observed patterns of hyperdistention and collapse rates across various PEEP levels provide valuable insights into the susceptibility of TB-ARDS patients to barotrauma. Notably, the identified optimal PEEP range between 15 and 17 cm H2O may guide ventilator management strategies in mitigating both hyperdistention and collapse; nonetheless, due to the high variability of lung compliances within groups, we strongly recommend individualized consideration for tailored respiratory support and evaluation.
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Respiración con Presión Positiva , Síndrome de Dificultad Respiratoria , Humanos , Síndrome de Dificultad Respiratoria/terapia , Síndrome de Dificultad Respiratoria/fisiopatología , Masculino , Estudios de Casos y Controles , Femenino , Persona de Mediana Edad , Adulto , Impedancia Eléctrica , Tuberculosis Pulmonar/complicaciones , Tuberculosis Pulmonar/fisiopatología , Tuberculosis/complicaciones , Anciano , Pulmón/fisiopatología , Rendimiento PulmonarRESUMEN
BACKGROUND: The association between red blood cell distribution width (RDW) to albumin ratio (RAR) and prognosis in patients with acute respiratory failure (ARF) admitted to the Intensive Care Unit (ICU) remains unclear. This retrospective cohort study aims to investigate this association. METHODS: Clinical information of ARF patients was collected from the Medical Information Mart for Intensive Care IV (MIMIC-IV) version 2.0 database. The primary outcome was, in-hospital mortality and secondary outcomes included 28-day mortality, 60-day mortality, length of hospital stay, and length of ICU stay. Cox regression models and subgroup analyses were conducted to explore the relationship between RAR and mortality. RESULTS: A total of 4547 patients with acute respiratory failure were enrolled, with 2277 in the low ratio group (RAR < 4.83) and 2270 in the high ratio group (RAR > = 4.83). Kaplan-Meier survival analysis demonstrated a significant difference in survival probability between the two groups. After adjusting for confounding factors, the Cox regression analysis showed that the high RAR ratio had a higher hazard ratio (HR) for in-hospital mortality (HR 1.22, 95% CI 1.07-1.40; P = 0.003), as well as for 28-day mortality and 60-day mortality. Propensity score-matched (PSM) analysis further supported the finding that high RAR was an independent risk factor for ARF. CONCLUSION: This study reveals that RAR is an independent risk factor for poor clinical prognosis in patients with ARF admitted to the ICU. Higher RAR levels were associated with increased in-hospital, 28-day and 60-day mortality rates.
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Biomarcadores , Índices de Eritrocitos , Mortalidad Hospitalaria , Humanos , Estudios Retrospectivos , Masculino , Femenino , Pronóstico , Persona de Mediana Edad , Anciano , Biomarcadores/sangre , Unidades de Cuidados Intensivos , Insuficiencia Respiratoria/sangre , Albúmina Sérica/análisis , Síndrome de Dificultad Respiratoria/sangre , Síndrome de Dificultad Respiratoria/mortalidadRESUMEN
The use of extracorporeal membrane oxygenation (ECMO) has grown rapidly, driven by the COVID-19 pandemic. Despite its widespread adoption, neurological complications pose a significant risk, impacting both mortality and survivors' quality of life. Detecting these complications is challenging due to sedation and the heterogeneous nature of ECMO-associated neurological injury. Still, consensus of neurologic monitoring during ECMO is lacking since utilization and effectiveness of current neuromonitoring methods are limited. Especially in view of the heterogeneous nature of neurological injury during ECMO support an easily acquirable biomarker tracing neuronal damage independently from the underlying pathomechanism would be favorable. In a single-center prospective study on 34 severe acute respiratory distress syndrome (ARDS) patients undergoing ECMO, we explored the potential of serum neurofilament light chain levels (NfL) as a biomarker for neurological complications and its predictive power towards the overall outcome of ECMO patients. Individuals experiencing neurological complications (41%) demonstrated a notable rise in NfL levels (Tbaseline median 92.95 pg/ml; T24h median 132 pg/ml (IQR 88.6-924 pg/ml), p = 0.008; T7d median 248 pg/ml (IQR 157-1090 pg/ml), p = 0.001). Moreover, under ECMO therapy, these patients exhibited markedly elevated concentrations compared to those without neurological complications (T24h median 70.75 pg/ml (IQR 22.2-290 pg/ml), p = 0.023; T7d median 128 pg/ml (IQR 51.8-244 pg/ml), p = 0.002). There was no significant difference in the NfL dynamics between surviving patients and those who died during or shortly after ECMO therapy. While NfL indicates neuro-axonal damage during intensive care with ECMO therapy, we could not identify any correlation between survival outcome and the levels of NfL, indicating that NfL may not serve as a prognostic marker for survival. Nevertheless, additional studies involving a larger patient cohort are required.
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Biomarcadores , COVID-19 , Oxigenación por Membrana Extracorpórea , Proteínas de Neurofilamentos , Humanos , Oxigenación por Membrana Extracorpórea/efectos adversos , Oxigenación por Membrana Extracorpórea/métodos , Biomarcadores/sangre , Masculino , Femenino , Persona de Mediana Edad , Proteínas de Neurofilamentos/sangre , Estudios Prospectivos , COVID-19/sangre , COVID-19/terapia , Adulto , Síndrome de Dificultad Respiratoria/sangre , Síndrome de Dificultad Respiratoria/terapia , Anciano , SARS-CoV-2RESUMEN
IMPORTANCE: Acute respiratory distress syndrome (ARDS) is associated with high mortality and morbidity. Extracorporeal membrane oxygenation (ECMO) is one of the interventions that have been in practice for ARDS for decades. OBJECTIVES: The purpose of the study was to investigate the outcomes of ECMO in pediatric trauma patients who suffered from ARDS. DESIGN: Observational cohort study. SETTING AND PARTICIPANTS: The Trauma Quality Improvement Program database for years 2017 to 2019 and 2021 through 2022 was accessed for the study. All children younger than 18 years old who were admitted to the hospital after trauma and suffered from ARDS were included in the study. Other variables included in the study were patients' demographics, clinical characteristics, Injury Severity Score (ISS), Glasgow Coma Scale (GCS) score, comorbidities, and outcomes. MAIN OUTCOMES AND MEASURES: ECMO is the exposure, and the outcomes are in-hospital mortality and hospital complications (acute kidney injury [AKI], pneumonia and deep vein thrombosis [DVT]). RESULTS: Of 453 patients who qualified for the study, propensity score matching found 50 pairs of patients. There were no significant differences identified between the groups, ECMO+ vs. ECMO- on patients' age in years (16 yr; interquartile range [IQR], 13.25-17 yr vs. 16 yr [14.25-17 yr]), race (White; 62.0% vs. 66.0%), sex (male; 78% vs. 76%), ISS (23 [IQR, 9.25-34] vs. 22 [9.25-32]), and GCS (15 [IQR, 3-15] vs. 13.5 [3-15]), mechanism of injury; and comorbidities. There was no difference between the groups, ECMO+ vs. ECMO-, in-hospital mortality (10.0% vs. 20.0%; p = 0.302), hospital complications (AKI 12.0% vs. 2.0%; p = 0.131), pneumonia (10.0% vs. 20.0%; p = 0.182 > ), and DVT (16% vs. 6%; p = 0.228). CONCLUSIONS AND RELEVANCE: No difference in mortality was observed in injured children who suffered from the ARDS and were placed on ECMO when compared with patients who were not placed on ECMO. Patients with trauma and ARDS who require ECMO have comparable outcomes to those who do not receive ECMO. A larger sample size study is needed to find the exact benefit of ECMO in this patients' cohort.
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Oxigenación por Membrana Extracorpórea , Mortalidad Hospitalaria , Síndrome de Dificultad Respiratoria , Heridas y Lesiones , Humanos , Oxigenación por Membrana Extracorpórea/métodos , Síndrome de Dificultad Respiratoria/terapia , Síndrome de Dificultad Respiratoria/mortalidad , Masculino , Femenino , Adolescente , Heridas y Lesiones/terapia , Heridas y Lesiones/complicaciones , Heridas y Lesiones/mortalidad , Estudios de Cohortes , Resultado del Tratamiento , Niño , Puntaje de Propensión , Puntaje de Gravedad del TraumatismoRESUMEN
BACKGROUND: Sepsis-induced pulmonary injury (SPI) is a common complication of sepsis with a high rate of mortality. N4-acetylcytidine (ac4C) is mediated by the ac4C "writer", N-acetyltransferase (NAT)10, to regulate the stabilization of mRNA. This study aimed to investigate the role of NAT10 in SPI and the underlying mechanism. METHODS: Twenty-three acute respiratory distress syndrome (ARDS) patients and 27 non-ARDS volunteers were recruited. A sepsis rat model was established. Reverse transcription-quantitative polymerase chain reaction was used to detect the expression of NAT10 and transferrin receptor (TFRC). Cell viability was detected by cell counting kit-8. The levels of Fe2+, glutathione, and malondialdehyde were assessed by commercial kits. Lipid reactive oxygen species production was measured by flow cytometric analysis. Western blot was used to detect ferroptosis-related protein levels. Haematoxylin & eosin staining was performed to observe the pulmonary pathological symptoms. RESULTS: The results showed that NAT10 was increased in ARDS patients and lipopolysaccharide-treated human lung microvascular endothelial cell line-5a (HULEC-5a) cells. NAT10 inhibition increased cell viability and decreased ferroptosis in HULEC-5a cells. TFRC was a downstream regulatory target of NAT10-mediated ac4C acetylation. Overexpression of TFRC decreased cell viability and promoted ferroptosis. In in vivo study, NAT10 inhibition alleviated SPI. CONCLUSION: NAT10-mediated ac4C acetylation of TFRC aggravated SPI through promoting ferroptosis.
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Ferroptosis , Receptores de Transferrina , Sepsis , Sepsis/metabolismo , Sepsis/complicaciones , Sepsis/etiología , Acetilación , Animales , Humanos , Ratas , Masculino , Receptores de Transferrina/metabolismo , Receptores de Transferrina/genética , Femenino , Lesión Pulmonar/metabolismo , Lesión Pulmonar/etiología , Lesión Pulmonar/patología , Modelos Animales de Enfermedad , Acetiltransferasas/metabolismo , Acetiltransferasas/genética , Persona de Mediana Edad , Antígenos CD/metabolismo , Antígenos CD/genética , Citidina/análogos & derivados , Citidina/farmacología , Línea Celular , Síndrome de Dificultad Respiratoria/metabolismo , Síndrome de Dificultad Respiratoria/etiología , Síndrome de Dificultad Respiratoria/patología , Ratas Sprague-Dawley , Supervivencia CelularRESUMEN
OBJECTIVES: To analyze the clinical significance of Toll-Like Receptor 7/Interleukin-23/Interleukin-17 (TLR7/IL-23/IL-17) signaling pathway in patients with Acute Respiratory Distress Syndrome (ARDS). METHOD: The clinical data of 85 patients with ARDS were retrospectively analyzed and set as the ARDS group, and the clinical data of 85 healthy participants during the same period were set as the healthy control group. Univariate and multivariate logistic regression were used to analyze risk the factors affecting the prognosis of ARDS patients. RESULTS: TheTLR7 mRNA expression and IL-23 and IL-17 levels in peripheral blood mononuclear cells were higher in the ARDS group than in the control group (p < 0.05). TLR7 mRNA expression, IL-23, IL-17, Surfactant Protein-D (SP-D), and Clara Cell protein-16 (CC-16) levels were the highest in the severe group, followed by the moderate group, and the lowest in the mild group, while Oxygenation Index (OI) was the lowest in the severe group, followed by the moderate group, and the highest in the mild group (p < 0.05). Multivariate logistic regression analysis found that the disease grade (severe), TLR7 mRNA expression, IL-23 level, and IL-17 level were the risk factors affecting the 28-d survival status of ARDS patients (OR > 1, p < 0.05). CONCLUSIONS: In ARDS patients, the TLR7/IL-23/IL-17 signaling pathway is activated. The expression of this pathway is closely related to the severity of the disease and the levels of lung injury markers, and it is a risk factor that may have a direct impact on the prognosis of ARDS patients.
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Interleucina-17 , Interleucina-23 , Síndrome de Dificultad Respiratoria , Transducción de Señal , Receptor Toll-Like 7 , Humanos , Síndrome de Dificultad Respiratoria/sangre , Síndrome de Dificultad Respiratoria/genética , Interleucina-17/sangre , Femenino , Masculino , Receptor Toll-Like 7/genética , Persona de Mediana Edad , Estudios Retrospectivos , Interleucina-23/sangre , Adulto , Anciano , Pronóstico , Estudios de Casos y Controles , Índice de Severidad de la Enfermedad , ARN Mensajero/análisis , Factores de Riesgo , Leucocitos Mononucleares/metabolismo , Relevancia ClínicaRESUMEN
PURPOSE OF REVIEW: This review aims to explore the latest evidence on long-term outcomes in patients admitted to the ICU because of acute respiratory failure (ARF). RECENT FINDINGS: As the survival rate of critically ill patients with acute respiratory failure improves, long-term mortality and disability still influence the quality of life of survivors and their caregivers. Patients admitted to the ICU because of ARF are at risk of developing the postintensive care syndrome, which presents with physical, cognitive and mental symptoms, all of which may impair their quality of life. Caregivers seem to be affected as well, which may lead to intergenerational trauma. The need for more care, including prone positioning, invasive support (e.g. mechanical ventilation, ECMO) and deep sedation are probably adjunctive risk factors for poor long-term outcomes. SUMMARY: There is not much data on the long-term outcomes of patients who have survived ARF. More follow-up studies should be conducted, especially in centers providing higher levels of costly care (e.g. ECMO). Randomized controlled trials on interventions for ARF should include patient-centered long-term outcomes in addition to mortality rates. The high mortality rates associated with ARF mandate collaboration among multiple centers to achieve an adequate sample size for studying the long-term outcomes of survivors.
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Enfermedad Crítica , Unidades de Cuidados Intensivos , Calidad de Vida , Insuficiencia Respiratoria , Humanos , Insuficiencia Respiratoria/terapia , Insuficiencia Respiratoria/mortalidad , Insuficiencia Respiratoria/etiología , Síndrome de Dificultad Respiratoria/terapia , Síndrome de Dificultad Respiratoria/mortalidad , Respiración Artificial , Factores de Riesgo , Cuidados Críticos/métodosRESUMEN
The advanced learning paradigm, learning using privileged information (LUPI), leverages information in training that is not present at the time of prediction. In this study, we developed privileged logistic regression (PLR) models under the LUPI paradigm to detect acute respiratory distress syndrome (ARDS), with mechanical ventilation variables or chest x-ray image features employed in the privileged domain and electronic health records in the base domain. In model training, the objective of privileged logistic regression was designed to incorporate data from the privileged domain and encourage knowledge transfer across the privileged and base domains. An asymptotic analysis was also performed, yielding sufficient conditions under which the addition of privileged information increases the rate of convergence in the proposed model. Results for ARDS detection show that PLR models achieve better classification performances than logistic regression models trained solely on the base domain, even when privileged information is partially available. Furthermore, PLR models demonstrate performance on par with or superior to state-of-the-art models under the LUPI paradigm. As the proposed models are effective, easy to interpret, and highly explainable, they are ideal for other clinical applications where privileged information is at least partially available.
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Síndrome de Dificultad Respiratoria , Síndrome de Dificultad Respiratoria/diagnóstico por imagen , Síndrome de Dificultad Respiratoria/terapia , Humanos , Modelos Logísticos , Respiración Artificial , Aprendizaje Automático , Registros Electrónicos de SaludRESUMEN
OBJECTIVE: The study aimed to evaluate the improvements in pulmonary ventilation following a sitting position in ventilated ARDS patients using electrical impedance tomography. METHODOLOGY: A total of 17 patients with ARDS under mechanical ventilation participated in this study, including 8 with moderate ARDS and 9 with severe ARDS. Each patient was initially placed in the supine position (S1), transitioned to sitting position (SP) for 30 min, and then returned to the supine position (S2). Patients were monitored for each period, with parameters recorded. MAIN OUTCOME MEASURES: The primary outcome included the spatial distribution parameters of EIT, regional of interest (ROI), end-expiratory lung impedance (ΔEELI), and parameters of respiratory mechanics. RESULTS: Compared to S1, the SP significantly altered the distribution in ROI1 (11.29 ± 4.70 vs 14.88 ± 5.00 %, p = 0.003) and ROI2 (35.59 ± 8.99 vs 44.65 ± 6.97 %, p ï¼ 0.001), showing reductions, while ROI3 (39.71 ± 11.49 vs 33.06 ± 6.34 %, p = 0.009), ROI4 (13.35 ± 8.76 vs 7.24 ± 5.23 %, p ï¼ 0.001), along with peak inspiratory pressure (29.24 ± 3.96 vs 27.71 ± 4.00 cmH2O, p = 0.036), showed increases. ΔEELI decreased significantly ventrally (168.3 (40.33 - 189.5), p ï¼ 0.0001) and increased significantly dorsally (461.7 (297.5 - 683.7), p ï¼ 0.0001). The PaO2/FiO2 ratio saw significant improvement in S2 compared to S1 after 30 min in the seated position (108 (73 - 130) vs 96 (57 - 129) mmHg, p = 0.03). CONCLUSIONS: The sitting position is associated with enhanced compliance, improved oxygenation, and more homogenous ventilation in patients with ventilated ARDS compared to the supine position. IMPLICATIONS FOR CLINICAL PRACTICE: It is important to know the impact of postural changes on patient pulmonary ventilation in order to standardize safe practices in critically ill patients. It may be helpful in the management among ventilated patients.
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Impedancia Eléctrica , Respiración Artificial , Síndrome de Dificultad Respiratoria , Sedestación , Humanos , Masculino , Femenino , Síndrome de Dificultad Respiratoria/terapia , Síndrome de Dificultad Respiratoria/fisiopatología , Persona de Mediana Edad , Anciano , Respiración Artificial/métodos , Respiración Artificial/normas , Tomografía/métodos , Tomografía/normas , Adulto , Posicionamiento del Paciente/métodos , Posicionamiento del Paciente/normasRESUMEN
OBJECTIVE: To investigate the prevalence of upper limb peripheral nerve injuries (PNI) in adult patients admitted to the intensive care unit (ICU) with acute respiratory distress syndrome (ARDS) undergoing prone positioning. METHODS: This systematic review with meta-analysis was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and Meta-analysis of Observational Studies in Epidemiology (MOOSE) reporting guidelines. Four electronic databases including PubMed, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), The Cochrane Library, and EMBASE were searched from inception to January 2024. The quality of the included studies was evaluated according to the Joanna Briggs Institute Critical Appraisal Tools. A proportion meta-analysis was conducted to examine the combined prevalence of upper limb PNI among patients requiring prone positioning. RESULTS: A total of 8 studies (511 patients) were pooled in the quantitative analysis. All studies had a low or moderate risk of bias in methodological quality. The overall proportion of patients with upper limb PNI was 13% (95%CI: 5% to 29%), with large between-study heterogeneity (I2 = 84.6%, P<0.001). Both ulnar neuropathy and brachial plexopathy were described in 4 studies. CONCLUSION: During the COVID-19 pandemic, prone positioning has been used extensively. Different approaches among ICU teams and selective reporting by untrained staff may be a factor in interpreting the large variability between studies and the 13% proportion of patients with upper limb PNI found in the present meta-analysis. Therefore, it is paramount to stress the importance of patient assessment both after discharge from the ICU and during subsequent follow-up evaluations. IMPLICATIONS FOR CLINICAL PRACTICE: Specialized training is essential to ensure safe prone positioning, with careful consideration given to arms and head placement to mitigate potential nerve injuries. Therefore, healthcare protocols should incorporate preventive strategies, with patient assessments conducted by expert multidisciplinary teams.
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Posicionamiento del Paciente , Traumatismos de los Nervios Periféricos , Síndrome de Dificultad Respiratoria , Extremidad Superior , Humanos , Posición Prona , Síndrome de Dificultad Respiratoria/etiología , Extremidad Superior/lesiones , Extremidad Superior/fisiopatología , Traumatismos de los Nervios Periféricos/etiología , Posicionamiento del Paciente/métodos , Unidades de Cuidados Intensivos/organización & administración , Unidades de Cuidados Intensivos/estadística & datos numéricos , COVID-19/complicacionesRESUMEN
This retrospective cohort study aims to describe the clinical characteristics and outcomes and assess risk factors for mortality across the epidemic waves in hospitalized COVID-19 patients in a major tertiary-care center in Pakistan. A total of 5368 patients with COVID-19, hospitalized between March 2020 and April 2022 were included. The median age was 58 years (IQR: 44-69), 41% were females, and the overall mortality was 12%. Comparative analysis of COVID-19 waves showed that the proportion of patients aged ≥ 60 years was highest during the post-wave 4 period (61.4%) and Wave 4 (Delta) (50%) (p < 0.001). Male predominance decreased from 65.2% in Wave 2 to 44.2% in Wave 5 (Omicron) (p < 0.001). Mortality rate was lowest at 9.4% in wave 5 and highest at 21.6% in the post-wave 4 period (p = 0.041). In multivariable analysis for risk factors of mortality, acute respiratory distress syndrome (ARDS) was most strongly associated with mortality (aOR 22.98, 95% CI 15.28-34.55, p < 0.001), followed by need for mechanical ventilation (aOR 6.81, 95% CI 5.13-9.05, p < 0.001). Other significant risk factors included acute kidney injury (aOR 3.05, 95% CI 2.38-3.91, p < 0.001), stroke (aOR 2.40, 95% CI 1.26-4.60, p = 0.008), pulmonary embolism (OR 2.07, 95% CI 1.28-3.35, p = 0.003), and age ≥ 60 years (aOR 2.45, 95% CI 1.95-3.09, p < 0.001). Enoxaparin use was associated with lower mortality odds (aOR 0.45, 95% CI 0.35-0.60, p < 0.001. Patients hospitalized during Wave 4 (aOR 2.22, 95% CI 1.39-3.56, p < 0.001) and the post-wave 4 period (aOR 2.82, 95% CI 1.37-5.80, p = 0.005) had higher mortality odds compared to other waves. The study identifies higher mortality risk in patients admitted in Delta wave and post-wave, aged ≥ 60 years, and with respiratory and renal complications, and lower risk with anticoagulation during COVID-19 waves.
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COVID-19 , Mortalidad Hospitalaria , Hospitalización , Humanos , COVID-19/mortalidad , COVID-19/epidemiología , Masculino , Femenino , Persona de Mediana Edad , Pakistán/epidemiología , Factores de Riesgo , Anciano , Estudios Retrospectivos , Adulto , Respiración Artificial , SARS-CoV-2/aislamiento & purificación , Síndrome de Dificultad Respiratoria/mortalidad , Centros de Atención Terciaria/estadística & datos numéricosRESUMEN
The optimal strategy for positive end-expiratory pressure (PEEP) titration in the management of severe acute respiratory distress syndrome (ARDS) patients remains unclear. Current guidelines emphasize the importance of a careful risk-benefit assessment for PEEP titration in terms of cardiopulmonary function in these patients. Over the last few decades, the primary goal of PEEP usage has shifted from merely improving oxygenation to emphasizing lung protection, with a growing focus on the individual pattern of lung injury, lung and chest wall mechanics, and the hemodynamic consequences of PEEP. In moderate-to-severe ARDS patients, prone positioning (PP) is recommended as part of a lung protective ventilation strategy to reduce mortality. However, the physiologic changes in respiratory mechanics and hemodynamics during PP may require careful re-assessment of the ventilation strategy, including PEEP. For the most severe ARDS patients with refractory gas exchange impairment, where lung protective ventilation is not possible, veno-venous extracorporeal membrane oxygenation (V-V ECMO) facilitates gas exchange and allows for a "lung rest" strategy using "ultraprotective" ventilation. Consequently, the importance of lung recruitment to improve oxygenation and homogenize ventilation with adequate PEEP may differ in severe ARDS patients treated with V-V ECMO compared to those managed conservatively. This review discusses PEEP management in severe ARDS patients and the implications of management with PP or V-V ECMO with respect to respiratory mechanics and hemodynamic function.