Diagnostic Accuracy of Plasma Ghrelin Concentrations in Pediatric Sepsis-Associated Acute Respiratory Distress Syndrome: A Single-Center Cohort Study.

Background: Ghrelin is the endogenous ligand of growth hormone secretagogue receptor 1a, which plays a role in regulating immunity and inflammation. The aim of this study is to assess the diagnostic value of plasma ghrelin in sepsis-associated pediatric acute respiratory distress syndrome (PARDS). Methods: We recruited patients who were admitted to the pediatric ICU (PICU) of the Children's Hospital of Chongqing Medical University between January 2019 and January 2020 and met the diagnostic criteria for sepsis. Data on clinical variables, laboratory indicators, plasma ghrelin concentrations, and inflammatory factors were collected and evaluated, and patients were followed up for 28 days. The area under the receiver-operating characteristic curves (AUROC) were determined using logistic regression to calculate and test cut-off values for ghrelin as a diagnostic indicator of sepsis-associated PARDS. The log-rank test was used to compare survival according to ghrelin levels. Main results: Sixty-six PICU patients (30 with ARDS and 36 without ARDS) who met the diagnostic criteria of sepsis were recruited. The ghrelin level was significantly higher in the ARDS group than in the non-ARDS group. The AUROC of ghrelin was 0.708 (95% confidence interval: 0.584-0.833) and the positivity cutoff value was 445 pg/mL. Sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio, and negative likelihood ratio of plasma ghrelin for the diagnosis of PARDS-associated sepsis were 86.7, 50.0, 59.1, 81.8, 1.734, and 0.266%, respectively. The survival rate of sepsis patients were significantly improved when the ghrelin level was >445 pg/mL. Conclusions: Ghrelin plasma levels were higher in sepsis-associated PARDS, and accompanied by increased levels of inflammatory factors. High ghrelin levels are a positive predictor of ICU survival in sepsis patients. Yet, there is no evidence to prove that elevated ghrelin is a promising diagnostic indicator of sepsis-associated PARDS. Trial registration: Clinicaltrials, ChiCTR1900023254. Registered 1 December 2018 - Retrospectively registered, http://www.clinicaltrials.gov/ChiCTR1900023254.

The epidemiology of hospital death following pediatric severe community acquired pneumonia.

BACKGROUND: Community acquired pneumonia is the primary cause of pediatric hospitalizations and deaths in children under 5 years of age. But the epidemiology of death in pediatric severe community acquired pneumonia was not well characterized. METHODS: This retrospective observational study was performed at the academic Emergency department and intensive care unit and we investigated the timing, cause, mode and attribution of death in children with severe community acquired pneumonia. RESULTS: Of 962 subjects with severe community acquired pneumonia, there were 57 non-survivors (5.9% mortality). Median time to death was 7 [IQR 3,16] days from severe community acquired pneumonia recognition. Patients dying ≤7 days were younger, had greater illness severity and higher rate of congenital heart disease, who were more likely to die of a cardiovascular cause. Multiple organ dysfunction syndrome predominated in deaths > 7 days. Unsuccessful cardiopulmonary resuscitation was the most common mode of death at all timepoints. Our findings suggested that in pediatric severe community acquired pneumonia, early deaths were due primarily to cardiovascular dysfunction, while later deaths were more commonly due to multiple organ dysfunction syndrome. CONCLUSIONS: Deaths from non-pulmonary factors accounted for a substantial portion of non-survivors. Respiratory dysfunction accounted for only a minority of deaths. Our study highlighted limitations associated with rescuing patients with severe pneumonia from death if extrapulmonary organ dysfunctions could not be simultaneously managed.

Incidence of Adverse Effects of Propofol for Procedural Sedation/Anesthesia in the Pediatric Emergency Population: A Systematic Review and Meta-Analysis.

BACKGROUND: To investigate the incidence of adverse effects of propofol among pediatric population for sedation or anesthesia. METHODS: We performed Cochrane Library, PubMed, CNKI, VIP, and Wanfang databases to research relevant literature. We did sensitivity analysis to assess the incidence of adverse effects of propofol among pediatric population for sedation or anesthesia. RESULTS: In 132 studies, eight RCTs were included in this analysis. The result showed that adverse events (bradypnea, hypotension, hypertension, and apnea) were significantly improved in the pediatric emergency population in the propofol group, but it had no effect on the incidence of cough attacks, desaturation, agitation, stridor, and laryngospasm. Furthermore, the subgroup analysis showed that those who received propofol for had decreased adverse effects compared with the patients who received ketamine treatment (SMD = 0.44, 95%CI = [0.28, 0.67], I 2 = 0%, and P = 0.0002), which demonstrated that propofol could decrease the incidence of adverse effects compared with ketamine and ketofol. CONCLUSIONS: The study demonstrated that propofol may decrease the incidence of bradypnea, hypotension, hypertension, and apnea, but it had no effect on the incidence of cough attacks, desaturation, agitation, stridor, and laryngospasm. Furthermore, more large RCTs are needed to assess incidence of adverse effects of propofol among pediatric population.

A meta-analysis of randomized controlled trials: Efficacy of selenium treatment for sepsis.

BACKGROUND: To understand the clinical outcomes of selenium therapy in patients with sepsis syndrome, we conducted a meta-analysis of randomized controlled trials (RCT). METHODS: A total of 13 RCTs comparing selenium and placebo for patients with sepsis were reviewed systematically. RESULTS: However, we could not detect the association of selenium treatment with a decreased mortality at different time course (relative risk [RR] [95% confidence interval, CI]: 0.94 [0.82-1.06] at day 28; 0.73 [0.36-1.47] at day 90; 1.16 [0.78-1.71] at 6 months; respectively). Selenium supplementation did not show favorable efficacy in the incidence of renal failure, secondary infection or duration of mechanical ventilation (RR [95% CI]: 0.65 [0.41-1.03]; 0.96 [0.87-1.06]; standard mean difference [SMD] [95% CI]: 0.17 [-0.30-0.63]; respectively). Interestingly, we found that selenium therapy was benefit for sepsis patients with reduced duration of vasopressor therapy, staying time in intensive care unit and hospital, and incidence of ventilator-associated pneumonia (SMD [95% CI]: -0.75 [-1.37 to -0.13]; -0.15 [CI: -0.25 to -0.04]; -1.22 [-2.44 to -0.01]; RR [95% CI]: 0.61 [0.42-0.89]; respectively). CONCLUSION: Based on our findings, intravenous selenium supplementation could not be suggested for routine use.

Efficacy and safety of immunosuppressive medications for steroid-resistant nephrotic syndrome in children: a systematic review and network meta-analysis.

BACKGROUND: Conventional meta-analyses and randomized controlled trials have shown inconsistent results regarding the efficacy of immunosuppressants for pediatric steroid-resistant nephrotic syndrome (SRNS). OBJECTIVE: To conduct a network meta-analysis aimed at evaluating the efficacy and safety of available immunosuppressive agents in pediatric patients with SRNS. STUDY METHODS: MEDLINE, the Cochrane Central Register of Controlled Trials, and EMBASE were searched on January 2017. Data from randomized controlled trials (RCTs) were included. The main outcomes analyzed were efficacy [number/portion with complete remission (CR), number/portion with partial remission (PR), and total number/portion in remission (TR)] and safety [adverse secondary event (ASE) rates]. RESULTS: A meta-analysis of 18 RCTs showed that tacrolimus was more efficacious for achieving CR than intravenous (i.v.) cyclophosphamide, mycophenolate mofetil (MMF), oral cyclophosphamide, leflunomide, chlorambucil, azathioprine, and plaebo/nontreatment (P/NT), and more efficacious than i.v. cyclophosphamide, oral cyclophosphamide, and P/NT in terms of TR outcomes. Cyclosporin was associated with a greater CR rate than i.v. cyclophosphamide, MMF, oral cyclophosphamide, chlorambucil, azathioprine, or P/NT, and associated with a greater TR rate than i.v. cyclophosphamide, oral cyclophosphamide, or P/NT. MMF was found to be more efficacious than i.v. cyclophosphamide and oral cyclophosphamide in terms of TR. CONCLUSIONS: Tacrolimus and cyclosporine may be preferred initial treatments for children with SRNS. MMF may be another option for this patient population. Further studies of the efficacy and safety of these three drugs in children with SRNS should be pursued.

B-type brain natriuretic peptide as a measure of the severity of hand-foot-mouth disease: a case-control study.

BACKGROUND: Hand-foot-mouth disease (HFMD) is an acute infectious disease caused by enteroviruses, and HFMD complicated by cardiopulmonary failure has a high mortality. B type natriuretic peptide (BNP) is widely applied in monitoring cardiovascular disorders, and thus, we investigated whether this index was associated with the severity of HFMD and the outcome in severe HFMD. METHODS: Serum BNP, lactate, and glucose levels as well as white blood cell (WBC) count, PaO2/FiO2, and cardiac output (CO) were analyzed in the 83 enrolled HFMD patients according to different conditions (common, severe, and critical; with and without complication; and survivors and non-survivors). The control group consisted of 29 patients with respiratory tract infections. RESULTS: No significant differences in CO were observed between the groups. Serum lactate, glucose, BNP, and WBC levels in the critical group were significantly higher than those in the severe, common, and control groups (p < 0.01 or 0.05). The PaO2/FiO2 ratio was significantly lower in the critical group (214.286 ± 154.346) than in the other groups. According to logistic regression analysis, the areas under the curve for serum BNP, glucose, and PaO2/FiO2 of the patients with complications were 0.774, 0.738, and 0.75, respectively. Moreover, the BNP level was significantly higher in HFMD patients with complications and non-survivors. CONCLUSION: Our findings indicate that BNP could be a biochemical indicator for severe (critical) HFMD and used for prognosis in terms of complications and death. Combined with Glu and PaO2/FiO2 and clinical symptoms of HFMD, the value of BNP as an indicator became more precise and specific. Our results may provide another valuable, objective biochemical indicator for severe HFMD. TRIAL REGISTRATION NUMBER: ChiCTR-DDT-14004576 . Name of registry: Chinese Clinical Trial Registry. Date of registration: 2014-09-21.

Vasoactive intestinal peptide protects alveolar epithelial cells against hyperoxia via promoting the activation of STAT3.

Oxidative stress injury and death in alveolar epithelial cells plays an important role in the pathogenesis of prolonged hyperoxia-induced lung impairment. A reduced survival of type II alveolar epithelial cells (AECIIs) may lead to abnormal repair, resulting in acute and chronic pulmonary diseases. Hyperoxia lung injury is associated with the secretion of various bioactive substances and the activation of multiple transcription factors. Vasoactive intestinal peptide (VIP), as a pulmonary sensory neuropeptide, performs a vital function in regulating cell proliferation and cell death through signal transducers and activators of transcription 3 (STAT3). In the present study, we investigated the effects of VIP and STAT3 on AECIIs upon the exposure of hyperoxia. MLE-12 cells were random to air (21% oxygen), hyperoxia (95% oxygen) and VIP treatment with or without STAT3 siRNA transfection. The proliferation of AECIIs was detected by MTT cell proliferation assay. The apoptosis rate was measured by flow cytometry. Mitochondrial membrane potential was evaluated by fluorescent dye JC-1 to understand mitochondrial and cell damage. The activation of STAT3 was assessed by western blot detection of phosphorylated STAT3. Compared with hyperoxia exposure alone, additional VIP treatment promoted cell proliferation, maintained the mitochondrial membrane potential and reduced the apoptosis and necrosis of AECIIs. The protective effects aforesaid were weakened after STAT3 expression was down regulated by siRNA. Cells with STAT3 siRNA transfection had a higher mortality and a sharper decline in the mitochondrial membrane potential as well as a lower proliferation compared with wild-type cells after hyperoxia exposure with VIP administration. VIP interference, a protective management, could decrease hyperoxia-induced cell injury and death and improve the survival of AECIIs exposed to hyperoxia, which might be associated with the activation of STAT3.

Role of vasoactive intestinal peptide in hyperoxia-induced injury of primary type II alveolar epithelial cells.

OBJECTIVE: We investigated the effect of VIP on primary type II alveolar epithelial cells (AECIIs) upon the exposure of hyperoxia. METHODS: AECIIs were isolated and purified from premature rats and exposed to air (21% oxygen), hyperoxia(95% oxygen), VIP+air and VIP+hyperoxia, respectively. The proliferation and apoptosis of AECIIs were detected by MTT cell proliferation assay, flow cytometry and western blot. The production of intracellular reactive oxygen species (ROS) was determined by 2 ', 7'-dichloro-dihydrotestosterone fluorescein diacetate (DCFH-DA) molecular probe and the total antioxidant capacity (TAOC) by ultraviolate spectro-photometer. RESULTS: Cell proliferation significantly increased and apoptosis decreased upon the treatment with VIP. In addition, the level of ROS in the hyperoxia+VIP group was significantly lower than in the hyperoxia group, in contrast, TAOC was higher in the hyperoxia+VIP group than that in the hyperoxia group. CONCLUSIONS: VIP exerts a protective role in the hyperoxia-induced oxidative stress damage in AECIIs, which probably attributed to its anti-oxidant and anti-apoptosis property.

Microbiological study of pathogenic bacteria isolated from paediatric wound infections following the 2008 Wenchuan earthquake.

On 12 May 2008, the Wenchuan earthquake struck in Sichuan, China. Within 1 month after the earthquake, 98 injured children were admitted to the Children's Hospital of Chongqing Medical University. According to clinical manifestations, 50 children were diagnosed with wound infections. Wound secretions were cultured for bacteria. Pathogen distribution and drug resistance were analyzed. A total of 99 pathogens were isolated; 16 (16%) were Gram-positive bacteria and 81 (82%) were Gram-negative bacteria. The distribution of pathogens isolated within 1 month after the earthquake was different to the distribution of pathogens in 546 general hospitalized cases in the y before the earthquake. The pathogens most frequently isolated 1 month after the earthquake were Acinetobacter baumannii (27%), Enterobacter cloacae (18%) and Pseudomonas aeruginosa (13%). The pathogens most frequently isolated in the y prior to the earthquake were Escherichia coli (27%), Staphylococcus aureus (23%) and coagulase-negative staphylococci (9%). The rate of isolated drug-resistant bacteria was higher in the earthquake cases than in the general hospitalized cases. In the cases injured in the earthquake, the rates of isolation of methicillin-resistant Staphylococcus aureus and extended-spectrum beta-lactamase-producing E. cloacae, E. coli and Klebsiella pneumoniae were higher than in the cases from before the earthquake. Multidrug-resistant and pandrug-resistant A. baumannii were isolated at a higher rate in cases after the earthquake than in those before the earthquake. These changes in the spectrum of pathogens and in the drug resistance of the pathogens isolated following an earthquake will provide the basis for emergency treatment after earthquakes.

[Risk factors for the occurrence and severity of crush syndrome in pediatric trauma victims after earthquake].

OBJECTIVE: To analyze the factors affecting the occurrence and severity of crush syndrome (CS) after crush injury (CI) in pediatric trauma victims in the Wenchuan earthquake. METHODS: Medical records of 98 patients who were transferred to our hospital were retrospectively reviewed. The risk factors, such as age, gender, time being besieged, type of injury, wound infection, hemodialysis, etc., which were assessed with T-test/chi(2)/Fisher's exact tests and logistic regression analysis for the occurrence of crush syndrome after crush injury. Possible risk factors influencing CS severity were analyzed. RESULTS: There were 15 patients with CS, and all these cases were from 59 patients with extremities crush injury. The incidence of CS reached 15.3% in pediatric trauma victims after earthquake and 25.4% in extremities crush injury. Six risk factors were assessed with logistic regression analysis for three outcomes relating to crush syndrome, they are age, time being szeged and closed CI, whose log-odds ratio (log-OR) respectively was 1.049, 1.221, and 0.068 (P < 0.05 for all). And no correlation was found between CS and gender, upper or lower limbs injury or wound infection. There was no significant difference in wounds infection rate between patients with open injury and those who underwent CS fasciotomy (P = 0.754), but there was significant difference between those patients who underwent CS fasciotomy and those who underwent other operative incisions (P < 0.05). Wound infection had a significant association with severity of CS (P = 0.041) as compared with other factors such as age, gender, and time being szeged. CONCLUSION: The occurrence of crush syndrome is mainly because of extremities crush injury and also has significant relations with age, time being szeged and closed crush injury in children. Infection of incisional wound after CS fasciotomy is a risk factor for aggravation of CS.

[Distribution and drug resistance of pathogenic bacteria isolated from infected wounds of children after Wenchuan earthquake].

OBJECTIVE: To investigate the distribution and the drug resistance pattern of pathogenic bacteria isolated from pediatric cases suffering from wounds infection following the Wenchuan earthquake. METHODS: Of the ninety-eight injured children, 50 had wound infection diagnosed by clinical examination. Specimens for culture were collected from the fifty injured children and the results of bacterial identification and antibiotic resistance were retrospectively reviewed. RESULTS: In the fifty injured children with wound infection, microbial growth was detected in 31 (62.0%) and 21 children suffered from mixed infections (the infection rate was 67.7%). Ninety-nine pathogens were isolated, gram positive bacteria accounted for 16.16% (16 strains), Gram negative bacteria accounted for 81.82% (81 strains), and fungus 2.02% (2 strains). Staphylococcus aureus (5 strains, 5.05%), Enterococcus faecalis (3 strains, 3.03%) and Enterococcus faecium (2 strains, 2.02%) were the primary Gram-positive bacteria identified and Gram-negative infections typically included Acinetobacter baumanii (27 strains, 27.27%), Enterobacter cloacae (18 strains, 18.18%) and Pseudomonas aeruginosa (13 strains, 13.13%). Acinetobacter baumanii was the most common organism isolated from wounds. Duration of being szeged and complications had a significant association with wound infection with Acinetobacter baumanii. Drug sensitivity tests displayed that the isolated bacteria were highly resistant to common antibiotics. One strain of Acinetobacter baumanii-calcoaceticus complex and six strains of Acinetobacter baumanii were resistant to all common antibiotics including imipenem/cilastatin. Vancomycin-resistant Gram-positive bacteria were not identified. CONCLUSION: Following the Wenchuan earthquake disaster, wound infection profiles of pediatric patients were significantly different, Acinetobacter baumanii was the main common organism isolated from wounds in contrast to the previous low isolation rate. The isolated bacteria were highly and multiple drug resistant and it was difficult to treat. Knowing the distribution and the drug resistance pattern of pathogen is of paramount importance in guiding the clinical treatment.