ObjectiveThe clinical characteristics of Klebsiella pneumoniae liver abscess (KPLA) and Klebsiella pneumoniae bloodstream infection (KP-BSI) are often reported, while the risk factors for KPLA combined with KP bloodstream infection (KPLA/KP-BSI) among KPLA are largely unknown. Therefore, this study aimed to investigate the clinical characteristics, risk factors, and outcomes of patients with KPLA complicated by KP-BSI.MethodsA retrospective study from May 2013 to October 2020 at a tertiary hospital compared KPLA patients with and without KP-BSI, analyzing clinical data.ResultsAmong all liver abscess cases during the study period, Klebsiella pneumoniae was the most common pathogen, accounting for 76.0% of isolates. Of 233 KPLA patients, 68.7% were male with a median age of 60.5 years. KPLA/KP-BSI occurred in 27.9%. Patients with KPLA/KP-BSI had higher male prevalence, abdominal surgery history, and higher APACHE II, SOFA, and CCI scores (p<0.05). Logistic regression showed SOFA score ≥ 2 (aOR 3.326) was a risk factor for KPLA/KP-BSI, while liver abscess size > 10 cm reduced the risk (aOR 0.144). KPLA/KP-BSI was associated with worse outcomes, including higher septic shock, acute kidney injury, transfusion rates, organ dysfunction, pneumonia, longer hospital stays, and higher mortality (all p<0.05).ConclusionNearly one-third of patients with KPLA have concurrent KP-BSI. A SOFA score ≥2 is an independent risk factor, whereas abscess diameter >10 cm is protective. KPLA/KP-BSI is associated with significantly higher rates of septic shock, organ dysfunction, and in-hospital mortality, warranting heightened clinical attention.

ObjectiveClinical practice guidelines (CPGs) support evidence-informed decision-making, but the randomized controlled trials (RCTs) cited as supporting evidence may have restricted eligibility criteria and limited external validity for clinically complex populations. This study aimed to describe exclusion criteria and underrepresented populations in RCTs cited by adult critical care CPGs published from October 2015 to October 2020.DesignSystematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.Data sourcesPubMed and Scopus electronic databases were searched from October 9, 2015, to October 9, 2020.Eligibility criteria for selecting studiesA CPG was included if it fulfilled one of the following criteria: (1) the target population was adult critically ill patients; (2) critical care experts were involved in its development; or (3) all authors agreed that it was relevant to critical care medicine (CCM). CPGs were excluded if (1) the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework was not used to develop the recommendations; (2) they were editorials, comments, meta-analyses, and reviews, duplicates, protocols, or irrelevant to CCM; (3) they were original studies that investigated the implementation of the CPGs; or (4) the topics specifically addressed critically ill child patients.Data extraction and analysisTwo independent reviewers extracted CPG characteristics, recommendations, RCT citations, and RCT exclusion criteria. Guideline quality was evaluated using the Appraisal of Guidelines for Research and Evaluation II (AGREE II) tool. Descriptive statistics were used for analysis.ResultsThirty-three CPGs publications were included. The overall average score for each AGREE II domain was >70%. These CPGs contained 1,134 recommendations and cited 1,231 RCT references. Only 8.7% of RCT citations had no exclusion criteria. The most frequent exclusion-related categories were age <18 years (37.9%), pregnancy (29.5%), moribund status (19.2%), surgical history (14.8%), renal impairment (14.2%), liver dysfunction (12.6%), hemodynamic instability (10.2%), traumatic brain injury (8.4%), allergy (8.2%), and coagulopathy (7.8%). Because the included guidelines primarily targeted adult patients, age <18 years should be interpreted as age-defined non-representation rather than inappropriate exclusion. After excluding this age-defined category, pregnancy, moribund status, surgical history, renal impairment, and liver dysfunction were the most frequent underrepresented categories.ConclusionAmong adult critical care CPGs published between 2015 and 2020, the RCT evidence cited in guideline recommendations frequently did not include several clinically important populations. These findings highlight the need for clinicians to consider the external validity of the underlying evidence when applying guideline recommendations to underrepresented or clinically complex patients.

OBJECTIVES:Carbapenem-resistant Acinetobacter baumannii (CRAB) is a major cause of hospital- and ventilator-associated pneumonia (HAP/VAP) with limited treatment options. Eravacycline (ERA) shows potent in vitro activity and favorable pulmonary pharmacokinetics, but clinical evidence for CRAB HAP/VAP remains scarce. We evaluated the real-world effectiveness and safety of ERA. METHODS:We conducted a retrospective multicenter cohort study at 12 hospitals in China (April 2022-March 2024). Adults with microbiologically confirmed CRAB HAP/VAP treated with ERA or best available therapy (BAT) for ≥ 4 days were propensity scores matched. Primary outcomes were clinical success at end of treatment (EOT) and 28-day mortality. RESULTS:After 3349 patients screened, 382 were included (ERA 204; BAT 178). Baseline characteristics were balanced. Clinical success at EOT was higher with ERA than BAT (63.2% vs 55.1%), while 28-day mortality was similar (40.1% vs 42.0%). ERA achieved higher microbiological eradication at EOT (45.1% vs 32.0%) and day 14 (36.8% vs 22.5%). Adverse events occurred less frequently with ERA. In targeted first-line treatment, ERA showed higher clinical success, greater microbiological eradication and faster clinical response without increased mortality. CONCLUSION:Eravacycline improved microbiological clearance, clinical response, and safety compared with BAT for CRAB HAP/VAP, particularly when used as targeted first-line therapy.

Background Staphylococcus aureus bloodstream infection (SA-BSI) is a life-threatening condition in ICU patients, often leading to progressive multi-organ dysfunction. Traditional static assessments may underestimate the dynamic nature of organ failure. We aimed to identify distinct organ dysfunction trajectories and evaluate their prognostic significance using a data-driven and interpretable machine learning approach.Methods ICU patients with SA-BSI from two independent cohorts admitted between 2008 and 2024 were retrospectively analyzed (MIMIC-IV, n=834; the Second Affiliated Hospital of Zhejiang University School of Medicine (SAHZU), n=151). Daily Sequential Organ Failure Assessment (SOFA) scores from Day -1 to +3 were used to derive trajectory subgroups via group-based trajectory modeling. Associations with in-hospital mortality were assessed using multivariable Cox regression and Kaplan-Meier analysis. An XGBoost model was developed to predict trajectory group membership based on baseline ICU admission variables, with interpretability assessed via SHAP values.Results Three reproducible SOFA trajectory groups were identified in both cohorts, representing stable, moderately worsening, and severely deteriorating clinical courses. Compared with the stable group, patients in the severely deteriorating group had a markedly increased risk of in-hospital mortality (HR 4.60, 95% CI 3.49-6.07), with consistent effects observed across both cohorts. The XGBoost model demonstrated strong predictive performance for identifying severely deteriorating trajectories (AUC 0.96), and SHAP analysis revealed biologically coherent predictors underlying each trajectory.Conclusions Early ICU data can predict dynamic organ dysfunction trajectories in SA-BSI patients. Trajectory-based phenotyping, combined with interpretable machine learning, offers a clinically valuable framework for early risk stratification and individualized ICU management.

Hyperammonemia, a clinical condition characterized by elevated serum ammonia levels, often leads to altered consciousness and can have severe neurological consequences. It predominantly affects patients with hyperammonemic encephalopathy (HE), urea cycle defects, medication-induced causes, or renal dysfunction. Herein, we report a rare fatal case of hyperammonemia triggered by Mycoplasma hominis infection, which presented with empyema and impaired consciousness. This case underscores the importance of recognizing non-hepatic etiologies of hyperammonemia, particularly infections caused by urease-producing pathogens like M. hominis, which can hydrolyze urea to ammonia, thereby driving up serum ammonia levels. We further review the diverse etiologies of hyperammonemia, emphasize the diagnostic challenges posed by non-hepatic causes-often overlooked in routine clinical evaluations-and discuss key therapeutic considerations, including prompt antimicrobial therapy, ammonia-lowering interventions, and management of underlying infection to improve patient outcomes.

This paper proposes the novel “Hot Pot Pattern” to conceptualize intensive care. The conventional treatment and monitoring methods form the foundational “Hot Pot Base,” and individualized interventions form the “Hot Pot Ingredients.” This model elucidates the integration of standardized care with personalized medicine inherent in intensive care management.

This study evaluated the predictive value of cell index (CI), cerebrospinal fluid procalcitonin (CSF PCT), and cerebrospinal fluid interleukin-6 (CSF IL-6) for detecting intracranial infection after neurosurgery. A two-center, prospective study analyzed CSF samples from ICU patients suspected of having intracranial infection following neurosurgery from January 2020 to June 2023. Patients with infection had longer operation times and longer stays in the ICU. The AUCs for single biomarkers ranged from 0.829 to 0.860, with the highest AUC of 0.938 observed for the combined biomarkers CI + CSF PCT + CSF IL-6. CI was most effective in patients with elevated CSF RBC counts, and PCT was most effective for detecting Gram-negative infections. The combined use of these biomarkers enhances early diagnosis of intracranial infection after neurosurgery and warrants further study.

Acute lung injury (ALI) or its more severe form, acute respiratory distress syndrome (ARDS), represents a critical condition characterized by extensive inflammation within the airways. Necroptosis, a form of cell death, has been implicated in the pathogenesis of various inflammatory diseases. However, the precise characteristics and mechanisms of necroptosis in ARDS remain unclear. Thus, our study seeks to elucidate the specific alterations and regulatory factors associated with necroptosis in ARDS and to identify potential therapeutic targets for the disease. We discovered that necroptosis mediates the progression of ALI through the activation and formation of the RIPK1/RIPK3/MLKL complex. Moreover, we substantiated the involvement of both MYD88 and TRIF in the activation of the TLR4 signaling pathway in ALI. Furthermore, we have developed a lipid micelle-encapsulated drug targeting MLKL in alveolar type II epithelial cells and successfully applied it to treat ALI in mice. This targeted nanoparticle selectively inhibited necroptosis, thereby mitigating epithelial cell damage and reducing inflammatory injury. Our study delves into the specific mechanisms of necroptosis in ALI and proposes novel targeted therapeutic agents, presenting innovative strategies for the management of ARDS.

Objective To evaluate whether the immunomodulatory drug thymosin α1 reduces mortality in adults with sepsis. Design Multicentre, double blinded, placebo controlled phase 3 trial. Setting 22 centres in China, September 2016 to December 2020. Participants 1106 adults aged 18-85 years with a diagnosis of sepsis according to sepsis-3 criteria and randomly assigned in a 1:1 ratio to receive thymosin α1 (n=552) or placebo (n=554). A stratified block method was used for randomisation, and participants were stratified by age (<60 and ≥60 years) and centre. Interventions Subcutaneous injection of thymosin α1 or placebo every 12 hours for seven days unless discontinued owing to discharge from the intensive care unit, death, or withdrawal of consent. Main outcome measure The primary outcome was 28 day all cause mortality after randomisation. All analyses were based on a modified intention-to-treat set, including participants who received at least one dose of study drug. Results Of 1106 adults with sepsis enrolled in the study, 1089 were included in the modified intention-to-treat analyses (thymosin α1 group n=542, placebo group n=547). 28 day all cause mortality occurred in 127 participants (23.4%) in the thymosin α1 group and 132 (24.1%) in the placebo group (hazard ratio 0.99, 95% confidence interval 0.77 to 1.27; P=0.93 with log-rank test). No secondary or safety outcome differed statistically significantly between the two groups. The prespecified subgroup analysis showed a potential differential effect of thymosin α1 on the primary outcome based on age (<60 years: hazard ratio 1.67, 1.04 to 2.67; ≥60 years: 0.81, 0.61 to 1.09; P for interaction=0.01) and diabetes (diabetes: 0.58, 0.35 to 0.99; no diabetes: 1.16, 0.87 to 1.53; P for interaction=0.04). Conclusions This trial found no clear evidence to suggest that thymosin α1 decreases 28 day all cause mortality in adults with sepsis. Trial registration ClinicalTrials.gov NCT02867267 .

Refractory hypoxemia following Acute Type A Aortic Dissection (ATAAD) surgery presents a significant clinical challenge. How to improve the refractory hypoxemia after ATAAD surgery is very critical for achiving perfect outcome of these patients. We report two cases of severe hypoxemia after ATAAD surgery that improved with inhaled nitric oxide (iNO) and prone positioning ventilation (PPV) therapy, despite traditional treatments including ventilator parameter optimization, performance of recruitment maneuvers, administration of glucocorticoids, diuresis and/or CRRT used for maintenance of a negative fluid balance, and secretion aspiration via fiberoptic bronchoscopy. Finally, these two patients were successful weaned from mechanical ventilation and subsequent discharge from the hospital.We provide the successful experience in the application of combination treatment of iNO and PPV in patients with refractory hypoxemia after ATAAD surgery, which will pave the way for the following randomized controlled clinical trials.

BACKGROUND:Pulse indicated continuous cardiac output (PiCCO) has largely replaced Swan-Ganz catheterization in shock patients. However, whether PiCCO monitoring can improve outcomes of shock patients, such as mortality, length of hospital stay, duration of mechanical ventilation, or laboratory parameters, remains unknown. METHODS:This retrospective cohort study included patients with shock in the intensive care unit (ICU) from January 2013 to January 2020. Patients were divided into PiCCO group and non-PiCCO group based on treatment with PiCCO monitoring or not. Demographic characteristics, Acute Physiology and Chronic Health Evaluation (APACHE) II scores, quick Sequential Organ Failure Assessment (qSOFA) scores, 14-day mortality, and N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels at 0, 1, 3 and 7 days after onset of shock, duration of mechanical ventilation, length of hospital stay and hospitalization costs were compiled and analyzed using propensity score matching (PSM). RESULTS:Real-world analysis of 1,583 ICU patients suffering shock after propensity score matching revealed that 14-day mortality did not differ between PiCCO and non-PiCCO groups (36.2% vs. 32.6%, P=0.343). Duration of mechanical ventilation, hospital stay, and hospitalization costs were also similar between the two groups (P>0.05). No differences in changes of NT-proBNP levels on days 0, 1, 3, and 7 as compared to baseline were noted between the two groups (P>0.05). CONCLUSIONS:The results of our real-world indicate that PiCCO monitoring may not shorten the duration of mechanical ventilation, length of hospital stay, or reduce hospitalization costs, nor will it bring survival benefits to ICU patients suffering shock.

BackgroundThe role of video laryngoscopy in critically ill patients requiring emergency tracheal intubation remains controversial. This systematic review and meta-analysis aimed to evaluate whether video laryngoscopy could improve the clinical outcomes of emergency tracheal intubation.MethodsWe searched the PubMed, Embase, Scopus and Cochrane databases up to 5 September 2024. Randomised controlled trials comparing video laryngoscopy with direct laryngoscopy for emergency tracheal intubation were analysed. The primary outcome was the first-attempt success rate, while secondary outcomes included intubation time, glottic visualisation, in-hospital mortality and complications.ResultsTwenty-six studies (6 in prehospital settings and 20 in hospital settings) involving 5952 patients were analysed in this study. Fifteen studies had low risk of bias. Overall, there was no significant difference in first-attempt success rate between two groups (RR 1.05, 95% CI 0.97 to 1.13, p=0.24, I2=89%). However, video laryngoscopy was associated with a higher first-attempt success rate in hospital settings (emergency department: RR 1.13, 95% CI 1.03 to 1.23, p=0.007, I2=85%; intensive care unit: RR 1.16, 95% CI 1.05 to 1.29, p=0.003, I2=68%) and among inexperienced operators (RR 1.15, 95% CI 1.03 to 1.28, p=0.01, I2=72%). Conversely, the first-attempt success rate with video laryngoscopy was lower in prehospital settings (RR 0.75, 95% CI 0.57 to 0.99, p=0.04, I2=95%). There were no differences for other outcomes except for better glottic visualisation (RR 1.11, 95% CI 1.03 to 1.20, p=0.005, I2=91%) and a lower incidence of oesophageal intubation (RR 0.42, 95% CI 0.24 to 0.71, p=0.001, I2=0%) when using video laryngoscopy.ConclusionsIn hospital settings, video laryngoscopy improved first-attempt success rate of emergency intubation, provided superior glottic visualisation and reduced incidence of oesophageal intubation in critically ill patients. Our findings support the routine use of video laryngoscopy in the emergency department and intensive care units.PROSPERO registration numberCRD 42023461887.

Objective To evaluate the effect of perioperative probiotics or synbiotics on the incidence of postoperative infections following major liver surgery. Design Meta-analysis Data sources PubMed, Embase, Scopus, and the Cochrane Library for relevant English-language studies published up to February 21st, 2024. Eligibility criteria Randomized controlled trials evaluating perioperative probiotics or synbiotics for preventing postoperative infections in patients undergoing major liver surgery. Data extraction and synthesis Outcomes included postoperative infection incidence, antibiotic therapy duration, length of stay in intensive care unit (ICU) and hospital. A random-effect model was adopted for the meta-analysis. The quality of included studies was evaluated using the Cochrane risk of bias tool. Results Ten studies involving 588 patients were included. Pooled analyses revealed that perioperative probiotics or synbiotics significantly reduced postoperative infection incidence (RR 0.36, 95% CI [0.24–0.54], P < 0.0001, I2 = 6%) and antibiotic therapy duration (MD −2.82, 95% CI [−3.13 to −2.51], P < 0.001, I2 = 0%). No significant differences were observed in length of stay in ICU (MD −0.25, 95% CI [−0.84–0.34], P = 0.41, I2 = 64%) or length of stay in hospital (MD −1.25, 95% CI [−2.74–0.25], P = 0.10, I2 = 56%). Conclusions This meta-analysis suggests that perioperative administration of probiotics or synbiotics may reduce the incidence of postoperative infections and duration of antibiotic therapy. Their use as adjunctive therapy during the perioperative period could be considered for patients undergoing major liver surgery.

BACKGROUND:Infectious diseases caused by bacterial and viral pathogens remain major contributors to global mortality and disease burden, especially for older adults. Despite progress in disease control, the pathogen-specific burden across multiple disease categories, especially among the elderly population, has not been comprehensively quantified. This study estimates the global and regional burden of 34 key pathogens in 2021, with a specific focus on mortality and disability-adjusted life years (DALYs) in older adults. METHOD:This study utilized data from the Global Burden of Disease (GBD) 2021 study to estimate mortality and DALYs attributable to 34 key bacterial and viral pathogens across 204 countries and territories. Pathogen-specific contributions were determined using the GBD comparative risk assessment framework and cause-of-death ensemble modeling. Age-standardized death and DALYs rate were calculated, and variations were examined across Socio-demographic Index (SDI) categories and geographic regions. Uncertainty intervals (UIs) were generated through Monte Carlo simulations. FINDINGS:In 2021, Staphylococcus aureus was the leading pathogen, responsible for 325,165 deaths (95 % UI: 281,827-356,269) and 4766,188 DALYs (95 % UI 4218,780-5202,881), with age-standardized rate of 32.40 death (95 % UI 27.94-35.53) and 459.37 DALYs (95 % UI 404.90-501.85) per 100,000 population. Pathogens such as Respiratory syncytial virus, Enteropathogenic E. coli, and Aeromonas caused the least global burden. Regionally, Staphylococcus aureus was the primary cause of mortality and DALYs in 15 of 21 GBD regions, with the highest mortality in Eastern Sub-Saharan Africa and the highest DALYs rate in Southern Sub-Saharan Africa. Streptococcus pneumoniae and Staphylococcus aureus were the leading contributors to infectious disease burden in elder populations, with their impact increasing with age. A strong inverse correlation was observed between SDI and age-standardized rate of death and DALYs, with lower SDI regions, such as Sub-Saharan Africa, bearing the highest burden. INTERPRETATION:This study highlights the disproportionate impact of infectious pathogens on older adults, particularly in low-SDI regions, and underscores the need for targeted interventions, resource allocation, and healthcare improvements to address this growing public health challenge. These findings provide critical insights to inform global strategies for reducing pathogen-related mortality and disability among the elderly population.

Sepsis-related acute lung injury/acute respiratory distress syndrome (ALI/ARDS) is associated with considerable morbidity and mortality, yet the efficacy of current treatments is limited. Previous studies have predominantly focused on the lung itself as an isolated organ, whereas the role of organ crosstalk in the pathogenesis of sepsis-related ALI/ARDS cannot be overlooked. Meanwhile, neglecting the discussion of heterogeneity in sepsis caused by different sources of infection may be another important obstacle to translating previous studies into clinical efficacy. In this review, we initially delineated the distinctions in pathogenesis between pulmonary and extrapulmonary sepsis-related ALI/ARDS in microbial species, pathogenesis, host response, and clinical manifestations. Additionally, systemic organ crosstalk mechanisms are summarized, including the commonality and specificity of systemic inflammation, lung and gut microbiome, as well as cascade cell injury and death in distant organs. Subsequently, organ crosstalk between lung and extrapulmonary in pulmonary sepsis and extrapulmonary sepsis-related ALI/ARDS are discussed by organs, including immunity, neuroendocrine, metabolism, and so forth. Furthermore, extracellular vesicles represent a promising avenue of research as potential players and targets in organ-lung crosstalk in sepsis. While the complexity of multi-organ interactions and the heterogeneity of septic patients present significant challenges, these issues are expected to be addressed by the emergence of organ-on-a-chip platforms, 3D organoid cultures, and multi-omics techniques.

Purpose Oral mucositis is a frequent adverse reaction in cancer treatment. Probiotics exhibit anti-inflammatory and immunomodulatory properties that could prevent the occurrence of severe oral mucositis (SOM) induced by chemotherapy or radiation therapy in patients. This meta-analysis aimed to investigate the influence of probiotics on the incidence of SOM in cancer patients undergoing chemotherapy and/or radiotherapy. Methods We conducted a comprehensive search in PubMed, Embase, the Cochrane Library, and the China National Knowledge Infrastructure (CNKI) from their inception to September 2023. Dichotomous variables are analyzed with odds ratios (ORs) with 95% CIs, and statistical significance was set at a two-tailed P <0 .05. The primary outcome indicator was the effect of probiotics on SOM. Secondary outcome indicators included the effect of probiotics on oral mucositis and the ratio of diarrhoea. Statistical analysis was conducted using RevMan (5.4) and Stata 17.0 software. Results The study included a total of 12 articles and involved 1055 patients. All patients had undergone either radiotherapy or chemotherapy. Our findings revealed that the experimental group, which received probiotics for treatment, exhibited a lower ratio of SOM compared to the control group that received traditional placebo treatment (OR=0.37, 95%CI [0.28, 0.50], P<0.01). Subgroup analysis revealed variations in the ratio of SOM based on therapeutic regimen, tumor type, and region. The overall ratio of oral mucositis was significantly lower in the experimental group compared to the control group (OR=0.19, 95%CI [0.09-0.39], P<0.01). The ratio of diarrhea in the two patient groups showed no significant difference (OR=0.85, 95%CI [0.24, 3.01], P>0.05). Conclusion The results of this meta-analysis suggest that probiotics could decrease the occurrence of SOM.

Background. A major challenge in the prevention and early treatment of acute kidney injury (AKI) is the lack of high-performance predictors in critically ill patients. Therefore, we innovatively constructed U-AKIpred (TM) for predicting AKI in critically ill patients within 12 h of panel measurement. Methods. The prospective cohort study included 680 patients in the training set and 249 patients in the validation set. After performing inclusion and exclusion criteria, 417 patients were enrolled in the training set and 164 patients were enrolled in the validation set. AKI was diagnosed by Kidney Disease: Improving Global Outcomes (KDIGO) criteria. Results. Twelve urinary kidney injury biomarkers (mALB, IgG, TRF, alpha 1MG, NAG, NGAL, KIM-1, L-FABP, TIMP2, IGFBP7, CAF22, and IL-18) exhibited good predictive performance for AKI within 12 h in critically ill patients. U-AKIpred (TM), combined with three crucial biomarkers (alpha 1MG, L-FABP, and IGFBP7) by multivariate logistic regression analysis, exhibited better predictive performance for AKI in critically ill patients within 12 h than the other 12 kidney injury biomarkers. The area under the curve (AUC) of the U-AKIpred (TM), as a predictor of AKI within 12 h, was 0.802 (95% CI: 0.771-0.833, P < .001) in the training set and 0.844 (95% CI: 0.792-0.896, P < .001) in the validation cohort. A nomogram based on the results of the training and validation sets of U-AKIpred (TM) was developed that showed optimal predictive performance for AKI. The fitting effect and prediction accuracy of U-AKIpred (TM) was evaluated by multiple statistical indicators. To provide a more flexible predictive tool, the dynamic nomogram (https://www.xsmartanalysis.com/model/U-AKIpredTM) was constructed using a web calculator. Decision curve analysis and a clinical impact curve were used to reveal that U-AKIpred (TM) with the three crucial biomarkers had a higher net benefit than these 12 kidney injury biomarkers, respectively. The net reclassification index and integrated discrimination index were used to improve the significant risk reclassification of AKI compared with the 12 kidney injury biomarkers. The predictive efficiency of U-AKIpred (TM) was better than the NephroCheck (R) when testing for AKI and severe AKI. Conclusion. U-AKIpred (TM) is an excellent predictive model of AKI in critically ill patients within 12 h and would assist clinicians in identifying those at high risk of AKI.

Background Although the optimization of brain oxygenation is thought to improve the prognosis, the effect of brain tissue oxygen pressure (PbtO2) for patients with severe traumatic brain injury (STBI) remains controversial. Therefore, the present study aimed to determine whether adding PbtO2 to intracranial pressure (ICP) monitoring improves clinical outcomes for patients with STBI. Methods PubMed, Embase, Scopus and Cochrane Library were searched for eligible trials from their respective inception through April 10th, 2024. We included clinical trials contrasting the combined monitoring of PbtO2 and ICP versus isolated ICP monitoring among patients with STBI. The primary outcome was favorable neurological outcome at 6 months, and secondary outcomes including the in-hospital mortality, long-term mortality, length of stay in intensive care unit (ICU) and hospital. Results A total of 16 studies (four randomized studies and 12 cohort studies) were included in the meta-analysis. Compared with isolated ICP monitoring, the combined monitoring was associated with a higher favorable neurological outcome rate at 6 months (RR 1.33, 95% CI [1.17–1.51], P < 0.0001, I2 = 0%), reduced long-term mortality (RR 0.72, 95% CI [0.59–0.87], P = 0.0008, I2 = 2%). No significant difference was identified in the in-hospital mortality (RR 0.81, 95% CI 0.66 to 1.01, P = 0.06, I2 = 32%), length of stay in ICU (MD 2.10, 95% CI [−0.37–4.56], P = 0.10, I2 = 78%) and hospital (MD 1.07, 95% CI [−2.54–4.67], P = 0.56, I2 = 49%) between two groups. However, the pooled results of randomized studies did not show beneficial effect of combined monitoring in favorable neurological outcome and long-term mortality. Conclusions Currently, there is limited evidence to prove that the combined PbtO2 and ICP monitoring may contribute to improved neurological outcome and long-term mortality for patients with STBI. However, the benefit of combined monitoring should be further validated in more randomized studies.

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