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The role of inflammatory cytokines in children with moderate to severe TBI (m-sTBI) is still incompletely understood. We aimed to investigate the associations between early plasma expression profiles of inflammatory cytokines and clinical outcomes in children with m-sTBI. We prospectively recruited children admitted to the intensive care unit (ICU) of a tertiary pediatric hospital due to m-sTBI from November 2022 to May 2023. Plasma interleukin (IL)-1ß, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12p70, IL-17A, interferon (IFN)-α, IFN-γ and tumor necrosis factor (TNF)-α concentrations were detected by flow cytometry on admission and on days 5 to 7. The primary outcome was in-hospital mortality. The secondary outcome was the 6-month functional outcome assessed by the Glasgow Outcome Scale Extended-Pediatrics (GOS-E Peds) score, dichotomized as favorable (1-4) or unfavorable (5-8). Fifty patients and 20 healthy controls were enrolled. Baseline IL-6, IL-8 and IL-10 levels were significantly higher in TBI patients than in healthy controls. Twelve patients died in the hospital. Compared with survivors, nonsurvivors had significantly increased baseline IL-6 and IL-8 levels. Baseline IL-5, IL-6 and IL-8 levels were also significantly greater in children with unfavorable versus favorable outcomes. The area under the receiver operating characteristic curve (AUC) of the IL-6 and IL-8 levels and motor Glasgow Coma Scale (GCS) score for predicting in-hospital mortality was 0.706, 0.754, and 0.776, respectively. Baseline IL-1ß, IL-2, IL-4, IL-10, IL-12p70, IL-17A, IFN-γ, IFN-α and TNF-α levels were not associated with in-hospital mortality or an unfavorable 6-month outcome. On days 5 to 7, the IL-6 and IL-8 levels were significantly decreased in survivors but increased in nonsurvivors compared to their respective baselines. CONCLUSION: After m-sTBI, the plasma profiles of inflammatory cytokines are markedly altered in children. The trends of IL-6 and IL-8 expression vary among m-sTBI children with different outcomes. Elevated plasma IL-6 and IL-8 levels are related to in-hospital mortality and unfavorable 6-month outcomes. TRIAL REGISTRATION: This trial was registered in the Chinese Clinical Trial Registry (Registration number: ChiCTR2200065505). Registered November 7, 2022. WHAT IS KNOWN: ⢠Inflammation is an important secondary physiological response to TBI. WHAT IS NEW: ⢠The plasma profiles of inflammatory cytokines are markedly altered in children with m-sTBI. Elevated IL-6 and IL-8 levels are related to mortality and unfavorable outcomes.
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Lesiones Traumáticas del Encéfalo , Citocinas , Humanos , Masculino , Femenino , Estudios Prospectivos , Niño , Citocinas/sangre , Lesiones Traumáticas del Encéfalo/sangre , Lesiones Traumáticas del Encéfalo/mortalidad , Preescolar , Biomarcadores/sangre , Mortalidad Hospitalaria , Estudios de Casos y Controles , Adolescente , Pronóstico , Lactante , Escala de Consecuencias de GlasgowRESUMEN
Septic shock is a life-threatening disease worldwide often associated with thrombocytopenia. Platelets play a crucial role in bridging the gap between immunity, coagulation, and endothelial cell activation, potentially influencing the course of the disease. However, there are few studies specifically evaluating the impact of thrombocytopenia on the prognosis of pediatric patients. Therefore, the study investigates effects of early thrombocytopenia in the prognosis of children with septic shock. Pediatric patients with septic shock from 2015 to 2022 were included monocentrically. Thrombocytopenia was defined as a platelet count of <100 × 109/L during the first 24 hours of septic shock onset. The primary outcome was the 28-day mortality. Propensity score matching was used to pair patients with different platelet counts on admission but comparable disease severity. A total of 419 pediatric patients were included in the analysis. Patients with thrombocytopenia had higher 28-day mortality (55.5% vs. 38.7%, p = .005) compared to patients with no thrombocytopenia. Thrombocytopenia was associated with reduced 28-PICU free days (median value, 0 vs. 13 days, p = .003) and 28-ventilator-free (median value, 0 vs. 19 days, p = .001) days. Among thrombocytopenia patients, those with platelet count ≤50 × 109/L had a higher 28-day mortality rate (63.6% vs. 45%, p = .02). Multiple logistic regression showed that elevated lactate (adjusted odds ratio (OR) = 1.11; 95% confidence interval (CI): 1.04-1.17; P <0.001) and white blood cell (WBC) count (OR = 0.97; 95% CI: 0.95-0.99; p = .003) were independent risk factors for the development of thrombocytopenia. Thrombocytopenia group had increased bleeding events, blood product transfusions, and development of organ failure. In Kaplan-Meier survival estimates, survival probabilities at 28 days were greater in patients without thrombocytopenia (p value from the log-rank test, p = .004). There were no significant differences in the type of pathogenic microorganisms and the site of infection between patients with and without thrombocytopenia. In conclusion, thrombocytopenia within 24 hours of shock onset is associated with an increased risk of 28-day mortality in pediatric patients with septic shock.
What is the context? Septic shock is a life-threatening disease worldwide, leading to higher mortality.Platelets play a crucial role in bridging the gap between immunity, coagulation, and endothelial cell activation.Although it is known that platelets are associated with prognosis, most studies have focused on adult populations. Limited data are available on the incidence of thrombocytopenia and its correlation with clinical outcomes , specifically, in pediatric patients with sepsis and septic shock. What is new? The present study suggests that thrombocytopenia within 24 hours of septic shock onset reflects a reliable tool for predicting the prognosis of septic shock in pediatric patients.Furthermore, elevated lactate and reduced white-blood-cell count were independent risk factors for the development of thrombocytopenia in pediatric patients with septic shock. What is the impact? This study suggests that thrombocytopenia within 24 hours of septic shock onset is associated with an increased risk of 28-day mortality and decreased ventilation-free, PICU-free days in pediatric patients with septic shock. In septic shock, thrombocytopenia is also associated with increased bleeding events, blood product transfusions, and organ dysfunction.
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Choque Séptico , Trombocitopenia , Humanos , Trombocitopenia/complicaciones , Trombocitopenia/sangre , Choque Séptico/complicaciones , Choque Séptico/mortalidad , Choque Séptico/sangre , Masculino , Femenino , Pronóstico , Estudios Retrospectivos , Niño , Preescolar , Lactante , Recuento de Plaquetas/métodosRESUMEN
The therapeutic efficacy of intravenous immuneglobulin (IVIG) on children with septic shock remains uncertain. Therefore, we endeavored to investigate the impact of administering intravenous immunoglobulin (IVIG) in the pediatric intensive care unit (PICU) on patient with septic shock. We retrospectively analyzed the data of children admitted to the PICU due to septic shock from January 2017 to December 2021 in a tertiary pediatric hospital. The main outcome was in-hospital mortality. Total 304 patients were enrolled. There were no significant differences in the PRISM-III score (11 vs. 12, P = 0.907), PIM-3 score (0.08 vs. 0.07, P = 0.544), pSOFA score (10 vs. 10, P = 0.852) between the No IVIG group and the IVIG group. Children who received IVIG required more continuous renal replacement therapy (CRRT) support (43% vs. 24%, P = 0.001) and longer duration of mechanical ventilation (MV) (6 vs. 3 days, P = 0.002), and longer length of stay (LOS) of PICU (7 vs. 4 days, P = 0.001) and LOS of hospital (18 vs. 11 days, P = 0.001) than children who did not receive. The 28-day survival analysis (P = 0.033) showed better survival rates in IVIG group, while the in-hospital mortality (43% vs. 52%, P = 0.136) was no significant difference. In the propensity score matched analysis, 71 pairs were established. The length of CRRT (2 vs. 3 days, P = 0.744), duration of mechanical ventilation (5 vs. 4 days, P = 0.402), LOS of PICU (7 vs. 5 days, P = 0.216), LOS of hospital (18 vs. 13 days, P = 0.290), in-hospital mortality (44% vs. 44%, P = 1.000) and 28-day survival analysis (P = 0.748) were not statistically different. After inverse probability weighted analysis, there was still no difference in mortality between the two groups (51% vs. 48%, P = 0.665). CONCLUSION: In children with septic shock, the use of intravenous immunoglobulin as an adjuvant therapy does not reduce in-hospital mortality. WHAT IS KNOWN: ⢠Guidelines suggest against the routine use of intravenous immuneglobulin in children with septic shock. Some small observational studies have reported conflicting result. WHAT IS NEW: ⢠The use of intravenous immunoglobulin as an adjuvant therapy does not reduce in-hospital mortality in children with septic shock.
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Choque Séptico , Humanos , Niño , Choque Séptico/tratamiento farmacológico , Inmunoglobulinas Intravenosas/uso terapéutico , Estudios Retrospectivos , Unidades de Cuidado Intensivo Pediátrico , Puntaje de PropensiónRESUMEN
Abnormal blood coagulation often occurs in critically ill patients, which seriously affects their prognosis. This retrospective study investigated the implications of changes in blood coagulation in patients with coronavirus disease 2019 (COVID-19). Records were reviewed for patients admitted with COVID-19 between February 4 and 16, 2020. The primary outcome was in-hospital death. A total of 85 patients were included, of whom 12 died in the hospital. The admission prothrombin time (PT), international normalized ratio (INR), and levels of D-dimer and fibrin/fibrinogen degradation products (FDP) were significantly higher in non-survivors than in survivors, while the reverse was true for prothrombin time activity (PT-act) and PaO2/FiO2. Multivariate logistic regression showed that PT-act < 75% was independently associated with mortality. The area under the receiver operating characteristic curves for PT-act, D-dimer, and FDP at admission could significantly predict mortality. The AUCs for PT-act were larger than those for D-dimer and FDP; however, there was no significant difference. After 2 weeks of treatment, the coagulation parameters of the surviving patients improved. COVID-19 is often accompanied by abnormal coagulation. PT-act at admission is able to predict mortality in patients with COVID-19 as can D-dimer and FDP levels. PT-act < 75% is independently associated with mortality.
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Coagulación Sanguínea , COVID-19 , Productos de Degradación de Fibrina-Fibrinógeno/metabolismo , Mortalidad Hospitalaria , Oxígeno/sangre , SARS-CoV-2 , Adulto , Anciano , Anciano de 80 o más Años , COVID-19/sangre , COVID-19/mortalidad , COVID-19/terapia , Femenino , Humanos , Masculino , Persona de Mediana Edad , Tiempo de Protrombina , Estudios RetrospectivosRESUMEN
BACKGROUND: Talaromyces marneffei (T. marneffei) is a thermally dimorphic fungus causing systemic mycosis. Due to the atypical symptoms and diverse imaging findings, T. marneffei-infected patients may be misdiagnosed thus preventing timely antifungal therapy. Moreover, HIV-negative patients with T. marneffei infection may be congenitally immunocompromised because of the mutation of immune-related genes. CASE PRESENTATION: We describe a case of an HIV-negative child who developed disseminated T. marneffei infection in a nonendemic area. Chest CT showed similar imaging changes of miliary pulmonary tuberculosis, while there was no other evidence of tuberculosis infection, and empirical antituberculosis treatment was not effective. Lymphocyte subset analysis showed reduced natural killer cells, and the immunoglobulin profile showed low levels of IgM, C3 and C4. A bone marrow smear revealed T. marneffei infection, and ascites culture also proved T. marneffei infection. Despite antifungal treatment, the child died of multiple organ failure. Two gene mutations in caspase recruitment domain-containing protein 9 (CARD9) were detected, which had not been reported previously in T. marneffei-infected patients. CONCLUSIONS: HIV-negative patients with CARD9 mutations may be potential hosts of T. marneffei. Abnormalities in the immunoglobin profile and lymphocyte subset may provide clues for immunocompromised patients, and further genetic testing is advised to identify gene mutations in HIV-negative patients with T. marneffei infection.
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Proteínas Adaptadoras de Señalización CARD/genética , Micosis , Talaromyces , Antifúngicos/uso terapéutico , Niño , China , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , Humanos , MutaciónRESUMEN
OBJECTIVE: Hyperglycaemia is common amongst children with traumatic brain injury (TBI). We aim to investigate the association between early hyperglycaemia and poor clinical outcomes in children with moderate to severe TBI. METHODS: We performed a retrospective study in a tertiary paediatric hospital between May 2012 and October 2014 of all patients with TBI who were aged <16 years with a Glasgow Coma Scale (GCS) of ≤13. The primary outcome was death. Secondary outcomes were 14 ventilation-free, 14 paediatric intensive care unit (PICU)-free and 28 hospital-free days. We defined hyperglycaemia as glucose >11.1 mmol/L (200 mg/dL). RESULTS: There were 109 patients with a median age of 54 months [inter-quartile range (IQR): 17-82]. Median glucose on arrival was 6.1 mmol/L (IQR: 5.2-9.8). Median GCS in our cohort was 8 (IQR: 6-12). Multivariate logistic regression demonstrated that initial hyperglycaemia [odds ratio (OR): 15.23; 95% confidence interval (CI): 3.74-62.00; P < 0.001], and GCS <8 (OR: 13.02; 95% CI: 2.31-73.33; P = 0.004) were risk factors for mortality. Multivariate linear regression showed that initial hyperglycaemia was a risk factor for reduced ventilation-free, PICU-free and hospital-free days. CONCLUSIONS: Early hyperglycaemia predicts for in-hospital mortality, reduced ventilation-free, PICU-free and hospital-free days in children with moderate to severe TBI.
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Lesiones Traumáticas del Encéfalo/complicaciones , Mortalidad Hospitalaria , Hiperglucemia/etiología , Hiperglucemia/mortalidad , Glucemia/metabolismo , Lesiones Traumáticas del Encéfalo/mortalidad , Niño , Preescolar , Estudios de Cohortes , Femenino , Escala de Coma de Glasgow , Humanos , Lactante , Unidades de Cuidado Intensivo Pediátrico , Tiempo de Internación , Modelos Lineales , Masculino , Factores de Riesgo , Resultado del TratamientoRESUMEN
OBJECTIVE: To investigate the distribution and drug sensitivity of pathogens and risk factors for ventilator-associated pneumonia (VAP) in children with congenial heart disease (CAD) after surgery. METHODS: According to the occurrence of VAP, 312 children with CAD who received mechanical ventilation after surgery for 48 hours or longer between January 2012 and December 2014 were classified into VAP (n=53) and non-VAP groups (n=259). Sputum samples were collected and cultured for pathogens in children with VAP. The drug sensitivity of pathogens was analyzed. The risk factors for postoperative VAP were identified by multiple logistic regression analysis. RESULTS: The sputum cultures were positive in 51 out of 53 children with VAP, and a total of 63 positive strains were cultured, including 49 strains of Gram-negative bacteria (78%), 9 strains of Gram-positive bacteria (14%) and 5 strains of funqi (8%). The drug sensitivity test showed that Gram-negative bacteria were resistant to amoxicillin, piperacillin, cefotaxime and ceftazidime, with a resistance rate of above 74%, and demonstrated a sensitivity to amikacin, polymyxin and meropenem (resistance rate of 19%-32%). Single factor analysis showed albumin levels, preoperative use of antibiotics, duration of mechanical ventilation, times of tracheal intubation, duration of anesthesia agent use, duration of acrdiopulmonary bypass, duration of aortic occlusion and use of histamin2-receptor blockade were significantly different between the VAP and non-VAP groups (P<0.05). The multiple logistic regression showed albumin levels (<35 g/L), duration of mechanical ventilation (≥ 7 d), times of tracheal intubation (≥ 3), duration of acrdiopulmonary bypass (≥ 100 minutes) and duation of aortic occlusion (≥ 60 minutes) were independent risk factors for VAP in children with CAD after surgery. CONCLUSIONS: Gram-nagative bacteria are main pathogens for VAP in children with CAD after surgery. The antibiotics should be used based on the distribution of pathogens and drug sensitivity test results of pathogens. The effective measures for prevention of VAP should be taken according to the related risk factors for VAP to reduce the morbidity of VAP in children with CAD after surgery.
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Cardiopatías Congénitas/cirugía , Neumonía Asociada al Ventilador/etiología , Antibacterianos/farmacología , Bacterias Gramnegativas/aislamiento & purificación , Humanos , Modelos Logísticos , Pruebas de Sensibilidad Microbiana , Neumonía Asociada al Ventilador/prevención & control , Factores de Riesgo , Esputo/microbiologíaRESUMEN
BACKGROUND: The incidence of Pseudomonas aeruginosa (P. aeruginosa) bacteremia in children ranks third to fourth among gram-negative bacilli bacteremia, which is one of the main conditional pathogens in hospitals. This study aimed to identify the clinical characteristics and risk factors of 60-day in-hospital mortality in children with P. aeruginosa bacteremia. METHODS: This retrospective study was conducted in a tertiary pediatric hospital between January 2015 and December 2021 including children with P. aeruginosa bacteremia. Kaplan-Meier survival analysis was used to investigate the time-to-event outcomes. Logistic regression was used to explore the independent risk factors for 60-day mortality. RESULTS: Overall, 75 patients with P. aeruginosa bacteremia episodes were identified. Immunosuppression (52%) was the most common underlying condition, followed by neutropenia (50.7%) and hematological malignancies (48%). Among 75 patients with P. aeruginosa bacteremia, 25 (33.3%) had septic shock, 30 (40%) had respiratory failure, and 20 (26.7%) had liver function impairment. The 60-day in-hospital mortality was 17.3%. In multivariate analysis, independent risk factors for 60-day mortality were respiratory failure [odds ratio (OR) 39.329; 95% CI:3.212-481.48, P = 0.004) and liver function impairment (OR 17.925; 95% CI:2.909-139.178, P = 0.002). CONCLUSION: Respiratory failure and liver function impairment seem to be related to poor prognosis in children with P. aeruginosa bacteremia.
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Bacteriemia , Insuficiencia Respiratoria , Humanos , Niño , Pseudomonas aeruginosa , Estudios Retrospectivos , Factores de Riesgo , Bacteriemia/tratamiento farmacológico , Antibacterianos/uso terapéuticoRESUMEN
OBJECTIVE: There is an amelioration in mortality rates of septic shock patients with malignancies over time, but it remains uncertain in children. Therefore, the authors endeavored to compare the clinical characteristics, treatment needs, and outcomes of septic shock children with or without malignancies. METHODS: The authors retrospectively analyzed the data of children admitted to the PICU due to septic shock from January 2015 to December 2022 in a tertiary pediatric hospital. The main outcome was in-hospital mortality. RESULTS: A total of 508 patients were enrolled. The proportion of Gram-negative bacteria and fungal infections in children with malignancies was significantly higher than those without malignancies. Septic shock children with malignancies had a longer length of stay (LOS) in the hospital (21 vs. 11 days, p<0.001). However, there were no statistically significant differences in the LOS of PICU (5 vs. 5 days, p = 0.591), in-hospital mortality (43.0 % vs. 49.4 %, p = 0.276), and 28-day mortality (49.2 % vs. 44.7 %, p = 0.452). The 28-day survival analysis (p = 0.314) also showed no significant differences. CONCLUSION: Although there are significant differences in the bacterial spectrum of infections, the septic shock children with or without malignancies showed a similar mortality rate. The septic shock children with malignancies had longer LOS of the hospital.
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OBJECTIVE: To explore the expression of α-smooth muscle actin (α-SMA) during the lung injury induced by hyperoxia in infantile rats. METHODS: Sixty-four male Sprague-Dawley (SD) rats about 3 weeks were randomly assigned into normal control group which exposured to room air [fraction of inspired oxygen (FiO(2)) was 0.21] and hyperoxia exposure group (95%O(2)) according to random digits table. Eight rats in each group were randomly sacrificed at day 1, 7, 14 and 21.Pulmonary tissue remodeling was observed by hematoxylin-eosin (HE) staining. Immunohistochemistry method was performed to evaluate the expression of α-SMA in pulmonary tissue, further Western blotting was also made to determine the expression of α-SMA. RESULTS: The early histopathologic changes after HE were inflammation and edema in pulmonary tissue, while the later changes were interstitial hyperplasia and fibroblast proliferation. The expression of α-SMA was very slight in bronchial epithelium, alveolar epithelium and alveolar interstitium in normal control group, but increased with the time of hyperoxia exposure prolonged and peaked at 21st day. Western blotting detected that the expression of α-SMA after hyperoxia exposure for 1 day and 7 days in hyperoxia exposure group presented no difference compared with normal control group (1.02±0.12 vs. 1.00±0.13, 1.05±0.14 vs. 0.99±0.12, both P>0.05), but the expression of α-SMA after hyperoxia exposure for 14 days and 21 days was increased compared with normal control group (1.27±0.21 vs. 1.05±0.15, 2.26±0.28 vs. 1.05±0.14, P<0.05 and P<0.01). CONCLUSIONS: Pulmonary fibrosis remodeling was caused by hyperoxia exposure. The expression of α-SMA in pulmonary tissue in hyperoxia exposure groups obviously increased, and could play an important role in pulmonary fibrosis remodeling.
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Actinas/metabolismo , Hiperoxia/metabolismo , Lesión Pulmonar/metabolismo , Animales , Hiperoxia/complicaciones , Pulmón/metabolismo , Lesión Pulmonar/etiología , Masculino , Ratas , Ratas Sprague-DawleyRESUMEN
Background: We assessed the outcomes and characteristics of culture-negative septic shock (CNSS) and culture-positive septic shock (CPSS) in pediatric intensive care unit (PICU). Methods: We performed a retrospective study on the data of children admitted to the PICU due to septic shock between January 2018 and December 2021. The primary outcome was in-hospital mortality. The secondary outcomes were the length of stay (LOS) of hospital, the need for mechanical ventilation (MV) and continue renal replacement therapy (CRRT). Results: Overall, 238 patients were enrolled. 114 patients (47.9%) had positive cultures (60 blood samples, 41 sputum samples, 17 pus samples, and 19 others), 18 of whom were cultured positive at two sites, 1 at three sites, and 3 had two different types of bacteria at same site. The in-hospital mortality was 47.1%. There were no significant differences in the in-hospital mortality (47.6% vs. 46.5%, P = 0.866), PRISM-III score (10 vs. 12, P = 0.409), PIM-3 score (0.08 vs. 0.07, P = 0.845), pSOFA score (10 vs. 10, P = 0.677) or the need for MV (64.5% vs. 68.4%, P = 0.524) and CRRT (29.8% vs. 34.2%, P = 0.470) between the CNSS group and the CPSS group. The Procalcitonin (8.89â ng/ml vs. 28.39â ng/ml, P = 0.001) and C-reactive protein (28â mg/L vs. 58â mg/L, P = 0.001) levels were significantly lower in the CNSS group than in the CPSS group, while WBC count (9.03 × 109/L vs. 5.02 × 109/L, P = 0.002) and serum sodium (137â mmol/L vs. 132â mmol/L, P = 0.001) was significantly higher in CNSS. The LOS of hospital was significantly longer (16 days vs. 11 days, P = 0.011) in the CPSS group than in the CNSS group, while the LOS of PICU (5 days vs. 4 days, P = 0.094) stay was not significantly different. Conclusion: Compared with children with CNSS, children with CPSS had higher PCT and CRP levels, but lower WBC count. Children with CPSS had longer LOS of hospital. However, positive or negative culture results were not associated with in-hospital mortality, the LOS of PICU, the need for MV or CRRT in children with septic shock.
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Objective: To explore the efficacy and safety of vancomycin as measured by pharmacokinetic/pharmacodynamic parameters in children with severe infection in the Pediatric Intensive Care Unit (PICU) and to determine the appropriate threshold for avoiding nephrotoxicity. Methods: The medical records of hospitalized children with severe infection treated with vancomycin in the PICU of a tertiary pediatric hospital from September 2018 to January 2021 were retrospectively collected. Univariate analysis was used to assess the correlation between vancomycin pharmacokinetic/pharmacodynamic parameters and therapeutic efficacy or vancomycin-related nephrotoxicity. Binary logistic regression was used to analyze the risk factors for vancomycin-related nephrotoxicity. The vancomycin area under the concentration-time curve over 24 h (AUC0-24) threshold was determined by receiver operating characteristic (ROC) curve analysis. Results: One hundred and 10 patients were included in this study. Seventy-six patients (69.1%) exhibited clinically effective response, while the rest exhibited clinically ineffective response. There were no significant differences in APACHE II score, steady-state trough concentration, peak concentration or AUC0-24 of vancomycin between the effective and ineffective groups. Among the 110 patients, vancomycin-related nephrotoxicity occurred in 15 patients (13.6%). Multivariate analysis showed that vancomycin treatment duration, trough concentration, and AUC0-24 were risk factors for vancomycin-related nephrotoxicity. The ROC curve indicated that AUC0-24 < 537.18 mg.h/L was a suitable cutoff point for predicting vancomycin-related nephrotoxicity. Conclusion: No significant correlations were found between the trough concentration or AUC0-24 of vancomycin and therapeutic efficacy when the daily dose of vancomycin was approximately 40 mg/kg d, while the trough concentration and AUC0-24 were both closely related to vancomycin-related nephrotoxicity. The combination of AUC0-24 and trough concentration for therapeutic drug monitoring may reduce the risk of nephrotoxicity.
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BACKGROUND: Coagulopathy in adult patients with traumatic brain injury (TBI) is strongly associated with unfavorable outcomes. However, few reports focus on pediatric TBI-associated coagulopathy. METHODS: We retrospectively identified children with Glasgow Coma Scale ≤ 13 in a tertiary pediatric hospital from April 2012 to December 2019 to evaluate the impact of admission coagulopathy on their prognosis. A classification and regression tree (CART) analysis using coagulation parameters was performed to stratify the death risk among patients. The importance of these parameters was examined by multivariate logistic regression analysis. RESULTS: A total of 281 children with moderate to severe TBI were enrolled. A receiver operating characteristic curve showed that activated partial thromboplastin time (APTT) and fibrinogen were effective predictors of in-hospital mortality. According to the CART analysis, APTT of 39.2 s was identified as the best discriminator, while 120 mg/dL fibrinogen was the second split in the subgroup of APTT ≤ 39.2 s. Patients were stratified into three groups, in which mortality was as follows: 4.5 % (APTT ≤ 39.2 s, fibrinogen > 120 mg/dL), 20.5 % (APTT ≤ 39.2 s and fibrinogen ≤ 120 mg/dL) and 60.8 % (APTT > 39.2 s). Furthermore, length-of-stay in the ICU and duration of mechanical ventilation were significantly prolonged in patients with deteriorated APTT or fibrinogen values. Multiple logistic regression analysis showed that APTT > 39.2 s and fibrinogen ≤ 120 mg/dL was independently associated with mortality in children with moderate to severe TBI. CONCLUSIONS: We concluded that admission APTT > 39.2 s and fibrinogen ≤ 120 mg/dL were independently associated with mortality in children with moderate to severe TBI. Early identification and intervention of abnormal APTT and fibrinogen in pediatric TBI patients may be beneficial to their prognosis.
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Trastornos de la Coagulación Sanguínea/sangre , Coagulación Sanguínea/fisiología , Lesiones Traumáticas del Encéfalo/sangre , Trastornos de la Coagulación Sanguínea/complicaciones , Trastornos de la Coagulación Sanguínea/mortalidad , Lesiones Traumáticas del Encéfalo/complicaciones , Lesiones Traumáticas del Encéfalo/mortalidad , Preescolar , China/epidemiología , Femenino , Mortalidad Hospitalaria/tendencias , Hospitalización/tendencias , Humanos , Lactante , Masculino , Tiempo de Tromboplastina Parcial , Pronóstico , Curva ROC , Estudios Retrospectivos , Tasa de Supervivencia/tendenciasRESUMEN
The production of reactive oxygen species (ROS) during hyperoxia contribute to alveolar epithelial apoptosis. In the present study, the molecular mechanisms of oxidative stress-induced alveolar epithelial cell apoptosis were investigated. The cytoprotective effects of N-acetylcysteine (NAC) were evaluated. Treatments using 500 muM H(2)O(2) can induce primary alveolar type II epithelial cell apoptosis. During this procedure, c-Jun N-terminal kinase (JNK) was activated. SP600125, a specific inhibitor of JNK, can partially block H(2)O(2)-induced alveolar type II epithelial cells (ATII cells). SP600125 also attenuated Bax protein content and p53 nuclear accumulation induced by H(2)O(2). NAC (5 mM) pretreatment decreased H(2)O(2)-induced ATII cell apoptosis. The high level of intracellular reactive oxygen species (ROS) induced by H(2)O(2) was also attenuated by NAC pretreatment. Taken together, H(2)O(2) can induce primary ATII cells apoptosis and increase JNK phosphorylation. NAC, a precursor of glutathione (GSH) synthesis, can protect ATII cells from H(2)O(2)-induced apoptosis through scavenging ROS.
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Acetilcisteína/farmacología , Células Epiteliales Alveolares/efectos de los fármacos , Apoptosis/efectos de los fármacos , Depuradores de Radicales Libres/farmacología , Peróxido de Hidrógeno/toxicidad , Proteínas Quinasas JNK Activadas por Mitógenos/metabolismo , Oxidantes/toxicidad , Estrés Oxidativo/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo , Células Epiteliales Alveolares/enzimología , Células Epiteliales Alveolares/patología , Animales , Antracenos/farmacología , Células Cultivadas , Citoprotección , Relación Dosis-Respuesta a Droga , Regulación hacia Abajo , Glutatión/metabolismo , Proteínas Quinasas JNK Activadas por Mitógenos/antagonistas & inhibidores , Masculino , Fosforilación , Inhibidores de Proteínas Quinasas/farmacología , Ratas , Ratas Sprague-Dawley , Factores de Tiempo , Proteína p53 Supresora de Tumor/metabolismo , Proteína X Asociada a bcl-2/metabolismoRESUMEN
INTRODUCTION: This retrospective study investigated the implications of changes in blood parameters and cellular immune function in patients with Coronavirus Disease 2019 (COVID-19). METHODS: Records were reviewed of 85 patients admitted with COVID-19 between February 4 and 16, 2020. The primary outcome was in-hospital death. RESULTS: Fourteen patients died. The baseline leukocyte count, neutrophil count and hemoglobin was significantly higher in non-survivors compared with survivors, while the reverse was true of lymphocyte count, platelet, PaO2/FiO2, CD3+ count and CD4+ count. The percentage of neutrophil count > 6.3×109/L in death group was significantly higher than that in survival group, and multivariate logistic regression showed neutrophil count > 6.3×109/L was independently associated with mortality. However, there were not significant difference in IgG, IgM, IgA, C3, C4 and the percentage of IgE > 100 IU/ml between the death group and survival group. Areas under the receiver operating characteristic curves of the following at baseline could significantly predict mortality: leukocyte, neutrophil, lymphocyte, CD3+ and CD4+ counts. CONCLUSIONS: For hospitalized patients with COVID-19, lymphocyte, CD3+ and CD4+ counts that marked decrease suggest a poor outcome. Admission neutrophil count > 6.3 ×109/L is independently associated with mortality. At admission, leukocyte, neutrophil, lymphocyte, CD3+ and CD4+ counts should receive added attention.
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COVID-19/sangre , COVID-19/inmunología , SARS-CoV-2/inmunología , Anciano , Linfocitos T CD4-Positivos/inmunología , COVID-19/mortalidad , China/epidemiología , Femenino , Mortalidad Hospitalaria , Humanos , Recuento de Leucocitos , Recuento de Linfocitos , Masculino , Persona de Mediana Edad , Neutrófilos , Pronóstico , Estudios Retrospectivos , SARS-CoV-2/aislamiento & purificación , SARS-CoV-2/metabolismoRESUMEN
OBJECTIVE: Some research has shown that p38 mitogen-activated protein kinase (p38MAPK) plays important roles in lung injuries induced by various factors. Its expression and role in hyperoxia-induced lung injury remains unknown. This study investigated the expression and role of p38MAPK in hyperoxia-induced lung injury juvenile rat model. METHODS: Hyperoxia-induced lung injury rat model was prepared by 90% O(2) exposure. The location and expression of p38MAPK in lung tissues were detected by immunohistochemistry and Western blot respectively. Apoptosis index of lung was evaluated by TUNEL technique. The effect of SB203580, a p38MAPK inhibitor, on the apoptosis index of lung was observed. RESULTS: The expression of phosphor-p38MAPK increased obviously after hyperoxia. Positive phosphor-p38MAPK cells were mainly distributed in the alveolar, airway epithelial cells, pulmonary vascular endothelium cells and infiltrative inflammatory cells. The apoptosis index of lung also significantly elevated. SB203580 inhibited the activation of p38MAPK, and reduced the apoptosis index of lung. CONCLUSIONS: The phosphor-p38MAPK increased and was expressed in many kinds of lung cells in lung injury rat model. It may play a role in the induction of apoptosis in hyperoxia-induced lung injury.
Asunto(s)
Hiperoxia/complicaciones , Proteínas Quinasas p38 Activadas por Mitógenos/fisiología , Animales , Apoptosis , Modelos Animales de Enfermedad , Femenino , Imidazoles/uso terapéutico , Immunoblotting , Lesión Pulmonar/tratamiento farmacológico , Lesión Pulmonar/enzimología , Lesión Pulmonar/etiología , Sistema de Señalización de MAP Quinasas , Masculino , Fosforilación , Piridinas/uso terapéutico , Ratas , Ratas Wistar , Proteínas Quinasas p38 Activadas por Mitógenos/análisisRESUMEN
BACKGROUND: Lactate is used to evaluate the prognosis of adult patients with trauma. However, the prognostic significance of admission serum lactate in the setting of pediatric traumatic brain injury (TBI) is still unclear. We aim to investigate the impact of admission lactate on the outcome in children with moderate to severe TBI. METHODS: This retrospective study was conducted in a tertiary pediatric hospital between May 2012 and Jun 2018 included children with an admission Glasgow Coma Scale (GCS) of ≤13. Two hundred and thirteen patients were included in the analysis and 45 patients died in hospital. RESULTS: Admission lactate and glucose were significantly higher in non-survivors than those in survivors (P < 0.05). Admission lactate was positively correlated with admission glucose and negatively correlated with GCS in all patients (n = 213), subgroup of isolated TBI (n = 112) and subgroup of GCS ≤ 8 (n = 133), respectively. AUCs of lactate could significantly predict the mortality and were higher than those of glucose in all patients, subgroup of isolated TBI and subgroup of GCS ≤ 8, respectively. Multivariate logistic regression showed that admission lactate (Adjusted OR = 1.189; 95% CI: 1.002-1.410; P = 0.047) was independently associated with mortality, while admission glucose (Adjusted OR = 1.077; 95% CI: 0.978-1.186; P = 0.133) wasn't an independent risk factor of death. Elevated admission lactate (> 2 mmol/L) was associated with death, reduced 14-day ventilation-free days, 14-day ICU-free days and 28-day hospital-free days. CONCLUSIONS: Admission serum lactate can effectively predict the mortality of children with moderate to severe TBI. Elevated admission lactate is associated with death, reduced ventilator-free, ICU-free, and hospital-free days. Admission serum lactate could be used as a prognostic biomarker of mortality in children with moderate to severe TBI.
Asunto(s)
Lesiones Traumáticas del Encéfalo/tratamiento farmacológico , Lactatos/administración & dosificación , Lesiones Traumáticas del Encéfalo/mortalidad , Niño , Preescolar , Femenino , Escala de Coma de Glasgow , Glucosa/administración & dosificación , Mortalidad Hospitalaria , Humanos , Lactante , Modelos Logísticos , Masculino , Estudios Retrospectivos , Factores de RiesgoRESUMEN
Hypoalbuminemia and anemia are frequent among in patients with traumatic brain injury (TBI). We assess whether serum albumin and hemoglobin at admission can predict outcome in children with moderate to severe TBI.This retrospective study was conducted in a tertiary pediatric hospital between May 2012 and Jun 2018 included children with an admission Glasgow Coma Scale of ≤13.A total of 213 patients were included of whom 45 died in hospital. Multivariate logistic regression showed that hypoalbuminemia (serum albumin <30âg/L) was independently associated with mortality (adjusted odds ratio [OR]â=â3.059; 95% confidence interval [CI]: 1.118-8.371; Pâ=â.030) in children with moderate to severe TBI, while anemia (hemoglobin <90âg/L) was not independently associated with mortality (adjusted ORâ=â1.742; 95% CI: 0.617-4.916; Pâ=â.295). Serum albumin was significantly superior to hemoglobin (area under the curve [AUC] 0.738 vs AUC 0.689, Pâ<â.05) under receiver operating characteristic curve analysis. Hypoalbuminemia was also associated with reduced 14-day ventilation-free days, 14-day intensive care unit (ICU)-free days, and 28-day hospital-free days.Serum albumin at admission was superior to hemoglobin in predicting the mortality in children with moderate to severe TBI and also associated with reduced ventilator-free, ICU-free, and hospital-free days.
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Lesiones Traumáticas del Encéfalo/sangre , Lesiones Traumáticas del Encéfalo/mortalidad , Hemoglobina Glucada/metabolismo , Mortalidad Hospitalaria , Albúmina Sérica/metabolismo , Anemia/complicaciones , Anemia/diagnóstico , Biomarcadores/sangre , Lesiones Traumáticas del Encéfalo/complicaciones , Lesiones Traumáticas del Encéfalo/terapia , Estudios de Casos y Controles , Niño , Preescolar , Cuidados Críticos , Femenino , Escala de Coma de Glasgow , Humanos , Hipoalbuminemia/complicaciones , Hipoalbuminemia/diagnóstico , Masculino , Valor Predictivo de las Pruebas , Respiración Artificial , Estudios RetrospectivosRESUMEN
OBJECTIVE: To study in vitro the influence of 60% oxygen and the protective effect of calcitonin gene-related peptide (CGRP) on type II alveolar epithelial cells (AEC II) isolated from the lung of premature rat. METHODS: AEC II were isolated from the lung of 19-day rat fetus, and they were then cultured in six-well plates. The cells were randomly divided into four groups: air group, hyperoxia group, hyperoxia plus CGRP group, hyperoxia plus CGRP and CGRP8-37 (CGRP receptor antagonist) group. Cells of air group and hyperoxia group were exposed to 21% air or 60% oxygen, respectively, while in hyperoxia plus CGRP group CGRP was added, and in hyperoxia plus CGRP and CGRP8-37 group CGRP and CGRP8-37 were added before exposure to 60% oxygen. Cells in four groups were cultured for 24 hours, and then ground into homogenates for detection of malondialdehyde (MDA), total antioxidant capacity (TAOC) and superoxide dismutase (SOD) with ultraviolet spectrophotometer. Reactive oxygen species (ROS) and apoptosis rate of AEC II were analyzed by flow cytometry and the mRNA level of surfactant associated protein C (SPC) was measured by reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: The levels of ROS, MDA and apoptosis rate were increased whereas TAOC, SOD and SPC mRNA expression declined in hyperoxia group compared with those in air group (all P<0.01). In contrast, MDA, ROS and apoptosis rate were significantly lower and levels of TAOC, SOD and SPC mRNA expression were significantly higher in hyperoxia plus CGRP group than those in hyperoxia group (all P<0.01). The differences in 6 parameters above between hyperoxia group and hyperoxia plus CGRP and CGRP8-37 group were not statistically significant. CONCLUSION: Exposure of AEC II from immature rat to 60% oxygen for 24 hours may produce oxidative injury, inducing apoptosis and decrease in SPC mRNA level of AEC II of premature rat in vitro, while CGRP may play a protective role against hyperoxic lung injury by its antioxidant property, and also inhibition of AEC II apoptosis and promotion of the SPC mRNA expression.
Asunto(s)
Células Epiteliales Alveolares/efectos de los fármacos , Péptido Relacionado con Gen de Calcitonina/farmacología , Oxígeno/toxicidad , Células Epiteliales Alveolares/metabolismo , Células Epiteliales Alveolares/patología , Animales , Animales Recién Nacidos , Apoptosis/efectos de los fármacos , Hipoxia de la Célula , Células Cultivadas , Femenino , Masculino , Malondialdehído/metabolismo , Ratas , Ratas Sprague-Dawley , Superóxido Dismutasa/metabolismoRESUMEN
OBJECTIVE: To investigate the effects of oxidative stress on the survival and apoptosis of alveolar epithelial type II (ATII) cells, as well as the mechanisms of apoptosis. METHODS: 500 mumol/L H(2)O(2) was added into primary ATII cells at different times and cell viability, apoptotic ratio and the expression of Bax and p53 were measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, flow cytometry (FCM) and Western blotting analysis, respectively. The change in mitochondrial membrane potential (MMP) was detected by fluorescence microscopy and FCM. RESULTS: The cell viability and MMP were decreased by H(2)O(2) compared with the controls (F(1)=85.211, F(2)=72.453, respectively, both P<0.05). The cell apoptotic ratios were increased with the time of the stimulation prolonged compared with the controls (F=54.002, P<0.05). H(2)O(2) increased Bax and p53 protein levels (F(1)=28.118, F(2)=43.456, both P<0.05). CONCLUSION: High level of oxidative stress can inhibit ATII cells proliferation, and induce cells apoptosis and decrease the MMP. Up-regulation of the expression of Bax and p53 may contribute to its apoptosis effects.