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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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).

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.

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).

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.

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.

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.

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.

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.

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.

Retrospective cohort study.

Single-centre intensive care unit in the Midlands, UK.

708 ARDS patients (458 COVID-19, 250 non-COVID-19).

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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).

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.

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.

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.

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.

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.

Notch signaling regulates macrophage infiltration and the inflammatory response by modulating CCR5 expression in ALI induced by LPS.

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.

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.

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.

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.

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.

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.

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).

Although CXR criteria for ARDS diagnosis could be replaced in future definitions, its importance for ARDS diagnosis should not be underestimated.

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).

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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).

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.

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.

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.

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.

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.

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.

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).

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.

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).

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.

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.

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.

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).

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.

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.

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.

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.

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).

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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).

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.

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).

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.

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.

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.

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.

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).

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.