OBJECTIVE:Severe infections can lead to substantial reductions in T cell counts, yet its prognostic relevance and potential cytokine-mediated mechanisms remain poorly defined in pediatric populations. This study aimed to investigate whether T cell counts are associated with mortality, and to what extent this association is mediated by circulating cytokines. DESIGN:Prospective cohort study. SETTING:A 55-bed PICU. PATIENTS:Children 28 days to 18 years old admitted to the PICU due to infections, excluding those with preexisting conditions known to potentially impact T cell counts. INTERVENTIONS:None. MEASUREMENTS AND MAIN RESULTS:A total of 252 patients were enrolled, with a median age of 4.16 years (interquartile range: 1.18-7.73), and 56.35% were male. CD3 + T cell count was nonlinearly associated with mortality ( p overall = 0.027; p nonlinear = 0.013), with a risk plateau beyond the inflection point at 705.14 cells/μL in restricted cubic spline models. The lower T cell group had markedly increased 30-, 60-, and 90-day mortality ( p < 0.05). Kaplan-Meier analysis showed that patients in the lower T cell group had significantly higher mortality ( p = 0.011). Multivariable Cox models confirmed an independent association between low T cell group and increased mortality risk, with a hazard ratio of 2.62 (95% CI, 1.12-6.14) for 90-day mortality. Mediation analysis showed that platelet-derived growth factor (PDGF)-AA mediates a substantial portion of this effect, accounting for 71.19% of the total pathway. CONCLUSIONS:Early T cell depletion independently predicts mortality in critically ill children with severe infections. These findings support the prognostic value of early immune profiling and suggest a potential immunoregulatory role for PDGF-AA.

BackgroundMaintaining high-quality cardiopulmonary resuscitation (CPR) in pediatric emergency departments remains challenging. Evidence supporting integrated quality improvement strategies combining video review and in situ simulation is limited.ObjectiveTo evaluate whether implementation of a video review-guided stepwise quality improvement strategy was associated with improved CPR process quality across three sequential implementation phases.MethodsThis single-center before-after quality improvement study included consecutive pediatric cardiac arrest cases treated between January 2025 and February 2026. A video review-guided stepwise intervention was implemented in three phases: baseline (Group A), structural optimization (Group B), and behavioral reinforcement with monthly in situ simulation (Group C). The primary outcomes were chest compression fraction (CCF) and return of spontaneous circulation (ROSC).ResultsFifteen pediatric cardiac arrest cases were included (n = 5 per group). Median CCF increased from 80.2% (74.8–85.0) in Group A to 84.0% (83.4–88.6) in Group B and 91.3% (91.0–91.5) in Group C. An overall comparison demonstrated a significant difference among the three phases (P = 0.035), with post hoc analysis showing a significant difference between Groups A and C (P = 0.016). The median number of prolonged chest compression interruptions per case decreased, and role allocation improved (P = 0.045). No significant difference in ROSC was observed (P = 0.999). Airway management and patient assessment were the leading causes of prolonged interruptions.ConclusionsImplementation of a video review-guided stepwise quality improvement strategy was associated with improved CPR process quality. This approach may provide a practical framework for continuous resuscitation quality improvement and warrants further evaluation in multicenter studies.

Introduction:Carbapenem-resistant Enterobacterales (CRE) strains carrying bla NDM variants pose a significant threat to the health of infected patients worldwide. Methods:This study isolated a carbapenem-resistant Escherichia coli (E. coli) strain carrying bla NDM-80 from a patient in an intensive care unit in China. Antimicrobial susceptibility testing, whole-genome sequencing (WGS), plasmid transformation assay, cloning experiment, and steady-state kinetic determinations were performed to investigate antimicrobial susceptibility, the characteristics of the genetic environment, the mechanism of resistance gene transmission, resistance gene function, and antibiotic hydrolysis ability. Results:The results indicated that E. coli carrying bla NDM-80 showed significant resistance to all β-lactam antibiotics except for aztreonam, aztreonam-avibactam, and cefiderocol. WGS analysis revealed that the strain belonged to sequence type (ST) 155 and the O4:H51 serotype. The bla NDM-80 was carried by an unconjugated plasmid, and its complete genetic structure was found to be IS5-bla NDM-80-ble-trpF-dsbD-IS26-nmuD-ISKox3. The bla NDM-80 had single amino acid substitutions such as V88L, D130N, and M154L compared to bla NDM-1, whereas it only had the D130N mutation compared to bla NDM-5. The bla NDM-80 and bla NDM-5 had similar antimicrobial resistance profiles. However, in the absence of the native promoter, the minimum inhibitory concentrations (MICs) of bla NDM-80 for imipenem, meropenem, cefepime, and cefiderocol were twice as high as those of bla NDM-1. Steady-state kinetic determinations revealed that NDM-80 likely had higher hydrolytic activity against imipenem, meropenem, cefepime, and cefiderocol than NDM-1. Discussion:This study is the first to report on the emergence of the bla NDM-80 variant, shedding light on its functional mechanism. Our findings enrich the repertoire of NDM resistance genes and highlight the need for increased surveillance of pathogens harboring bla NDM variants.

Abstract: Pediatricians and acute care physicians caring for ill patients with respiratory failure often encounter the decision to intubate children for respiratory support and/or to protect the airway. There are several Standard Operating Procedures (SOPs) or protocols such as the 3-3-2 Rule, Mallampati Score, Modified Mallampati Test, and Lemon Criteria, to evaluate whether a difficult airway exists so that preparedness for successful intubation can be ensured. Pediatricians are particularly concerned that there are usually no tailor-made tools or protocols to follow. The authors think that there are a few issues associated with the 3-3-2, Mallampati, and LEMON approaches. The Mallampati approach is only part of the more comprehensive LEMON approach to oropharyngeal patency, and patient cooperation is often required. The LEMON approach amalgamates the 3-3-2 and Mallampati approaches, together with the intrinsic problems associated with these two methods. We present a novel NIMO approach that consolidates existing techniques for intubating difficult airways. By integrating assessments of the Neck (3-3-2), Incisors (Inter-incisor distance), Mouth (Mallampati), and Oropharynx (LEMON), this systematic framework optimizes and streamlines clinical workflow and minimizes the limitations of current tools.

OBJECTIVE:Carbapenem-resistant Klebsiella pneumoniae (CRKP) central nervous system (CNS) infections are difficult to treat in children because effective and safe therapeutic options are limited. We report a paediatric case of CRKP meningitis successfully treated with ceftazidime-avibactam (CZA) combination with intraventricular polymyxin B (PMB). METHODS:A 9-y-old child with severe traumatic brain injury and multiple prior neurosurgical procedures developed CRKP meningitis. After pathogen identification, antimicrobial therapy was switched to CZA plus intraventricular PMB, and the ventriculoperitoneal shunt was externalized. Clinical outcomes, cerebrospinal fluid (CSF) parameters, microbiological clearance, and plasma and CSF concentration of CZA were monitored during treatment. RESULTS:After CRKP was identified, therapy was adjusted to CZA (62.5 mg/kg every 8 h, administered as a 2-h infusion) plus intraventricular PMB based on susceptibility results. Fever resolved within 3 d of CZA initiation. CSF cultures became negative, and CSF parameters gradually normalized. Neurological status improved, and the patient was transferred to a rehabilitation facility. Pharmacokinetic analysis showed blood-brain barrier penetration rates of 19.4% for ceftazidime and 29.9% for avibactam. CONCLUSIONS:This report adds to the limited pharmacokinetic/pharmacodynamic (PK/PD) evidence for ceftazidime-avibactam in paediatric CNS infections. It also supports the potential role of ceftazidime-avibactam combined with intraventricular polymyxin B as a therapeutic option for CRKP meningitis in children. Further studies are needed to optimize dosing strategies and evaluate long-term safety in the paediatric population.

Background: Rates of carbapenem-resistant organism (CRO) colonization and infection are rising in pediatric intensive care units (PICUs), mainly due to underlying comorbidities, frequent invasive procedures, prolonged hospitalization, and extensive use of broad-spectrum antibiotics. Colonized patients can act as reservoirs for nosocomial transmission of drug-resistant bacteria, posing a serious threat to other children and healthcare workers. Prevention and control of CRO are therefore of urgent clinical importance. Methods: Based on active screening measures, we analyzed risk factors for intestinal CRO colonization and subsequent nosocomial infection in critically ill children. Pulsed-field gel electrophoresis (PFGE) was used to determine molecular homology between colonizing and infecting strains isolated from the same patient. Results: A total of 1069 children were admitted to our PICU between January 2021 and September 2022. Seventy-seven cases of intestinal CRO colonization were detected, with a colonization rate of 7.2%. Of these colonized children, 15 developed subsequent CRO infection, and PFGE confirmed that the infecting strains were homologous to the colonizing ones. Independent risk factors for CRO colonization included underlying neuromuscular disease (OR 7.048, 95% CI 3.003-16.545, P<0.001) and longer hospital stay (OR 1.063, 95% CI 1.034-1.092, P<0.001). Among colonized children, independent risk factors for subsequent nosocomial infection were carbapenem exposure (OR 4.041, 95% CI 1.310-12.470, P=0.014), absence of contact isolation (OR 0.033, 95% CI 0.002-0.496, P=0.010), and longer hospital stay (OR 1.083, 95% CI 1.002-1.170, P=0.045). Conclusion: Intestinal CRO colonization significantly increases the risk of subsequent homologous nosocomial infection in PICU children. Rational carbapenem use,aprompt contact isolation following colonization and shorten hospitalization time are crucial strategies to reduce CRO-related nosocomial infections.

ObjectiveExtracorporeal membrane oxygenation (ECMO) serves as a vital rescue therapy for neonates with refractory cardiopulmonary failure, yet domestic clinical data regarding ECMO use in preterm infants remain scarce. This study sought to summarize clinical experiences and long-term prognostic outcomes of ECMO support among preterm infants in China.MethodsWe conducted a retrospective analysis of preterm infants receiving ECMO between January 2018 and November 2025 using data from the Pediatric Extracorporeal Life Support Alliance of China (PELSAC). The primary study outcomes were ECMO weaning success and survival to hospital discharge. Secondary outcomes included ECMO-associated complications, intracranial hemorrhage and hypoxic-ischemic brain injury detected by cranial imaging, and neurodevelopmental delay assessed at corrected age 18–24 months. Clinical outcomes were compared between infants with birth gestational age ≤34 weeks and those >34 weeks.ResultsSix out of 23 participating PELSAC centers (26.1%) implemented ECMO for 22 preterm infants, including 8 infants with gestational age ≤34 weeks and 14 infants over 34 weeks. The cohort had a median gestational age of 34 (32–36) weeks, a median birth weight of 2.5 (1.80–3.63) kg, and a median cannulation weight of 2.2 (1.80–2.70) kg. The median ECMO runtime was 112 (19–245) hours. 18 infants (81.8%) were successfully weaned, and 17 (77.3%) survived discharge. Complications were limited to one cannulation-site bleed and one thrombosis. Post-ECMO MRI detected brain injury in 9 of 17 survivors (52.9%), including 5 intracranial hemorrhages (29.4%) and 4 isolated hypoxic–ischemic lesions. At 18–24 months corrected age, 10 survivors (58.8%) had normal neurodevelopment, while 7 (41.2%) had developmental delay. Outcomes did not differ significantly between the ≤34-week and >34-week subgroups.ConclusionECMO in preterm infants (≥32 weeks’ gestation, ≥1.8 kg) achieves a high survival rate, although neurological complications remain common and require close surveillance. These findings support the potential for wider clinical application of ECMO in carefully selected preterm infants.

Objectives:To characterize the clinical features, laboratory parameters, and outcomes of pediatric patients with acute hypoxemic respiratory failure (AHRF) and concurrent hemodynamic instability requiring extracorporeal membrane oxygenation (ECMO), and to identify risk factors associated with mortality. Methods:This retrospective study was conducted in the Pediatric Intensive Care Unit (PICU) of the Children's Hospital of Fudan University, China. We enrolled patients aged 28 days-18 years with AHRF and hemodynamic instability despite mechanical ventilation who received ECMO support between January 2015 and December 2021. The primary outcome was 28-day in-hospital mortality. Data including demographics, comorbidities, laboratory findings, ventilator settings, and rescue therapies were analyzed. Multivariable logistic regression analysis was used to identify independent risk factors for survival. Receiver operating characteristic (ROC) curves and Kaplan-Meier survival curves were subsequently constructed to evaluate the predictive performance and compare cumulative survival rates, respectively. Results:Out of 57 eligible patients, 52 (91.2%) were included in the final analysis. The overall mortality rate was 53.8%. Successful weaning, achieved in 34 patients, correlated strongly with improved survival (p < 0.001). Before ECMO initiation, survivors had significantly higher PaO2 (median: 64.4 vs. 60.5 mmHg, p = 0.011) and P/F ratio (75.9 vs. 61.8, p = 0.007) than non-survivors. The P/F ratio emerged as a significant predictor of survival on ROC analysis, yielding an AUC of 0.766 (95% CI: 0.629 and an optimal cut-off 77.9. Conclusion:For pediatric patients with severe AHRF and hemodynamic compromise placed on VA-ECMO, lower pre-ECMO PaO2 and P/F ratio were associated with poor prognosis.

OBJECTIVES:Nutritional management is crucial for improving outcomes in children on prolonged mechanical ventilation (PMV); but detailed data are lacking. This study aimed to investigate the nutritional management of children on PMV in China and to explore their association with clinical outcomes. METHODS:This multicenter prospective observational cohort study enrolled children (aged 28 days to 18 years) who received mechanical ventilation for ≥ 21 consecutive days (PMV) from 11 tertiary hospitals across China between April 2021 and September 2022. Data on demographics and nutritional indicators (including calorie intake, protein intake, and laboratory test) were collected at enrollment (Day 1), Day 14, and Day 28. Nutritional status was assessed using Screening Tool for the Assessment of Malnutrition in Pediatrics (STAMP) screening tool and World Health Organization (WHO) age-specific Z-scores. The primary outcome was in-hospital mortality. RESULTS:Among 296 children, in-hospital mortality rate was 31.8%. All were at high nutritional risk at the time of enrollment, and 51.4% were malnourished. Non-survivors received full enteral nutrition significantly less frequently than survivors at all time points (e.g., 58.5% vs. 82.2% at Day 1, p < 0.001). Linear mixed models showed non-survivors had persistently lower median caloric and protein intake (calories: 42.9 vs. 53.3 kcal/kg/day; protein: 1.2 vs. 1.6 g/kg/day; both p < 0.05). Hemoglobin levels were persistently lower in non-survivors, with no significant difference in serum albumin. CONCLUSION:Children on prolonged mechanical ventilation are at high nutritional risk, with total parenteral nutrition, low caloric intake and protein intake, and low hemoglobin being more pronounced in non-survivors.

Background/Objectives: Sleep disturbances have an impact on children’s physical and psychological development, yet little is known about the changes and factors influencing sleep after PICU discharge. To explore the trajectory of changes in sleep quality of critically ill children and to identify factors affecting sleep quality three months after Pediatric Intensive Care Unit (PICU) discharge. Methods: A longitudinal observation study was conducted between November 2022 and November 2023 at a tertiary children’s hospital. The Children’s Sleep Habits Questionnaire (CSHQ) was used at six time points: PICU-admission (T0), 1 week (T1), 2 weeks (T2), 1 month (T3), 2 months (T4), and 3 months (T5) after PICU discharge. The CSHQ is a 33-item parent-report outcome measure evaluating sleep problems. Total scores range between 33 and 99 points. A score of ≤41 indicates normal sleep; a score of >41 indicates sleep disturbance. Data were analyzed using the latent category growth model, univariate analysis, and multifactorial logistic regression. Results: Parents of 237 children completed all follow-up surveys. Prevalence of sleep disorders at T0-T5 of children with a score >41 were 46.5%, 83.5%, 69.7%, 54.3%, 50.2%, and 51.7%, respectively. General linear modeling revealed significant changes in CSHQ scores over time (F = 63.77, p < 0.05). The trajectories of identifying sleep changes were divided into three latent categories: High Sleep Disorder Group (n = 15, 6.33%), Moderate Sleep Disorder Group (n = 110, 45.2%), and No Sleep Disorder Group (n = 115, 48.52%). The trajectories were significantly different among preschool age, baseline sleep habit scores, surgery, and length-of-stay in pediatric wards (p < 0.05). The child’s age and surgical history were independent factors of sleep disturbance. Conclusions: The observed peak in sleep disturbances at 1-month post-PICU suggests that this period may be a critical window to develop and implement targeted interventions to improve sleep. The persistent sleep disorders highlight the need for long-term monitoring.

BACKGROUND:Elevated lactate is associated with vascular endothelial dysfunction, a factor that can contribute to organ failure in sepsis. However, the specific mechanisms involved have yet to be fully elucidated. Here, we investigated the role of enolase 1 (ENO1) lactylation in modulating the functions of endothelial cells (ECs) in sepsis pathogenesis. METHODS:The septic mouse model was established using two methods: cecal ligation and puncture (CLP) and intraperitoneal injection of LPS. AAV-ENO1 shRNA was administered to ablate ENO1 in vascular endothelial cells of mice. Tail vein injection of .5% Evans Blue Dye (EBD) was utilised to assess microvascular permeability in septic mice. Post-translational modification (PTM) mass spectrometry was employed to detect key proteins undergoing lactylation in endothelial cells. Additionally, CCK-8 assay, Transwell assay, and scratch wound healing assay were performed to evaluate the fundamental functions of ECs. Further investigations were conducted through Western blotting, Co-immunoprecipitation (CO-IP), RT-qPCR, RNA immunoprecipitation (RIP) and RNA sequencing to examine genes/proteins involved in vascular endothelial injury and their interactions. RESULTS:We found that elevated lactate in sepsis promoted the lactylation of ENO1 at the K71 residue, facilitated by the increased activity of the lactyltransferase P300. This modification reduced the binding of TRIM21 mRNA to ENO1, thereby preventing its degradation by limiting the recruitment of CNOT6. Consequently, the stability and expression of TRIM21 mRNA were enhanced. Elevated TRIM21 subsequently binds to vascular endothelial-cadherin (VE-Cadherin), promoting its ubiquitination and degradation, disrupting endothelial adherens junctions (AJs) and increasing endothelial permeability. Targeting the lactylation of ENO1 at K71 with a specific inhibitory peptide alleviated endothelial injury and improved survival rates in septic mice. CONCLUSIONS:These findings suggest that ENO1 lactylation plays a pivotal role in vascular endothelial dysfunction during sepsis. Inhibiting lactylation may offer a therapeutic strategy for sepsis treatment.

Abstract This study analysed bacterial infections and antimicrobial resistance (AMR) profiles of the top five pathogens in adult intensive care units (ICUs) and paediatric ICUs (PICUs) in China from 2017 to 2022, aiming to inform AMR surveillance and treatment guidelines. Antimicrobial susceptibility was assessed via automated systems or the Kirby-Bauer method, interpreted per Clinical and Laboratory Standards Institute breakpoints, and analysed using WHONET 5.6. 22,278 and 152,117 unduplicated clinical bacterial isolates were collected from 17 PICUs and 44 adult ICUs. The rate of Gram-negative bacteria was higher in adult ICUs than in PICUs (78.5% vs. 62.6%, P < 0.001). The top five clinical isolates in both departments were Staphylococcus aureus , Acinetobacter baumannii , Klebsiella pneumoniae , Pseudomonas aeruginosa , and Escherichia coli. From 2017 to 2022, E. coli , K. pneumoniae , and P. aeruginosa generally showed decreased resistance to most antimicrobial agents in adult ICUs, but increased resistance in PICUs. Resistance of A. baumannii and S. aureus to most antimicrobial agents decreased in both PICUs and adult ICUs. The resistance proportions of E. coli to ceftazidime-avibactam, ceftriaxone, and imipenem; K. pneumoniae to ceftazidime-avibactam and ceftriaxone; and P. aeruginosa to amikacin were higher in PICUs than in ICUs. For other detected antibacterial agents, all five pathogens showed higher resistance in adult ICUs than in PICUs ( P < 0.05). These data reveal a severe AMR burden in ICUs, with notable differences between PICUs and adult ICUs. Enhanced ICU-specific AMR surveillance, rigorous infection control, and optimised antibiotic stewardship are imperative to counter multidrug-resistant pathogens. Although escalating resistance trends remain a major concern in PICUs, significant reductions in resistance for several pathogens in adult ICUs likely reflect the impact of strengthened antimicrobial stewardship and infection control programs in China.

While caspofungin is increasingly used to treat invasive fungal infections in pediatric intensive care unit (PICU) patients, its pharmacokinetic profile in this population remains poorly understood, and current dosing regimens are not firmly supported by scientific evidence. This study aimed to characterize the population pharmacokinetics of caspofungin in critically ill children and to identify dosing strategies for optimal exposure. The prospective clinical study was conducted among pediatrics in PICU. Population pharmacokinetic analysis and Monte Carlo simulations were performed. A total of 138 plasma samples collected from 29 pediatric patients (0.33-16 years) were included in the final analysis. The two-compartment model with allometric scaling on body surface area (BSA, exponential 1 for volume of distribution and 0.66 for clearance) accurately described time courses of caspofungin. Extracorporeal membrane oxygenation (ECMO) significantly increased the central volume of distribution (effect coefficient 18.2). There was no significant difference in area under the concentration curve (AUC) between patients with and without ECMO support. Simulations demonstrated that tAUCss,24h/MIC-based PTA results showed no significant differences between ECMO and non-ECMO groups and supported the current dosing regimen. A fixed maintenance dose (MD) is appropriate for patients with BSA ≥ 1.4 m², while the standard BSA-based MD remains preferable for those with BSA <1.4 m². Our study confirmed the recommended caspofungin dosing regimen in Chinese critically ill PICU patients. Although the number of patients receiving ECMO in this study was limited, future studies with a larger ECMO population are warranted to further validate these findings.This study is registered with ClinicalTrials.gov as NCT04961593.

Indoleamine-2,3-dioxygenase 1 (IDO1) is the rate-limiting enzyme in tryptophan (Trp) catabolism along kynurenine (Kyn) pathway. Increased IDO1 activity has been noticed in patients with sepsis, while IDO1's involvement in sepsis, especially in the initial cytokine storm phase is not yet completely understood. Using the GEO database and clinical samples of sepsis, current study revealed that IDO1-AHR-CYP1A1 axis was significantly upregulated and closely related to cytokine storm in septic patients. With cell models of cytokine storm, it was found that IDO1 promoted cytokine storm and the apoptosis of model cells via AHR-CYP1A1, and IDO1-AHR-CYP1A1 axis correlated classic cytokine storm signal pathway including STAT3, NF-κB/STAT1, JNK/p38. With mouse models of septic cytokine storm, it was shown that IDO1 inhibitors could block the upregulated IDO1-AHR-CYP1A1 axis, reduce the enhanced inflammatory cytokine levels, decrease the phosphorylation of classic cytokine storm signal pathway, rescue organ damage, and increase survival rate. It was also found that IDO1 activation occurred after the increase of inflammatory cytokine levels. Therefore, classic cytokine storm signal pathways, inflammatory cytokines and IDO1-AHR-CYP1A1 axis form a tripartite interaction loop to promote cytokine storm. IDO1 inhibitors were able to block this process.

OBJECTIVES:To investigate the clinical sub-phenotype (SP) of pediatric acute kidney injury (AKI) and their association with clinical outcomes. METHODS:General status and initial values of laboratory markers within 24 hours after admission to the pediatric intensive care unit (PICU) were recorded for children with AKI in the derivation cohort (n=650) and the validation cohort (n=177). In the derivation cohort, a least absolute shrinkage and selection operator (LASSO) regression analysis was used to identify death-related indicators, and a two-step cluster analysis was employed to obtain the clinical SP of AKI. A logistic regression analysis was used to develop a parsimonious classifier model with simplified metrics, and the area under the curve (AUC) was used to assess the value of this model. This model was then applied to the validation cohort and the combined derivation and validation cohort. The association between SPs and clinical outcomes was analyzed with all children with AKI as subjects. RESULTS:In the derivation cohort, two clinical SPs of AKI (SP1 and SP2) were identified by the two-step cluster analysis using the 20 variables screened by LASSO regression, namely SPd1 group (n=536) and SPd2 group (n=114). The simplified classifier model containing eight variables (P<0.05) had an AUC of 0.965 in identifying the two clinical SPs of AKI (P<0.001). The validation cohort was clustered into SPv1 group (n=156) and SPv2 group (n=21), and the combined derivation and validation cohort was clustered into SP1 group (n=694) and SP2 group (n=133). After adjustment for confounding factors, compared with the SP1 group, the SP2 group had significantly higher incidence rates of multiple organ dysfunction syndrome and death during the PICU stay (P<0.001), and SP2 was significantly associated with the risk of death within 28 days after admission to the PICU (P<0.001). CONCLUSIONS:This study establishes a parsimonious classifier model and identifies two clinical SPs of AKI with different clinical features and outcomes.The SP2 group has more severe disease and worse clinical prognosis.

Sepsis-associated acute kidney injury (S-AKI) is a prevalent and life-threatening complication in hospitalized and critically ill patients. Recent researches indicates that immunoproteasome, especially proteasome 20S subunit beta 8 (PSMB8), is highly associated with various kidney diseases. This study aims to investigate the potential involvement of PSMB8 in S-AKI and its impact on apoptosis and inflammation. The model of S-AKI induced by LPS (10 mg/kg) was assessed by histological examination. ELISA and Real-time PCR were used to detect the levels of inflammatory cytokines in the renal cortex. The role of shPSMB8 in LPS-induced apoptosis was detected by flow cytometry. Finally, western blot was performed to assess the NF-kappa B signaling pathway related proteins, and the nuclear translocation of NF-kB P65 was detected by immunofluorescence microscopy. PSMB8 knockdown substantially protected against renal injury by reducing blood urea nitrogen and creatinine levels and ameliorating inflammation. PSMB8 knockdown inhibited renal expression of interleukin (IL)-1R, IL-6, tumor necrosis factor-alpha (TNF-alpha) and COX-2 to improve inflammatory response. Mechanistic studies demonstrated that downregulation of PSMB8 blocked LPS-induced S-AKI phosphorylation and nuclear translocation of NF-kappa B P65. Collectively, our results suggest that inhibition of PSMB8 significantly contributes to S-AKI via regulation of NF kappa B. These findings reveal the pathogenic role of PSMB8 in AKI and suggest a novel therapeutic target for the condition.

OBJECTIVE:This study aimed to analyze the profiles and evolution of Staphylococcus aureus in the pediatric intensive care units (PICUs) of 17 hospitals in China from 2016 to 2022. METHODS:Susceptibility testing was performed to bacterial strains with a uniform monitoring protocol, which was provided by the US Clinical and Laboratory Standards Institute (CLSI) and used by the China Antimicrobial Surveillance Network (CHINET). The results were interpreted in accordance with the performance standards for antimicrobial susceptibility testing issued by the US Clinical and Laboratory Standards Institute. RESULTS:Twenty-six thousand six hundred thirteen bacterial strains were isolated from 17 PICUs in China from 2016 to 2022, 3,147 of which were Staphylococcus aureus, ranking second among etiological agents of infections from PICUs. In 2022, Staphylococcus aureus had the highest detection rate, being 36.19%. And in 2021, MRSA had the highest detection rate, being 10.35% in Staphylococcus aureus. There were statistically significant differences in the annual detection rate of gram-positive bacteria, Staphylococcus aureus and MRSA between the years from 2016 to 2022 (P < 0.05). More males were found with Staphylococcus aureus or methicillin-resistant Staphylococcus aureus, but there were no statistical differences in gender distribution between any two years (P < 0.05). The top 3 highest detection rate of Staphylococcus aureus in age groups were infants (1244, 39.7%), toddlers (741, 23.7%), and children at school age and older (731, 23.4%). For MRSA, The top 3 in age groups were infants (91, 38.9%), children at school age and older (87, 29.1%), and toddlers (48, 20.5%). The detection rate of Staphylococcus aureus was statistically different in the distribution of age stratification (P < 0.05). There was no statistically significant difference in these two aspects of MRSA (P > 0.05). The top 3 highest detection rate of Staphylococcus aureus in infected sites were the lower respiratory tract (2,552, 81.7%), bloodstream (217, 6.5%), and skin wounds (110, 3.9%). For MRSA, The top 3 in infected sites were the lower respiratory tract (156, 77.9%), skin wounds (47, 8.8%), and bloodstream (15, 6.6%). The detection rate of Staphylococcus aureus and MRSA was statistically different in the distribution of infected sites (P < 0.05). All the strains of Staphylococcus aureus were sensitive to tigecycline, nitrofurantoin, vancomycin, and linezolid. The resistant rate of Staphylococcus aureus, to penicillin G was as high as 87.5% at least, to erythromycin was as high as 51.8% at least, to benzocillin was as high as 38.0% at least, to cefoxitin was as high as 35.5% at least, and to clindamycin was as high as 32.7% at least. All the strains of MRSA were sensitive to vancomycin, linezolid, quinupristin/dalfopristin, and tigecycline. Of these 234 strains of MRSA, 179 (76.5%) were resistant to erythromycin, 116 (49.6%) to clindamycin, 39 (16.7%) to tetracycline, 29 (12.4%) to levofloxacin, 27 (11.5%) to ciprofloxacin, 27 (11.5%) to moxifloxacin, 14 (6.0%) to TMP-SMX, eight (3.4%) to rifampicin, and six (2.6%) to gentamicin. CONCLUSIONS:Staphylococcus aureus is the most common gram-positive bacterium in PICUs. Infants are most likely to be infected by Staphylococcus aureus and methicillin-resistant Staphylococcus aureus. And the lower respiratory tract is the most common infected site of Staphylococcus aureus. Staphylococcus aureus has a high resistant rates to commonly used antimicriobials in pediatrics, but no strains resistant to vancomycin and/or linezolid were found. When considering Staphylococcus aureus infection clinically, it is necessary to select antimicrobials reasonably based on the patient's age, infected site and local epidemiological characteristics.

Background: The prognostic factors of extracorporeal membrane oxygenation (ECMO) as a kind of rescue therapy for children with refractory septic shock (RSS) and the optimal timing for ECMO intervention are critical for clinical work, but they are currently unclear. The study aims to explore the risk factors of prognosis of children with RSS on ECMO support and the optimal timing of ECMO intervention. parameters, and prognosis of enrolled children receiving ECMO support who were admitted consecutively to eight major pediatric ECMO centers in Chinese mainland from 2018-2020 were collected for analysis. Results: A total of 41 children with RSS were enrolled in the study, with a median age of 35.5 [interquartile range (IQR), 2, 169] months, of whom 25 (61.0%) were male. The overall survival discharge rate was 51.2%. For the survivors, the lactate value was 5.2 mmol/L and increased by 20% at the point of 6 hours after the diagnosis of RSS, while for the non-survivors, it was 11.2 mmol/L and increased by 60% (P=0.02 and 0.002). Those children who received ECMO support sooner had a higher survival rate (P=0.03). The median interval time from diagnosis of RSS to ECMO initiation was 6 (IQR, 5.0, 12.0) hours in the survival group and 13.8 (IQR, 9.5, 19.0) hours in the non-survival group (P=0.03). The mortality rate increased by 7.17 times when the interval exceeded 13.8 hours and by 10.96 times when the interval exceeded 20 hours. The multivariate analysis revealed that the 6-hour lactate value and the time interval between the diagnosis of RSS and ECMO initiation were significant predictors of prognosis in children with RSS. Conclusions: High 6-hour lactate value in children with RSS strongly predicts high mortality. The survival discharge rate of children with RSS may be improved when ECMO is initiated within 13.8 hours from RSS diagnosis.

Home mechanical ventilation improves survival of critically ill children but partially affects quality of life. Studies in China have more often analyzed the risk factors for death from prolonged mechanical ventilation in hospitalized children while less attention has been paid to children with home mechanical ventilation. This study aimed to describe the quality of life of children with home mechanical ventilation and the influencing factors. It was a prospective cohort study. The cohort population was children undergoing prolonged mechanical ventilation in the Pediatric Intensive Care Unit, with the outcome of whether they were alive or dead at 1-year follow-up after discharge. Standardized scores for quality of life were calculated using TNO-AZL Children’s Health-Related Quality of Life and TNO-AZL Preschool Children Quality of Life. Multiple linear regression was used to analyze the factors affecting the quality of life. A total of 106 children were included, and 11 children (10.38