Purpose: Pediatric delirium is a serious complication in critically ill children with limited effective treatments. This study aims to evaluate the efficacy and safety of Psychomotor Therapy (PMT)-a comprehensive rehabilitation system integrating motor, cognitive, emotional, and psychological domains-in treating pediatric delirium, and to characterize its underlying mechanisms through electroencephalographic (EEG) and brain network analyses. Patients and Methods: This is a single-center, assessor-blinded, randomized controlled trial. A total of 34 participants (22 children with delirium aged 2 months to 14 years, meeting Richmond Agitation-Sedation Scale [RASS] and Cornell Assessment of Pediatric Delirium [CAPD] criteria, plus 6 children without any neurological disorders, managed within the same clinical environment) will be enrolled. Participants will be randomized to receive either PMT plus routine care or routine care alone. The PMT intervention will be administered once daily for 3 days. Primary outcome is the change in CAPD score. Secondary outcomes include delirium duration, EEG parameters, length of PICU stay, and safety. Assessments will be conducted at multiple time points before and after intervention. Results: This is a study protocol; as data collection is currently ongoing (January 2023-July 2026), final results are not yet available for analysis or reporting. Conclusion: The study has been approved by the ethics boards of Shanghai Yangzhi Rehabilitation Hospital and Shanghai Children's Hospital and will adhere to the Declaration of Helsinki. Findings will be disseminated via scientific conferences and publications. Key strengths include the first investigation of brain functional networks in pediatric delirium, incorporation of an environmental control group to mitigate confounding, and pioneering application of PMT. Limitations include single-center design and geographical restriction to Shanghai, necessitating future multi-center studies with larger samples.
Objective: To assess the outcome of patients with cancer-related sepsis requiring continuous renal replacement therapy (CRRT) in a single-center pediatric intensive care unit (PICU). Method: Children with sepsis who necessitate CRRT from January 2017 to December 2021 were enrolled. The patients with leukemia/lymphoma or solid tumors were defined as underlying cancer. Multivariate logistic regression analysis was performed to identify the death risk factors in patients with cancer-related sepsis. Results: A total of 146 patients were qualified for inclusion. Forty-six (31.5%) patients with cancer-related sepsis and 100 (68.5%) non-cancer-related sepsis. The overall PICU mortality was 28.1% (41/146), and mortality was significantly higher in cancer-related sepsis patients compared with non-cancer patients (41.3% vs . 22.0%, p = 0.016). Need mechanical ventilation, p-SOFA, acute liver failure, higher fluid overload at CRRT initiation, hypoalbuminemia, and high inotropic support were associated with PICU mortality in cancer-related sepsis patients. Moreover, levels of IL-6, total bilirubin, creatinine, blood urea nitrogen, and international normalized ratio were significantly higher in non-survivors than survivors. In multivariate logistic regression analysis, pediatric sequential organ failure assessment (p-SOFA) score (OR:1.805 [95%CI: 1.047-3.113]) and serum albumin level (OR: 0.758 [95%CI: 0.581-0.988]) were death risk factors in cancer-related sepsis receiving CRRT, and the AUC of combined index of p-SOFA and albumin was 0.852 (95% CI: 0.730-0.974). Conclusion: The overall PICU mortality is high in cancer-related sepsis necessitating CRRT. Higher p-SOFA and lower albumin were independent risk factors for PICU mortality. (c) 2024 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
Objective: To summarize the pathogenic characteristics of bloodstream infection (BSI)-induced severe sepsis and analyze the influence factors in pediatric intensive care unit (PICU). Methods: Pediatric patients who were diagnosed with severe sepsis caused by BSI in the PICU of Children's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from January 2016 to December 2021 were retrospectively selected and divided into survival group and death group according to their discharge outcomes. Clinical characteristics, laboratory parameters, pathogenic characteristics and drug resistance of the patients were collected. The characteristics of pathogens, clinical and laboratory indicators were summarized, and the influencing factors of death in children with severe sepsis caused by BSI were analyzed based on binary multivariate logistic regression. Results: A total of 132 patients, aged [M (Q1, Q3)] 36 (10, 119) months, with BSI-induced severe sepsis were enrolled in this study, including 81 males and 51 females. There were 38 cases aged 36 (15, 120) months in the death group, including 23 males and 15 females. There were 94 cases, aged 36 (8, 108) months, in the survival group, including 58 males and 36 females. A total of 132 strains of pathogens were isolated, including 87 strains (65.9%) of Gram-negative bacteria. The top 5 pathogens were Klebsiella pneumoniae (24 cases, 18.2%), Escherichia coli (17 cases, 12.9%), Acinetobacter baumannii (13 cases, 9.8%), Pseudomonas aeruginosa (10 cases, 7.6%) and Staphylococcus aureus (10 cases, 7.6%). The proportion of multi-drug resistant bacteria in hospital-acquired BSI was higher than that in community-acquired BSI [52.9% (36/68) vs 15.6% (10/64), P=0.001]. The proportions of community-acquired infection were 58.5% (55/94) and 23.7% (9/38) in the survival and death groups, respectively, the difference was statistically significant (P<0.001). The proportion of central venous catheter insertion before bloodstream infection in the death group was higher than that in the survival group [63.2% (24/38) vs 42.6% (40/94), P=0.034]. According to the binary multivariate logistic regression analysis, hospital-acquired infection (OR=4.80, 95%CI: 1.825-12.621, P=0.001), absolute neutrophil count (ANC) (OR=0.93, 95%CI: 0.863-0.993, P=0.030) and decreased albumin (OR=0.89, 95%CI: 0.817-0.977, P=0.014) were risk factors for death. Conclusions: The common pathogen of BSI-induced severe sepsis in PICU is Gram-negative bacteria. The proportion of multi-drug resistant organisms of BSI obtained in hospitals is high. Children with severe sepsis due to BSI with nosocomial acquired infection, ANC and decreased albumin have a high risk of death.
BACKGROUND:Advanced glycation end product receptor (RAGE) acts as a receptor of pro-inflammatory ligands and is highly expressed in alveolar epithelial cells (AECs). Autophagy in AECs has received much attention recently. However, the roles of autophagy and RAGE in the pathogenesis of acute lung injury remain unclear. Therefore, this study aimed to explore whether RAGE activation signals take part in the dysfunction of alveolar epithelial barrier through autophagic death.METHODS:Acute lung injury animal models were established using C57BL/6 and Ager gene knockout (Ager -/- mice) mice in this study. A549 cells and primary type II alveolar epithelial (ATII) cells were treated with siRNA to reduce Ager gene expression. Autophagy was inhibited by 3-methyladenine (3-MA). Lung injury was assessed by histopathological examination. Cell viability was estimated by cell counting kit-8 (CCK-8) assay. The serum and bronchoalveolar lavage fluid (BALF) levels of interleukin (IL)-6, IL-8 and soluble RAGE (sRAGE) were evaluated by Enzyme-linked immunosorbent assay (ELISA). The involvement of RAGE signals, autophagy and apoptosis was assessed using western blots, immunohistochemistry, immunofluorescence, transmission electron microscopy and TUNEL test.RESULTS:The expression of RAGE was promoted by lipopolysaccharide (LPS), which was associated with activation of autophagy both in mice lung tissues and A549 cells as well as primary ATII cells. sRAGE in BALF was positively correlated with IL-6 and IL-8 levels. Compared with the wild-type mice, inflammation and apoptosis in lung tissues were alleviated in Ager-/- mice. Persistently activated autophagy contributed to cell apoptosis, whereas the inhibition of autophagy by 3-MA protected lungs from damage. In addition, Ager knockdown inhibited LPS-induced autophagy activation and attenuated lung injury. In vitro, knockdown of RAGE significantly suppressed the activation of LPS-induced autophagy and apoptosis of A549 and primary ATII cells. Furthermore, RAGE activated the downstream STAT3 signaling pathway.CONCLUSION:RAGE plays an essential role in the pathogenesis of ATII cells injury. Our results suggested that RAGE inhibition alleviated LPS-induced lung injury by directly suppressing autophagic apoptosis of alveolar epithelial cells.
目的 了解2岁以下儿童不同体型匀称度的流行现状及其风险因素,为制定早期干预措施提供依据.方法 数据来源于2020-2022年上海市儿童医院儿童保健科生长发育评估与随访系统,共计纳入8 474名2岁以下儿童,测量体格生长发育指标,并回顾性收集儿童出生及父母情况等构建数值表,采用SPSS 26.0软件分析不同体型匀称度的流行情况和风险因素,组间比较采用x2检验,回归采用多因素Logistic回归分析.结果 研究纳入2岁以下常规健康体检男童3 813例,女童4 661例,其中消瘦、超重、肥胖总检出率分别为1.5%,19.0%,7.8%,男童超重、肥胖的检出率均高于女童(x2分别为17.597、12.653,P<0.01).出生体质量>4 000g、大于胎龄儿、头围偏大儿童发生超重和肥胖的风险均增加,出生体质量<2 500g儿童发生肥胖的风险高于正常组,头围偏小、小于胎龄儿人群的消瘦风险较高(P<0.05).父母超重或肥胖的儿童发生超重肥胖风险高于正常人群(P<0.05),剖宫产为儿童期肥胖的风险因素(RR=1.33,95%CI:1.15~1.53,P<0.01).Logistic回归分析结果显示,男童、头围、相对于胎龄的出生体质量、父母BMI是儿童超重、肥胖的有效预警指标(P<0.01).结论 2岁以内儿童超重、肥胖检出率较高,消瘦现象仍然存在,儿童体格良性发展需多方共同努力,实现早期预防和干预.
Background Continuous renal replacement therapy (CRRT) has been considered as an adjuvant therapy for sepsis. However, the novel biomarker to evaluate the benefits of CRRT is limited. The aim of this study was to explore the novel biomarkers involved in the impact of CRRT in pediatric sepsis. Methods The serum proteomic profiles on the 7th day after CRRT (CRRT 7th day) compared with before CRRT (CRRT 1st day) was determined in 3 children with sepsis as a discovery set. The screened candidates were confirmed in the validation cohort including patients received CRRT (CRRT group) and without CRRT (non-CRRT group). We defined that pediatric sequential organ failure assessment score (pSOFA) in pediatric patients with sepsis decreased by 2 points or more on the CRRT 1st day compared with CRRT initiation as CRRT responders. The changes of serum biomarkers were compared between CRRT responders and CRRT non-responders. Moreover, correlation analysis was further conducted in pediatric sepsis. Results A total of 145 differentially expressed proteins were found according to the serum proteomics profiles. By visualizing the interaction between the differential proteins, 6 candidates (Lysozyme C [LYZ], Leucine-rich alpha-2-glycoprotein [LRG1], Fibromodulin [FMOD], Alpha-1-antichymotrypsin [SERPINA3], L-selectin [SELL], Monocyte differentiation antigen CD14 [CD14]) were screened. In the validation cohort, serum levels of LYZ and LRG1 showed a higher trend on the CRRT 7th day than that on the 1st day in the non-CRRT group. However, the changes in levels of LYZ and LRG1 on the 7th day was significant in the CRRT group (p = 0.016, p = 0.009, respectively). Moreover, the levels of LYZ and LRG1 on the CRRT 7th day in the CRRT group were significantly higher than that in the non-CRRT group (p < 0.001, p = 0.025). Decreased levels of CD14 were associated with sepsis recovery, but not associated with CRRT. There were no significantly difference in serum FMOD, SERPINA3, and SELL levels. Importantly, serum LYZ and LRG1 levels changed in CRRT responders, but not CRRT non-responders. Further analysis indicated that serum LYZ levels were correlated to total platelet counts, aspartate aminotransferase (ALT), alanine aminotransferase (AST), and albumin levels, and serum LRG1 level were correlated to total platelet count and TBIL levels on the 1st day in the CRRT group. Protein–protein interaction network analysis displayed that serum LYZ and LRG1 were involved in the process of inflammatory response, leucocytes adhesion to vascular endothelial cell, as well as complement activation. Conclusion Elevated serum LYZ and LRG1 levels are associated with clinical benefits of CRRT during sepsis.
BackgroundMyeloid-derived suppressor cells (MDSCs) expansion is an important mechanism underlying immunosuppression during sepsis. Though continuous renal replacement therapy (CRRT) may attenuate hyperinflammatory response in sepsis, its role in regulating MDSCs is unknown. The aim of this study was to assess the potential role of CRRT involved in sepsis-induced MDSCs expansion in pediatric sepsis. MethodThe proportion of polymorphonuclear MDSCs (PMN-MDSCs) was detected before CRRT (pre-CRRT), at 24 hours after CRRT (CRRT 1(st) day) and on the 7(th) day after CRRT (CRRT 7(th) day). The correlation analyses were performed to elucidate the relationship of MDSCs with clinical indexes in sepsis. ResultsTotally 22 pediatric patients with sepsis were enrolled [median age 44 (IQR15, 83) months]. PMN-MDSCs were expanded in pediatric sepsis compared with healthy controls (4.30% vs. 0.37%, P=0.04). The proportion of PMN-MDSCs showed a decreased tendency on the CRRT 7(th) day compared with that on the CRRT 1(st) day in survivors (2.29% vs.5.32%, P = 0.088). There was no significant difference in the proportion of PMN-MDSCs between survivors and non-survivors before CRRT (4.51% vs. 3.33%, P=0.745). The levels of interleukin 6 (IL-6) was decreased on the CRRT 7(th) day compared with CRRT 1(st) day in survivors. In the subgroups of patients with significantly decreased IL-6 levels after CRRT, the proportion of PMN-MDSCs on the CRRT 7(th) day were also significantly decreased compared with that on the CRRT 1(st) day (2.21% vs. 6.67%, P = 0.033). ConclusionThe proportion of PMN-MDSCs was down-regulated on the CRRT 7(th) day in survivors with sepsis. The reduced PMN-MDSCs expansion may relate to decreased IL-6 level.
Miao, H.1; Cui, Y.1; Lu, Y.1; Sun, T.1; Dou, J.1; Ren, Y.1; Wang, C.2; Zhang, Y.3 Author Information
Objective:The aim of this study was to assess the prognostic value of the lung ultrasound (LUS) score in patients with pediatric acute respiratory distress syndrome (pARDS) who received extracorporeal membrane oxygenation (ECMO).Methods:A prospective cohort study was conducted in a pediatric intensive care unit (PICU) of a tertiary hospital from January 2016 to June 2021. The severe pARDS patients who received ECMO were enrolled in this study. LUS score was measured at initiation of ECMO (LUS-0 h), then at 24 h (LUS-24 h), 48 h (LUS-48 h), and 72 h (LUS-72 h) during ECMO, and when weaned from ECMO (LUS-wean). The value of LUS scores at the first 3 days of ECMO as a prognostic predictor was analyzed.Results:Twenty-nine children with severe pARDS who received ECMO were enrolled with a median age of 26 (IQR 9, 79) months. The median duration of ECMO support was 162 (IQR 86, 273) h and the PICU mortality was 31.0% (9/29). The values of LUS-72 h and LUS-wean were significantly lower in survivors than that in non-survivors (both P < 0.001). Daily fluid balance volume during the first 3 days of ECMO support were strongly correlated with LUS score [1st day: r = 0.460, P = 0.014; 2nd day: r = 0.540, P = 0.003; 3rd day: r = 0.589, P = 0.001]. The AUC of LUS-72 h for predicting PICU mortality in these patients was 1.000, and the cutoff value of LUS-72 h was 24 with a sensitivity of 100.0% and a specificity of 100.0%. Furthermore, patients were stratified in two groups of LUS-72 h ≥ 24 and LUS-72 h < 24. Consistently, PICU mortality, length of PICU stay, ratio of shock, vasoactive index score value, and the need for continuous renal replacement therapy were significantly higher in the group of LUS-72 h ≥ 24 than in the group of LUS-72 h < 24 (all P < 0.05).Conclusion:Lung ultrasound score is a promising tool for predicting the prognosis in patients with ARDS under ECMO support. Moreover, LUS-72 h ≥ 24 is associated with high risk of PICU mortality in patients with pARDS who received ECMO.
Background Extracorporeal membrane oxygenation (ECMO) has been increasingly used as rescue therapy for severe pediatric acute respiratory distress syndrome (PARDS) over the past decade. However, a contemporary comparison of venovenous (VV) and venoarterial (VA) ECMO in PARDS has yet to be well described. Therefore, the objective of our study was to assess the difference between VV and VA ECMO in efficacy and safety for infection-associated severe PARDS patients. Methods This prospective multicenter cohort study included patients with infection-associated severe PARDS who received VV or VA ECMO in pediatric intensive care units (PICUs) of eight university hospitals in China between December 2018 to June 2021. The primary outcome was in-hospital mortality. Secondary outcomes included ECMO weaning rate, duration of ECMO and mechanical ventilation (MV), ECMO-related complications, and hospitalization costs. Results A total of 94 patients with 26 (27.66%) VV ECMO and 68 (72.34%) VA ECMO were enrolled. Compared to the VA ECMO patients, VV ECMO patients displayed a significantly lower in-hospital mortality (50 vs. 26.92%, p = 0.044) and proportion of neurologic complications, shorter duration of ECMO and MV, but the rate of successfully weaned from ECMO, bleeding, bloodstream infection complications and pump failure were similar. By contrast, oxygenator failure was more frequent in patients receiving VV ECMO. No significant intergroup difference was observed for the hospitalization costs. Conclusion These positive findings showed the conferred survival advantage and safety of VV ECMO compared with VA ECMO, suggesting that VV ECMO may be an effective initial treatment for patients with infection-associated severe PARDS.
To assess the outcome of extracorporeal membrane oxygenation (ECMO) for severe adenovirus (Adv) pneumonia with refractory hypoxic respiratory failure (RHRF) in paediatric patients. A retrospective observational study was performed in a tertiary paediatric intensive care unit (PICU) in China. Patients with RHRF caused by Adv pneumonia who received ECMO support after mechanical ventilation failed to achieve adequate oxygenation between 2017 and 2020 were included. The outcome variables were the in-hospital survival rate and the effects of ECMO on the survival rate. In total, 18 children with RHRF received ECMO. The median age was 19 (9.5, 39.8) months, and the median ECMO duration was 196 (152, 309) h. The in-hospital survival rate was 72.2% (13/18). Thirteen patients (72.2%) required continuous renal replacement therapy (CRRT) due to fluid imbalance or acute kidney injury (AKI). At ECMO initiation, compared with survivors, nonsurvivors had a lower PaO2/FiO2 ratio [49 (34.5, 62) vs. 63 (56, 71); p = 0.04], higher oxygen index (OI) [41 (34.5, 62) vs. 30 (26.5, 35); p = 0.03], higher vasoactive inotropic score (VIS) [30 (16.3, 80) vs. 100 (60, 142.5); p = 0.04], longer duration from mechanical ventilation to ECMO support [8 (4, 14) vs. 4 (3, 5.5) h, p=0.02], and longer time from confirmed RHRF to ECMO initiation [9 (4.8, 13) vs. 5 (1.3, 5.5) h; p = 0.004]. Patients with PaO2/FiO2 <61 mmHg or an OI >43 and hypoxic respiratory failure for more than 9 days before the initiation of ECMO had worse outcomes. ECMO seemed to be effective, as severe paediatric Adv pneumonia patients with RHRF had a cumulative survival rate of 72.2% in our study. Our study provides insight into ECMO rescue in children with severe Adv pneumonia.
Objective:To investigate the clinical characteristics and prognosis of children with acute pancreatitis(AP)admitted to the pediatric intensive care unit(PICU).Methods:The etiology, clinical data, imaging features, complications, and outcomes of children with AP admitted to PICU at Shanghai Children′s Hospital from July 2016 to June 2021 were retrospectively analyzed.Results:Totally, 47 patients with AP including 24 males and 23 females were enrolled.The mean age was 84(48, 144)months.Four patients with mild AP, 5 patients with moderately severe AP(MSAP)and 38 cases with severe AP(SAP)were diagnosed.The main etiology was drug-related pancreatitis in 23 cases(48.9%). The organ dysfunction mainly included shock in 28 cases(59.6%), acute respiratory failure in 21 cases(44.7%), gastrointestinal disorders in 30 cases(63.8%), and coagulopathy in 29 cases(61.7%). The complications included capillary leakage syndrome in 18 cases(38.3%)and hyperglycemia(>8 mmol/L)in 24 cases(51.1%). Serum amylase and lipase levels were increased in 47 cases(100%). There were significant differences in blood lactate[3.0(2.1, 4.5)mmol/L vs.1.6(1.1, 3.1)mmol/L, P=0.013], and the use of vasoactive drugs[15.0(0, 75.0)vs.0(0, 8.8), P=0.035] between drug-induced pancreatitis and non-drug-induced pancreatitis.All the patients′conditions were improved after treatment and transferred out of PICU. Conclusion:The etiology of acute pancreatitis in children is mainly drug-related, and the main organ dysfunction includes shock, acute respiratory failure, gastrointestinal dysfunction and coagulation dysfunction.The prognosis of childhood pancreatitis is good.
Objective:To summarize the clinical features, imaging changes, treatment, and prognosis of children with severe autoimmune encephalitis (AE).Methods:A retrospective study was conducted on patients with severe AE admitted to PICU of Shanghai Children’s Hospital from June 2017 to May 2020. Clinical features, treatment protocols and follow-up data were collected.Results:A total of 27 children were included, among which 18 cases (66.7%) were girls. The on-set age was (7.9±3.2) years. Eighteen cases were diagnosed with anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis. Fever (77.8%), headache (40.7%) and vomiting (44.4%) were most of prodromal symptoms in children with severe AE. Patients’ neurological symptoms showed seizures (88.9%), mental behavior abnormalities (81.5%), speech disorders (70.4%) and dyskinesia (70.4%). Moreover, epileptic discharge and slow wave activity were critical feature of electroencephalogram (EEG) abnormalities, and the abnormal signal changes on T2-weighted and FLAIR sequence of head MRI were in the posterior horn of the lateral ventricle. In addition, the main comorbidities included refractory status epilepticus (RSE), cardiovascular dysfunction, central hypoventilation syndrome and acute intracranial hypertension syndrome. For patients with central respiratory failure, the median duration of mechanical ventilation was 19.8 (14.8, 29.1) days. According to treatment protocol, the first-line immune treatment included the combination therapies of methylprednisolone, intravenous immunoglobulin (IVIG) and therapeutic plasma exchange (TPE). Eighteen cases were given with methylprednisolone [10-30 mg/(kg. d), 3-5 d] + IVIG (2 g/kg, within 2 d) + TPE, 1 case was treated with methylprednisolone [10-30 mg/(kg·d), 3-5 d] + TPE and 8 cases were given with[10-30 mg/(kg·d), 3-5 d] + IVIG (2 g/kg, within 2 d). Sequential therapy was given with methylprednisolone (1-2 mg/kg), gradually reduced from 3 to 6 months. Finally, 16 children (59.3%) had neurological damages at the first discharge, among which 8 cases (29.6%) were with dyskinesia, 5 cases (18.5%) were with speech disturbance, and 5 cases (18.5%) were with abnormal mental behaviors.Conclusions:The most of first clinical symptom is epileptic seizures in pediatric severe AE, and most of these patients are diagnosed with Anti-NMDA receptor encephalitis. RSE, cardiovascular dysfunction, central respiratory and acute intracranial hypertension syndrome constitute to main organ dysfunctions.
目的:探讨儿童重症监护病房(PICU)收治意外伤害的临床特征和危险因素。方法:回顾性总结上海交通大学附属儿童医院2017年1月至2019年12月因意外伤害收住PICU的患儿。分存活组和死亡组,比较临床特点与实验室指标的差异,多因素Logistic回归筛选死亡的危险因素和受试者工作特征曲线确定其阈值。结果:(1)意外伤害患儿253例,占同期PICU住院总数的5.2%。男137例(54.2%),女116例(45.8%),平均中位年龄45(19,96)个月。前3位病因依次为坠落伤82例(32.4%)、交通意外70例(27.7%)、异物39例(15.4%)。死亡22例,病死率8.7%。(2)死亡组入院时平均动脉压低于存活组( P<0.05),总住院时间较长( P<0.001),格拉斯哥昏迷评分、小儿死亡风险评分Ⅲ(PRISM Ⅲ)组间差异显著( P均<0.001)。死亡组患儿入PICU时血乳酸明显升高( P<0.001),血红蛋白、纤维蛋白原低于存活组,活化部分凝血活酶时间与凝血酶原时间明显延长( P均<0.001)。(3)多因素Logistic回归分析显示入院时PRISM Ⅲ评分、血乳酸和凝血酶原时间是死亡的独立危险因素。受试者工作特征曲线分析显示,PRISM Ⅲ评分预测意外伤害患儿死亡的曲线下面积最高,为0.987(95% CI 0.976~0.999, P<0.001),阈值11分,敏感度与特异度分别为100%和95.7%;血乳酸的曲线下面积为0.886(95% CI 0.810~0.961, P<0.001),阈值为3.1 mmol/L,敏感度85.7%,特异度77.3%;凝血酶原时间的曲线下面积为0.835(95% CI 0.730~0.941, P<0.001),阈值为13.9 s,敏感度86.6%,特异度72.7%。 结论:近3年本院PICU收治意外伤害主要为坠落伤、交通意外和异物损伤。入院时PRISM Ⅲ评分、血乳酸和凝血酶原时间是预测死亡的独立危险因素。
Background. Systemic inflammatory response and vascular endothelial cell injury during sepsis lead to coagulopathy. Fibrinogen has been reported as a biomarker of coagulopathy; however, the prognostic value of fibrinogen remains undefined in pediatric patients with sepsis. The aim of this study was to assess fibrinogen level on pediatric intensive care unit (PICU) admission and to elucidate the relationship between fibrinogen levels and in-hospital mortality in children with sepsis. Methods. We conducted a database study. The sepsis database was divided into a training set (between July 2014 and June 2018) and a validation set (from July 2018 to June 2019). The clinical and laboratory parameters on PICU admission and in-hospital mortality in sepsis database were collected and analyzed. Results. A total of 819 pediatric patients were included from database as a training set. The overall hospital mortality was 12.1% (99/819). The fibrinogen levels were significantly lower in nonsurvivors than survivors. Multivariate logistic regression analysis showed significant associations between fibrinogen, lactate level, and hospital mortality (fibrinogen: odds ratio (OR), 0.767 (95% CI: 0.628-0.937), P=0.009; lactate: OR, 1.346 (95% CI: 1.217-1.489), P<0.001, respectively), which was confirmed in a validation set (0.616 [95% CI: 0.457-0.829], P=0.001; 1.397 [95% CI: 1.245-1.569], P<0.001, respectively). The hospital mortality of patients with fibrinogen<1 g/L, 1-2 g/L, 2-3 g/L, or over 3 g/L displayed an obvious difference (62.5% vs. 27.66% vs. 18.1% vs. 4.2%, respectively). Furthermore, the area under the receiver operating characteristic curve (ROC) for fibrinogen in predicting hospital mortality was 0.780 (95% CI: 0.711-0.850) in pediatric patients with sepsis. Conclusions. Fibrinogen is a valuable prognostic biomarker for pediatric sepsis. The level of fibrinogen lower than 2 g/L on PICU admission is closely related to the greater risk of hospital death in pediatric sepsis.
Background: Thyroid hormone plays an important role in the adaptation of metabolic function to critically ill. The relationship between thyroid hormone levels and the outcomes of septic shock is still unclear. The aim of this study was to assess the predictive value of thyroid hormone for prognosis in pediatric septic shock. Methods: We performed a prospective observational study in a pediatric intensive care unit (PICU). Patients with septic shock were enrolled from August 2017 to July 2019. Clinical and laboratory indexes were collected, and thyroid hormone levels were measured on PICU admission. Results: Ninety-three patients who fulfilled the inclusion criteria were enrolled in this study. The incidence of nonthyroidal illness syndrome (NTIS) was 87.09% (81/93) in patients with septic shock. Multivariate logistic regression analysis showed that T4 level was independently associated with in-hospital mortality in patients with septic shock (OR: 0.965, 95% CI: 0.937-0.993, p= 0.017). The area under receiver operating characteristic (ROC) curve (AUC) for T4 was 0.762 (95% CI: 0.655-0.869). The cutoff threshold value of 58.71 nmol/L for T4 offered a sensitivity of 61.54% and a specificity of 85.07%, and patients with T4 < 58.71 nmol/L showed high mortality (60.0%). Moreover, T4 levels were negatively associated with the pediatric risk of mortality III scores (PRISM III), lactate (lac) level in septic shock children. Conclusions: Nonthyroidal illness syndrome is common in pediatric septic shock. T4 is an independent predictor for in-hospital mortality, and patients with T4 <58.71 nmol/L on PICU admission could be with a risk of hospital mortality.
Background Sepsis induces the release of lipid mediators, which control both lipid metabolism and inflammation. However, the role of serum apolipoprotein A-V (ApoA5) in sepsis is poorly understood in pediatric patients. Methods ApoA5 was screened from serum proteomics profile in lipopolysaccharide- (LPS-) treated mice for 2 h, 24 h, and controls. Then, we conducted a prospective pilot study, and patients with sepsis admitted to a pediatric intensive care unit (PICU) were enrolled from January 2018 to December 2018. Serum ApoA5 levels on PICU admission were determined using enzyme-linked immunosorbent assays (ELISA). Blood samples from 30 healthy children were used as control. The correlation of ApoA5 with the clinical and laboratory parameters was analyzed. Logistic regression analyses and receiver operating characteristic curve (ROC) analysis were used to investigate the potential role of serum ApoA5 as a prognostic predictor for PICU mortality in pediatric patients with sepsis. Results A total of 101 patients with sepsis were enrolled in this study. The PICU mortality rate was 10.9% (11/101). Serum ApoA5 levels on PICU admission were significantly lower in nonsurvivors with sepsis compared with survivors (P = 0.009). In subgroup analysis, serum levels of ApoA5 were significantly correlated with sepsis-associated multiple organ dysfunction syndrome (MODS) (P < 0.001), shock (P = 0.002), acute kidney injury (AKI) (P < 0.001), acute liver injury (ALI) (P = 0.002), and gastrointestinal (GI) dysfunction (P = 0.012), but not respiratory failure, brain injury, and pathogenic species (all P > 0.05). Correlation analyses revealed significant correlations of serum ApoA5 with Ca2+ concentration. Remarkably, the area under ROC curve (AUC) for serum ApoA5 levels on PICU admission was 0.789 for prediction of PICU mortality with a sensitivity of 75% and a specificity of 84.5% at a threshold value of 822 ng/mL. Conclusions Serum ApoA5 level is associated with sepsis-associated shock, AKI, ALI, GI dysfunction, or MODS in children. Moreover, the findings of the present study suggest a prognostic value of ApoA5 in children with sepsis, and lower serum ApoA5 than 822 ng/mL predicts worse outcome in pediatric sepsis.
Background: Sepsis-associated liver injury (SALI) is a risk factor of poor outcome in patients with sepsis. The early warning biomarkers for identifying SALI remain poorly defined. Aims: To identify the potential predictors of occurrence of SALI in pediatric patients with sepsis. Methods: We retrospectively analyzed the sepsis database based on the medical records of patients admitted to the pediatric intensive care unit (PICU) in Shanghai Children's Hospital from July 2014 to June 2018. Patients' demographics, co-morbidities and laboratory variables were collected. Univariate and multivariate logistic analysis were used to explore risk factors of SALI, and receiver operating characteristic (ROC) curve analysis was used to evaluate their predictive significances for SALI occurrence. Results: Of 1,645 eligible patients, 1,147 patients were included, and 105 cases had SALI. The indexes including AST-to-platelet ratio index (APRI), γ-GT and lactate dehydrogenase (LDH) were independent risk factors for SALI. Moreover, APRI was powerful to predict SALI in children (AUC: 0.889, 95% CI: 0.851-0.927) with a sensitivity of 84.6 % and a specificity of 84.3 % at the cutoff point of 0.340. APRI was superior to LDH and not inferior to γ-GT for predicting SALI. Conclusion: APRI is an independent risk factor of SALI occurrence, and elevated APRI within 24 h after PICU admission (>0.340) is a potential predictor for SALI in children.
Objective To investigate the association and predictive value of aspartate transaminase to platelet ratio index(APRI) in sepsis-associated liver injury(SALI). Methods We retrospectively ana-lyzed the medical records of patients with sepsis admitted to PICU in Shanghai Children′s Hospital of Shanghai Jiaotong University from April 2015 to March 2017. According to whether liver injury occurred in the sepsis patients during hospitalization,all the patients were divided into SALI group (n=34) and sepsis group(n=222). The clinical characteristics,serological indexes within 24 hours in the PICU,and the ratio of aspartate transaminase to alanine transaminase( AAR) and APRI were collected and analyzed. The receiver operating characteristic( ROC) curve was used to evaluate the power of APRI for the prediction of SALI. Results (1)A total of 256 patients were enrolled in this study. There were 34 cases with SALI,and there were 222 patients with sepsis only,the incidence of SALI was 13. 3%. (2) The values of APRI and AAR were both higher in the SALI group compared with the sepsis group[APRI:7. 12(1. 71,26. 96) vs. 0. 38 (0. 21,0. 83),P<0. 001;AAR:1. 43(0. 94,2. 69) vs. 2. 17(1. 35,2. 96),P<0. 05]. (3)The multivariate Logistic regression analysis showed that total bilirubin, APRI, AAR and platelet were the independent risk factors of SALI(P<0. 05). (4)In addition,the area under the ROC curve(AUC)for the APRI was 0. 891 (95%CI 0. 815-0. 966,P<0. 001),cut-off value was 1. 73,which was superior to total bilirubin(AUC =0. 744,95%CI 0. 634-0. 853,P<0. 001) and platelet(AUC=0. 726,95%CI 0. 611-0. 841,P<0. 001). The clinical sensitivity and specificity of the APRI for identification of SALI from sepsis was 80. 0% and 92. 2%, respectively. Conclusion APRI is an independently risk factor for the occurrence of SALI and is a precursory marker for SALI.
INTRODUCTION:Acute myeloid leukemia (AML) is a common malignancy of the hematopoietic system. In bone marrow samples of AML patients, PDIA3 expression was higher than that in the samples of healthy controls. We aimed at exploring the effect of PDIA3 siRNA on proliferation, apoptosis, migration, and invasion of AML HL-60 and HEL cells.MATERIALS AND METHODS:RT-PCR was performed to identify PDIA3 expression. Cell proliferation was assessed by MTT. Flow cytometry analysis and transwell were used to detect cell apoptosis, migration and invasion. Gene set enrich-ment analysis (GSEA) was employed to explore the PDIA 3-associated pathways in AML. Western blotting was used for protein expression detection.RESULTS:PDIA3 siRNA significantly inhibited the proliferation of AML cells at 24 and 48 h. PDIA3 siRNA notably enhanced the percentage of apoptotic cells. The migration and invasion abilities of HL-60 and HEL cells in the PDIA3 siRNA group were significantly suppressed compared with those in the control and siNC groups. GSEA of the Cancer Genome Atlas dataset showed that Kyoto Encyclopedia of Genes and Genomes oxidative phosphorylation and amino sugar and nucleotide sugar metabolism pathways could be correlated with PDIA3 expression; this was further confirmed in AML cells by Western blotting. MAPK signaling was also blocked by PDIA3 siRNA.CONCLUSION:PDIA3 siRNA effectively enhanced apoptosis, and suppressed proliferation, invasion, and migration of AML cells by regulating oxidative phosphorylation and amino sugar and nucleotide sugar metabolism pathways, and MAPK signaling, which can provide novel therapeutic targets for AML.