Postoperative Risk Factors and Outcome of Patients With Liver Transplantation Who Were Admitted to Pediatric Intensive Care Unit: A 10-Year Single-Center Review in China.

INTRODUCTION: The aim of this study was to present our 10-year experience of pediatric intensive care unit (PICU) management with pediatric liver recipients and to understand the importance of close interdisciplinary cooperation in 2 hospitals. METHODS: A retrospective chart review study was performed according to our hospital's medical records and the pediatric liver transplant database of Renji hospital. RESULTS: A total of 767 patients received liver transplantation (LT) performed in Renji hospital between October 2006 and December 2016, of which 97 of them were admitted to PICU in our center for various complications developed after transplantation. 8.8% (16/208) and 14.4% (81/559) of patients were transferred to PICU in stages I and II, respectively, and was comparable in the 2 stages (P = .017). The majority of patients was late postoperative children (median 185 post-LT days) in stage I. More patients were transferred to PICU directly in stage II. PICU admitted more younger (median 8.2 months) and early postoperative patients in stage II. The median length of PICU stay was 11.0 (6.0-20.5) days. The median length of mechanical ventilation was 5.0 (0.0-12.0) days. The most frequent complications were pulmonary complications (52 [53.6%] patients), surgical complications (22 [22.7%] patients), sepsis (7 [7.2%]), and other miscellaneous complications (16 [16.5%] patients). The overall 28-day PICU mortality was 25.8% (n = 25) and 64.0% (n = 16) of the deaths happened in the early postoperative period. There was significant difference concerning mortality in children with surgical complications and medical problems (54.5% [12/22] vs 17.3% [13/75], P = .001). Multivariate analysis by regression showed that the pediatric risk of mortality III score was the only independent prognostic factor (P = .031). CONCLUSIONS: Multiple complications occur in children with LT. Although challenging, interdisciplinary cooperation between different hospitals is an effective mean to enable children to maximize the benefit gained from LT in China.

Respiratory Variations in Aortic Blood Flow to Predict Volume Responsiveness in Ventilated Children With Leukemia and Neutropenic Septic Shock.

OBJECTIVES: To investigate whether respiratory variations in aortic blood flow by echocardiography can accurately predict volume responsiveness in ventilated children with leukemia and neutropenic septic shock. DESIGN: A prospective study. SETTING: A 25-bed PICU of a tertiary hospital. PATIENTS: Mechanically ventilated children with leukemia who had been exposed to anthracyclines and exhibited neutropenic septic shock were enrolled. INTERVENTIONS: Transthoracic echocardiography was performed to monitor the aortic blood flow before and after fluid administration. MEASUREMENTS AND MAIN RESULTS: After volume expansion, left ventricular stroke volume increased by greater than or equal to 15% in 16 patients (responders) and less than 15% in 14 patients (nonresponders). The performance of respiratory variation in velocity time integral of aortic blood flow and respiratory variation in peak velocity of aortic blood flow for predicting volume responsiveness, as determined by the area under the receiver operating characteristic curve, was 0.74 (95% CI, 0.55-0.94; p = 0.025) and 0.71 (95% CI, 0.53-0.90; p = 0.048), respectively. Positive end-expiratory pressure was higher in nonresponders than in responders (p = 0.035). CONCLUSIONS: Respiratory variation in velocity time integral of aortic blood flow and respiratory variation in peak velocity of aortic blood flow derived from transthoracic echocardiography showed only a fair reliability in predicting volume responsiveness in ventilated children with leukemia and neutropenic septic shock.

Autologous cord blood transplantation for metastatic neuroblastoma.

Auto-SCT is a common approach for metastatic neuroblastoma with the intention to rescue hematopoiesis after megadose chemotherapy. PBSC or BM is the usual stem cell source for auto-SCT. Auto-CBT for neuroblastoma has very rarely been performed. Currently, case reports are available for two patients only. We performed 13 auto-SCTs for high-risk neuroblastoma from 2007 to 2013, including four cases of metastatic neuroblastoma aged 11-64 months treated with auto-CBT. All four patients had partial or CR to upfront treatments before auto-CBT. Nucleated cell dose and CD34+ cell dose infused were 2.8-8.7 × 10(7) /kg and 0.36-3.9 × 10(5) /kg, respectively. Post-thawed viability was 57-76%. Neutrophil engraftment (>0.5 × 10(9) /L) occurred at 15-33 days, while platelet engraftment occurred at 31-43 days (>20 × 10(9) /L) and 33-65 days (>50 × 10(9) /L) post-transplant, respectively. There was no severe acute or chronic complication. Three patients survived for 1.9-7.7 yr without evidence of recurrence. One patient relapsed at 16 months post-transplant and died of progressive disease. Cord blood may be a feasible alternative stem cell source for auto-SCT in patients with stage 4 neuroblastoma, and outcomes may be improved compared to autologous PBSC or BM transplants.

Artificial intelligence promotes shared decision-making through recommending tests to febrile pediatric outpatients.

BACKGROUND: To promote the shared decision-making (SDM) between patients and doctors in pediatric outpatient departments, this study was designed to validate artificial intelligence (AI) -initiated medical tests for children with fever. METHODS: We designed an AI model, named Xiaoyi, to suggest necessary tests for a febrile child before visiting a pediatric outpatient clinic. We calculated the sensitivity, specificity, and F1 score to evaluate the efficacy of Xiaoyi's recommendations. The patients were divided into the rejection and acceptance groups. Then we analyzed the rejected examination items in order to obtain the corresponding reasons. RESULTS: We recruited a total of 11,867 children with fever who had used Xiaoyi in outpatient clinics. The recommended examinations given by Xiaoyi for 10,636 (89.6%) patients were qualified. The average F1 score reached 0.94. A total of 58.4% of the patients accepted Xiaoyi's suggestions (acceptance group), and 41.6% refused (rejection group). Imaging examinations were rejected by most patients (46.7%). The tests being time-consuming were rejected by 2,133 patients (43.2%), including rejecting pathogen studies in 1,347 patients (68.5%) and image studies in 732 patients (31.8%). The difficulty of sampling was the main reason for rejecting routine tests (41.9%). CONCLUSION: Our model has high accuracy and acceptability in recommending medical tests to febrile pediatric patients, and is worth promoting in facilitating SDM.

[Establishment of a transgenic cell line with stable expression of human CD14].

OBJECTIVE: To establish a transgenic cell line with stable expression of CD14. METHODS: Total RNA extracted from peripheral blood mononuclear cells was treated with RNAase-free DNAase, the human CD14 gene was cloned and sequenced through the RT-PCR, T-A clone techniques and ABI PRISM377 machine. Eukaryotic expression vector pcDNA3.1(+)/CD14 was constructed by cleaving with double restriction endonucleases EcoR I/Xba I and ligating with T4 ligase. The human cervical cancer cell line Hela was transfected with the positive recombinant plasmid pcDNA3.1(+)/CD14 using superfect transfection reagent. Positive clones were selected by G418 at a concentration of 0.5 µg/µl and the expression of human CD14 on the transfected Hela cells was confirmed by quantitative PCR and immunofluorescent assay. RESULTS: There was significantly difference om expression of CD14 mRNA between the blank pcDNA3.1(+) transfected cells and pcDNA3.1(+)/CD14 transfected cells (P<0.01). The fluorescence was significantly stronger on the stable cell line Hela-CD14 than that on the transiently transfected Hela cells,and no visible fluorescence was observed in blank vector transfected cells. CONCLUSION: The transfectant cell line Hela-CD14 with stable expression of human CD14 has been successfully established, which can be used to study human CD14 molecular and CD14-associated monocyte/macrophage cell diseases.

Evaluating IL-6 and IL-10 as rapid diagnostic tools for Gram-negative bacteria and as disease severity predictors in pediatric sepsis patients in the intensive care unit.

Background: To explore the diagnostic performance of interleukin (IL)-6 and IL-10 in discriminating Gram bacteria types and predicting disease severity in intensive care unit (ICU)-hospitalized pediatric sepsis patients. Method: We retrospectively collected Th1/Th2 cytokine profiles of 146 microbiologically documented sepsis patients. Patients were categorized into Gram-positive (G+) or Gram-negative (G-) sepsis groups, and cytokine levels were compared. Subgroup analysis was designed to eliminate the influence of other inflammatory responses on cytokine levels. Results: After propensity score matching, 78 patients were matched and categorized according to Gram bacteria types. Compared with G+ sepsis, IL-6 and IL-10 were significantly elevated in G- sepsis (p < 0.05). Spearman test proved the linear correlation between IL-6 and IL-10 (r = 0.654, p < 0.001), and their combination indicators (ratio and differences) were effective in identifying G- sepsis. In the subgroup analysis, such cytokine elevation was significant regardless of primary infection site. However, for patients with progressively deteriorating organ function [new or progressive multiple organ dysfunction syndrome (NPMODS)], differences in IL-6 and IL-10 levels were less significant between G+ and G- sepsis. In the receiver operating characteristic (ROC) curves of the G- sepsis group, the area under the curve (AUC) value for IL-6 and IL-10 was 0.679 (95% CI 0.561-0.798) and 0.637 (95% CI 0.512-0.762), respectively. The optimal cutoff value for diagnosing G- sepsis was 76.77 pg/ml and 18.90 pg/ml, respectively. While for the NPMODS group, the AUC for IL-6 and IL-10 was 0.834 (95% CI 0.766-0.902) and 0.781 (95% CI 0.701-0.860), respectively. Conclusion: IL-6 and IL-10 are comparably effective in discriminating G+/G- sepsis in pediatric intensive care unit (PICU) patients. The deteriorated organ function observed in ICU patients reveals that complex inflammatory responses might have contributed to the cytokine pattern observed in severe sepsis patients, therefore confounding the discriminating efficacy of Th1/Th2 cytokines in predicting Gram bacteria types.

Comparison of Global and Regional Compliance-Guided Positive End-Expiratory Pressure Titration on Regional Lung Ventilation in Moderate-to-Severe Pediatric Acute Respiratory Distress Syndrome.

Purpose: To investigate the difference in the positive end-expiratory pressure (PEEP) selected with chest electrical impedance tomography (EIT) and with global dynamic respiratory system compliance (Crs) in moderate-to-severe pediatric acute respiratory distress syndrome (pARDS). Methods: Patients with moderate-to-severe pARDS (PaO2/FiO2 < 200 mmHg) were retrospectively included. On the day of pARDS diagnosis, two PEEP levels were determined during the decremental PEEP titration for each individual using the best compliance (PEEPC) and EIT-based regional compliance (PEEPEIT) methods. The differences of global and regional compliance (for both gravity-dependent and non-dependent regions) under the two PEEP conditions were compared. In addition, the EIT-based global inhomogeneity index (GI), the center of ventilation (CoV), and standard deviation of regional delayed ventilation (RVDSD) were also calculated and compared. Results: A total of 12 children with pARDS (5 with severe and 7 with moderate pARDS) were included. PEEPC and PEEPEIT were identical in 6 patients. In others, the differences were only ± 2 cm H2O (one PEEP step). There were no statistical differences in global compliance at PEEPC and PEEPEIT [28.7 (2.84-33.15) vs. 29.74 (2.84-33.47) ml/cm H2O median (IQR), p = 0.028 (the significant level after adjusted for multiple comparison was 0.017)]. Furthermore, no differences were found in regional compliances and other EIT-based parameters measuring spatial and temporal ventilation distributions. Conclusion: Although EIT provided information on ventilation distribution, PEEP selected with the best Crs might be non-inferior to EIT-guided regional ventilation in moderate-to-severe pARDS. Further study with a large sample size is required to confirm the finding.

Signaling pathways and intervention therapies in sepsis.

Sepsis is defined as life-threatening organ dysfunction caused by dysregulated host systemic inflammatory and immune response to infection. Over decades, advanced understanding of host-microorganism interaction has gradually unmasked the genuine nature of sepsis, guiding toward new definition and novel therapeutic approaches. Diverse clinical manifestations and outcomes among infectious patients have suggested the heterogeneity of immunopathology, while systemic inflammatory responses and deteriorating organ function observed in critically ill patients imply the extensively hyperactivated cascades by the host defense system. From focusing on microorganism pathogenicity, research interests have turned toward the molecular basis of host responses. Though progress has been made regarding recognition and management of clinical sepsis, incidence and mortality rate remain high. Furthermore, clinical trials of therapeutics have failed to obtain promising results. As far as we know, there was no systematic review addressing sepsis-related molecular signaling pathways and intervention therapy in literature. Increasing studies have succeeded to confirm novel functions of involved signaling pathways and comment on efficacy of intervention therapies amid sepsis. However, few of these studies attempt to elucidate the underlining mechanism in progression of sepsis, while other failed to integrate preliminary findings and describe in a broader view. This review focuses on the important signaling pathways, potential molecular mechanism, and pathway-associated therapy in sepsis. Host-derived molecules interacting with activated cells possess pivotal role for sepsis pathogenesis by dynamic regulation of signaling pathways. Cross-talk and functions of these molecules are also discussed in detail. Lastly, potential novel therapeutic strategies precisely targeting on signaling pathways and molecules are mentioned.

The clinical outcomes and biomarker features of severe sepsis/septic shock with severe neutropenia: a retrospective cohort study.

BACKGROUND: Severe sepsis/septic shock with severe neutropenia often leads to poor prognosis. However, it is unknown if severe neutropenia is associated with different clinical outcomes and biomarker features in severe sepsis/septic patients. METHODS: This retrospective cohort study enrolled 141 severe sepsis/septic shock patients admitted to intensive care unit of Shanghai Children's Medical Center between January 2015 and November 2019. Patients were followed up for the development of ventilation support, the use of vasoactive drugs, continuous renal replacement therapy (CRRT) procedure, and mortality. Biomarkers that reflect the level of inflammation in severe sepsis/septic shock patients with neutropenia were compared to that in patients without neutropenia. RESULTS: Of 141 patients enrolled, 54 patients suffered from severe sepsis/septic shock with severe neutropenia. In patients with severe sepsis/septic shock, severe neutropenia as a complication was an independent risk factor for the use of vasoactive drugs (RR 9.796; 95% CI: 3.774, 25.429; P<0.001), but not for ventilation support (RR 0.157; 95% CI: 0.06, 0.414; P<0.001), CRRT procedure (RR 1.032; 95% CI: 0.359, 2.969; P=0.953) or 28-day mortality (RR 1.405; 95% CI: 0.533, 3.708; P=0.492). Severe sepsis/septic patients with severe neutropenia had a higher plasma level of the following biomarkers: c-reaction protein (CRP) (180.5 vs. 121 mg/mL, P<0.001), procalcitonin (PCT) (12.15 vs. 2.7 ng/mL; P=0.005), interleukin (IL)-6 (316.83 vs. 55.77 pg/mL, P<0.001), IL-10 (39.165 vs. 10.09 pg/mL, P<0.001), interferon (IFN)-γ (6.155 vs. 3.71 pg/mL, P=0.016), and the percentage of regulatory T cells (Tregs) (2.7% vs. 2.09%, P=0.003). Based on the receiver operating characteristic curves, IL-10 exhibited high specificity (79.4%) in evaluating the prognosis of septic patients with neutropenia. CONCLUSIONS: In patients with severe sepsis/septic shock, being complicated with severe neutropenia is associated with higher proportion of using vasoactive drugs, and those patients tend to have higher plasma levels of IL-6, IL-10, IFN-γ and percentage of Treg.

The Clinical Characteristics of ARDS in Children With Hematological Neoplasms.

In order to explore the clinical characteristics of pediatric patients admitted to the pediatric intensive care unit (PICU) who suffered from hematological neoplasms complicated with acute respiratory distress syndrome (ARDS), we retrospectively analyzed 45 ARDS children with hematological neoplasms who were admitted to the PICU of Shanghai Children's Medical Center from January 1, 2014, to December 31, 2020. The 45 children were divided into a survival group and a non-survival group, a pulmonary ARDS group and an exogenous pulmonary ARDS group, and an agranulocytosis group and a non-agranulocytosis group, for statistical analysis. The main clinical manifestations were fever, cough, progressive dyspnea, and hypoxemia; 55.6% (25/45) of the children had multiple organ dysfunction syndrome (MODS). The overall mortality rate was 55.6% (25/45). The vasoactive inotropic score (VIS), pediatric critical illness scoring (PCIS), average fluid volume in the first 3 days and the first 7 days, and the incidence of MODS in the non-survival group were all significantly higher than those in the survival group (P < 0.05). However, total length of mechanical ventilation and length of hospital stay and PICU days in the non-survival group were significantly lower than those in the survival group (P < 0.05). The PCIS (OR = 0.832, P = 0.004) and the average fluid volume in the first 3 days (OR = 1.092, P = 0.025) were independent risk factors for predicting death. Children with exogenous pulmonary ARDS were more likely to have MODS than pulmonary ARDS (P < 0.05). The mean values of VIS, C-reactive protein (CRP), and procalcitonin (PCT) in children with exogenous pulmonary ARDS were also higher (P < 0.05). After multivariate analysis, PCT was independently related to exogenous pulmonary ARDS. The total length of hospital stay, peak inspiratory pressure (PIP), VIS, CRP, and PCT in the agranulocytosis group were significantly higher than those in the non-agranulocytosis group (P < 0.05). Last, CRP and PIP were independently related to agranulocytosis. In conclusion, children with hematological neoplasms complicated with ARDS had a high overall mortality and poor prognosis. Children complicated with MODS, positive fluid balance, and high VIS and PCIS scores were positively correlated with mortality. In particular, PCIS score and average fluid volume in the first 3 days were independent risk factors for predicting death. Children with exogenous pulmonary ARDS and children with agranulocytosis were in a severely infected status and more critically ill.

Is there possibility of vertical transmission of COVID-19: a systematic review.

In order to investigate the clinical features of pregnant women and their neonates with coronavirus disease 2019 (COVID-19) and the evidence of vertical transmission of COVID-19, we retrieved studies included in PubMed, Medline and Chinese databases from January 1, 2000 to October 25, 2020 using relevant terms, such as 'COVID-19', 'vertical transmission' et al. in 'Title/Abstract'. Case reports and case series were included according to the inclusion and exclusion criteria. We conducted literature screening and data extraction, and performed literature bias risk assessment. Total of 13 case series and 16 case reports were collected, including a total of 564 pregnant women with COVID-19 and their 555 neonates, of which 549 neonates received nucleic acid test for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and 18 neonates was diagnosed with COVID-19. The positive rate is 3.28%. Amniotic fluid of one woman was tested positive for SARS-CoV-2. The majority of infected neonates were born under strict infection control and received isolation and artificial feeding. Up till now, there is no sufficient evidence to exclude the possibility of vertical transmission for COVID-19 based on the current available data.

Pre-Consultation System Based on the Artificial Intelligence Has a Better Diagnostic Performance Than the Physicians in the Outpatient Department of Pediatrics.

Artificial intelligence (AI) has been deeply applied in the medical field and has shown broad application prospects. Pre-consultation system is an important supplement to the traditional face-to-face consultation. The combination of the AI and the pre-consultation system can help to raise the efficiency of the clinical work. However, it is still challenging for the AI to analyze and process the complicated electronic health record (EHR) data. Our pre-consultation system uses an automated natural language processing (NLP) system to communicate with the patients through the mobile terminals, applying the deep learning (DL) techniques to extract the symptomatic information, and finally outputs the structured electronic medical records. From November 2019 to May 2020, a total of 2,648 pediatric patients used our model to provide their medical history and get the primary diagnosis before visiting the physicians in the outpatient department of the Shanghai Children's Medical Center. Our task is to evaluate the ability of the AI and doctors to obtain the primary diagnosis and to analyze the effect of the consistency between the medical history described by our model and the physicians on the diagnostic performance. The results showed that if we do not consider whether the medical history recorded by the AI and doctors was consistent or not, our model performed worse compared to the physicians and had a lower average F1 score (0.825 vs. 0.912). However, when the chief complaint or the history of present illness described by the AI and doctors was consistent, our model had a higher average F1 score and was closer to the doctors. Finally, when the AI had the same diagnostic conditions with doctors, our model achieved a higher average F1 score (0.931) compared to the physicians (0.92). This study demonstrated that our model could obtain a more structured medical history and had a good diagnostic logic, which would help to improve the diagnostic accuracy of the outpatient doctors and reduce the misdiagnosis and missed diagnosis. But, our model still needs a good deal of training to obtain more accurate symptomatic information.

The bone marrow niche components are adversely affected in sepsis.

Multiple organ dysfunction is an important cause of death in patients with sepsis. Currently, few studies have focused on the impact of sepsis on bone marrow (BM), especially on the cell components of BM niche. In this study, we performed mouse sepsis models by intraperitoneal injection of LPS and cecal ligation and puncture (CLP). The changes of niche major components in the mouse BM among vascular structures, mesenchymal stem cells and Treg cells were observed and analyzed. The results showed that pathological changes in BM was earlier and more prominent than in other organs, and various cell components of the BM niche changed significantly, of which vascular endothelial cells increased transiently with vascular remodeling and the regulatory T cells decreased over a long period of time. These results indicated that the components of the BM niche underwent series of adaptive changes in sepsis.

The therapeutic effect of high-volume hemofiltration on sepsis: a systematic review and meta-analysis.

BACKGROUND: Sepsis remains the leading cause of death in the intensive care unit (ICU), despite the treatment of sepsis has progressed. As a mode in continuous renal replacement therapy (CRRT), continuous veno-venous hemofiltration (CVVH) has been widely used in the treatment of sepsis. Whether high ultrafiltrate volume in CVVH is beneficial for sepsis survival remains controversial. We performed a systematic review and meta-analysis to evaluate the treatment effect of high-volume hemofiltration (HVHF) on sepsis. METHODS: A systematic search was conducted on the Medline, Embase, and Cochrane library to June 21, 2019, the keywords included "sepsis" "continuous blood purification" "continuous renal replacement therapy" "continuous veno-venous hemofiltration" and "continuous veno-venous hemodiafiltration". Summery statistic in this review was risk ratio (RR) and was performed by RevMan 5.2. RESULTS: Five randomized controlled trials (RCT) were included which contained 241 participants. Mortality related endpoints and other observations (length of stay, organ function evaluation, effect on hemodynamics, cytokine clearance and respiratory function) were used to assess the treatment effect of HVHF in sepsis. Three trials reported 28-day mortality, one of three trails also reported 60- and 90-day mortality; one trail did not specify the type of mortality; the fifth article reported hospital mortality. The pooled risk ratio for three trails of 28-day mortality was 0.96 (0.67, 1.38). Three trails reported length of stay related data. Four trails reported organ failure related scores. All trails reported the effect of HVHF on hemodynamics. Three trails reported cytokine clearance. Only two trails reported respiratory function related indicators. After analysis, the risk of bias in all trails was low. CONCLUSIONS: The meta-analysis results suggested that treatment programs contained HVHF did not change the outcomes of patients with sepsis. So far, related studies on the use of HVHF in critically ill patients with sepsis or septic shock is rare. Researchers should consider additional large multicenter randomized controlled trials.

The effect of high-frequency oscillatory ventilation or airway pressure release ventilation on children with acute respiratory distress syndrome as a rescue therapy.

BACKGROUND: To investigate the effects of high-frequency oscillatory ventilation (HFOV) or airway pressure release ventilation (APRV) as a rescue therapy on children with moderate and severe acute respiratory distress syndrome (ARDS). METHODS: We retrospectively enrolled 47 children with ARDS who were transitioned from synchronized intermittent mandatory ventilation (SIMV) to either HFOV or APRV for 48 h or longer after failure of SIMV. The parameters of demographic data, arterial blood gases, ventilator settings, oxygenation index (OI), and PaO2/FiO2 (PF) ratio during the first 48 h of HFOV and APRV were recorded. RESULTS: There was no significant difference between the HFOV and APRV groups with survival rates of 60% and 72.7%, respectively. Compared to pre-transition, the mean airway pressures at 2 and 48 h after transition were higher in both groups (P<0.01), and the PF ratio at 2 and 48 h in both modes was significantly improved (P<0.001). PF ratio and PaCO2 have significant differences at 48 h between two groups. The OI at 2 h after transition had no improvement in either group and was substantially lower at 48 h relative to the pre-transition level (P<0.001) in both groups. At 48 h after the transition to both HFOV and APRV, the survivors had lower mean airway pressures, higher PF ratios, and a lower OIs than non-survivors (P<0.01). CONCLUSIONS: There was no significant difference on the survival rates of HFOV and APRV application as a rescue therapy for ARDS, but improved oxygenation at 48 h reliably discriminated survivors from non-survivors in both groups.

The Comparative Immunological Characteristics of SARS-CoV, MERS-CoV, and SARS-CoV-2 Coronavirus Infections.

Immune dysfunction and aberrant cytokine storms often lead to rapid exacerbation of the disease during late infection stages in SARS-CoV and MERS-CoV patients. However, the underlying immunopathology mechanisms are not fully understood, and there has been little progress in research regarding the development of vaccines, anti-viral drugs, and immunotherapy. The newly discovered SARS-CoV-2 (2019-nCoV) is responsible for the third coronavirus pandemic in the human population, and this virus exhibits enhanced pathogenicity and transmissibility. SARS-CoV-2 is highly genetically homologous to SARS-CoV, and infection may result in a similar clinical disease (COVID-19). In this review, we provide detailed knowledge of the pathogenesis and immunological characteristics of SARS and MERS, and we present recent findings regarding the clinical features and potential immunopathogenesis of COVID-19. Host immunological characteristics of these three infections are summarised and compared. We aim to provide insights and scientific evidence regarding the pathogenesis of COVID-19 and therapeutic strategies targeting this disease.

Effect of high-volume hemofiltration on children with sepsis.

BACKGROUND: Sepsis has always been a challenge in pediatric intensive care unit (PICU) with poor prognosis. In order to evaluate the effect between routine continuous renal replacement therapy (CRRT) and high-volume hemofiltration (HVHF) in children with sepsis, we performed out this prospective, randomized, controlled, open-label trial. METHODS: Forty-seven children with sepsis were enrolled from January 2015 to December 2016. Twenty-two patients in Control group received routine CRRT and 25 patients in HVHF group received HVHF within 6 hours after the diagnosis of sepsis. The oxygenation index, serum creatinine, urea, lactate, inflammatory cytokines (IL-6, IL-10, and TNF-α), pediatric risk of mortality III (PRISM III) and 28-day mortality rate were collected and compared. RESULTS: The oxygenation index in HVHF group and Control group was significantly increased at 48 hours (P<0.01) and 72 hours after treatment (P<0.05). The same result of arterial lactate was observed. Serum creatinine, urea, IL-6, IL-10, TNF-α and PRISM III score were significantly ameliorated after 72 hours treatment in HVHF group (P<0.01), while there was no significant difference in Control group. After 72 hours of treatment, the oxygenation index, lactate, serum creatinine, urea, TNF-α, IL-6, IL-10 and PRISM III score in HVHF group were significantly improved compared with Control group (P<0.01). There is no significant difference on 28-day mortality between the two groups (P>0.05). CONCLUSIONS: HVHF might be an effective treatment for children with sepsis.

Nutritional survey in critically ill children: a single center study in China.

BACKGROUND: The incidence of malnutrition in children, who were admitted to the pediatric intensive care unit (PICU), has kept high level over the past 30 years. In addition, nutrition status of critically ill children deteriorates further during the changing of their conditions and may have a negative effect on patients' outcomes. This study aimed to determine the nutritional status of critically ill children and to survey current nutrition practices and support in PICU. METHODS: In this prospective observational study, 360 critically ill children stayed in the PICU not less than 3 days from Feb. to Nov. in 2017 were enrolled. Each patient underwent nutrition assessment. Nutritional status was determined using Z-scores of length/height-for-age (HAZ), weight-for-age (WAZ), weight-for-height (WHZ), body mass index-for-age (BAZ), based on the World Health Organization child growth standards. We also observed the patients' intake of calories and protein during the first 10 days after admission. RESULTS: Three hundred and sixty were enrolled in the study. One hundred and eighty-six patients (51.67%) were malnourished at PICU admission, above 50% and 56.45% (105/186) of malnourished patients had severe malnutrition. Except fasting in case of clinical instability in 5.3% (19/360), nutrition was provided in the form of oral feeding in 26.6% (96/360), enteral nutrition (EN) in 56.1% (202/360), parenteral nutrition (PN) in 6.4% (23/360) and mixed support (EN + PN) in 5.6% (20/360). Totally 384 times interruption of feeding happened in the process of EN, and 1.9 times feeding interruption happened to each patient. Twenty-seven point two percent of these patients had more than three times feeding interruption. The severe malnutrition group had significantly greater length of ICU stay and higher mechanical ventilation support rate (P=0.007, P=0.029). Total 44 (44/360, 12.22%) patients died in the study, and the malnutrition was not statistically different between survivor group and death group (P=0.379). More than 85% of the patients had lower daily nutritional intake compared with prescribed goals. Sixty-eight point three percent of the patients received the required calories during EN with median time of 2 [2-4] days. Only 32.7% of patients underwent EN received estimated protein requirements. CONCLUSIONS: These results showed that malnutrition was common among children admitted to PICU. Furthermore, nutrition delivery was generally inadequate in critically ill children, and nutritional status was getting worsening during PICU.

Peg-Asparaginase-Associated Pancreatitis in Chemotherapy-Treated Pediatric Patients: A 5-Year Retrospective Study.

BACKGROUND: Asparaginase-associated pancreatitis (AAP) is one of the most common complications occurring in patients with asparaginase-treated acute lymphoblastic leukemia (ALL). Peg-asparaginase (peg-asp), a chemically recombined asparaginase with lower hyposensitivity and better patient tolerance, is now approved as the first line asparaginase formulation in ALL chemotherapy regimens. Due to the differences in pharmacokinetic characteristics and administration procedure between l-asp and peg-asp, this study aimed to investigate the clinical manifestations of peg-asp-associated pancreatitis. METHOD: Patients with peg-asp-associated pancreatitis diagnosed within a 5-year period (July 2014 to July 2019) were identified and retrospectively studied. The clinical manifestations, laboratory findings, and imaging results of patients with AAP were analyzed. AAP patients were further classified into mild/moderate and severe groups based on criteria used in previous studies. Clinical outcomes were compared between groups. RESULTS: A total of 38 patients were enrolled in this study. The underlying disease included ALL (n=35) and lymphoma (n=3). The majority of patients developed AAP during the first phase, called remission induction (n=26, 68.4%), after a median of 2 peg-asp doses (range: 1-11). The DVLP regimen (n=23) is the most common peg-asp regimen used in AAP patients. Abdominal pain occurred after a median of 14.5 days (range: 1-50) from the last peg-asp administration, accompanied by abdominal distension (n=14), nausea (n=17), vomiting (n=21), and fever (n=19). Serum amylase elevation was reported in all AAP patients, of whom 65.8% (n=25) exhibited an elevation in the level of this enzyme three times the upper normal level, fulfilling the Atlanta criteria. The level of serum lipase (median days of elevation=23 days, range: 4-75) was significantly elevated compared with that of serum amylase (median days of elevation=9 days, range: 2-71) and persisted at a markedly high level after the level of serum amylase returned to normal. Common local complications included abdominal ascites (n=10) and peripancreatic fluid collection (n=8). Approximately 42.1% (n=16) of patients with severe AAP experienced systemic complications (septic shock or hypovolemic shock) or severe local complications (pseudocyst), among whom 5 failed to recover. Approximately 84.8% (n=28/33) of the remaining patients resumed chemotherapy; among them, peg-asp formulation in 30.3% (n=10/33) of these patients was adjusted, while asparaginase treatment in 39.4% (n=13/33) was permanently discontinued. Five patients experienced an AAP relapse in later stages of asparaginase treatment. Comparison between mild/moderate and severe AAP patients showed a statistically significant difference in the number of pediatric intensive care unit stays (p=0.047), survival rate (p=0.009), AAP prognosis (p=0.047), and impacts on chemotherapy (p=0.024), revealing a better clinical outcome in mild/moderate AAP patients. CONCLUSION: Early recognition and management of AAP is essential in reversing the severity of AAP. The existing AAP criteria had a low strength in determining the severity of pediatric AAP. A well-defined AAP definition could help distinguish patients with high anticipated risk for redeveloping AAP and ALL relapse, in order to prevent unnecessary withdrawal of asparaginase. Our study could serve as a basis for conducting future large cohort studies and for establishing an accurate definition of pediatric AAP.

The prognostic value of left ventricular systolic function and cardiac biomarkers in pediatric severe sepsis.

Echocardiography and cardiac biomarkers, such as cardiac troponin I (cTnI) and N-terminal pro-B-type natriuretic peptide (NT-pro BNP) are useful tools to evaluate cardiac dysfunction. Left ventricular systolic dysfunction (LVSD) is common in pediatric severe sepsis. The aim of this study is to evaluate the prognostic value of LVSD, cTnI, and NT-pro BNP for pediatric severe sepsis.A prospective, single center, observational study was conducted. Severe sepsis children were enrolled in the study from December 2015 to December 2016 in pediatric intensive care unit of Shanghai Children's Medical Center. Recorded general information, transthoracic echocardiography were performed at day 1, 2, 3, 7, and 10, using Simpson to measure left ventricular end-diastolic dimension and left ventricular end-systolic dimension, obtained echocardiography parameters: left ventricular ejection fraction (LVEF), left ventricular fractional shortening, left ventricular end-diastolic volume, left ventricular end- systolic volume, stroke volume, cardiac output. At the same time collecting the blood sample to measure cTnI, NT-pro BNP. The definition of LVSD was LVEF <50%. According to the prognosis of 28 days, children with severe sepsis were divided into survived group and nonsurvived group.Total of 50 pediatric patients who were diagnosed with severe sepsis (including septic shock) were enrolled, the incidence of LVSD was 52%. The 28-day mortality rate of severe sepsis was 34%. Multivariate logistic regression analyses for predictors of death in pediatric severe sepsis revealed that the 28-day mortality of severe sepsis was associated with mechanical ventilation (MV) within the first 6 hours of admission (odds ratio [OR], 0.01; 95% confidence interval [CI], 0.00-0.07) and total MV time (OR, 0.81; 95% CI, 0.68-0.97). The receiver operating characteristic curves LVEF (area under curve = 0.526), cTnI (area under curve = 0.480), and NT-pro BNP (area under curve = 0.624) were used to predict the 28-day mortality in pediatric severe sepsis. Follow-up echocardiography parameters for survived group and nonsurvived group showed no significant changes in LVEF, LVFS, stroke volume index, cardiac index (CI), left ventricular end-diastolic volume index and left ventricular end-systolic volume index at day 1, 2, 3, 7, and 10, except for CI at day 1 and 2. Kaplan-Meier plot of 28-day mortality and LVSD in pediatric severe sepsis showed there were no statistical differences (χ = 0.042, P = .837).LVSD occurs frequently in pediatric with severe sepsis. The 28-day mortality rate of severe sepsis was also high. In this study, none of LVSD, cTnI, and NT-proBNP was associated with the prognosis of pediatric severe sepsis.