Personalized mechanical ventilation guided by ultrasound in patients with acute respiratory distress syndrome (PEGASUS): study protocol for an international randomized clinical trial.

BACKGROUND: Acute respiratory distress syndrome (ARDS) is a frequent cause of hypoxemic respiratory failure with a mortality rate of approximately 30%. Identifying ARDS subphenotypes based on "focal" or "non-focal" lung morphology has the potential to better target mechanical ventilation strategies of individual patients. However, classifying morphology through chest radiography or computed tomography is either inaccurate or impractical. Lung ultrasound (LUS) is a non-invasive bedside tool that can accurately distinguish "focal" from "non-focal" lung morphology. We hypothesize that LUS-guided personalized mechanical ventilation in ARDS patients leads to a reduction in 90-day mortality compared to conventional mechanical ventilation. METHODS: The Personalized Mechanical Ventilation Guided by UltraSound in Patients with Acute Respiratory Distress Syndrome (PEGASUS) study is an investigator-initiated, international, randomized clinical trial (RCT) that plans to enroll 538 invasively ventilated adult intensive care unit (ICU) patients with moderate to severe ARDS. Eligible patients will receive a LUS exam to classify lung morphology as "focal" or "non-focal". Thereafter, patients will be randomized within 12 h after ARDS diagnosis to receive standard care or personalized ventilation where the ventilation strategy is adjusted to the morphology subphenotype, i.e., higher positive end-expiratory pressure (PEEP) and recruitment maneuvers for "non-focal" ARDS and lower PEEP and prone positioning for "focal" ARDS. The primary endpoint is all-cause mortality at day 90. Secondary outcomes are mortality at day 28, ventilator-free days at day 28, ICU length of stay, ICU mortality, hospital length of stay, hospital mortality, and number of complications (ventilator-associated pneumonia, pneumothorax, and need for rescue therapy). After a pilot phase of 80 patients, the correct interpretation of LUS images and correct application of the intervention within the safe limits of mechanical ventilation will be evaluated. DISCUSSION: PEGASUS is the first RCT that compares LUS-guided personalized mechanical ventilation with conventional ventilation in invasively ventilated patients with moderate and severe ARDS. If this study demonstrates that personalized ventilation guided by LUS can improve the outcomes of ARDS patients, it has the potential to shift the existing one-size-fits-all ventilation strategy towards a more individualized approach. TRIAL REGISTRATION: The PEGASUS trial was registered before the inclusion of the first patient, https://clinicaltrials.gov/ (ID: NCT05492344).

Exploring the lung-gut direction of the gut-lung axis in patients with ARDS.

Acute respiratory distress syndrome (ARDS) represents a life-threatening inflammatory reaction marked by refractory hypoxaemia and pulmonary oedema. Despite advancements in treatment perspectives, ARDS still carries a high mortality rate, often due to systemic inflammatory responses leading to multiple organ dysfunction syndrome (MODS). Indeed, the deterioration and associated mortality in patients with acute lung injury (LI)/ARDS is believed to originate alongside respiratory failure mainly from the involvement of extrapulmonary organs, a consequence of the complex interaction between initial inflammatory cascades related to the primary event and ongoing mechanical ventilation-induced injury resulting in multiple organ failure (MOF) and potentially death. Even though recent research has increasingly highlighted the role of the gastrointestinal tract in this process, the pathophysiology of gut dysfunction in patients with ARDS remains mainly underexplored. This review aims to elucidate the complex interplay between lung and gut in patients with LI/ARDS. We will examine various factors, including systemic inflammation, epithelial barrier dysfunction, the effects of mechanical ventilation (MV), hypercapnia, and gut dysbiosis. Understanding these factors and their interaction may provide valuable insights into the pathophysiology of ARDS and potential therapeutic strategies to improve patient outcomes.

Acceptability of the Venting Wisely pathway for use in critically ill adults with hypoxaemic respiratory failure and acute respiratory distress syndrome (ARDS): a qualitative study protocol.

INTRODUCTION: Hypoxaemic respiratory failure (HRF) affects nearly 15% of critically ill adults admitted to an intensive care unit (ICU). An evidence-based, stakeholder-informed multidisciplinary care pathway (Venting Wisely) was created to standardise the diagnosis and management of patients with HRF and acute respiratory distress syndrome. Successful adherence to the pathway requires a coordinated team-based approach by the clinician team. The overall aim of this study is to describe the acceptability of the Venting Wisely pathway among critical care clinicians. Specifically, this will allow us to (1) better understand the user's experience with the intervention and (2) determine if the intervention was delivered as intended. METHODS AND ANALYSIS: This qualitative study will conduct focus groups with nurse practitioners, physicians, registered nurses and registered respiratory therapists from 17 Alberta ICUs. We will use template analysis to describe the acceptability of a multicomponent care pathway according to seven constructs of acceptability: (1) affective attitude;,(2) burden, (3) ethicality, (4) intervention coherence, (5) opportunity costs, (6) perceived effectiveness and (7) self-efficacy. This study will contribute to a better understanding of the acceptability of the Venting Wisely pathway. Identification of areas of poor acceptability will be used to refine the pathway and implementation strategies as ways to improve adherence to the pathway and promote its sustainability. ETHICS AND DISSEMINATION: The study was approved by the University of Calgary Conjoint Health Research Ethics Board. The results will be submitted for publication in a peer-reviewed journal and presented at a scientific conference. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov NCT04744298.

Identifying novel clinical phenotypes of acute respiratory distress syndrome using trajectories of daily fluid balance: a secondary analysis of randomized controlled trials.

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

Continuous estimation of respiratory system compliance and airway resistance during pressure-controlled ventilation without end-inspiration occlusion.

BACKGROUND: Assessing mechanical properties of the respiratory system (Cst) during mechanical ventilation necessitates an end-inspiration flow of zero, which requires an end-inspiratory occlusion maneuver. This lung model study aimed to observe the effect of airflow obstruction on the accuracy of respiratory mechanical properties during pressure-controlled ventilation (PCV) by analyzing dynamic signals. METHODS: A Hamilton C3 ventilator was attached to a lung simulator that mimics lung mechanics in healthy, acute respiratory distress syndrome (ARDS) and chronic obstructive pulmonary disease (COPD) models. PCV and volume-controlled ventilation (VCV) were applied with tidal volume (VT) values of 5.0, 7.0, and 10.0 ml/kg. Performance characteristics and respiratory mechanics were assessed and were calibrated by virtual extrapolation using expiratory time constant (RCexp). RESULTS: During PCV ventilation, drive pressure (DP) was significantly increased in the ARDS model. Peak inspiratory flow (PIF) and peak expiratory flow (PEF) gradually declined with increasing severity of airflow obstruction, while DP, end-inspiration flow (EIF), and inspiratory cycling ratio (EIF/PIF%) increased. Similar estimated values of Crs and airway resistance (Raw) during PCV and VCV ventilation were obtained in healthy adult and mild obstructive models, and the calculated errors did not exceed 5%. An underestimation of Crs and an overestimation of Raw were observed in the severe obstruction model. CONCLUSION: Using the modified dynamic signal analysis approach, respiratory system properties (Crs and Raw) could be accurately estimated in patients with non-severe airflow obstruction in the PCV mode.

[Corticosteroids in intensive care medicine]. / Kortikosteroide in der Intensivmedizin.

In the case of septic shock, recent studies show benefits from a combination of hydrocortisone and fludrocortisone, but clear guideline recommendations are still lacking. For severe community-acquired pneumonia, early corticosteroid therapy is recommended. Corticosteroid therapy should not be used in influenza-associated community-acquired pneumonia. In contrast, a significantly lower 28-day mortality rate was observed for COVID-19 by the use of dexamethasone. Current guidelines also recommend the use of corticosteroids in Acute Respiratory Distress Syndrome. These recommendations are based primarily on studies that started steroid therapy early. However, many questions such as the type of corticosteroid, the timing and duration of therapy, and the dosage still remain unanswered.

Racial and ethnic disparities post-hospitalization for COVID-19: barriers to access to care for survivors of COVID-19 acute respiratory distress syndrome.

Racial and ethnic health disparities in the incidence and severity of Coronavirus Disease 2019 (COVID-19) have been observed globally and in the United States. Research has focused on transmission, hospitalization, and mortality among racial and ethnic minorities, but Long COVID-19 health disparities research is limited. This study retrospectively evaluated 195 adults who survived COVID-19 associated acute respiratory distress syndrome (C-ARDS) in New York City from March-April 2020. Among survivors, 54% met the criteria for Long COVID syndrome. Hispanic/Latinx patients, were more likely to be uninsured (p = 0.027) and were less frequently discharged to rehabilitation facilities (p < 0.001). A cross-sectional telephone survey and interview were conducted with a subset of survivors (n = 69). Among these, 11% reported a lack of follow-up primary care post-discharge and 38% had subsequent emergency room visits. Notably, 38% reported poor treatment within the health care system, with 67% attributing this to racial or ethnic bias. Thematic analysis of interviews identified four perceived challenges: decline in functional status, discrimination during hospitalization, healthcare system inequities, and non-healthcare-related structural barriers. Sources of resilience included survivorship, faith, and family support. This study highlights structural and healthcare-related barriers rooted in perceived racism and poverty as factors impacting post-COVID-19 care.

Prospective, randomized, controlled trial assessing the effects of a driving pressure-limiting strategy for patients with acute respiratory distress syndrome due to community-acquired pneumonia (STAMINA trial): protocol and statistical analysis plan.

BACKGROUND: Driving pressure has been suggested to be the main driver of ventilator-induced lung injury and mortality in observational studies of acute respiratory distress syndrome. Whether a driving pressure-limiting strategy can improve clinical outcomes is unclear. OBJECTIVE: To describe the protocol and statistical analysis plan that will be used to test whether a driving pressure-limiting strategy including positive end-expiratory pressure titration according to the best respiratory compliance and reduction in tidal volume is superior to a standard strategy involving the use of the ARDSNet low-positive end-expiratory pressure table in terms of increasing the number of ventilator-free days in patients with acute respiratory distress syndrome due to community-acquired pneumonia. METHODS: The ventilator STrAtegy for coMmunIty acquired pNeumoniA (STAMINA) study is a randomized, multicenter, open-label trial that compares a driving pressure-limiting strategy to the ARDSnet low-positive end-expiratory pressure table in patients with moderate-to-severe acute respiratory distress syndrome due to community-acquired pneumonia admitted to intensive care units. We expect to recruit 500 patients from 20 Brazilian and 2 Colombian intensive care units. They will be randomized to a driving pressure-limiting strategy group or to a standard strategy using the ARDSNet low-positive end-expiratory pressure table. In the driving pressure-limiting strategy group, positive end-expiratory pressure will be titrated according to the best respiratory system compliance. OUTCOMES: The primary outcome is the number of ventilator-free days within 28 days. The secondary outcomes are in-hospital and intensive care unit mortality and the need for rescue therapies such as extracorporeal life support, recruitment maneuvers and inhaled nitric oxide. CONCLUSION: STAMINA is designed to provide evidence on whether a driving pressure-limiting strategy is superior to the ARDSNet low-positive end-expiratory pressure table strategy for increasing the number of ventilator-free days within 28 days in patients with moderate-to-severe acute respiratory distress syndrome. Here, we describe the rationale, design and status of the trial.

Exogenous surfactant for lung contusion causing ARDS: A systematic review of clinical and experimental reports.

This systematic review aimed to summarize the available data on the treatment of pulmonary contusions with exogenous surfactants, determine whether this treatment benefits patients with severe pulmonary contusions, and evaluate the optimal type of surfactant, method of administration, and drug concentration. Three databases (MEDline, Scopus, and Web of Science) were searched using the following keywords: pulmonary surfactant, surface-active agents, exogenous surfactant, pulmonary contusion, and lung contusion for articles published between 1945 and February 2023, with no language restrictions. Four reviewers independently rated the studies for inclusion, and the other four reviewers resolved conflicts. Of the 100 articles screened, six articles were included in the review. Owing to the limited number of papers on this topic, various types of studies were included (two clinical studies, two experiments, and two case reports). In all the studies, surfactant administration improved the selected ventilation parameters. The most frequently used type of surfactant was Curosurf® in the concentration of 25 mg/kg of ideal body weight. In most studies, the administration of a surfactant by bronchoscopy into the segmental bronchi was the preferable way of administration. In both clinical studies, patients who received surfactants required shorter ventilation times. The administration of exogenous surfactants improved ventilatory parameters and, thus, reduced the need for less aggressive artificial lung ventilation and ventilation days. The animal-derived surfactant Curosurf® seems to be the most suitable substance; however, the ideal concentration remains unclear. The ideal route of administration involves a bronchoscope in the segmental bronchi.

Dual lumen venopulmonary extracorporeal membrane oxygenation cannulation technique using the ProtekDuo.

In this video tutorial, we present the cannulation technique for venopulmonary extracorporeal membrane oxygenation using the ProtekDuo dual-lumen cannula in a patient with acute respiratory distress syndrome.

Heterogeneity of immune cells and their communications unveiled by transcriptome profiling in acute inflammatory lung injury.

Background: Acute Respiratory Distress Syndrome (ARDS) or its earlier stage Acute lung injury (ALI), is a worldwide health concern that jeopardizes human well-being. Currently, the treatment strategies to mitigate the incidence and mortality of ARDS are severely restricted. This limitation can be attributed, at least in part, to the substantial variations in immunity observed in individuals with this syndrome. Methods: Bulk and single cell RNA sequencing from ALI mice and single cell RNA sequencing from ARDS patients were analyzed. We utilized the Seurat program package in R and cellmarker 2.0 to cluster and annotate the data. The differential, enrichment, protein interaction, and cell-cell communication analysis were conducted. Results: The mice with ALI caused by pulmonary and extrapulmonary factors demonstrated differential expression including Clec4e, Retnlg, S100a9, Coro1a, and Lars2. We have determined that inflammatory factors have a greater significance in extrapulmonary ALI, while multiple pathways collaborate in the development of pulmonary ALI. Clustering analysis revealed significant heterogeneity in the relative abundance of immune cells in different ALI models. The autocrine action of neutrophils plays a crucial role in pulmonary ALI. Additionally, there was a significant increase in signaling intensity between B cells and M1 macrophages, NKT cells and M1 macrophages in extrapulmonary ALI. The CXCL, CSF3 and MIF, TGFß signaling pathways play a vital role in pulmonary and extrapulmonary ALI, respectively. Moreover, the analysis of human single-cell revealed DCs signaling to monocytes and neutrophils in COVID-19-associated ARDS is stronger compared to sepsis-related ARDS. In sepsis-related ARDS, CD8+ T and Th cells exhibit more prominent signaling to B-cell nucleated DCs. Meanwhile, both MIF and CXCL signaling pathways are specific to sepsis-related ARDS. Conclusion: This study has identified specific gene signatures and signaling pathways in animal models and human samples that facilitate the interaction between immune cells, which could be targeted therapeutically in ARDS patients of various etiologies.

Throat microbiota drives alterations in pulmonary alveolar microbiota in patients with septic ARDS.

OBJECTIVES: The translocation of intestinal flora has been linked to the colonization of diverse and heavy lower respiratory flora in patients with septic ARDS, and is considered a critical prognostic factor for patients. METHODS: On the first and third days of ICU admission, BALF, throat swab, and anal swab were collected, resulting in a total of 288 samples. These samples were analyzed using 16S rRNA analysis and the traceability analysis of new generation technology. RESULTS: On the first day, among the top five microbiota species in abundance, four species were found to be identical in BALF and throat samples. Similarly, on the third day, three microbiota species were found to be identical in abundance in both BALF and throat samples. On the first day, 85.16% of microorganisms originated from the throat, 5.79% from the intestines, and 9.05% were unknown. On the third day, 83.52% of microorganisms came from the throat, 4.67% from the intestines, and 11.81% were unknown. Additionally, when regrouping the 46 patients, the results revealed a significant predominance of throat microorganisms in BALF on both the first and third day. Furthermore, as the disease progressed, the proportion of intestinal flora in BALF increased in patients with enterogenic ARDS. CONCLUSIONS: In patients with septic ARDS, the main source of lung microbiota is primarily from the throat. Furthermore, the dynamic trend of the microbiota on the first and third day is essentially consistent.It is important to note that the origin of the intestinal flora does not exclude the possibility of its origin from the throat.

[COVID-19 in the intensive care unit]. / Intensivmedizinische Therapie von COVID-19.

The acute respiratory failure as well as ARDS (acute respiratory distress syndrome) have challenged clinicians since the initial description over 50 years ago. Various causes can lead to ARDS and therapeutic approaches for ARDS/ARF are limited to the support or replacement of organ functions and the prevention of therapy-induced consequences. In recent years, triggered by the SARS-CoV-2 pathogen, numerous cases of acute lung failure (C-ARDS) have emerged. The pathophysiological processes of classical ARDS and C-ARDS are essentially similar. In their final stages of inflammation, both lead to a disruption of the blood-air barrier. Treatment strategies for C-ARDS, like classical ARDS, focus on supporting or replacing organ functions and preventing consequential damage. This article summarizes the treatment strategies in the intensive care unit.

Causes and attributable fraction of death from ARDS in inflammatory phenotypes of sepsis.

BACKGROUND: Hypoinflammatory and hyperinflammatory phenotypes have been identified in both Acute Respiratory Distress Syndrome (ARDS) and sepsis. Attributable mortality of ARDS in each phenotype of sepsis is yet to be determined. We aimed to estimate the population attributable fraction of death from ARDS (PAFARDS) in hypoinflammatory and hyperinflammatory sepsis, and to determine the primary cause of death within each phenotype. METHODS: We studied 1737 patients with sepsis from two prospective cohorts. Patients were previously assigned to the hyperinflammatory or hypoinflammatory phenotype using latent class analysis. The PAFARDS in patients with sepsis was estimated separately in the hypo and hyperinflammatory phenotypes. Organ dysfunction, severe comorbidities, and withdrawal of life support were abstracted from the medical record in a subset of patients from the EARLI cohort who died (n = 130/179). Primary cause of death was defined as the organ system that most directly contributed to death or withdrawal of life support. RESULTS: The PAFARDS was 19% (95%CI 10,28%) in hypoinflammatory sepsis and, 14% (95%CI 6,20%) in hyperinflammatory sepsis. Cause of death differed between the two phenotypes (p < 0.001). Respiratory failure was the most common cause of death in hypoinflammatory sepsis, whereas circulatory shock was the most common cause in hyperinflammatory sepsis. Death with severe underlying comorbidities was more frequent in hypoinflammatory sepsis (81% vs. 67%, p = 0.004). CONCLUSIONS: The PAFARDS is modest in both phenotypes whereas primary cause of death among patients with sepsis differed substantially by phenotype. This study identifies challenges in powering future clinical trials to detect changes in mortality outcomes among patients with sepsis and ARDS.

Endotyping in ARDS: one step forward in precision medicine.

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

Time to split: biomarker trajectories in pediatric acute respiratory distress syndrome hint at underlying disease.

Pediatric acute respiratory distress syndrome (ARDS) is severe, noncardiac hypoxemic respiratory failure that carries a substantial risk of death. Given the complexity of this clinically defined syndrome and the repeated failure of therapeutic trials, there has been an effort to identify subphenotypes of ARDS that may share targetable mechanisms of disease. In this issue of the JCI, Yehya and colleagues measured 19 plasma biomarkers in 279 children over the first seven days of ARDS. Increases in select tissue injury makers and inflammatory cytokines in peripheral blood were associated with multiple organ dysfunction syndrome and death, but not persistent ARDS. These findings argue that splitting patients by clinical and molecular phenotype may be more informative than lumping them under the umbrella diagnosis of ARDS. However, future studies are needed to determine whether these plasma factors represent targetable pathways in lung injury or are a consequence of systemic organ dysfunction.

Driving pressure, as opposed to tidal volume based on predicted body weight, is associated with mortality: results from a prospective cohort of COVID-19 acute respiratory distress syndrome patients.

OBJECTIVE: To evaluate the association between driving pressure and tidal volume based on predicted body weight and mortality in a cohort of patients with acute respiratory distress syndrome caused by COVID-19. METHODS: This was a prospective, observational study that included patients with acute respiratory distress syndrome due to COVID-19 admitted to two intensive care units. We performed multivariable analyses to determine whether driving pressure and tidal volume/kg predicted body weight on the first day of mechanical ventilation, as independent variables, are associated with hospital mortality. RESULTS: We included 231 patients. The mean age was 64 (53 - 74) years, and the mean Simplified Acute and Physiology Score 3 score was 45 (39 - 54). The hospital mortality rate was 51.9%. Driving pressure was independently associated with hospital mortality (odds ratio 1.21, 95%CI 1.04 - 1.41 for each cm H2O increase in driving pressure, p = 0.01). Based on a double stratification analysis, we found that for the same level of tidal volume/kg predicted body weight, the risk of hospital death increased with increasing driving pressure. However, changes in tidal volume/kg predicted body weight were not associated with mortality when they did not lead to an increase in driving pressure. CONCLUSION: In patients with acute respiratory distress syndrome caused by COVID-19, exposure to higher driving pressure, as opposed to higher tidal volume/kg predicted body weight, is associated with greater mortality. These results suggest that driving pressure might be a primary target for lung-protective mechanical ventilation in these patients.

Accuracy of the Verbal Autopsy questionnaire in the diagnosis of COVID-19 deaths in a Brazilian capital.

The Verbal Autopsy (VA) is a questionnaire about the circumstances surrounding a death. It was widely used in Brazil to assist in postmortem diagnoses and investigate excess mortality during the Coronavirus Disease 2019 (COVID-19) pandemic. This study aimed to determine the accuracy of investigating acute respiratory distress syndrome (ARDS) using VA. This is a cross-sectional study with prospective data collected from January 2020 to August 2021 at the Death Verification Service of Sao Luis city, Brazil. VA was performed for suspected COVID-19 deaths, and one day of the week was randomly chosen to collect samples from patients without suspected COVID-19. Two swabs were collected after death and subjected to reverse transcription-polymerase chain reaction (RT-PCR) for SARS-CoV-2 detection. Of the 250 cases included, the VA questionnaire identified COVID-19-related ARDS in 67.2% (52.98% were positive for COVID-19). The sensitivity of the VA questionnaire was 0.53 (0.45-0.61), the specificity was 0.75 (0.64-0.84), the positive predictive value was 0.81 (0.72-0.88), and the negative predictive value was 0.44 (0.36-0.53). The VA had a lower-than-expected accuracy for detecting COVID-19 deaths; however, because it is an easily accessible and cost-effective tool, it can be combined with more accurate methods to improve its performance.

Effects of mechanical ventilation on the interstitial extracellular matrix in healthy lungs and lungs affected by acute respiratory distress syndrome: a narrative review.

BACKGROUND: Mechanical ventilation, a lifesaving intervention in critical care, can lead to damage in the extracellular matrix (ECM), triggering inflammation and ventilator-induced lung injury (VILI), particularly in conditions such as acute respiratory distress syndrome (ARDS). This review discusses the detailed structure of the ECM in healthy and ARDS-affected lungs under mechanical ventilation, aiming to bridge the gap between experimental insights and clinical practice by offering a thorough understanding of lung ECM organization and the dynamics of its alteration during mechanical ventilation. MAIN TEXT: Focusing on the clinical implications, we explore the potential of precise interventions targeting the ECM and cellular signaling pathways to mitigate lung damage, reduce inflammation, and ultimately improve outcomes for critically ill patients. By analyzing a range of experimental studies and clinical papers, particular attention is paid to the roles of matrix metalloproteinases (MMPs), integrins, and other molecules in ECM damage and VILI. This synthesis not only sheds light on the structural changes induced by mechanical stress but also underscores the importance of cellular responses such as inflammation, fibrosis, and excessive activation of MMPs. CONCLUSIONS: This review emphasizes the significance of mechanical cues transduced by integrins and their impact on cellular behavior during ventilation, offering insights into the complex interactions between mechanical ventilation, ECM damage, and cellular signaling. By understanding these mechanisms, healthcare professionals in critical care can anticipate the consequences of mechanical ventilation and use targeted strategies to prevent or minimize ECM damage, ultimately leading to better patient management and outcomes in critical care settings.

Randomized Controlled Trial of Telementoring During Resource-Limited Patient Care Simulation Improves Caregiver Performance and Patient Survival.

OBJECTIVES: To determine the impact of telementoring on caregiver performance during a high-fidelity medical simulation model (HFMSM) of a critically ill patient in a resource-limited setting. DESIGN: A two-center, randomized, controlled study using a HFMSM of a patient with community-acquired pneumonia complicated by acute respiratory distress syndrome. SETTING: A notional clinic in a remote location staffed by a single clinician and nonmedical assistant. PARTICIPANTS: Clinicians with limited experience managing critically ill patients. INTERVENTIONS: Telemedicine (TM) support. MEASUREMENTS: The primary outcome was clinical performance as measured by accuracy, reliability, and efficiency of care. Secondary outcomes were patient survival, procedural quality, subjective assessment of the HFMSM, and perceived workload. MAIN RESULTS: TM participants (N = 11) performed better than non-TM (NTM, N = 12) in providing expected care (accuracy), delivering care more consistently (reliability), and without consistent differences in efficiency (timeliness of care). Accuracy: TM completed 91% and NTM 42% of expected tasks and procedures. Efficiency: groups did not differ in the mean (± sd) minutes it took to obtain an advanced airway successfully (TM 15.2 ± 10.5 vs. NTM 22.8 ± 8.4, p = 0.10) or decompress a tension pneumothorax with a needle (TM 0.7 ± 0.5 vs. NTM 0.6 ± 0.9, p = 0.65). TM was slower than NTM in completing thoracostomy (22.3 ± 10.2 vs. 12.3 ± 4.8, p = 0.03). Reliability: TM performed 13 of 17 (76%) tasks with more consistent timing than NTM. TM completed 68% and NTM 29% of procedural quality metrics. Eighty-two percent of the TM participants versus 17% of the NTM participants simulated patients survived (p = 0.003). The groups similarly perceived the HFMSM as realistic, managed their patients with personal ownership, and experienced comparable workload and stress. CONCLUSIONS: Remote expertise provided with TM to caregivers in resource-limited settings improves caregiver performance, quality of care, and potentially real patient survival. HFMSM can be used to study interventions in ways not possible with real patients.