Search Results (57)

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

Background/Objectives: Severe COVID-19 pneumonia damages alveolar type II cells and disrupts surfactant homeostasis, contributing to acute respiratory distress syndrome (ARDS). Surfactant proteins (SP-A, SP-B, SP-C, SP-D) are critical for reducing alveolar surface tension and for innate immune defense. We aimed to evaluate whether surfactant protein gene expression varies with the severity of COVID-19. Methods: Peripheral blood was collected from 122 adults with confirmed COVID-19, categorized as asymptomatic (no symptoms), mild (requiring hospitalization), or severe (requiring ICU admission). We quantified mRNA expression of surfactant protein genes (SFTPA1, SFTPA2, SFTPB, SFTPC, SFTPD) in blood cells using RT-qPCR. Relative expression was normalized to GAPDH and compared among the groups using the 2^−ΔΔCt method. Outliers (Ct values > 3 SD from the mean) were excluded before analysis. Results: Distinct surfactant gene expression patterns were markedly associated with disease severity. Transcripts of SFTPB and SFTPC decreased with increasing severity of the disease. Notably, SFTPC expression was ~49-fold higher in mild cases compared to asymptomatic COVID-19-positive patients (p < 0.0001), but then decreased by ~54-fold in severe cases relative to mild (p < 0.0001), returning to near-baseline levels. In contrast, SFTPA2 and SFTPD were dramatically upregulated in severe cases. SFTPA2 was ~50-fold higher in severe versus mild cases (p < 0.0001), and SFTPD was ~4346-fold higher in severe versus asymptomatic cases (p < 0.0001; ~9.6-fold higher than in mild). SFTPA1 showed only a modest ~1.4-fold decrease in severe cases (vs. mild). All noted differences remained statistically significant after outlier exclusion. Conclusions: COVID-19 severity is correlated with profound changes in surfactant gene expression in blood. Critically ill patients exhibit loss of key surfactant components (SP-B and SP-C transcripts) alongside an excessive SP-D response. These preliminary findings suggest an imbalance that may contribute to lung injury in severe disease. However, further validation is needed to establish surfactant proteins, such as SP-D, as biomarkers of COVID-19 severity. Full article

Adenovirus is a frequent cause of mild, usually self-limited infections in infants and young children. Severe infections occur in immunocompromised patients but are rarely observed in healthy, immunocompetent adults. However, there have been outbreaks of infections with different adenoviral (Ad) types around the world that have resulted in acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) in some of those infected. Ad14p1 is the predominant circulating strain of Ad14 worldwide that has caused ARDS. An explanation for the severity of illness caused by Ad14p1 infection in immunocompetent patients is unknown. Previously, we have shown that A549 cells infected with Ad14 repress macrophage pro-inflammatory responses, whereas cells infected with Ad14p1 fail to repress macrophages and instead can increase pro-inflammatory responses. Adenoviral infection has been shown to modulate host miRNA expression, and we hypothesized that differences in miRNA expression between Ad14- and Ad14p1-infected cells might explain the differential responses of macrophages to Ad14- and Ad14p1-infected cells. Analysis of host miRNA showed that 98 miRNAs are differentially expressed when infection reaches full cytopathic effect (CPE), the same point at which Ad14 and Ad14p1 CPE corpses induce differential inflammatory responses in macrophages. Only 10 of the miRNAs that were enriched in Ad14 CPE corpses were expressed at levels that are potentially biologically relevant. Pathway enrichment analysis showed that the differentially expressed miRNAs might explain the increased pathogenesis of Ad14p1 through strain-related loss of modulation of cytokine expression when compared with prototype Ad14. Overall, the data suggest a role for viral regulation of host miRNA expression in pathogenesis by regulating host inflammatory responses through the delivery of de-regulated miRNAs by viral CPE corpses to macrophages. Full article

Background/Objectives: Anemia is common in critically ill patients, yet red blood cell (RBC) transfusion without active bleeding does not consistently improve outcomes and carries risks such as pulmonary injury, fluid overload, and increased costs. Optimal transfusion thresholds remain debated, with some guidelines recommending a restrictive target of 7 g/dL instead of a more liberal target of 9 g/dL. Methods: We conducted a systematic review and meta-analysis following PRISMA guidelines, searching PubMed, EMBASE, and LILACS from January 1995 to October 2024. Thirteen randomized controlled trials involving 13,705 critically ill adults were included, with 6855 assigned to liberal and 6850 to restrictive transfusion strategies. The risk of bias was assessed using the Cochrane Risk of Bias Tool 2, and the pooled effect sizes were estimated with a random-effects model. We registered the protocol in PROSPERO International Prospective Register of Systematic Reviews (CDR42024589225). Results: No statistically significant difference was observed in 30-day mortality between restrictive and liberal strategies (odds ratio [OR] 1.02; 95% confidence interval [CI], 0.83–1.25; I² = 49%). Similarly, no significant differences emerged for the 90-day or 180-day mortality, hospital or intensive care unit (ICU) length of stay, dialysis requirement, or incidence of acute respiratory distress syndrome (ARDS). However, patients in the restrictive group received significantly fewer RBC units. The trial sequential analysis (TSA) indicated that the evidence accrued was insufficient to definitively confirm or exclude an effect on the 30-day mortality, as the required sample size was not reached. Conclusions: In conclusion, while our meta-analysis found no statistically significant difference in the short-term mortality between restrictive and liberal transfusion strategies, larger trials are needed to fully determine whether any clinically meaningful difference exists in critically ill populations. Full article

Objectives: To compare the health status, exercise capacity, and health-related quality of life (HRQoL) in survivors of COVID-19-associated acute respiratory distress syndrome (ARDS) at 8, 12, and 24 months post-diagnosis. Methods: We conducted a prospective, single-center follow-up study embedded within a larger multicenter cohort of adults with COVID-19 who required hospital admission. Eligible participants underwent clinical interviews, physical examinations, chest radiography, and the 6-min walk test (6MWT). Standardized scales were used to assess post-traumatic stress disorder (PTSD), anxiety, depression, and HRQoL. Results: Out of 1295 patients with COVID-19, 365 developed ARDS, of whom 166 survived. After excluding deaths and loss to follow-up, 95 patients were monitored for 24 months. Over 60% of patients had persistent symptoms, though significant improvements were recorded in quality of life and physical recovery. More than 70% recovered their previous physical capacity, but 15% did not return to their usual lifestyle habits. Symptoms such as arthralgia and fatigue decreased, but cognitive issues, such as memory loss and insomnia, persisted. Radiological improvements were noted, although pulmonary function remained impaired. The prevalence of PTSD and anxiety decreased, while depression remained stable at around 30%. Conclusions: Long COVID continues to impose significant physical, mental, and social challenges. Symptoms like fatigue and anxiety have a profound impact on daily life. Strategies are urgently needed to help patients regain health and resume their normal lives. Full article

Background and Objectives: Acute respiratory distress syndrome (ARDS) is a severe form of acute lung injury with high mortality, characterized by hypoxemic respiratory failure and diffuse lung damage. Despite advancements in care, no definitive biomarkers have been established for ARDS diagnosis and prognostic stratification. Soluble receptor for advanced glycation end-products (sRAGE), a marker of alveolar epithelial injury, has shown promise as a prognostic indicator in ARDS. This study evaluates sRAGE’s utility in predicting 28-day mortality. Materials and Methods: A retrospective cohort study was conducted at a tertiary care ICU in Serbia from January 2021 to June 2023. Adult patients meeting the Berlin definition of ARDS were included. Exclusion criteria included pre-existing chronic respiratory diseases and prolonged mechanical ventilation before diagnosis. Serum sRAGE levels were measured within 48 h of ARDS diagnosis using enzyme-linked immunosorbent assay (ELISA). Clinical severity scores, laboratory markers, and ventilatory parameters were recorded. Logistic regression and survival analyses were used to assess the prognostic value of sRAGE for 28-day mortality. Results: A cohort of 121 patients (mean age 55.5 years; 63.6% male) was analyzed. Non-survivors exhibited higher median sRAGE levels than survivors (5852 vs. 4479 pg/mL, p = 0.084). The optimal sRAGE cut-off for predicting mortality was >16,500 pg/mL (sensitivity 30.4%, specificity 86.9%). Elevated sRAGE levels were associated with greater disease severity and an increased risk of 28-day mortality in ARDS patients, highlighting its potential as a prognostic biomarker. The main findings, while indicative of a trend toward higher sRAGE levels in non-survivors, did not reach statistical significance. Conclusions: The main findings, while indicative of a trend toward higher sRAGE levels in non-survivors, did not reach statistical significance (p = 0.084). sRAGE demonstrates potential as a prognostic biomarker in ARDS and has moderate correlation with 28-day mortality. Integrating sRAGE with other biomarkers could enhance risk stratification and guide therapeutic decisions. The retrospective design limits the ability to establish causation, underscoring the need for multicenter prospective studies. Full article

Background: Nitric oxide (NO) plays a key role in various physiological processes. Inhaled NO (iNO) has been studied for treating acute respiratory distress syndrome (ARDS). During the COVID-19 pandemic, interest grew in its potential role for patients with COVID-19 ARDS, with studies showing improved oxygenation over 48 h. Methods: This is a retrospective study of adult patients with severe COVID-19 ARDS and refractory hypoxemia admitted to the medical ICU requiring mechanical ventilation and treated with iNO. The effect on oxygenation, respiratory, and ventilation parameters is measured. Significant improvement is defined as an increase in PaO₂/FiO₂ ≥ 20% from a baseline. Results: This study includes 87 patients (55 men, mean age 58.7 ± 15.2) with 164 iNO connections (mean 1.9 per patient). iNO is independently associated with a significant PaO₂/FiO₂ ratio improvement, with an OR of 1.26 (95% CI 1.09–1.46), even after accounting for these potential confounders. The time to maximal PaO₂/FiO₂ improvement is 14.5 ± 5.0 h for men and 78.5 ± 5.5 h for women, with respective ratio increases of 42.5 ± 8.1 and 52.5 ± 13.6 mmHg. Conclusions: Our study demonstrates that severe ARDS COVID-19 patients may benefit from inhaled nitric oxide, with delayed oxygenation improvements lasting up to 96 h and slower responses observed in women, raising the possibility that current guidelines against its use could be reconsidered. Full article

Background/Objectives: SARS-CoV-2 was responsible for the global pandemic. Approximately 10–15% of patients with COVID-19 developed respiratory failure with adult acute respiratory distress syndrome (ARDS), which required treatment in the Intensive Care Unit (ICU). The cytokine storm observed in severe COVID-19 was frequently handled with steroids. Synergically, tocilizumab, an anti-interleukin-6 receptor monoclonal antibody, gained popularity as a cytokine storm-suppressing agent. However, immunosuppression was proven to increase the predisposition to infections with resistant bacteria. Our study aimed to assess the relationship between positive tests for secondary infections and the survival of patients with severe COVID-19-attributed ARDS treated with immunosuppressive agents. Methods: This study included 342 patients qualified for the ICU and mechanical ventilation (MV). The patients were divided based on the type of immunomodulating therapy and the culture tests results. Results: The results showed the highest survival rate among patients <61 years, favoring the combined treatment (tocilizumab + steroids). Atrial fibrillation (AF) and coronary heart disease (CHD) correlated with a lower survival rate than other comorbidities. Tocilizumab was associated with an increased risk of positive pathogen cultures, which could potentially cause secondary infections; however, the survival rate among these patients was higher. Conclusions: MV and ICU procedures as well as the application of tocilizumab significantly decreased the mortality rate in patients with severe COVID-19-related ARDS. The suppression of cytokine storms played a crucial role in survival. Tocilizumab was found to be both efficient and safe despite the ‘side effect’ of the increased risk of positive results for secondary infections. Full article

Background: We report a case of an adult patient with newly diagnosed human immunodeficiency virus (HIV) infection, acquired immune deficiency syndrome (AIDS), and acute respiratory distress syndrome (ARDS) secondary to pneumocystis and cytomegalovirus pneumonia that were present on presentation, which were successfully managed with venovenous extracorporeal membrane oxygenation (VV-ECMO). Case Presentation: A 40-year-old patient with a past medical history of asthma was admitted to a local hospital due to dyspnea, cough, and wheezing, where the patient was diagnosed with HIV infection, ARDS, and combined pneumocystis and cytomegalovirus pneumonia. Their pulmonary function quickly declined, necessitating mechanical ventilation (MV). After all conventional therapies failed, the patient was transferred to a tertiary medical center for VV-ECMO therapy. The patient was successfully treated with antiretroviral therapy (ART), antibiotics, antivirals, steroids, and 48 days of VV-ECMO support, with complete resolution of their respiratory symptoms. The patient was discharged on hospital day 82. Conclusions: HIV-positive patients with ARDS that is complicated by opportunistic pulmonary infections can be successfully managed with ART, appropriate anti-infective therapies, and VV-ECMO. Full article

Background: Mesenchymal stem cells (MSCs)-derived extracellular vesicles (EVs) have been proposed as an alternative to live-cell administration for Acute Respiratory Distress Syndrome (ARDS). MSC-EVs can be chiefly influenced by the environment to which the MSCs are exposed. Here, lipopolysaccharide (LPS) priming of MSCs was used as a strategy to boost the natural therapeutic potential of the EVs in acute lung injury (ALI). Methods: The regenerative and immunemodulatory effect of LPS-primed MSC-EVs (LPS-EVs) and non-primed MSC-EVs (C-EVs) were evaluated in vitro on alveolar epithelial cells and macrophage-like THP-1 cells. In vivo, ALI was induced in adult male rats by the intrapulmonary instillation of HCl and LPS. Rats (n = 8 to 22/group) were randomized to receive a single bolus (1 × 10⁸ particles) of LPS-EVs, C-EVs, or saline. Lung injury severity was assessed at 72 h in lung tissue and bronchoalveolar lavage. Results: In vitro, LPS-EVs improved wound regeneration and attenuated the inflammatory response triggered by the P. aeruginosa infection, enhancing the M2 macrophage phenotype. In in vivo studies, LPS-EVs, but not C-EVs, significantly decreased the neutrophilic infiltration and myeloperoxidase (MPO) activity in lung tissue. Alveolar macrophages from LPS-EVs-treated animals exhibited a reduced expression of CXCL-1, a key neutrophil chemoattractant. However, both C-EVs and LPS-EVs reduced alveolar epithelial and endothelial permeability, mitigating lung damage. Conclusions: EVs from LPS-primed MSCs resulted in a better resolution of ALI, achieving a greater balance in neutrophil infiltration and activation, while avoiding the complete disruption of the alveolar barrier. This opens new avenues, paving the way for the clinical implementation of cell-based therapies. Full article

Background: Severe acute respiratory syndrome (SARS) and acute respiratory distress syndrome (ARDS) are often considered separate clinico-radiological entities. Whether these conditions also present a single process-specific systemic biomolecular phenotype and how this relates to patient outcomes remains unknown. A prospective cohort study was conducted, including adult patients admitted to the ICU and general floors for COVID-19-related (COVID+) or non-COVID-19-related (COVID−) acute respiratory failure during the main phase of the pandemic. The primary objective was to study blood biomarkers and outcomes among different groups and severity subsets. Results: A total of 132 patients were included, as follows: 67 COVID+, 54 COVID− (with 11 matched control subjects for biomarker reference), and 58 of these patients allowed for further pre- and post-analysis. The baseline apelin (APL) levels were higher in COVID+ patients (p < 0.0001 vs. COVID− patients) and in SARS COVID+ patients (p ≤ 0.02 vs. ARDS), while the IL-6 levels were higher in ARDS COVID− patients (p ≤ 0.0001 vs. SARS). Multivariable logistic regression analyses with cohort biomarkers and outcome parameters revealed the following: (i) log-transformed neprilysin (NEP) activity was significantly higher in COVID+ patients (1.11 [95% CI: 0.4–1.9] vs. 0.37 [95% CI: 0.1–0.8], fold change (FC): 1.43 [95% CI: 1.04–1.97], p = 0.029) and in SARS patients (FC: 1.65 [95% CI: 1.05–2.6], p = 0.032 vs. non-SARS COVID+ patients, and 1.73 [95% CI: 1.19–2.5], p = 0.005 vs. ARDS COVID− patients) and (ii) higher lysyl oxidase (LOX) activity and APL levels were respectively associated with death and a shorter length of hospital stay in SARS COVID+ patients (Odds Ratios (OR): 1.01 [1.00–1.02], p = 0.05, and OR: −0.007 [−0.013–0.0001], p = 0.048). Conclusion: Process-specific blood biomarkers exhibited distinct profiles between COVID+ and COVID− patients, and across stages of severity. NEP and LOX activities, as well as APL levels, are particularly linked to COVID+ patients and their outcomes (ClinicalTrials.gov Identifier: NCT04632732). Full article

(1) Background: The COVID-19 pandemic presented significant challenges in managing acute respiratory distress syndrome (ARDS), with extracorporeal membrane oxygenation (ECMO) being a critical but resource-intensive intervention. (2) Methods: This retrospective study analyzed veno-venous (VV) ECMO therapy in ARDS patients before and during the pandemic at a high-volume ECMO center in Germany. The study used a reduced ECMO team (one medical and one nursing specialist) to optimize patient care with limited resources, aiming to offer insights for future pandemic management. Data from 181 adult patients (age ≥ 18) with severe ARDS were analyzed: 57 pre-pandemic and 124 during the pandemic. (3) Results: Despite increased isolation measures during the pandemic (25% pre-COVID-19 vs. 79% during COVID-19, p < 0.0001), there was no significant change in transportation mode (ground vs. air) or ECMO implantation times at local hospitals. Similarly, time and distance for primary ECMO transport remained unchanged between the two periods. Complication rates related to ECMO circuit placement and prolonged transport were also insignificant across groups. However, ECMO therapy duration (median 12 days pre-COVID-19 vs. 19 days during COVID-19, p < 0.0001) and hospital stays (median 3 days pre-COVID-19 vs. 7 days during COVID-19, p < 0.01) were longer during the pandemic. Mortality rates were also higher during the pandemic (49% pre-COVID-19 vs. 65% during COVID-19, p < 0.05). (4) Conclusions: In conclusion, a reduced ECMO team proved to be an effective resource-saving strategy that maintained high-quality care with low complication rates, despite the additional challenges posed by pandemic-related isolation measures. Full article

Background: Leptospirosis, a zoonotic disease prevalent in tropical regions, often leads to severe complications such as Weil’s disease and acute respiratory distress syndrome (ARDS). This pioneering meta-analysis investigated the role of corticosteroids in treating severe leptospirosis, addressing a critical gap in the current clinical knowledge. Methods: We systematically reviewed studies from PubMed and Scopus, focusing on randomized controlled trials and observational cohort studies involving adult patients diagnosed with leptospirosis. Five studies comprising 279 participants met the inclusion criteria. Results: Although some studies suggest potential benefits, particularly for pulmonary complications, the evidence remains inconclusive due to the limited number of studies and their methodological limitations. Notably, while four of the five reviewed studies indicated a possible positive role of corticosteroids, the single randomized controlled trial showed no significant benefit, highlighting the need for more robust research. Conclusions: While the current evidence provides a basis for potential benefits, it is not sufficient to make definitive clinical recommendations. Further research is essential to clarify the role of corticosteroids in the treatment of severe leptospirosis, with the aim of improving patient outcomes and guiding clinical practices effectively. Full article

Purpose: This study aimed to evaluate the efficacy of sivelestat sodium on mortality, oxygenation index, and serum markers in patients with acute respiratory distress syndrome (ARDS) associated with Coronavirus Disease 2019 (COVID-19). Methods: A retrospective analysis was conducted on adult inpatients admitted to the Intensive Care Unit (ICU). The study compared clinical characteristics, laboratory indices, and mortality rates between patients treated with and without sivelestat sodium. Cox regression analysis was employed to assess the effect of sivelestat sodium on the risk of death, oxygenation index, and improvement of serum markers in patients with COVID-19-associated ARDS. Results: A total of 110 patients with COVID-19-associated ARDS were included, with 45 patients in the sivelestat group and 65 patients in the control group. The overall patient mortality rate was 69.1%, with 62.2% in the sivelestat group and 73.8% in the control group. After five days of treatment, the median change from baseline in the oxygenation index was 21 mmHg in the medicated group and −31 mmHg in the control group (p < 0.05). Analysis of the oxygenation index as a clinical endpoint event showed a significantly higher rate of improvement in the sivelestat group compared to the control group (57.8% vs. 38.5%, p < 0.05), and the odds of raising the oxygenation index after treatment were 2.05 times higher in the sivelestat group than in the control group (HR = 2.05, 95%CI: 1.02–4.15, p < 0.05). Among patients with a baseline oxygenation index < 200 mmHg, patients in the sivelestat group had an 86% lower risk of death compared to the control group (HR = 0.14, 95%CI: 0.02–0.81, p < 0.05). Conclusions: Sivelestat sodium demonstrated a significant improvement in the oxygenation index of patients with COVID-19-associated ARDS and was found to considerably reduce the risk of death in patients with a baseline oxygenation index of <200 mmHg. Full article

Background: Few data are available concerning the outcome of patients denied venovenous extracorporeal membrane oxygenation (VV-ECMO) relative to severe acute respiratory distress syndrome (ARDS) due to COVID-19. Methods: We compared the 90-day survival rate of consecutive adult patients for whom our center was contacted to discuss VV-ECMO indication. Three groups of patients were created: patients for whom VV-ECMO was immediately indicated (ECMO-indicated group), patients for whom VV-ECMO was not indicated at the time of the call (ECMO-not-indicated group), and patients for whom ECMO was definitely contraindicated (ECMO-contraindicated group). Results: In total, 104 patients were referred for VV-ECMO support due to severe COVID-19 ARDS. Among them, 32 patients had immediate VV-ECMO implantation, 28 patients had no VV-ECMO indication, but 1 was assisted thereafter, and 44 patients were denied VV-ECMO for contraindication. Among the 44 patients denied, 30 were denied for advanced age, 24 for excessive prior duration of mechanical ventilation, and 16 for SOFA score >8. The 90-day survival rate was similar for the ECMO-indicated group and the ECMO-not-indicated group at 62.1 and 61.9%, respectively, whereas it was significantly lower (20.5%) for the ECMO-contraindicated group. Conclusions: Despite a low survival rate, 50% of patients were at home 3 months after being denied for VV-ECMO for severe ARDS due to COVID-19. Full article