Osteosarcoma (OS) is among the most frequently occurring bone tumors, particularly in children. Clinical treatment of OS is limited due to several factors including resistance to chemotherapy drugs and metastasis, and the underlying molecular mechanisms remain unclear. In the present study, tripartite motif containing 37 (TRIM37) expression levels were upregulated in tumor samples and associated with the development of drug resistance in OS. Furthermore, chemotherapy drug treatment (doxorubicin, cisplatin and methotrexate) induced TRIM37 expression in OS cells in vitro. TRIM37 mRNA and protein were upregulated in 41 pediatric osteosarcoma clinical specimens. To further elucidate the effect of TRIM37, gain and loss-of-function analysis was performed. Overexpression of TRIM37 induced cell proliferation and drug resistance ability of OS cells, whilst TRIM37 knockdown suppressed cell growth rate and restored chemosensitivity. TRIM37-regulated genes were subsequently analyzed by expression microarray and gene set enrichment analysis. Using the Wnt/β-catenin inhibitor XAV-939, the present study demonstrated that TRIM37-induced chemoresistance is partially dependent on the activation of the Wnt/β-catenin signaling pathway. Collectively, the results of the present study suggest that TRIM37 may have a key role in the development of OS and in the ability for the cells to acquire drug resistance, thus it may be a novel target for the treatment of OS.
BACKGROUND:The latest sepsis definition includes both infection and organ failure, as evidenced by the sequential organ failure assessment (SOFA) score. However, the applicability of the pediatric SOFA score (pSOFA) is not yet determined. This study evaluated the effectiveness of both pSOFA and system inflammatory reaction syndrome (SIRS) scores in predicting sepsis-related pediatric deaths.METHODS: This is a retrospective multi-center cohort study including hospitalized patients <18 years old with diagnosed or not-yet-diagnosed infections. Multivariate analyses were carried out to evaluate risk factors for in-hospital mortality. According to Youden index (YI), three sub-categories of pSOFA were screened out and a new simplified pSOFA score (spSOFA) was formed. The effectiveness and accuracy of prediction of pSOFA, SIRS and spSOFA was retrieved from the area under the receiver operating characteristic curve (AUROC) and Delong's test.RESULTS: A total of 1,092 participants were eligible for this study, and carried a 23.4% inhospital mortality rate. The 24-h elevated pSOFA score (24 h-pSOFA), bloodstream infection, and mechanical ventilation (MV) requirement were major risk factors associated with sepsis-related deaths. The AUROC analysis confirmed that the spSOFA provided good predictive capability in sepsis-related pediatric deaths, relative to the 24 h-pSOFA and SIRS.CONCLUSIONS: The pSOFA score performed better than SIRS in diagnosing infected children with high mortality risk. However, it is both costly and cumbersome. We, therefore, proposed spSOFA to accurately predict patient outcome, without the disadvantages. Nevertheless, additional investigations, involving a large sample population, are warranted to confirm the conclusion of this study.
ObjectivesIn the early stage of sepsis, identifying high-risk paediatric patients with a poor prognosis and providing timely and adequate treatment are critical. This study aimed to evaluate the effect of average body temperature within 24 hours of admission on the short-term prognosis of paediatric patients with sepsis.DesignA retrospective cohort study.SettingA single-centre, tertiary care hospital in China, containing patient data from 2010 to 2018.Participants1144 patients with sepsis were included.InterventionNone.Primary and secondary outcome measuresThe main outcome measure was in-hospital mortality, which was defined as death from any cause during hospitalisation. The secondary outcome was the length of hospital stay.ResultsThe LOWESS method showed a roughly ‘U’-shaped relationship between body temperature on the first day and in-hospital mortality. Multivariate logistic regression showed that severe hypothermia (OR 14.72, 95% CI 4.84 to 44.75), mild hypothermia (OR 3.71, 95% CI 1.26 to 10.90), mild hyperthermia (OR 3.41, 95% CI 1.17 to 9.90) and severe hyperthermia (OR 5.15, 95% CI 1.84 to 14.43) were independent risk factors for in-hospital mortality. Compared with other variables, the Wald χ2value of temperature on the first day minus the degree of freedom was the highest.ConclusionsWhether hypothermic or hyperthermic, the more abnormal the temperature on the first day is, the higher the risk of in-hospital death in children with sepsis.
Objectives: This study aimed to compare the efficacy of double plasma molecular adsorption system (DPMAS) with half-dose plasma exchange (PE) to that of full-dose PE in pediatric acute liver failure (PALF). Methods: This multicenter, retrospective cohort study was conducted in 13 pediatric intensive care units in Shandong Province, China. DPMAS+PE and single PE therapies were performed in 28 and 50 cases, respectively. The patients’ clinical information and biochemical data were obtained from the patients’ medical records. Results: The severity of illness did not differ between the 2 groups. At 72 hours after treatment, comparing with PE group, the rates of decline of Pediatric model for End-stage Liver Disease and Pediatric Sequential Organ Failure Assessment scores as well as total bilirubin blood ammonia and interleukin-6 were significantly higher, while the short-term effective rate (75.0% vs 44.0%, P = 0.008) was significantly higher in the DPMAS+PE group. The volume of plasma consumption (26.5 vs 51.0 mL/kg, P = 0.000) and the rate of adverse events (3.6% vs 24.0%, P = 0.026) were lower in the DPMAS+PE group than in the PE group, respectively. However, there was no statistical difference in the 28-day mortality between the 2 groups (21.4% vs 40.0%, P > 0.05). Conclusions: For PALF patients, both DPMAS + half-dose PE and full-dose PE could improve the liver function, while DPMAS + half-dose PE could significantly reduce plasma consumption without obvious adverse effects in contrast with full-dose PE. Thus, DPMAS + half-dose PE may be a suitable alternative method for PALF in the context of the increasingly tight blood supply situation.
Objective: To identify the pathogens and compare the clinical characteristics between different type pathogen infection among children with community-acquired pneumonia (CAP) requiring bronchoalveolar lavage. Study design: Children <14 years old hospitalized with CAP requiring bronchoalveolar lavage were enrolled between February 2019 to January 2020. Multiplex reverse transcription polymerase chain reaction (mRT-PCR) and loop-mediated isothermal amplification (LAMP) were used for pathogen detection. The demographic and clinical characteristics were compared between different type pathogen infection groups. Results: Among 1166 children studied, ≥1 pathogen was detected in 1084 (93.0%) children and co-infection was detected in 215 (18.4%) children. Mycoplasma pneumoniae, Streptococcus pneumoniae and adenovirus were the most frequently detected pathogens. Children infected with atypical bacteria alone were older and more likely to display a fever, cough, decreased breath sounds, consolidation, single lobar infiltration, mucosal erosion and/or necrosis and plastic bronchitis. Children with virus-atypical bacteria co-infection were more prone to manifest fatigue, chest pain, tachypnea, chest indrawing, and mucosal erosion and/or necrosis. Those infected with virus alone or co-infected with ≥3 pathogens were liable to display changes in bronchial morphology. Conclusions: Pathogens were detected in 93.0% of enrolled children. M. pneumoniae infection might be the greatest pediatric disease burden due to CAP in North China. Keywords: Children; community-acquired pneumonia; bronchoalveolar lavage fluid; etiology; co-infection.
Background: The sepsis version 3.0 highlights the co-existence of infection with organ dysfunction, assessed by the Sequential Organ Failure Assessment (SOFA) score. However, the prognostic accuracy of the Pediatric SOFA score (pSOFA) for in-hospital mortality was not fully validated. We compared the performance of the pSOFA with the SIRS criteria as predictors of in-hospital mortality in children with infectious disease and evaluate whether the pSOFA is suitable to be used in pediatric intensive care units (PICU) in Shandong Province, China.Methods::A retrospective multicenter cohort study was conducted on children hospitalized with confirmed or suspected infection, between January 2011 and December 2019, in three PICUs of three tertiary care hospitals in Shandong Province. The maximum pSOFA score and SIRS criteria within the first 24 hr of PICU admission were calculated. Univariate and multivariate logistic regressions were conducted to analyze the risk factors for in-hospital mortality. Three sub-components of the pSOFA score with relatively good predictive value were identified according to the Yuden Index and formed a simple-pSOFA score. The efficiency and diagnostic ability of these scores were compared by measuring the area under the receiver operating characteristic curve (AUROC) and Delong’s test.Results: 1092 patients were included and the overall in-hospital mortality was 23.4%. Multivariate logistic regressions showed that high 24h pSOFA score, bloodstream as the main infection site, and the need for MV were the risk factors for in-hospital mortality. The AUROC analysis verified that simple-pSOFA had the best diagnostic ability in predicting in-hospital mortality of infected children compared with the 24h pSOFA score and SIRS criteria. The sensitivity and specificity of 24h pSOFA score ≥2 were the highest, 97.6% and 78.9%, respectively.Conclusions: The pSOFA score was superior to SIRS criteria in identifying children with infection and a high risk of mortality, but it is expensive and time-consuming to complete the pSOFA score. Simple-pSOFA score is superior to pSOFA score in early identification of infected children with a high risk of death, but further validation studies with a larger size is needed.
Introduction: Familial chylomicronemia syndrome (FCS) is a rare genetic disease. FCS usually manifests by the age of 10 years, and 25% of cases of FCS occur during infancy. Here we present a case of FCS in a male infant and summarize our experiences on the diagnosis and therapy of this case. Patient concerns: A male infant aged 1 month and 8 days had recurrent hematochezia and hyperchylomicronemia. Diagnosis: FCS based on symptoms and genetic test. Interventions: Plasma exchange therapy. Outcomes: His development was normal with a good spirit and satisfactory weight gain, and no hematochezia occurred again. Conclusion: Genetic test is important for accurate diagnosis of FCS, and we identified a new mutation of lipoprotein lipase gene c.88C>A which conformed to autosomal recessive inheritance. Plasma exchange therapy can be applied to infants with FCS with low risk and good outcomes.
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