Background: Bronchopulmonary dysplasia (BPD) is a complex chronic lung disease caused by the interaction between lung development and prenatal and postnatal injury events. Up to one-third of infants with BPD further develop pulmonary vascular dysfunction, leading to chronic pulmonary hypertension (PH). Infants with BPD-PH face increased mortality, a higher risk of adverse neurodevelopmental outcomes, and a lack of effective treatments. Methods: A total of 30 study participants were recruited from the Children’s Hospital Affiliated to Shandong University, with the data collection period spanning from January 2023 to May 2025. Through metabolite analysis, we observed significant differences in arginine concentration. Subsequently, in vitro experiments were conducted to investigate the effects of arginine on the proliferation and migration abilities of vascular endothelial cells and to elucidate the underlying molecular mechanisms. Finally, in vivo experiments were performed to validate the protective role of arginine in BPD-PH. Results: The results of the in vitro experiments indicate that arginine inhibits the proliferation and migration of vascular endothelial cells. Molecular mechanism studies revealed that arginine reduces the expression of α-smooth muscle actin, hypoxia-inducible factor-1α, and related proteins through the arginyl-tRNA synthetase-1 (RARS1)-hairy and enhancer of split homologue-1 (HES1) pathway, RARS1 directly interacts with HES1, and this process is enhanced by arginine, thereby alleviating vascular endothelial cell dysfunction. Further in vivo experiments demonstrated that arginine supplementation protects against hyperoxia-induced lung injury and PH in neonatal rats. Conclusion: Our results indicate that arginine alleviates BPD-PH by promoting vascular endothelial cell remodeling through the RARS1-HES1 pathway. Arginine supplementation may represent a novel therapeutic alternative for preventing BPD.
The excess accumulation of fluid in the extracellular space of the heart determines a condition of “myocardial interstitial edema.” Myocardial edema is present in multiple pathological conditions observed in the intensive care setting: fulminant myocarditis, sepsis-induced cardiomyopathy, cardiac arrest, capillary leak syndrome, and extracorporeal circulation. Fluid accumulation in the interstitium can occur rapidly, leading to severe heart failure and potentially progressing to cardiogenic shock. Early diagnosis and prompt therapy are crucial. Understanding the factors and diseases that can disrupt myocardial fluid homeostasis and contribute to the development of interstitial edema allows for a targeted therapeutic approach, aimed at reducing fluid accumulation and clinical detrimental effects.
Background: Community-acquired pneumonia is a leading cause of emergency department (ED) presentation, hospitalization, and in-hospital mortality. CURB-65 is the most widely used bedside risk stratification tool; however, it does not capture tissue hypoperfusion. We evaluated the combined discriminative performance of CURB-65 and admission serum lactate for predicting intensive care unit (ICU) admission and in-hospital mortality. Methods: This was a retrospective, single-center cohort study conducted at a university hospital ED (January 2023–July 2025). After excluding patients with missing lactate (n = 204), incomplete CURB-65 components (n = 307), or other reasons (n = 36), a total of 317 out of 864 consecutive patients with pneumonia were included. Predictors were assessed using binary logistic regression; the area under the curve (AUC) were compared using the DeLong method. Calibration was assessed with the Hosmer–Lemeshow test; internal validation used bootstrap resampling (1000 iterations). Results: Median age was 70 years (interquartile range: 57–80); 47.9% were female. ICU admission occurred in 60 patients (18.9%), and in-hospital mortality occurred in 25 (7.9%). Both CURB-65 (odds ratio: 2.48; 95% confidence interval: 1.75–3.50; P < 0.001) and lactate (odds ratio: 1.40; 95% confidence interval: 1.23–1.59; P < 0.001) were independently associated with ICU admission. For ICU admission, AUCs were 0.778 (CURB-65), 0.796 (lactate), and 0.850 (combined; ΔAUC: 0.071, P < 0.001). For in-hospital mortality, AUCs were 0.763, 0.806, and 0.858 (ΔAUC: 0.094, P = 0.003). The combined model showed excellent calibration (Hosmer–Lemeshow P > 0.90) and high negative predictive value (91.1% for ICU; 98.0% for mortality). Conclusion: Adding serum lactate to CURB-65 significantly improved discriminative performance for ICU admission and in-hospital mortality in ED pneumonia patients. The high negative predictive value supports its utility for ruling out adverse outcomes in low-risk patients.
Background: Septic shock is a severe subtype of sepsis associated with poor clinical outcomes, representing a major challenge in critical care medicine. Sedation management is a core component of comprehensive treatment for patients with septic shock. Dexmedetomidine, a highly selective α2-adrenergic receptor agonist, has shown potential prognostic benefits in the general sepsis population, but its efficacy and mortality impact in septic shock patients remain controversial and lack targeted systematic evaluation. Methods: This meta-analysis followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines. We searched PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, and Wanfang databases for studies published up to October 1, 2025, and included randomized controlled trials (RCTs). We quantitatively analyzed key outcomes (intensive care unit [ICU] mortality, 28-day mortality, length of ICU stay), and assessed the methodological quality of included RCTs with the Risk of Bias 2.0 tool (RoB 2.0). Results: This study is registered in the International Platform of Registered Systematic Review and Meta-analysis Protocols (INPLASY) with the number INPLASY202510103. A total of 11 moderate-to-high quality RCTs involving 836 patients were included. Compared with controls (conventional treatment, propofol, or midazolam), dexmedetomidine showed no statistically significant benefits in ICU mortality (odds ratio: 0.72, 95% confidence interval [CI]: 0.46–1.12; I 2 = 0%; P = 0.14), 28-day mortality (odds ratio: 0.75; 95% CI: 0.53–1.07; I 2 = 34%; P = 0.11), or ICU length of stay (mean difference: ‐0.45; 95% CI: ‐1.09 to 0.20; I 2 = 31%; P = 0.18). Exploratory subgroup analyses stratified by control regimens yielded results consistent with the overall findings, but the statistical power was limited because of the small number of studies in each subgroup, so these results should be interpreted with caution. Sensitivity analysis confirmed the stability of the overall pooled results, and both funnel plot inspection and Egger’s test indicated minimal risk of publication bias. Conclusion: Dexmedetomidine shows no statistically significant benefits in reducing 28-day mortality or shortening ICU stay in patients with septic shock, despite its preclinical anti-inflammatory and organ-protective effects. This differs from findings in broader sepsis populations, highlighting the need for severity stratification and targeted research.
Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiovascular disease. The objective of this article is to briefly review the incidence, diagnosis, clinical manifestations, and management of HCM. The article outlines the pathophysiology, clinical implications, and risk assessment of HCM, and discusses future directions in its management and care. HCM is characterized by a pathophysiology that is mutation-specific, leading to variability in HCM spectrum of clinical manifestations. HCM often can cause increased arrhythmogenesis of the left ventricle. Poor management of HCM can result in left ventricular remodeling, increased myocardial oxygen consumption, secondary mitral regurgitation, heart failure from systolic and diastolic dysfunction, and sudden cardiac death. Pharmacological therapy is the mainstay of treatment of HCM. Management of shock in HCM can be challenging. A suggested pathway for managing shock in HCM is included in this article. The clinical manifestations of common cardiac clinical scenarios in HCM differ from the conventional presentation in non-HCM patients. As such, HCM patients who present with acute myocardial infarction (AMI) are not likely to get prompt revascularization. On the contrary, HCM patients can clinically present mimicking AMI. There are no distinct guidelines for the management of HCM patients with suspected AMI. Early identification along with referral to HCM centers of excellence for appropriate monitoring and management are critical in the care of HCM.
Background: Continuous renal replacement therapy (CRRT) is commonly used to manage sepsis-associated acute kidney injury (SA-AKI) as a form of extracorporeal blood purification. However, the current consensus report from the 28th Acute Disease Quality Initiative workgroup does not provide explicit recommendations for the use of CRRT in SA-AKI, because of insufficient high-quality evidence regarding its efficacy. This study aimed to evaluate whether CRRT provides clinical benefits compared with non-CRRT therapy in patients with SA-AKI. Methods: All randomized controlled trials published up to October 11, 2025, in 9 Chinese and English databases were reviewed and included in the study. A meta-analysis was performed on the experimental group (CRRT group) and control group (non-CRRT group) using risk ratios (RRs), weighted mean differences (WMDs), and 95% confidence intervals (CIs). The certainty of evidence for each outcome was evaluated using the Grading of Recommendations Assessment, Development and Evaluation approach. Results: A total of 37 studies involving 3117 subjects were included. Compared with the non-CRRT group, CRRT was associated with reduced 28-day mortality (RR: 0.42, 95% CI: 0.30–0.58, P < 0.01), hospital mortality (RR: 0.39, 95% CI: 0.28–0.54, P < 0.01), and incidence of cardiovascular events (RR: 0.39, 95% CI: 0.28–0.55, P < 0.01). CRRT was also associated with shorter intensive care unit length of stay (WMD: ‐3.97, 95% CI: ‐4.71 to ‐3.22, P < 0.01) and in-hospital length of stay (WMD: ‐4.51, 95% CI: ‐5.51 to ‐3.51, P < 0.01). Conclusion: CRRT may be associated with reduced 28-day and hospital mortality rates, a lower incidence of cardiovascular events, and shorter intensive care unit and in-hospital stays in patients with SA-AKI than standard therapy alone. However, the overall certainty of evidence assessed using the Grading of Recommendations Assessment, Development and Evaluation approach was low to very low, primarily because of limited sample sizes, methodological bias, and clinical heterogeneity among the included studies. Therefore, the findings should be interpreted with caution. Future high-quality, multicenter international randomized controlled trials with standardized CRRT protocols and longer follow-up durations are warranted to validate these results and optimize the clinical application of CRRT in SA-AKI.
Background: Oxygen therapy with high-flow nasal cannula (HFNC) is being increasingly used in patients with acute heart failure (AHF), but its impact on short-term outcomes has been poorly reported. This study aims to compare short-term outcomes in patients with AHF and respiratory distress who received initial oxygen therapy with HFNC versus noninvasive ventilation (NIV) in the emergency department (ED). Methods: In this prospective observational study, we included all patients diagnosed with AHF in 35 Spanish EDs during January–February 2022 who received either HFNC or NIV as initial oxygen therapy. Patient allocation to initial HFNC or NIV was left to the discretion of the treating emergency physician. The primary outcome was 30-day all-cause mortality. Secondary outcomes included treatment failure (defined as the need for switch of oxygen therapy techniques or escalation to NIV to mechanical ventilation), intensive care unit admission, endotracheal intubation, in-hospital mortality, a composite endpoint of intubation or 7-day mortality, and prolonged hospitalization (>7 days). Associations were expressed as adjusted odds ratios (aOR) with 95% confidence intervals (CIs), using age, sex, and significant patient- and episode-related characteristics as covariates. Results: Of 4301 patients with AHF, 330 (7.7%) were included (median age: 83 years; 57% women): 71 received HFNC and 259 received NIV. Patient characteristics did not significantly differ between groups. A total of 66 (20.1%) patients died during 30-day follow-up with no significant difference between HFNC (21.4%) and NIV (19.8%) groups (aOR: 1.09; 95% CI: 0.55–2.17). There was a significantly higher rate of treatment failure in the HFNC group (23.9% vs. 2.3%, aOR: 17.9; 95% CI: 5.90–54.2), but no significant differences were found for the other secondary endpoints. Conclusion: In patients with AHF and respiratory distress treated in the ED, there was no significant difference in 30-day all-cause mortality between those receiving HFNC or NIV as initial oxygen therapy.
Cardiac arrest occurs rapidly, requires high timeliness in treatment, and has a poor prognosis. Cardiopulmonary resuscitation (CPR) is a key intervention to save the lives of patients with cardiac arrest. In recent years, CPR has made significant progress with the update of evidence-based research and technological development. The evolution of specific recommendations in international guidelines reflects the changes in the certainty of and understanding about emerging evidence. To unravel the logical progression of cognitive development in the CPR field, this review systematically clarifies the evidence base and evolutionary history of recommendations for core components of adult CPR, including the chain of survival, interruptions in compressions, high-quality CPR, early defibrillation, dispatcher-assisted CPR, extracorporeal CPR, and temperature control. Moreover, it identifies knowledge gaps and proposes potential development directions to provide systemic insights and strategic thinking in CPR for providers, researchers, and healthcare administrators.
Introduction: Overcrowding in the emergency departments (EDs) has many negative effects on patients, healthcare staff, and the healthcare system. Overcrowding in ED can negatively affect the safety attitudes of healthcare staff. This study aimed to examine the relationship between ED overcrowding and the safety attitudes of healthcare staff. Methods: This cross-sectional descriptive study included 336 healthcare staff working in the EDs of 4 hospitals located in the southeast of Türkiye. Data were collected between February 16, 2024, and March 30, 2024. Statistical analyses were performed using IBM SPSS Statistics for Windows, Version 26.0 (IBM Corp., Armonk, NY), and the significance level was determined as P < 0.05. Results: As a result of 43 days of data collection, the National Emergency Department Overcrowding Scale score was determined as “extremely busy but not overcrowded” for 21 days, “overcrowded” for 17 days, and “severely overcrowded” for 5 days. As the National Emergency Department Overcrowding Scale score increased, the scores of teamwork climate (r: −0.236), safety climate (r: −0.248), job satisfaction (r: −0.254), perceptions of management (r: −0.302), and working conditions (r: −0.348) decreased significantly ( P < 0.001). Doctors and experienced staff had higher safety attitude scores. All subdimension scores decreased on days when crowding increased. ED overcrowding negatively affects the safety attitudes of healthcare staff. In particular, critical subdimensions such as teamwork, safety recognition, and job satisfaction weaken as crowding increases. Conclusion: This study revealed that overcrowding in the EDs has a significant effect on the safety attitudes of healthcare staff and that healthcare systems should develop multidisciplinary solutions to this problem.
Background: Patients with heart failure (HF) complicated by renal dysfunction (RD) carry an exceedingly poor prognosis, and there is a lack of precise predictive biomarkers. 4-Hydroxynonenal (4-HNE) can exacerbate cardiorenal injury, but its association with HF complicated by RD remains unclear. We aimed to investigate the predictive value of plasma-free 4-HNE for adverse clinical outcomes in patients with HF complicated by RD. Methods: This prospective study enrolled 114 patients with HF (New York Heart Association class III–IV) and RD (estimated Glomerular Filtration Rate [eGFR] ≤ 60 mL/min/1.73 m 2 ). Plasma-free 4-HNE levels were measured upon hospital admission. The primary outcome was in-hospital mortality. Secondary outcomes included major adverse cardiovascular events (MACE) and a reduction rate in N-terminal pro-B-type natriuretic peptide (NT-proBNP) ≥30%. Predictive value was assessed using receiver operating characteristic curves and logistic regression analyses. Results: The area under the curves of 4-HNE for predicting in-hospital mortality, MACE, and NT-proBNP reduction ≥30% were 0.700, 0.772, and 0.639, respectively. Multivariate regression analysis showed that 4-HNE was an independent predictive factor for in-hospital mortality (odds ratios [OR]: 3.74 [1.73–9.37]), MACE (OR: 7.21 [2.28–18.38]), and failure to achieve NT-proBNP reduction ≥30% (OR: 0.40) (all P < 0.05). Conclusion: Plasma-free 4-HNE can predict in-hospital mortality, MACE, and NT-proBNP reduction in patients with HF complicated by RD. This finding indicates that 4-HNE serves as an independent predictive factor for adverse short-term outcomes, thereby facilitating the clinical identification of high-risk patient populations.
Background: Since it remains unclear whether Shen-fu injection (SFI) could be used in hemorrhagic shock (HS), this study aimed to explore the effects of SFI on lung injury caused by HS in a porcine model. Methods: After HS induction, we randomly assigned 32 pigs into 4 groups: group I (n = 8, no resuscitation); group Ⅱ (n = 8, resuscitated with shed blood); group III (n = 8, resuscitated with shed blood and saline at a dose of 3 mL/kg); and group IV (n = 8, resuscitated with shed blood and SFI at a dose of 3 mL/kg. After 6 hours of HS, we analyzed interleukin (IL)-6, IL-8, IL-4, and IL-10 levels of lung tissue using an enzyme-linked immunosorbent assay. Apoptosis in the lung was evaluated using an immunohistochemistry staining assay and transmission electron microscopy. Results: In a porcine model of HS, 23 of 32 animals survived for 6 hours across 4 groups. Cytokine analysis revealed that group IV exhibited significantly reduced levels of proinflammatory cytokines, including IL-6 and IL-8, concomitant with elevated concentrations of anti-inflammatory cytokines, specifically IL-4 and IL-10 ( P < 0.05). Additionally, group IV demonstrated significantly elevated superoxide dismutase enzymatic activity, alongside enhanced Na + -K + -ATPase and Ca 2+ -ATPase activities, coupled with markedly reduced malondialdehyde levels ( P < 0.05). Immunohistochemical analysis revealed downregulated caspase-3 expression and upregulated Bcl-2 expression in group IV, collectively indicating attenuated apoptotic activity. Ultrastructural examination of pulmonary tissues further demonstrated that SFI administration effectively ameliorated alveolar edema, hemorrhage, and inflammatory cell infiltration, while concurrently mitigating epithelial cell apoptosis and mitochondrial injury relative to the other experimental groups. Conclusion: SFI may protect against lung injury in a porcine HS model.
Sepsis is a common syndrome with a high mortality rate worldwide, characterized by complex physiological, pathological, and biochemical abnormalities. The complement system, an essential component of innate immunity, consists of approximately 30 proteins that undergo a series of cascading enzymatic reactions to form a membrane attack complex, leading to cell lysis. Sepsis-induced complement activation drives endothelial cells toward a proinflammatory and prothrombotic phenotype. This review highlights the complex interactions among the complement, coagulation, and inflammatory systems, examines the prognostic significance of complement activation in patients with sepsis, and discusses the potential clinical applications of complement inhibitors.
Background: This study aimed to characterize fatal heat stroke (HS) and develop a risk-prediction model for early identification of high-risk patients. Methods: Patients with HS were divided into survival and nonsurvival groups based on discharge outcomes. Baseline demographics and laboratory parameters were compared. After univariate logistic regression identified candidate variables ( P < 0.05), stepwise multivariate logistic regression was performed to select independent predictors of mortality for the final model. A combined predictive model was constructed and evaluated using the Hosmer–Lemeshow test and area under the receiver operating characteristic curve (AUC). Differences in AUCs between models were compared using DeLong test. The optimal cutoff value was determined using the Youden index. Internal validation of the final model was performed using the bootstrap method with 1000 resamples. Results: A total of 209 patients with HS were analyzed, including 165 survivors (78.9%). Nonsurvivors were significantly older, had a higher proportion of females, and exhibited elevated respiratory rate, international normalized ratio, hydroxybutyrate dehydrogenase, cardiac troponin I (cTnI), neutrophil-to-lymphocyte ratio, systemic immune-inflammation index (SII), quick Sequential (Sepsis-related) Organ Failure Assessment (qSOFA), and Acute Physiology and Chronic Health Evaluation II scores, along with lower lymphocyte percentage (all P < 0.05). Multivariate logistic regression identified age, cTnI, qSOFA, and SII as independent risk factors for mortality. The combined model demonstrated excellent discriminatory power (AUC = 0.955 vs. age = 0.897; qSOFA = 0.789; cTnI = 0.847; SII = 0.596; DeLong P < 0.05), outperforming all individual predictors. Conclusion: Older age, elevated cTnI, higher qSOFA, and SII scores independently predict mortality in HS patients. The combination of these factors offers superior predictive value. Trial Registration: Chinese Clinical Trial Registry; www.chictr.org.cn; ChiCTR2400079671.
