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.

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.

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 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.

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.

Effect of etanercept on refractory systemic-onset juvenile idiopathic arthritis.

BACKGROUND: Treatment of systemic-onset juvenile idiopathic arthritis (So-JIA) is challenging, and the efficacy of injectable recombinant human tumor necrosis factor type 1 receptor-antibody fusion protein (etanercept) on So-JIA has been controversial. METHODS: We retrospectively studied 12 patients with refractory systemic juvenile arthritis treated with etanercept at our hospital in the past 5 years. The 12 patients were divided into a corticosteroid-dependent group (n=7) and an ineffective group (n=5) on the basis of their responses to treatment before the administration of etanercept. Etanercept was added to the treatment without substantially changing the original regimens in general, and doses, and signs of efficacy including alleviation or resolution of symptoms such as high fever, inflammatory arthropathy, eruption rash, hydrohymenitis, as well as changes in the levels of laboratory inflammatory markers such as the white blood cell count, erythrocyte sedimentation rate, levels of C-reactive protein and serum ferritin were recorded. RESULTS: Etanercept was withdrawn after the first dose from one patient in the corticosteroid-dependent group because of a systemic allergic rash, and was also withdrawn from one patient in the ineffective group after 2 months of treatment owing to inefficacy; the remaining 10 patients completed the entire treatment protocol, at which point etanercept was discontinued. At that time, clinical symptoms and laboratory inflammatory markers of the remaining patients were within the normal range and the mean dose of prednisone was 0.18 mg/kg per day, an 81% decrease from the mean dose at baseline. At present, the corticosteroid has been discontinued and only methotrexate maintenance treatment is used in 3 patients; the other 7 patients are treated with prednisone and methotrexate maintenance therapy. All of the 10 patients are in a medicated remission with no recurrence. CONCLUSIONS: In the treatment of patients with refractory So-JIA, the principles of individual therapy and combinations of drugs should be followed. Etanercept is an important and valid candidate for use in such combined treatment strategies.

[The protective effect of keratinocyte growth factor on lipopolysaccharide-induced acute lung injury in rat].

OBJECTIVE: To investigate the protective effect of keratinocyte growth factor (KGF) on lipopolysaccharide (LPS)-induced acute lung injury (ALI) and its potential mechanism in rats. METHODS: Thirty-six Sprague-Dawley (SD) rats were randomly divided into three groups, each group with 12 rats. LPS (5 mg/kg) was injected intravenously to induce ALI in model group, and same amount of normal saline was injected in control group and KGF group. The rats in KGF group were treated with KGF (5 mg/kg) intratracheally after injection of LPS. The rats were sacrificed after 8 hours, histologic assessments, wet/dry weight (W/D) ratio, pulmonary vascular permeability, lung epithelial cell permeability, the proliferation and repair capacity of type II alveolar epithelial cells (ATII) were analyzed. RESULTS: Under optical microscope, it was found that KGF could reduce injury to lung tissue induced by LPS. Compared with the model group, KGF could decrease pulmonary vascular permeability [(0.026+/-0.049)% vs. (0.087+/-0.027)%], lung epithelial cell permeability [(0.692+/-0.017)% vs. (0.931+/-0.029)%] and W/D ratio (4.778+/-0.243 vs. 6.869+/-0.153, P<0.05 or P<0.01), enhance the proliferation and repair capacity of ATII cells (ATII cells: 6.083+/-1.781 vs. 4.666+/-1.923, injury area (mm2): 2.946+/-0.453 vs. 6.181+/-0.975, P<0.05 and P<0.01). CONCLUSION: KGF could reduce the injury to the lung in LPS-induced ALI, and it plays a protective role through enhancing the proliferation and repair capacity of ATII cells.

Clinical characteristics and treatment of severe encephalitis associated with neurogenic pulmonary edema caused by enterovirus 71 in China.

BACKGROUND: Hand-foot-mouth disease has become a major public health issue in children in China. In the present prospective study we investigated the clinical characteristics and emergency management of children with severe encephalitis associated with NPE caused by enterovirus 71. METHODS: The study was conducted in 2 pediatric intensive care units (PICUs) over a 2-month period. Clinical records were reviewed of critically ill children with severe encephalitis associated with NPE caused by EV71 who were admitted to PICUs during the period of May to June 2008 in Fuyang. RESULTS: We reviewed the complete records of 36 children, of whom 23 (63.9%) were male and 13 (36.1%) female. Their age ranged from 4 to 48 months, with an average of 15.8 months. All children except one were under 3 years of age. The overall mortality in these children was 19.4%. The average duration of critical life threatening signs and symptoms was 2.1 days (12 hours-5 days). Nervous system diseases included brainstem encephalitis in 27 children (75%), brainstem encephalitis associated with myelitis in 6 children (16.7%), and general encephalitis in 3 chidren (8.3%), respectively. In 12 patients of NPE (33.3%) pink or bloody bubble sputum and asymmetric pulmonary edema or hemorrhage was the primary manifestation but no typical exanthema was observed. Five children died of acute onset of NPE and / or pulmonary hemorrhage with rapid progression of cardiopulmonary failure within hours after admission. Therapeutic management consisted of mechanical ventilation and administration of mannitol, methylprednisolone, intravenous immunoglobulin (IVIG) and vasoactive drugs, associated with the need of fluid volume resuscitation in 9 (25%) of the 36 children. CONCLUSIONS: In children less than 3 years of age found to be affected by severe EV71 encephalitis associated with NPE, one fifth may die. The major organ systems infected by severe EV71 include the central nervous system, the respiratory system, and the cardiovascular system. Early diagnosis and evaluation, respiratory support, treatment of intracranial hypertension, and mainttenance of function of the cardiovascular system are the most important therapeutic measures.

[Value of plasma beta-Glucan in early diagnosis of invasive fungal infection in children].

OBJECTIVE: The incidence of invasive fungal infection (IFI) has risen dramatically along with the prolongation of immunocompromised individuals' lifespan. This study aimed to investigate the incidence of IFI among high risk pediatric patients and to evaluate the diagnostic value of circulating (1,3)-beta-D-glucan (BG) in IFI. METHODS: High risk pediatric inpatients from hemato-oncology department and ICU were enrolled from November 2007 to June 2008. All the patients had persistent fever for 4 to 7 days or longer. Circulating BG levels were detected once or twice weekly until the signs and symptoms improved, or IFI was excluded, or death. Circulating BG levels were determined by the GKT-5M Set Kinetic Fungus Detection Kit. Detection of plasma BG was judged positive when the level was > or = 10 pg/mL. RESULTS: A total of 130 patients were enrolled. Two patients with candidemia were classified as proven IFI, 20 as probale IFI,7 as possible IFI, and 101 without IFI. The patients with proven or probable IFI had a longer length of hospital stay (P< 0.05) and an increased mortality rate (P< 0.05). The patients with IFI demonstrated a higher plasma level of BG than those without IFI (P< 0.01). The sensitivity, specificity, positive and negative predictive values for plasma BG detction were 81.8%, 82.4%, 48.6% and 95.7% respectively. Positive BG results occurred before the abnormal results on computed tomography scan or fungal culture or simultaneously in 72.2% of the cases. CONCLUSIONS: IFI is not rare among pediatric high-risk patients. Circulating BG detection is accurate to a certain extent in the diagnosis of IFI. It is a useful adjunct means for IFI screening in high-risk patients.