Search Results (1,312)

Lower respiratory tract infections remain a leading cause of morbidity and mortality among Intensive Care Unit patients, with severe cases often progressing to acute respiratory distress syndrome (ARDS). This life-threatening syndrome results from alveolar–capillary membrane injury, causing refractory hypoxemia and respiratory failure. Early detection and management are critical to treat the underlying cause, provide protective lung ventilation, and, eventually, improve patient outcomes. The 2012 Berlin definition standardized ARDS diagnosis but excluded patients on non-invasive ventilation (NIV) or high-flow nasal cannula (HFNC) modalities, which are increasingly used, especially after the COVID-19 pandemic. By excluding these patients, diagnostic delays can occur, risking the progression of lung injury despite ongoing support. Indeed, sustained, vigorous respiratory efforts under non-invasive modalities carry significant potential for patient self-inflicted lung injury (P-SILI), underscoring the need to broaden diagnostic criteria to encompass these increasingly common therapies. Recent proposals expand ARDS criteria to include NIV and HFNCs, lung ultrasound, and the SpO₂/FiO₂ ratio adaptations designed to improve diagnosis in resource-limited settings lacking arterial blood gases or advanced imaging. However, broader criteria risk overdiagnosis and create challenges in distinguishing ARDS from other causes of acute hypoxemic failure. Furthermore, inter-observer variability in imaging interpretation and inconsistencies in oxygenation assessment, particularly when relying on non-invasive measurements, may compromise diagnostic reliability. To overcome these limitations, a more nuanced diagnostic framework is needed—one that incorporates individualized therapeutic strategies, emphasizes lung-protective ventilation, and integrates advanced physiological or biomarker-based indicators like IL-6, IL-8, and IFN-γ, which are associated with worse outcomes. Such an approach has the potential to improve patient stratification, enable more targeted interventions, and ultimately support the design and conduct of more effective interventional studies. Full article

Background and Objectives: Diabetes mellitus (DM) significantly impacts post-surgical recovery and fracture healing; however, few studies have specifically investigated the impact of DM on outcomes in patients undergoing surgical stabilization of rib fractures (SSRF). This study investigated the potential influence of DM on perioperative outcomes following SSRF, using data from Taiwan’s National Health Insurance Research Database (NHIRD). Materials and Methods: Data of 1603 patients with multiple rib fractures who underwent SSRF between 2001 and 2019 were retrospectively analyzed. Patients were categorized into three groups: no DM, DM without chronic complications, and DM with chronic complications. The associations between DM status and perioperative outcomes, including hospital length of stay (LOS), in-hospital mortality, readmission rates, and complications such as pneumonia, surgical site infection (SSI), acute myocardial infarction (AMI), and total hospital costs were determined using univariate and multivariable regression analyses. Results: The mean age of the 1603 patients was 52.0 years, and 71% were male. Patients with DM and chronic complications had higher risks of 14-day readmission (adjusted odds ratio [aOR] = 2.99; 95% confidence interval [CI]: 1.18–7.62), 15–30 day readmission (aOR = 3.28; 95% CI: 1.25–8.60), SSI (aOR = 2.90; 95% CI: 1.37–6.14), AMI (aOR = 3.44; 95% CI: 1.28–9.24), and acute respiratory distress syndrome (ARDS) (aOR = 1.96; 95% CI: 1.03–3.74). In conclusion, DM, particularly DM with chronic complications, significantly increases the risk of adverse short-term outcomes following SSRF. Conclusions: These findings emphasize the need for enhanced care for patients with DM to optimize the outcomes of SSRF. Full article

Introduction: Leptospirosis is an under-recognized zoonosis that affects both tropical and temperate regions. While it is often associated with exposure to contaminated water or infected animals, its presentation and epidemiology in Mediterranean countries remain incompletely understood. This retrospective cohort study investigates the clinical and epidemiological profile of leptospirosis in Crete, Greece, a region where data are scarce. Methods: All adult patients with laboratory-confirmed leptospirosis admitted to three major public hospitals in Crete, Greece, between January 2019 and December 2023 were included in the analysis. Diagnosis was made through serologic testing along with compatible clinical symptoms. Results: A total of 17 patients were included. Their median age was 48 years, with a predominance of males (70.6%). Notably, more than half of the patients had no documented exposure to classic risk factors such as rodents or standing water. Clinical presentations were varied but commonly included fever, fatigue, acute kidney injury, and jaundice. Of the patients who underwent imaging, most showed hepatomegaly. The median delay from symptom onset to diagnosis was 11 days, underscoring the diagnostic challenge in non-endemic areas. Ceftriaxone was the most frequently administered antibiotic (76.5%), often in combination with tetracyclines or quinolones. Despite treatment, three patients (17.6%) died, all presenting with severe manifestations such as ARDS, liver failure, or shock. A concerning increase in cases was noted in 2023. Conclusions: Leptospirosis can present with severe and potentially fatal outcomes even in previously healthy individuals and in regions not traditionally considered endemic. The relatively high mortality and disease frequency noted emphasize the importance of maintaining a high index of suspicion. Timely diagnosis and appropriate antimicrobial therapy are essential to improving patient outcomes. Additionally, the need for enhanced public health awareness, diagnostic capacity, and possibly environmental surveillance to control this neglected but impactful disease better, should be emphasized. Full article

Acute respiratory distress syndrome (ARDS) is an inflammatory pulmonary condition that remains at alarming rates of fatality, with neutrophils playing a vital role in its pathogenesis. Beyond their classical antimicrobial functions, neutrophils contribute to pulmonary injury via the release of reactive oxygen species, proteolytic enzymes, and neutrophil extracellular traps (NETs). To identify targets for treatment, it was found that epigenetic mechanisms, including histone modifications, hypomethylation, hypermethylation, and non-coding RNAs, regulate neutrophil phenotypic plasticity, survival, and inflammatory potential. It has been identified that neutrophils in ARDS patients exhibit abnormal methylation patterns and are associated with altered gene expression and prolonged neutrophil activation, thereby contributing to sustained inflammation. Histone citrullination, particularly via PAD4, facilitates NETosis, while histone acetylation status modulates chromatin accessibility and inflammatory gene expression. MicroRNAs have also been shown to regulate neutrophil activity, with miR-223 and miR-146a potentially being biomarkers and therapeutic targets. Neutrophil heterogeneity, as evidenced by distinct subsets such as low-density neutrophils (LDNs), varies across ARDS etiologies, including COVID-19. Single-cell RNA sequencing analyses, including the use of trajectory analysis, have revealed transcriptionally distinct neutrophil clusters with differential activation states. These studies support the use of epigenetic inhibitors, including PAD4, HDAC, and DNMT modulators, in therapeutic intervention. While the field has been enlightened with new findings, challenges in translational application remain an issue due to species differences, lack of stratification tools, and heterogeneity in ARDS presentation. This review describes how targeting neutrophil epigenetic regulators could help regulate hyperinflammation, making epigenetic modulation a promising area for precision therapeutics in ARDS. Full article

Objectives: COVID-19, caused by the SARS-CoV-2 virus, has infected over 777 million individuals and led to approximately 7 million deaths worldwide. Despite significant efforts to develop effective therapies, treatment remains largely supportive, especially for severe complications like acute respiratory distress syndrome (ARDS). Numerous compounds from diverse pharmacological classes are currently undergoing preclinical and clinical evaluation, targeting both the virus and the host immune response. Methods: Despite the large number of articles published and after a preliminary attempt was published, we discarded the option of a systematic review. Instead, we have done a description of therapies with these results and a tentative mechanism of action. Results: Preliminary studies and early-phase clinical trials have demonstrated the potential of Mesenchymal Stem Cells (MSCs) in mitigating severe lung damage in COVID-19 patients. Previous research has shown MSCs to be effective in treating various pulmonary conditions, including acute lung injury, idiopathic pulmonary fibrosis, ARDS, asthma, chronic obstructive pulmonary disease, and lung cancer. Their ability to reduce inflammation and promote tissue repair supports their potential role in managing COVID-19-related complications. This review demonstrates the utility of MSCs in the acute phase of COVID-19 and postulates the etiopathogenic role of mitochondria in Long-COVID. Even more, their combination with other therapies is also analyzed. Conclusions: While the therapeutic application of MSCs in COVID-19 is still in early stages, emerging evidence suggests promising outcomes. As research advances, MSCs may become an integral part of treatment strategies for severe COVID-19, particularly in addressing immune-related lung injury and promoting recovery. However, a full pathogenic mechanism may explain or unify the complexity of signs and symptoms of Long COVID and Post-Acute Sequelae (PASC). Full article

Increased epithelial and endothelial permeability, along with dysregulated inflammatory responses, are key aspects of acute respiratory distress syndrome (ARDS) pathophysiology, which not only impact the lungs but also contribute to detrimental organ crosstalk with distant organs, ultimately leading to multiple organ dysfunction syndrome (MODS)—the primary cause of morbidity and mortality in patients with lung injury (LI) and ARDS. It is predominantly manifested by hypoxemic respiratory failure and bilateral pulmonary infiltrates, which cannot be fully attributed to cardiac failure or hypervolemia, but rather to alveolo-capillary barrier dysfunction, dysregulated systemic and pulmonary inflammation, immune system abnormalities, and mechanical stimuli-related responses. However, these pathological features are not uniform among patients with ARDS, as distinct subphenotypes with unique biological, clinical, physiological, and radiographic characteristics have been increasingly recognized in recent decades. The severity of ARDS, clinical outcomes, mortality, and efficacy of applied therapeutic measures appear significant depending on the respective phenotype. Acknowledging the heterogeneity of ARDS and defining distinct subphenotypes could significantly modify therapeutic strategies, enabling more precise and targeted treatments. To address these issues, a comprehensive literature search was conducted in PubMed using predefined keywords related to ARDS pathophysiology, subphenotypes, and personalized therapeutic approaches. Optimizing the identification and characterization of discrete ARDS subphenotypes—based on clinical, biological, physiological, and radiographic criteria—will deepen our understanding of ARDS pathophysiology, promote targeted recruitment in prospective clinical studies to define patient clusters with heterogeneous therapeutic responses, and support the shift toward individualized treatment strategies. Full article

Background: Lymphopenia has been associated with in-hospital, early, and late mortality. We aimed to elucidate differences in baseline characteristics in patients with lymphopenia with and without acute respiratory distress syndrome (ARDS) and determine predictors of in-hospital mortality in this patient population. Methods: Patients ≥ 18 years of age with lymphopenia were identified in the National Inpatient Sample (2017–2021) and stratified according to ARDS diagnosis. Predictors of in-hospital mortality were determined using multivariate analyses with a logistic regression model. Results: From 183,185 patients with lymphopenia, 10,420 (5.7%) had ARDS, of which 92.8% had coronavirus disease 2019. The patients with ARDS suffered from more in-hospital mortality (47% versus 6.7%, p < 0.001). ARDS increased the odds of in-hospital mortality by eight-fold (odds ratio [OR]: 7.91 [7.06–8.86], p < 0.001). Age ≥ 65 years (OR: 4.88 [3.98–5.99]), moderate/severe liver disease (OR: 2.53 [1.87–3.42]), and metastatic cancer (OR: 2.18 [1.68–2.82]) were among the strongest positive predictors of in-hospital mortality (all p < 0.001). Conclusions: Patients with lymphopenia who have ARDS have higher in-hospital mortality, likely due to the condition’s clinical course. Lymphopenia may be a marker of immune dysregulation and systemic involvement in ARDS. Full article

Background/Objectives: Postoperative acute respiratory distress syndrome (ARDS) is a recognized complication with reported prevalence rates of up to 20% and highly variable mortality. However, there is limited published evidence comparing the outcomes of postoperative ARDS with those of medical ARDS. We aimed to evaluate the prevalence, hospital mortality, and healthcare costs of postoperative ARDS in Spain between 2000 and 2022 and to compare them with those of medical ARDS. Methods: We performed a nationwide, registry-based study of all hospitalizations for postoperative ARDS in Spain between 1 January 2000 and 31 December 2022 using the Minimum Basic Data Set (MBDS) Registry. Results: We identified a total of 93,192 ARDS patients, of which 40,601 had postoperative ARDS. The postoperative ARDS prevalence varied between 0.05 and 0.22%, accounting for 45–50% of total ARDS cases recorded during the study period. Hospital mortality was lower in postoperative ARDS compared with medical ARDS during the first phase (2000–2015) (47.0% vs. 49.9%, p < 0.001) and converged during the second phase (2017–2022) (42.7% vs. 43.2%, p = 0.413). Postoperative ARDS was associated with a longer hospital stay and 1.5 times higher healthcare costs compared with medical ARDS. During the COVID-19 pandemic, mortality rates declined but costs peaked in both groups. The incidence of digestive tract infection was higher in postoperative ARDS. Conclusions: The prevalence of postoperative ARDS remained stable, except during the COVID-19 pandemic, and its hospital mortality declined and equalized with that of medical ARDS. However, the costs associated with postoperative ARDS remained significantly higher. Full article

Introduction: Esophagectomy for esophageal cancer traditionally involves delayed postoperative oral feeding due to concerns about complications like anastomotic leakage. Enhanced Recovery After Surgery (ERAS) protocols favor early oral feeding (EOF), but its safety and benefits remain debated. This systematic review and meta-analysis compared EOF versus late oral feeding (LOF) after esophagectomy. Methods: We systematically searched PubMed, Scopus, Web of Science, EMBASE, and the Cochrane Library through March 2025 for primary studies comparing EOF (≤7 days post-op) with LOF (>7 days or delayed) in adult patients after esophagectomy. Outcomes included anastomotic leakage, pneumonia, other complications, gastrointestinal recovery, length of hospital stay (LOS), quality of life (QoL), and mortality. Results: Twenty-nine studies involving 3962 patients were included. There was no significant difference in the risk of anastomotic leakage between the two groups (RR: 1.03, 95% CI: 0.80–1.33, p = 0.82, I² = 0%). EOF was associated with a significantly shorter time to first flatus (Cohen’s d: −1.26, 95% CI: −1.93 to −0.58, p < 0.001) and first defecation (Cohen’s d: −0.87, 95% CI: −1.51 to −0.22, p = 0.01) and a shorter LOS (p = 0.01). No significant differences were found for other complications (acute respiratory distress syndrome [ARDS], chyle leak, conduit issues, ileus, sepsis, wound infection) or mortality rates (in-hospital, 30-day, 90-day, overall). QoL assessment suggested potential improvement in emotional function with EOF. Conclusions: EOF after esophagectomy appears safe, as it does not increase the risk of anastomotic leakage or other major complications compared to LOF. It is associated with faster gastrointestinal recovery and shorter hospital stays, supporting its use within ERAS protocols. Full article

Steel corrosion prediction in concrete infrastructure remains a critical challenge for durability assessment and maintenance planning. This study presents a comprehensive framework integrating domain expertise with advanced machine learning for carbonation-induced corrosion prediction. Four Gaussian Process Regression (GPR) variants were systematically developed: Baseline GPR with manual optimization, Expert Knowledge GPR employing domain-driven dual-kernel architecture, GPR with Automatic Relevance Determination (GPR-ARD) for feature selection, and GPR-OptCorrosion featuring specialized multi-component composite kernels. The models were trained and validated using 180 carbonated mortar specimens with 15 systematically categorized variables spanning mixture, material, environmental, and electrochemical parameters. GPR-OptCorrosion achieved superior performance (R² = 0.9820, RMSE = 1.3311 μA/cm²), representing 44.7% relative improvement in explained variance over baseline methods, while Expert Knowledge GPR and GPR-ARD demonstrated comparable performance (R² = 0.9636 and 0.9810, respectively). Contrary to conventional approaches emphasizing electrochemical indicators, automatic relevance determination revealed supplementary cementitious materials (silica fume and fly ash) as dominant predictive factors. All advanced models exhibited excellent generalization (gaps < 0.02) and real-time efficiency (<0.006 s), with probabilistic uncertainty quantification enabling risk-informed infrastructure management. This research contributes to advancing machine learning applications in corrosion engineering and provides a foundation for predictive maintenance strategies in concrete infrastructure. Full article

Background: Sepsis and septic shock are major contributors to global morbidity and mortality. The “cytokine storm,” a hyper-inflammatory response, plays a central role in sepsis pathophysiology, leading to multi-organ failure. Extracorporeal cytokine adsorption therapies, such as CytoSorb, Toraymyxin, Oxiris, HA330/380, and Seraph 100 Microbind, aim to mitigate the inflammatory response by removing circulating cytokines and other mediators. Methods: A comprehensive search of Scopus and PubMed was conducted for studies published from January 2020 to May 2025. The search terms included “sepsis,” “septic shock,” and “extracorporeal cytokine adsorption.” Relevant studies, including clinical trials and meta-analyses, were included to assess the efficacy and safety of these therapies. Results: Extracorporeal cytokine adsorption has shown promising results in reducing cytokine levels, improving organ function, and decreasing vasopressor requirements. However, evidence regarding mortality reduction remains inconsistent. Studies have demonstrated benefits in sepsis, ARDS, and cardiogenic shock, improving organ recovery and inflammatory markers. Conclusions: Extracorporeal cytokine adsorption is a potential adjunctive therapy in sepsis management, offering improvements in organ function and inflammatory control. While the mortality benefit remains uncertain, ongoing research and large-scale clinical trials are essential to define its clinical role and optimize its application. Full article

Background Veno-venous extracorporeal membrane oxygenation (VV-ECMO) supports critically ill patients with respiratory failure. However, ECMO may induce systemic inflammation, hemolysis, and hemodilution, potentially resulting in endothelial activation and damage. Therefore, this study explored the longitudinal changes in circulating markers of inflammation, hemolysis, and endothelial activation and damage in patients with COVID-19 on VV-ECMO. Methods Plasma was obtained before, within 48 h as well as on day 4, week 1, and week 2 of ECMO support and after decannulation. Circulating markers were measured using Luminex, ELISA, and spectrophotometry. Human pulmonary endothelial cells were exposed to patient plasma, and in vitro endothelial permeability was assessed using electric cell-substrate impedance sensing. Results From April 2020 to January 2022, plasma was collected from 14 patients (71.4% male; age 54 (45–61) years). IL-6 levels decreased (1.238 vs. 0.614 ng/mL, p = 0.039) while ICAM-1 increased (667 vs. 884 ng/mL, p = 0.003) over time when compared to pre-ECMO. Angiopoietin-1 decreased after ECMO initiation (7.57 vs. 3.58 ng/mL, p = 0.030), whereas angiopoietin-2 increased (5.20 vs. 10.19 ng/mL, p = 0.017), particularly in non-survivors of ECMO. Cell-free hemoglobin decreased directly after VV-ECMO initiation but remained stable thereafter (55.29 vs. 9.19 mg/dL, p = 0.017). Moreover, the plasma obtained at several time points during the ECMO run induced in vitro pulmonary endothelial hyperpermeability. Conclusions This exploratory study shows that patients on VV-ECMO support due to COVID-ARDS exhibit progressive endothelial activation and damage but not inflammation and hemolysis. Larger prospective studies are necessary to elucidate pathophysiological pathways leading to endothelial activation and damage, thereby reducing organ failure in these critically ill patients. Full article

Background and Objectives: This study aims to identify risk factors associated with MDRO infections and assess their impact on patient outcomes in Egyptian ICUs. Materials and Methods: The widespread overuse of antimicrobials has led to antibiotic multidrug resistance, posing significant challenges in intensive care units (ICUs) and leading to increased morbidity, mortality, and healthcare costs. A prospective observational study was conducted over 12 months, including 113 adult patients admitted to the ICU with confirmed bacterial infections. Comprehensive medical assessments and routine investigations were performed, including multisource cultures based on clinical suspicion. Patient histories, underlying conditions, and disease progression were documented. Patients were classified into two groups: those infected with MDROs and those without MDRO infections. Results: Significant differences were observed between patients with and without MDRO infections regarding temperature, pH, PaO₂, HCO₃, serum creatinine levels, high-dose inotropes, and inotrope dependence (p-values: 0.01, 0.028, 0.036, 0.008, <0.001, 0.013, 0.029, 0.039, <0.001, and 0.003, respectively). Additionally, cerebrovascular stroke and renal failure were significantly more frequent in MDRO-infected patients (p-values: 0.048 and 0.007, respectively). MDROs accounted for 42% of infections. The most commonly detected MDRO was Klebsiella spp. (52%). Patients with MDRO infections showed significantly higher mortality (42.6%), increased incidence of ARDS, invasive ventilation, and longer ventilation durations. Independent risk factors included prior antibiotic use (OR: 3.2; 95% CI: 1.5–6.8) and invasive device presence (OR: 2.7; 95% CI: 1.2–5.9). Conclusions: Cerebrovascular stroke and renal failure appear to be risk factors for MDRO infections. MDRO infections in ICUs are associated with poor clinical outcomes and increased complications. Improved antimicrobial stewardship and targeted prevention strategies are urgently required. Full article

Background: Acute respiratory distress syndrome (ARDS) secondary to tuberculosis (TB) is rare and associated with high mortality. Management is further complicated by comorbidities and ICU-related complications. Methods: We report a 43-year-old woman with post-polio sequelae and uncontrolled diabetes who developed ARDS due to pulmonary TB, complicated by recurrent nosocomial infections and gastrointestinal bleeding. Early bronchoscopy and GeneXpert MTB/RIF PCR were performed on ICU Day 2, enabling anti-TB therapy initiation by ICU Day 3. The patient received lung-protective ventilation, prone positioning, tailored antibiotics, and multidisciplinary care. Results: The patient’s clinical course was complicated by two episodes of ventilator-associated pneumonia and gastrointestinal bleeding, but with individualized management, she achieved ventilator weaning and functional recovery. Conclusions: Early TB recognition in ARDS is crucial. Multidisciplinary ICU management, including prudent steroid use, improves outcomes. Full article

In patients with respiratory diseases, a panel of markers is often used to assess disease severity and progression. Here we test whether the serum lipid signature may surge as a reliable alternative marker to monitor systemic hypoxia, a frequent unfavourable outcome in acute respiratory distress syndrome (ARDS) and chronic obstructive pulmonary diseases (COPD). We recruited 9 healthy controls, 10 COPD patients, and 10 ARDS patients. Various markers related to inflammation, redox imbalance, and iron handling were measured alongside lipid profiles obtained through untargeted lipidomic analysis. The results show that serum lipids were moderately lower in COPD patients and significantly reduced in ARDS patients compared to the controls. Six lipid classes (cholesteryl esters, coenzyme Q, phosphatidylinositol, sterols, hexosylceramides, and phosphatidylethanolamine) exhibited significant changes (ANOVA p < 0.05) and correlated with the Horowitz index (P/F), suggesting their potential as markers of hypoxia severity. While conventional markers also correlated with P/F, the lipid signature was more specific and reliable. This study highlights that hypoxia in pulmonary diseases depresses circulating lipids, with certain lipid classes offering more precise predictions of hypoxia severity. Expanding this research to larger populations could support the lipid signature as a clinical tool. Full article