Characteristics and spectrum changes of PICU cases during the COVID-19 pandemic: a retrospective analysis.

Objective: This study aims to compare the changes in the disease spectrum of children admitted to the Pediatric Intensive Care Units (PICU) during the COVID-19 pandemic with the three years prior to the pandemic, exploring the impact of the COVID-19 pandemic on the disease spectrum of PICU patients. Methods: A retrospective analysis was conducted on critically ill children admitted to the PICU of Hunan Children's Hospital from January 2020 to December 2022, and the results were compared with cases from the same period between January 2017 and December 2019. The cases were divided into pre-pandemic period (January 2017-December 2019) with 8,218 cases, and pandemic period (January 2020-December 2022) with 5,619 cases. General characteristics, age, and gender were compared between the two groups. Results: Compared to the pre-pandemic period, there was a 31.62% decrease in the number of admitted children during the pandemic period, and a 52.78% reduction in the proportion of respiratory system diseases. The overall mortality rate decreased by 87.81%. There were differences in age and gender distribution between the two periods. The length of hospital stay during the pandemic showed no statistical significance, whereas hospitalization costs exhibited statistical significance. Conclusion: The COVID-19 pandemic has exerted a certain influence on the disease spectrum of PICU admissions. Implementing relevant measures during the pandemic can help reduce the occurrence of respiratory system diseases in children. Considering the changes in the disease spectrum of critically ill PICU children, future clinical prevention and treatment in PICUs should continue to prioritize the respiratory, neurological, and hematological oncology systems.

Development and validation of an early mortality risk model for pediatric hemophagocytic lymphohistiocytosis: a comparison with HScore, PELOD-2, P-MODS, and pSOFA.

There has been no severity evaluation model for pediatric patients with hemophagocytic lymphohistiocytosis (HLH) that uses readily available parameters. This study aimed to develop a novel model for predicting the early mortality risk in pediatric patients with HLH using easily obtained parameters whatever etiologic subtype. Patients from one center were divided into training and validation sets for model derivation. The developed model was validated using an independent validation cohort from the second center. The prediction model with nomogram was developed based on logistic regression. The model performance underwent internal and external evaluation and validation using the area under the receiver operating characteristic curve (AUC), calibration curve with 1000 bootstrap resampling, and decision curve analysis (DCA). Model performance was compared with the most prevalent severity evaluation scores, including the PELOD-2, P-MODS, and pSOFA scores. The prediction model included nine variables: glutamic-pyruvic transaminase, albumin, globulin, myohemoglobin, creatine kinase, serum potassium, procalcitonin, serum ferritin, and interval between onset and diagnosis. The AUC of the model for predicting the 28-day mortality was 0.933 and 0.932 in the training and validation sets, respectively. The AUC values of the HScore, PELOD-2, P-MODS and pSOFA were 0.815, 0.745, 0.659 and 0.788, respectively. The DCA of the 28-day mortality prediction exhibited a greater net benefit than the HScore, PELOD-2, P-MODS and pSOFA. Subgroup analyses demonstrated good model performance across HLH subtypes. The novel mortality prediction model in this study can contribute to the rapid assessment of early mortality risk after diagnosis with readily available parameters.

Evaluating antibiotic regimens for streptococcal toxic shock syndrome in children.

INTRODUCTION: Streptococcal toxic shock syndrome (STSS) is a severe consequence of infections from Streptococcus pyogenes. The early identification and timely intervention with appropriate anti-infective agents are pivotal for managing pediatric STSS. This study evaluates the effectiveness of various treatment regimens for STSS in children. METHODS: Clinical data of children with STSS resulting from ß-hemolytic streptococcal infections in two hospitals were retrospectively analyzed from January 2009 to April 2023. Additionally, literature from the China National Knowledge Infrastructure on pediatric STSS was examined. Antimicrobial treatments were categorized into four groups based on their compositions, with an additional categorization for adjunct therapeutic drugs. RESULTS: Of 32 confirmed STSS cases, all displayed sensitivity to ampicillin, ß-lactam antibiotics, and vancomycin, but resistance to clindamycin, erythromycin, and tetracycline. From the literature, 23 studies with 50 cases were extracted, leading to a total of 82 patients for evaluation. The efficacy rates varied significantly among the four treatment groups. Notably, the standard penicillin-containing group exhibited the highest efficacy (86.4%), while the group with macrolides/unused antibiotics registered a 0% efficacy rate. The other two groups demonstrated efficacy rates of 32.1% and 42.3%. CONCLUSION: For pediatric STSS, Streptococcus pyogenes shows notable sensitivity to ampicillin. Implementing timely ß-lactam antibiotics, specifically penicillin, in conjunction with clindamycin and intravenous immunoglobulins enhances the treatment success rate.

Fasudil and SR1001 synergistically protect against sepsis-associated pancreatic injury by inhibiting RhoA/ROCK pathway and Th17/IL-17 response.

Sepsis is defined as a dysregulated host response to infection that can result in organ dysfunction and high mortality, which needs more effective treatment urgently. Pancreas is one of the most vulnerable organs in sepsis, resulting in sepsis-associated pancreatic injury, which is a fatal complication of sepsis. The aim of this study was to investigate the effect of combination of fasudil and SR1001 on sepsis-associated pancreatic injury and to explore the underlying mechanisms. The model of sepsis-associated pancreatic injury was induced by cecal ligation and puncture. Pancreatic injury was evaluated by HE staining, histopathological scores and amylase activity. The frequency of Th17 cells was analyzed by flow cytometry. Serum IL-17 level was determined by ELISA. Protein levels of RORγt, p-STAT3, GEF-H1, RhoA and ROCK1 were determined by Western blot. The apoptosis of pancreatic cells was examined by TUNEL analysis and Hoechst33342/PI staining. Compared to the sham group, the model group showed significant pathological injury including edema, hyperemia, vacuolization and necrosis. After treatment with fasudil, model mice showed an obvious reduction of Th17 cells and IL-17. SR1001 significantly reduced the expressions of GEF-H1, RhoA and ROCK1 in the model mice. The combination treatment with fasudil and SR1001 significantly inhibited the differentiation of Th17 cells, expressions of IL-17, GEF-H1, RhoA and ROCK1, which were more effective than each mono-treatment. In addition, our data revealed a remarkable decrease of apoptosis in pancreatic acinar cells culturing with fasudil or SR1001, which was further inhibited by their combination culture. Lipopolysaccharide remarkably upregulated the differentiation of Th17 cells in vitro, which could be significantly downregulated by fasudil or SR1001, and further downregulated by their combination treatment. Taken together, the combination of fasudil with SR1001 has a synergistic effect on protecting against sepsis-associated pancreatic injury in C57BL/6 mice.

[Value of complement component 3 in predicting the prognosis of children with sepsis]. / 补体C3å¯¹å„¿ç«¥è„“æ¯’ç—‡æ‚£è€ é¢„åŽçš„é¢„æµ‹ä»·å€¼.

OBJECTIVES: To investigate changes in complement component 3 (C3) levels in children with sepsis and its correlation with the severity of sepsis and to explore the significance of C3 in predicting mortality in children with sepsis. METHODS: A retrospective analysis was conducted on 529 children with sepsis who were admitted to the Pediatric Intensive Care Unit in Hunan Children's Hospital between November 2019 and September 2021. The children were categorized into two groups based on their prognosis at day 28 after sepsis diagnosis: the survival group (n=471) and the death group (n=58). Additionally, the children were divided into normal C3 group (n=273) and reduced C3 group (n=256) based on the median C3 level (0.77 g/L) within 24 hours of admission. Clinical data and laboratory markers were compared between the groups, and assess the predictive value of C3 levels in relation to sepsis-related mortality. RESULTS: The death group exhibited significantly lower C3 levels compared to the survival group (P<0.05). Multivariate logistic regression analysis revealed that higher pediatric Sequential Organ Failure Assessment (p-SOFA) scores and lower C3 levels were closely associated with sepsis-related mortality (P<0.05). The receiver operating characteristic curve (ROC) analysis demonstrated that combination of p-SOFA scores and C3 levels yielded an area under the ROC curve of 0.852, which was higher than that of each indicator alone (P<0.05). CONCLUSIONS: C3 can serve as an indicator to assess the severity and prognosis of sepsis in children. The combination of p-SOFA scores and C3 levels holds good predictive value for mortality in children with sepsis.

[Drug treatment efficacy in 32 children with streptococcal toxic shock syndrome]. / 32ä¾‹å„¿ç«¥é“¾çƒèŒä¸­æ¯’æ€§ä¼‘å ‹ç»¼åˆå¾è¯ç‰©æ²»ç–—ç–—æ•ˆåˆ†æž.

OBJECTIVES: To study the efficacy of different drug treatment regimens in children with streptococcal toxic shock syndrome (STSS). METHODS: Clinical data of children diagnosed with STSS confirmed by bacterial culture and treated in Hunan Children's Hospital and Chenzhou First People's Hospital from January 2009 to April 2023 were retrospectively collected. The efficacy of different drug treatment regimens was analyzed. The children were divided into four groups based on the treatment regimens: standard group (regimens containing penicillin), Group A (carbapenem + glycopeptides/linezolid), Group B (carbapenems, broad-spectrum antibiotics, glycopeptides/linezolid used alone or in combination, excluding the regimens in Group A), and Group C (macrolides/not receiving antimicrobial drugs). RESULTS: A total of 32 cases of STSS were included. Antimicrobial susceptibility testing showed that all strains were sensitive to beta-lactam antibiotics such as ampicillin and vancomycin, while resistant to clindamycin, erythromycin, and tetracycline. There was a statistically significant difference in the efficacy rate among the four groups (P<0.05). The standard group exhibited the highest efficacy rate (100%), while the efficacy rates for Group A, Group B, and Group C were 40%, 40%, and 0%, respectively. CONCLUSIONS: The use of antimicrobial regimens containing penicillin can improve the therapeutic efficacy of STSS in children.

Proteomic Analysis of Pediatric Hemophagocytic Lymphohistiocytosis: a Comparative Study with Healthy Controls, Sepsis, Critical Ill, and Active Epstein-Barr virus Infection to Identify Altered Pathways and Candidate Biomarkers.

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening hyperinflammatory syndrome characterized by excessive activation of the immune system, along with uncontrolled proliferation of activated macrophages and lymphocytes. The clinical features of HLH often overlap with the clinical features of other severe inflammatory conditions such as sepsis, hindering accurate and timely diagnosis. In this study, we performed a data-independent acquisition mass spectrometry-based plasma proteomic analysis of 33 pediatric patients with HLH compared with four control groups: 39 healthy children, 43 children with sepsis, 39 children hospitalized in the pediatric intensive care unit without confirmed infections, and 21 children with acute Epstein-Barr virus infection. Proteomic comparisons between the HLH group and each of the control groups showed that HLH was characterized by alterations in complement and coagulation cascades, neutrophil extracellular trap formation, and platelet activation pathways. We identified eight differentially expressed proteins in patients with HLH, including plastin-2 (LCP1), vascular cell adhesion protein 1, fibrinogen beta chain, fibrinogen gamma chain, serum amyloid A-4 protein, extracellular matrix protein 1, apolipoprotein A-I, and albumin. LCP1 emerged as a candidate diagnostic marker for HLH with an area under the curve (AUC) of 0.97 in the original cohort and an AUC of 0.90 (sensitivity = 0.83 and specificity = 1.0) in the validation cohort. Complement C1q subcomponent subunit B was associated with disease severity in patients with HLH. Based on comparisons with multiple control groups, this study provides a proteomic profile and candidate biomarkers of HLH, offering researchers novel information to improve the understanding of this condition.

Clinical characteristics and outcomes of children with Kawasaki disease combined with sepsis in the pediatric intensive care unit.

Background: Kawasaki disease (KD) is a vascular inflammatory disease with unknown pathogenesis. There are few studies on KD combined with sepsis worldwide. Purpose: To provide valuable data regarding clinical characteristics and outcomes related to pediatric patients with KD combined with sepsis in pediatric intensive care unit (PICU). Methods: We retrospectively analyzed the clinical data of 44 pediatric patients admitted in PICU at Hunan Children's Hospital with KD combined with sepsis between January 2018 and July 2021. Results: Of the 44 pediatric patients (mean age, 28.18 ± 24.28 months), 29 were males and 15 were female. We further divided the 44 patients into two groups: KD combined with severe sepsis (n=19) and KD combined with non-severe sepsis (n=25). There were no significant between-group differences in leukocyte, C-reactive protein, and erythrocyte sedimentation rate. Interleukin-6, interleukin-2, interleukin-4 and procalcitonin in KD with severe sepsis group were significantly higher than those in KD with non-severe sepsis group. And the percentage of suppressor T lymphocyte and natural killer cell in severe sepsis group were significantly higher than those in non-severe group, while the CD4+/CD8+ T lymphocyte ratio was significantly lower in KD with severe sepsis group than in KD with non-severe sepsis group. All 44 children survived and were successfully treated after intravenous immune globulin (IVIG) combined with antibiotics. Conclusion: Children who develop with KD combined with sepsis have different degrees of inflammatory response and cellular immunosuppression, and the degree of inflammatory response and cellular immunosuppression is significantly correlated with the severity of the disease.

Decreased NK cells in cases of severe adenovirus pneumonia with liver dysfunction in pediatric intensive care unit: Evidence from 330 patients.

BACKGROUND: Although the human adenovirus infection is common, adenovirus infection with liver dysfunction is rare. METHODS: To retrospectively analyze and compare the clinical characteristics and outcomes of pediatric patients diagnosed with severe adenovirus pneumonia with and without liver dysfunction, who were admitted to the pediatric intensive care unit of Hunan Children's Hospital (South China University) between January 2018 and June 2022. RESULTS: Of the 330 severe adenovirus pneumonia cases analyzed (mean age, 19.88 ± 18.26 months), 102 were girls and 228 were boys. They were divided into two groups: those with liver dysfunction (n = 54) and without liver dysfunction (n = 276). Comparison analysis showed no significant between-group differences in body mass index and levels of white blood cells, neutrophils, platelets, albumin, total bilirubin, direct bilirubin, indirect bilirubin, creatine kinase, procalcitonin, creatinine, and urea nitrogen. However, the levels of alanine aminotransferase (175.99 U/L vs 30.55 U/L) and aspartate transaminase (215.96 U/L vs 74.30 U/L) were significantly higher in patients with liver dysfunction compared to those without liver dysfunction. Further analysis showed that pediatric patients with liver dysfunction had a significantly lower percentage of natural killer (NK) cells (6.93% vs 8.71%) and higher mortality rate (22% vs 9%) than those without liver dysfunction. CONCLUSION: A decrease in serum NK cell levels in pediatric patients with severe adenovirus pneumonia could serve as a marker for monitoring the onset or progression of hepatic damage.

Decreased NK cells in cases of severe adenovirus pneumonia with liver dysfunction in pediatric intensive care unit: Evidence from 330 patients

Background: Although the human adenovirus infection is common, adenovirus infection with liver dysfunction is rare. Methods: To retrospectively analyze and compare the clinical characteristics and outcomes of pediatric patients diagnosed with severe adenovirus pneumonia with and without liver dysfunction, who were admitted to the pediatric intensive care unit of Hunan Children’s Hospital (South China University) between January 2018 and June 2022. Results: Of the 330 severe adenovirus pneumonia cases analyzed (mean age, 19.88 ± 18.26 months), 102 were girls and 228 were boys. They were divided into two groups: those with liver dysfunction (n = 54) and without liver dysfunction (n = 276). Comparison analysis showed no significant between-group differences in body mass index and levels of white blood cells, neutrophils, platelets, albumin, total bilirubin, direct bilirubin, indirect bilirubin, creatine kinase, procalcitonin, creatinine, and urea nitrogen. However, the levels of alanine aminotransferase (175.99 U/L vs 30.55 U/L) and aspartate transaminase (215.96 U/L vs 74.30 U/L) were significantly higher in patients with liver dysfunction compared to those without liver dysfunction. Further analysis showed that pediatric patients with liver dysfunction had a significantly lower percentage of natural killer (NK) cells (6.93% vs 8.71%) and higher mortality rate (22% vs 9%) than those without liver dysfunction. Conclusion: A decrease in serum NK cell levels in pediatric patients with severe adenovirus pneumonia could serve as a marker for monitoring the onset or progression of hepatic damage (AU)

A Three-Step Screening Procedure for Early Identification of Children at High Risk of Hemophagocytic Lymphohistiocytosis.

PURPOSE: The first step in diagnosing hemophagocytic lymphohistiocytosis (HLH) is to suspect its presence and then order the appropriate diagnostic tests. The development of screening procedures for HLH could facilitate early diagnosis. In this study, we evaluated the utility of fever, splenomegaly, and cytopenias as screening criteria for identifying pediatric HLH at an early stage, built a screening model using commonly measured laboratory parameters, and developed a step-wise screening procedure for pediatric HLH. METHODS: The medical records of 83,965 pediatric inpatients, including 160 patients with HLH, were collected retrospectively. The utility of fever, splenomegaly, hemoglobin level, and platelet and neutrophil counts at hospital admission as screening criteria for HLH was evaluated. For HLH patients who might be missed by screening based on the presence of fever, splenomegaly, and cytopenias, a screening model using common laboratory parameters was developed. Following that, a three-step screening procedure was then developed. RESULTS: The criteria of cytopenias affecting two or more lineages plus fever or splenomegaly had a sensitivity of 51.9% and a specificity of 98.4% for identifying HLH in pediatric inpatients. Our screening score model comprises six parameters: splenomegaly, platelet count, neutrophil count, albumin level, total bile acid level, and lactate dehydrogenase level. The use of the validation set had a sensitivity of 87.0% and a specificity of 90.6%. A three-step screening procedure has been developed: Step 1: Is fever or splenomegaly present? (Yes: risk for HLH should be considered, go to Step 2; No: less likely HLH); Step 2: Are cytopenias affecting at least two lineages? (Yes: consider HLH; No: go to Step 3); Step 3: Calculate the screening score. Is the sum of the score greater than 37? (Yes: consider HLH; No: less likely HLH). The overall sensitivity and specificity of the three-step screening procedure were 91.9% and 94.4%, respectively. CONCLUSION: A significant proportion of pediatric HLH patients present at the hospital without having all three symptoms: fever, splenomegaly, and cytopenias. Our three-step screening procedure, utilizing commonly available clinical and laboratory parameters, can effectively identify pediatric patients who may be at high risk for HLH.

Use of dual genomic sequencing to screen mitochondrial diseases in pediatrics: a retrospective analysis.

Mitochondrial diseases (MDs) were a large group multisystem disorders, attributable in part to the dual genomic control. The advent of massively sequencing has improved diagnostic rates and speed, and was increasingly being used as a first-line diagnostic test. Paediatric patients (aged < 18 years) who underwent dual genomic sequencing were enrolled in this retrospective multicentre study. We evaluated the mitochondrial disease criteria (MDC) and molecular diagnostic yield of dual genomic sequencing. Causative variants were identified in 177 out of 503 (35.2%) patients using dual genomic sequencing. Forty-six patients (9.1%) had mitochondria-related variants, including 25 patients with nuclear DNA (nDNA) variants, 15 with mitochondrial DNA (mtDNA) variants, and six with dual genomic variants (MT-ND6 and POLG; MT-ND5 and RARS2; MT-TL1 and NARS2; MT-CO2 and NDUFS1; MT-CYB and SMARCA2; and CHRNA4 and MT-CO3). Based on the MDC, 15.2% of the patients with mitochondria-related variants were classified as "unlikely to have mitochondrial disorder". Moreover, 4.5% of the patients with non-mitochondria-related variants and 1.43% with negative genetic tests, were classified as "probably having mitochondrial disorder". Dual genomic sequencing in suspected MDs provided a more comprehensive and accurate diagnosis for pediatric patients, especially for patients with dual genomic variants.

[Risk factors for early acute kidney injury after cardiac arrest in children in the pediatric intensive care unit and a prognostic analysis]. / é‡ç—‡ç›‘æŠ¤å®¤æ‚£å„¿å¿ƒè„åœæåŽæ—©æœŸå‡ºçŽ°æ€¥æ€§è‚¾æŸä¼¤çš„å±é™©å› ç´ åŠé¢„åŽåˆ†æž.

OBJECTIVES: To investigate the risk factors for acute kidney injury (AKI) in children with cardiac arrest (CA) and the influencing factors for prognosis. METHODS: A retrospective analysis was performed on the medical records of the children who developed CA in the pediatric intensive care unit (PICU) of Hunan Children's Hospital from June 2016 to June 2021. According to the presence or absence of AKI within 48 hours after return of spontaneous circulation (ROSC) for CA, the children were divided into two groups: AKI (n=50) and non-AKI (n=113). According to their prognosis on day 7 after ROSC, the AKI group was further divided into a survival group (n=21) and a death group (n=29). The multivariate logistic regression analysis was used to investigate the risk factors for early AKI in the children with CA and the influencing factors for prognosis. RESULTS: The incidence rate of AKI after CA was 30.7% (50/163). The AKI group had a 7-day mortality rate of 58.0% (29/50) and a 28-day mortality rate of 78.0% (39/50), and the non-AKI group had a 7-day mortality rate of 31.9% (36/113) and a 28-day mortality rate of 58.4% (66/113). The multivariate logistic regression analysis showed that long duration of cardiopulmonary resuscitation (OR=1.164, 95%CI: 1.088-1.246, P<0.001), low baseline albumin (OR=0.879, 95%CI: 0.806-0.958, P=0.003), and adrenaline administration before CA (OR=2.791, 95%CI: 1.119-6.961, P=0.028) were closely associated with the development of AKI after CA, and that low baseline pediatric critical illness score (OR=0.761, 95%CI: 0.612-0.945, P=0.014), adrenaline administration before CA (OR=7.018, 95%CI: 1.196-41.188, P=0.031), and mechanical ventilation before CA (OR=7.875, 95%CI: 1.358-45.672, P=0.021) were closely associated with the death of the children with AKI after CA. CONCLUSIONS: Albumin should be closely monitored for children with ROSC after CA, especially for those with long duration of cardiopulmonary resuscitation, low baseline pediatric critical illness score, adrenaline administration before CA, and mechanical ventilation before CA, and such children should be identified and intervened as early as possible to reduce the incidence of AKI and the mortality rate.

Single-Cell Transcriptional Profiling Reveals Low-Level Tragus Stimulation Improves Sepsis-Induced Myocardial Dysfunction by Promoting M2 Macrophage Polarization.

Background: Sepsis can lead to multiple organ damage, of which the heart is one of the most vulnerable organs. Vagal nerve stimulation can reduce myocardial injury in sepsis and improve survival rates. However, the potential impact of low-level tragus stimulation and disparate cell populations on sepsis-induced myocardial dysfunction remains undetermined. Methods: A cardiac single-cell transcriptomic approach was used for characterizing cardiac cell populations that form the heart. Single-cell mRNA sequencing data were used for selecting all cardiac macrophages from CD45+ cells. Then, echocardiography, western blot, flow cytometry, immunofluorescence, and immunohistochemistry were performed to verify the single-cell mRNA sequencing results. Results: Using single-cell mRNA sequencing data, we uncovered the multiple cell populations contributing to myocardial injury in sepsis under low-level tragus stimulation, thereby illustrating a comprehensive map of the cardiac cellular landscape. Pseudotiming analysis in single-cell sequencing showed that low-level vagal nerve stimulation played an anti-inflammatory role by promoting cardiac monocytes into M2 macrophages, which significantly increased α7nAChR expression in heart tissues. Echocardiography assessment indicated that low-level vagal nerve stimulation could also improve cardiac functions in mice with sepsis-induced myocardial dysfunction. In addition, the heart tissues of mice from the sepsis group with low-level tragus stimulation had significantly lower interleukin-1ß expression levels than those from the sepsis group. Flow cytometry analysis showed that different acetylcholine concentrations promoted cardiac monocytes into M2 macrophages in in vitro experiments. Conclusion: Low-level tragus stimulation could improve sepsis-induced myocardial dysfunction by promoting cardiac monocytes to M2 macrophages.

Development of a screening score for Hemophagocytic Lymphohistiocytosis among pediatric patients with acute infection of Epstein-Barr virus.

Background and aims: Deciding when to suspect hemophagocytic lymphohistiocytosis (HLH) and perform diagnostic tests in patients with acute infection of Epstein-Barr virus (EBV) is challenging, given the high prevalence of EBV infection, the life-threatening risk of EBV-HLH, the relatively low incidence of EBV-HLH, and the wide spectrum of disease presentations. The aim of this study was to develop an EBV-HLH screening model for pediatric patients diagnosed with acute infection of EBV. Methods: An inpatient cohort with 3183 pediatric patients who were diagnosed with active infection of EBV was used to construct and validate the EBV-HLH screening score model. The model parameters were selected from common laboratory parameters using the method of Akaike Information Criterion-optimal selection through cross-validation under logistic regression. Performance of the score was evaluated and compared with the performance of screening methods using the number of cytopenias lineages. Results: The EBV-HLH screening score has five parameters, including hemoglobin, platelet, neutrophil, albumin, and lactate dehydrogenase. Using a cut-of value of 29, the scoring model had a sensitivity of 89.2% and a specificity of 89.5% in the validation set. The false negative rate, false positive rate, positive predictive value, and negative predictive value in the validation set was 10.8%, 10.5%, 26.8%, and 99.5%, respectively, similar to that of the training set. Conclusions: With five common laboratory parameters, the EBV-HLH score provides a simple tool to assist the identification of EBV patients who require further evaluation of HLH. Further studies are needed to evaluate the generalizability of the score and optimize the diagnose process for EBV-HLH.

Epidemiology of Cardiopulmonary Arrest and Outcome of Resuscitation in PICU Across China: A Prospective Multicenter Cohort Study.

Objective: To investigate the epidemiology and the effectiveness of resuscitation from cardiopulmonary arrest (CPA) among critically ill children and adolescents during pediatric intensive care unit (PICU) stay across China. Methods: A prospective multicenter study was conducted in 11 PICUs in tertiary hospitals. Consecutively hospitalized critically ill children, from 29-day old to 18-year old, who had suffered from CPA and required cardiopulmonary resuscitation (CPR) in the PICU were enrolled (December 2017-October 2018). Data were collected and analyzed using the "in-hospital Utstein style." Neurological outcome was assessed with the Pediatric Cerebral Performance Category (PCPC) scale among children who had survived. Factors associated with the return of spontaneous circulation (ROSC) and survival at discharge were evaluated using multivariate logistic regression. Results: Among 11,599 admissions to PICU, 372 children (3.2%) had CPA during their stay; 281 (75.5%) received CPR, and 91 (24.5%) did not (due to an order of "Do Not Resuscitate" requested by their guardians). Cardiopulmonary disease was the most common reason for CPA (28.1% respiratory and 19.6% circulatory). The most frequent initial dysrhythmia was bradycardia (79%). In total, 170 (60.3%) of the total children had an ROSC, 91 had (37.4%) survived till hospital discharge, 28 (11.5%) had survived 6 months, and 19 (7.8%) had survived for 1 year after discharge. Among the 91 children who were viable at discharge, 47.2% (43/91) received a good PCPC score (1-3). The regression analysis results revealed that the duration of CPR and the dose of epinephrine were significantly associated with ROSC, while the duration of CPR, number of CPR attempts, ventricular tachycardia/ventricular fibrillation (VT/VF), and the dose of epinephrine were significantly associated with survival at discharge. Conclusion: The prevalence of CPA in critically ill children and adolescents is relatively high in China. The duration of CPR and the dose of epinephrine are associated with ROSC. The long-term prognosis of children who had survived after CPR needs further improvement.

Fulfillment status of hypertriglyceridemia and hypofibrinogenemia in children with hemophagocytic lymphohistiocytosis and risks of multiple organ dysfunction syndrome and early mortality.

BACKGROUND: Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening disorder. How to stratify high risk patients is one of the current challenges for the treatment of HLH. HLH patients usually fulfill multiple but not all eight diagnostic criteria. Different combinations of the fulfilled criteria may naturally cluster into previously undescribed subsets or phenotypes that may have different pathophysiology and demonstrate different risks for a poor outcome. The objectives of this study were to identify HLH subgroups according to the fulfillment of diagnostic criteria and evaluate the risk of multiple organ dysfunction syndrome (MODS) and 30-day mortality for subgroups. We retrospectively collect medical records of patients with discharge diagnosis of HLH between June 2015 and October 2018 from a tertiary children's hospital in China. Latent class analysis was used to identify class defining variables from HLH diagnostic items, and subgroups were defined according to different combinations of the class defining variables. RESULTS: Triglyceride and fibrinogen were identified as the class defining variables. When evaluated in combinations, patients with hypertriglyceridemia and normal fibrinogen levels during hospitalization had the lowest risks for MODS (27.8%, OR = 1) and 30-day mortality (18.8%, OR = 1), and patients with normal triglyceride and hypofibrinogenemia had the highest risks for MODS (86.2%, OR = 16.24, P = 0.0002) and 30-day mortality (57.1%, OR = 5.78, P = 0.0187). The fulfillment status of hypertriglyceridemia and hypofibrinogenemia within 72 h of hospital admission was also associated with the risk of adverse outcomes. CONCLUSIONS: The fulfillment status of hypertriglyceridemia and hypofibrinogenemia were associated with the risks of MODS and 30-day mortality among pediatric HLH patients. Further studies are needed to validate this association and investigate its clinical utility in the severity evaluation for HLH.

Proteomic analysis identified potential age-associated prognostic biomarkers in pneumonia-derived paediatric sepsis.

PURPOSE: Our aim was to investigate the age-associated plasma protein profiles in pneumonia-derived sepsis between infants and toddlers and identify potential age-adapted prognostic markers for poor outcome of pneumonia-derived pediatric sepsis. EXPERIMENTAL DESIGN: A nested case-control study strategy was applied. The plasma proteomes of pneumonia-derived pediatric septic patients with different outcomes between infants and toddlers were respectively analysed compared to their age-matched controls. RESULTS: Compared to toddlers, pneumonia-derived sepsis in infants was characterized by increased upregulation of protein processing in the ER, proteasome and antigen processing and presentation; and reduced downregulation in complement and coagulation cascades and cholesterol metabolism. Among them, the pentose phosphate pathway as well as the complement and coagulation cascades were possibly associated with poor outcome of pneumonia-derived sepsis. Furthermore, we confirmed that HP, THBS1, and SAA1/2 were potential prognostic markers for poor outcome of pneumonia-derived sepsis in infant patient groups. CONCLUSIONS AND CLINICAL RELEVANCE: Age-associated plasma protein profiles of pneumonia-derived pediatric septic patients provided potential age-adapted biomarkers for a more precise prognosis of poor outcome in pneumonia-derived pediatric sepsis and helped to improve the survival of septic children.

Diagnostic Time Lag of Pediatric Haemophagocytic Lymphohistiocytosis and Patient Characteristics: A Retrospective Cohort Study.

The difficulties and challenges of applying the HLH-2004 diagnostic criteria to early identification and diagnosis of haemophagocytic lymphohistiocytosis have been fully addressed in previous studies. However, the distribution of the diagnostic time lag of haemophagocytic lymphohistiocytosis and related patient characteristics remain unclear. This study investigated the time lags between symptom onset and diagnosis and between hospital admission and diagnosis among pediatric patients with haemophagocytic lymphohistiocytosis, and identified factors that associated with a shorter or longer diagnostic time lag. The cohort of patients with haemophagocytic lymphohistiocytosis was drawn from a tertiary children's hospital and consisted of 122 pediatric patients. The distributions of symptom-to-diagnosis and admission-to-diagnosis time lags were assessed. Clinical characteristics within 48 h of admission and the fulfillment of HLH-2004 diagnostic criteria were compared among admission-to-diagnosis time lag categories. Logistic regression analyses were conducted to identify factors associated with an admission-to-diagnosis time lag >3 days. The median interval from first symptom onset to HLH diagnosis was 12 days (range 4-71 days) and the median interval from hospital admission to HLH diagnosis was 2 days (range 0-23 days). The following factors were negatively associated with admission-to-diagnosis > 3 days: Epstein-Barr virus infection; admission through pediatric intensive care unit; diagnosis established without NK-cell activity and soluble CD25 tests; the performance of all readily available diagnostic tests for HLH (within 48 and 72 h); concurrent fever, splenomegaly, and cytopenias within 48 h; hemophagocytosis, hypertriglyceridemia and/or hypofibrinogenemia within 48 h; and elevated ferritin, total bilirubin, alanine aminotransferase, and prothrombin time within 48 h. Our findings suggest that performance of adequate diagnostic tests for HLH is essential for early diagnosis of HLH. Once suspected, immediate and adequate diagnostic tests for HLH should be arranged for PICU patients. Improvements in diagnostic procedures and monitoring plans are needed to promote early diagnosis of HLH.

Expanding the genotypes and phenotypes for 19 rare diseases by exome sequencing performed in pediatric intensive care unit.

Phenotypes of some rare genetic diseases are atypical and it is a challenge for pediatric intensive care units (PICUs) to diagnose and manage such patients in an emergency. In this study, we investigated 58 PICU patients (39 deceased and 19 surviving) in critical ill status or died shortly without a clear etiology. Whole exome sequencing was performed of 103 DNA samples from their families. Disease-causing single-nucleotide variants (SNVs) and copy number variants (CNVs) were identified to do genotype-phenotypes analysis. In total, 27 (46.6%) patients received a genetic diagnosis. We identified 34 pathogenic or likely pathogenic SNVs from 26 genes, which are related to at least 19 rare diseases. Each rare disease involved an isolated patient except two patients caused by the same gene ACAT1. The genotypic spectrum was expanded by 23 novel SNVs from gene MARS1, PRRT2, TBCK, TOR1A, ECE1, ARX, ZEB2, ACAT1, CPS1, VWF, NBAS, COG4, and INVS. We also identified two novel pathogenic CNVs. Phenotypes associated with respiratory, multiple congenital anomalies, neuromuscular, or metabolic disorders were the most common. Twenty patients (74.1%) accompanied severe infection, 19 patients (70.1%) died. In summary, our findings expanded the genotypes and phenotypes of 19 rare diseases from PICU with complex characteristics.